tbuckley/cabot-search huggingface dataset:
Impact of tumor site on bevacizumab (BEV) efficacy in metastatic colorectal cancer (mCRC).
Authors: Hui-Li Wong, Kathryn Maree Field, Anna Lomax, Mark Tacey, Jeremy David Shapiro, Joseph James McKendrick, Allan Solomon Zimet, Desmond Yip, Louise M. Nott, Ross Jennens, Gary Edward Richardson, Jeanne Tie, Suzanne Kosmider, Phillip Parente, Lionel Lim, Prasad Cooray, Ben Tran, Jayesh Desai, Rachel Wong, Peter Gibbs
Journal: Journal of Clinical Oncology (2014)

e14558 Background: With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for an individual patient (pt). While the prognostic impact of primary tumor site on CRC outcomes is established, emerging data suggest potential differences in response to biologic therapies. Here we explore the impact of tumor site on BEV efficacy in pts with mCRC. Methods: Analysis of pts enrolled in an Australian prospective multicenter mCRC registry. Pts diagnosed from July 2009 to December 2013 and treated with first line chemotherapy were included. Tumor site was defined as: right colon (RCC) – cecum to transverse, left colon (LCC) – splenic flexure to rectosigmoid, and rectum (RC). Kaplan Meier and Cox models were used for survival analyses. Results: Of 541 pts, 160 (29.6%) had RCC, 201 (37.2%) LCC and 180 (33.3%) RC primaries. Median age was 69, 66 and 63 years respectively (p=0.002). There was no significant difference in performance status (PS), comorbidities or number of metastatic sites. RCC was associated with peritoneal (32.5, 19.4 vs 6.1%, p<0.0001) and RC with lung disease (27.5, 26.4 vs 40%, p=0.008). Overall survival (OS) was longest in pts with RC, followed by LCC and RCC (median: 29.7, 22.4 and 18.9 months, p=0.001). 339 (62.7%) pts received BEV. Progression-free survival (PFS) was superior for BEV-treated pts in all groups, though not reaching statistical significance for RC pts (table). Similar trends were observed for OS, although these were dependent on some clinical factors (data not shown). Conclusions: As previously reported, tumor site appears to be prognostic in mCRC, with RC and RCC associated with best and worst outcomes respectively. Pts who received BEV in addition to chemotherapy had superior PFS and OS, with the effect appearing greatest in RCC pts. Although known prognostic factors were adjusted for, other clinicopathologic differences that may contribute to pt outcomes cannot be excluded. Pt accrual is ongoing and molecular analyses are planned. Median PFS (months) BEV vs No BEV HR* 95% CI P RCC 8.8 vs 5.6 0.54 0.35-0.84 0.006 LCC 11.1 vs 6.2 0.67 0.46-0.97 0.035 RC 13.8 vs 9.2 0.80 0.54-1.19 0.270 *Adjusted for age, sex, PS, comorbidity.
Duration of chemotherapy for advanced non-small cell lung cancer: An updated systematic review and meta-analysis
Authors: Y. Soon, M. R. Stockler, M. Boyer, L. Askie
Journal: Journal of Clinical Oncology (2008)

8013 Background: The optimal duration of chemotherapy to maximize survival and quality of life (QOL) in advanced non- small cell lung cancer (NSCLC) is unclear. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) comparing longer versus shorter durations of chemotherapy. Methods: We searched MEDLINE, EMBASE, CENTRAL, annual meeting proceedings of ASCO and World Conference on Lung Cancer to December 07 for RCTs comparing 1) a defined number of cycles of chemotherapy versus continuing until disease progression, 2) a defined number of cycles versus a higher number of cycles of the same chemotherapy and, 3) a defined number of cycles of initial chemotherapy vs the same initial chemotherapy followed by additional cycles of a different chemotherapy. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), adverse events (AE), and QOL. Hazard ratios (HR), confidence intervals (CI), p-values (p) were estimated with fixed effects models using Revman 4.2.8. Results: We found 13 RCTs including 2416 patients. Longer durations of chemotherapy prolonged PFS significantly (HR 0.78, 95% CI 0.72 to 0.86, p < 0.00001) but not OS (HR 0.94, 95%CI 0.87 to 1.01, p = 0.10). Subgroup analysis revealed that effects on PFS were greater with 3rd generation chemotherapy regimes such as paclitaxel, vinorelbine, gemcitabine or docetaxel (HR 0.73 versus 0.92 p value for interaction = 0.02). AE were more frequent with longer durations of chemotherapy. QOL was assessed in 7 trials with variable results. Conclusions: Continuing 3rd generation chemotherapy beyond 3 or 4 cycles significantly increased progression free survival but not overall survival and produced more adverse events. Future trials should determine if extending treatment with targeted agents rather than chemotherapy can improve progression free and overall survival without increasing toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly, sanofi- aventis
Satraplatin: A new treatment option for patients with hormone refractory prostate cancer
Authors: F. E. Nathan, C. Sternberg, O. Sartor, D. Petrylak, F. Witjes, K. Wosikowski, M. E. Petrone, M. Rozencweig
Journal: Journal of Clinical Oncology (2005)

4802 Background: There is no chemotherapeutic agent specifically approved for second-line treatment for hormone-refractory prostate cancer (HRPC). Satraplatin (S) is a third-generation oral platinum compound studied in a variety of tumors, including HRPC. Results of previous phase II and III trials suggested activity in HRPC. A randomized trial conducted by the EORTC in 50 patients evaluated S as first-line therapy in HRPC. The median progression-free survival (PFS) was longer in the satraplatin + prednisone (S + P) arm than in the P alone arm. This difference was statistically significant (p = 0.023). Furthermore, a >50% decrease from baseline PSA value was seen in 9 of 27 patients (33%) in the combination arm compared to 2 of 23 (9%) patients in the P arm (p = 0.046). We have initiated a randomized phase III trial evaluating S as second line therapy for HRPC. Methods: The primary objective is to compare time to tumor progression (TTP) and PFS in patients with HRPC, randomized to either S + P or placebo + P, after failure of 1 prior chemotherapy regimen. Eligible patients include men ≥ 18 years with stage D2 metastatic HRPC with progressive disease after a minimum of 2 courses of 1 prior cytotoxic chemotherapy regimen. The final analysis will be performed after 637 events of disease progression have been observed. Using a significance level of 0.034, the trial has 85% power to detect a 30% improvement in TTP. Results: Accrual is ongoing. Conclusions: Results of 2 studies, SWOG 99–16 and TAX327, demonstrated a survival advantage for the docetaxel-containing arm, and docetaxel is approved for use in HRPC. However, the duration and response to first line chemotherapy is limited, and there is an unmet medical need for agents that provide palliation and improve survival. S has demonstrated in vitro activity against taxane-resistant cell lines and significantly prolonged PFS for untreated HRPC patients in a randomized setting. These observations formed the scientific rationale for GPC Biotech to initiate an international multi-center, double-blind, randomized phase III trial comparing S + P to placebo + P as second-line cytotoxic therapy for men with HRPC. The trial is open and actively accruing patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GPC Biotech AG, GPC Biotech GPC Biotech GPC Biotech GPC Biotech GPC Biotech
Spontaneous Mutations of Bcor and Jak1/2 genes Lead to an Aggressive Leukemia of B-1 Progenitor B Cells
Authors: Sheryl M Gough, Liat Goldberg, Marbin Pineda, Robert L Walker, Yuelin J Zhu, Sven Bilke, Paul S Meltzer, Peter D Aplan
Journal: Blood (2014)
Confidence Crisis Among General Surgery Residents
Authors: Dawn M. Elfenbein
Journal: JAMA Surgery (2016)

In the surgical community, there is concern that general surgery residents are choosing subspecialty training in large numbers because of a crisis in confidence at the end of training. Confidence is an essential quality of surgeons, and recent studies have attempted to quantify and measure it in graduating general surgery residents.To systematically review the quality of evidence provided and to critically analyze the language used to describe the findings using quantitative methods.A systematic review of the PubMed indexed literature on general surgery resident confidence was performed in March 2015. A summative table of each study's hypothesis, definition of confidence, quality using the Medical Education Research Study Quality Instrument, influence using Web of Science citations, results, and conclusions was created, and qualitative coding was applied to identify emerging themes. No date restrictions were used in the search.Fifteen survey studies have been performed that measure confidence or readiness to practice. Although 5 studies had neutral or positive conclusions, most studies reported low confidence in general surgery graduates. There are conflicting data about definitions of confidence. The relationships between confidence, autonomy, and competence are varied and complex. Comparisons with the past are frequent.Confidence is difficult to define and measure. Despite limitations, survey studies are used to shape discourse and influence policies. Social and cultural factors influence self-efficacy, and focusing on operative volume and autonomy alone may not address all of the reasons that some residents express concerns about readiness to practice.
Aging, inflammation, immunity and periodontal disease
Authors: Jeffrey L. Ebersole, Christina L. Graves, Octavio A. Gonzalez, Dolph Dawson, Lorri A. Morford, Pinar Emecen Huja, James K. Hartsfield, Sarandeep S. Huja, Subramanya Pandruvada, Shannon M. Wallet
Journal: Periodontology 2000 (2016)

Abstract The increased prevalence and severity of periodontal disease have long been associated with aging, such that this oral condition affects the majority of the adult population over 50 years of age. Although the immune system is a critical component for maintaining health, aging can be characterized by quantitative and qualitative modifications of the immune system. This process, termed ‘immunosenescence’, is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasia and autoimmunity, presumably reflecting the prolonged antigenic stimulation and/or stress responses that occur across the lifespan. Interestingly, the global reduction in the host capability to respond effectively to these challenges is coupled with a progressive increase in the general proinflammatory status, termed ‘inflammaging’. Consistent with the definition of immunosenescence, it has been suggested that the cumulative effect of prolonged exposure of the periodontium to microbial challenge is, at least in part, a contributor to the effects of aging on these tissues. Thus, it has also been hypothesized that alterations in the function of resident immune and nonimmune cells of the periodontium contribute to the expression of inflammaging in periodontal disease. Although the majority of aging research has focused on the adaptive immune response, it is becoming increasingly clear that the innate immune compartment is also highly affected by aging. Thus, the phenomenon of immunosenescence and inflammaging, expressed as age‐associated changes within the periodontium, needs to be more fully understood in this era of precision and personalized medicine and dentistry.
NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016
Authors: Steven M. Horwitz, Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, John C. Byrd, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Thomas M. Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T. Hoppe, Mark S. Kaminski, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Matthew Lunning, Auayporn Nademanee, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A. Saad, Lubomir Sokol, Lode J. Swinnen, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer, Hema Sundar, Pierluigi Porcu
Journal: Journal of the National Comprehensive Cancer Network (2016)

Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.
Loss of Programmed Death Ligand-1 Expression on Donor T Cells Lessens Acute Graft-Versus-Host Disease Lethality
Authors: Asim Saha, Roddy S. O'Connor, Govindarajan Thangavelu, Scott B. Lovitch, Durga Bhavani Dandamudi, Caleph B. Wilson, Benjamin G. Vincent, Kazutoshi Aoyama, Patricia A. Taylor, Angela Panoskaltsis-Mortari, Rocio Foncea, Joel S. Burrill, Lili Guo, Catarina Sacristan, Scott N. Furlan, Nathaniel W. Snyder, Ian A. Blair, Michael C. Milone, Michael L. Dustin, James L. Riley, David A. Bernlohr, Laurence A. Turka, William J. Murphy, Brian T. Fife, David H. Munn, Jeffrey S. Miller, Jonathan S. Serody, Leslie Kean, Gordon J. Freeman, Arlene H. Sharpe, Bruce R. Blazar
Journal: Blood (2015)
The Proinflammatory Protein S100A9 Suppresses Erythropoietin Elaboration in Patients with Myelodysplastic Syndromes
Authors: Thomas Cluzeau, Kathy L McGraw, Brittany Irvine, Erico Masala, Lionel Ades, Ashley A Basiorka, Ghulam J Mufti, Jaroslaw P. Maciejewski, Sheng Wei, Pierre Fenaux, Valeria Santini, Alan F. List
Journal: Blood (2015)
Preclinical Development Of ROR1 Peptide Based Vaccine With Activity Against Chronic Lymphocytic Leukemia In ROR1 Transgenic Mice
Authors: Jian Yu, Bing Cui, George F. Widhopf, Liguang Chen, Laura Rassenti, Zhengran Wang, Shuyu Ma, Tomoko Hayashi, Dennis A. Carson, Thomas J. Kipps
Journal: Blood (2013)
Comparing Painful Stimulation vs Rest in Studies of Pain
Authors: Christian Büchel, Stephan Geuter, Christian Sprenger
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Heterogeneity of acquired KRAS and EGFR mutations in colorectal cancer patients treated with anti-EGFR monoclonal antibodies.
Authors: M. Pia Morelli, Michael J. Overman, Arvind Dasari, Syed Mohammad Ali Kazmi, Eduardo Vilar Sanchez, Cathy Eng, Bryan K. Kee, Laurel Deaton, Chris R. Garrett, Frank Diehl, Philipp Angenendt, Scott Kopetz
Journal: Journal of Clinical Oncology (2013)

3512 Background: Although KRAS and EGFR extracellular domain acquired mutations were detected in two small cohorts and correlated with acquired resistance to anti-EGFR monoclonal antibodies (MAb), the frequency, co-occurrence, and distribution of these acquired mutations is unknown. In this study we evaluated the presence of acquired KRAS and EGFR mutations in cfDNA from CRC patients (pts) treated with anti-EGFR monoclonal antibody. Methods: Plasma was collected from EGFR-MAb refractory mCRC pts as part of the ATTACC (Assessment of Targeted Therapies Against Colorectal Cancer) program. Eligible pts had documentation of pre-treatment KRAS wild type tumor. The cfDNA was extracted from the plasma and analyzed by BEAMing technology for acquired KRAS and EGFR mutation. Results: The plasma from 55 patients was analyzed for EGFR and KRAS mutation. The S492R EGFR mutation was detected in 4 pts (7%) treated with cetuximab. Acquired KRAS mutations were detected in 26 of the 55 KRAS wt samples analyzed (47%). Although codon 61 and 146 mutations are rare in untreated CRCs (2% and 1% of the MDACC population, respectively), these atypical KRAS mutations predominated in acquired resistance (Q61H=33% and A146T=10%). Mutations in more than one KRAS codon are exceedingly rare in the primary tumor. In our study we detected more than one KRAS or EGFR mutation in 30% of the population (p&lt;0.001), suggesting the development of multiple independent clones in individual patients. Compared to 8 patients with known KRAS mutations, the average number of mutant reads in the 26 patients with acquired mutation was substantially lower (p&lt;0.01) despite similar tumor burden. Of note, acquired concomitant KRAS mutations were also found in a BRAF V600 mutant patient previously treated with anti-EGFR MAb and a BRAF inhibitor. Conclusions: KRAS and EGFR acquired mutation are present at low concentrations in cfDNA from mCRC pts refractory to anti-EGFR MAb and they are not mutually exclusive, suggesting heterogeneity of the resistant clones. Anti-EGFR MAb refractory patients showed a higher incidence of atypical KRAS mutation and higher incidence of multiple codon KRAS mutations compared with overall CRC patient.
Use of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
Authors: Y. Elkerm, I. M. Ali, A. A. Elsaid
Journal: Journal of Clinical Oncology (2010)

e11101 Background: Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that over expresses HER2. We investigated its efficacy and safety after excision of early stage breast cancer and completion of chemotherapy. Methods: Two hundred breast cancer patients with HER2-positive tumors were randomly assigned to either intervention or control arm. Both arms received 3 cycles of FEC followed by 3 cycles of docetaxel. In addition, the intervention arm received trastuzumab every 3 weeks for one year concomitantly with docetaxel. The primary end points was 3-year disease-free survival. Results: Disease free survival at 3 years was better in the intervention group as compared to the group who did not receive the antibody (89 percent vs. 78 percent; hazard ratio for recurrence or death 0.42, 95 percent confidence interval, 0.21 to 0.88; p = 0.01. Trastuzumab group was not associated with decreased left ventricular ejection fraction or cardiac failure. Conclusions: Addition of trastuzumab to adjuvant therapy in HER2 over-expressing breast cancer can improve 3-year disease-free survival. No significant financial relationships to disclose.
A phase 2 trial of TRC105 with bevacizumab for bevacizumab refractory glioblastoma.
Authors: Manmeet Singh Ahluwalia, Lisa R. Rogers, Rekha T. Chaudhary, Herbert B. Newton, Ben K. Seon, Manoj A. Jivani, Bonne J. Adams, Ronald L. Shazer, Charles P. Theuer
Journal: Journal of Clinical Oncology (2016)

2035 Background: Endoglin is an endothelial cell membrane receptor highly expressed on tumor vessels that is essential for angiogenesis. It is upregulated by hypoxia and VEGF inhibition and may be an important mechanism of VEGF resistance. The combination of TRC105, an anti-endoglin monoclonal antibody, in combination with bevacizumab (Bev) has demonstrated activity in Bev refractory cancer patients with non-CNS tumors. We hypothesized that TRC105 administered with Bev would improve overall survival in glioblastoma patients who progressed on Bev. Methods: Patients with previously treated, recurrent glioblastoma (GBM) with radiographic progression following Bev therapy, KP status ≥ 70%, and adequate organ function were treated with TRC105 10 mg/kg weekly as a single agent (six patients) and then in combination with Bev 10 mg/kg every two weeks (16 patients). The primary endpoint for treatment with TRC105 and Bev was overall survival (OS), with the null hypothesis being OS of 4.0 months and alternative hypothesis being OS of 7.0 months. Results: Twenty-two patients (median age 54.5; M:F 16:6, median prior therapies 3) were enrolled; one patient did not receive TRC105 and was not included in the efficacy analysis. Initially, six patients were treated with TRC105 as a single agent. TRC105 was well tolerated in patients with GBM; each of six patients progressed by 1.40 months of treatment. Sixteen patients were treated with TRC105 and bevacizumab: adverse events (AEs) characteristic of each drug were not increased in frequency or severity during concurrent dosing. Fifteen patients were evaluable for efficacy of the combination and median overall survival (OS) was 5.75 months (95% CI: 4.21, 9.86), which exceeded the historic OS of 4.0 months seen in this patient population with Bev alone. No responses were seen by RANO criteria and median PFS was 1.81 months (95% CI: 1.25, 2.07) Conclusions: The combination of TRC105 and Bev was well tolerated in Bev refractory GBM patients. OS was 5.75 months, which exceeded the historic OS of 4.0 months. Treatment with the combination of TRC105 and Bev is currently being evaluated in Bev naïve GBM patients in a randomized Phase 2 trial. Clinical trial information: NCT01564914.
STAT5b Gene Mutations and Their Association with a Unique Immunophenotype of CD4+CD56+TCRαβ Type LGL Leukemia
Authors: Takahiro Tanahashi, Kazuyuki Matsuda, Nodoka Sekiguchi, Sayaka Nishina, Noriko Senoo, Kaoko Sakai, Hitoshi Sakai, Toshiro Ito, Takeki Mitsui, Yok Lam Kwong, Fumihiro Ishida
Journal: Blood (2014)
Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain
Authors: Lian Cui, Xuerong Miao, Lingli Liang, Ishmail Abdus-Saboor, William Olson, Michael S. Fleming, Minghong Ma, Yuan-Xiang Tao, Wenqin Luo
Journal: Neuron (2016)
Massive, Clinical Grade Expansion Of Polyclonal T Cells Using Blinatumomab For Adoptive Autologous Cellular Therapy Of CLL Patients
Authors: Josée Golay, Anna D’amico, Gianmaria Borleri, Maria Chiara Finazzi, Giulia Quaresmini, Martino Introna, Alessandro Rambaldi
Journal: Blood (2013)
Можливості використання комплексних рослинних препаратів у лікуванні функціональних порушень біліарного тракту у хворих на цукровий діабет II типу
Authors: Ye.S. Sirchak
Journal: GASTROENTEROLOGY (2016)

Наведено результати комплексного обстеження та лікування 60 хворих на цукровий діабет ІІ типу з дискінезією жовчновивідних шляхів. Доведена клінічна ефективність препарату рослинного похо­дження Рафахолін Ц у комплексному лікуванні даного контингенту пацієнтів.