tbuckley/cabot-search huggingface dataset:
Attempts to inhibit the development of large intestinal cancer by VPS extract of the Coriolus versicolor mushroom
Authors: Bela Toth, Melissa Coles
Journal: Cancer Research (2005)

1199  The aims of these investigations were to reveal the preventive and therapeutic activity of VPS which is extracted from the fruit body of the Coriolus versicolor mushroom. VPS is 35% polysaccharide, with 92% of that composed of the glucose polymer considered to be the active constituent. The experiment consisted of: group 1, 1,2-dimethylhyrazine diHCl (1,2-DMH) was administered as ten weekly subcutaneous injections at 20 μg/g starting at 9 weeks of age; group 2 received 2% VPS in diet starting at 7 weeks of age, followed by 1,2-DMH as described in group 1; group 3 was treated with 1,2-DMH as described in group 1, followed by 2% VPS in diet starting at 21 weeks of age. Each group consisted of 30 female Swiss mice which were kept for life. To date, 26 mice have died in each group. Of these, the number of animals with large intestinal tumors and the total number of these tumors were: group 1, 26 and 280; group 2, 25 and 294; group 3, 24 and 360. The average number of tumors per animal was: group 1, 10.8; group 2, 11.3; and group 3, 13.8. Our findings, thus, demonstrate no inhibition of carcinogenesis by VPS. The average survival time of animals in group 1 is 284 days (range 121-399); in group 2, 277 days (range 145-395); and in group 3, 273 days (range 104-416). The neoplasms occurred mainly in the colon, rectum, and a few in the cecum. The lesions were diagnosed as polypoid adenomas and adenocarcinomas. In view of our failure to inhibit carcinogenesis and because of the extensive use of VPS as a nutritional supplement by cancer patients in the USA and elsewhere, caution is recommended. Supported by NIH grant 5 RO1 AT001739.
REPLY:
Authors: Fang Lei, Ye‐Mao Liu, Feng Zhou, Juan‐Juan Qin, Xiaodong Huang, Bing‐Hong Zhang, Hongliang Li, Yufeng Yuan
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. We appreciate Philips and colleagues' interest in our report on the associations between liver injury markers and coronavirus disease 2019 (COVID‐19) mortality.(1) They raised the question regarding the application of liver injury markers. However, several of their interpretations of our results are misleading or incorrect. We understand that the use of aspartate aminotransferase (AST) in isolation cannot comprehensively characterize liver injury. To fully explore the associations of liver injury with COVID‐19, we investigated the dynamic patterns of four respective and extensively applied markers of liver injury: alanine aminotransferase (ALT), AST, alkaline phosphatase, and total bilirubin. Their associations with COVID‐19 mortality were clearly demonstrated. Importantly, we found that the increased levels of all four indicators are consistently associated with higher risk of COVID‐19 death, with AST having the largest hazard ratio. Therefore, in our study, liver injury was characterized by four markers, rather than only AST as mentioned by Philips et al. Until recently, the definition of acute liver injury (ALI) has been inconsistent in the literature.(2) In our study, ALI was defined by ALT, which has been extensively applied in more than 1,000 studies. However, the international normalized ratio (INR), proposed by Philips et al., is a marker of coagulopathy, which can occur in many pathological conditions.(3,4) Although prolonged prothrombin time/INR can occur in chronic liver disease, this condition is more likely to happen at the advanced stage of liver injury because of diminished clotting factor production.(4) Remarkably, COVID‐19 per se is often associated with a major blood hypercoagulability.(5) Thus, INR, as a measure of unspecific and synthetic coagulation, was not appropriate for specifically predicting liver injury in the setting of COVID‐19 and would lead to confounding conclusions. Based on our rational study design and rigorous statistical analyses, we insist that liver injury exists in the setting of COVID‐19. These findings are further clinically meaningful that indicators of liver injury need to be timely monitored because of their strong association with COVID‐19 mortality.
Abstract A70: Studying the signaling pathways of tumorigenic epithelial fallopian tube subpopulations during early tumorigenesis
Authors: Angela Russo, Matthew Dean, Dan Lantvit, Joanna E. Burdette
Journal: Clinical Cancer Research (2020)

Abstract Survival rates for high-grade serous ovarian carcinoma (HGSOC) patients have not substantially improved over the past decades, mainly because the disease is only detected at the metastatic stage. The findings of early premalignant lesions in the fallopian tube, but not in the ovary, suggested that HGSOCs may originate from the fallopian tube epithelium (FTE) and metastasize to the ovary. Studying the mechanisms of HGSOC genesis from the correct cell of origin is critical to the early detection of the disease. Our main goal is to determine how genetic and molecular alterations contribute to the early events of HGSOC genesis from FTE. Deletion of PTEN alone in FTE is sufficient to lead to tumor formation and peritoneal dissemination, suggesting that loss of PTEN may play a pivotal role in the early events of the tumorigenic cascade. Herein we show that loss of PTEN in the FTE upregulates markers of tumor-initiating cells (TIC) such as WNT4, LGR5, ALDH1, c-Kit, CD44, and Dll4. We also discovered that the TIC markers are confined in a specific population of cells with increased diameter that we call TICHigh as compared to a smaller population that we call TICLow. In fact, when these two populations are separated by flow cytometry-based sorting, the TICHigh retains all the TIC markers. In addition, using a limiting dilution assay, we found that the TICHigh subpopulation forms tumor at a faster rate in vivo and colonize more the ovary ex vivo. In addition, TICHigh forms bigger spheroids and are more resistant to chemotherapeutic agents, suggesting that more targeted therapy may be developed for these stem-like, tumorigenic subpopulations. We also show that loss of PAX2 is mediating the TICHigh phenotype and that activation of AKT is not sufficient to induce the TIC phenotype whereas p70S6K activation is required. These findings suggest that therapies to re-express PAX2 may prevent development of HGSOC. Together, these findings provide a novel model to study the mechanism of fallopian tube tumor initiation and invasion to the ovary mediated by loss of PTEN, which may help to define early events of human ovarian carcinogenesis. Citation Format: Angela Russo, Matthew Dean, Dan Lantvit, Joanna E. Burdette. Studying the signaling pathways of tumorigenic epithelial fallopian tube subpopulations during early tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A70.
Effectiveness of a stop smoking service in reducing cigarette smoking in patients referred from a National Health Service dermatology centre
Authors: L.F. Soriano, H. Poole, J.R. Ingram, R.A. Abbott
Journal: British Journal of Dermatology (2020)

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Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity
Authors: Nancy J. Ames, Jennifer J. Barb, Kornel Schuebel, Sarah Mudra, Brianna K. Meeks, Ralph Thadeus S. Tuason, Alyssa T. Brooks, Narjis Kazmi, Shanna Yang, Kelly Ratteree, Nancy Diazgranados, Michael Krumlauf, Gwenyth R. Wallen, David Goldman
Journal: Gut Microbes (2020)

Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.
Aquaporin-7 Regulates the Response to Cellular Stress in Breast Cancer
Authors: Chen Dai, Verodia Charlestin, Man Wang, Zachary T. Walker, Maria Cristina Miranda-Vergara, Beth A. Facchine, Junmin Wu, William J. Kaliney, Norman J. Dovichi, Jun Li, Laurie E. Littlepage
Journal: Cancer Research (2020)

The complex yet interrelated connections between cancer metabolism, gene expression, and oncogenic driver genes have the potential to identify novel biomarkers and drug targets with prognostic and therapeutic value. Here we effectively integrated metabolomics and gene expression data from breast cancer mouse models through a novel unbiased correlation-based network analysis. This approach identified 35 metabolite and 34 gene hubs with the most network correlations. These hubs have prognostic value and are likely integral to tumor metabolism and breast cancer. The gene hub Aquaporin-7 (Aqp7), a water and glycerol channel, was identified as a novel regulator of breast cancer. AQP7 was prognostic of overall survival in patients with breast cancer. In mouse breast cancer models, reduced expression of Aqp7 caused reduced primary tumor burden and lung metastasis. Metabolomics and complex lipid profiling of cells and tumors with reduced Aqp7 revealed significantly altered lipid metabolism, glutathione metabolism, and urea/arginine metabolism compared with controls. These data identify AQP7 as a critical regulator of metabolic and signaling responses to environmental cellular stresses in breast cancer, highlighting AQP7 as a potential cancer-specific therapeutic vulnerability. SIGNIFICANCE: Aquaporin-7 is identified as a critical regulator of nutrient availability and signaling that responds to cellular stresses, making it an attractive therapeutic target in breast cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/19/4071/F1.large.jpg.
Real-time ultrasound-guided external intracerebral hemorrhage drain placement
Authors: Cong Feng, Sai Huang, Li Chen, Xuan Zhou, Li-Li Wang, Fa-Qin Lv, Tan-Shi Li
Journal: Military Medical Research (2020)

Abstract We report a new minimally invasive technique utilizing interventional ultrasound for precise external intracerebral hemorrhage drain (EICHD) placement in pigs.
Bioinspired structural color particles with multi-layer graphene oxide encapsulated nanoparticle components
Authors: Yuxiao Liu, Yuetong Wang, Yu Wang, Yilai Shu, Hui Tan, Yuanjin Zhao
Journal: Bioactive Materials (2020)

Because of the unique features of spherical symmetry, angle-independency, good monodispersity, controllable components and morphologies, structural color particles (SCPs) have found great significances in various fields such as sensing, monitoring, biological assays, etc. Here, inspired by the melanosome-derived bright structural colors and the self-adhesivity of mussels, we present a kind of bioinspired SCPs assembled from polydopamine (PDA)-adhered multi-layer graphene oxide (GO) encapsulated silica nanoparticles (SNs). It is demonstrated that compared with traditional SCPs, the designed particles possess brighter and more vibrant structural colors, and no complicated modification is required during the functionalization process due to the abundant inherent functional groups of GO. The resultant SCPs are verified to be capable for direct hybridization chain reaction and multiplexed nucleic acid assays. These properties indicate the promising prospects of our designed SCPs.
High-Sensitivity Cardiac Troponin-T and N-Terminal Prohormone of B-Type Natriuretic Peptide in Relation to Cardiovascular Outcomes in Type 1 Diabetes
Authors: Tina Costacou, Amy K. Saenger, Trevor J. Orchard
Journal: Diabetes Care (2020)

OBJECTIVE High-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), biomarkers of cardiovascular disease (CVD) and heart failure, respectively, have not been widely studied in type 1 diabetes (T1D). We evaluated whether their assessment in T1D enhances the prediction of CVD and major adverse cardiovascular events (MACE). RESEARCH DESIGN AND METHODS hs-cTnT and NT-proBNP were analyzed on the Roche Cobas E601 using the first available stored specimen (n = 581; mean age 29 years and diabetes duration 21 years). CVD was defined as CVD death, myocardial infarction, coronary revascularization, angina, ischemia, or stroke, and MACE as CVD death, myocardial infarction, or stroke. RESULTS Median hs-cTnT (5.0 ng/L; interquartile range &amp;lt;3.0, 10.0) was higher among men (P &amp;lt; 0.0001), whereas median NT-proBNP (22.0 ng/L; 7.0, 61.0) did not differ by sex. In Cox models, log hs-cTnT (hazard ratio [HR] 1.38, P = 0.0006) and log NT-proBNP (HR 1.24, P = 0.0001) independently predicted CVD during 21 years of follow-up. However, their addition to models, singly or together, did not significantly improve CVD prediction. Furthermore, a marginally significant sex interaction was observed (P = 0.06), indicating that the hs-cTnT prediction was limited to men. hs-cTnT and NT-proBNP also predicted MACE, although only NT-proBNP remained significant (HR 1.27, P = 0.0009) when the biomarkers were included in a model simultaneously. Nonetheless, their addition to multivariable models did not enhance MACE prediction. CONCLUSIONS Sex differences were observed in the concentration and predictive ability of hs-cTnT and NT-proBNP in T1D. Overall, their addition to traditional risk factor models increased the area under the curve for neither CVD nor MACE.
Cutaneous adverse events with febuxostat after previous reactions to allopurinol: comment on the article by Singh and Cleveland
Authors: Neus Quilis, Paloma Vela, Boris A Blanco Cáceres, Cesar Diaz-Torne, Enrique Calvo-Aranda, Francisca Sivera, Alejandro Prada-Ojeda, Fernando Pérez Ruiz, Eliseo Pascual, Mariano Andrés
Journal: Annals of the Rheumatic Diseases (2020)

Dear Editor,

We read with interest the recent article by Singh and Cleveland on the hypersensitivity risk of allopurinol (ALP) and febuxostat (FBX) compared with colchicine.1 A common challenge when using ALP, linked to hypersensitivity reactions, is the potential development of cutaneous adverse reactions (CARs). Most are often mild, non-specific rashes; however, severe CARs, including Stevens-Johnson syndrome (SJS), may occur, but with a low incidence (0.69 cases per 1000 person-years) in non-Asian populations.2 In the EuroSCARs study, ALP was the reason for 5% of all severe CARs.3 So, FBX is often chosen as urate-lowering agent on the background of an ALP-related CAR. However, these patients were not eligible for the pivotal trials of FBX4 and were excluded from the recent analysis by Singh and Cleveland.1 Therefore, the accurate rate of FBX-related CARs in patients who previously suffered from ALP, and the mechanisms behind, remain undetermined to date.

We have …
Fructose-coated Angstrom silver inhibits osteosarcoma growth and metastasis via promoting ROS-dependent apoptosis through the alteration of glucose metabolism by inhibiting PDK
Authors: Xiong-Ke Hu, Shan-Shan Rao, Yi-Juan Tan, Hao Yin, Ming-Jie Luo, Zhen-Xing Wang, Jin-Hua Zhou, Chun-Gu Hong, Zhong-Wei Luo, Wei Du, Ben Wu, Zi-Qi Yan, Ze-Hui He, Zheng-Zhao Liu, Jia Cao, Yang Wang, Wei-Yi Situ, Hao-Ming Liu, Jie Huang, Yi-Yi Wang, Kun Xia, Yu-Xuan Qian, Yan Zhang, Tao Yue, Yi-Wei Liu, Hong-Qi Zhang, Si-Yuan Tang, Chun-Yuan Chen, Hui Xie
Journal: Theranostics (2020)

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects. Methods: A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis. Results: The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Conclusion: Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.
Surgeon who said covid-19 was a hoax has been suspended pending GMC investigation
Authors: Clare Dyer
Journal: BMJ (2020)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Surgeon who said covid-19 was a hoax has been suspended pending GMC investigation Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
LAM is another small airway disease: lessons from microCT
Authors: Arnaud Bourdin, Anne Sophie Gamez, Isabelle Vachier, Bruno Crestani
Journal: European Respiratory Journal (2020)

Among interstitial lung diseases, the presence of cysts is a characteristic of lymphangioleiomyotosis (LAM). Insight was gained thanks to genetic studies which unravelled the involvement of the tuberous sclerosis complex (TSC)-mTOR pathway. Accordingly, both sirolimus (an mTOR inhibitor) and everolimus (an inducer of autophagic flux) gained approval in the treatment of LAM [1]. Now the question is how and when these drugs should be best initiated. In a way very similar to what currently stands in COPD, the earliest looks the best. Intuitively, the main issue is then to justify what would be the most appropriate outcome to improve and/or to prevent. Understanding the natural history of the disease would then allow for early interventions based on early events. MicroCT should become routine part of pathology when assessing lung samples <https://bit.ly/2XYTYoq>
Response to: ‘Unified definition of relapse-free survival should be used for evaluating survival benefit in oesophageal adenocarcinoma’ by Li
Authors: Anita Lavery, Jaine K Blayney, Richard C Turkington
Journal: Gut (2020)

We appreciate the commentary of Dr Li regarding our study on the application of the DNA Damage Immune Response (DDIR) assay to predict benefit from neoadjuvant chemotherapy in oesophageal adenocarcinoma (OAC).1 2 We do not agree that there is a single, unified definition of relapse-free survival (RFS) and, indeed, the variation in definitions is a well-described problem in clinical trials. A key difference is the inclusion of deaths in the absence of evidence of tumour regrowth as recurrences, rather than censored events. The Food and Drug Administration (FDA) has commented that the ‘application of the definition of relapse or disease-free …
Characteristics of Adults With Congenital Heart Defects in the United States
Authors: Michelle Gurvitz, Julie E. Dunn, Ami Bhatt, Wendy M. Book, Jill Glidewell, Carol Hogue, Angela E. Lin, George Lui, Claire McGarry, Cheryl Raskind-Hood, Alissa Van Zutphen, Ali Zaidi, Kathy Jenkins, Tiffany Riehle-Colarusso
Journal: Journal of the American College of Cardiology (2020)