Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study presents a case of metastatic sarcomatoid renal cell carcinoma (RCC) treated with systemic chemotherapy followed by mammalian target of rapamycin inhibitor maintenance therapy. A 63-year-old male presented with lumbago, and lumbar vertebral tumors were detected by magnetic resonance imaging. Subsequent computed tomography (CT) revealed a right renal tumor and CT-guided biopsy of the right renal and left sacroiliac tumors determined pure sarcomatoid carcinoma without a clear cell component. Two cycles of combination chemotherapy comprising of gemcitabine (1,500 mg/m2 on day one) and doxorubicin (50 mg/m2 on day one) resulted in a 20% reduction in the longest diameter of the right renal tumor. However, due to grade 3 neutropenia, the chemotherapy was discontinued and temsirolimus (25 mg once weekly), which binds to the cytoplasmic protein, FKBP-12, and inhibits mTOR, was administered. Stable disease was maintained for 19 months with temsirolimus and no major adverse events, with the exception of grade 2 nausea, were observed. The patient succumbed to their disease at 30 months following the initiation of treatment. These results suggested that systemic chemotherapy followed by temsirolimus maintenance is a feasible treatment option for patients with metastatic sarcomatoid RCC.
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PMID:Successful mammalian target of rapamycin inhibitor maintenance therapy following induction chemotherapy with gemcitabine and doxorubicin for metastatic sarcomatoid renal cell carcinoma. 2495 97

Low back pain (LBP) is the leading cause of disability in the elderly. Intervertebral disc degeneration (IDD) was considered as the main cause for LBP. Degeneration of cartilaginous endplate was a crucial harmful factor during the initiation and development of IDD. Oxidative stress was implicated in IDD. However, the underlying molecular mechanism for the degeneration of cartilaginous endplate remains elusive. Herein, we found that oxidative stress could induce apoptosis and autophagy in endplate chondrocytes evidenced by western blot analysis, flow cytometry, immunofluorescence staining, GFP-LC3B transfection, and MDC staining. In addition, we also found that the apoptosis of endplate chondrocytes was significantly increased after the inhibition of autophagy by bafilomycin A1 shown by flow cytometry. Furthermore, mTOR pathway upstream autophagy was greatly suppressed suggested by western blot assay. In conclusion, our study strongly revealed that oxidative stress could increase autophagy and apoptosis of endplate chondrocytes in intervertebral disc. The increase of autophagy activity could prevent endplate chondrocytes from apoptosis. The autophagy in endplate chondrocytes induced by oxidative stress was mTOR dependent. These findings might shed some new lights on the mechanism for IDD and provide new strategies for the treatments of IDD.
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PMID:Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc. 2832 Dec 70

Intervertebral disc degeneration (IDD) is the most common cause leading to low back pain, a highly prevalent, costly and crippling condition worldwide. Overexpression of miR-21 has been shown to promote proliferation of nucleus pulposus (NP) cells. However, it remains unclear whether miR-21 can promote the degradation of type II collagen (Col II) and aggrecan, two main extracellular matrix components within the disc. Here, the miRNA microassay assay identified 29 differentially expressed miRNAs in NP tissues from IDD patients compared with healthy controls. Following qRT-PCR validation, miR-21 expression was significantly upregulated in degenerated NP tissues, and showed a positive correlation with disc degeneration grade. Through gain-of-function and loss-of-function studies in human NP cells, miR-21 was shown to inhibit autophagy and then upregulate the expression of matrix metalloproteinase (MMP)-3 and MMP-9, leading to increased degradation of Col II and aggrecan. Mechanistically, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-21, and activated PTEN/ Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in miR-21-induced autophagy inhibition and Col II and aggrecan breakdown. Taken together, these results suggest that miR-21 contributes to Col II and aggrecan catabolism by inhibiting autophagy via the PTEN/Akt/mTOR signaling pathway in human NP cells.
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PMID:MiR-21 promotes ECM degradation through inhibiting autophagy via the PTEN/akt/mTOR signaling pathway in human degenerated NP cells. 2971 Apr 70