tbuckley/cabot-search huggingface dataset:
Phase II prevention trial of celecoxib in women at increased risk for breast cancer
Authors: B. Arun, C. Logan, G. Yin, G. Yun, G. G. Hortobagyi, D. Browne, N. Sneige
Journal: Journal of Clinical Oncology (2007)

1501 Background: Tamoxifen and raloxifen reduce the risk of estrogen receptor (ER) positive breast cancer. Acceptance of SERMs is low due to toxicities. New agents with a better toxicity profile which also will prevent ER-negative breast cancer are needed. The cyclooxygenase II inhibitor celecoxib has antiproliferative, and antiangiogenetic properties and is a putative breast cancer prevention agent. Our objective in this prospective short-term prevention study was to evaluate the effect of celecoxib on biomarkers in breast tissue and serum of high risk women. Methods: High risk individuals with a history of atypical hyperplasia, or lobular carcinoma insitu, or Gail risk greater than 1.67%, or previous history of ER negative breast cancer were eligible. After signing informed consent subjects underwent baseline fine needle aspiration (FNA) of the breast and serum collection for biomarker analysis. Subjects started celecoxib at 400 mg po BID for 6 months and underwent repeat FNA and serum collection. Biomarker endpoints included changes in ER and KI-67 expression in breast tissue analyzed by immunohistochemistry and insulin like growth factor binding protein (IGFBP-1) in serum analyzed by ELISA. The difference in biomarkers before and after treatment was assessed using a Wilcoxon signed rank test. Results: 49 patients were enrolled and accrual has been completed. Median age was 51 years and 57% of women were postmenopausal. The mean pre- and post treatment ER expression was 35.5% and 31%, respectively. The difference in ER expression was not significant (p = 0.1). The mean pre- and post treatment KI-67 expression was 1.68% and 1.60%, respectively. The difference was not significant (p = 0.8). However, there was a statistically significant difference in pre- and post treatment IGFBP-1 levels (p=0.023), with pre-and post treatment levels being 6.81ng/ml and 11.51ng/ml, respectively. No grade 3 or 4 toxicities were observed and there was no drop-out from the study. Conclusions: We have found a significant modulation of IGFBP-1 levels with 6 months celecoxib treatment in women who are at increased risk of developing breast cancer. The acceptable side effect profile and modulation of the biomarker (IGFBP-1) provides support for continued evaluation of celecoxib as a breast cancer prevention agent. No significant financial relationships to disclose.
Gene expression differences in current versus former smokers lung squamous preneoplasia.
Authors: C. J. Mascaux, C. D. Coldren, B. Haibe-Kains, G. Anthoine, A. Haller, V. Ninane, A. Burny, J. P. Sculier, F. R. Hirsch
Journal: Journal of Clinical Oncology (2010)

10575 Background: The study of the molecular biology of the lung carcinogenesis would help finding biomarkers for early diagnosis and targets for chemoprevention. The present study aim to characterize genomic profiles between current and formers smokers in lung squamous carcinogenesis. Methods: 122 bronchial biopsies (67/55 from current/former smokers) at successive stages of lung squamous carcinogenesis (normal, hyperplasia, metaplasia, mild, moderate and severe dysplasia, carcinoma in situ and invasive carcinoma) obtained by fluorescence bronchoscopy in 74 high risk individuals (40/34 current/former smokers) were analyzed by gene expression microarrays (Mascaux, J Thorac Oncol 2009 4(9) S282). Results: 740 genes were significantly differentially expressed (FDR 0.05) between biopsies from current versus former smokers in bronchial pre-invasive lesions. The most significantly associated pathways was metabolism of xenobiotic by cytochrome CP450 eg CYP1A1, CYP2A6, ALDH1L1, but genes related to cancer pathways were also found, ie metallopeptidases, IGF binding proteins, cell growth and proliferation (ie EGF), or apoptosis (ie survivin). Our findings in lung preneoplasia were consistent by gene set enrichement analyses. (GSEA) with data previously reported on normal bronchial epithelial cells (Spira, PNAS 2004 101(27) 10143). Association between gene expression differences observed between the early steps of lung carcinogenesis in our study and between current and former smokers in normal bronchial epithelial cells in Spira study were analysed by GSEA. Some associations were observed: genes down-regulated in current smokers were also down-regulated in transition to squamous metaplasia including cancer genes like eg BCL2, FGF2, AKT3 and eicosanoid signaling eg PTGDR, PLA2G5. Conclusions: Genes discriminating current and former smokers during lung carcinogenesis include genes involved in metabolism of xenobiotic by cytochrome CP450, cell proliferation and apoptosis. Cigarette smoke exposure effects on normal epithelial cells and on preneoplasia from different data sets are related. Genes related to current smoking like eicosanoid signaling genes are involved in the early steps of carcinogenesis. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bristol-Myers Squibb/ImClone, Boehringer Ingelheim, Lilly, Merck Serono, OSI/Genentech/ Roche, Pfizer, Syndax AstraZeneca, Biogen Idec, Genentech, Genmab, Merck, OSI, Syndax, Ventana-Roche Abbott Laboratories
A phase II trial of gefitinib and pegylated interferon alfa 2b (PEG-IFN) in previously-treated renal cell carcinoma (RCC)
Authors: D. W. Shek, J. Longmate, D. Quinn, K. Margolin, P. Twardowski, D. Gandara, C. Pan, P. Lara
Journal: Journal of Clinical Oncology (2009)

e16115 Background: Modulation of the epidermal growth factor receptor (EGFR) pathway is relevant to IFN activity in RCC. Cell lines sensitive to IFN's antiproliferative effects downregulate EGFR, while IFN treatment of resistant cells precludes such an effect. (Eisenkraft et al, Cancer Res. 1991) Lack of EGFR down-regulation may thus be responsible in part for IFN resistance. To explore this hypothesis, we conducted a trial of the EGFR tyrosine kinase inhibitor gefitinib plus PEG-IFN in RCC patients (pts). Methods: Unresectable or metastatic RCC pts (no limit on prior therapies; performance status 0–2, and adequate end-organ function) were eligible. Prior IFN was allowed. Dose schedule: PEG-IFN SQ weekly (6μg/kg/week or 4 μg/kg/week) × 12 weeks and gefitinib 250 mg po daily until progression. A 6-month progression free survival (PFS) rate of 50% was considered promising (vs. 30%) in a two-stage design incorporating the Green-Dahlberg rule. We accrued 21 patients in the first-stage of accrual. Results: Pt characteristics: Males -16; median age - 56 years; Prior nephrectomy - 12. All had &gt; 1 prior systemic therapy . Accrual slowed with increased use of small molecule kinase inhibitors, bevacizumab, and temsirolimus for RCC. At 6 months, PFS was 26% (95% CI: 9%, 49%); 20% (4 pts) had died. Best responses by RECIST: complete (1), partial (4), stable (8); progression (4). Response duration: CR (35+ months) and PR (3, 5, 5, 38+ months). Median time to treatment failure was 18.4 weeks (95%CI: 7.4, 24.9). Median PFS and overall survival were 23 and 53 weeks, respectively. Most common treatment-related toxicities were leucopenia, thrombocytopenia, rash, nausea, diarrhea, and hyperglycemia. Conclusions: Although gefitinib plus PEG-IFN did not meet the pre-specified 6-month PFS of 50%, it appears to have activity similar to other first-line therapies even in this previously-treated setting. (Supported by Astra Zeneca) [Table: see text]
Flavonoid profiling of a traditional Chinese medicine formula of Huangqin Tang using high performance liquid chromatography
Authors: Tao Li, Shuaixing Zhuang, Yiwei Wang, Yanli Wang, Weihao Wang, Huihui Zhang, Li Chen, Dunfang Wang, Zhongming Zhou, Weipeng Yang
Journal: Acta Pharmaceutica Sinica B (2016)

The quality control processes for herbal medicines have been problematic. Flavonoids are the major active components of Huangqin Tang (HQT, a traditional Chinese medicine formula). In this study, we used a combinative method approach consisting of chromatographic fingerprinting (high performance liquid chromatography; HPLC), quantitative methods and a pharmacodynamic evaluation model to analyze the flavonoids of HQT obtained from different sources. Ten batches of HQT were analyzed by the HPLC fingerprinting method and 26 common peaks were detected, of which 23 peaks corresponded with the chemical profile of HQT. In addition, 11 major compounds were identified by LC–MS analysis (liquid chromatography–tandem mass spectrometer; LC–MSn) and quantified by the HPLC quantitative method approach. The studied 10 batches of HQT were found to be homogeneous in their composition with a similarity between 0.990 and 1.000. The distribution of the 11 identified compounds was found to be very similar among the batches. Only slight pharmacodynamic differences were detected between the different batches, confirming the homogeneity of HQT. The results of this study prove that the combination of chromatographic fingerprinting and quantitative analysis can be readily used for comprehensive quality control of herbal medicines.
Vascular endothelial growth factor (VEGF) gene polymorphisms associated with prognosis for patients with colorectal cancer
Authors: Y. Chae, J. Kim, S. Sohn, Y. Cho, J. Moon, S. Jeon, J. Park, I. Lee, G. Choi, S. Jun
Journal: Journal of Clinical Oncology (2007)

4125 Background: Vascular endothelial growth factor (VEGF) or its family may be considered to play an important role in lymphangiogenesis and lymphatic tumor spread, thereby affecting prognosis of colorectal cancer. Accordingly, the present study analyzed VEGF gene polymorphisms and their impact on the prognosis for patients with colorectal cancer. Patients and Methods: Four hundred and sixty-five consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tumor tissue and 3 VEGF (-2578C &gt; A, -634G &gt; C, and +936C &gt; T) gene polymorphisms determined using a PCR/DHPLC (Polymerase chain reaction/Denaturing high-performance liquid chromatography) assay. Results: The median age of the patients was 64 years (range, 21–89), and 264 (56.7%) patients had colon cancer and 201 (48.2%) patients rectal cancer. Pathologic stages evaluable (n=464) after surgery were as follows: stage I (n=79, 17.0%), stage II (n=157, 33.8%), stage III (n=157, 33.8%), and stage IV (n=71, 15.3%). Multivariate survival analysis including stage, differentiation, and CEA level showed that survival for patients with the -634CC (overall survival [OS]: hazard ratio [HR]=0.175, P&lt;0.001; progression-free survival [PFS]: HR=0.554, P=0.040) or GC genotype (OS: HR=0.158, P&lt;0.001; PFS: HR=0.630, P=0.044) were better than for patients with the -634GG genotype, whereas the +936TT (OS: HR=65.959, P&lt;0.001; PFS: HR=2.823, P=0.016) or CT genotype (OS: HR=16.116, P&lt;0.001; PFS: HR=3.507, P&lt;0.001) were associated with a worse survival compared to the CC genotype. In haplotype analysis, the -2578A/-634G/+936T haplotype exhibited a significantly worse survival when compared to the wild -2578C/-634G/+936C haplotype (OS: HR=4.670, P&lt;0.001; PFS: HR=3.624, P&lt;0.001). Conclusions: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome. No significant financial relationships to disclose.
Factitious mourning: painless patienthood
Authors: M R Phillips, N G Ward, R K Ries
Journal: American Journal of Psychiatry (1983)

Of 20 patients who falsely reported the deaths of loved ones in order to assume the patient role, most presented with depression and suicidal ideation secondary to reported multiple dramatic deaths for which there was no available verification, and many had histories of factitious physical symptoms, manipulative suicide attempts, substance abuse, and sociopathy. Diagnostic categories were of limited usefulness for these patients. Factitious symptoms can better be understood as one form of dysfunctional care-eliciting behavior. The authors recommend early and repeated confrontations in a firm but nonjudgmental manner combined with referral to outpatient psychotherapy focused on the underlying characterological problems.
Bimodal Differentiation Prospectives for Promyelocytes<xref ref-type="fn" rid="FN2">2</xref>
Authors: H J Radzun, M R Parwaresch, S Bödewadt, C Sundström, K Lennert
Journal: JNCI Journal of the National Cancer Institute (1985)

In accordance with the long-range goal to demonstrate the direct derivation of blood monocytes from promyelocytes in human bone marrow, the promyelocytic cell line HL-60 in the present study was differently stimulated with various inducers for the purpose of documenting its capability to evolve into granulocytes or monocytes-macrophages. Each differentiation line was monitored with the use of marker enzymes, antigens, and cell-specific monoclonal antibodies. In addition, studies were done on normal human bone marrow and leukemias. The results provided strong evidence for the close cytogeneic relationship of granulocytes and monocytes and for a common progenitor at the maturation stage of promyelocytes-myelocytes for both cell lineages.
Effective Translation of an Intensive Lifestyle Intervention for Hispanic Women With Prediabetes in a Community Health Center Setting
Authors: Michelle A. Van Name, Anne W. Camp, Elizabeth A. Magenheimer, Fangyong Li, James D. Dziura, Abmaridel Montosa, Anisha Patel, William V. Tamborlane
Journal: Diabetes Care (2016)

OBJECTIVE The Diabetes Prevention Program (DPP) demonstrated that weight loss from intensive lifestyle intervention (ILI) in adults with prediabetes could decrease progression to type 2 diabetes. Inner-city, low-income Hispanic women are at high risk for developing type 2 diabetes; however, this type of intervention is not well established in this group. We hypothesized that a DPP intervention modified for a community health center (CHC) setting would decrease weight and improve metabolic measures in Hispanic women with prediabetes. RESEARCH DESIGN AND METHODS Women diagnosed with prediabetes on a screening oral glucose tolerance test were recruited from a CHC. Participants (90% of whom were Hispanic) were randomized to either usual care (age 43 ± 9.7 years, BMI 35.2 ± 7.3 kg/m2) or ILI (age 43.8 ± 10.8 years, BMI 35.4 ± 8.5 kg/m2), structured as 14 weeks of group sessions focused on food choices, behavior change, physical activity, and weight loss. One year after enrollment, 122 women repeated baseline measures. RESULTS Groups had similar baseline weight, BMI, and fasting and 2-h glucose. One year later, the ILI group had lost 3.8 kg (4.4%), while the usual care group had gained 1.4 kg (1.6%, P &amp;lt; 0.0001). Two-hour glucose excursion decreased 15 mg/dL (0.85 mmol/L) in the ILI and 1 mg/dL (0.07 mmol/L) in the usual care group (P = 0.03). Significant decreases favoring the ILI group were noted in BMI, percent body fat, waist circumference, and fasting insulin. CONCLUSIONS A 14-week ILI program based on the DPP can effectively be translated into a predominantly Hispanic CHC setting, resulting in decreased weight, improved fasting insulin, and smaller glucose excursions 1 year after enrolling in the program.
Don’t Neglect Cultural Diversity in Oncology Care
Authors: Teresita Muñoz-Antonia
Journal: Journal of the National Comprehensive Cancer Network (2014)

The growing Hispanic population in the United States mandates the need for oncology providers to become more familiar with disease patterns and cultural belief systems that can impact cancer care. “Culturally competent care” should be the mandate of all providers. This comprises awareness of cultural differences, communication in a manner that the patient understands, and respect.
Transplantable Immunoglobulin-Secreting Tumors in Rats. V. Monoclonal Immunoglobulins Secreted by 250 Ileocecal Immunocytomas in LOU/Wsl Rats2
Authors: Hervé Bazin, Andreé Beckers, Christian Deckers, Martine Moriamé
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Transplantable Immunoglobulin-Secreting Tumors in Rats. V. Monoclonal Immunoglobulins Secreted by 250 Ileocecal Immunocytomas in LOU/Wsl Rats Get access Hervé Bazin, Hervé Bazin Search for other works by this author on: Oxford Academic PubMed Google Scholar Andreé Beckers, Andreé Beckers Search for other works by this author on: Oxford Academic PubMed Google Scholar Christian Deckers, Christian Deckers Search for other works by this author on: Oxford Academic PubMed Google Scholar Martine Moriamé Martine Moriamé Faculty of Medicine, University of Louvain, 4 avenue Chapelle-aux-Champs, B-1200 Brussels, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 4, October 1973, Pages 1359–1361, https://doi.org/10.1093/jnci/51.4.1359 Published: 01 October 1973 Article history Received: 19 June 1973 Accepted: 27 June 1973 Published: 01 October 1973
Possible individualized therapy by early assessment of response during neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma patients by 18-FDG-PET
Authors: B. L. Brücher, H. Wieder, R. Busch, K. Becker, F. Lordick, M. Molls, J. Siewert, M. Schwaiger
Journal: Journal of Clinical Oncology (2006)

4060 Background: Response evaluation by positron emission tomography with the glucose analog [18F]-fluorodeoxyglucose (FDG-PET) has been used in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant radiochemotherapy (RTx/CTx). This prospective study was undertaken to compare FDG-PET assessment of tumor response during RTx/CTx with histopathology in patients with ESCC, and to correlate the findings with survival. Methods: Patients (n=61) with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) underwent preoperative, simultaneous RTx/CTx followed by esophagectomy between 1996 and 2005. The patients underwent FDG-PET prior to and 2 weeks after the begin of RTx/CTx (20Gray). Histopathological response was quantified as the percentage of residual tumor cells. The threshold pre-therapy-to-during-therapy decrease in standardized uptake value by FDG-PET used to define metabolic responders (ΔSUV R ) was -30%. Results: Receiving-operator-curve analysis (ROC) for determination of metabolic response revealed an area-under-curve (AUC) of 7140 (p=0.005) with a sensitivity of 76%, specificity (70%), a positive predictive value of 81% and a negative predictive value of 64% (p&lt;0.0001). Responder by FDG-PET during the neoadjuvant treatment (p=0.016) as well as Histopathology (p&lt;0.0001) showed substantially better survival compared to nonresponders. Conclusions: Changes in tumor metabolic activity by FDG-PET during neoadjuvant RTx/CTx allows an accurate determination of response due to the multimodal approach in patients with ESCC. This stratification may lead to a change of the neoadjuvant into a definitive therapy concept in nonresponders (individualized tumor therapy). [Table: see text]
Prevalence of BRCA mutations in a cohort of young high-risk breast cancer patients
Authors: B. Bahadini, J. Herzog, G. Somlo, P. Frankel, S. Sand, D. MacDonald, K. Blazer, J. N. Weitzel
Journal: Journal of Clinical Oncology (2004)

9662 Background:BRCA mutations are responsible for a modest percentage of breast cancers in young women. High risk breast cancer (HRBC), stage II disease with 10 or more positive axillary lymph nodes, stage IIIA, or IIIB inflammatory disease is associated with a poor prognosis (5-year survival of less than 50% following standard adjuvant chemotherapy). Beginning in 1989, high dose chemotherapy (HDCT) with autologous stem cell rescue was tested in clinical trials at COH for HRBC patients to improve their outcome. Recent data suggests a benefit in the inflammatory subset. The young age of the participants in HDCT trial (median age of 44 years, compared to a median age of 62 years for all new cases), suggested that many of these patients may have had inherited susceptibility mutations, since early age of onset is a typical feature of hereditary breast cancer. The influence of BRCA genotype on presentation or outcome of breast cancer treatment remains uncertain. Methods: We screened DNA samples from 120 HRBC patients, enrolled in an IRB-approved prospective registry after informed consent, by conformation sensitive gel electrophoresis to determine the proportion with an abnormal BRCA genotype. Results:We previously reported mutational analysis for BRCA1 in this high risk cohort (6 deleterious BRCA1 mutations and 13 variants of unknown significance, VUS), here we report the data for BRCA2 analysis (with complete data on 19 of 27 exons to date). All variants were confirmed by direct sequencing. Detectable BRCA2 variants were found in 9.2% of subjects (one clearly deleterious frame-shift mutation and 10 variants of unknown significance). Further characterization of each VUS indicated that 4 were suspect, while ancillary data indicated others were less likely to be pathologic. Conclusion:Overall, 25% of this HRBC cohort had BRCA variants (5.8% clearly deleterious mutations and 19% VUS) including 2 of 21 inflammatory cases. BRCA mutational analysis in this high risk cohort may expand our understanding of genetic basis of HRBC and help elucidate the prognostic implications of inherited BRCA mutations, although more BRCA carriers would be required for analysis of clinial outcome after HDCT. No significant financial relationships to disclose.
<i>JAMA Cardiology</i>: A New Cardiovascular Journal
Authors: Robert O. Bonow
Journal: JAMA Cardiology (2016)

The accelerating pace of cardiovascular science and practice provides new opportunities for prevention, diagnosis, and treatment, along with the hope of a better future for individuals with heart disease and those at risk of disease.2][3] Gaps in knowledge and the variability in resource use and implementation of proven interventions [4][5][6][7] underscore the need for ongoing research and education.To address the growing need for science discovery and dissemination, JAMA Cardiology has arisen as the newest member of the JAMA Network of journals.With weekly Online First publication and monthly issues in print and online, JAMA Cardiology will publish the findings of important research as Original Investigations, including clinical trials and meta-analyses, Brief Reports, and Research Letters, along with scholarly Reviews and timely opinion articles by thought leaders in the form of Viewpoints, Invited Commentaries, and Editorials.The journal will focus on all aspects of cardiovascular medicine, including hypertension, ischemic heart disease, heart failure, stroke, valvular heart disease, rhythm disorders, peripheral artery disease, cardiac critical care, and resuscitation science.We will publish articles in the disciplines of genetics, epidemiology and prevention, diagnostic testing and imaging, interventional and pharmacologic therapeutics, translational research, health care policy and outcomes, and global health.In addition to cutting-edge research investigations and state-of-the art reviews, practical clinical information will include guidelines synopses, evidence reviews, and clinical challenges, and many of our articles will offer our readers continuing medical education.The vision for JAMA Cardiology is to serve both the research and clinical communities and become the definitive journal for cardiovascular investigators, clinicians, and trainees throughout the world.A taste of the content to be found in future issues of the journal is represented in this week's inaugural Online First issue.Fox and colleagues 8 from the National Heart, Lung, and Blood Institute-sponsored Jackson Heart Study examine prediction models for major cardiovascular events in African American individuals.The report of this seminal study is accompanied by an editorial by Goff and Lloyd-Jones, 9 who discuss the implications of this study in light of the 2013