9 research outputs found
Effect of arginase II on L-arginine depletion and cell growth in murine cell lines of renal cell carcinoma
Inorganic Phosphate Modulates the Expression of the NaPi-2a Transporter in the trans
Inorganic phosphate (Pi) homeostasis is maintained by the tight regulation of renal Pi excretion versus reabsorption rates that are in turn modulated by adjusting the number of Pi transporters (mainly NaPi-2a) in the proximal tubules. In response to some hormones and a high dietary Pi content, NaPi-2a is endocytosed and degraded in the lysosomes; however, we show here that some NaPi-2a molecules are targeted to the trans-Golgi network (TGN) during the endocytosis. In the TGN, NaPi-2a interacts with PIST (PDZ-domain protein interacting specifically with TC10), a TGN-resident PDZ-domain-containing protein. The extension of the interaction is proportional to the expression of NaPi-2a in the TGN, and, consistent with that, it is increased with a high Pi diet. When overexpressed in opossum kidney (OK) cells, PIST retains NaPi-2a in the TGN and inhibits Na-dependent Pi transport. Overexpression of PIST also prevents the adaptation of OK cells to a low Pi culture medium. Our data supports the view that NaPi-2a is subjected to retrograde trafficking from the plasma membrane to the TGN using one of the machineries involved in endosomal transport and explains the reported expression of NaPi-2a in the TGN
Recombinant antibodies generated from both clonal and less abundant plasma cell immunoglobulin G sequences in subacute sclerosing panencephalitis brain are directed against measles virus
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Systemic chemotherapies retain anti-tumor activity in desmoid tumors independent of specific mutations in CTNNB1 or APC: A multi-institutional retrospective study
Determine if specific CTNNB1 or APC mutations in desmoid tumor (DT) patients were associated with differences in clinical responses to systemic treatments.
We established a multi-institutional dataset of previously-treated DT patients across four US sarcoma centers, including demographic and clinicopathologic characteristics, treatment regimens, and clinical and radiographic responses. CTNNB1 or APC mutation status was determined from prior pathology records, or archival tissue was requested and analyzed by Sanger sequencing and/or next-generation sequencing. Evaluable patients with mutation results were analyzed to determine clinical progression-free survival (cPFS), RECIST 1.1 PFS (rPFS), time to next treatment (TTNT), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazard regression were performed to identify differences in cPFS, rPFS, TTNT, and OS by mutation subtype, DT location and treatment regimen.
259 evaluable patients were analyzed for at least one of the survival outcomes, with 177 patients having mutation data. First and second line cPFS, rPFS and TTNT were not significantly affected by mutation subtype, however APC mutant DTs demonstrated non-statistically significant inferior outcomes. Extremity/trunk DT location and treatment with doxorubicin-based, methotrexate/vinca alkaloids and sorafenib regimens were associated with better clinical outcomes compared to surgery, or "other" therapies including estrogen-receptor blockade and imatinib. Overall survival was significantly worse with APC or CTNNB1 negative/other mutations.
Mutation subtype did not affect responses to specific systemic therapies. APC mutations and non-extremity DT locations remain prognostic for worse outcomes, and earlier initiation of systemic therapy for these higher-risk DTs should be prospectively evaluated