Secreted semaphorin 5A suppressed pancreatic tumour burden but increased metastasis and endothelial cell proliferation

Background:

Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, and promotes tumour growth and metastasis. In this study, we examine whether (1) pancreatic cancer cells secrete SEMA5A and (2) that secreted SEMA5A modulates certain phenotypes associated with tumour progression, angiogenesis and metastasis through various other molecular factors and signalling proteins.

Methods and results:

In this study, we show that human pancreatic cancer cell lines secrete the extracellular domain (ECD) of SEMA5A (SEMA5A-ECD) and overexpression of mouse Sema5A-ECD in Panc1 cells (not expressing SEMA5A; Panc1-Sema5A-ECD; control cells - Panc1-control) significantly increases their invasion in vitro via enhanced ERK phosphorylation. Interestingly, orthotopic injection of Panc1-Sema5A-ECD cells into athymic nude mice results in a lower primary tumour burden, but enhances the micrometastases to the liver as compared with Panc1-control cells. Furthermore, there is a significant increase in proliferation of endothelial cells treated with conditioned media (CM) from Panc1-Sema5A-ECD cells and a significant increase in microvessel density in Panc1-Sema5A-ECD orthotopic tumours compared with those from Panc1-control cells, suggesting that the increase in liver micrometastases is probably due to increased tumour angiogenesis. In addition, our data demonstrate that this increase in endothelial cell proliferation by Sema5A-ECD is mediated through the angiogenic molecules – interleukin-8 and vascular endothelial growth factor.

Conclusion:

Taken together, these results suggest that a bioactive, secreted form of Sema5A-ECD has an intriguing and potentially important role in its ability to enhance pancreatic tumour invasiveness, angiogenesis and micrometastases.     

Techniques for colorectal anastomosis

Colorectal anastomotic leak remains one of the most feared post-operative complications, particularly after anterior resection of the rectum with, the shift from abdomino-peritoneal resections to total mesorectal excision and primary anastomosis. The literature fails to demonstrate superiority of stapled over hand-sewn techniques in colorectal anastomosis, regardless of the level of anastomosis, although a high stricture rate was noted in the former technique. Thus, improvements in safety aspects of anastom...     

Polycystic Ovary Syndrome (PCOS), Diagnostic Criteria,and AMH

The polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and a notable proportion of women of reproductive age are affected. It may constitute a risk factor for cancer development. Different factors could result in different manifestations and many of these are related to predispositions. It is essential to establish criteria to achieve an exact diagnosis of PCOS, especially among adolescent patients because of the overlap between features of PCO syndrome and physiological findings in puberty. Day by day the technology of ultrasonography is improving and accuracy is increasing, but remains dependent on the specific equipment available. Some factors are inter-related in determining PCOS prognosis. Serum AMH is synthesized by small antral follicles, which are precisely those seen on ultrasound and could help us to diagnose PCOS but there are many aspects that still require elucidation. In this mini- review we have attempted to identify some of these correlations.     

Simeprevir plus sofosbuvir for eight or 12 weeks in treatment‐naïve and treatment‐experienced hepatitis C virus genotype 4 patients with or without cirrhosis

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4‐infected patients with METAVIR F0‐F4 fibrosis. Sixty‐three patients (33 treatment‐naïve and 30 peg‐interferon/ribavirin (Peg‐IFN/RBV)‐experienced) enrolled in a partly randomized, open‐label, multicentre, phase IIa study. Patients with F0‐F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82‐97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg‐IFN/RBV null responders. The most commonly reported treatment‐emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4‐infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight‐ and 12‐week regimens.     

Effects of two anaesthetic regimes, MS-222 and eugenol, on plasma biochemical profile in Barbus sharpeyi

For choosing an anaesthetic agent for a particular purpose, the different properties has been notified such as the convenience for use, safety for the fish, humans and the environment, effectiveness, physiological disturbances and its cost. Invariably, in any study with clove oil, it has been regarded as an effective and acceptable alternative to other anaesthetics. The aim of the present study was to investigate effects of two anaesthetic regimes, MS-222 and eugenol, on plasma biochemical parameters in Barbus sharpeyi. B. sharpeyi fingerlings (mean weight, 5?g?±?1; mean length, 6?cm?±?1) were exposed to MS-222 (100?ppm) and eugenol (40?ppm) for induction of anaesthesia. Blood samples were taken to verify the effects of these anaesthetics on plasma biochemical parameters may use as an indicator of stress at time 0 (designated for each tank at the time of exposure to anaesthetic agent), 0.5, 1, 2 and 24?h after exposure by caudal severance. Plasma biochemical parameters concentrations were not significantly affected in B. sharpeyi (p?<?0.05). These results were expected because the trials were conducted in short-term exposures. Ion balance appears to be altered only in long-term stressing condition. Based on the results of this study, eugenol appears to be a safe anesthetic for use in B. sharpeyi.     

Gelfoam haemostatic agent with or without autologous bone marrow-derived stem cells for the regeneration of critical-size mandibular defects in the rabbit

This study evaluated the effect of Gelfoam sponge with and without autologous bone marrow-derived stem cells (BMSCs) on bone regeneration in critical-size mandibular defects. The study involved 56 New Zealand rabbits assigned to four groups (14 in each). The osseous defects in group I were irrigated with normal saline, those in group II were grafted with autogenous tibial bone, and those in group III were filled with Gelfoam sponge. Group IV defects were treated as for group III, but the interface between the Gelfoam sponge and bone surface was injected with BMSCs. At the end of 4 weeks, seven rabbits in each group were euthanized; the remaining animals were euthanized at the end of the experiment, at 8 weeks postoperative. The percentage area of newly formed bone was significantly higher in group IV at week 4 (0.030 ± 0.01%) and week 8 (0.060 ± 0.03%) than in group I (0.01 ± 0.00% and 0.02 ± 0.00%, respectively) and group III (0.08 ± 0.01% and 0.015 ± 0.02%, respectively), but was lower than that in group II (0.038 ± 0.02% and 0.082 ± 0.01%, respectively). Thus, the combination of Gelfoam and autologous BMSCs promoted the regeneration of mandibular critical-size defects better than the use of Gelfoam alone. However, the amount of newly generated bone was lower than in defects grafted with autogenous bone.