tbuckley/cabot-search huggingface dataset:
Abstract 705: Combinatorial therapeutic targeting of BMP2 and MEK in NF1-null malignant peripheral nerve sheath tumors
Authors: Sidra Ahsan, Daochun Sun, Michael A. Tainsky
Journal: Cancer Research (2015)

Abstract Our lab has identified and validated bone morphogenetic protein 2 (BMP2) signaling pathways as a therapeutic target in malignant peripheral nerve sheath tumors (MPNSTs), independent of the NRAS and MEK1/2 regulation. BMP2/SMAD signaling is associated with enhanced motility and invasion, a hallmark feature of the biological aggressiveness of MPNSTs. We have shown that inhibition of BMP2 leads to decreased motility and invasiveness in MPNST cell lines. Consistent with our data, gene expression studies from NF1 patient tissue samples demonstrated that increased expression of BMP2 is associated with malignancy in NF1 patients. Ras-GAP related domain (GRD) is the most widely studied functional target of Nf1 implicated in tumorigenesis, however, therapeutic interventions targeting Ras activity have met with limited success. Our objective is to target the BMP2/SMAD pathway, involved in migration and invasion, in combination with MEK inhibitors to develop a novel therapeutic approach for treatment of MPNSTs. The mechanism by which NF1-deficiency leads to activation of BMP2 signaling pathways, and consequently increased cellular motility and invasion is unknown. Using NF1(+/-) and NF1 knockdown MPNST cell lines, we are investigating the transcriptional regulation of BMP2 by NF1 to identify signaling mechanisms downstream of NF1 mediating increase in BMP2 levels. We will present data showing that BMP2 is regulated at the level of transcript stability upon NF1 deficiency. We will identify and design a rational approach of targeting of the molecular components involved in stability of the BMP2 3′ UTR in MPNSTs. Furthermore, we will present a combinatorial approach that targets the growth and proliferative potential of MPNSTs by RAS-MEK inhibitors, along with motility and invasive capability by inhibition of the BMP2-Smad axis for better targeting of these tumors. The overall goal of our research is to use the regulation of BMP2 transcriptional control to define mechanism-based novel druggable targets that can be exploited in combinatorial therapies with RAS-MEK inhibitors to treat NF1-related tumors. Citation Format: Sidra Ahsan, Daochun Sun, Michael A. Tainsky. Combinatorial therapeutic targeting of BMP2 and MEK in NF1-null malignant peripheral nerve sheath 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 705. doi:10.1158/1538-7445.AM2015-705
Does race affect outcomes in triple negative breast cancer (TNBC)?
Authors: S. Ahmed, M. M. Mirza, A. Farooq, L. Kronish, M. Jahanzeb, J. C. Sachdev
Journal: Journal of Clinical Oncology (2009)

e17543 Background: TNBC is associated with a worse prognosis than luminal subtypes. There is discordance among studies assessing the impact of race on outcomes of TNBC. Our objective was to assess whether African American (AA) vs. Caucasian (CA) race predicted survival outcomes for women with TNBC treated at a single institution in Memphis, TN. Secondary objectives were to examine the association of race with patient and tumor characteristics. Methods: Patients with stage I-III TNBC were identified from our breast cancer database and confirmed by review of pathology reports. Event free survival (EFS) was measured from the date of surgery to the date of first recurrence (locoregional, distant, or contralateral), death from breast cancer or last follow-up. Breast cancer specific survival (BCSS) was measured from the date of surgery to the date of death from breast cancer or last follow-up. Fisher's exact test was used for association between variables, Kaplan Meier method for survival estimates, and log rank test for survival comparison between groups (p &lt; 0.05: significant). Cox proportional hazards models with patient, tumor and treatment variables were fitted for EFS and BCSS. Results: Of the 105 patients with TNBC, 71% were AA. There was no significant association between race and stage at diagnosis (p = 0.68). 71% of AA women were &lt; 55 years old and 43% were pre-menopausal vs. 50% and 23% of CA women respectively. There was a trend towards association of race with age and menopausal status (p = 0.08). Ninety three percent of the patients received neo/adjuvant chemotherapy. With a median follow up of 26 months, 26% of AA vs. 20% of CA women had an event (p = 0.62). Overall 3 year EFS and BCSS estimates were 69% and 82% respectively. Racial differences in EFS and BCSS for AA vs. CA (65% vs. 80% and 78% vs. 89%, respectively) did not achieve statistical significance (log rank p = 0.22 for EFS and 0.26 for BCSS). Race was not a significant predictor of EFS or BCSS on uni-variable or multi-variable analysis. Stage at diagnosis retained significance for EFS and BCSS on uni-variable and multi-variable testing. Conclusions: Race did not affect outcomes in our cohort of TNBC patients treated similarly. The high event rate underscores the poor prognosis of TNBC and the need for more effective therapies. No significant financial relationships to disclose.
Predicting and reducing risk of radiation pneumonitis in patients with non-small cell lung cancer: A literature review
Authors: V. K. Mehta
Journal: Journal of Clinical Oncology (2005)

7344 Background: Radiotherapy (RT) improves locoregional control and survival in patients with non-small cell lung cancer (NSCLC), but radiation pneumonitis (RP) is common. Many studies evaluated potential risk factors for RP, but the reliability and clinical utility of these risk factors remains largely undetermined. Methods: Studies were identified by a MEDLINE literature search using search terms related to lung cancer, RP, and RT, as well as from the bibliographies of these and other articles. Results: Several patient-specific and treatment-specific risk factors were proposed (Table), but they did not increase risk of RP consistently in clinical studies. Controversy also existed about which dosimetric parameter to use (Table), and whether a low dose to a high volume of normal lung or a high dose to a low volume was more likely to result in RP. Reducing RT dose to reduce risk of toxicity might also reduce the therapeutic effect of RT. A rational approach is to treat all patients as having unacceptable risk of RP and reduce the risk by using evolving RT strategies and cytoprotective agents (Table). Conclusion: Predicting which patients will have clinically significant RP remains elusive, so RT strategies for NSCLC should be designed to reduce the risk of toxicity without impairing therapeutic efficacy. Radiation Pneumonitis: Risk Prediction and Reduction Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune MedImmune
COPD and depression: Prevalence and interaction
Authors: Alina Dovgan, Yuriy Mostovoy, Tetyana Konstantynovych, Hanna Demchuk
Journal: European Respiratory Journal (2014)

Modern edition of GOLD-2013 considers that COPD courses with comorbidities significantly affecting prognosis. Depression Disorders (DD) are the most important comorbidities of COPD. Many studies have proposed different models of the relationship between COPD and DD, most of which consider the mechanism of DD as the interaction of different pathogenic factors (smoking, hypoxia, quality of life). The aim of our research to study the prevalence of DD in COPD patients and to evaluate its effect on the disease. 43 patients with COPD (men - 30 (69.7%)), age 65.1+2,3 ys., 10.6+3,2 ys. Of COPD duration and 21 healthy persons, representative to the COPD group. COPD patients were examined by traditional pulmonological methods. DD are studed by the standardized methodology Zounge. Assessing the impact of DD on COPD performed considering the clinical symptoms, the analisis of results on mMRC and CAT. DD diagnosed in 10 (23.2%) patients and were shown in 6 (13.9%) patients - mild depression, and 4 patients (9.3%) - subdepressive states, whereas in the control group identified 1 (4.7%) case of masked depression (p<0.001). It was determined that the mean scores on the scales mMRC and CAT were significantly higher in patients with COPD with comorbid DD and were (3.8 ± 0.02) and (33 ± 0.05) scores, compared to patients without them, who had - (2,5 ± 0,02) and (25 ± 0,05) scores, (p<0.001). Patients with COPD have a significantly higher prevalence of depressive disorders in comparison to healthy, indicating that their secondary and somatic conditioning. Presence of COPD patients depressive disorders negatively affect the flow and control of the disease, which is manifested significantly higher on scales mMRC and CAT.
Associations of polymorphisms in genes antioxidant enzymes and detoxification enzymes and breast cancer risk in residents of the west Siberian region.
Authors: N. A. Ermolenko Kostrykina, U. A. Boyarskih, E. Voronina, A. G. Sushko, I. A. Selezneva, A. F. Lazarev, V. D. Petrova, M. L. Filipenko, U. A. Boyarskikh
Journal: Journal of Clinical Oncology (2010)

e12023 Background: Improper work of enzymes involved in the metabolism of reactive oxygen derivatives and detoxification enzymes potentially increase the risk of cancer cell appearance. Polymorphic variants of antioxidant enzymes genes attenuate or stimulate this process by directly modulating the content and quality of protein products of these genes. Hence, their genetic polymorphism can be a risk factor for oncological diseases. We examined the russian residents of the Altai Region in order to clear out the impact of single nucleotide substitutions in the MnSOD (rs4880), GPX1 (rs1050450), GSTP1 (rs1695) genes and deletions in the GSTM1 and GSTT1 genes on the risk of sporadic and familiar BC. Methods: The group consisted of 960 Caucasian women with BC aged 20-79 years (288-familial BC, 672 – sporadic BC), control group consisted of 480 Caucasian women aged 19-84 years without a history of cancer. Genotyping was carried out by real-time PCR using competitive Taq-Man probes (MnSOD, GPX1, GSTP1) or with allele-specific PCR using SYBR Green intercalating dye (GSTM1, GSTT1). Results: The frequencies of in MnSOD, GPX1, GSTP1 polymorphic loci genotypes in control DNA samples and in samples from patients with sporadic BC corresponded to the Hardy-Weinberg distribution in both groups. The frequencies of genotypes in the control group determined in our study did not differ from the data published for Caucasian female residents of Europe, Australia, USA. For rs1050450 (GPX1 gene) the odds ratio (OR) for sporadic breast cancer was 0.74 (95% confidence interval: 0.58–0.94) when homozygous carriers of the minor allele were compared with the homozygous carriers of the wild type (p = 0.012). Conclusions: No significant associations of polymorphisms in MnSOD, GSTP1,GSTM1, GSTT1 and BC development were detected. No significant financial relationships to disclose.
Abstract 15321: Enhanced Therapeutic Effects of Human iPS Cell Derived Cardiomyocyte Transplantation by the Combination of Cell Sheets With the Pedicle Omental Flap Technique in a Porcine Ischemic Cardiomyopathy Model
Authors: Masashi Kawamura, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Yukiko Imanishi, Emiko Ito, Nagako Sougawa, Kenji Miki, Takuji Kawamura, Masaru Ishida, Ai Kawamura, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2013)

INTRODUCTION: Transplantation of beating cells constructed from human induced pluripotent stem cell derived cardiomyocytes(hiPS-CMs) to infarct myocardium is a promising approach for treating ischemic cardiomyopathy(ICM). However, poor blood supply to the transplanted cell sheets is a concern related to the effectiveness and durability of this treatment. The pedicle omentum flap covering the transplanted cell sheets reportedly supports survival and function of the transplanted somatic tissue-derived cells. Herein, we hypothesize that the combined pedicle omentum flap may enhance survival and the therapeutic effects of hiPS-CM sheet transplantation therapy for ICM treatment. METHODS: Treatment by Wnt signaling molecules in retrovirally established human iPS cells produced hiPS-CMs, which were magnetically labeled by superparamagnetic iron oxide(SPIO), which was followed by cultivation in temperature-responsive dishes to generate scaffold-free hiPS-CM sheets. A porcine ICM model was induced by placing an am...
Improvement of Tolerability and Adverse Events Occurrence during Treatment with Dasatinib Used on a Compassionate Basis in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP).
Authors: Bruno Martino, Giovanna Rege Cambrin, Antonella Gozzini, Fabio Stagno, Massimo Breccia, Giorgina Specchia, Ester Orlandi, Ester Pungolino, Franca Falzetti, Sara Galimberti, Carmen Fava, Antonio Marino, Francesco Nobile
Journal: Blood (2007)
Unusual Aspects of Breast Cancer
Authors: Henry Mark Kuerer, Kelly K. Hunt, S. Eva Singletary, Frederick C. Ames
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.9.2573 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11331339 Unusual Aspects of Breast Cancer Case 3. Blue Hives During Lymphatic Mapping for Breast Cancer Henry Mark KuererxHenry Mark KuererSearch for articles by this author , Kelly K. HuntxKelly K. HuntSearch for articles by this author , S. Eva SingletaryxS. Eva SingletarySearch for articles by this author , Frederick C. AmesxFrederick C. AmesSearch for articles by this author Show More The University of Texas M.D. Anderson Cancer Center, Houston, TX, Copyright © 2001 American Society of Clinical Oncology https://doi.org/10.1200/JCO.2001.19.9.2573 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Assay for Cell Tumorlgenicity in Subhuman Primates Treated With Antilymphocyte Globulin
Authors: John C. Petricciani, Ruth L. Kirschstein, Roslyn E. Wallace, David P. Martin
Journal: JNCI Journal of the National Cancer Institute (1972)

African green and rhesus monkeys treated with antilymphocyte globulin were used to test for the tumorigenic potential of human cell cultures derived from normal and malignant tissues. Newborn, infant, and juvenile monkeys served equally well as conditioned hosts to support the growth of human epidermoid carcinoma cells. Normal human cells tested in the same manner showed no gross or microscopic evidence of tumor formation. The results suggest that the subhuman primate treated with anti-lymphocyte globulin may be a sensitive test system for assessment of the tumorigenicity of cells.
Numbers of host "helper" T cells and proliferating cells predict survival in diffuse small-cell lymphomas.
Authors: L J Medeiros, L J Picker, A B Gelb, J G Strickler, S W Brain, L M Weiss, S J Horning, R A Warnke
Journal: Journal of Clinical Oncology (1989)

Diffuse small-cell lymphomas of B-lineage comprise a group of immunophenotypically related lymphoid malignancies that display variable clinical aggressiveness. We compared a variety of clinical, pathologic, and immunologic characteristics of 64 B-lineage diffuse small-cell lymphomas to patient survival in an effort to define prognostically relevant subtypes of these neoplasms. Neither clinical parameters nor histological subclassification correlated with patient outcome. In contrast, three immunologic features of these lymphomas showed a statistically significant relationship with actuarial survival. Neoplasms that manifested greater than or equal to 25% Ki-67+ cells (proliferation-associated antigen), less than 25% Leu 4+ cells (pan-T antigen), or less than 15% Leu 3+ cells (helper/inducer T-subset antigen) were associated with significantly decreased patient survival as compared to neoplasms with the reverse phenotype (P = .02, P = .003, P = .0005, respectively). Leu 3 findings were of particular importance in initial biopsies (P = .0007), while the Ki-67 findings were significant regardless of time of biopsy (P = .01 for biopsies at diagnosis and P = .004 for other biopsies). These data indicate that immunologic analysis can demonstrate subsets of diffuse small-cell lymphoma with different biologic potential, and suggest that such analysis be included in the routine work-up of patients with this type of neoplasm.
Risk factors for lymph node metastasis in submucosally invasive colorectal cancer.
Authors: Liyong Huang, Xinxiang Li, Sanjun Cai
Journal: Journal of Clinical Oncology (2015)

542 Background: The aim of this study was to identify risk factors for lymph node metastasis (LNM) in submucosally invasive colorectal cancer (SICC) that might be used in selecting patients for local excision. Methods: Records were reviewed from consecutive patients who had undergone curative resection of SICC at the Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, between 2006 and 2013. Clinical features such as age, gender, tumor size, and location were reviewed. Histopathologic examinations including tumor growth type, growth pattern at the invasive front, histopathological type, depth of tumor invasion, tumor budding, lymphovascular invasion, and neural invasion were performed. The expression of E-cadherin, p53, and Ki-67 were examined by immunohistochemistry. The association between the clinicopathologic factors and LNM was evaluated. Results: A total of 265 patients (140 men and 125 women) treated for SICC were included. The overall LNM rate was 12.8%. The incidence of LNM was significantly associated with growth pattern at the invasive front (p=0.028), tumor budding (p=0.006), histopathological type (p&lt;0.001), and lymphovascular invasion (p&lt;0.001). Other clinicopathologic and immunohistochemical factors were irrelevant to LNM. In multiple variable logistic analysis, histopathological type, and lymphovascular invasion were the two independent risk factors of LNM (p=0.015 and p=0.007, respectively). Conclusions: Histopathological type and lymphovascular invasion are significant independent risk factors for LNM in SICC. Careful selection for local excision in SICC should be considered.
Exploratory analysis of survival benefit and prior docetaxel (D) treatment in COU-AA-301, a phase III study of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Oscar B. Goodman, Kim N. Chi, Arturo Molina, Christopher Logothetis, Robert J. Jones, John Staffurth, Scott A. North, Nicholas J. Vogelzang, Fred Saad, Paul N. Mainwaring, Stephen John Harland, Jinhui Li, Thian San Kheoh, Christopher M. Haqq, Howard I. Scher, Karim Fizazi
Journal: Journal of Clinical Oncology (2012)

4558 Background: AA, a selective androgen biosynthesis inhibitor, blocks the action of CYP17, thereby inhibiting adrenal and intratumoral androgen production. AA has demonstrated improved overall survival (OS) by 4.6 months (mos) vs placebo (HR=0.74) in patients (pts) previously treated with D. Methods: COU-AA-301 is a randomized double blind study of AA (1 g) + P (5 mg po BID) vs placebo + P administered to mCRPC pts post-D with a primary endpoint of OS. To further evaluate primary survival result robustness, we performed post hoc exploratory analyses to assess whether the timing of first and last dose of D and reason for D discontinuation impacted OS. Results: At randomization, treatment arms were balanced with respect to baseline characteristics, prior D use, and reasons for discontinuation. In both arms, almost half (45%) discontinued D due to progressive disease (PD); remainder discontinued D after completing all planned cycles (37%), due to toxicity (12%), or for other reasons (5%) per investigator. Median OS from first and last dose of D were longer with AA vs placebo (Table). Median OS was longer with AA vs placebo in pts who discontinued D for PD, or for all other reasons. Conclusions: These exploratory analyses suggest that the OS benefit of AA in mCRPC was maintained when calculated from first or last dose of prior D, and whether or not pts discontinued D for PD. Pts in AA arm of this study had a prolonged median OS of &gt; 32 mos from time of initial D therapy. Congruity among these analyses and lack of dependence on D timing demonstrate robustness of the primary survival result. [Table: see text]
Spontaneous Tumors of NFS Mice Congenic for Ecotropic Murine Leukemia Virus Induction Loci2
Authors: Torgny N. Fredrickson, Herbert C. Morse, Wallace P. Rowe
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Spontaneous Tumors of NFS Mice Congenic for Ecotropic Murine Leukemia Virus Induction Loci Get access Torgny N. Fredrickson, Torgny N. Fredrickson Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert C. Morse, Herbert C. Morse Search for other works by this author on: Oxford Academic PubMed Google Scholar Wallace P. Rowe Wallace P. Rowe Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 73, Issue 2, August 1984, Pages 521–524, https://doi.org/10.1093/jnci/73.2.521 Published: 01 August 1984 Article history Received: 17 January 1984 Accepted: 23 March 1984 Published: 01 August 1984
Detection of estrogen receptor in bone marrow from patients with metastatic breast cancer.
Authors: U Berger, J L Mansi, P Wilson, R C Coombes
Journal: Journal of Clinical Oncology (1987)

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.
GPs call for an end to CQC inspections
Authors: Matthew Limb
Journal: BMJ (2016)

GPs at a special conference have called on the BMA to campaign for the abolition of general practice inspection by the Care Quality Commission (CQC).

They want a new system of self regulation under a peer led quality assurance scheme.

The BMA’s conference of local medical committees, the local representative bodies for GPs, was held in London on 30 January to discuss problems facing general practice. Local representatives and national leaders attacked the CQC’s inspections for causing stress for doctors and undermining GPs’ confidence. …