tbuckley/cabot-search huggingface dataset:
Heparin Does Not Increase Live Births in Pregnant Women with Previous Unexplained Recurrent Miscarriages: A Systematic Review and Meta-Analysis
Authors: Murtadha K. Al-Khabori, Zainab S. Al-Hosni, Hajer M. Al Ghaithi, Altaf M. Al Maamari, Wafa S. Bessiso, Khalil Al Farsi, Mohammed Al-Huneini, Arwa Z. Al-Riyami, Shahina Daar
Journal: Blood (2012)
Abstract 194: Deregulation of miR-222-ABCG2 regulatory module in tongue squamous cell carcinoma contributes to chemoresistance and enhanced metastatic potential
Authors: Anxun Wang, Luodan Zhao, Qianting He, Tingting Zhao, Wei Wang, Xiaofeng Zhou
Journal: Cancer Research (2015)

Abstract Chemoresistance often associated with other clinical characteristics, such as enhanced metastatic potential. However, the underlying molecular mechanism remains unclear. Our previous studies had revealed that microRNA-222 (miR-222) regulates the cell invasion [Cancer Genomics Proteomics 2009 6:131-138], and plays a role in cell proliferation in tongue squamous cell carcinoma (TSCC) [FEBS Lett. 2010 584(18):4115-20]. The aim of this study is to elucidate the role of miR-222-ABCG2 pathway in the association of cisplatin (cDDP) resistance with enhanced cell migration and invasion ability in TSCC. First, we confirmed the association between cDDP resistance (measured by IC50) and metastatic potential (assessed by migration and invasion assays) using TSCC cell lines and primary cultures from TSCC cases. The siRNA-mediated ABCG2 knockdown led to enhanced cDDP responsiveness, and reduced metastatic potential in TSCC cells. On the contrary, ABCG2 overexpression induced cDDP resistance, and enhanced cell migration and invasion in TSCC cells. Bioinformatics analysis revealed that ABCG2 is a target gene of miR-222, and the direct interaction of miR-222 with ABCG2 mRNA was confirmed by luciferase reporter gene assay. Functional analyses indicated that miR-222 downregulated the expression of ABCG2 gene and enhanced cDDP responsiveness, as well as reduced cell migration and invasion in TSCC cells. Thus, our results confirmed the association between cDDP resistance and enhanced metastatic potential in TSCC. ABCG2 is a direct target gene of miR-222, and deregulation of miR-222-ABCG2 regulatory module in TSCC contributes to both cDDP resistance and enhanced metastatic potential. Citation Format: Anxun Wang, Luodan Zhao, Qianting He, Tingting Zhao, Wei Wang, Xiaofeng Zhou. Deregulation of miR-222-ABCG2 regulatory module in tongue squamous cell carcinoma contributes to chemoresistance and enhanced metastatic potential. [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 194. doi:10.1158/1538-7445.AM2015-194
448. Lentivector Knock-Down of CCR5 in Hematopoietic Stem Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice
Authors: Renier Myburgh, Sandra Ivic, Michael S. Pepper, Gustavo Gers-Huber, Duo Li, Annette Audige, Mary-Aude Rochat, Vincent Jaquet, Stephan Regenass, Patrick Salmon, Karl-Heinz Krause, Roberto F. Speck
Journal: Molecular Therapy (2015)

Gene engineered CD34+ hematopoietic stem cells (HSCs) can be used to generate an HIV-1 resistant immune system. In this study, we combine CCR5 knock-down from a highly efficient miRNA lentivector and pre-transplantation selection of transduced HSCs. Low level transduction of HSCs and subsequent sorting by flow cytometry yielded >90% transduced cells. Mice transplanted with these cells showed functional and persistent resistance to a CCR5-tropic HIV strain (YU-2): viral load was significantly decreased over months, and human CD4+ T cells were preserved. In one mouse, viral mutations, presumably to a CXCR4-tropic strain, overcame HIV resistance. Our results suggest that HSC-based CCR5 knock-down may lead to efficient control of HIV in vivo. As a certain threshold of transduced HSCs is required, improved transduction procedures or in vitro/in vivo selection strategies might be necessary if this is to be translated to clinics. We overcome a major limitation of previous HIV gene therapy humanized mice studies, namely the generation of chimeric mice in which only a proportion of the cells in vivo are anti-HIV engineered. We produce mice where practically all CD4+ T-cells are transduced resulting in long-term suppression of HIV. This underlines the promising future of gene engineering HIV resistant CD34+ cells which produce a constant supply of HIV resistant progeny.
Upfront Treatment with Novel Agents Improves the Survival of Symptomatic Patients with Multiple Myeloma Who Are Older Than 65 Years
Authors: Meletios A. Dimopoulos, Efstathios Kastritis, Maria Roussou, Maria Gavriatopoulou, Magdalini Migkou, Maria Gkotzamanidou, Agapi Parcharidou, Dimitra Gika, Evangelos Terpos
Journal: Blood (2010)
Intracellular free calcium concentration, Ca++ channel and calmodulin level in experimental hypertension in rats.
Authors: Akira Baba, Kazuya Fukuda, Masato Kuchii, Masako Ura, Hiroyuki Yoshikawa, Masanori Hamada, Takuzo Hano, Ichiro Nishio, Yoshiaki Masuyama
Journal: Circulation (1987)

Using fluorescent calcium indicator quin2, we studied intracellular free calcium concentration in platelets that have a number of features similar to vascular smooth muscle cells. Intracellular free calcium concentration in platelets of male SHR was significantly higher at 4, 11 and 28 weeks old compared with age-matched male WKY. However, no significant difference was observed in platelets cytosolic free calcium level of DOCA-salt hypertensive and two-kidney, one clip hypertensive rats in the chronic stage. Cardiac Ca++ channels were estimated by means of radioligand binding method with [3H]-nimodipine. No significant changes were observed in the concentration and affinity of cardiac Ca++ channel in SHR, DOCA-salt hypertensive and two-kidney, one clip hypertensive rats. Calmodulin levels in mesenteric arteries of SHR were significantly decreased in comparison with those of WKY. However no significant differences were observed in DOCA-salt hypertensive rats in the chronic stage. These results indicate that the increase in intracellular free calcium concentration of SHR is not the secondary change caused by high blood pressure. It is impossible to detect the ratio of the three states (open, resting and inactivated) of Ca++ channel. Therefore, there remains a possibility of the changes in the ratio of the states of Ca++ channel. The observed abnormalities of Ca++ regulation may contribute to the pathogenesis of hypertension.
Abstract 4567: Activation of T-cell protein tyrosine phosphatase suppresses keratinocyte survival and proliferation following UVB irradiation
Authors: Hyunseung Lee, Mihwa Kim, Liza D. Morales, Thomas J. Slaga, Dae Joon Kim
Journal: Cancer Research (2015)

Abstract Chronic exposure of UV radiation can contribute to the development of skin cancer by promoting PTK signaling. Studies show that exposure to UV radiation increases the ligand-independent activation of PTKs and induces PTP inactivation. In the present work, we report that TC-PTP activity is stimulated during the initial response to UVB irradiation which leads to suppression of keratinocyte cell survival and proliferation via the down-regulation of STAT3 signaling. Our results show that TC-PTP-deficient keratinocyte cell lines expressed a significantly increased level of phosphorylated STAT3 after exposure to low dose UVB. This increase corresponded with increased cell proliferation in TC-PTP-deficient keratinocytes following UVB irradiation. Loss of TC-PTP also reduced UVB-induced apoptosis. In corroboration with these results, overexpression of TC-PTP in keratinocyte cell lines yielded a decrease in phosphorylated STAT3 levels, which corresponded with a significant decrease in cell proliferation in response to low dose UVB. We demonstrate that TC-PTP activity was increased upon UVB exposure and overexpression of TC-PTP in keratinocyte cell lines further increased its activity in the presence of UVB. Treatment of TC-PTP-deficient keratinocytes with the STAT3 inhibitor STA21 significantly reduced cell viability following UVB exposure in comparison with untreated TC-PTP-deficient keratinocytes, confirming that the effect of TC-PTP on cell viability is mediated by STAT3 dephosphorylation. Combined, our results indicate that UVB-mediated activation of TC-PTP plays an important role in the STAT3-dependent regulation of keratinocyte cell proliferation and survival. Furthermore, these results suggest that TC-PTP may be a novel potential target for the prevention of UVB-induced skin cancer. Note: This abstract was not presented at the meeting. Citation Format: Hyunseung Lee, Mihwa Kim, Liza D. Morales, Thomas J. Slaga, Dae Joon Kim. Activation of T-cell protein tyrosine phosphatase suppresses keratinocyte survival and proliferation following UVB irradiation. [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 4567. doi:10.1158/1538-7445.AM2015-4567
Abstract 1757: The new molecular target therapy of Hsp90 inhibition in esophageal squamous cell carcinoma
Authors: Masahiro Yamamura, Tsutomu Nohno, Akira Yamauchi, Naoki Katase, Makoto Okawaki, Akira Sawaki, Hideo Matsumoto, Toshihiro Hirai, Yoshiyuki Yamaguchi
Journal: Cancer Research (2015)

Abstract Heat shock protein 90 (HSP90) has numerous cellular functions, including promotion of proper protein folding, and stabilizes a number of oncogenic proteins, many of which are overexpressed in cancers. The objective of this study is to evaluate an antitumor effect of HSP90 inhibitor, AUY922, in esophageal squamous cell carcinoma(ESCC) cell lines. ESCC cell lines were treated with AUY922 to examine the effect on proliferation assay, apoptosis assay, Western blotting, and chemotaxis assay. AUY922 inhibited cell proliferation in ESCC cells in a dose- and time-dependent manner. Growth inhibitory effect of AUY922 for ESCC cells was higher than CDDP. With flowcytometry and immunostaining, we showed that AUY922 induced apoptosis in ESCC cells and inhibited chemotaxis of ESCC cells. These antitumor effects of AUY922 were due to inhibition of cell proliferation through suppression of phosphorylation of the client proteins. The HSP90 inhibitor is useful as an antitumor drug in ESCC by inhibiting proliferation of ESCC cells through novel mechanism. Citation Format: Masahiro Yamamura, Tsutomu Nohno, Akira Yamauchi, Naoki Katase, Makoto Okawaki, Akira Sawaki, Hideo Matsumoto, Toshihiro Hirai, Yoshiyuki Yamaguchi. The new molecular target therapy of Hsp90 inhibition in esophageal squamous cell carcinoma. [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 1757. doi:10.1158/1538-7445.AM2015-1757
Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients
Authors: Qing Wang, Andrea De Luca, Colette Smith, Robert Zangerle, Helen Sambatakou, Fabrice Bonnet, Colette Smit, Philipp Schommers, Alicia Thornton, Juan Berenguer, Lars Peters, Vincenzo Spagnuolo, Adriana Ammassari, Andrea Antinori, Eugenia Quiros Roldan, Cristina Mussini, Jose M. Miro, Deborah Konopnicki, Jan Fehr, Maria A. Campbell, Monique Termote, Heiner C. Bucher
Journal: Annals of Internal Medicine (2016)

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.
Pregnancy leads to long-lasting changes in human brain structure
Authors: Elseline Hoekzema, Erika Barba-Müller, Cristina Pozzobon, Marisol Picado, Florencio Lucco, David García-García, Juan Carlos Soliva, Adolf Tobeña, Manuel Desco, Eveline A Crone, Agustín Ballesteros, Susanna Carmona, Oscar Vilarroya
Journal: Nature Neuroscience (2016)
Alternating Nilotinib 400 mg twice daily and Imatinib 400 mg once daily as Frontline Treatment of Ph+ Chronic Myeloid Leukemia. A Phase 2 Multicentric Study of the GIMEMA CML Working Party
Authors: Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Antonella Gozzini, Fabio Stagno, Giovanna Rege Cambrin, Ivana Pierri, Luigia Luciano, Giorgina Specchia, Elisabetta Abruzzese, Bruno Martino, Adele Capucci, Monica Bocchia, Francesco Cavazzini, Mario Tiribelli, Gabriele Gugliotta, Francesca Palandri, Sandra Durante, Simona Soverini, Nicoletta Testoni, Fabrizio Pane, Giuseppe Saglio, Giuliana Alimena, Giovanni Martinelli, Michele Baccarani
Journal: Blood (2011)
The significance of EGFR pathway mutations for the efficacy of bevacizumab in metastatic colorectal cancer
Authors: Izuma Nakayama, Shinozaki Eiji, Wakatsuki Takeru, Ogura Mariko, Ichimura Takashi, Takahari Daisuke, Ozaka Masato, Suenaga Mitsukuni, Chin Keisho, Mizunuma Nobuyuki
Journal: Annals of Oncology (2015)
Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours
Authors: A.F. Leary, M. Quinn, K. Fujiwara, R.L. Coleman, E. Kohn, T. Sugiyama, R. Glasspool, I. Ray-Coquard, N. Colombo, M. Bacon, A. Zeimet, A. Westermann, E. Gomez-Garcia, D. Provencher, S. Welch, W. Small, D. Millan, A. Okamoto, G. Stuart, K. Ochiai
Journal: Annals of Oncology (2016)
Treatment of Idiopathic Myelofibrosis Employing siRNA for Heat Shock Protein 47 (siRNA/HSP47) Encapsulated in Liposomes.
Authors: Junichi Watanabe, Takuya Matsunaga, Kazuyuki Murase, Yasushi Sato, Taiko Nagaya, Hirotoshi Ishiwatari, Sho Takahashi, Koichi Takada, Masayoshi Kobune, Kazuya Shimoda, Mine Harada, Yoshiro Niitsu
Journal: Blood (2007)
Serum gammaglutamyl transpeptidase, alkaline phosphatase, and alfa-fetoprotein in small HCCs.
Authors: B. I. Carr, P. Pancoska, R. A. Branch
Journal: Journal of Clinical Oncology (2011)

e14528 Background: We previously analyzed a large cohort of unresectable HCC patients, ordered by survival. Significant new prognostic factors included gamma glutamyltranspeptidase (GGTP) and alkaline phosphatase (ALKP), as well as previously-described alfa-fetoprotein (AFP). We wished to extend this approach to analysis of small tumors, which could have significance for screening, given AFP limitations. Methods: A further 557 patients with small HCCs who were diagnosed by screening, were analyzed for baseline serum GGTP, ALKP and AFP and ordered by tumor mass (size x number) and tumor number (one or > one). Results: 355 patients (pts) had tumor mass <3 (small) and 202 pts had mass >3 (larger). Small vs. larger tumors with GGTP >45 IU/l were 42% vs. 64%, AFP >25 ng/ml were 32% vs. 43%, ALKP >120 IU/l were 19% vs. 30%. Liver function was excellent, with total bilirubin being <1.3 mg/dl in 88% of each group and albumin being >3g/dl 96% of small and 95% of larger tumors. Thus, GGTP was elevated in 50% more pts than AFP in each group. The cohort was then analyzed according to presence of a single (73% of total) or more than one tumor. For 1 vs. >1 tumor, results were: elevated GGTP 46% vs. 59%, elevated AFP 37% vs. 41%, elevated ALKP 16% vs. 22%. Total bilirubin and albumin levels were similarly normal. For tumor mass <3, 100% of pts had a single tumor; for tumor mass >3, 25% pts had a single tumor and 75% had >1. Age was remarkable as at <65 yrs (61% of pts) all pts had only a single tumor with <3 tumor mass at <3cm diameter. For pts >65 yr (39% of pts) there was a steady increase in tumor size and # with age. Conclusions: For pts with small tumors and normal bilirubin who were diagnosed by radiological screening, there was a much higher % with elevated serum GGTP than AFP.
Abstract 5208: Neovascularization in brain metastasis is through both angiogenesis and vasculogenesis
Authors: Stephanie Mok, Lee-Cyn Ang, Christopher J. Howlett, Zia A. Khan
Journal: Cancer Research (2015)

Abstract Metastatic brain tumors are the most common brain tumor in adults with an incidence 10 times greater than primary brain tumors. A variety of malignancies eventually spread to the brain, with a majority arising from cancers of the lung, breast, kidney, and skin. Experimental studies using breast and melanoma cell lines have recently shown that growth of metastatic brain tumors may occur by utilizing pre-existing blood vessel, or by co-opting rather than inducing new vessel formation. Whether the same mechanisms of vascular utilization and expansion play a role in human metastatic brain tumors is unknown and is the focus of the present study. We examined the immuno-phenotype of blood vessels in primary and metastatic human brain tumors to determine the presence of new blood vessels formation. Glioblastoma multiforme (n = 12) and secondary tumors from melanoma (n = 10), breast (n = 10), kidney (n = 5), and lung (n = 13) all showed extensive immunoreactivity for endothelial marker CD31. We also found a significant number of endothelial cells expressing Ki-67, most notably among breast carcinoma, glioblastoma multiforme and melanoma cases, indicating microvessel proliferation and angiogenesis. Interestingly, both primary and secondary metastatic tumors also showed vascular endothelial cells concomitantly expressing stem cell markers, such as Oct4, suggesting that some of these microvessels are derived through vasculogenesis. These findings show that both proliferation of endothelial cells and de novo endothelial differentiation may underlie metastatic tumor growth to different degrees depending on their site of primary origin. Currently, our laboratory is determining the exact contribution of angiogenesis and vasculogenesis in brain metastasis. Our findings show that neo-vessels are evident in brain metastasis. Elucidating the source of these vessels may uncover new treatment targets for patients with brain metastasis. Citation Format: Stephanie Mok, Lee-Cyn Ang, Christopher J. Howlett, Zia A. Khan. Neovascularization in brain metastasis is through both angiogenesis and vasculogenesis. [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 5208. doi:10.1158/1538-7445.AM2015-5208
Genomic analysis of circulating tumor cells (CTC) from patients with castration-resistant prostate cancer (CRPC) as predictive biomarkers.
Authors: D. C. Danila, A. Anand, J. Yao, M. Gierszewska, M. Kramer, S. Muller, M. Fleisher, W. R. McCombie, H. I. Scher
Journal: Journal of Clinical Oncology (2011)

4540 Background: CTC are representative of the genomic makeup of a tumor and can provide the molecular snapshot of the disease at the time treatment is being considered. We explored the frequency of mutations in genes identified in the prostate genomic profiling project at MSK in CTC from patients with CRPC. Methods: We used fluorescence-activated cell sorting (FACS) methodology to enrich EpCAM+, CD45-, DAPI- cells. For genomic profiling in CTC in low number of cancer cells found in clinical samples, we optimized the RainDance PCR technology followed by Illumina sequencing. Results: Blood samples from124 patients with progressive CRPC were processed by FACS to isolate an average 100-fold more EpCAM+ events compared to the FDA cleared CellSearch assay. By FACS, >10 or >50 events were isolated in 88% or 58% of patients, in whom 32% and 10% had unfavorable (>5 cells/7.5 ml) CTC counts using CellSearch, respectively. The isolated EpCAM+ events express prostate-specific mRNAs (PSA, AR, TMPRSS2-ERG), detected by an analytically validated multiplex RT-PCR. Sufficient high quality DNA for adequate genomic sequencing coverage was obtained from as few 50 EpCAM+ events (EPE), with a recovery rate of 89% from FACS sorted samples. In a heterogeneous cell population, the detection threshold of a mutation was established at 1:4 alleles. Selected missense mutations in AR, and TP53 found in CTC but not in paired WBC, after confirmation by Sanger sequencing, are currently being further analyzed. Conclusions: Somatic mutations detected in CTC isolated from patients with CRPC can serve as predictive markers of tumor sensitivity to targeted therapies. We established standard operating procedures for specimen processing, and confirmed the sequencing coverage and polymorphism detection thresholds in heterogeneous cell population. In the context of available samples collected from patients enrolled in AR-targeted clinical trials, we will generate data to qualify genomic profiling of CTC as predictive biomarkers.
Early Response to Botezomib Combined Chemotherapy Can Be Helpful for Prediction of Progression Free Survival in Patients with Multiple Myeloma Who Were Ineligible for Stem Cell Transplantation
Authors: Ho Sup Lee, Yang Soo Kim, Kihyun Kim, Jin Seok Kim, Hyo Jung Kim, Chang-Ki Min, Cheolwon Suh, Hyeon-Seok Eom, Sung-Soo Yoon, Jae Hoon Lee, Min Kyoung Kim, Sung Hyun Kim, Sung Hwa Bae, Yeung-Chul Mun, Deog Yeon Jo, Joo Seop Chung
Journal: Blood (2011)