tbuckley/cabot-search huggingface dataset:
Standard cisplatin/infusional 5-fluorouracil (PF) vs docetaxel (T) plus PF (TPF) as neoadjuvant chemotherapy for nonresectable locally advanced squamous cell carcinoma of the head andneck (LA-SCCHN): a phase III trial of the EORTC Head and Neck Cancer Group (EORTC #24971)
Authors: J. B. Vermorken, E. Remenar, C. van Herpen, J. Germa Lluch, S. Stewart, T. Gorlia, M. Degardin, K. Schollen, J. Bernier
Journal: Journal of Clinical Oncology (2004)

5508 Background: Data from 5 phase II studies support the notion that T may add to the efficacy of PF in LA-SCCHN (Posner et al. ASCO 20: 203b, 2001). Based on our phase I-II experience with TPF (Schrijvers et al. Ann Oncol 15: 638, 2004), we undertook a phase III trial comparing TPF with PF in such patients (pts). Methods: Eligible pts included nonresectable LA-SCCHN (excluding nasopharynx, nasal & paranasal cavities), measurable disease, adequate organ function, WHO performance status (PS) 0–1, age 18–70 yrs, signed informed consent. Stratification included primary tumor site and institution. Treatment arms were: Arm 1 (PF): P 100 mg/m2 day (d) 1, then F 1000 mg/m2 CI d1–5 q 21 d; Arm 2 (TPF): T 75 mg/m2 d1, P 75 mg/m2 d1, then 5-FU 750 mg/m2 CI d1–5 q 21 d. Planned treatment included 4 cycles unless progression (PD), unacceptable toxicity or pt refusal. Thereafter (interval 4–7 wks), all pts received protocol defined radiotherapy (RT: conventional, accelerated/ hyperfractionated) unless PD after cycle 1 or 2. Surgery before RT (neck dissection) or 3 months (mo) after RT (residual disease) was permitted. The planned sample size of 348 pts and 260 events had 85% power to detect a hazard ratio (HR) of 0.67 (median 10 vs 15 mo) for the primary endpoint of progression-free survival (PFS), using a 5% 2-sided test. Results: 358 pts were accrued (181 to PF and 177 to TPF). Pt/tumor characteristics (age, sex, PS, primary site, T&N stage) were well balanced. After a median follow-up of 32 mo, TPF demonstrated significantly superior PFS (HR 0.72; [95% CI 0.56;0.91]; p=0.006), overall survival (HR 0.73; [95% CI 0.57; 0.94]; p=0.016) and response rate (RR: 67.8% vs 53.6%; p=0.007), while the PF arm showed greater grade 3–4 nausea (7.3% vs 0.6%), vomiting (5.0% vs 0.6%) and stomatitis (11.2% vs 4.6%) and more toxic deaths (5.5% vs 2.3%). Conclusions: TPF (→RT) is superior to PF (→RT) in terms of RR, PFS, OS and is better tolerated. No significant financial relationships to disclose.
Mutagenicity of Metronidazole: Presence of Several Active Metabolites in Human Urine2
Authors: William T. Speck, Aaron B. Stein, Herbert S. Rosenkranz
Journal: JNCI Journal of the National Cancer Institute (1976)

Mutagenic activity was found in the urine of 10 patients given therapeutic dosages of metronidazole orally or per vagina. Paper chromatographic separation revealed that mutagenicity in the urine was associated with unmodified metronidazole and at least four of its known urinary metabolites. Activity was also recovered in a region of the chromato- gram heretofore not assigned to a metronidazole metabolite.
Prognosis following transcatheter arterial chemoembolization for patients with recurrent hepatocellular carcinoma after initial successful percutaneous ablation therapy
Authors: M. Morimoto, K. Numata, T. Ogura, A. Nozaki, K. Tanaka
Journal: Journal of Clinical Oncology (2008)

15673 Background: Recent studies have shown the prognosis and the prognostic factors for hepatocellular carcinoma (HCC) after initial transcatheter arterial chemoembolization (TACE), however, no studies have reported the prognosis following TACE for recurrent HCC. The current study investigated the prognosis following TACE for recurrent HCC patients received initial successful percutaneous ablation therapy. Methods: The inclusion criteria were patients with multinodular HCC, Child-Pugh class A or B, without extrahepatic metastasis or vessel invasion. Eighty patients without a history of any treatment (initial-TACE group) and 31 patients with recurrent HCC after initial percutaneous ablation therapy (recurrent-TACE group) were enrolled in this study and retrospectively analyzed. Results: There were no differences between the backgrounds of both groups at study entry. The 1-, 2-, 3-year overall survival rates of initial-TACE group and recurrent-TACE group were 81%, 53%, 47%, and 91%, 73%, 52%, respectively. Child-Pugh class A, tumor size up to 3cm in maximum diameter, serum alpha-fetoprotein (AFP) level less than 100ng/mL, and serum protein induced by vitamin K absence or antagonist II (PIVKA-II) level less than 300AU/mL were factors related to a good prognosis in initial-TACE group, and serum AFP level less than 100ng/mL was a factor in recurrent-HCC group. Conclusions: There were no differences in overall survival rates between initial-TACE group and recurrent- TACE group. The only prognostic factor identified in recurrent-TACE group was serum AFP level. No significant financial relationships to disclose.
Antioestrogens in treatment of breast cancer.
Journal: BMJ (1974)

results, such as age, parity, and social status, failed to show any apparent bias.Furthermore, you appear to have overlooked the fact that the two studies differed in two essentials: (1) Coxon et al. investigated the use of abdominal decompression in a population of normal pregnant women and found that this had no prophylactic effect on the incidence of pre-eclampsia or the mean birth weight.We studied only those
A quarter century of suicide in a major urban jail: implications for community psychiatry
Authors: C J DuRand, G J Burtka, E J Federman, J A Haycox, J W Smith
Journal: American Journal of Psychiatry (1995)

The authors' goal was to identify factors that increase the risk of suicide in urban jails.They examined and verified all suicides as of 1992 in a representative large jail in Detroit since the beginning of record keeping in 1967 to 1992.There were 37 suicides over this time period. Inmates charged with murder or manslaughter were 19 times more likely to commit suicide than were inmates with other charges. Thirty-nine percent of the suicides were committed by individuals charged with murder. All 37 suicides were by hanging, and most occurred at night within 31 days of admission. Many of the inmates who committed suicide had made previous attempts while incarcerated. Thirty-nine percent of the suicides were committed by individuals charged with murder, constituting 2% of the admissions (two per day).An important risk factor in jail suicide not previously identified is the charge of murder or manslaughter. Treatment and prevention programs should recognize these inmates as belonging in a very high-risk category.
Alcoholic patients with secondary depression
Authors: M Schuckit
Journal: American Journal of Psychiatry (1983)

This study of alcoholic patients with and without secondary depression showed that the two groups were almost identical in demographic characteristics, early-life antisocial problems, quantity and frequency of drinking, and family history of affective disorder. The depressed patients reported slightly more alcoholism in their first-degree male relatives and tended to have more alcohol-related life problems. The only significant difference between the two groups was that the depressed patients were heavier users of drugs other than alcohol. Thus severe depression in alcoholics may be related to a greater intake of drugs in addition to alcohol.
Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: Additional analysis from phase IA study.
Authors: Joseph W. Kim, Joaquim Bellmunt, Thomas Powles, Yohann Loriot, Nicholas J. Vogelzang, Cristina Cruz Zambrano, Howard A. Burris, Siew-leng Melinda Teng, Xiaodong Shen, Jean-Marie Bruey, Zachary Boyd, Priti S. Hegde, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2015)

297 Background: Metastatic urothelial bladder cancer (UBC) is a mutationally-complex disease in which PD-L1 expression in the tumor microenvironment may inhibit immune-mediated antitumor responses. MPDL3280A is a PD-L1-targeting antibody with an engineered Fc domain that disrupts PD-L1/PD-1 and PD-L1/B7.1 signaling. Methods: MPDL3280A was studied in a phase Ia metastatic UBC expansion cohort. UBC pts received MPDL3280A 15 mg/kg IV q3w for ≤16 cycles. Efficacy-evaluable pts were dosed by January 27, 2014 (≥12 week follow-up) with a data cutoff of April 21, 2014. RECIST v1.1 was used to assess ORR. PD-L1 expression (by immune cell IHC) was centrally evaluated from archival biopsies. In-tumor gene expression and peripheral biomarker analyses were done on pts dosed by Nov 20, 2013, with a cutoff of January 1, 2014. Results: In the UBC cohort, 33 IHC 2/3 pts, 36 IHC 0/1 pts, and 1 PD-L1 pt with unknown IHC were efficacy-evaluable. Median pt age was 65 y (36-89), and 73% were male. Visceral and liver metastases were present in 74% and 33% of pts, respectively. 73% had ≥2 prior therapies, and 91% had prior platinum. The unconfirmed ORR was 52% (95% CI, 34-69; 3 CRs, 14 PRs) in IHC 2/3 pts and 14% (95% CI, 6-28; 5 PRs) in IHC 0/1 pts. The median DOR was not yet reached (0.1+ to 42+ w in IHC 2/3 pts, n=17; 6+ to 19+ w in IHC 0/1 pts, n=5). 19/22 responding pts had ongoing responses. Median PFS was 24 w in IHC 2/3 pts (5 to 50+ w, n=33) and 8 w in IHC 0/1 pts (0.1+ to 30+ w, n=36). Of 74 pts evaluable for safety, all grade treatment-related AEs occurred in 65%, most often fatigue, decreased appetite and nausea. 5% had treatment-related G3-4 AEs. No treatment-related deaths were seen. The median follow-up was 5.4 mos (1+ to 12 mos, n=70). IHC 2/3 tumors had low expression of a baseline myeloid marker gene signature, including IL8 and IL1B, which was associated with MPLD3280A response. Additionally, circulating inflammatory markers (e.g., CRP) and tumor burden markers (e.g., HCG) decreased in responders by cycle 2. Updated data will be presented. Conclusions: MPDL3280A was well tolerated in UBC pts. Rapid and durable responses were seen and correlated with PD-L1 IHC status on immune cells. Biomarkers suggest a potential role for myeloid biology in primary resistance to MPDL3280A. Clinical trial information: NCT01375842.
Abstract 15229: Impact of Age on Strut Coverage and Neointimal Response to Sirolimus Eluting Stent
Authors: Zhao Sun, Xing Lei, Jin Chengmei, Ren Xuefeng, Jingbo Hou, Shaosong Zhang, Bo Yu, Ik-kyung Jang
Journal: Circulation (2013)

Abstract Background: Recent studies reported that older age is associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: A total of 119 patients wit...
Resection of non resectable liver metastases after chemotherapy: Prognostic factors and long term results
Authors: R. Adam, V. Delvart, G. Pascal, D. Castaing, D. Azoulay, S. Giachetti, B. Paule, F. Levi, F. Kunstlinger, H. Bismuth
Journal: Journal of Clinical Oncology (2004)

3550 Background: Chemotherapy allows an increased number of patients with primarily non resectable colorectal liver metastases (CRLM) to be further resected after tumor downstaging. However the benefit of this “rescue surgery” is still debated and prognostic factors of outcome are lacking Methods: From February 1988 to December 2000, 1400 consecutive patients with CLRM were managed at a single institution. From these, 295 (21%) were primarily resected and 1105 (79%) initially non resectable were treated by systemic chemotherapy using either oxaliplatin or irinotecan regimens. Non resectable patients were routinely reexplored every 3–4 courses.Surgery was reconsidered when potentially curative after response to chemotherapy. Fifteen factors assumed to be predictive of survival were evaluated by uni- and multivariate analysis in patients secondarily resected Results: In the non resectable group, 139 “good responders” (13%) could be secondarily submitted to hepatic resection after an average of 10 courses of chemotherapy. CRLM were initially non resectable because too large (7%), ill-located (15%), multinodular (55%) or associated to extrahepatic tumor (22%). Operative mortality within 2 months was 0.7% (1/139). Tumor recurrence was treated by repeat hepatectomy in 50 patients (36%) and pulmonary resection in 27 (19%). After a mean follow up of 5.3±3.2 years, overall 5-year survival was 36% (disease-free : 22%) compared to 47% for primarily resected patients (p= 0.02). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival : rectal primary, number of metastases ≥3, CA 19–9 level > 100 UI/L and concomitence of peritoneal or lymph nodes metastases. 5-year survival according to the presence of 0,1, 2, 3 or 4 of these factors was respectively 60%, 30–40%, 10–18% and 0–3%. Conclusions: Effective chemotherapy allows 13% of patients with irresectable CRLM to be rescued by liver surgery with a hope of long term remission. Although lower than that of initially resectable patients, the overall 5-year survival is 36% for a similar risk of mortality. 4 preoperative factors are able to predict long-term survival. No significant financial relationships to disclose.
An adaptive randomized discontinuation trial of XL184 (BMS-907351) in patients (pts) with advanced solid tumors.
Authors: M. S. Gordon, G. Edelman, M. D. Galsky, D. C. Smith, P. Schoffski, K. Houggy, Y. Lee, F. Schimmoller, X. Shen, R. Kurzrock
Journal: Journal of Clinical Oncology (2010)

TPS188 Background: XL184 is an oral, potent inhibitor of MET, VEGFR2, and RET with promising activity in phase I and II trials. We designed a phase II randomized discontinuation trial to evaluate the activity of XL184 in various solid tumors where MET signaling plays an important role. Pts with breast, gastric/gastroesophageal junction, small cell lung, non-small cell lung, ovarian, pancreatic, hepatocellular, melanoma, and prostate cancer are being evaluated in this study. The aim is to assess XL184 clinical activity in a blinded, randomized setting while minimizing exposure to placebo (P) and enriching the study population with disease stabilization using an open label treatment phase prior to randomization. Methods: Approximately 600 pts with a diagnosis of advanced, metastatic, or recurrent solid tumors are eligible for one of nine tumor-specific cohorts. The study consists of two stages: open label Lead-In Stage (Stage1), and double-blinded Randomized Stage (Stage2). In Stage1, all pts receive XL184 daily for 12 weeks. At the end of Stage1, complete/partial responders by modified RECIST continue to receive XL184; progressive disease (PD) pts discontinue XL184; stable disease (SD) pts are randomized 1:1 to receive XL184 or P in Stage2 until PD. Pts randomized to P may cross over to XL184 upon PD. Efficacy endpoints include objective response rate (ORR) in Stage1, and progression free survival in Stage2 evaluated when 52 events (PD or death) are observed per cohort. Fifty two events achieve 80% power to detect a hazard ratio of 0.5 with a 2-sided alpha of 0.1. Accrual will be stopped early for cohorts that demonstrate a low randomization rate due to overwhelming ORR, PD, low SD rate (SDR), or low accrual. The stopping guidelines employ lower 95% confidence limits for ORR to evaluate anti-tumor activity, and conditional probabilities to project futility. Two hundred pts are required to identify cohorts for early stopping, and 400 pts are required for full accrual in Stage2 for two cohorts with a high SDR and favorable safety profile. Clinical efficacy will be correlated with tumor pathway dysregulation as assessed in archival tumor tissue to further characterize the cohort(s) which benefit from XL184 treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis Bristol-Myers Squibb, Exelixis Exelixis Bristol-Myers Squibb, Exelixis
Resistance of stem-like cells from neuroblastoma cell lines to commonly used anticancer drugs
Authors: S. D. Vangipuram, Z. J. Wang, W. D. Lyman
Journal: Journal of Clinical Oncology (2009)

10054 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood. Recent studies have shown that most cancers contain a small number of stem-like cells which may be responsible for cancer progression and relapse. For this study, we investigated the cytotoxicity of 4 commonly used anti-cancer drugs on stem-like cells isolated from neuroblastoma cell lines. Methods: Cell surface marker CD133 positivity was used to define stem-like cells. Three neuroblastoma lines were screened for the expression of stem cell marker CD133 by FACS analysis. CD 133+ cells were isolated by positive selection using magnetic micro-beads. The cytotoxicity of four cancer drugs Cisplatin (0–50μg/ml), Etopside (0–200μg/ml), Doxorubicin (0–200ng/ml), and Carboplatin (0–200μMl) was studied on CD133+ and CD133- populations, by MTT and PI/Annexin binding assays. Results: Neuroblastoma lines SK-N-BE and SK-N-SH had 2% and 8% cells expressing CD133 respectively, while SH-SY-5Y had no CD133 expressing cells. CD133 + cells showed significant resistance to all four drugs in the MTT assay as well as the PI/Annexin binding assay compared to CD 133 - cells. Conclusions: This study suggests that CD133+ cells in neuroblastoma cell lines are more resistant to conventional anti-cancer drugs compared to CD133- cells. Targeting these stem-like cell populations could lead to development of more effective treatment for neuroblastoma. [Table: see text] No significant financial relationships to disclose.
Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism
Authors: Joni Nikkanen, Saara Forsström, Liliya Euro, Ilse Paetau, Rebecca A. Kohnz, Liya Wang, Dmitri Chilov, Jenni Viinamäki, Anne Roivainen, Päivi Marjamäki, Heidi Liljenbäck, Sofia Ahola, Jana Buzkova, Mügen Terzioglu, Nahid A. Khan, Sini Pirnes-Karhu, Anders Paetau, Tuula Lönnqvist, Antti Sajantila, Pirjo Isohanni, Henna Tyynismaa, Daniel K. Nomura, Brendan J. Battersby, Vidya Velagapudi, Christopher J. Carroll, Anu Suomalainen
Journal: Cell Metabolism (2016)
Outcome prediction in adult core binding factor (CBF) acute myeloid leukemia (AML) with gene expression profiling: A Cancer and Leukemia Group B (CALGB) study
Authors: P. Paschka, M. D. Radmacher, G. Marcucci, A. S. Ruppert, T. Vukosavljevic, S. P. Whitman, K. Mrózek, C. Liu, R. A. Larson, C. D. Bloomfield
Journal: Journal of Clinical Oncology (2007)

7011 Background: In CBF AML with t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) [abbreviated inv(16)], KIT mutations (mutKIT) and, in inv(16), trisomy 22 predict outcome and may guide the development of novel risk-adapted therapies. However, prognosis of patients (pts) lacking the aforementioned markers is less clear. Therefore, we profiled gene expression in t(8;21) (n=22) or sole inv(16) (n=25) pts who lacked mutKIT to identify signatures predictive of outcome. All pts were treated on CALGB trials incorporating consolidation therapy with multiple courses of higher dose cytarabine. Methods: Gene expression profiling was performed using Affymetrix U133 plus 2.0 arrays on diagnostic samples. As differences in gene expression distinguished all t(8;21) pts from all inv(16) pts, indicating two different biological entities, we pursued outcome prediction separately for each cytogenetic group. Gene expression-based outcome predictors for event-free survival (EFS) were constructed using a cross-validated prediction algorithm. Results: Among t(8;21) pts, EFS for predicted good (n=13) and poor (n=9) outcome groups differed strikingly (P=0.005; estimated 3-year EFS rates: 69% v 11%). Prediction was correct for 77% of pts. Among sole inv(16) pts, EFS for predicted good (n=18) and poor (n=7) outcome groups also differed (P=0.08; 3-year EFS rates: 78% v 29%). Prediction was correct for 76% of pts. FLT3 mutations appeared not to account for differences in EFS between the predicted groups; only the predicted outcome groups were associated with EFS (all baseline clinical characteristics at P&gt;0.10). Pts with predicted poor outcome had higher expression of genes with leukemogenic potential such as WT1 [t(8;21) and inv(16)], CCNA1 [t(8;21)] and the oncogene MYCN [inv(16)]. Conclusions: Gene expression profiling improves outcome prediction in CBF AML pts lacking the known prognostic markers. Future studies should explore the clinical usefulness of targeting products of over- expressed genes, such as WT1 encoding a potential target for immunotherapy in AML. No significant financial relationships to disclose.
Poliomyelitis and Encephalitis
Authors: L. H. Murray
Journal: BMJ (1947)

meningeal symptom developed paralysis which was usually very severe. (Case 22 was excluded from these tables.)Summary Forty-four patients convalescent from poliomyelitis, who were old enough to describe their symptoms, were questioned at length regarding their early symptoms and also the amount of physical activity during the early days of the disease.The so-called meningitic symptoms appear in nearly all cases during the pre-paralytic stage of the disease and are of great value in diagnosis.These symptoms are often more suggestive of involvement of nerve roots than of meninges.They consist of pain in the head, neck, dorsal, lumbar, or sacral spine, scapular region, thighs, or the lower chest.The meningitic symptoms may be slight or severe.At their onset the patient may be afebrile and may feel quite well.The meningitic symptoms may abate and the patient feel better shortly before paralysis develops.Physical activity of any kind during the pre-paralytic stage increases the danger of severe, paralysis.Complete physical rest in bed during the whole of the pre-paralytic stage seems to protect the patient from severe paralysis.
The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis
Authors: Jordi Heijman, Vincent Algalarrondo, Niels Voigt, Jonathan Melka, Xander H.T. Wehrens, Dobromir Dobrev, Stanley Nattel
Journal: Cardiovascular Research (2015)

Atrial fibrillation (AF) is an extremely common clinical problem associated with increased morbidity and mortality. Current antiarrhythmic options include pharmacological, ablation, and surgical therapies, and have significantly improved clinical outcomes. However, their efficacy remains suboptimal, and their use is limited by a variety of potentially serious adverse effects. There is a clear need for improved therapeutic options. Several decades of research have substantially expanded our understanding of the basic mechanisms of AF. Ectopic firing and re-entrant activity have been identified as the predominant mechanisms for arrhythmia initiation and maintenance. However, it has become clear that the clinical factors predisposing to AF and the cellular and molecular mechanisms involved are extremely complex. Moreover, all AF-promoting and maintaining mechanisms are dynamically regulated and subject to remodelling caused by both AF and cardiovascular disease. Accordingly, the initial presentation and clinical progression of AF patients are enormously heterogeneous. An understanding of arrhythmia mechanisms is widely assumed to be the basis of therapeutic innovation, but while this assumption seems self-evident, we are not aware of any papers that have critically examined the practical contributions of basic research into AF mechanisms to arrhythmia management. Here, we review recent insights into the basic mechanisms of AF, critically analyse the role of basic research insights in the development of presently used anti-AF therapeutic options and assess the potential value of contemporary experimental discoveries for future therapeutic innovation. Finally, we highlight some of the important challenges to the translation of basic science findings to clinical application.