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1.
The role of tumor suppressor genes in the pathogenesis of canine melanoma is incompletely understood. The genes encoding the tumor suppressors p53, Rb, p21 (waf-1), p16 (ink-4a), and PTEN have been postulated to contribute to the pathogenesis of melanoma in humans and experimental animal models. To assess whether inactivation of these genes similarly contributes to the origin and progression of canine melanoma, we examined their expression in seven distinct canine melanoma cell lines and in 31 retrospective samples (representing 29 dogs) of spontaneous canine melanoma. Various patterns suggestive of loss of tumor suppressor function emerged in these cell lines. The most frequently observed abnormality was loss or significant reduction of p16 expression in six of seven cell lines and in 21 of 26 tumor samples. Loss or significant reduction of PTEN expression was seen in four of seven cell lines and in 13 of 27 tumor samples. Although p53 was detectable in all the cell lines and in 24 of 30 tumors, exclusion of p53 from the nuclear compartment was observed in each of the cell lines and in 18 of 25 tumor samples. These results indicate that loss of function of these tumor suppressor proteins is a common occurrence that may contribute to the origin of canine melanoma. In our sample population, abnormalities in the expression or localization of one or more tumor suppressor proteins occurred with similar frequency in malignant and benign tumors; thus, additional work is necessary to determine how these proteins may impact disease progression and response to therapy.  相似文献   

2.
MicroRNA-145 (miRNA-145; miR-145) is aberrantly expressed in most of human cancers and plays a significant role in carcinogenesis and cancer progression. In the current study, we focused on how miR-145 plays a role in canine and human malignant melanomas. MiR-145 was significantly downregulated in canine malignant melanoma tissues and canine melanoma cell lines, as well as human melanoma cell lines tested. The ectopic expression of miR-145 showed a significant growth inhibition in both canine and human melanoma cells tested, and the effect was achieved partly by suppressing c-MYC in canine melanoma LMeC and in human melanoma A2058 and Mewo cells. At the same time, a suppressive tendency on cell migration in canine melanoma KMeC cells and significant suppression of cell migration in human melanoma A2058 cells by suppressing FASCIN1 were also found. These findings suggest that miR-145 acts as a tumor suppressor in both canine and human malignant melanomas.  相似文献   

3.
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4.
The probiotic Lactobacillus brevis KB290 is a natural producer of cell‐bound exopolysaccharide (EPS), and the plasmid‐encoded glycosyltransferase genes are responsible for this EPS production. KB290 forms unique rugose colonies inside an agar medium; this characteristic is useful for detecting and enumerating KB290 in the gut or feces. However, the genetic elements associated with this morphology remain unclear. Here, we aimed to investigate the relation between the plasmid eps genes and rugose colony morphology in KB290. The plasmid‐cured mutants formed smooth colonies, and the rugose colony morphology was restored after complementation with the eps genes. The eps genes were successfully cloned and expressed in other L. brevis and L. plantarum strains. In these transformant strains, the presence of the EPS, consisting of glucose and N‐acetylglucosamine, correlated with rugose colonies, indicating that EPS is responsible for rugose colony formation. To the best of our knowledge, this is the first report identifying the genetic factors influencing rugose colonies in Lactobacillus strains. This rugose colony formation may serve as a useful selective marker for KB290 in routine laboratory and research settings and can be used to detect the spontaneous loss of plasmids in this strain.  相似文献   

5.
Fascin‐1 expression was examined in 9 cutaneous melanocytomas and 47 oral melanomas. The cases were scored on the basis of extent and intensity of staining, and combined scores were calculated. Fascin‐1 expression was observed in 5/9 (56%) melanocytomas and 46/47 (98%) melanomas. The combined score for fascin‐1 was significantly greater in stage III/IV melanomas than in stage I/II melanomas (P < 0.05). In addition, strong fascin‐1 staining was associated with a significantly shortened survival time (P < 0.05). The results of this study suggest that fascin‐1 overexpression correlates with the malignancy of canine melanoma and has the potential to be a new immunohistochemical marker to predict the clinical course of canine melanoma. In addition, targeted therapy for fascin‐1 may represent a new strategy for the treatment of canine melanoma.  相似文献   

6.
REASONS FOR PERFORMING STUDY: Equine melanomas occur most commonly in grey horses at age 5 years or more. Generally, benign and malignant melanomas are distinguished by microscopy, but a more distinct classification would be helpful. OBJECTIVES: The objectives of this study were to gain further evidence concerning the occurrence of melanotic tumours, and to evaluate the impact of heredity on melanoma development. METHODS: A clinical study was conducted on a defined population of 296 grey horses of Lipizzaner breed. Individuals were classified according to their stage of disease using a 0-5 scale. Heritability was estimated on a sample of 296 grey horses with pedigrees traced back as far as 32 generations. RESULTS: Of the 296 horses, dermal melanomas were present in 148 horses (50%), 68 of which were more than age 15 years; 51 of these were melanoma-bearing. In 75.6% of cases, melanotic tumours were detected underneath the tail. Although melanoma-bearing grey horses were encountered up to stage 4, none of the affected individuals suffered any severe clinical effect or was handicapped in performance. Statistical analysis revealed highly significant effects of stud and age (P < 0.0001), explaining 28% of the total variability. CONCLUSIONS: In contrast to melanomas in solid-coloured horses characterised by early metastases, melanomas in grey horses showed less malignancy. Affected individuals often had encapsulated nodules or structures similar to human blue nevi. Grey horse-specific genetic factors inhibiting metastatic processes may be responsible for this phenomenon. POTENTIAL CLINICAL RELEVANCE: Although the obtained heritability estimate of 0.36 with a standard error of 0.11 indicates a strong genetic impact on the development of melanoma in ageing grey horses, a possible influence of the genes with large effects was also suggested. Therefore, further analysis is required of melanoma development in the ageing grey horse.  相似文献   

7.
Melanoma is a common neoplastic disease of dogs with variable presentation and biological behavior. Canine malignant melanoma is a rapidly metastatic disease that generally is incurable. The loss of function of cellular safeguards built into the genetic program and of immune surveillance systems that cooperate to prevent tumor formation and progression appear to be important underlying causes of canine malignant melanoma. In effect, many existing cancer treatments restore the function of 1 or the other of these mechanisms. For example, chemotherapy and radiotherapy often kill tumor cells by initiating a genetic suicide mechanism (apoptosis), and immunotherapy initiates or enhances a response by the body's immune cells to identify and destroy cancer cells by mechanisms that rely on direct cytotoxicity or apoptotic cell death. Nevertheless, standard therapeutic approaches have not proved effective in treatment of canine malignant melanoma, with only marginal improvement in the outcome of dogs with this disease. The advantages of an improved understanding of the molecular basis of canine cancer are underscored by recent promising advances in diagnosis and in immunologic and genetic therapies that may help reduce the mortality of dogs affected with malignant melanoma.  相似文献   

8.
DNA聚合酶β(DNA polymerase beta,POLB) 属于DNA聚合酶X家族中的一员,主要参与真核生物DNA的复制、DNA损伤修复、基因重组以及细胞周期调控等多种生物代谢过程。POLB所在的DNA修复基因与癌基因、抑癌基因、细胞周期调节基因以及细胞凋亡基因共同维持着细胞基因组的稳定性和完整性。若特异性敲除POLB会导致胚胎致死。近年来研究发现,POLB与细胞的生长发育、周期调控等息息相关。POLB表达下降使得上述的癌基因、抑癌基因受到损伤后却不能得到正确修复,从而导致细胞周期的紊乱、增殖失控。因此,本文将从POLB的基因结构、生物学功能、POLB在动物方面的研究等几个方面的相关研究进展进行综述,重点阐述其生物学功能,以期更深入了解 POLB,为畜禽品种的改良奠定理论基础。  相似文献   

9.
Abstract

It has been shown that mammalian proto-oncogenes may be centrally involved in cell transformation in vitro and the formation of tumors in vivo. As part of a study on the evolutionary aspects of tumor formation, we have screened cell lines derived from brown bullhead Ictalurus nebulosus (BB), rainbow trout Oncorhynchus mykiss (RTG-2), common carp Cyprinus carpio (EPC), and chinook salmon Oncorhynchus tshawytscha (CHSE-214) for the presence or expression of sequences homologous to the mammalian proto-oncogenes. Southern blotting of DNA isolated from the fish cell lines showed multiple fragments having homology to v-src, v-raf, v-ras h, and v-erb-b DNA probes. In addition, monoclonal antibodies against the viral or cellular oncogenes of mammalian cells were able to recognize fish proteins that may be related to the myc, abl, fos, ras k, and p53 gene products. This study shows that proto-oncogenes are well conserved evolutionarily in vertebrates and may be factors involved in the acquisition of the transformed phenotype in fish.  相似文献   

10.
Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pig breeds. Since some of them are able to infect human cells, they might represent a risk for xenotransplantation using pig cells or organs. However, the expression and biological role of PERVs in healthy pigs as well as in porcine tumours is largely unknown. Since we and others have recently shown overexpression of a human endogenous retrovirus, HERV-K, in human melanomas, we studied the expression of PERVs in melanomas of selectively bred Munich miniature swine (MMS) Troll. This breeding herd of MMS Troll is characterised by a high prevalence of melanomas, which histologically resemble various types of cutaneous melanomas in humans. Several genetic factors have been defined when studying inheritance of melanomas and melanocytic nevi in MMS Troll. Here we show that the polytropic PERV-A and PERV-B as well as the ecotropic PERV-C are present in the genome of all melanoma bearing MMS Troll investigated. Most interestingly, in the spleen, but not in other organs, recombinant PERV-A/C proviruses were found. PERV expression was found elevated in melanomas when compared to normal skin and viral proteins were expressed in melanomas and pulmonary metastasis-derived melanoma cell cultures. During passaging of these cells in vitro the expression of PERV mRNA and protein increased and virus particles were released as shown by RT activity in the supernatant and by electron microscopy. Genomic RNA of PERV-A, -B and -C were found in pelleted virus particles. Although PERV expression was elevated in melanomas and pulmonary metastasis-derived cell cultures, the function of the virus in tumour development is still unclear.  相似文献   

11.
Feline ocular melanomas show a high malignant behaviour, but adjunctive therapies are non‐existent. The aim of this pilot study was to determine, whether feline ocular melanomas harbour mutations comparable to mutations in human melanomas and to evaluate the gene expression status of genes known to be involved in initiation and progression of human melanomas. Mutation hotspot regions of several genes of feline ocular melanomas were analysed by DNA sequencing and RNA expression levels of the respective genes and others were evaluated by quantitative real‐time polymerase chain reaction (RT‐qPCR). Common mutations found in human melanomas are not present in feline tumours. Gene expression analysis revealed a significant upregulation of KIT and LTA4H, as well as a downregulation of GNAQ, GNA11, BRAF and RASSF1 in feline ocular melanomas. As KIT seems to harbour a potential as target gene in human uveal melanomas, future studies should further investigate the potential of KIT as target for adjunctive therapy in feline ocular melanomas.  相似文献   

12.
The current report describes a malignant melanoma in the dermis of a 13-year-old bay Thoroughbred mare. Microscopic examination revealed that tumor cells were arranged in cords and packets within an abundant collagenous stroma containing scattered myxomatous foci. Tumor cells stained positively for S-100, neuron-specific enolase, and vimentin and some contained melanin granules. Some clusters of tumor cells were also positive for pancytokeratin. Expression of epithelial cell markers has been described in small numbers of human melanomas but has not been reported previously in equine melanomas.  相似文献   

13.
Neoplasia in both animals and humans results in part from lasting activation of tumor-promoting genes ("oncogenes") or diminished function of genes responsible for preventing neoplastic induction ("tumor suppressor genes"). The concept of "genetic addiction" has emerged to indicate that neoplastic cells cannot maintain a malignant phenotype without sustained genotypic abnormalities related to aberrant activity of oncogene(s) and/or inactivity of tumor suppressor gene(s). Interestingly, some genetic abnormalities reliably produce distinct morphologic patterns that can be used as structural signatures indicating the presence of a specific molecular alteration. Examples of such consistent genetic/microanatomic pairings have been identified for mutated oncogenes, such as rising mucin-producing capacity with RAS overexpression, and mutated tumor suppressor genes-including PTEN eliciting cell hypertrophy, RB1 dictating neuroendocrine differentiation, and TRP53 encouraging sarcomatous transformation. Familiarity with the concept of genetic addiction, as well as the ability to recognize such regular genomic-phenotypic relationships, are of paramount importance for comparative pathologists who are engaged in phenotyping genetically engineered mice to help unravel genomic intricacies in both health and disease.  相似文献   

14.
Feline melanoma: a comparative study of ocular, oral, and dermal neoplasms   总被引：2，自引：0，他引：2  
Melanomas diagnosed in 29 cats over an 11 year period included 19 ocular (16 intraocular, three palpebral), five oral, and five dermal melanomas. Intraocular melanomas involved the ciliary body and iris in 12; the whole eye was involved in four. The average age of cats with intraocular melanomas was 11 years; the female : male ratio was 9 : 7. Histologically, eight intraocular tumors were mixed, six were epithelioid, and two were spindle cell. Ten of 16 cats (62.5%) with intraocular melanomas were killed because of the tumor at a mean of 156 days; four are living with no evidence of disease (average, 255 days). The mean time of death in cats with palpebral melanoma was 409 days. Metastasis occurred in 63% of cats with intraocular melanoma and all cats with palpebral melanoma. Four cats with oral melanoma were killed at a mean of 61 days; all had metastasis. Of five cats with cutaneous melanoma, one was killed with metastasis at 90 days; three cats were alive without evidence of recurrence or metastasis greater than 365 days after surgery. Results of this study indicate that in the cat, ocular melanomas are more common than oral and dermal melanomas, and ocular and oral melanomas are more malignant than dermal melanomas, with higher rates of mortality and metastasis.  相似文献   

15.
Abstract

A poorly differentiated subcutaneous neoplasm occurred in a white bass Morone chrysops collected from a freshwater lake in Oklahoma. The neoplasm was a solitary soft round mass that bulged from the anal fin. Histologically, the neoplasm was lobular and consisted of islands of spindle-to- stellate cells separated by clefts. The islands frequently contained capillary profiles and deposits of an amorphous eosinophilic material. The lesion was mesenchymal and suggestive of a poorly differentiated hemangiopericytoma, though it might have derived from nerve sheath, pigment cells, fibroblasts, or smooth muscle. An epizootic of another type of dermal neoplasm, a poorly differentiated spindle cell tumor, has been reported in gizzard shad Dorosoma cepedianum residing in the same lake. However, etiology of the neoplasms from both the white bass and the shad remains uncertain.  相似文献   

16.
Malignant melanoma (MM) is one of the most aggressive cancers in dogs and in humans. However, the molecular mechanisms of its development and progression remain unclear. Presently, we examined the expression profile of microRNAs (miRs) in canine oral MM tissues and paired normal oral mucosa tissues by using the microRNA‐microarray assay and quantitative RT‐PCR. Importantly, a decreased expression of miR‐203 was significantly associated with a shorter survival time. Also, miR‐203 and ‐205 were markedly down‐regulated in canine and human MM cell lines tested. Furthermore, the ectopic expression of miR‐205 had a significant inhibitory effect on the cell growth of canine and human melanoma cells tested by targeting erbb3. Our data suggest that miR‐203 is a new prognostic factor in canine oral MMs and that miR‐205 functions as a tumour suppressor by targeting erbb3 in both canine and human MM cells.  相似文献   

17.
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18.
Various somatic cell nuclear transfer (SCNT) techniques for mammalian species have been developed to adjust species-specific procedures to oocyte-associated differences among species. Species-specific SCNT protocols may result in different expression levels of developmentally important genes that may affect embryonic development and pregnancy. In the present study, porcine oocytes were treated with demecolcine that facilitated enucleation with protruding genetic material. Enucleation and donor cell injection were performed either simultaneously with a single pipette (simplified one-step SCNT; SONT) or separately with different pipettes (conventional two-step SCNT; CTNT) as the control procedure. After blastocysts from both groups were cultured in vitro, the expression levels of developmentally important genes (OCT4, NANOG, EOMES, CDX2, GLUT-1, PolyA, and HSP70) were analyzed by real-time quantitative polymerase chain reaction. Both the developmental rate according to blastocyst stage as well as the expression levels CDX2, EOMES, and HSP70 were elevated with SONT compared to CTNT. The genes with elevated expression are known to influence trophectoderm formation and heat stress-induced arrest. These results showed that our SONT technique improved the development of SCNT porcine embryos, and increased the expression of genes that are important for placental formation and stress-induced arrest.  相似文献   

19.
Absence of p21 WAF1 and p27 Kip1 Gene Mutations in Various Feline Tumours   总被引：1，自引：0，他引：1  
The coding regions of tumour suppressor and cell cycle regulatory genes p21 WAF1 and p27 Kip1 were investigated in 101 feline tumours of various types. No damaging mutations were present in the analysed areas of the genes  相似文献   

20.
BackgroundMalignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor.ObjectivesIn this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs).MethodsA hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system.ResultsTCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells.ConclusionsSCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.  相似文献   

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