tbuckley/cabot-search huggingface dataset:
Pomalidomide–dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial
Authors: S Ailawadhi, J R Mikhael, B R LaPlant, K M Laumann, S Kumar, V Roy, D Dingli, P L Bergsagel, F K Buadi, S V Rajkumar, R Fonseca, M A Gertz, P Kapoor, T Sher, S R Hayman, A K Stewart, A Dispenzieri, R A Kyle, W I Gonsalves, C B Reeder, Y Lin, R S Go, N Leung, T Kourelis, J A Lust, S J Russell, A A Chanan-Khan, M Q Lacy
Journal: Leukemia (2017)
Soyfood intake, ERa gene polymorphisms, and breast cancer risk
Authors: Qi Dai, Qiuyin Cai, Xiao-Ou Shu, Zhixian Ruan, Yu-Tang Gao, Wei Zheng
Journal: Cancer Research (2004)

492   Results from  in vivo  and  in vitro  studies suggest that soyfoods and their constituents may be protective against breast cancer. Analytical epidemiologic studies, however, are inconsistent. Soyfoods are the major sources of isoflavones, a group of phytoestrogens showing both weak estrogenic and antiestrogenic activities. These phytochemicals have been shown to compete with endogenous estrogens for estrogen receptors in many  in vitro  and  in vivo  systems. In this study, we evaluated whether the association of soyfood intake with breast cancer risk may be modified by genetic polymorphisms in the ERa gene. Included in this analysis were 1,069 breast cancer cases and 1,166 age-frequency-matched community controls who were recruited into the Shanghai Breast Cancer Study, had completed interview and donated a blood sample. Participation and blood donation rates were over 90% and 80%, respectively. Genotyping assays were completed for the  Pvu II and  Xba I polymorphisms using PCR-RFLP technique. Overall, soy protein intake was weakly related to breast cancer risk. In the stratified analyses by  Pvu II polymorphism, the risk of breast cancer was reduced with increasing intake of soy protein among women with the  Pvu II PP genotype, with adjusted ORs (95% CI) of 1.00, 0.78 (0.36-1.70), 0.66 (0.31-1.43), 0.31 (0.13-0.73) and 0.60 (0.26-1.38) across quintile intake of soy protein (p for trend, 0.05). However, soy protein intake was not associated with breast cancer risk among women with the  Pvu II Pp or pp genotypes. Stratified analysis by  Xba I polymorphism showed that the inverse association of soy protein with breast cancer also appeared primarily among women with the X allele, although the trend test was not statistically significant (p for trend, 0.11). These results suggest that soy consumption may be associated with a reduced risk of breast cancer only among a subset of women with a wild type allele in the ERa gene.
Raising Japanese Quail Under Germfree and Conventional Conditions and Their Use in Cancer Research&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: James A. Reyniers, Miriam R. Sacksteder
Journal: JNCI Journal of the National Cancer Institute (1960)

Japanese quail (Coturnix coturnix japonica Temminck and Schlegel) have been raised as both conventional and germfree animals. The small size of this fowl and the ease with which it can be raised on practical diets demonstrate its usefulness as a laboratory animal, particularly in germfree experiments. Approximately 40 to 50 adult Coturnix can be maintained in one germfree isolator (RSU-500). Because of their relatively short generation time (about 80 to 90 days from egg to egg), it is possible to raise a colony of germfree birds. A special semisolid diet made up with 60 percent water is satisfactory for raising Coturnix. Such a diet is particularly useful in germfree isolators because there is less waste and dust and no need to supply water separately. Conventional Coturnix—birds hatched in a standard incubator and raised in the laboratory—will produce fertile eggs as early as 40 days of age. The hens continue to produce ca. 1 egg a day during the laying period, which may continue for 75 days—the period of observation—if the animals are raised in the laboratory. On the diets described the birds show good gains in body weight and good egg production. At 60 days of age the average weight of the adult female was 120 gm. and of the adult male 100 gm. The average weight at hachting was 5.6 gm. for both sexes. Similar studies are under way with germfree birds but sufficient data are not yet available for presentation. Conventional Coturnix are responsive to injection of methylcholanthrene in benzene and develop fibrosarcomas as early as 17 days after injection. In comparison, chickens require about 75 days to develop tumors under similar conditions. Quail tumors are transmissible to other quail by means of tumor-tissue homogenates. With successive passages there is a decrease in time to appearance of tumor. All of 24 conventional Coturnix tested, when injected in the breast muscle with 0.01 to 0.2 ml. of the 10−2 dilution of Rous sarcoma virus, developed tumors by the 8th day post inoculation. Filtrates of quail tumors have been transmitted to other quail and from quail to chickens.
Phase 3 study to evaluate the efficacy and safety of naldemedine for the treatment of opioid-induced constipation (OIC) in cancer patients.
Authors: Toshiyuki Harada, Nobuyuki Katakami, Toru Murata, Katsunori Shinozaki, Masakazu Tsutsumi, Takaaki Yokota, Masatsugu Arai, Yura Suzuki, Masaru Narabayashi, Narikazu Boku
Journal: Journal of Clinical Oncology (2016)

10016 Background: While opioid analgesics play a central role in managing cancer pain, opioid-induced constipation (OIC) is one of the most common side effects. Naldemedine (NAL) is a peripherally-acting μ-opioid receptor antagonist (PAMORA) being developed to treat OIC. Methods: The studies consisted of a 2-week double-blind placebo-controlled study (DBT) and a 12-week single-arm open-label extension study (EXT). In DBT, cancer patients with OIC, defined as ≤ 5 spontaneous bowel movements (SBMs) during a 2-week screening period, were randomized 1:1 to either oral NAL 0.2 mg QD or placebo (PBO). Patients who completed DBT could receive NAL in EXT. The primary endpoint of DBT evaluating the efficacy/safety of NAL was SBM responder rate (percentage of patients with ≥ 3 SBMs/week and an increase from baseline of ≥ 1 SBM/week) during 2-week treatment period. SBM responder rate was compared between NAL and PBO groups with the chi-square test for Full Analysis Set population. A total sample size of 190 (95 per arm) patients provided 90% power to detect a between-group difference by 23.5% in SBM responder rate with two-sided significance level of 0.05. The main objective of EXT was to assess the long term safety. Results: A total of 193 patients were randomized in DBT: 97 in NAL and 96 in PBO group, and 131 patients were enrolled in EXT. In DBT, NAL significantly improved SBM responder rate than PBO (71.1% vs 34.4%, respectively; P < 0.0001). NAL greatly improved the change from baseline in frequency of SBMs (5.16 vs 1.54, P < 0.0001), SBMs accompanied by feeling of incomplete evacuation (2.76 vs 0.71, P < 0.0001) and SBMs without straining (3.85 vs 1.17, P = 0.0005) per week than PBO. Incidences of any adverse event (AE) reported during treatment period in DBT were 44.3% and 26.0% in NAL and PBO, of which diarrhea was the only AE observed in ≥ 5% of patients (19.6% vs 7.3%). No clinically meaningful changes in opioid withdrawal scores and pain intensity were observed between the groups. In EXT, 107 patients completed a 12-week treatment and the safety profile appeared similar to DBT. Conclusions: NAL improved OIC and was generally well tolerated. NAL is a potential new treatment option for OIC in cancer patients. Clinical trial information: 132340, 132342.
Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases
Authors: Michael H. Ross, Alison K. Esser, Gregory C. Fox, Anne H. Schmieder, Xiaoxia Yang, Grace Hu, Dipanjan Pan, Xinming Su, Yalin Xu, Deborah V. Novack, Thomas Walsh, Graham A. Colditz, Gabriel H. Lukaszewicz, Elizabeth Cordell, Joshua Novack, James A. J. Fitzpatrick, David L. Waning, Khalid S. Mohammad, Theresa A. Guise, Gregory M. Lanza, Katherine N. Weilbaecher
Journal: Cancer Research (2017)

Abstract Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment. In a preclinical model of breast cancer, β3 was strongly expressed on bone metastatic cancer cells, but not primary mammary tumors or visceral metastases. In tumor tissue from breast cancer patients, β3 was significantly elevated on bone metastases relative to primary tumors from the same patient (n = 42). Mechanistic investigations revealed that TGFβ signaling through SMAD2/SMAD3 was necessary for breast cancer induction of β3 within the bone. Using a micelle-based nanoparticle therapy that recognizes integrin αvβ3 (αvβ3-MPs of ∼12.5 nm), we demonstrated specific localization to breast cancer bone metastases in mice. Using this system for targeted delivery of the chemotherapeutic docetaxel, we showed that bone tumor burden could be reduced significantly with less bone destruction and less hepatotoxicity compared with equimolar doses of free docetaxel. Furthermore, mice treated with αvβ3-MP-docetaxel exhibited a significant decrease in bone-residing tumor cell proliferation compared with free docetaxel. Taken together, our results offer preclinical proof of concept for a method to enhance delivery of chemotherapeutics to breast cancer cells within the bone by exploiting their selective expression of integrin αvβ3 at that metastatic site. Cancer Res; 77(22); 6299–312. ©2017 AACR.
Antibiotic use in South East Asia and policies to promote appropriate use: reports from country situational analyses
Authors: Kathleen Anne Holloway, Gitanjali Batmanabane, Monika Puri, Klara Tisocki
Journal: BMJ (2017)

<b>Kathleen Holloway and colleagues</b> discuss findings from a rapid assessment of antibiotic use and policies undertaken by South East Asian countries to drive further actions to reduce inappropriate use
Novel signal transducer and activator of transcription 1 mutation disrupts small ubiquitin-related modifier conjugation causing gain of function
Authors: Elizabeth P. Sampaio, Li Ding, Stacey R. Rose, Phillip Cruz, Amy P. Hsu, Anuj Kashyap, Lindsey B. Rosen, Margery Smelkinson, Tatyana A. Tavella, Elise M.N. Ferre, Meredith K. Wierman, Christa S. Zerbe, Michail S. Lionakis, Steven M. Holland
Journal: Journal of Allergy and Clinical Immunology (2017)
DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment
Authors: Qiang Lv, Chaoliang He, Fenli Quan, Shuangjiang Yu, Xuesi Chen
Journal: Bioactive Materials (2017)

Melanoma has been a serious threat to the human health; however, effective therapeutic methods of this cancer are still limited. Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy. In this paper, a chemo-immunotherapy system of DOX, IL-2 and IFN-γ based on poly(γ-ethyl-L-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-L-glutamate) (PELG-PEG-PELG) hydrogel was developed for local treatment of melanoma xenograft. The drug release process of this system exhibited a short term of burst release (the first 3 days), followed by a long-term sustained release (the following 26 days). The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats, showing a good biodegradability and biocompatibility. The DOX/IL-2/IFN-γ co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro, through increasing the ratio of cell apoptosis and G2/S phage cycle arrest. Moreover, the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model, which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Overall, the strategy of localized co-delivery of DOX/IL-2/IFN-γ using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.
Spontaneous murine mammary tumours demonstrate a range of sensitivities to adoptively transferred T cells: defining the molecular and histological determinants of regression versus progression
Authors: Erika M. Wall, Katy Milne, Michele Martin, Brad H. Nelson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1164 

To investigate T cell responses to spontaneous mammary tumours and define mechanisms of immune evasion, we developed a novel transgenic mouse model involving spontaneously arising, epitope-tagged mammary tumours. CD8+ and CD4+ T cell epitopes from ovalbumin were added to the C-terminus of the HER2/ neu oncogene to enable recognition by T cell receptor transgenic CD8+ (OT-I) and CD4+ (OT-II) T cells. C57Bl/6 transgenic mice expressing neu OTI/OTII in mammary epithelium together with a dominant-negative p53 transgene (DN p53 ) develop spontaneous mammary carcinomas at 6-10 months of age. T cell responses to these tumours were studied by adoptive transfer of naive OT-I and/or OT-II T cells into tumour-bearing mice. In mice that received OT-II cells, minimal or no T cell proliferation was observed in response to neu OTI/OTII-expressing tumours, even as late as 13 days post transfer. By contrast, OT-I T cells, infused alone or with OT-II T cells, proliferated vigorously within 3 days of adoptive transfer and subsequently infiltrated ∼75% of tumours by day 6 where they formed the major constituent (∼74%, n=8) of the CD8+ immune infiltrate. This resulted in complete regression of 19% (11/59) of tumours, with the remaining tumours showing partial regression (25%), stabilized growth (15%) or progressive disease (41%). Intriguingly, many non-regressing tumours continued to express neu OTI/OTII yet showed greatly reduced lymphocytic infiltrates at later time points (> day 11). Similarly, tumours generated from cell lines of progressive tumours failed to become infiltrated by OT-I or OT-II cells, suggesting they developed mechanisms to physically exclude T cells. To our knowledge, this is the first demonstration of CD8+ T cells eradicating established, spontaneously generated mammary tumours. We are currently investigating the mechanism(s) by which progressive tumours impair the infiltration and/or function of CD8+ T cells, and whether this can be reversed by combining adoptive T cell therapy with other treatments, such as chemotherapy, that disrupt tumour architecture.
Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis
Authors: Holger Woehrle, Martin R. Cowie, Christine Eulenburg, Anna Suling, Christiane Angermann, Marie-Pia d'Ortho, Erland Erdmann, Patrick Levy, Anita K. Simonds, Virend K. Somers, Faiez Zannad, Helmut Teschler, Karl Wegscheider
Journal: European Respiratory Journal (2017)

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial. Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias). The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased. On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies.
蛍光/光音響イメージングを用いた強化された光線療法のための機能的長期循環性単層カーボンナノチューブ【Powered by NICT】
Authors: Xie Lisi, Wang Guohao, Zhou Hao, Zhang Fan, Guo Zhide, Liu Chuan, Zhang Xianzhong, Zhu Lei
Journal: Biomaterials (2016)
ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary
Authors: Lee A. Fleisher, Joshua A. Beckman, Kenneth A. Brown, Hugh Calkins, Elliot L. Chaikof, Kirsten E. Fleischmann, William K. Freeman, James B. Froehlich, Edward K. Kasper, Judy R. Kersten, Barbara Riegel, John F. Robb
Journal: Circulation (2007)
Human-monoclonal-antibody therapy protects nonhuman primates against advanced Lassa fever
Authors: Chad E Mire, Robert W Cross, Joan B Geisbert, Viktoriya Borisevich, Krystle N Agans, Daniel J Deer, Megan L Heinrich, Megan M Rowland, Augustine Goba, Mambu Momoh, Mathew L Boisen, Donald S Grant, Mohamed Fullah, Sheik Humarr Khan, Karla A Fenton, James E Robinson, Luis M Branco, Robert F Garry, Thomas W Geisbert
Journal: Nature Medicine (2017)
Clinical, histological and immunohistochemical markers of resistance to methyl aminolaevulinate photodynamic therapy in Bowen disease
Authors: T. Gracia-Cazaña, N. Salazar, J. Vera-Álvarez, J. Aguilera, N. López-Navarro, E. Herrera-Ceballos, S. González, Á. Juarranz, Y. Gilaberte
Journal: British Journal of Dermatology (2017)
Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation
Authors: Laura E. Jackson, Sucheta Kulkarni, Huabo Wang, Jie Lu, James M. Dolezal, Sivakama S. Bharathi, Sarangarajan Ranganathan, Mulchand S. Patel, Rahul Deshpande, Frances Alencastro, Stacy G. Wendell, Eric S. Goetzman, Andrew W. Duncan, Edward V. Prochownik
Journal: Cancer Research (2017)

Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels of glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion to acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response to complex energetic, enzymatic, and metabolic cues. Here we utilized a mouse model of hepatocyte-specific PDC inactivation to determine the need for this metabolic link during normal hepatocyte regeneration and malignant transformation. In PDC "knockout" (KO) animals, the long-term regenerative potential of hepatocytes was unimpaired, and growth of aggressive experimental hepatoblastomas was only modestly slowed in the face of 80%-90% reductions in AcCoA and significant alterations in the levels of key tricarboxylic acid (TCA) cycle intermediates and amino acids. Overall, oxphos activity in KO livers and hepatoblastoma was comparable with that of control counterparts, with evidence that metabolic substrate abnormalities were compensated for by increased mitochondrial mass. These findings demonstrate that the biochemical link between glycolysis and the TCA cycle can be completely severed without affecting normal or neoplastic proliferation, even under the most demanding circumstances. Cancer Res; 77(21); 5795-807. ©2017 AACR.
Prognostic implications of abnormalities of chromosome 13 and the presence of multiple cytogenetic high-risk abnormalities in newly diagnosed multiple myeloma
Authors: M Binder, S V Rajkumar, R P Ketterling, P T Greipp, A Dispenzieri, M Q Lacy, M A Gertz, F K Buadi, S R Hayman, Y L Hwa, S R Zeldenrust, J A Lust, S J Russell, N Leung, P Kapoor, R S Go, W I Gonsalves, R A Kyle, S K Kumar
Journal: Blood Cancer Journal (2017)

Fluorescence in situ hybridization evaluation is essential for initial risk stratification in multiple myeloma. While the presence of specific cytogenetic high-risk abnormalities (HRA) is known to confer a poor prognosis, less is known about the cumulative effect of multiple HRA. We studied 1181 patients with newly diagnosed multiple myeloma who received novel agents as first-line therapy. High-risk abnormalities were defined as t(4;14), t(14;16), t(14;20) and del(17p). There were 884 patients (75%) without any HRA and 297 patients (25%) with HRA, including 262 (22%) with one HRA and 35 (3%) with two HRA. The presence of one HRA (versus zero, hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.32-2.05, p<0.001) and the presence of two HRA (versus zero, HR 3.15, 95% CI 2.00-4.96, p<0.001) were of prognostic significance after adjusting for other prognostic factors. Abnormalities of chromosome 13 were of prognostic significance independent of the established HRA: Monosomy 13 (HR 1.27, 95% CI 1.04-1.56, P=0.022) and del(13q) (HR 0.48, 95% CI 0.28-0.81, P=0.006) with opposite effects. Patients with HRA experienced worse overall survival suggesting a cumulative adverse effect of multiple HRA. Abnormalities of chromosome 13 were of prognostic significance after adjusting for other prognostic factors.
68Ga-DOTA-TATE PET/CT for Molecular Imaging of Somatostatin Receptor Expression in Metastasizing Epithelioid Hemangioendothelioma
Authors: Thorsten Derlin, Katja Hueper, Bisharah Soudah
Journal: Clinical Nuclear Medicine (2017)

Epithelioid hemangioendothelioma (EHE) is a rare tumor originating from vascular endothelial or pre-endothelial cells. It has the potential to metastasize. We present the case of a 51-year-old woman with metastasizing EHE who underwent both F-FDG and Ga-DOTA-TATE PET/CT for staging of disease and for evaluation of targeted radionuclide therapy potential. On Ga-DOTA-TATE PET scans, intense tracer accumulation was observed in metastases. Besides the increased glucose metabolism in EHE, this case highlights the potential of Ga-DOTA-TATE PET/CT for restaging of EHE and the option of targeted radionuclide therapy in this entity.
An Evolutionary Genomic Perspective on the Breeding of Dwarf Chickens
Authors: Ming-Shan Wang, Newton O Otecko, Sheng Wang, Dong-Dong Wu, Min-Min Yang, Yi-Long Xu, Robert W Murphy, Min-Sheng Peng, Ya-Ping Zhang
Journal: Molecular Biology and Evolution (2017)

The evolutionary history for dwarfism in chickens remains an enigma. Herein, we explore the evolution of the Serama, the smallest breed of chicken. Leveraging comparative population genomics, analyses identify several genes that are potentially associated with the growth and development of bones and muscles. These genes, and in particular both POU1F1 and IGF1, are under strong positive selection. Three allopatric dwarf bantams (Serama, Yuanbao, and Daweishan) with different breeding-histories, form distinct clusters and exhibit unique population structures. Parallel genetic mechanisms underlay their variation in body size. These findings provide insights into the multiple and complex pathways, depending on genomic variation, that chicken can take in response to aviculture selection for dwarfism.