tbuckley/cabot-search huggingface dataset:
Breast cancer molecular profiles and tumor response of neoadjuvant doxorubicin and paclitaxel: The I-SPY TRIAL (CALGB 150007/150012, ACRIN 6657)
Authors: L. J. Esserman, C. Perou, M. Cheang, A. DeMichele, L. Carey, L. J. van 't Veer, J. Gray, E. Petricoin, K. Conway, D. Berry
Journal: Journal of Clinical Oncology (2009)

LBA515 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
Vascular Smooth Muscle Cells in Atherosclerosis
Authors: Martin R. Bennett, Sanjay Sinha, Gary K. Owens
Journal: Circulation Research (2016)

The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis.
Antitumor Immunity. II. Viability, Tumorigenicity, and Immunogenicity of Neuraminidase-Treated Tumor Cells: Effective Immunization of Animals With a Tumor Vaccine 2
Authors: P. K. Ray, V. S. Thakur, K. Sundaram
Journal: JNCI Journal of the National Cancer Institute (1976)

A dimethylbenzdithionaphthene (DBDN)-induced fibrosarcoma showed reduced transplantability if previously treated with Vibrio cholerae neuraminidase (VCN). However, the reduced transplantability of VCN-treated tumor cells was not associated with any loss of their viability or tumorigenic capability, but appeared to be due to their increase in immunogenicity. High doses of VCN-treated tumor cells could grow even in normal individuals. Lower doses, which did not induce tumor development in normal individuals, did so if injected into immunosuppressed animals. Although X-irradiation of VCN-treated tumor cells reduced their tumorigenic potential, it did not impair their increased immunogenic properties. Thus a suitable method for the preparation of a "tumor vaccine" was provided. The immunization of animals with the vaccine and a working hypothesis regarding its mechanism of action were described.
Prospective study of wide local excision and endocrine therapy WithOut RadioTHerapy (WORTH) for node-negative, estrogen receptor-positive early breast cancer with negative histologic margins (WORTH trial, Protocol 1): Three-year interim results
Authors: S. Ohsumi, H. Inaji, Y. Ohashi, K. Suemasu, R. Nishimura, N. Masuda, S. Akashi-Tanaka, S. Murakami, T. Ikeda, T. Nishi
Journal: Journal of Clinical Oncology (2008)

615 Background: Although numerous clinical trials have been attempted to categorize breast cancer (BC) subgroups where radiotherapy (RT) to the breast can be abbreviated after breast-conserving surgery (BCS), none have yet realized such subgroups, except for CALGB 9343. However, based on analysis of at 5-mm intervals of the surgical materials in patients (Pts) with complete removal of histologic margins, a Japanese institution has found approximately 1 % annual local recurrence (LR) rate without RT in histologically defined tumor-free tissues 5 mm from the histologic margins. We have conducted a trial to confirm the guidelines of the 5-mm policy in breast conservation without RT using an entry criterion with more stringent screening factors. Methods: We started a prospective trial in Oct. 2002, in which we enrolled the BC Pts after BCS who fulfilled all the following 7 criteria from 13 hospitals, and treated them with tamoxifen or anastrozole alone for 5 years: 1) tumor size of 3 cm or less by palpation; 2) node-negative pathology; 3) without any preoperative treatment; 4) age at operation of 50 years or older and postmenopausal; 5) excised surgical materials were sliced at 5-mm intervals with all slices showing 5-mm tumor free tissues from the margins; 6) histologically without lymphovascular involvement (LI); and 7) with ER-positive tumors. We planned to enroll 120 Pts. The sequential probability ratio test was applied to monitor the annual LR rate would not exceed 1 %. Results: A total of 123 Pts were enrolled in the study, and entry was closed in March 2005. The median age, tumor size (by palpation) and follow-up period were 64 years (range: 51–84), 1.5 cm (range: 0–30) and 36 months (range: 13–58), respectively. Three Pts (0.8 events/100 person-years; 95% CI, 0.26 to 2.51) had LR, and another Pt had distant metastasis. All Pts are alive. Conclusions: Postoperative RT to the breast could be abbreviated in node negative postmenopausal women of 50 years or older with a small (3 cm or less) ER-positive BC showing no LI who had BCS where the surgical materials fulfilled the 5-mm criteria in case where hormone therapy was administered. No significant financial relationships to disclose.
Relationship of germline polymorphisms to docetaxel toxicity in the ROSE/TRIO-012 trial.
Authors: Sambasivarao Damaraju, Vera Gorbunova, Karen A. Gelmon, Jose Angel Garcia Saenz, Serafin Morales, Dany Youssef Abigerges, Jean-Luc Canon, Igor Lifirenko, Graham Lawrence Cohen, Guy Heinrich Maria Jerusalem, Francois Thireau, Rodrigo Fresco, Vincent Houé, Michael F. Press, Ashok Narasimhan, John Robert Mackey
Journal: Journal of Clinical Oncology (2015)

540 Background: TRIO-012 is a double blinded, multinational trial that randomized 1,144 patients with advanced breast cancer to receive first-line docetaxel (Doc) in combination with ramucirumab or placebo. Our objective is to address genetic predisposition to Doc toxicity. In this independent validation study, we selected single nucleotide polymorphisms (SNPs) previously associated with taxane-induced adverse events (AEs; fatigue, myalgia, peripheral neuropathy), including CYP3A5*3 reported by our group to be strongly associated with Doc toxicity. Methods: Germline SNPs were studied in participants who gave prospective consent for peripheral blood DNA genotyping. All subjects received Doc until unacceptable toxicity or progressive disease. From these, 399 subjects predominantly of Caucasian origin were analysed here. Toxicity grades 0-1 (controls; low toxicity) vs. grade > 2 (cases, high toxicity) were compared. Dominant genotypic model was assumed; Chi-square test with 10000 permutations were employed using SVS v8.3 and p < 0.05 considered statistically significant. Results: Each reported variant conferred risk. CYP3A5*3 allele (rs776746; OR 2.16 [1.18-3.96]), TNF-alpha (rs1800629), NAV1 (rs478472), NOS3 (rs1799983) were associated with fatigue. SNPs associated with myalgia were FACND2 (rs7637888), HIF1-alpha (rs11549465) and NDRG1 (rs2233335). XKR4 (rs4737264) showed association with peripheral neuropathy. SNPs in ABCC2, SLCO1B3 and VEGF-R1 genes showed associations with all three individual AEs tested. In a combined analysis of all the AEs, CYP3A5*3 allele retained significance (OR 1.9 [1.08-3.37]; as did IL1-beta (rs16944) and CYP2C8 (rs11572080). Conclusions: We confirm our previous finding that CYP3A5*3 genotype determines toxicity by its influence on Doc metabolism (EurJCancer 8(7),175,2010). NDRG1, FACND2 and XKR4, SNPs previously associated with paclitaxel-induced neuropathy, were now associated with Doc-induced myalgia or neuropathy. In conclusion, we report a subset of variants analysed conferring genetic predisposition to both paclitaxel and Doc AEs. The pleotropic drug effects on multiple genes/pathways appear to contribute to the overall phenotype of taxane toxicity.
Long-term Survival of Hospitalized Patients with a Heart Failure Discharge Code: Early Experience of a Community-Based Study
Authors: Joseph Kim, Eyal Shahar, Paul G. McGovern, Cheryl Barber, Sue Duval, Russell V. Luepker
Journal: Circulation (2001)

P47 Survival after hospitalization for heart failure (HF) is poorly described in the community setting, particularly after accounting for the type of admission. We performed an interim analysis (n=3,627) of data gathered from a 50% random sample of patients 35-84 years old who were discharged in 1995 from Twin Cities area hospitals with an ICD9 428 code (HF). Patients were classified by case-type: I (incident case, admitted for HF), II (prevalent case, admitted for HF), III (incident case, developed HF during hospitalization), IV (prevalent case, HF progression during hospitalization), and V (prevalent case, hospitalization unrelated to HF). Follow-up through 1998 was performed using a statewide death certificate registry. The table below shows heterogeneity of short and long-term survival by case-type. Prevalent cases with evidence of HF progression on admission (case-type II) or during hospitalization (case-type IV) had the worst 3-year survival. Patients with evidence of HF progression after an admission that was unrelated to HF (case-types III and IV) had a higher 28-day mortality than those admitted for HF (case-types I and II); however, these differences dissipated after 3 years of follow-up. A hospital-based perspective of the epidemiology of HF should consider the five different case-types behind a HF discharge code. Table 1.
p53-Inducible Micrornas 192 and 215 Regulate p53 Expression and IGF1 Axis in Multiple Myeloma.
Authors: Flavia Pichiorri, Sung-Suk Suh, Luciana De Luca, Cristian Taccioli, Don Benson, Craig Hofmeister, Rami Aqeilan, Carlo M. Croce
Journal: Blood (2009)
Abstract 13598: Prediction of the Development of Atrial Fibrillation in Patients With Chronic Heart Failure by the Combination of Atrial Late Potential and Cardiac I-123 Metaiodobenzylguanidine Imaging
Authors: Takeshi Okada, Takahisa Yamada, Yuji Okuyama, Takashi Morita, Yoshio Furukawa, Koji Tanaka, Yusuke Iwasaki, Hiromichi Ueda, Masato Kawasaki, Yuki Kuramoto, Takashi Naitou, Tadao Fujimoto, Masatake Fukunami
Journal: Circulation (2010)
Do Leukemic Cells and Mesenchymal Stem Cells (MSCs) From AML Patients Share The Same Chromosomal Defect? A Cytogenetics, FISH and aCGH/Snpa Study
Authors: Paolo Bernasconi, Irene Dambruoso, Manuel Gotti, Marina Boni, Rita Zappatore, Celeste Calvello, Claudia del Fante, Gianluca Viarengo, Marilla Cervio, Cesare Perotti
Journal: Blood (2013)
Effect of Hormonal Status on Incidence and Morphology of Hepatomas In Rats Fed &lt;italic&gt;N,N&lt;/italic&gt;-Dimethyl-&lt;italic&gt;p&lt;/italic&gt;-(&lt;italic&gt;m&lt;/italic&gt;-tolylazo)aniline
Authors: A. S. Mulay, R. W. O'Gara
Journal: JNCI Journal of the National Cancer Institute (1962)

Osborne-Mendel rats fed a diet containing N,N-dimethyl-p-(m-tolylazo)aniline developed liver lesions similar to those observed in rats fed N,N-dimethyl-p-phenylazoaniline, N,N-dimethyl-p-(l-naphthylazo)aniline, or N,N -dimethyl -p-(2-naphthylazo)aniline. Liver tumors were found in 58 of 75 animals. Twenty-nine of these tumors appeared to be pure hepatomas and 29 were adenohepatomas. On the basis of histologic study it is suggested that the hepatic tumor induced by N,N-dimethyl-p-(m-tolylazo)amline is a single tumor of mixed morphological appearance and that the tumor probably arises from hepatic cells that undergo dedifferentiation under the influence of the azo dye. Cirrhosis, bileduct proliferation, multilocular cysts, cholangiofibrosis, groups of hepatic cells with vacuolated or basophilic cytoplasm, hyperplastic nodules, hepatomas, and adenohepatomas were found in the livers of some animals in nearly all groups. The relation of these lesions to each other and the influence of sex and sex hormones on their incidence are discussed. Tumor incidence was 100 percent in intact males and 44 percent in intact females. Ovariectomy increased the incidence to 80 percent, and implantation of testosterone pellets in ovariectomized rats restored the incidence of hepatic tumors to the level seen in intact female rats. Orchiectomy did not influence the incidence of hepatic tumors, but the tumors were smaller and fewer than in the intact animal. Implantation of diethylstilbestrol pellets in orchiectomized rats failed to reduce the incidence of hepatic tumors but increased the proportion of hepatomas in comparison with adenohepatomas.
Towards test and treat strategy for HIV in sub-Saharan Africa
Authors: Sabin Nsanzimana, Steve Kanters, Edward Mills
Journal: BMJ (2015)

Antiretroviral treatment for everyone with HIV will help control the epidemic in Africa 

Ending the AIDS epidemic has now become a realistic priority for global health policy makers. The Joint United Nations Programme on HIV/AIDS (UNAIDS) announced that 15 million people are now receiving antiretroviral treatment (ART) and that by 2020, 90% of all people with HIV should know their HIV status, 90% of those diagnosed should have access to antiretroviral treatment, and 90% of people receiving treatment should maintain viral suppression (the 90-90-90 targets).1 CD4 cell thresholds have historically guided initiation of treatment, but results from the HIV Prevention Trials Network 052 Trial,2 the Strategic Timing of Antiretroviral Treatment (START) Study,3 and the TEMPRANO Trial4 provide compelling evidence that the benefits of early initiation outweigh any reasons for delay. This evidence has formed the scientific basis for the 90-90-90 targets.

In October 2015, the World Health Organization (WHO) released new treatment guidelines that advocate starting ART immediately, …
Abstract 18780: Diminished Left Ventricular Myocardial Oxygen Demand During Dobutamine Stress Testing in the Elderly Reduces the Appearance of Inducible Wall Motion Abnormalities Indicative of Ischemia
Authors: Sujethra Vasu, Timothy Morgan, Dalane W Kitzman, Craig A Hamilton, Caroline Chiles, Sandra Soots, Vinay Thohan, W. Gregory Hundley
Journal: Circulation (2013)

Background: It has been observed that dobutamine stress may be less sensitive in the elderly and in those with LVH. We hypothesized that, in the elderly, a reduced increment in myocardial oxygen demand with dobutamine produces false negative results. Methods: We prospectively performed dobutamine cardiovascular magnetic resonance (DCMR) on 276 consecutively recruited individuals aged 55-85 years with risk factors for CAD. Rate pressure product (RPP), assessment of LV wall motion and volumes, aortic pulse wave velocity (PWV a measure of aortic stiffness) and first pass gadolinium enhanced LV perfusion defects (PD) indicative of ischemia were obtained on a 1.5T scanner at rest and after dobutamine infused to achieve 80% of the maximum predicted heart rate. Myocardial oxygen demand was assessed by the systolic pressure volume area (PVA), measured as LV stroke work (SW), [mean arterial pressure * stroke volume] plus potential energy [(1/2*end-systolic pressure) * end-systolic volume]}. All measures were assessed independently by personnel blinded to other data or participant identifiers. Differences were assessed with t-test; p &lt; 0.05 was significant. DCMR PD was considered as the gold standard for the detection of ischemia. Results: Participants averaged 68±8 years, were 80% white, 90% hypertensive, 43% diabetic and 55% men; all achieved target heart rate. With dobutamine, RPP increased 85% and LV end-diastolic volume index decreased. No subject had an inducible WMA without concomitant PD, but 28 had PD without inducible WMA (Table). In these false negatives, PVA was significantly lower (p= 0.03) and LVSW (p = 0.06) and PWV (p= 0.13) had strong trends toward being lower. The sensitivity of DCMR WMA for identifying PD indicative of ischemia was 33%. Conclusion: With dobutamine stress testing, the elderly had declines in LV preload and PVA. These findings provide a novel mechanistic explanation of why the elderly may have false negative wall motion during dobutamine stress.
3D modeling of human cancer: A PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus
Authors: Francesca Del Bufalo, Teresa Manzo, Valentina Hoyos, Shigeki Yagyu, Ignazio Caruana, Jeffrey Jacot, Omar Benavides, Daniel Rosen, Malcolm K. Brenner
Journal: Biomaterials (2016)
Acquired Toxoplasmosis
Authors: J. K. A. Beverley, E. Skipper, S. C. Marshall
Journal: BMJ (1955)

One of us (S. C. M.) recently became infected with Toxoplasma gondii when working in the laboratory.Brief mention was made of this in a recent publication on acquired toxoplasmosis (Skipper et al., 1954) in which two cases of the glandular variety of the disease and one other possible case resembling typhus fever were described.The laboratory infection is now reported because it furnishes yet another example of mild adeno- pathy, with little constitutional disturbance, due to the toxoplasma.Case ReportOn August 31, 1953, S. C. M., for purposes of animal passage, set out to fill a sterile syringe with mouse peritoneal exudate rich in the Rh strain of toxoplasma.As the needle became blocked he removed it, set it aside point uppermost, and fitted a fresh one.Shortly afterwards he pricked his left third finger on the upturned needle.Realizing what he had done, he tried, unsuccessfully, to make the puncture bleed and applied tincture of iodine.Nine days later (September 9) he felt shivery and tired, suffered from headache, and discovered an enlarged painful gland in the left axilla.On September 12 his temperature was 1020 F. (38.9'C.) and the following day he had a rigor.In spite of a 48-hour course of penicillin, prescribed by his family doctor, his fever continued and ranged between 100 and 103.80 F. (37.8 and 39.9' C.).When examined on September 16 he was sweating and looked ill.The skin of his finger was red where it had been .pricked,and two enlarged, tender, discrete glands, each the size of a walnut, were present in the left axilla.Some smaller tender glands were felt in the posterior triangles of the neck.The edge of the liver could be felt, but it was not tender.The blood
The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group.
Authors: N Petrelli, H O Douglass, L Herrera, D Russell, D M Stablein, H W Bruckner, R J Mayer, R Schinella, M D Green, F M Muggia
Journal: Journal of Clinical Oncology (1989)

A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.
Brief Communication: Additional Evidence of Type-C Particles in Human Placentas2
Authors: Mina Lee Vernon, John Milton McMahon, Joseph James Hackett
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Brief Communication: Additional Evidence of Type-C Particles in Human Placentas Get access Mina Lee Vernon, Mina Lee Vernon Search for other works by this author on: Oxford Academic PubMed Google Scholar John Milton McMahon, John Milton McMahon Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph James Hackett Joseph James Hackett 3Microbiological Associates, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 987–989, https://doi.org/10.1093/jnci/52.3.987 Published: 01 March 1974 Article history Received: 23 October 1973 Accepted: 07 November 1973 Published: 01 March 1974
Treatment of advanced bronchoalveolar carcinoma with the Hsp90 inhibitor STA-9090.
Authors: S. Nichols, J. W. Goldman, M. Mulay, I. Laux, S. Riehl, M. Dinolfo, L. S. Rosen
Journal: Journal of Clinical Oncology (2010)

e18137 Background: Treatment options for bronchoalveolar carcinoma (BAC) include conventional chemotherapy and erlotinib in tumors that harbor activating EGFR mutations. The chaperone Hsp90 regulates the folding, stability and activity of many signal transduction proteins important in NSCLC, including EGFR, KRAS, MET and HER2. STA-9090 is a potent, next-generation Hsp90 inhibitor that is structurally unrelated to the first-generation ansamycin class of Hsp90 inhibitors, such as 17-AAG and IPI-504, and has shown superior activity and an improved safety profile relative to these agents in preclinical studies. Methods: We report the case of a 66-year-old white male with metastatic BAC, treated with STA-9090 on a phase I study. Results: The patient was diagnosed with BAC in 2006. Molecular profiling showed wild type KRAS and EGFR, and EGFR was not amplified on FISH testing. Prior treatment included erlotinib, bevacizumab, carboplatin, paclitaxel, pemetrexed, and topotecan with progression of disease on each, and an investigational rexinoid with a three month stabilization of disease. He enrolled in a phase I solid tumor study of STA-9090, and began weekly infusions at 150 mg/m2 for 3 weeks (followed by a rest week). The treatment was well tolerated, with adverse events of mild diarrhea and moderate hypophosphatemia. Target lesions were reduced by 25% after cycle 4 (SD per RECIST), and that response was maintained. The dose of STA-9090 was increased to 180 mg/m2 starting at Cycle 8 and continues to be well-tolerated through Cycle 11. The 11 month treatment duration compares favorably with the average 2-3 month duration of prior regimens. Conclusions: Reduction in tumor size and prolonged stabilization, and a well-tolerated AE profile are encouraging and support the evaluation of STA-9090 in patients with NSCLC, including BAC. A phase II study of STA-9090 in patients with advanced NSCLC is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Synta