The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.

Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendati...

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Revised American thyroid association guidelines for the management of medullary thyroid carcinoma

Simple Summary Pancreatic cancer is difficult to treat. Novel treatment strategies are urgently needed to improve the survival rate, which is approximately 10% five years after diagnosis. The use of nanomedicines, which are formulated within a characteristic size range that favors its specific delivery to the diseased tissue, is being actively explored in cancer treatment. However, fibrosis (the abnormal accumulation of a cell type called fibroblasts and the fibrous protein network that they create) is characteristically seen in pancreatic cancer and hinders the delivery of nanomedicines into cancerous tissue. The decreased efficiency of delivery limits the therapeutic effects of nanomedicine in pancreatic cancer. We call this the “fibrotic barrier” to nanomedicine. To overcome the fibrotic barrier, we could target the fibrotic process and/or optimize the nanomedicine design. In this review, we give a detailed overview of strategies to overcome the fibrotic barriers in pancreatic cancer and highlight key gaps in our understanding. Abstract Pancreatic cancer is notorious for its dismal prognosis. The enhanced permeability and retention (EPR) effect theory posits that nanomedicines (therapeutics in the size range of approximately 10–200 nm) selectively accumulate in tumors. Nanomedicine has thus been suggested to be the “magic bullet”—both effective and safe—to treat pancreatic cancer. However, the densely fibrotic tumor microenvironment of pancreatic cancer impedes nanomedicine delivery. The EPR effect is thus insufficient to achieve a significant therapeutic effect. Intratumoral fibrosis is chiefly driven by aberrantly activated fibroblasts and the extracellular matrix (ECM) components secreted. Fibroblast and ECM abnormalities offer various potential targets for therapeutic intervention. In this review, we detail the diverse strategies being tested to overcome the fibrotic barriers to nanomedicine in pancreatic cancer. Strategies that target the fibrotic tissue/process are discussed first, which are followed by strategies to optimize nanomedicine design. We provide an overview of how a deeper understanding, increasingly at single-cell resolution, of fibroblast biology is revealing the complex role of the fibrotic stroma in pancreatic cancer pathogenesis and consider the therapeutic implications. Finally, we discuss critical gaps in our understanding and how we might better formulate strategies to successfully overcome the fibrotic barriers in pancreatic cancer.

/pdf/therapeutic-strategies-to-overcome-fibrotic-barriers-to-3kiur3uj.pdf

Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment

Mammaglobin 1 mediates progression of trastuzumab‐resistant breast cancer cells through regulation of cyclins and NF‐κB

Antibodies are provided that specifically bind to Acting Binding Protein Girdin (Akt Phosphorylation Enhancer), a new substrate of serine/threonine kinase. Additionally, methods of making hybridomas for producing said antibodies and methods of detecting girdin using said antibodies are provided herein. The antibodies and methods are useful for detecting girdin in tissue samples, such as tissue samples from subjects having or suspected of having a disorder in which any of cell motility, cell movement, and angiogenesis is involved.

Antibodies against actin-binding protein girdin and methods of making and using the same

Actomyosin contractility regulates various cellular processes including proliferation and differentiation while dysregulation of actomyosin activity contributes to cancer development and progression. Previously, we have reported that actomyosin-generated tension at adherens junctions is required for cell density-dependent inhibition of proliferation of normal skin keratinocytes. However, it remains unclear how actomyosin contractility affects the hyperproliferation ability of cutaneous squamous cell carcinoma (cSCC) cells. In this study, we find that actomyosin activity is impaired in cSCC cells both in vitro and in vivo. External application of tensile loads to adherens junctions by sustained mechanical stretch attenuates the proliferation of cSCC cells, which depends on intact adherens junctions. Forced activation of actomyosin of cSCC cells also inhibits their proliferation in a cell-cell contact-dependent manner. Furthermore, the cell cycle arrest induced by tensile loading to adherens junctions is accompanied by epidermal differentiation in cSCC cells. Our results show that the degree of malignant properties of cSCC cells can be reduced by applying tensile loads to adherens junctions, which implies that the mechanical status of adherens junctions may serve as a novel therapeutic target for cSCC.

Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells.

Although spindle cell lipoma (SCL) is a subtype of lipoma, the characteristics of SCL are observed in both lipomatous and non-lipomatous tumors. In this article, we present a case of SCL with ossification mimicking atypical lipomatous tumors/well-differentiated liposarcomas (ALTs/WDLs). Considering the findings of magnetic resonance imaging and needle biopsy, which exhibited ALTs/WDLs, marginal resection was performed. Histopathological findings demonstrated mature adipocytes and spindle cells without atypia and no malignant osteoid tissue in the ossified region. In addition, immunohistochemistry (IHC) showed positive staining for CD34, heterogeneous retinoblastoma protein deficiency, and negative staining for mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase. Fluorescence in-situ hybridization showed negative amplification of MDM2. The final diagnosis of the tumor was established using IHC as an extremely rare SCL with ossification.

Atsushi Enomoto

Papers

Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment

Mammaglobin 1 mediates progression of trastuzumab‐resistant breast cancer cells through regulation of cyclins and NF‐κB

Antibodies against actin-binding protein girdin and methods of making and using the same

Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells.

Spindle Cell Lipoma with Ossification Mimicking Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma: A Case Report.