tbuckley/cabot-search huggingface dataset:
Abstract 3048: Study of mitochondria in multi-drug resistance and Polyphyllin D anti-cancer effect in hepatocellular carcinoma
Authors: Brandon Ho Ngai, Jacky Fong Chuen Loo, Siu Kai Kong
Journal: Cancer Research (2015)

Abstract Liver cancer, being the sixth common cancer, causes approximately 700,000 deaths worldwide annually. Major treatment relies on chemotherapies because of the late diagnosis in many cases of liver cancer. However, the results are not satisfactory since the cancer cells develop multi-drug resistance (MDR), which greatly hampers the efficacy of multiple kinds of structurally different drugs, during the course of treatment. Several mechanisms of MDR were identified, the most notable one is the over-expression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and multi-drug resistance protein 1 (MRP-1), on plasma membrane. These transporters act as efflux pump of various types of chemo-drugs to accentuate the MDR phenotype. Nevertheless, the complete picture of MDR formation is yet to be explored. As mitochondria contribute vitally in apoptosis and energy production, in which both criteria are substantially altered in cancer context, we hypothesized that the organelle also takes part in the development of MDR in liver cancer. In our study, with the support of conventional assays such as western blotting and confocal imaging analysis, we adopted a novel approach by making use of the tunable resistive pulse sensing (TRPS) technique to characterize isolated mitochondria of HepG2 and R-HepG2, which corresponds to the native and multi-drug resistant liver cancer cell lines respectively. We identified a difference in volume and amount of mitochondria present in HepG2 and R-HepG2, plus the expression of P-gp and MRP-1 on mitochondria of R-HepG2. These suggest a potential role of mitochondria in MDR. On the other hand, a drug candidate Polyphyllin D (PD) was found to exert selective potency against R-HepG2. However, the mechanism is not lucid. We investigated the possible participation of mitochondria in this phenomenon and identified PD causes stronger swelling and membrane potential depolarization to isolated mitochondria of R-HepG2. Future attempt in elucidating pathways involved in PD toxicity will bring insight on designing therapeutics against cancer cells with MDR phenotype. This study also suggested future research in mitochondria can aid the discovery of more mechanisms in MDR development. Citation Format: Brandon Ho Ngai, Jacky Fong Chuen Loo, Siu Kai Kong. Study of mitochondria in multi-drug resistance and Polyphyllin D anti-cancer effect in hepatocellular 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 3048. doi:10.1158/1538-7445.AM2015-3048
Abstract 2156: FGFR2 regulates Mre11 expression and double-strand break repair via the MEK-ERK-POU1F1 pathway in breast tumorigenesis
Authors: Yuan-Ling Huang, Wen-Cheng Chou, Chia-Ni Hsiung, Ling-Yueh Hu, Hou-Wei Chu, Chen-Yang Shen
Journal: Cancer Research (2015)

Abstract Purpose: The association between breast cancer risk and genetic variants of fibroblast growth factor receptor 2 (FGFR2) has been identified and repeatedly confirmed; however, the mechanism underlying FGFR2 in breast tumorigenesis remains obscure. Given that breast tumorigenesis is particularly related to DNA double-strand-break-repair (DSBR), we examined the hypothesis that FGFR2 is involved in DSBR. Experimental design: This study started with the demonstration that FGFR2 impaired DSBR. Subsequent screening of the expression of genes functionally related to DSBR was performed and possible signaling pathways downstream of FGFR2 were examined. Data from independent breast cancer patient cohorts was used to confirm that difference in progression of patients can be explained by the findings identified in cell model. Results: Expression of Mre11, a vital exonuclease in DSBR, is downregulated by FGFR2, which is further linked to decreased DSBR. Analysis of the Mre11 promoter revealed that POU1F1 mediates FGFR2-induced Mre11 downregulation. Furthermore, ERK, downstream of FGFR2, directly interacts with and phosphorylates POU1F1, increasing POU1F1 binding capacity to the Mre11 promoter and repressing Mre11 expression, which consequently affects DSBR and sensitizes breast cancer cells to chemotherapeutic treatments. The importance of the FGFR2-Mre11-DSBR link in cancer progression is suggested by the finding that genotypes of FGFR2 and Mre11 are associated with survival of breast cancer patients and that FGFR2 expression correlates with cancer prognosis specifically in patients receiving chemotherapy. Conclusion: This study yields important insight into the role of FGFR2 in breast tumorigenesis and may facilitate development of a useful therapeutic approach for breast cancer. With the move toward personalized therapy, which has gradually become a clinical reality, the findings of the present study suggest that FGFR2 expression may be a potential biomarker for selecting a suitable subgroup of breast cancer patients to receive chemotherapy or to determine the optimal chemotherapeutic dose. Citation Format: Yuan-Ling Huang, Wen-Cheng Chou, Chia-Ni Hsiung, Ling-Yueh Hu, Hou-Wei Chu, Chen-Yang Shen. FGFR2 regulates Mre11 expression and double-strand break repair via the MEK-ERK-POU1F1 pathway in breast tumorigenesis. [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 2156. doi:10.1158/1538-7445.AM2015-2156
Reform UK abortion law, say health organisations
Authors: Jacqui Wise
Journal: BMJ (2016)

The UK’s abortion law is not fit for purpose and should be reformed, the editor in chief of the Journal of Family Planning and Reproductive Health Care has said.1

Sandy Goldbeck-Wood, clinical lead for abortion services at Cambridge University Hospitals, argued that the current law is paternalistic and out of step with technical advances in safe medical abortion.

She said that many women presenting to abortion services in early pregnancy believe that they have a right to make their own choice, as they would in most of Europe, but that British law still requires …
Histone deacetylase activity in peripheral blood of patients with malignant pleural mesothelioma.
Authors: T. Nakano, K. Tamura, T. Otsuki, H. Ohkuwa, H. Kamiya, E. Masachika, M. Honda, K. Mikami, Y. Nogi, R. Maeda, C. Tabata, K. Fukuoka
Journal: Journal of Clinical Oncology (2011)

e21165 Background: Histone deacetylase (HDAC) modulates gene expression through the deacetylation of lysine residues on histone proteins and acts transcriptional repressors of genes. HDAC is currently the focus of new target for cancer therapy, because of its role in cell cycling, apoptosis and differentiation. There is an increasing amount of preclinical data on the effectiveness of HDAC inhibition in mesothelioma cell lines and mouse xenograft models, but no clinical data on HDAC activity in malignant pleural mesothelioma (MPM) has been published. Methods: We evaluated HDAC activity in the peripheral blood mononuclear cells (1x105) of patients with MPM (n=37) and healthy volunteers without asbestos exposure (n=25) using HDAC fluorometric assay. Results: The level of HDAC activity was significantly higher in patients with MPM than that in normal subjects (p=0.0008, MPM=134,778 ± 84,357 arbitrary fluorescence units, normal subject=64,314 ± 63,070 AFU) The median HDAC activity in epithelioid subtype (n=26) was higher than that in non-epithelioid subtype (n=11, biphasic/sarcomatoid: 5/6), which was not statistically significant. MPM with early clinical stage (IMIG T1 stage, n=4) showed an increase in HDAC activity, and there was no significant difference among the IMIG clinical stages. Conclusions: MPM patients had a markedly increased level of HDAC activity in peripheral blood mononuclear cells. These findings suggest that HDAC activity can be surrogate marker in predicting clinical response to HDAC inhibitor for mesothelioma treatment.
Abstract 2492: Eradication of breast cancer with bone metastasis by autologous formalin- fixed tumor vaccine (AFTV) and radiation
Authors: Fumito Kuranishi, Yoji Uemae, Tadao Ohno, Yusuke Sumi
Journal: Cancer Research (2015)

Abstract INTRODUCTION) Bone-metastatic mammary carcinoma patients show the downhill course to a tragic ending despite of intensive chemo-radiation therapy, except an our case concomitantly treated with AFTV (AACR2013, World J Surg Oncol 2013; 11:127). We here report, as the second successful case, eradication of a large bone metastasis of advanced breast cancer after treatment with AFTV and radiation. (CASE) A 47-years old female with stage II breast cancer was operated in July, 2000. Left axillar recurrence was found 13 years later by ultrasonography and FNBC. PET scan revealed a huge bone metastasis in sternum. She was treated with radiation and AFTV (J Neurosurgery 2014;4:1) in Oct. - Nov. 2013. Follow-up PET (Sep. 2014) showed no hot spot, and we diagnosed the patient, complete remission. (CONCLUSION) Complete remission of bone metastasis of mammary carcinoma is very rare. The initial successful case beared triple-negative breast cancer. Treatment with AFTV and radiation without intensive chemotherapy like the present case will be acceptable to any patient with bone-metastatic mammary carcinoma, though a large scale clinical trial should be required to confirm the therapeutic efficacy of AFTV. Citation Format: Fumito Kuranishi, Yoji Uemae, Tadao Ohno, Yusuke Sumi. Eradication of breast cancer with bone metastasis by autologous formalin- fixed tumor vaccine (AFTV) and radiation. [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 2492. doi:10.1158/1538-7445.AM2015-2492
Use of cone beam computed tomography in implant dentistry: current concepts, indications and limitations for clinical practice and research
Authors: Michael M. Bornstein, Keith Horner, Reinhilde Jacobs
Journal: Periodontology 2000 (2016)

Diagnostic radiology is an essential component of treatment planning in the field of implant dentistry. This narrative review will present current concepts for the use of cone beam computed tomography imaging, before and after implant placement, in daily clinical practice and research. Guidelines for the selection of three-dimensional imaging will be discussed, and limitations will be highlighted. Current concepts of radiation dose optimization, including novel imaging modalities using low-dose protocols, will be presented. For preoperative cross-sectional imaging, data are still not available which demonstrate that cone beam computed tomography results in fewer intraoperative complications such as nerve damage or bleeding incidents, or that implants inserted using preoperative cone beam computed tomography data sets for planning purposes will exhibit higher survival or success rates. The use of cone beam computed tomography following the insertion of dental implants should be restricted to specific postoperative complications, such as damage of neurovascular structures or postoperative infections in relation to the maxillary sinus. Regarding peri-implantitis, the diagnosis and severity of the disease should be evaluated primarily based on clinical parameters and on radiological findings based on periapical radiographs (two dimensional). The use of cone beam computed tomography scans in clinical research might not yield any evident beneficial effect for the patient included. As many of the cone beam computed tomography scans performed for research have no direct therapeutic consequence, dose optimization measures should be implemented by using appropriate exposure parameters and by reducing the field of view to the actual region of interest.
A risk model for secondary cytoreductive surgery in recurrent ovarian cancer: An evidence-based proposal for patient selection.
Authors: W. Tian, D. Chi, J. Sehouli, C. Trope, R. Jiang, A. Ayhan, G. Cormio, Y. Xing, G. Breitbach, E. I. Braicu, C. A. Rabbitt, H. Oksefjell, C. Fotopoulou, H. Meerpohl, A. Du Bois, J. S. Berek, R. Y. Zang, P. Harter
Journal: Journal of Clinical Oncology (2011)

5053 Background: This study aims to redefine the role of secondary cytoreductive surgery (SCR) and develop a risk model for predicting outcomes of SCR in patients with recurrent ovarian cancer. Methods: Individual data of patients with recurrent ovarian cancer undergoing SCR from seven world-wide centers were pooled analyzed. The risk model was developed based on the factors impacting on SCR outcome. Additional data of 117 patients were used for external validation and to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared to 27.0 months and 15.6 months in those with residual disease of 0.1-1cm and >1cm, respectively (P< 0.0001). Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete SCR was associated with six variables: FIGO stage (OR=1.32), residual disease after primary cytoreduction (OR=1.69), progression-free interval (OR=2.27), ECOG performance status (OR=2.23), CA125 (OR=1.85) and ascites at recurrence (OR=2.79). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low risk group, in which the proportion of complete cytoreduction was 53.4% compared to 20.1% in the high risk group (OR=4.55). In external validation, the sensitivity and specificity of the model was 83.3% and 57.6%, respectively. Conclusions: SCR may be recommended for selected patients with recurrent ovarian cancer. This model may well predict the outcome of SCR and determine who benefit from SCR.
Low Prevalence of “Ideal Cardiovascular Health” in a Community-Based Population
Authors: Claudia Bambs, Kevin E. Kip, Andrea Dinga, Suresh R. Mulukutla, Aryan N. Aiyer, Steven E. Reis
Journal: Circulation (2011)

Cardiovascular health is a new construct defined by the American Heart Association (AHA) as part of its 2020 Impact Goal definition. The applicability of this construct to community-based populations and the distributions of its components by race and sex have not been reported.
A Report on Cancer of the Skin
Journal: JAMA (1934)

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Abstract 159: LncRNA RoR enhances the c-Myc mRNA stability in colon cancer
Authors: Jianguo Huang
Journal: Cancer Research (2015)

Abstract Background: Emerging evidence has implicated long non-coding RNAs (lncRNAs) as master gene regulators; and they are often aberrantly expressed in a variety of human diseases including cancer. One of the mechanisms of lncRNA-mediated gene expression involves modulation of translation or mRNA stability by interacting with RNA binding proteins. We have previously demonstrated that lncRNA-RoR is a strong negative regulator of p53 in response to DNA damage. The present study was to determine whether and how lncRNA-RoR regulates c-Myc in colon cancer. Methods: MTT assays were used to determine cell growth. Colon cancer tissue array was used to determine the level of lncRNA-RoR in colon cancer tissues by qRT-PCR. Interaction between lncRNA-RoR and RNA binding proteins was confirmed by RNA co-immunoprecipitation and RNA precipitation. LncRNA-RoR knockout in colon cancer cells was through CRISPR/Cas9 system. Dual fluorescent in situ hybridization (FISH) was used to determine the relative levels of lncRNA-RoR and c-Myc mRNA, and their co-localizations in colon cancer specimens. The effect of lncRNA-RoR on tumor growth was determined by a xenograft mouse model. Results: Ectopic expression of lncRNA-RoR upregulated, whereas RoR-siRNA inhibited c-Myc mRNA and protein level, which was further confirmed by lncRNA-RoR knockout. Mechanistically, we showed that lncRNA-RoR directly interacted with RNA binding proteins, hnRNP U and hnRNP D, both of which are implicated in stability of c-Myc mRNA. This interaction was further confirmed by RNA immunoprecipitation. In consistent with these findings, ectopic expression of lncRNA-RoR stimulated cell proliferation but knockout of lncRNA-RoR significantly decreased cell proliferation. Moreover, ectopic expression of lncRNA-RoR in HCT-116 cells significantly promoted tumor growth in a xenograft mouse model. Finally, qPCR array showed the significant upregulation of lncRNA-RoR in colon cancer tissues. Similarly dual FISH revealed a strong correlation between lncRNA-RoR and c-Myc mRNA in colon cancer tissues. Conclusion: It is well known that c-Myc mRNA has a very short half-life and regulation of c-Myc mRNA stability is complex. Our results suggest a novel mechanism of regulation of c-Myc mRNA stability involving lncRNA-RoR, hnRNP U and hnRNP D. Citation Format: Jianguo Huang. LncRNA RoR enhances the c-Myc mRNA stability in colon 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 159. doi:10.1158/1538-7445.AM2015-159
685. Restoration of Antiviral Immunity Following Hematopoietic Stem Cell Transplantation with Virus-Specific T-Lymphocyte Therapy
Authors: Michael D. Keller, Jamie C. Hoover, Patrick J. Hanley, Sarah McCormack, Cecilia Barese, Elizabeth Williams, Neha Joshi, Maria Martin-Manso, Lauren Roesch, Conrad R. Cruz, Allistair Abraham, Kirsten Williams, Blachy Davila, Evelio Albuerne-Perez, David Jacobsohn, Catherine M. Bollard
Journal: Molecular Therapy (2016)

Background: Adoptive immunotherapy using virus-specific cytotoxic T-lymphocyte (VST) products has been successful in restoring antiviral immunity after hematopoietic stem cell transplantation (HSCT). VST may be produced from a stem cell donor in 10-14 days using current rapid protocols, or banked, partially-HLA matched VST may be used as an "off the shelf" treatment. Objective: To evaluate the clinical efficacy of HSCT donor-derived VST and third-party VST for prevention or treatment of CMV, EBV, and adenovirus following HSCT. Design/Methods: VST were cultured from HSCT or third-party donors using a GMP-compliant rapid-manufacture protocol. VST were tested for specificity and non-alloreactivity via IFN-γ ELISpot and cytotoxicity assays. Patients were monitored for 45 days following infusion for toxicity and for up to 22 months for immune reconstitution. Results: Nineteen patients received VST on existing protocols, of which 15 products were derived from HSCT donors, and 6 were from partially matched, third-party donors. Sixteen patients were treated for CMV (N=11), EBV (N=5), and/or adenovirus infections(n=3), of which fourteen (88%) had partial or complete antiviral responses. Immune reconstitution against targeted viruses was seen using IFN-g ELISpot at a median time of 28 days following infusion. Three patients developed grade I-II GVHD within 45 days of VST infusion, all of which was treatment responsive. Sixteen of the 19 patients remain alive and free of active viral infection up to 22 months post-VST infusion. Conclusions: VST are effective for the restoration of antiviral following HSCT. Expansion of targeted viruses may further extend the utility of this therapy.
FoxO Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress.
Authors: Zuzana Tothova, Ramya Kollipara, Brian J. Huntly, Benjamin H. Lee, Diego H. Castrillon, Emmanuelle A. Passegue, Dana E. Cullen, Elizabeth P. McDowell, Suzan Lazo-Kallanian, Ifor R. Williams, Ronald A. DePinho, D. Gary Gilliland
Journal: Blood (2006)
Abstract 1055: Genome-wide DNA methylation analysis in precancerous conditions associated with hepatitis B virus and hepatitis C virus infection
Authors: Eri Arai, Ying Tian, Masahiro Gotoh, Yoriko Takahashi, Hidenori Ojima, Tomoo Kosuge, Yae Kanai
Journal: Cancer Research (2015)

Abstract The aim of this study is to reveal the significance of DNA methylation alterations in precancerous conditions associated with hepatitis virus infection. Genome-wide DNA methylation analysis using Infinium HumanMethylation450 BeadChip (Illumina) has been performed in 36 specimens of normal liver tissue obtained from patients without hepatocellular carcinomas (HCCs), 12 and 24 specimens of noncancerous liver tissues obtained from hepatitis B virus (HBV) infection-positive and hepatitis C virus (HCV) infection-positive patients with HCCs, respectively, and 24 samples of HCC themselves. On 21,106 CpG sites, alterations of DNA methylation levels were already evident in tissue specimens showing chronic hepatitis and liver cirrhosis, which are considered to be precancerous conditions, compared to normal liver tissues, and were inherited by HCC themselves. Unsupervised hierarchical clustering analysis based on DNA methylation levels at the 21,106CpG sites appropriately classified tissue specimens into normal, precancerous and cancerous clusters, indicating that DNA methylation alterations may participate continuously in hepatocarcinogenesis from the precancerous stage until cancers have become established. The incidence of DNA methylation alterations was higher at the precancerous stage of HCV-positive patients than that of HBV-positive patients. The incidence of DNA methylation alterations that actually occurred at the chronic hepatitis and liver cirrhosis stages but were restored in HCC themselves, which may be associated with inflammation or fibrosis, but may not participate in carcinogenesis itself, was at the almost equal levels regardless of probe annotations or hepatitis viruses. Many Infinium probes showing DNA methylation alterations participating continuously in multistage hepatocarcinogenesis were shared between HBV-positive and HCV-positive patients: only a small number of probes showed HBV-positive patient-specific DNA methylation alterations. On the other hand, DNA hypermethylation on regions around the transcription start sites was especially frequent during carcinogenesis in HCV-positive patients. We now intend to make the carcinogenetic risk estimation based on DNA methylation profiles at the precancerous stage clinically practical using liver biopsy specimens obtained prior to interferon therapy from patients who are followed up because of chronic liver diseases. Citation Format: Eri Arai, Ying Tian, Masahiro Gotoh, Yoriko Takahashi, Hidenori Ojima, Tomoo Kosuge, Yae Kanai. Genome-wide DNA methylation analysis in precancerous conditions associated with hepatitis B virus and hepatitis C virus infection. [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 1055. doi:10.1158/1538-7445.AM2015-1055