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Current staging system for small cell lung cancer (SCLC) categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion.
We studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated.
84% (364/432) of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30–3.10), age (HR, 1.04; 95% CI, 1.03–1.06), and extensive stage (HR, 1.39; 95% CI, 1.06–1.84) were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25–0.42) was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001). Among SCLC patients of either limited (median 180 vs. 460, p<0.0001) or extensive (median 125 vs. 207, p<0.0001) stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively.
Citation: Chou P-C, Lin S-M, Lo C-Y, Chen H-C, Wang C-W, Chou C-L, et al. (2012) Endobronchial Mucosa Invasion Predicts Survival in Patients with Small Cell Lung Cancer. PLoS ONE 7(10): e47613. https://doi.org/10.1371/journal.pone.0047613
Editor: Pan-Chyr Yang, National Taiwan University Hospital, Taiwan
Received: May 1, 2012; Accepted: September 19, 2012; Published: October 4, 2012
Copyright: © Chou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
Small cell lung cancer (SCLC), accounting for 20% of lung tumors, is relative sensitive to cytotoxic chemotherapy and radiation therapy [1]. SCLC which arises from or is related to the pulmonary neuroendocrine cell possesses distinctive cellular and molecular biologic characteristics compared with the non-small cell lung cancer [2], [3]. Despite a high response rate to chemotherapy and radiotherapy, SCLC remains associated with a poor long term survival due to its rapid relapse [4].
SCLC patients are staged according to a two-stage system, which was developed by the Veterans Administration Lung Cancer Study Group [5], as having limited stage disease or extensive-stage disease. Clinical stage at initial presentation is one of the most powerful prognostic factors identified in most studies [6], [7]. 60 to 65% of patients have extensive disease at diagnosis with median survival of approximately 9 months, while about 18 months of median survival was reported in patients with limited-stage disease [5]. Due to other independent prognostic factors, there remains heterogeneity among studies [8], [9]. The identification of risk factors could explain the variability observed in survival and be useful in stratification for subgroup for new therapeutic strategies.
SCLC often occurs initially as a centrally located endobronchial tumor [10], a characteristics which made this cancer ideal for bronchoscopic examination. Indeed, the initial histological diagnosis of SCLC is often rendered via bronchoscopic examination [10]. Evidence suggests that abnormal findings in bronchoscopic examination is associated with early relapse or SCLC [11]. In addition, SCLC patients with endobronchial mucosa invasion by tumor are less sensitive to chemotherapy when compared with those without endobronchial mucosa invasion [11]. However, the association between endobronchial mucosa invasion and survival outcome in patients with SCLC has not been well addressed.
This study is designed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion in the whole cohort and in subgroups stratified as limited and extensive stages.
Patients and Methods
Study Subjects
Medical records from Jan. 1998 through Dec. 2005 were reviewed for all of the patients diagnosed with small cell lung cancer (SCLC) at the Chang Gung Memorial Hospital, Taiwan, a tertiary-care transfer center. The diagnosis was based on histological examination of biopsy specimens or on fine-needle aspiration cytology. There were 765 patients with SCLC during this period of time. All patients had been explained about the indications of the bronchoscopy, which is one part of the diagnostic processes. Among them, 432 patients received bronchoscopic examination for tissue proof and staging of SCLC, and were enrolled in the analysis. Patients without bronchoscopic examination, or patients with previous or co-existent malignancies other than SCLC were excluded from analysis. No additional bronchoscopic examination was performed for this study. The institutional review board of Chang Gung Memorial Hospital approved this study and waived the requirement for informed consent. An IRB certificate of approval of the study in English version has been attached together with the representative patient's signed permit for bronchoscopic examination in English and Chinese Version in the supporting files.
Staging and Diagnostic Procedures
All patients had a complete history, physical examination, evaluation of performance status and investigations to define the extent of their disease, which included routine hematology and biochemistry, chest X-ray, bronchoscopy, computed tomography (CT) scan of the thorax, including the upper part of abdomen or ultrasound examination of the abdomen, and radionuclide bone scan. Routine biochemistry included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlkP), lactate dehydrogenase (LDH) and measurement of serum electrolytes (sodium, potassium, and chloride), serum creatinine and blood urea nitrogen. A brain CT scan was not mandatory unless neurological symptoms were present. Patients were classified into limited-stage or extensive-stage disease according to Veterans' Administration Lung Cancer Study Group [5]. Limited disease (LD) was defined as that confined to one thorax, including the bilateral mediastinal and supraclavicular nodes; any involvement beyond these confines was defined as extensive disease (ED). Patients with pleural effusion were included in the ED category. The Eastern Cooperative Oncology Group (ECOG) performance status [12] and location of tumor on initial diagnosis of SCLC were recorded. Extra-pulmonary involvement was defined as SCLC with distant metastasis other than intra-thoracic lymph node metastasis.
The study also recorded administrated therapies in all the patients, including radiotherapy, chemotherapy, concurrent chemo-radiotherapy (CCRT), and best supportive care. Chemotherapy denoted etoposide (60 mg/m2) given on day 1 and cisplatin (60 mg/m2) given on day 1–3 on a monthly basis for 4–6 cycles as the first line chemotherapy. In patients who are unresponsive to the first line chemotherapy or intolerant of toxicity, topotecan (1.2 mg/m2) given on day 1–5 on a monthly basis will be prescribed instead. In this study, 161 patients (51.2%) received less than 3 cycles of chemotherapy, 99 (31.5%) received 3 to 5 cycles of chemotherapy, and 54 (17.2%) received 6 cycles of chemotherapy. There were 30 patients receiving 2nd line topotecan chemotherapy. CCRT included administration of thoracic radiotherapy concurrently with etoposide and cisplatin within the first 6 weeks of chemotherapy.
Bronchoscopic Study
The probable location of the lesion was determined initially by conventional posterior anterior chest radiography with or without chest CT. A flexible fiberoptic bronchoscope (BF-P240 or BF-40, Olympus, Tokyo, Japan) was then inserted via nostril after local spray of 2% xylocaine for anesthesia. The heart rate and oxygen saturation of each patient was monitored by a pulse oximeter during the procedure. In all patients, visual inspection of the larynx, vocal cords, trachea, carina, and all segmental orifices of both lungs was performed. Normal saline solution was instilled through the bronchoscope, with aspiration of washings for cytologic examination. Bronchial biopsies were done with forceps, and a minimum of three biopsies were taken. Bronchial biopsies were performed on suspicious lesions including endobronchial nodules and narrowing or obliteration of the bronchial lumen by swollen mucosa. Mucosal involvement was confirmed by histological examination (Figure 1). The endobronchial mucosal invasion was defined as tumor extends above the lamina propria of the mucosae. Each patient received at least 3 pieces of samples (4.5 mean, range 3 to 6) from the involved site. All samples were embedded in paraffin, and cut at the same thickening at fixed distance into 4 slides. Patient will be classified if any of the slides presented with tumor extends above the lamina propria.
(A) Initial CXR showed right hilar lesions. (B) Bronchoscopy revealed narrowed bronchus due to external compression (upper figure), and mucosal invasion (lower figure). (C) In histologic examination of the biopsied tissue, endobronchial mucosal invasion (EMI) has been identified with tumor (thin arrow) extends above lamina propria (thick arrow) under high power field examination (400X).
Statistical Methods
Descriptive statistics were employed to examine the demographic characteristics of the study population. Survival time was expressed as median and Inter-quartile range (IQR). The variables between two groups were compared using the Student t test for continuous variables and the chi-square or the Fisher exact test for categorical variables. Univariate analyses were primarily used for variable selection, based on a p-value under 0.1. The selected variables were entered into a multivariable stepwise regression analysis that identified the net effects of each individual factor. Odds ratios (OR) and their 95% confidence intervals (CI) were used to assess independent contribution of significant factors. The selected variables were further analyzed with the Cox proportional hazard model to adjust for potential confounding effects between each other factor. Hazard ratio (HR) with 95% confidence interval (CI) was used to report the result. The survival curves were estimated by the method of Kaplan and Meier, and the curves were compared according to one factor by the log rank test. Analyses were performed using SPSS software version 12.0 (Chicago, IL, USA).
Patient Characteristics
Table 1 lists the patient characteristics, including sex, age, smoking status, performance status, clinical staging, chemotherapy received and tumor location. There were 364 (84%) patients found to have endobronchial mucosal invasion by cancer cells on bronchoscopic examination. The characteristics of patients with or without endobronchial mucosal invasion are similar (Table 1), though patients with endobronchial mucosa invasion tended to have less courses of chemotherapy due to poor response to chemotherapy and more rapid disease progression.
The Duration of Survival
The median survival of all the patients with SCLC was 161 (IQR, 46–348) days; 206 (IQR, 79–403) days for limited stage patients, and 137(IQR, 40–314) days for extensive stage patients (Table 2). Using Kaplan-Meier analysis, survival time was measured from the date of diagnosis, and death from all causes during the period of follow up was taken as the outcome. Patients with mucosal invasion had worse survival than patients without (Hazard Ratio [HR] 2.03, 95% CI 1.55–2.42, p<0.0001) (Figure 2). The median survival for patients with endobronchial mucosa invasion was 145 (IQR, 39–322) days, while the median survival for those without mucosal invasion was 290 (IQR, 129–626) days. In extensive stage patients, patients with endobronchial mucosa invasion had worse survival than those without (HR 1.8, 95% CI 1.27–2.33, p = 0.0005) (Figure 3) with a shorter median survival of 125 days (IQR, 31–277 days, P<0.001) compared with that of patients with intact mucosa (207 days, IQR, 123–449 days). In limited stage patients, patients with endobronchial mucosa invasion also had worse survival than those without (HR 2.27, 95% CI 1.57–3.04, p<0.0001) (Figure 4) with a shorter median survival of 180 days (IQR, 60–353 days; P<0.001) compared with that of patients with intact mucosa (460 days, IQR, 215–742 days).
The dashed line represents patients with intact mucosa; the continuous line represents patients with mucosa invasion.
The dashed line represents patients with intact mucosa; the continuous line represents patients with mucosa invasion.
The dashed line represents patients with intact mucosa; the continuous line represents patients with mucosa invasion.
Univariate Analysis
Univariate analysis (Table 3) allowed us to identify the possible factors potentially associated with survival time less than the median survival (161 days) in SCLC patients of the whole cohort. We analyzed the association between decreased survival days and variables including age, gender, performance status, clinical staging, mucosal invasion, and administration of therapy of the patients. The results revealed that age (OR, 1.04; 95% CI, 1.02–1.05), extensive stage (OR, 1.61; 95% CI, 1.10–2.36), and endobronchial mucosal invasion (OR, 2.21; 95% CI, 1.28–3.80) were significantly associated with a decrease in survival, while good performance status with ECOG scale ≤2 (OR, 0.19; 95% CI, 0.12–0.30) and receiving chemotherapy more than 4 cycles (OR, 0.41; 95% CI, 0.30–0.56) are associated with a better survival. In patients with measurable tumor size, univariate analysis revealed no difference in size between patients with longer survival and those with shorter survival (5.70±3.74 vs 5.61±2.22, p = 0.432; respectively).
The Cox's Proportional Hazard Analysis
The Chi-squared test revealed high correlations between good performance status with ECOG scale ≤2 and chemotherapy received (p<0.0001). However, there was no significant correlation identified among age, extensive stage, endobronchial mucosal invasion, and chemotherapy received. Therefore, age, extensive stage, endobronchial mucosal invasion, and chemotherapy received were introduced into Cox's proportional hazard model. The results (Table 4) showed that age (HR, 1.04; 95% CI, 1.03–1.06), extensive stage (HR, 1.39; 95% CI, 1.06–1.84), and endobronchial mucosal invasion (HR, 2.01; 95% CI, 1.30–3.10) were independent contributing factors for shorter survival, while chemotherapy received (HR, 0.32; 95% CI, 0.25–0.42) was an independent contributing factor for better outcome.
This study demonstrated that 84% (364/432) of SCLC patients had endobronchial mucosal invasion by cancer cells while the cancer was initially diagnosed. Although the baseline characteristics were similar between patients with and without endobronchial involvement, SCLC patients with endobronchial mucosal involvement were at significantly higher risk of decreased survival times even after adjusting subjects' age, sex, clinical staging, and administrated therapy. Among SCLC patients of either limited or extensive stages, the median survival for patients with endobronchial mucosal invasion was shorter than those without, respectively.
Many studies had tried to identify the clinical and laboratory parameters to predict long-term survival in small cell lung cancer [6], [7], [13], [14]. Compatible with previous reports, our results also indicated that age [6] and extensive stage [7] were independent contributing factors for shorter survival time, while receiving chemotherapy [7] no less than 4 courses was an independent contributing factor for better outcome. Recently, other prognostic factors such as both baseline circulating tumor cell number and change in circulating tumor cell number after chemotherapy have been reported as an independent prognostic factor for SCLC [15]. A previous study reported a much higher rate of relapsing tumor and a worse response to chemotherapy in SCLC patients with abnormal findings on bronchoscopic examination [11]. However, their study did not employ multivariate analysis to evaluate the independent predictive power of endobronchial mucosal involvement on survival. By means of Cox proportional hazard model, our study discloses that endobronchial mucosal invasion is an independent prognostic factor for poor outcome in SCLC patients even under controlling of other associated variables. The predictive power for poor survival of endobronchial mucosal involvement is as strong as that of extensive stage. Therefore, apart from currently recognized prognosticators, circulating tumor cell number and endobronchial mucosal invasion may be taken into consideration for risk stratification of patients in clinical practice and helping clinicians make appropriate treatment decisions for individual patients.
Although it is believed that SCLC arises from or is related to the pulmonary neuroendocrine cells [2], [3], emerging evidence also indicates the possibility that a non-neuroendocrine cell, such as adult lung stem cells and progenitor cells [16], can adopt neuroendocrine characteristics through gene mutation [17]. The key step of endobronchial mucosa invasion is disruption of basement membrane by cancer cells. Previous studies [18], [19] have proposed a model of invasion and metastasis by cancer cells in which the basement membrane (BM) plays an important role as a barrier against tumor cell invasion [20]. There have been several reports claiming that disruption of the BM in various tumors significantly correlated with tumor progression and therefore with reduced patient survival [21]–[24]. The association between endobronchial mucosa invasion and poor survival in SCLC patients could be attributed to higher tumor invasiveness with release of proteolytic enzymes resulting in degradation of BM. The expression of E-cadherin, a calcium-dependent cell-cell adhesion receptor that restricts invasion of cells and reduces metastasis, in tumor cells offers a favorable overall survival in SCLC patients [25]. On the other hand, activation or alternation of c-Met pathway leads to higher cell proliferation and invasion capacity is associated with poor prognosis in SCLC [25]–[27]. Although miRNAs were proposed to be implicated in alternation of SCLC tumor biological behavior, such as tumor invasiveness or chemoresistance [28], [29], a recent study did not find any reported miRNA was prognostic or related to malignant behavior in SCLC patients [30]. Disruption in epigenetic control of cell proliferation, including DNA methylation [31], [32] has been shown to contribute to prolonged and uncontrolled cell survival. Further study is warranted to investigate whether there are aberrant miRNA profiles or epigenetic disruption, or expression of E-cadherin or c-Met activation in SCLC with high potential for endobronchial mucosal invasion.
Even stratified as limited or extensive stage, the presence of endobronchial mucosa invasion among SCLC patients also predicts a decreased survival in each subgroup. Interestingly, the median survival time (207 days) for patients with extensive staged SCLC and endobronchial mucosa invasion is similar to the median survival for patients with limited staged SCLC in the whole cohort (206 days). The presence of endobronchial mucosa invasion may be used to identify the patients at higher risk for poor outcome. Thereafter, routine bronchoscopic examination for endobronchial invasion and frequent monitoring during treatment may be considered for all the SCLC patients. For patients with endobronchial mucosa invasion, even in limited stage, intensive therapeutic intervention may be considered. However, the impact of endobronchial invasion on SCLC outcomes needs to be confirmed by further prospective studies. In addition, the combination of Veteran Affair Administration Lung Cancer Study Group staging system and presence of endobronchial mucosa invasion may provide a better predictive power for prognosis in patients with SCLC.
In conclusion, the present study showed that SCLC patients with endobronchial mucosa involvement had shorter survival time than patients without endobronchial mucosa involvement. The endobronchial mucosa involvement is an independent predictor for decreased survival in SCLC patients, even after taking age, sex, clinical staging, and administrated treatment into account. Our study advances the notion that detection of mucosa invasion by bronchoscopic examination is mandatory in patients with SCLC. The presence of endobronchial mucosa involvement may offer a new predictor of outcome and be used in risk stratification among SCLC patients.
Supporting Information
Document S1.
An IRB certificate of approval of the study in English version.
Document S2.
Representative patient's signed permit for bronchoscopic examination in English Version.
Document S3.
Representative patient's signed permit for bronchoscopic examination in Chinese Version.
Author Contributions
Conceived and designed the experiments: HPK PCC SML. Performed the experiments: CYL HCC CLC CTY HCL CHW. Analyzed the data: HPK PCC SML. Contributed reagents/materials/analysis tools: CYL HCC CLC CTY HCL CHW. Wrote the paper: PCC SML. Histologic examination of the biopsied tissue: CWW.
- 1. Boring CC, Squires TS, Tong T, Montgomery S (1994) Cancer statistics, 1994. CA Cancer J Clin 44: 7–26.
- 2. Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, et al. (1985) Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45: 2913–2923.
- 3. Linnoila RI, Mulshine JL, Steinberg SM, Funa K, Matthews MJ, et al. (1988) Neuroendocrine differentiation in endocrine and nonendocrine lung carcinomas. Am J Clin Pathol 90: 641–652.
- 4. Albain KS, Crowley JJ, LeBlanc M, Livingston RB (1990) Determinants of improved outcome in small-cell lung cancer: an analysis of the 2,580-patient Southwest Oncology Group data base. J Clin Oncol 8: 1563–1574.
- 5. Simon GR, Wagner H (2003) Small cell lung cancer. Chest 123: 259S–271S.
- 6. Paesmans M, Sculier JP, Lecomte J, Thiriaux J, Libert P, et al. (2000) Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer 89: 523–533.
- 7. Yip D, Harper PG (2000) Predictive and prognostic factors in small cell lung cancer: current status. Lung Cancer 28: 173–185.
- 8. Chute JP, Venzon DJ, Hankins L, Okunieff P, Frame JN, et al. (1997) Outcome of patients with small-cell lung cancer during 20 years of clinical research at the US National Cancer Institute. Mayo Clin Proc 72: 901–912.
- 9. Kawahara M, Fukuoka M, Saijo N, Nishiwaki Y, Ikegami H, et al. (1997) Prognostic factors and prognostic staging system for small cell lung cancer. Jpn J Clin Oncol 27: 158–165.
- 10. Marsh BR, Frost JK, Erozan YS, Carter D (1974) Role of fiberoptic bronchoscopy in lung cancer. Semin Oncol 1: 199–203.
- 11. Ihde DC, Cohen MH, Bernath AM, Matthews MJ, Bunn PA, et al. (1978) Serial fiberoptic bronchoscopy during chemotherapy for small cell carcinoma of the lung: early detection of patients at high risk of relapse. Chest 74: 531–536.
- 12. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, et al. (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5: 649–655.
- 13. Paesmans M, Lafitte JJ, Lecomte J, Berghmans T, Efremidis A, et al. (2011) Validation and comparison of several published prognostic systems for patients with small cell lung cancer. European Respiratory Journal 38: 657–663.
- 14. Metze K (2011) Pitfalls in the assessment of prognostic factors. Lancet Oncol 12: 1095–1096.
- 15. Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, et al. (2012) Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol 30: 525–532.
- 16. Sutherland KD, Proost N, Brouns I, Adriaensen D, Song JY, et al. (2011) Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung. Cancer Cell 19: 754–764.
- 17. Park KS, Liang MC, Raiser DM, Zamponi R, Roach RR, et al. (2011) Characterization of the cell of origin for small cell lung cancer. Cell Cycle 10: 2806–2815.
- 18. Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327–336.
- 19. Liotta LA (1984) Tumor invasion and metastases: role of the basement membrane. Warner-Lambert Parke-Davis Award lecture. Am J Pathol 117: 339–348.
- 20. Terranova VP, Hujanen ES, Martin GR (1986) Basement membrane and the invasive activity of metastatic tumor cells. J Natl Cancer Inst 77: 311–316.
- 21. Nakagawa H, Yagihashi S (1994) Expression of type IV collagen and its degrading enzymes in squamous cell carcinoma of lung. Jpn J Cancer Res 85: 934–938.
- 22. Havenith MG, Arends JW, Simon R, Volovics A, Wiggers T, et al. (1988) Type IV collagen immunoreactivity in colorectal cancer. Prognostic value of basement membrane deposition. Cancer 62: 2207–2211.
- 23. Albrechtsen R, Nielsen M, Wewer U, Engvall E, Ruoslahti E (1981) Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin. Cancer Res 41: 5076–5081.
- 24. ten Velde GP, Havenith MG, Volovics A, Bosman FT (1991) Prognostic significance of basement membrane deposition in operable squamous cell carcinomas of the lung. Cancer 67: 3001–3005.
- 25. Chang MH, Lee K, Lee KY, Kim YS, Kim YK, et al. (2012) Prognostic role of integrin beta1, E-cadherin, and rac1 expression in small cell lung cancer. APMIS 120: 28–38.
- 26. Song J, Li M, Tretiakova M, Salgia R, Cagle PT, et al. (2010) Expression patterns of PAX5, c-Met, and paxillin in neuroendocrine tumors of the lung. Arch Pathol Lab Med 134: 1702–1705.
- 27. Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, et al. (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63: 6272–6281.
- 28. Guo L, Liu Y, Bai Y, Sun Y, Xiao F, et al. (2010) Gene expression profiling of drug-resistant small cell lung cancer cells by combining microRNA and cDNA expression analysis. Eur J Cancer 46: 1692–1702.
- 29. Miko E, Czimmerer Z, Csanky E, Boros G, Buslig J, et al. (2009) Differentially expressed microRNAs in small cell lung cancer. Exp Lung Res 35: 646–664.
- 30. Lee JH, Voortman J, Dingemans AM, Voeller DM, Pham T, et al. (2011) MicroRNA expression and clinical outcome of small cell lung cancer. PLoS One 6: e21300.
- 31. Iwasaki Y, Sunaga N, Tomizawa Y, Imai H, Iijima H, et al. (2010) Epigenetic Inactivation of the Thyroid Hormone Receptor β1 Gene at 3p24.2 in Lung Cancer. Annals of Surgical Oncology 17: 2222–2228.
- 32. PELOSI G, FUMAGALLI C, TRUBIA M, SONZOGNI A, REKHTMAN N, et al. (2010) Dual Role of RASSF1 as a Tumor Suppressor and an Oncogene in Neuroendocrine Tumors of the Lung. Anticancer research 30: 4269–4281.


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Hey there, time traveller!
This article was published 19/12/2012 (1676 days ago), so information in it may no longer be current.
We know that we are up to our ears in the holiday season when we see all of the poinsettias for sale in garden centres and retail shops. You can hardly go into any business that in not either selling these wonderful holiday plants or displaying one to make their own business premises look more attractive during the festive season.
Many of us purchase at least one poinsettia to add seasonal beauty to our indoor spaces. Before you make the purchase, however, it is a good idea to look around at your interior and see how you can incorporate a poinsettia or two into your indoor landscape.
Of course, one of the best ways to display a poinsettia is to let it stand alone as a specimen plant in the home. If you are planning to do this, however, you should think carefully about the plant you will buy.
It is important that a specimen plant be displayed in an attractive container, as the container is an integral part of the whole arrangement that will add immeasurably to the overall beauty of the display. A very large poinsettia displayed in a decorative urn, for example, will wow your guests during the holidays.
A specimen plant is just that — a specimen; it must be spectacular enough to stand on its own. Do not try to skimp on either quality or size; purchase a large, perfectly shaped plant that will be in scale with the location in which you plan to place it.
Nothing looks more forlorn than a rather small, nondescript plant that is trying — unsuccessfully — to be a stunning specimen plant. If you do not wish to spend the dollars to purchase a true specimen plant, then consider ways that you can incorporate a less expensive poinsettia into the indoor landscape.
One way to use a rather small plant, perhaps one with only two or three blooms, is to include it in a dish garden with other plants that you might have on hand. If you are unsure how to do this, observe some of the dish gardens — often sold as basket arrangements — in your local garden centre.
You will get some ideas on what plants might be included in the dish garden besides the poinsettia. You can either actually plant the dish garden or you can simply place several pots into the container and cover the pot rims with Spanish moss to make the arrangement appear that it is really growing in the container.
If you want to purchase a larger poinsettia but still think that it is not worthy of "specimen" status, you might group a couple of your houseplants together with the poinsettia. A poinsettia will combine nicely with a small peace lily, a pot of coleus, a table fern, a dieffenbachia or many other plants — use what you have.
It goes without saying that any poinsettia will look best if it is displayed in an attractive jardinière. Slip the pot out of its greenhouse sleeve before placing it into the jardinière to facilitate good drainage; otherwise, excess water will be held around the base of the pot by the sleeve and cause the roots to become sodden.
Another alternative display to the specimen plant is to obtain several smaller, less than perfect plants and group them into a display. You could even use a plant stand that accommodates three plants — perhaps one that you use in your outdoor garden.
You could use various sized boxes or flower pots in lieu of a plant stand and simply arrange them where you want the display and drape a colourful holiday cloth — even a Christmas tablecloth would work — over the boxes (pots) and then put the poinsettias in place.
Perhaps you might add a few shiny Christmas balls or a few large cones to the arrangement. Many poinsettias that you buy will come with an attractive bow, but you can replace this bow with a more spectacular one or supplement the existing bow by adding a few cones or other decorations to the bow.
Rather than purchasing the traditional red poinsettia, you may wish to create a display using another colour; if you do, the display will not look out of place in the post-Christmas season.
Poinsettias come in rich burgundy, lovely pinks and salmons, as well as ivory, and the ivory ones can be coloured just about any colour you wish — even black!
Whether you choose a large specimen, a small tabletop plant or several mid-sized poinsettias for your holiday décor, take care of the plants diligently so that they remain attractive throughout the holiday season.
* Keep the planting medium evenly moist
* Don't locate the poinsettias where there are cold drafts
* Try to place the plants where they will get at least strong indirect light some direct sun would be even better.
Merry Christmas!
Albert Parsons is a consultant for garden design and landscaping who lives in Minnedosa.
» email@example.com


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J. D. Controls Wafer Type Butterfly Valve have been developed with extensive application, design and manufacturing expertise. J. D. High Performance Slim-Seal, Concentric design Butterfly Valves are reliable, maintenance free shutoff with permanently gas-tight seal with an integrally moulded or replaceable elastomer body liner. J. D. Butterfly Body having two nos. flange locating holes for sizes up to 12 and from size 14 and above 04 nos. for easy alignment of valve during installation. Flange locating hole confirm to as per ANSI B 16.5 Class 125 & Class 150 / BS 10 Table D, E, F / PN 6, PN 10, PN 16 or other international standard. J. D. High performance butterfly valves are also available with Full-Lugs type body with raised faces and flanged ends connection.
J. D. Butterfly Valve, Wafer Type, Slim-Seal design, maintenance free shutoff. This butterfly valves excess other conventional valves such as gate valve and globe valves in all aspects, especially in terms of light weight, less number of component, no flange gaskets required and economical operation and maintenance costs.
J. D. Slim Seal design Butterfly Valves body seat mechanism have a very low torque, tight shut off with zero leakage, compact actuator selection, and long life smooth easy operation. The slim-seal, center disc design valves are widely available with different combination of body, seat & disc materials to satisfy the need of most industrial application.
Standard Test :
Body Test: 1.5 times the working pressure with water. This test is performed after valve assembly and with disc in half position open, it is called as a body hydro test.
Seat Test: 1.5 times the working pressure with water.
Function / Operation Test: At the time of final inspection, each valve and its actuator (Flow-Control Lever / Gear / Pneumatic Actuator), under goes a complete operating test (Open/Close). This test carried out without pressure and at ambient temperature. It ensures the correct operation of the valve / actuator assembly with accessories such as solenoid valve, limit switches, air filter regulator etc.
Special Test: On request, any other test can be carried out according to special instruction by client.
Application :


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With that little catch phrase, so end many nights in orchestra pits in and around LA. Local tradition holds that whenever a substitute player finishes his or her first night on a show, if they are particularly "on" (and they usually are!) someone in the orchestra will yell out, "Yeah, (name here)!" immediately after the exit music. It's a nice accolade from fellow players in response to a good first performance. About ten years ago at the Pantages Theatre, after a great substitute performance by bassist Kenny Wild, "Yeah, Kenny!" could be heard throughout the pit and it stuck…even if Kenny is not there. So now, after the usual accolades to the evening's players someone will always add "Yeah, Kenny!" and it cracks everyone up and puts all in a good mood for the evening hang or the drive home.
I think it's a fitting tribute to a guy who has always been one of my favorite musicians in LA, a bassist of extraordinary feel and versatility, with a personality that is so infectious with good will and optimism that you can't help but rise to the occasion whenever he sits next to you. That, and his playing are what has made him a mainstay in the Los Angeles studio scene for over 30 years.
Before I moved here 27 years ago, I was a fan of the band Seawind. They burst on the local music scene, after honing their songs and performance in Hawaii, with a debut album on Creed Taylor's revered jazz label, CTI. It was a change for Creed's label, which was used to releasing sides from jazz artists like Joe Farrell and George Benson. Their songs had a fresh sound with a tight horn section and featured incredible vocalist Pauline Wilson (then-wife of drummer Bob Wilson), keys/saxophonist Larry Williams and, of course, Kenny Wild on bass. It heralded a new direction in pop music. Almost every player in the band became popular in the studios appearing on countless recordings that were made during that rich time in LA's music history.
Recently, Seawind got back together for a reunion CD and subsequent tour of Japan, where they were extremely popular. I've been listening every chance I get and it is so much fun to hear the band play new renditions of some of their most popular tunes and introduce new ones. The CD is engineered and mixed by Steve Sykes with a big sound that while modern in its aural space brings me right back to the high energy of the band's original sound.
Seawind's Reunion CD can be found here at seawindjazz.com along with the latest news about the band.


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Metal Gear Solid 2 is just about 10 days away, and to commemorate the month of its release, Konami JPN has made the subject of its latest calendar download the Metal Gear RAY, the show-stealing star of the latest game which bears its name. Enjoy Yoji Shinkawa's mechanical designs one last time and slap this on your desktop.
1024 x 768
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Hi, I'm with Tx/Rx in Houston. We called dibs a little while back, but I haven't gotten word back from the receiving hackerspace I was trying to set up. You could be our receiving hackerspace though, the arc distance from Durham to Houston is about 1050 miles.

On Thu, Jan 13, 2011 at 11:58 AM, Ashley McClelland <email@example.com> wrote:

 Hi all,

I popped into your IRC channel today because I saw you guys had signed up for the cupcake challenge but didn't have a receiving hackerspace down on the spreadsheet yet. I tentatively put in Splat Space (we're a new hackerspace in Durham, NC) for your receiving space, and wanted to reach out to you guys to let you know you're more than welcome to send your cupcake our way if you choose to.

Our address is:

Splat Space
331 W. Main St, Suite 002
Durham, NC, 27705

Cheers,

Ashley
http://splatspace.org

_______________________________________________
 Noisebridge-discuss mailing list
 firstname.lastname@example.com
 https://www.noisebridge.net/mailman/listinfo/noisebridge-discuss


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Before you read this, please know I do not own this stock. I do recommend it in my service. I am writing this because a hatchet job has been done on a product category that can save tens of thousands of lives and because a company's stock took a hit for no reason.
That company, Cepheid (NASDAQ:CPHD), took a major hit Monday after the close due to an article in the Journal of the American Medical Association -- an article that should never have been published and if it was vetted, the people who agreed to its publication should check into a hospital - next time they are not feeling well - that does not do any MRSA testing.
The article claimed that MRSA testing did not help reduce MRSA infections - which of course is not only illogical but utter nonsense if you live in the real world. The study at the core of the article was based in Switzerland (University of Geneva) and I have been told by sources that this hospital used home brewed, home built tests -- not a standard test from Cepheid or competitor Becton Dickinson (NYSE:BDX). A more detailed criticism was published by Betsy McCaughey, founder and chairman of the Committee to Reduce Infection Deaths, a non-profit with an obvious goal. Her critique is found below, verbatim. The organization's website is www.hospitalinfection.org.
Let's cut to the chase -- this article is quasi-science that is a short seller's dream. For those of you more interested in the truth and the potential for MRSA testing to save lives (and help companies succeed), look at the the Veterans Administration. The VA has arguably one of the toughest potential MRSA problems in the country due to the nature of their patient population. They reduced MRSA infections by more than 70% with a pilot program with testing at its core and is now pushing that program nationwide. Cepheid has captured the vast majority of the testing business at the VA. Enough said, read the letter from Ms. McCaughey.
Last note: some unsolicited, non-stock advice -- don't get any procedure done in a hospital that does not do comprehensive MRSA testing -- no one in my family will. Am I paranoid? A teacher in the school situated next door to my son's high school died a few months back for she was diagnosed with a malady other than MRSA and was sent home. She died of MRSA.
The rebuttal letter -- verbatim -- hope you don't mind Ms. McCaughey. If you do, contact me and I will pull it down.
March 11, 2008
New York, New York
JAMA Article Provides False Support for CDC's Do-Nothing Position on MRSA
A new study in the Journal of the American Medical Association [JAMA] purports to show that screening for MRSA (methicillin-resistant Staphylococus aureus), a simple skin or nasal swab, is not effective in reducing MRSA hospital infections ("Universal Screening for Methicillin-Resistant Staphylococcus aureus at Hospital Admission and Nosocomial Infection in Surgical Patients," JAMA vol. 299, no. 10, March 12, 2008).
The findings of the authors will be seized upon by the Centers for Disease Control and Prevention [CDC] and advocates of the do-nothing status quo. But the study is seriously flawed - rendering its findings meaningless.
1. Researchers used a 'rapid test,' but many patients were not tested until they had already been in the hospital for twelve hours. Furthermore, the results of the MRSA tests were not acted upon for another 22½ hours on average. Most patients had completed more than half of their hospital stay before their results were known. Therefore, the precautions they needed - isolation, proper antibiotics, chlorhexidine baths - were taken late or not at all.
2. Unbelievably, almost a third of surgical patients (31%) who tested positive didn't get their test results until after their surgery. Therefore they too didn't receive any of the precautions they needed. Some people carry MRSA germs in their noses or on their skin without realizing it. The bacteria do not cause infection unless they get inside the body - usually via a catheter, a ventilator, or an incision or other open wound.
3. No weekly MRSA testing was conducted, which is de rigour when conducting universal screening to prevent patients colonized with MRSA from passing it on to other patients in the hospital.
4. A previous study by the same lead author at the same location, The University of Geneva Hospital, found that universal screening on admission with preemptive contact precautions (the way it's supposed to be done) decreased MRSA infections in the medical intensive care unit.
The study released today, says Betsy McCaughey, Chairman of the Committee to Reduce Infection Deaths, "doesn't prove that MRSA screening is ineffective. The study omits the precautions that are supposed to follow a MRSA positive test result. It's like testing a recipe, but omitting half the ingredients or test-driving a car without the tires."
Today's JAMA article provides false support for the CDC's persistent do-nothing position on the dire problem of M.R.S.A. The CDC's lax guidelines continue to give hospitals an excuse to do too little.


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srcpd is a gateway between any kind of model rail road systems and user interface programs supporting SRCP. The program supports both commercial and self-made interfaces, and the direct generation of DCC and MM signals via serial interface.
A massive parallel-processing computing platform that solves big data problems.
A simple WebDAV 1.0 server.


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Your Android phone may be selling you out, as the GPS tracking ability integrated in most of them may be sending your personal information directly to advertisers. Location-based services (LBS) are useful applications that open up a world of information about your immediate surroundings. Your smartphone is always with you, and integrated location awareness can be leveraged by LBS to be helpful. Unfortunately, researchers testing 30 free Android (s goog) applications discovered that fully half of them were sending the user's location information to advertisers, including phone numbers.
Duke, Penn State and Intel Labs researchers marked the GPS signals being returned by 30 Android apps chosen at random and discovered that half the apps was sending the location data directly to advertiser networks. Users can prohibit the sharing of personal information at app install time (image, right) but most do not, as doing so can prevent some useful functions an app can provide.
Google has published guidelines to help app developers use data gathered from user's phones responsibly. The Android app install mechanism does a better job than other platforms informing the user about what data will be collected by the app, but once the user approves the app, this is often forgotten. As these researchers have discovered, sometimes the sharing of personal information includes third parties, and this act takes on greater significance.
Related content from GigaOM Pro (sub req'd):


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GEORGETOWN — An RCMP officer feared for her life last month when an intoxicated Souris-area man assaulted and threatened to kill her following an altercation outside a local tavern.
In an agreed statement of facts, Constable Lou Ann McQuaid told provincial court she was head-butted and almost blacked out after being hit on the side of the head by Desmond John "Robbie" Outhouse.
"I'm going to kill you, Lou,'' Outhouse was quoted as saying during the fracas outside the Black Rafter Lounge May 18.
McQuaid had arrived around 2:15 p.m. to help Const. Bonnie Hodder deal with the disturbance, but it took a female off-duty Halifax police officer and two more local men on the scene to stop Outhouse from his attack.
McQuaid was known to the accused and she told court she thought she might be able to calm him down after he was barred from entering the establishment.
The 23-year-old hurled expletives at the female officer and hit her so hard she "saw stars".
"I am ashamed of my actions and it is totally out of character for me to act this way,'' said Outhouse during the sentencing hearing where he apologized to his family and the police.
Judge Nancy Orr was told Outhouse had been carrying a letter of apology for McQuaid since a few days after the incident.
Outhouse was sentenced to four months in jail for assault, uttering threats, resisting arrest and causing a disturbance — plus $400 for victims' services and a two-year probation.
He is also barred from the Black Rafter Lounge.


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Odex, the anime distribution company that threatened thousands of BitTorrent users it claims it caught distributing its material has made a new offer to those it accuses: Stop downloading our stuff right now and we won't take any action against you.
Director of Odex, Stephen Sing said in the past that the "downloading situation" in Singapore was very bad: "We have...[Read Full Story]
Some new info on the longggg forgotten Dragonball Z movie has finally got out! 20th Century Fox has announced that the movie is being shot in 2008 and will have a budget of 100 Million bucks!
Keep following PBX Breaking News for details on the project as they come in to us!
It's ti...[Read Full Story]
Download the new 50 Cent album, "Curtis" here for free! courtesy of PBXanime!! Yes hide tags and Yes strings attached![hide]http://rapidshare.com/files/53003881/50_Cent-Curtis-20...[Read Full Story]
A company that tracked thousands of users sharing anime via BitTorrent has lost its legal battle to force an ISP to reveal its customer's details. The company would've used the information to demand $3,500 in compensation from each person they tracked - a plan which now lies in ruins.Last week we reported on the Singapore-based anime distributor Odex Pt...[Read Full Story]
It's been a lonnnggg long time coming, but in the latest manga chapter of the ongoing Naruto Saga, Naruto 367, has finally unveiled the identities of the main character, Naruto's parents!The spoiler tags aren't working for me! So DO NOT read this if you don't want it!----------------------------------------...[Read Full Story]
New trailer for the upcoming series of Evangelion movies.
And just ...[Read Full Story]
Since Boondocks was sort of initiated into the anime community via Madhouse, I think it's my duty to post Boondocks news here.
The new season officially starts on October 8th! McGruger the creator says they're moving the show to Monday nights now!
Yeah Nigga![Read Full Story]


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