Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HER-2/neu oncogene encodes a Mr 185,000 transmembrane phosphoglycoprotein which is overexpressed in 25-35% of breast and ovarian neoplasms and portends a poor prognosis. We have studied the feasibility of targeting this oncoprotein, designated p185, with radioiodinated murine monoclonal antibodies (muMABs) 4D5 and 7C2, which recognize distinct epitopes on its extracellular domain. The rates of internalization and catabolism of these antibodies were analyzed by cellular radioimmunoassay and electron microscopy. After binding to NIH3T3 HER-2/neu cells, which show high surface expression of p185, the muMABs were endocytosed via coated pits, routed to lysosomes, and degraded. Approximately 44% of 125I-4D5 and 39% of 125I-7C2 were catabolized by tumor cells after 24 h. The biodistribution of radiolabeled 4D5 and 7C2 were evaluated in beige/nude mice bearing s.c. NIH3T3 HER-2/neu grafts. A high specificity of localization was seen with tumor:organ ratios of activity generally ranging from 5:1 to 30:1. However, the percentage injected dose of radioactivity per gram of tumor declined sharply from 25% at 24 h to 5% at 120 h postinjection. Treating the animals with 400-700 muCi 131I-4D5 caused a marked inhibition of tumor growth, although no mice were cured. Unlabeled 4D5 had no effect on tumor progression in this model, but administering 400-700 muCi of 131I-DA4-4, an isotype-matched irrelevant muMAB, resulted in an intermediate degree of growth retardation. Analysis of kinetic blood data and whole-body time-activity curves indicated that the irrelevant conjugate remained in the body 2-3 times longer than 131I-4D5. Radioiodinated anti-HER-2/neu muMABs are attractive agents for radioimmunodiagnosis and radioimmunotherapy of aggressive HER-2/neu-positive breast and ovarian carcinomas, but effective strategies for retarding intratumoral catabolism may be necessary to optimize their clinical utility.
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PMID:Radiolabeled antibody targeting of the HER-2/neu oncoprotein. 134 16

Nasopharyngeal carcinoma develops with extremely high incidence in discrete populations and geographic locations. It is consistently associated with the ubiquitous Epstein-Barr herpesvirus (EBV). The structure of EBV DNA indicates that the tumor is a clonal proliferation that developed subsequent to EBV infection. Specific viral genes are consistently expressed within all cells of the tumor. This consistent expression may indicate that the viral gene products are required for tumor growth. Genetic or environmental factors may affect the expression of these critical viral genes or cellular genes and contribute to tumor progression.
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PMID:Epstein-Barr virus infection in nasopharyngeal carcinoma. 136 43

Cryotherapy was applied to 182 rectal cancer patients in the Department of General Surgery, University of Ulm, between 4/1982 and 4/1991. Recipients of this tumor freezing therapy were patients whose general condition was bad, patients with an advanced inoperable carcinoma, patients with tumor recurrence and patients refusing operation. Rectal carcinomas, mostly in an advanced stage, were usually freezed several times. Only 4 patients with general inoperability reached the survival time margin of 5 years. In 18 patients local tumor destruction was possible by application of cryotherapy. In 80% of cases disagreeable tumor symptoms like tenesma, mucous discharge and oozing hemorrhages could be reduced or completely removed. Perianal pain and intense tumor bleeding could be relieved temporarily or definitely in only 50% of patients. An artificial anus could be avoided in 80% of cases by local tumor destruction/reduction or arrest of tumor growth. The mean survival time of patients with tumor recidivation was 11 months after onset of the recurrence. Tumor progression, incontinence and iatrogenic rectal perforation made an artificial anus necessary in 14 patients.
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PMID:[Cryotherapy in rectal cancer. A palliative local tumor treatment]. 137 57

We have investigated the in vivo role of 2 different adhesion molecules, LFA-1 and LECAM-1, in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which undergo a peculiar spontaneous regression due to generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated administration of anti-LFA-1 monoclonal antibody (FD441.8 MAb), i.p. or at the site of virus inoculation, enhanced tumor growth and delayed regression, while i.p. administration of anti-LECAM-1 MEL-14 MAb gave rise to tumors that grew progressively and caused host death. Evaluation of the immunological response in MAb-treated mice showed reduced generation of virus-specific CTL precursors (p) in the spleen of animals given FD441.8 MAb i.p.; CTLp frequency in locally treated mice overlapped with that of control mice injected with virus only. FD441.8 MAb treatment did not interfere with CTL homing in the tumor, since the frequency of M-MSV-specific CTLps in sarcomas was similar in treated and control mice. Cytofluorimetric analysis indicated that the majority of tumor-infiltrating lymphocytes (TIL) from MAb-treated mice were covered by anti-LFA-1 MAb, and lacked cytotoxic activity when assayed against target cells bearing relevant tumor antigens. Instead, in mice injected i.p. with MEL-14 MAb, a very low frequency of CTLps was detected in lymph nodes draining the tumor area, and within the tumor. Our results indicate that enhanced tumor growth, depending on the MAb used, is the resultant of an inhibitory effect on different T-lymphocyte functions. Tumor progression in anti-LFA-1 MAb-injected mice is explained mostly by blockage of CTL lytic activity at the tumor site; in mice receiving i.p. MEL-14 MAb treatment, by the failure of naive T lymphocytes to enter peripheral lymph nodes and subsequently by the lack of generation of tumor-specific CTLs.
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PMID:Role of adhesion molecules in the immune reaction to M-MSV-induced tumors. 138 41

Brain tumors are highly resistant to therapy. Their diffuse infiltrative nature and the relative inaccessibility of brain tissue to blood and lymph are barriers to surgical and cytotoxic treatments alike. The purpose of this study was to produce immune cells specifically reactive with an anaplastic rat glioma (RT2) and determine whether those cells could affect tumor progression in the brain. RT2-specific cytotoxic cells were prepared by priming rats in vivo with RT2 tumor cells and Corynebacterium parvum and stimulating the primed lymphocytes in vitro with irradiated RT2 tumor cells and interleukin-2 (IL-2). Cultured cells exhibited a high level of cytotoxicity against RT2, but not C6 (an allogeneic glioma), 3M2N (a syngeneic mammary tumor), or CSE (a syngeneic fibrosarcoma) tumor cells. To generate a model for therapy, rats were injected intracerebrally with RT2, generating progressing brain tumors, which killed untreated rats in approximately 2 weeks. To test the therapeutic potential of the effector cells, tumor-bearing rats were treated by intravenous injection of lymphocytes on Day 5 of tumor growth. Treated rats also received a 5-day course of systemic IL-2 beginning on Day 5. Treatment with IL-2 alone, RT2-primed spleen cells, or RT2-primed spleen cells stimulated in vitro with C6 did not affect rat survival. However, tumor-bearing rats treated with RT2-stimulated lymphocytes exhibited increased survival or were cured. Systemic IL-2 was an essential adjunct, because survival was not affected by treatment with effector cells alone. Therapy initiated on Day 8 of tumor progression lacked effect on survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Successful treatment of a malignant rat glioma with cytotoxic T lymphocytes. 140 33

It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer. The most important carcinogenic chemicals are associated with life-style factors, whereas agents related to other environmental, occupational, or medical exposure are numerically less important. Most chemical agents exert their carcinogenic effects as electrophilic reactants covalently binding to DNA. Certain agents such as asbestos are carcinogenic by virtue of their physical properties. Several short-term tests have been used to screen for chemical carcinogens. Whole-animal studies remain the standard for predicting carcinogen risk in humans, although major limitations in such studies exist. Ionizing radiation also exerts its carcinogenic effect through damage to cellular macromolecules including DNA. Excess cancer risk appears after a latent period of several years following exposure. Risk increases in approximately a linear fashion in proportion to the radiation energy, cumulative dose, and a variety of host biologic factors. The greatest source of average radiation exposure to the US population is from the uranium decay product radon.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Risk factors for cancer. 141 59

The effect of dehydroepiandrosterone (DHEA) (2 mg, twice daily p.o.) on the growth of the dimethylbenz (a) anthracene (DMBA)-induced mammary carcinoma was studied in intact and ovariectomized adult female rats. DHEA treatment stimulated the tumor growth in ovariectomized animals. Conversely, the tumors of intact rats treated with DHEA progressed to a lesser extent than those of intact untreated animals (p < 0.01). Plasma levels of DHEA were higher in DHEA-fed than in untreated animals (p < .01), whereas E2 concentrations were unchanged after DHEA administration. Estrogen receptor (ER) concentrations in tumor tissue of ovariectomized animals given DHEA were no different form those found in intact rats, whereas ER were undetectable in untreated ovariectomized rats. The data indicate that DHEA stimulates the growth of DMBA-induced mammary tumors in ovariectomized rats, while it reduces the tumor progression in intact animals.
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PMID:Opposite effects of dehydroepiandrosterone on the growth of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas. 144 10

The field of experimental head and neck oncology continues to expand in both scope and meaningful observations. During the past year, research has focused intensively on factors responsible for disease development, genetic alterations that contribute to cancer progression, tumor growth factors and their modulation, and the biologic and clinical significance of cell-surface antigen expression. In the field of carcinogenesis, various dietary components that either promote or inhibit head and neck cancer development have been identified. Clinical trials that utilize various vitamins and their precursors such as beta-carotene have been reported. Genetic studies have demonstrated that head and neck cancers are heterogeneous in their oncogene expression; potentially, a reflection of the differential effect of various environmental carcinogenic exposures. Finally, the relationship between modulation of normally occurring cell-surface antigens and tumor aggressiveness has been demonstrated by several investigators throughout the past year. Significantly, animal models and human clinical trials have demonstrated that modulation of cell surface components by biologic agents alters the behavior of head and neck cancer and its relationship to the host.
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PMID:Experimental head and neck oncology. 149 56

One hundred fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumors entered a prospective multicenter trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumors, and five with other endocrine GEP tumors) to determine the efficacy of 200 micrograms Sandostatin three times a day in the control of tumor growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a "negative" selection of patients included in the trial and suggesting that Sandostatin cannot prevent disease progress when it is far advanced. In the evaluation of 68 patients monitored for at least 3 months, partial regression was observed in 4.4%, stable disease in 50%, and tumor progression in 45%. However, an initially favorable response frequently occurred with a decrease in response later: 54.4% at 3 months to 38% at 12 months for the whole group of patients. Proven inhibition of tumor growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatin exerts a beneficial effect on tumor growth in patients with metastatic endocrine GEP tumors. This beneficial effect decreases with time and is as yet unpredictable in the individual patient.
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PMID:Gastroenteropancreatic endocrine tumors: effect of Sandostatin on tumor growth. The German Sandostatin Study Group. 151 29

Brain catecholamines (CA) were studied in discrete brain areas of benzo(a)pyrene (b(a)p) induced fibrosarcoma bearing mice. Dopamine (DA) and norepinephrine (NE) levels decreased significantly in different brain areas especially in corpus striatum and hypothalamus with the tumor progression, indicating an inverse relationship between brain DA and NE levels and tumor growth. Since impaired hormonal and immunological functions are manifestation of systemic alteration during tumor growth, it appears that during malignant growth an alteration of these brain CA may play an important role in the regulation of systemic alterations.
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PMID:Alteration of brain catecholamines during growth of benzo(a)pyrene induced murine fibrosarcoma. 152 21


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