Human BKV large T genome detection in prostate cancer and benign prostatic hyperplasia tissue samples by nested PCR: A case-control study.

Human BK polyomavirus (BKPyV) is a latent infectious agent in the genitourinary tract associated with hemorrhagic cystitis and nephropathy. This virus can be a risk factor for various human malignancies, including prostate cancer (PCa). It may contribute to prostate cancer development, as it demonstrates oncogenic properties by encoding oncoproteins. This study assessed the prevalence of this virus in benign and malignant prostate tissues. Between 2009 and 2019, 49 formalin-fixed paraffin-embedded (FFPE) PCa and 49 benign prostatic hyperplasia (BPH) samples were gathered from the pathology department of a tertiary care university hospital. They were used as cases and controls, respectively. After deparaffinization and DNA extraction, nested PCR was applied to identify the BKPyVgp5 gene (LTAg) using inner and outer primers. The nested PCR showed a 278-bp bond corresponding to the BKPyVgp5 genome (LTAg) in 53.1% (26/49) of PCa and 14.3% (7/49) of BPH (p<0.001). The presence of BKV was significantly associated with an increased risk of PCa development (OR=6.78, 95% CI=2.55-18.02, p<0.001). The BKV LTAg gene was significantly more prevalent in PCa samples than in BPH samples. These results demonstrate the presence of the virus in prostate cancer tissues.

CFTR mutations causing congenital unilateral absence of the vas deferens (CUAVD) and congenital absence of the uterus (CAU) in a consanguineous family.

Cystic fibrosis (CF) is one of the most common recessive genetic diseases, with a wide spectrum of phenotypes, ranging from infertility to severe pulmonary disease. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are considered the main genetic cause for CF. In this study, we recruited a consanguineous Iranian pedigree with four male patients diagnosed with congenital unilateral absence of the vas deferens (CUAVD), and one female patient diagnosed with congenital absence of the uterus (CAU). Testicular biopsy of one patient was performed, and hematoxylin and eosin (H and E) staining of testis sections displayed the presence of germ cell types ranging from spermatogonia to mature spermatids, indicating obstructive azoospermia. To explore the underlying genetic factor in this familial disorder, we therefore performed whole-exome sequencing (WES) on all available family members. WES data filtration and CFTR haplotype analysis identified compound heterozygous mutations in CFTR among four patients (two CUAVD patients carried p.H949Y and p.L997F, and one CUAVD and the female CAU patient carried p.H949Y and p.I148T). All these mutations were predicted to be deleterious by at least half of the prediction software programs and were confirmed by Sanger sequencing. Our study reported that CFTR compound heterozygous mutations in a consanguineous Iranian family cause infertility in both sexes.

Corrigendum to "Exosomes derived from TRAIL-engineered mesenchymal stem cells with effective anti-tumor activity in a mouse melanoma model" [International Journal of Pharmaceutics 549 (2018) 218-229].

Exosomes are biological nano-sized vesicles (~30-200 nm in diameter) that are produced by a wide range of cells and play several roles in cell-cell communications. These vesicles contain membrane and cytoplasmic components of producing cells. Mesenchymal stem cells (MSCs) are the ideal producer of exosomes. The secreted vesicles from MSCs are promising biological vehicles for cell-free therapy in regenerative medicine, cancer therapy and targeted delivery of therapeutic agents to the tumor cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising member of the TNF family with selective effect on cancerous cells. Recent evidences showed that the membrane TRAIL-armed exosomes possess anti-tumor activity. However, the effect of in vivo administration of TRAIL-armed exosomes has not been reported so far. In the current study, mesenchymal stem cells expressing TRAIL/GFP proteins were prepared with the help of a non-viral vector based on polyethylenimine 25 kDa. Then, exosomes containing TRAIL protein (Exo-TRAIL) were isolated from the supernatant of genetically engineered MSCs and characterized. Antitumor activity of both MSC-derived exosomes and Exo-TRAIL was investigated in vitro and in vivo in three models. The results indicated that the co-injection of both Exo-TRAIL and tumor cells delayed the tumor appearance. Besides, the tumor volume/weight was efficiently decreased in tumor bearing mice. Moreover, it was shown that multi-dose injections of Exo-TRAIL reduced the tumor size while single dose treatment with Exo-TRAIL did not show significant anti-tumor activity. To conclude, these results suggested that MSC-derived Exo-TRAIL has a potential capacity for cancer treatment.

Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score.

Mesenchymal stem cell-derived exosome is a safe and effective delivery platform with a potential capacity to exert immunomodulation effect and peripheral tolerance toward auto-reactive cells via bearing regulatory and tolerogenic molecules. Inflammation and neurodegeneration are the clinical manifestation of multiple sclerosis (MS). In order to fight against MS, the efficient choices are the ones, which prevent inflammation and induce remyelination. In this regard, the previously reported LJM-3064 aptamer which showed considerable affinity toward myelin and demonstrated remyelination induction was employed as both targeting ligand and therapeutic agent. Thus, in the current study, the carboxylic acid-functionalized LJM-3064 aptamer was covalently conjugated to the amine groups on the exosome surface through EDC/NHS chemistry. The obtained results showed that the aptamer-exosome bioconjugate could promote the proliferation of oligodendroglia cell line (OLN93) in vitro. Moreover, in vivo administration of the prepared aptamer-exosome bioconjugate in female C57BL/6 mice as a prophylactic measure produced a robust suppression of inflammatory response as well as lowered demyelination lesion region in CNS, resulting in reduced in vivo severity of the disease. The prepared platform employing exosome-based nanomedicine as a novel approach for managing MS would hopefully pave the way to introduce a versatile approach toward an effective clinical reality.

Exosomes derived from TRAIL-engineered mesenchymal stem cells with effective anti-tumor activity in a mouse melanoma model.

Exosomes are biological nano-sized vesicles (~30-200 nm in diameter) that are produced by a wide range of cells and play several roles in cell-cell communications. These vesicles contain membrane and cytoplasmic components of producing cells. Mesenchymal stem cells (MSCs) are the ideal producer of exosomes. The secreted vesicles from MSCs are promising biological vehicles for cell-free therapy in regenerative medicine, cancer therapy and targeted delivery of therapeutic agents to the tumor cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising member of the TNF family with selective effect on cancerous cells. Recent evidences showed that the membrane TRAIL-armed exosomes possess anti-tumor activity. However, the effect of in vivo administration of TRAIL-armed exosomes has not been reported so far. In the current study, mesenchymal stem cells expressing TRAIL/GFP proteins were prepared with the help of a non-viral vector based on polyethylenimine 25 kDa. Then, exosomes containing TRAIL protein (Exo-TRAIL) were isolated from the supernatant of genetically engineered MSCs and characterized. Antitumor activity of both MSC-derived exosomes and Exo-TRAIL was investigated in vitro and in vivo in three models. The results indicated that the co-injection of both Exo-TRAIL and tumor cells delayed the tumor appearance. Besides, the tumor volume/weight was efficiently decreased in tumor bearing mice. Moreover, it was shown that multi-dose injections of Exo-TRAIL reduced the tumor size while single dose treatment with Exo-TRAIL did not show significant anti-tumor activity. To conclude, these results suggested that MSC-derived Exo-TRAIL has a potential capacity for cancer treatment. [corrected].

Less radical surgery for patient with early-stage cervical cancer.

INTRODUCTION: Surgery in cervical cancer should be used with intention of cure. Radical abdominal trachelectomy is a feasible operation for selected patients with stage Iα-1ß cervical cancer which fertility can be preserved. CASE REPORT: A 30-years-old woman with squamous cell cervical cancer stage (1 A II) diagnosed at September 2011 expressed a wish for fertility-sparing treatment. Radical abdominal hysterectomy and pelvic and para-aortic lymphadenectomy were performed which showed no evidence of lymphatic metastasis. Subsequently, at last follow-up (5 months post-surgery), good oncologic outcomes were found after this procedure. This was the first case of fertility-sparing radical trachelectomy procedures performed at our institution. CONCLUSIONS: Trachelectomy represents a valuable conservative surgical approach for early stage invasive cervical cancer.