tbuckley/cabot-search huggingface dataset:
Abstract 429: Novel role of CXCL12/CXCR4 signaling axis in obesity-induced prostate cancer progression in HiMyc mice
Authors: Achinto Saha, Jorge Blando, John DiGiovanni
Journal: Cancer Research (2015)

Abstract Obesity has been shown to increase prostate cancer (PCa) progression and disease severity in men. In previous studies, we showed that diet-induced obesity (DIO, 60 kcal% fat) increased the incidence and severity of invasive adenocarcinomas in HiMyc transgenic mice compared to mice on a control diet (10 kcal% fat) whereas calorie restriction (30% CR) completely prevented the formation of adenocarcinomas. Increased tumor progression was associated with changes in expression of a large number of cytokines, chemokines and growth factors suggesting that altered growth factor and inflammatory signaling pathways in the tumor microenvironment may be key targets for preventing and controlling PCa progression and especially obesity-related PCa progression. Therefore, in this study we investigated the role of white adipose tissue (WAT)-derived factors on obesity-driven PCa progression in HiMyc mice. We first isolated RNA from the stromal vascular fraction (SVF) of the periprostatic WAT from HiMyc mice maintained on DIO and control diet. qPCR analyses showed a dramatic increase in expression of various chemokines, cytokines, growth and angiogenesis factors in the SVF of obese HiMyc mice. Among them, both CXCL12 and its receptors CXCR4 and CXCR7, were significantly upregulated in SVF from obese HiMyc mice. Recently, we developed a PCa cell line from the ventral prostate of HiMyc mice (HMVP2 cells) and a normal cell line from FVB/N mice (NMVP cells). Two additional cell lines (HMVP2A1 and HMVP2A2) were isolated from the original HMVP2 cells after subsequent tumor formation in FVB/N mice and growth in culture. HMVP2 and the derivative cell lines have characteristics of cancer stem cells and produce tumors in syngeneic mice. Western blot analyses showed expression of both CXCR4 and CXCR7 in the following order HMVP2A2 &amp;gt;HMVP2A1&amp;gt; HMVP2&amp;gt;NMVP cells, which followed their ability to produce tumors in vivo. Furthermore, CXCL12 treatment stimulated migration and invasion of HMVP2 cells (but not NMVP cells), which was inhibited by the CXCR4 antagonist, AMD3100. CXCL12 treatment also led to rapid activation of Akt, Stat3 and NFκB signaling in HMVP2 but not in NMVP cells. These data suggest that CXCL12 has differential effects on PCa cells from HiMyc mice compared to normal prostate cells that may play a role in driving tumor progression. In addition, these data suggest that targeting the CXCL12/CXCR4/CXCR7 axis could lead to novel approaches for offset the effects of obesity on PCa progression, thereby reducing PCa mortality. Citation Format: Achinto Saha, Jorge Blando, John DiGiovanni. Novel role of CXCL12/CXCR4 signaling axis in obesity-induced prostate cancer progression in HiMyc mice. [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 429. doi:10.1158/1538-7445.AM2015-429
Combined Cardiac Surgery and Total Thyroidectomy:A Case Report
Authors: Katsuhiko Matsuyama, Yuichi Ueda, Hitoshi Ogino, Takaaki Sugita, Jyunichiro Nishizawa, Keiji Matsubayashi, Shinichiro Yoshimura, Tatsuya Yoshioka, Yoshiyuki Tokuda
Journal: Circulation (1999)

A 65-year-old woman with aortic stenosis, ischemic heart disease, and Graves' disease had complained of effort angina. She then suffered from liver dysfunction due to treatment with antithyroid drugs. One year after the start of radioiodine administration, she demonstrated unstable angina with palpitation and sweating. Laboratory studies revealed a recurrent hyperthyroid state, and a second coronary angiogram revealed progressive ischemic heart disease. Combined coronary artery bypass grafting, aortic valve replacement, and total thyroidectomy were performed. The postoperative course was uneventful without any problems associated with hyperthyroidism or hypothyroidism. Combined cardiac surgery and total thyroidectomy can be performed safely if the perioperative levels of thyroid hormone are maintained at euthyroid or hypothyroid levels. (Jpn Circ J 1999; 63: 1004 - 1006)
Open toe sandals syndrome
Authors: Andrew M Borman, Elizabeth M Johnson
Journal: BMJ (2016)

Is fear of summer foot exposure contributing to the workload of mycology labs, ask Andrew Borman and Elizabeth Johnson 

The diagnosis and management of infections are common uses of resources and finances in many healthcare settings, including the NHS. Our laboratory routinely tests for dermatophytes, a group comprising three types of fungi that infect and grow in dead keratin. These fungi can cause infections of the skin, hair, and nails (tinea corporis, also known as ringworm), groin (tinea cruris), scalp (tinea capitis), and skin of the feet (tinea pedis, also known as athlete’s foot). Dermatophyte infection of the nails is known as tinea unguium. At our laboratory we receive and process samples of skin, hair, and nails from patients across the south-west of England who present to general practitioners with suspected dermatophytosis.

Over the years we have …
Higher tamoxifen use as chemoprophylaxis in patients with ductal carcinoma in situ (DCIS) in the last decade.
Authors: Erin E. Roesch, Lai Wei, Bhuvaneswari Ramaswamy
Journal: Journal of Clinical Oncology (2012)

191 Background: The incidence of DCIS over the last two decades has increased, with over 62,000 new cases diagnosed annually in the United States. Tailored management of DCIS is still a work in progress and currently treatment options are varied. We sought to identify changes in patterns of care in individual and physician choices for surgery and chemoprophylaxis over the last two decades at our institution. Methods: We performed a retrospective chart review and identified 773 eligible patients using the James Cancer Registry and the NCCN database at The Ohio State University between 1990 and 2010. We compared the proportion of patients undergoing mastectomy vs breast conserving surgery (BCT), use of radiation and hormone therapy, and recurrence rates between the years 1990-2000 and 2001-2010 using Chi-square test. Results: There was no significant difference in race (p=0.21) or age (p=0.09) among patients diagnosed with DCIS between 1990-2000 (Group A, N=462) and 2001-2010 (Group B, N=311). There was no significant difference in mastectomy rates between the two groups (31% vs. 27%, p= 0.26). Patients less than 50 years old were more likely to undergo mastectomy in both groups (p=0.02). Use of radiation therapy following BCT was similar between the two groups (52% vs. 53%, p=0.76). Interestingly more patients received hormone therapy during 2001-2010 than 1990-2000 (48% vs. 26%, p &lt; 0.0001). Patients undergoing mastectomy were less likely to receive radiation (2% vs. 74%, p&lt;0.0001) and hormone therapy (25% vs. 39%, p&lt;0.0001). There was no significant correlation between race and type of surgery. We are in the process of comparing recurrence rates between the two groups which will be reported. Conclusions: Previously published studies have reported higher rates of mastectomy among patients with early stage breast cancer in the recent years. Data from our institution over the last two decades did not corroborate this finding, although interestingly we have found increasing use of tamoxifen therapy for DCIS in the second decade. Understanding current practices is helpful in designing future studies for management of DCIS using novel prognostic assays such as Oncotype Dx assay.
Elucidation of the Molecular Mechanisms by Which Inflammatory and Anti-Inflammatory Monokines Regulate Interferon (IFN)- γ Production.
Authors: Jianhua Yu, Brian Becknell, Shujun Liu, Rossana Trotta, Micheal S. Jaung, Tiffany Hughes, Guido Marcucci, Michael B. Weinstein, Michael A. Caligiuri
Journal: Blood (2004)
PI3K/AKT Pathway as a Potential Therapeutic Target In Myelodysplastic Syndrome
Authors: Denise C Rezende, Lorena Zaida Pacheco, Luis Arthur F. Pelloso, Maria L. Chauffaille, Marçal C.A Silva, Elisa Kimura, Rafael L Casaes-Rodrigues, Helena Segreto, Mihoko Yamamoto, Daniella Marcia Maranhao Bahia Kerbauy
Journal: Blood (2010)
Abstract 3115: miR-30a-5p functions as a tumor suppressor gene in gastric cancer
Authors: Jimin Min, Tae-su Han, Boram Choi, Keun Hur, Hyuk-Joon Lee, Han-Kwang Yang
Journal: Cancer Research (2015)

Abstract Gastric cancer (GC) is the second leading cause of cancer-related death. MicroRNAs(miRNAs) are an abundant class of negative gene regulator and regulate multiple gene targets. miRNAs control a wide range of biological functions such as cellular proliferation, differentiation and apoptosis. Moreover, many miRNAs are highly conserved, and their deregulation is often associated with human malignancies. The aims of this study are to determine the miR-30a functions as a tumor suppressor gene and to evaluate whether the miR-30a-5p is able to use the diagnostic or prognostic marker in GC. To identify the gastric tumor-associated miRNAs, miRNA microarray was performed using the gastric cancer tissues. Among them, miR-30a-5p was down-regulated in GC tissues compared to normal mucosa. qRT-PCR was employed to confirm the microarray results. MiR-30a-5p expression was frequently down-regulated in our GC cohort, (n = 55, P&amp;lt;0.0001). To determine the miR-30a-5p biological functions in GC, miR-30a-5p mimic or inhibitor was treated in GC cell lines. Ectopic expression of miR-30a-5p decreased cell growth, migration capacity and colony formation in vitro. Some previous studies have elucidated that miR-30a-5p is associated with metastasis in some cancer types. Accordingly, we confirmed its expression in our GC cohort with lymph node metastasis (n = 13) using qRT-PCR. MiR-30a-5p was significantly down-regulated in lymph node metastasis tissues than normal or tumor tissues. Taken together, the miR-30a-5p expression was frequently down-regulated in GC and lymph node metastasis. In addition, the miR-30a-5p suppressed tumorigenesis. Therefore, we suggest that miR-30a-5p activation may be a useful strategy of GC patient therapy and it can serve as a diagnostic or prognostic marker for GC. Citation Format: Jimin Min, Tae-su Han, Boram Choi, Keun Hur, Hyuk-Joon Lee, Han-Kwang Yang. miR-30a-5p functions as a tumor suppressor gene in gastric cancer. [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 3115. doi:10.1158/1538-7445.AM2015-3115
Adrenergic urticaria in a patient with cholinergic urticaria
Authors: S. Mihara, M. Hide
Journal: British Journal of Dermatology (2007)

Adrenergic urticaria is a rare form of urticaria, induced by a stress-induced concomitant release of epinephrine and norepinephrine. Here we describe the case of a 60-year-old female patient presenting with disseminated erythematous papules surrounded by a white halo and vitiligo lesions on the hands, arms, and feet. Histological examination of one of the erythematous papules showed a dermal inflammatory infiltrate composed of lymphocytes and eosinophils of perivascular and interstitial localization. After 2 weeks of treatment with antihistamines, the lesions disappeared completely.
Baseline Metabolic Tumour Volume Predicts Outcome in High Tumor Burden Follicular Lymphoma. A Pooled Analysis of Three Multicenter Studies
Authors: Michel Meignan, Annibale Versari, Anne Ségolène Cottereau, Loïc Chartier, Jehan Dupuis, Sami Boussetta, Ilaria Grassi, Rene-Olivier Casasnovas, Corinne Haioun, Hervé Tilly, Massimo Federico, Gilles A. Salles, Stefano Luminari, Judith Trotman
Journal: Blood (2015)
Correlation of Clinical Response to Nilotinib with BCR-ABL Mutation Status in Advanced Phase Chronic Myelogenous Leukemia (CML-AP) Patients with Imatinib-Resistance or Intolerance.
Authors: Giuseppe Saglio, Dong-Wook Kim, Andreas Hochhaus, Simona Soverini, P. Erben, Susan Branford, Ariful Haque, Neil Gallagher, Yaping Shou, Timothy Hughes, G. Martinelli, Jerald Radich
Journal: Blood (2007)
Abstract 2486: Site-specific antibody-drug conjugation through an engineered glycotransferase and a chemically reactive sugar
Authors: Zhongyu Zhu, Ramakrishnan Boopathy, Jinyu Li, Ponraj Prabakaran, Simona Colantonio, Yang Feng, Yanping Wang, Marzena A. Dyba, Dimiter S. Dimitrov
Journal: Cancer Research (2015)

Abstract Conjugation of small molecule drugs to specific sites on the antibody molecule has been increasingly used for the generation of relatively homogenous preparations of antibody-drug conjugates (ADCs) with physicochemical properties similar or identical to those of the naked antibody. We previously developed a method for conjugation of small molecules to glycoproteins through existing glycans by using an engineered glycotransferase and a chemically reactive sugar as a handle to conjugate a small molecule. Here, for the first time, we report the use of this method with some modifications to generate an ADC from a monoclonal antibody, m860, which we identified from a human naïve phage display Fab library by panning against the extracellular domain of human HER2. M860 bound to cell surface-associated HER2 with affinity comparable to that of trastuzumab (Herceptin®), but to a different epitope. The ADC m860 was generated by enzymatically adding a reactive keto-galactose to galactose-free m860 using an engineered glycotransferase and conjugating the reactive m860 to aminooxy auristatin F with a non-cleavable linker. It exhibited exceptional serum stability and potent and specific cell-killing activity against HER2 positive cancer cells, including trastuzumab-resistant breast cancer cells. This unique ADC may have utility as a potential therapeutic for HER2 positive cancers alone or in combination with other drugs. Our results also validate the keto-galactose/engineered glycotransferase method for generation of functional ADCs, which could potentially also be used for preparation of ADCs targeting other disease markers. This project was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by federal funds from the National Cancer Institute, NIH, under contract N01-CO-12400, HHSN261200800001E as well as by the SU2C-St.Baldrick's Foundation. Citation Format: Zhongyu Zhu, Ramakrishnan Boopathy, Jinyu Li, Ponraj Prabakaran, Simona Colantonio, Yang Feng, Yanping Wang, Marzena A. Dyba, Dimiter S. Dimitrov. Site-specific antibody-drug conjugation through an engineered glycotransferase and a chemically reactive sugar. [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 2486. doi:10.1158/1538-7445.AM2015-2486
Genetic Obesity and the Risk of Atrial Fibrillation
Authors: Neal A. Chatterjee, Franco Giulianini, Bastiaan Geelhoed, Kathryn L. Lunetta, Jeffrey R. Misialek, Maartje N. Niemeijer, Michiel Rienstra, Lynda M. Rose, Albert V. Smith, Dan E. Arking, Patrick T. Ellinor, Jan Heeringa, Honghuang Lin, Steven A. Lubitz, Elsayed Z. Soliman, Niek Verweij, Alvaro Alonso, Emelia J. Benjamin, Vilmundur Gudnason, Bruno H. C. Stricker, Pim Van Der Harst, Daniel I. Chasman, Christine M. Albert
Journal: Circulation (2016)

Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding, reverse causation, and bias. The primary objective of this study was to evaluate the causal association between BMI and AF by using genetic predictors of BMI.
Interferon Gamma +874A/T Polymorphism in Children with Idiopathic Thrombocytopenic Purpura
Authors: Fatih Demircioglu, Hale Ören, Sefa Kizildag, Sebnem Yilmaz, Berna Atabay, Meral Turker, Canan Vergin, Gulersu Irken
Journal: Blood (2008)
Abstract 1253: Selectivity of regulated IRE1 dependent decay of RNA controls pro-oncogenic signaling in glioblastoma
Authors: Eric Chevet
Journal: Cancer Research (2015)

Abstract Glioblastoma multiforme (GBM) is the most lethal form of glioma with an overall survival at 5 years nearly null (&amp;lt; 5%). Increasing evidences point towards the RNase activity of IRE1 as a central player in GBM development, particularly in cancer cell invasion and tumor vascularization. Indeed, IRE1 promotes XBP1 mRNA splicing, a well-described cytoprotective transcription factor that is required for cancer cell survival. Moreover, regulated IRE1 dependent decay of RNA (RIDD) leads to opposite effects on cell fate depending the ER stress intensity or duration and on the target RIDD substrates. Recent studies unraveled the presence of somatic mutations on the IRE1 gene in GBM that could play a driver role but without providing any functional information. Here, we have sequenced IRE1 exons in 23 human GBMs and identified a new somatic mutation on the IRE1 gene. Interestingly, using biochemical approaches and an orthotopic tumor graft mouse model we show that this variant displays an altered RIDD selectivity in particular towards the specific RIDD substrates already characterized in GBM (SPARC and PER1) and also miR-17, a previously described RIDD substrate whose expression has also a prognostic value in GBM. IRE1-dependent gene expression pattern alterations lead to major functional consequences in terms of tumor phenotype including (i) a magnified induction of the inflammatory and pro-angiogenic pathways based on transcriptome signatures and (ii) an increase of the aggressiveness/infiltration potential of U87 derived tumors in mice. This study provides the first evidence that RIDD substrates selectivity can be modulated and unravels the first mechanistic example of how a somatic mutation in the IRE gene can provide adaptive advantages to glioblastoma cells. Note: This abstract was not presented at the meeting. Citation Format: Eric Chevet. Selectivity of regulated IRE1 dependent decay of RNA controls pro-oncogenic signaling in glioblastoma. [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 1253. doi:10.1158/1538-7445.AM2015-1253
A phase II study of gemcitabine (GEM) given at fixed-dose rate (FDR) infusion, low-dose cisplatin (CDDP), and bevacizumab in metastatic pancreatic cancer (PanCa)
Authors: A. H. Ko, E. Dito, B. Schillinger, R. Hajnal, A. P. Venook, E. K. Bergsland, J. Allen, S. Rajpal, M. A. Tempero
Journal: Journal of Clinical Oncology (2006)

4041 Background: The objectives of this study are to determine safety and efficacy in pts with metastatic PanCa treated with a novel combination consisting of FDR GEM, low-dose CDDP, and BEV. We present here interim results of the first 35 pts. Methods: Chemotherapy-naive pts with histologically confirmed PanCa and documented extrapancreatic metastases received the following: GEM 1000 mg/m 2 at FDR infusion (10 mg/m 2 /min), CDDP 20 mg/m 2 , and BEV 10 mg/kg, all administered on dd 1 and 15 of a 28-dd cycle. Pts were monitored by CT scans every 2 cycles and monthly serum CA19–9 measurements. Results: 35 pts (15M,20F; median age 60 y.o. [range 39–85]; ECOG PS 0–1) have been enrolled betw 6/2004 and 1/2006 (med f/u, 288 dd; range, 50–542). 18 pts remain alive, with 7 still undergoing study rx. Pts received a median of 4 cycles of rx (range, 0.5–12). Reasons for study discontinuation: 15 pts had progressive dz (med # of cycles, 6; range, 0.5–10); 2 pts completed max # of allowable rx cycles (twelve); 2 pts came off rx 2 o to cumulative asthenia after plateau in response with 8 and 10 cycles of rx. Other major events inc. 2 bowel perforations, one associated with placement of a duodenal stent; 3 major GI bleeds; 1 malignant HTN; and 1 stroke-like sx. 3 pts d/c’ed rx 2 o to prolonged rx delays (two persistent bowel obstruction, one grade 3 renal/liver function abnls). Addn grade 3/4 toxicities inc. 7 pts with LFT abnls (20%), 4 with HTN (11.4%), and 3 with thromboembolic events (8.6%). Hematologic toxicities were rare (grade 3/4 neutropenia 5.7%, plts 2.9%). 7 pts (20%) required dose reduction of GEM and 2 required d/c of CDDP. No rx-associated deaths were observed. 7 of 33 evaluable pts (21.2%) have had an unconfirmed response (1 CR, 6 PR) and 15 pts (45.5%) have had stable dz for &gt; 2 cycles, inc. 2 with minor response, for an overall dz control rate of 66.7%. 13 of 21 pts (61.9%) with elev. baseline CA19–9 levels (≥2X ULN) have had ≥50% biomarker decline during rx. Updated efficacy data will be presented at the meeting. Conclusions: The toxicity profile observed in this trial is similar to that previously reported with other BEV-containing regimens. Rates of disease control and CA 19–9 response are encouraging, suggesting this combination is deserving of further study. [Table: see text]
673. Therapeutic Efficacy of Retroviral Replicating Vector (RRV) -Mediated Prodrug Activator Gene Therapy for Pancreatic Cancer
Authors: Kazuho Inoko, Kei Hiraoka, Akihito Inagaki, Mizuna Takahashi, Toshihiro Kushibiki, Koji Hontani, Hironobu Takano, Shoki Sato, Toru Nakamura, Takahiro Tsuchikawa, Toshiaki Shichinohe, Douglas J. Jolly, Noriyuki Kasahara, Satoshi Hirano
Journal: Molecular Therapy (2016)

Pancreatic ductal adenocarcinoma is one of the most lethal cancers, thus new therapeutic strategies for this disease are urgently needed. Retroviral replicating vectors (RRV)-mediated prodrug activator gene therapy with Toca 511 (vocimagene amiretrorepvec), an optimized RRV encoding yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU), is showing promising clinical activity in patients with recurrent high grade glioma, and is now being evaluated in a multi-center Phase II/III clinical trial. In the present study, we evaluated the therapeutic efficacy of RRV-mediated prodrug activator gene therapy in preclinical models of pancreatic cancer. We first examined the replication kinetics of RRV expressing the GFP reporter gene (RRV-GFP) in murine (Pan02) and human (MIAPaCa-2, BxPC-3, PANC-1 and SUIT-2) pancreatic cancer cell lines by flow-cytometric analysis and quantitative PCR. In all of these pancreatic cancer lines, RRV-GFP inoculated at MOI=0.05 (~5% initial transduction levels) showed rapid viral replication subsequently resulting in high levels of transduction, with the majority of pancreatic cancer lines reaching >90% GFP-positive cells over time. Next, we tested in vitro cytotoxicity by MTS assay after prodrug treatment of pancreatic cancer cells (Pan02 and MIAPaCa-2) transduced with Toca 511. In RRV-transduced pancreatic cancer cells, significant (~90%) cytotoxicity was induced by exposure to 0.1-1.0 mM 5-FC prodrug for 4 days, compared to untransduced and RRV-GFP transduced controls. We then evaluated in vivo therapeutic efficacy of Toca 511/5-FC prodrug activator gene therapy in Pan02 pancreatic tumor models established subcutaneously in immunocompetent syngeneic C57BL/6 mice. While 5-FC treatment alone showed no obvious inhibition of tumor growth as well as the nontreated control group, the majority (n=7/8) of Toca 511-transduced tumors showed complete regression after 5-FC treatment. Notably, systemic biodistribution studies showed no detectable RRV signals in genomic DNA from normal tissues of treated mice. In orthotopic models using luciferase-marked MIAPaCa-2 tumors established in the pancreas in nude mice, significant inhibition of bioluminescent signals was observed by optical imaging after 5-FC administration in mice with Toca 511-infected tumors, as compared to untreated control tumors. Thus, RRVs are highly efficient vehicles for delivering prodrug activator genes such as yCD to pancreatic cancer cells, thereby achieving significant cell killing upon pro-drug administration. Further preclinical studies are ongoing toward translating this novel therapeutic strategy into clinical trials for patients with pancreatic cancer.