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Publications (31)81.95 Total impact
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Article: Enfermedad de Castleman, un diagnóstico diferencial que no se debe olvidar en los tumores de mediastino: Caso clínicoRevista medica de Chile 06/2014; 142(6):782-785. DOI:10.4067/S0034-98872014000600013 · 0.37 Impact Factor
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ABSTRACT: Castleman's disease is an uncommon lymphoproliferative disorder which can be unicentric or multicentric. Hialine vascular variant is the most common pathologic form, which is usually unicentric and presenting as mediastinal tumors. We report a 31-year-old female with a history of retrosternal pain. A chest CAT sean showed a tumor in the posterior mediastinum. The patient was operated and the tumor excised. The pathology report showed a Castleman's disease. No other tumors were found in the patient, who had a favorable evolution.Revista medica de Chile 06/2014; 142(6):782-5. · 0.37 Impact Factor
Article: The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance.[Show abstract] [Hide abstract]
ABSTRACT: Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernán Henríquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval, p < 0.05). For survival analyses, the Kaplan-Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (p = 0.02) and tumors with lymph node metastases (p < 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (p = 0.03). Moreover, PI3K (p = 0.004), AKT (p = 0.01), p-AKT (p = 0.01), P70S6K1 (p = 0.04), p-P70S6K1 (p = 0.001), and eIF-4E (p = 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (p = 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2014; 465(1). DOI:10.1007/s00428-014-1588-4 · 2.56 Impact Factor
Article: Mo1659 The PI3K/AKT/mTOR Pathway in Gastric Cancer and Its Potential Relationship With Mir-125b, Mir-451 and Mir-101Gastroenterology 05/2014; 146(5):S-629. DOI:10.1016/S0016-5085(14)62276-9 · 13.93 Impact Factor
Article: Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population[Show abstract] [Hide abstract]
ABSTRACT: Cervical cancer is a major health concern among women in Latin America due to its high incidence and mortality. Therefore, the discovery of molecular markers for cervical cancer screening and triage is imperative. The aim of this study was to use a genome wide methylation approach to identify novel methylation biomarkers in cervical cancer. DNA from normal cervical mucosa and cervical cancer tissue samples from Chile was enriched with Methylated DNA Immunoprecipitation (MeDIP), hybridized to oligonucleotide methylation microarray and analyzed with a stringent bioinformatics pipeline to identify differentially methylated regions (DMRs) as candidate biomarkers. Quantitative Methylation Specific PCR (qMSP) was used to study promoter methylation of candidate DMRs in clinical samples from two independent cohorts. HPV detection and genotyping were performed by Reverse Line Blot analysis. Bioinformatics analysis revealed GGTLA4, FKBP6, ZNF516, SAP130, and INTS1 to be differentially methylated in cancer and normal tissues in the Discovery cohort. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). ZNF516 promoter methylation was the best biomarker, with both sensitivity and specificity of 90% (AUC = 0.92), results subsequently found in a Prevalence cohort. Together, ZNF516 and FKBP6 exhibited a sensitivity of 84% and specificity of 81%, when considering both cohorts. Our genome wide DNA methylation assessment approach (MeDIP-chip) successfully identified novel biomarkers that differentiate between cervical cancer and normal samples. These biomarkers need to be further explored in case-control and prospective cohorts to validate them as cervical cancer biomarkers.Epigenetics: official journal of the DNA Methylation Society 11/2013; 9(2). DOI:10.4161/epi.27120 · 5.11 Impact Factor
Article: Immunohistochemical Expression of Vascular Endothelial Growth Factor A in Advanced Gallbladder Carcinoma.[Show abstract] [Hide abstract]
ABSTRACT: Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The molecular mechanisms involved in the pathogenesis of GBC remain poorly understood. The vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and is an attractive target for cancer therapy. We characterized VEGF-A expression in advanced GBC and its relation to clinicopathologic features. VEGF-A expression was examined by immunohistochemistry in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 chronic cholecystitis. The cases were classified as low or high expression to evaluate the association of VEGF-A expression level with clinicopathologic variables. The Kaplan-Meier method was used to estimate survival as a function of time, and survival differences were analyzed by the log-rank test. High expression of VEGF-A was observed in 81% (183/224) of tumors and 5.1% (2/39) of chronic cholecystitis (P<0.0001). The VEGF-A expression had a significant relationship with histologic grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF-A is associated with a poor prognosis in patients with advanced GBC (P=0.0116). Our results indicate that VEGF-A is highly expressed in GBC and correlates with poor prognosis, suggesting that VEGF-A expression could be used as a biomarker for predicting malignant behavior and for identifying a subset of patients who may benefit from anti-VEGF-A therapies.Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 10/2013; DOI:10.1097/PAI.0b013e3182a318a9 · 2.06 Impact Factor
Article: Erratum to: Early gallbladder carcinoma has a favorable outcome but Rokitansky–Aschoff sinus involvement is an adverse prognostic factor[Show abstract] [Hide abstract]
ABSTRACT: The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We subjected 190 early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in cholecystectomy specimens sampled entirely according to an established protocol, to detailed analysis. Average patient age was 57.9 years (29-95). In more than half of the cases (114/190; 60 %), the tumor was inapparent by gross examination. In 81 cases (42.6 %), carcinomatous epithelium abutted the muscularis, whereas 57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with muscularis. Intraepithelial extension into Rokitansky-Aschoff sinuses (RAS) was found in 34 cases (17.8 %). At the time of data analysis, 171 patients (99 %) were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4 % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal group (93.2 and 92.1 %, respectively) were not statistically different from that of the muscle-abutting group (89.7 % and 88.2 % ; p = 0.334). Patients with RAS involvement had a significantly shorter survival than those without (p < 0.001). Of the 33 patients with RAS involvement, 13 (39 %) died of disease, whereas only 6 of the 154 patients (4 %) without RAS involvement died of disease. Disease-related mortality in these cases occurred relatively late (median 48 months). EGBC has a very good prognosis with a 90 % 10-year survival rate. It is seen on average in patients almost a decade younger than those with advanced cancers. RAS involvement is an independent prognostic factor, and additional surgery may have to be considered for such cases. Occasional recurrences are encountered several years later, which suggests a field-effect phenomenon and warrants long-term follow-up.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 09/2013; 463(6). DOI:10.1007/s00428-013-1478-1 · 2.56 Impact Factor
- Cancer Research 08/2013; 73(8 Supplement):2956-2956. DOI:10.1158/1538-7445.AM2013-2956 · 9.28 Impact Factor
Article: Immunohistochemical Expression of Phospho-mTOR Is Associated With Poor Prognosis in Patients With Gallbladder Adenocarcinoma[Show abstract] [Hide abstract]
ABSTRACT: Context.-Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear. Objective.-To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma. Design.-Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of P < .05, and Kaplan-Meier curves were constructed for survival analysis. Results.-Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (P < .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (P = .02). Conclusions.-Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. Phospho-mTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy.Archives of pathology & laboratory medicine 04/2013; 137(4):552-7. DOI:10.5858/arpa.2012-0032-OA · 2.88 Impact Factor
Article: Cellular FLICE-like Inhibitory Protein Long Form (c-FLIPL) Overexpression is Related to Cervical Cancer Progression.[Show abstract] [Hide abstract]
ABSTRACT: Cervical cancer is a leading cause of cancer deaths in women worldwide and infection by high-risk human papillomavirus types is a precursor event. The cellular FLICE-like inhibitory protein (c-FLIP) has been found to be overexpressed in several types of cancers and could be associated with cervical cancer progression because of its ability to inhibit the apoptotic process. To detect c-FLIP expression in cervical cancer, an immunohistochemical staining was performed, using tissue microarrays, on a series of 536 archival biopsy samples, including normal cervical tissues, low-grade and high-grade squamous intraepithelial lesions, and squamous cervical carcinomas. The epithelium in the normal cervix and low-grade squamous intraepithelial lesions mainly stained negatively for c-FLIP, whereas high-grade intraepithelial lesions and cancer samples showed an elevated expression of c-FLIP. A direct association was observed between the increasing grade of the lesion and the intensity of c-FLIP staining, in which the frequency of intense c-FLIP expression increased from 12.5% in the normal tissue to 82.1% in the cervical cancer tissue. An increased expression of c-FLIP may be an important factor in the progression of cervical cancer. This finding could aid in identifying patients with preneoplastic lesions at greater risk of developing cervical cancer. c-FLIP expression in cervical tissue may be a potential cervical cancer progression marker.International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 03/2013; DOI:10.1097/PGP.0b013e31825d8064 · 1.63 Impact Factor
Article: Connective Tissue Growth Factor Immunohistochemical Expression Is Associated With Gallbladder Cancer Progression[Show abstract] [Hide abstract]
ABSTRACT: Context.- Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Design.- Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P < .05. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Results.- Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Conclusions.- Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.Archives of pathology & laboratory medicine 02/2013; 137(2):245-250. DOI:10.5858/arpa.2011-0628-OA · 2.88 Impact Factor
Article: AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines.[Show abstract] [Hide abstract]
ABSTRACT: Gallbladder carcinoma is a highly malignant tumor and a public health problem in some parts of the world. It is characterized by a poor prognosis and its resistance to radio and chemotherapy. There is an urgent need to develop novel therapeutic alternatives for the treatment of gallbladder carcinoma. The mammalian target of the rapamycin (mTOR) signaling pathway is activated in about 50% of human malignancies, and its role in gallbladder carcinoma has previously been suggested. In the present study, we investigated the phosphorylation status of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues and evaluated the effect of three mTOR inhibitors on cell growth and migration in gallbladder carcinoma cell lines. Immunohistochemical staining of phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. Protein expression of AKT/mTOR members was also evaluated in eight gallbladder carcinoma cell lines by Western blot analysis. We selected two gallbladder carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin, RAD001, and AZD8055 on cell viability, cell migration, and protein expression. Our results showed that phospho-p70S6K is highly expressed in dysplasia (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%, 121/137). No statistical correlation was observed between phospho-p70S6K status and any clinical or pathological features, including age, gender, ethnicity, wall infiltration level, or histological differentiation (P < 0.05). In vitro treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB cancer cells (P < 0.001). Our findings confirm the upregulation of this signaling pathway in gallbladder carcinoma and provide a rationale for the potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder carcinoma.OncoTargets and Therapy 01/2013; 6:1373-1384. DOI:10.2147/OTT.S46897 · 2.31 Impact Factor
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ABSTRACT: Gallbladder cancer is an infrequent neoplasia with noticeable geographical variations in its incidence around the world. In Chile, it is the main cause of death owing to cancer in women over 40 years old, with mortality rates up to 16.5 per 100,000 cases. The prognosis is poor with few therapeutic options; in advanced cases there is only a 10% survival at 5 years.Several studies mention the possible role of DNA methylation in gallbladder carcinogenesis. This epigenetic modification affects tumor suppressor genes involved in regulation pathways, cell cycle control, cell adhesion and extracellular matrix degradation, in a sequential and cumulative way. Determining DNA methylation patterns would allow them to be used as biomarkers for the early detection, diagnosis, prognosis and/or therapeutic selection in gallbladder cancer.Clinical Epigenetics 07/2012; 4(1):11. DOI:10.1186/1868-7083-4-11 · 6.22 Impact Factor
Article: Quiste Broncogénico de Localización Poco Habitual: Reporte de 2 Casos y Revisión de la LiteraturaInternational Journal of Morphology 12/2011; 29(4):1313-1316. DOI:10.4067/S0717-95022011000400040 · 0.20 Impact Factor
Article: Hyalinizing Cholecystitis and Associated Carcinomas: Clinicopathologic Analysis of a Distinctive Variant of Cholecystitis With Porcelain-like Features and Accompanying Diagnostically Challenging Carcinomas[Show abstract] [Hide abstract]
ABSTRACT: We describe a clinicopathologically distinct subtype of cholecystitis, the extensively calcific version of which has been presented in the clinical literature as "porcelain gallbladder (PG)." This cholecystitis, which we propose to refer to as hyalinizing cholecystitis (HC), is characterized by dense, paucicellular hyaline fibrosis transforming the gallbladder (GB) wall into a relatively thin and uniform band. The process diffusely effaces most of the normal structures of GB, and some cases show calcifications. To determine the clinicopathologic associations of HC, we systematically analyzed 4231 cholecystectomies (606 of which had carcinoma) histopathologically, in addition to a targeted search in our databases. Ninety-six cases of HC were identified (1.6% of cholecystectomies). Patients with HC were a decade older than ordinary cholecystitis patients (56 vs. 47; P<0.001), suggesting that HC may be a long-term complication of chronic injury in some patients. Calcifications of variable amounts and degrees were identified in two thirds of the cases. In addition, 10 cases showed diffuse marked calcifications and were considered separately as "complete porcelain" GB. Thirty-eight HC cases had carcinoma with a calculated frequency of 15% and an odds ratio of cancer risk of 4.6. Only 42% of the invasive cases were associated with calcifications; none of the 10 diffusely calcific cases had carcinoma. HC-related carcinomas were challenging diagnostically. They did not form distinct masses or any significant thickening (mean thickness, 2.6 vs. 4.0 mm in ordinary adenocarcinomas; P<0.002). Microscopically, they had widely scattered and bland-appearing glands embedded in the thin band of hyaline stroma of HC, commonly showing a disappearing lining, leaving behind the granular, necrotic intraluminal debris (regression) with or without calcifications, which could be the only sign of cancer in some sections. The morphologic features that allowed the recognition of these glands as malignant included their longitudinal axis parallel to the surface, their irregular contours, clear cytoplasm with distinct borders, nuclear irregularities, and washed-off chromatin. Surface epithelium, if preserved (and it was not in most cases), typically showed carcinoma in situ of either denuding or micropapillary types. HC-associated carcinomas, with a median survival of 7 months, appeared to have a clinical course at least as aggressive as that of regular carcinomas (median survival 12 months; P=0.02). In conclusion, HC is a distinct clinicopathologic entity, which is often associated with carcinoma, and the carcinomas arising from this group are often very subtle and prone to misdiagnosis microscopically. As HC is typically devoid of epithelium, any glandular elements on the wall of HC should be regarded as a suspect for carcinoma. This study also confirms recent findings in the radiology literature-it is not the complete (diffusely calcific) PG that is associated with cancer. Instead, a distinct, histopathologically defined form of cholecystitis, HC with minimal or no calcifications (incomplete PG), is associated with invasive carcinoma. Thus, imaging protocols ought to focus on the correlates of HC rather than fixating on calcifications. Further studies into the pathogenesis of this process and its mechanisms of progression to carcinoma are warranted.The American journal of surgical pathology 06/2011; 35(8):1104-13. DOI:10.1097/PAS.0b013e31822179cc · 4.59 Impact Factor
Article: Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas[Show abstract] [Hide abstract]
ABSTRACT: The information in the literature on squamous cell and adenosquamous carcinomas of the gallbladder is highly limited. In this study, 606 resected invasive gallbladder carcinoma cases were analyzed. Squamous differentiation was identified in 41 cases (7%). Those without any identifiable glandular-type invasive component were classified as pure squamous cell carcinomas (8 cases) and those with the squamous component constituting 25–99% of the tumors were classified as adenosquamous carcinomas (26 cases) and included into the analysis. The remaining 7 that had <25% squamous component were classified as adenocarcinoma with focal squamous change and excluded. The clinicopathological characteristics of adenosquamous carcinoma/squamous cell carcinomas were documented and contrasted with that of ordinary gallbladder adenocarcinomas. The average patient age was 65 years (range 26–81); female/male ratio, 3.8. In only 13%, there was a preoperative clinical suspicion of malignancy. Grossly, 58% presented as thickening and hardening of the wall and 6% were polypoid. In 12%, mucosa adjacent to the tumor revealed squamous metaplasia. All pure squamous cell carcinomas had prominent keratinization. Giant cells and tumor-infiltrating eosinophils were observed in 29 and 51% of the squamous cell carcinomas/adenosquamous carcinomas versus 10% (P=0.02) and 6% (P=0.001) in gallbladder adenocarcinomas, respectively. All but three cases had 'advanced' (pT2 and above) carcinomas. Follow-up was available in 31 patients: 25 died of disease (median=5 months, range 0–20), and 6 were alive (median=64 months, range 5–112.5). The survival of patients with squamous cell carcinomas/adenosquamous carcinomas was significantly worse than that of gallbladder adenocarcinomas (P=0.003), and this adverse prognosis persisted when compared with stage-matched advanced gallbladder adenocarcinoma cases (median=11.4 months, P=0.01). In conclusion, squamous differentiation was noted in 7% of gallbladder carcinomas. The incidence of adenosquamous carcinoma (defined as 25–99% of the tumor being squamous) was 4%, and that of pure squamous cell carcinoma (without any documented invasive glandular component) was 1%. Pure squamous cell carcinomas often showed prominent keratinization. The overall prognosis of adenosquamous carcinoma/squamous cell carcinoma appears to be even worse than that of ordinary adenocarcinomas. Most patients died within a few months; however, those few who were alive beyond 2 years in this cohort experienced long-term survival.Keywords: adenosquamous; carcinoma; gallbladder; squamousModern Pathology 04/2011; 24(8):1069-1078. DOI:10.1038/modpathol.2011.68 · 6.36 Impact Factor
Article: Abstract 3026: Concurrent gene promoter hypermethylation and reduced immunohistochemical expression of potential biomarkers in cervical cancer: A Phase I biomarker development trialCancer Research 04/2011; 71(8 Supplement):3026-3026. DOI:10.1158/1538-7445.AM2011-3026 · 9.28 Impact Factor
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ABSTRACT: BACKGROUND: The absence of lymph node involvement (N0) in gastric cancer is associated with a better survival. However some N0 gastric tumors still have a bad prognosis. AIM: To study demographic and morphological variables associated with prognosis in N0 gastric carcinoma. Material and METHODS: Review of pathological records of a regional general hospital, identifying patients with a N0 gastric cancer surgically excised between 1986 and 2003. Results: In the study period, 459 gastrectomies were performed for gastric cancer and in 32%, the tumor was devoid of lymph node involvement. These later patients were followed for a median of 64 months with a 71% five years actuarial survival. Bivariate analysis identified age, tumor size, gastric wall infiltration, pathological type according to Lauren and Ming, lymphovascular involvement, number of lymph nodes excised and TNM stage as prognostic values Multivariate analysis disclosed the level of gastric wall infiltration, the presence of a poorly differentiated tumor, lymphatic vascular involvement, number of excise lymph nodes and tumor size as independent prognostic factors. Conclusions: N0 gastric tumors are found in 32% of gastrectomies for gastric cancer and have a 71% five years actuarial survival. Gastric wall infiltration, pathological degree of differentiation tumor size and lymphovascular involvement are independent prognostic factors.Revista medica de Chile 04/2011; 139(4):432-8. · 0.37 Impact Factor
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ABSTRACT: Background: The degree of tumor infi ltration and lymph node involvement are the most relevant pathological features to determine prognosis of advanced gastric cancer. Aim: To determine the association between clinical and pathological features of advanced gastric cancer and patient survival. Material and Methods: The pathological records of patients with advanced gastric cancer subjected to gastrectomy and lymph node excision between 1986 and 2007 were analyzed. Follow up was performed according to data in the clinical records and death certifi cates obtained at the Chilean National Death Registry. The main outcome analyzed was survival after surgery. Results: The records of 299 patients aged 62 ± 11 years (68% males), were analyzed. Mean follow up ranged from 1 to 206 months. Five and 10 years actuarial survival was 39 and 34%, respectively. The pathological predictors of survival were microscopic tumor stage, tumor size and location, Bormann classifi cation, infi ltration level, degree of differentiation, pathological type of tumor according to Lauren, Ming y Nakamura, lymph node involvement and the absence of residual tumor after surgical excision. Conclusions: The pathological study of the surgical piece in advanced gastric cancer has important prognostic implications.Revista Chilena de Cirugia 04/2011; 63(2-63):154-161. · 0.18 Impact Factor
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ABSTRACT: Background: Early gastric cancer corresponds to those tumors that only involve mucosa and submucosa. It is associated with a high survival rate. Aim: To determine pathological factors associated with survival in early gastric cancer. Material and Methods: Analysis of pathological records of 106 patients, with a median age of 63 years (60% males), subjected to a gastrectomy for early gastric cancer. Follow up was performed according to data in the clinical records and death certifi cates obtained at the Chilean National Death Registry. Results: Five years global survival of patients was 91%. Lymph node involvement was more common among tumors bigger than 35 mm, with a low degree of differentiation and among those tumors classifi ed as diffuse according to Lauren. Survival was signifi cantly lower for bigger tumors, those with of a low degree of differentiation, diffuse tumors according to Lauren and those with lymph node involvement. Conclusions: Early gastric cancer has a high fi ve years survival. Bigger tumors, those with a low degree of differentiation and those with lymph node involvement are associated with lower survival rates.Revista Chilena de Cirugia 04/2011; 63(2-63):162-169. · 0.18 Impact Factor
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Universidad de La Frontera
Ciudad Temuco, Araucanía, Chile
- • Center of Molecular Pathology Laboratory/ Department of Pathology
- • Departamento de Anatomía Patológica
- • Faculty of Medicine


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IEEE membership options for an individual and IEEE Xplore subscriptions for an organization offer the most affordable access to essential journal articles, conference papers, standards,
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This paper presents for the first time a 60-GHz receiving switched-beam antenna on organic liquid crystal polymer (LCP) platform. A 4 × 1 quasi-Yagi array is incorporated with a 4 × 4 Butler matrix beamforming network and GaAs low-noise amplifiers on an LCP substrate. The active beam is controlled by GaAs single-pole-double-throw switches to access the four output states of the Butler matrix. The entire 4 × 1 active array is 1.4 cm × 1.75 cm and consumes 1.1 W of dc power. Successful comparisons of the measured and simulated results verify a working phased array with a return loss better than 10 dB across the frequency band of 56.7-63.7 GHz. A comparison of radiation patterns demonstrate beam steering of ±40° with a peak active gain of 27.5 dB. The combined antenna and receiver noise performance at 60 GHz exhibits an estimated merit G/T of -18.6 dB/K and noise figure of 5.4 dB.
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NEW YORK, May 2, 2011 /PRNewswire/ -- On April 29, more than two billion people watched as Kate Middleton married her love, Prince William, and became royalty. Although only 1900 people were invited to attend the wedding, people around the world watched with rapture and were there in spirit. Although you may not have been an invited guest, you can now commemorate the wedding of the century with your very own Kate Middleton Bridal Doll.
The Kate Middleton Bridal Doll, designed by the world-renowned Franklin Mint, is a beautiful and authentic replica of the new Princess. The Franklin Mint's Royal Bridal Doll features all the fine details one would expect from The Franklin Mint, including a miniature replica of the famous Scroll and Diamond Tiara George VI gave the Queen Mother just before ascending to the throne.
"Millions of mothers, daughters, grandmothers and granddaughters woke up in the wee hours of the morning to share the joy of this fairy tale wedding. There is no better way to hold onto that beautiful memory than with this unique heirloom, a symbol that dreams really can come true. The Franklin Mint is known for its unique and enduring commemorative gifts, and the Kate Middleton dolls are truly the best work we have done in our fifty year history," said Gwynne Gorr, Chief Marketing Officer of The Franklin Mint.
This remarkable replica of the Princess comes with a Certificate of Authenticity and a display stand. It retails for $295.00 USD. If you purchase both the Kate Middleton Engagement Doll and the Kate Middleton Bridal Doll together, you will enjoy free shipping.
The Franklin Mint is currently taking orders for the doll at www.franklinmint.com or via phone at 1-800-TheMint. Orders can also be placed through mail-in requests to The Franklin Mint, 801 Springdale Drive, Franklin Center, PA 19341.
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10 years of experience
10 years of experience
Setauket-East Setauket
14 Technology Dr
East Setauket, NY 11733 Phone number & directions
14 Technology Dr
East Setauket, NY 11733 Phone number & directions
License & Identifications
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Douglas Dougherty:
View the full profile to get information on:
- Qualifications
- What's important to you
View full profile
Patient Reviews
Have you visited Dr. Dougherty? Share your experience.
Write a Review
Write a Review
Specialties & Research
Dr. Douglas Dougherty, MD, PHD is board certified in Diagnostic Radiology and Neuroradiology.
Education & Awards
Dr. Dougherty graduated from Stony Brook University.
Dr. Dougherty has 4 hospital affiliations:
- John T Mather Memorial Hospital
- Winthrop University Hospital
Home > Find a Radiologist > NY > East Setauket Radiologists > Dr. Douglas Dougherty, MD, PHD
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- Additional Information
- Dr. Douglas Andrew Dougherty MD and PHD is a male Diagnostic Radiologist, has 10 years of experience and practices in Diagnostic Radiology and Neuroradiology.
- Where does Dr. Douglas A. Dougherty practice?
- Dr. Douglas Dougherty has 6 office locations.
Dr. Douglas Dougherty practices Diagnostic Radiology and Neuroradiology near East Setauket, NY.
Additional practice locations include: Port Jefferson, NY and Riverhead, NY.
See East Setauket Radiologists.


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I just wanted to let you know that you did a wonderful job. My mother
sent me a meal for my anniversry and my wife and I loved it.Thank-you
The succulent, sweet taste of Maine Mussels is the perfect way to start any Lobster dinner.
Harvested in a hidden cove up the coast by a family that has been doing it for generations, these Mussels have a meat to shell ratio of 50%. We recommend one pound per person as an appetizer. Try them steamed with a little wine and garlic. We'll even send you the recipe in our new Cooking Guide!


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From prostate-specific antigen (PSA) to precursor PSA (proPSA) isoforms: a review of the emerging role of proPSAs in the detection and management of early prostate cancer
Article first published online: 3 JUL 2012
DOI: 10.1111/j.1464-410X.2012.11329.x
© 2012 BJU International
BJU International
Volume 112, Issue 6, pages 717–728, October 2013
Additional Information
How to Cite
Hori, S., Blanchet, J.-S. and McLoughlin, J. (2013), From prostate-specific antigen (PSA) to precursor PSA (proPSA) isoforms: a review of the emerging role of proPSAs in the detection and management of early prostate cancer. BJU International, 112: 717–728. doi: 10.1111/j.1464-410X.2012.11329.x
Publication History
- Issue published online: 13 SEP 2013
- Article first published online: 3 JUL 2012
Funded by
- Medical Research Council/The Prostate Cancer Charity Clinical Research Training Fellowship
- University of Cambridge Raymond and Beverly Sackler Studentship
- Abstract
- Article
- References
- Cited By
- proPSA;
- prostate;
- prostatic neoplasm;
- diagnosis;
- management
What's known on the subject? and What does the study add?
Despite the popularity of PSA blood testing for prostate cancer, there are a number of important limitations of this popular serum marker including the limited ability to accurately distinguish patients with and without prostate cancer and those who harbour an aggressive form of the disease. This is especially true when the total PSA is <10 ng/mL. Thus, significant efforts have been placed to find new serum markers that can help overcome these limitations.
In this review article, we discuss the emerging role of the various precursor forms of PSA (proPSAs), with a special emphasis on [-2]proPSA in the detecion and management of early prostate cancer. The clinical utility of Prostate Health Index (phi) is also discussed.
- Despite the overall success of prostate-specific antigen (PSA) blood test, its use as a serum marker for prostate cancer has been limited due to the lack of specificity, especially in men presenting with a total PSA (tPSA) level of <10 ng/mL. PSA testing has also resulted in an increase in the number of patients being diagnosed with low-grade, potentially clinically insignificant prostate cancer.
- There is therefore an urgent need for new markers that can accurately detect as well as differentiate patients with aggressive vs unaggressive prostate cancer.
- In this review, we discuss the emerging role of precursor forms of PSA (proPSAs) and the Prostate Health Index (phi) measurement in the detection and management of early stage prostate cancer.
- A literature search was conducted using PubMed® to identify key studies.
- Studies to date suggest that [-2]proPSA, a truncated form of proPSA is the most cancer-specific form of all, being preferentially expressed in cancerous prostatic epithelium and being significantly elevated in serum of men with prostate cancer.
- There is evidence to suggest that %[-2]proPSA measurement ([-2]proPSA/free PSA [fPSA] × 100) improves the specificity of both tPSA and fPSA in detecting prostate cancer.
- phi incorporating [-2]proPSA, fPSA and tPSA measurements has also yielded promising results and appears superior to tPSA and fPSA in predicting those patients with prostate cancer. Increased phi levels also seem to preferentially detect patients harbouring more aggressive disease.
- Further studies in the form of large, multicentre, prospective trials with detailed health economic analyses are required to evaluate the true clinical applicability of these novel markers.


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Originally written on Razzball | Last updated 4/2/13
Mike Trout who?! AL Rookie of the Year last year and runner-up for the MVP. He also had one of the best rookie years ever. I know, Random Italicized voice. I was being facetious to show my excitement for Bryce Harper. Like Bryce Harper is so good I've forgotten all about Mike Trout. He's the Angels center fielder. He's got a girlfriend, but I bet I could weasel my way in with my slanted words. Forget it, Random Italicized voice. Like you forgot Mike Trout? I hate you! Rudy's mentioned this before, but there's very few hitters that have top 20 overall potential. You have to be able to hit 45+ homers (Stanton, Bautista) without killing you in any category or be consistently excellent across four categories (Pujols, Fielder, Votto, Cano) or have the potential for your homers and steals to total 50 (Trout, Braun, McCutchen, CarGo, Jones, Kemp, Upton). It's slightly early to put Harper in that last group. But the potential is there, as he showed yesterday when Harper touc...
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Security and Defense Publications
Population Age Structure and Its Relation to Civil Conflict: A Graphic MetricJul 07, 2011
The authors use population age structure and recent history of civil unrest to project risks of civil conflict into the future. more
The Peace Process in Colombia with the Autodefensas Unidas de Colombia-AUCJul 07, 2011
In July 2003, the government of President Álvaro Uribe took the unprecedented step of opening formal peace talks with the AUC. This publication is the collection of papers that resulted from a conference hosted by the Wilson Center to explore key issues in the Government-AUC peace talks, the prospects for an eventual negotiated settlement, and the key challenges ahead. more
The Human Dimensions of Environmental Insecurity: Some Insights from South AsiaJul 07, 2011
This article presents the key insights that emerged from a regional research project that explored environment and security links in the context of South Asia. more
ECSP Report 7: BibliographyJul 07, 2011
The guide lists by theme literature that has come to the attention of ECSP in the past year on population, environmental change, and security issues. more
ECSP Report 4: Official Statements and New PublicationsJul 07, 2011
Excerpts from recent official statements in which environmental issues are cited in the context of security institutions and national interests, and reviews by experts of new publications. more
52. Stratified Stability: NATO's New Strategic Concept?Jul 07, 2011
Although the elements that will contribute to NATO's new mission have begun to emerge at the 50th anniversary of its founding, the shape of the concept itself still requires definition. This paper is intended to advance that process of definition. If the needs of NATO are to be met, then the Alliance will have to adopt a strategic mission that upholds international order, yet sets limits on that mission. Such a mission must meet the needs of Alliance members and partners for stability ; whether in the face of local conflict in some regions, or the international threat of "rogue states" and the terrorist campaigns of both state sponsored and non-state actors. more
Chapter Two: Institutionalizing Responses to Environment, Conflict, and CooperationJul 07, 2011
Alexander Carius and Geoffrey D. Dabelko analyze gaps in institutional responses to environment and conflict. more
Flash Points and Tipping Points: Security Implications of Global Population ChangesJul 07, 2011
"Population distortions - in which populations grow too young, or too fast, or too urbanized - make it difficult for prevailing economic and administrative institutions to maintain stable socialization and labor-force absorption," says author Jack A. Goldstone. more
Seguridad y Defensa en America del Norte: Nuevos dilemas geopolíticosJul 07, 2011
The book's authors collaborate to put forth an analysis of North American national defense policies and their implications on transnational and border security. Issues of migration and organized crime are touched upon, providing readers with an greater, in-depth understanding of security problems faced by the region as a whole. more
The United Nations and Environmental Security: Recommendations for the Secretary-General's High-Level Panel on Threats, Challenges, and ChangeJul 07, 2011
As part of the UN Foundation's United Nations and Global Security Initiative, the Environmental Change and Security Project invited international experts to provide fresh intellectual insights into environmental security. Complete set of policy briefs. more


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Forest Hills, Pennsylvania REO Properties, Forest Hills, Pennsylvania Bank REO Homes, Forest Hills, Pennsylvania Foreclosure Properties
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Real estate investors and homebuyers can search for Forest Hills,Pennsylvania REO properties and foreclosed homes for free. Property page can give you full information about current foreclosure property and have no restrictions and limitations. All property info is totally free, use contact information like phone and email address to request more specific data.
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REO in all Pennsylvania Cities


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Racquet for a tether ball game
Abstract available in
Claims available in
Description (OCR text may contain errors)
Des. 192,740
Patented May 8., 1962 United States Patent 0 ice RACQUET FOR A TETHER BALL GAME Joseph M. Ziabicki, 2307 Mohr Ave., Racine, Wis.
Filed July 24, 1961, Ser. No. 66,031
Term of patent 14 years oooooo ooooooooggsoooo References Cited in the file of this patent FIGURE 1 is a perspective view of racquet for a tether ball game embodying my new design the balance UNITED STATES PATENTS of the holes being omitted for convenience of illustration;
D. 160,646 Milo Oct. 24, 1950 FIGURE 2 1s a top plan view thereof, but on an on D. 168,788 Forsyth "flu-Huh Feb. 10 1953 Scale 110 792 s hoole Ian 3 1871 FIGURE 3 is a sectional View, taken along line 3-3 c y in FIGURE 2, but on an enlarged scale, and
FOREIGN PATENTS Norway July 12, 1948 FIGURE 4 is a sectional view thereof, taken along line 55 in FIGURE 2, but on an enlarged scale.
OTHER REFERENCES The Sporting Goods Dealer, January 1935, page 71, Varsity Badminton Racket.
I claim:
The ornamental design for a r-acquet for a tether ball game, substantially as shown and described.
Referenced by
Original Image


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Search Results: 'Medicinal Plants'
Medicinal Plants and Viruses
eBook (ePub): $7.50
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Medicinal Plants and Viruses - How many antiviral plants are there? Are any effective against a specific ailment? I researched the information and included it in this book. MERS is too new to have... More > any documented research. SARS has one study with one plant listed. Download the preview for free. You will get the entire list of antiviral plants and find out that Licorice is a good candidate for SARS.< Less
Medicinal Plants for Diabetes
eBook (ePub): $12.00
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Fifty five plants are listed with a short description of beneficial effects related to diabetes. A few common ones are Ginger, Grape, Beans, Ginseng, Pumpkin, Oats and Flax. A few not so common... More > include Bitter Melon, Neem (Indian People's Pharmacy) and Quava. This is a good place to start on the road to nutritional health.< Less
Medicinal Plants for Cancers & Tumors
eBook (ePub): $8.99
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More than 90 plants are listed with a short description of beneficial effects related to cancers and tumors. A few common ones are Ginger, Grape, Beans, Ginseng, Clove, Chamomile, Horseradish,... More > Turmeric, Oregano and Green Tea. A few not so common include Dogodogo, Tropical Almond, Gotu Kola and Burdock. Eat healthy and be healthy.< Less
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You find one or two studies on the heart about every year. Next year the information will change or tell you something new. I condensed the information and tried to make it readable. Artichoke,... More > Garlic, Ginger, Green Tea, Oats, Tomato, Onion, Flax, Wheat Germ Oil, Rosemary and Sage. These are some of the familiar plants that are beneficial to your heart. Or try a Lavender bath for circulatory disorders. Good for your heart, good for you.< Less
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Elderberry Juice! That's it, you don't need anything else.... Well, Thyme is Commission E approved for Coughs and Bronchitis, you could add some fresh Thyme to your Chicken soup along with a little... More > Commission E approved Onion. Maybe a little Garlic. Radish Honey juice for Whooping Cough sounds a little far fetched so I won't mention it. But the Teas, a little Anise or Clove with some Mint and Honey.< Less
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The following is a hardcopy of seven E-books, minus the Fiji/Tropical information. Medicinal Plants for Colds and Flu. Medicinal Plants for Cancers and Tumors. Medicinal Plants for... More > Diabetes. Medicinal Plants and Heart Health. Medicinal Plants and Viruses. Medicinal Plants for Wounds, Cuts and Burns. Medicinal Plants and Dental Hygiene.< Less
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Just as season's first snow melts, forecasters say 3-5 inches possible Monday
First snow gone in a flash, but new storm looms
For anyone out early — really early — Saturday, the Japanese Garden area of Memphis Botanic Garden presented a scene worthy of a winter postcard, with newly fallen snow gracing the scenic arched bridge, employees say.
"It had just enough powder on it to make it very attractive," said Walton Griffin, director of finance for the botanic garden.
By late morning, however, that scene and others across Memphis had vanished with the season's first measurable snowfall.
To be sure, the 1-inch snow that fell overnight wasn't too memorable, lasting barely long enough for kids to put their boots on and carry saucer sleds to the nearest hill or park.
But consider this storm Round One. A much more significant wintry assault is expected Monday.
The National Weather Service has issued a winter storm watch that will be in effect from 6 a.m. Monday until noon Tuesday. Snow is expected to begin falling Monday afternoon and intensify in the evening, with 3-5 inches of total accumulation possible.
"We'll just have to see how it pans out," said weather service meteorologist Marlene Mickelson. "The forecast can change in a few hours."
The snow that greeted residents Saturday morning measured an inch in Memphis, Mickelson said, but there were unofficial reports of 2.5 inches in Brownsville, Tenn., about 50 miles away. Parts of Northeast Arkansas received up to 3 inches.
The snow melted quickly as temperatures rose into the upper-30s.
The snow and the upcoming storm watch come amid an usually cold winter, with below-normal temperatures in December and January resulting in high heating bills for area residents.
"We haven't had winter for so long," Mickelson said. "We've gotten spoiled in the last 10 years by all the mild winters."
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rogerfederer.com - 50th straight victory on grass
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50th straight victory on grass
Roger won his 50th straight match on grass, beating Juan Martin Del Potro 6-2, 7-5, 6-1 to reach the third round at Wimbledon.
He had led 2-0 in the third set before rain halted play yesterday. When they resumed, Roger needed only 11 minutes to complete the match, winning three straight games before Del Potro held serve in the sixth game.
Roger broke the Argentine five times and saved the only break point he faced. The four-time defending champion finished with 33 winners and made only 23 errors - one less than Del Potro.
"It was done quickly like I was hoping, but I was ready to go five sets in case," said Roger. "Fifty is a great number to achieve. I'm delighted about that but I haven't won the tournament."
Roger will next face Marat Safin. The Russian beat Aisam-Ul-Haq Qureshi of Pakistan 6-4, 6-2 7-6 (4).
"He's always a player who can upset anybody on any day. I hope he's not going to have one of those crazy good days against me," concluded Roger.


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