tbuckley/cabot-search huggingface dataset:
Functional dissection of the 11q14 amplicon in breast cancer implicates GAB2 as a driver oncogene
Authors: Melanie Bocanegra, Anna Bergamaschi, Young Kim, Anita Langerod, Jessica Kao, Anne-Lise Borresen-Dale, Jonathan Pollack
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4431 

Previous studies have identified chromosome cytobands 11q12-q14 as a gene dense region harboring multiple independent amplicons involved in tumorigenesis. By combining array-based comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH) analysis on breast tumors (n=145) and cell lines (n=45), we have identified localized recurrent amplification at 11q14 that includes the docking protein GAB2, known to function in EGFR signaling. Although recent studies engineering GAB2 overexpression in mammary epithelial cells have implicated GAB2 as a candidate oncogene, its role in breast cancer progression when amplified is not well understood. We therefore used small interfering RNAs (siRNAs) to assess the phenotypic response to GAB2 knockdown in breast cancer cell lines harboring amplification of the 11q14 region. Knockdown of GAB2 using two independent siRNAs targeting GAB2 (in comparison to two mismatch control siRNAs) was associated with decreased cell proliferation in the two cell lines tested (MDA-MB-468 and SUM 52) with GAB2 amplification and/or overexpression. Moderate effects on proliferation were also observed in a cell line (BT474) harboring ERBB2 amplification, consistent with the possibility that GAB2 can function downstream of ERBB2. Our studies implicate amplification/overexpression of GAB2 as contributing to the high proliferation rates of breast cancer cells, and suggest the potential utility of targeting GAB2 in breast tumors with amplification or overexpression.
Relationship of completion of planned treatment and timing of adjuvant chemotherapy to survival in patients with colorectal cancer (CRC).
Authors: S. Ahmed, I. Ahmad, T. Zhu, S. K. Yadav, F. M. Arnold, K. Haider, R. Alvi, A. Sami
Journal: Journal of Clinical Oncology (2010)

3652 Background: Adjuvant therapy results in significant improvement in disease free survival (DFS) and overall survival (OS) in patients with localized CRC. Although addition of oxaliplatin based therapy improves outcome, little is known about the significance of timing of adjuvant therapy and its completion in such patients. Our study aims to determine the prognostic impact of timing of adjuvant therapy and its completion in early-stage CRC. Methods: Medical records of patients with stage III colon and stage II and III rectal cancer diagnosed between 1993 and 2000 in the province of Saskatchewan were reviewed. Cox proportional hazards models were used to assess the prognostic importance of various clinico- pathologic factors including age (65 vs. < 65 years), gender, disease stage (2 vs.3), tumor site (colon vs. rectal), grade (3 vs. < 3), failure to complete adjuvant treatment, number of examined lymph nodes (< 12 vs. ≥ 12), timing of adjuvant therapy (< 56 vs. ≥ 56 days), and T status (T4 vs. < T4). Results: 663 eligible patients with a median age of 66 years were identified. M:F was 58:42. 8% patients had stage III disease and 55% had colon cancer. All patients with rectal cancer received radiation treatment. Median follow-up was 54.6 months. 65% patients received adjuvant therapy < 56 days of surgery. Five-year DFS and OS of patients who received adjuvant therapy < 56 days of surgery was 54.6% and 59.5% respectively compared with 51.9% and 57.1% respectively of patients who received adjuvant therapy ≥ 56 days (p = NS). Overall 79% patients received all planned treatment. Five-year DFS and OS of patients who completed planned treatment was 56.7% and 62.3% respectively compared with 42.1% and 45% respectively of patients who did not complete adjuvant therapy (p < 0.0001). No clinical factor significantly correlated with completion of planned treatment. On multivariate analysis old age, T4 tumor, grade 3 disease, stage III tumor, failure to complete adjuvant treatment, and rectal tumor were identified as poor prognostic factors. Conclusions: Although time to adjuvant therapy following surgical resection did not impact the outcomes, failure to complete planned therapy was associated with an inferior outcome. No significant financial relationships to disclose.
Abstract 17457: Selective, Extra-Corporal LDL-C Apheresis Markedly Reduces Atherosclerotic Vessel-Wall Inflammation in High-Risk Patients
Authors: Diederik F Van Wijk, Barbara Sjouke, Fleur van der Valk, Andrea Bochem, Marion Koopman, Hein Verberne, Aart Nederveen, Kees Hovingh, Willem Mulder, John Kastelein, Erik Stroes
Journal: Circulation (2012)

Background:   Low-density lipoprotein cholesterol (LDL-C) plays a pivotal role in the pathogenesis of cardiovascular disease. Inflammation has been accepted as a partly independent contributor in the development of complicated plaques and ensuing clinical events. The exact relation between LDL-cholesterol and vessel wall inflammation is less well characterized.    Methods:   We selec0ted patients with familial hypercholesterolemia (FH) characterized by profoundly elevated LDL-cholesterol (LDL-C) levels, who could not be treated with statins due to statin-intolerance. In these patients, we performed weekly LDL-apheresis using a selective LDL-C removal column (DALI) during a period of 8 weeks. As control groups we selected age and sex-matched healthy individuals with normal LDL-C, as well as high-risk patients with intermediately elevated LDL-C. In all patients vascular inflammation (target-to-background-ratio (TBR) by 18F-fluorodeoxyglucose (FDG)-positron emission topography (PET) in the ascending aorta and carotids were assessed. TBR measurements were repeated in FH-patients after 8 weeks of LDL-apheresis.    Results:   Inflammatory activity (TBR max ) of the aorta in FH-patients as well as in high-risk patients with increased LDL-C levels was significantly higher compared to TBR max  in healthy control subjects (p max  of the ascending aorta was decreased by 18.4% (SD 14.1), whereas the TBR max  of the carotids was decreased by 10.9% (SD 9.0)(both p    Conclusions:   Potent, selective LDL-C lowering by extra-corporeal LDL-C apheresis profoundly reduces the increased inflammatory activity of the atherosclerotic vessel-wall in patients with elevated LDL-C levels and overt atherosclerosis. These data lend proof for a direct, causal role of LDL-C in eliciting vascular inflammation, implying that potent LDL-C lowering strategies have the potential to reduce vessel-wall inflammation in patients with overt atherosclerosis.
Intraperitoneal administration of small interfering RNA targeting nuclear factor kappa B with paclitaxel successfully prolong the survival of murine xenograft with peritoneal metastasis of gastric cancer
Authors: M. Inoue, S. Matsumoto, N. Tokuyasu, H. Saitoh, S. Tsujitani, M. Ikeguchi
Journal: Journal of Clinical Oncology (2008)

14678 Background: Activation of nuclear factor-kappa B (NF-κB) is associated with increased tumor growth, metastasis, resistance to chemotherapeutic agents and poor prognosis. As such, NF-κB is a potential target for antitumor therapy. We invesigated whether intraperitoneal administration of NF-κB p65 siRNA and paclitaxel was effective in the treatment of peritoneal metastasis of gastric cancer. Methods: NF-κB p65 expression were evaluated by western blot. Apoptosis were evaluated cell cycle analysis and Hoechst staining. siRNA transfection were evaluated immunofluorescence microscopy and immunohistochemistry. Murine xenograft model were received i.p.injection of a single suspension of MKN1 or MKN45. Results: <in vitro>NF-κB p65 normally resides in the cytoplasm and is upregulated in the nucleus in response to paclitaxel. NF-κB p65 expression was diminished by NF-κB p65 siRNA. Pre-G1 cells, corresponding to apoptotic cells, increased after transfection of NF-κB p65 siRNA compared with control siRNA in the treatment of paclitaxel. Hoechst 33258 staining showed exclusive apoptosis of MKN-45 after treatment of paclitaxel and NF-κB p65 siRNA. <In vivo>Abundant fluorescence was demonstrated in the surface of intraperitoneal nodules of gastric cancer when the siRNA/liposome complex was administered. And, NF-κB expression was reduced mainly in the surface of intraperitoneal nodules where siRNA was transfected when mice were treated with NF-κB p65 siRNA/liposome. Although equivalent numbers of cancer cells were injected, cancer growth rates differed among the treatment groups.NFκ-B p65 siRNA/liposome and paclitaxel treated group tend to be inhibited the growth than other groups. Survival of mice treated NFκ-BsiRNA/liposome and paclitaxel was significantly prolonged for all treatment groups compared with other groups. Conclusions: Intraperitoneal administration of NF-κB p65 siRNA and paclitaxel inhibited cancer growth in mice with peritoneal metastasis of gastric cancer. Therefore, intraperitoneal administration of NF-κB p65 siRNA and paclitaxel might cause a breakthrough in the treatment of peritoneal metastasis of gastric cancer. No significant financial relationships to disclose.
Antitumor Immunity. V. BCG-Induced Growth Inhibition of Murine Tumors. Effect of Hydrocortisone, Antiserum Against Theta Antigen, and Gamma-Irradiated BCG
Authors: P. K. Ray, T. B. Poduval, K. Sundaram
Journal: JNCI Journal of the National Cancer Institute (1977)

Dimethylbenzdithionsaphthene (DBDN)-induced fibrosarcoma transplantable in syngeneic Swiss mice was a weakly immunogenic tumor and did not regress spontaneously. BCG from India, when incubated with the lethal dose of DBDN-induced fibrosarcoma and subsequently inoculated sc into the susceptible animal markedly inhibited growth of the tumor. Animals that did not show any tumors developed tumor-specific immunity. BCG, if administered separately and not inoculated with the tumor cells, did not show similar response. The close contact between the BCG organism and the tumor cell seemed to be an essential requirement for BCG-induced tumor-growth inhibition. Hydrocortisone-treated animals showed tumor growth even when a BCG-tumor admixture was incorporated, indicating the immunologic nature of the phenomenon. Animals preinoculated with anti-O-serum also showed tumor growth when the BCG-tumor admixture was given. This, however, pointed out a major role of O-bearing lymmphocytes in BCG-induced-tumor-growth inhibition.
Capecitabine (X) vs bolus 5-FU/leucovorin (LV) as adjuvant therapy for colon cancer (the X-ACT study): positive efficacy results of a phase III trial
Authors: J. Cassidy, W. Scheithauer, J. McKendrick, H. Kröning, M. P. Nowacki, J. F. Seitz, C. Twelves, G. Van Hazel, A. Wong, E. Díaz-Rubio
Journal: Journal of Clinical Oncology (2004)

3509 Background Treatment with capecitabine (XELODA), a tumor-activated oral fluoropyrimidine, led to significantly superior response rates and improved safety over bolus 5-FU/LV in 1st-line metastatic colorectal cancer patients. MethodsPatients with resected Dukes' C colon cancer were randomized to oral X (1250 mg/m2 twice daily days 1–14, every 3 weeks) or i.v. 5-FU/LV (Mayo Clinic regimen: LV 20 mg/m2+ 5-FU 425 mg/m2 days l-5, every 4 weeks) for 24 weeks' treatment. The primary endpoint was at least equivalence in disease-free survival (DFS). Results A total of 1987 patients from 164 centers were randomized between 11/98 and 11/01. The arms were well balanced for prognostic factors. Median follow-up is 3.8 years. The primary endpoint of the study was met. X was at least equivalent to 5-FU/LV with regard to DFS in the per protocol population (HR 0.89 [95% CI 0.76–1.04]). In the intent to treat (ITT) analysis there was a strong trend towards superior DFS for X vs 5-FU/LV (HR 0.87 [95% CI 0.75–1.00], p = 0.0528), and a trend to superiority for overall survival (OS; ITT: HR 0.84 [95% CI 0.69–1.01], p = 0.0706). Relapse-free survival (RFS) was superior for X vs 5-FU/LV (ITT: HR 0.86 [95% CI 0.74–0.99], p = 0.041). The results seen in the entire population were maintained in patients ≥ 70 years. The favorable safety profile of X compared to 5-FU/LV has been described earlier (Scheithauer, Ann Oncol 2003;14:1735–43). Conclusion The primary endpoint of the study was met. The trend to superiority in DFS and OS, supported by superior RFS and safety mean that X should replace 5-FU/LV in the adjuvant therapy of colon cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche Roche
Tumor-Associated Antigen (TAA) and Anti-TAA Antibodies in the Serum of BALB/c Mice With Plasmacytomas
Authors: Jean-Pierre Kolb, Marie-France Poupon, Geneviève Lespinats
Journal: JNCI Journal of the National Cancer Institute (1974)

Sera from BALB/c mice bearing plasmacytomas were studied for the possible presence of soluble tumor-associated antigen (TAA) and anti-TAA antibodies. The antibodies were detected by passive hemagglutination, sheep red blood cells being sensitized by a soluble tumor extract as a source of antigen. TAA was detected by inhibition of the hemagglutination of a syngeneic antitumor immune serum. Sera were hemagglutinating (antibody activity), inhibitory (antigen activity), or neutral. A neutral pool of serum was submitted to exclusion chromatography, and the fraction containing the Ig 7S split with acid into 2 fractions: The one of high molecular weight (A) was hemagglutinating (antibody?); the other of low molecular weight (B) was inhibitory (antigen ?). The mixture A+B was neither hemagglutinating nor inhibitory. The peak of lowest molecular weight (albumin fraction) contained free antige.
Combined treatment image guided-intensity modulated radiotherapy (IG-IMRT) plus high-dose rate brachytherapy (HDR) and hormonotherapy (HT) as treatment for high-risk prostate cancer: Five-year result of a phase II study
Authors: B. Guix, J. Bartrina, I. Henriquez, R. Serrate, P. Palombo, J. Vendrell, J. Tello
Journal: Journal of Clinical Oncology (2007)

15571 Background: To report early and late toxicity and preliminary biochemical outcome in 345 patients with high-risk (Gleason &gt;=7; PSA&gt;20 or T2c-T3) clinically localized prostate cancer treated with combined high-dose-rate brachytherapy and IMRT (IMRT-HDR) to the prostate and seminal vesicles with 24–36 months of hormononal treatment (goserelin+bicalutamide) (HT). Methods: Between 12/1999 and 10/2003, 345 patients with PSA&gt;20, Gleason score&gt;6 and/or T2c-T3 N0 M0 prostate cancer were treated with IG-IMRT followed by HDR implant to the prostate and HT. Patients were randomly assigned to receive HT for 24 (group 1, 172 patients) or 36 months (group 2, 173 patients). Acute and late toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. PSA failure was defined as nadir +2.0 ng/ml. Results: All patients completed treatment. One patient included in the group 1 and none of the group 2 experienced grade 3 rectal toxicity (rectal ulcer). Seven patients in each group (4.0%) developed acute Grade 2 urinary symptoms, and none experienced urinary retention. No patient (0%) developed Grade 4 rectal complications or grade 3 or 4 urinary complications. With a median follow-up of 44 months, the 5-year actuarial PSA relapse-free survival rates for the whole group of patients was 95.7 %. No statistical differences between group 1 and 2 patients were found. Conclusions: High-dose IG-IMRT+HDR and HT was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute and late rectal and urinary complications were significantly low, compared with what has been observed with high-dose conventional, 3D-conformal or IMRT-only. Short-term PSA control rates seem to be at least comparable to those achieved with 3D-EBRT or IMRT. Both treatment regimes were very effective. Longer follow-up is needed to know if better PSA control rate are achieved with longer HT. No significant financial relationships to disclose.
Could the Discrepancy in Perceived Emotional Care Received and Provided Be a Barrier to Active Diabetes Self-management? Insights From the Second Diabetes Attitudes, Wishes and Needs (DAWN2) Study
Authors: Katharine D. Barnard, Richard I.G. Holt, Pamela A. Dyson, Michael H. Cummings, Naresh Kanumilli, Simon O’Neill, Gwen Hall
Journal: Diabetes Care (2015)

Low-fat diets and regular physical activity are recommended for good health, but U.K. household expenditure on butter, sugar, preserves, and soft drinks has risen steadily; fewer than half of men (46%) and women (37%) report walking for 10 min at least once per month and 67% of men and 57% of women are overweight or obese (1). With 86% of people with type 2 diabetes and 62% of those with type 1 diabetes being overweight or obese (1), their lifestyles are likely to be influenced by the overall societal trend for busy lives, quick meals, and little physical activity.

The global second Diabetes Attitudes, Wishes and Needs (DAWN2) study was a multi-stakeholder survey conducted in 17 countries (2), exploring factors affecting diabetes self-management and support for people with diabetes. Nearly half of the people with diabetes surveyed (45%) reported diabetes-related distress and ∼14% had likely depression (3). Emotional support from health care professionals was reported by only 32% of people with diabetes (3). Global DAWN2 results demonstrated notable differences in findings concerning people with diabetes among participating countries (3). Here, we provide a descriptive analysis of key U.K. DAWN2 data examining potential barriers to active and optimal self-management among people with diabetes.

DAWN2 (ClinicalTrials.gov identifier NCT01507116) methodology has been published previously (2). Data were generated through stakeholder-specific questionnaires, including standardized instruments …
Direct activation of STING in the tumor microenvironment partially overcomes immune tolerance in neu-N transgenic mice
Authors: Jeremy Foote, James M Leatherman, Todd D Amstrong, Laureen Ojalvo, David Kanne, Elizabeth M Jaffee, Tom Dubensky, Leisha Emens
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts STING signaling induces interferon-β production by intratumoral dendritic cells (DCs), driving T cell priming within the tumor microenvironment. However, the impact of antigen-specific tolerance on this process is not well studied. We therefore examined the efficacy of in situ
O085 : Lanreotide reduces liver volume yet accelerates muscle wasting and weight loss in symptomatic polycystic liver disease
Authors: F. Temmerman, T.A. Ho, R. Vanslembrouck, W. Coudyzer, J. Billen, F. Dobbels, J. van Pelt, B. Bammens, Y. Pirson, F. Nevens
Journal: Journal of Hepatology (2015)
Phase II study of hyperfractionated radiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer
Authors: M. Ikeda, H. Ueno, T. Okusaka, C. Morizane, Y. Ito, Y. Kagami, H. Ikeda
Journal: Journal of Clinical Oncology (2005)

4111 Background: As shown in our previous phase I study (Oncology 2004, 67:215–221), hyperfractionated radiation therapy (HFRT) with concurrent administration of protracted 5-fluorouracil (5-FU) infusion appears to be feasible and effective in locally advanced pancreatic cancer (LAPC). The present phase II study was conducted to assess the efficacy and toxicity of HFRT with protracted 5-FU infusion in patients (pts) with LAPC. Methods: Eligibility criteria included locally advanced unresectable pancreatic cancer, histological or cytological confirmation of adenocarcinoma, 20–74 years of age, Karnofsky performance status of ≥70, and no prior chemotherapy or radiotherapy. All pts received two fractions of 1.2 Gy each per day for 5 days a week over 5.3 weeks (total dose, 64.8 Gy) and protracted 5-FU infusion (200 mg/m2/day) during the course of radiation therapy. After this therapy, patients received gemcitabine (1000 mg/m2 weekly x 3 every 4 weeks) for at least 4 courses. Results: Thirty-nine of 40 enrolled pts were assessable for efficacy and toxicity. Of the 39 pts, 35 (90%) pts completed the scheduled course of treatment. Although no complete response was seen, a partial response was obtained in 16 (41%) pts and 18 (47%) pts showed stable disease according to RECIST criteria. At the time of analysis, although 20 pts developed distant metastasis, local progression has not been observed. The median time to progression was 7.8 months, and the median overall survival was 13.2 months with 1-year survival rates of 56%. The most common grade 3–4 toxicities observed during radiation therapy were anorexia (59%), nausea (21%), gastric or duodenal ulcer (13%), and fatigue (13%). Hematological toxicity was mild and transient. With regard to late complications, one patient developed treatment-resistant gastric ulcer. Conclusions: HFRT with protracted 5FU infusion showed good local control and survival with an acceptable toxicity profile in pts with LAPC. No significant financial relationships to disclose.
Shining a Light on the Dark Side
Authors: Linda Ray
Journal: Annals of Internal Medicine (2016)

Letters5 January 2016Shining a Light on the Dark SideLinda Ray, MDLinda Ray, MDFrom Beaumont, Texas.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:A local reporter tweeted me about the anonymous essay "Family Secrets" (1). My copy of Annals was still sitting on the kitchen table, and I immediately read the essay as well as Laine and colleagues' editorial that reviewed the journal's decision to print it (2). I hope that someone at the American College of Physicians understands the consequences of printing an anonymous report of what is likely more about the embarrassment of someone who did not stand up when he or she should have (and still is not doing so because of the anonymous nature of the ...References1. Anonymous.. Our family secrets. Ann Intern Med. 2015;163:321. [PMID: 26280420]. doi:10.7326/M14-2168 LinkGoogle Scholar2. Laine C, Taichman DB, LaCombe MA. On being a doctor: shining a light on the dark side [Editorial]. Ann Intern Med. 2015;163:320. [PMID: 26280419]. doi:10.7326/M15-1144 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Beaumont, Texas.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0515. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOn Being a Doctor: Shining a Light on the Dark Side Christine Laine , Darren B. Taichman , and Michael A. LaCombe Shining a Light on the Dark Side Gaetan Sgro , Mark T. Gladwin , Alexander Teng , Akshata Moghe , and Shanta M. Zimmer Shining a Light on the Dark Side Jordan Cohen and Richard I. Levin Shining a Light on the Dark Side Elizabeth Allemann Shining a Light on the Dark Side Christine Laine , Darren B. Taichman , and Michael A. LaCombe Shining a Light on the Dark Side Alvaro F. Vargas Pelaez Shining a Light on the Dark Side Shafik Dharamsi Metrics 5 January 2016Volume 164, Issue 1Page: 68-69KeywordsBehaviorChild abuseConflicts of interestDisclosureMedical education ePublished: 5 January 2016 Issue Published: 5 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...