tbuckley/cabot-search huggingface dataset:
Impacts of microRNA-215 on cell proliferation and chemotherapy resistance in colon cancer and osteosarcoma
Authors: J. Ju, B. Song, Y. Wang
Journal: Journal of Clinical Oncology (2009)

2542 Background: Translational control plays a key role in resistance to anti-cancer drug treatment. MicroRNAs regulate gene expression at the post-transcriptional level, mainly by interacting with 3'-UTR of their mRNA targets. Methods: miR-215 was ectopically expressed by transient transfection in both human colon cancer cell lines and osteosarcoma cell lines. The impact of miR-215 on cell proliferation, cell cycle control, chemosensitivity and down stream targets were characterized. The expression of miR-215 in colorectal cancer specimens and normal adjacent tissues was quantified by real time-qRT-PCR analysis. Results: In this study, we discovered that miR-215 down-regulates the expression of both dihydrofolate reductase (DHFR) and thymidylate synthase (TS), two of the most important chemotherapeutic targets, in human osteosarcoma U-2 OS and colon cancer HCT-116 (wt-p53) cell lines. Cells with elevated miR-215 expression are more resistant to DHFR inhibitor methotrexate (MTX) or TS inhibitor Tomudex (TDX) treatment. Ectopically over-expressing miR-215 triggers reduced cell proliferation and increased G2 arrest, at least in part, through the induction of p53 and p21. miR-215 transfected cells with reduced proliferating phenotype were resist to MTX or TDX treatment due to deceased cell cycle in S phase. The expression of endogeneous miR-215 was highly elevated in CD133 +/HI CD44 +/HI colon cancer stem cells compared to CD133 - CD44 - colon cancer cells, suggesting that tumor stem cells may be avoiding cellular and DNA damage caused by chemotherapy with a reduced proliferating phenotype mediated by certain miRNAs such as miR-215. The elevated expression of miR-215 in colon cancer stem cells with slow proliferation rate and resistance to chemotherapy further supports the role of miR-215 in cell proliferation and chemotherapy resistance. Conclusions: miR-215 may have a unique potential as a novel therapeutic target and biomarker candidate in cancer. No significant financial relationships to disclose.
Preliminary evaluation of chemotherapy plus residual tumor excision for testis conservation to provide justification for a randomized trial versus orchidectomy to reduce metabolic syndrome in patients with germ cell cancer
Authors: R. Oliver, J. Shamash, V. Nargund
Journal: Journal of Clinical Oncology (2009)

5087 Background: There is evidence that early andropause due to testicular atrophy may be playing a role in the increased metabolic syndrome and cardiac deaths seen with follow up of GCC patients even those on surveillance. In a randomized trial of 1,477 stage I seminomas a single course of carboplatin produced a 78% reduction of contra lateral testicular GC. This, has increased awareness of the effectiveness of chemotherapy on primary tumours This abstract updates our experience.assessing chemo-response of primary GCC in past 30 years. Methods: Testicular GCC patients receiving chemotherapy with primary tumour in situ during 1978–2001 have been reviewed. 62 had advanced disease and 20 had stage I. Results: In 30/82 (37%) the testis normalised and was retained. Median follow-up is 132 months. 7 of these patients developed second GCC. Actuarial 5, 10, and 15 year relapse free survival was 81% and 76%. All relapses are new tumours without evidence of metastasis and are disease free after orchidectomy alone (15, 17, 35, 45, 48, 72, and 156 months). 22 additional patients (28%) who underwent orchidectomy for apparent treatment failure had necrotic tissue/mature teratoma involving less than 50% of the testis and could have been candidates for tumour enucleation. Patients with stage 1 tumours and seminoma histology showed significantly higher preservation rate that approached 100% if one included those showing necrosis or mature teratoma involving less than 50% of the testis. There have been 6 pregnancies to date in wives of 3 patients. 5 of 6 patients studied in detail have recovered sperm, the highest count (100x10 6 ) being the only patient who was successfully treated for bilateral testis tumours. Conclusions: This preliminary study suggests that up to 50% of all cases and 90% of stage I seminoma cases with tumours small enough for tumour enucleation for incomplete responders could have successful testis preservation after chemotherapy safely up to 10 years though in the future a randomized patient preference driven trial is needed to establish its acceptability, safety and value in reducing androgen deficiency. No significant financial relationships to disclose.
Antibody to CD137 Activated by Extracellular Adenosine Triphosphate Is Tumor Selective and Broadly Effective<i>In Vivo</i>without Systemic Immune Activation
Authors: Mika Kamata-Sakurai, Yoshinori Narita, Yuji Hori, Takayuki Nemoto, Ryo Uchikawa, Masaki Honda, Naoka Hironiwa, Kenji Taniguchi, Meiri Shida-Kawazoe, Shoichi Metsugi, Taro Miyazaki, Naoko A. Wada, Yuki Ohte, Shun Shimizu, Hirofumi Mikami, Tatsuhiko Tachibana, Natsuki Ono, Kenji Adachi, Tetsushi Sakiyama, Tomochika Matsushita, Shojiro Kadono, Shun-ichiro Komatsu, Akihisa Sakamoto, Sayuri Horikawa, Ayano Hirako, Koki Hamada, Sotaro Naoi, Nasa Savory, Yasuko Satoh, Motohiko Sato, Yuki Noguchi, Junko Shinozuka, Haruka Kuroi, Ami Ito, Tetsuya Wakabayashi, Masaki Kamimura, Fumihisa Isomura, Yasushi Tomii, Noriaki Sawada, Atsuhiko Kato, Otoya Ueda, Yoshito Nakanishi, Mika Endo, Kou-ichi Jishage, Yoshiki Kawabe, Takehisa Kitazawa, Tomoyuki Igawa
Journal: Cancer Discovery (2020)

Abstract Agonistic antibodies targeting CD137 have been clinically unsuccessful due to systemic toxicity. Because conferring tumor selectivity through tumor-associated antigen limits its clinical use to cancers that highly express such antigens, we exploited extracellular adenosine triphosphate (exATP), which is a hallmark of the tumor microenvironment and highly elevated in solid tumors, as a broadly tumor-selective switch. We generated a novel anti-CD137 switch antibody, STA551, which exerts agonistic activity only in the presence of exATP. STA551 demonstrated potent and broad antitumor efficacy against all mouse and human tumors tested and a wide therapeutic window without systemic immune activation in mice. STA551 was well tolerated even at 150 mg/kg/week in cynomolgus monkeys. These results provide a strong rationale for the clinical testing of STA551 against a broad variety of cancers regardless of antigen expression, and for the further application of this novel platform to other targets in cancer therapy. Significance: Reported CD137 agonists suffer from either systemic toxicity or limited efficacy against antigen-specific cancers. STA551, an antibody designed to agonize CD137 only in the presence of extracellular ATP, inhibited tumor growth in a broad variety of cancer models without any systemic toxicity or dependence on antigen expression. See related commentary by Keenan and Fong, p. 20. This article is highlighted in the In This Issue feature, p. 1
Infant feeding clusters are associated with respiratory health and allergy at school age in the PARIS birth cohort
Authors: Hélène Amazouz, Blandine de Lauzon‐Guillain, Mélisande Bourgoin‐Heck, Jocelyne Just, Nicole Beydon, Guillaume Lezmi, Fanny Rancière, Isabelle Momas
Journal: Allergy (2020)

As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort.Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy.Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitization at 8 years.Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.
Battling chronic pain and learning self-advocacy: the long journey of becoming pain free
Authors: Mary Johnson
Journal: British Journal of Sports Medicine (2020)

I had returned to running for about 6 months following a stress fracture in my left femur when I started noticing pain high up in my right hamstring. It got to the point where I knew something was wrong, but it didn’t hurt to run. My massage therapist/strength coach and physical therapist said that if I could run without pain, it would be fine, so I continued to run. A lot. Six months after the pain began, I was doing a ton of volume leading up to the 2016 Boston Marathon. It still didn’t hurt when I ran, but the pain after training continued to worsen. By this time, I was worried I had a pelvic stress fracture. I saw an orthopaedic doctor, who told me that I didn’t have a stress fracture and was okay to just run through the discomfort. In addition to the work I’d done to return from my femoral stress fracture, my husband and I also wanted to start a family, so I viewed this as my last chance to run marathons pre-baby. When I ran a marathon in April 2016, then another in May 2016… it wasn’t a good decision, but I thought it was at least an informed decision.



Figure 1 

By the fall of 2016, my hamstring tightness had gotten …
Phase II study of oxaliplatin combined with S-1 (SOX) as first-line therapy for patients with advanced gastric cancer (AGC)
Authors: H. Takiuchi, W. Koizumi, Y. Yamada, N. Boku, Y. Komatsu, N. Fuse, K. Muro, A. Tsuburaya
Journal: Journal of Clinical Oncology (2009)

4553 Background: Oral fluoropyrimidine S-1 is one of the standard 1st-line chemotherapy for patients with AGC in Japan, and oxaliplatin is active against AGC in combination with fluoropyrimidine. This study evaluates the efficacy and safety of oxaliplatin in combination with S-1 in AGC. Methods: Eligibility criteria were: pathologically confirmed AGC, no prior chemotherapy, age &gt; 20, measurable lesions, ECOG PS &lt; 2, adequate organ function, written informed consent. Oxaliplatin was administered intravenously at a dose of 100 mg/m 2 on day 1, and S-1 was administered orally twice daily on days 1–14 at a dose of 80 mg/m 2 /day, repeated every three weeks. The primary endpoint was objective response with RECIST guidelines. The sample size of 52 patients has an 80% power to demonstrate a 60% response rate (RR) with a one-sided type I error of 2.5%. Results: Between Apr. and Dec. 2007, 55 patients were enrolled at 8 centers in Japan. 51 patients were assessable for efficacy and 54 were assessable for safety. Patient characteristics: male/female = 34/17; median age 63 (range 30–77); PS 0–1/2 = 50/1; diffuse type/intestinal type = 35/16; metastatic/recurrent = 47/4. Median cycles 6.5 (range: 1–16). Thirty patients achieved in PR, and RR was 58.8% (95%CI: 44.2–72.4). Disease control rate (CR+PR+SD) was 84.3% (43/51; 95%CI: 71.4–93.0). One patient received subsequent curative surgery and achieved pCR. Median progression free survival was 6.5 months (95%CI: 4.8–11.3). Median time to treatment failure was 4.8 months (95%CI: 4.0–5.6). Grade 3–4 major adverse reactions were neutropenia (22.2%), thrombocytopenia (13.0%), leucopenia (3.7%), anorexia (5.6%), nausea (1.9%), and sensory neuropathy (3.7%). No treatment-related death was observed. Conclusions: The SOX regimen was well-tolerated and showed promising activity. This regimen may become one of the standard chemotherapy for ACG. One-year overall survival rate will be present at the meeting. [Table: see text]
Small-bowel cryptococcosis diagnosed by double-balloon endoscopy in patient without human immunodeficiency virus
Authors: Túlio Riguetti Prazeres, Marcela Almeida Menezes de Vasconcellos, Marcella Salazar Sousa, Evelin Sánchez Ortiz, Ulysses Ribeiro Junior, Sérgio Carlos Nahas, Adriana Vaz Safatle-Ribeiro
Journal: Endoscopy (2020)

A 45-year-old man presented with a 2-year history of diarrhea and anasarca. His work involved opening tunnels and exploding rocks. He had no cardiovascular abnormalities or proteinuria. Celiac disease and human immunodeficiency virus (HIV) serologies were negative. Total protein (2.6 g/dL), albumin (1.5 g/dL), ionized calcium (3.09 mg/dL), vitamin D (6.7 ng/mL), and immunoglobulin (IgM 29 mg/dL, IgG 357 mg/dL, IgA 60 mg/dL) levels were low. Sodium and potassium were normal.
TIP30 inhibits B cell proliferation and functions as tumor suppressor in hematopoietic tissue
Authors: Weihua Tang, Jill Pecha, Mitsuhiro Ito, Kristy Bruck, Christine M. Eischen, Hua Xiao
Journal: Cancer Research (2005)

2514  TIP30 is a Tat-interacting protein that can increase Tat-mediated transcription and is a putative tumor suppressor that can sensitize cells to apoptosis and inhibit tumorigenesis. We recently reported that TIP30-deficient mice of C57BL/6 /129SvJ mixed genetic background had a high incidence of hepatocellular carcinoma and other tumors. Moreover, TIP30 overexpression represses ERα-mediated c-myc transcription, whereas TIP30 deficiency enhances c-myc transcription in both the absence and presence of estrogen. We show here that TIP30 plays an important role in the regulation of B-cell development and proliferation, and those congenic C57BL/6 TIP30-deficient mice are prone to the development of B-cell lymphoma. We have kept a cohort of congenic C57BL/6 TIP30−/−, TIP30+/− and wild-type mice for long-term observation for analysis of the development of spontaneous malignancy. 26.7% of female TIP30−/− and 20% TIP30+/− mice were dead at an average age of 12.9 and 14.8 months (p
Correction: Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning
Authors: Takahiro Seki, Kayoko Hosaka, Carina Fischer, Sharon Lim, Patrik Andersson, Mitsuhiko Abe, Hideki Iwamoto, Yanyan Gao, Xinsheng Wang, Guo-Hua Fong, Yihai Cao
Journal: The Journal of Experimental Medicine (2020)
Symptomatic and Asymptomatic Viral Shedding in Pediatric Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Roberta L. DeBiasi, Meghan Delaney
Journal: JAMA Pediatrics (2020)

Mi Seon Han, MD, PhD; Eun Hwa Choi, MD, PhD; Sung Hee Chang, MD; Byoung-Lo Jin, MD; Eun Joo Lee, MD; Baek Nam Kim, MD; Min Kyoung Kim, MD; Kihyun Doo, MD; Ju-Hee Seo, MD, PhD; Yae-Jean Kim, MD, PhD; Yeo Jin Kim, MD; Ji Young Park, MD, PhD; Sun Bok Suh, MD, PhD; Hyunju Lee, MD, PhD; Eun Young Cho, MD; Dong Hyun Kim, MD; Jong Min Kim, MD; Hye Young Kim, MD, PhD; Su Eun Park, MD, PhD; Joon Kee Lee, MD, PhD; Dae Sun Jo, MD, PhD; Seung-Man Cho, MD; Jae Hong Choi, MD; Kyo Jin Jo, MD; Young June Choe, MD, PhD; Ki Hwan Kim, MD; Jong-Hyun Kim, MD, PhD
SP0052 Detection of antigen-specific t cells
Authors: P Bowness
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Antigen-specific T cells are thought to drive the inflammatory response in a number of rheumatic diseases including RA and the spondyloarthropathies. T cells recognise specific combinations of antigenic peptides bound to of HLA molecules, and subsequently proliferate and perform effector functions including cytokine secretion. Techniques have been developed to detect these T cells (usually <i>ex vivo</i> or <i>in vitro</i>), based upon their antigenic specificity, their function, and their clonality. Some techniques combine these attributes. Recently fluorescent-labelled multimers (usually tetramers) of synthetic HLA/peptide combinations have been used to stain T cells of defined antigen specificity. The use of HLA /peptide tetramers has greatly increased our understanding of the role of T cells in viral infections and given some insight into rheumatic diseases. Other techniques have been developed that detect cytokines produced in response to specific antigens (i.e. detecting function), or that detect populations of T cells carrying the same or related T cell receptors. Our ability to detect antigen-specific T cells has important implications for our understanding of disease pathogenesis, and for monitoring disease progress. These methodologies also offer therapeutic potential.
Support for Transition from Adolescent to Adult Health Care Among Adolescents With and Without Mental, Behavioral, and Developmental Disorders — United States, 2016–2017
Authors: Rebecca T. Leeb, Melissa L. Danielson, Rebecca H. Bitsko, Robyn A. Cree, Shana Godfred-Cato, Michelle M. Hughes, Patrick Powell, Bradley Firchow, Laura C. Hart, Lydie A. Lebrun-Harris
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Clinical guidelines recommend that primary care providers (PCPs) provide guidance and support to ensure a planned transition from pediatric to adult health care for adolescents, beginning at age 12 years (1). However, most adolescents do not receive the recommended health care transition planning (2). This is particularly concerning for adolescents with diagnosed mental, behavioral, and developmental disorders (MBDDs) (3), who account for approximately 20% of U.S. adolescents (4). Childhood MBDDs are linked to increased long-term morbidity and mortality; timely health care transition planning might mitigate adverse outcomes (5,6). CDC analyzed pooled, parent-reported data from the 2016 and 2017 National Survey of Children's Health (NSCH), comparing adolescents, aged 12-17 years, with and without MBDDs on a composite measure and specific indicators of recommended health care transition planning by PCPs. Overall, approximately 15% of adolescents received recommended health care transition planning: 15.8% (95% confidence interval [CI] = 14.1%-17.5%) of adolescents with MBDDs, compared with 14.2% (95% CI = 13.2%-15.3%) of adolescents without MBDDs. Relative to peers without MBDDs and after adjusting for age, adolescents with anxiety were 36% more likely to receive recommended health care transition planning, and those with depression were 69% more likely; adolescents with autism spectrum disorder (ASD) were 35% less likely to receive such transition planning, and those with developmental delay* were 25% less likely. Fewer than 20% of adolescents with MBDDs receiving current treatment met the transition measure. These findings suggest that a minority of adolescents with MBDDs receive recommended transition planning, indicating a potential missed public health opportunity to prevent morbidity and mortality in a population at high risk for health care disengagement (1). Improving access to comprehensive and coordinated programs and services,† as well as increasing provider training concerning adolescents' unique mental and physical health care needs (7), could help increase the number of adolescents benefiting from successful health care transitions (4).
First-in-Human study of JNJ-55920839 in healthy volunteers and patients with systemic lupus erythematosus: a randomised placebo-controlled phase 1 trial
Authors: Jarrat Jordan, Jacqueline Benson, Walter Winn Chatham, Richard Alan Furie, William Stohl, James Cheng-Chung Wei, Stanley Marciniak, Zhenling Yao, Bhaskar Srivastava, Jessica Schreiter, Matteo Cesaroni, Ashley Orillion, Loqmane Seridi, Marc Chevrier
Journal: The Lancet Rheumatology (2020)
SAT0112 Variations in population’s pyramids of patients with chronic low back pain in a rural area
Authors: FP Torres, D Ybañez-García, P Pérez-Caballero, M Morales, A Llópis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To analyse the differences in the variables age and sex of patients with chronic low back pain, regarding the general population. <h3>Methods</h3> It was carried a longitudinal study out of the patients that they went to the External Consultation of Rheumatology from the Requena Hospital (Valencia), demanding specialised attendance to present a chronic low back pain, sex and age were picked up. A statistical study was realised determining absolute and relative frequencies, and chi2 test with a level of trust of 95%. <h3>Results</h3> A total of 483 patients were selected, males 146(30.2%) and women 337(69.8%), with a relationship female/male of 0.43. The mean age was of 55.82 ± st 13,32 and range 16–90. In women it was of 56,90 ± st 13,13 and in males of 53,32 ± st 13,47. It was found a significant relationship between age groups and sex (p &lt; 0.05). <h3>Conclusion</h3> Prevalence of the feminine sex, with variations in the age groups. It was more accused after the 65 years old. Regarding the general population, the LBP it's exceptional in patients minor of 35 years and it is more frequent in patients older than 46 years, existing the biggest differences in the groups 46–65 years old. <h3>References</h3> Pérez MS. Diagnóstico de Salud Municipal. Requena. Area de Salud Pública. Diputación de Valencia, 1993:7–36 Reumatos 90?. Estudio sociosanitario sobre las enfermedades reumáticas en España. Gabinete de estudios Pfizer y Liga Reumatologica Española. 1999