tbuckley/cabot-search huggingface dataset:
Abstract 5728: The synergistic effect of Cucurbitacin B and radiation treatment
Authors: Mei Zhang, Liangjie Yin, Shanmin Yang, Jinsheng Hong, Chun Chen, Deping Han, Yanqiang Hou, Bingrong Zhang, Luqiang Huang, Amy Zhang, Sadasivan Vidyasagar, Paul Okunieff, Lurong Zhang
Journal: Cancer Research (2012)

Abstract Cucurbitacin B (CB), a small molecule purified from Trichosanthes kirilowii Maximowicz, possesses a potent antitumor effect. In this study, we investigated the combined effect of CB and ionizing radiation (IR) on aggressive 4T1 breast cancer cells. In a clonogenic assay, different doses of CB (0, 1.7, or 5 nM) and IR (0, 2, 4, or 6 Gy) were applied to 4T1 cells either in a single regimen or in combination. The surviving fraction at 2 Gy was greatly reduced with the increased doses of CB. The results calculated with CompuSyn program indicated that the combination index (CI) was &amp;lt;1 and the dose reducing index (DRI) was &amp;gt;1, suggesting that the combination of CB and IR has a synergistic effect against cancer cells. Our studies of the underlying mechanism revealed that: 1) CB enhanced IR-induced loss of mitochondria potential, as evidenced by a 10-20% increase in the transition of aggregative JC-1 (representing healthy cells) into monomeric JC-1 (representing early apoptotic cells); 2) cell-cycle analysis revealed that although samples treated with CB or 3 Gy alone had 38% or 29% of cells, respectively, in the G2-M phase as compared to 23% of the vehicle control, the combined treatment encouraged 51% of cells to accumulate in the G2-M phase; and 3) the Western blot assay indicated that survival-related molecules (e.g., phosphorylated Stat 3, c-Myc, Bcl-2, and Bcl-xL) were downregulated, while apoptosis-related molecules (e.g., caspase-9, p21, and p53) were upregulated in the combined treatment group. The data reveal that the systemic administration of CB will not only stop the spread of micrometastases but also enhance local tumor control, which will result in better treatment outcomes. The clinical value of CB should be further explored. 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 5728. doi:1538-7445.AM2012-5728
NEW TRANSCATHETER TREATMENT OF THE DILATED ISCHEMIC CARDIOMYOPATHY WITH REVIVENT SYSTEM
Authors: Salvatore Brugaletta, Manel Castella, Marco Hernandez-Enriquez, Horst Sievert, Petr Neuzil, Giedrius Davidavicius, Claudio Muneretto, Louis Labrousse, Jose Luis Pomar, Manel Sabate, Montserrat Gutierrez
Journal: Journal of the American College of Cardiology (2016)
Abstract P4-08-03: False Positive HER-2 Testing by Fluorescence In Situ Hybridization in Human Breast Cancer
Authors: B Ramsey, A Hanlon Newell, M Troxell, S Olson, E Keenan, S-W. Luoh
Journal: Cancer Research (2010)

Abstract Background: Testing for human epidermal growth factor receptor-2 (HER-2) is routinely performed after breast cancer diagnosis by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). FISH is more accurate and reproducible, often considered the gold standard, and a more reliable predictor of a patient's response to HER-2 directed therapies in clinical practice. The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule located in close proximity to HER-2 on chromo some 17q11-12 and has been shown to be an independent adverse prognostic marker in breast cancer. Methods: We performed western blotting analysis of protein extracts from 563 annotated frozen breast tumors, collected from 1988 - 1998. GRB7 and HER-2 bands were assigned low or high values compared to specific protein controls, and tubulin bands. HER-2 FISH was performed on a subset of these tumors using an FDA approved Path Vysion kit on 4 μm frozen sections. HER-2 and chromosome 17 centromere (CEP17) signals were enumerated according to ASCO/CAP guidelines. Results: Sixty-six tumors (11.5%) over-expressed HER-2 and GRB7 proteins by Western analysis, 66 (11.5%) over-expressed HER-2 but not GRB7, and 30 (5.5%) over-expressed GRB7 but not HER-2. All 32 tumors (32/32) submitted to FISH analysis that over-expressed both HER-2 and GRB7 proteins demonstrated HER-2 gene amplification, while only one out of thirty-five (1/35) tumors that over-expressed HER-2 without GRB7 protein over-expression were HER-2 amplified. Interestingly, 7 of 28 tumors over-expressing GRB7 but not HER-2 protein were amplified for the HER-2 gene. Clinical laboratory HER-2 IHC testing confirmed the absence of HER-2 protein over-expression in all 7 of these tumors. Conclusions: Our study demonstrates that about ten percent of human breast cancers that test positive with FISH for HER-2 gene amplification do not over-express HER-2 protein, which may influence sensitivity to HER-2 directed therapy. All tumors that show false positive HER-2 gene amplification over-express GRB7 protein, suggesting the presence of GRB7 driven gene amplification in these tumors. Given that the HER-2 FISH probe contains GRB7 sequences, it is possible that HER-2 FISH false positivity may reflect GRB7 gene amplification. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-03.
Spanish abortion reform faces opposition
Authors: J. Webster
Journal: BMJ (1995)

Spain's minority socialist government will face strong opposition when it introduces a bill reforming the current abortion law which only permits abortion now in exceptional ethical, therapeutic, or genetic circumstances. Women would have the right to an abortion in the first 12 weeks of pregnancy, provided that they wait for 3 days after receiving compulsory counseling. The government's normal parliamentary allies have stated that they will vote against the bill. This includes Josep Antoni Duran Lleida, the leader of the Unio Democratica, which has close ties with the Catholic church and is one of the Catalan nationalist parties that holds the balance of power. 12,000 abortions are performed annually in Spain. Doctors who work in the national health system send women who qualify for legal abortions to a specified group of private clinics. However, thousands more abortions are performed illegally in private clinics, some of which advertise in the newspapers. Prosecutions are few. Two doctors in Malaga were condemned, and then pardoned. One of them, Alberto Stolzenburg, received a 6-year sentence and was banned from practicing for a further 6 years in 1993. His lawyer, Carlos Laranager, states that the medical profession is split over the issue. While the profession officially condemns abortion, doctors' unions, who represent physicians in the national health system, support it. When the bill was first introduced a year ago, 40% (versus 27% who did not) of the population wanted a change in the law. It was part of the promised electoral program in 1993; its failure to pass that year made some accuse the prime minister, Felipe Gonzalez, of being in the Catalan nationalists' pocket. The Catholic church is in the background; its members are forbidden to vote for any parties which support abortions.
Coexpression and Synergistic Role of Multiple Atypical Chemokine Binders in Breast Cancer.
Authors: Z. Ou, X. Zeng, J. Li, L. Tang, X. Gu, Z. Shen, Z. Shao
Journal: Cancer Research (2009)

Abstract Background: The expression and role of Duffy antigen receptor for chemokine (DARC), D6 and ChemoCentryx chemokine receptor (CCX-CKR) in breast cancer have already been studied independently in the past several years. However, the relationship and importance of these atypical chemokine binders (ACB) are still unclear. In this large scale clinical study, we invastigated the characteristics of multiple ACB simultaneously. Material and Methods: The protein levels of DARC, D6 and CCX-CKR were analyzed by immunohistochemistry in 517 patients with invasive breast cancer, 29 patients with noninvasive breast cancer. All of these cases come from the Cancer Hospital of Fudan University during 2001-2006, with complete clinicopathological data and follow-up data, including survival information. Results: In the invasive breast cancer patients, triple, double and single positive expression of these ACB were 135 cases (26.1%), 154 cases (29.8%) and 121 cases (23.4%), respectively. On the other hand, 107 cases (20.7%) were complete negative. The triple positive staining was significantly conversely correlated with lymph node metastasis, disease stage, relapse-free survival (RFS) as well as overall survival (OS). DARC, D6, and CCX-CKR were independent factors that influenced lymph node metastasis and their coexpression was favorable prognostic factor for RFS and OS. Discussion: Our results confirmed that DARC, D6, and CCX-CKR play a negative role in breast cancer. Furthermore, their triple or double high coexpression is more favorable for the patients, suggesting that multiple ACB may provide better protection against metastasis and relapse by synergistically regulating chemokine network in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4166.
Retail Drug Prices Found Higher in U.S. Than Abroad
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Retail Drug Prices Found Higher in U.S. Than Abroad Get access Francis X. Mahaney Francis X. Mahaney Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 18, 21 September 1994, Pages 1377–1378, https://doi.org/10.1093/jnci/86.18.1377 Published: 21 September 1994
Abstract 3269: Basal VEGF protein expression in skeletal muscle, adipose tissue and mammary tumors of PyMT mice
Authors: Linda Vona-Davis, Gerald Audet, Sarah McLaughlin, Mark Olfert
Journal: Cancer Research (2012)

Abstract Obesity is associated with the overall risk of certain cancers, including breast cancer. The prevailing view is that metabolic alterations associated with obesity result in the production of excess vascular endothelial growth factor (VEGF) thereby establishing a local and systemic environment that favors the development and progression of breast cancer. We need to understand how VEGF from adipose is integrated with mammary tumor growth and vascular activity to modulate tumor progression. The MMTV-PyMT mouse is a clinically-relevant model for studying breast cancer progression as mammary tumors grow spontaneously over time; however, little is known about the distribution of VEGF between various organs. We sought to compare the basal VEGF protein expression in skeletal muscle, adipose tissue and mammary tumors from MMTV-PyMT mice and compared these levels against background nontransgenic FVB/N mice. Normal expression of VEGF protein was 69.4 ± 2.1 pg/mL in skeletal muscle and 59.0 ± 7.3 pg/mL in adipose tissue of wild-type (FVB background) control mice. The average expression level of VEGF protein in mammary tumors of MMTV-PyMT mice was 61.8 ± 31.3 pg/mL. Adipose tissue of MMTV-PyMT exhibited 324% greater (191.2 ± 37.6 pg/mL, p&amp;lt;0.01) VEGF protein expression compared to adipose tissue of control FVB mice, and 309% greater (p&amp;lt;0.05) VEGF protein compared to tumor VEGF expression. These data imply that stromal expression of VEGF may be a critical determinant regulating the angiogenic phenotype in breast cancer, and further suggests that cross-talk between the stromal environment and tumor is likely to be essential in promoting tumor growth and progression. NIH 5T32-HL090610, AHA 10BGIA3630002, ACS 116837IRG0906101 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 3269. doi:1538-7445.AM2012-3269
Squamous Cell Carcinoma of the Tonsil Incidentally Detected by 18F-Choline PET/CT
Authors: Giorgio Treglia, Luca Ceriani, Jessica Barizzi, Francesco Bertagna, Luca Giovanella
Journal: Clinical Nuclear Medicine (2014)

We report a case of squamous cell carcinoma of the tonsil incidentally detected by F-choline PET/CT. A 55-year-old male patient with a history of prostate cancer underwent F-choline PET/CT for restaging. PET/CT revealed a focal area of increased F-choline uptake corresponding to the left tonsil. No other areas of abnormal F-choline uptake were detected in the rest of the body. Based on these PET/CT findings, the patient underwent clinical examination and biopsy of the left tonsil. Histology demonstrated the presence of a squamous cell carcinoma of the tonsil.
Abstract 3652: HDAC inhibitors activate NF-κB in human leukemia cells through an ATM/NEMO-dependent DNA Damage-related pathway
Authors: Roberto R. Rosato, Sarah S. Kolla, Stefanie K. Hock, Jorge A. Almenara, Peter Atadja, Paul Dent, Steve Grant
Journal: Cancer Research (2010)

Abstract The ability of HDAC inhibitors (HDACIs) to induce sustained activation of NF-κB (p65/RelA) has been attributed to reversible RelA acetylation (Chen et al., Science 293:1653-7, 2001), a phenomenon that diminishes HDACI antineoplastic activity (Dai et al., Mol Cell Biol. 25:5429-44, 2005). However, the process by which HDACIs initially activate NF-κB has yet to be elucidated. To address this question, mechanisms underlying HDAC inhibitor (HDACI)-mediated NF-κB activation were investigated in human myeloid leukemia cells. Exposure of U937 and other leukemia cells to the pan-HDACI LBH-589 induced reactive oxygen species (ROS) and p65/RelA activation, the NF-κB-dependent induction of Mn-SOD2 mRNA and protein accompanied by ROS elimination, and sequential induction of XRCC1 (single strand) followed by γ-H2A. X (double strand) DNA breaks. LBH-589 lethality was significantly attenuated by siRNA knockdown of the chromatin-linked DNA damage protein histone H1.2. U937 IκBα super-repressor cells lacking serine 32 and 36 IκBα phosphorylation sites displayed diminished HDACI-mediated NF-κB activation/Mn-SOD2 induction, accompanied by enhanced ROS accumulation, DNA damage, and apoptosis. In contrast, TRAF2 siRNA knockdown blocked TNFα- but not HDACI-mediated NF-κB activation and lethality. The Mn-SOD2 mimetic TBAP prevented HDACI-induced NF-κB activation and nuclear localization, while dramatically attenuating DNA damage and apoptosis. Notably, LBH-589 exposure activated ATM (on serine 1981) and increased its association with NEMO, events comprising a recently described “inside-out” nuclear NF-κB activation pathway (Wu et al., Science 311:1110-1, 2006). Notably, siRNA NEMO or ATM knockdown blocked HDACI-mediated NF-κB nuclear translocation/activation, diminished MnSOD2 induction, and potentiated oxidative injury, DNA damage and cell death. Similarly, SUMOylation-site mutant NEMO (K277A and/or K309A) cells exposed to LBH-589 displayed diminished association of ATM with NEMO, reduced NEMO and p65/RelA nuclear localization/activation, and MnSOD2 down-regulation. These events were accompanied by increased ROS production, γ-H2A. X formation, and enhanced lethality. Collectively, these findings indicate that in human leukemia cells, HDACIs activate the cytoprotective NF-κB pathway through an ATM/NEMO-dependent process involving the induction of ROS and DNA damage. They also raise the possibility that blocking NF-κB activation via the atypical DNA damage-related ATM/NEMO nuclear pathway has the potential to enhance HDACI antileukemic activity. 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 3652.
Obscure overt gastrointestinal bleeding due to Necator americanus diagnosed by double-balloon enteroscopy
Authors: Bernard Reyes-Leiva, Jose De León, Fernando Castellanos, Edder Sandoval, Iván García-Martínez
Journal: Endoscopy (2015)

A 63-year-old woman from a rural area of Guatemala was referred to our center because of intermittent melena, weight loss of 5 kg, dyspnea, and malaise of 3 months’ duration. In addition, she was experiencing generalized, poorly localized, cramping abdominal pain that was partially relieved with the use of antispasmodics. Her past medical history was significant for hypertension and diabetes mellitus type 2 of 10 years’ duration.
Abstract 4059: Identifying the key domain of CHK1 interaction with MEPE/OF45 and the key ubiquitination site of CHK1
Authors: Guangnan Chen, Dan Yan, Ya Wang
Journal: Cancer Research (2011)

Abstract Background: Previously, we reported that MEPE/OF45 interacting with CHK1 protects CHK1 from degradation and cells from DNA damage-induced killing (Nucleic Acids Res, 37: 7447-7454 2009; Brit J Cancer 102: 862-866, 2010). To further investigate the nature of the CHK1 stabilization and its effects on cell sensitivity to DNA damage inducers, we designed this study to identify the key domain of CHK1 interaction with MEPE/OF45 and the key ubiquitination site of CHK1. Methods: GST-MEPE/OF45 was expressed in E. coli BL 21. HA-wild type CHK1 and various CHK1 truncated mutations were expressed in 293FT. GST pull-down assay was used to identify the key domain of CHK1 interacting with MEPE/OF45. To identify the ubiquitination site of CHK1, GFP-CHK1 with different Lys mutations were co-transfected with Ub-expression vector to 293FT, and 48 hours later, whole cell lysate were prepared, Western blot was carried out using a GFP monoclonal antibody to detect ubiquitinaed CHK1. The CHK1 half-life was used to detect the stabilization of CHK1 and a clonogenic assay was used to detect the sensitivity of cells to DNA damage inducers. Results: The key domain of CHK1 interacting with MEPE/OF45 and the key site of CHK1 ubiquitination were identified. Most importantly, the mutation of CHK1 with the main domain or key site affected CHK1 stabilization and cell sensitivity to DNA damage inducers. Conclusion: The interaction of CHK1 with MEPE/OF45 plays an important role in preventing CHK1 ubiquitination and; therefore, stabilizes CHK1, which further affects cell sensitivity to DNA damage inducers. Because CHK1 is an essential DNA damage response protein, these results provide valuable information for understanding the role of CHK1 in genomic integrity, which could be used for improving cancer treatment. 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 4059. doi:10.1158/1538-7445.AM2011-4059
AI-08 * SUBGROUP-SPECIFIC DEREGULATION OF COAGULATION AND ANGIOGENIC GENE EXPRESSION PROFILES IN MEDULLOBLASTOMA- EVIDENCE FOR CROSS-TALK BETWEEN GROWTH FACTOR AND COAGULATION PATHWAYS
Authors: E. D'Asti, M. Kool, S. Pfister, J. Rak
Journal: Neuro-Oncology (2014)

INTRODUCTION: Pediatric medulloblastoma (MB) is comprised of 4 distinct disease subtypes including WNT, SHH, group 3, and group 4, which co-segregate with specific clinical features and activation of distinct oncogenic pathways. Oncogenes deregulate tumour cell interactions with the vascular system including the expression, activity, and signaling properties of specific coagulation factors and their cellular receptors. The latter are often activated in aggressive cancers and involved in shaping the tumour microenvironment via coupling of coagulant, inflammatory, and angiogenic responses. Key elements of this circuitry include the tissue factor (TF), PAR-1, and PAR-2 receptors. We studied whether coagulation system effectors are expressed and activated in a manner corresponding to MB subtypes. METHODS: Using R2: microarray analysis and visualization platform, we mined MB datasets for differential expression of coagulation and angiogenesis-related factors between tumour subtypes. Focusing on TF and PAR-1 receptors, we determined whether their expression is correlated with known drivers of growth factor and pro-angiogenic pathways. We evaluated the relevance of these relationships in DAOY MB cells in vitro following SHH and HGF treatment. RESULTS: TF and PAR-1 mRNA expression is upregulated in SHH tumours and correlated with levels of MET receptor. Using DAOY as a model of SHH MB, we documented selective upregulation of PAR-1 mRNA following combined treatment with SHH + HGF. This induced hypersensitivity to a PAR-1 agonist upregulating the expression of the pro-inflammatory and pro-angiogenic factor interleukin-1β. CONCLUSION: Coagulation factors are differentially expressed between MB subtypes, and change the cellular phenotype in a manner dependent on the activation state of key oncogenic pathways. These data suggest a reciprocal interaction between classical oncogenic pathways and coagulation signaling in SHH MB and implicate the coagulation system in tumour progression.
Survival and clinicpathologic characteristics of invasive adenocarcinoma of the uterine cervix
Authors: A. C. Melo, G. H. Advíncula, C. C. Carmo, D. Herchenhorn, P. A. Mora
Journal: Journal of Clinical Oncology (2008)

16559 Background: Carcinoma of the uterine cervix is one of the most common malignancies among women. The relative proportion and absolute incidence of cervical adenocarcinoma (AC) compared with squamous cell carcinoma (SCC) has increased; in the 1950s 5% of all cervical carcinomas were adenocarcinoma, in the 1990s this proportion increased to 25%. It remains controversial whether or not patients with adenocarcinoma have a worse prognosis; questions remain about whether cervical adenocarcinoma metastasizes earlier or is detected later by the cervical Papanicolaou test, or whether a poorer response to radiotherapy or the inclusion of special subtypes (such as clear cell carcinoma, which is known for its dismal prognosis) could account for an apparent poorer prognosis. Methods: This retrospective study was done in the Clinical Oncology Department of the Brazilian National Cancer Institute with 278 cases of primary AC of the uterine cervix diagnosed between 2002 and 2004. Clinical and pathological data were reviewed; survival was analyzed according to the Kaplan- Meier method. Results: Median age at presentation was 48 years; 50,4% of the patients were married and 66,9% were white. On histologic evaluation pure adenocarcinoma was found in 80,9% of the cases (n = 225), adenosquamous carcinoma in 14,4% (n = 40), clear cell carcinoma in 2,9% (n = 8) and other variants in 1,8% (n = 5). At diagnosis anemia was found in 29,5% of the patients, but 61,5% had metrorrhagia; 6,8% had hydronephrosis and 7,6% had high creatinine levels. Using FIGO stage 38,8% were stage I, 38,8% stage II, 17,9% stage III and 4,5% stage IV. Surgical treatment was used in 93 cases, radiochemotherapy combination in 69 cases and brachitherapy 129 cases. The median survival time was 34,9 months; 1-year, 3-year and 5-year overall survival rates were 81,2%; 67,2% and 54% respectively. The median survival time for the FIGO stage I, II, III and IV was 38,1; 35,4; 18,5 and 3,6 months. Conclusions: Adenocarcinomas are becoming more common, this report shows a similar survival to that found in previous reports and demonstrates a high rate of early FIGO stages. No significant financial relationships to disclose.
O115 PEGINTERFERON LAMBDA FOR THE TREATMENT OF CHRONIC HEPATITIS B (CHB): A PHASE 2B COMPARISON WITH PEGINTERFERON ALFA IN PATIENTS WITH HBeAg-POSITIVE DISEASE
Authors: H.L. Chan, S.H. Ahn, T.-T. Chang, C.-Y. Peng, D. Wong, C.S. Coffin, S.G. Lim, P.-J. Chen, H.L. Janssen, P. Marcellin, L. Serfaty, S. Zeuzem, D. Cohen, L. Critelli, D. Xu, E. Cooney
Journal: Journal of Hepatology (2014)