text:
Pancreatic cancer
Pancreatic cancer | |
Classification and external resources | |
DiseasesDB | 9510 |
MedlinePlus | 000236 |
eMedicine | med/1712 |
MeSH | D010190 |
Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors, is adenocarcinoma (tumors exhibiting glandular architecture on light microscopy) arising within the exocrine component of the pancreas. A minority arise from islet cells, and are classified as neuroendocrine tumors. The signs and symptoms that eventually lead to the diagnosis depend on the location, the size, and the tissue type of the tumor, and may include abdominal pain, lower back pain, and jaundice (if the tumor compresses the bile duct), unexplained weight loss, and digestive problems.
Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States[1] and the twelfth worldwide.[2] Pancreatic cancer has an extremely poor prognosis: for all stages combined, the 1- and 5-year relative survival rates are 25% and 6%, respectively;[3] for local disease the 5-year survival is approximately 15% [3][4] while the median survival for locally advanced and for metastatic disease, which collectively represent over 80% of individuals,[4] is about 10 and 6 months respectively.[5] Individuals vary, however - some are only diagnosed when they are already terminally ill and therefore only have a few days or weeks. Others have slower progression and may live a couple of years even if surgery is not possible. Men are 30% more likely to get pancreatic cancer than are women.
Signs and symptoms[edit]
Early pancreatic cancer often does not cause symptoms,[6] and the later symptoms are usually nonspecific and varied.[6] Therefore, pancreatic cancer is often not diagnosed until it is advanced.[6] Common symptoms include:
- Pain in the upper abdomen that typically radiates to the back[6] (seen in carcinoma of the body or tail of the pancreas)
- Heartburn - acid stomach
- Poor appetite or nausea and vomiting[6]
- Diarrhea, loose stools.
- Significant weight loss (cachexia)
- Painless jaundice (yellow tint to whites of eyes (sclera) or yellowish skin, possibly in combination with darkened urine)[6] when a cancer of the head of the pancreas (75% of cases)[7] obstructs the common bile duct as it runs through the pancreas. This may also cause pale-colored stool and steatorrhea. The jaundice may be associated with itching as the salt from excess bile can cause skin irritation.
- Trousseau syndrome, in which blood clots form spontaneously in the portal blood vessels, the deep veins of the extremities, or the superficial veins anywhere on the body, may be associated with pancreatic cancer.
- Pulmonary embolisms due to pancreatic cancers producing blood clotting chemicals.
- Diabetes mellitus, or elevated blood sugar levels. Many patients with pancreatic cancer develop diabetes months to even years before they are diagnosed with pancreatic cancer, suggesting new onset diabetes in an elderly individual may be an early warning sign of pancreatic cancer.[8]
- Clinical depression has been reported in association with pancreatic cancer, sometimes presenting before the cancer is diagnosed. However, the mechanism for this association is not known.[9]
- Symptoms of pancreatic cancer metastasis. Typically, pancreatic cancer first metastasizes to regional lymph nodes, and later to the liver or to the peritoneal cavity and, rarely, to the lungs;[10] it rarely metastasizes to bone or brain.[11]
Risk factors[edit]
Risk factors for pancreatic cancer may include:[6][12]
- Family history: 5–10% of pancreatic cancer patients have a family history of pancreatic cancer. The genes have not been identified. Pancreatic cancer has been associated with the following syndromes: autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2 gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene, hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and the familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene.[13][14] There may also be a history of familial pancreatitis.[13]
- Age. The risk of developing pancreatic cancer increases with age. Most cases occur after age 60, while cases before age 40 are uncommon.
- Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of nonsmoking after heavy smoking is associated with a risk ratio of 1.2.[15]
- Diets low in vegetables and fruits.[16]
- Diets high in red meat. Processed meat consumption is positively associated with pancreatic cancer risk, and red meat consumption was associated with an increased risk of pancreatic cancer in men.[17]
- Diets high in sugar-sweetened drinks (soft drinks).[18] In particular, limited epidemiological studies link the common soft drink sweetener fructose with growth of pancreatic cancer cells.[19]
- Obesity[20]
- Diabetes mellitus is both risk factor for pancreatic cancer, and, as noted earlier, new onset diabetes can be an early sign of the disease.
- Chronic pancreatitis has been linked, but is not known to be causal. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.
- Helicobacter pylori infection[21][22]
- Gingivitis or periodontal disease[23]
- Partial gastrectomy[24][25]
It is controversial whether alcohol consumption is a risk factor for pancreatic cancer. Overall, the association is consistently weak and the majority of studies have found no association.[26][27][28][29] Although drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, chronic pancreatitis associated with alcohol consumption is less frequently a precursor for pancreatic cancer than other types of chronic pancreatitis.[30]
Some studies suggest a relationship,[31] the risk increasing with increasing amount of alcohol intake.[32][33] The risk is greatest in heavy drinkers,[34][35][36] mostly on the order of four or more drinks per day.[37] There appears to be no increased risk for people consuming up to 30g of alcohol a day,[29][38][39] which is approximately 2 alcoholic beverages/day,[39] so most people who take alcohol do so at a level that "is probably not a risk factor for pancreatic cancer".[36] A pooled analysis concluded, "Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day".[39]
Several studies caution that their findings could be due to confounding factors.[35][40] Even if a link exists, it "could be due to the contents of some alcoholic beverages"[41] other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.[42]
Most patients with pancreatic cancer experience pain, weight loss, or jaundice.[43]
Pain is present in 80% to 85% of patients with locally advanced or advanced metastatic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it can be associated with anorexia, early satiety, diarrhoea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine. Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion.
The initial presentation varies according to location of the cancer. Malignancies in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau sign), or a previous attack of pancreatitis are sometimes noted. Courvoisier sign defines the presence of jaundice and a painlessly distended gallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones. Tiredness, irritability and difficulty eating because of pain also exist. Pancreatic cancer is often discovered during the course of the evaluation of aforementioned symptoms.
Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity. When a cutoff above 37 U/mL is used, this marker has a sensitivity of 77% and specificity of 87% in discerning benign from malignant disease. CA 19-9 might be normal early in the course, and could be elevated because of benign causes of biliary obstruction.[44] Imaging studies, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) can be used to identify the location and form of the cancer. The definitive diagnosis is made by an endoscopic needle biopsy or surgical excision of the radiologically suspicious tissue. Endoscopic ultrasound is often used to visually guide the needle biopsy procedure.[45] Nonetheless, pancreatic cancer is usually staged using a CT scan. In fact, a histologic diagnosis is not usually required for resection of the tumor, rather histologic analysis helps determine which chemotherapeutic regimen to start.[46]
The development of pancreatic cancer may involve the over-expression of oncogenes, inactivation of tumor suppressor genes or the deregulation of various signaling proteins.[47] Mutations leading to carcinoma may be accelerated by genetic or environmental factors and other risk factors already described. Specific mutations vary among and even within the cyto-histologic categories discussed below.
Exocrine pancreas cancers[edit]
The most common form of pancreatic cancer (ductal adenocarcinoma) is typically characterized by moderately to poorly differentiated glandular structures on microscopic examination. Pancreatic cancer has an immunohistochemical profile that is similar to hepatobiliary cancers (e.g. cholangiocarcinoma) and some stomach cancers; thus, it may not always be possible to be certain that a tumour found in the pancreas arose from it.
The genetic events that cause ductal adenocarcinoma have been well characterized. The most common are KRAS mutations (96%), CDKN2A mutations/deletions (75%), TP53 mutations (55%), SMAD4 deletions/mutations (50%), and SWI/SNF mutations/deletions (35%).[48][49]
Pancreatic carcinoma is thought to arise from progressive tissue changes. Three types of precancerous lesion are recognised: pancreatic intraepithelial neoplasia – a microscopic lesions of the pancreas, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms both of which are macroscopic lesions.[50] The cellular origin of these lesions is debated.
The second most common type of exocrine pancreas cancer is mucinous.[citation needed] [discuss] The prognosis is slightly better.[citation needed] [discuss]
Other exocrine cancers include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells.[51]
Pancreatic cystic neoplasms[edit]
Pancreatic cystic neoplasms are a broad group of pancreas tumors that have varying malignant potential.[discuss]
Pancreatic neuroendocrine tumors[edit]
Endocrine pancreatic tumors have been variously called islet cell tumors, pancreas endocrine tumors (PETs), and pancreatic neuroendocrine tumors (PNETs).[52] The annual clinically recognized incidence is low, about five per one million person-years.[51] However, autopsy studies incidentally identify PETs in up to 1.5%[5] most of which would remain inert and asymptomatic.[5]
The majority of PNETs are usually categorized as benign[53][54][55] but the definition of malignancy in pancreas endocrine tumors has been ambiguous. A small subset of endocrine pancreatic tumors are incontrovertible pancreatic endocrine cancers, that make up about 1% of pancreas cancers.[51][52] Low- to intermediate-grade neuroendocrine carcinomas of the pancreas may be called islet cell tumors. Some sources have also termed these pancreatic carcinoid,[52] a practice that has sometimes been strongly condemned.[citation needed] Definitional migration has caused some complexity of PNET classification,[52] which has adversely affected what is known about the epidemiology and natural history of these tumors.[52] It is probable that some of these tumors have been included in ICD-O-3 histology classifications 8240–8245, in that they were labeled pancreatic carcinoid tumours[52][56] but most islet cell carcinomas have been coded as ICD-O-3 system 8150–8155.[52]
The more aggressive endocrine pancreatic cancers are known as pancreatic neuroendocrine carcinomas (PNEC). Similarly, there has likely been a degree of admixture of PNEC and extrapulmonary small cell carcinoma.[citation needed]
According to the American Cancer Society, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking has been reported as responsible for 20–30% of pancreatic cancers.[57]
The ACS recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing red meat intake, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically.[58][59] In 2006, a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[60] The evidence in support of this lies mostly in small case-control studies.[16]
A long-term study found that people who consumed in the range of 300 to 449 international units (IU) of vitamin D daily had a 43% lower risk of pancreatic cancer than those who took less than 150 IU per day;[61][62] 150 IU is appreciably less than what was then, or is now, recommended.[63] The World Health Organization (WHO) International Agency for Research on Cancer (IARC) concluded that there were insufficient studies in pancreatic cancer. Furthermore, while the IARC found evidence for an inverse association between vitamin D and colorectal cancer to be persuasive, it found evidence for a causal link to be limited, and also found that randomized controlled trials (RCTs) were inconclusive.[64] Taking too much vitamin D may be harmful.[63] Poor general diet, obesity, and relative physical inactivity can be risk factors in some cancers, so the role of vitamin D itself is not certain.[65]
A Harvard study from 2007 showed a modest inverse trend between blood circulation of B vitamins, such as B12, B6, and folate and pancreatic cancer incidence, but not when the vitamins were ingested in tablet form.[66] However, the results of a meta-analysis of randomized trials by Rothwell and colleagues indicate that taking a daily low-dose aspirin regimen for more than five years decreases the risk of developing pancreatic adenocarcinoma (ductal pancreatic cancer) by 75%.[67]
People who may have a high risk of pancreatic cancer due to a family history can be followed, but there is no consensus on what constitutes optimal monitoring.
Exocrine pancreas cancer[edit]
Treatment of pancreatic cancer depends on the stage of the cancer.[68] Although only localized cancer is considered suitable for surgery with curative intent at present, only 20% of cases present with localised disease at diagnosis.[69] Surgery can also be performed for palliation, if the malignancy is invading or compressing the duodenum or colon. In such cases, bypass surgery might overcome the obstruction and improve quality of life but is not intended as a cure.[45]
The Whipple procedure is the most common attempted curative surgical treatment for cancers involving the head of the pancreas. This procedure involves removing the pancreatic head and the curve of the duodenum together (pancreato-duodenectomy), making a bypass for food from stomach to jejunum (gastro-jejunostomy) and attaching a loop of jejunum to the cystic duct to drain bile (cholecysto-jejunostomy). It can be performed only if the patient is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can, therefore, be performed in only the minority of cases.
Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy.[68] Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches.[70]
After surgery, adjuvant chemotherapy with gemcitabine has been shown in several large randomized studies to significantly increase the 5-year survival (from approximately 10 to 20%), and should be offered if the patient is fit after surgery (Oettle et al. JAMA 2007, Neoptolemos et al. NEJM 2004, Oettle et al. ASCO proc 2007).
Those with inoperable pancreatic cancer may have significant abdominal pain. A celiac plexus block (CPB), which destroys the nerves that transmit pain from the abdomen, is a safe and effective way to reduce the pain. CPB generally reduces the need to use pain killers like opioids, which have significant negative side effects.[71]
Principles of radiation therapy in pancreas adenocarcinoma are reviewed extensively in guidelines by the National Comprehensive Cancer Network.[72] Radiation can be considered in several situations. One situation is the addition of radiation therapy after potentially curative surgery. Groups in the US have been more apt to use adjuvant radiation therapy than groups in Europe.[73]
In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the United States Food and Drug Administration in 1998, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug primarily for a nonsurvival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis.
A Canadian-led Phase III randomised controlled trial, reported in 2005, involved 569 patients with advanced pancreatic cancer, led the US FDA in 2005 to license erlotinib (Tarceva) in combination with gemcitabine as a palliative regimen for pancreatic cancer. This trial compared the outcome of gemcitabine/erlotinib to gemcitabine/placebo, and demonstrated improved survival rates, improved tumor response and improved progression-free survival rates.[74][75] Other trials are now investigating the effect of the above combination in the adjuvant (post surgery) and neoadjuvant (pre-surgery) settings.
Addition of oxaliplatin to Gemcitabine (Gem/Ox) was shown to confer benefit in small trials, but is not yet standard therapy.[76]
Pancreatic neuroendocrine tumors[edit]
The majority of these tumors are histologically benign. Treatment of pancreatic endocrine tumors, including the less common malignant tumors, may include:
- Watchful waiting: incidentally identified small tumors, for example on a computed tomography (CT) scan performed for other purposes, may conceptually not always need intervention, but criteria for watchful waiting are unclear.
- Surgery: tumors within the pancreas only (localized tumors), or with limited metastases, may be removed. For localized tumors, the surgical procedure is much less extensive than the types of surgery used to treat pancreatic adenocarcinoma.
- Hormone therapy: if the tumor is not amenable to surgical removal and is causing symptoms by secreting functional hormones, a synthetic hormone analog medication, octreotide, may lessen the symptoms, and sometimes also slows tumor growth.
- Radiation therapy: occasionally used if there is pain due to anatomic extension, such as metastasis to bone.
- Radiolabeled hormone: some PNETs absorb a hormone called norepinephrine and these may respond to nuclear medicine medication, radiolabeled MIBG therapy (or, experamentally, other hormones), given intravenously.
- Chemotherapy and targeted medication for PNETs receive Wikipedia discussion in the relevant section of that article.
Exocrine pancreatic cancer (adenocarcinoma and less common variants) typically has a poor prognosis, partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis.
Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered, and it has been suggested the cancer can also prompt the onset of diabetes and vice versa.[78] It can be associated with pain, fatigue, weight loss, jaundice, and weakness. Additional symptoms are discussed above.
For pancreatic cancer:
- For all stages combined, the 1-year relative survival rate is 25%, and the 5-year survival is estimated as less than 5% [79] to 6%.[3]
- For local disease, the 5-year survival is approximately 20%.[3][4]
- For locally advanced and for metastatic disease, which collectively represent over 80%[4] to 85-90%[13] of individuals, the median survival is about 10 and 6 months, respectively.[5] Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months;[13] complete remission is very rare.[13]
Outcomes with pancreatic endocrine tumors, many of which are benign and completely without clinical symptoms, are much better, as are outcomes with symptomatic benign tumors; even with actual pancreatic endocrine cancers, outcomes are rather better, but variable.[52][80]
Globally, as of 2010, pancreatic cancer resulted in 310,000 deaths up from 200,000 in 1990.[81] In 2010, an estimated 43,000 people in the US were diagnosed with pancreas cancer[3] and almost 37,000 died from the disease.[3] Pancreatic cancer has one of the highest fatality rates of all cancers, and is the fourth-highest cancer killer among both men and women worldwide.[82] Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year.[83]
See also[edit]
- Category:Deaths from pancreatic cancer
- Category:Pancreatic cancer survivors
- Gastrointestinal cancer
- Pancreatic Cancer Action (organisation in the UK)
- Lustgarten Foundation for Pancreatic Cancer Research (organization in the US)
- ^ Hariharan, D.; Saied, A.; Kocher, H. M. (2008). "Analysis of mortality rates for pancreatic cancer across the world". HPB 10 (1): 58–62. doi:10.1080/13651820701883148. PMC 2504856. PMID 18695761.
- ^ http://globocan.iarc.fr/Pages/fact_sheets_population.aspx
- ^ a b c d e f "American Cancer Society: Cancer Facts & Figures 2010: see page 4 for incidence estimates, and page 19 for survival percentages".
- ^ a b c d National Cancer Institute. General Information About Pancreatic Cancer. http://www.cancer.gov/cancertopics/pdq/treatment/pancreatic/HealthProfessional
- ^ a b c d Benson AB, Myerson RJ, and Sasson AR. Pancreatic, Neuroendocrine GI, and Adrenal Cancers. Cancer Management 13th edition. http://www.cancernetwork.com/cancer-management/pancreatic/article/10165/1802606
- ^ a b c d e f g "What You Need To Know About Cancer of the Pancreas — National Cancer Institute". 2002-09-16. p. 4/5. Retrieved 2007-12-22.
- ^ Dragovich, Tomislav (13 September 2011). "Pancreatic Cancer". Medscape Reference.
- ^ Pannala R, Basu A, Petersen GM, Chari ST (January 2009). "New-onset Diabetes: A Potential Clue to the Early Diagnosis of Pancreatic Cancer". The Lancet Oncology 10 (1): 88–95. doi:10.1016/S1470-2045(08)70337-1. PMC 2795483. PMID 19111249.
- ^ Carney CP, Jones L, Woolson RF, Noyes R, Doebbeling BN (2003). "Relationship between depression and pancreatic cancer in the general population". Psychosomatic Medicine 65 (5): 884–8. doi:10.1097/01.PSY.0000088588.23348.D5. PMID 14508036.
- ^ Medscape > Pancreatic Cancer Author: Tomislav Dragovich. Chief Editor: Jules E Harris. Updated: 5 May 2011
- ^ AJCC Cancer Staging Manual 2nd edition; Chapter 15; Pancreas – original pages 95–98; page 95 for citation regarding "...lesser degree of involvement of bones and brain and other anatomical sites." http://www.cancerstaging.org/products/csmanual2ed.pdf
- ^ "ACS :: What Are the Risk Factors for Cancer of the Pancreas?". Archived from the original on 12 October 2007. Retrieved 2007-12-13.
- ^ a b c d e Ghaneh P, Costello E, Neoptolemos JP (August 2007). "Biology and management of pancreatic cancer". Gut 56 (8): 1134–52. doi:10.1136/gut.2006.103333. PMC 1955499. PMID 17625148.
- ^ Efthimiou E, Crnogorac-Jurcevic T, Lemoine NR, Brentnall TA (February 2001). "Inherited predisposition to pancreatic cancer". Gut 48 (2): 143–7. doi:10.1136/gut.48.2.143. PMC 1728218. PMID 11156628.
- ^ Iodice S, Gandini S, Maisonneuve P, Lowenfels AB (July 2008). "Tobacco and the risk of pancreatic cancer: a review and meta-analysis". Langenbeck's Archives of Surgery 393 (4): 535–45. doi:10.1007/s00423-007-0266-2. PMID 18193270.
- ^ a b Chan JM, Wang F, Holly EA (September 2005). "Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area". Cancer Epidemiology, Biomarkers & Prevention 14 (9): 2093–7. doi:10.1158/1055-9965.EPI-05-0226. PMID 16172215.
- ^ Larsson SC, Wolk A (January 2012). "Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies". Br J Cancer. Online first (3): 603–7. doi:10.1038/bjc.2011.585. PMC 3273353. PMID 22240790.
- ^ "Soft Drink and Juice Consumption and Risk of Pancreatic Cancer: The Singapore Chinese Health Study".
- ^ Liu H, Huang D, McArthur DL, Boros LG, Nissen N, Heaney AP (2010). "Fructose Induces Transketolase Flux to Promote Pancreatic Cancer Growth". Cancer Res 70 (15): 6368–76. doi:10.1158/0008-5472.CAN-09-4615. PMID 20647326. Retrieved 2013-10-25.
- ^ "Obesity Linked to Pancreatic Cancer". American Cancer Society. Cancer Epidemiology, Biomarkers & Prevention (Vol. 14, No. 2: 459–466). 2005-03-06. Archived from the original on 5 February 2008. Retrieved 2008-03-05.
- ^ Raderer, M.; Wrba, F.; Kornek, G.; Maca, T.; Koller, D.Y.; Weinlaender, G.; Hejna, M.; Scheithauer, W. (1998). "Association between Helicobacter pylori Infection and Pancreatic Cancer". Oncology 55 (1): 16–19. doi:10.1159/000011830. PMID 9428370.
- ^ Stolzenberg-Solomon, R. Z.; Blaser, M. J.; Limburg, P. J.; Perez-Perez, G.; Taylor, P. R.; Virtamo, J.; Albanes, D. (2001). "Helicobacter pylori Seropositivity as a Risk Factor for Pancreatic Cancer". JNCI Journal of the National Cancer Institute 93 (12): 937–941. doi:10.1093/jnci/93.12.937.
- ^ Michaud DS, Joshipura K, Giovannucci E, Fuchs CS (January 2007). "A prospective study of periodontal disease and pancreatic cancer in US male health professionals". Journal of the National Cancer Institute 99 (2): 171–5. doi:10.1093/jnci/djk021. PMID 17228001.
- ^ van Rees BP, Tascilar M, Hruban RH, Giardiello FM, Tersmette AC, Offerhaus GJ. (1999). "Remote partial gastrectomy as a risk factor for pancreatic cancer: potential for preventive strategies". Ann Oncol. 10 Suppl 4: 204–207. PMID 10436823.
- ^ Tersmette AC, Giardiello FM, Tytgat GN, Offerhaus GJ. (1995). "Carcinogenesis after remote peptic ulcer surgery: the long-term prognosis of partial gastrectomy". Scand J Gastroenterol Suppl. 212: 96–99. doi:10.3109/00365529509090306. PMID 8578237.
- ^ National Institute on Alcohol Abuse and Alcoholism Alcohol and Cancer - Alcohol Alert No. 21-1993
- ^ American Cancer SocietyCoffee and Alcohol Do Not Pose a Risk for Pancreatic Cancer
- ^ Villeneuve PJ, Johnson KC, Hanley AJ, Mao Y (February 2000). "Alcohol, tobacco and coffee consumption and the risk of pancreatic cancer: results from the Canadian Enhanced Surveillance System case-control project. Canadian Cancer Registries Epidemiology Research Group". European Journal of Cancer Prevention 9 (1): 49–58. doi:10.1097/00008469-200002000-00007. PMID 10777010.
- ^ a b Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS (May 2001). "Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts". Cancer Epidemiology, Biomarkers & Prevention 10 (5): 429–37. PMID 11352851.
- ^ Cancer Research UK Pancreatic cancer risks and causes
- ^ Ahlgren JD (April 1996). "Epidemiology and risk factors in pancreatic cancer". Seminars in Oncology 23 (2): 241–50. PMID 8623060.
- ^ Cuzick J, Babiker AG (March 1989). "Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease". International Journal of Cancer 43 (3): 415–21. doi:10.1002/ijc.2910430312. PMID 2925272.
- ^ Harnack LJ, Anderson KE, Zheng W, Folsom AR, Sellers TA, Kushi LH (December 1997). "Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women's Health Study". Cancer Epidemiology, Biomarkers & Prevention 6 (12): 1081–6. PMID 9419407.
- ^ Schottenfeld, D. and J. Fraumeni, ed. Cancer epidemiology and prevention. 2nd ed., ed. Vol. 1996, Oxford University Press: Oxford[page needed]
- ^ a b Ye W, Lagergren J, Weiderpass E, Nyrén O, Adami HO, Ekbom A (August 2002). "Alcohol abuse and the risk of pancreatic cancer". Gut 51 (2): 236–9. doi:10.1136/gut.51.2.236. PMC 1773298. PMID 12117886.
- ^ a b Silverman DT, Brown LM, Hoover RN, et al. (November 1995). "Alcohol and pancreatic cancer in blacks and whites in the United States". Cancer Research 55 (21): 4899–905. PMID 7585527.
- ^ Olsen GW, Mandel JS, Gibson RW, Wattenberg LW, Schuman LM (August 1989). "A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet". American Journal of Public Health 79 (8): 1016–9. doi:10.2105/AJPH.79.8.1016. PMC 1349898. PMID 2751016.
- ^ "Pancreatic cancer risk factors". Info.cancerresearchuk.org. 2008-11-04. Retrieved 2009-09-15.
- ^ a b c "In summary, a weak positive association between alcohol intake during adulthood and pancreatic cancer risk was observed in the highest category of intake (≥30g/day or approximately 2 alcoholic beverages/day). Associations with alcohol intake were stronger among individuals who were normal weight. Thus, our findings are consistent with a modest increase in risk of pancreatic cancer for alcohol intakes of at least 30 grams/day." Genkinger JM, Spiegelman D, Anderson KE, et al. (March 2009). "ALCOHOL INTAKE AND PANCREATIC CANCER RISK: A POOLED ANALYSIS OF FOURTEEN COHORT STUDIES". Cancer Epidemiology, Biomarkers & Prevention 18 (3): 765–76. doi:10.1158/1055-9965.EPI-08-0880. PMC 2715951. PMID 19258474.
- ^ Zatonski WA, Boyle P, Przewozniak K, Maisonneuve P, Drosik K, Walker AM (February 1993). "Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland". International Journal of Cancer 53 (4): 601–7. doi:10.1002/ijc.2910530413. PMID 8436433.
- ^ Durbec JP, Chevillotte G, Bidart JM, Berthezene P, Sarles H (April 1983). "Diet, alcohol, tobacco and risk of cancer of the pancreas: a case-control study". British Journal of Cancer 47 (4): 463–70. doi:10.1038/bjc.1983.75. PMC 2011343. PMID 6849792.
- ^ Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, Runia S, Boyle P (February 1992). "Lifetime consumption of alcoholic beverages, tea and coffee and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands". International Journal of Cancer 50 (4): 514–22. doi:10.1002/ijc.2910500403. PMID 1537615.
- ^ Bakkevold KE, Arnesjø B, Kambestad B (April 1992). "Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs, and diagnosis related to stage and tumour site. A prospective multicentre trial in 472 patients. Norwegian Pancreatic Cancer Trial". Scandinavian Journal of Gastroenterology 27 (4): 317–25. doi:10.3109/00365529209000081. PMID 1589710.
- ^ Frank J. Domino M.D. (2007). 5 minutes clinical suite version 3. Philadelphia, PA: Lippincott Williams & Wilkins.[page needed]
- ^ a b Philip Agop, "Pancreatic Cancer". ACP PIER & AHFX DI Essentials. American College of Physicians. 4 Apr 2008. Accessed 7 Apr 2009.[page needed]
- ^ Tempero MA, Arnoletti JP, Behrman S, et al. (September 2010). "Pancreatic adenocarcinoma". J Natl Compr Canc Netw 8 (9): 972–1017. PMC 3135380. PMID 20876541.
- ^ Sarkar FH, Banerjee S, Li Y (November 2007). "Pancreatic cancer: pathogenesis, prevention and treatment". Toxicol. Appl. Pharmacol. 224 (3): 326–36. doi:10.1016/j.taap.2006.11.007. PMC 2094388. PMID 17174370.
- ^ Shain, AH; Giacomini, CP; Matsukuma, K; Karikari, CA; Bashyam, MD; Hidalgo, M; Maitra, A; Pollack, JR (31 January 2012). "Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer". Proceedings of the National Academy of Sciences of the United States of America 109 (5): E252–9. doi:10.1073/pnas.1114817109. PMC 3277150. PMID 22233809.
- ^ Jones, S; Zhang, X; Parsons, DW; Lin, JC; Leary, RJ; Angenendt, P; Mankoo, P; Carter, H; Kamiyama, H; Jimeno, A; Hong, SM; Fu, B; Lin, MT; Calhoun, ES; Kamiyama, M; Walter, K; Nikolskaya, T; Nikolsky, Y; Hartigan, J; Smith, DR; Hidalgo, M; Leach, SD; Klein, AP; Jaffee, EM; Goggins, M; Maitra, A; Iacobuzio-Donahue, C; Eshleman, JR; Kern, SE; Hruban, RH; Karchin, R; Papadopoulos, N; Parmigiani, G; Vogelstein, B; Velculescu, VE; Kinzler, KW (26 September 2008). "Core signaling pathways in human pancreatic cancers revealed by global genomic analyses". Science 321 (5897): 1801–6. doi:10.1126/science.1164368. PMC 2848990. PMID 18772397.
- ^ Delpu Y, Hanoun N, Lulka H, Sicard F, Selves J, Buscail L, Torrisani J, Cordelier P (2011). "Genetic and epigenetic alterations in pancreatic carcinogenesis". Curr Genomics 12 (1): 15–24. doi:10.2174/138920211794520132. PMC 3129039. PMID 21886451.
- ^ a b c Johns Hopkins Medicine; The Sol Goldman Pancreas Cancer Research Center. Types of Pancreas Tumors. http://pathology.jhu.edu/pancreas/BasicTypes1.php
- ^ a b c d e f g h Yao, J. C.; Eisner, M. P.; Leary, C.; Dagohoy, C.; Phan, A.; Rashid, A.; Hassan, M.; Evans, D. B. (2007). "Population-Based Study of Islet Cell Carcinoma". Annals of Surgical Oncology 14 (12): 3492–3500. doi:10.1245/s10434-007-9566-6. PMC 2077912. PMID 17896148.
- ^ "The prognosis of patients with PENs is difficult to predict, in part because the definition of malignancy in PENs has been ambiguous. By some, PENs have been defined as malignant only when lymph nodes are involved or liver metastases are documented. Other investigators have included vascular invasion or invasion of adjacent structures as evidence of malignancy. However, the concept that a PEN removed successfully without recurrence was therefore biologically benign could be challenged. In fact, strict separation of PENs into benign and malignant groups may be less clinically useful than the definition of prognostic factors."Hochwald, S. N.; Zee, S.; Conlon, K.; Colleoni, R.; Louie, O.; Brennan, M.; Klimstra, D. (2002). "Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases with a Proposal for Low-Grade and Intermediate-Grade Groups". Journal of Clinical Oncology 20 (11): 2633–2642. doi:10.1200/JCO.2002.10.030. PMID 12039924.
- ^ "One of the most controversial aspects of PENs has been the prediction of prognosis."Klimstra, D. S. (2007). "Nonductal neoplasms of the pancreas". Modern Pathology 20: S94–S112. doi:10.1038/modpathol.3800686. PMID 17486055.
- ^ "The classification of these tumors remains controversial, and prognosis is difficult to predict" Wendy L. Frankel (2006) Update on Pancreatic Endocrine Tumors. Archives of Pathology & Laboratory Medicine: July 2006, Vol. 130, No. 7, pp. 963–966. http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2006)130[963:UOPET]2.0.CO;2
- ^ Modlin http://onlinelibrary.wiley.com/doi/10.1002/cncr.11105/pdf
- ^ "Can Cancer of the Pancreas Be Prevented?". American Cancer Society. Archived from the original on 12 October 2007. Retrieved 2007-12-13.
- ^ Coughlin SS, Calle EE, Patel AV, Thun MJ (December 2000). "Predictors of pancreatic cancer mortality among a large cohort of United States adults". Cancer Causes & Control 11 (10): 915–23. doi:10.1023/A:1026580131793. ISSN 0957-5243. PMID 11142526.
- ^ Zheng W, McLaughlin JK, Gridley G, et al. (September 1993). "A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States)". Cancer Causes & Control 4 (5): 477–82. doi:10.1007/BF00050867. PMID 8218880.
- ^ Larsson SC, Håkansson N, Näslund I, Bergkvist L, Wolk A (February 2006). "Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study". Cancer Epidemiology, Biomarkers & Prevention 15 (2): 301–05. doi:10.1158/1055-9965.EPI-05-0696. PMID 16492919.
- ^ "Health | Vitamin D 'slashes cancer risk'". BBC News. 2006-09-15. Retrieved 2009-09-15. The BBC quoted the lead researcher: "I would make no specific recommendation for vitamin D supplementation to prevent pancreatic cancer until we can carry out a trial to determine definitively who might benefit from such an intervention." The BBC quoted Henry Scowcroft, science information officer at the charity Cancer Research UK: "The results of this study don't mean that people should take vitamin D supplements to ward off pancreatic cancer, especially as vitamin D can be harmful in large quantities...As the authors themselves point out, this is the very first study to find any association between the disease and vitamin D intake...So this result needs to be repeated in other large studies, and scientists need to show exactly how vitamin D might prevent pancreatic cancer before we could issue any specific lifestyle advice."
- ^ "Vitamin D May Cut Pancreatic Cancer". Webmd.com. 2006-09-12.
- ^ a b Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx Dietary Reference Intakes for Calcium and Vitamin D IOM, 30 November 2010: "The IOM finds that the evidence supports a role for vitamin D and calcium in bone health but not in other health conditions. Further, emerging evidence indicates that too much of these nutrients may be harmful, challenging the concept that "more is better."
- ^ World Health Organization; International Agency for Research on Cancer (IARC). Vitamin D and Cancer. IARC Working Group Reports Vol.5, International Agency for research on Cancer, Lyon, 25 November 2008
- ^ Lipson P. Vitamin D: Still more questions than answers. http://blogs.forbes.com/sciencebiz/2010/08/18/vitamin-d-still-more-questions-than-answers/ "Vitamin D deficiency is common in people with poor diets (including obese people) and in people who are relatively inactive. These are independent risk factors for... some cancers. And while some cellular mechanisms have been discovered that may lend plausibility to a vitamin D hypothesis, there are as... yet no convincing data that allow us to draw conclusions about vitamin D and these diseases."
- ^ Schernhammer E, Wolpin B, Rifai N, et al. (June 2007). "Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts". Cancer Research 67 (11): 5553–60. doi:10.1158/0008-5472.CAN-06-4463. PMID 17545639.
- ^ Rothwell P, Fowkes F, Belch, J.n B, Rifai N, et al. (Jan 2011). "Effect of daily aspirin on long term risk of death due to cancer: analysis of individual patient data from randomised trials". Lancet 337 (9759): 31–41. doi:10.1016/S0140-6736(10)62110-1. PMID 21144578.
- ^ a b "Surgical Treatment of Pancreatic Cancer". Johns Hopkins University. Retrieved 5 September 2009.
- ^ Corbo V, Tortora G, Scarpa A (2012) Molecular pathology of pancreatic cancer: from bench-to-bedside translation. Curr Drug Targets
- ^ "Laparoscopic Pancreas Surgery". Johns Hopkins University. Retrieved 5 September 2009.
- ^ Arcidiacono, PG.; Calori, G.; Carrara, S.; McNicol, ED.; Testoni, PA. (2011). "Celiac plexus block for pancreatic cancer pain in adults". In Arcidiacono, Paolo G. Cochrane Database Syst Rev (3): CD007519. doi:10.1002/14651858.CD007519.pub2. PMID 21412903.
- ^ Pancreatic Adenocarcinoma (access to the guideline section of the website is free, but may require registration; see sections "PANC-F" and "MS") http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf
- ^ Neoptolemos JP, Stocken DD, Friess H, et al. (March 2004). "A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer". The New England Journal of Medicine 350 (12): 1200–10. doi:10.1056/NEJMoa032295. PMID 15028824.
- ^ "Tarceva (erlotinib) Tablets. NDA 21-743, S003. Supplemental NDA: Pancreatic Cancer, Briefing Document, ODAC Meeting 13 September 2005". September 2005. Retrieved 2009-09-15.
- ^ Moore MJ, et al. (May 2007). "Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group". Journal of Clinical Oncology 25 (15): 1960–1966. doi:10.1200/JCO.2006.07.9525. PMID 17452677.
- ^ Demols A, Peeters M, Polus M, et al. (February 2006). "Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study". British Journal of Cancer 94 (4): 481–85. doi:10.1038/sj.bjc.6602966. PMC 2361170. PMID 16434988.
- ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov 11, 2009.
- ^ Wang F, Herrington M, Larsson J, Permert J (January 2003). "The relationship between diabetes and pancreatic cancer". Molecular Cancer 2: 4. doi:10.1186/1476-4598-2-4. PMC 149418. PMID 12556242.
- ^ "WHO | Cancer". Who.int. Retrieved 2009-09-15.
- ^ Fesinmeyer, M. D.; Austin, M. A.; Li, C. I.; De Roos, A. J.; Bowen, D. J. (2005). "Differences in Survival by Histologic Type of Pancreatic Cancer". Cancer Epidemiology Biomarkers & Prevention 14 (7): 1766–1773. doi:10.1158/1055-9965.EPI-05-0120.
- ^ Lozano, R (15 December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. PMID 23245604.
- ^ "Pancreatic Cancer — National Cancer Institute, U.S. National Institutes of Health (Accessed 28 April 2011)". Cancer.gov. Retrieved 2009-09-15.
- ^ Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007). "Cancer statistics, 2007". CA 57 (1): 43–66. doi:10.3322/canjclin.57.1.43. PMID 17237035.
External links[edit]
Wikimedia Commons has media related to Pancreatic cancer. |


text:
Cinnamaldehyde | |
(2E)-3-phenylprop-2-enal |
Other names
Cinnamic aldehyde; trans-cinnamaldehyde |
Identifiers | |
CAS number | 104-55-2 |
PubChem | 637511 |
ChemSpider | 553117 |
EC number | 203-213-9 |
ChEBI | CHEBI:16731 |
ChEMBL | CHEMBL293492 |
IUPHAR ligand | 2423 |
RTECS number | GD6475000 |
Jmol-3D images | Image 1 |
Properties | |
Molecular formula | C9H8O |
Molar mass | 132.16 g/mol |
Appearance | Yellow oil |
Odor | pungent, cinnamon-like |
Density | 1.0497 g/mL |
Melting point | −7.5 °C; 18.5 °F; 265.6 K |
Boiling point | 248 °C; 478 °F; 521 K |
Solubility in water | Slightly Soluble |
Solubility | soluble in ether, chloroform insoluble in petroleum ether miscible with alcohol, oils |
Refractive index (nD) | 1.6195 |
Hazards | |
R-phrases | R36 R37 R38 |
S-phrases | S26 S36 |
Flash point | 71 °C; 160 °F; 344 K |
LD50 | 3400 mg/kg (rat, oral) |
Related compounds | |
Related compounds | Cinnamic acid |
(verify) (what is: / ?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa) |
Infobox references |
Cinnamaldehyde is the organic compound that gives cinnamon its flavor and odor.[1] This pale yellow, viscous liquid occurs naturally in the bark of cinnamon trees and other species of the genus Cinnamomum. The essential oil of cinnamon bark is about 90% cinnamaldehyde.
Structure and synthesis[edit]
Cinnamaldehyde was isolated from cinnamon essential oil in 1834 by Dumas and Péligot[citation needed] and synthesized in the laboratory by Chiozza in 1854.[citation needed]
The natural product is trans-cinnamaldehyde. The molecule consists of a phenyl group attached to an unsaturated aldehyde. As such, the molecule can be viewed as a derivative of acrolein. Its color is due to the π → π* transition: increased conjugation in comparison with acrolein shifts this band towards the visible.[2]
Several methods of laboratory synthesis exist, but cinnamaldehyde is most economically obtained from the steam distillation of the oil of cinnamon bark. The compound can be prepared from related compounds such as cinnamyl alcohol, (the alcohol form of cinnamaldehyde), but the first synthesis from unrelated compounds was the aldol condensation of benzaldehyde and acetaldehyde.
Cinnamaldehyde occurs widely, and closely related compounds give rise to lignin. All such compounds are biosynthesized starting from phenylalanine, which undergoes conversion.[3]
Cinnamoyl-CoA reductase is an enzyme responsible for the production of cinnamoyl-CoA from cinnamaldehyde.
As a flavorant[edit]
The most obvious application for cinnamaldehyde is as flavoring in chewing gum, ice cream, candy, and beverages; use levels range from 9 to 4900 parts per million (ppm) (that is, less than 0.5%). It is also used in some perfumes of natural, sweet, or fruity scents. Almond, apricot, butterscotch, and other aromas may partially employ the compound for their pleasant smells. Cinnamaldehyde can be used as a food adulterant; powdered beechnut husk aromatized with cinnamaldehyde can be marketed as powdered cinnamon.[4]
As an agrichemical[edit]
Cinnamaldehyde is also used as a fungicide.[5] Proven effective on over 40 different crops, cinnamaldehyde is typically applied to the root systems of plants. Its low toxicity and well-known properties make it ideal for agriculture. Cinnamaldehyde is an effective insecticide, and its scent is also known to repel animals, such as cats and dogs.[5] It has recently been recognized as a very effective insecticide for mosquito larvae.[6] As little as 29 ppm of cinnamaldehyde kills half of Aedes aegypti mosquito larvae in 24 hours.[7][8]
As an antimicrobial[edit]
Another use for cinnamaldehyde is as an antimicrobial. Researchers from the University of Illinois at Chicago (who were funded by the Wm. Wrigley Jr. Company) have found that cinnamic aldehyde, when used in Big Red, prevented oral bacterial growth by more than 50%.[9] It is especially effective against bacteria living at the back of the tongue, reducing anaerobic bacteria populations by about 43%.
As an anticancer agent[edit]
Recent research documents anticancer activity of cinnamaldehyde/cinnamic aldehyde observed in cell culture and animal models of the disease. Proliferation, invasion, and tumor growth were inhibited in a murine A375 model of human melanoma, though only at high doses not achievable through dietary intake.[10]
Miscellaneous uses[edit]
Cinnamaldehyde is also known as a corrosion inhibitor for steel and other ferrous alloys in corrosive fluids. It can be used in combination with additional components such as dispersing agents, solvents and other surfactants. Its high refractive index of 1.6220 makes it a fairly safe and useful fluid for examining gemstone rough for inclusions.
Derivatives of cinnamaldehyde[edit]
Numerous derivatives of cinnamaldehyde are commercially useful. Dihydrocinnamyl alcohol, which occurs naturally but is produced by double hydrogenation of cinnamaldehyde, is used to confer the fragrances of hyacinth and lilac. Cinnamyl alcohol similarly occurs naturally and has the odor of lilac. Dihydrocinnamaldehyde is produced by the selective hydrogenation of the alkene subunit. α-Amyl- and α-hexylcinnamaldehyde are important commercial fragrances, but they are not prepared from cinnamaldehyde.[4]
Cinnamaldehyde is used in agriculture because of its low toxicity, but it is a skin irritant.
The level of coumarin detected in 'cinnamon' extracts and powders has concerned the German Federal Institute for Risk Assessment (BfR).[11]
- ^ "Cinnamon". Transport Information Service. Gesamtverband der Deutschen Versicherungswirtschaft e.V. Retrieved 2007-10-23.
- ^ Kozo Inuzuka, Bulletin of the Chemical Society of Japan Vol.34, [No.11(1961)pp.1557-1560] http://www.journalarchive.jst.go.jp/english/jnlabstract_en.php?cdjournal=bcsj1926&cdvol=34&noissue=11&startpage=1557
- ^ Boerjan, W.; Ralph, J. and Baucher, M., "Lignin Biosynthesis", Annu. Rev. Plant Biol. 2003. 54:519–46, 2003, 54, pages 519–546,doi:10.1146/annurev.arplant.54.031902.134938
- ^ a b Karl-Georg Fahlbusch, Franz-Josef Hammerschmidt, Johannes Panten, Wilhelm Pickenhagen, Dietmar Schatkowski, Kurt Bauer, Dorothea Garbe, Horst Surburg "Flavors and Fragrances" in Ullmann's Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a11_141
- ^ a b "Cinnamaldehyde Use". PAN Pesticides Database. Retrieved 2007-10-23.
- ^ Cornelia Dick-Pfaff: Wohlriechender Mückentod, 19.07.2004
- ^ "Cinnamon Oil Kills Mosquitoes". www.sciencedaily.com. Retrieved 2008-08-05.
- ^ Cheng SS, Liu JY, Tsai KH, Chen WJ, Chang ST (July 2004). "Chemical composition and mosquito larvicidal activity of essential oils from leaves of different Cinnamomum osmophloeum provenances". J. Agric. Food Chem. 52 (14): 4395–4400. doi:10.1021/jf0497152. PMID 15237942.
- ^ "Popular Chewing Gum Eliminates Bacteria That Cause Bad Breath". Science Daily. Retrieved 2009-09-22.
- ^ Cabello CM, Bair WB, Lamore SD, Ley S, Bause AS, Azimian S, Wondrak GT (January 2009). "The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth". Free Radic. Biol. Med. 46 (2): 220–231. doi:10.1016/j.freeradbiomed.2008.10.025. PMC 2650023. PMID 19000754.
- ^ High daily intakes of cinnamon: Health risk cannot be ruled out. BfR Health Assessment No. 044/2006, 18 August 2006, 15p Bundesinstitut für Riskoberwertung
External links[edit]

subset: commoncrawl


text:
Savvy Week in Review: February 5
Perhaps it's the short month kicking everyone into high gear. This week, the blogosphere was overflowing with intriguing ideas. We've handpicked a few of our faves. Enjoy!
~ The Savvy Sisters
How much do you "charge" for your content? by @ckochster
If you require registration in exchange for content, read this.
7 Rules for Perfect Press Releases by @aprildunford
Here's how to make headlines with your news.
10 Tips For Content Marketing Success by @TopRank
562 people thought this post was worth reading. We agree.
Social Media Usage in Content Marketing Jumps 500% in Two Years by @juntajoe
This quick post from Joe Pulizzi looks at which content products (eBooks, blogs, etc) are increasing, holding steady and decreasing in terms of distribution.
Prospect Intelligence is a Terrible Thing to Waste - by @ardath421
Ardath Albee provides some great insights into how to create forms with your prospect in mind.
B2B Social Media Case Study #1 - Building a Presence - by @basebot
John Bottom of Base One presents the first of three B2B social media case studies (pdf - no registration required). This installment in the series outlines how conference call company Powwownow successfully established a solid presence in social media resulting in increased Web traffic, blog readership, and registrations.
5 Questions with Linchpin Author Seth Godin - by @jackiehuba
Seth Godin answers Jackie Huba's questions about his new book, Linchpin, Are You Indispensable? What do you think of Godin's belief that the truly great marketers must be "artists?"
Minding the Gap - by @missrogue
I love Tara Hunt. The thoughts and insights on her blog often delve much deeper than other business bloggers, treading into territory that is more emotional than analytical. In this post, she discusses the widening gap between business and human values.
Case Study: How Marketingprofs Uses Twitter - by @mackcollier
Technically, this post isn't from last week, but we can't believe we missed it the first time around. Great interview with Ann Handley, Chief Content Officer at MarketingProfs (and Savvy B2B friend).


text:
- Description
- Wine Info
- Shipping
Experience the fine flavor of Spain's signature varietal with this famous Rioja from Bodegas Montecillo.
Founded in 1874, this Spanish winery selects only the finest Tempranillo grapes for this Montecillo Crianza. Made from vines that are at least 25 years old, the wine is aged for more than one year in oak barrels and one year in the bottle before release. Upon drinking, the taster will find a medium-bodied wine, with noticeable tannins and good forward cherry fruit wrapped in oaky spice.
Packed into wooden crate and measures 14.5" x 5" x 4.5".
Personalize It!
Complete the personalization option during checkout and we'll add an engraved, silver-plated hang tag to your gift. Select one or two lines of up to 18 characters per line, or choose an elegant three character monogram.Due to the alcoholic content of this gift, an adult signature is required upon delivery.
Gift #16975 -
2 Day Express Delivery $0.00
Upgrade Shipping- 3 Day Express Delivery +$0.00
- Overnight Delivery +$0.00
- Standard Shipping +$0.00
+ FedEx Adult Signature Fee $4.00
For holiday delivery, GiftTree can hold your gift and have it shipped to arrive anytime. To use this option, select "Ship Later" on the next page.
- Winemaker's Notes:The Montecillo Crianza Tinto is cherry red in color, clean and bright. The wine is well-assembled complex aromas of red fruits and fine woods. It's intense and tasty, long in the mouth with a lingering finish.


text:
BeerAdvocate on your phone?! True story. Try the beta now.
Tickets for American Craft Beer Fest are on sale now! (May 30 & 31 in Boston, MA)
Prairie 'Merica - Prairie Artisan Ales
Displayed for educational use only; do not reuse. |
Ratings: 486 | Reviews: 77 | Show All Ratings:
Reviews by BradleyR:
More User Reviews:
3.99/5 rDev -3.4%
look: 4.25 | smell: 4.5 | taste: 4 | feel: 3.25 | overall: 3.75
Poured into my DFH snifter...
A. Pale gold, foggy, bountiful three finger head, very thick lacing, pillowy foam.
S. Grape skin, yeast, apple, honeysuckle, wine, sage.
T. Honey, white wine, apricot, grass, cracked pepper.
M. Bone dry, well-carbed, sweet on the edge of the palate but with a cutting, herbal, bitter, dry finish.
O. A very nice beer with an out of balance mouthfeel. Finish is extremely yeasty and dry, to the detriment of all the other pleasant qualities the brew presents. Even so, it glows with craftsmanship. This was made with love and the quality of the ingredients is notable in the flavor profile, which is complex and enjoyable. It's just too bad the finish is so over the top in its dryness and bitterness.
Serving type: bottle
02-16-2014 23:16:11 | More by siege06nd
Prairie 'Merica from Prairie Artisan Ales
out of 100
based on 486 ratings.


text:
Fishfinders, marine GPS, marine stereos, marine radios, marine electronic accessories with top brand names including Garmin, Furuno, Humminbird and Lowrance can be found at Gander Mountain. Our marine electronics provide high-performance features at highly competitive prices. Shop now for all your boating and marine electronics.
Results 1 - 1 of 1 Page 1 of 1
Cobra BT 200 Waterproof Handset with Bluetooth Wireless ...
Receive calls from Bluetooth capable phones
Noise-cancelling handset
12V plug for easy power hook-up
Results 1 - 1 of 1 Page 1 of 1
Sign-up to receive
exclusive offers & updates


text:
Craftsman 6 pc. Metric 12 pt. 1/2 in. dr. Easy-to-Read Socket Accessory Set
Item# 00934575000 | Model# 34575Specifications & Dimensions
Product Overview: | |
Number of Sockets: | 6 |
Contact Points: | 12 point |
Drive Size: | 1/2 in. |
Marking Text Size: | Easy-to-read |
Set: | Set |
Socket Depth: | Standard |
Unit of Measure: | Metric |
Included with Item: | |
Case Included: | No |
Ratchet Included: | No |
Warranties & Coverage: | |
General Warranty: | Guaranteed forever |
Materials: | |
Material: | Chrome vanadium steel |
Ratings & Reviews
Product Description
6 Pc. Metric Socket Accessory Set Gives you Visibility and Grip
With the versatility of a 12 point design and the strength of alloyed steel, this Craftsman metric 1/2 in. socket accessory set delivers the torque you need for bigger metric fasteners. Whether you're tying down an engine block or torquing hard inside an appliance, this tool set gives you the grip you need to get the job done on your own terms. And featuring high visibility sizes paired with a clearly organized molded plastic tray, it keeps you moving fast, and finding the right size quick.
Whether you're working with a ratchet, extension, angle adapter, or torque wrench, this 6 pc. metric socket accessory set clicks in and gets turning. And backed by the dependability of the Craftsman Forever Guarantee, it's a tool box addition that will get you through decades of fast turning, high torque work. Toss this tray in your tool box and get the job done right with Craftsman.
- Craftsman metric 1/2 in. socket accessory set includes: 27, 28, 29, 30, 32, and 36mm
- Molded tray included to increase organization
- 12 point design delivers more torque positions and angles
- Polished steel finish wipes clean after the dirtiest jobs
- Clear markings make size identification quick and easy
- Perfect for work in low light conditions
- Permanent high contrast markings are clear and fade resistant
- Works with any 1/2 in. ratchet, extension, breaker bar or torque wrench
- Backed by the Craftsman Forever Warranty
- Available for Gift Wrap
Added on July 26, 2010
Overall, others give this:
Savanna, IL
via sears.com
Needing bigger sockets for larger jobs and these are a good choice.
Spanaway, WA
via sears.com
...and if something does go wrong that's why you bought craftsman for their no hassle warranty. Bought this kit for the 24mm to work on my dirt bike was a little cheaper per socket to buy the set then an individual.
Puxico, MO
via sears.com
these sockets are very strong and when needed do the job.
Glenwood Springs, CO
via sears.com
More good quality, affordable mechanic's tools from Craftsman. Who needs Snap On?
El Paso, TX
via sears.com
Great set of sockets! Still made in the USA. most of the new ones are made in china now. love the sockets, chrome is good, fit is good and on sale you cant beat it
The reviewer indicated they are affiliated with this product.
Charlestown, IN
via sears.com
U.S. made, well-tempered, quick I.D. should be on ALL Craftsman sockets.
Union, NJ
via sears.com
got this set , its made in the usa. Not china knockoff. have used this set and has not failed yet. satisifed. dont change anything with the specs of this socket set. It not the thickness of my old v series but gets the job done. if they would go back to the thickness of the old v series sockets that would be a plus but i am satisified with this set. i recomend it to anyone. Stay away from the china ones by craftsman. Compare them in the store and you will see that the gauge is thiner by ones made in china which makes them more prone to crack under high torque applications.
Lansing, MI
via sears.com
The reviewer indicated they are affiliated with this product.
San Gabriel, CA
via sears.com
i came to purchase this item because i am always having to borrow my friend's tools to get axles out or the job ends up requiring it and i have to go run and get it. so i decided to finally go get my own set at Sears. They have this one which comes in a nice organizer and the size is really easy to read. it comes weith all the sizes to fix most import vehicles. one of the best investments i have made. thanks again Sears
Highland, NY
via sears.com
WIth a warranty that is unmatched on the retail level, these sockets are unbeatable. Anyone working on automotive applications these days need to have a full set of metric sockets, these add on to a regular set to give you the tools you need for any job in your garage.
- Free shipping! Orders $59 or more Offer ends 05-Apr-2014 See details.
- Spend $199 in tools from Sears and enroll in the Tool of the Month - www.sears.com/toolofthemonth Offer ends 31-Dec-2014 See details.
- Use your Sears Card and Save! Extra 5% off Tool items Sold By Sears when you use your Sears Card. Offer ends 31-Dec-2014 See details.


text:
About Us
Line of Defense Tactics
World of Tanks: Xbox 360 Edition
Infested Planet
Warlords (2014)
Halo: Spartan Assault
Skylanders: Swap Force Expansion Packs
Plants vs. Zombies: Garden Warfare
Democracy 3
GN Unplugged
Hooked Up
Indie Spotlight
Now Loading
Pixels & Bits
Defunct Games
Russell Archey
Tom Bitterman
Sean Cahill
Nathan Carter
Nathaniel Cohen
Sean Colleli
Jeremy Duff
Dave Gamble
Travis Huinker
Charles Husemann
Randy Kalista
Dan Keener
Jeff Kintner
Cyril Lachel
Cary Lange
Matt Mirkovich
Sam Stewart
John Yan
My Settings
Zeno Clash $5 off this week
Posted by:
at 9/1/2010 7:48 PM
More On:
Zeno Clash: Ultimate Edition
Atlus Inc
Xbox 360
The folks at Atlus have a deal for you this week as
Zeno Clash:Ultimate Edition
, their odd FPS melee game is on sale for 800 points this weekend. That's a full 400 points ($5) off the regular price of the game. Sean
really liked
the game and if you want to check out this odd game now is your chance to do so.
ZENO CLASH ULTIMATE EDITION™ PRICE REDUCED TO 800 MICROSOFT POINTS ON Xbox LIVE® Arcade FOR A LIMITED TIME
Hurry! This offer is only available this week!
IRVINE, CALIFORNIA -- August 31, 2010 -- Atlus U.S.A., Inc. today shouted from the rooftops that Xbox LIVE® Gold Members can punch, kick, and headbutt their time away, for thirty-three percent off with Zeno Clash Ultimate Edition™ on Xbox LIVE® Arcade for the Xbox 360® video game and entertainment system from Microsoft. This critically acclaimed, first-person melee action adventure brawler, normally priced at 1200 Microsoft Points, is included in the XBLA Deal of the Week for only 800 Microsoft Points!
Zeno Clash Ultimate Edition recently released with praise, honored for its unique visual style. 1UP.com says "Zeno Clash remains the same gorgeous, grotesque, unique experience it was on PC, and a game well worth its...price tag on Live," giving it an A- on their review. GameZone states "...the strange, brutal, and somehow beautiful world that ACE Team has created here is one that you won't want to miss out on," scoring it 9/10 on their review.
The vastly enhanced Zeno Clash Ultimate Edition features new modes including all-new online and split-screen cooperative mode for the Tower and Pit Challenges, along with new combat moves, new weapons, and a whole new Zeno Rush gameplay mode. Zeno Rush mode lets players compete against themselves and each other (via online leaderboards) in trying to complete select scenarios from the single-player campaign in the shortest times possible. All this added content, combined with a series of tweaks and improvements based on fan feedback, deliver the definitive version of the critically acclaimed game.
Zeno Clash Ultimate Edition is available on Xbox LIVE® Arcade for 800 Microsoft Points, for a limited time. Visit the official game website (www.zenoclash.com) for more information.
About Zeno Clash Ultimate Edition
In the land of Zenozoik, the city of Halstedom is ruled by a powerful clan, one which Ghat has betrayed by committing a terrible sin. Now, Ghat's brothers and sisters are pursuing him and his companion Deadra through strange and twisted lands, beyond the boundaries of the sane to the ends of the world. What was Ghat's crime and why did he commit it? The bare-knuckled brawl to reach the truth has just begun.
Key Features
* Fascinating world of grotesque beauty--Equal parts breathtakingly beautiful and utterly disturbing, prepare to be swallowed up in a surreal fantasy world powered by the Source engine. Explore lush environments and confront bizarre animal-humanoid foes on your mission of discovery and redemption.
* Visceral first person fighting--Combat is up close, personal, and entirely satisfying. Start with a series of punches, kicks, and grabs, follow up with a knee to the enemy's face, and hit him with a finishing move to send him flying yards away. Learn new moves to mix it up. Guns and melee weapons offer additional power and tactical options.
* Ultimate edition additions--The already highly praised gameplay has received an overhaul that includes combat rebalancing, interface enhancements, improved animations, new modes, and new gameplay content.
* New cooperative play modes--Enlist a friend to take on enemy waves in Tower Challenge, a special survival mode that offers additional replayability beyond the single-player campaign. Play cooperatively online, or locally via split screen. With leaderboards to rank you against your friends, the challenge never ends!
Zeno Clash Ultimate Edition has been rated "T" for Teen with Blood and Gore, Mild Suggestive Themes, and Violence by the ESRB.
About Atlus U.S.A., Inc.
Located in Irvine, California and founded in 1991, Atlus U.S.A., Inc. is renowned for its proud tradition of publishing exceptional role-playing games with strong niche appeal. The Atlus library of critically acclaimed video games includes Demon's Souls, Odin Sphere, the Trauma Center series, and the award-winning Shin Megami Tensei series. For more information, visit http://www.atlus.com.
For breaking news, special promotions, insider info, and more, visit http://www.atlus.com/faithful to join the ranks of the Atlus Faithful!
©2007-2009 ACE TEAM SOFTWARE. All rights reserved. ACE Team, the ACE Team logo, Zeno Clash, the Zeno Clash logo are trademarks and/or registered trademarks of ACE Team Software. Licensed to and published by Atlus U.S.A., Inc.
Gaming News
Copyright © 1997 - 2014 Gaming Nexus.
All rights reserved. All trademarks are properties of their respective owners.


text:
Follow Us:
Follow Us on Twitter Like Us on Facebook Follow Us on Google+ Watch videos on our Youtube channelBiomedical Imaging Research Institute
Featured Item
Clinical Cardiovascular Imaging Program
Clinician scientists develop and validate technical methods for optimal clinical applications.
Learn MoreFeatured Research
Translational Cardiovascular Imaging Program
The Translational Cardiac Imaging Program aims to improve our current understanding of heart disease.
Learn MoreInstitute Director
Debiao Li, PhD
"The purpose of our research is early detection and personalized treatment of diseases."
Learn MoreFeatured News
The NIH funds research to develop reliable evaluation of CAD using Myocardial BOLD MRI with CO2.
Learn More


text:
Image Number: 0350-0907-1408-5257
This image is available for editorial and educational use only. Contact Customer Service to inquire about additional uses.
This image is available under 'Rights Managed' licensing and is available for immediate download.
*Prints may not be reproduced!
Keywords: art print, art prints, clipart, clip art, image, images, picture, pictures, posters, photo, photos, poster, photograph, photographs, stock photo, stock photos, stock photography, web graphics , agriculture, alps, animals, apiary, bee hives, beehives, beekeeper, beekeeping, bees, bugs, hives, honey, honey bees, insects, italian, italy, krys bailey, pollenation
search tips
Artist Login


text:
Indiana Democrat Gubernatorial Candidate John Gregg held a meet-and-greet in Chesterton last night, at Steelworkers Local 6787, following a stop in South Bend earlier where he talked about reforms he recently proposed to the Indiana Department of Child Services. including the launch of a statewide adoption promotion effort... and an increase in services for adoptive parents, like counseling and medical needs of adopted children. Gregg will face Republican Mike Pence and Libertarian Rupert Boneham this November.
Read more: http://www.indiana105.com/news/region-news/28884-gregg-stops-in-region.html
LAURA WALUSZKO Region News Team |
SCOTT ROSENBERG Region News Team |
BRENT BROWN Region News Team |
JAY STEVENS Region News Team |
KARL BERNER Region News Team |
ANNIE FOX Region News Team |
Flash is not supported on this device. If you wish to listen to this audio, you must download and play an mp3 using an mp3 player on your device. CLICK HERE


text:
2 search results for "Haguenau"
Last Updated Radios
Old Paths Radio Network - W...
Radio GFM
Radio Mania
Life FM 100.9
Radio Latte Miele
Rádio Studio FM
Military Brotherhood Radio
A7 Radio
Joy 92 - KSDA-FM
Sky Sports News Radio
KRFH - KRFH-cc
Avto Radio - Rostov-na-Donu
Radio Tout-Haiti
Virgin Radio Vendée
CIXL-FM Giant FM
Kansas Public Radio - KANU
Agapito Estereo
The Rock Party
Tezulutlan F.M.
Radio Vyshka
Geras FM Rock
Haguenau - Radio Stations on your iPhone, iPad, iPod Touch, Android, Blackberry, and other app-enabled mobile phones. Get in touch via the Contact Us below if you're interested in these apps. Also, find the top new songs, playlists, and music on our website!


text:
FORT WORTH -- A 27-year-old mechanic was critically burned from his waist up Thursday after a fire at a west Fort Worth auto shop, a fire official said.
Clifton Atkins suffered second- and third-degree burns in the blaze at Complete Auto Repair at White Settlement Road and Roberts Cut Off, authorities said."I heard the sound of tools and then I heard screaming," said Kari Scarbro, a dog groomer who works next door. "It was awful; he was really burned."Atkins was listed in critical condition Thursday afternoon at Parkland Memorial Hospital in Dallas, a hospital spokeswoman said.The fire was reported at 9:52 a.m., said Lt. Kent Worley, a fire spokesman. Atkins was working on a car's fuel pump in an "open air workspace" when witnesses heard an explosion."His brother came out after hearing the commotion and was able to pull him away and get him on the ground and get the fire out," Worley said. "But at that point he had already received extensive burns."The car he was working on was destroyed, and several other cars were damaged, Worley said. The shop's back wall was also damaged. Fire investigators estimated the damage at about $45,000.A helicopter ambulance took Atkins to the Dallas hospital.Investigators were still trying to figure out how the fire started, Worley said."It all happened quickly," he said. "Obviously something triggered an explosion or a flash fire."Employees at neighboring businesses stood on the sidewalk and watched as Atkins was loaded into the helicopter. Scarbro said that after the explosion she ran to the auto shop and saw Atkins' burns.He was conscious and possibly in shock because "he was just sitting there," she said."I know him pretty good so I'm just praying for him," she said. "He's going to have a long road."Have more to add? News tip? Tell us


text:
Warmth Manga (Fan Art)
Artist description:
for ty lee happy birthday i always though u were charming like charmander ~♥ I LOVE YOU
used ref
Created Oct 20, 2011. Unless noted Copyright 2011
rathian619 .
We encourage you to submit a comment and let the artist know what you think of this drawing. Please log in or join to post a comment.
Post a comment
aww he looks so sweet :D i like the flames :D i really like how you draw the eyes, a sweet drawing 5/5h ^.^
Free drawing tools
All drawings on our website are created with our free web based drawing tools.
Drawing tools
Top draws this month
Check out some of the hottest drawings created by our members this week.
View top drawings
Draw and chat live
DrawChat is a chat room where you can draw and chat live with other members.
Start DrawChat


text:
This profile currently has no timeline events.
This profile currently has no photos. Send photos to firstname.lastname@example.com.
- Edit
Top 10 of 2011: Statistics
2 years agoAs part the of the buildup to the start of spring practices, BOL will regularly look back and rank the top 10 moments in various categories from 2011, including statistics: More
- Edit
Upon Further Review: Kent State
3 years agoChris Walsh takes a look back at Saturday's game vs. Kent State and names his play, player, stat and hit of the game, while pointing out some things you may not have noticed More
Recruits Predict Drew Bullard
This profile currently has no predictions.
Drew Bullard is a 6-3, 232-pound Outside Linebacker from Florence, AL. He has committed to Alabama Crimson Tide.
- Early Enrollee
- Walk-On
- Gray Shirt
- Video Highlights
- Medical Redshirt
- Primary
- Secondary
- Keeper
- Primary (Inactive)
- Secondary (Inactive)
- Keeper (Inactive)


text:
Technology executive Blake Lewin could be sending his sons to a high school within walking distance of their home in Gwinnett County, Georgia. Instead, they're up at 5:30 each morning -- without complaining -- for the 20-mile commute to the Center for Design and Technology.
Back in July, we kicked off Edutopia's first-ever Project-Based Learning Camp by posing a big question: How can educators turn the Gulf oil disaster into meaningful learning for students?
Sample | Privacy Policy


text:
Bullhead Denim Co Mid Rise Eve Indigo Skinny Jeans for $29.95
@ pacsun.com | 0 comments | clothing, jeans
2 days ago
2 days ago
Bullhead Denim Co Rincon Slim Straight Derailer Jeans for $24.49
@ pacsun.com | 0 comments | clothing, jeans
4 days ago
$9.99 Pronto Blue Jeans | Men's Wearhouse for $9.99
@ menswearhouse.com | 2 comments | clothing, jeans
10 days ago
Fatboy JNS-BLU Fatboy Original Jeans Beanbag for $159.99 + $5.00 shipping
@ moofi.woot.com | 0 comments | fatboy, original, jeans, beanbag
11 days ago
Celebrity Pink Jeans Juniors' Floral-Print Skinny Jeans for $24.99
@ www1.macys.com | 0 comments | clothing, jeans
15 days ago
a month ago
Canvas Men's Denim Painter Jeans from Lands' End for $14.99
@ landsend.com | 0 comments | clothing, jeans
a month ago
50% Off Diesel Men's and Women's Denim, Shoes and More: Clothing & Accessories
@ amazon.com | 3 comments | shoes, jeans, footwear
a month ago
Eddie Bauer: All Chinos and Jeans 40% Off
@ eddiebauer.com | 1 comment | clothing, men-and-women, jeans, chinos, pants
a month ago
2 months ago
Up to 50% Off + Extra 40% Off + Earn Gap Cash
@ gap.com | 2 comments | clothing, accessories, jeans, coupon-code
2 months ago
High Waist Ankle Length Jeans for $21.99
@ cicihot.com | 0 comments | clothing, pants, jeans, high-waist
2 months ago
3 months ago
35% Off Purchase at Old Navy, Gap and Banana Republic
@ oldnavy.gap.com | 0 comments | clothing, jeans, men, maternity
3 months ago
3 months ago
Levi's - Today only 40% off and free shipping for ALL orders. Use code CYBER40 at checkout.
@ us.levi.com | 4 comments | clothing, jeans, levis, cybermonday
3 months ago
Levi's - 40% off with FREE Shipping! Today Only! (11/27)
@ us.levi.com | 19 comments | clothing, levis, jeans, clothes
4 months ago
U.S. Polo Assn. Men's and Women's Jeans and Pants for $19.99
@ uspoloassn.com | 0 comments | clothing, pants, jeans
4 months ago
Target: 40% Off Sweaters and Jeans for Everyone
@ target.com | 0 comments | clothing, women-men-kids, jeans, sweaters
4 months ago
Levi's - 30% OFF Order Plus Free Shipping
@ us.levi.com | 0 comments | clothing, jeans, shirts, men, women
4 months ago
4 months ago
4 months ago
Nudie Jeans Hank Rey Org Dark Ropy at International Jock Limited Time Only* for $139 + free shipping
4 months ago
4 months ago
4 months ago
4 months ago
Levi's Mid Rise Skinny Jeans - Studio Blue for $35 + free shipping
@ us.levi.com | 2 comments | jeans, clothing, womens, skinny
5 months ago
5 months ago
Sponsored Deals
They're like ads, but good.
OK, yes, companies pay a little something to be Sponsored Deals. But we don't allow just any old crap in this section. Sponsored Deals are proposed to us by other retailers, manufacturers, and even other daily deal sites. If we find the deal compelling enough that our members will appreciate us bringing it to their attention, we'll feature it here. Believe it or not, we have a reputation to uphold. If your store would like to be considered for this space, please contact us for details. But if your deal is lame, or sketchy, no amount of money will let you buy your way in.
Community Deals
It's whatever you want it to be.
Pretty much, anyway. This is where you find the deals that wooters like you have ferreted out and brought to light. We're thinking it'll turn into a massive database of discounted products from around the Web, constantly expanding to absorb the newest deals from the very moment their prices are slashed, with each deal immediately rated by hordes of savvy voters to spotlight the very greatest deals in the world today. Hey, we can dream, right?
We use a fancy algorithm to determine which deals are catching the most buzz – they're under the Popular tab, which is the default view of this section. You can look for the most popular deals today, this week, or this month. The Fresh tab features the most recently submitted deals, so that's where to look for deals that everybody else doesn't know about yet. And the Search bar does what a Search bar does, only, uh, much wootier! Yeah! Right on!
Ask The Community
They probably won't bite.
Organic bullets? Vegetarian haggis? Cheap tickets to Antarctica? The best high-performance sweatsocks for under $100? If you're looking for a deal that doesn't appear to show up in our Community Deals section, throw the question to your fellow cheapskates. Or answer a question for one of your fellow cheapskates. Or vote for your favorite questions, or your favorite answers, or… maybe we should call this section "Ask, Answer, Comment On, And Vote In The Community", but that won't fit on the page.


text:
Bracelet Charm (1)
Agate (1)
Birthstone (2)
Multi-Color (2)
Gold (1)
Sterling Silver (2)
White (2)
Yellow (1)
Compare up to 5 Items
Receive a $50 Offer When You Sign Up for Email*
No Thank You
*Valid for new registrations only. A welcome email will be sent with your offer information. Privacy Policy


text:
MRCPCH Part 2: Questions and Answers for the New Format Exam
Limited Stock - Order Soon
This title is directed primarily towards health care professionals outside of the United States. It is a revision book of questions and answers for Part 2 of the MRCPCH exam - all in the new examination format. Questions have been written in the three styles used in the new examination.
Table of ContentsAuthor Information
By Kate H. Creese, MB, BCh, DCH, DRCOG, MRCPCH, Specialist Registrar in Paediatrics, Department of Paediatrics, Children's Hospital of Wales, Cardiff, UK; Colin V. E. Powell, MBChB, DCH, MRCP, FRACP, FRCPCH, MD, Consultant Paediatrician, Department of General Paediatrics, Children's Hospital for Wales, Cardiff, UK; and Patrick H. T. Cartlidge, DM, FRCP, FRCPCH, Senior Lecturer in Child Health and Honorary Consultant Paediatrician, Department of Health, Wales College of Medicine, Cardiff University, Cardiff, UK
Customer Reviews
- Paperback
- 420 Pages
- Trim Size: 6 1/8 X 9 1/5 in
- Imprint: Churchill Livingstone
- Copyright: 2008


text:
Updated: 11:48 a.m. Tuesday, Feb. 11, 2014 | Posted: 11:48 a.m. Tuesday, Feb. 11, 2014
By HILLEL ITALIE
The Associated Press
Former U.S. Rep. Gabrielle Giffords is working on a book about gun control.
The Arizona Democrat and her husband, the retired Navy captain and astronaut Mark Kelly, are collaborating on "Enough: Our Fight to Keep America Safe from Gun Violence."
The book is based on an essay by Giffords that appeared in The New York Times last April, when she responded to the fatal shootings of 20 children and six educators in Newtown, Conn., in December 2012. Giffords chastised senators who blocked gun legislation that included expanded background checks and a ban on assault weapons.
"'Enough' was one of the first words Gabby said to me after we learned about the Newtown, Conn., massacre," Kelly said in a statement issued Tuesday by the book's publisher, Scribner. "As Second Amendment supporters and gun owners ourselves, we hope our book rouses the long-overdue conversation our country needs to make responsible changes to our gun laws so that no more precious lives are lost."
Scribner, an imprint of Simon & Schuster, announced that "Enough" was scheduled for release in June. Scribner previously published "Gabby: A Story of Courage, Love and Resilience," in which Giffords and Kelly told of the former congresswoman's miraculous recovery from being shot in the head in 2011.
For both books, Giffords and Kelly were represented by Robert Barnett, the Washington attorney whose other clients have included President Barack Obama and former President George W. Bush.
Copyright The Associated Press
© 2014 Cox Media Group. By using this website,
you accept the terms of our Visitor Agreement and Privacy Policy, and understand your options regarding Ad Choices.
Portions of Content Provided by Rovi
Corporation. © 2013 Rovi Corporation
Already have an account? Sign In
{* #registrationForm *} {* traditionalRegistration_displayName *} {* traditionalRegistration_emailAddress *} {* traditionalRegistration_password *} {* traditionalRegistration_passwordConfirm *}Already have an account? Sign In
{* #registrationFormBlank *} {* registration_firstName *} {* registration_lastName *} {* traditionalRegistration_displayName *} {* traditionalRegistration_emailAddressBlank *} {* registration_birthday *} {* registration_gender *} {* registration_postalZip *} {* traditionalRegistration_passwordBlank *} {* traditionalRegistration_passwordConfirmBlank *} {* agreeToTerms *}We have sent you a confirmation email. Please check your email and click on the link to activate your account.
We look forward to seeing you frequently. Visit us and sign in to update your profile, receive the latest news and keep up to date with mobile alerts.
Don't worry, it happens. We'll send you a link to create a new password.
{* #forgotPasswordForm *} {* forgotPassword_emailAddress *}We have sent you an email with a link to change your password.
We've sent an email with instructions to create a new password. Your existing password has not been changed.
To sign in you must verify your email address. Fill out the form below and we'll send you an email to verify.
{* #resendVerificationForm *} {* resendVerification_emailAddress *}Check your email for a link to verify your email address.


text:
Electromagnetic Locks
An electromagnetic lock is a device used to control the access through a door. It consists of an electromagnet mounted in or on the door frame and a matching plate that is affixed to the door. When energized, the electromagnet holds the plate with a retention force that may exceed 1000 lbs, thus effectively locking the door. BuyAccess.com carries electromagnetic door locks in a range of holding forces to suit different applications.
They are typically controlled through security systems, keypads, key switches, card access systems, 'request to exit' buttons, and/or by special devices worn by persons who's safety could be comprised by uncontrolled egress.
Vista VM600DB Electromagnetic Lock w/ Door Position Switch & Magnetic Bond Sensor
$103.86 -
Vista VM600 Electromagnetic Lock
$88.12 -
Vista VM300B Electromagnetic Lock w/ Bond Sensor
$72.70 -
Vista VM300 Electromagnetic Lock
$65.14 -
Vista VM1290DB Electromagnetic Lock Direct Retrofit For Locknetics 390+ w/ Bond Sensor & Door Position Switch
$143.94 -
Vista VM1290 Electromagnetic Lock Direct Retrofit For Locknetics 390+
$132.19 -
Vista VM1200DB Electromagnetic Lock w/ Bond Sensor & Door Position Switch
$143.94 -
Vista VM1200 Electromagnetic Lock
$132.19 -
Vista ASB-VM1200 Aluminum Spacer Bracket
$24.34 -
Securitron ZA-32/62SS Adjustable Z-Bracket M32/M62 Stainless Steel
$98.18 -
Securitron ZA-32/62CL Adjustable Z-Bracket M32/M62 Clear
$85.54 -
Securitron ZA-32/62BK Adjustable Z-Bracket M32/M62 Black
$92.63 -
Securitron UHB-CL-8 Universal Header Bracket Clear 9-1/2"
$43.43 -
Securitron UHB-BK-8 Universal Header Bracket Black 9-1/2"
$50.67 -
Securitron TJ-68CL Inswing Door Kit M68 Clear
$76.38 -
Securitron TJ-38CL Inswing Door Kit M38 Clear
$76.38Out of stock
Securitron SWB Wood Door Bracket
$51.98 -
Securitron SMSS Surface Mount Strike Housing
$89.21 -
Securitron SMLS Surface Mount Lock Housing
$92.26 -
Securitron SAMN Shear Aligning Electromagnetic Lock w/ Narrow Strike Plate
$481.16 -
Securitron SAMM Shear Aligning Electromagnetic Lock Metric Version
$431.81Out of stock
Securitron SAMD Shear Aligning Electromagnetic Lock w/ Door Position Switch
$511.71 -
Securitron SAMBD Shear Aligning Electromagnetic Lock w/ Mag Bond Sensor & Door Position Switch
$553.43 -
Securitron SAMB Shear Aligning Electromagnetic Lock w/ Mag Bond Sensor
$523.46 -
Securitron SAM2-24 Shear Aligning Magnalock
$378.35 -
Securitron SAM Shear Aligning Electromagnetic Lock
$481.16 -
Securitron MM15GDT E-Mag Electromagnetic Lock w/ Conduit Option, Door Position & Tamper Switch
$305.50 -
Securitron MM15G E-Mag Electromagnetic Lock w/ Conduit Option
$263.79 -
Securitron MM15DT E-Mag Electromagnetic Lock w/ Door Position & Tamper Switch
$290.81 -
Securitron MM15 E-Mag Electromagnetic Lock


text:
Mayoral Candidate Robert Brown Offers Vision of Where He Wants to Lead Macon
Standing in front of the Douglas Theatre downtown, Robert Brown laid out a portion of his plan on how he wants Macon to be perceived.
Brown, one of four democrats in the mayoral race, said he sees the city free of violent criminals. He also wants to have modernized infastructures, and get the citizens more involved in different aspects of downtown.
Brown used the backdrop of the theatre, because he wants the Martin Luther King corridor, to be the "Gateway to Macon".
He proposed one idea of how to clean up the city, and keep it maintained, is by using the surrounding college and university students to do work. According to Brown, the students would be volunteers for the projects, but they would be able to use the experience towards their field of study.
Another plan of Browns, is to initiate a group he calls the "Young Ambassadors for Macon Music." Brown said the group would be a choir or quartet that would travel the country to raise money and awareness for the city. Brown said this would not be another tax payer supported entity. The group would be self-sufficient.
Brown also said the city has too much music history that cannot be lost. More people need to be aware of what has happened in Macon, and those who have come from Macon.


text:
Tubal Sterilization (cont.) Medical Author:
Avi J Sklar, MD, FACOG, FACS, FRCSC
Medical Editor:
Melissa Conrad Stöppler, MD, Chief Medical Editor
Melissa Conrad Stöppler, MD, Chief Medical EditorMelissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology. IN THIS ARTICLEOtherh Tubal Ligation AlternativesIf you feel you want a permanent solution to birth control, discuss your options with your health care professional. Many younger women who choose this procedure regret their decision later. The younger the woman, the more likely she will regret choosing this permanent form of birth control. Your doctor will discuss your current number of children, your plans for your future and family, and will want to talk with your spouse. This is an important decision. Women with certain medical conditions may not be suited for this procedure. Tubal ligation is surgery. Many couples, in looking at their birth control options, especially when they are ready to stop having children, weigh the benefits and risks of whether the woman would undergo tubal sterilization or the man a vasectomy. Tubal ligation is not temporary. Do not think of it as a procedure to be easily reversed. When reversal is attempted, the operation becomes major surgery and is only successful about 50% to 80% of the time (meaning the woman is able to become pregnant after reversal). Next Page: Must Read Articles Related to Tubal Sterilization
Birth Control FAQs
The practice of birth control is as old as human existence. Your choice of birth control method involves factors such as how easy it is to use, safety, risks, c...learn more >>
Birth Control Overview
The practice of birth control is as old as human existence. Today, the voluntary control of fertility is of paramount importance to modern society.learn more >>
Birth Control Permanent Methods
Sterilization is considered a permanent method of birth control that a man or woman chooses. Although sterilization, or a tubal ligation, for women and vasectom...learn more >>
Women's Health
Find out what women really need.
From WebMD
Women's Conditions Resources
- How Sleep Helps Your Skin
- Cosmetic Cover-ups for Dry, Itchy Skin
- Tips for Dealing With Menopause Symptoms
Featured Centers
Health Solutions From Our Sponsors
Read What Your Physician is Reading on Medscape
Tubal Sterilization »
Prior to the 1960s, female sterilization in the United States was generally performed only for medical indications (when additional pregnancies would be hazardous to the mother).


text:
Caesar was stabbed today. It was a bad day for him! But a good day for you, because we found you pretty Greco-Roman inspired fashions. Because maybe if Caesar had looked a little prettier no one would have stabbed him, yes? Yes.
Shopping Guide: Be-Wear The Ides Of March
- 3 years ago by Jennifer Wright
- 1 Comment »
- Share a Tip
What Lipstick Would Greek Goddesses Wear? |
Recommended by The Gloss:
What We're Reading:


text:
deanna shelton
Senior Director – Human Resources
A member of the Stream Energy team since mid-2005, Deanna Shelton is responsible for the full life cycle of recruitment and employment of the Stream Energy workforce and further coordinates employee training, administers human resources policies and programs and provides consultative support to leadership team on employee relations, performance management and compensation programs.
Deanna brings to bear on the firm's behalf more than a dozen years of Human Resources management experience across various industries including utilities, technology, legal services, and retail. From 2003 through 2005, Deanna held the position of Human Resources Manager for Atrana Solutions, Inc. (a Dallas software development company), where she directed human resource policies and procedures as well as created staffing planning and recruitment processes. Prior thereto, she was Director – Human Resources for FHI, Inc. (a multi-state retail stores operator) tasked with strategic human resources leadership and with a primary emphasis in payroll and benefits administration.
Deanna earned a Bachelor of Business Administration degree from Wayland Baptist University (where she was a member of its intercollegiate women's basketball program). Deanna & her partner Doneen are the proud parents of a son.


text:
What Does DogFriendly.com Offer? Select From Our Pull-Down Menu Dog-Friendly Hotels & Lodging Dog-Friendly City Guides ...Attractions, Restaurants & More Dog-Friendly Ski Resorts Dog-Friendly Camping/RV Parks Dog-Friendly Beach Guide Dog-Friendly Outdoor Dining Dog-Friendly Attraction Guide Dog-Friendly Park Guide Off-Leash Dog Parks Public Transportation & Dogs Dog Camps Dog-Friendly Events Dog Photo Gallery Dog & Pet Store Dog Travel Guide Books Top 10 Dog-Friendly Cities Top 10 Dog-Friendly Resorts DogFriendly.com's Newsletter Book Reseller Information Advertise with DogFriendly.com Online Press Kit About Us/Contact Us
U.S. Dog Travel Guides
Dog City Guides
Outdoor Dining
Dog Parks
Dog & Pet Store
Campgrounds & RV Parks
Dog Travel Books
Mobile Apps
Dog Photos
Lakeview Inn Kingston
Lakeview Inn KingstonDog-Friendly Hotels1200 North Kentucky StreetKingston,Tennessee 37763Call 866-676-3077 To Book This Hotel Get Map or Directions The Lakeview Inn Kingston is conveniently located on Interstate 40 West and Exit 352 at the junction of Hwy 58, facing a beautiful lake in Kingston Ten. Kingston Waterfront Park is 1 mile, and the Lakeside Golf Course is a short 3 miles from the Lakeview Inn. The pet friendly Lakeview Inn Kingston provides guests free parking and free wireless internet access. Start your day with free coffee and danishes served in our lobby, and The Mexican Grill is on premises for lunch and dinner. Our front desk is open 24 hours, and guest laundry facilities are available. All guest rooms feature free wi-fi, free local calls, microwave, mini-fridge, cable TV with HBO, and a/c. Pet fee is $10 per pet, per day. For extended stay rates, please contact the hotel directly.Dogs of all sizes are allowed. Dogs are allowed for a nightly pet fee.
=indicates DogFriendly.com's dog-friendly advertisers!
Air Travel
Highway Guides
Books and Ebooks
List Your Property
About Us
Press Kit
Contact Us
Recommend Places


text:
VIDEO: Sarah McLachlan Performs New Christmas Song 'Find Your Voice'
We are thrilled to announce the release of the new single Find Your Voice"."The soon to be holiday classic by Sarah McLachlan was co-written with longtime collaborator Pierre Marchand. The track, featuring the background vocals and percussion from the students of the Sarah McLachlan School of Music, is set to hit airwaves November 28th and is the first original holiday release since the Double Platinum Wintersong. The accompanying music video will debut in Canada on CBC November 28th and word wide December 4th. Check out McLachlan singing her new single below!
"Christmas is a difficult time for many both economically and emotionally and I hope this Gift of Music can help in some small way." Sarah McLachlan continues "My holiday wish is that we can all find the good in everyone and in every situation and be kind to each other. I wish you all a very happy, peaceful holiday filled with love, laughter and light!"
"Find Your Voice" will be offered free of charge at SarahMcLachlan.com in the hopes that people's generosity will allow the Sarah McLachlan School of Music to continue providing exceptional opportunities for at-risk youth to learn music. 100% of the proceeds made from the song will go to support the school. The song is also be available as part of a worldwide release on iTunes and via digital music services.
Grammy award winning singer Sarah McLachlan recently completed a critically acclaimed North American symphonic tour and is set to release a highly anticipated new album in early 2013.
PDF Print
More On: Sarah McLachlan,
Related Links |
Rachael Sage Releases New Single & EP; Confirms Tour and Festival Dates March 11, 2014 |
Sarah McLachlan to Play Fox Theatre, 7/6 March 03, 2014 |
Photo Coverage: The Tenors Play a Valentine's Day Concert at NYCB Theatre by Genevieve Rafter Keddy - February 15, 2014 |
VIDEO: Singer/Songwriter Sarah McLachlan Appears in Audi Super Bowl Spot February 03, 2014 |
Sarah McLachlan to Release New Album 'Shine On', 5/6; Performs on JAY LENO Tonight January 30, 2014 |
About Author
- HUNTER HAYES Set to Release New Album 'Storyline', 5/6
- Cast of Las Vegas' JERSEY BOYS to Perform on THE QUEEN LATIFAH SHOW Tomorrow
- GOO GOO DOLLS & DAUGHTRY to Hit the Road This June
- Queen and Adam Lambert Announce North American Tour!
- SNL Ratings Slip with Lena Dunham as Host
- Broadway Actress and Star of THE HONEYMOONERS Shelia MacRae Passes Away at 92
- VIDEO: Lifetime's THE TRIP TO BOUNTIFUL, with Cicely Tyson, Premieres Tonight
- Cast of Broadway's LES MISERABLES to Perform on ABC's GOOD MORNING AMERICA, 3/13
- CUNY TV's ASIAN AMERICAN LIFE Features KUNG FU's Cole Horibe, Beg. Today
- 'TONIGHT SHOW' & 'LATE NIGHT' Deliver Strong Showings with L+3


text:
If you're ordering a replacement, then you must have worn out the original Spot! Great job keeping your Spot On program going strong! Plush dog is made of polyester and is surface wash only.
Do you have a question? Chat with Us Live
All of our in-stock items ship the same day you order if your order is placed by 6 p.m. ET. Engrave & Ship today items will be shipped out the same day if personalization is approved by 3pm ET. Delivery to the 48 contiguous states takes 2-5 business days. Delivery to Hawaii, Alaska and Puerto Rico takes 5-7 business days. We will not deliver to a Post Office box.
We stand behind our products, period. If you need to return an unused stock product, we'll be happy to credit your account, exchange the item or give you a merchandise refund if returned within 30 days from receipt of your order.
(based on 1 review)
Ratings Distribution
5 Stars
4 Stars
3 Stars
2 Stars
1 Stars
Reviewed by 1 customer
Displaying review 1
Back to top
Big hit!
By Tracie
from Orange County, Ca
Comments about Baudville Spot On - Plush Dog:
So cute. It was a bit hit. Will continue to use it in our recognition program.
Want this item customized with your logo or organization's name?


text:
First look at PHX Sky Train going up at Sky Harbor airport
Other Slide Shows
- Maricopa Mugs: March Arrest Photos Volume 1
- Family, friends and fellow officers say final goodbye to fallen Phoenix police detective
- First F-35 arrives at Luke Air Force Base
- Bonds back in Giants uniform as camp coach
- Skydiver hit by plane
- Photos: Scottsdale nightlife, March. Vol. 1


text:
Link Shelving Elements
Filed under: Decor
If conventional shelving doesn't offer the versatility that you're looking for, perhaps modular shelving would be a better option. These Link Shelving Elements are made of molded polypropylene. They are stackable and can be arranged in any number of ways, with any number of units to create as large as (or as small of) a system as you need. The units come in four colors: light gray, olive medium gray, white/ivory, and light green. Each measures 15.75" x 23.5" and extends x 19.5" deep. Price: $150 per piece.
[via BLTD]