tbuckley/cabot-search huggingface dataset:
Abstract 2107: YAP protein expression and subcellular localization in pediatric liver tumors
Authors: Michael J. LaQuaglia, James Grijalva, Kaly Mueller, Antonio Perez-Atayde, Heung Bae Kim, Ghazaleh Sadri-Vakili, Khashayar Vakili
Journal: Cancer Research (2015)

Abstract Purpose: Currently, there is no effective chemotherapy for the treatment of hepatocellular carcinoma (HCC). Both HCC and hepatoblastoma (HB) remain lethal in their metastatic forms. Therefore, understanding the molecular mechanisms of tumor survival and proliferation is critical for developing novel therapies. Our lab has shown that YAP, a transcription factor, is involved in liver regeneration. Specifically, increases in nuclear YAP have been coupled with expression of genes important for cell proliferation. We therefore sought to examine whether there is increased nuclear localization of YAP in liver tumors. Methods: Tumor tissue and normal liver tissue from 3 pediatric patients with HCC (all males, mean age 10.63 years), and 6 HB patients (4 males and 2 females, mean age 2.99 years) were stained for YAP using immunohistochemistry. Multiple high-power fields were photographed for each sample. Using ImageJ software, the number of YAP-positive nuclei were counted and expressed as a mean percentage of total nuclei. Results: The percentage of nuclei staining positive for YAP was increased in tumor cells compared to normal liver in 3/3 of the HCC tumors. In addition, YAP nuclear staining was significantly increased in 2/6 of the HB tumors. Conclusion: All HCC tumors and 33% of the HB showed an increase in the nuclear localization of transcription factor YAP. The increased activity of YAP in the nuclei of tumor cells may indicate a crucial role for YAP in tumor proliferation and survival. Targeting YAP or its upstream pathway (Hippo) may provide a novel target for therapy. Citation Format: Michael J. LaQuaglia, James Grijalva, Kaly Mueller, Antonio Perez-Atayde, Heung Bae Kim, Ghazaleh Sadri-Vakili, Khashayar Vakili. YAP protein expression and subcellular localization in pediatric liver tumors. [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 2107. doi:10.1158/1538-7445.AM2015-2107
Predictors and prognostic significance of tachycardiomyopathy: insights from a cohort of 1269 patients undergoing atrial flutter ablation
Authors: Béatrice Brembilla‐Perrot, João Pedro Ferreira, Vladimir Manenti, Jean Marc Sellal, Arnaud Olivier, Thibaut Villemin, Daniel Beurrier, Christian De Chillou, Pierre Louis, Alice Brembilla, Yves Juillière, Nicolas Girerd
Journal: European Journal of Heart Failure (2016)
Main public health issue is failure to use contraception
Authors: H. D Simpson
Journal: BMJ (1995)

EDITOR,--The letter from the Committee on Safety of Medicines to all doctors about the increased risk of thromboembolism in women taking oral contraceptives containing desogestrel and gestodene,1 and the manner in which it was released to the press, has caused predictable public panic. Surely the data should have been presented in the context of the wider issue of the provision of effective contraception. As has been pointed out, protective effects against other diseases must also be balanced, but most importantly the data must be viewed …
Adjuvant multipeptide vaccination in high-risk early melanoma patients
Authors: P. Filipazzi, L. Pilla, R. Patuzzo, C. Castelli, A. Maurichi, G. Tragni, M. Maio, G. Parmiani, M. Santinami, L. Rivoltini
Journal: Journal of Clinical Oncology (2008)

3014 Background: The optimal use of antitumor vaccines is to prevent recurrence after surgery for early disease, when disease burden is still limited and immune functions mostly conserved. Methods: We designed a phase II randomized trial of multipeptide vaccination in stage IIB-C/III melanoma patients. The vaccine includes HLA-A*0201-restricted peptides derived from 4 melanoma antigens (MelanA/MART-1[26–35L], gp100[209–217/210M], NY-ESO-1[157–165V], Survivin-1[96–104]) emulsified in Montanide. The administration is preceded by treatment with low-dose cyclophosphamide (CTX; 300mg/m2), aimed at reducing frequency and activity of regulatory T cells (Treg), and followed by administration of low-dose IL-2 (3x106 IU) to promote specific T cell expansion. The study will enroll 160 patients (80/arm), randomized to observation vs vaccination, consisting in 13 vaccinations given over a period of 3 years. Stage III patients begin vaccination one months prior to nodal dissection, so that tumor and vaccine-draining lymph nodes (LN) are also studied for immune responses. Results: As yet, 37 melanoma patients (18 vaccine vs 19 observation arm) have been enrolled. Peptide-specific CD8+ T cells are significantly enhanced after vaccination in peripheral blood (mean fold increase: 3.5, range 1.3–11.2) of treated but not control patients, as evaluated by IFNγ Elispot. These increases are confirmed by HLA-multimer staining, CD107a mobilization assay and short-term in vitro culture. Resected LN of vaccinated vs control patients show also improved peptide recognition by IFNγ Elispot (mean fold increase: 4, range 1.1–8) and HLA-multimer staining. LN immunohistochemical analysis further demonstrates a significant increment in the percentage of CD8+/GranzymeB+ T cells in treated patients. In contrast, CTX does not seem to significantly affect the frequency of Treg (CD4+CD25+Foxp3+) cells, nor their ability to secrete IL-10 or TGFβ. Conclusions: Multipeptide-based vaccination increases the frequency and the activation state of melanoma-specific T cells in lymphoid organs and peripheral blood of melanoma patients. Clinical data concerning disease-free and overall survival will early define whether this level of anti-melanoma T cell immunity could reduce recurrence risk in cancer patients. No significant financial relationships to disclose.
Delhi hospitals are told not to turn away patients with suspected dengue fever
Authors: Vidya Krishnan
Journal: BMJ (2015)

A 3 year old girl’s death on 16 September has taken the death toll from dengue viral fever in the current outbreak in India to 15, while the number of cases reported in the capital has risen to nearly 2000.1

While private and government hospitals struggle to cope with the number of patients, the government of the national capital territory has taken a series of measures to ensure that patients get appropriate medical attention.

Delhi’s health minister, Satyendra Jain, has directed private hospitals and …
THE PHARMACOLOGY OF TRIS(HYDROXYMETHYL) AMINOMETHANE (THAM)
Authors: GABRIEL G. NAHAS
Journal: Pharmacological Reviews (1962)

THAM is a titrating agent in vivo as well as in vitro , and its ionized fraction acts in the kidney as a non-reabsorbable cation. Since, at normal blood pH, THAM is 70% ionized, the larger part of the compound remains in the extracellular fluid and is rapidly excreted in the presence of a functional kidney. By reducing the pCO2 in the extracellular space, THAM could reduce intracellular pH as well. However, such a reduction of intracellular pCO2 is limited by TIJAM's depressant effect on ventilation, an effect which rapidly restores to normal and then elevates plasma pCO2 in the presence of an alkaline pH. The fraction of THAM which penetrates into the cells is, at intracellular pH, 90% ionized and may overtitrate the intracellular spaces. As ionized THAM accumulates in the cell, K+ moves out in order to restore the normal Donnan ratio. In addition to this action on by migration, THAM does not act as a simple buffer inside the cell but most likely interacts with enzyme systems. These interactions remain to be determined and distinguished from the pH effect of THAM. Compounds similar to THAM which would penetrate at a relatively slow rate into cells and modify intracellular pH would be very useful (90) in experimental work in order to alter the activity of specific enzymes. However, their ready availability is unlikely, primarily because of the instability of most organic compounds in vivo . Meanwhile, THAM is a very useful tool for the physiologists and pharmacologists who wish to study the effects of acid-base balance alterations. When used judiciously it has also been helpful in clinical medicine. During acidosis, severe metabolic disturbances overwhelm homeostatic mechanisms and many forms of therapy become ineffective. The administration of THAM, by restoring pH of body fluids to normal, potentially can provide optimum conditions for the restoration of homeostasis and for standard therapeutic procedures.
Increased prevalence of monoclonal gammopathy, abnormal immunoglobulin levels, and recurrent infections in family members of patients with familial Waldenstrom’s macroglobulinemia
Authors: Z. R. Hunter, L. Ioakimidis, J. D. Soumerai, C. J. Patterson, L. Xu, X. Leleu, B. T. Ciccarelli, A. Sacco, S. Adamia, E. Hatjiharissi, S. P. Treon
Journal: Journal of Clinical Oncology (2008)

8540 Background: Waldenstrom’s macroglobulinemia (WM) is a B-cell malignancy characterized by IgM secreting lymphoplasmacytic lymphoma. Recurrent sinus infections are commonly observed in WM patients. Familial prevalence of B-cell disorders is seen in up to 20% of patients with WM (Treon et al, Ann Oncol 2006). Methods: We sought to delineate familial predilections for WM by examining a large cohort of first and second degree family members of WM patients with and without familial histories for B-cell disorders. One hundred forty five family members were enrolled, of whom 87 were in a family with a familial history. Prior medical history, complete blood counts, serum laboratories, immunoglobulin levels, serum immunofixation studies, peripheral blood and cheek cell DNA were collected as part of this IRB approved study. Results: An increased incidence of recurrent sinusitis (32.9% vs. 12.1%; p=0.004), abnormally low IgA (18.5% vs. 1.9%; p=0.003), elevated total IgM (25.9% vs. 9.4%; p=0.03), and presence of a monoclonal gammopathy (22.9% vs. 1.9%; p=0.0004) were observed among family members of WM patients with a familial B-cell disorders history. Seventeen of the 19 family members with a monoclonal gammopathy within the familial cohort had an IgM monoclonal protein, and 2 had an IgG monoclonal protein. No significant differences in complete blood counts were observed among cohorts. Conclusions: Among family members of patients with WM with a familial B-cell disorders history, a significantly higher incidence of recurrent sinus infections, abnormally low IgA and elevated IgM levels were observed, along with a ten-fold increased incidence of monoclonal gammopathies. These observations may have important implications in the pathogenesis of WM, and screening efforts for family members of WM patients. Molecular studies to elucidate the underlying genetic basis for these observations are currently underway in our laboratory. No significant financial relationships to disclose.
Pimasertib (Pim) and Sar245409 (Sar) - a Mek and Pi3K/Mtor Inhibitor Combination: a Phase Ib Trial with Expansions in Selected Genotype-Defined Solid Tumors
Authors: R.S. Heist, J.R. Infante, F. Campana, C. Egile, V. Jego, L. Damstrup, M. Mita, E. Grande, N. Rizvi
Journal: Annals of Oncology (2014)
Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs
Authors: Qiwei Wang, Bo Chen, Meng Cao, Jianfei Sun, Hao Wu, Peng Zhao, Jing Xing, Yan Yang, Xiquan Zhang, Min Ji, Ning Gu
Journal: Biomaterials (2016)
What is the Clinical and Cost Effectiveness of Erythropoietin-Stimulating Agents for the Treatment of Patients with Cancer-Treatment Induced Anaemia? Insights from Cumulative Meta-Analyses (Cma) and Lessons for Cost-Effectiveness Analyses
Authors: M. Haasova,, L. Crathorne,, N. Huxley,, C. Hyde,
Journal: Annals of Oncology (2014)
Abstract 003: Progenitor Cells Suppress T-Lymphocyte Proliferation Via a Paracrine Mechanism
Authors: Frederieke van den Akker, Krijn R Vrijsen, Janine C Deddens, Pieter A Doevendans, Joost P Sluijter
Journal: Circulation Research (2013)

PURPOSE: Limited treatment options are available for heart failure patients. Stem cell therapy has recently become a potential new way of repairing injured cardiac tissue. Different progenitor cell sources have been investigated, but most promising for cardiac therapy are mesenchymal stem cells (MSC) and cardiomyocyte progenitor cells (CMPC). Cardiac stem cell therapy using MSC or CMPC improved cardiac function, despite low engraftment of the cells. Paracrine factors, produced by the injected cells, presumably cause these improvements. Many studies are performed on the paracrine effects, yet modulation of the immune response in cardiac stem cell therapy, especially the strong influence of T-lymphocytes on adverse remodeling, has not been explored extensively. Methods: Human fetal MSC and CMPC were characterized and tested for multipotency. The immunosuppressive properties of both cell types were tested in co-culture with allogeneic peripheral blood mononuclear cells (PBMC) or T-lymphocytes stimulated with IL-2 and PMA. Proliferation was measured by CFSE-analysis using flow cytometry. Results: Proliferation of PBMC and T-lymphocytes was significantly reduced in the presence of MSC (65 ± 8%) or CMPC (97 ± 0.6%). In addition, production of inflammatory cytokines IFN-gamma and TNF-alpha was strongly downregulated. This effect was observed in both direct cell contact as well as in transwell co-culture systems (MSC: 58 ± 10%; CMPC: 62 ± 9%). Transfer of conditioned medium from these co-cultures to unrelated, activated PBMC or T-lymphocytes abrogated proliferation in these cells to a similar extent as the original co-culture (MSC: 51 ± 8%; CMPC: 97 ± 0.7%). Interestingly, exosomes isolated from the conditioned medium of MSC and CMPC prevented T-lymphocyte proliferation in a dose-dependent fashion. At a concentration of 1.5μg, T-lymphocyte proliferation was significantly suppressed (MSC-exosomes: 73 ± 12%; CMPC-exosomes: 77 ± 10%). Conclusion: Both MSC and CMPC have a strong capacity for in vitro immunosuppression, which is mediated by paracrine factors. One potent immunosuppressive factor secreted by both MSC and CMPC are exosomes, which prevented T-lymphocyte proliferation in a dose-dependent fashion.
Effects of swallowing therapy on oropharyngeal function in head and neck cancer patients
Authors: J. Logemann, A. Rademaker, B. Pauloski, D. Lundy, M. G. Bernstein, C. Stangl, D. Santa, A. Campanelli, L. Kelchner, B. Klaben, M. Harris
Journal: Journal of Clinical Oncology (2008)

6046 Background: Head and neck cancer patients exhibit significant swallowing impairment after completion of tumor treatment. The most effective type of swallowing therapy for these patients has not been defined. Methods: This multi-center Phase III prospective randomized clinical trial tested which of two swallowing therapy protocols resulted in the best swallowing outcomes. The two therapy programs are: 1) aggressive range of motion (ROM) exercises with postural sensory therapy and 2) postural sensory therapy alone (PS). Planned enrollment was 99 patients per study arm. This sample size had 85% power to detect a difference in the primary outcome of 15% at a Type I error rate of 5%. Patients included those whose treatment was chemoradiation, supraglottic laryngectomy, anterior or posterior resection with primary or skin graft closure, anterior or posterior resection with distal or free flap closure. Both therapy protocols involved a one month treatment program followed by one month of rest followed by one month of exercise (ROM) or refresher (PS). Primary outcome measure was the percentage of patients with at least 50% oral intake at 3 months post cancer treatment. Other outcomes included physiologic measures determined from videofluorography at 6 visits between 1 and 12 months post cancer treatment completion. Results: Seventy-three patients were randomized (33 ROM, 40 PS). 58 patients were assessed at 3 months and 34 at 12 months. Fifty-five patients had chemoradiation while 18 had surgical treatment. There were no significant differences in the primary outcome measure (ROM 52%, PS 48%, p=0.99 by Fisher's exact test) or in other measures of swallow function. Conclusions: Neither swallowing therapy program was superior. No significant intervention-related adverse events were reported in either group. There were no significant differences between the treatment groups in the amount and types of foods eaten, saliva weight or mucositis. Frequency of some swallowing disorders decreased over time (e.g. reduced laryngeal elevation, reduced tongue strength) while others did not (e.g. reduced vertical tongue movement) indicating that both swallowing therapies may result in selective improvements in swallow physiology. No significant financial relationships to disclose.
Phase I/II study of oral fluoropyrimidine S-1 plus oral Leucovorin as first-line treatment for metastatic colorectal cancer
Authors: T. Yoshino, W. Koizumi, K. Yamaguchi, Y. Miyata, T. Kato, Y. Toh, A. Sawaki, I. Hyodo, T. Nishina, N. Boku
Journal: Journal of Clinical Oncology (2007)

4093 Background: The results of phase I portion of the treatment with the oral S-1 (a new oral fluoropyrimidine) plus oral leucovorin (LV) in patients (pts) with untreated metastatic colorectal cancer (mCRC) was reported at ESMO 2006. Dose limiting toxicities (DLTs) were grade 3 stomatitis/pharyngitis, nausea, diarrhea, ileus and exanthema. The recommended doses (RDs) for this phase II portion were determined to be S-1 40 mg/m 2 and LV 25 mg/body orally given twice daily on days 1 to 14 of a 28-day cycle. The PK profiles of S-1 plus LV were similar to those of S-1 monotherapy and UFT plus LV, respectively. The main purpose of this phase II portion is to evaluate the efficacy and safety of S-1 plus LV at RD level in pts with untreated mCRC. Methods: Pts were eligible as follows; unresectable mCRC with no prior chemotherapy or receiving adjuvant chemotherapy completed at least 6 months before, histologically proven adenocarcinoma, PS(ECOG) 0–2, age 20 to 75, measurable lesions, adequate organ function and written informed consent. The pts received 40 mg/m 2 of S-1 plus 25 mg/body of LV twice daily as RD in this phase II portion. The primary endpoint was the objective response rates (RRs), and secondary endpoints were time to progression (TTP) and toxicities. Results: Between Sep 2004 and Jun 2006, 56 pts of 65 enrolled pts received the treatment at RD level. The objective RRs were 55% (36 of 65) for all pts and 55% (31 of 56) for pts at RD. Disease control rates (DCRs) were 86% (56 of 65) for all pts and 86% (48 of 56) for pts at RD. Median TTP was 5.5 months for pts at RD, with a median follow-up of 5.5 months. The median survival time is under observation. During the 6 months from starting the treatment, the most common grade 3/4 toxicities at RD were as follows: diarrhea, 23%; stomatitis, 20%; anorexia, 18%; and neutropenia 13%. Conclusions: A combination of S-1 plus oral LV is an effective, well tolerated, and convenient regimen in pts with untreated mCRC, without the addition of either oxaliplatin or irinotecan. The updated results of the objective RRs, DCRs, TTP reviewed extramurally, and detailed safety profile will be presented at the meeting. This trial was supported by Taiho pharmaceutical co., Ltd., Tokyo, Japan. No significant financial relationships to disclose.
Use of molecular classification combined with p53 and topoisomerase IIa expression to identify tumors highly responsive to FEC regimen: A tissue microarray
Authors: N. Berrada, R. Conforti, S. Delaloge, M. Spielmann, F. Andre
Journal: Journal of Clinical Oncology (2009)

546 Background: Identification of highly responsive tumors to specific regimen is needed in order to better tailor post-operative chemotherapy regimen. We previously reported using a tissue microarrays that basal-like and HER2-overexpressing tumors derive higher benefit from adjuvant chemotherapy than luminal-like tumors. Previous studies have reported that p53+/basal-like tumors, and HER2+/topoisomerase IIa + tumors were highly sensitive to alkylating agents and anthracyclines respectively. In the present study, we have evaluated whether p53+/basal-like and HER2+TopIIa+ tumors derive high benefit from an alkylating/anthracyclines based chemotherapy. Methods: A tissue microarrays was built with tumor samples from 823 patients randomized between FEC/FAC regimen and no chemotherapy. Basal-like breast cancers were defined as HER2-/ER-/EGFR+ and/or CK5/6+ tumors. HER2-overexpressing were defined using HER2 expression by IHC (3+ score). P53 and topoisomerase IIa expression were assessed by IHC. Treatment effect was assessed by Cox model that included prognostic parameters and stratification variables. Predictive value for treatment effect were assessed by interaction test and test for heterogeneity. Results: 823 patients were included. 12.5% and 12.9% patients presented a basal-like and HER2-overexpressing breast cancer respectively. P53 and topoisomerase IIa were expressed in 20% and 35% patients. Hazard ratio for relapse associated with FEC/FAC regimen was 0.79 (95%CI: 0.62–1). Hazard ratio associated with FEC/FAC were 0.31 (0.1–0.97 ) and 1.19 (0.38–3.7 ) in patients with p53+/basal-like and p53- basal-like breast cancer. A p53/basal-based classification was associated with a trend for heterogeneity (p = 0.15). Hazard ratio associated with FEC/FAC were 0.34 (0.11–1.0 ) and 1.27(0.32–4.9) in patients with topIIa+/HER2+ and topIIa-/HER2+ breast cancer. A HER2/TopIIa classification was associated with a trend for heterogeneity (p = 0.07). Conclusions: The present study suggest that p53+/basal-like cancer and TopIIA+/HER2 cancers derive high benefit from adjuvant FEC/FAC regimen. This finding requires further validation given multihypothesis testing and subgroup analysis. No significant financial relationships to disclose.
Not yet standard: retinoids versus second primary tumors.
Authors: S M Lippman, W K Hong
Journal: Journal of Clinical Oncology (1993)

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.1993.11.7.1204 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8315418 Not yet standard: retinoids versus second primary tumors. S M LippmanxS M LippmanSearch for articles by this author , W K HongxW K HongSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.7.1204 First Page PDF © 1993 by American Society of Clinical Oncology