Patient-matched analysis identifies deregulated networks in prostate cancer to guide personalized therapeutic intervention.

Prostate cancer (PrCa) is the second most common malignancy in men. More than 50% of advanced prostate cancers display the TMPRSS2-ERG fusion. Despite extensive cancer genome/transcriptome data, little is known about the impact of mutations and altered transcription on regulatory networks in the PrCa of individual patients.

[The level of evidence for the use of biomarkers in the early detection of prostate cancer].

To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review.

Virilizing oncocytic adrenocortical carcinoma: clinical and immunohistochemical studies.

Context: Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign.

Setting: Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman.

Patient: She presented a recent and progressive virilization syndrome, associated with high blood pressure.

Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity.

Obesity favours the occurrence of locally disseminated prostate cancer in the periprostatic adipose tissue (PPAT) surrounding the prostate gland. Here we show that adipocytes from PPAT support the directed migration of prostate cancer cells and that this event is strongly promoted by obesity. This process is dependent on the secretion of the chemokine CCL7 by adipocytes, which diffuses from PPAT to the peripheral zone of the prostate, stimulating the migration of CCR3 expressing tumour cells.

Sphingosine Kinase 1 urothelial expression is increased in patients with neurogenic detrusor overactivity.

Unlabelled: To evaluate the expression of sphingosine kinase 1 (SPK1) in the bladder wall in patients with neurogenic lower urinary tract dysfunction and its association with clinical, urodynamic and pathological features.

Materials And Methods: The expression of SPK1 was studied in bladder wall specimens obtained from cystectomy using immunohistochemistry in ten patients with spinal cord injury (n=8) or multiple sclerosis (n=2) with urodynamically proven neuropathic bladder dysfunction, and in controls (n=5). Inflammation and fibrosis were analysed with histological criteria and SPK1 expression was determined by individual immunohistochemical staining.

Mannose-6-phosphate receptor: a target for theranostics of prostate cancer.

The development of personalized and non-invasive cancer therapies based on new targets combined with nanodevices is a major challenge in nanomedicine. In this work, the over-expression of a membrane lectin, the cation-independent mannose 6-phosphate receptor (M6PR), was specifically demonstrated in prostate cancer cell lines and tissues. To efficiently target this lectin a mannose-6-phosphate analogue was synthesized in six steps and grafted onto the surface of functionalized mesoporous silica nanoparticles (MSNs).

Normotensive incidentally discovered pheochromocytomas display specific biochemical, cellular, and molecular characteristics.

Context: A number of incidentally discovered pheochromocytomas are not associated with hypertension. The characteristics of normotensive incidentally discovered pheochromocytomas (NIPs) are poorly known.

Objective: The purpose of this work was to assess the clinical, hormonal, histological, and molecular features of NIPs.

Vaginal lubrication after cervicovaginal stimulation is facilitated by phosphodiesterase type 5 inhibition in ovariectomized mice.

Introduction: Nitric oxide synthases (NOSs) and estrogen receptors are expressed in the vagina.

Aim: We aimed to assess the impact of sildenafil on vaginal lubrication according to the hormonal status and to determine the role of the neuronal isoform of NOS (nNOS).

Methods: Four-week-old C57/BL6 female mice were sham operated or ovariectomized.

Prognostic interest in discriminating muscularis mucosa invasion (T1a vs T1b) in nonmuscle invasive bladder carcinoma: French national multicenter study with central pathology review.

Purpose: Predictive factors of T1 nonmuscle invasive bladder cancer evolution that could guide treatment decision making are lacking. We assessed the prognostic value of muscularis mucosa invasion in nonmuscle invasive bladder cancer.

Materials And Methods: In a national multicenter study patients with primary T1 nonmuscle invasive bladder cancer were recruited from 6 French hospitals.

Adrenocortical tumors: improving the practice of the Weiss system through virtual microscopy: a National Program of the French Network INCa-COMETE.

The Weiss score is the reference method to distinguish between a benign and a malignant adrenocortical tumor (ACT). A program was initiated to improve the reproducibility of the pathologic diagnosis of ACTs in France through the National INCa-COMETE Network. Twelve pathologists from all Reference Centers of the Network analyzed 50 selected ACTs using a web-based virtual microscopy approach in a blind design, allowing to determine the intraobserver and interobserver reproducibilities of the Weiss system.

First evidence of sphingosine 1-phosphate lyase protein expression and activity downregulation in human neoplasm: implication for resistance to therapeutics in prostate cancer.

This is the first report of sphingosine 1-phosphate lyase (SPL) protein expression and enzymatic activity in human neoplasm. This enzyme drives irreversible degradation of sphingosine 1-phosphate (S1P), a bioactive lipid associated with resistance to therapeutics in various cancers, including prostate adenocarcinoma. In fresh human prostatectomy specimens, a remarkable decrease in SPL enzymatic activity was found in tumor samples, as compared with normal adjacent tissues.

Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens.

Purpose: Sphingosine kinase-1 (SphK1) was shown in preclinical models and non-genitourinary cancers to be instrumental in cancer progression, adaptation to hypoxia and in tumour angiogenesis. No data were available in human prostate cancer. The present study was designed to assess SphK1 expression and activity in radical prostatectomy specimens and to research correlations with clinical features.

Activation of sphingosine kinase-1 in cancer: implications for therapeutic targeting.

Sphingolipid metabolites are critical to the regulation of a number of fundamental biological processes including cancer. Whereas ceramide and sphingosine mediate and trigger apoptosis or cell growth arrest, sphingosine 1-phosphate promotes proliferation, cell survival and angiogenesis. The delicate equilibrium between the intracellular levels of each of these sphingolipids is controlled by the enzymes that either produce or degrade these metabolites.

Urothelial carcinoma of the bladder, lipid cell variant: clinicopathologic findings and LOH analysis.

In this report, we present the clinicopathologic features of 27 cases of the lipid cell variant of urothelial bladder carcinoma. This is a rare variant of bladder cancer recognized by the current WHO classification of urologic tumors. The lipid cell component varied from 10% to 50% of the tumor specimen; in 11 cases the lipid cell component composed greater than 30% of the tumor.

Sphingosine kinase-1 is central to androgen-regulated prostate cancer growth and survival.

Background: Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival.

Maffucci syndrome and adrenal cortex tumor.

We report the second known case of Maffucci syndrome associated with an adrenal cortex tumor. Endocrine tumors have been reported in patients with multiple enchondromas, although the underlying mechanism of this combination is unknown. Maffucci syndrome is characterized by abnormalities of several mesodermal derivates.

Preclinical toxicity, toxicokinetics, and antitumoral efficacy studies of DTS-201, a tumor-selective peptidic prodrug of doxorubicin.

Purpose: There is a clear clinical need for cytotoxic drugs with a lower systemic toxicity. DTS-201 (CPI-0004Na) is a peptidic prodrug of doxorubicin that shows an improved therapeutic index in experimental models. The purpose of the current study was to complete its preclinical characterization before initiation of phase I clinical trials.

[Rare malignant tumours of the prostate].

Among the rare malignant tumours of the prostate it is advisable to differentiate epithelial tumours with histologic variants of adenocarcinomas and non glandular carcinomas and mesenchymal tumours which represent less than 1% of these malignant tumours.

Synchronous epidermoid cyst and mature teratoma of the testis: an unusual association.

We describe here the first case of a synchronous epidermoid cyst and mature teratoma of the testis occurring in a young man presenting a with bilateral testicular tumor. After a clinical, biological and ultrasound evaluation, testis-sparing surgery was performed on the left testis and a total orchiectomy on the right side in accordance with oncological principles. Histopathological examination revealed a simple epidermoid cyst on the left side and a mature teratoma on the right side, following Price's criteria.