tbuckley/cabot-search huggingface dataset:
Second-line chemotherapy by FOLFIRI in patients with advanced small bowel adenocarcinoma: A multicenter AGEO study.
Authors: A. Zaanan, M. Gauthier, D. Malka, C. Locher, J. Gornet, A. Thirot-Bidault, D. Tougeron, J. Taïeb, F. Bonnetain, T. Aparicio
Journal: Journal of Clinical Oncology (2010)

e14523 Background: Small bowel adenocarcinoma (SBA) is a rare tumour with poor prognosis. First-line platinum-based chemotherapy is active in patients with advanced SBA but data regarding second-line chemotherapy are lacking. The aim of this study was to evaluate the efficacy and tolerability of FOLFIRI as second-line chemotherapy in patients with advanced SBA. Methods: We analyzed all consecutive patients who received second-line chemotherapy by FOLFIRI among 93 patients with advanced SBA included from 1996 to 2008 in our previous retrospective study (Zaanan et al, ASCO GI 2008; abstract 15017). Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using Kaplan Meier method. Cox models were applied for multivariate analyses. Results: Among 51 patients who received second-line chemotherapy, 28 patients (male, 57%; median age, 53 years; metastatic disease, 96%) were treated with FOLFIRI. The primary tumour was located in the duodenum (43%), jejunum (43%) or ileum (14%). First-line chemotherapy included FOLFOX (n = 19) or LV5FU2-cisplatin (n = 9). National Cancer Institute common toxicity criteria grade 3-4 were observed in 48% of patients. The main toxicity was hematologic with 37% of grade 3-4 neutropenia. After a median follow-up of 21.5 months, all patients had tumour progression and 22 patients died. Objective response rate was 20% and disease control rate 52%. Median PFS and OS were 3.2 and 10.5 months, respectively. No clinical, biological or tumour characteristics were related to PFS or OS by multivariate analysis. Conclusions: Second-line chemotherapy with FOLFIRI produced disease control in half of patients with advanced SBA treated by first-line platinum-based chemotherapy. Nevertheless, the short median PFS observed in this study should encourage the evaluation of other treatments including targeted therapies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, sanofi-aventis Pfizer, sanofi-aventis Pfizer, sanofi-aventis
Neoplastic Effects of Oral Administration of (±)-&lt;italic&gt;trans&lt;/italic&gt;-7 ,8-Dihydroxy-7,8-dihydrobenzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene and Their Inhibition by Butylated Hydroxyanisole&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L W Wattenberg, D M Jerina, L K Lam, H Yagi
Journal: JNCI Journal of the National Cancer Institute (1979)

The neoplastic effects of administration of benzo[a]pyrene (BP) and (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) by oral intubation to noninbred female Ha:ICR mice have been determined. Under the experimental conditions, BP induced papillomas of the forestomach. BP 7,8-dihydrodiol also induced papiliomas of the forestomach and was more potent than BP. In addition, administration of BP 7,8-dihydrodiol caused a large number of pulmonary adenomas and lymphomas. Butylated hydroxy anisole (BHA) added to the diet at a concentration of 5 mg/g inhibited BP-induced neoplasia of the forestomach. BHA also inhibited neoplasia of the forestomach, lungs, and lymphoid tissues that was caused by administration of BP 7,8-dihydrodiol. These data suggest that the inhibitory effect of BHA on BP carcinogenesis may entail events that occur subsequent to the formation of BP 7,8-dihydrodiol.
A Continuous Line of Rous Sarcoma Virus-Transformed Chick Embryo Cells2
Authors: Marshall Dinowitz
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article A Continuous Line of Rous Sarcoma Virus-Transformed Chick Embryo Cells Get access Marshall Dinowitz Marshall Dinowitz Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 2, February 1977, Pages 307–312, https://doi.org/10.1093/jnci/58.2.307 Published: 01 February 1977 Article history Received: 11 February 1976 Accepted: 18 June 1976 Published: 01 February 1977
Association between FDG-PET and tumor vitality: Understanding the prognostic value of FDG uptake in early stage non-small cell lung cancer
Authors: C. Dooms, A. van Baardwijk, E. Verbeken, R. van Suylen, D. De Ruysscher, J. F. Vansteenkiste
Journal: Journal of Clinical Oncology (2008)

22211 Background: The prognostic value of quantitative 18-fluoro-2-deoxyglucose (FDG) uptake on positron emission tomography (PET) is controversial in unselected non-small cell lung cancer (NSCLC) patients. We assessed in vivo FDG uptake, measured as maximum standardized uptake value (SUVmax), in selected stage I-II NSCLC for its prognostic value and association with in vitro quantitative morphometry of tumor vitality. Methods: Prospective FDG-PET data were available in 91 consecutive patients operated for pathological stage I-II NSCLC. Overall survival data were collected retrospectively. Quantitative morphometry was performed of tumor architecture, viable tumor cell density and immunohistochemical biomarkers for apoptosis (caspase-3), cell proliferation (Ki-67), hypoxia (HIF-1α and CAIX), and microvessel density (CD31). A full model algorithm for logistic regression was applied to caspase-3, Ki-67, CAIX, HIF-1α and CD31 as independent variables and FDG uptake ≥median as dependent variable. Results: SUVmax and partial volume corrected (PVC) SUVmax ≥median were associated with an increased risk of death in univariable analysis. After correcting for stage, tumor size and age in multivariable analysis, only PVC SUVmax ≥median was significantly associated with an increased risk of death. A highly significant association between FDG uptake and tumor size (p<0.0001) became less significant after PVC (p=0.03). Viable tumor cell density was significantly associated with SUVmax (p=0.04) and clearly more significant after PVC (p=0.007). Ki-67 length density had a significant association with SUVmax (p=0.036) and even stronger association with PVC SUVmax (p=0.005). No association was found between FDG uptake and caspase-3, HIF-1α, CAIX or CD31 length density. In multivariable regression analysis, only Ki-67 and CAIX length density met a 0.05 significance level to explain an FDG uptake ≥median. Conclusion: FDG uptake has a prognostic value in stage I-II NSCLC. A high FDG uptake is associated with characteristics of tumor vitality represented by viable tumor cell density, cell proliferation and extracellular acidification. No significant financial relationships to disclose.
Reliability of ultrasound gastric volume assessment for the prevention of aspiration pneumonia
Authors: Anahi Perlas, Liisa Davis, Cyrus Tse
Journal: European Respiratory Journal (2013)

We have developed and validated a mathematical model (Volume = 27 + 14.6 x Right-lat CSA - 1.28 age) that accurately predicts gastric fluid volume based on a cross-sectional area of the gastric antrum obtained with 2D ultrasound in the right lateral decubitus position (Right-lat CSA).  An accurate assessment of gastric volume can help tailor anesthetic or airway management to prevent aspiration penumonia in intensive care or anesthetic practice. We hypothesize that ultrasound gastric volume assessment has substantial intra-rater and inter-rater reliability (intraclass correlation coefficient > 0.6). We hereby present interim data (n=8) from a prospective, randomized, blinded study (final n=24). Three blinded raters perfomed bedside ultrasound assessment for determination of gastric fluid volume on subjects randomized to ingest 0 to 400 mL of apple juice in 100 mL intervals after an 8 hour fasting period. A standardized scanning protocol was used. The procedure was repeated after 24 hours on the same subjects for determination of intra-rater reliability. Preliminary results suggest there is sustantial intra-rater reliability (ICC = 0.75) and almost perfect inter-rater reliability (ICC = 0.84). In conlcusion, our preliminary results suggest that bedside sonographic assessment of gastric volume has substantial to almost perfect reliability.
Carotid Artery Stiffness Decreases with Habitual Physical Activity in a Healthy Adult Population
Authors: B. Balkau, L. Mhamdi, H. BecK-Nielsen, M. Walker, E. Ferrannini, C Palombo, M. Kozàkovà
Journal: Circulation (2005)

Habitual physical activity is believed to retard the atherosclerotic process by reducing established cardiovascular risk factors and by slowing aging of the arterial wall. Aim of the present study was to evaluate the effect of habitual physical activity on carotid artery structure and function in a healthy adult Caucasian population. Our study cohort (from the RISC [Relationship between Insulin Sensitivity and Cardiovascular disease] Study) included 752 subjects, aged between 30-60 years (mean±SD=43±8), free of cardiovascular disease. All subjects were normotensive, their plasma lipid profile and fasting glucose levels were within normal limits, and their oral glucose tolerance test was normal. An ultrasound examination of the left common carotid artery (CCA) and an ACTIGRAPH recording of physical activity were performed according to standard protocols in 18 European centers. Carotid ultrasound images of left CCA were digitized and intima-media thickness (IMT) was measured by a single operator at the near and far wall, and the mean IMT CCA was calculated. In a subgroup of 531 subjects, systo-diastolic differences in left CCA diameter were measured on B-mode ultrasound images, 2 mm before the carotid bulb, in 5 consecutive cardiac cycles. Pressure-strain elastic modulus (Ep) was calculated as an index of carotid stiffness. ACTIGRAPH was worn for on average 5.5 days . In univariate analysis, both CCA IMT and Ep were directly related to age, waist circumference, body mass index, systolic blood pressure, and plasma LDL cholesterol, glucose and insulin concentrations (with r’s=+0.16-0.41, p<0.001-0.0001), while they were lower in women and negatively related to ACTIGRAPH parameters (average number of counts per day worn or per minute worn) (with r’s=-0.11-0.25, p<0.01-0.0001). In multivariate analysis, age, waist circumference, LDL cholesterol and systolic blood pressure were independent predictors of CCA IMT, whereas sex, age, waist circumference, and physical activity parameters were independent predictors of Ep. Conclusion: In an adult, healthy population, levels of habitual physical activity is independently associated with improved CCA compliance rather than CCA wall thickness.
Cross-platform performance of genes predictive of pathologic response to doxorubicin-paclitaxel containing regimens
Authors: G. Bianchini, Y. Zhao, M. Zambetti, L. Pusztai, G. Mariani, M. L. Carcangiu, P. Valagussa, L. Gianni, R. Simon
Journal: Journal of Clinical Oncology (2008)

11061 Background: Estrogen Receptor (ER) positive breast cancers have shown a lower rate of pathologic complete response (pCR) after neoadjuvant chemotherapy (NC) than ER negative tumors. However, the long-term benefits of adjuvant chemotherapy are evident in both subsets according to ER status. This might suggest some benefit for patients without pCR. Methods: Fifty-eight patients with ER positive locally-advanced breast cancer received NC with doxorubicin and paclitaxel (ATx3 ⟶wTx12) (Gianni L JCO 2005). RT-PCR assays were used to quantify expression of 384 genes on paraffin-embedded core biopsies. To reduce the possible confounding effect of the intermediate response phenotype, we developed a predictor comparing best responders (BR=pCR + breast residual ≤3 mm) versus gross residual disease (RD). An internal accuracy estimate was performed using complete leave-one-out cross validation. As external validation we applied the predictor’s genes derived from the Milan cases to an Affymetrix-based dataset of MD Anderson (Hess KR JCO 2006). The main differences of this dataset were the stage (I-III) and the NC regimen (Tx4 or wTx12 ⟶FACx4). A model based on the genes identified from the Milan cases was developed on a training set of MD Anderson cases and then applied in the validation set of the MD Anderson. All the analyses were performed by BRB-ArrayTools. Results: Nine best responder and 19 RD cases were identified. A 32 gene model was developed and complete cross-validation provided performance estimates of Accuracy 96%, Sensitivity 1.0, Specificity 0.95, PPV 0.9, NPV 1.0. Fifty-seven corresponding probes were identified on the Affymetrix platform. Nine pCR (breast) and 37 not- pCR ER positive cases were available in the training set. A 6 probes model (5 genes: TOP2A, MELK, BIRC5, KIFC1, BUB1 all higher in pCR- Breast group) was selected in the training set for its high sensitivity. This model was applied to 4 pCR and 30 not-pCR cases in the validation set and its performance was: Accuracy: 82%, Sens: 1, Spec: 0.8, PPV: 0.4, NPV:1. Conclusions: The identified genes provided good predictive accuracy in slightly dissimilar clinical cases from different institutions assayed on a different platform. An external validation of the identified models is warranted. No significant financial relationships to disclose.
Abstract 1437: The activity of plasma membrane V-ATPases is critical for the invasion of breast cancer cells
Authors: Kristina Cotter, Joseph Capecci, Souad Sennoune, Markus Huss, Martin Maier, Raul Martinez-Zaguilan, Michael Forgac
Journal: Cancer Research (2015)

Abstract The V-ATPases are a family of ATP-driven proton pumps that have been implicated in breast cancer cell invasion. V-ATPases are found both intracellularly and on the plasma membrane of specialized acid-secreted cells and invasive cancer cells. As available inhibitors of the V-ATPase are membrane-permeable, it has not yet been examined whether intracellular or plasma membrane pumps are critical for invasiveness. It has been proposed that V-ATPases promote invasiveness by localizing to the plasma membrane. To test this hypothesis, we utilized two approaches to specifically inhibit the V-ATPases at the plasma membrane. First, we stably transfected invasive MB231 breast cancer cells with a V5-tagged construct of the membrane-embedded subunit c. This allows for extracellular expression of the V5 epitope. We then found that addition of an anti-V5 antibody specifically inhibited plasma membrane V-ATPase activity as well as in vitro invasion and migration of MB231 cells. Second, we utilized a biotin-conjugated form of the specific V-ATPase inhibitor bafilomycin to inhibit plasma membrane pumps. When bound to streptavidin, this compound is membrane impermeable. Addition of streptavidin-bound biotin-bafilomycin also inhibited in vitro invasion and migration of MB231 cells. These studies suggest that V-ATPases at the plasma membrane play a critical role in breast cancer cell invasion. We hypothesize that plasma membrane V-ATPases participate in invasion by creating an acidic microenvironment that promotes the activity of pH-dependent proteases. Overall, these results have significant implications for targeting the pump to prevent breast cancer metastasis. Citation Format: Kristina Cotter, Joseph Capecci, Souad Sennoune, Markus Huss, Martin Maier, Raul Martinez-Zaguilan, Michael Forgac. The activity of plasma membrane V-ATPases is critical for the invasion of breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1437. doi:10.1158/1538-7445.AM2015-1437
A phase I trial of vorinostat in children with refractory solid tumors: A Children's Oncology Group Study
Authors: M. Fouladi, J. Park, J. Sun, C. Fraga, M. M. Ames, C. F. Stewart, R. J. Gilbertson, J. Zweibel, P. C. Adamson, S. M. Blaney
Journal: Journal of Clinical Oncology (2007)

9569 Background: Vorinostat, an orally administered histone deacetylase inhibitor, has potent antitumor activity against human cell lines in vitro (IC 50 0.5 to 5 μM) and in xenograft models. A phase I trial of vorinostat was conducted in children with recurrent or refractory solid tumors to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), pharmacokinetics (PK) of vorinostat, and to assess accumulation of histone acetylation in peripheral blood mononuclear cells (PBMCs). Methods: Vorinostat was administered once daily at dose levels of 180, 230, and 300 mg/m 2 /d. Courses were 28 days in duration, without interruption. PK analysis was performed during the 1st course. Vorinostat's ability to induce acetyl-histone (H3) accumulation in vivo was studied by western blot analysis. Results: 30 patients, 17 males, median age 15 years (range 4–21), were enrolled; 24 patients were fully evaluable for toxicity. At 180 mg/m 2 /d, 1/6 pts developed DLT (deep vein thrombosis) and at 230 mg/m 2 /d 1/6 pts developed DLT (hypokalemia). At 300 mg/m 2 /d, DLTs consisted of reversible hypokalemia (n=1), neutropenia (n=1) and thrombocytopenia (n=2), defining the MTD as 230 mg/m 2 /d. Other non-dose limiting grade 3 or 4 toxicities included elevated ALT/AST, hyperbilirubinemia, leucopenia, and lymphopenia. Western blot analysis of PBMC protein isolates found clear evidence of dose- dependent accumulation of acetylated H3 histones. 1 patient with a spindle cell sarcoma received 8 courses and 1 patient with a low-grade astrocytoma had an unconfirmed minor response. Conclusions: Vorinostat is well tolerated in children with recurrent or refractory solid tumors and inhibits histone deacetylase activity in PBMC. The recommended phase II dose for children with solid tumors is 230 mg/m 2 /d. No significant financial relationships to disclose.
Minimal Residual Disease Evaluated As Bcl2/Igh Rearrangement After Conventional Treatment Does Significantly Impact On Progression-Free Survival of Patients Affected by Follicular Lymphoma: The Experience of the Ancillary Trial Conducted by the Fondazione Italiana Linfomi (FIL)
Authors: Sara Galimberti, Stefano Luminari, Elena Ciabatti, Rossana Testi, Alessandra Dondi, Marco Ladetto, Pier Paolo Piccaluga, Ilaria Del Giudice, Anna Gazzola, Luigia Monitillo, Barbara Mantoan, Irene della Starza, Marzia Cavalli, Luca Arcaini, Alessandra Tucci, Francesco Di Raimondo, Luigi Rigacci, Alessandro Pulsoni, Umberto Vitolo, Daniele Vallisa, Giovanni Bertoldero, Gianluca Gaidano, Mario Petrini, Massimo Federico
Journal: Blood (2012)
Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion.
Authors: R P Edwards, W Gooding, B C Lembersky, K Colonello, R Hammond, C Paradise, C D Kowal, A J Kunschner, M Baldisseri, J M Kirkwood, R B Herberman
Journal: Journal of Clinical Oncology (1997)

PURPOSE To compare the toxicity, pharmacokinetics, and efficacy seen in ovarian cancer patients treated with escalating doses of intraperitoneal (I.P.) interleukin-2 (IL-2) by two different infusion schedules. PATIENTS AND METHODS Forty-five patients were sequentially entered onto a phase I/II study in groups of four at fixed dosage tiers of 6 x 10(4), 6 x 10(5), 6 x 10(6), and 3 x 10(7) IU/m2/d in either of two schedules: (A) intermittent weekly infusions of 24 hours' duration; or (B) alternating continuous 7-day infusions followed by 7-day intervals without therapy. Eligibility criteria included &gt; or = six courses of prior platinum-based chemotherapy and laparotomy-confirmed persistent or recurrent ovarian cancer. RESULTS Forty-one eligible patients received I.P. IL-2 and were assessable for toxicity, but six patients were not assessable for response, which left 35 patients assessable for response. Significant locoregional dose-limiting toxicity was seen with the 7-day infusions (including bowel perforation), with 600,000 IU/m2 as the maximum-tolerated dose (MTD), but catheter infection was the only significant complication seen with the 24-hour infusions, for which an MTD was not established. Among 35 assessable patients, there were six laparotomy-confirmed complete responses (CRs) and three partial responses, for an overall response rate of 25.7% (nine of 35). The median survival time of the cohort was 13.7 months and the overall 5-year survival probability was 13.9%. For the nine patients who demonstrated responses (six on the 24-hour infusion and three on the 7-day infusion), the median survival time has not been reached (range, 27 to 90+ months). CONCLUSION I.P. IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to I.P. IL-2 therapy or other factors that cannot be controlled for in a single-arm study.
Microenvironment Assessment, Disease Characteristics and Prognosis In HIV-Associated (HIV-cHL) and HIV-Negative Classical Hodgkin Lymphoma: The Influence Of Epstein Barr Virus (EBV)
Authors: Paul G. Rubinstein, Shylendra Sreenivasappa, Marina Messinger, Adam M. Petrich, Jonathan Moreira, Locke J. Bryan, Victoria Angelova, Shweta Gupta, Ariela Noy, Ingrid Sumpter, Ethel Cesarman, Amy Chadburn
Journal: Blood (2013)
A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis
Authors: Haiyang Yu, Mykyta Artomov, Sebastian Brähler, M. Christine Stander, Ghaidan Shamsan, Matthew G. Sampson, J. Michael White, Matthias Kretzler, Jeffrey H. Miner, Sanjay Jain, Cheryl A. Winkler, Robi D. Mitra, Jeffrey B. Kopp, Mark J. Daly, Andrey S. Shaw
Journal: Journal of Clinical Investigation (2016)

Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes.