tbuckley/cabot-search huggingface dataset:
Effects of adjuvant chemotherapy on the protein C anticoagulant pathway in patients with early stage breast cancer
Authors: S. D. Mukherjee, M. Levine, S. Beaudin, L. Shin, S. Caruso, P. Liaw
Journal: Journal of Clinical Oncology (2006)

8563 Background: Although chemotherapy treatment is associated with an increased risk of thrombosis, the pathogenic mechanisms are poorly understood. We have previously shown that treatment of endothelial cells with adriamycin and epirubicin impairs the protein C anticoagulant pathway by downregulating EPCR (endothelial protein C receptor), an endothelial receptor required for the conversion of protein C to the anticoagulant enzyme activated protein C (APC). In this study, we examined the effects of adriamycin- and epirubicin-containing chemotherapy on the protein C anticoagulant pathway in early stage breast cancer patients. Methods: We collected blood samples from 20 patients patients with early stage breast cancer undergoing adjuvant CEF (cyclophosphamide, epirubicin and 5-fluorouracil) or CMF (cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy on days 1, 2 and 8 for the first 2 cycles of treatment. Markers of protein C generation (protein C, thrombin-antithrombin (TAT) complexes, and APC) were measured on these days. Results: Plasma protein C levels were significantly lower at cycle 2 day 8 (0.88 ± 0.14 U/ml) compared to pre-chemotherapy levels (1.07 ± 0.23 U/ml) (p=0.0036). Plasma TAT levels were significantly higher at cycle 2 day 8 (2.87 ± 0.79 μg/L) compared to pre-chemotherapy levels (2.01 ± 1.24 μg/L) (p=0.02). Based on the APC levels, the patients appear to fall into two categories in terms of their ability to generate APC. The first group (n=16) has elevated APC levels that parallel the elevated TAT levels, whereas the second group (n=4) has low APC levels despite elevated TAT levels. Conclusions: Impaired ability to generate APC in a subpopulation of patients may reflect chemotherapy-induced impairment of the protein C pathway through the downregulation of EPCR. This pilot study provides new mechanistic insights into the prothrombotic effects of chemotherapy agents. No significant financial relationships to disclose.
Urinary EGFR as a marker of urinary bladder cancer.
Authors: Hannah Louise Regan, Douglas G Ward, Richard T Bryan
Journal: Journal of Clinical Oncology (2015)

327 Background: Better biomarkers must be found to develop clinically useful urine tests for urothelial bladder cancer (UBC). Our objective was to identify proteins released by bladder cancer cells in vitro and assess their potential as urinary biomarkers. EGFR was identified as a promising biomarker and is overexpressed in numerous cancers including UBC. EGFR is a member of the ErbB family of transmembrane tyrosine kinase receptors. It is a 170kDa protein that facilitates cell growth and differentiation by acting upon downstream signaling pathways. Methods: We used shotgun proteomics to identify the proteins released into culture media by 8 UBC cell lines. These data were compared with protein expression data from the Human Protein Atlas. EGFR was measured by ELISA in the urine of 436 patients with primary bladder cancer (prior to commencing treatment) and 60 non-UBC control subjects (all samples were obtained from the Bladder Cancer Prognosis Programme). Outcomes were, presence of bladder cancer (yes/no) and bladder cancer-specific survival. Data were analysed with Mann-Whitney tests and Cox multivariable modelling. Results: EGFR was selected as a candidate biomarker because it was released by 5 out of 8 bladder cancer cell lines, but not by a ‘normal urothelium’ cell line, and is documented as highly overexpressed in UBC in the Human Protein Atlas. A soluble form of EGFR is detectable in urine and is increased in some patients with high-grade bladder cancer. With a cut-off defined as mean + 2 SD (630pg EGFR/mg creatinine), elevated urinary EGFR was an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, p&lt;0.001). In multivariable models urinary EGFR and EpCAM (previously reported) are strong independent predictors of bladder cancer-specific survival. Urinary EGFR is not useful as a diagnostic marker. Conclusions: Aggressive bladder cancers shed the ectodomain of EGFR into urine. Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of those patients with the most aggressive bladder cancers, expediting their care to improve outcomes.
Is AIDS an Epidemic Form of African Kaposi's Sarcoma?: Discussion Paper
Authors: Jonathan Weber
Journal: Journal of the Royal Society of Medicine (1984)

Marked epidemiologic similarities have been noted between the acquired immunodeficiency syndrome (AIDS) and the endemic form of Kaposis sarcoma occurring in Equatorial Africa.  This paper examines the hypothesis that Kaposis sarcoma in Africa is a sexually transmitted infectious disease that is spread predominantly by male homosexual intercourse and that the cause of AIDS is also the agent responsible for African Kaposis sarcoma introduced into a susceptible population.  Kaposis sarcoma is an extremely common tumor in Equatorial Africa predominantly affecting men 25-60 years of age.  Its prevalence is highly area-specific.  The epidemiology of Kaposis sarcoma in Africa strongly suggests an infectious etiology although no single etiologic agent has been isolated.  With the emergence of AIDS which exhibits epidemic Kaposis sarcoma as a major manifestation homosexual intercourse must be considered a possible cause of the male predominance seen in African Kaposis sarcoma.  Although the literature contains no references to homosexuality in Equatorial Africa pastoral tribes in this area have the highest incidence of polygamy in the world.  Tribal elders may have over 20 wives thus reducing young adult males options for heterosexual contact.  It is possible that young adult males practice a period of homosexuality before heterosexual marriage.  The pattern of delayed male age at marriage (30 years or over) could also be a contributing factor.  The epidemiologic similarities between AIDS and African Kaposis sarcoma are further strengthened by immunologic changes common to both diseases although the African data are inadequate.  In addition men at risk of AIDS and African Kaposis sarcoma share evidence of past exposure to an identical range of viral and protozoan infections.  The theory outlined in this paper could explain the emergence of AIDS in the US subsequently in Haiti and AIDS cases seen in Europe before 1979.
A “cohesive moral community” is already patrolling behavioral science
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2015)

Abstract Authors of non-liberal proposals experience more collegial objections than others do. These objections are often couched as criticism of determinism, reductionism, or methodological individualism, but from a scientific viewpoint such criticism could be easily answered. Underneath it is a wish to harness scientific belief in service of positive social values, at the cost of reducing objectivity.
A Comprehensive Study of Osteogenic Calcium Phosphate Silicate Cement: Material Characterization and In Vitro/In Vivo Testing
Authors: Tianxing Gong, Zhiqin Wang, Yixi Zhang, Yubiao Zhang, Mingxiao Hou, Xinwei Liu, Yu Wang, Lejun Zhao, N. Dorin Ruse, Tom Troczynski, Urs O. Häfeli
Journal: Advanced Healthcare Materials (2015)

Vertebral compression fractures can be successfully restored by injectable bone cements. Here the as‐yet unexplored in vitro cytotoxicity, in vivo biodegradation, and osteoconductivity of a new calcium phosphate silicate cements (CPSC) are studied, where monocalcium phosphate (MCP; 5, 10, and 15 wt%) is added to calcium silicate cement (CSC). Setting rate and compressive strength of CPSC decrease with the addition of MCP. The crystallinity, microstructure, and porosity of hardened CPSC are evaluated by X‐ray diffractometer, Fourier transform infrared spectroscopy, and microcomputed tomography (CT). It is found that MCP reacts with calcium hydroxide, one of CSC hydration products, to precipitate apatite. While the reaction accelerates the hydration of CSC, the formation of calcium silicate hydrate gel is disturbed and highly porous microstructures form, resulting in weaker compressive strength. In vitro studies demonstrate that CPSC is noncytotoxic to osteoblast cells and promotes their proliferation. In the rabbit tibia implantation model, clinical X‐ray and CT scans demonstrate that CPSC biodegrades slower and osseointegrates better than clinically used calcium phosphate cement (CPC). Histological studies demonstrate that CPSC is osteoconductive and induces higher bone formation than CPC, a finding that might warrant future clinical studies.
ACE inhibitors/ARB and the risk of breast cancer recurrence after surgery in Japanese population: A pilot study.
Authors: Takeo Fujii, Osamu Takahashi, Teruo Yamauchi
Journal: Journal of Clinical Oncology (2012)

52 Background: Angiotensin II can work as a growth promoter via angiotensin II type1 receptor (AT1R). In an in vivo study, Angiotensin Converting Enzyme Inhibitor (ACEI)/Angiotensin Receptor Blocker (ARB) down regulates vascular endothelial growth factor and activates apoptosis pathway through AT1R. In some clinical studies, the efficacy of ACEI/ARB to cancer patients has been investigated; however, the results are various. This has not been examined in Asian population. We investigated breast cancer patients in a single institution if the recurrence rate is related to ACEI/ARB use. Methods: This retrospective study will evaluate disease-free survival (DFS) for Japanese patients who were diagnosed with invasive breast cancer and had curative surgery between January 2004 and December 2006 at St Luke’s International Hospital. We will compare DFS of two groups with and without ACEI/ARB use. DFS is defined as the interval between curative surgery and the recurrence of breast cancer. Recurrence of disease was confirmed by radiographically or pathologically. Patients who took ACEI/ARB are defined as those who had taken them for at least 6 months after initial diagnosis. The following patient data will be extracted from their medical records; age, stage, body mass index, menopausal status, biomarker status (ER, PgR, and HER2), usage of bisphosphonate, usage of statin, diabetes, surgical procedure. Results: A total of 1,163 patients were analyzed. 76 were ACEI/ARB user and 1,087 were non-user. The recurrence rate of ACEI/ARB users was 17.1% (13/76). In comparison, that of non-users was 12.2% (133/1,087). The odds ratio (OR) was 1.480 (95 % CI: 0.793-2.762 p=0.218). Kaplan-Meier analysis did not show a significant difference between them (log-rank test p=0.194). Conclusions: Our study is the first one to evaluate the efficacy of ACEI/ARB in breast cancer recurrence among Asian population. Recurrence rate did not differ in the two groups although molecular biology suggested antitumor effect of ACEI/ARB. We will further explore if any confounding factors lie between the two groups, and plan to conduct a prospective study if ACEI/ARB exhibits antiproliferative effect in postoperative cancer patients.
Multimodal endoscope can quantify wide-field fluorescence detection of Barrett’s neoplasia
Authors: Bishnu Joshi, Xiyu Duan, Richard Kwon, Cyrus Piraka, B. Elmunzer, Shaoying Lu, Emily Rabinsky, David Beer, Henry Appelman, Scott Owens, Rork Kuick, Nobuyuki Doguchi, D. Turgeon, Thomas Wang
Journal: Endoscopy (2015)

<b>Background and study aims:</b> To demonstrate the clinical use of a multimodal endoscope with a targeted fluorescently labeled peptide for quantitative detection of Barrett's neoplasia. <b>Patients and methods:</b> We studied 50 patients with Barrett's esophagus using a prototype multimodal endoscope with a fluorescently labeled peptide. Co-registered fluorescence and reflectance images were converted to ratios to correct for differences in distance and geometry over the image field of view. The ratio images were segmented using a unique threshold that maximized the variance between high and low intensities to localize regions of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). <b>Results:</b> Early neoplasia (HGD and EAC) was identified with 94 % specificity and 96 % positive predictive value at a threshold of 1.49. The mean results for HGD and EAC were significantly greater than those for squamous/Barrett's esophagus and low grade dysplasia by one-way analysis of variance (ANOVA). The receiver operator characteristic curve for detection of early neoplasia had an area under the curve of 0.884. No adverse events associated with the endoscope or peptide were found. <b>Conclusion:</b> A multimodal endoscope can quantify fluorescence images from targeted peptides to localize early Barrett's neoplasia. (ClinicalTrials.gov number NCT01630798.)
Gene expression signatures for prognosis in NSCLC, coupled with signatures of oncogenic pathway deregulation, provide a novel approach for selection of molecular targets
Authors: R. P. Petersen, A. Bild, H. Dressman, M. -B. M. Joshi, D. H. Conlon, M. West, J. R. Nevins, D. H. Harpole
Journal: Journal of Clinical Oncology (2005)

7020 Background: Gene microarray analysis can identify signatures that reflect unique aspects of individual tumors and provide precise prognostic information. Previously, we identified gene expression signatures reflecting the deregulation of oncogenic signaling pathways. In this study, we coupled gene expression data with the ability to identify the state of critical regulatory pathways within an individual tumor to determine prognosis. Methods: We prepared RNA from 101 stage I non-small cell lung cancer (NSCLC) tumor samples (51 squamous, 50 adenocarcinomas) for gene expression analysis with the Affymetrix U133 GeneChip. Each group consisted of 25 patients who died within 2 years of resection and 25 patients with a >5year survival. We developed predictive models that accurately distinguished patients with good vs. poor prognosis. We validated the model with a leave-one-out cross validation, with distinct training and validation sample sets. These data were used to predict the status of Ras, Src, β-cat, E2F & Myc pathways and then analyzed by hierarchical clustering to identify patterns of pathway deregulation. Results were expressed as a probability of pathway activation and Kaplan-Meier survival analysis was performed stratifying for pathway status. Results: The predictive model had 80% accuracy in distinguishing patients with respect to survival. Kaplan-Meier analysis revealed that patient subgroups defined by distinct patterns of pathway deregulation exhibited statistically significant differences in disease-free survival. Tumors with deregulated Ras and Myc pathways had much worse prognosis than those with only deregulated Ras (69% vs 20% 2-yr survival, p<0.05). Conclusions: The capacity to stratify NSCLC patients according to individual risks using genomic-based prognostic tools provides opportunity for personalized treatment decisions. The use of gene expression data to predict the status of oncogenic signaling pathways provides an opportunity to better characterize the oncogenic process, and may provide a path to selecting targeted therapeutics. Investigations are underway for EGFR, HER2-neu and VEGF pathways. No significant financial relationships to disclose.
Optimizing obatoclax administration schedule: Safety and efficacy of 3-hour versus 24-hour infusion in combination with carboplatin and etoposide for patients with extensive-stage small cell lung cancer (ES-SCLC).
Authors: A. Chiappori, M. T. Schreeder, M. M. Moezi, J. Stephenson, L. Blakely, R. Salgia, Q. S. Chu, H. J. Ross, D. S. Subramaniam, M. S. Berger
Journal: Journal of Clinical Oncology (2010)

e13531 Background: Previous studies with obatoclax (Ob), a pan-BCL-2 antagonist, identified infusional CNS effects as dose- limiting adverse events (AEs) that occur with greater frequency and intensity with 3-hr versus 24-hr infusions of Ob. This phase I study of Ob used both infusion schedules to compare the safety and efficacy when used in combination with carboplatin (Carb) and etoposide (Et). Methods: As previously reported (ASCO, 2009, Ab 3576) this phase I study evaluated Ob given on a 21-day (D) cycle together with Carb (AUC 5 D1) and Et (100 mg/m2 D1-3), in separate fixed dose escalations using Ob as a 3-hr infusion D1-3 (15 mg, 30 mg and 45 mg) and as a 24-hr infusion D1-3 (30 mg, 45 mg and 60 mg). Eligible patients (pts) had ES-SCLC, measurable disease, ≤1 prior therapy, ECOG PS ≤1, and adequate organ function. 3-6 pts were enrolled into ascending dose cohorts with standard DLT rules. Results: 25 pts were enrolled (14 males; median age 66). 18 pts were previously untreated (12 in 3-hr group; 6 in 24-hour group). Since only chemotherapy-naive pts were to be enrolled in phase II, safety and efficacy data from those pts are presented here. Preliminary safety data indicate that AEs of all grades with >33% difference between the arms were somnolence (83% in 3-hr vs. 0% in 24-hr), euphoric mood (58 vs. 0%), dysguesia (50 vs. 0%), hyponatremia (8 vs. 50%), and chest pain (42 vs. 0%). CNS AEs were generally transient and without sequelae. The RR, PDs during the planned 6 cycles of combination therapy, median PFS, and median OS all demonstrated a trend in favor of the 3-hr infusion arm. Minimum follow-up for all 18 pts is 10.4 months. Conclusions: Although associated with a higher incidence of some (particularly CNS) AEs, Ob 3-hr infusion in combination with Carb and Et showed a trend toward higher RR, PFS, and OS than 24-hour infusion. 3-hr infusions with Carb and Et have been studied further in a randomized, phase II trial in pts with chemotherapy-naïve ES-SCLC which has now completed enrollment. RR % Progression during 6 cycles Median PFS (days) Median OS (days) 3-hr 100 1/12 197 (126-390) 312+* (175-516+) 24-hr 66 2/6 185 (43-224) 198 (80-315+) * Median not reached No significant financial relationships to disclose.
Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC
Authors: Kathleen Machiels, João Sabino, Leen Vandermosten, Marie Joossens, Ingrid Arijs, Magali de Bruyn, Venessa Eeckhaut, Gert Van Assche, Marc Ferrante, Jan Verhaegen, Kristel Van Steen, Filip Van Immerseel, Geert Huys, Kristin Verbeke, Albert Wolthuis, Anthony de Buck Van Overstraeten, Andre D'Hoore, Paul Rutgeerts, Séverine Vermeire
Journal: Gut (2015)

Pouchitis is the most common complication after colectomy with ileal pouch-anal anastomosis (IPAA) for UC and the risk is the highest within the 1st year after surgery. The pathogenesis is not completely understood but clinical response to antibiotics suggests a role for gut microbiota. We hypothesised that the risk for pouchitis can be predicted based on the faecal microbial composition before colectomy.Faecal samples from 21 patients with UC undergoing IPAA were prospectively collected before colectomy and at predefined clinical visits at 1 month, 3 months, 6 months and 12 months after IPAA. The predominant microbiota was analysed using community profiling with denaturing gradient gel electrophoresis followed by quantitative real-time PCR validation.Cluster analysis before colectomy distinguished patients with pouchitis from those with normal pouch during the 1st year of follow-up. In patients developing pouchitis, an increase of Ruminococcus gnavus (p<0.001), Bacteroides vulgatus (p=0.043), Clostridium perfringens (p=0.011) and a reduction of two Lachnospiraceae genera (Blautia (p=0.04), Roseburia (p=0.008)) was observed. A score combining these five bacterial risk factors was calculated and presence of at least two risk factors showed a sensitivity and specificity of 100% and 63.6%, respectively.Presence of R. gnavus, B. vulgatus and C. perfringens and absence of Blautia and Roseburia in faecal samples of patients with UC before surgery is associated with a higher risk of pouchitis after IPAA. Our findings suggest new predictive and therapeutic strategies in patients undergoing colectomy with IPAA.
Gene Mutation Profile of Pancreatic Cancer in Japanese Patients and Its Association with Prognosis
Authors: Hideyuki Hayashi, Hideki Ueno, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Kazuaki Shimada, Hitoshi Ichikawa, Nobuyoshi Hiraoka, Takashi Kohno, Takuji Okusaka
Journal: Annals of Oncology (2014)
Abstract P116: African Americans Have the Highest Risk of Stroke-Events and In-Hospital Mortality With Atrial Fibrillation Related Hospitalizations Among All Racial/Ethnic Groups: A Nationwide Analysis
Authors: Mohit Turagam, Poonam Velagapudi, Alexis Visotcky, Aniko Szabo, Abraham Kocheril
Journal: Circulation (2012)

Introduction: There continues to be an increase nationwide in hospitalizations for atrial fibrillation (AF). However the impact of age, race and gender on in-patient mortality and stroke events for AF hospitalizations is unknown. Methods: This is a cross-sectional study utilizing data from the 2008 Nationwide Inpatient Sample (NIS). NIS is the largest, all-payer, hospitalization database in USA. We identified all AF-related hospitalizations through the presence of the appropriate ICD-9-CM codes. We calculated the adjusted odds of in-hospital mortality and stroke events with respect to age, gender and race in AF patients using multivariate logistic regression. All analyses were adjusted for the survey design. Results: There were an estimated to 425,470 AF-related hospitalizations in 2008 with 4,041(0.95%) in-hospital deaths and 3,531(0.83%) stroke-related events associated with such hospitalizations, respectively. Table 1 shows the results related to in-hospital mortality and stroke events, adjusted for other comorbidities such as history of diabetes, hypertension, coronary artery disease, myocardial infarction, congestive heart failure and dyslipidemia. Conclusion: African Americans have the highest risk of stroke-events and in-hospital mortality with AF related hospitalizations among all racial/ethnic groups. Increasing age is associated with a large increase in the risk of in-hospital mortality, and a smaller increase in stroke events. Gender was not found to be an independent risk factor for either stroke events or in-hospital mortality for AF. Further research is needed to better characterize the natural history and treatment outcomes in this cohort. Table 1 Odds ratio and confidence limits for in-hospital mortality and stroke events adjusted for co-morbidities. Predictor Comparison In-hospital mortality In-hospital stroke events Point Estimate 95% Wald Confidence Limits p-value Point Estimate 95% Wald Confidence Limits p-value Sex Female vs Male 1.019 0.864 - 1.201 0.82 1.076 0.903 - 1.282 0.41 Race / Ethnicity Black vs White 2.123 1.625 - 2.774 0.0007 2.030 0.731 - 1.450 0.004 Hispanic vs White 1.495 1.068 - 2.093 0.28 1.479 1.061 - 2.062 0.26 Asian or Pacific Islander vs White 1.364 0.752 - 2.477 0.70 0.976 0.481 - 1.982 0.79 Native American vs White 0.732 0.227 - 2.358 0.30 0.260 0.037 - 1.856 0.14 Other vs White 1.083 0.659 - 1.779 0.60 1.282 0.807 - 2.036 0.17 Age 62 - 72 vs ≤ 61 2.454 1.723 - 3.496 0.028 1.277 0.995 - 1.640 0.75 73 - 80 vs ≤ 61 3.997 2.847 - 5.612 0.0001 1.287 0.990 - 1.674 0.69 &gt; 80 vs ≤ 61 7.900 5.721 - 10.910 &lt;.0001 1.476 1.147 - 1.901 0.018