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, New breakthroughs in kidney stone research: helping to develop more effective treatment strategies
Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. Stone formation is highly prevalent, with a high incidence worldwide and increasing year by year.And a recurrence rate of up to 50% within the first 5 years of the initial stone episode. Obesity, diabetes, hypertension and metabolic syndrome are considered risk factors for stone formation, which, in turn, can lead to hypertension, chronic kidney disease and end-stage renal disease.Management of symptomatic kidney stones has evolved from open surgical lithotomy to minimally invasive endourological treatments leading to a reduction in patient morbidity, improved stone......
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, Erbin and Acar: Opening a new chapter in colorectal cancer immunotherapy
Cancer immunotherapy has been successfully used in many types of cancer, including colorectal cancer (CRC), one of the leading causes of cancer death worldwide. However, current immunotherapy strategies based on targeting PD1/PDL1 are mostly effective in less than 30 percent of CRC patients. Therefore, improving the effectiveness and developing more useful or alternative strategies are crucial for the treatment of CRC patients. Platelets/megakaryocytes (MKs) are the key components in blood system functionally associated with hemostasis and thrombosis. Platelets are also considered as immune ‘‘cells,’’ which may recruit and activate immune cells to initiate immune response. Nevertheless......
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, Uncovering the mystery of liver fibrosis, new research may open up effective treatment strategies
Liver fibrosis is the convergent point of various liver diseases, such as alcohol consumption, non-alcoholic steatohepatitis (NASH), viral hepatitis, autoimmune hepatitis, and cholestatic liver disease.The common effect of all of these factors on the liver is the generation of a chronic inflammation resulting in an abnormal wound healing response. The generation of a fibrotic response in the liver gives rise to the accumulation of extracellular matrix (ECM) components, leading to fibrous scar formation. The architecture of the liver is disrupted by the presence of a fibrous scar, which causes hepatocyte loss and the deregulation of the normal functioning of the liver, ultimately result......
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, Cisplatin chemotherapy resistance revealed: TAMs release CCL22 as the culprit!
Tumor surrounding stromal cells, including tumor-associated macrophages (TAMs),crosstalk with the cancer cells to promote oncogenesis, tumor malignant progression, and drug resistance. Esophageal squamous cell carcinoma (ESCC) is among the deadliest types of solid tumors, with the extremely low 5-year overall survival (OS) rate, due to the high recurrence after chemotherapy. Cisplatin is widely used as a standard chemotherapy to treat ESCC patients; however, a plethora of patients suffer from chemoresistance. TAMs-secreted non-cellular substances, such as cytokines, growth factors, or non-coding RNA, function as important factors to provide a permissive microenvironment for tumor growt......
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, Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis
Tumor-associated macrophages (TAMs) are often associated with chemoresistance and resultant poor clinical outcome in solid tumors. Here, we demonstrated that TAMs-released chemokine-C-C motif chemokine 22 (CCL22) in esophageal squamous cell carcinoma (ESCC) stroma was tightly correlated with the chemoresistance of ESCC patients. TAMs-secreted CCL22 was able to block the growth inhibitory and apoptosis promoting effects of cisplatin on ESCC cells. Mechanistically, CCL22 stimulated intratumoral diacylglycerol kinase α (DGKα) to produce phosphatidic acid (PA), which suppressed the activity of NADPH oxidase 4 (NOX4) and then blocked the overproduction of intratumoral reactive species oxyge......
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, Targeting Erbin-mitochondria axis in platelets/ megakaryocytes promotes B cell-mediated antitumor immunity
The roles of platelets/megakaryocytes (MKs), the key components in the blood system,in the tumor microenvironment and antitumor immunity are unclear. In patients withcolorectal cancer, the number of platelets was significantly increased in patientswith metastasis, and Erbin expression was highly expressed in platelets from patientswith metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasisin mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient plateletshave increasing mitochondrial oxidative phosphorylation and secrete lipid metaboliteslike acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM.Notably, Acar en......