ABSTRACT
BACKGROUND: Several studies had suggested the potential role of calcium signaling in prostate cancer (PCa) prognosis and agressiveness. We aimed to investigate selected proteins contributing to calcium (Ca2+ ) signaling, (Orai, stromal interaction molecule (STIM), and transient receptor potential (TRP) channels) and involved in cancer hallmarks, as independent predictors of systemic recurrence after radical prostatectomy (RP). METHODS: A case-control study including 112 patients with clinically localized PCa treated by RP between 2002 and 2009 and with at least 6-years' follow-up. Patients were divided into two groups according to the absence or presence of systemic recurrence. Expression levels of 10 proteins involved in Ca2+ signaling (TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, STIM1, STIM2, Orai1, Orai2, and Orai3), were assessed by immunohistochemistry using tissue microarrays (TMAs) constructed from paraffin-embedded PCa specimens. The level of expression of the various transcripts in PCa was assessed using quantitative polymerase chain reaction (qPCR) analysis. RNA samples for qPCR were obtained from fresh frozen tissue samples of PCa after laser capture microdissection on RP specimens. Relative gene expression was analyzed using the 2-âµâµCt method. RESULTS: Multivariate analysis showed that increased expression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 was significantly associated with a lower risk of systemic recurrence after RP, independently of the prostate-specific antigen (PSA) level, percentage of positive biopsies, and surgical margin (SM) status (P = .007, P = .01, P < .001, P = .0065, P = .007, and P = .01, respectively). For TRPC4, TRPV5, and TRPV6, this association was also independent of Gleason score and pT stage. Moreover, overexpression of TRPV6 and Orai2 was significantly associated with longer time to recurrence after RP (P = .048 and .023, respectively). Overexpression of TRPC4, TRPV5, TRPV6, and Orai2 transcripts was observed in group R- (3.71-, 5.7-, 1.14-, and 2.65-fold increase, respectively). CONCLUSIONS: This is the first study to suggest the independent prognostic value of certain proteins involved in Ca2+ influx in systemic recurrence after RP: overexpression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 is associated with a lower risk of systemic recurrence. TRPC4, TRPV5, and TRPV6 appear to be particularly interesting, as they are independent of the five commonly used predictive factors, that is, PSA, percentage of positive biopsies, SM status, Gleason score, and pT stage.
Subject(s)
Calcium Release Activated Calcium Channels/biosynthesis , Calcium Signaling , Neoplasm Recurrence, Local/metabolism , Prostatic Neoplasms/metabolism , Transient Receptor Potential Channels/biosynthesis , Aged , Biomarkers, Tumor/biosynthesis , Case-Control Studies , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/pathology , Predictive Value of Tests , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , RiskABSTRACT
The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca2+-activated K+ channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca2+ homeostasis in epithelial cancers.
Subject(s)
Breast Neoplasms/metabolism , Calcium Signaling , Cell Movement , Colorectal Neoplasms/metabolism , Neoplasm Proteins/metabolism , Receptors, sigma/metabolism , Small-Conductance Calcium-Activated Potassium Channels/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Calcium/metabolism , Cell Line, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Female , Humans , Male , Neoplasm Proteins/genetics , ORAI1 Protein/genetics , ORAI1 Protein/metabolism , Receptors, sigma/genetics , Small-Conductance Calcium-Activated Potassium Channels/genetics , Sigma-1 ReceptorABSTRACT
AIM: Dysbaric osteonecrosis (DON) continues to be a significant occupational hazard that has significant medical and social consequences for professional divers. This review aims to evaluate the prevalence and risk factors of DON among professional divers and to summarize the scientific knowledge regarding distribution of the lesions as well as disease prognosis and treatment. METHOD: A literature review using the Medline database. RESULTS: The prevalence of DON varies between 0 and 70.6% in professional divers, and its prevalence is highest in Turkey, Hawaii, Korea and Japan but is dependent on activity and medical monitoring. The risk of DON is very low for military divers who strictly obey the decompression rules and who undergo periodic medical examination. DON pre- dominately occurs in the proximal part of the femur and humerus. In a majority of cases, DON will progress despite the absence of further dysbaric exposure. CONCLUSION: The pathophysiology of the disease is incompletely understood and other etiological factors are perhaps being overlooked.
Subject(s)
Diving/adverse effects , Occupational Diseases/etiology , Osteonecrosis/etiology , Cross-Sectional Studies , Femur , Humans , Humerus , Observational Studies as Topic , Occupational Diseases/diagnosis , Occupational Diseases/epidemiology , Occupational Diseases/therapy , Osteonecrosis/diagnosis , Osteonecrosis/epidemiology , Osteonecrosis/therapy , Prognosis , Risk FactorsABSTRACT
A 21-year-old woman presented with keloids on her back and her chest. All these scars appeared spontaneously without previous trauma, dermatologic disease or surgery. The spontaneous keloids are lesions rarely described in caucasoid subjects. Their exact physiopathology is still unknown. After a brief review of the literature, the therapeutic strategies will be described.
Subject(s)
Keloid , Adult , Back/pathology , Female , Humans , Keloid/pathology , Keloid/surgery , Prognosis , Rare Diseases , Thorax/pathology , Treatment OutcomeABSTRACT
The authors present a series of 51 cases of buccopharyngeal Kaposi's sarcoma observed in patients with AIDS. The diagnosis of Kaposi's sarcoma is generally obvious due to its appearance, its constantly violaceous colour and its site, especially palatine and velar. When Kaposi's sarcoma is the first manifestation of the disease, it appears to be associated with a relatively favourable pejorative connotation when the nevertheless extremely modest median survival of these patients is compared with that of patients who initially presented with an opportunistic infection not associated with Kaposi's sarcoma. Buccopharyngeal Kaposi's sarcoma is usually only an epiphenomenon. It is rare that the local course requires any tumour reduction treatment. When such treatment is required, radiotherapy with 35 Gys is currently considered to be the best solution.
