tbuckley/cabot-search huggingface dataset:
Prediction of the non-sentinel node metastasis in patients without clinically axillary lymph node metastasis, with implication of breast cancer subtypes.
Authors: Shusei Tominaga
Journal: Journal of Clinical Oncology (2012)

e13060 Background: The accuracy of the nomogram about non-sentinel lymph node metastasis (NSLNM ) in breast cancer patients is still controversial to avoid axillary dissection particularly sentinel lymph node biopsy was positive. The aim of this study was to evaluate the necessity of adding breast cancer subtypes to the NSLNM nomgram variables. Methods: Between 2009 and 2011, consecutive breast cancer patients without clinically axillary lymph node metastasis (n=140) who received sentinel lymph node biopsy at Higashiosaka General Hospital were studied retrospectively. Twenty-two patients were turned out that breast cancer already spread to the sentinel nodes and all of 22 patients received complete axillary lymph node dissection. Results: Twelve patients had only sentinel lymph node metastases(Group S), 10 patients had non-SLN metastases (Group A). Patient characteristics and average probability of spread to additional lymph node developed by Memorial Sloan-Kettering Cancer Center (MSKCC) Nomogram were almost the same results in both groups. However, subtypes of Group S consisted of 8 HER2 positive , 2 triple negative, and 2 luminal A cases, subtypes of Group A consisted of 4 luminal A and 6 luminal B cases. Conclusions: Our data suggested that luminal type breast cancer tends to spread to non-sentinel lymph node metastasis and adding HER2, Ki-67, and intrinsic biological subtypes may improve predictivity of MSKCC nomogram.
Effects of Intermittent Fasting on Health, Aging, and Disease
Authors: Rafael de Cabo, Mark P. Mattson
Journal: New England Journal of Medicine (2019)

Evidence is accumulating that eating in a 6-hour period and fasting for 18 hours can trigger a metabolic switch from glucose-based to ketone-based energy, with increased stress resistance, increased longevity, and a decreased incidence of diseases, including cancer and obesity.
Human IgA binds a diverse array of commensal bacteria
Authors: Delphine Sterlin, Jehane Fadlallah, Olivia Adams, Claire Fieschi, Christophe Parizot, Karim Dorgham, Asok Rajkumar, Gaëlle Autaa, Hela El-Kafsi, Jean-Luc Charuel, Catherine Juste, Friederike Jönsson, Thomas Candela, Hedda Wardemann, Alexandra Aubry, Carmen Capito, Hélène Brisson, Christophe Tresallet, Richard D. Cummings, Martin Larsen, Hans Yssel, Stephan von Gunten, Guy Gorochov
Journal: The Journal of Experimental Medicine (2019)

In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1−IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota.
Comparing treatment effects of a convenient vibratory positional device to CPAP in positional OSA: a crossover randomised controlled trial
Authors: Yingjuan Mok, Alvin Tan, Pon Poh Hsu, Audrey Seow, Yiong Huak Chan, Hang Siang Wong, Yvonne Poh, Keith K H Wong
Journal: Thorax (2020)

Objectives Up to 77% of patients with obstructive sleep apnoea (OSA) have positional OSA (POSA) but traditional positional therapy (PT) methods have failed as they were poorly tolerated. New convenient vibratory PT devices have been invented but while recent studies suggest high treatment efficacy and adherence, there are no published data comparing these devices directly with continuous positive airway pressure (CPAP). Our objective is to evaluate if a convenient vibratory PT device is non-inferior to CPAP in POSA treatment. Methods In this crossover randomised controlled trial, we enrolled patients with POSA with significant daytime sleepiness (Epworth Sleepiness Scale (ESS)≥10). POSA diagnosis was based on: (1) total Apnoea/Hypopnoea Index (AHI)&gt;10/hour and non-supine AHI&lt;10/hour (2) supine AHI≥2 × non-supine AHI. Patients used their initial allocated devices (PT or CPAP) for 8 weeks before crossing to the alternative intervention after a 1 week washout. The primary aim is to measure changes in ESS between the two treatments. Secondary outcomes include sleep study parameters and patient treatment preference (ClinicalTrials.gov: NCT03125512 ). Results 40 patients completed the trial between April 2017 and December 2018. Difference in ESS after 8 weeks of device use (PT minus CPAP) was 2.0 (95% CI 0.68 to 3.32), exceeding our predetermined non-inferiority margin of 1.5. AHI on CPAP was lower than with PT (4.0±3.2 vs 13.0±13.8 events/hour, respectively, p=0.001), although both were lower than at baseline. Time spent supine was significantly lower with PT than CPAP (p&lt;0.001). 60% of patients preferred CPAP, 20% preferred PT, while 20% preferred neither device. Conclusions The non-inferiority ESS endpoint for PT compared with CPAP was not met and the results were inconclusive. Future trials with larger sample sizes or in less symptomatic patients are warranted to provide further insight into the role of these new vibratory PT devices.
Seroprevalence of Aspergillus IgG and disease prevalence of chronic pulmonary aspergillosis in a country with intermediate burden of tuberculosis: a prospective observational study
Authors: M.-R. Lee, H.-L. Huang, L.-C. Chen, H.-C. Yang, J.-C. Ko, M.-H. Cheng, I.-W. Chong, L.-N. Lee, J.-Y. Wang, G. Dimopoulos
Journal: Clinical Microbiology and Infection (2020)

Chronic pulmonary aspergillosis (CPA) is an emerging global disease with tuberculosis (TB) being the most important risk factor. Epidemiologic data on the seroprevalence of Aspergillus IgG and prevalence of CPA in different areas, especially in country with intermediate burden of TB, are lacking.We prospectively recruited healthy volunteers, TB close contacts, active TB patients and participants with old pulmonary TB in Taiwan during 2012-2019. We measured serum Aspergillus fumigatus and niger-specific IgG levels and assessed if the participants were having CPA.A total of 1242 participants (including 200 healthy volunteers, 326 TB close contacts, 524 active TB patients and 192 old TB cases) were recruited. Using 27 mgA/L (milligrams of antigen-specific antibodies per liter) as cut-off level, the seropositive rate of A. fumigatus-specific IgG was 33.0% (66/200), 37.7% (123/326), 26.5% (139/524) and 43.2% (83/192) among the four groups, respectively. In multivariate logistic regression, pulmonary cavitation (OR 1.73; 95% CI 1.07-2.80), female sex (OR 1.49; 95% CI 1.14-1.95), old TB (OR 1.59; 1.05-2.42) were independent risk factors for Aspergillus IgG positivity. One (0.2%) active TB patient and four (2.1%) old TB patients developed CPA. Correlation between A. fumigatus and A. niger-specific IgG was high (Spearman correlation coefficient: 0.942).Geographic variation in Aspergillus IgG seroprevalence and CPA prevalence exists. A universal cut-off value for Aspergillus IgG may not exist. In areas and populations in which background Aspergillus IgG level is unknown, Aspergillus IgG may be better used as a test of exclusion for CPA using prespecified cut-off level.
Biointerface engineering nanoplatforms for cancer-targeted drug delivery
Authors: Huaiyu Zhang, Shujun Dong, Zhongmin Li, Xiangru Feng, Weiguo Xu, Catrina Mae S. Tulinao, Yang Jiang, Jianxun Ding
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Over the past decade, nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy. Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis. Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery. Keeping in mind the biological framework of the tumor microenvironment, biomembrane-camouflaged nanoplatforms have been a research focus, reflecting their superiority in cancer targeting. In this review, we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancer-targeted drug delivery, which are classified according to the membranes from different cells. The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.
Значение экстрацеллюлярных везикул в патогенезе и диагностике неалкогольной жировой болезни печени (обзор литературы)
Authors: Yu.M. Stepanov, O.Yu. Lukianenko
Journal: GASTROENTEROLOGY (2019)

Экстрацеллюлярные везикулы (ЭВ) — это небольшие мембранные везикулы, выделяемые клетками во внеклеточную среду. ЭВ представлюют собой коммуникационные молекулы и могут влиять на целый ряд целевых клеток в окружающей их клеточной среде, а также могут оказывать дистанционное действие. ЭВ рассматриваются в качестве высокочувствительных биомаркеров хронических заболеваний печени. В статье приведен обзор современных литературных данных о роли ЭВ в патогенезе неалкогольной жировой болезни печени (НАЖБП), а также диагностическом значении ЭВ в разрезе НАЖБП. Рассмотрены вопросы классификации ЭВ, строение ЭВ, описаны молекулы, входящие в состав ЭВ. Уделено внимание особенностям идентификации ЭВ в сыворотке крови. Подробно рассмотрены вопросы роли ЭВ в формировании и развитии НАЖБП. В cтатье показано, что в прогрессировании НАЖБП имеют значение как ЭВ, происходящие из гепатоцитов, так и внепеченочные и бактериальные ЭВ. Показано, что значение ЭВ при НАЖБП не ограничивается формированием дисметаболических изменений, а включает развитие воспаления и фиброза печени. С другой стороны, ЭВ могут использоваться в качестве транспортеров экзогенных молекул РНК в клетки печени. ЭВ-ассоциированные ncRNA уверенно признаются в качестве важных регуляторов биологических процессов как в физиологических, так и в патологических условиях.
Unshielding Multidrug Resistant Cancer through Selective Iron Depletion of P-Glycoprotein–Expressing Cells
Authors: Mihály Cserepes, Dóra Türk, Szilárd Tóth, Veronika F.S. Pape, Anikó Gaál, Melinda Gera, Judit E. Szabó, Nóra Kucsma, György Várady, Beáta G. Vértessy, Christina Streli, Pál T. Szabó, Jozsef Tovari, Norbert Szoboszlai, Gergely Szakács
Journal: Cancer Research (2019)

Abstract Clinical evidence shows that following initial response to treatment, drug-resistant cancer cells frequently evolve and, eventually, most tumors become resistant to all available therapies. We compiled a focused library consisting of &amp;gt;500 commercially available or newly synthetized 8-hydroxyquinoline (8OHQ) derivatives whose toxicity is paradoxically increased rather than decreased by the activity of P-glycoprotein (Pgp), a transporter conferring multidrug resistance (MDR). Here, we deciphered the mechanism of action of NSC297366 that shows exceptionally strong Pgp-potentiated toxicity. Treatment of cells with NSC297366 resulted in changes associated with the activity of potent anticancer iron chelators. Strikingly, iron depletion was more pronounced in MDR cells due to the Pgp-mediated efflux of NSC297366–iron complexes. Our results indicate that iron homeostasis can be targeted by MDR-selective compounds for the selective elimination of multidrug resistant cancer cells, setting the stage for a therapeutic approach to fight transporter-mediated drug resistance. Significance: Modulation of the MDR phenotype has the potential to increase the efficacy of anticancer therapies. These findings show that the MDR transporter is a “double-edged sword” that can be turned against resistant cancer.
Origin and Evolution of Carboxysome Positioning Systems in Cyanobacteria
Authors: Joshua S MacCready, Joseph L Basalla, Anthony G Vecchiarelli
Journal: Molecular Biology and Evolution (2019)

Carboxysomes are protein-based organelles that are essential for allowing cyanobacteria to fix CO2. Previously, we identified a two-component system, McdAB, responsible for equidistantly positioning carboxysomes in the model cyanobacterium Synechococcus elongatus PCC 7942 (MacCready JS, Hakim P, Young EJ, Hu L, Liu J, Osteryoung KW, Vecchiarelli AG, Ducat DC. 2018. Protein gradients on the nucleoid position the carbon-fixing organelles of cyanobacteria. eLife 7:pii:e39723). McdA, a ParA-type ATPase, nonspecifically binds the nucleoid in the presence of ATP. McdB, a novel factor that directly binds carboxysomes, displaces McdA from the nucleoid. Removal of McdA from the nucleoid in the vicinity of carboxysomes by McdB causes a global break in McdA symmetry, and carboxysome motion occurs via a Brownian-ratchet-based mechanism toward the highest concentration of McdA. Despite the importance for cyanobacteria to properly position their carboxysomes, whether the McdAB system is widespread among cyanobacteria remains an open question. Here, we show that the McdAB system is widespread among β-cyanobacteria, often clustering with carboxysome-related components, and is absent in α-cyanobacteria. Moreover, we show that two distinct McdAB systems exist in β-cyanobacteria, with Type 2 systems being the most ancestral and abundant, and Type 1 systems, like that of S. elongatus, possibly being acquired more recently. Lastly, all McdB proteins share the sequence signatures of a protein capable of undergoing liquid-liquid phase separation. Indeed, we find that representatives of both McdB types undergo liquid-liquid phase separation in vitro, the first example of a ParA-type ATPase partner protein to exhibit this behavior. Our results have broader implications for understanding carboxysome evolution, biogenesis, homeostasis, and positioning in cyanobacteria.
Minding the Gap for Survivors of Childhood Cancer
Authors: Stephanie M. Smith, Michael P. Link, Karen E. Effinger
Journal: JAMA Oncology (2020)

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
Heterogeneity of Diffuse Histiocytic Lymphoma According to the Kiel Classification
Authors: P Meusers, H Bartels, G Brittinger, H Common, E Dühmke, H H Fülle, U Gunzer, R Heniz, E König, K Musshoff, H Pralle, U Schmalhorst, H Theml, G R Krüger, K Lennert
Journal: New England Journal of Medicine (1979)
Single Hormone Receptor–Positive Breast Cancer—Signal or Noise?
Authors: Vasily Giannakeas
Journal: JAMA Network Open (2020)

Yunhai Li, PhD; Dejuan Yang, PhD; Xuedong Yin, PhD; Xiang Zhang, PhD; Jiefeng Huang, MD; Yusheng Wu, MD; Mengxue Wang, MD; Zhiying Yi, MD; Hongyuan Li, PhD; Hongzhong Li, PhD; Guosheng Ren, MD
Nanotechnology, in silico and endocrine-based strategy for delivering paclitaxel and miRNA: Prospects for the therapeutic management of breast cancer
Authors: Mohammad Azam Ansari, Muthu Thiruvengadam, Zeba Farooqui, Govindaswamy Rajakumar, Qazi Mohammad Sajid Jamal, Mohammad A. Alzohairy, Ahmad Almatroudi, Mohammad N. Alomary, Ill-Min Chung, Ebtesam Abdullah Al-Suhaimi
Journal: Seminars in Cancer Biology (2019)
Use of Epidermal Growth Factor Receptor Inhibitor Erlotinib to Treat Palmoplantar Keratoderma in Patients With Olmsted Syndrome Caused by <i>TRPV3</i> Mutations
Authors: Céline Greco, Stéphanie Leclerc-Mercier, Sarah Chaumon, François Doz, Smail Hadj-Rabia, Thierry Molina, Claude Boucheix, Christine Bodemer
Journal: JAMA Dermatology (2020)

Olmsted syndrome is a genodermatosis characterized by painful and mutilating palmoplantar keratoderma (PPK) that progresses from infancy onward and lacks an effective treatment. It is most often caused by mutations in the transient receptor potential vanilloid 3 (TRPV3) gene. In animal models and keratinocyte cell lines, TRPV3 signaling leads to epidermal growth factor receptor (EGFR) transactivation.To examine the possibility of blocking EGFR transactivation with the inhibitor erlotinib hydrochloride to treat PPK in patients with Olmsted syndrome due to TRPV3 mutations.In this case series, 3 patients from 2 unrelated families who had TRPV3-mutation-associated PPK were treated with erlotinib from May 5, 2018, through May 13, 2019.Clinical follow-up included evaluation of PPK progression, pain and interventions for pain, as well as erlotinib dose adjustment based on treatment effect, plasma levels, and tolerance.The 3 patients (2 brothers aged 15 and 17 years and a 13-year-old girl) had severe palmoplantar hyperkeratosis, intolerable pain with erythromelalgia, severe growth delay, anorexia, and insomnia, which had been progressing since infancy despite numerous therapies. Two patients were confined to wheelchairs owing to intense pain and joint restrictions because of hyperkeratosis. All patients experienced depression and did not engage in social activities. Within 3 months of initiating therapy with erlotinib, hyperkeratosis and pain disappeared. All patients were able to touch the ground with their feet, wear shoes, and walk. Anorexia and insomnia remitted and paralleled improved growth. In addition, the patients resumed social activities. These improvements were sustained across 12 months of treatment and follow-up. The doses of erlotinib used were lower than those used in oncology, and only mild to moderate adverse effects were noted.The findings of this study report improvement of PPK in patients with Olmsted syndrome caused by TRPV3 mutations when treated with erlotinib. Targeting EGFR transactivation with erlotinib therapy may result in clinical remission in an orphan disease that lacks an effective intervention.
Restoration of Temozolomide Sensitivity by PARP Inhibitors in Mismatch Repair Deficient Glioblastoma is Independent of Base Excision Repair
Authors: Fumi Higuchi, Hiroaki Nagashima, Jianfang Ning, Mara V.A. Koerner, Hiroaki Wakimoto, Daniel P. Cahill
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Emergence of mismatch repair (MMR) deficiency is a frequent mechanism of acquired resistance to the alkylating chemotherapeutic temozolomide (TMZ) in gliomas. Poly(ADP-ribose) polymerase inhibitors (PARPi) have been shown to potentiate TMZ cytotoxicity in several cancer types, including gliomas. We tested whether PARP inhibition could re-sensitize MSH6-null MMR-deficient gliomas to TMZ, and assessed the role of the base excision repair (BER) DNA damage repair pathway in PARPi-mediated effects. Experimental Design: Isogenic pairs of MSH6 wild-type and MSH6-inactivated human glioblastoma (GBM) cells (including both IDH1/2 wild-type and IDH1 mutant), as well as MSH6-null cells derived from a patient with recurrent GBM were treated with TMZ, the PARPi veliparib or olaparib, and combination thereof. Efficacy of PARPi combined with TMZ was assessed in vivo. We used genetic and pharmacological approaches to dissect the contribution of BER. Results: While having no detectable effect in MSH6 wild-type GBMs, PARPi selectively restored TMZ sensitivity in MSH6-deficient GBM cells. This genotype-specific restoration of activity translated in vivo, where combination treatment of veliparib and TMZ showed potent suppression of tumor growth of MSH6-inactivated orthotopic xenografts, compared with TMZ monotherapy. Unlike PARPi, genetic and pharmacological blockage of BER pathway did not re-sensitize MSH6-inactivated GBM cells to TMZ. Similarly, CRISPR PARP1 knockout did not re-sensitize MSH6-inactivated GBM cells to TMZ. Conclusions: PARPi restoration of TMZ chemosensitivity in MSH6-inactivated glioma represents a promising strategy to overcome acquired chemoresistance caused by MMR deficiency. Mechanistically, this PARPi-mediated synthetic phenotype was independent of BER blockage and was not recapitulated by loss of PARP1.
Post hoc analysis of relationship between baseline white blood cell count and renal and hepatic function and response in a randomized phase III trial of decitabine in patients age 65 or older with acute myeloid leukemia.
Authors: Jacques Delaunay, Grzegorz Mazur, Mark D Minden, Agnieszka Wierzbowska, Mark M. Jones, Peter G. Tarassoff, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2012)

6632 Background: A phase III trial (NCT00260832) in patients (N=485) ≥65y with newly diagnosed acute myeloid leukemia (AML) was conducted (Kantarjian, JCO; in press). Every 4 wk, patients received decitabine (DAC) 20 mg/m 2 (1-h intravenous infusion, 5 successive days) or treatment choice (TC) with either supportive care or cytarabine (20 mg/m 2 subcutaneous injection daily, 10 successive days). This post hoc analysis examined whether baseline (BL) renal and hepatic function and white blood cell (WBC) counts were associated with response to DAC or TC. Methods: For patients with available data, BL WBC count and markers of renal function (blood urea nitrogen [BUN], creatinine) and liver function (ALT, AST, albumin) were tabulated for patients with/without a response to DAC or TC. Response was defined as morphologic complete remission (CR), CR with incomplete blood count recovery (CRi), or partial remission (PR). Results: Nonresponders had a higher mean BL creatinine vs responders (86.78 vs 80.23 mmol/L, respectively; P=.005); with no differences in BL BUN levels. There were no other between-group differences. Conclusions: This analysis suggests that there is no relationship between BL WBC or hepatic function and response to treatment with DAC or TC. Although there was no difference in BL BUN, higher mean creatinine levels in nonresponders may suggest a prognostic relationship but further studies are needed to clarify. [Table: see text]