tbuckley/cabot-search huggingface dataset:
Sorafenib combined with carboplatin/paclitaxel for advanced non-small cell lung cancer: A phase I subset analysis
Authors: J. H. Schiller, K. T. Flaherty, M. Redlinger, K. Binger, J. Eun, O. Petrenciuc, P. O’Dwyer
Journal: Journal of Clinical Oncology (2006)

7194 Background: The EGFR is often overexpressed in advanced non-small-cell lung cancer (NSCLC) - a solid tumor associated with a poor prognosis. Oncogenic k-ras mutations and raised serum VEGF predict poor outcome in NSCLC. In vitro targets of sorafenib include Raf, which is downstream of EGFR and k-ras. Sorafenib also targets the VEGFR-2/-3 tyrosine kinases, involved in tumor angiogenesis. Preclinically, sorafenib targets the tumor and tumor endothelium to inhibit tumor growth. Methods: This subanalysis of a Phase I trial with a Phase II expansion in NSCLC was performed to evaluate the safety (adverse events graded by NCI-CTC 2.0) and preliminary anti-tumor activity (response by RECIST, PFS, TTP) of oral sorafenib combined with carboplatin/paclitaxel in 15 patients with advanced, progressive NSCLC. Carboplatin (AUC 6)/paclitaxel (225 mg/m 2 ) was administered on Day 1, and sorafenib (100, 200, or 400 mg bid) on Days 2–18 of each 21-day treatment cycle. Results: Drug-related adverse events were reported by 73% (11/15) of patients, but were mostly grade 1–2 (53%) in severity; none was grade 4. The most common drug-related events at any grade were dermatologic (Hand-foot skin reaction [20%]; rash [60%]), and gastrointestinal (diarrhea [20%]; anorexia [13%]). There were no drug-related cardiovascular adverse events. Three patients reported grade 1–2 drug-related bleeding events (epistaxis n = 2; other n = 1). Of the 14 evaluable patients, four (29%) had a confirmed PR as best response, seven (50%) had SD, and three (21%) had PD. Therefore, the disease control rate (objective response plus SD) was 79%. Duration of response was 25 weeks. Median PFS was 34 weeks. Discussion: This sorafenib combination was well tolerated and showed promising preliminary anti-tumor activity in patients with advanced, progressive NSCLC. [Table: see text]
MMR and CMR in Chronic Phase Chronic Myeloid Leukemia Patients: Role of Sokal Score and Different Tyrosine Kinase Inhibitors On Time of Their Obtention, Maintenance and Failure-Free Survival
Authors: Mauricette Michallet, Hélène Labussière-Wallet, Mohamad Sobh, Stéphane Morisset, Madeleine Etienne, Marie Y. Detrait, Sophie Ducastelle, Fiorenza Barraco, Xavier Thomas, Oriane Le Borgne, Isabelle Tigaud, Sandrine Hayette, Franck E. Nicolini
Journal: Blood (2012)
Anti-Tumor Activity of Low Dose Ocaratuzumab in Previously Treated Follicular Lymphoma Patients with Low-Affinity CD16 Polymorphisms
Authors: Phuong H Le, Andres Forero-Torres, Nam H. Dang, Mitchell R Smith, Brian K Link, Kristen N. Ganjoo, Kensei Tobinai, Minna Du, Adrienne O'Reilly, Vinay Jain
Journal: Blood (2012)
Clinical Phenotype and Response to Imatinib of Chronic Myelogenous Leukemia Patients Harbouring Atypical BCR-ABL Transcripts. A Retrospective Analysis From the French Group of CML (Fi-LMC) and the French Group of Molecular Biologists for Hematological Malignancies (GBMHM).
Authors: Benedicte Deau, Mathias Montveneur, Valérie Coiteux, Aline Renneville, Francoise Rigal-Huguet, Eric Delabesse, Michel Tulliez, Dominique Bories, Aude Charbonnier, Marie-Joelle Mozziconacci, Thibault Legay, Eric Lippert, Francois-Xavier Mahon, Delphine Rea, Jean-Michel Cayuela, Shanti Amé, Marie-Pierre Gaub, Martine Gardembas, Odile Blanchet, Bruno Audhuy, Agnès Buzyn, Elisabeth Mac Intyre, Anna-Lisa Andreoli, Oumedaly Reman, Nathalie Contentin, Christian Bastard, Jean-Christophe Ianotto, Valérie Ugo, Jean-Jacques Kiladjian, Said Brahimi, Viviane Dubruille, Jean-Francois Brantus, Mohamad Sobh, Stephane Morisset, Claude Preudhomme, Sandrine Hayette, Franck E Nicolini
Journal: Blood (2010)
A prospective study to evaluate the efficacy of curcumin in the management of advanced carcinoma cervix.
Authors: S. K. Jain, N. Singh, D. Sharma, G. K. Rath, P. K. Julka, P. Heera, B. Ayan, S. Sen, S. Thulkar, S. Duttagupta
Journal: Journal of Clinical Oncology (2010)

TPS261 Background: Cervical cancer is the most common gynecologic cancer in India accounting for 132,082 new cases annually with a mortality of 74,118. Most cases present at an advanced stage of disease. Human papilloma virus (HPV) is the causative factor of cervical cancer. Curcumin (Diferuloylmethane) is obtained from curcuma longa. It acts as a chemo preventive agent with antioxidant, anti-inflammatory and antitumorogenic properties with low/nil pharmacological toxicity. In this study we elucidate the role of curcumin as an Objectives: Primary: To determine the efficacy of curcumin with radiotherapy and chemotherapy in improving the 5-year survival rate in advanced cases of cervical cancer. Secondary:To determine whether curcumin supplementation affects HPV, PCNA and P16 INK4a levels in exfoliated cervical cancer cells.adjuvant to chemo and radiotherapy in advanced cervical cancer patients. Curcumin is supplied as capsules of 500 mg each. The total daily dose of curcumin is 4 gram (8 capsules). Methods: Patient eligibility criteria: Invasive squamous cell carcinoma cervix, stages II-IIIB, ages 19 to 64 years, no history of prior malignancy, an ECOG ≤2, normal hematological and biochemical parameters, no evidence of HIV/AIDS. After informed consent, patients are treated with concurrent chemoradiation (radiotherapy 50 Gy/25 fractions over 5 weeks + intracavitory HDR brachytherapy 7Gy to point A three times, interdigitated starting at the end of 4 th week of treatment). Curcumin capsules are given for 42 days starting from first day of radiotherapy. Adverse events are recorded according to CTCAE V3. Study started after institute ethics committee approval. Of total planned 375 patients, 85 are accrued till date. Cervical scrapes are collected at baseline, 6 weeks (1st follow-up), 3 months (2nd follow-up), 6 months (3rd follow-upp) and 1 year (4th follow-up) post-treatment. HPV status, PCNA and P16INK4A protein expression are evaluated by immunocytochemistry. CT scan is done at 6 months to see the response. Primary endpoint: 5-year disease-free survival rate. The secondary endpoint: response rate by clinical examination and CT scan and to estimate down regulation of HPV, PCNA and P16 INK 4a with treatment. No significant financial relationships to disclose.
Long Term Followup of Bystander Vaccine Therapy in Mantle Cell Lymphoma (MCL),
Authors: Bijal D. Shah, Jianguo Tao, Lubomir Sokol, Paul A. Chervenick, Marcie Tomblyn, Javier Pinilla-Ibarz, Lynn Moscinski, Scott Antonia, Eduardo M. Sotomayor, Sophie Dessureault
Journal: Blood (2011)
Glioblastoma in the elderly: Treatment planning, toxicity, and efficacy in an ambulatory practice.
Authors: W. P. Mason, Z. Lwin, D. MacFadden, A. AL-Zahrani, N. Laperriere, C. Menard, B. A. Millar, A. Sahgal, C. Massey, L. E. Coate
Journal: Journal of Clinical Oncology (2011)

2063 Background: Treatment of Glioblastoma (GB) in the elderly remains controversial. Elderly patients are often excluded from clinical trials, and even when included may not represent the typical patient population seen in clinic. In this analysis, we examined the effect of age on treatment planning, toxicity, and efficacy. Methods: Consecutive neuro-oncology patients attending our institution between 2004-2008 were reviewed. The total radiation dose, chemotherapy regimens, toxicities and efficacy were extracted from patient records, and comparisons drawn between older and younger patients using a threshold of 70 years of age as the cut point. Treatment toxicity was analyzed using Fisher’s exact test, and logistic regression models. Survival times were analyzed using Kaplan-Meier plots, log-rank tests and Cox proportional hazards models. Results: 421 patients were included in this analysis and the median survival for the entire group was 9.8 months. 290 patients were <70 (median age 57, range 13-69.8) and 131 ≥70 (median age 76, range 70.1-93.1). Patients ≥70 were more likely to be planned for best supportive care (BSC) and all treated patients ≥70 received <60Gy +/- temozolomide (TMZ), p<0.001. Patients age ≥70 demonstrated inferior survival (1 year OS 54% versus 16% for those <70 and ≥70, respectively, HR: 3.46, p<0.001). In patients treated with BSC only, there was no difference in survival according to age (median survival 2 months in both groups, HR: 0.89, p=0.75). However, in those patients age ≥70 treated with higher doses of radiotherapy (40 to <60 Gy +/- TMZ), equivalent survival was observed as compared to those <70 (1 year OS 27% in both groups, HR: 1.37, p=0.13). Conclusions: Overall, elderly patients were more likely to be treated with BSC and palliative intent therapy. However, in those patients fit enough to be treated with higher dose radiation +/- TMZ, outcomes were similar despite patient age. Therefore, selected patients over the age of 70 may tolerate and benefit from radical radiotherapy regimens.
Autologous Human T Cells and Allogeneic Antigen-Presenting Cells Permit Effective Adoptive Transfer of B-CLL Cells Into Immune Deficient Mice.
Authors: Davide Bagnara, Matthew Kaufman, Carlo Calissano, Sonia Marsilio, Philip Chum, Xiao J. Yan, Peter K Gregersen, Annette Lee, Kanti R Rai, Nicholas Chiorazzi
Journal: Blood (2009)
Quantitative Phosphoproteomics Identified a New Syk-Lyn-Axl Signalling Pathway Involved In Resistance to Nilotinib In Chronic Myeloid Leukemia Cells.
Authors: Romain Gioia, Cedric Leroy, Claire Drullion, Valérie Lagarde, Serge Roche, Francois-Xavier Mahon, jean-Max Pasquet
Journal: Blood (2010)
ACY-241, a Novel, HDAC6 Selective Inhibitor: Synergy with Immunomodulatory (IMiD®) Drugs in Multiple Myeloma (MM) Cells and Early Clinical Results (ACE-MM-200 Study)
Authors: Ruben Niesvizky, Paul G. Richardson, Nashat Y. Gabrail, Sumit Madan, Andrew J. Yee, Steven N Quayle, Ingrid Almeciga-Pinto, Simon S Jones, Lee Houston, Denise Hayes, John Van Duzer, Catherine Wheeler, Nikolaus S. Trede, Noopur S. Raje
Journal: Blood (2015)
LR11 Plays a Critical Role in Leukemogenesis of Acute Myeloid Leukemia by Regulating Adhesion and Homing Ability to Bone Marrow.
Authors: Keigo Nishii, Chiaki Nakaseko, Masahiro Takeuchi, Naomi Shimizu, Chikako Ohwada, Shokichi Tsukamoto, Takeharu Kawaguchi, Atsuko Yamazaki, Meiji Jiang, Atsushi Iwama, Hideaki Bujo
Journal: Blood (2012)
QOL-02EPILEPSY FOLLOWING LOW GRADE GLIOMA SURGERY: SINGLE CENTRE EXPERIENCE
Authors: Erjon Agushi, Elvira Lekka, Rajiv Mohanraj, Christos Gkolemis, Konstantina Karabatsou
Journal: Neuro-Oncology (2015)

OBJECTIVE: Review the incidence of seizures and the value of prophylactic antiepileptic drug (AED) treatment following surgery for Low Grade Gliomas (LGGs). DESIGN: Retrospective study. SUBJECTS: All patients who underwent surgery for LGG between 2010-15 at our centre. METHODS: Retrospective review. RESULTS: 91 out of 137 patients received AEDs preoperatively;70 due to initial presentation and 21 prophylactically.20/137 patients (14.6%) had seizures in the immediate postoperative period (14 days).Incidence of seizures in the immediate postoperative period was significantly lower in patients established on AEDs compared to the ones who received AEDs as prophylaxis or did not receive AED at all (10.0 vs 28.57 vs 15.22%, p = 0.10), but this difference became insignificant in the follow up period of 1 year (p = 0.69). 35 craniotomies were performed awake; seizures in the immediate postoperative period were more frequent in awake surgery but this was not significant (20 vs 12.75%, p = 0.29). The extent of resection, demonstrated an inverse trend on seizures at 1 year; only 3.3% of the patients who underwent total resection suffering seizures vs 12.5% of near total and 19.51% subtotal debulking or biopsy (p = 0.09). CONCLUSIONS: Patients established on regular AEDs tend to have fewer seizures in the immediate post operative period, but this difference becomes insignificant at 1 year. Awake craniotomy has no significant impact in the immediate and long term seizure activity. The extent of resection is a valid prognostic predictor of seizure activity.
Chronic Myeloid Leukemia Stem Cells and Their Differentiated Progeny Display Divergent Drug Sensitivities to Imatinib Mesylate and Interferon-Alpha.
Authors: William Matsui, Greg R. Angstreich, Milada S. Vala, James P. Barber, Anita L. Hawkins, Constance A. Griffin, Carol Ann Huff, B. Douglas Smith, Richard J. Jones
Journal: Blood (2004)
Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing in cancer
Authors: Jin Li, Lilin Wang, Harvey Mamon, Matthew Kulke, Ross Berbeco, Mike Makrigiorgos
Journal: Cancer Research (2008)

1796  Introduction: The Polymerase Chain Reaction (PCR) has become the cornerstone of molecular diagnosis, with almost every genetic test aiming to identify DNA sequence variation incorporating PCR. A commonly encountered problem is that variant DNA sequences exist in the presence of a large majority of wild type alleles such as when DNA is obtained from heterogeneous cancer biopsies or when fetal alleles are sought in maternal blood. As a result, downstream assays are severely limited in their ability to identify subtle genetic changes that can have profound impact in clinical decision-making and outcome. We describe Co-amplification at Lower Denaturation temperature (COLD-PCR), a novel form of PCR that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences irrespective of the mutation type or position on the sequence (Nature Medicine, In Press).  Methods: In COLD-PCR, an intermediate annealing temperature is used during PCR-cycling to allow cross-hybridization of mutant and wild type alleles; hetero-duplexes, which melt at lower temperatures than homo-duplexes, are then selectively denatured and amplified at Critical Denaturation Temperature (Tc), while homo-duplexes remain double-stranded and do not amplify efficiently. By fixing the denaturation temperature to Tc, mutations at any position along the sequence are enriched during COLD-PCR amplification. To validate COLD-PCR, we used serial dilutions of DNA from tumor-derived cell lines containing point mutations or micro-deletions at different positions along p53 exon 8 and Kras exon 1 (codons 12-13), or samples with micro-deletions in EGFR exon 19. In addition, genomic DNA from a series of colon and lung cancer surgical specimens, and plasma-circulating DNA collected under IRB approval were utilized for validation on clinical specimens.  Results: By replacing regular PCR with COLD-PCR prior to application of a range of assays (Sanger sequencing; Pyrosequencing; MALDI-TOF; dHPLC; RFLP; and Taqman) we improved mutation detection sensitivity up to 100-fold and identified several additional p53/Kras/EGFR mutations in heterogeneous cancer samples. 4 of 43 surgical samples and 3 of 10 plasma samples tested contained clinically important mutations that were not detected by any of the methods tested when preceded by regular-PCR, but they were detectable following COLD-PCR.  Conclusion: Replacement of regular PCR with COLD-PCR provides a universal boost to most mutation detection technologies and enables them to be used with the required confidence in routine screening of cancer specimens for somatic mutations, including low-level mutation screening of surgical/FFPE tumor samples or bodily fluids. COLD-PCR is also anticipated to find application in pre-natal diagnosis, in infectious diseases and in epigenetics.
Carcinoma of uterine cervix: Top ranking in our country
Authors: D. Uddin, K. N. Begum, H. Akthar, M. Faruqui
Journal: Journal of Clinical Oncology (2009)

e16580 Background: Carcinoma of cervix is worldwide, the most frequent gynecological cancer particularly in developing countries like ours. Carcinoma of the cervix uterine is the second commonest gynecological cancer in the developed countries and top ranking in the developing countries like ours. Methods: One hundred and fifty women having carcinoma of the cervix uteri were prospectively studied in the department of Gynaecology and Obstetrics and Radiotherapy department of Rajshahi Medical College Hospital from January 2004 to December 2007. The cases were diagnosed clinically and confirmed by histopathological examination. Results: In all 150 patients of carcinoma of the cervix were selected for this study. There mean age was 50.12 yrs. Most of the patients (78%) had marriage between the age of 10–15 years; 8% married below 10 years and 14% between 16–20 years of age.In this study the all were multipara; 30% patients had 6 pregnancies throughout life. 10% had more than 10 pregnancies, 8% had 8 pregnancies, 4% had 9 pregnancies, 14% had 5 pregnancies and 16% had 4 pregnancies.The study shows that the distribution of patients according to the staging of the carcinoma. 54 (36%) were of III A stage. 39 (26%) in II B stage, 21 (14%) in III B stage, 9 (6%) in IV A stage, 6 (4%) in I B stage, and 3 (2%) in IV B stage. No patient presented with O or IA stage. Conclusions: The study showed that the majority of the patients were between the ages of 40–50. HPV types 16/18 has a significant role for the development of the disease. Religious practices are of important role for its causation. It is less frequent in Jew and most frequent in Hindu. Histopathologically 90%-95% are squamous cell carcinoma and 1–5% are adnocarcinoma.From the findings it is observed that early marriage, creation of awareness about sex hygiene, discourage to have multiple sexual partners and marriages, discourage to have multiple pregnancies and providing adequate health care and health education to the women could reduce the development of carcinoma of cervix. No significant financial relationships to disclose.
Abstract B14: TP53 synthetic lethal targets in colon cancer
Authors: Charles C. Weige, Changlong Liu, Erin L. Anderson, Carolyn E. Banister, Joseph Richardson, Carlo Contreras, Phillip J. Buckhaults
Journal: Cancer Research (2017)

Abstract We have performed a genome-wide screen for pathways that are synthetic lethal with TP53 mutations in colon cancer. RKO colon cancer cells are wild type for TP53, and display robust p53-dependent growth arrest and apoptosis. We utilized an isogenic pair of RKO cells differing only in TP53 gene status (wild type vs homozygous null derivative) to screen a genome-wide GeCKO CRISPR library. After infection of these cells with the library and culturing for one week in vitro, we performed deep amplicon sequencing to identify CRISPR guide RNAs that were underrepresented in TP53 knockout cells. Multiple CRISPR guide RNAs targeting the CHEK1 and SHH genes were underrepresented in TP53 knockout cells. To validate these targets, we used CRISPR genome engineering to create an independent panel of six RKO clones with biallelic disruption of TP53, and tested small molecule inhibitors of CHEK1 (UCN01) and the SHH receptor SMO (Cyclopamine). TP53 null cells were tenfold more sensitive to UCN01, and 100-fold more sensitive to Cyclopamine, compared to TP53 wild type cells. Finally, the relevance of these findings to human colon cancers was confirmed by the establishment and treatment of colon cancer organoid avatars with either wild type or mutant TP53. Normal colon organoids, and tumor organoids with wild type TP53 were unaffected by either drug, whereas TP53 mutant organoids were significantly growth inhibited. Future studies will focus on testing these and additional targets, alone and in combination, against primary colon tumor and normal avatars and other preclinical models of TP53-mutant colon cancer. Citation Format: Charles C. Weige, Changlong Liu, Erin L. Anderson, Carolyn E. Banister, Joseph Richardson, Carlo Contreras, Phillip J. Buckhaults. TP53 synthetic lethal targets in colon cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B14.
Should endoscopic ablation therapy for Barrett’s-associated neoplasia be limited to academic or tertiary referral centers?
Authors: Fariha Ramay, Bruce Greenwald
Journal: Endoscopy (2017)

Highly effective endoscopic therapies are now available for the management of Barrett’s esophagus (BE)-associated dysplasia and early stage adenocarcinoma. In many circumstances, complete endoscopic resection of mucosal adenocarcinoma (stage T1a) is associated with a high rate of success and a low rate of local or lymph node recurrence [1] [2]. This is typically followed by endoscopic radiofrequency ablation (RFA) of the residual Barrett’s tissue to prevent development of metachronous cancer.
Identification and Molecular Characterization of Two Recurrent Genomic Deletions (Type A and Type B) on 7p12 in IKZF1 Gene in a Large Cohort of BCR-ABL1-Positive Acute Lymphoblastic Leukemia (ALL): on Behalf of the GIMEMA ALL Working Party
Authors: Ilaria IacoBucci, Clelia Tiziana Storlazzi, Emanuela Ottaviani, Annalisa Lonetti, Anna Ferrari, Sabina Chiaretti, Monica Messina, Daniela Cilloni, Nicoletta Testoni, Cristina Papayannidis, Francesca Messa, Annalisa Astolfi, Luciana Impera, Antonella Vitale, Francesca Arruga, Fabrizio Pane, Pier Paolo Piccaluga, Pietro D’Addabbo, Sabrina Colarossi, Simona Soverini, Marco Vignetti, Francesca Paoloni, Stefania Paolini, Giuseppe Saglio, Michele Baccarani, Robert Foà, Giovanni Martinelli
Journal: Blood (2008)
A Multicenter, Case-Control Study Evaluating the Characteristics and Outcome of ITP Patients Refractory to, Rituximab, Splenectomy and Both TPO Receptor Agonists
Authors: Matthieu Mahévas, Mathieu Gerfaud-Valentin, Guillaume Moulis, Louis Terriou, Sylvain Audia, Sophie Guenin, Guillaume Le guenno, Gilles A. Salles, Corinne Haioun, Olivier Lambotte, jean-François Viallard, Stéphane Cheze, Cecile Tomowiak, Bruno Royer, Odile Debouverie, Arnaud Hot, Isabelle Durieu, Antoinnette Perlat, Mohamed Hamidou, Nicolas Limal, Marc Michel, Bertrand Godeau
Journal: Blood (2015)
IMPACT TESTING OF DIFFERENT ICE HOCKEY BOARD DESIGNS
Authors: Kai-Uwe Schmitt, Markus Muser, Hansjuerg Thueler, Othmar Bruegger
Journal: British Journal of Sports Medicine (2017)

Background Impact to boards is a frequent cause of injury in ice hockey. Improving the board design to reduce the biomechanical loading of a player at impact is one option to prevent injury. Objective Compare the impact performance of different ice hockey boards and investigate whether so-called “flexible” board designs are to be preferred over standard designs. Design Impact testing of ice hockey boards under laboratory conditions using a dynamic pendulum as well as anthropometric test devices (crash test dummies). Experimental Setting Three board elements including glazing (total length: 7 to 9 m; total height: 2.9 to 3 m) were mounted in the laboratory. A total of 8 systems were tested: two systems featured a standard design while 6 systems represented recent designs that claim to be more flexible. The test conditions were chosen based on previous studies. A pendulum (mass: 60 kg) impacted the boards at heights of 1 m (below handrail) and 1.4 m (on glazing) with velocities of 3.37 m/s and 4.76 m/s. The dummy experiments used a fully instrumented ES-2 dummy that impacted the board in a standing position (mimicking a body check position) at 4.76 m/s. Main Outcome Measurements The deformation of the boards was measured at 1 m and 1.4 m height. Additionally biomechanical relevant measures were recorded using the dummy. The performance of the board and the biomechanical loading of a player were assessed. Results Generally a “flexible” board design allows for more deformation than a standard design, but the performance varies strongly between different board models/ products. While standard boards deformed 13.4±3.6 mm and 30.7±13.1 mm at 1 m and 1.4 m height, respectively, “flexible” boards deformed 40.1±13.3 mm and 56.2±17.7 mm. Acrylic glazing enables more deformation than glass glazing (10–60% increase). The results were consistent for dummy and pendulum impacts. Conclusions Recent board designs exhibit a larger deformation performance compared to standard designs.