Non-Structural protein 1 (NS1) gene of Canine Parvovirus-2 regresses chemically induced skin tumors in Wistar rats

The Non-Structural protein 1 of Canine Parvovirus-2 (CPV2.NS1) plays a major role in viral cytotoxicity and pathogenicity. CPV2.NS1 has been proven to cause apoptosis in HeLa cells in vitro in our laboratory. Here we report that CPV2.NS1 has no toxic side effects on healthy cells but regresses skin tumors in Wistar rats. Histopathological examination of tumor tissue from CPV2.NS1 treated group revealed infiltration of mononuclear and polymorphonuclear cells with increased extra cellular matrix, indicating signs of regression. Tumor regression was also evidenced by significant decrease in mitotic index, AgNOR count and PCNA index, and increase in TUNEL positive apoptotic cells in CPV2.NS1 treated group. Further, CPV2.NS1 induced anti-tumor immune response through significant increase in CD8⁺ and NK cell population in CPV2.NS1 treated group. These findings suggest that CPV2.NS1 can be a possible therapeutic candidate as an alternative to chemotherapy for the treatment of cancer.     

Tumor promoting effect of phenolphthalein on development of lung tumors induced by N-ethyl-N-nitrosourea in transgenic mice carrying human prototype c-Ha-ras gene

In order to examine tumor modifying effects of phenolphthalein (PhP), female transgenic mice carrying human prototype c-Ha-ras gene (rasH2 mice) were given a single intraperitoneal injection of 60 mg/kg body weight of N-ethyl-N-nitrosourea (ENU), followed by the diet containing 12,000 ppm PhP for 26-week. Histopathologically, alveolar hyperplasias, adenomas and adenocarcinomas were observed in the ENU + PhP group, but only hyperplasias and adenomas were observed in the ENU alone group. The incidence and multiplicity of adenocarcinomas in the ENU + PhP group was significantly increased as compared to that in the ENU alone group. The combined multiplicity of adenomas and adenocarcinomas in this group was also significantly higher than that of the ENU alone group. In addition, the ratio of area of adenomas in the ENU + PhP group was significantly higher than that in the ENU alone group. The result of our study suggests that PhP has a clear tumor promoting effect in the lung of rasH2 mice.     

R2R3-MYB转录因子在果树花青素合成中的调控作用

摘要：花青素是一种重要的水溶性色素,该色素影响果实色泽表现,对人体具有非常重要的营养保健价值,已成为当前果树领域研究的热点之一。与花青素的合成路径密切相关的调控因子目前已有较深入的研究。花青素生物合成由一系列结构基因编码的酶催化完成,而其关键结构基因的表达主要受R2R3-MYB转录因子调控。近年大量研究表明,R2R3MYB的调 控作用受外界因子如温度,激素,光等的影响。本文在介绍果实花青素的种类、功能和合成的基础上,就R2R3-MYB的结构特征及其在花青素合成调控中的作用进行了概述,旨在为研究果树花青素形成的分子机理提供信息。     

Clinical approach to tumors of the skin and subcutaneous tissues

With skin tumors, "a lump is only a lump" until a definitive diagnosis has been made. It is nearly impossible to make an accurate diagnosis solely on clinical signs. In some instances, fine-needle aspirate may be diagnostic; however, in all instances biopsy is the preferred method for definitively diagnosing canine and feline skin tumors. Prognosis and treatment depend on the diagnosis.     

Benign and malignant epithelial tumors of the rete testis in mice

Two papillary cystadenomas and one papillary cystadenocarcinoma in the rete testis were found in two of 500 very old male JCL:ICR mice; the hosts had no other tumors. One mouse had bilateral cystic tumors. A 5 x 3 x 3 mm papillary cystadenoma was observed in the rete of the right testis. A 7 x 3 x 3 mm tumor with a mixed pattern of papillary cystadenocarcinoma and papillotubular adenocarcinoma was found in the rete of the left testis; the latter extended from the mediastinum to the ductuli efferents and the caput epididymis. The other mouse had a 9 x 5 x 5 mm papillary cystadenoma of borderline malignancy in the rete of the right testis. The mice had no clinical signs.     

Effects of astaxanthin supplementation on chemically induced tumorigenesis in Wistar rats

Background

Astaxanthin (ASTA) is a fat-soluble xanthophyll with powerful antioxidant functions. It is extracted from e.g. salmon, an important food source for certain human populations known to have a reduced risk of tumor development. It is possible that ASTA plays a role in cancer chemoprevention in such populations. The purpose of this study was to investigate the effects of dietary ASTA on chemically induced mammary tumorigenesis using N-methyl-N-nitroso-urea (MNU) in immature Wistar rats.

Methods

Thirty-six 37 days old juvenile female Wistar rats were at random allocated to 4 groups of which Groups 1 and 2 received a single dose of 55 mg MNU/kg body weight. The effects of ASTA was evaluated by giving rats of Groups 2 and 4 a dose of 50 mg ASTA/kg/day for the entire duration of the study. Group 3 rats received feed added alimentary oil.Necropsy and histopathological examinations were carried out on each rat 14 months after the administration of MNU. Haematological values and antioxidative status were determined. Oxidative stress was evaluated by monitoring superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in hepatic tissue. Lipid peroxidation and carbonylation of proteins was determined in protein extracts from the liver.

Results

Tumor development occurred only in rats of Groups 1 and 2, i.e. MNU exposed animals. Frequency of tumor development in general and average number of tumors per animal were insignificant between these two groups. Mammary gland tumors developed in equal frequencies in Group 1 and 2 rats, respectively. Although only rather few tumors were found in the mammary glands, a substantial number of other tumors were found in Group 1 and 2 rats, but at equal rates.Biochemical analyses showed significant higher levels of GPx, malondialdehyde and dinitrophenylhydrazine in Group 1 rats that for rats in all other groups thus indicating protective effects of ASTA on MNU induced hepatic oxidative stress.

Conclusions

Supplementation with ASTA did not reduce tumorigenesis induced by MNU in Wistar rats. However, supplementation with ASTA seemed to have anti-inflammatory effects.     

Nine cases of granular cell tumors in B6C3F1 mice

The histological characteristics of 9 cases of granular cell tumors (GCTs) observed in B6C3F1 mice were examined to determine their cellular origin. Seven of the 9 cases were found in the uterus and other 2 cases were in the subcutaneous tissue. Tumor cells had abundant granules in the cytoplasm which were stained with PAS and were resistant to diastase treatment. Ultrastructurally, the granules were identified as lysosomes. The cell surface had cytoplasmic processus showing interdigitation with adjacent cells. A character feature of the tumor cells was the presence of a desmosome-like structure on their cell surface but no basal lamina was demonstrated. Although GCTs have been considered to be derived from Schwann cells on the basis of their ultrastructural features and S-100 protein-immunopositive findings, the absence of basal lamina in the present cases may raise a controversy as to their origin.     

The nature of immunity to Snyder-Theilen fibrosarcoma virus induced tumors in cats

Snyder-Theilen fibrosarcoma virus (ST-FeSV) induced tumors evoked a vigorous immune response in adolescent cats. The response was characterized histologically by a lymphoid and histiocytic cell infiltrate beginning around the 9th day post inoculation. Hyperemia edema, hemorrhage, and necrosis of the tumors occurred shortly thereafter. Gross regression of the tumors commenced around the 15th day. Viable fibrosarcoma cells could be recovered as almost pure cultures from tumors biopsied on the 9th day. Biopsies taken between days 9 and 15 contained progressively fewer tumor cells and increasing numbers of lymphoid cells, histiocytes, giant cells, and normal fibroblasts. Tumor cells in such mixed cultures did not replicate as fast as normal and died out within 7 to 14 days. Viable tumor cells were not recovered from biopsies taken after day 15. Fibrosarcoma regression was associated with the appearance of tumor cell specific cytotoxic lymphocytes and antibodies in the blood. Cell mediated immunity, as determined by a chromium release assay, consisted of both antibody dependent and independent mechanisms. Fluorescent and complement dependent cytolytic antibodies were detected in the blood at the same time as cytotoxic lymphocytes, but persisted after regression. In a preliminary experiment, serum from tumor regressor cats was injected into susceptible kittens, and the kittens were then challenged with ST-FeSV transformed fibroblasts or whole FeSV. Immune serum did not prevent the appearance of initial growth of tumors, but did slow their subsequent growth and increased the rate of regression. Immune serum had a much more dramatic inhibitory effect on the accompanying retrovirus infection.     

蛋白聚糖在骨骼肌发育中作用的研究进展

蛋白聚糖是一类由1个核心蛋白和1个或多个共价连接的糖胺聚糖组成的大分子,根据分布位置不同,主要分为细胞膜表面蛋白聚糖,包括多配体蛋白聚糖家族(syndecans)、磷脂酰肌醇蛋白聚糖-1(glypican-1);细胞外基质蛋白聚糖,包括串珠蛋白聚糖(perlecan)、核心蛋白聚糖(decorin)。在不同类型的参与骨骼肌生理活动的大分子中,蛋白聚糖在过去几年中引起了极大的关注。蛋白聚糖通过调控一些细胞因子,如成纤维细胞生长因子(FGF-2)、肝细胞生长因子(HGF)影响骨骼肌卫星细胞的活化、增殖和迁移,从而影响骨骼肌的发育、修复和维持过程。     

Inhibitory effects of interleukin-10 plasmid DNA on the development of atopic dermatitis-like skin lesions in NC/Nga mice

Interleukin (IL)-10 exerts potent anti-inflammatory effects by suppression of both T-help (Th) 1 and Th2 cells. Previous studies have reported that IL-10 can ameliorate various inflammatory disorders. The present study was performed to examine whether IL-10 plasmid DNA could suppress development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice, as an initial step towards the development of an appliance for use in dogs with AD. Intradermal injection of IL-10 plasmid DNA markedly inhibited the development of AD-like skin lesions, as evidenced by a marked decrease in skin symptoms and reduced inflammation within the skin lesions. Efficacy was confirmed by significant decreases in eosinophil ratio and serum IgE concentration, and a reduction in the number of Staphylococcus aureus recovered from the ear. Moreover, relative mRNA expression levels of IL-4 and interferon-γ in the skin lesions of mice injected with IL-10 plasmid DNA were also decreased compared with those of control mice. Of note, higher serum IL-10 levels in mice injected with IL-10 plasmid DNA were maintained compared with those in control mice. Taken together, the results indicate that IL-10 plasmid DNA can suppress the development of AD-like skin lesions by suppressing both Th1 and Th2 cell responses. Beneficial effects of IL-10 plasmid DNA may be expected in dogs with AD.     

The pentobarbital anesthetized dog: an animal model for assessing chemically induced changes in renal function and ultrastructure

An experimental procedure was devised using the pentobarbital-anesthetized dog that could be used for the comprehensive evaluation of the renal effects of chemicals. After IV or renal arterial administration of 0.9% saline solution (vehicle), 12 renal function determinants were continuously monitored for periods of 2 and 6 hours. At the completion of the 2 or 6 hours of study, the kidneys of a number of dogs (usually between 1 and 7) in each vehicle-treated group were subjected to a modification of the intravascular perfusion-of-fixative technique to evaluate the ultrastructural status of the outer cortical, inner cortical, and outer medullary tissue. The remaining dogs (at least 3) in each vehicle-treated group were given a nonnephrotoxic, but maximally effective, diuretic dose of ethacrynic acid, which enabled an assessment of the functional integrity of the thick ascending limb of Henle's loop. Renal function and glomerular and tubular ultrastructure remained stable in the pentobarbital-anesthetized dog for up to 6 hours after administration of vehicle. Sustained infusion of inulin (included in the procedure to estimate glomerular filtration rate) throughout the duration of the experiments, and pentobarbital anesthesia of various durations did not alter the morphologic status of the canine nephron. The procedure used for the renal perfusion of fixative circumvented any manipulation of the kidneys before fixation and allowed for the acquisition of normal (unaltered) appearing tissue from all areas of the kidneys. The responses of pentobarbital-anesthetized dogs to ethacrynic acid administration were similar when given 2 and 6 hours after the vehicle administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intra-articular administration of dimethylsulfoxide on chemically induced synovitis in immature horses

The effects of intra-articular administration of dimethylsulfoxide (DMSO) on chemically induced synovitis in the middle carpal joint of 6 weanling horses were evaluated. Following aseptic collection of synovial fluid, the middle carpal joint of each forelimb was injected with 50 mg of Na-monoiodoacetate to induce synovitis. Eight days after injection, synovial fluid was obtained and the right middle carpal joints were injected with 2 ml of 40% DMSO in lactated Ringer solution. The corresponding joints of the left limb (control) were injected with 2 ml of lactated Ringer solution. Sampling and treatments were repeated on post-injection days 11 and 14, for a total of 3 treatments. Horses were visually evaluated daily for lameness and joint effusion. Synovial fluid was evaluated for color and clarity, differential and total WBC count, total protein content, and hyaluronic acid concentration. The Kaegi gait analysis system provided an objective assessment of lameness prior to inducing synovitis, again on day 7, and on day 17. At necropsy (day 17), synovial fluid, synovial membrane, and articular cartilage specimens were collected. Joint effusion was evident 12 hours after injection of Na-monoiodoacetate in all joints. Mild lameness was evident at 24 hours; however, the lameness resolved by 72 hours. Objective assessment of lameness did not reveal significant differences between treatment or control limbs. Hyaluronic acid concentrations increased significantly (P = 0.023) above baseline values in most joints over the study period. Synovial fluid WBC counts increased significantly (P = 0.002) following Na-monoiodoacetate injection and remained significantly (P = 0.002) above baseline values throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epididymal interstitial (Leydig) cell tumors in B6C3F1 mice

Six primary interstitial cell tumors of the epididymis were identified from 46,752 male B6C3F1 mice used in chronic toxicity and carcinogenicity studies. Five of the tumors occurred at the end of 2-year studies; none were attributed to treatment. None of the mice with epididymal tumors had a primary testicular tumor. Histologically, tumors were characterized by a nodular or diffuse proliferation of tumor cells in the epididymal interstitium. Most cells were polygonal with highly vacuolated cytoplasm (vacuolated cells) or eosinophilic cytoplasm (eosinophilic cells). Smaller hyperchromatic cells with scant basophilic cytoplasm (basophilic cells) and cells with yellow-brown pigment characteristic of lipofuscin (pigmented cells) were less common. In each tumor two or more cell types were present. Extension of these tumors through the capsule, invasion of the testis, or metastasis did not occur. By electron microscopy both eosinophilic and vacuolated cell types had a large round or oval nucleus with sparse heterochromatin, abundant mitochondria with tubulovesicular cristae, and frequent desmosome structures between cell membranes. Vacuolated cells contained numerous lipid droplets. Morphological features of the epididymal tumors are similar to those of the testicular interstitial (Leydig) cell tumor in mice and rats.     

LPS诱导小鼠子宫内膜炎模型的建立

为了建立小鼠子宫内膜炎模型,为子宫内膜炎的发病机理及其防治方法的研究提供合适的动物疾病模型,在小鼠子宫内灌注不同浓度的脂多糖(LPS),分别于灌注后12、24、36 h和48 h收集子宫,观察子宫组织形态学变化,检测子宫组织髓过氧化物酶(MPO)和一氧化氮(NO)的含量。结果在灌注LPS后可见小鼠子宫上皮细胞脱落、水肿、充血、出血和炎性细胞浸润。灌注1.25、2.5 mg/m L和5 mg/m L的LPS作用12 h,小鼠子宫组织MPO和NO含量极显著高于对照组(P0.01);灌注2.5 mg/m L和5 mg/m L的LPS作用24 h,小鼠子宫组织MPO和NO含量极显著高于对照组(P0.01)。表明采用子宫灌注LPS法成功建立小鼠子宫内膜炎模型,且每只小鼠灌注20μL浓度为2.5~5.0 mg/m L的LPS作用12~24 h为最佳的建模条件。