The limited therapeutic strategies available for stroke leave many patients disabled for life. This study assessed the potential of programmed death-ligand 1 (PD-L1) and hepatocyte growth factor (HGF)-engineered mesenchymal stem cell-derived exosomes (EXO-PD-L1-HGF) in enhancing neurological recovery post-stroke. EXO-PD-L1-HGF, which efficiently endocytosed into target cells, significantly diminishes the H
Fourteen patients with caustic necrosis of the digestive tract extending beyond the pylorus were included in a multicenter retrospective study to define a surgical strategy. Twelve patients underwent esophagogastrectomy. Two patients had total gastrectomy without esophagectomy. In addition, all patients underwent duodenal stripping (n = 7) or pancreaticoduodenectomy (n = 7). Immediate biliopancreatic reconnection was performed in ten patients. Four patients had biliary diversion and/or pancreatic duct ligation.Seven in-hospital deaths occurred after a mean delay of 27 days (range 16-45 days). There were two late deaths occurring 6 and 12 months postoperatively. Morbidity was noted in 86% of survivors. Acute or chronic airway tract injuries were incurred by 57% of patients. Among the five long-term survivors two were able to feed orally and had preserved voice function. One long-term survivor could resume oral feeding only, another was considered psychologically unfit for digestive reconstruction but had normal voice function and the last patient was deprived of oral feeding and phonation.Early radical debridement is capable of saving patients with gastrointestinal necrosis extending beyond the pylorus. Necrosis of the duodenum can be managed by pancreaticoduodenectomy or by duodenal stripping, with similar results. Immediate reconnection of the bile and pancreatic ducts to a small bowel Roux-en-Y loop appears preferable to biliary diversion and pancreatic duct ligation. Normal oral feeding and the preservation of voice function can sometimes be achieved but depends on late scarring of the airway-alimentary tract junction. Quality of life is often compromised by prolonged hospital stays, staged surgical procedures and the handicap of a feeding jejunostomy and tracheal tube.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, the prevalence and mortality rates of which are very high in Taiwan. The study aimed at evaluating the contribution of XRCC7 G6721T, together with cigarette smoking and alcohol drinking lifestyles, to the risk of HCC. In this hospital-based case-control study, the association of XRCC7 single nucleotide polymorphism G6721T with HCC risk was examined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) among 298 HCC patients and 889 age- and gender-matched healthy controls. The results showed that the percentages of TT, GT, and GG XRCC7 G6721T were 53.0, 41.3, and 5.7 % in the HCC patient group and 48.9, 43.1, and 8.0 % in the non-cancer control group, respectively. We have further stratified the populations by genders, cigarette smoking, and alcohol drinking status to investigate their combinative contributions with XRCC7 G6721T genotype to HCC risk. The results showed that the GG genotype of XRCC7 G6721T conducted a protective effect on HCC susceptibility which was obvious among males and drinkers, but not females, smokers, non-smokers, or non-drinkers (p = 0.0058, 0.0069, 0.1564, 0.2469, 0.9354, and 0.3416, respectively). Our results suggested that the GG and GT genotypes of X-ray repair cross-complementing group 7 (XRCC7) G6721T had no effect on HCC risk to the whole population, but had a protective effect on HCC risk among males and alcohol drinkers.
Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. Interaction of COX-2 with its specific EP receptors on the surface of cancer cells has been reported to induce cancer invasion. However, the effects of COX-2 on migration activity in human chondrosarcoma cells are mostly unknown. In this study, we examined whether COX-2 and EP interaction are involved in metastasis of human chondrosarcoma.We found that over-expression of COX-2 or exogenous PGE2 increased the migration of human chondrosarcoma cells. We also found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of the COX-2 which was higher than that in normal cartilage. By using pharmacological inhibitors or activators or genetic inhibition by the EP receptors, we discovered that the EP1 receptor but not other PGE receptors is involved in PGE2-mediated cell migration and alpha2beta1 integrin expression. Furthermore, we found that human chondrosarcoma tissues expressed a higher level of EP1 receptor than normal cartilage. PGE2-mediated migration and integrin up-regulation were attenuated by phospholipase C (PLC), protein kinase C (PKC) and c-Src inhibitor. Activation of the PLCbeta, PKCalpha, c-Src and NF-kappaB signaling pathway after PGE2 treatment was demonstrated, and PGE2-induced expression of integrin and migration activity were inhibited by the specific inhibitor, siRNA and mutants of PLC, PKC, c-Src and NF-kappaB cascades.Our results indicated that PGE2 enhances the migration of chondrosarcoma cells by increasing alpha2beta1 integrin expression through the EP1/PLC/PKCalpha/c-Src/NF-kappaB signal transduction pathway.
Hepatocellular carcinoma (HCC) is third most frequent cause of cancer-related deaths worldwide.Liver transplantation (LT) is a potentially curative treatment and is the best treatment option for patients with decompensated cirrhosis.Although advanced HCCs are considered as contraindication for LT due to dismal prognosis, certain patients of HCCs with solitary metastasis in adrenal gland without any other extra-hepatic disease can still be managed by local resection of the adrenal gland metastasis and sequential LT.Herein we present our experience of sequential 4 cases of HCC solitary metastasis to adrenal gland that were treated by local resection and LT. Materials and Methods:Database of 937 patients that underwent LT at china medical university hospital was retrospectively analyzed.Four HCC patients that had solitary adrenal metastasis were evaluated for the outcome after living donor liver transplantation (LDLT).Three patients were diagnosed to have HCC whereas one patient was diagnosed with mixed HCC-Cholangiocarcinoma on explant pathology.All the four patients had underlying cirrhosis with solitary adrenal metastasis without any extrahepatic spread of primary disease.The adrenal gland metastasis was confirmed by pre-LT positive emission tomography (PET) scan.Results: Four patients (mean age, 53 years; M:F, 2:2) underwent LDLT for HCC with single adrenal metastasis (right adrenal gland=2 patients; and left adrenal gland=2 patients) .In three patients the adrenalectomy was performed during the recipient surgery whereas one patient underwent LDLT six months after the adrenal metastasis resection (Table 1).Follow up period ranged from 9 months to 59 months.Survival in first two patients was 52 and 59 months, respectively.The first patient developed lung metastasis and expired due to overwhelming sepsis at 52 nd post-LT month.The second patient in this series continue to have recurrence free survival at 59 months post-LT.The survival in third and fourth patients was 28 months and 9 months, respectively.The fourth patient in addition had mixed HCC-cholangiocarcinoma on histopathological analysis. Conclusion:Limited extrahepatic metastasis due to HCC can still be resected and LT can be performed if liver resection not possible with a good overall survival.The adrenalectomy can be done as a single stage procedure during LT surgery with modest long-term outcome.
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