tbuckley/cabot-search huggingface dataset:
mTOR expression in pancreatic adenocarcinoma and its correlation with survival
Authors: A. Rajan, I. Tolocica, O. El-Zammar, N. Chittoria, M. Singh, N. Newman, A. Gajra
Journal: Journal of Clinical Oncology (2008)

22169 Background: Mammalian target of rapamycin (mTOR) is a cytoplasmic kinase involved in cell proliferation and survival that is overexpressed in many solid organ tumors, including pancreatic cancer. We studied expression of mTOR and phospho-mTOR (pmTOR) in tumor samples by immunohistochemistry and correlated it with patient survival. Methods: A single-institution, retrospective analysis was conducted and 48 patients diagnosed with pancreatic adenocarcinoma between 2/2001 and 1/2006 were identified from our tumor registry. Diagnostic tissue was available in 47 cases (fine needle aspirates - 21 cases; tissue blocks - 26 cases). Immunohistochemical analysis was performed on paraffin-embedded tissue using commercially available antibodies to mTOR and pmTOR. Results were expressed as a total score (T) that was the sum of a distribution score (D) and an intensity (I) score. Slides stained positive for T ≥ 3 and negative for T ≤ 2. Clinical data was available for 44 patients including age, gender, date of diagnosis and date of death. Overall survival (OS) was calculated from the date of diagnosis to the date of death and expressed in months. Results: The median age of our patients was 66 years. 21 (48%) were male and 23 (52%) female. 25/47 (53.2%) slides were positive and 22/47 (46.8%) were negative for mTOR expression. 29/47 (61.7%) slides were positive and 18/47 (38.3%) were negative for pmTOR expression. 44/48 patients could be evaluated for OS. Median OS was 5.5 months in males and 4.5 months in females. Cox regression analysis showed a statistically significant association between age and survival (RR 1.04, CI 1.01–1.06, p=0.02) but no statistically significant correlation between expression of mTOR (RR 0.86, CI 0.7–1.05, p=0.14) or pmTOR (RR 1.13, CI 0.94–1.36, p=0.18) and survival. Conclusions: More than half the samples of pancreatic adenocarcinoma studied showed evidence of phosphorylation of mTOR. Expression of mTOR or pmTOR did not show a statistically significant correlation with survival. Since many tumor samples showed expression of pmTOR it is plausible that multiple biological and clinical factors determine response to therapy and survival and the use of mTOR inhibitors in combination with standard chemotherapy could be considered. No significant financial relationships to disclose.
Production and Characterization of Xenogeneic Antisera to a Human Renal Cell Carcinoma-Associated Antigen&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Ghose, P Belitsky, J Tai, D T Janigan
Journal: JNCI Journal of the National Cancer Institute (1979)

Antisera to human renal cell carcinomas were produced by the immunization of goats and rabbits with dissociated tumor cells and/or tumor homogenates from single donors. After absorptions with human red blood cells and homogenates of human liver, lung, spleen, and heart, all the immune sera reacted on immunofluorescence with the brush border of the proximal convoluted tubules of adult and fetal human kidneys and with the proximal convoluted tubular epithelia of rabbits, guinea pigs, rats, and mice. After further absorption with pooled normal human kidney homogenates, the immune sera on immunofluorescence showed cytoplasmic staining of smears and sections of 21 of the 22 human renal cell carcinomas tested. These sera did not show any staining of normal adult human tissues including normal kidney adjacent to the carcinomas, perirenal fibroblasts and peripheral blood leukocytes from the patients, human fetal kidneys, transplanted renal adenocarcinoma of BALB/c mice, and several human tumors tested, i.e., transitional cell carcinoma of the bladder, adenocarcinomas of the breast and colon, squamous cell carcinoma of the lungs, malignant lymphoma, and melanoma. Autoradiography of tissue sections with 131I-labeled antitumor globulins revealed greater localization of radioactivity in tumors than in adjacent normal kidney. Membrane immunofluorescence with the immune sera rendered tumor-specific after appropriate absorptions revealed tumor-associated antigens on the surfaces of all 5 human renal carcinoma cell lines tested.
Abstract MP037: Plasma Organochlorine Concentration and Risk of Diabetes: the Nurses' Health Study
Authors: Hongyu Wu, Kimberly A Bertrand, Anna L Choi, Frank B Hu, Francine Laden, Philippe Grandjean, Qi Sun
Journal: Circulation (2012)

Background: Animal experiments have suggested that exposure to persistent organic pollutants (POPs) may lead to increased risk of type 2 diabetes. Although recent human studies supported this hypothesis, evidence from prospective investigations is sparse. Objective: To examine the associations of plasma POP concentrations with risk of incident type 2 diabetes in a prospective setting among US women. Methods: Study population was comprised of participants from two independent nested case-control studies in the Nurses’ Health Study, in which major polychlorinated biphenyl (PCB 118, 138, 153, and 180), p-p'- dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and hexachlorobenzene (HCB) were measured. A non-parametric approach was used to derive standardized scores for plasma concentrations of lipid-adjusted POPs within each study to minimize between-study variation of the POP measurements. Risk of incident type 2 diabetes during the follow-up period (1990-2008) across the tertiles of the scores was examined. Results: Of 1,120 participants, we identified 48 incident type 2 diabetes cases. After adjusting for covariates assessed at blood draw in 1990, including smoking status, body mass index, and total fish intake, plasma HCB concentration was positively associated with type 2 diabetes risk: odds ratio (OR) (95% confidence interval [CI]) was 2.77 (1.17, 6.55, P for trend =0.022) comparing the highest vs. lowest tertile. Other POPs were not significantly associated with diabetes: the ORs (95% CI) were 1.10 (0.51, 2.34, P for trend =0.81) for p-p'-DDE, 0.93 (0.44, 1.95, P for trend =0.86) for DDT, and 0.88 (0.39, 1.97, P for trend =0.76) for sum of the 4 major PCBs, comparing the extreme tertiles. Conclusion: The significant association of plasma HCB concentration with diabetes risk supports a role of POP exposure in the etiology of type 2 diabetes. More prospective data are warranted to confirm these findings.
Autonomic orienting responses in 15-year-old male subjects and criminal behavior at age 24
Authors: A Raine, P H Venables, M Williams
Journal: American Journal of Psychiatry (1990)

This prospective study analyzed relationships between skin conductance and heart rate measures of orienting in a noninstitutionalized sample of 101 15-year-old male subjects and criminal behavior as assessed at age 24 years. Subjects with a criminal record at age 24 (N = 17) had significantly smaller skin conductance responses and smaller heart rate deceleratory and acceleratory responses than the other subjects (N = 84). Lack of any skin conductance response was significantly more prevalent in subjects with a criminal record (31%) than in the control subjects (10%). These results implicate deficits in orienting with the later development of criminal behavior. The authors hypothesize that the genetic predisposition to criminal behavior may find its expression in part through smaller autonomic orienting.
Phase II trial of O<sup>6</sup>-benzylguanine (O<sup>6</sup>BG) and BCNU in patients with advanced melanoma
Authors: T. F. Gajewski, J. Sosman, A. C. Peterson, S. Gerson, E. Dolan, E. Vokes
Journal: Journal of Clinical Oncology (2004)

7524 Background: While alkylating agents such as BCNU are active in melanoma, they give response rates of only 10–15%. BCNU induces DNA damage by formation of a chloroethyl adduct at the O6 position of guanine. This modification can be repaired by alkylguanine DNA alkyltransferase (AGT), and melanoma tumor cells can express high levels of AGT. O6BG is a potent inhibitor of AGT. We hypothesized that addition of O6BG would improve the clinical response to BCNU in patients with advanced melanoma. Methods: Patients had measurable disease, adequate organ function, PS≤ 2, and a corrected DLCO of ≥ 70% predicted. Patients were accrued into 2 cohorts based on whether or not they received prior chemotherapy. O6BG (120 mg/m2) was administered i.v. over 1 hour, followed by BCNU (40 mg/m2) i.v. over 1 hour, as an outpatient. PBMC were collected pre- O6BG and 18 hours later to assess for AGT depletion. Treatment cycles were repeated every 6 weeks and response using RECIST criteria was assessed every 2 cycles. Results: 42 patients were enrolled, 22 chemo-naive and 20 with prior chemo. In the chemo-naive cohort there were 1 CR, 4 SD, 13 PD, and 4 non-evaluable (NE) patients; the median time to progression (TTP) was 80d and the median survival (MS) was 211d. In the prior chemo cohort there were no objective responses, 3 SD, 15 PD, and 2 NE patients; the median TTP was 40d and the MS was 120d. The NE patients had clinical disease progression. AGT was effectively depleted from PBMC in the 15 patients tested (p<0.001). Grade 3/4 toxicities included thrombocytopenia (n=24), neutropenia (19), anemia (10), lymphopenia (7), fever (2), fatigue (2), hyponatremia (2), neuropathy (1), vomiting (1), decreased DLCO (1), and death (1). Toxicities were similar in the two cohorts. Conclusions: O6BG/BCNU was successfully administered on an outpatient basis and depleted AGT from PBMC. However, significant myelosuppression was seen and the clinical response rate was not greater than what is expected with BCNU alone. Although this regimen should not be explored further, administration of O6BG with other alkylating agents with greater single agent activity should be considered. No significant financial relationships to disclose.
Natural history of male psychological health: VIII. Antecedents of alcololism and "orality"
Authors: G E Vaillant
Journal: American Journal of Psychiatry (1980)

The author reports a prospective study of the mental health and alcohol use of 184 men first studied during their college years. When the men were 50 years old a rater blind to all other data classified the subjects' alcohol use as little (N = 48), social (N = 110), or abuse (N = 26). The warmth of the men's childhood environment and their personality stability in college were assessed by other raters blind to data on subjects' lives after college. Vignettes identifying "oral" adult behavior (pessimism, self-doubt, passivity, and dependence) were collected for each man by a rater blind to subjects' alcohol use and childhood ratings. Poor childhood, personality instability in college, and adult evidence of personality disorder were correlated with oral-dependent behavior but not with alcohol abuse. The 26 problem drinkers seem to have been depressed and unable to cope as a consequence--not a cause--of their inability to control their alcohol consumption.
HEAD INJURY AND POSTTRAUMATIC NEUROSIS
Authors: D P KIDRON
Journal: JAMA (1934)

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Trends in chemotherapy use and survival for patients with metastatic non-small cell lung cancer
Authors: B. Byrne, J. Crawford, G. Gay, J. Bonner, L. Gaspar
Journal: Journal of Clinical Oncology (2004)

7072 Background: In clinical trials chemotherapy improves survival in patients with Stage IV non-small cell lung cancer (NSCLC). We searched the National Cancer Database (NCDB) to analyze the effects of age, race and sex on the use of chemotherapy and to see if chemotherapy improves survival on a population basis. Methods: The NCDB was searched for newly reported cases of metastatic NSCLC in 1985,1990, 1995, and 2000. Data was recorded for histology, age, sex, race, whether chemotherapy was given, and survival. The Pearson Chi-Square test was used to analyze the effect of age, race, and gender on patients receiving chemotherapy. The relative survival rates of patients undergoing chemotherapy were compared to patients not receiving this treatment modality. Results: 79,436 cases of metastatic NSCLC were identified. The percentage of all patients who received chemotherapy increased from 26.8% (95% Confidence interval 25.7%–28.0%) in 1985 to 45.9% (CI: 45.3%–46.6%) in 2000. The use of chemotherapy in patients greater than 70 yrs old increased from 15.7% (CI: 13.6%–17.9%) in 1985 to 34.6% (CI: 33.7%–35.5%) in 2000. In patients less than 70 yrs old, white women (58.5%) were most likely to receive chemotherapy; whereas, non-white men (47.1%) were least likely. For patients greater than 70 yrs old, white men (37.1%) were most likely to receive chemotherapy as compared to other demographic groups. Survival data is presented in the table below. Conclusions: Over the last 15 years, chemotherapy is being used more frequently in patients with metastatic NSCLC with an associated survival benefit at one and two years. Patient age, gender and race impact the likelihood of receiving chemotherapy and warrant further study. No significant financial relationships to disclose.
Abstract 17397: Establishing the Cost-Effectiveness of Chronic Total Occlusion Percutaneous Coronary Intervention: A Decision-Analytic Model
Authors: Hemal Gada, Patrick L Whitlow, Thomas H Marwick
Journal: Circulation (2012)

Introduction. In the setting of chronic stable angina, successful percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) has been shown to produce significant improvement in ang...
Increase of Peroxidation in Carcinogenesis
Authors: Raymond J. Shamberger, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1972)

Mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and treated with 0.04% croton oil had more tumors and a greater percentage with tumors than a group of 0.004% croton resin-treated mice. In a second experiment addition of corn oil to the croton resin increased the number of tumors. Skin treated with DMBA and croton oil had greater peroxidation and more tumors than skin treated with DMBA and croton resin. Peroxides could not be detected throughout the experiment. Peroxidation in 2 experiments increased after DMBA initiation but returned to normal on about day 45. Antioxidants applied on days 2–21 in another experiment, when peroxidation increased, decreased the tumor incidence. At the conclusion of the DMBA-croton oil versus the DMBA-croton resin experiments, small tumors regressed more than large tumors. Regression of tumors observed at 16–18 weeks may be linked to an increase of lysosomal enzyme activity observed before regression.
Reply to the letter to the editor ‘A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma’ by Hines et al.
Authors: G. Rosati, P. Mosconi, V. Torri, G. Apolone, F.E. Johnson, R. Fossati
Journal: Annals of Oncology (2016)

We appreciate the opportunity to address comments by Hines and Al-Rajabi [1] regarding our recent publication on post-surgical surveillance in colorectal cancer patients [2]. Hines and Al-Rajabi [1] contend that we should not have called ‘minimal’ our less intensive program and that we should not have concluded that ‘our findings support the conclusions of other randomized clinical trials, which shows that the early diagnosis of cancer recurrence is not associated with overall survival benefit’.
Abstract 3562: High Serum Level of Neopterin Predicts Cardiac Events in Chronic Heart Failure Patients With Preserved Left Ventricular Systolic Function
Authors: Toshiki Sasaki, Tetsuro Shishido, Hiroki Takahashi, Takanori Arimoto, Takehiko Miyashita, Takuya Miyamoto, Joji Nitobe, Tetsu Watanabe, Yasuchika Takeishi, Isao Kubota
Journal: Circulation (2009)

Background: More than 40% of patients hospitalized with heart failure have preserved left ventricular ejection fraction (LVEF) and are at high risk for cardiac events. The purpose of this study was...
Metronomic capecitabine as second-line treatment for patients with hepatocellular carcinoma with preserved liver function: A phase II study.
Authors: F. de Rosa, V. Agostini, S. Di Girolamo, P. Andreone, F. Trevisani, L. Bolondi, A. D. Pinna, C. Serra, R. Golfieri, G. Biasco, G. Brandi
Journal: Journal of Clinical Oncology (2011)

e14608 Background: The antiangiogenic drug sorafenib is standard treatment for advanced hepatocellular carcinoma (HCC) not suitable for surgical or loco-regional therapies in patients with preserved liver function. Many second-line drugs are currently under investigation, but none has proven effective so far. Metronomic chemotherapy is characterized by antiangiogenic activity as well and good tolerability. Therefore we started a phase II clinical study to assess efficacy of metronomic capecitabine in advanced HCC patients. Methods: This phase II trial allowed inclusion of 90 HCC patients (pts) in two sub-studies: first-line systemic treatment (60 pts) and second-line after sorafenib (30 pts.) Main inclusion criteria were Child-Pugh liver function class A and progressive disease not candidate for surgery or loco-regional treatments. Treatment schedule was capecitabine 500 mg bid after meals continuously. In case of severe toxicity up to two weeks off-therapy were permitted for recovery; no dose adjustment was allowed. Primary endpoint is three-months progression-free survival rate (PFS3mo), assessed by RECIST 1.1. This preliminary analysis aims at evaluating efficacy and toxicity of metronomic capecitabine after progression on sorafenib treatment. Results: Patients’ accrual ended in December 2010. A total of 30 pts pre-treated with sorafenib have been included; of these, 12 had relapsed after surgery and 24 had been previously managed with percutaneous ablations or chemoembolizations. 23 pts are currently assessable for efficacy. We observed no objective responses, 9 stable disease and 14 progressive disease, for a PFS3mo of 39%. Overall and progression-free survival will be evaluated in a further analysis with longer follow-up. All patients are assessable for toxicity. The most common adverse events were asthenia, nausea, diarrhoea and pruritus, generally mild and tolerable. Conclusions: Metronomic capecitabine is well tolerated and can be active in HCC patients after progression under sorafenib treatment. The extent of clinical benefit will be determined in the final analysis.
Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in<i>MOCS3</i>,<i>IFIT3</i>and<i>SERPINA12</i>
Authors: Victoria E Jackson, Ioanna Ntalla, Ian Sayers, Richard Morris, Peter Whincup, Juan-Pablo Casas, Antoinette Amuzu, Minkyoung Choi, Caroline Dale, Meena Kumari, Jorgen Engmann, Noor Kalsheker, Sally Chappell, Tamar Guetta-Baranes, Tricia M McKeever, Colin N A Palmer, Roger Tavendale, John W Holloway, Avan A Sayer, Elaine M Dennison, Cyrus Cooper, Mona Bafadhel, Bethan Barker, Chris Brightling, Charlotte E Bolton, Michelle E John, Stuart G Parker, Miriam F Moffat, Andrew J Wardlaw, Martin J Connolly, David J Porteous, Blair H Smith, Sandosh Padmanabhan, Lynne Hocking, Kathleen E Stirrups, Panos Deloukas, David P Strachan, Ian P Hall, Martin D Tobin, Louise V Wain
Journal: Thorax (2016)

<h3>Background</h3> Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants. <h3>Objective</h3> To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation. <h3>Methods</h3> 3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array. An analysis of risk of COPD was carried out using ever smoking controls (n=4784). Associations with %predicted FEV<sub>1</sub> were tested in cases. We followed-up signals of interest (p&lt;10<sup>−5</sup>) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays. <h3>Results</h3> Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in <i>MOCS3</i> (rs7269297, p<sub>discovery</sub>=3.08×10<sup>−6</sup>, p<sub>replication</sub>=0.019) and a rare SNP in <i>IFIT3</i>, which emerged in the meta-analysis (rs140549288, p<sub>meta</sub>=8.56×10<sup>−6</sup>). In the meta-analysis of % predicted FEV<sub>1</sub> in cases, the strongest association was shown for a splice variant in a previously unreported region, <i>SERPINA12</i> (rs140198372, p<sub>meta</sub>=5.72×10<sup>−6</sup>). We also confirmed previously reported associations with COPD risk at <i>MMP12, HHIP</i>, <i>GPR126</i> and <i>CHRNA5</i>. No associations in novel regions reached a stringent exome-wide significance threshold (p&lt;3.7×10<sup>−7</sup>). <h3>Conclusions</h3> This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions <i>MOCS3</i>, <i>IFIT3</i> and <i>SERPINA12</i>, which warrant further study.
Paclitaxel/Nab-Paclitaxel in Combination with Anti-Angiogenic Therapy: an in Vitro Study
Authors: C. Lo Nigro, O. Garrone, F. Tonissi, L. Lattanzio, A. Ghiglia, D. Vivenza, M. Monteverde, M.C. Merlano
Journal: Annals of Oncology (2014)