Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the world's deadliest infectious diseases and urgently requires new antibiotics to treat drug-resistant strains and to decrease the duration of therapy. During infection, Mtb encounters numerous stresses associated with host immunity, including hypoxia, reactive oxygen and nitrogen species, mild acidity, nutrient starvation, and metal sequestration and intoxication. The Mtb proteostasis network, composed of chaperones, proteases, and a eukaryotic-like proteasome, provides protection from stresses and chemistries of host immunity by maintaining the integrity of the mycobacterial proteome. In this Review, we explore the proteostasis network as a noncanonical target for antibacterial drug discovery.
 ...
PMID:Targeting the Proteostasis Network for Mycobacterial Drug Discovery. 2946 83

Prostate cancer is the most prevalent malignancy in men, and the identification of novel oncogenes is clinically valuable for early screening, prevention and treatment. Recently, the studies have revealed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of cancers including prostate cancer. The present study aims to identify a novel lncRNA that correlated with the survival time of prostate cancer patients and try to explore its biological functions in prostate cancer cells. After analysing the prostate carcinoma dataset of the Cancer Genome Atlas (TCGA), the lncRNA FAM66C was screened with its expression highly correlated with patient survival time, tumour stage and Gleason pattern. Real-time PCR showed that FAM66C highly expressed in prostate cancer cells, and knockdown FAM66C by siRNAs resulted in significant inhibition of cell growth. Furthermore, the results indicated that FAM66C promoted cell growth due to increasing cell proliferation but not decreasing cell apoptosis. In addition, FAM66C activated the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation. The result of Western Blotting and lysosomal acidity detection showed that knockdown FAM66C increased the protein ubiquitination and the lysosomal acidity. Moreover, inhibition of proteasome pathway could increase the activation of EGFR-ERK signalling and cell proliferation. Taken together, these results suggested that lncRNA FAM66C activate EGFR-ERK signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. SIGNIFICANCE OF THE STUDY: We demonstrated that lncRNA FAM66C was associated with clinical progression. In addition, highly expressed lncRNA FAM66C in prostate cancer cell lines promoted cell proliferation. Moreover, lncRNA FAM66C activate the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signalling to promote cell proliferation by inhibiting proteasome pathway in prostate cancer. This study might provide lncRNA FAM66C as a potential therapeutic target gene of prostate cancer.
 ...
PMID:Long non-coding RNA FAM66C is associated with clinical progression and promotes cell proliferation by inhibiting proteasome pathway in prostate cancer. 3243 Sep 27

Multiple myeloma (MM) is a hematological malignancy with a poor prognosis while with a long and progressive outcome. To date, the therapeutic options are restricted to few drugs, including thalidomide or its derivates and autologous transplantation including stem-cell transplantation. More recently, the use of both proteasome inhibitors and monoclonal antibodies have been included in MM therapy, but the clinical results are still under evaluation. Unfortunately, death rates (within the 5-year overall survival rates) are still very high (45%), with no relevant improvement over the past 10 years. Here, we discuss data supporting a new therapeutic approach against MM, based on a common phenotype of tumor malignancies, which is the acidic microenvironment. Extracellular acidity drastically reduces the efficacy of both anti-tumor drugs and the immune reaction against tumors. Pre-clinical data have shown that anti-acidic drugs, such as proton pump inhibitors (PPIs), have a potent cytotoxic effect against human MM cells, thus supporting their use in the treatment of this malignancy. Here, we discuss also similarities between MM and type II diabetes mellitus (DM) with high risk of developing MM, suggesting that both anti-diabetic drugs and a hypocaloric diet may help in curing MM patients.
 ...
PMID:The Acidic Microenvironment: Is It a Phenotype of All Cancers? A Focus on Multiple Myeloma and Some Analogies with Diabetes Mellitus. 3314 95