tbuckley/cabot-search huggingface dataset:
Caffeine consumption and risk of breast cancer in a large prospective cohort of women
Authors: K. Ishitani, J. Lin, J. E. Manson, J. E. Buring, S. M. Zhang
Journal: Journal of Clinical Oncology (2008)

11060 Background: Given the high prevalence of consumption of caffeinated beverages and foods, an association between caffeine intake and risk of breast cancer would be of great public health importance. However, prospective data relating consumption of coffee and other caffeinated beverages and foods to breast cancer risk are limited. We evaluated these associations among women enrolled in a large completed randomized trial of aspirin and vitamin E for chronic disease prevention. Methods: Detailed dietary information was obtained by the food frequency questionnaire at baseline (1992–1995) among 38,453 women who were aged 45 years or older and free of cancer and cardiovascular disease. During an average of 10 years of follow-up, we identified 1188 invasive breast cancer cases. Cox proportional hazards regression models were used to calculate the relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two- sided. Results: Consumption of caffeine was not statistically significantly associated with overall risk of breast cancer. The multivariable RRs of breast cancer were 1.02 (95% CI = 0.84 to 1.23) for caffeine (top vs. bottom quintile. The associations did not differ significantly by menopausal status, postmenopausal hormone use, or body mass index. However, among women with benign breast disease, a significant positive association with breast cancer risk was observed for the highest quintile of caffeine (multivariable RR = 1.32; 95% CI = 1.00 to 1.76) and for the highest category of coffee (≥4 cups/day) (multivariable RR = 1.35; 95% CI = 1.01 to 1.81). In addition, caffeine consumption was significantly positively associated with risk of developing ER-PR- breast cancer (multivariable RR = 1.68; 95% CI = 1.01 to 2.81) and breast tumors of >2 cm in size (multivariable RR = 1.79; 95% CI = 1.18 to 2.73). Conclusions: Data from this large prospective cohort show no overall association between consumption of caffeine and caffeinated beverages and foods and risk of breast cancer. The possibility of an increased risk among women with benign breast disease or for tumors that are ER-PR- or greater than 2 cm in size warrants further study. No significant financial relationships to disclose.
Metformin as firstline treatment for type 2 diabetes: are we sure?
Authors: Rémy Boussageon, François Gueyffier, Catherine Cornu
Journal: BMJ (2016)

Rémy Boussageon, lecturer1, François Gueyffier, professor23, Catherine Cornu, clinical research physician234Department of General Practice, Faculty of Poitiers, 86000 Poitiers, France UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Claude Bernard University. CNRS, Lyon, FranceLouis Pradel Hospital, Lyon University, Lyon, France INSERM Clinical Investigation Centre (CIC1407), Lyon, FranceCorrespondence to: R Boussageon, 11 route du Clos Bardien, 79290 Saint Martin de Sanzay, France remy.boussageon2{at}wanadoo.frAccepted 19 November 2015
Low‐Density Granulocytes Are Increased in Antiphospholipid Syndrome and Are Associated With Anti–β<sub>2</sub>‐Glycoprotein I Antibodies: Comment on the Article by Yalavarthi et al
Authors: L. L. van den Hoogen, R. D. E. Fritsch‐Stork, J. A. G. van Roon, T. R. D. J. Radstake
Journal: Arthritis & Rheumatology (2016)
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Authors: Jianhui Chang, Yingying Wang, Lijian Shao, Remi-Martin Laberge, Marco Demaria, Judith Campisi, Krishnamurthy Janakiraman, Norman E Sharpless, Sheng Ding, Wei Feng, Yi Luo, Xiaoyan Wang, Nukhet Aykin-Burns, Kimberly Krager, Usha Ponnappan, Martin Hauer-Jensen, Aimin Meng, Daohong Zhou
Journal: Nature Medicine (2015)
Treatment with bevacizumab in patients with metastatic colorectal cancer (mCRC).
Authors: Janja Ocvirk, Martina Rebersek, Marko Boc, Maja Ebert Motara, Tanja Mesti
Journal: Journal of Clinical Oncology (2012)

e14083 Background: This study was designed to prospectively evaluate the safety and toxicity of bevacizumab in mCRC patients (pts) with mCRC pts in routine clinical practice as well as selection of pts. Methods: Baseline characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected from 273 mCRC pts who started bevacizumab-containing therapy between January 2008 and August 2010. Results: The data from 273 pts (median age 62) were included in the evaluation. The ECOG performance status (PS) at baseline was 0 in 60%, 1 in 37% and 2 in 3% of pts. Eighty pts (29%) received adjuvant chemotherapy, and 84 (31%) received chemotherapy ± bevacizumab or cetuximab for prior treatment of metastatic disease. Majority of the 273 pts received irinotecan-based chemotherapy (65%). Complete response (CR) was reported in 7%, partial response (PR) in 31% and stable disease (SD) in 36% of the first-line treated pts. In pts previously treated for metastatic disease CR, PR and SD were 6%, 24% and 45%, respectively. In the first-line pts median progression-free survival (PFS) was 10.9 months (95% confidence interval [CI], 9.8 - 12.0), while median overall survival (OS) was 24.3 months (95% CI, 21.4 – 30.3). PFS was 10, 9 and 8.7 months and OS was 16.7, 13.5 and 12.8 months in pts previously treated for metastatic disease with chemotherapy, chemotherapy + cetuximab or chemotherapy + bevacizumab, respectively. Two-year survival rate was 51% in the first-line pts and 32%, 14% and 38% in pts previously treated for metastatic disease with chemotherapy, chemotherapy + cetuximab and chemotherapy + bevacizumab, respectively. Metastasectomy was performed in 39 (15.5%) of the pts. One hundred and nine pts received bevacizumab with subsequent chemotherapy and CR, PR and SD were 1%, 9% and 30%. Overall rates of bevacizumab-related grade 1-2/3-4 adverse events were: proteinuria 38/9 %, hypertension 16/3 %, thromboembolic events 1/5 %, infection 2/3 %, bleeding 2/1 % and fistula 0/1 %. Conclusions: The authors concluded that bevacizumab-containing therapy and use of bevacizumab for long period of time demonstrated efficacy and good tolerability when used as a first-, second- and third-line treatment in routine clinical practice.
Bioflavonoids as poisons of human topoisomerase IIα and β
Authors: Omari Bandele, Neil Osheroff
Journal: Cancer Research (2007)

769   Type II topoisomerases are the primary targets of some of the most successful anticancer drugs used to treat human malignancies. Topoisomerase II removes knots and tangles from the genetic material by creating transient double-stranded breaks in the backbone of DNA. Agents that increase enzyme-mediated DNA cleavage are called topoisomerase II poisons due to their ability to convert topoisomerase II from an essential enzyme to a potent cellular toxin. Many anticancer drugs kill cells by acting as topoisomerase II poisons. Furthermore, naturally occurring topoisomerase II poisons such as bioflavonoids are an integral component of the human diet. Studies suggest that the dietary intake of these compounds provides numerous health benefits to adults, including a reduction in several forms of cancer. Despite the therapeutic effects of bioflavonoids, they also display clastogenic properties. Ingestion of bioflavonoids by pregnant women has been linked to the initiation of specific types of infant leukemias. The mechanistic basis for the physiological actions of these compounds is not known, as they have a variety of effects on human cells. However, it has been suggested that at least some of the cellular effects of bioflavonoids are mediated through their actions on topoisomerase II. While most poisons display activity against topoisomerase IIα and β, the relative contribution of the two isoforms to either the therapeutic or leukemogenic properties of these drugs are not known. Therefore, the present study more fully defines the activity and mechanism of action of bioflavonoids against human topoisomerase IIα and β. Genistein and several other bioflavonoids enhanced DNA cleavage mediated by both enzyme isoforms, however, topoisomerase IIβ was more sensitive to most of the compounds. Consistent with previous reports, bioflavonoids required -OH groups at the 5,7, and 4’ positions for enhanced enzyme-induced DNA scission. Our studies indicate that the 5- and 4’-OH moieties of isoflavones are important because they mediate binding to topoisomerase II. The presence of additional -OH groups on the pendant phenyl ring appear to increase sensitivity of topoisomerase IIβ to these compounds. Protein mutagenesis identified one of the consensus ATP binding sites on topoisomerase IIα as a potential site of interaction of genistein. Although bioflavonoids can undergo redox cycling, they do not alter the DNA cleavage activity of the enzyme through a quinone-based mechanism. Finally, bioflavonoids increased DNA cleavage by topoisomerase IIα and β in cultured human CEM leukemia cells, however, genistein induced significantly less phosphorylation of histone H2AX than did etoposide. These results provide insight into the mechanism of action of bioflavonoids against human type II topoisomerases. This work is supported by NIH grants GM33944 and CA09582.
Polymorphisms in epidermal growth factor (EGF) and proteinase activated receptor 1 (PAR-1) associated with tumor recurrence in localized adenocarcinoma (EA) of the esophagus treated with surgery alone
Authors: G. Lurje, J. M. Leers, A. Pohl, A. Oezcelik, W. Zhang, D. Yang, J. A. Hagen, S. R. DeMeester, T. R. DeMeester, H. J. Lenz
Journal: Journal of Clinical Oncology (2009)

4564 Background: Tumor angiogenesis is a well-recognized aspect of human cancer biology and is mediated at least in part by EGF and PAR-1, which in turn may impact the process of tumor growth and progression. Systemic tumor recurrence after curative resection continues to be a significant problem in the management of patients with localized EA. Further, it is being increasingly recognized that esophageal squamous cell carcinoma and EA are separate and distinct disease groups and need to be considered individually. We therefore designed a large retrospective study of EA patients to identify novel molecular markers of prognosis to better define tumor stage and progression, and help to define novel targets, as well as surrogate-endpoints of disease progression and response to therapy. Methods: Between 1992 and 2005 normal esophageal tissue samples from 239 patients with localized EA treated with surgery alone were obtained at University of Southern California medical facilities. The median follow-up was 3.2 years. 114 out of 239 (48%) patients had tumor recurrence, with a probability of 5-year recurrence of 0.62 ± 0.04. DNA was isolated from formalin-fixed paraffin-embedded specimens and 10 angiogenesis related and functional gene polymorphisms were analyzed using a PCR-RFLP and 5´-end [γ-33P] ATP-labeled PCR method. Results: PAR-1 -506 ins/del (p-value=0.003; log-rank test) and EGF +61 A&gt;G (p-value=0.034; log-rank test) are adverse prognostic markers in univariate analysis. After adjusting for covariates (gender, T1-, N-category, type of surgery) in the multivariable model, "high-expression" variants of PAR-1 (any insertion allele) (RR: 1.81; adjusted p-value = 0.011) and EGF (A/A) (RR: 1; adjusted p-value=0.035) remained significantly associated with time to recurrence, compared to other genotype combinations of PAR-1 (RR: 1) and EGF (RR: 0.65). Conclusions: This study supports the role of functional EGF and PAR-1 polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence. Prospective and biomarker-embedded clinical trials are needed to validate our findings. [Table: see text]
Abstract 19280: Computational Fluid Dynamics Predicts Correlations between Transluminal Contrast and Pressure Gradients in Models of Stenosed Arteries
Authors: Albert C Lardo, Jung H Seo, Parastou Eslami, Rajat Mittal
Journal: Circulation (2012)

Background: Recent computed tomography coronary angiography (CTCA) studies have noted the presence of transluminal contrast gradients (TCG) in stenosed arteries but the mechanism and significance of TCG is unknown. Objective: Use computational fluid dynamics (CFD) modeling to determine mechanisms of contrast dispersion and correlate TCG to transstenotic pressure gradient (TPG) in models of stenosed coronary arteries. Methods: Simulations of flow and contrast dispersion in simple 2-dimensional models of coronary stenosis were carried out. Models with symmetric and asymmetric stenosis of varying severities (25%-75%) were employed. Key parameters including Reynolds and Womersley numbers were also varied. Simulations predict the variations of flow, pressure and contrast concentration in arterial models. Data from the simulations was analyzed to generate correlations between and contrast dispersion patterns and TPG with increasing stenosis severity. For extracting transluminal correlations, pressure and contrast concentration are averaged across the cross-section of the lumen and the contrast gradient is normalized by the maximum concentration at the inlet of the model. Results: Simulations predict the variations of flow, pressure and contrast concentration in arterial models (see figure). The data shows a direct but nonlinear correlation between TCG and TPG. A comparison of contrast dispersion in symmetric and one-sided stenoses also indicates that the correlation between TCG and TPG is sensitive to lesion geometry; the TCG for a symmetric lesion correlates to a higher TPG than a one-sided lesion. Conclusions: The current result is the first direct evidence that TCG may encode for vessel hemodynamics and that lesion geometry also modulates this relationship. CFD modeling provides data for determining important mechanistic insights into TCG and may be used to “decode” flow resistance from CTCA exams.
c-myc enhances the cytotoxicity of small molecule activators of p53
Authors: Mark Wade, Geoffrey M. Wahl
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2805 

Historically, cancer treatments have employed agents that act in relatively non-specific ways to reduce tumor size and burden. However, the non-specificity often leads to toxicity in normal tissues, which can have serious side effects in patients undergoing treatment. Many human cancers bear discrete molecular hallmarks that provide information regarding their etiology and may also present a target for chemotherapeutic intervention. The understanding of genetic and biochemical alterations leading to carcinogenesis allows rational design of drugs with maximal efficacy in tumors and minimal side effects in normal cells. Knowledge of tumor genotype may allow individuals to be treated with specifically tailored chemotherapeutics. The c-myc oncogene is implicated in the initiation or progression of over one third of human cancers. Activation of c-myc can induce proliferation or apoptosis in a context-dependent setting; consequently, cells defective for the activation of apoptosis are selected for during c-myc-induced tumorigenesis. The tumor suppressor p53, an inducer of apoptosis and cell cycle arrest, is a critical block to c-myc-induced tumorigenesis in many mouse models. This is supported by data showing that p53, or its positive regulator p19Arf, are mutated or deleted respectively in murine tumors that overexpress c-myc. The p53 pathway can also be attenuated without genetic alterations in arf or p53 itself, due to overexpression of the p53 negative regulator, mdm2. Arf loss or mdm2 overexpression are also observed in human cancers that retain wild type p53. These same tumors often express high levels of c-myc. The ability to re-activate the tumor suppressor function of wild type p53 in such tumors could improve current cancer treatments and lead to development of novel chemotherapeutic agents. Activation of myc can lead to increased p53 activity via enhanced p53 mRNA transcription, or by upregulation of arf and subsequent inhibition of mdm2. We investigated the stabilization of p53 and its transcriptional activity following activation of c-myc in human fibroblasts. Our principal findings are that stabilization of p53 by c-myc does not require induction of DNA damage, upregulation of p14Arf, p53 mRNA transcription or relocalization of mdm2 as previously suggested. We also find that p53 transcriptional activation following treatment with the chemotherapeutic drug actinomycinD (ActD) is enhanced in cells with activated c-myc. Furthermore, the ability of the small molecule inhibitor of mdm2, Nutlin, to stimulate p53 transcriptional activation is also enhanced by c-myc. The co-operation between c-myc and both ActD and Nutlin leads to enhanced cytotoxicity in fibroblasts that did not require p14Arf. Together these data suggest that reactivation of the p53 pathway may be particularly effective in tumors that overexpress c-myc.
Genotyping single-nucleotide polymorphisms (SNPs) in ERCC1 and XRCC3 genes for efficacy prediction in chemotherapy of non-small cell lung cancer (NSCLC)
Authors: C. Zhou, S. Ren, S. Zhou, L. Zhang, Z. Zhang, Q. Deng, J. Zhang
Journal: Journal of Clinical Oncology (2008)

8098 Background: SNPs of DNA repair genes are found to be predictors to efficacy of chemotherapy in NSCLC. The aim of this study was to investigate the relationship between SNPs of ERCC1 and XRCC3 with the efficacy to first-line chemotherapy. Methods: Chemo-naive NSCLC patients who were treated with various regimens for 4 cycles or up to disease progressionwere were enrolled from Dec.1 2006 to May 31 2007. SNPs were screened in DNA isolated from peripheral blood with the help of real- time PCR by TaqMan probes. The screened SNPs were ERCC1 Asn118Asn (C/T) and XRCC3 Thr241Met (C/T). Results: 130 patients were enrolled in this study, including M/F: 57/43%, stage IIIb/IV: 34/66%; Adeno/Squa/other Ca.: 58/22/20%; ECOG PS 0–1/2: 77/23%, Chemotherapy regimens: Gemcitabine/cisplatin vs vinorelbine/cisplatin vs paclitaxel/cisplatin: 34.6 vs 33.8 vs 23.8% with median age of 61years old. Overall response rate was 17.7%, stable disease 64.6% and disease progression 17.7%. Response and disease progression rate in ERCC1 T/T or C/T genotype patients were 12% and 22%, and in C/C were 21% and 15%(P=0.309), while in XRCC3 T/T or C/T genotyping patients were 15.8% and 5.2%, and in C/C were 18.0% and 19.8%(p=0.193) respectively. 83 patients were alive at the last followed-up date of Nov 30, 2007, with overall one year survival rate of 51.5%, 54% in ERCC1 T/T(5/13) or C/T(22/37) and 50% in C/T patients; 68% in XRCC3 T/T or T/C (13/19) and 39.6% in C/C patients. Survival data is not available now and will be presented at the conference. Side effects were non-special and acceptable. Conclusions: SNPs of ERCC1 and XRCC3 might have some roles in the efficacy of first-line chemotherapy in NSCLC. Preliminary survival results showed the SNP of XRCC3 might be a strong predictor to the survival of NSCLC treated by cisplatin-based chemotherapy. No significant financial relationships to disclose.
Erythroblastic Synartesis: An Auto-immune Dyserythropoiesis
Authors: Elisabeth M. Cramer, Isabel Garcia, Jean-Marc Massé, Jean-Marc Zini, Patrick Lambin, Eric Oksenhendler, Fadila Souni, Mark Smith, Georges Flandrin, Janine Breton-Gorius, Gérard Tobelem, Nicole Casadevall
Journal: Blood (1999)
Induction of Tumors in the Liver of Hamsters by an Avian Adenovirus (CELO)2
Authors: Wayne A. Stenback, Jeffrey P. Andersen, Kenneth J. McCormick, John J. Trentin
Journal: JNCI Journal of the National Cancer Institute (1973)

The oncogenic activity of CELO virus, an avian adenovirus, was tested in randombred or LSH/LAK inbred hamsters inoculated as newborns. Approximately 50% of the animals developed tumors, usually at the site of injection. The randombred hamsters appeared to be slightly more susceptible to tumor formation. Injection by the subcutaneous (sc) route el icited more tumors than did injection by the intraperitoneal (ip) or intracerebral (ic) routes. In approximately 4% of the animals, remote tumors of the liver were found. These liver tumors were classified as hepatocellular carcinomas or hepatomas (in 4 inbred hamsters; in 1 randombred),adenocarcinomas (in 5 randombred), and sarcomas (in 2 inbred). They developed in animals whether inoculated ip, sc, or ic. No local tumors were found in these animals. Electron microscopic examination revealed a preponderance of cytoplasmic type A virus particles, especially in the hepatocellular carcinomas of inbred animals, and sporadic occurrence of budding type C and "spoked" hamster virus particles. All liver tumors tested (except the 2 sarcomas) induced antibodies to CELO T antigen.
Removal of Neoplasms of the Urinary Bladder
Authors: Edwin Beer
Journal: JAMA (1983)

This brief preliminary report is written with the object of calling the attention of the profession to a new and simple method of destroying new growths of the urinary bladder. Even though my experience is not extensive, limited as it is to two large papillary growths, still the observations made leave no doubt in my mind that the Oudin current, employed as I have employed it, will prove effective in the cure of benign papillomata, as well as useful in malign tumors, papillomatous or not, both as a hemostatic and as a cauterizing agent.<sup>1</sup>My experiences also suggest the usefulness of these currents in many other conditions both in the bladder and in other parts, e. g. tuberculous ulcers of the bladder, prostatic hypertrophy, growths in the urethra, etc. In March, 1908, I hit on the idea of using the high-frequency current as I now use it. Expert electric
After Surgery for Breast Cancer: Which Mode of Surveillance?
Authors: J J T Tate, P C Clifford, G T Royle, R B Buchanan, I Taylor
Journal: Journal of the Royal Society of Medicine (1989)

Five hundred and ten women attending a specialized breast clinic for follow-up after surgery of early breast cancer (Stage I and II) have been studied. Recurrence was found most often (58%) in symptomatic women who returned to the clinic earlier than planned. Only 3% of asymptomatic patients had recurrent disease. It is concluded that counselling in symptoms of recurrent breast cancer would allow more efficient follow-up.