Lipoprotein Lipase as a Candidate Target for Cancer Prevention/Therapy

Epidemiological studies have shown that serum triglyceride (TG) levels are linked with risk of development of cancer, including colorectal and pancreatic cancers, and their precancerous lesions. Thus, it is assumed that serum TG plays an important role in carcinogenesis, and the key enzyme lipoprotein lipase (LPL), which catalyzes the hydrolysis of plasma TG, may therefore be involved. Dysregulation of LPL has been reported to contribute to many human diseases, such as atherosclerosis, chylomicronaemia, obesity, and type 2 diabetes. Recently, it has been reported that LPL gene deficiency, such as due to chromosome 8p22 loss, LPL gene polymorphism, and epigenetic changes in its promoter region gene, increases cancer risk, especially in the prostate. In animal experiments, high serum TG levels seem to promote sporadic/carcinogen-induced genesis of colorectal and pancreatic cancers. Interestingly, tumor suppressive effects of LPL inducers, such as PPAR ligands, NO-1886, and indomethacin, have been demonstrated in animal models. Moreover, recent evidence that LPL plays important roles in inflammation and obesity implies that it is an appropriate general target for chemopreventive and chemotherapeutic agents

A New Secured Technique for Suprahepatic Vena Caval Anastomosis in Porcine Liver Transplantation

It is well recognized that hemorrhage or kinking of the suprahepatic vena caval anastomosis is the most fatal complication apparent within 24 hr after orthotopic liver transplantation in the pig. A secured technique for suprahepatic vena caval anastomosis is described in detail herein. Our technique include (1) the use of a diaphragmatic cuff, (2) the closure of phrenic vein orifices using transfixation technique, and (3) the application of "stay-suture" in the orifice of right phrenic vein. This technique has added significantly to the strength of the suprahepatic vena caval anastomosis, and there has been no experiences of uncontrollable bleeding and kinking of suprahepatic vena caval anastomosis in 48 porcine orthotopic transplants of the liver. In conclusion, we believe that this technique described herein is a simplified and secured method to avoid the hemorrhage and kinking of suprahepatic anastomosis in porcine liver transplantation

Undifferentiated Sarcoma of the Salivary Gland in a Mongolian Gerbil (Meriones unguiculatus)

A subcutaneous mass was found in the lower ventral neck region of a 55-week-old male Mongolian gerbil (Meriones unguiculatus). Histopathologically, the mass involved salivary glands and featured diffuse proliferation of pleomorphic neoplastic cells with large necrotic foci. The lesion was well demarcated from the surrounding tissue, although invasive growth to fibrous septa was occasionally observed. The neoplastic cells were mainly arranged in irregular sheets with severe cellular atypia, round to oval nuclei and varying amounts of eosinophilic cytoplasm. Mitotic figures and multinucleated giant cells were frequent. Immunohistochemical analysis revealed that the neoplastic cells were strongly positive for vimentin and S-100 and negative for NSE, cytokeratin, α-SMA, c-kit, factor VIII, CD34, α-1-antitrypsin, lysozyme and MSR-A. Based on the results, the mass was diagnosed as an undifferentiated sarcoma of the salivary gland. To the best of our knowledge, this is the first report of such a tumor in Mongolian gerbils

Improved Techniques for Orthotopic Liver Transplantation in Pigs: A preliminary study

Orthotopic liver transplantations were performed on 12 pigs between November, 1986 and February, 1987. Survivals and causes of death were assessed according to the type of surgical procedure employed. Six operations were carried out according to the original procedure of Terblanche et al, whereas for other six animals, the transplantation was conducted by our modified procedure in which cannulation was made into the splenic vein without splenectomy at the veno-venous (v-v) bypass and a diaphragmatic cuff was used for the anastomosis of suprahepatic vena cava. 1/6 animals with original procedure and 5/6 with our modified procedure survived for more than 7 days. The total ischemic time was significantly short in the group subjected to the modified procedure. The major cause of death in the group on which the original procedure was conducted was gastric ulceration, accounting for 67% of the mortality, whereas in the modified procedure group, the mortality rate was reduced significantly to 17%. This operative technique has provided excellent survival rates in our transplanted animals

Differential effects of allopregnanolone and diazepam on social behavior through modulation of neural oscillation dynamics in basolateral amygdala and medial prefrontal cortex

Effective treatments for major depressive disorder (MDD) have long been needed. One hypothesis for the mechanism of depression involves a decrease in neuroactive steroids such as allopregnanolone, an endogenous positive allosteric modulator of the γ-aminobutyric acid–gated chloride channel (GABAA) receptor. In our previous study, we discovered that allopregnanolone, not diazepam, exhibited antidepressant-like effects in the social interaction test (SIT) of social defeat stress (SDS) model mice. However, the dynamics of neuronal activity underlying the antidepressant-like effect remain unknown. In the current study, we conducted local field potentials (LFPs) recordings from the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) during the SIT to elucidate the relationship between the antidepressant-like effect and neuronal oscillation. We discovered that allopregnanolone has antidepressant-like effects in the SIT of SDS model mice by decreasing intervals of repetitive social interaction (inter-event intervals), resulting in increase of total social interaction time. We also found that theta and beta oscillation increased in BLA at the onset of social interaction following administration of allopregnanolone, which differed from the effects of diazepam. Theta and beta power in BLA within the social interaction zone exhibited a positive correlation with interaction time. This increase of theta and beta power was negatively correlated with inter-event intervals. Regarding theta-band coordinated activity between the BLA and mPFC, theta power correlation decreased at the onset of social interaction with the administration of allopregnanolone. These findings suggest that theta activity in BLA following social interaction and the reduced theta-band coordinated activity between the BLA and mPFC are implicated in social interaction, which is one of the antidepressant behaviors. These differences in neural activity could elucidate the distinctive mechanism underlying antidepressant-like effects of neuroactive steroids, as opposed to benzodiazepines

Ovarian Metastasis in Patients with Colorectal Carcinoma

The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over.</p

The impact of triple drug immunosuppression on clinical results of cadaveric kidney transplantation: a comparison of conventional immunosuppression.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.</p

Renal transplantation from HLA-haploidentical living-related donors: the effects of donor-specific blood transfusions and different immunosuppressive regimens.

One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.</p

Application of back-propagation neural networks to the modeling and control of multiple-input, multiple-output processes

Certain properties of back-propagation neural networks have been found to be useful in structuring models for multiple-input, multiple-output (MIMO) processes. The network's simplicity and its ability to identify the non-linearity can have wide impacts on the construction of model-based control system. Care must be taken to train the network with consistent data that contains sufficient dynamic information. A predictive control system based on the network model was proposed. Although the controller is relatively simple in terms of concept and computation, it shows excellent performances both in servo and regulator problems. Model prediction error sometimes causes a cyclic behavior in process responses; however, it can be stabilized by imposing certain constraints of controller action. The constraints are also effective for noisy measurements. Use of neural networks for modeling and control of MIMO system appears to be very promising with its ability to treat non-linearity and process interactions