tbuckley/cabot-search huggingface dataset:
Abstract 2142: Dietary grape polyphenol resveratrol regulates Rac activity to increase mammary tumor growth and metastasis
Authors: Linette Castillo-Pichardo, Luis A. Cubano, Suranganie Dharmawardhane
Journal: Cancer Research (2012)

Abstract Resveratrol is a natural compound from grapes and peanuts that is structurally similar to estrogen and can act as an estrogenic or antiestrogenic compound, depending on the concentration. In vitro, high concentrations of resveratrol can have proapoptotic, antigrowth, anti-inflammmatory, antiangiogenic, and anti-invasive properties in cancer cells. However, we reported that resveratrol at low, physiologically relevant, concentrations acts similar to estrogen and promotes breast cancer cell migration via actin cytoskeletal changes regulated by Rac; a small GTPase that plays a pivotal role in cancer cell migration/invasion, and thus, metastasis. Herein, we investigated the effects of dietary resveratrol on mammary tumor growth and metastasis in immunocompromised mouse models of cancer metastasis. Interestingly, our findings suggest promotion of mammary tumor growth and metastasis to lung, liver, and kidney by resveratrol in tumors derived from the low metastatic estrogen receptor (ER)α(−), ERα(+) MDA-MB-231 and the highly metastatic ER(-) MDA-MB-435 cancer cell lines. To determine the role of Rac in resveratrol-mediated mammary tumor progression, the activity of Rac was measured in tumors from resveratrol-treated mice. Our results show a significant increase in tumoral Rac activity, consistent with the concentration of resveratrol that induced the highest metastatic efficiency. Taken together, our findings demonstrate a cancer-promoting role for dietary concentrations of resveratrol in metastatic cancer via Rac activation. Therefore, this study illuminates the importance of further delineating resveratrol's concentration dependent molecular mechanisms, particularly in breast cancer, before it can be tested in the clinic or used as a dietary supplement for cancer patients. This study was supported by DoD/BCRP W81XWH-08-1-0258 to LCP, DoD/BCRP W81XWH-07-1-0330 to SD, the UCC Pilot Project Program, and the UCC Postdoctoral Program sponsored by the PR Science, Technology and Research Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Universidad Central del Caribe or the PR Science, Technology and Research Trust. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2142. doi:1538-7445.AM2012-2142
<i>Thorax</i>protocol review: working with trialists to improve trial quality
Authors: Murali Shyamsundar, Alan R Smyth, Daniel F McAuley
Journal: Thorax (2016)

The purpose of clinical trials is to evaluate the safety and efficacy of treatment interventions such as drugs, devices and diagnostic tests.It is therefore essential for the safety of those receiving these interventions, as well as for scientific integrity, that these trials are conducted according to a protocol that is scientifically and ethically sound.The importance of a properly designed trial was recognised in the early years of modern clinical research as demonstrated by the works of Sir Ronald A Fisher in his Principles of experimental design in the 1920s. 1 The first randomised trial in 1946 investigated the effectiveness of streptomycin for TB. 2 Since then, the methodological rigour of clinical trials has continued to improve.Recent notable improvements include the prospective registration of trials (which is now a requirement for research ethics approval in the UK), 3 efforts to improve trial protocols, 4 standardisation of the definitions of interventions 5 and outcomes, 6 as well as improved reporting of clinical trials. 7ore recently, in the setting of evidence that the reporting of clinical trials is not consistent with the trial protocol, the role of full protocol publication is increasingly recognised. 8he process of protocol publication has various benefits including an improvement in the standard of reporting in medical research. 9Thorax is now offering protocol review for authors.
Abstract A57: The novel function of nuclear ErbB-2 in regulating transcription of rRNA genes
Authors: Long-Yuan Li, Hsiuyi Chen, Yi-Hsien Hsieh, Ying-Nai Wang, Hsiao-Ju Chu, Chang-Hai Tsai, Mien-Chie Hung
Journal: Cancer Research (2011)

Abstract Accumulating evidence shows that deregulation of ribosomal RNA (rRNA) synthesis and translation control can facilitate tumorigenesis. The ErbB2 growth factor receptor is overexpressed in many human tumors and has been detected in the nucleus, but the role of nuclear ErbB2 is obscure. Here, we demonstrated a novel function of nuclear ErbB2 in enhancing rRNA gene transcription by RNA polymerase-l (RNA Pol I). Nuclear ErbB2 physically associates with β-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli. RNAi-mediated knockdown of ErbB2 reduced pre-rRNA and protein synthesis. In contrast, wild-type ErbB2 augmented pre-rRNA level, protein production and cell size/cell growth, but not by an ErbB2 mutant which is defective in nuclear translocation. Chromatin immunoprecipitation assays revealed that ErbB2 enhances binding of RNA Pol I to rDNA. Additionally, ErbB2 associated with rDNA, RNA Pol I, and β-actin, suggesting how it could stimulate rRNA production, protein synthesis, and increased cell size and cell growth. Lastly, ErbB2-potentiated RNA Pol I transcription could be stimulated by ligand and was not substantially repressed by inhibition of PI3-K and MEK/ERK, the main ErbB2 effector signaling pathways. Together, our findings indicate that nuclear ErbB2 functions as a regulator of rRNA synthesis and cellular translation, which may contribute to tumor development and progression. This work was supported by National Health Research Institutes NHRI-EX100-9603BC, National Science Council NSC95-2311-B-039-002 and NSC99-3111-B-039-001 and Department of Health DOH99-TD-I-111-TM026 and DOH100-TD-C-111-005 (to LYL), Taiwan. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A57.
Is Dietary Fat a Risk Factor for Prostate Cancer?
Authors: K. J. Pienta, P. S. Esper
Journal: JNCI Journal of the National Cancer Institute (1993)

Is Dietary Fat a Risk Factor for Prostate Cancer?lations (2,[14][15][16], furthermore, have implicated environmental factors such as diet in the development of prostate cancer.These results may explain why latent cancers found at autopsy occur at a similar frequency around the world but the incidence of cancers that manifest themselves clinically is higher in western Europe, the United States, and Canada, where the fat content of the diet is higher than in developing countries.Migrants who move from low-risk areas to the United States, for example, gradually assume the higher risk of the U.S. population (77).
Abstract 1909: Cytoprotective autophagy is involved in resistance towards MET inhibitors in human gastric adenocarcinoma cells
Authors: Magali Humbert, Michaela Medová, Daniel M. Aebersold, Mario P. Tschan, Yitzhak Zimmer
Journal: Cancer Research (2012)

Abstract MET, also known as hepatocyte growth factor receptor, is a receptor tyrosine kinase (RTK) that plays an important role both in normal cellular function as well as in oncogenesis. In many different cancer types, abnormal activation of MET is related to poor prognosis and various strategies to inhibit its function, including small molecule inhibitors, are currently in preclinical and clinical evaluation. Although promising results have been obtained with a variety of different MET RTK inhibitors, different resistance mechanisms were found. We hypothesized that autophagy, a self-digesting recycling mechanism for cellular organelles and macromolecules with cytoprotective functions, might be involved in resistance towards MET inhibitors. Autophagy induced upon MET inhibition might support cancer cell survival. We therefore aimed at investigating the involvement of autophagy upon MET inhibition in GTL-16 gastric adenocarcinoma cells. First, we treated GTL-16 cells with the MET inhibitor PHA665752. We observed a marked induction of autophagy in these cells upon MET inhibition as measured by LC3I/LC3II conversion and GFP-LC3 dot formation. Similar results were seen in another gastric adenocarcinoma cell line, namely MKN-45. Next, to investigate if MET inhibition-mediated induction of autophagy is a protective mechanism, we treated GTL-16 cells with PHA665752 in combination with compounds that influence autophagic activity. Interestingly, a combination treatment of MET and autophagy inhibitors (3-Methyladenine, 3-MA) significantly (MWU, p&amp;lt;0.001) decreased cell viability as determined by an MTT assay. In contrast, using the autophagy activator lithium chloride in combination with MET inhibitors, cell viability was significantly increased (p&amp;lt;0.01). All data were confirmed using a second MET-inhibitor. To exclude that 3-MA autophagy independent functions account for the increased cell death during treatment with PHA665752, we inhibited autophagy by knocking down the key autophagy gene ATG7 in GTL-16 cells using lentiviral vectors expression small hairpin (sh)RNA targeting ATG7. These “autophagy knockdown” GTL-16 cells displayed a significant increase in cell death upon MET inhibition as compared to GTL-16 control cells expressing a scrambled control shRNA. In conclusion, our results point to a cytoprotective function of autophagy in response to MET inhibition. The use of MET in combination with autophagy inhibitors may represent a novel therapeutic option for the treatment of gastric carcinoma with aberrant MET activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1909. doi:1538-7445.AM2012-1909
Abstract 5496: ‘Salan’ titanium(IV) complexes: A new class of anti-cancer agents.
Authors: Ori Braitbard, Sigalit Meker, Maya Stolarov, Jacob Hochman, Edit Tshuva
Journal: Cancer Research (2013)

Abstract Early attempts at using titanium compounds (derivatives of titanocene dichloride and budotitane) as anti-cancer treatment were essentially unsuccessful. The main reason was their rapid hydrolysis in biological media, leading to a variety of unidentified products that hampered the elucidation of mechanistic aspects. Lately, we have introduced a new class of Ti(IV) complexes of salan type diamino bis(phenolato) ligands. These compounds demonstrate substantially enhanced hydrolytic stability, as well as cytotoxic activity towards a variety of cancer cell lines in vitro. The IC50 of different derivatives of these compounds towards murine mammary carcinoma, lymphoma, multi-drug resistant lymphoma, as well as human leukemia, melanoma and pancreatic cancer cell lines, is in the range of 0.6 - 5.7μM, as compared to 70-100μM of the older titanium compounds and to 50-60μM of cisplatin (Manna C.M. et al. ChemMedChem, 7, 703 (2012)). Exposure of murine T-69 and human OVCAR-1 and HT-29 cell lines to one of the salan Ti(IV) compounds resulted in increased levels of p53 and growth arrest in G-1 of the cell cycle implying activation of the apoptotic pathway in response to Ti(IV) complexes.The well-identified and highly stable hydrolysis products of the titanium compounds, which had previously been formulated into nanoparticles to enhance solubility and assist cellular penetration (Meker, S. et al. Angew. Chem. Int. Ed. 51,10515 (2012)), were active both in vitro (IC50 -0.45μM) in murine lymphoma and in vivo (50% tumor growth inhibition) of the same lymphoma cells following their introduction into syngeneic mice. These findings suggest the potential use of solubilized active titanium compound derivatives as a new class of anti-cancer agents. Citation Format: Ori Braitbard, Sigalit Meker, Maya Stolarov, Jacob Hochman, Edit Tshuva. ‘Salan’ titanium(IV) complexes: A new class of anti-cancer agents. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5496. doi:10.1158/1538-7445.AM2013-5496
Abstract 1267: The RING domain of TRAF2 inhibits TNFα-induced cell death independent of NF-κB activation
Authors: Laiqun Zhang, Ken Blackwell, Zhaohui Shi, Hasem Habelhah
Journal: Cancer Research (2010)

Abstract TNFα is a pleiotropic cytokine that activates both the pro-survival IKK/NF-κB and the pro-apoptotic FADD/caspase-8 pathways. TNF receptor associated factor 2 and 5 (TRAF2/5) contain N-terminal RING domains, and TRAF2/5 RING domain-mediated RIP1 ubiquitination is believed to be essential for NF-κB activation and inhibition of cell death in response to TNFα stimulation. In support of this notion, TRAF2/5 double knockout (TRAF2/5 DKO) cells are sensitive to TNFα-induced apoptosis. In addition, the RING domain-deleted TRAF2 (TRAF2-ΔR) has been widely used in the field as a dominant negative to block TNFα-induced JNK and IKK activation in transient overexpression systems. Here, we report that stable expression of TRAF2-ΔR in TRAF2/5 DKO cells at a physiological level completely restores normal TNFα-induced NF-κB activation, but that it neither restores RIP1 polyubiquitination nor inhibits cell death. We also found that the basal and inducible expression of anti-apoptotic proteins in TRAF2-ΔR-expressing cells is normal, yet these cells remain sensitive to TNFα-induced cell death because anti-apoptotic proteins were not recruited to the TNFR1 complex efficiently. This suggests that two events are required for the inhibition of TNFα-induced cell death: i) NF-κB-dependent expression of anti-apoptotic proteins such as cIAP1/2 and cFLIP; and ii) TRAF2 RING domain-dependent retention of cIAP1 in the TNFR1 complex. Ablation of either event leads to caspase-8 activation and cell death in response to TNFα stimulation. Our data also suggest that RIP1 ubiquitination is not essential for TNFα-induced NF-κB activation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1267.
PROJECTED COST OF COMPUTED TOMOGRAPHY-DERIVED FRACTIONAL FLOW RESERVE IN SUSPECTED CORONARY ARTERY DISEASE: EFFECT OF ENHANCED IMAGE QUALITY AND TECHNOLOGY REFINEMENTS
Authors: Michail Papafaklis, Michael Igoumenidis, Kostas Athanasakis, Ioannis Andreou, Lampros Michalis
Journal: Journal of the American College of Cardiology (2015)
P13.01 * GAMMA KNIFE RADIOSURGERY FOR THE MANAGEMENT OF VESTIBULAR SHWANNOMAS IN NEUROFIBROMATOSIS TYPE 2 PATIENTS: TUMOR CONTROL AND HEARING PRESERVATION
Authors: K. Abdel Karim, N. El Mashad, W. Reda, A. El-Shehaby, R. Emad
Journal: Neuro-Oncology (2014)

OBJECTIVE: Gamma knife radiosurgery GKS for the treatment of the patients with Neurofibromatosis type 2 (NFII) is used for many years to achieve better tumor control, and to avoid postoperative neurological deficits. This study aimed at exploring the effect of GKS on the control rate, factors affecting such control, neurological morbidity, and the hearing preservation with such management. METHODS: Between February 2002 and October 2012, seventy-nine patients with vestibular schwannomas associated with NF II were treated by gamma knife radiosurgery at our centre. Fifty-seven patients harbouring 91 tumours were available for follow up for a minimum of 12 months after treatment. The follow up duration ranged from 12 to 126 months (mean 47.8 months). We treated 31 females (54 %) and 26 males (46 %) with a mean age of 26.8 years (range 9-56 years). Twenty one lesions (23.1%) were correlated to a family history of NFII. Seventy-two lesions were bilateral (79.1%). Thirty-six lesions (39.6 %) had previous surgeries, and only three lesions (3.3%) received previous radiotherapy. Before treatment, 45 lesions (49.5%) were associated with serviceable hearing. The mean target volume was 5.26 cc (range 0.1 to 27.5 cc). The mean marginal dose was 11.93 Gy (range 8 to 13 Gy), with a mean isodose of 52.57% (range 40-95%), and mean percent coverage was 94.23% (range 77-100%). RESULTS: Regarding the overall radiological response, 24 lesions (26.4%) had regressed, 57 (62.6%) remained stable, and 10 (11%) had progressed with 89% tumor control. Progression free survival at 3, 5, and 10 years were (99, 91.8, and 42.9 %). Univariate analysis showed that better tumor control correlates with older age, smaller lesion size, and follow up duration. While, preserved hearing correlates with younger age, smaller lesions, hearing grade, and no previous surgery or radiotherapy. The multivariate analysis showed that the tumor control was affected by bilaterality, family history, and selectivity index. Regarding the hearing outcome, it was affected by age and bilaterality. Edema developed in only 4 lesions (4.4%). Three patients complained of facial palsy which was temporary and resolved after medical treatment in less than a year. Using a median dose of 12 Gy maintained serviceable hearing in 27 lesions with a 60% hearing preservation rate. CONCLUSION: Gamma knife radiosurgery for NFII patients is a safe and effective treatment modality that can achieve excellent tumor control with preserved hearing and low risk of neurological morbidity.
Abstract 826: Potential Combination Therapy to Combat Endometrial Cancer
Authors: Takiko Daikoku, Lindsey Jackson, Sudhansu K. Dey
Journal: Cancer Research (2011)

Abstract Endometrial cancer (EMC) is the most common gynecological malignancy causing approximately 7,000 deaths each year in the United States. The underlying causes of EMC are not clearly understood, and treatment options for patients with advanced stages are limited. The gene with the highest frequency of alteration in EMC is Phosphatase and tensin homolog (Pten). The loss of Pten results in increased PI3K activity with enhanced Akt activation. Increased levels of activated Akt (pAkt) stimulate both cyclooxygenase-2 (COX-2) and mammalian targets of rapamycin complex 1 (mTORC1) activity. Although these activities are also heightened in human EMC, it is not clear whether they are the critical players in cancer initiation and progression or whether they work interactively. Animal models that spontaneously develop cancers are powerful tools for studying mechanisms of cancer initiation and progression and for developing treatment strategies. We recently generated an EMC mouse model in which uterine Pten was conditionally deleted by crossing floxed Pten mice with progesterone receptor (PR)-Cre (PRcre/+) mice. All PtenloxP/loxP/PRcre/+ mice developed EMC by one month of age with invasion occurring by 3 months. Tumor phenotypes in these mice mimic many aspects of human EMC. Using this mouse model, we found that uteri of these mice show heightened levels of COX-2 and mTORC1 activities. These observations led us to examine whether inhibiting COX-2 and/or mTORC1 activities reduces the growth of EMC. PtenloxP/loxP/PR+/+ (control) and PtenloxP/loxP/PRcre/+ mice were treated with rapamycin (an inhibitor of mTORC1 signaling) and/or celecoxib (an inhibitor of COX-2 activity) by oral gavages every alternate day starting from 30 days of age for 29 days. We found that although treatment with rapamycin or celecoxib attenuated tumor growth, maximum reduction in tumor growth and progression was noted for PtenloxP/loxP/PRcre/+ females receiving both rapamycin and celecoxib. These results suggest that a combined treatment with celecoxib and rapamycin is an effective therapeutic strategy for combating EMC. This study was supported in parts by grants from NIH-P01-CA-77839 (S.K.D), Concern Foundation (T.D.) and Ohio Cancer Research Associates (T.D.). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 826. doi:10.1158/1538-7445.AM2011-826
“War on drugs” has harmed public health and human rights, finds new analysis
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The global “war on drugs” has damaged public health and human rights and should be refocused towards drug decriminalisation and strengthening of health services, a major new analysis has concluded.

Drug laws designed to protect public health and safety have contributed to “lethal violence, communicable disease transmission, discrimination, forced displacement, unnecessary physical pain, and the undermining of people’s right to health,” said the Johns Hopkins-Lancet Commission on Public Health and International Drug Policy.1

The report argued that decriminalising non-violent minor drug offences and strengthening health and social services would be more effective than current approaches, on the basis of “compelling evidence” from countries …
Abstract 1893: Soy consumption and colorectal cancer risk in humans: a meta-analysis
Authors: Lin Yan, Edward L. Spitznagel, Maarten C. Bosland
Journal: Cancer Research (2010)

Abstract The purpose of the present study was to determine the relationship between soy consumption and colorectal cancer risk in humans by conducting a meta-analysis of available epidemiologic studies. We systematically reviewed publications obtained through a Medline literature search and identified four cohort and seven case-control studies on soy and colorectal cancer risk that met the inclusion criteria. We extracted the risk estimate (hazard ratio, relative risk or odds ratio) of the highest and the lowest reported categories of intake from each study and conducted this analysis using a random-effects model. Our analysis did not find that soy consumption was associated with colorectal cancer risk (combined risk estimate: 0.90, 95% CI: 0.79, 1.03) nor the separate analyses on colon cancer (combined risk estimate: 0.88, 95% CI: 0.74, 1.06) and rectal cancer (combined risk estimate: 0.88, 95% CI: 0.67, 1.14). However, when separately analyzed on the basis of gender, we found soy was associated with an approximately 21% reduction in colorectal cancer risk in women (combined risk estimate: 0.79, 95% CI: 0.65, 0.97; P = 0.026), but not in men (combined risk estimate: 1.10, 95% CI: 0.90, 1.33). Thus, consumption of soy foods may be associated with a reduction in colorectal cancer risk in women, but not in men. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1893.