tbuckley/cabot-search huggingface dataset:
Abstract 4281: Mitochondrial DNA copy number, urinary isoprostanes and colorectal cancer risk
Authors: Bharat Thyagarajan, Renwei Wang, Woon-Puay Koh, Helene Barcelo, Jennifer Adams-Haduch, Weihua Guan, Roberd M. Bostick, Jian-Min Yuan, Myron D. Gross
Journal: Cancer Research (2016)

Abstract Previous epidemiological studies on mitochondrial DNA (mtDNA) copy number and risk of colorectal cancer have yielded mixed results. One study reported a positive association, another reported an inverse association, and a third, a U-shaped association of mtDNA copy number with colorectal cancer risk. Since oxidative stress is one of the proposed underlying mechanisms that may link mtDNA copy number variation to colorectal cancer risk, we conducted a matched case-control study of incident colorectal cancer nested within the Singapore Chinese Health Study. Pre-diagnostic blood and urine samples were obtained from 448 colorectal cancer cases and 869 age- and sex-matched controls. The mtDNA copy number in peripheral white cells was measured using real time PCR and urinary F2-isoprostanes were quantified using a liquid chromatography mass spectrometry based method. Conditional logistic regression was used to estimate associations of mtDNA copy number and urinary F2-isoprostanes with incident colorectal cancer. The odds ratios (OR) and 95% confidence intervals (95% CI) for those in the highest relative to those in the lowest quartiles of relative mtDNA copy numbers and urinary F2-isoprostanes were 1.02 (95% CI 0.72 - 1.43; p for trend = 0.56) and 1.11 (95% CI 0.78-1.59; p for trend = 0.35) respectively. Urinary F2-isoprostanes levels were not associated with the mtDNA copy number among the controls (r = 0.03; p = 0.33). The results of this prospective study suggest that white blood cell mtDNA copy number or urinary levels of F2-isoprostanes in biospecimens collected several years prior to the diagnosis of colorectal cancer may not be associated with risk of developing colorectal cancer. Citation Format: Bharat Thyagarajan, Renwei Wang, Woon-Puay Koh, Helene Barcelo, Jennifer Adams-Haduch, Weihua Guan, Roberd M. Bostick, Jian-Min Yuan, Myron D. Gross. Mitochondrial DNA copy number, urinary isoprostanes and colorectal cancer risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4281.
Autologous Stem Cell Transplantation in Patients of High and Intermediate Risk Acute Myeloid Leukemia:-Perspective of a Developing Country.
Authors: Velu Nair, Satyaranjan Das, Sanjeevan Sharma, Ajay Sharma, Deepak Kumar Mishra, Shilajit Bhattacharya, Jasmeet Kaur, Prosenjit Ganguli, SR Mehta, Naresh Kumar
Journal: Blood (2009)
Abstract 1796A: Race and gender differences in lung cancer: examining the effect of smoking history and depression on hospitalization costs
Authors: Baqar A. Husaini, Van A. Cain, Robert S. Levine
Journal: Cancer Research (2016)

Abstract Objective: Incidence rates of lung cancer (LC) are reported to have declined in the nation. However, the role of depression and tobacco history relative to hospitalization cost for LC remains unknown. Tennessee, being a tobacco producing State, provides an opportunity to examine two issues: (i) Prevalence of LC, depression, and history of tobacco use among LC patients by race and gender; (ii) Effect of depression and smoking history on hospitalization costs by sub-groups of LC patients. Methods: We extracted data pertaining to depression, smoking history, and demographics on patients discharged with all lung cancer (adenocarcinoma, ICD-9 codes 160-165) from the 2008 Tennessee Hospital Discharge Data System (HDDS). The sample (n = 6,665) had patients that were mostly white (86%) and male (57%), with an average age of 67 years. We computed age-adjusted LC rates for race and gender (per CDC methodology), and compared the costs for LC patients with depression/ smoking history with LC patients without depression/smoking history. Results: LC rates (per 100K) were higher among blacks than whites (146.6 vs. 131.6, p&amp;lt;.000), and higher among male than female patients (174.9 vs. 118.0, p&amp;lt;.00). While nearly 40% of LC patients had a smoking history (more males than females had a history with no racial variation), 25% had depression (more females and whites were depressed). Further, the total hospitalization cost for 2008 was 50% higher for LC patients with depression plus smoking history compared to peers without depression/smoking history ($122,500 vs. 80,522, p&amp;lt;.000). Conclusion: LC rates are higher among blacks and males who also have more smoking history. Depression is higher among females and whites with LC. Further, both depression and smoking history adds significantly to the hospitalization costs. These results point to: (i) costs savings might be realized by treating depression first among the LC patients, and (ii) population-based smoking cessation programs need to be vigorously implemented to reduce lung cancer and associated co-morbidities. ___________________ This presentation at the Eight AACR annual Conference, New Orleans, April 16-20, 2016, was partially supported by grants from CDC #U58CCU422782, a sub-contract #ED-07-20811-09, and a NCI/NIH grant (5U54CA163066) to Tennessee State University, B. Husaini, PI. Citation Format: Baqar A. Husaini, Van A. Cain, Robert S. Levine. Race and gender differences in lung cancer: examining the effect of smoking history and depression on hospitalization costs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1796A.
High-grade neuroendocrine carcinoma of the uterine cervix: Outcomes and the role of chemotherapy.
Authors: B. Naraev, M. J. Goodheart, T. M. O'Dorisio, T. R. Halfdanarson
Journal: Journal of Clinical Oncology (2011)

e15512 Background: High-grade neuroendocrine carcinoma of the uterine cervix (cNEC) is a rare and aggressive cancer, and the optimal treatment remains uncertain. We report 36 cases seen at the University of Iowa between 1977 and 2010. Methods: Cases were identified by searching our institutional database. Only patients (pts) with pathology-confirmed cNEC were included. Results: 36 cases with follow-up information were identified. The median age at diagnosis was 49 years (range 26 – 77). FIGO staging was IB1 for 14 pts (39%), IB2 for 3 (8%), II for 7 (19%), and 12 (34%) had stage III or higher. 17 pts (47.2%) underwent resection, 20 pts (56%) had radiation therapy (RT), and 27 pts (82%) received chemotherapy (ChT). The median survival (MS) for the entire cohort was 20.7 months (ms) with 23% 5-year overall survival (5-OS) and 8% 10-year OS. Stage was a strong predictor of survival. Pts with stage IB1 or less had longer MS and 5-OS compared to those with higher stage (MS 42 vs. 11.1 ms, p=0.008, 5-OS 47 vs. 6%). Complete resection predicted better outcome (MS: 50 vs 9.3 ms, p=0.0004, 5-OS: 50 vs. 0%). Of 17 resected pts, 7 recurred after a median of 19.4 ms (range 7.5 – 43), and all but 1 died. RT was not associated with outcome regardless of surgery. Resected pts had MS of 43.8 ms with RT vs. 128.5 ms without RT, (p=0.76). Pts with unresectable disease demonstrated MS of 11.8 ms with, and 10.5 ms without RT (p=0.8). ChT was beneficial in pts with unresectable disease. Pts receiving ChT had MS of 10.8 ms vs. 2.7 ms (p=0.006) in those who did not. None of these pts survived > 5 years. Platinum with etoposide was used in 73%. Partial response or stable disease were seen in 50% with mean duration of response of 9.1 ms. Second line ChT at progression was used in 44.4%. Pre- and post-operative ChT in resectable disease did not impact survival (MS 45 ms on ChT vs. 156.5 ms with no ChT (p=0.37). Conclusions: The prognosis of advanced cNEC is very poor and surgery in early stages resulted in the best outcome. RT was not associated with improved survival in this study. ChT seems beneficial in unresectable disease, but the effect of the second line ChT remains undefined. Overall, the treatment outcomes remain unsatisfactory; better treatment options are needed.
Abstract 1825: ONC201 induces cell death in androgen receptor positive prostate cancer cells and shows synergistic effect with anti-prostate cancer drugs
Authors: Avital Lev, Amriti R. Lulla, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2016)

Abstract Prostate cancer is the most common cancer and the second leading cause of cancer related death among men in the United States. Current therapy for advanced prostate cancer is mainly based on androgen deprivation, though in many cases tumors become androgen-independent and resistant to available treatments. Thus, accessing novel therapies for prostate cancer and resistant tumors remains an important goal in the field. ONC201 is a first-in-class small molecule anti-cancer drug, shown to selectively induce cell death in most cancer cells tested in contrast to matched normal cells. In this study we investigated the single-agent and combination efficacy of ONC201 on a panel of prostate cancer cell lines with varied androgen receptor (AR) and receptor tyrosine kinases (RTKs) expression status. Our preliminary data suggests that the pro-apoptotic effects of ONC201 correlate with expression of androgen receptor and other receptor tyrosine kinases (RTKs). Specifically, high AR and low RTK (c-MET, EGFR, HER2 and IGFR) expression demonstrated higher sensitivity to ONC201 as compared to low AR and high RTK expression as evaluated by cell viability using the Cell-Titer Glo assay. We further modeled these findings in ONC201-sensitive 22Rv1 and ONC201-resistant DU145 cell lines. ONC201 induced robust apoptosis (cleaved PARP) in ONC201-sensitive 22Rv1 cells as compared to ONC201-resistant DU145 cells In addition, ONC201-sensitive 22RV1 cells showed abrogation of total AR expression 72 hours following treatment with ONC201. Thus, AR and RTK status seem to be emerging efficacy markers for response of ONC201 in prostate cancer cells. We are further investigating the involvement of ONC201 in the signal transduction pathway of AR and other RTKs in prostate cancer. Lastly, our initial screening for treatment of cells with a combination of ONC201 and FDA-approved therapies for prostate cancer showed synergistic potential of ONC201 with everolimus and docetaxel in both AR-dependent and independent cells. As expected, synergism of anti-androgen MDV3100 (enzalutamide) with ONC201 was restricted to AR positive prostate cancer cell lines. Our results indicate that ONC201 has therapeutic potential both as a single agent and in combination therapy for prostate cancer. Our long-term goal is to integrate our pre-clinical studies and translate the findings to single agent/combination trials of ONC201 for prostate cancer patients. Citation Format: Avital Lev, Amriti R. Lulla, David T. Dicker, Wafik S. El-Deiry. ONC201 induces cell death in androgen receptor positive prostate cancer cells and shows synergistic effect with anti-prostate cancer drugs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1825.
Abstract 3797: Validation of a novel antibody against fibulin-3 for targeted therapy of glioblastoma
Authors: Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Ennio Antonio Chiocca, Mariano S. Viapiano
Journal: Cancer Research (2016)

Abstract Glioblastomas (GBM) are highly invasive brain tumors that resist cytotoxic and antiangiogenic therapies, resulting in a high rate of recurrence. Fibulin-3 is an extracellular matrix protein secreted by GBM cells but absent from normal brain. This protein activates Notch signaling to promote tumor invasion and resistance to apoptosis. Conditional knockdown of fibulin-3 reduces GBM growth, invasion and vascularization, thus extending survival. Here we report the initial validation of a function-blocking antibody against this unique GBM target. We first identified the Notch-activating motif of fibulin-3 and developed an immunizing peptide against a key sequence within this motif. A monoclonal antibody generated against this peptide (mAb428.2) showed high affinity for fibulin-3 (Kd 5 nM) and no cross-reactivity against highly homologous fibulin-4 or -5. Antibody mAb428.2 detected fibulin-3 in the stroma and capillaries of human GBM without cross-reactivity against normal brain. The antibody (50-250 μg/ml) blocked the activation of Notch induced by fibulin-3 in GBM cells and caused GBM cell cytotoxicity but had no effects on astrocytes or HEK293 cells. Treatment of mice carrying subcutaneous GBM stem-cell (GSC) derived tumors with mAb428.2 (30 mg/kg IV, q24h x 8 days) resulted in tumor slowdown and extended median survival (47% and 64% in two different GSC models). mAb428.2-treated tumors showed decreased BrdU uptake and increased inflammatory reaction in the tumor stroma (macrophage infiltration and cytokine levels). Mice bearing intracranial tumors did not respond to mAb428.2 when delivered by IV or IP routes, likely due to the inability of the antibody to cross the blood brain barrier. This deficiency was overcome by direct intraparenchymal delivery of the mAb428.2 using chronic infusion (0.3 mg of mAb in 200 μl delivered at 1 μl/h over 7d), which resulted in a 26% increase in median survival. These encouraging results suggest that targeted reagents against fibulin-3 may be of clinical importance for novel combination therapies against GBM. Citation Format: Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Ennio Antonio Chiocca, Mariano S. Viapiano. Validation of a novel antibody against fibulin-3 for targeted therapy of glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3797.
A cohort study of gastric-type adenocarcinoma (GAS) of the uterine cervix: Multi-institutional study by Gynecologic Cancer Study Group of the Japan Clinical Oncology Group (JCOG).
Authors: Shin Nishio, Yoshiki Mikami, Takeo Otsuki, Nobuo Yegashi, Toyomi Satoh, Hiroyuki Yoshikawa, Motoaki Saitou, Aikou Okamoto, Takahiro Kasamatsu, Tsutomu Miyamoto, Tanri Shiozawa, Yumiko Yoshioka, Ikuo Konishi, Atsumi Kojima, Kazuhiro Takehara, Eisuke Kaneki, Hiroaki Kobayashi, Kimio Ushijima, Toshiharu Kamura
Journal: Journal of Clinical Oncology (2014)

5595 Background: GAS is a novel variant of mucinous adenocarcinoma of the uterine cervix. A Japanese group reported that GAS represents more aggressive disease compared with usual-type endocervical adenocarcinoma (UEA), possibly due to chemoresistancy (ASCO 2013). However, the conclusion remains to be confirmed by larger series. Methods: Patients were enrolled at the Gynecologic Cancer Study Group of the JCOG after receiving approval from Institutional Review Board. The study group comprised women with stage I to II disease who underwent surgery without receiving neoadjuvant chemotherapy between 2000 and 2009. The study variables included the incidence of GAS as evaluated by central pathological review (CPR) and the diffences in clinicopathologic features between GAS and UEA. In addition, outcomes of patients with each type were statistically compared. Results: Among 393 cases of endocervical adenocarcinoma enrolled, 328 cases met the CPR and eligibility criteria for further analysis. A total of 95 of 328 (28.9%) tumors were re-classified as GAS. As compared with UEA, GAS was more significantly associated with a bulky mass, deep stromal invasion, lymph vascular space invasion, parametrial invasion, ovarian metastasis, positive ascitic fluid cytology, pelvic lymph node metastasis, and pathological (p) T stage, but was not related to the degree of histological differentiation. Disease-free survival (p<0.0001) and overall survival (p<0.0001) were poorer in patients with GAS than in those with UEA. When the data were analyzed according to disease stage, patients with a diagnosis of pTIA-IB1 adenocarcinoma had poorer outcomes (p<0.0001), but the difference in outcomes as compared with patients who had pTIB2 or more advanced disease was not significant. Conclusions: GAS is significantly associated with histopathologic predictors of poor outcomes as well as with poorer survival outcomes, and therefore is considered to be distinct entity which should be distinguished from UEA. Clinical trial information:UMIN000007987
ATNT-22A PHASE 1 STUDY OF TPI 287 CONCURRENT WITH FRACTIONATED STEREOTACTIC RADIOTHERAPY (FSRT) IN TREATMENT OF BRAIN METASTASES FROM ADVANCED BREAST AND NON-SMALL CELL LUNG (NSCL) CANCER
Authors: Solmaz Sahebjam, Nam D. Tran, H. Michael Yu, John Arrington, Hatem H. Soliman, Tawee Tanvetyanon, Dung-Tsa Chen, Jennifer Cooksey, Michael Hayes, Michael E. Montejo, Nikhil G. Rao, George Farmer, Peter A. Forsyth, Peter A. Johnstone
Journal: Neuro-Oncology (2015)

BACKGROUND: TPI 287, a member of taxanes diterpenoid (taxoid) family, is a microtubule-stabilizer with significant cytotoxic activity. In vivo studies have demonstrated that TPI 287 penetrates the blood brain barrier and significantly reduces the formation of large brain metastases in models of human breast cancer brain metastasis. The radiosensitizing effect of taxanes has been well established. METHODS: This phase I study (3 + 3 design) explores the safety, recommended phase II dose (RP2D), pharmacokinetics (PK), and antitumor activity (local control rate, distant intra-cranial control rate, progression-free survival) of TPI 287 administered concurrently with FSRT (NCT02187822). Patients with up to 3 untreated brain metastases (maximum diameter of each brain lesion ≤ 5 cm, maximum tumor volume ≤ 120 cc) from breast cancer or NSCLC are eligible. Eligible patients are treated with FSRT to target brain metastases (25 Gy in 5 daily fractions). TPI 287 is administered intravenously once per week, for total of 3 doses. The first dose of TPI 287 is given concurrently with the first fraction of FSRT. Once the RP2D is determined, an additional 10 patients will be enrolled in an expansion safety cohort, for a planned total enrollment of 36 patients. Effect of treatment on quality of life measures will be evaluated. RESULTS: As of June 2015, a total of 4 patients have been enrolled in the first two dose escalation cohorts (14 and 28 mg/m2). No treatment-related grade 3/4 adverse events (AEs) have been observed. No dose limiting toxicity has been reported, and maximal tolerated dose has not been reached. TPI 287 dose escalation continues. CONCLUSIONS: Preliminary data to date indicate that administration of TPI 287 concurrent with FSRT is well tolerated. Updated safety and efficacy results will be presented.
P1087 : Prediction of death as a continuum of risk of mortality in severe alcoholic hepatitis based on baseline and dynamic models
Authors: A. Louvet, J. Labreuche, F. Artru, J. Boursier, J. O’Grady, S. Naveau, R. Carithers, E. Diaz, G. Lassailly, A. Cannesson-Leroy, V. Canva-Delcambre, S. Dharancy, T. Morgan, A. Duhamel, P. Mathurin
Journal: Journal of Hepatology (2015)
Dermoscopic Evaluation of Melanocytic Nevi Changes With Combined Mitogen-Activated Protein Kinase Pathway Inhibitors Therapy for Melanoma
Authors: Marie Perier-Muzet, Amélie Boespflug, Nicolas Poulalhon, Julie Caramel, Anne-Laure Breton, Luc Thomas, Stephane Dalle
Journal: JAMA Dermatology (2016)
Effect of democratic reforms on child mortality: a synthetic control analysis
Authors: Hannah Pieters, Daniele Curzi, Alessandro Olper, Johan Swinnen
Journal: The Lancet Global Health (2016)

The effects of political regimes on health are unclear because empirical evidence is neither strong nor robust. Traditional econometric tools do not allow the direction of causality to be established clearly. We used a new method to investigate whether political transition into democracy affected child mortality.We used a synthetic control method to assess the effects of democratisation on child mortality as a proxy of health in countries that underwent transition from autocracy to democracy that lasted for at least 10 years between 1960 and 2010. Democracy was indicated by a score greater than 0 in the Polity2 index. We constructed synthetic controls (counterfactuals) based on weighted averages for factors such as child mortality, economic development, openess to trade, conflict, rural population, and female education from a pool of countries that remained autocracies during the study period.Of 60 countries that underwent democratic transition in the study period, 33 met our inclusion criteria. We were able to construct good counterfactuals for 24 of these. On average, democratisation reduced child mortality, and the effect increased over time. Significant reductions in child mortality were seen in nine (38%) countries, with the average reduction 10 years after democratisation being 13%. In the other 15 countries the effects were not significant. At the country level yhe effects were heterogeneous, but the differences did not correlate with geographic, economic, or political indicators. The effect of democratisation, however, was stronger in countries with above average child mortality before transition than in countries with below average child mortality.Our results are consistent with the interpretation that democratic reforms have the greatest effects when child mortality is a direct concern for a large part of the population. Future research could focus on identifying the precise mechanism through which the effects emerge.European Union 7th Framework Programme and KU Leuven Methusalem Fund.
Improved Survival of Patients with Multiple Myeloma and the Impact of Transplantation and Novel Agents: An Analysis of the Korean Multiple Myeloma Working Party (KMMWP).
Authors: Kihyun Kim, Seok Jin Kim, Byung Soo Kim, Deog-Yeon Jo, Hye Jin Kang, Jin Seok Kim, Yeung-Chul Mun, Chul Soo Kim, Sang Kyun Sohn, Hyeon Seok Eom, Jae-Yong Kwak, Hyeok Shim, Hwi-Joong Yoon, Jong-Youl Jin, Chang-Ki Min, Ho Jin Shin, Hyun Chun Shin, Jong-Ho Won, Je-Jung Lee, Jung Hye Kwon, Young-Don Joo, Young Rok Do, Sung Hyun Kim, Sukjoong Oh, Cheolwon Suh, Junglim Lee, Sung-Soo Yoon, Min Kyoung Kim, Soo-Mee Bang, Hun-Mo Ryoo, Bong-Seog Kim, Hawk Kim, Hyo-Jung Kim, Yang Soo Kim, Chong Won Park, Gyeong-Won Lee, Seongkyu Park, Joon Seong Park, Ho Young Kim, Dong Soon Lee, Jae Hoon Lee
Journal: Blood (2009)
Generic Drug Approvals Since the 1984 Hatch-Waxman Act
Authors: Ravi Gupta, Aaron S. Kesselheim, Nicholas Downing, Jeremy Greene, Joseph S. Ross
Journal: JAMA Internal Medicine (2016)

This study uses US Food and Drug Administration data to identify approved generic drugs manufactured between September 30, 1984, and January 11, 2016 and compares the effects of number of generic drugs associated with brand-name drugs.
Charles Desmond Ross Pengelly
Authors: John Scotson
Journal: BMJ (2016)

Charles Desmond Ross Pengelly, referred to as Desmond, was a well known figure in Manchester medical circles He was born in Penzance, Cornwall, in March 1923 and graduated from Bristol in 1946. He did two house jobs in his teaching hospital and then did his national service in the Royal Army Medical Corps. As he was not of a military disposition, army life was not to his liking—that is, until he was given a posting to Baguley Sanatorium, Manchester, where he dealt mainly with pulmonary tuberculosis.

After leaving the army he held posts in his home county of Cornwall, after which decided to apply for a senior registrar post at Manchester Royal Infirmary. When he arrived in Manchester, in December 1955, the temperature was below freezing, and the fog was such that it was impossible to see across the road. He joked that the Manchester weather operated in his favour because …