tbuckley/cabot-search huggingface dataset:
Validation of weekly-dose cisplatin combined with radiation therapy in locally advanced head and neck cancer
Authors: B. C. Boulmay, C. E. Riggs, M. Lawson, C. Morris, W. M. Mendenhall
Journal: Journal of Clinical Oncology (2007)

6076 Background: Impressive outcomes have been achieved using multiagent neoadjuvant and concomitant chemotherapy combined with radiation in definitive treatment of head and neck cancer; these are associated with significant toxicities. The purpose of this study was to determine the efficacy and toxicities of single-agent weekly (CDDP) during curative-intent radiation therapy. Methods: 36 patients with AJCC Stage II (3%), Stage III (14%), Stage IV (83%) squamous cell carcinoma of the larynx, hypopharynx, oropharynx and oral cavity treated from 6/2000 to 11/2003 were retrospectively reviewed. Subjects received 72 Gy irradiation given either by hyperfractionation or IMRT technique with CDDP 30 mg/m 2 /wk throughout the radiation course. Cisplatin was held for Grade III/IV toxicities. The endpoints were best response, percentage of Grade III/IV toxicities, disease-free survival (DFS), overall survival (OS). Results: The median number of cycles of CDDP administered was 6. Grade III/IV toxicities: 11% of patients had anemia, 6% thrombocytopenia, 33% leukopenia, 0% renal failure, and 25% developed Grade III/IV mucositis; 1 patient (3%) died due to complications directly related to therapy. Responses to therapy included 72% CR, 17% PR, and 5% SD. Median follow-up for all patients was 19 months (34.5 months for living patients), DFS at 3 years (yrs.) was 59%, and OS at 3 yrs, was 40%. Nine patients died of disease up to 2.6 (median, 0.7) yrs. after treatment, while 11 died of intercurrent diseases up to 5.1 (median, 1.8) yrs. later. Fifteen are alive (2 with recurrence) at median 2.7 yrs. after treatment. Conclusion: Concomitant weekly CDDP with full-course radiation is feasible, tolerable, highly active, and comparable to more complex, costly and toxic regimens. Intercurrent disease was a significant contributor to mortality in our population. Our regimen is an attractive alternative to sequential chemoradiotherapy programs. No significant financial relationships to disclose.
Post-radiation metabolic tumor volume (MTV) and survival in esophageal cancer.
Authors: Alex Cruz, Michael D. Chuong, Jill M. Weber, Edward Eikman, Harry Lomas, Jose Mario Pimiento, Khaldoun Almhanna, Ravi Shridhar, Sarah E. Hoffe, Ken Meredith
Journal: Journal of Clinical Oncology (2012)

9 Background: PET-CT is an important tool for staging and evaluating treatment response in esophageal cancer. Metabolic tumor volume (MTV) has been reported as a prognostic factor in other malignancies. We evaluated the utility of post-radiation MTV in esophageal cancer patients treated with chemoradiotherapy (CRT). Methods: We evaluated pre- and post-treatment PET/CT scans in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC) treated with neoadjuvant/definitive intent. We measured the significance of the post-treatment MTV 2.0-5.0 which was defined as the metabolic volume above a threshold SUV of x. Cox regression models were used to determine any significance between MTV 2.0 -5.0 and disease free survival (DFS) or overall survival (OS). Multivariate analysis was performed. Results: We identified 63 patients (13 SCC, 50 AC) with a median follow-up of 12.0 months (range, 1.9-38.6). The median time to post-radiation PET/CT scan after completion of CRT was 40.1 days (range, 20-93). Thirty-seven (58.7%) patients underwent surgical resection. Univariate analysis revealed no significant correlation between post-treatment MTV and OS (MTV 2.0 p = 0.968; MTV 3.0 p = 0.945; MTV 4.0 p = 0.890; MTV 5.0 p = 0.316). There was also no significant correlation with respect to DFS (MTV 2.0 p = 0.956; MTV 3.0 p = 0.658; MTV 4.0 p = 0.695; MTV 5.0 p = 0.690). Multivariate analysis revealed that SCC histology and surgical resection were associated with improved OS while age, gender, post-radiation MTV 2.0-5.0 , and stage were not. Earlier stage and surgical resection were associated with improved DFS while post-radiation MTV 2.0-5.0 , age, gender, and histology were not. Conclusions: Although other studies have shown post-radiation MTV to be a significant prognostic factor, our data demonstrate no significant correlation with MTV and survival among esophageal cancer patients.
Shortened telomeres in peripheral lymphocytes are associated to complex chromosome anomalies and to second cancers in Hodgkin’s lymphoma patients
Authors: P. P. Carde, R. M’Kacher, A. Bennaceur-Griscelli, S. Koscielny, A. Bernheim, T. Girinsky
Journal: Journal of Clinical Oncology (2005)

6512 Background: Longer telomeres protect against chromosome instability. Telomeres and chromosomes of peripheral lymphocytes were assessed in Hodgkin Lymphoma (HL) patients, in relation to second cancer (SC). Methods: 3 cohorts of HL patients: untreated HL (n = 70, mean age 33); SC after HL (n = 28 [myelodysplasia 2, non Hodgkin L 6, solid tumor 20], mean age 52); no disease or complication at long term (NED HL, n = 18, mean age 58). 2 types of controls: healthy donors (n = 30, mean age 32.5); untreated solid tumors (n = 70, mean age 41). Peripheral blood was irradiated in vitro (200 & 400 cGy). Chromosomal abnormalities were scored by FISH painting of chromosomes 1, 3 and 4. Telomere length was measured by TRF assay & Q-FISH. Results: In circulating lymphocytes of untreated HL, it was observed shorter telomeres (mean 8.3kb [5.8–12kb]), more frequent spontaneous chromosomal anomalies & increased in vitro radiosensitivity, than in both control populations (f.i. donors: mean 11.7kb [10.5–12.7kb], p<10–3). In untreated HL, shorter telomeres were correlated to chromosomal abnormalities (p <10–3) & radiosensitivity (p=0.001). Telomeres were alike in untreated HL 8.3 kb [5.8–12kb] and 5 years after treatment 7.6 kb [3.8–11.8kb] (ns). In SC after HL, increased chromosomal abnormalities & in vitro radiation sensitivity, and shorter telomeres (6.6 kb [5.2–8.1 kb]) were observed compared to NED HL (9.7kb [8.1–11.3 kb], p<10–4). Conclusions: In peripheral lymphocytes of untreated HL, telomere shortening correlated with complex chromosomal abnormalities; these anomalies are special to HL, as compared to other untreated tumors, and they further develop in patients who experience SC, irrespective of treatment. These observations may lead to key findings in the mechanism, and prevention, of second carcinogenesis. No significant financial relationships to disclose.
Blood Eosinophils and Serum IgE Predict Response to Omalizumab in Patients with Severe Allergic Asthma: Innovate Trial Post-Hoc Analysis
Authors: Volkan Manga, Marc Humbert, Ratko Djukanovic, Steve Greenberg, Theodore A. Omachi, Benjamin Trzaskoma, Roland Buhl
Journal: Journal of Allergy and Clinical Immunology (2016)
Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes
Authors: Mohammed Eslam, Alessandra Mangia, Thomas Berg, Henry Lik Yuen Chan, William L. Irving, Gregory J. Dore, Maria Lorena Abate, Elisabetta Bugianesi, Leon A. Adams, Mustafa A.M. Najim, Luca Miele, Martin Weltman, Lindsay Mollison, Wendy Cheng, Stephen Riordan, Janett Fischer, Manuel Romero‐Gomez, Ulrich Spengler, Jacob Nattermann, Antony Rahme, David Sheridan, David R. Booth, Duncan McLeod, Elizabeth Powell, Christopher Liddle, Mark W. Douglas, David van der Poorten, Jacob George
Journal: Hepatology (2016)

A genome‐wide exome association study has identified the transmembrane 6 superfamily member 2 ( TM6SF2 ) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls ( P = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted ≥F2 fibrosis in CHC and NAFLD assessed cross‐sectionally (odds ratio = 1.39, 95% confidence interval 1.04‐1.87, and odds ratio = 1.62, 95% confidence interval 1.03‐2.52, respectively; P &lt; 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. Conclusion: The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (H epatology 2016;64:34–46)
Disparities in Consistent Retention in HIV Care — 11 States and the District of Columbia, 2011–2013
Authors: Sharoda Dasgupta, Alexandra M. Oster, Jianmin Li, H. Irene Hall
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In 2013, 45% of new human immunodeficiency virus (HIV) infection diagnoses occurred in non-Hispanic blacks/African Americans (blacks) (1), who represent 12% of the U.S.* Antiretroviral therapy (ART) improves clinical outcomes and reduces transmission of HIV, which causes acquired immunodeficiency syndrome (AIDS) (2). Racial/ethnic disparities in HIV care limit access to ART, perpetuating disparities in survival and reduced HIV transmission. National HIV Surveillance System (NHSS) data are used to monitor progress toward reaching the National HIV/AIDS Strategy goals to improve care among persons living with HIV and to reduce HIV-related disparities.(†) CDC used NHSS data to describe retention in HIV care over 3 years and describe differences by race/ethnicity. Among persons with HIV infection diagnosed in 2010 who were alive in December 2013, 38% of blacks with HIV infection were consistently retained in care during 2011-2013, compared with 50% of Hispanics/Latinos (Hispanics) and 49% of non-Hispanic whites (whites). Differences in consistent retention in care by race/ethnicity persisted when groups were stratified by sex or transmission category. Among blacks, 35% of males were consistently retained in care compared with 44% of females. Differences in HIV care retention by race/ethnicity were established during the first year after diagnosis. Efforts to establish early HIV care among blacks are needed to mitigate racial/ethnic disparities in HIV outcomes over time.
Abstract B49: Investigating kinase inhibitor resistance mechanisms through quantitative network mapping of the human kinase interactome
Authors: Feixiong Cheng, Zhongming Zhao
Journal: Clinical Cancer Research (2015)

Abstract The human kinases have become one of the most important classes of drug targets in the pharmaceutical industry. More than 20 drugs targeting one or more kinases have been approved for clinical use in a variety of cancers, including lung, breast, melanoma, colorectal, pancreatic, and prostate cancers. However, patients treated with those kinase inhibitors eventually develop resistance, and their prolong survivals are typically only a few months. So far, no general model has emerged to address the kinase inhibitor resistance. In this study, we constructed a systems biology-based framework to catalogue the human kinome (kinases and their interactions), including 538 kinase genes, in the broader context of the human interactome. Specifically, we constructed three networks: a kinase-substrate interaction network containing 7,346 pairs connecting 379 kinases to 36,576 phosphorylation sites in 1,961 substrates, a protein-protein interaction network (PPIN) containing 92,699 pairs, and an atomic resolution PPIN containing 4,278 pairs. We identified the conserved regulatory phosphorylation motifs (e.g., Ser/Thr-Pro) using a sequence logo analysis. We found the typical anticancer target selection strategy that uses network hubs as drug targets might lead to a high adverse drug reaction risk. Furthermore, we found the distinct network centrality of kinases creates a high anticancer drug resistance risk by feedback or crosstalk mechanisms within cellular networks. This notion is supported by the systematic network and pathway analyses that anticancer drug resistance genes are significantly enriched as hubs and heavily participate in multiple signaling pathways. Collectively, this comprehensive human kinome map sheds light on anticancer drug resistance mechanisms and provides an innovative resource for rational kinase inhibitor design. Note: This abstract was not presented at the conference. Citation Format: Feixiong Cheng, Zhongming Zhao. Investigating kinase inhibitor resistance mechanisms through quantitative network mapping of the human kinase interactome. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B49.
Toxicity of etoposide, doxorubicin, and cisplatin in gastric cancer.
Authors: J A Sparano, P H Wiernik
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.5.938 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2332775 Toxicity of etoposide, doxorubicin, and cisplatin in gastric cancer. J A SparanoxJ A SparanoSearch for articles by this author , P H WiernikxP H WiernikSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.5.938 PDF "Toxicity of etoposide, doxorubicin, and cisplatin in gastric cancer.." Journal of Clinical Oncology, 8(5), pp. 938–939© 1990 by American Society of Clinical Oncology
A dose-finding pharmacokinetic study of IT-101, the first de novo designed nanoparticle therapeutic, in refractory solid tumors
Authors: J. C. Oliver, Y. Yen, T. W. Synold, T. Schluep, M. Davis
Journal: Journal of Clinical Oncology (2008)

14538 Background: IT-101 is the first de novo designed experimental nanoparticle therapeutic for cancer and is comprised of a cyclodextrin-based polymer conjugate of camptothecin (CPT) that self-assembles into nanoparticles with diameter of ca. 40 nm and near neutral surface charge. The nanoparticle properties have been designed to accomplish extended circulation, tumor penetration, and slow intracellular drug release to enhance the mechanism of action of the CPT. Methods: Patients with refractory solid tumors received IT-101 by 90 minute IV infusions on days 1, 8, and 15 of a 28 day cycle over a dose range of 6 mg/m2/wk to 18 mg/m2/wk. Dose escalation was conducted with a Simon’s design. Dose limiting toxicity (DLT) was determined over the first cycle. Progressive disease (PD) was defined by RECIST (CT) results. Pharmacokinetics of free and total CPT in blood and urine were collected over after the 1st dose. Patients completing 6 cycles with stable disease (SD) or better were eligible to receive compassionate IT-101 at the same dose level every other week (QOW). Results: Twelve patients [6 (6 mg/m2), 3 (12 mg/m2), and 3 (18 mg/m2)] were enrolled. 4 of 12 (33%) had PD by CT. 8 of 12 (66%) did not have PD. (6-SD and 2 clinical deterioration (CD). Hematologic toxicity was the DLT. The MTD was < 30 mg/m2/mo. In patients receiving > 2 cycles, SD was observed at cumulative doses of 18 mg/m2/mo to 27 mg/m2/mo. Three patients (pancreatic, renal cell, NSCLC) completed 6 cycles and received treatment QOW with a PFS of ≥18, 14, and 11 months, respectively. Over 7 days, the mean plasma total CPT and free CPT t½ β were 39 ± 1.1 and 51 ± 1.5 hrs, respectively. The AUC of free and total CPT were linear with 9.9 ± 4.0 % of the CPT dose free. Urinary excretion averaged 16 ± 9.1% of the total CPT dose in the first 48 hrs. Conclusions: These data appear to demonstrate that IT-101 is safe, tolerable, and is associated with acceptable toxicity at the MTD. SD was maintained in patients treated beyond 6 cycles QOW at doses of 6 to 9 mg/m2/wk. In addition, twice monthly regimens maintained SD with minimal drug-related toxicity. A QOW schedule (allowing for 99% elimination of CPT) is warranted in future clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Insert Therapeutics Insert Therapeutics Insert Therapeutics
Chemoembolization with doxorubicin drug-eluting beads for unresectable hepatocelluar carcinoma with portal vein thrombosis.
Authors: E. B. McIntosh, R. Dhanasekaran, J. S. Kauh, B. F. El-Rayes, D. A. Kooby, R. S. Williams, H. S. Kim
Journal: Journal of Clinical Oncology (2010)

e14638 Background: Conventional transarterial chemoembolization (TACE) and yttrium-90 radioembolization (Y-90) have long been used as palliative care for patients with unresectable hepatocellular carcinoma (HCC). TACE with doxorubicin drug eluting beads (DEB) is a novel locoregional treatment modality for unresectable HCC. Current study explores survival after doxorubicin DEB compared to conventional TACE and Y-90 for unresectable HCC with portal vein thrombosis (PVT). Methods: Consecutive patients with HCC and PVT who received transcatheter therapy with Doxorubicin DEB, conventional TACE, or Y-90 as sole therapy were studied. Patients who underwent resection, transplantation, or combination therapies have been excluded from the study. Survival was obtained from the date of first transcatheter therapy and from the diagnosis of HCC. 6 month, 1 year and 2 year cumulative mortality was calculated. Statistical analysis was performed using Kaplan Meier Estimator with a log rank test, Chi-square and independent T-tests. Results: A total of 49 patients were included in the study. 40 (81.6%) received therapy with DEB (group A) and 9 (18.4%) underwent conventional TACE or Y-90 (group B). Of group B, 4 (44.4%) received conventional TACE and 5 (55.6%) received Y-90. Age (p = 0.140), sex (p = 1.000), race (p = 0.127) and Child-Pugh Class (p = 0.609) in the two groups were statistically similar. Median survivals from the diagnosis of HCC in groups A and B were 536 days (276-796) and 138 days (9-267) (p = 0.004). The survival rates in group A and B at 6 months, 1 year and 2 years were 80%, 62%, 36% vs. 33%, 22%, 11%. Median survival from the first transcatheter therapy was 535 days after DEB, 31 days after conventional TACE, and 54 days after Y90 (p = 0.006). Conclusions: Preliminary results indicate favorable survivals with transcatheter therapy with Doxorubicin DEB over conventional TACE and Y-90 for unresectable HCC and PVT. No significant financial relationships to disclose.
A new approach for presurgical margin assessment by reflectance confocal microscopy of basal cell carcinoma
Authors: M. Venturini, G. Gualdi, A. Zanca, L. Lorenzi, G. Pellacani, P.G. Calzavara-Pinton
Journal: British Journal of Dermatology (2015)

Surgical excision represents the most common elective treatment for basal cell carcinoma (BCC). Several noninvasive approaches have been proposed for in vivo determination of tumour margin, in order to achieve radical removal.To propose a new approach through the combination of dermoscopy and reflectance confocal microscopy (RCM) for lateral margin detection in BCC.Ten patients with lesions clinically suggestive of nonpigmented BCCs with ill-defined margins were enrolled. All BCCs were dermoscopically evaluated first and the ill-defined margins were marked with a superficial cut and then inspected using RCM.RCM evaluation showed BCC foci beyond the presurgical marker in three out of 10 lesions. Histology confirmed the RCM results: the presence of BCC features across the cut, corresponding to two superficial BCCs and a morpheaform BCC.This new procedure helped to improve the identification of proper margins for surgical excision in nonpigmented BCC with clinically and dermoscopically ill-defined margins.
481 FOUR-WEEK THERAPY WITH PEGINTERFERON ALFA-2B/ RIBAVIRIN EFFECTIVELY PREDICTS SUSTAINED VIROLOGIC RESPONSE IN TREATMENT-NAIVE AND PREVIOUS-TREATMENT-FAILURE PATIENTS WITH HCV-1 TREATED WITH BOCEPREVIR PLUS PEGINTERFERON ALFA-2B/RIBAVIRIN
Authors: J.M. Vierling, E.J. Lawitz, F. Poordad, M.S. Sulkowski, M. Bourliere, M. Buti, C. Cooper, J.S. Galati, J.K. Albrecht, N. Boparai, C.A. Brass, M. Burroughs, V. Sniukiene, S. Bruno
Journal: Journal of Hepatology (2011)
Reduction in the risk of back pain persists at least 30 months after discontinuation of teriparatide treatment: a meta-analysis
Authors: Jean-Yves Reginster, M. C. Nevitt, P. Chen, R. K. Dore, D. P. Kiel, J. R. Zanchetta, E. V. Glass, J. H. Krege
Journal: Annals of the Rheumatic Diseases (2005)
Acute myeloid leukemia with inv(16)(p13.1q22), abnormal eosinophils, and absence of peripheral blood and bone marrow blasts
Authors: Zareema Mangaru, Shashirekha Shetty, Valeria Visconte, Hien D. Liu, Heesun J. Rogers
Journal: American Journal of Hematology (2015)

Acute myeloid leukemia with inv(16)(p13.1q22),abnormal eosinophils, and absence of peripheral blood and bone marrow blastsTo the Editor: Acute myeloid leukemia (AML) with inv(16)(p13.1q22)[inv( 16)] or t(16;16)(p13.1;q22)[t(16;16)] is one of the biologically distinct AMLs in the category of AML with recurrent genetic abnormalities that does not account for blast percentage in the 2008 World Health Organization (WHO) classification.AML with inv(16) accounts for 5-8% of AML and it is usually associated with a relatively favorable prognosis with complete remission rates of 87% [1][2][3].It usually presents as acute myelomonocytic leukemia and increased eosinophils by morphology in the bone marrow (BM) and/or peripheral blood (PB).One of the most distinctive features is the presence of abnormally large, coarse, purple-violet granules in the eosinophils and eosinophilic precursors.Vacuolation or hypersegmentation can be often observed in eosinophils.Monocytic and