tbuckley/cabot-search huggingface dataset:
A single-arm, phase II feasibility study of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in potentially resectable gastric or gastroesophageal junction adenocarcinoma.
Authors: M. Ryu, Y. Choi, B. Kim, Y. Park, H. Kim, H. Jung, G. Lee, K. Kim, J. Yook, Y. Kang
Journal: Journal of Clinical Oncology (2011)

96 Background: The aim of this study was to evaluate feasibility and safety of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in patients with potentially resectable adenocarcinoma of stomach or gastroesophageal junction. Methods: Forty-one patients with clinical stage T3-4N0M0 or T2-4N+M0 determined by CT, endoscopic ultrasonography, and laparoscopy were enrolled between DEC 2008 and MAR 2010. Gastrectomy with D2 lymph node dissection was conducted after 3 cycles of DOS chemotherapy. DOS chemotherapy consists of docetaxel 50 mg/m 2 iv (day1), oxaliplatin 100 mg/m 2 iv (day1), and S-1 40 mg/m 2 po bid (days1-14) at 3 weeks interval. After curative gastrectomy, the patients were given 1 year of adjuvant chemotherapy with S-1 (40 mg/m 2 D1-28, every 6 weeks). Results: All patients finished the planned neoadjuvant chemotherapy. Twenty-three (56%) patients achieved a partial response, and the remaining 18 patients had stable disease by CT scan after 3 cycles of DOS chemotherapy. No disease progression was observed during the neoadjuvant chemotherapy. A median 4.7 weeks (range, 4.0-7.6) after the start of the 3 rd cycle of DOS chemotherapy, 39 (95%) patients underwent R0 resection with no pathologic residual disease in 4 (10%) patients. Hematologic toxicities were common including grade 4 neutropenia (32%), grade 3 thrombocytopenia (17%), and febrile neutropenia (10%). However, hematologic toxicities were generally transient and manageable. There were no grade 3 or 4 non-hematologic toxicities with frequency &gt; 5% of patients. With all toxicities taken together, 21 (51%) patients experienced grade 3 or 4 toxicities (except grade 3 neutropenia). There was no treatment-related death, and surgical complications included only mild wound problem in 4 (10%) patients. Conclusions: In this study, neoadjuvant DOS chemotherapy could induce a sufficient down-staging and R0 resection of locally advanced gastric cancer with mild and manageable toxicities. A phase III randomized trial is planned for evaluating the benefit of neoadjuvant DOS chemotherapy in patients with locally advanced gastric cancer. [Table: see text]
Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis
Authors: Aleena Banerji, Paula Busse, Mustafa Shennak, William Lumry, Mark Davis-Lorton, Henry J. Wedner, Joshua Jacobs, James Baker, Jonathan A. Bernstein, Richard Lockey, H. Henry Li, Timothy Craig, Marco Cicardi, Marc Riedl, Ahmad Al-Ghazawi, Carolyn Soo, Ryan Iarrobino, Daniel J. Sexton, Christopher TenHoor, Jon A. Kenniston, Ryan Faucette, J. Gordon Still, Harvey Kushner, Robert Mensah, Chris Stevens, Joseph C. Biedenkapp, Yung Chyung, Burt Adelman
Journal: New England Journal of Medicine (2017)

Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency.We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a 2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients), in two administrations 14 days apart. Patients assigned to lanadelumab were enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4 patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic profile of lanadelumab was assessed by measurement of plasma levels of cleaved high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and 400-mg groups as compared with the placebo group.No discontinuations occurred because of adverse events, serious adverse events, or deaths in patients who received lanadelumab. The most common adverse events that emerged during treatment were attacks of angioedema, injection-site pain, and headache. Dose-proportional increases in serum concentrations of lanadelumab were observed; the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma from patients with hereditary angioedema with C1 inhibitor deficiency to levels approaching that from patients without the disorder. From day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the placebo group. All patients in the 300-mg group and 82% (9 of 11) in the 400-mg group were attack-free, as compared with 27% (3 of 11) in the placebo group.In this small trial, administration of lanadelumab to patients with hereditary angioedema with C1 inhibitor deficiency reduced cleavage of high-molecular-weight kininogen and attacks of angioedema. (Funded by Dyax; ClinicalTrials.gov number, NCT02093923 .).
Clinical response to dorsal duct drainage via the minor papilla in refractory obstructing chronic calcific pancreatitis
Authors: Chang-Il Kwon, Mark Gromski, Stuart Sherman, Ihab El Hajj, Jeffrey Easler, James Watkins, Lee McHenry, Glen Lehman, Evan Fogel
Journal: Endoscopy (2017)

<b>Background and study aims</b> Complete stone removal from the main pancreatic duct might not be achieved in all patients with obstructive chronic calcific pancreatitis. We report our results for endoscopic dorsal pancreatic duct (DPD) bypass of obstructing stones in the ventral pancreatic duct (VPD). <b>Patients and methods</b> 16 patients with obstructive chronic calcific pancreatitis were treated with a DPD bypass. Clinical success was defined as significant pain relief and no hospital admissions for pain management during the ongoing treatment period. <b>Results</b> Among 16 patients meeting entry criteria, 10 (62.5 %) had a history of unsuccessful endoscopic therapy, and 8 had failed extracorporeal shockwave lithotripsy (ESWL). Clinical success was achieved in 12 patients (75 %). Among these responders, 10 patients (83.3 %) had markedly improved or complete pain relief after the first stent placement, which persisted throughout the follow-up period; 11 patients (91.7 %) were able to discontinue their daily analgesics. <b>Conclusions</b> In selected patients with obstructive chronic calcific pancreatitis, the DPD bypass may be considered as a rescue endoscopic therapy, potentially obviating the need for surgery when standard endoscopic methods and ESWL fail.
SURG-30. USING THE NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE AS A PREDICTIVE ASSESSMENT TOOL FOR SURVIVAL IN PATIENTS WITH PRIMARY GLIOBLASTOMA
Authors: Timothy Ung, Douglas Ney, Denise Damek, Samy Yousseff, Kevin Lillehei, David Ormond
Journal: Neuro-Oncology (2016)

The neurologic assessment in neuro-oncology (NANO) scale is a standardized metric designed to measure neurologic function in neuro-oncology. Current available neuroradiological evaluation criteria fail to use specific clinical criteria for tumor recurrence. Additionally, existing clinical measures of patient performance such as the Karnofsky Performance Scale (KPS) and the Eastern Cooperative Oncology Group (ECOG) are generalized and do not incorporate specific neurologic performance criteria in assessment of the patient, nor are they used to predict glioma progression. Currently, it is not known whether or not the NANO scale can be used as a reliable predictor of survival in patients with glioblastoma (GBM). To evaluate this, we performed a retrospective review of all 78 patients (45 male and 33 female) with primary GBM from January 1, 2010 through December 31, 2012. We applied the NANO scale, KPS, ECOG, MacDonald criteria, and the RANO criteria to patients at the time of diagnosis as well as well as during 3-month, 6-month and 1-year time points to assess for disease prognosis and survival. Patients with a higher initial NANO scale score (4+) demonstrated a worse prognosis when compared to patients with a lower initial score (0-3). Disease progression as defined by the NANO scale was a predictor of decreased survival in patients at 6-months and 1-year. A decrease in KPS >20 points was predictive of survival at 3 and 6-month time points, a two point increase in ECOG score was predictive only at 3-months, and radiologic evaluation (RANO and MacDonald) were predictive at 3 and 6-months. Only the NANO scale was predictive of patient survival at 1-year. Comparatively, NANO recurrence is a better predictor of decreased survival when compared to RANO and MacDonald at 6-months and 1 year. NANO recurrence appears to be a useful adjunct as a predictor of overall survival in malignant glioma.
NORDIC9: A randomized phase II trial exploring treatment of older patients with metastatic colorectal cancer (mCRC) by comparing full dose monotherapy (S-1 followed by irinotecan) with reduced combination regimen (S-1/oxaliplatin followed by S-1/irinotecan)
Authors: S.B. Winther, P. Østerlund, Å Berglund, B. Glimelius, C. Qvortrup, H. Sorbye, P. Pfeiffer
Journal: Annals of Oncology (2016)
GENT-27. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF N-ETHYL-N-NITROSOUREA INDUCED RAT GLIOMAS
Authors: Wajid Sayeed, Michael Blough, Gregory Cairncross
Journal: Neuro-Oncology (2016)

Gliomas affecting children and young adults are genetically distinct from those in older adults. Next-generation sequencing has revealed unique mutations, methylation patterns, and expression profiles, which now define age- and location-specific glioma subtypes. While most gliomas that arise in children and young adults have no known cause, epidemiologic studies have shown an association between maternal consumption during pregnancy of foods high in N-nitroso-compounds (NOCs) and the development of brain tumors in their children. Likewise, in utero exposure to NOCs is known to cause astrocytomas, oligodendrogliomas, and glioblastomas in young rats. Here we test the hypothesis that ENU-induced gliomas bear genomic and epigenetic alterations that resemble those found in the gliomas of children and young adults. The possibility that some gliomas are caused by exposures that are preventable and occur in utero is the clinical rationale for this study. Pregnant Sprague-Dawley rats were exposed to intravenous ENU and their offspring monitored by MRI for the development of gliomas. Animals were euthanized when they developed large gliomas (i.e., >5mm) or became symptomatic. Tumour tissues were harvested, cultured and analyzed histopathologically and immunohistochemically (IHC); RNA and DNA were also extracted from these tissues for sequencing and methylation studies. In our first cohort, all control pups were glioma-free and 11/11 pups exposed in utero developed MRI-detectable astrocytic gliomas. All tumours expressed ATRX, one expressed Olig2 and none were IDH R132H positive by IHC. Next-generation sequencing of tumor tissues is planned and three rat glioma cell lines have been established.
Adherence to guidelines for colorectal cancer prevention and its relationship to this cancer in the Basque country: a case-control study
Authors: B. Chao-Seijo, V. Ovejas-Arza, I. Alegria-Lertxundi, C. Aguirre, L. Bujanda, F.J. Fernandez, F. Polo, I. Portillo, M.C. Etxezarraga, I. Zabalza, M. Larzabal, M.M. de Pancorbo, A.M. Rocandio, M. Arroyo-Izaga
Journal: Annals of Oncology (2016)
Жорсткість печінки за даними зсувнохвильової еластографії у хворих на цукровий діабет типу 2 з неалкогольною жировою хворобою печінки залежно від активності процесу НАЖХП
Authors: O.B. Dynnyk, G.P. Mykhalchishin, N.M. Kobyliak, P.M. Bodnar
Journal: GASTROENTEROLOGY (2014)

Зсувнохвильова еластографія є одним із найбільш перспективних неінвазивних методів діагностики фіброзу та стеатозу при хронічних дифузних захворюваннях печінки, що можуть використовуватись як альтернатива біопсії. З огляду на її широке впровадження в клінічну практику групами вчених з усього світу все більше уваги приділяється вивченню факторів, які можуть впливати на еластометрію та її діагностичну ефективність. Наше дослідження, присвячене вивченню змін жорсткості паренхіми печінки методом зсувнохвильової еластографії/еластометрії у хворих із неалкогольною жировою хворобою печінки, за даними одновимірного кореляційного і множинного лінійного регресійного аналізу, показало, що незалежними детермінантами, асоційованими зі зростанням жорсткості паренхіми печінки, є ступінь інсулінорезистентності, ожиріння та активність трансаміназ.
Frederic Salkeld Plumpton
Authors: Miles Rucklidge
Journal: BMJ (2017)

Born in Sunderland, Frederic Salkeld Plumpton (“Eric”) was educated at Sedbergh School, where his passion for outdoor activities was born. He won an exhibition to Christchurch College, Oxford, and completed his training at the London Hospital, where he met his future wife, Janet. At Oxford he was involved in expeditions to the Himalayas, the Rockies, and the Arctic and later drove from Australia through Asia …
Agonist Stimulation, Talin-1, and Kindlin-3 Are Crucial for α¶bβ3 activation in a Human Megakaryoblastic Cell Line, CMK
Authors: Tsuyoshi Nakazawa, Seiji Tadokoro, Kazunobu Kiyomizu, Hirokazu Kashiwagi, Shigenori Honda, Yoshiaki Tomiyama, Yuzuru Kanakura
Journal: Blood (2011)
Testosterone levels and quality of life (QoL) in male patients with hormone-independent cancers (HIC).
Authors: S. B. Fleishman, H. Khan, M. J. Guarino, M. Suhail, R. A. Strebel, P. Homel, V. Rosenwald, T. Mirzoyev, T. F. Wozniak, K. Suppiah
Journal: Journal of Clinical Oncology (2010)

9140 Background: Symptoms secondary to hormone changes significantly impact QoL in cancer patients. This cross-sectional study examines prevalence of hypogonadism and its correlation with symptoms. Methods: Serum, demographic variables, and medical histories were collected from 428 male HIC subjects at 3 diverse cancer centers. Morning blood samples were analyzed for Total Testosterone (TT), Free T (FT), Bio-available T (BAT), and Sex Hormone Binding Globulin. Functional Assessment of Cancer Therapy-Prostate (FACT-P) QoL questionnaire was used to measure physical, social, emotional and functional domains plus sexual function. Exclusion criteria: men <18 yrs, prostate cancer (ca), testicular ca, male breast ca, known hypogonadism, and HIV. Results: Mean and median TT was 337.46 and 310 ng/dl (interquartile range: 190-443). Mean age of subjects was 62.05±13.17 years. The Table summarizes the study results. The crude prevalence of hypogonadism (defined as TT<300ng/dl) was 48% (95%CI, 43-53%). The prevalence (95% CI) based on FT (hypogonadal <52pg/dl) and BAT (hypogonadal <95ng/dl for men <70 years of age and <60 ng/dl for men 70 and older) were 78% (73-82%) and 66% (61-70%), respectively. Hypogonadal subjects had decreased Total QoL score on FACT-P (p=0.01) and decreased 3 item sexual function subset (p=0.003) (Satisfaction with sex life, erectile function, “I feel like a man”). Conclusions: The prevalence of hypogonadism is unexpectedly high. Confirming previous studies, measurement of FT or BAT detected a higher prevalence of hypogonadism than TT alone. Comparison with the FACT-P shows significant reduction of both overall QoL and sexual function for hypogonadal men. A placebo-controlled T replacement trial could explore improvement of overall QoL and sexual function in hypogonadal male cancer patients. Mean ± SEM TT ng/dl FT pg/ml BAT ng/dl FACT-Ptotal score FACT-P sexual function score Eugonadal (n = 211) 487.1 ± 11.62 50.3 ± 1.48 93.6 ± 2.8 79.8 ± 1.13 9.6 ± 0.31 Hypogonadal (n = 196) 176.3 ± 6.00 24.7 ± 1.09 45.1 ± 2.2 75.6 ± 1.23 8.3 ± 0.30 P value <0.001 <0.001 <0.001 0.01 0.003 No significant financial relationships to disclose.
Analysis of overall survival by number of radium-223 injections received in an international expanded access program (iEAP)
Authors: G. Paganelli, G. Procopio, M. Cabria, E. Cortesi, M. Tucci, A. Farnesi, L. Mango, S. Baldari, A. Hamzaj, O. Caffo, P. Marchetti, F. Dalla Pozza, P.A. Zucali, F. Saad, S. Nilsson, D. Heinrich
Journal: Annals of Oncology (2016)
Polymorphisms in One-Carbon Metabolism Genes and Overall Survival in Diffuse Large B-Cell Lymphoma (DLBCL).
Authors: James R. Cerhan, Matthew J. Maurer, Patricia Hartge, Stephen J. Chanock, Thomas M. Habermann, Wendy Cozen, Scott Davis, Charles F. Lynch, Richard K. Severson, Nathaniel Rothman, Lindsay M. Morton, Sophia S. Wang
Journal: Blood (2007)
RARE-37. SURGICAL MANAGEMENT OF INCIDENTAL DIFFUSELY INFILTRATING GLIOMAS: A SINGLE INSTITUTIONAL EXPERIENCE
Authors: Michael Opoku-Darko, John Kelly
Journal: Neuro-Oncology (2016)

Uncommonly, diffusely infiltrating gliomas (DIGs) are identified incidentally while asymptomatic. Early surgical management of these tumors has been suggested to improve outcome. We set out to identify and review the characteristics and outcomes of patients with incidental, asymptomatic DIGs. All DIGs surgically treated by the lead author between 2012 and 2016 were analyzed in order to identify cases that were discovered incidentally. Patients with incidentally discovered were identified and retrospectively reviewed. “Incidental” was defined as a finding on imaging that was obtained for a reason not attributable to the glioma, such as trauma, headache or neurological symptoms not attributable to the lesion. 327 patients between the ages of 19-83 underwent surgery for DIGs. Eleven (4m, 7f) patients (11/367 3.00%) were identified that harboured incidental gliomas. The most common reasons for head imaging were imaging performed to evaluate symptoms attributable to a different problem (4, 36.4%), imaging screening for other diagnoses (4, 36.4%) and trauma (3, 25%). Pathology of these lesions (based on WHO 2007 criteria) included Astrocytoma GrII (n=3), Oligodendroglioma GrII (n=4), Oligoastrocytoma GrII (n=2), and Glioblastoma (n=2). Eight tumors (8/11, 72.7%) harboured IDH1 (R132H) mutations. Two patients underwent biopsies only due to large size and extensive infiltration of the tumors, the 9 remaining patients underwent surgical resection of their tumors. No patients in this small cohort experienced post-operative complications. This retrospective cohort of incidentally discovered surgically managed DIGs demonstrates that the majority of lesions are IDH mutated and low grade. Incidentally discovered lesions are usually of small size and can be managed with low surgical risk. Ongoing follow-up will be required in order to determine progression-free and overall survival in this group of patients.
IMST-50. DEVELOPMENT AND EXPRESSION OF A T CELL ENGAGER TARGETED TO GLIOBLASTOMA BY CHLOROTOXIN
Authors: Rebecca Cook, Lydia Meador, Apisara Ausvasomrit, Thanchanok Boonsompong, Braeden Schaefer, Tsafrir Mor, Joseph Blattman, Rachael Sirianni
Journal: Neuro-Oncology (2016)

Bispecific T cell activating molecules are potent inducers of T cell destruction against target cells of interest and are commonly composed of two single chain variable fragments from distinct antibodies held together by a short peptide linker. We have developed a bispecific fusion protein (anti-CD3/Ctx) composed of the variable fragment of an antibody targeting mouse CD3 linked to chlorotoxin for the purpose of activating T cells specifically against glioblastoma cells in vivo. After bringing T cells into close contact with glioma cells, anti-CD3/Ctx is theorized to promote the formation of an immunological synapse that will allow for perforin and granzyme-mediated destruction of tumor cells. By activating T cells with anti-CD3, the need for MHC presentation of antigens on the tumor cells is circumvented, an obstacle that is difficult to overcome with other immunotherapies. We have cloned the sequence encoding His-tagged anti-CD3/Ctx into a tobamovirus-based plant expression vector (ICON Genetics, Germany) for the transient expression of anti-CD3/Ctx in the tobacco relative Nicotiana benthamiana. Peak expression of anti-CD3/Ctx was found to occur five days post infiltration of plants with agrobacteria harboring the expression vector. The fusion protein was purified from leaf extracts by a 50-80% ammonium sulfate fractionation followed by TALON affinity chromatography. Expression level and purity were analyzed by SDS-PAGE and immunoblotting. Biochemical characterization is ongoing.
17P deletion and TP53 gene mutation (17P/TP53) testing behaviour and treatment patterns for chronic lymphocytic leukemia (CLL) patients in France, Germany, Italy, Spain and UK (EU5)
Authors: F.A. Bermudez Canta, L. Mitrofan, Y.B. Karanis, H. Mistry, C. Anger
Journal: Annals of Oncology (2016)
TMOD-03. CELL-OF-ORIGIN FOR GBM AND ITS APPLICATION FOR TRANSLATIONAL RESEARCH
Authors: Jungeun Kim
Journal: Neuro-Oncology (2016)

Glioma is a devastating disease because low-grade tumors inevitably progress into incurable high-grade GBMs. Among all probable explanations, such progressive nature could be attributed to the innate properties of its cell-of-origin. An ideal approach to identify the cell-of-origin for glioma is to analyze growth advantages of mutant cells in each brain cell types prior to malignancy. Our lab models glioma using a mouse genetic system called Mosaic Analysis with Double Markers (MADM), which generates GFP-labeled TSG-null cells and RFP-labeled sibling wildtype cells. By design, increased ratio of green-to-red cell numbers (G/R ratio) serves as the indication of tumor initiation long before malignancy. Using MADM, we found that after introducing p53/Nf1 mutations into neural stem cells (NSCs), significant aberrant expansion only occurred in oligodendrocyte precursor cells (OPCs, G/R ratio > 100), but not in any other NSC-derived lineages or NSCs themselves. Furthermore, introducing p53/Nf1 mutations directly into OPCs consistently led to gliomagenesis, further suggesting OPCs as the cell-of-origin in this model [Liu 2011 Cell]. Surprisingly, a close examination revealed a lack of overall OPC density increase in mutant brains in comparison to WT brains despite of the large G/R ratio, suggesting that green mutant OPCs actively out-compete WT OPCs to overtake the brain. Intrinsic competitive nature of OPCs could explain the inevitable progression of low-grade glioma since cells with “advantageous” mutations would kill other OPCs to make space for their own expansion. Under the same notion, traditional cytotoxic treatment could backfire by providing selective pressure that enriches resistant tumor cells. To look for alternative methods, we demonstrated that blocking the competitiveness of mutant OPCs with genetic methods completely prevented gliomagenesis in the mouse model. Currently, we are using cell culture-based assays and in vivo drug testing to identify potential anti-competition drugs that could be translated into clinical settings.