视黄酸及干扰素对胃癌细胞系MKN45中p16,p21,c-myc基因表达的影响

目的探讨全反式视黄酸及干扰素两种因子对胃癌MKN45细胞的影响.方法将视黄酸及干扰素同时加入胃癌细胞系MKN45中进行细胞培养,用MTT法测定细胞的生长状况,并通过Northern blot和免疫组化测定p16,p21及c-myc的表达情况.结果干扰素（IFN）协同全反式视黄酸（ATRA）可有效地抑制MKN45细胞生长,癌细胞经联合用药诱导后p16和p21基因的表达水平提高,c-myc基因表达水平下降.视黄酸受体RARα基因在MKN45细胞中呈低水平表达,经ATRA和IFN诱导后表达水平提高.结论 ATRA联合IFN诱导可调节p16和p21基因的表达水平,抑制胃癌MKN45细胞生长,这可能与细胞中RARα基因高水平表达有一定关系.     

Radiosensitivity and capacity for radiation-induced sublethal damage repair of canine transitional cell carcinoma (TCC) cell lines

Understanding the inherent radiosensitivity and repair capacity of canine transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to treat this disease. The objective of this study was to evaluate the parameters surviving fraction at 2 Gy (SF(2) ), α/β ratio and capacity for sublethal damage repair (SLDR) in response to radiation. Dose-response and split-dose studies were performed using the clonogenic assay. The mean SF(2) for three established TCC cell lines was high at 0.61. All the three cell lines exhibited a low to moderate α/β ratio, with the mean being 3.27. Two cell lines exhibited statistically increased survival at 4 and 24 h in the dose-response assay. Overall, our results indicate that the cell lines are moderately radioresistant, have a high repair capacity and behave similarly to a late-responding normal tissue. These findings indicate that the radiation protocols utilizing higher doses with less fractionation may be more effective for treating TCC.     

Squamous cell carcinoma in a digit of the hind limb with systemic metastasis in a 17-year-old female koala

We encountered a case of cutaneous squamous cell carcinoma (SCC) in a 17-year-old female koala at a zoo. A fragile, papillary, elevated mass was found on the third digit of the right hind limb. SCC was identified histopathologically: squamous cell-like polygonal tumor cells showed a nest-like growth pattern with epidermal down growth, central keratinization and necrotic foci, and invaded dermal connective tissues. Metastatic lesions were observed in various organs, including the lung and axillary lymph node: in the lung, multiple metastatic foci similar to the primary lesion, and in the axillary lymph node, individual polygonal tumor cells infiltrated the sinusoids. Immunohistochemistry revealed that the tumor cells were positive for proliferating cell nuclear antigen, which exhibited 32–33% of labeling indices in the tumor cells. To our knowledge, this is the first report of a case of SCC in a digit of a koala.     

Cellular localization of Visudyne® as a function of time after local injection in an in vivo model of squamous cell carcinoma: an investigation into tumor cell death

Objective To evaluate the effects of time on cellular localization of Visudyne^® after local injection. Animals Twenty athymic nude mice. Procedures A squamous cell carcinoma (SCC) cell line (A‐431) was injected into right and left dorsolumbar subcutaneous tissue of each mouse, representing treatment (T) and control (C) tumors. In experiment 1 (Exp 1; n = 10) and 2 (Exp 2; n = 10), the T tumors received a local injection of Visudyne^® (0.1 mg/cm³), and C tumors received an equal dose of 5% dextrose in water (D5W). Mice were randomly subdivided into two groups (A and B; n = 5 per group). Mice in Exp 1A and B were sacrificed 1 and 30 min after local injection, respectively. Experiment 1A and B tumors were evaluated by fluorescence microscopy to determine drug localization. Experiment 2A and B tumors were exposed to LED illumination 1 and 30 min after injection, respectively, and evaluated by transmission electron microscopy (TEM) to determine ultrastructural tumor cell damage. Results Fluorescence was detected within the cytoplasm of T tumors in both Exp 1A and B. Significance was detected in fluorescence intensity between T1 min vs. T30 min (P = 0.03) and between T1 min and C1 min tumors (P = 0.01), respectively. Tumors in Exp 2A and B demonstrated evidence of apoptotic cell death. Conclusions Fluorescence microscopy demonstrated higher Visudyne^® concentration within SCC cytoplasm of 1 min compared with 30‐min tumors. Transmission electron microscopy results revealed that tumors treated by photodynamic therapy (PDT) within 30 min of local injection undergo cellular apoptosis.     

The use of quantitative PCR to detect Felis catus papillomavirus type 2 DNA from a high proportion of queens and their kittens

Squamous cell carcinomas are common feline skin cancers that have been associated with infection with Felis catus papillomavirus type 2 (FcaPV-2). Currently, little is known about the epidemiology of FcaPV-2 infection. The aim of this study was to develop a real-time PCR assay to quantify FcaPV-2 DNA in plucked hairs and skin swabs from 11 healthy breeding queens and their kittens. Samples were taken prior to kittening and then 2, 7 and 28 days after kittening to determine the age at which the kittens were first exposed to the virus. FcaPV-2 DNA was amplified from all of the queens and from 91% of the kittens at 2 days of age. There was a wide range in the quantity of FcaPV-2 DNA detected, from 1 to 92,520 copies per swab, and from 0.01 to 234 copies per copy of reference gene DNA in the hair plucks. The quantity of FcaPV-2 DNA detected in samples collected from the kittens was strongly correlated to that of their respective queens and the mean viral DNA load was similar for cats within a household but varied significantly between households. This is the first time that quantitative PCR has been used to detect FcaPV-2 DNA and the results suggest that the virus is ubiquitous but there is a wide variation of viral DNA loads. Kittens appear to be exposed to FcaPV-2 early in life, presumably from direct contact with their queen. These results are important when determining if FcaPV-2 infection of cats is preventable.     

A Case of Metastatic Adrenocortical Carcinoma Diagnosed with Steroidogenic Factor-1 in a Sprague-Dawley Rat

This report describes the morphological and immunohistochemical characteristics of an adrenocortical carcinoma with distant metastasis in a Sprague-Dawley rat. Macroscopically, a single large mass was observed in the adrenal gland, and multiple nodules were noted in the lung, liver and thyroid. Histologically, the adrenal tumor consisted of a solid growth of eosinophilic round cells with nuclear atypia. Vascular invasion was present, and multiple metastatic lesions were also observed in the lungs, liver, and mediastinal lymph nodes. Immunohistochemically, the nuclei of these tumor cells were positive for Steroidogenic Factor-1 (SF-1). In the thyroid, tumor cells histologically resembling adrenal cells were immunohistochemically negative for SF-1 but positive for calcitonin; thus the lesion was diagnosed as thyroid C-cell carcinoma. From these results, the present case was diagnosed as adrenocortical carcinoma with distant metastases. SF-1 could be a valuable marker for the differential diagnosis of adrenocortical tumors versus other endocrine tumors such as C-cell carcinoma.     

A novel MCT1 and MCT4 dual inhibitor reduces mitochondrial metabolism and inhibits tumour growth of feline oral squamous cell carcinoma

Monocarboxylate transporters (MCTs) support tumour growth by regulating the transport of metabolites in the tumour microenvironment. High MCT1 or MCT4 expression is correlated with poor outcomes in human patients with head and neck squamous cell carcinoma (HNSCC). Recently, drugs targeting these transporters have been developed and may prove to be an effective treatment strategy for HNSCC. Feline oral squamous cell carcinoma (OSCC) is an aggressive and treatment‐resistant malignancy resembling advanced or recurrent HNSCC. The goals of this study were to investigate the effects of a previously characterized dual MCT1 and MCT4 inhibitor, MD‐1, in OSCC as a novel treatment approach for feline oral cancer. We also sought to determine the potential of feline OSCC as a large animal model for the further development of MCT inhibitors to treat human HNSCC. In vitro, MD‐1 reduced the viability of feline OSCC and human HNSCC cell lines, altered glycolytic and mitochondrial metabolism and synergized with platinum‐based chemotherapies. While MD‐1 treatment increased lactate concentrations in an HNSCC cell line, the inhibitor failed to alter lactate levels in feline OSCC cells, suggesting an MCT‐independent activity. In vivo, MD‐1 significantly inhibited tumour growth in a subcutaneous xenograft model and prolonged overall survival in an orthotopic model of feline OSCC. Our results show that MD‐1 may be an effective therapy for the treatment of feline oral cancer. Our findings also support the further investigation of feline OSCC as a large animal model to inform the development of MCT inhibitors and future clinical studies in human HNSCC.     

Ovarian mixed germ-cell tumor comprising mature teratoma and embryonal carcinoma in a four-toed hedgehog (Atelerix albiventris)

This report describes the clinical and histopathological characteristics of a rare mixed germ-cell tumor comprising teratoma and embryonal carcinoma in the left ovary of a 10-month-old four-toed hedgehog, with chief complaints of loss of appetite and lethargy. Laparotomy revealed a swollen left ovary with small disseminated peritoneal nodules, and bilateral ovariohysterectomy was performed. The left ovary had a mature teratoma with well-differentiated fat, bone, cartilage, salivary gland, trachea, keratin cyst, and nervous tissues, and an embryonal carcinoma consisting of poorly-differentiated epithelial cells arranged in tubular, alveolar, or solid patterns. Immunohistochemically, the embryonal carcinoma cells were positive for placental alkaline phosphatase and c-KIT. This is the first case of mature teratoma with embryonal carcinoma in the ovary of a hedgehog.