tbuckley/cabot-search huggingface dataset:
An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer
Authors: M. Tsao, C. Zhu, A. Sakurada, T. Zhang, M. Whitehead, S. Kamel-Reid, K. Ding, L. Seymour, F. Shepherd
Journal: Journal of Clinical Oncology (2006)

7005 Background: BR.21 demonstrated a significant survival benefit for patients with advanced non-small cell lung cancer (NSCLC) who received erlotinib vs. placebo (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58–0.85, p&lt;0.001). Tyrosine kinase (TK) domain mutations and high EGFR gene copy number by fluorescent in situ hybridization (FISH) have been associated with significantly higher response rates to erlotinib, while high gene copy number is a better predictor of survival benefit than mutations. K-ras mutation has been associated with non-responsiveness to EGFR TK inhibitors and poorer outcome for patients treated with erlotinib and chemotherapy. The survival impact of K-ras mutation on single agent erlotinib therapy in NSCLC patients remains unknown. Methods: 731 patients were randomized to BR.21 (488 erlotinib, 243 placebo). K-ras mutation analysis was conducted by sequencing in 246 patient samples. Results: K-ras analysis was successful in 206 patients; 30 (14.6%) demonstrated oncogenic mis-sense mutations on codon 12 or 13 (22 on the erlotinib arm and 8 on the placebo arm). For all 206 patients with known K-ras genotype, the HR for erlotinib was 0.77 (95% CI 0.57–1.06, p=0.06). For the 176 K-ras wild type patients, the univariate HR for erlotinib was 0.69 (95% CI 0.49–0.97, p=0.03). In contrast, the HR for the thirty K-ras mutant patients was 1.67 (95% CI 0.62–4.5, p=0.31), with an interaction p value of 0.09. Overall response rates were 5% (1/20) in K-ras mutant patients, and 10.2% (10/98) in K-ras wild type patients. In patients with K-ras genotype known, the multivariate Cox regression model showed that K-ras mutation was significantly associated with shorter survival (HR 1.63, 95% CI 1.06–2.51, p=0.03). Conclusion: In BR.21, patients with K-ras mutation do not appear to derive any survival benefit from erlotinib therapy. However, the numbers of patients are small and results need to be confirmed in other studies. (Supported by the Canadian Cancer Society, Ontario Cancer Research Network, the Jacqueline Seroussi Memorial Foundation for Cancer Research and OSI Pharmaceuticals). [Table: see text]
Single agent bevacizumab and bevacizumab in combination with docetaxel and cisplatin as induction therapy for resectable IB-IIIA non-small cell lung cancer
Authors: N. A. Rizvi, V. Rusch, B. Zhao, E. Senturk, L. Schwartz, M. Fury, R. Downey, N. Rizk, L. Krug, M. G. Kris
Journal: Journal of Clinical Oncology (2007)

18045 Background: Bevacizumab (Bev) improves response and survival in patients with advanced non-squamous lung cancer with chemotherapy however there are limited data as single agent therapy and in early stage NSCLC. Methods: Patients with resectable stage IB-IIIA NSCLC were eligible. Patients with adenocarcinoma (Cohort 1) received preoperative Bev and docetaxel and cisplatin (DC). Patients with squamous histology, central location or recent hemoptysis received DC induction therapy without Bev (Cohort 2). Cohort 1 received Bev (15 mg/kg) followed by CT 2 weeks later to assess single agent Bev response. Subsequently D (75 mg/m 2 ) and C (75 mg/m 2 ) were given q 3 weeks; an additional 2 cycles of Bev was administered with C2 and C3 of DC (total of 3 preoperative doses of Bev). Cohort 2 received DC alone followed by resection. Both cohorts received adjuvant Bev x 1 year. Study endpoints included response to single agent Bev, downstaging, safety and survival. Results: 19 patients of planned 70 were enrolled (11 Cohort 1 and 8 Cohort 2). On Cohort 1, there were 2 clinical stage IIB and 9 IIIA patients. After single agent Bev (by bimensional measurement), &gt; 10% reduction in tumor size was observed after 2 weeks in 6/11 patients (- 20%, 15%, 16%, 15%, 13% and 20%). After Bev + DC, there were 6/10 (60%) PRs and DC delivery was 96%. 6/10 patient underwent R0 resection; 1 R2 and 2 were unresectable. 1 patient developed hemoptysis preoperatively and 1 patient developed an upper GI bleed post-operatively. There were otherwise no Bev related operative complications observed. 5/9 patients were downstaged by induction treatment. 3 patients received adjuvant bevacizumab to date (median 5.7 cycles). 8 patients were treated on Cohort 2 (3 with stage IB, 1 with IIB and 4 with IIIA). All 8 patients underwent R0 resection. DC delivery was 94% and there were 6/8 PRs. Downstaging was observed in 5/8 patients and 6/8 are receiving adjuvant Bev (median # cycles to date = 6.7). Conclusions: Bev as a single agent demonstrates regression of tumors after 2 weeks. To date, Bev has been safely administered in the neoadjuvant and adjuvant setting. Preoperative chemotherapy is well tolerated with more than 90% full dose drug delivery. The study is ongoing. Supported by Genentech, Inc. [Table: see text]
An open-label, fixed sequence, two period study to evaluate the potential induction of GW572016 metabolism by carbamazepine
Authors: J. M. Herendeen, D. A. Smith, A. Stead, C. Bowen, K. M. Koch, A. P. Beelen
Journal: Journal of Clinical Oncology (2004)

3081 Background: GW572016 is an oral, dual EGFR/ErbB2 tyrosine kinase inhibitor that blocks signal transduction pathways implicated in cancer growth. In vitro studies indicate that GW572016 is metabolized predominantly by CYP3A4 and CYP3A5, and to lesser extent by CYP2C19. Therefore, the potential for a drug-drug interaction exists when GW572016 is co-administered with drugs that modulate CYP3A4 activity. The objective of this study was to assess the effect of carbamazepine (CBZ), an inducer of CYP3A4, on the pharmacokinetics (PK) of GW572016. Methods: This was an open-label, fixed sequence, two period crossover study in healthy adult subjects. In Period 1, subjects received a single oral dose of 250 mg GW572016, followed by a 1-week washout period. During Period 2, subjects received CBZ 100 mg BID for Days 1–3 and 200 mg BID for Days 4–20. On Day 21, a single oral dose of GW572016 was co-administered with CBZ and plasma samples for PK analysis of GW572016 were obtained over a 48-hour period. Results: Twenty-four subjects (2 F: 22 M), median age 34.5 years (range 20–47 years) were enrolled in this study. Geometric least square means and 90% confidence interval estimates for AUCinf,Cmax and t1/2 ratios are listed in the table below. Carbamazepine treatment resulted in a 72% and 58% decrease in the GW572016 AUCinf and Cmax, respectively. There was no statistically significant effect of CBZ on the half-life of GW572016. Conclusion: In conclusion, exposure following a single oral dose of GW572016 was reduced after administration of CBZ for 21 days. Dose adjustment may be necessary to avoid therapeutic failure when GW572016 is co-administered with CYP3A4 inducers such as CBZ. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Phase I study of an antitumor vaccination using α(1,3) galactosyltransferase expressing allogeneic tumor cells in patients (Pts) with refractory or recurrent non-small cell lung cancer (NSCLC)
Authors: J. C. Morris, N. Vahanian, J. E. Janik, L. Moses, L. Tennant, S. Pittaluga, W. Gao, P. Albert, T. Seregina, C. J. Link
Journal: Journal of Clinical Oncology (2005)

2586 Background: Lung cancer remains a leading cause of cancer death. Current treatments have limited impact on outcome. In a phase I trial, we examined the safety and feasibility of antitumor vaccination in Pts with advanced NSCLC with three irradiated genetically altered human lung cancer cell lines engineered to express xenotransplantation antigens by retroviral transfer of the murine α(1,3) galactosyltrasferase gene (HyperAcute Lung Cancer Vaccine). Methods: Pts. with stage IV, recurrent or refractory NSCLC, ECOG PS ≤2, prior chemotherapies ≤2, adequate bone marrow and organ function, and albumin ≥3.0 g/dL were eligible. Cohorts of 3–6 Pts each were scheduled to receive intrademal injections of 3 x 10 6, 10 x 10 6, 30 x 10 6, or 100 x 10 6 vaccine cells every 4-weeks x 4. Toxicity was assessed using the CTC v3.0 and response determined by RECIST criteria. Results: To date, 7 Pts, 5 males, 2 females, median age 56 yrs (range, 41–72), median number of prior chemotherapies = 1 (range, 1–2) were treated. Four Pts have received 4/4 vaccinations, 2 Pts received 3 vaccinations and 1 Pt received 2 vaccinations. Adverse events (≤CTC grade 2) attributable to the vaccine include injection site pain/discomfort, local skin reaction, fatigue, and hypertension. Other adverse events (≤grade 2) include bradycardia, cough, diarrhea, dyspnea, headache, hyperglycemia, hyponatremia, nausea, pleural effusion, and vomiting. One patient had syncope (grade 3) that was unlikely to be related to the vaccine. Four patients had stable disease for >16 weeks (range, 17–28 weeks) and three others progressed. Conclusions: Preliminary data indicate that antitumor vaccination with genetically altered allogeneic human lung cells expressing α(1,3) galactosyltrasferase is safe and feasible. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NewLink Genetics NewLink Genetics
Immunologic prediction of relapse in patients with pemphigus vulgaris (PV) in clinical remission
Authors: Maryam Daneshpazhooh, Vahid Zafarmand Sedigh, Kamran Balighi, S. Hamed Hosseini, Ali Ramezani, Mohammad-Sadegh Kalantari, Narges Ghandi, Maryam Ghiasi, Azita Nikoo, Cheyda Chams-Davatchi
Journal: Journal of the American Academy of Dermatology (2016)
A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal cell carcinoma (RCC)
Authors: E. Banu, O. Rixe, C. Linassier, J. P. Machiels, M. Baudard, F. Ringeisen, T. Velu, M. A. Lefrere-Belda, J. M. Limacher, S. Oudard
Journal: Journal of Clinical Oncology (2006)

2581 Background: MUC1 is a glycoprotein often over-expressed and underglycosylated in renal cell carcinoma (RCC) making it an attractive antigenic target for tumor-specific immunotherapy. TG4010 is a cancer vaccine based on a modified vaccinia virus, strain MVA, expressing both MUC1 and Interleukin 2 (MVA-MUC1-IL2). The objective of this phase II, non-randomized study was to determine the efficacy of TG4010 alone and in combination with cytokines. Methods: Thirty seven patients (pts) with progressive metastatic RCC expressing MUC1 in at least 50% of the tumour cells were treated by subcutaneous injections of TG4010, 10 8 pfu/inj weekly, for 6 weeks then every three weeks until progression. At progression, TG4010 was continued in combination with Interferon α2a (INF) and Interleukin 2 (IL2). Results: Treatment efficacy and toxicities were previously presented at ASCO 2005 (abstr 4653). No objective responses have been observed, however, 7 pts (19%) remained stable for more than 6 months with TG4010 alone, 3 of them more than 22 months. After progression on TG4010 alone 22 pts received TG4010 in combination with cytokines. Six pts (27%) have been stabilized more than 6 months. The median TTP were 2.6 months (95% CI, 2.4–2.9 months) for TG4010 alone and 3.5 months (95% CI, 0.2–6.7 months) for the combined treatment. There were 24 deaths, with a median OS of 19 months (95% CI, 10–27.9) for the whole population. Seven pts were treated by sorafenib after immunotherapy failure. After censoring pts at the introduction of sorafenib, the median OS was 16 months (95% CI, 6–26), with 41% of pts alive at 2-years. The most frequent adverse effects related to TG4010 were minor to moderate injection site reactions, fatigue and flu-like symptoms. Twelve out of 24 pts evaluable for MUC1 ELISpot show evidence for MUC1-specific CD8+ T cell response while 14 out of 21 evaluable for MUC1 specific T cell proliferation were responsive. Conclusions: The cancer vaccine TG4010 alone and in combination with IL2 and INF induces some disease stabilizations in pts with progressive metastatic RCC and can improve survival in a population selected for MUC1 positivity, which is a factor of poor prognosis. [Table: see text]
Thrombomodulin Is Upregulated in Cardiomyocyte During Cardiac Hypertrophy and Promotes Cardiomyocyte Survival
Authors: Yi-Heng Li, Hsing-Chun Chung, Kou-Gi Shyu, Guey-Yueh Shi, Hua-Lin Wu
Journal: Journal of the American College of Cardiology (2009)
Abstract 15746: Airway Ciliary Dysfunction in Patients with Transposition of the Great Arteries
Authors: Maliha Zahid, Omar Khalifa, William Devine, Cyrus Yau, Richard Francis, Dong M Lee, KImimasa Tobita, Peter Wearden, Linda Leatherbury, Steven Webber, Cecilia W Lo
Journal: Circulation (2012)

Background: Transposition of the great arteries (TGA) is a congenital heart defect with the aorta transposed anteriorly and inserted into the morphological right ventricle (D-TGA). When associated ...
Immunoprecipitation of Intracisternal A-Particle-Associated Antigens From Preimplantation Mouse Embryos&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: T T Huang, P G Calarco
Journal: JNCI Journal of the National Cancer Institute (1981)

Murine intracisternal A-particles (IAP) are endogenous retrovirus particles expressed in large numbers in certain neoplastic tissues and during early stages of normal preimplantation mouse (outbred ICR) embryogenesis. IAP-associated antigens synthesized by preimplantation mouse embryos were precipitated by a rabbit (New Zealand White) antibody prepared against IAP from murine myeloma 104E. Characterization of the embryo immunoprecipitates with the use of one- and two- dimensional polyacrylamide gel electrophoresis revealed that a group of five proteins was synthesized by two- to eight-cell stages, but only three of these (molecular weight of 67,000, 69,000, and 73,000) correlated with the morphologic expression of IAP in embryos. ONly the proteins with molecular weights of 75,000 and 77,000 were detected in morulae and blastocysts, when embryos were IAP-negative. This is the first biochemical identification of endogenous retrovirus-associated antigens in preimplantation mouse embryos.
CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer
Authors: E.G. Chiorean, D.D. Von Hoff, M. Reni, F.P. Arena, J.R. Infante, V.G. Bathini, T.E. Wood, P.N. Mainwaring, R.T. Muldoon, P.R. Clingan, V. Kunzmann, R.K. Ramanathan, J. Tabernero, D. Goldstein, D. McGovern, B. Lu, A. Ko
Journal: Annals of Oncology (2016)

A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial.Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks.Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively.This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.
Kaposi sarcoma secondary to endogenous adrenocorticotropic hormone‐dependent Cushing syndrome
Authors: A. Mayor‐Ibarguren, M.C. Roldán‐Puchalt, T. Sancho‐Bueso, C. Pérez‐López, J. Álvarez‐Linera, R. Frutos, C. Álvarez‐Escolá, R. Regojo‐Zapata, M.J. Beato‐Merino, P. Herranz‐Pinto, B. Lecumberri
Journal: British Journal of Dermatology (2015)

Kaposi sarcoma (KS) is an angioproliferative tumour that develops as a result of an infection by human herpesvirus 8, which is considered a necessary cause but not sufficient. Other factors - genetic, immunological and environmental - might play a role in the development of the disease. We report a case of KS secondary to endogenous Cushing syndrome (ECS) due to a pituitary adenoma, an association that has been reported only once. We also conducted a search through the Medline and PubMed databases for cases involving KS and ECS, finding only three additional cases that shared common clinical and prognostic features with ours. ECS might favour the development of KS due to immunosuppression. Dermatologists and other clinicians should be aware of this association, as it might be an underdiagnosed condition. It also has an important impact on the management of KS, and based on this review it relies on a good prognosis when ECS is well controlled.
Immunohistochemical expression of ER and PR and outcomes in patients with newly diagnosed uterine leiomyosarcoma.
Authors: M. M. Leitao, M. L. Hensley, R. R. Barakat, R. O'Cearbhaill, R. A. Soslow
Journal: Journal of Clinical Oncology (2010)

5076 Background: To assess the immunohistochemical (IHC) expression of estrogen receptor (ER) and progesterone receptor (PR) in patients with uterine leiomyosarcoma (LMS). To assess the prognostic significance of ER and PR expression in LMS. Methods: We identified all cases of uterine LMS at our institution from 7/82-7/07 for whom ER and PR IHC analysis was performed at initial diagnosis. We only included cases considered high grade and in which IHC was performed at our institution. Cases were also excluded if the only IHC analysis was from tissue obtained at the time of recurrence or progression. ER or PR IHC expression was considered positive (+) if more than 5% of cells stained. Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier estimates and compared with log-rank test where indicated. Results: We identified 43 cases of high-grade LMS. Median age was 52 years (26-73). Disease was confined to the uterine body in 20 cases (47%). Eighteen (42%) of 43 cases were ER+ and 17/42 (41%) were PR+. At last follow-up, 33 (77%) had recurred or progressed and 23 (54%) had died. Median follow-up for survivors was 48.4 months (4-142.4). PR+, but not ER+, was associated with improved PFS (p = 0.002) and OS (p = 0.03). Adjusting for stage, ER expression was associated with PFS (p = 0.01), but not OS (p = 0.3). PR expression maintained its significant association with both PFS (p = 0.002) and OS (p = 0.05) after adjusting for stage. Neither ER or PR expression was associated with outcome in cases with disease outside the uterine body. However, in cases with disease confined to the uterine body, the median PFS for ER+ or PR+ cases was not reached for both compared to 16.9 months (95% CI: 8.1-25.7) for ER- cases (p = 0.03) and 13.5 months (95% CI: 5.9-21.1) for PR- cases (p = 0.001). In the 10 PR+ patients, only 1 recurred and died compared to the 10 PR- patients, in which 9 recurred and 5 died. In the 9 ER+ patients, 2 recurred and died compared to the 11 ER+ patients, in which 8 recurred and 4 died. Conclusions: ER and PR expression is associated with outcome in patients with true high-grade uterine LMS confined to the uterine body. PR expression seems able to identify cases confined to the uterine body that will have the best outcomes. No significant financial relationships to disclose.
Risk of oxalate nephropathy with the use of cyanide antidote hydroxocobalamin in critically ill burn patients
Authors: Matthieu Legrand, Thibault Michel, Michel Daudon, Mourad Benyamina, Axelle Ferry, Sabri Soussi, Véronique Maurel, Maïte Chaussard, Marc Chaouat, Maurice Mimoun, Jérôme Verine, Vincent Mallet, Alexandre Mebazaa
Journal: Intensive Care Medicine (2016)
Bevacizumab/irinotecan in recurrent malignant glioma: A retrospective analysis of MRI, FET-PET, and clinical performance.
Authors: M. Nowosielski, M. Hutterer, G. Tinkhauser, R. Irschick, D. Waitz, D. Putzer, G. Stockhammer, W. Recheis, W. Jaschke, T. Gotwald
Journal: Journal of Clinical Oncology (2010)

e12545 Background: Treatment of recurrent malignant glioma with bevacizumab (Avastin)/irinotecan yields high radiologic response rates. Avastin rapidly reduces contrast enhancement in MRI by restoring the blood-brain barrier. Therefore tumor evaluation using classical MacDonald's response criteria may be insufficient. In this retrospective study we aim to complement classical MR imaging criteria with T2 volumetry and FET-PET data to evaluate patients with recurrent malignant glioma treated with Avastin/irinotecan and to compare these imaging data to the patient's clinical performance status (CPS). Methods: 13 patients were treated with 10 mg/kg Avastin and 125 mg/kg irinotecan. MRI and FET-PET scans were performed in 8 weeks intervals, clinical examination was done biweekly. MR scanning included T1/T2 sequences with/without contrast application. Tumor volume was assessed using T2 and T1 post contrast volumetry applying standard MacDonald's response criteria. FET-PET was done applying a standard dose of 18F-fluoroethyltyrosine (18F-FET) using a standardized uptake threshold value of 1.6. CPS was assessed using a scoring system including Karnofsky performance index and clinical examination. Results: In the first follow-up PET results matched with T1 post contrast volumetry, T2 volumetry and CPS out of 13 patients in 9 (69%), 5 (38%) and 6 (46%) cases, respectively. 2 patients died before the second follow-up. Out of 11 patients PET results matched with T1 post contrast volumetry, T2 volumetry and CPS in 6 (55%), 5 (45%) and 6 (55%) cases, respectively. 4 nonresponsive patients with rapid clinical deterioration demonstrated early progress in PET-imaging which was not predictable on anatomic imaging. Conclusions: During the course of Avastin/irinotecan therapy PET-scan and MR imaging results are highly variable due to changes of tumor growth pattern (i.e., transformation to gliomatosis cerebri). PET scans predicted early tumor progression in nonresponding patients in this study group. No significant financial relationships to disclose.