Polymorphisms in toll-like receptor 3 and 4 genes as prognostic and outcome biomarkers in melanoma patients.

Melanoma is one of the most aggressive tumors, and in the setting of rising incidence and mortality, there is an urgent need to identify new prognostic markers. Toll-like receptors (TLRs), are aberrantly expressed in numerous cancers, including melanoma. TLR signaling provides a microenvironment that is involved in antitumor immune response, chronic inflammation, cancer cell proliferation and evasion of immune destruction. In the present study, we investigated whether single nucleotide polymorphisms (SNPs) in TLR3 and TLR4 genes are associated with clinicopathologic features, progression and survival of melanoma patients. The study was conducted on 120 melanoma patients. DNA extracted from peripheral blood was genotyped for TLR3 polymorphisms rs5743312 and rs3775291 (L412F) and TLR4 polymorphisms rs4986790 (D299G) and rs4986791 (T399I), by TaqMan Real-Time PCR Assays. Kaplan-Meier survival curves were compared by the log-rank test. TLR3 polymorphism L412F was associated with a higher mitotic index ( P = 0.035). TLR4 D299G and T399I polymorphisms were associated with indicators of melanoma severity, nodal metastases ( P = 0.005 and P = 0.007, respectively) and advanced stage III ( P = 0.005 and P = 0.004, respectively). Cox regression analysis showed that the presence of tumor-infiltrating lymphocytes (TILs) predicted better overall survival (HR = 0.318; P = 0.004). TLR4 T399I polymorphism was significantly associated with worse survival, P = 0.025. The overall survival rates were significantly lower for patients carrying variant allele T of TLR4 T399I SNP (TC and TT genotypes combined) ( P = 0.008, log-rank test), compared to wild-type genotype CC. Our findings indicate that TLR4 polymorphisms T399I (rs4986791) and D299G (rs4986790) could be potential prognostic and survival markers for melanoma patients.

GLI-1 polymorphisms of Hedgehog pathway as novel risk and prognostic biomarkers in melanoma patients.

In adult organisms, deregulation of the sonic hedgehog (SHH) signaling pathway is significantly correlated with different malignancies. Currently, data associating genetic polymorphisms in the SHH pathway with melanoma are scarce and largely unknown. The objective of our study was to elucidate an association between gene polymorphisms in the SHH pathway and prognosis of melanoma skin cancer patients. The current study investigated the association of PTCH1 (rs357564), SMO (rs2228617) and GLI1 (rs2228224, rs2228226), polymorphisms with melanoma predisposition and prognosis. Single-nucleotide polymorphisms were assessed by TaqMan SNP Genotyping Assays. The study involved 93 melanoma patients and 97 individuals in the control group. Melanoma patients with the variant mutant genotype GG of GLI1 rs2228226 polymorphism had poorer overall survival and recurrence-free survival (P = 0.0001 and P = 0.037, respectively). The multivariate analysis revealed that disease progression [hazard ratio (HR) = 14.434, P = 0.0001] and the GLI1 rs2228226 polymorphism (HR = 4.161, P = 0.006) persisted as independent prognostic factors. Mutated allele carriers (combined heterozygous and mutated genotypes) for GLI1 rs2228224 G and GLI1 rs2228226 G allele significantly increased melanoma risk [odds ratio (OR) = 2.261, P = 0.007; OR = 2.176, P = 0.010]. Our study demonstrated that genetic variants in GLI1, downstream member of the HH signaling pathway, are the risk factors for melanoma susceptibility and it can be a novel marker for melanoma prognosis. As a crucial SHH signaling member, GLI1 can also be regarded as a novel drug target for anti-cancer treatment in melanoma.

Platelet gel in wound treatment in patient with pemphigus vulgaris and Type 2 diabetes mellitus: Case report.

Treatment of wounds, especially in patients with systemic diseases, is very difficult and time consuming, and it represents great challenge. Complications like infections and impaired healing are regularly seen in these patients, sometimes leaving almost no other treating option, but amputation surgery. In wound healing process, platelets play one of key roles, both in hemostasis, and, by releasing many growth factors, in reepithelization and tissue remodeling. Platelet concentrates are defined as autologous or homologous platelet derivatives with a platelet concentration higher than it is usually in human blood. Concentration of platelets needed to affect wound healing should be 1,000,000/µl. This is a report about patient with pemphigus vulgaris and Type 2 diabetes mellitus, who got injury of the left lower leg. Traditional surgical methods of wound closure and vacuum-assisted closure therapy were ineffective. Homologous platelet gel was used topically, resulting in wound closure, without any adverse effects.

Skin vascularisation field by the ascending branch of the peroneal artery ramus perforans.

BACKGROUND/AIM: Soft tissue defects in the distal third of the lower leg are persistent and constitute a major problem in the reconstructive surgery. This study presents an analysis of the anatomical vascularization filed of ascending branch of the peroneal artery ramus perforans (PARS). The aim of this study was to assess reliability of the distal flap on the antero-lateral aspect of a lower leg distal third. METHODS: Direct gentiana violet injection into the interosseal perforator of ten fresh cadaveric lower legs with subsequent corrosion acrylic preparation was performed to reveal vascularization filed of the ascending branch of the PARP. Height, length, diameter and communication of perforating branch and its subsequent smaller ascending and descending branches were determined. The CAMIA software was used. RESULTS: Our results show that the PARP is always present. Its origin from the peroneal artery is at the medial height of 66 mm when measured from the inferior border of the lateral malleolus. Medium length of ramus perforans is 51.7mm. After transition through the interosseous membrane, ramus perforans divides into ascending and descending branches. The diameter proximal to the level of bifurcation is 1.37 mm (variation 1.0-1.8 mm), and the diameter of the ascending branch distal to the level of bifurcation is 1 mm. Using CAMIA software, the medium length, width and area of the vascularization filed labeled with gentian violet were calculated to be 164 mm (variation 125-210 mm), 66 mm (57-77 mm), and 10,305 mm2 (6,385 mm2-14,341 mm2), respectively. CONCLUSION: Our results support the use of fasciocutaneous distal flap, vascularized by the ascending branch of the PARP for reconstruction of soft tissue defects in the distal third of the lower limb, malleolar regions and dorsum.

Embolism of brain tissue in intrapartum and early neonatal deaths: report of 9 cases.

We report the clinical features and pathological findings in 9 cases of intrapartum and early neonatal death associated with embolism of brain tissue to the pulmonary and systemic circulation following difficult delivery. All except 1 of the cases in this series were born at, or near to, term, were vertex presentations, and were normally grown. All followed instrumental delivery and in 5, at least one mode of assisted delivery had failed. Whilst some evidence of cranial trauma was present in 7 cases, only 3 had skull fractures and 7 showed intracranial hemorrhage, although this was described as minor in 3. Emboli of brain tissue were identified in the pulmonary circulation in all cases. Fragments of brain were also seen in vessels of other organs, in particular the heart, in 6 cases. Emboli were highlighted by immunostaining for glial fibrillary acid protein. Brain emboli should be sought in all post mortems of unexplained intrapartum or early neonatal death following difficult delivery, even in the absence of overt cranial trauma. Disseminated intravascular coagulation is a frequent association. Extensive sampling for histology, particularly of the lungs and coronary vessels, is essential if this condition is not to be missed.