tbuckley/cabot-search huggingface dataset:
Evaluation of 1p and 19q deletion by chromogenic in situ hybridization (CISH) in paraffin-embedded central nervous system oligodendroglial tumors (CNSOT).
Authors: S. R. Bella, R. Theaux, F. Papalini, J. Suarez, A. Guidi, L. Armando, R. Sambuelli, S. Gomez, C. Bernhardt, D. Lerda
Journal: Journal of Clinical Oncology (2010)

e12557 Background: In the CNSOT, allelic losses on the arms of chromosomes 1p and 19q are not only a marker for molecular diagnosis but they are also preditive for quimiosensibility and survival. The main purpose of this study was to investigate the pathologic features and 1p/19q status with chromogenic in situ hybridization (CISH) technique in a group of CNSOT. Methods: Specimens used for the present study were surgically resected at Sanatorio Allende (20 cases) or Clinica Reina Fabiola (10 cases) between November 2007–August 2008. Paraffin-embedded tumor tissue was available. Tumors were classified morphologically and graded according to the WHO system by two experienced neuropathologist. Chromogenic in situ hybridization (CISH) technique was done for investigation of 1p/19q status in paraffin-embedded tissue. Results: 1) 27 were diagnosed as oligodendrogliomas and 3 as oligoastrocitoma. 2) In twelve patients (40%) deletion in both chromosomes was observed (1p and 19q). Of them, six had oligodendroglioma WHO grade II, and six were oligodendroglioma WHO grade III. The rest of samples (18/30; 60%) did not show deletion in the chromosomes studied. Conclusions: This study has shown that CISH, as an objective assay, has proven to be a reliable technique to detect gene status, specifically deletion in oligodendrogliomas. These results suggests that this molecular genetic analysis may aid therapeutic decisions and predict outcome in CNSOT, based on observations that deleted tumors may benefit from addition of alkylating agents and radiotherapy to surgery No significant financial relationships to disclose.
Cloning and expression of SgCYP450-4 from Siraitia grosvenorii
Authors: Dongping Tu, Xiaojun Ma, Huan Zhao, Changming Mo, Qi Tang, Liuping Wang, Jie Huang, Limei Pan
Journal: Acta Pharmaceutica Sinica B (2016)

CYP450 plays an essential role in the development and growth of the fruits of Siraitia grosvenorii. However, little is known about the SgCYP450-4 gene in S. grosvenorii. Here, based on transcriptome data, a full-length cDNA sequence of SgCYP450-4 was cloned by reverse transcriptase-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends (RACE) strategies. SgCYP450-4 is 1677 bp in length (GenBank accession No. AEM42985.1) and contains a complete open reading frame (ORF) of 1422 bp. The deduced protein was composed of 473 amino acids, the molecular weight is 54.01 kDa, the theoretical isoelectric point (PI) is 8.8, and the protein was predicted to possess cytochrome P450 domains. SgCYP450-4 gene was highly expressed in root, diploid fruit and fruit treated with hormone and pollination. At 10 days after treatment with pollination and hormones, the expression of SgCYP450-4 had the highest level and then decreased over time, which was consistent with the development of fruits of S. Grosvenorii. Hormonal treatment could significantly induce the expression of SgCYP450-4. These results provide a reference for regulation of fruit development and the use of parthenocarpy to generate seedless fruit, and provide a scientific basis for the production of growth regulator application agents.
The Curative Potential Of Fludarabine125, Melphalan100, and Busulfan4 As a Conditioning Regimen For Myeloid Malignancies Of Elderly Patients
Authors: Tomoaki Ueda, Aki Sato, Kazuya Sakai, Hiroyuki Muranushi, Yusuke Okamoto, Taku Tsukamoto, Hiroyuki Sugiura, Hiroyuki Matsui, Tomoyasu Jo, Kazuya Okada, Takeshi Maeda, Tatsuhito Onishi, Akane Kunitomi, Yasunori Ueda
Journal: Blood (2013)
Clinical implication of body size phenotype on heart rate variability
Authors: Hye Jin Yoo, Soon Young Hwang, Kyung Mook Choi, Sei Hyun Baik, Eun Mi Lee, Eung Joo Kim, Seung-Woon Rha, Chang Gyu Park, Dong Joo Oh, Hong Seog Seo
Journal: Metabolism (2016)
Abstract 3534: Inhibition of melanoma cell survival through p62/LC3B autophagic signaling
Authors: Heather G. Hambright, Addanki P. Kumar, Rita Ghosh
Journal: Cancer Research (2016)

Abstract The primary objectives of this study were i) systematic evaluation of the differences in basal autophagic activity between melanocytes and malignant melanoma cells to determine whether these differences may be selectively targeted using the ROS inducer, Nexrutine (NX); ii) determination of NX selectivity in inhibiting melanoma cell survival and iii) specific involvement of autophagy signaling protein, SQSTM1/p62 in NX-mediated autophagic cell survival. NX is obtained from the bark of the cork tree, Phellodendron amurense. A panel of melanocyte and melanoma cells was evaluated for basal autophagy level and effect of NX treatment, including protein levels and turnover of p62 and LC3B (+/- CQ), and number of autophagic puncta per cell. Trypan blue, MTT, and Annexin V-APC were used to evaluate the effect of NX on cell death, proliferation and apoptosis. Genetic approach using siRNA for p62 and overexpression using HA-p62 followed by survival, proliferation, and autophagy measurements were used to further evaluate the possibility of p62 as a molecular target for inhibition of autophagy seen using NX. We found that i) melanoma cells displayed high autophagic flux compared with melanocytes, ii) NX treatment a) inhibited autophagy in melanoma cells, b) inhibited melanoma cell survival, and c) induced apoptosis in melanoma cells, iii) knockdown of p62 resulted in a lesser inhibition of cell viability and autophagy after NX treatment in high p62-expressing melanoma cells, and iv) overexpression of p62 sensitized low p62-expressing normal melanocytes and melanoma cells to NX-mediated cell death and autophagy inhibition, suggesting that p62 is a bonafide molecular target of NX. Overall, we show that Nexrutine is able to inhibit the inherent high level of pro-survival autophagy in melanoma cells, leading to loss of cell viability and induction of apoptosis, while melanocytes remain unaffected by NX at the same doses. Further, SQSTM1/p62 was found to be a critical mediator of the NX-mediated inhibition of autophagy and cell viability. This study demonstrates that NX maybe a promising novel, non-toxic agent for melanoma. Supported by R21 CA125719 &amp; ACRCF (RG); NIDCR T32 DE14318/COSTAR (HGH) Citation Format: Heather G. Hambright, Addanki P. Kumar, Rita Ghosh. Inhibition of melanoma cell survival through p62/LC3B autophagic signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3534.
Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response
Authors: Erik Bovinder Ylitalo, Elin Thysell, Emma Jernberg, Marie Lundholm, Sead Crnalic, Lars Egevad, Pär Stattin, Anders Widmark, Anders Bergh, Pernilla Wikström
Journal: European Urology (2016)

Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation.To identify molecular subgroups of PC bone metastases of relevance for therapy.Fresh-frozen bone metastasis samples from men with CRPC (n=40), treatment-naïve PC (n=8), or other malignancies (n=12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription-polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n=77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n=12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n=284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non-AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non-AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored.We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.
Abstract LB-031: Generation of inducible oncogenic chromosomal translocations using CRISPR-Cas9 genomic editing
Authors: Lee Spraggon, Luciano Martelotto, Julija Hmeljak, Emily Slotkin, Lu Wang, Jorge Reis-Filho, Marc Ladanyi
Journal: Cancer Research (2016)

Abstract Specific, reciprocal chromosomal translocations are found in numerous cancers, typically leading to the formation and expression of fusion genes with oncogenic properties. It has been demonstrated that by inducing double-stranded breaks (DSBs) in genomic DNA, using either zinc fingers nucleases (ZF), transcription activator-like effector nucleases (TALENs), or the CRISPR-Cas9 system, it is possible to faithfully recapitulate such chromosomal translocations in human cell lines. A potential pitfall is that the induction of the chromosomal translocation generates a constitutively active oncogenic fusion product, which can be detrimental to cell growth or viability in certain heterologous cell types. To overcome these obstacles, we have combined homology directed repair (HDR) with CRISPR-Cas9 genome editing to generate conditionally inducible chromosomal translocations. As proof of principle, we have used this approach to engineer human cell lines to carry the molecular hallmark present in Ewing Sarcoma, the t(11;22)(q24;q12) translocation. Our approach allows for the de novo generation and capture of the desired chromosomal translocation in the context of a conditional allele. Whole genome sequencing (WGS) and fluorescence in situ hybridization (FISH) confirmed the accuracy of our genomic editing approach, whilst analysis of mRNA and protein levels confirmed the selective inducibility and generation of biologically functional EWSR1-FLI1 fusion oncogene. Therefore, our approach establishes an innovative platform for constructing isogenic and conditionally inducible biologically relevant models for a variety of cancers driven by chromosomal translocations. Citation Format: Lee Spraggon, Luciano Martelotto, Julija Hmeljak, Emily Slotkin, Lu Wang, Jorge Reis-Filho, Marc Ladanyi. Generation of inducible oncogenic chromosomal translocations using CRISPR-Cas9 genomic editing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-031.
Case 40-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, William F. Crowley, William R. Welch
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 37-year-old man was admitted to the hospital because of a mass in the right suprarenal region.He was well until one year earlier, when he began to have morning headaches. Ten months before entry he saw a physician, who found that the blood pressure was 180/100 mm Hg in the arm and 180 mm Hg systolic in the leg. The results of other studies, including an electrocardiogram, an x-ray film of the chest, an intravenous pyelographic examination and determination of the urinary vanillyl-mandelic acid (VMA) and catecholamines, were reported to be normal. Medication was prescribed, but . . .
Abstract 2958: A cancer-specific monoclonal antibody against podocalyxin developed by CasMab technology inhibited the tumor growth by antibody-dependent cellular cytotoxicity
Authors: Yukinari Kato, Satoshi Ogasawara, Akiko Kunita, Yuki Fujii, Mika K. Kaneko
Journal: Cancer Research (2016)

Abstract Background: Podocalyxin (PODXL) is a CD34-related sialomucin and a well-known marker of embryonic stem cells. PODXL is expressed in many cancers including brain tumors, breast cancers, and colorectal cancers. Overexpression of PODXL is an independent predictor of progression, metastasis, and poor outcome. In contrast, PODXL is highly expressed in normal cells such as vascular endothelial cells (VECs) or renal podocytes. Although many monoclonal antibodies (mAbs) against PODXL have been established, they bind to both cancer and normal cells. We recently established CasMab technology for developing cancer-specific mAbs, which could target only cancer cells, although those membranous proteins are highly expressed in both cancer and normal cells. Methods: We immunized mice with human PODXL, which was overexpressed in a glioblastoma cell line. Cancer-specific mAbs were screened using flow cytometry against PODXL-expressing cancer and normal cells. The cancer specificity was confirmed using immunohistochemistry against breast cancer tissues. A mouse-human chimeric anti-PODXL mAb was produced and antibody-dependent cellular cytotoxicity (ADCC) was investigated in vitro. The in vivo efficacy of anti-PODXL mAbs was evaluated using xenograft models of PODXL-expressing cell lines. Results: One clone of anti-PODXL mAbs, which was established by CasMab technology, reacted with PODXL-expressing many cancer cell lines including breast cancers, brain tumors, and malignant mesotheliomas, whereas it did not bind to VECs in flow cytometry. The anti-PODXL mAb reacted only with PODXL-expressing cancer cells, not with VECs in breast cancer tissues in immunohistochemistry. Furthermore, the anti-PODXL mAb possesses ADCC activity in vitro and anti-tumor effect in vivo. Conclusion: The anti-PODXL mAb established by CasMab technology could be useful for targeting PODXL in cancer, although PODXL is highly expressed in many normal cells. Citation Format: Yukinari Kato, Satoshi Ogasawara, Akiko Kunita, Yuki Fujii, Mika K. Kaneko. A cancer-specific monoclonal antibody against podocalyxin developed by CasMab technology inhibited the tumor growth by antibody-dependent cellular cytotoxicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2958.
Abstract 3823: Staphylococcal nuclease and tudor domain containing 1 (SND1) in development and progression of hepatocellular carcinoma
Authors: Nidhi Jariwala, Devaraja Rajasekaran, Rachel Gredler, Maaged Akiel, Chadia Robertson, Paul Fisher, Arun Sanyal, Devanand Sarkar
Journal: Cancer Research (2016)

Abstract Staphylococcal nuclease and tudor domain containing 1 (SND1) is identified as an oncogene in hepatocellular carcinoma (HCC) and overexpression of SND1 has been correlated with HCC progression. Here, we present effect of liver specific overexpression of human SND1 in a novel transgenic mouse model. We observe greater tumor load and tumor volume in transgenic mice than wildtype mice, when subjected to chemical carcinogenesis. Approximately 30% of transgenic animals manifest spontaneous tumorigenesis with age. Liver specific expression of cancer stem cell markers such as EpCAM and CD133 as well as inflammatory markers was found to be higher in transgenic mice. SND1 overexpressing hepatocytes show increased activation of insulin and NFκB signaling pathways compared to wildtype hepatocytes. However, no significant differences in liver weight or liver function was noted among transgenic and wildtype animals. Overall, our findings confirm that overexpression of SND1 in vivo plays a vital role in development and progression of HCC. Thus, molecular targeting of SND1 seems to be potential therapeutic intervention for HCC management in patients. Citation Format: Nidhi Jariwala, Devaraja Rajasekaran, Rachel Gredler, Maaged Akiel, Chadia Robertson, Paul Fisher, Arun Sanyal, Devanand Sarkar. Staphylococcal nuclease and tudor domain containing 1 (SND1) in development and progression of hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3823.
Abstract 3672: Coordinated roles of CHD1 and SPOP in prostate cancer pathogenesis
Authors: Divya Vasudevan, Mirjam Blattner, Lesa D. Deonarine, Yu Chen, Mark A. Rubin, Christopher E. Barbieri
Journal: Cancer Research (2016)

Abstract Prostate cancer (PCa) is a clinically heterogeneous disease, consequently presenting challenges while designing efficacious therapeutic strategies across diverse patient cohorts. There is an increasing need to improve our understanding of the disease by classifying PCa into distinct molecular subtypes characterized by specific genomic alterations. To this end, loss of the gene encoding chromodomain helicase DNA binding protein 1 (CHD1) represents one of the largest classes of recurrent gene deletions detected exclusively in PCa, hallmarking up to 20% of characterized tumors. CHD1 is well known to facilitate the assembly of euchromatin during transcription. Therefore, we hypothesized that loss of CHD1 would induce a significant change in overall transcription and alter prostate cell fate, promoting tumorigenesis. To confer a high degree of physiological relevance to our studies, we utilized genetically engineered mouse (GEM) models harboring prostate-specific CHD1 deletions. Since loss of CHD1 has a significant tendency to co-occur with mutations in the SPOP gene, we generated GEM models that also co-express the SPOP F133V transgene. We derived organoid lines from GEM prostates to recapitulate prostate histology in a three dimensional matrix, which allowed us to track changes at the molecular level and overall phenotype as they relate to PCa development. We found that CHD1 loss associated strongly with the presence of an increased luminal cell population compared to wild type controls. Since luminal cells are recognized to be cells of origin in PCa, this observation is consistent with the notion that CHD1 deletion represents a pro-tumorigenic event. Additionally, our data indicates that co-occurrence of CHD1 deletions and SPOP mutations may confer a growth advantage to prostate cells. The overarching goal of this study is to define the coordinated role of CHD1 loss and SPOP mutations in PCa, highlight altered signaling pathways and phenotypes, and nominate potential therapeutic strategies for patients with this PCa subtype. Citation Format: Divya Vasudevan, Mirjam Blattner, Lesa D. Deonarine, Yu Chen, Mark A. Rubin, Christopher E. Barbieri. Coordinated roles of CHD1 and SPOP in prostate cancer pathogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3672.
Pathogen- and antibiotic-specific effects of prednisone in community-acquired pneumonia
Authors: Sebastian A. Wirz, Claudine A. Blum, Philipp Schuetz, Werner C. Albrich, Christoph Noppen, Beat Mueller, Mirjam Christ-Crain, Philip E. Tarr
Journal: European Respiratory Journal (2016)

In a double-blind, randomised, placebo-controlled trial of hospitalised patients with community-acquired pneumonia (CAP), we demonstrated shorter time to clinical stability (TTCS) with adjunct corticosteroid therapy compared with placebo. We did a pre-planned, exploratory analysis of any association between microbiological diagnosis, antibiotic treatment and procalcitonin level and effect of prednisone on TTCS, mortality, and CAP complications (n=726 participants, enrolled between December 2009 and May 2014). Multiplex viral real time PCR was systematically performed in nasopharyngeal swabs beginning November 2011 (n=489). Other investigations and treatments were at the discretion of the physician. Effect modification was tested with inclusion of interaction terms in the statistical models. Reduced TTCS with prednisone was seen in all microbiological, antibiotic, procalcitonin and afebrile patient subgroups. We found evidence for a different prednisone response in patients with pneumococcal pneumonia in whom intravenous antibiotic duration was not shorter (interaction p=0.01) with prednisone, as was observed in the remaining study population. In patients without macrolide treatment, rehospitalisations were not lower with prednisone (interaction p=0.04). After adjustment for multiple testing, these subgroup effects were no longer significant. Prednisone was associated with shorter TTCS independent of CAP aetiology. In pneumococcal pneumonia, prednisone effects on secondary endpoints may be less favourable.
Abstract 5176: Orthotopic syngeneic tumor models for preclinical evaluation of cancer immunotherapy strategies
Authors: Juan Zhang, Sheng Guo, Zhensheng Wang, zhongliang Li, Meng Qiao, Qian Shi
Journal: Cancer Research (2016)

Abstract Background: The recent successes of cancer immunotherapies have stimulated interest in the potential application of these approaches in many solid and hematologic tumors. Syngeneic tumor models have been widely used in cancer immunotherapy assessment. However, most of these experimental models were established as subcutaneous models, while there may be significant difference in immune microenvironment comparing orthotopic vs. subcutaneous tumors. In addition, drug delivery and metabolism are different in orthotopic tumors vs. subcutaneous tumors. To address this unmet need, we set out to validate a panel of orthotopic syngeneic models for anti-cancer therapeutics (mainly immunotherapeutics) evaluation. Results: A large collection of orthotopic syngeneic models covering breast cancer, liver cancer and various hematological cancers were established in immunocompetent mice. Survival curves were established and the responsiveness to anti-PD1, anti-PDL1 and anti-CTLA4 antibodies were evaluated in the orthotopic models. Orthotopic liver tumors were monitored with ultrasound imaging to obtain longitudinal growth curves. The correlation in drug efficacy between the orthotopic model and its subcutaneous counterpart was analyzed. The role of NK cells in the development of a panel of systemic hematological tumor models was investigated with NK depleting antibodies. Conclusion: Despite the obvious difficulties, orthotopic syngeneic models represent closer model systems to human diseases and may be a valuable tool to the evaluation of cancer immunotherapies and their combination strategies. Citation Format: Juan Zhang, Sheng Guo, Zhensheng Wang, zhongliang Li, Meng Qiao, Qian Shi. Orthotopic syngeneic tumor models for preclinical evaluation of cancer immunotherapy strategies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5176.