tbuckley/cabot-search huggingface dataset:
Mutation in <i>BRAF</i> V600E: A Poor Prognostic Marker in Stage III Colon Cancers With Deficient MMR?—Reply
Authors: Frank A. Sinicrope, Qian Shi, Steven R. Alberts
Journal: JAMA Oncology (2017)

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 Oncology 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 Oncology journal
Colorectal Polyp Surveillance in a Single Gastroenterology Unit
Authors: M UdDin, A Eltayab, M McGrath, M Goepanang, K Nanda, D Long
Journal: Endoscopy (2004)

Introduction: Colorectal cancer is a major cause of mortality and morbidity. The frequency of surveillance colonoscopy is an important clinical problem that demands attention. The American Gastroenterology Association and the British Society of Gastroenterology have suggested increasing interval between colonoscopies in patients with history of colorectal polyps.
Interleukin-21 promotes thymopoiesis recovery following hematopoietic stem cell transplantation
Authors: Aurélie Tormo, Fatemeh Khodayarian, Yun Cui, Edouard Al-Chami, Reem Kanjarawi, Beatriz Noé, Huijie Wang, Moutih Rafei
Journal: Journal of Hematology & Oncology (2017)

Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice. Lymphocyte reconstitution was first assessed using a hematological analyzer and a flow cytometer on collected blood samples. Detailed flow cytometry analysis was then performed on the BM, thymus, and spleen of transplanted animals. Finally, the effect of human IL-21 on thymopoiesis was validated in humanized mice. Using a major histocompatibility complex (MHC)-matched allogeneic BMT model, we found that IL-21 administration improves immune reconstitution by triggering the proliferation of BM Lin−Sca1+c-kit+ (LSK) subsets. The pharmacological effect of IL-21 also culminates in the recovery of both hematopoietic (thymocytes) and non-hematopoietic (stromal) cells within the thymi of IL-21-treated recipient animals. Although T cells derived from all transplanted groups proliferate, secrete various cytokines, and express granzyme B similarly in response to T cell receptor (TCR) stimulation, full regeneration of peripheral naïve CD4+ and CD8+ T cells and normal TCRvβ distribution could only be detected in IL-21-treated recipient mice. Astonishingly, none of the recipient mice who underwent IL-21 treatment developed graft-versus-host disease (GVHD) in the MHC-matched allogeneic setting while the graft-versus-tumor (GVT) effect was strongly retained. Inhibition of GVHD onset could also be attributed to the enhanced generation of regulatory B cells (B10) observed in the IL-21, but not PBS, recipient mice. We also tested the thymopoiesis-stimulating property of human IL-21 in NSG mice transplanted with cord blood (CB) and found significant improvement in de novo human CD3+ T cell development. In sum, our study indicates that IL-21 represents a new class of unforeseen thymopoietin capable of restoring thymic function following BMT.
Современные достижения европейской панкреатологии (по материалам 44-й встречи Европейского клуба панкреатологов)
Authors: N.B. Gubergrits
Journal: GASTROENTEROLOGY (2013)

В статье изложены результаты основных научных исследований в области панкреатологии, проведенных в 2011–2012 гг. Представлены достижения ведущих панкреатологов Европы в изучении этиологии, патогенеза, диагностики, лечения панкреатитов, опухолей поджелудочной железы.
John Richard Newton
Authors: K K Chan
Journal: BMJ (2017)

John Richard Newton obtained his membership of the Royal College of Obstetricians and Gynaecologists within five years of qualifying, collecting the Queen Charlotte’s and Chelsea Hospital Board of Governors research prize along the way. His love for research continued throughout his career and resulted in the publication of 231 peer reviewed papers, 92 other published papers as senior author, six books, and numerous book chapters. John was awarded the Lawson Tait chair of obstetrics and gynaecology at the University of Birmingham in January 1979 and held it until he retired on 1 August 2000. His contribution to family planning and contraception is well known. John was also interested in fertility problems and helped to bring modern fertility treatment …
Consequences of Gene Promoter Hypermethylation in Colorectal Cancer
Authors: EJP Fox, DT Leahy, AM Lennon, R Geraghty, D Keegan, A White, HE Mulcahy, JM Hyland, D Fennelly, DP O'Donoghue, K Sheahan
Journal: Endoscopy (2004)

Background: Promoter hypermethylation of tumour suppressor genes has been established as an important mechanism for gene inactivation. Transcriptional silencing of MGMT by aberrant promoter hypermethylation has been described in a variety of neoplasms, and tumours with high levels of MGMT are likely to be drug-resistant. Promoter hypermethylation of MLH1 has been implicated in a subset of colorectal cancers (CRC) that show microsatellite instability (MSI). We investigated the relationship between MLH1-promoter hypermethylation, MGMT-promoter hypermethylation in a series of colorectal cancers. Design: This study included 110 prospective cases of colorectal cancer. The methylation status of the hMLH1 and MGMT promoters was investigated in each case using methylation-specific PCR. MSI testing was performed using the National Cancer Institute consensus panel of five microsatellite markers. Results were correlated with clinical and pathological features. Results: MGMT-promoter-hypermethylation was detected in 3 of 9 (33%) MSI-H, in 1 of 2 (50%) MSI-L and in 31 of 96 (32%) microsatellite-stable tumours (MSS). MLH1-promoter-hypermethylation was detected in 6 of 9 (66%) MSI-H, in 0 of 2 MSI-L and in 6 of 99 (6%) MSS tumours. Hypermethylation of the MLH1 and MGMT promoters was detected in 18% and 39.5% of cases, respectively. No correlation was detected between hypermethylation of MLH1 or MGMT and tumour site or differentiation. We did observe an inverse correlation between MLH1 and MGMT promoter hypermethylation (p<0.001).
Improved overall survival in daily practice of adjuvant chemotherapy in pancreatic cancer patients: Taiwanese single-center study.
Authors: Shih-Hung Yang, Jhe-Cyuan Guo, Hsu Wu, Yu-Wen Tien, Sung Hsin Kuo
Journal: Journal of Clinical Oncology (2016)

e15719 Background: Although overall survival (OS) benefit of adjuvant chemotherapy had been demonstrated in the CONKO-001 study, the application of it in daily practice of pancreatic cancer patients did not reach a universal consensus. Methods: Pancreatic cancer patients who had received curative surgery were retrospectively reviewed at National Taiwan University Hospital between January 2001 and December 2013. Neuroendocrine tumors were excluded. Results: Three hundred and nineteen patients were identified (M/F: 193/126; median age of years: 66, range 26-91). Preoperative ECOG performance status (PS) was 0-1 in majority (90.6%) of patients. R0 resection was obtained in 257 (80.6%) patients. The majority of patients (N = 275) had ductal adenocarcinoma (Ad) or adenosquamous carcinoma (As). Adjuvant chemotherapy had been administered in 78 (24.5%) patients, mostly with diagnosis after 2005. The regimens were gemcitabine (N = 28), 5-FU/5-FU analog (N = 36), both (N = 12), or unknown (N = 2). Median OS was 21.7 (95% CI: 17.4-26.1) months in the adjuvant(+) group and 15.8 (95% CI: 13.2-18.4) months in the adjuvant(-) group (P = 0.037). The OS benefit was significant not only in the whole study group but also in the Ad/As subgroup. Comparing with adjuvant(-) group, adjuvant chemotherapy neither lowered the recurrence rate (78.2% vs. 68.0%, P = 0.087) nor improved the median recurrence-free survival (RFS, 9.0 months vs. 9.2 months, P = 0.875). The choice of gemcitabine, 5-FU/5-FU analog or combination had no impacts on OS or RFS. In univariate analyses, R1 margin, ECOG PS ≧1, lymphovascular invasion (LVI), pathological T3, pathological N1 and poor differentiation were poor prognostic factors. In the multivariate analysis, including adjuvant chemotherapy, all of these characteristics except LVI were independent prognostic factors. Conclusions: In pancreatic cancer patients with good preoperative ECOG PS, adjuvant chemotherapy with either gemcitabine- or 5-FU/5-FU analog- based regimen should be recommended.
An unusual pelvis radiograph
Authors: Yu Xi Terence Law, Welras Long, King Chien Joe Lee
Journal: BMJ (2017)

A 95 year old woman was admitted to hospital after a fall. She had sustained a hip fracture. She had Alzheimer’s disease, hypertension, and type 2 diabetes mellitus, for which she was taking metformin. A radiograph of the pelvis was obtained (fig 1⇓). Other than the hip fracture, what is the likely diagnosis?



Fig 1  Radiograph of the pelvis



### Answer

#### Short answer

Right femoral neck fracture (incidental finding of emphysematous cystitis).

#### Discussion

The pelvic radiograph shows a ring of radiolucent gas with central mottled lucencies in the expected location of the bladder, suggestive of emphysematous cystitis (fig 2⇓). A right femoral neck …
Long-Term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Chronic Lymphocytic Leukemia (CLL): 10-Year Follow-up of the Gcllsg CLL3X Trial
Authors: Isabelle Krämer, Stephan Stilgenbauer, Sascha Dietrich, Sebastian Böttcher, Matthias Ritgen, Donald Bunjes, Matthias Zeis, Michael Stadler, Joerg Thomas Bittenbring, Ute Hegenbart, Michael Hallek, Michael Kneba, Norbert Schmitz, Hartmut Döhner, Peter Dreger
Journal: Blood (2016)
Abstract 298: CaMKII-Mediated Phosphorylation of InsP3R2 Activates Hypertrophic Gene Transcription
Authors: Sankar Natesan, Joshua T Maxwell, Paul R Hale, Gregory A Mignery
Journal: Circulation Research (2012)

Inositol 1,4,5-triphosphosphate receptors are a family of intracellular Ca2+ channels, modulated by the ligands InsP3 and Ca2+ in response to an array of neuro-hormonal stimuli to release Ca2+ from internal stores. In cardiac myocytes, the InsP3R2, CaMKII and CaM are components of a macromolecular signalplex. However, modulation of InsP3R’s Ca2+ channel and the underlying mechanism(s) that converge and integrate nuclear hypertrophic signals to initiate transcription is not fully established. Here, we delineate the mechanistic regulation of nuclear InsP3R2’s bidirectional Ca2+ channel activity and its effect on the activation of nuclear hypertrophic signaling. We show that, endothelin-1 (ET1) stimulates elevated InsP3 induced Ca2+ release into the nucleus from perinuclear InsP3 receptors. This elevated nuclear Ca2+ release is due to CaMKIIδ mediated phosphorylation of cytoplasmic oriented InsP3R2 inhibiting Ca2+ release to the cytoplasm. This increase in nuclear Ca2+ activates Ca2+ sensitive transctiption factors thereby activating gene expression. The elevated nuclear Ca2+ and gene expression can be attenuated by CaMKII inhibitor KN-93 and InsP3R antagonist 2-ABP. We also show that, exogenous InsP3R2 was phosphorylated by both cytoplasmic (CaMKIIδC) and nuclear (CaMKIIδB) isoforms of CaMKIIδ. Intriguingly, CaMKIIδC phosphorylates endogenous InsP3R2 in cardiomyocytes more efficiently than CaMKIIδB and not by its kinase-dead derivatives. In conclusion, our findings demonstrate that, InsP3R2 mediated Ca2+ signaling integrates and vectors the GPCR activated hypertrophic signals to the nucleus triggering gene transcription underlying cardiac hypertrophy.
Хвороба Гоше (сучасний погляд на проблему)
Authors: V.B. Yagmur
Journal: GASTROENTEROLOGY (2020)

У статті наведений огляд літератури, присвяченої найпоширенішій із лізосомальних хвороб накопичення — хворобі Гоше. Патологія пов’язана з дефектом гена, що кодує фермент глюкоцереброзидазу, яка розщеплює цереброзиди. При зниженні активності ферменту в клітинах ретикулоендотеліальної системи накопичуються сфінголіпіди, здорові клітини заміщаються дефектними. Описано клінічні прояви трьох форм хвороби, алгоритми її діагностики та сучасне специфічне лікування.
Risk factors of pneumothorax in advanced and/or metastatic soft tissue sarcoma patients during pazopanib treatment.
Authors: Kenji Nakano, Noriko Motoi, Junichi Tomomatsu, Tabu Gokita, Keisuke Ae, Taisuke Tanizawa, Takashi Shimoji, Seiichi Matsumoto, Shunji Takahashi
Journal: Journal of Clinical Oncology (2015)

e21527 Background: After the approval of pazopanib for the treatment of STS, pneumothorax was reported as an unexpected adverse event during pazopanib treatment. However, the incidence and risk factors of pneumothorax during pazopanib treatment for STS have not been established yet. Methods: We retrospectively reviewed STS patients treated with pazopanib between November 2012 and December 2014 in our institute and evaluated the incidence, treatment details and risk factors of pneumothorax of STS patients during pazopanib treatment. Results: A total of 58 patients were enrolled; 45 of them had lung and/or pleural lesions at start of pazopanib. Pathological diagnoses were as follows; 13 leiomyosarcoma, 9 synovial sarcoma, 9 liposarcoma, 27 other histologic subtypes. During the median follow-up time of 219 days (range; 23-659), median treatment days of pazopanib were 107 (range; 5-659) and 13 pneumothorax events occurred in 6 patients; the incidence of pneumothorax was 0.56 per treatment-year. The median onset day of pneumothorax was day 95 (range 6-311). No patients died of pneumothorax, but pazopanib was interrupted in 10 events and the chest drainage was necessary in 8 events; pazopanib continuation or restart after the recovery from pneumothorax was able to be performed in 9 of 13 events. The median progression-free survival of patients with and without pneumothorax were 144 and 128 days (p = 0.89) and the median overall survival were 293 and 285 days (p = 0.69), respectively. By logistic regression analyses, the maximum diameter of the lung metastases ≥ 30 mm (hazard ratio = 13.3, 95 % CI; 1.1 – 155.4, p = 0.039) and the presence of past histories of pneumothorax before the pazopanib induction (hazard ratio; 16.6, 95 % CI; 1.1 – 256.1, p = 0.045) were predictive of pneumothorax significantly. Conclusions: Pneumothorax was observed in 10.3 % of STS patients during pazopanib treatment, and the incidence of pneumothorax was 0.56 per treatment-year; there were not significant differences in patients’ prognoses by the presence of pneumothorax. The diameter of lung metastases and the past histories of pneumothorax could be useful for evaluating the risk of pneumothorax in pazopanib treatment.
Mtor expression in carcinoma in situ adjacent to seminoma
Authors: Joan Sweet
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3581 

Background: In the seminiferous tubules (ST), developing germ cells are nourished by Sertoli cells (SC). At puberty, SC mature and form the blood-testis barrier. Dysfunctional germ cells are associated with testicular germ cell tumors (TGCT). Intratubular germ cell neoplasia unclassified (IGCNU) is the precursor lesion of TGCT and an immature SC characterized by staining with low molecular weight keratin (LMWK), has been described in tubules with IGCNU.    mTOR is a Ser/Thr kinase in the PI3K/Akt/mTOR pathway that regulates cell growth and it has been implicated in tumorigenesis. In the testis, the binding of FSH to SC causes the phosphorylation and activation of P70S6K, a transcription factor activated by mTOR which regulates Sertoli/germ cell anchoring junctions and cytoskeleton organization necessary for normal spermatogenesis. S6-RP, a ribosomal protein activated by P70S6K, is indicative of mTOR activity. This study investigates the mTOR pathway by immunohistochemistry (IHC) in IGCNU adjacent to seminoma (SE).    Design: A representative section from each of 10 radical orchiectomy specimens containing SE and adjacent IGCNU was examined by light microsocopy and IHC was performed for the following markers: LMWK, D2-40, mTOR and S6-RP on serial sections. The slides were scanned using the T3 ScanScope by Aperio Technologies (0.5 micrometre /pixel). IGCNU containing tubules were identified by the presence of D2-40 positive cells. IGCNU tubules in three random fields at 7x magnification were examined for staining with LMWK, p-mTOR (Ser 2448) and S6RP.    Result: D2-40 stained IGCNU cells and SE. LMWK stained immature SC in the seminiferous tubules (ST). An average of 30% of SC in IGCNU tubules per field were positive for LMWK, 11% of SC in IGCNU tubules for mTOR and 34% of SC in IGCNU tubules for S6-RP. Staining for all antibodies in the same tubule was seen in 6% of IGCNU tubules, indicating that mTOR and S6-RP stain a select proportion of SC in ST containing immature SC.    Conclusion: Mature SC are required for germ cell maturation and spermatogenesis. Therefore, the persistence of immature SC in IGCNU may be involved in the pathogenesis of TGCT. mTOR has been implicated in the cell adhesion between SC and spermatids in the seminiferous epithelium. The expression of mTOR in immature SC may indicate dysregulation of maturation with abnormal SC-germ cell adhesion and may be involved in tumorigenesis. Since Rapamycin is an inhibitor of mTOR, these findings may have implications for the therapy of IGCNU.
Infection Exposure Promotes<i>ETV6-RUNX1</i>Precursor B-cell Leukemia via Impaired H3K4 Demethylases
Authors: Guillermo Rodríguez-Hernández, Julia Hauer, Alberto Martín-Lorenzo, Daniel Schäfer, Christoph Bartenhagen, Idoia García-Ramírez, Franziska Auer, Inés González-Herrero, Lucia Ruiz-Roca, Michael Gombert, Vera Okpanyi, Ute Fischer, Cai Chen, Martin Dugas, Sanil Bhatia, René Martin Linka, Marta Garcia-Suquia, María Victoria Rascón-Trincado, Angel Garcia-Sanchez, Oscar Blanco, Maria Begoña García-Cenador, Francisco Javier García-Criado, César Cobaleda, Diego Alonso-López, Javier De Las Rivas, Markus Müschen, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt
Journal: Cancer Research (2017)

Abstract ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B-cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here, we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/precursor cells (HSC/PC) and postnatal infections for human-like pB-ALL. In our model, ETV6-RUNX1 conferred a low risk of developing pB-ALL after exposure to common pathogens, corroborating the low incidence observed in humans. Murine preleukemic ETV6-RUNX1 pro/preB cells showed high Rag1/2 expression, known for human ETV6-RUNX1 pB-ALL. Murine and human ETV6-RUNX1 pB-ALL revealed recurrent genomic alterations, with a relevant proportion affecting genes of the lysine demethylase (KDM) family. KDM5C loss of function resulted in increased levels of H3K4me3, which coprecipitated with RAG2 in a human cell line model, laying the molecular basis for recombination activity. We conclude that alterations of KDM family members represent a disease-driving mechanism and an explanation for RAG off-target cleavage observed in humans. Our results explain the genetic basis for clonal evolution of an ETV6-RUNX1 preleukemic clone to pB-ALL after infection exposure and offer the possibility of novel therapeutic approaches. Cancer Res; 77(16); 4365–77. ©2017 AACR.
When Somatic Mutations Are Associated With a Higher Aggressive Behavior—A Story of Announced Evidence
Authors: Esther Diana Rossi, Maurizio Martini, Luigi Maria Larocca
Journal: JAMA Oncology (2017)

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 Oncology 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 Oncology journal
NSAIDs for Chronic Low Back Pain
Authors: Wendy T. M. Enthoven, Pepijn D. Roelofs, Bart W. Koes
Journal: JAMA (2017)

<h3>Clinical Question</h3> Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with greater pain relief than placebo, other drugs, and nondrug treatments for patients with chronic low back pain? <h3>Bottom Line</h3> Compared with placebo, NSAIDs are associated with a small but significant improvement in pain and disability in patients with chronic low back pain, although this difference became nonsignificant when studies with high risk for bias were excluded. The associated benefits were smaller than the minimal clinically important difference.