Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chickens could be protected against lethal lymphoblastic leukaemia due to the nonproducer JMV Marek's disease (MD) tumour transplant by infection with the herpesvirus of turkeys (HVT) or various strains of MD virus. However, solid JMV tumours developed in MD virus-infected birds at the site of intramuscular or subcutaneous transplantation, but tumours never developed at the site of MD virus inoculation. The incidence and extent of local tumour growth, the development of metastases and the inhibition of tumour regression were related to the pathogenicity of the MD virus strains used for pre-treatment of the chickens. Infection of chickens with reticulo-endotheliosis virus (REV-C) or with chick syncytial virus (CSV), which are nonprotective against MD virus or JMV transplants, stimulated local tumour development of the attenuated JMV-A variant of the JMV transplant. Chickens which did not reject local tumours died of visceral JMV tumour metastases. A direct helper mechanism of viral infection on the oncogenicity of transplants was excluded. The results suggested that virus-induced immunosuppression stimulated the development of local JMV tumours which never occurred in normal chickens. Immunity to the JMV transplant, including resistance to lethal leukaemia and successful regression of local tumours, did not coincide with immunity to MD virus-induced visceral lymphomas or nerve lesions. Vaccinal induced tumour immunity evidently was defective. The significance of these results is discussed with reference to immunological functions of MD tumour-specific antigens.
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PMID:Stimulation of local solid tumour development of the nonproducer Marek's disease tumour transplant JMV by virus-induced immunosuppression. 1877 Feb 43

Metastatic carcinoma of urogenital origin is a common cause of mortality in free-ranging California sea lions (Zalophus californianus). The etiology of this cancer is likely multifactorial, with viral infection, genetic factors, and exposure to environmental organochlorine contaminants possible contributing factors. In this study, expression of estrogen receptor alpha (ER alpha), progesterone receptor (PR), p53, and Ki67 were evaluated by immunohistochemistry in 12 sea lions with metastatic carcinoma, genital epithelial dysplasia, and intraepithelial neoplasia; 4 with genital epithelial dysplasia and intraepithelial neoplasia without metastases; and 6 control animals. Dysplastic and neoplastic lesions were identified in multiple areas of the cervix, vagina, penis, prepuce, and urethra in affected animals, suggesting multicentric development. Lesions were graded according to degree of epithelial dysplasia and infiltration and lesions of different grades were evaluated separately. Estrogen receptor expression was lower in intraepithelial lesions compared with normal genital epithelium, and expression in metastatic lesions was completely absent. There was progesterone receptor expression in neoplastic cells in intraepithelial lesions of all grades and in metastases, with no significant difference between lesion grades or between control and affected epithelium. Ki67 index and p53 expression increased with lesion grade and were higher in lesions than normal epithelium. Metastatic tumors exhibited highly variable morphology; however, proliferation index, ER alpha, PR, and p53 expression were similar in tumors with different patterns of growth. These results suggest that endogenous hormones, environmental contaminants that interact with steroid hormone receptors, and alterations in p53 may play a role in urogenital carcinogenesis in California sea lions.
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PMID:Tumor morphology and immunohistochemical expression of estrogen receptor, progesterone receptor, p53, and Ki67 in urogenital carcinomas of California sea lions (Zalophus californianus). 2008 May 1

Tumor cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. Signal transducer and activator of transcription (STAT) 3 regulates all of these processes in a surprisingly large number of human cancers. Consequently, the STAT3 protein is emerging as an ideal target for cancer therapy. This paper reports the generation of an oncolytic adenovirus (M4), which selectively blocks STAT3 signaling in tumor cells as a novel therapeutic strategy. M4 selectively replicated in tumor cells and expressed high levels of antisense STAT3 complementary DNA during the late phase of the viral infection in a replication-dependent manner. The viral progeny yield of M4 in tumor cells was much higher than that of the parent adenoviral mutants, Ad5/dE1A. M4 effectively silenced STAT3 and its target genes in tumor cells while sparing normal cells and exhibited potent antitumoral efficacy in vitro and in vivo. Systemic administration of M4 significantly inhibited tumor growth in an orthotopic gastric carcinoma mouse model, eliminated abdominal cavity metastases and prolonged survival time. In summary, M4 has low toxicity and great potential as a therapeutic agent for different types of cancers.
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PMID:A novel oncolytic adenovirus selectively silences the expression of tumor-associated STAT3 and exhibits potent antitumoral activity. 3210 25

Head and neck cancer arises from a series of molecular alterations progressive from dysplasia to carcinoma in situ, and finally invasive carcinoma. Risk factors associated with head and neck cancer include tobacco, alcohol and viral infection. There are genetic alterations in pre-cancerous cells that contribute to transformation. The accumulation of these alterations facilitates tumor development. Additionally, the tumor microenvironment enables tumor progression. The cooperative effect of molecular alterations in the tumor cells and compensatory microenvironment changes enable tumors to invade and metastasize. This review focuses on the genes and molecules altered during the progression of head and neck cancer with an emphasis on the genetic, molecular and phenotypic changes during the pathogenesis of head and neck cancer. Therapeutic strategies that target key changes in the tumor cells and/or stromal cells in the tumor microenvironment are discussed.
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PMID:The molecular pathogenesis of head and neck cancer. 2003 20

Soft tissue Rosai-Dorfman disease (STRDD) is rare, previously reported only as single cases and few series. Simian virus 40 (SV40), a polyomavirus, has been identified in lymphoid processes and has a controversial role in neoplasia etiology. Occasional cytoplasmic pink granular inclusions and nuclear changes led us to explore a viral etiology. Only unpublished STRDD from our files with adequate material, soft tissue location, and diagnostic confirmation were included. Immunohistochemistry and follow-up were obtained. Eighteen STRDD patients, 4 male and 14 female, had 29 lesions; 5 with 2 or more lesions. Ages ranged from 8 to 81 years (mean 42.6 years and median 42.5 years). Soft tissue Rosai-Dorfman disease locations include trunk or proximal extremity (n = 19), distal extremity (n = 5), "abdominal" (n = 3), face (n = 1), and unknown subcutaneous site (n = 1). Sizes ranged from 0.5 to 13.7 cm (median, 2.4 cm). Previous disease included lymphoma, buttocks injection site, diabetes and hypothyroidism, and radiation for chronic dermopathy. No patients had a preceding or concurrent known viral infection; none had lymphadenopathy at present. None were known to be immunocompromised. Soft tissue Rosai-Dorfman disease was rapidly progressing. Initial pathologic diagnosis ranged from Rosai-Dorfman disease or inflammatory pseudotumor to inflammatory malignant fibrous histiocytoma. Grossly STRDDs were multilobulated, tan-yellow, and firm; morphologically, circumscribed, and subcutaneous-based. All had sheets of polygonal histiocytes with abundant pale eosinophilic cytoplasm, emperipolesis, plasma cells, and lymphocytes scattered and within clusters. Focal spindle cell change and mild pleomorphism were each observed in 3 patients; 2 had focal necrosis, none with mitoses. Small granular pink cytoplasmic inclusions and nuclear viral-like changes were observed. By immunohistochemistry, all STRDDs were positive for S100 protein, negative for CD1a, Epstein-Barr virus, and latent membrane protein, yet 3 (all abdominal, 1 multicentric) of the 9 studied were focally positive for cytoplasmic and nuclear SV40 polyomavirus. All were treated by local excision. Follow-up on 14 patients older than 8 to 16 years revealed recurrence in 3 patients with persistent multiple lesions, one with abdominal location. There were no metastases or death from disease. Soft tissue Rosai-Dorfman disease is a rapidly evolving, mostly solitary and nonrecurrent trunk and proximal extremity subcutaneous lesion in middle-aged females. More than one third can have persistent multicentric disease. It is important to recognize STRDD, to separate it from malignancy. Epstein-Barr virus/latent membrane protein was negative but polyomavirus was positive in 3 patients with abdominal STRDD, one with multicentric persistent disease. The relationship of polyomavirus to the evolution of abdominal STRDD should be further explored.
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PMID:Soft tissue Rosai-Dorfman disease: 29 new lesions in 18 patients, with detection of polyomavirus antigen in 3 abdominal cases. 2085 Jun 91

Oncolytic herpes simplex virus 1 (HSV-1) viruses armed with immunomodulatory transgenes have shown potential for enhanced antitumor therapy by overcoming tumor-based immune suppression and promoting antitumor effector cell development. Previously, we reported that the new oncolytic HSV-1 virus, OncSyn (OS), engineered to fuse tumor cells, prevented tumor growth and metastasis to distal organs in the 4T1/BALB/c immunocompetent breast cancer mouse model, suggesting the elicitation of antitumor immune responses (Israyelyan et al., Hum. Gen. Ther. 18:5, 2007, and Israyelyan et al., Virol. J. 5:68, 2008). The OSV virus was constructed by deleting the OS viral host shutoff gene (vhs; UL41) to further attenuate the virus and permit dendritic cell activation and antigen presentation. Subsequently, the OSVP virus was constructed by inserting into the OSV viral genome a murine 15-prostaglandin dehydrogenase (15-PGDH) expression cassette, designed to constitutively express 15-PGDH upon infection. 15-PGDH is a tumor suppressor protein and the primary enzyme responsible for the degradation of prostaglandin E2 (PGE2), which is known to promote tumor development. OSVP, OSV, and OS treatment of 4T1 tumors in BALB/c mice effectively reduced primary tumor growth and inhibited metastatic development of secondary tumors. OSVP was able to significantly inhibit the development and accumulation of 4T1 metastatic tumor cells in the lungs of treated mice. Ex vivo analysis of immune cells following treatment showed increased inflammatory cytokine production and the presence of mature dendritic cells for the OSVP, OSV, and OS viruses. A statistically significant decrease in splenic myeloid-derived suppressor cells (MDSC) was observed only for OSVP-treated mice. These results show that intratumoral oncolytic herpes is highly immunogenic and suggest that 15-PGDH expression by OSVP enhanced the antitumor immune response initiated by viral infection of primary tumor cells, leading to reduced development of pulmonary metastases. The availability of the OSVP genome as a bacterial artificial chromosome allows for the rapid insertion of additional immunomodulatory genes that could further assist in the induction of potent antitumor immune responses against primary and metastatic tumors.
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PMID:Oncolytic herpes simplex virus 1 encoding 15-prostaglandin dehydrogenase mitigates immune suppression and reduces ectopic primary and metastatic breast cancer in mice. 2154 7

Infection of metastatic lymphoma cells (ESbL) by a low dose of a non-lytic strain of Newcastle disease virus (NDV) leads to viral replication followed by strong cell surface expression of viral antigens, especially hemagglutinin neuraminidase (HN). The expressed HN was functional and facilitated cell-cell interactions and cell attachment. This was shown for NDV infected tumor cells, lymphocytes, fibroblasts and endothelial cells. The interactions could be strongly inhibited by antibodies against the viral HN protein. Increased binding was also seen with HN c-DNA transfectants expressing the HN as the only viral protein. Viral infection did not influence proliferation and lysability of the infected tumor cells. Following intravenous injection of tumor cells, the number of hepatic metastases was significantly reduced when the cells had been pre-infected with NDV. This reduction of metastases correlated with an increased survival time of the animals. As potential mechanisms of these NDV effects we propose augmentation of cell-eel interactions and immune functions and reduction of invasive capacity of NDV infected, as compared to non-infected tumor cells.
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PMID:Adhesive function of newcastle-disease virus hemagglutinin in tumor-host interaction. 2155 72

A 34-year-old female presented with anorectal pain and rectal bleeding due to an extensive rectal tumour. A trephine loop ileostomy was fashioned and biopsies were initially reported to show a poorly differentiated cloacogenic carcinoma. CT revealed numerous liver metastases. A histological review and immunohistochemical studies subsequently favoured a primitive neuroectodermal tumour (PNET). Stem-cell supported chemoradiotherapy resulted in complete resolution of her primary tumour and liver metastases. Serial CT scanning and endoscopy revealed no recurrence after 7 years of follow-up, when she presented with a malignant anal fissure. Imaging and subsequently abdominoperineal resection revealed no evidence of metastases from either the anal cancer or the PNET tumour. Histopathology showed a T1N0R0 basaloid squamous carcinoma originating from grade III squamous intraepithelial neoplasia with no obvious wart viral infection.
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PMID:PNET/Ewing's sarcoma of the rectum: a case report and review of the literature. 2169 96

The relationship between stress and illness is complex. The susceptibility to stress varies from person to person. Among the factors that influenced the susceptibility to stress are genetic vulnerability, coping style, type of personality and social support. Not all stress has negative effect. Studies have shown that short-term stress boosted the immune system, but chronic stress has a significant effect on the immune system that ultimately manifest an illness. It raises catecholamine and suppressor T cells levels, which suppress the immune system. This suppression, in turn raises the risk of viral infection. Stress also leads to the release of histamine, which can trigger severe broncho-constriction in asthmatics. Stress increases the risk for diabetes mellitus, especially in overweight individuals, since psychological stress alters insulin needs. Stress also alters the acid concentration in the stomach, which can lead to peptic ulcers, stress ulcers or ulcerative colitis. Chronic stress can also lead to plaque buildup in the arteries (atherosclerosis), especially if combined with a high-fat diet and sedentary living. The correlation between stressful life events and psychiatric illness is stronger than the correlation with medical or physical illness. The relationship of stress with psychiatric illness is strongest in neuroses, which is followed by depression and schizophrenia. There is no scientific evidence of a direct cause-and-effect relationship between the immune system changes and the development of cancer. However, recent studies found a link between stress, tumour development and suppression of natural killer (NK) cells, which is actively involved in preventing metastasis and destroying small metastases.
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PMID:Life event, stress and illness. 2258 33

Respiratory neoplasms are rare in birds. This report describes carcinoma of the bronchial epithelium in a red-shouldered hawk (Buteo lineatus) that presented with weakness and lethargy lasting 4 days that progressed to seizures. Grossly, the caudal air sac and coelomic cavity contained approximately 15 ml of dark brown cloudy fluid that displaced the intestines cranially. Nodular plaques were present on the viscera and air sacs. Microscopic examination of tissues revealed a mass that expanded the bronchial lumen and was composed of papillary proliferations of rows of small cuboidal epithelial cells that were small and uniform in size with a low mitotic index. Metastases were present on the surfaces of caudal air sac, kidney, and multifocal peritoneal surfaces of the coelomic cavity. Clinical signs were most likely the result of West Nile virus infection, which was confirmed by immunohistochemistry of brain tissue.
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PMID:Bronchial carcinoma in a red-shouldered hawk (Buteo lineatus). 2294 89


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