tbuckley/cabot-search huggingface dataset:
Phase II trial of pelvic radiation, weekly cisplatin, and 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) for locally advanced cervical and vaginal cancer.
Authors: C. Kunos, S. E. Waggoner, K. M. Zanotti, R. DeBernardo, N. Fusco, A. Heugel, J. Knazek, R. Adams, T. Radivoyevitch, A. Dowlati
Journal: Journal of Clinical Oncology (2011)

5034 Background: This on-going clinical trial assesses the safety and clinical activity of 3x weekly intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) co-administered with 1x weekly intravenous cisplatin and daily pelvic radiation in patients with locally advanced cervical and vaginal cancer. 3-AP potently inhibits ribonucleotide reductase and clinically is being evaluated as a chemoradiation sensitizer. Here, we report the preliminary toxicity and response data. Methods: Patients with stage IB2 to IVB cervical cancer (n = 12) or stage II to IV vaginal cancer (n = 2) underwent 2-hour 3-AP infusions (25 mg/m2) 3x weekly during 5 weeks of cisplatin (40 mg/m2, 70 mg maximum) chemoradiation. Brachytherapy followed. Toxicity was monitored by common terminology criteria for adverse events v3.0. Response was assessed by exam and 3-month posttherapy positron emission tomography (PET/CT). Institutional review board approval was provided for conduct of research. Results: 14 patients tolerated 206 (98%) of 210 planned 3-AP infusions. Four patients experienced reversible 3-AP-related grade 3 leukopenia or thrombocytopenia. Two patients had reversible, possibly 3-AP-related, grade 3 hypokalemia and hyponatremia. One patient with pre-existing portal hypertension had a less than 30-day post-chemoradiation grade 4 hemorrhage secondary to an iatrogenic Mallory-Weiss tear of gastric varices, occurring before brachytherapy and resulting in death. 13 (93%) of 14 patients achieved durable complete clinical responses (median follow-up 9 months, range 3-18 months). 10 (91%) of 11 patients had 3-month PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. Conclusions: 3-AP given 3x weekly co-administered with cisplatin chemoradiation is well tolerated and associated with a high clinical and metabolic response. Further accrual is on-going (Grant: Case Western Reserve University 5U01 CA062502).
Expression and Functional Analysis of Autotaxin, a Relevant Motility and Survival Factor, in FLT3-ITD Positive Acute Myeloid Leukemia and Primary Hematopoietic Stem Cells.
Authors: Claudia Ortlepp, Christine Steudel, Sina Koch, Angela Jacobi, Satu Kyttaelae, Martin Ryser, Sebastian Brenner, Martin Bornhaeuser, Gerhard Ehninger, Christian Thiede
Journal: Blood (2008)
Fertility preservation: Are we telling patients what they want to know?
Authors: S. B. Goldfarb, J. F. Kelvin, B. Thom, J. Kaplan, A. Margolies, S. Corcoran, M. S. McCabe, C. Hudis, E. M. Basch, M. N. Dickler
Journal: Journal of Clinical Oncology (2011)

e19657 Background: Over 125,000 patients of reproductive age are diagnosed with cancer annually in the US. Many have not yet started or completed their families at the time of diagnosis and are distressed about the possibility of treatment-induced infertility. Informing patients about fertility preservation (FP) options before therapy may optimize quality of life after treatment. This study evaluated the information (info) patients received about effects of therapy on fertility, early menopause, and FP options, as well as satisfaction with the info and preferred means of receiving it. Methods: An IRB approved cross-sectional study was performed using gender specific surveys developed at MSKCC with input from a multidisciplinary committee. Surveys were mailed to all living patients 18-45 yo who began treatment at MSKCC between 1/01/06 and 6/30/08. Surveys were also administered to consecutive patients with breast, lymphoma, testicular, sarcoma and colorectal cancers at MSKCC outpatient clinics. Results: The survey was completed by 272/601 (45%) women and 149/321 (46%) men overall. At the time of diagnosis 62% had children and 54% were interested in future childbearing. An MSKCC provider initiated fertility discussions with 48% of women and 51% of men. Although fertility was discussed with most patients (78% women, 82% men), info was not sufficient to meet patients’ needs. Women reported they had not received adequate info about effects of treatment on fertility (55%), early menopause (53%), and options for FP (77%). Fewer men felt they had not received adequate info about effects of treatment on fertility (25%) and options for FP (31%). Based on their ranking, patients preferred to receive fertility info in person from their physician or a fertility specialist, or through written material. Conclusions: Many cancer survivors wish to have children after treatment. To optimize success and satisfaction, patients should be adequately informed about the effects of therapy on fertility, early menopause, and options for FP. These findings are informing an institution-wide fertility program and have led to the development of patient education materials, a process for referring patients to reproductive specialists and an intranet fertility site for providers.
Long Term Outcome of Gastric MALT Lymphoma Patients Treated with Anti-Helicobacter (Antibiotic and Proton-Pump Inhibitor) Regimens.
Authors: Claudio Chini, Graziella Pinotti, Anastasios Stathis, Ilaria Proserpio, Francesco Bertoni, Franco Cavalli, Emanuele Zucca
Journal: Blood (2007)
68. Immunovirotherapy: Enhancing Personalized T Cell Therapy with Oncolytic Measles Virus Vaccination
Authors: Elena S. Czink, Tobias Speck, Johannes Heidbuechel, Jessica Albert, Birgit Hoyler, Dirk Jaeger, Christof von Kalle, Guy Ungerechts, Christine E. Engeland
Journal: Molecular Therapy (2016)

Oncolytic viruses directly reduce tumor burden by selective lytic replication in malignant cells, which designates these vectors as a potent platform for targeted cancer therapy. Lately the focus of oncolytic research has shifted towards the immunostimulatory potential of viral infection within the tumor microenvironment. Oncolytic viruses can be considered to act as an autologous tumor vaccine with the capacity to induce a tumor-specific T cell response. We hypothesize that oncolytic measles virus (MV) expressing a tumor-associated antigen (TAA) can specifically support T cell activation and persistence after adoptive transfer of TAA-specific T cells. We modified the Schwarz vaccine-derived measles virus to encode either OVA as a model antigen or one of the endogenous melanoma antigens trp-2 or gp100. TAA insertion did not impede viral replication and oncolysis compared to the parental virus. For in vivo studies, we have generated a new immunocompetent mouse model for MV oncolysis, B16-hCD46. Transduction of hCD46-positive B16 tumor cells with the novel viruses induces a strong virus-mediated expression of the tumor antigens, serving as a specific and lasting stimulus for adoptively transferred T cells. With the increasing availability of tumor sequencing data, this study has direct implications for future clinical trials of personalized immunovirotherapy.
PWE-093 Incidence of abnormal findings on abdominal computerised tomography and correlation with endoscopic follow-up and findings
Authors: U Thalheimer, R Robson, A O'Connor, R Borgstein, J Wright
Journal: Gut (2010)

<h3>Introduction</h3> An increasing number of patients undergo computerised tomography (CT) of the abdomen, leading to increased demand for endoscopy. Our aim was to investigate the incidence of abnormal GI findings on abdominal CT scans in an unselected cohort of patients, the incidence of endoscopy generated and the correlation with any endoscopic findings. <h3>Methods</h3> All abdominal CT scans performed at the North Middlesex University Hospital were evaluated from January to June 2005. CT reports were assessed for abnormalities relating to the GI tract, and endoscopy reports, histology reports and further radiology reports were reviewed. <h3>Results</h3> A total of 1407 abdominal CT scans (1092 patients) were identified. 199 (14%) of these for 185 patients (17%), had abnormal findings relating to the GI tract. The site of the abnormality was the colon in 115, the upper GI tract in 67, small bowel in 15 patients (multiple sites in 13). Histology was available for 84 patients diagnosing malignancy in 42 (50%). 38 out of the 185 patients (20.5%) had an endoscopic procedure related to the CT findings. In 20 patients out of the 38 (53%) endoscopy confirmed the presence of an abnormality compatible with the CT findings. Malignancy was the cause in 13 of these (34%). One out of seven patients (14%) under the age of 50 had a malignant finding as compared to 12 out of 31 (39%) of patients above the age of 50. Of the 149 patients who did not undergo an endoscopic procedure, 38 had an non-endoscopic procedure or decision (eg, other imaging, surgery or biopsy). 35 had undergone an endoscopic procedure prior to CT, 35 had a known cause for the abnormality and six were known to have a significant non-GI pathology. Six patients had small bowel abnormalities and in eight a specific cause was suggested that did not require further endoscopic diagnosis. 30 patients (16%) had no endoscopy without any obvious explanation and in these a potential diagnosis could have been missed. From these findings a new pathway for endoscopy for GI abnormalities on CT has been developed. <h3>Conclusion</h3> Abnormal findings on unselected abdominal CT scans are frequent in our practice and are compatible with abnormal endoscopic findings in half the patients investigated. Over 6 months, abnormal CT of the GI tract generated 38 new endoscopy requests with an incidence of endoscopic abnormality in half and cancer in a third. We therefore conclude that endoscopy to investigate abnormal gastrointestinal tract findings on CT scanning at the North Middlesex hospital is a necessary investigation with a high incidence of pathology encountered.
Sustained enjoyment of life and mortality at older ages: analysis of the English Longitudinal Study of Ageing
Authors: Paola Zaninotto, Jane Wardle, Andrew Steptoe
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To test whether the number of reports of enjoyment of life over a four year period is quantitatively associated with all cause mortality, and with death from cardiovascular disease and from other causes. <b>Design and setting</b>&nbsp;Longitudinal observational population study using the English Longitudinal Study of Ageing (ELSA), a nationally representative sample of older men and women living in England. <b>Participants</b>&nbsp;9365 men and women aged 50 years or older (mean 63, standard deviation 9.3) at recruitment. <b>Main outcome measures</b>&nbsp;Time to death, based on mortality between the third phase of data collection (wave 3 in 2006) and March 2013 (up to seven years). <b>Results</b>&nbsp;Subjective wellbeing with measures of enjoyment of life were assessed in 2002 (wave 1), 2004 (wave 2), and 2006 (wave 3). 2264 (24%) respondents reported no enjoyment of life on any assessment, with 1833 (20%) reporting high enjoyment on one report of high enjoyment of life, 2063 (22%) on two reports, and 3205 (34%) on all three occasions. 1310 deaths were recorded during follow-up. Mortality was inversely associated with the number of occasions on which participants reported high enjoyment of life. Compared with the no high enjoyment group, the hazard ratio for all cause mortality was 0.83 (95% confidence interval 0.70 to 0.99) for two reports of enjoyment of life, and 0.76 (0.64 to 0.89) for three reports, after adjustment for demographic factors, baseline health, mobility impairment, and depressive symptoms. The same association was observed after deaths occurring within two years of the third enjoyment measure were excluded (0.90 (0.85 to 0.95) for every additional report of enjoyment), and in the complete case analysis (0.90 (0.83 to 0.96)). <b>Conclusions</b>&nbsp;This is an observational study, so causal conclusions cannot be drawn. Nonetheless, the results add a new dimension to understanding the significance of subjective wellbeing for health outcomes by documenting the importance of sustained wellbeing over time.
The Finnish experience to save asthma costs by improving care in 1987-2013
Authors: Tari Haahtela, Fredrik Herse, Jussi Karjalainen, Timo Klaukka, Miika Linna, Riikka-Leena Leskelä, Olof Selroos, Eeva Reissell
Journal: Journal of Allergy and Clinical Immunology (2016)
The Phosphatidylinositol-3-Kinase Inhibitor BKM120 Impairs Proliferation and Induces Pro-Apoptotic Effects In Acute Myeloid Leukemia
Authors: Matteo Allegretti, Maria Rosaria Ricciardi, Martina Vincenzi, Roberto Licchetta, Simone Mirabilii, Sergio Amadori, Robin Foà, Agostino Tafuri
Journal: Blood (2013)
COX-2 -765G>C promoter polymorphism and risk of colorectal polyps.
Authors: Joon-Ho Yu, Jeannette Bigler, John Whitton, Rachel D. Sparks, Yutaka Yasui, Justin Sibert, John D. Potter, Cornelia M. Ulrich
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2370 

Background: Cyclooxygenase-2 has been shown to play a key role in the regulation of inflammation. Its inhibition is associated with a reduced risk of colon cancer. The COX-2 -765G>C promoter variant is located in a putative SP1 binding site. In vitro functional data show that the -765C allele reduces COX-2 expression and is also associated with decreased serum concentrations of C-reactive protein in patients following coronary bypass surgery. Method: In a Minnesota-based case-control study of cases with adenomas (n=494) or hyperplastic polyps (n=186), vs. polyp-free controls (n=584), we investigated the role of the COX-2 -765G>C promoter polymorphism. Multiple logistic regression analysis was used, adjusting for age, BMI, caloric intake, alcohol, fiber, sex, hormone use, and smoking. Results: Genotype frequencies among controls were GG=0.69, GC=0.27, CC=0.03. The COX-2 -765C allele was not associated with a statistically significant altered risk of colorectal polyps; however, there was an indication for a risk reduction among those homozygous variant CC. For colorectal adenomas, multivariable-adjusted odds ratios by genotype compared to GG as reference were GC 1.00 (95% CI 0.74-1.35) and CC 0.53 (95% CI 0.22-1.28). For hyperplastic polyps, the comparable adjusted odds ratios were GC 0.97 (95% CI 0.65-1.46) and CC 0.24 (95% CI 0.05-1.11). Risk associated with the -765C variant differed by aspirin or other NSAID use. Among non-users of aspirin or other NSAIDs, the CC genotype conferred a significant decrease in risk of adenomas (see table). Use of aspirin or other NSAIDs reduced risk of adenomas only among those with the -765GG (wildtype) and -765CG genotypes. Conclusion: These data suggest that COX-2 expression may be beneficially suppressed –and risk of colorectal polyps reduced –by aspirin or other NSAIDs in -765GG (wildtype) individuals, and by the -765C allele in non-users of aspirin or other NSAIDs. Table: Risk of colorectal polyps associated with COX-2 -765G>C genotypes stratified by aspirin or other NSAID use.



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Abexinostat (S78454/PCI-24781), an Oral Pan-Histone Deacetylas (HDAC) Inhibitor in Patients with Refractory or Relapsed Hodgkin's Lymphoma, Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia. Results of a Phase I Dose-Escalation Study in 35 Patients
Authors: Franck Morschhauser, Louis Terriou, Bertrand Coiffier, Gilles Salles, Ioana Kloos, Nicolas Tavernier, Stephane Depil, Vincent Ribrag
Journal: Blood (2012)
FLT3 and KIT Mutated Pediatric Acute Myeloid Leukemia (AML) Samples Are More Sensitive In Vitro to the Tyrosine Kinase Inhibitor SU11657.
Authors: Bianca F. Goemans, Christian M. Zwaan, Desiree de Lange, Jacqueline Cloos, Dirk Reinhardt, Karel Hahlen, Brenda E.S. Gibson, Ursula Creutzig, GertJan J.L. Kaspers
Journal: Blood (2006)
Poor outcomes associated with +der(22)t(9;22) and −9/9p in patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia receiving chemotherapy plus a tyrosine kinase inhibitor
Authors: Nicholas J. Short, Hagop M. Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C. Cameron Yin, Guillermo Garcia‐Manero, Jorge E. Cortes, Rebecca Garris, Susan M. O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M. Kadia, Naval G. Daver, Christopher B. Benton, Ghayas C. Issa, Marina Konopleva, Elias Jabbour
Journal: American Journal of Hematology (2016)

Abstract In patients with Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well‐established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first‐line intensive chemotherapy plus either imatinib ( n = 36), dasatinib ( n = 74), or ponatinib ( n = 42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse‐free survival (RFS; P = 0.42) or overall survival (OS; P = 0.51). When individual ACAs were evaluated, +der(22)t(9;22) and/or −9/9p in the absence of high hyperdiploidy (HeH) was present in 16% of patients and constituted a poor‐risk ACA group. Patients with one or more poor‐risk ACAs in the absence of HeH had significantly shorter RFS (5‐year RFS rate 33% versus 59%, P = 0.01) and OS (5‐year OS rate 24% versus 63%, P = 0.003). Poor‐risk ACAs were prognostic in patients who received imatinib and dasatinib but not in those who received ponatinib. By multivariate analysis, this poor‐risk ACA group was independently associated with worse RFS (HR 2.03 [95% CI 1.08‐3.30], P = 0.03) and OS (HR 2.02 [95% CI 1.10‐3.71], P = 0.02). Patients with Ph+ ALL who have +der(22)t(9;22) and/or −9/9p in the absence of HeH have relatively poor outcomes when treated with chemotherapy plus a TKI.
Cardiopulmonary outcomes in pediatric surivors of Hodgkin's lymphoma.
Authors: K. C. Burns, J. Correll, D. A. Kent, N. Bakeer, J. P. Perentesis, R. Nagarajan
Journal: Journal of Clinical Oncology (2011)

9578 Background: Hodgkin’s lymphoma (HL) has an excellent cure rate in pediatric patients. However, survivors are at risk for cardiopulmonary complications from their therapy. Cardiac toxicity includes cardiomyopathy, pericarditis, congestive heart failure, valvular disease, or premature coronary artery disease, while pulmonary complications include pulmonary fibrosis and pneumonitis. Risk factors include anthracycline and bleomycin chemotherapy as well as chest radiation. Methods: A retrospective review examined survivors of HL followed in the CCHMC Cancer Survivor Center. All patients were diagnosed under the age of 21 and were at least 5 years from diagnosis. Cardiopulmonary dysfunction was assessed as ECHO shortening fraction <30% or MUGA ejection fraction <55 and PFT DLCO <80%. Demographic and treatment variables were also examined. Results: 89 patients with HL had an average age of 13.5 (5.0-20.7) years at diagnosis and an average length of follow-up from diagnosis to last ECHO of 10.3 (1.5-29.2) years. There were 45 males. 85 (95%) received anthracycline with an average dose of 220mg/m2 (140-370), 82 (91%) received an average of 70 units/m2 of bleomycin (30-120) and 61 (69%) had chest radiation. Of the 89 patients, 21 (24%) had a cardiac abnormality at any time with 18 (20%) persisting 3+ years from diagnosis. 13 (15%) had a cardiac abnormality 5+ years from diagnosis. 12 of the 13 had a CTC (v3.0) grade of 1 and 1 patient had a grade of 3. Of the13 with cardiac abnormalities, 3 required medications. 44 patients (49%) had a DLCO of less than 80% at some point. This persisted in 23 (25%) at 3+ years and in 15 (17%) patients at 5+ years post therapy. Of that 15, 10 patients had a CTC (v3.0) grade of 2 and 2 patients had a grade of 3. 3 patients were referred to pulmonology. 2 of the 89 patients had both an abnormal SF and DLCO at 5 years. Conclusions: With long follow up about 20% of patients had an abnormal ECHO result with 15% persisting after 5 years. Nearly half of the patients had a DLCO of less than 80%, but most were never symptomatic and did not require intervention. Despite having cardiopulmonary abnormalities at some point in time most will continue to do well. The subset that does develop these complications deserves further investigation.
High Relapse Rate of Acute Myeloid Leukemia with Translocation (8;21) or Inversion (16) in Elderly Patients Treated with Conventional Chemotherapy.
Authors: Thomas Prebet, Fanny Bernard, Anne Etienne, Aude Charbonnier, Marie Joelle Mozziconacci, Diane Coso, Anne-Marie Stoppa, Danièle Sainty, Jean Albert Gastaud, Norbert Vey
Journal: Blood (2007)
Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment
Authors: Yohko Kitagawa, Naganari Ohkura, Yujiro Kidani, Alexis Vandenbon, Keiji Hirota, Ryoji Kawakami, Keiko Yasuda, Daisuke Motooka, Shota Nakamura, Motonari Kondo, Ichiro Taniuchi, Terumi Kohwi-Shigematsu, Shimon Sakaguchi
Journal: Nature Immunology (2016)
The MTHFR C677T genotype and risk of adenoma recurrence: results from a randomized double blind clinical trial of folic acid supplementation
Authors: Zonglin Deng, Jinhui Zhang, Roberd M. Bostick, Kim E. Creek, Xijiang Miao, Dawen Xie
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3711 

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. The MTHFR C677T TT genotype has clear functional effects on enzyme function and has been associated with decreased risk of colorectal cancer in multiple studies. However, the association between MTHFR genotype and the risk of colorectal adenoma, the precursor lesion to most colorectal cancers is not clear. In the current study we investigate the association between MTHFR genotype and risk of developing one or more adenomas or advanced adenomas in a large, randomized, double-blind, factorial design trial of folic acid and aspirin supplementation. Eligible subjects were enrolled between July 1994 and March 1998 and were between the ages of 21 and 80 years in good health and had a positive history of at least one histologically confirmed colorectal adenoma removed prior to enrollment. Follow-up colonoscopy was scheduled approximately three years after the qualifying exam. Advanced adenoma was defined as adenomas with >25% villous features, large size (> 1 cm diameter), severe dysplasia or invasive cancer. We used generalized linear regression analyses to estimate RRs and 95% CIs to assess the association between genotype and risk of adenoma while adjusting for age, sex, clinical center, follow-up time, and treatment status. The MTHFR 677 TT genotype was associated with a slight decrease in the risk of any follow-up adenoma compared to the wildtype CC genotype (RR 0.89 (95% CI 0.62 to 1.27)) and to any advanced adenoma (RR 0.72 (95% CI 0.34 to 1.53)), nor did genotype modify the effects of folate supplementation. Our data suggests that the MTHFR C677T polymorphism may be inversely associated with the development of advanced adenomas. Future investigations will be needed to clarify these findings.