tbuckley/cabot-search huggingface dataset:
Microenvironmental Metabolism Regulates Antitumor Immunity
Authors: Verra M. Ngwa, Deanna N. Edwards, Mary Philip, Jin Chen
Journal: Cancer Research (2019)

Abstract Metabolic reprogramming of cancer cells and the tumor microenvironment are emerging as key factors governing tumor growth, metastasis, and response to therapies including immune checkpoint inhibitors. It has been recognized that rapidly proliferating cancer cells, tumor-infiltrating lymphocytes, and vascular endothelial cells compete for oxygen and nutrients. Tumor cells and other cell types in the microenvironment not only compete for nutrients, but they also simultaneously produce immunosuppressive metabolites, leading to immune escape. In addition, commensal microbial metabolites can influence regulatory T cells and inflammation in the intestine, thus playing an essential role in cancer prevention or cancer promotion. In this review, we summarize recent advances on metabolic interactions among various cell types in the tumor microenvironment, with a focus on how these interactions affect tumor immunity. We also discuss the potential role of blood vessel metabolism in regulating immune cell trafficking and activation.
TP53 mutations Are Associated with Mutated MYD88 and CXCR4, and Confer an Adverse Outcome in Waldenström Macroglobulinemia
Authors: Joshua Gustine, Kirsten Meid, Patricia Severns, Toni Dubeau, Nickolas Tsakmaklis, Christopher Patterson, Guang Yang, Xia Liu, Maria Demos, Amanda Kofides, Jiaji Chen, Manit Munshi, Maria Luisa Guerrera, Gloria Chan, Jorge J. Castillo, Zachary Hunter, Steven P Treon, Lian Xu
Journal: Blood (2017)
Abstract 18757: Access to Routine Care and Risks for 30-Day Readmission in Patients With Cardiovascular Disease
Authors: Matthew E Dupre, Hanzhang Xu, Bradi B Granger, Alicia Nelson, Erik Churchill, Janese M Willis, Lesley H Curtis, Eric D Peterson
Journal: Circulation (2017)

Introduction: Studies have not examined whether patient-reported difficulties in access to routine medical care are associated with rehospitalization in patients with cardiovascular disease (CVD). ...
Hematologic malignancies developing in previously healthy individuals who received hematopoietic growth factors: Implications for use of colony stimulating factors in healthy volunteers participating in early phase clinical studies and in healthy blood product donors
Authors: A. E. Lyons, L. Balasubramanian, L. A. Andritsos, A. Evens, T. Kuzel, J. M. Vose, P. J. Bierman, D. J. Kuter, S. M. Devine, C. L. Bennett
Journal: Journal of Clinical Oncology (2006)

2559 Background: Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHu-MGDF aka MGDF) and recombinant granulocyte colony stimulating factor (G-CSF) promote the maturation of hematopoietic progenitor cells. Healthy volunteers/donors have received MGDF in phase I/II clinical trials and G-CSF in allogeneic peripheral blood stem cell transplantation procedures. Herein, we review clinical findings for five previously healthy volunteers/donors who developed hematologic malignancies after the use of MGDF or G-CSF. Methods: Clinical information related to hematologic malignancies were reviewed for three volunteers who had participated in a phase I/II clinical trial with MGDF and two donors who underwent G-CSF mobilized peripheral blood stem cell harvesting procedures for sibling allogeneic stem cell transplantation for acute leukemia. Results: Mantle cell, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia were diagnosed three to five years after exposure among three volunteers who received MGDF. For one of these patients, autoimmune thrombocytopenia and antibodies to MGDF that cross-reacted with endogenous thrombopoietin had developed shortly after MGDF administration and persisted until lymphoma chemotherapy was administered. Following chemotherapy, all three achieved complete remission, although one patient subsequently relapsed. Acute myelogenous leukemia was diagnosed four to five years after exposure in two donors who underwent G-CSF primed stem cell harvests prior to their siblings’ allogeneic stem cell transplantation. Following intensive chemotherapy, one of these patients died from acute leukemia and the second is now in complete remission. Conclusion: Controversy exists over the appropriateness of administering hematopoietic growth factors to healthy individuals. While a causal relationship with hematologic malignancies is uncertain, long-term follow-up among healthy individuals who receive hematopoietic growth factors is needed. No significant financial relationships to disclose.
Conversion, Compromise, and Conversation—Moving to a Sensible Middle When Addressing Implantable Cardioverter-Defibrillator Therapy
Authors: J. Rod Gimbel, Bruce L. Wilkoff
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Assessment of cancer screening practices after BRCA testing in Michigan.
Authors: Julie Zenger Hain, Sarah Mange, Janice Bach, Debra Duquette, Jennifer McLosky, Lindsay Dohany, Jacquelyn Roberson, Katie Biro, Nancie Petrucelli, Daniela Iacoboni, Samira Ahsan, Sofia Merajver, Kara J. Milliron, Jessica Everett, Dana Zakalik
Journal: Journal of Clinical Oncology (2013)

1557 Background: Women who harbor BRCA1/2 mutations are at increased risk for breast and ovarian cancer and are advised to undergo high risk surveillance and/or preventative surgery. The compliance with screening guidelines in these women is not well known. This study aims to evaluate the uptake and screening practices of women with known deleterious BRCA mutations and BRCA true negatives who received genetic counseling in the state of Michigan. Methods: A telephone survey coordinated by the Michigan Department of Community Health was conducted on pts seen at 8 genetics clinics between 10/07 to 10/09. Each center was staffed by board certified genetics professionals who provided pre and post-test genetic counseling. Pts who were found to carry a deleterious BRCA mutation, or to be negative for a known familial mutation, were queried regarding adherence to NCCN guidelines. Results: 138 of 253 (55%) pts responded to the phone survey, with an elapsed time of 1.7 to 4.6 years from post-test counseling session. Among BRCA mutation carriers over age 25 years with no cancer history or mastectomy, 11 of 21 pts (52%) adhered to MRI screening guidelines, 3 pts (14%) reported two MRIs, and 7 (33%) pts had no MRI screening in the preceding year. 18 of 21 pts (86%) reported having a screening mammogram in the preceding year and the remaining 3 had two or more. 8 of 20 (40%) pts had two clinical breast exams. Of the women who had breast cancer and no mastectomy, 5 of 9 (56%) pts did not have MRI screening. Of the BRCA true negatives with no cancer history, CA-125 or transvaginal ultrasound was performed in 7 (19%) and 8 (20%) of 37 pts, respectively. Conclusions: This study reveals sub-optional compliance with screening guidelines in women who were identified to be carriers of BRCA mutations or those who were true negatives, despite pre and post-test genetic counseling and communication of established management guidelines. Some recommended screening measures were under-utilized in BRCA mutation carriers, and some were over-utilized in the true negatives. Additional interventions are needed to improve adherence to evidence-based screening guidelines aimed at promoting early detection, with an emphasis on appropriate utilization of limited healthcare resources.
Phase II multicenter study of chemotherapy (chemo)-naive castration-resistant prostate cancer (CRPC) not exposed to ketoconazole (keto), treated with abiraterone acetate (AA) plus prednisone
Authors: C. Ryan, E. Efstathiou, M. Smith, M. Taplin, G. Bubley, C. Logothetis, T. Kheoh, C. Haqq, A. Molina, E. J. Small
Journal: Journal of Clinical Oncology (2009)

5046 Background: AA is a potent inhibitor of the enzyme CYP17, a major contributor to androgen biosynthesis. Keto is also known to inhibit this enzyme but AA is many-fold stronger in its action. 33 pts with progressive metastatic disease, normal organ function, ECOG performance status (PS) 0–1, and no prior chemo were enrolled. Pts with prior keto treatment were excluded. AA (1000 mg qd) plus prednisone (5mg bid) were administered orally in 28 day cycles. Methods: Results: At baseline median age was 71.0 (range 52–85) yrs and median PSA was 24.7 (range 7.1–1110.0) ng/mL;19/26 pts (73%) had an ECOG PS of 0 and 7/26 (27%) had PS of 1; the median number of prior hormonal therapies was 2; all pts were on LHRHa and 73% of pts had received anti-androgen, all of whom had undergone prior anti-androgen withdrawal. Pts were evaluated at each cycle for PSA response according to PSAWG criteria. 27 pts have available data for PSA response. Total maximal PSA declines of ≥30%, ≥50%, ≥90% were observed in 89% (24/27), 85% (23/27) and 41% (11/27) pts, respectively. Week 12 PSA declines displayed a similar and sustained trend: ≥30%, ≥50% and ≥90% PSA decline in 82%, 78%, and 26% of pts. Post-treatment ECOG PS score was 0 in 24 (92%) pts: 19% experienced improvement in PS (PS 1 to 0 in 5 pts) and 19/19 pts maintained a PS of 0; Median time to PSA progression has not been reached. Majority of adverse events were grades 1–2. Incidence of hypokalemia - 12%; HTN - 6%; edema - 15%. One pt experienced a grade 3 drug-related HTN. Conclusions: Abiraterone acetate plus prednisone has significant anti-cancer activity in patients with metastatic CRPC not previously treated with ketoconazole or chemotherapy, as demonstrated by declines in PSA and improvement in performance status, and is well-tolerated. [Table: see text]
Is anemia due to chronic disease the main cause of anemia in cancer patients?
Authors: Gungor Utkan, Gokce Kenar, Hakan Akbulut, Ahmet Demirkazik, Handan Onur, Fikri Icli
Journal: Journal of Clinical Oncology (2013)

e20655 Background: Causes of anemia in cancer patients are often multifactorial. It may be atrributed to underlying nutritional deficiencies, such as cobalamin, folate, iron. The aim of our study is to determine prevalence of anemia and evaluate anemia parameters in newly diagnosed cancer patients. Methods: 310 newly diagnosed cancer patients (gastrointestinal tract (GIT) cancers, 35.8%; non-GIT malignancies, 64.2%) and 301 healthy individuals as control group were retrospectively evaluated in terms of anemia parameters: complete blood count (CBC) , ferritin, transferrin saturation (TSAT) , serum iron (SI), vitamin B12, folate levels. The exclusion criteria were, to be treated with cytotoxic treatments or radiotherapy before, and having a story of hemorrhage within last 3 months. Results: Anemia was observed in 49.7% of newly diagnosed cancer patients and in 13.7% of control group (P&lt; 0.001). Mean ferritin level was 153 ng/mL in patients group and 47 ng/mL in control group (P&lt; 0.001). By contrast, in patient group, SI and TSAT were lower (P&lt; 0.001). Folate deficiency (≤ 3.1 ng/mL) was seen more frequent in patient group than control group (6.5% and 1%, P&lt; 0.001). Cobalamin deficiency (≤ 200 pg/mL) was also seen more frequent in patients group than control group (39.3% and 17.7% , P&lt; 0.001). Anemia parameters were similar in both groups of patients with GIT cancers and non-GIT cancers. Conclusions: In the current study, we found that nutritional deficiencies are more prevalent in newly diagnosed cancer patients than control group. However ferritin levels were higher in cancer patients, SI and TSAT levels were lower. This situation can be explained by acute phase response. Both cobalamin and folate deficiencies may cause ineffective erythropoiesis and also pancytopenia. If cytotoxic therapies will be administered additionally to cobalamin or folate deficient cancer patients, duration of bone marrow depression may become longer. In conclusion, we suggest to evaluate anemia parameters routinely at the time of diagnosis in cancer patients. This may provide an opportunity to replace these nutritional factors earlier and to reduce the requirement of transfusion.
Vijyarangam Senthilkumar Shanmugam
Authors: Damian Wren, Camilla Blain, Niranjanan Nirmalananthan, Anthony Pereira
Journal: BMJ (2019)

Vijyarangam Senthilkumar Shanmugam (“Kumar”) was an incredible, brave, and sincere doctor. He completed his medical training in 2000, graduating from Madurai Medical College in India. On the eve of his final practical MBBS examination, he was riding his “bullet” motorbike to pay a visit to the temple in Madurai. On the way, he was forced to swerve to avoid some boys playing a ball game, one of whom ran out into the road. He crashed, breaking his forearm. He abandoned the motorbike and returned to his digs, where he attempted to reset his arm by himself. Eventually, his friends persuaded him …
From Root to Tips: Sporulation Evolution and Specialization in<i>Bacillus subtilis</i>and the Intestinal Pathogen<i>Clostridioides difficile</i>
Authors: Paula Ramos-Silva, Mónica Serrano, Adriano O Henriques
Journal: Molecular Biology and Evolution (2019)

Bacteria of the Firmicutes phylum are able to enter a developmental pathway that culminates with the formation of highly resistant, dormant endospores. Endospores allow environmental persistence, dissemination and for pathogens, are also infection vehicles. In both the model Bacillus subtilis, an aerobic organism, and in the intestinal pathogen Clostridioides difficile, an obligate anaerobe, sporulation mobilizes hundreds of genes. Their expression is coordinated between the forespore and the mother cell, the two cells that participate in the process, and is kept in close register with the course of morphogenesis. The evolutionary mechanisms by which sporulation emerged and evolved in these two species, and more broadly across Firmicutes, remain largely unknown. Here, we trace the origin and evolution of sporulation using the genes known to be involved in the process in B. subtilis and C. difficile, and estimating their gain-loss dynamics in a comprehensive bacterial macroevolutionary framework. We show that sporulation evolution was driven by two major gene gain events, the first at the base of the Firmicutes and the second at the base of the B. subtilis group and within the Peptostreptococcaceae family, which includes C. difficile. We also show that early and late sporulation regulons have been coevolving and that sporulation genes entail greater innovation in B. subtilis with many Bacilli lineage-restricted genes. In contrast, C. difficile more often recruits new sporulation genes by horizontal gene transfer, which reflects both its highly mobile genome, the complexity of the gut microbiota, and an adjustment of sporulation to the gut ecosystem.
Multiple Plasticity Regulators Reveal Targets Specifying an Induced Predatory Form in Nematodes
Authors: Linh T Bui, Erik J Ragsdale
Journal: Molecular Biology and Evolution (2019)

Abstract The ability to translate a single genome into multiple phenotypes, or developmental plasticity, defines how phenotype derives from more than just genes. However, to study the evolutionary targets of plasticity and their evolutionary fates, we need to understand how genetic regulators of plasticity control downstream gene expression. Here, we have identified a transcriptional response specific to polyphenism (i.e., discrete plasticity) in the nematode Pristionchus pacificus. This species produces alternative resource-use morphs—microbivorous and predatory forms, differing in the form of their teeth, a morphological novelty—as influenced by resource availability. Transcriptional profiles common to multiple polyphenism-controlling genes in P. pacificus reveal a suite of environmentally sensitive loci, or ultimate target genes, that make up an induced developmental response. Additionally, in vitro assays show that one polyphenism regulator, the nuclear receptor NHR-40, physically binds to promoters with putative HNF4α (the nuclear receptor class including NHR-40) binding sites, suggesting this receptor may directly regulate genes that describe alternative morphs. Among differentially expressed genes were morph-limited genes, highlighting factors with putative “on–off” function in plasticity regulation. Further, predatory morph-biased genes included candidates—namely, all four P. pacificus homologs of Hsp70, which have HNF4α motifs—whose natural variation in expression matches phenotypic differences among P. pacificus wild isolates. In summary, our study links polyphenism regulatory loci to the transcription producing alternative forms of a morphological novelty. Consequently, our findings establish a platform for determining how specific regulators of morph-biased genes may influence selection on plastic phenotypes.
Hybrid lipids, peptides, and lymphocytes: new era in type 1 diabetes research
Authors: Abdel Rahim A. Hamad, Mohanraj Sadasivam, Hamid Rabb
Journal: Journal of Clinical Investigation (2019)

Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing β cells in islets of Langerhans. Many genetic and immunological insights into autoimmune disease pathogenesis were initially uncovered in the context of T1D and facilitated by preclinical studies using the nonobese diabetic (NOD) mouse model. Recently, the study of T1D has led to the discovery of fatty acid esters of hydroxyl fatty acids (FAHFAs), which are naturally occurring hybrid peptides that modulate inflammation and diabetes pathogenesis, and a hybrid lymphocyte that expresses both B and T cell receptors. Palmitic acid esters of hydroxy stearic acids (PAHSAs) are the most extensively studied FAHFA. In this issue of the JCI, Syed et al. have shown that PAHSAs both attenuate autoimmune responses and promote β cell survival in NOD mice. Given the lack of effective T1D therapies and the paucity of known side effects of PAHSAs, this lipid may have therapeutic potential for individuals at risk for or newly diagnosed with T1D.
Early decrease in basophil sensitivity to Ara h 2 precedes sustained unresponsiveness after peanut oral immunotherapy
Authors: Sarita U. Patil, Johanna Steinbrecher, Agustin Calatroni, Neal Smith, Alex Ma, Bert Ruiter, Yamini Virkud, Michael Schneider, Wayne G. Shreffler
Journal: Journal of Allergy and Clinical Immunology (2019)
Use of Port-A-Cath in pediatric cancer patients: Experience from a tertiary cancer center in south India
Authors: T. Singh, C. Satheesh, J. Ankit, K. V. Sajeevan, L. Appaji, B. Arunakumari, M. Padma, H. S. Mamatha
Journal: Journal of Clinical Oncology (2009)

e20747 Background: Implanted subcutaneous (s.c.) central venous port accesses including Port-A-Cath (PAC) facilitate the administration of chemotherapy or blood products and are frequently used in children with cancer. We present our experience of PACs in paediatric cancer patients from a tertiary cancer centre in South India. Methods: A total of 20 patients with paediatric malignancies requiring PAC were included in the study. Aim was to review our experience of PAC and analyse the outcome in paediatric cancer patients in Indian setting. A record of all complications and final outcome were analysed. Results: A total of 20 PAC were placed. Disease distribution included ALL(80%), AML(5%), NHL(5%), neuroblastoma (5%) and RMS (5%). PAC has been in place for 2 to 36 months (cumulative 400 months). Portal infection (Coagulase-negative staphylococci) was observed in four patients of whom 3 patients had their PAC removed (portal occlusion also seen in one of the pt). Conclusions: Although, catheter-related infections demanded PAC removal in 15% of our patients, their benefits (excluding cost 300 $) argue for continued PAC use in the paediatric cancer population as it is safe and has many advantages compared to traditional CVCs in use. Strict indications, meticulous implantation technique, and adequate handling are, however, mandatory. No significant financial relationships to disclose.
Results of upfront therapy for marginal zone lymphoma (MZL).
Authors: Fernando Cabanillas, Jose Luis Ortega, Noridza Rivera-Rodriguez, Blanca Rodriguez, Wandaly Ibis Pardo, Orestes Antonio Pavia, Margarita Bruno, Karen J. Santiago
Journal: Journal of Clinical Oncology (2013)

e19510 Background: MZL is an indolent NHL composed of 3 subtypes: extranodal (MALT), splenic marginal zone (SMZL) and nodal marginal zone (NML). While MALT usually presents with early stage, the others frequently present with advanced disease. Early stage MALT is usually treated with XRT or antibiotics with ~85-90% failure free survival (FFS) and overall survival (OS), while for SMZL watch and wait or splenectomy (Spl) have been the mainstay of therapy. Spl leads to improvement but rarely to CR. 5 yr FFS and OS with Spl have been 45% and 80%. At 10 yrs FFS and OS are 22% and 62%. NML is usually managed with watch and wait. The 5 yr FFS and OS for NML have been 30% and 60%. Watch and wait and Spl are used in part because advanced MZL is considered incurable. Rituximab (R) as well fludarabine (F) are active in this disorder but traditionally are given after relapse. Methods: Instead of watch and wait or Spl, we have used upfront chemo with curative intent for SMZL and NML as well as for advanced MALT. For early stage MALT we used either XRT alone or antibiotics. We hereby report on 44 pts with MZL of which 31 were MALT, 9 SMZL, 4 NMZL. For the purpose of analysis we divided the pts in 2 groups. Group 1 consists of 22 early stage MALT who were all treated with either XRT (N=17) or antibiotics +/- surgery (N=5). Group 2 consists of 22 cases who were treated with chemo alone. This group is made up of 9 MALT (4 advanced stage, 3 early stage but with transformation, 2 early stage but in whom XRT was contraindicated), 9 advanced stage SMZL, 4 NML. Chemo for group 2 consisted of F, mitoxantrone, dexamethasone, rituximab (FND-R) (N=14) or R-CHOP (N=8). Maintenance R was used in 70% of group 2. Results: Of the whole group, 100% were CR and only 2 relapsed at 70 and 75 months; both relapses were stage I MALT and had received XRT only. Both were salvaged with FND-R and remain NED 27 and 39 months from relapse. At 10 yrs, FFS was 80% and OS=100%. None of the 22 in group 2 have relapsed. The long-term toxicity has been acceptable. Conclusions: The excellent FFS and OS using upfront chemotherapy in group 2, suggests that this disorder is curable and our results should be confirmed in a prospective trial. For those with early stage MALT, XRT alone +/- antibiotics and when necessary salvage with FND-R, should be tested.