tbuckley/cabot-search huggingface dataset:
Abstract 3125: miR-9-3p plays a tumor-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells
Authors: Takaaki Higashi, Hiromitsu Hayashi, Hideaki Takeyama, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Hirohisa Okabe, Hidetoshi Nitta, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba
Journal: Cancer Research (2015)

Abstract Background: Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Despite recent advance in cancer treatment including the development of molecular target drugs, the prognosis in patients with hepatocellular carcinoma (HCC) still remains poor. The inactivation of the Hippo-pathway lead to TAZ/YAP overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). While there are several reports of miR targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC. Methods: miR expression was analyzed using the Human miFinder 384HC miScript miR PCR Array and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumor-suppressor miR targeting TAZ using miRBase. We examined the functional role of miR-9-3p targeting TAZ using miR-9-3p mimic and inhibitor in HCC cell lines (HLF and HuH1 with high and low TAZ expressions, respectively). Results: In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions by real-time PCR. By western blotting, TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. TAZ nuclear localization was indeed inhibited with a treatment with miR-9-3p mimics in HLF cells, and was inversely accelerated with a treatment of miR-9-3p inhibitors in HuH1 cells. Treatment of miR-9-3p mimic inhibited cell proliferative ability by downregulating the phosphorylation of Erk1/2 and Akt signals in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared to control in HuH1. On the other hand, cell invasiveness was not affected by miR-9-3p. Conclusions: miR-9-3p was identified as the tumor-suppressor miR targeting TAZ expression in HCC cells. miR-9-3p played a crucial role in cell proliferation, but not in invasion, via Akt and Erk1/2 signals in HCC cells. Citation Format: Takaaki Higashi, Hiromitsu Hayashi, Hideaki Takeyama, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Hirohisa Okabe, Hidetoshi Nitta, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba. miR-9-3p plays a tumor-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells. [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 3125. doi:10.1158/1538-7445.AM2015-3125
Abstract A66: Runx3 drives metastatic programs in pancreas cancer
Authors: Martin C. Whittle, Libing Feng, Ashley Dotson, Fiona Pakiam, Sunil R. Hingorani
Journal: Cancer Research (2016)

Abstract The extreme proclivity of pancreatic ductal adenocarcinoma (PDA) for metastatic spread is the principal cause of mortality for this disease, even for patients who successfully undergo surgical resection of the primary tumor. We have engaged in a concerted effort to define the fundamental molecular and cellular drivers of PDA through the use of cognate genetically engineered mouse models that recapitulate the spectrum of human PDA. Recently, we incorporated conditional deletion of Smad4 into the KPC mouse model and noted a significant attenuation of metastatic burden in the resultant KPDC mice. Gene expression analysis identified the Runt family transcription factor Runx3 as highly expressed in metastatic KPC tumors, but minimally expressed in PDA from KPDC mice. We showed that aberrant expression of Runx3 strongly enhanced the metastatic potential of PDA through an orchestrated program that stimulated cancer cell invasion and migration and also helped generate a niche for disseminated cells to establish themselves in foreign tissues (such as the liver or lung) and form metastases. Runx3 expression additionally inhibited proliferation by upregulating expression of the cell cycle inhibitor Cdkn1a (p21), initiating a metastatic switch that favored PDA dissemination over local outgrowth. We have also identified influences of Runx3 expression on key developmental and immune-regulatory signaling pathways that are known to be aberrantly regulated in PDA. Because Runx3 has been shown to interact with Smad4 and p53, the genomic context of PDA expressing Runx3 critically modulates its function through de novo or altered protein complex formation. Defining the dichotomous, contextual roles of Runx3 as both a tumor “suppressor” and “promoter” may provide insight into the proximal cause of lethality in patients, thereby informing clinical prioritization of local versus systemic therapies for individual patients with PDA. Citation Format: Martin C. Whittle, Libing Feng, Ashley Dotson, Fiona Pakiam, Sunil R. Hingorani.{Authors}. Runx3 drives metastatic programs in pancreas cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A66.
Statins are linked to reduced Alzheimer’s risk, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Regular use of statins is associated with reduced risk of Alzheimer’s disease, but this reduction varies in people of different ethnicity and among different statins, a retrospective analysis of US clinical data has shown.1

Serum cholesterol levels are associated with the deposition of beta amyloid and the pathology of Alzheimer’s disease, so lowering cholesterol may influence its onset and progression. Research has found that statins may protect against the risk of Alzheimer’s, but randomised trials have been inconclusive, and previous cohort studies cannot be widely generalised.

Researchers in the new study analysed administrative claims data from a 20% …
Pregnancy Outcomes after Clinical Recovery from AKI
Authors: Jessica Sheehan Tangren, Camille E. Powe, Elizabeth Ankers, Jeffrey Ecker, Kate Bramham, Michelle A. Hladunewich, S. Ananth Karumanchi, Ravi Thadhani
Journal: Journal of the American Society of Nephrology (2016)

The effect of clinically recovered AKI (r-AKI) on future pregnancy outcomes is unknown. We retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital to assess whether a previous episode of r-AKI associated with subsequent adverse maternal and fetal outcomes, including preeclampsia. AKI was defined as rise in serum creatinine concentration to 1.5-fold above baseline. We compared pregnancy outcomes in women with r-AKI without history of CKD (eGFR>90 ml/min per 1.73 m
Over-the-scope clip placement and endosponge insertion for prevention of pancreatic enzyme-induced duodenal damage after large duodenal endoscopic resection
Authors: Edris Wedi, Irina Tchoumak, Carlo Jung, Juergen Hochberger
Journal: Endoscopy (2016)

A 61-year-old woman with familial adenomatous polyposis and previous proctocolectomy was admitted for resection of duodenal adenomas (Spigelman classification IV). A formation of two confluent adenomas with low grade dysplasia, measuring 3.5 × 2.5 cm with a central depression (laterally spreading tumor mixed type; Paris IIa + c), was found at the lower duodenal knee (D2/D3) ([Fig. 1 a]).
Abstract IA16: Reconstructing compartment−specific regulatory programs in pancreatic cancer
Authors: H. Carlo Maurer, Jing He, Mariano J. Alvarez, Federico Giorgi, Sam Holmstrom, Andrea Califano, Kenneth P. Olive
Journal: Cancer Research (2016)

Abstract Pancreatic cancer is characterized by an expansive, desmoplastic stroma that responds to neoplastic signals from the malignant epithelium while also instigating a cacophony of signals from diverse stromal cell types that in turn modulate the malignant process. Several published efforts have reported the global signaling profiles of bulk pancreatic tumors, which have proven useful for defining different molecular subtypes of the disease. However, in order to facilitate the precise assessment of both neoplastic and stromal signaling profiles, we developed a robust pipeline to perform RNA-sequencing from laser-capture microdissected tissues. We applied this technique to a collection of 200+ frozen primary pancreatic ductal adenocarcinomas, deriving both malignant epithelial and stromal gene expression profiles from each. These compartment-specific profiles may serve to define novel molecular subtypes grounded in the biology of the distinct compartments. This technique also enabled profiling of the epithelium and stromal from microscopic PanIN-1 proliferations, facilitating the precise delineation of changes arising during malignant progression. Using computational modelling of paired epithelial and stromal samples, we developed a novel digital deconvolution model that generates virtual compartment-specific gene expression signatures from bulk pancreatic tumor profiles. Thus, findings from our experimentally dissected sample set can be leveraged to analyze multiple publically-available gene expression datasets. In order to learn more about the regulatory processes that drive malignancy in both the epithelial and stromal compartments, we used a systems biology approach to reconstruct their global regulatory networks in pancreatic cancer. Briefly, regulatory models comprising ~700,000 interactions were computationally reconstructed for each compartment from the LCM-RNA-seq datasets using the ARACNe algorithm. These networks then served as a scaffold for the application of the MARINa and VIPER algorithms, which define master regulatory proteins whose activity drives (or restrains) the PanIN-1 to PDA progression. We will discuss early results of master regulator analyses that illuminate both oncogenic signaling in the epithelium, and large-scale changes in stromal microenvironment that occur during progression from PanIN-1 to PDA. Citation Format: H. Carlo Maurer, Jing He, Mariano J. Alvarez, Federico Giorgi, Sam Holmstrom, Andrea Califano, Kenneth P. Olive.{Authors}. Reconstructing compartment−specific regulatory programs in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA16.
A Human Variant of Growth Factor Independence 1 (GFI136N) Predisposes to Myeloid Leukemia In Mice
Authors: Cyrus Khandanpour, Lothar Vassen, Marie-Claude Gaudreau, Joseph Krongold, Bert van der Reijden, Joop Jansen, Ulrich Duehrsen, Tarik Moroy
Journal: Blood (2010)
Abstract 4373: Targeting lung cancer stem cells with inhibition of multiple drug resistance by demethoxylcurcumin-carrying chitosan-antibody core-shell nanoparticles
Authors: Shih-Hwa Chiou
Journal: Cancer Research (2015)

Abstract Lung adenocarcinoma (LAC) has been clinically realized to be one of the most deadly malignant tumors with relatively low in 5-year survival rate. High recurrence rates and drug-resistance potential have been reported in LAC even after completion of combined therapy. Herein we demonstrate that cisplatin treatment selecting for resistance with high self-renewal and invasive capabilities in cisplatin-resistant LAC cell (CisR-LAC). For overcoming the multi-drug resistance (MDR) in CisR-LAC, we designed a multifunctional nanocarrier with enhanced targeting ability and inhibition of MDR inhibition in CisR-LAC. The platform provide a high anti-MDR efficacy via a facile synthesis scheme using an amphiphilic chitosan to encapsulate a demethoxylcurcumin (DMC), as a core phase, following surface modification of an anti-EGFR layer, forming a CHC-DMC/anti-EGFR core-shell nanostructure. Experimental outcomes revealed an enhanced therapeutic efficacy of the DMC, forming DMC nano-precipitates in lysosome and endosome, as a result of efficient cellular endocytosis of the core-shell nanoparticles, by a synergistic action of both MDR inhibition and efficacious cell killing. Animal study showed a significant therapeutic efficacy against CisR-LAC-xenograft lung tumor using the core-shell nanocarriers, by a reduction of as high as 5-folded tumor volume compared with control groups. This result indicated the multi-therapeutic efficacy of the multifunctional CHC-DMC/anti-EGFR core-shell nanoparticle, providing a potential capability in anti-MDR LAC for better clinical translation. Note: This abstract was not presented at the meeting. Citation Format: Shih-Hwa Chiou. Targeting lung cancer stem cells with inhibition of multiple drug resistance by demethoxylcurcumin-carrying chitosan-antibody core-shell nanoparticles. [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 4373. doi:10.1158/1538-7445.AM2015-4373
Outcomes of Salvage Stem Cell Transplantation in Hodgkin Lymphoma in a Single Institution in the Modern Era
Authors: Tatyana Feldman, Larysa Sanchez, Lina Starovoitova, Ewelina Protomastro, Yucai Wang, Neil Shah, Michele L. Donato, Scott D. Rowley, David H. Vesole, Alan P Skarbnik, Andrew L. Pecora, Andre Goy
Journal: Blood (2015)
224. Development of Safer & Optimized CAR-T Cells Using Lentiviral Vectors
Authors: Sophie Agaugue, Emeline Sarry, Ana Bejanariu, Klervi Even-Desrumeaux, Abdel Zemmar, Cecile Bauche
Journal: Molecular Therapy (2015)

Chimeric antigen receptors (CAR) modified T cells have shown very promising clinical results in hematological malignancies. CAR are usually composed of a scFv antigen binding domain linked to a spacer and intracellular signaling domains. CAR introduction into T cells leads to cells with optimal effector functions and with a new antigen binding ability. This strategy is well suited to skirt immune escape mechanisms. Despite their efficacy, CAR-T cells still show toxicity due to a cytokine storm, even if it is manageable. Improving the safety while maintaining or even improving the anti-tumor efficacy of CAR-T cells is therefore a crucial therapeutic challenge. Based on our proprietary lentiviral vector technology, we are developing a CAR-T cell platform aiming at producing innovative CAR-T cells. The development conducted by Theravectys are: -Development of proprietary lentiviral vectors coding for CAR of the second (containing the CD3ζ and the 4-1BB cosignaling domains) and third generations (containing the CD3ζ, the CD28 and the 4-1BB domains) directed against CD19 (for CD19+ leukemias and lymphomas), LMP-1 and -2 (for EBV-induced leukemias). Our lentiviral vectors will allow optimal expression of CAR therefore leading to a better efficacy of CAR-T cells. Hematological malignancies will be used as a benchmark.-Development of an inducible RUSH (Retention Using Selective Hook) system which is based on the streptavidin anchored to the membrane of the endoplasmic reticulum (ER) through a hook, and on the SBP (streptavidin binding protein) introduced into the CAR structure. The interaction between the streptavidin-hook and the SBP-CAR allows the CAR retention inside the ER. The addition of biotin displaces the equilibrium of binding of streptavidin towards biotin instead of SBP, thus leading to the release of the CAR from the ER and its expression to the cytoplasmic membrane. The release of the CAR will stop with drug exhaustion (or antagonist) and remaining cells can be easily reactivated through reintroduction of biotin. This system will increase safety of CAR-T cells. A CD19-CAR RUSH will be used as a proof-of-concept of the RUSH system. Most of the scFv used to date are of murine origin. Neutralizing antibodies against these murine scFv can limit the efficacy of CAR. As an alternative, we are screening and engineering specific humanized camelid nanobodies to be used as binding domains since they are highly homologous to the human VH domain of antibodies and they display high antigen binding capacities. The proof-of-concept will be made with a second generation CAR containing a nanobody directed against Her2 as a binding domain. Theravectys' technological platforms allows flexibility and reactivity in the CAR design, production and evaluation, thus leading to the fast generation of safe and optimized CAR-T cells.
High Skp2 Expression Is an Independent Predictor of Unfavorable Outcome in 333 Patients with Diffuse Large B Cell Lymphoma (DLBCL).
Authors: Ritsuko Seki, Koichi Ohshima, Fumio Kawano, Toshihiko Murayama, Yukiyoshi Moriuchi, Ryosuke Ogawa, Kazuya Shimoda, Hitoshi Suzushima, Hiroyuki Tsuda, Nobuyuki Arima, Kunihiro Tsukazaki, Keiko Suzuki, Masahito Iwahashi, Atae Utsunomiya, Tadashi Matsumoto, Takashi Okamura
Journal: Blood (2007)
Abstract 5423: Identification of immunotargets in Hedgehog medulloblastoma for immunotherapy
Authors: Grace S. Tan, Tom Curran
Journal: Cancer Research (2015)

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Although approximately 75% of patients survive with current therapies, the associated complications drastically affect their quality of life, including severe neurological impairment and secondary cancers. Approximately 30% of MB cases exhibit activated hedgehog signaling pathway (HH-MB). Recent clinical trials using small molecular HH inhibitors exhibit promising results. Unfortunately, there are also indications of high rates of resistance and relapses, affirming the pressing need to develop complimentary therapies. Although immunotherapy has previously been proposed to treat MB, unique antigens are rare and monoclonal antibody therapies may not ensure tumor cytotoxicity, without additional adjuvants and associated severe side effects. However, recent successful developments of various cancer immunotherapies, especially the chimeric antigen receptor modified T-cell therapy, have rekindled interest in MB immunotherapies. To address the heterogeneity of MB and to develop a precision immunotherapy, we propose to identify uniquely or differentially overexpressed cell surface proteins in HH-MB, using human MB microarray and RNA-Seq data. Our preliminary studies have identified 39 potential candidates that are differentially expressed in HH-MB. We are currently confirming the presence and cellular localization of these candidate proteins using human MB tissue microarrays. This work is supported by NIH (T32 HL07915 [GST]) and Stand Up To Cancer - St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. Citation Format: Grace S. Tan, Tom Curran. Identification of immunotargets in Hedgehog medulloblastoma for immunotherapy. [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 5423. doi:10.1158/1538-7445.AM2015-5423
Identification of the Histone Deacetylase Inhibitor (HDACi), AR-42, as a Novel Anti-Leukemia Stem Cell Agent in Acute Myeloid Leukemia (AML).
Authors: Duane Hassane, Marlene Balys, Guido Marcucci, John C. Byrd, Craig T. Jordan, Monica L. Guzman
Journal: Blood (2009)
Induction Therapy with High-Dose Dex Alone in Newly Diagnosed Myeloma Patients Produces a 57% Partial Response and Is Predictive of Progression Free Survival.
Authors: David A. Irvine, Michael J. Barnett, Ryan Brinkman, Donna L. Forrest, Donna E. Hogge, Julye Lavoie, Linda Lei, Stephen H. Nantel, Thomas J. Nevill, Janet Nitta, John Shepherd, Kevin Song, Cynthia Toze, Heather Sutherland
Journal: Blood (2006)
Factors associated with synchronous ovarian and endometrial cancer: A population-based case control study.
Authors: M. M. AlHilli, S. C. Dowdy, A. Weaver, J. St. Sauver, G. L. Keeney, A. Mariani, K. C. Podratz, J. N. Bakkum-Gamez
Journal: Journal of Clinical Oncology (2011)

5107 Background: To estimate the incidence of synchronous endometrial cancer (EC) and ovarian cancer (OC) in the female population, among all women with EC, and in young women (<45 years) and determine factors associated with synchronous EC/OC. Methods: All cases of synchronous EC/OC and EC alone diagnosed in women residing in Olmsted County, Minnesota between 1/1/1945 and 12/31/2008 were identified. Incidence was estimated using the population denominator from decennial census data. For each case of synchronous EC/OC, 3 controls with EC alone matched by age and date of cancer diagnosis were randomly selected.Clinical and pathologic data were abstracted.Conditional logistic regression models were fit to evaluate the association between each factor and case/control status. Results: The incidence of synchronous EC/OC and EC (age-adjusted to the 1970 US female total) in 1945-2008 was 0.6 and 18.7 per 100,000 person-yrs, respectively. Among all women diagnosed with EC, 3.2% were synchronous EC/OC.In women under the age of 45, the incidence of EC/OC and EC was 0.08 and 1.6 per 100,000 person-yrs respectively.Thus, among women <45 yrs with EC, 5.2% were synchronous EC/OC. Seventeen cases of EC/OC and 50 controls with EC alone were identified.The mean age of patients with EC/OC was 56 yrs (range 39-73; 2<45 yrs). OC histologies were predominantly endometrioid 6(35%) and serous 5(29%).Stage I EC was diagnosed in 93% of cases and 88% of controls.EC/OC was associated with biopsy-proven endometriosis (p=0.05). EC alone was more likely to be associated with a history of dysfunctional uterine bleeding (p=0.038), whereas EC/OC was more likely to present with a pelvic mass (p=0.005). Women with EC alone were more likely to have used combined oral contraceptives (p<0.05).There was no difference in BMI, parity, age at menopause, infertility, or polycystic ovarian syndrome between cases and controls. Conclusions: Among young women with EC, the incidence of synchronous EC/OC appears to be lower than previously reported. Endometriosis was more common in women with EC/OC, while use of oral contraceptives was less common. There does not appear to be a difference in hyperestrogenic conditions between the two groups.