tbuckley/cabot-search huggingface dataset:
Effect of high MMP2 and low MMP9 baseline serum levels on outcome in patients with HER2-positive inflammatory breast cancer (IBC) treated with bevacizumab (BEV)- and trastuzumab (TRA)-based neoadjuvant chemotherapy (NAC) in the BEVERLY 2 study.
Authors: Emeline Tabouret, Anthony Goncalves, Francois Bertucci, Jean-Yves Pierga, Thierry Petit, Christelle Levy, Jean-Marc Ferrero, Mario Campone, Joseph Gligorov, Florence Lerebours, Henri Hubert Roche, Thomas Denis Bachelot, Yves Toiron, Jean-Paul Borg, Olivier L. Chinot, Patrice Viens
Journal: Journal of Clinical Oncology (2015)

600 Background: Addition of BEV to TRA-based NAC in HER2-positive IBC has been associated with high pathological complete response (pCR) rate and favorable outcome in the BEVERLY 2 phase II trial (Pierga, Lancet Oncol, 2012; Viens, SABCS, 2013). Matrix metalloproteinase (MMP) 2 and 9 are matrix-degrading enzymes involved in tumor growth, invasion and angiogenesis. The plasma levels of which were recently associated with response to BEV in high-grade glioma (Tabouret, Neuro-Oncology, 2014). We examined the prognostic impact of MMP2 and MMP9 serum levels in Beverly 2 patients (pts). Methods: Serum levels of MMP2 and MMP9 were analyzed, using ELISA, in 45/52 samples from pts included in the BEVERLY 2 trial. Serums were analyzed at baseline and before surgical resection, and correlated to pCR, disease-free survival (DFS) and overall survival (OS). Results: Baseline (b) MMP2 and MMP9 serum levels were independent from pts characteristics including age, hormone receptor status, SBR grade, circulating tumor cells and endothelial cells, and were not correlated to pCR. As continuous variables (ROC curves), bMMP2 was significantly associated with relapse (p = 0.002) and death (p = 0.049) risks, while bMMP9 was only associated with death risks (p = 0.035). Using median value as cutoff, univariate analyses identified high bMMP2 as correlated to better DFS (p = 0.001) and OS (p = 0.032), while low bMMP9 was correlated to better OS (p = 0.022) and tended to be associated to longer DFS (p = 0.071). In multivariate analyses (DFS only, same cutoff), both bMMP2 (p = 0.003, Hazard Ratio [HR]: 10.614) and bMMP9 (p = 0.041, HR: 3.534) remained correlated to DFS. Between baseline and pre-surgery time points, significant increase in MMP2 and decrease in MMP9 levels (p < 0.001 for both) were observed in 100% and 87% of pts, respectively but did not correlate with outcome. Conclusions: High bMMP2 and low bMMP9 serum levels were associated with a better outcome in HER2-positive IBC pts treated with BEV- and TRA-based NAC. Their predictive value should be evaluated in randomized trial.
Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR)
Authors: Wanshui Yang, Li Liu, Yohei Masugi, Zhi Rong Qian, Reiko Nishihara, NaNa Keum, Kana Wu, Stephanie Smith-Warner, Yanan Ma, Jonathan A Nowak, Fatemeh Momen-Heravi, Libin Zhang, Michaela Bowden, Teppei Morikawa, Annacarolina da Silva, Molin Wang, Andrew T Chan, Charles S Fuchs, Jeffrey A Meyerhardt, Kimmie Ng, Edward Giovannucci, Shuji Ogino, Xuehong Zhang
Journal: Gut (2017)

Although evidence suggests an inverse association between calcium intake and the risk of colorectal cancer, the mechanisms remain unclear. The calcium-sensing receptor (CASR) is expressed abundantly in normal colonic epithelium and may influence carcinogenesis. We hypothesized that calcium intake might be associated with lower risk of CASR-positive, but not CASR-negative, colorectal cancer.We assessed tumour CASR protein expression using immunohistochemistry in 779 incident colon and rectal cancer cases that developed among 136 249 individuals in the Nurses' Health Study and Health Professionals Follow-Up Study. Duplication method Cox proportional hazards regression analysis was used to assess associations of calcium intake with incidence of colorectal adenocarcinoma subtypes by CASR status.Total calcium intake was inversely associated with the risk of developing colorectal cancer (ptrend=0.01, comparing ≥1200 vs <600 mg/day: multivariable HR=0.75, 95% CI 0.60 to 0.95). For the same comparison, higher total calcium intake was associated with a lower risk of CASR-positive tumours (ptrend=0.003, multivariable HR=0.67, 95% CI 0.51 to 0.86) but not with CASR-negative tumours (ptrend=0.67, multivariable HR=1.15, 95% CI 0.75 to 1.78; pheterogeneity=0.06 between the CASR subtypes). The stronger inverse associations of calcium intake with CASR-positive but not CASR-negative tumours generally appeared consistent regardless of sex, tumour location and source of calcium.Our molecular pathological epidemiology data suggest a causal relationship between higher calcium intake and lower colorectal cancer risk, and a potential role of CASR in mediating antineoplastic effect of calcium.
World Medical Association Declaration of Helsinki
Authors: None Not Available
Journal: JAMA (2000)

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Пізні діабетичні ускладнення у хворих на цукровий діабет 2-го типу з HCV-інфекцією
Authors: M.A. Derbak
Journal: GASTROENTEROLOGY (2013)

У роботі наведені результати обстежень 317 хворих на цукровий діабет (ЦД) 2-го типу, які лікувались в ендокринологічному та хірургічному відділеннях Закарпатської обласної клінічної лікарні ім. А. Новака протягом 2010–2012 рр. Вивчена частота та характеристика пізніх діабетичних ускладнень у хворих на ЦД 2-го типу з HCV-інфекцією та без неї. Встановлено, що у хворих на ЦД 2-го типу з HCV-інфекцією значно частіше, ніж у хворих без вірусу, реєструються такі ускладнення, як синдром діабетичної стопи та діабетична нефропатія.
Prognostic factors of gallbladder Cancer: A report of 53 cases
Authors: Hajar Ouahbi, Mariem Benhami, Attassi Meryem, Lamiae Amaadour, Zineb Benbrahim, El'emrabet Fatima Zahra, Arifi Samia, Chakib Nejjari, Nawfal Mellas
Journal: Annals of Oncology (2017)
The choice of irinotecan or oxaliplatin-based chemotherapy in metastatic colo-rectal cancer as first line treatment: Impact on survival (ERCC1 and TOPO1 adjusted analysis)
Authors: Eugeniu Banu, Andreea Serban, Karoly Hajdu Adrian, Irma Banciu Tunde, Codrina Banu Adela
Journal: Annals of Oncology (2017)
Feasibility of collaborative precision medicine oncology between academic- and community-based hospitals.
Authors: Lorna Rodriguez-Rodriguez, Mark Krasna, Kim M. Hirshfield, Veronica Rojas, Gregory Riedlinger, Siraj Mahamed Ali, Vincent A. Miller, Shridar Ganesan
Journal: Journal of Clinical Oncology (2017)

e18015 Background: The Rutgers Cancer Institute of New Jersey (CINJ) is conducting an ongoing, prospective, observational clinical trial that is evaluating use of comprehensive genomic profiling (CGP) and molecular tumor board (MTB) review to assist in caring for patients with rare or refractory cancers. As part of this precision medicine approach to cancer care, CINJ has formed a partnership with community hospitals (Meridian Health) to enroll patients in this study, and to actively participate in MTB meetings. The purpose of this cohort analysis is to evaluate the feasibility of using CGP to identify clinically-relevant genomic alterations as an aid to guiding point-of-care management in a community hospital setting. Methods: Meridian Health staff was trained in patient selection, enrollment, and follow-up. CGP was performed by Foundation Medicine, Inc. The patient case’s clinical history, pathology, and CGP results were presented at an MTB meeting. The enrolling physicians (n = 11) were invited to attend the MTB in person or through web-accessible video conferencing. A letter listing MTB consensus recommendations on potential treatment options was sent to the referring physician, and patient follow-up was scheduled at regular intervals. Results: 35 patients were enrolled by Meridian Health. Gyn and GI cancers were the most common types at enrollment (each 26%, 9 out of 35), followed by breast cancer (20%, 7 out of 35). At study enrollment, the mean KPS was 91%, and 23 patients (66%) had stage IV disease. The median duration between study enrollment and MTB presentation was 44 days. 3 patients were excluded because of deteriorated clinical status at the time of the MTB. MTB-based treatment options were implemented in 9 of 32 patients (28%). This result is similar to those reported in published analyses of patients enrolled at CINJ. Conclusions: Collaborations between an academic cancer center and a community hospital is a feasible approach to facilitating access to precision medicine for cancer patients treated in the community. A larger cohort is needed to determine the impact on patient’s outcomes.
Value Tools for Patients in Cancer Care
Authors: Katy Winckworth-Prejsnar, Lisa Korin Lentz, Elizabeth A. Nardi, Sandhya Pruthi, C. Lyn Fitzgerald, Robert W. Carlson
Journal: Journal of the National Comprehensive Cancer Network (2017)

In order to empower patients as partners in their healthcare decisions, there is an identified need for value tools that provide enough information to help them make decisions regarding their cancer care journey. NCCN convened a multistakeholder working group to identify the gaps and needs of current value tools and develop a set of findings and recommendations for the evolution of value tools for patients. The findings and recommendations of the working group were then presented at the Value Tools for Patients in Cancer Care Patient Advocacy Summit in December 2016, and multistakeholder roundtable panel discussions explored these findings and recommendations along with additional items. This article encapsulates the discussion from the NCCN Working Group meetings and the NCCN Patient Advocacy Summit, including identified gaps and needs in defining value in cancer care, identified principles and parameters of value tools for patients in cancer care, and consensus statements and recommendations offered by the NCCN Working Group.
Endothelial NF-κB Blockade Abrogates ANCA-Induced GN
Authors: Mira Choi, Adrian Schreiber, Claudia Eulenberg-Gustavus, Claus Scheidereit, Jan Kamps, Ralph Kettritz
Journal: Journal of the American Society of Nephrology (2017)

ANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA-activated neutrophils interact with the endothelium, resulting in necrotizing vasculitis. We tested the hypothesis that endothelial NF- κ B mediates necrotizing crescentic GN (NCGN) and provides a specific treatment target. Reanalysis of kidneys from previously examined murine NCGN disease models revealed NF- κ B activation in affected kidneys, mostly as a p50/p65 heterodimer, and increased renal expression of NF- κ B–dependent tumor necrosis factor α (TNF- α ). NF- κ B activation positively correlated with crescent formation, and nuclear phospho-p65 staining showed NF- κ B activation within CD31-expressing endothelial cells (ECs) in affected glomeruli. Therefore, we studied the effect of ANCA on NF- κ B activation in neutrophil/EC cocultures in vitro . ANCA did not activate NF- κ B in primed human neutrophils, but ANCA-stimulated primed neutrophils activated NF- κ B in ECs, at least in part via TNF- α release. This effect increased endothelial gene transcription and protein production of NF- κ B–regulated interleukin-8. Moreover, upregulation of endothelial NF- κ B promoted neutrophil adhesion to EC monolayers, an effect that was inhibited by a specific IKK β inhibitor. In a murine NCGN model, prophylactic application of E-selectin–targeted immunoliposomes packed with p65 siRNA to downregulate endothelial NF- κ B significantly reduced urine abnormalities, renal myeloid cell influx, and NCGN. Increased glomerular endothelial phospho-p65 staining in patients with AAV indicated that NF- κ B is activated in human NCGN also. We suggest that ANCA-stimulated neutrophils activate endothelial NF- κ B, which contributes to NCGN and provides a potential therapeutic target in AAV.
Endogenous Immunoglobulin-Derived Neoepitopes Are Processed and Form a Sizeable Fraction of the HLA Class I Ligandome of Human Lymphoma Cells
Authors: Cornelis A.M. van Bergen, Dirk M. van der Steen, Michel G.D. Kester, Marvyn T. Koning, Peter A. van Veelen, Marieke Griffioen, J.H. Frederik Falkenburg, Mirjam H.M. Heemskerk, Hendrik Veelken, Marcelo A Navarrete
Journal: Blood (2016)
SWOG S1203: A Randomized Phase III Study of Standard Cytarabine Plus Daunorubicin (7+3) Therapy Versus Idarubicin with High Dose Cytarabine (IA) with or without Vorinostat (IA+V) in Younger Patients with Previously Untreated Acute Myeloid Leukemia (AML)
Authors: Guillermo Garcia-Manero, Megan Othus, John M. Pagel, Jerald P. Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A. Strickland, Mark Litzow, Mary Lynn Savoie, Bruno C. Medeiros, Mikkael A. Sekeres, Tara L. Lin, Geoffrey L. Uy, Bayard L Powell, Jonathan E. Kolitz, Richard A. Larson, Richard M. Stone, David F. Claxton, James Essell, Selina Luger, Sanjay R. Mohan, Anna Moseley, Frederick R. Appelbaum, Harry P. Erba
Journal: Blood (2016)
<i>BRCA1/2</i> reversion mutations in pancreatobiliary cancer identified from patient biopsies.
Authors: Laurie M. Gay, Erica Gornstein, Garrett Michael Frampton, James Sun, Samantha Morley, Andreas Heilmann, Jon Chung, Sugganth Daniel, Shakti Ramkissoon, Eric Allan Severson, James Suh, Jo-Anne Vergilio, Philip J. Stephens, Vincent A. Miller, Julia Andrea Elvin, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2017)

4130 Background: Germline genomic alterations (GA) in BRCA1 or BRCA2 ( BRCA) are associated with increased risk of pancreatic cancer. Tumors with BRCA GA may be more sensitive to platinum (Pt) therapies or PARP inhibitors (PARPi). However, secondary reversion mutations (revGA) that may restore BRCA function and underlie reduced sensitivity to Pt compounds or PARPi can arise. Methods: DNA extracted from FFPE tumor tissue obtained during routine clinical care for 7077 patients with predominantly relapsed, refractory or metastatic pancreatobiliary carcinoma was analyzed using comprehensive genomic profiling (CGP) for all classes of GA: base substitutions, indels, rearrangements, and copy number changes. RevGA were any GA that could restore the reading frame if in cis with a nonsense or frameshift (fs) GA. Tumor tissue only was used to predict germline (g BRCA) or somatic status by an algorithm with a call rate of 85% and &gt; 95% accuracy. Results: 417/7077 (5.9% ± 0.5%) tumors had ≥1 deleterious BRCA GA; 205 (2.9% ± 0.4%) had a predicted g BRCA GA. Significantly fewer women had deleterious BRCA GA (182/417; 43.6%)(p = 0.02); g BRCA GA frequency did not differ significantly (96/205; 46.8%)(p = NS). Overall, 49.1% of patients were women. 12 samples harbored potential revGA: pancreatic ductal adenocarcinoma (ACa) (7) or acinar cell carcinoma (Ca) (2), gallbladder ACa (2), and pancreatobiliary Ca NOS (1). 10/12 samples with revGA were metastases. Potential revGA were of 3 types: overlapping indel (7), compensatory fs (4), and missense (2). One case harbored 2 indels, both with potential to excise a fs GA. Apparent g BRCA were present in 7 cases, only somatic BRCA GA in 3 cases, and g BRCA/somatic status was ambiguous in 2 cases. For 2 patients, testing of multiple samples reveals the acquisition of revGA over time. KRAS mutation frequencies were similar for all samples (57.1%), BRCA-mutated samples (58.8%) and revGA-positive samples (58.3%). Clinical histories for patients with revGA will be presented. Conclusions: CGP of 7077 pancreatobiliary carcinomas reveals 5.9% had ≥1 deleterious BRCA GA, nearly 50% of which were g BRCA. Although rare, revGA can be acquired over time and potentially compensatory missense, fs and indel mutations were observed.
Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator’s Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial
Authors: James Larkin, David Minor, Sandra D'Angelo, Bart Neyns, Michael Smylie, Wilson H. Miller, Ralf Gutzmer, Gerald Linette, Bartosz Chmielowski, Christopher D. Lao, Paul Lorigan, Kenneth Grossmann, Jessica C. Hassel, Mario Sznol, Adil Daud, Jeffrey Sosman, Nikhil Khushalani, Dirk Schadendorf, Christoph Hoeller, Dana Walker, George Kong, Christine Horak, Jeffrey Weber
Journal: Journal of Clinical Oncology (2017)

Purpose Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator’s choice chemotherapy (ICC; dacarbazine 1,000 mg/m 2 every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m 2 every 3 weeks). Patients were treated until they experienced progression or unacceptable toxicity, with follow-up of approximately 2 years. Results Two hundred seventy-two patients were randomly assigned to nivolumab (99% treated) and 133 to ICC (77% treated). More nivolumab-treated patients had brain metastases (20% v 14%) and increased lactate dehydrogenase levels (52% v 38%) at baseline; 41% of patients treated with ICC versus 11% of patients treated with nivolumab received anti–programmed death 1 agents after randomly assigned therapy. Median OS was 16 months for nivolumab versus 14 months for ICC (hazard ratio, 0.95; 95.54% CI, 0.73 to 1.24); median progression-free survival was 3.1 months versus 3.7 months, respectively (hazard ratio, 1.0; 95.1% CI, 0.78 to 1.436). Overall response rate (27% v 10%) and median duration of response (32 months v 13 months) were notably higher for nivolumab versus ICC. Fewer grade 3 and 4 treatment-related adverse events were observed in patients on nivolumab (14% v 34%). Conclusion Nivolumab demonstrated higher, more durable responses but no difference in survival compared with ICC. OS should be interpreted with caution as it was likely impacted by an increased dropout rate before treatment, which led to crossover therapy in the ICC group, and by an increased proportion of patients in the nivolumab group with poor prognostic factors.
Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study
Authors: Aditi Shastri, Anjali Budhathoki, Stefan K. Barta, Noah Kornblum, Olga Derman, Ramakrishna Battini, Radha Raghupathy, Amit K. Verma, Paul S. Frenette, Ira Braunschweig, Murali Janakiram
Journal: American Journal of Hematology (2017)

Abstract Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 10 6 CD34 + cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 10 6 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 10 6 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation.