tbuckley/cabot-search huggingface dataset:
Molecular targeting of IGF-I receptor for human pancreatic cancer
Authors: Y. Adachi, H. Yamamoto, A. Imsumran, Y. Wang, R. Li, Y. Min, Y. Arimura, C. Lee, Y. Shinomura, D. P. Carbone, K. Imai
Journal: Journal of Clinical Oncology (2007)

14051 Background: Pancreatic cancer is one of the worst prognostic diseases. Continuous tumor growth depends on the altered regulation of the cell cycle that is modulated by signals from growth factors and their receptors, including insulin-like growth factors (IGF) and IGF-I receptor (IGF-Ir). It have been reported that blockade of IGF-Ir can suppress tumorigenicity and induce regression of established tumors. Recently several approaches of targeting IGF-Ir have been reported, including monoclonal antibodies and tyrosine kinase inhibitors. Methods: To study the mechanism of this effect and develop potential targeted therapeutics, we have constructed truncated IGF-Irs that function as dominant negative inhibitor (IGF-Ir/dn) and short hairpin RNA for IGF-Ir (shIGF-Ir). Those were cloned into recombinant adenoviruses (ad-IGF-Ir/dn and ad-shIGF-Ir). The effects of these adenoviruses were studied in human pancreatic cancer cell lines, BxPC3, Panc1, and AsPC1. We assessed efficiency of IGF-Ir signaling blockade, the effect of the adenoviruses on cell growth, steady-state, radiation, and chemotherapy induced apoptosis, and in vivo therapeutic efficacy in xenografts. Results: The blockade for IGF-Ir suppressed tumorigenicity of cancer cells both in vitro and in vivo and increased the amount of steady-state apoptosis in cancer cells. IGF-Ir/dn effectively blocked both IGF-I and IGF-II signaling through Akt-1 and shIGF-Ir reduced both IGF-Ir expression and ligands inducing phosphorylaion. The blockade for IGF-Ir increased chemotherapy and radiation induced apoptosis in vitro and the combination therapy with chemotherapy was very effective against established tumors in mice. Conclusions: These data suggest that the blocking of IGF-Ir signals, by ad-IGF-Ir/dn or ad-shIGF-Ir, may be a useful therapeutic strategy for pancreatic cancers. No significant financial relationships to disclose.
Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma
Authors: Lise M. Lindahl, Andreas Willerslev-Olsen, Lise M. R. Gjerdrum, Pia R. Nielsen, Edda Blümel, Anne H. Rittig, Pamela Celis, Bjorn Herpers, Jürgen C. Becker, Birgitte Stausbøl-Grøn, Mariusz A. Wasik, Maria Gluud, Simon Fredholm, Terkild B. Buus, Claus Johansen, Claudia Nastasi, Lukas Peiffer, Linda Kubat, Michael Bzorek, Jens O. Eriksen, Thorbjørn Krejsgaard, Charlotte M. Bonefeld, Carsten Geisler, Tomas Mustelin, Erik Langhoff, Michael Givskov, Anders Woetmann, Mogens Kilian, Thomas Litman, Lars Iversen, Niels Odum
Journal: Blood (2019)
We are falling behind on TB elimination targets: can whole-genome sequencing guide our efforts?
Authors: Nicole Wheeler
Journal: Thorax (2019)

TB remains a leading cause of morbidity and mortality worldwide, despite international eradication efforts. The WHO’s ‘End Tuberculosis Strategy’ set the ambitious goal of achieving a 90% reduction in the incidence by the year 2035; yet, we are currently only achieving a 2% reduction per year.1 There is a pressing need to develop more effective control strategies in order to meet this target. A major challenge to eradication efforts is the increasing proportion of TB infections that are resistant to antibiotics.2 Approximately half a million new cases of multidrug-resistant TB (MDR-TB) emerge each year, and of these, approximately 8.5% are classed as extensively drug-resistant (XDR).2 Because MDR-TB is difficult to treat at the individual level, targeting the key drivers of this increase is important for curbing resistance. To do this, we need a clear understanding of what these key drivers are.

Identifying drug resistance in TB cases is challenging, due to the expense of diagnosis, the time required for culture-based methods (weeks to months) and the lack of standardisation of testing methods for some second-line drugs.3 This delay in identification prolongs the opportunity for these strains to transmit to others. Whole-genome sequencing (WGS) has improved in cost and throughput, allowing an increase in its use.4 Resistance emerges predominantly through mutation,5 making TB a relatively simple paradigm for WGS identification of resistance. Thanks to a growing understanding of the mechanisms underlying resistance, we are now able to detect most MDR-TB (87%–89%) and XDR-TB (77%–79%) using WGS data.5 In line with these advances, large genomic collections of TB spanning different countries are being released, and used to study resistance.6 In this issue of Thorax , Cohen et al 7 explore the value of combining these large collections to trace the global emergence and spread …
A Study of Illness in a Group of Cleveland Families
Authors: William S. Jordan, David Stevens, Sidney Katz, John H. Dingle
Journal: New England Journal of Medicine (1956)

THE continuing development and improvement of tissue-culture methods have simplified the study of infectious agents, such as poliomyelitis1 , 2 and Coxsackie3 viruses, originally isolated in animal hosts, and have made possible the primary isolation of previously unidentified viruses.4 5 6 7 Of the last group, some, often referred to as "orphan" viruses, have not yet been related clearly to disease6 , 7; others, variously designated as the adenoidal-degeneration (AD), respiratory-infection (RI), acute-respiratory-disease (ARD) or adenoidal-pharyngeal-conjunctival (APC) group of viruses,4 , 5 , 8 9 10 11 have been related etiologically to certain respiratory diseases.8 9 10 11 12 13 Interest in this new group of respiratory viruses prompted a study of their role in the causation of . . .
Real-time dynamic and sequential tracking of tumor propagation and associated immune responses in the CNS microenvironment.
Authors: Alex Yee-Chen Huang, Jay T. Myers, Youmna Othman, Deborah Sim Barkauskas, Agne Petrosiute
Journal: Journal of Clinical Oncology (2012)

9520 Background: Ex vivo experimental systems are often unable to fully capture complex intercellular communication between tumor cells and surrounding tissues - a critical feature in understanding cancer development and immune evasion. Imaging modality such as bioluminescence lacks the resolution necessary to discern subtle structural differences and heterogeneity in the tumor niche. Microscopic examination of fixed specimens is devoid of the 3-dimensional context or evolution of tumor progression within the same host. Methods: New insights have come from studies involving the use of intravital 2-photon laser scanning microscopy (2P-LSM), which allows deep visualization (&gt;300um) with single-cell resolution (&lt;1um), thus enables direct observation of cellular behavior in intact tissues at a suitable dynamic spatial-time resolution. We study the role of tumor niche in shaping immune repertoire and develop strategies to modify tumor niche to enhance anti-tumor immunity. Results: One example is our study of glioblastoma multiforme (GBM), which contains a cellular hierarchy with a CD133+ sub-population representing self-renewing and tumorigenic GBM stem cells (GSCs). In a xeno-transplant model, GSC was capable of tumor initiation in the mouse brain. To directly test the relative tumorigenic potential of GSCs (CD133+) and non-GSCs (CD133 - ), we inoculated paired tumor populations from the same primary GBM tumor cells and monitored tumor competition by serial 2P-LSM through implanted cranial windows. Serial 2P-LSM imaging shows that after 35 days, GBM formation was driven exclusively by GSCs but not non-GSCs. To interrogate tumor-associated immune responses, we inoculated syngeneic mouse glioma tumors into C57BL/6 mice. Using this and CNS-inflammatory models, we have begun to undercover the role of perivascular antigen-presenting cells and microglia in guiding the recruitment of CNS-bound lymphocytes. Conclusions: Our data provide the first direct functional evidence that CSCs are responsible for tumor propagation in GBM, and represent an in vivo experimental platform to monitor immunotherapeutic interventions.
Combined effects of targeting angiogenesis with bevacizumab and the VEGF signaling inhibitor AZD2171 in a xenograft model of human head and neck cancer
Authors: Alexandre Bozec, Frederique Penault-Llorca, Patricia Formento, Clelia Dental, jean-louis fischel, Gerard Milano
Journal: Cancer Research (2007)

2120  Most anti-angiogenic agents target vascular endothelial growth factor-A (VEGF) or the VEGF receptor-2 (VEGFR-2). To investigate the effects of combining these two approaches, we evaluated the in vivo anti-tumor efficacy of bevacizumab, a highly specific monoclonal antibody directed against VEGF, and AZD2171, an oral, highly potent and selective VEGF signaling inhibitor of all VEGFR tyrosine kinases (VEGFR-1, -2 and -3). Investigations were performed using a VEGF-secreting human head and neck tumor cell line, CAL33, injected in the flank of 6-week-old female nude mice. When mean tumor volume reached 250 mm3, mice received bevacizumab (5 mg/kg/day i.p.), AZD2171 (2.5 mg/kg/day p.o.) or the combined regimen for 12 days. The drug interaction on tumor growth was analyzed using the combination ratio (CR): CR=FTvAZD2171x FTvbevacizumab/FTvAZD2171+bevacizumab, where FTv is the fractional tumor volume. Both AZD2171 and bevacizumab strongly inhibited tumor growth and the combination of both drugs produced an additive effect (CR=0.8±0.09). Tumor growth was measured in animals (n=5/treatment group) that were not sacrificed at the end of treatment period. The effects were longer lasting post treatment with bevacizumab with or without AZD2171 compared with AZD2171 alone. The results on tumor growth were paralleled by immunohistochemical data with an increase in tumor necrosis and the number of necrotic tumor vessels, and an inhibition of tumor cell proliferation (Ki67). Time-dependent changes in these parameters were influenced more rapidly and strongly by AZD2171 than bevacizumab, with the combination producing greater than additive effects. As AZD2171 showed direct anti-proliferative effects on tumor cells at concentrations that were 20,000 fold higher than that required for comparable inhibition of VEGF-stimulated HUVEC proliferation(IC50=8 µM on CAL33 in vitro), such a direct effect on tumor cell could not explain the observed in vivo effect. In summary, the combination of bevacizumab and AZD2171 showed additive and greater than additive effects on tumor growth inhibition and tumor/vessel necrosis, respectively. These preclinical data suggest that combining these two anti-angiogenic agents may be of interest in the clinical setting.
Prehospital Hemorrhage Control—Leveraging Successes From Cardiac Arrest to Optimize Population-Level Effectiveness
Authors: Jason Haukoos, Comilla Sasson
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Markers of microbial exposure lower the incidence of atopic dermatitis
Authors: Liliane Chatenoud, Paola Bertuccio, Federica Turati, Carlotta Galeone, Luigi Naldi, Lucienne Chatenoud, Carlo La Vecchia, Jean‐François Bach
Journal: Allergy (2019)

Abstract Background The hygiene hypothesis proposes that reduced exposure to infectious agents in early life would explain the increase of allergic and autoimmune diseases observed over the past decades in high‐income countries. Methods We conducted a matched case‐control study on incident atopic dermatitis (AD). Cases were 426 outpatient children with a first diagnosis of incident AD. Controls were 426 children attending a pediatric/dermatological visit for nonatopic disorders matched to cases (1:1). Particular attention was paid to the time elapsed between the markers of microbial exposure and disease onset, and we considered for controls the same time window of exposures from birth as his/her matched case. Odds ratios (ORs) were computed using multivariable conditional logistic regression models, according to center, sex, age, and period of enrollment, and including as potential confounders a family history of any allergy in parents, type of delivery, having siblings, keeping pets, age at weaning, and having had ≥4 infections. Results The OR of AD first occurrence was 0.35 ( P ‐value = .039) for children who had experienced ≥4 infections compared with those with no infections. A decreasing trend in risk was observed with increasing number of siblings ( P ‐value = .023), the protective effect reaching about 40% for children with 2 or more siblings (OR = 0.62; P ‐value = .048). Pet keeping, in particular daily contact with dogs, was inversely associated with AD risk (OR = 0.40; P ‐value = .004). Conclusions These results support the hygiene hypothesis in its broad sense. Early‐life environmental exposures, including pathogens and commensals, act as “microbes contact carriers” influencing immune system balance early in life.
Impaired plasma membrane localization of ubiquitin ligase complex underlies 3-M syndrome development
Authors: Pu Wang, Feng Yan, Zhijun Li, Yanbao Yu, Scott E. Parnell, Yue Xiong
Journal: Journal of Clinical Investigation (2019)

3-M primordial dwarfism is an inherited disease characterized by severe pre- and postnatal growth retardation and by mutually exclusive mutations in three genes, CUL7, OBSL1, and CCDC8. The mechanism underlying 3-M dwarfism is not clear. We showed here that CCDC8, derived from a retrotransposon Gag protein in placental mammals, exclusively localized on the plasma membrane and was phosphorylated by CK2 and GSK3. Phosphorylation of CCDC8 resulted in its binding first with OBSL1, and then CUL7, leading to the membrane assembly of the 3-M E3 ubiquitin ligase complex. We identified LL5β, a plasma membrane protein that regulates cell migration, as a substrate of 3-M ligase. Wnt inhibition of CCDC8 phosphorylation or patient-derived mutations in 3-M genes disrupted membrane localization of the 3-M complex and accumulated LL5β. Deletion of Ccdc8 in mice impaired trophoblast migration and placental development, resulting in intrauterine growth restriction and perinatal lethality. These results identified a mechanism regulating cell migration and placental development that underlies the development of 3-M dwarfism.
Current and Future Imaging Methods for Evaluating Response to Immunotherapy in Neuro-Oncology
Authors: Benjamin B. Kasten, Neha Udayakumar, Jianmei W. Leavenworth, Anna M. Wu, Suzanne E. Lapi, Jonathan E. McConathy, Anna G. Sorace, Asim K. Bag, James M. Markert, Jason M. Warram
Journal: Theranostics (2019)

Imaging plays a central role in evaluating responses to therapy in neuro-oncology patients.The advancing clinical use of immunotherapies has demonstrated that treatment-related inflammatory responses mimic tumor growth via conventional imaging, thus spurring the development of new imaging approaches to adequately distinguish between pseudoprogression and progressive disease.To this end, an increasing number of advanced imaging techniques are being evaluated in preclinical and clinical studies.These novel molecular imaging approaches will serve to complement conventional response assessments during immunotherapy.The goal of these techniques is to provide definitive metrics of tumor response at earlier time points to inform treatment decisions, which has the potential to improve patient outcomes.This review summarizes the available immunotherapy regimens, clinical response criteria, current state-of-the-art imaging approaches, and groundbreaking strategies for future implementation to evaluate the anti-tumor and immune responses to immunotherapy in neuro-oncology applications.
Rate of Reoperation Decreased Significantly After Year 2002 in Patients With Crohn's Disease
Authors: Takahide Shinagawa, Keisuke Hata, Hiroki Ikeuchi, Kouhei Fukushima, Kitaro Futami, Akira Sugita, Motoi Uchino, Kazuhiro Watanabe, Daijiro Higashi, Hideaki Kimura, Toshimitsu Araki, Tsunekazu Mizushima, Michio Itabashi, Takeshi Ueda, Kazutaka Koganei, Koji Oba, Soichiro Ishihara, Yasuo Suzuki
Journal: Clinical Gastroenterology and Hepatology (2019)
Anti‐CD19 chimeric antigen receptor‐modified T‐cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B‐cell acute lymphoblastic leukemia: An open‐label pragmatic clinical trial
Authors: Huiwen Jiang, Chenggong Li, Ping Yin, Tao Guo, Lin Liu, Linghui Xia, Yaohui Wu, Fen Zhou, Lisha Ai, Wei Shi, Xuan Lu, Huafang Wang, Lu Tang, Qiuzhe Wei, Jun Deng, Runming Jin, Wei Xiong, Jian Dong, Heng Mei, Yu Hu
Journal: American Journal of Hematology (2019)

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD- CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD- CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD- CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.
Monitoring of Cell Layer Integrity with a Current‐Driven Organic Electrochemical Transistor
Authors: Leona V. Lingstedt, Matteo Ghittorelli, Maximilian Brückner, Jonas Reinholz, N. Irina Crăciun, Fabrizio Torricelli, Volker Mailänder, Paschalis Gkoupidenis, Paul W. M. Blom
Journal: Advanced Healthcare Materials (2019)

Abstract The integrity of CaCo‐2 cell barriers is investigated by organic electrochemical transistors (OECTs) in a current‐driven configuration. Ion transport through cellular barriers via the paracellular pathway is modulated by tight junctions between adjacent cells. Rupturing its integrity by H 2 O 2 is monitored by the change of the output voltage in the transfer characteristics. It is demonstrated that by operating the OECT in a current‐driven configuration, the sensitive and temporal resolution for monitoring the cell barrier integrity is strongly enhanced as compared to the OECT transient response measurement. As a result, current‐driven OECTs are useful tools to assess dynamic and critical changes in tight junctions, relevant for clinical applications as drug targeting and screening.
Breast cancer in the young (≤35 years): A single center study from the All India Institute of Medical Sciences.
Authors: Vinod Raina, Ajay Gogia, B. K. Mohanti, S. V. S. Deo, N. K. Shukla, Vishnu kumar Sreenivas
Journal: Journal of Clinical Oncology (2013)

e12539 Background: Breast cancer in young women (&lt;/= 35 years) is uncommon and accounts for 1-2 % of all breast cancer in the West. There is limited data on breast cancer in the young from India. The aim of our study was to assess clinical, pathological parameters and outcome in young breast cancer patients. Methods: We carried out an analysis of 271 patients of young breast cancer patients (&lt;/=35 years) registered between 2000 to 2012 at I.R.C.H, AIIMS, New Delhi, India. Results: The median age was 31 years (range 18-35). The median duration of symptoms was 10 months (range 0.25-60). Breast lump was the commonest (93%) presenting symptom (left &gt;right side). Ninety percent of patients were married and median age at first child birth was 23 years. Positive family history was elicited in only 15 patients. The TNM stage distribution was: stage I was 3 %, stage II- 20%, stage III- 55%, and stage IV- 22%. The median clinical tumour size was 5.1 cm. Modified radical mastectomy was the commonest surgical procedure and this was done in 80 % of cases. The histopathological analysis showed 93% had infiltrating ductal carcinoma. Thirty percent of tumours were high grade and 55% had pathological node positive disease. ER/PR and her-2neu positivity was 33% and 30% respectively. Triple negative breast cancer (TNBC) constituted 33%. Fifty five patients presented with metastasis. A combination of anthracycline and taxanes were used in the majority of patients and Trastuzumab could be used only in 6 cases out of 72 patients who were Her-2 neu positive. With a median follow up of 30 months (non metastatic group), three years disease free survival (DFS) and overall survival (OS) was 50% and 60%. Higher nodal stage, tumour size (&gt;5 cm), negative hormonal status (triple negative) and visceral metastasis at baseline predicted poor outcome. Conclusions: Young women constituted 8 % of breast cancer cases, this proportion is much higher than the published Western figures of 1-2 % and reflects younger age of our population. Even in this young group ER/ PR positivity was 33% and almost a third were her-2 neu positive. Higher nodal stage, tumour size (&gt;5 cm), triple negativity and visceral metastasis at baseline predicted poor outcome.