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)

One hundred thirty-one cases of conjunctival melanoma in which biopsies had been performed were studied to determine potential factors that might affect outcome in patients with these lesions. Two groups of lesions were identified: those associated with primary acquired melanosis (melanoma with PAM, 98 cases, 74.8 per cent) and those without primary acquired melanosis (melanoma without PAM, 33 cases, 25.2 per cent). The overall mortality rate in the 131 cases was 26 per cent (34 of 131); the mortality rate due to melanoma with PAM was 25.5 per cent (25 of 98), and that due to melanoma without PAM was 27.3 per cent (9 of 33). If PAM was associated with the lesion, the presence of atypical melanocytes within the epithelium (pagetoid invasion) was a sensitive indicator of subsequent metastasis. Tumor thickness may also be useful for predicting subsequent metastases. None of the histologic parameters studied proved useful for predicting outcome in patients who had melanomas without PAM. The presence or absence of nevi had no effect on prognosis.
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PMID:Malignant melanoma of the conjunctiva. 397 96

Certain tumors require platelets for metastases, and many of these aggregate platelets in vitro. We have studied their in vitro interaction by extracting a PAM from SV40-transformed 3T3 fibroblasts. The preparation is enriched with membrane vesicles and requires an intact sedimentable sialolipoprotein for activity. PAM aggregates platelets after a lag period (J Lab Clin Med 93:332, 1979) and requires plasma as a cofactor(s). Two plasma components have been identified with the use of PRP or GFP. The first component shortens the platelet aggregation lag period after preincubation of PAM with plasma at 37 degrees C for 10 min prior to its addition to PRP or GFP and is labile to heating at 56 degrees C for 30 min. However, the activated PAM (formed by incubation with plasma at 37 degrees C) is stable at 56 degrees C for 30 min. This labile factor appears to be a component(s) of the complement alternative pathway, since it is inactivated by treatment of plasma with cobra venom or zymosan; and guinea pig PRP deficient in C' 4 can be aggregated by PAM. The second component is a plasma factor that is stable to heating at 56 degrees C. Activated PAM can be sedimented at 100,000 x g. The sediment, when suspended in Veronal buffer, pH 7.4, does not aggregate GFP, however, addition of plasma heated at 56 degrees C restores the platelet aggregation response. Thus a material extracted from SV40 3T3 fibroblasts aggregates platelets in vitro in the presence of two factors: (1) a component(s) of the alternative complement pathway that activates PAM and shortens the platelet aggregation lag period and (2) a heat-stable factor that is required for activated PAM to aggregate platelets.
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PMID:Plasma requirement for the aggregation of rabbit platelets by an aggregating material derived from SV40-transformed 3T3 fibroblasts. 625 81

One hundred and fifty-six patients with extremity melanomas of known level or thickness who were perfused prophylactically with l-phenylalanine mustard (1-PAM) between January 1974 and December 1978 were studied retrospectively to determine the effect of variation of drug dosage and temperature on regional toxicity and disease control. The median drug dosage of 1-PAM for 57 patients undergoing axillary perfusion was 0.85 mg/kg (range 0.48-1.0 mg/kg) and the median dosage was 1.2 mg/kg (range 0.59-1.69 mg/kg) for 99 patients undergoing iliac perfusions. Sixty-five percent of patients achieved a maximum skin temperature of between 101 degrees and 102 degrees F during perfusion. Determinate survival in the entire group was 93% at 5 years; 10% of patients developed positive regional nodes; and 2.5% developed local or intransit metastases. Based on analysis of other series of patients with extremity melanoma with equivalent Clark's level 5-year determinate survival might be expected to be between 65 and 80%. The expected incidence of nodal metastases should be 19.1%-24.0% and the incidence of local and intransit metastases should be 3-6%. While this series suggests a survival advantage for a series of extremity melanomas treated by regional chemotherapy when compared to other series treated by wide excision +/- regional node dissection, the results obtained were independent of dosage of drug administered or maximal temperature attained over the range studied. This suggests consideration be given to exploring other dose ranges of drugs and heat in an effort to achieve equivalent control with lower regional toxicity.
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PMID:Effect of variation of drug dosage on disease control and regional toxicity in prophylactic perfusion for Stage I extremity melanoma. 650 95

This study investigates the incorporation of three intravenously administered radiolabeled fatty acids, [9,10-3H]palmitate (3H-PAM), [1-14C]arachidonate (14C-ACH) and [1-14C]docosahexaenoate (14C-DHA), into lipids of intracerebrally implanted tumor and contralateral brain cortex in awake rats. A suspension of Walker 256 carcinosarcoma cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of an 8- to 9-week-old Fischer-344 rat. Seven days later, the awake rat was infused intravenously for 5 min with 3H-PAM (6.4 mCi/kg), 14C-ACH (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty min after the start of infusion, the rat was killed and intracranial tumor mass and brain cortex were removed for lipids analysis. Each radiolabel was incorporated more into tumor than into brain cortex. Ratios of net incorporation rate coefficients (k*) into tumor as compared with brain were 4.5, 3.4 and 1.7 for 3H-PAM, 14C-ACH and 14C-DHA, respectively. Lipid radioactivity comprised more than 80% of total tumor or brain radioactivity for each probe. Phospholipids contained 58%, 89% and 68% of tumor lipid radioactivity, and 58%, 82% and 74% of brain lipid radioactivity, for 3H-PAM, 14C-ACH and 14C-DHA, respectively. Incorporation coefficients (k*i) for a phospholipid class (i)--choline phosphoglycerides (PC), inositol monophosphoglycerides (PI), ethanolamine phosphoglycerides (PE), serine phosphoglycerides (PS), and sphingomyelin (SM)--were greater in tumor than in brain for each fatty acid probe, except that values for k*PE and k*PS using 14C-DHA were equivalent. Differences in k*i between tumor and brain were largest for SM and PC and the change in k*PC accounted for 65-90% of the increase in the net phospholipid incorporation rate for each probe. Differences in k*PI, k*PE and k*PS were smaller than those in were smaller than those in k*PC and k*SM, and varied with the probe. Differences in k*i were related to differences in tumor and brain phospholipid composition and metabolism. The results indicate that suitably radiolabeled fatty acids may be used to image and characterize metabolism of lipid compartments of a brain tumor in vivo using positron emission tomography.
Clin Exp Metastasis 1994 May
PMID:Differences in rates of incorporation of intravenously injected radiolabeled fatty acids into phospholipids of intracerebrally implanted tumor and brain in awake rats. 819 96

The objective of the paper was the retrospective evaluation of oncological results after dissection radical (RND), modified (MND) and selective (SND) on cervical lymph nodes in laryngeal and hypopharyngeal carcinoma. On the basis of obtained study results, an answer was sought whether and what prognostic factors in metastases to the regional cervical lymph nodes should influence the choice of therapeutic method, and the survival. The study material comprised 986 patients treated during the period 1970-1991 in the Department of Otolaryngology-PAM in Szczecin due to laryngeal and hypopharyngeal carcinoma. In this group, apart from treating the primary changes, the cervical lymph nodes were operated on (Neck Dissection-ND). Data concerning the patients were obtained from: a/ case histories, b/ follow-up, c/ correspondence, d/ USC data. Clinical status of cervical lymph nodes, their histopathological state were assessed postoperatively. The patients' survival period after the treatment of carcinoma was estimated too. The occurrence of neoplastic disease recurrence in cervical lymph nodes was also taken into consideration. All data were collected in Personal Computer memory IBC (PC 386). In processing the data use was made of calculating and data base program Medikus. A linear regression model was elaborated for investigating the degree to which certain factors influence the appearance of nodal recurrence. Hierarchy was established for the factors whose influence on the occurrence of recurrence was the strongest. It becomes apparent from the accomplished studies that metastases to the regional cervical lymph nodes occurred most frequently in hypopharyngeal cancers (81.6%). The clinical assessment is burdened with an error claiming 31% of discrepancy as compared to results of histopathological examination (Tab. 3). Occult metastases were recorded in hypopharyngeal carcinoma about 20%, and in glottic one about 13%. It was revealed that the presence of metastases in lymph nodes, an increase affecting the stage of pT and pN reduced the chances of survival in a significant manner (Tab. 7 and 8). The greatest influence on the appearance of nodal recurrence was exerted by the following factors: number of metastatic nodes, size of nodes, component N, mode of treatment. It has been disclosed that the risk of nodal recurrence increases sixfold with the rise of factor N, twofold with the rise of the number of metastatic nodes, and 1,6 fold when the size of nodes increases by 1 cm. No differences were observed in the percentages of survivals following the operative treatment RND and MND, with the stage being N1-2 (Fig. 1). Radiotherapy applied after MND and RND failed to exert any meaningful positive influence on the overall percentage of survivals (Tab. 4). As compared with therapeutic dissection, better oncological results, scored after prophylactic removal of cervical lymphatic system, provide the basis for elective performance of prophylactic procedures in hypopharyngeal and laryngeal carcinomata.
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PMID:[An attempt to evaluate prognosis in cases of metastasis from laryngeal and hypopharyngeal carcinoma to cervical lymph nodes]. 919 19

The purpose of this study was to develop an experimental model of squamous cell carcinoma that can be used to identify molecular and immunologic changes associated with primary events in malignant transformation, and those associated with metastatic tumor progression in the presence of host homeostatic and immunologic factors. Metastatic variants were derived following in vivo tumor progression of the in vitro transformed squamous cell carcinoma line Pam 212. The parental and metastatic cell lines exhibited similar morphologic features and molecular markers of an epithelial lineage, including an epithelial morphology in culture, cell surface expression of integrin alpha6beta4, and expression of mRNA of cytokeratins K6 and K14. When the growth and metastatic phenotype of the parental and reisolate cell lines was compared, the reisolate cell lines were found to exhibit a greater rate of growth and incidence of metastasis than the parental cell line when reimplanted in vivo. The difference in the growth rate of the parental cell line and the variants observed in vivo was not detected when growth of these lines was compared in vitro, suggesting that the growth advantage and selection of these variants requires tumor-host interaction. The metastatic variants exhibited a similar growth advantage in normal immunocompetent and SCID Balb/c mice, indicating that the growth advantage in vivo is not due to T or B lymphocyte-dependent immune factor(s). We conclude that metastatic variants derived following in vivo tumor progression of an in vitro transformed squamous cell carcinoma line exhibit a differential growth advantage in vivo that requires the host environment. Comparison of these in vitro transformed and in vivo derived metastatic variant cell lines with phenotypic differences in growth and metastasis should prove useful for dissecting the role of tumor and host factor(s) in malignant transformation and metastatic tumor progression of squamous cell carcinoma.
Clin Exp Metastasis 1997 Sep
PMID:Metastatic variants derived following in vivo tumor progression of an in vitro transformed squamous cell carcinoma line acquire a differential growth advantage requiring tumor-host interaction. 924 55

In an attempt to improve tumor response and survival among patients with colorectal cancer metastases confined to the liver, we developed an experimental (rats and pigs) and clinical isolated hepatic perfusion (IHP) technique to exploit maximally the steep dose-response relation of may anticancer drugs. In this overview we present our experimental and clinical results with mitomycin C (MMC) and melphalan (L-Pam). In rats, treatment with a four times higher maximally tolerated dose (MTD) of MMC during IHP compared to hepatic artery infusion (HAI) resulted in higher, more effective intratumoral concentrations of MMC. As a result, only in the IHP-treated rats were complete remissions observed and long-term survival achieved. Hepatotoxic side effects were minimal and transient in all animals. In the clinical phase I/II study with MMC 30 mg/m2 administered as a bolus in the isolated circuit, two of nine patients had a complete remission, with a median survival of 17 months. Four patients developed venoocclusive disease (VOD) of the liver, and as a result one patient died. Therefore we consider MMC unsuitable for further IHP studies. Meanwhile experiments in rats showed that IHP with the L-PAM MTD of 12 mg/kg was even more effective than MMC and did not cause hepatotoxic side effects. In the phase I/II dose-findings study with L-PAM in IHP, the MTD in humans was approximately 3.0 mg/kg. As in the rats, systemic toxicity was dose-limiting. The median survival of the whole group was 18 months. We have started a phase II study of L-PAM in IHP with a fixed dose of 200 mg L-PAM to determine if IHP can significantly increase the median survival and complete remission rate compared to other treatment modalities. Results from this study are expected by the end of 1997.
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PMID:Phase I/II studies of isolated hepatic perfusion with mitomycin C or melphalan in patients with colorectal cancer hepatic metastases. 967 Feb 71

Human and murine squamous cell carcinomas (SCC) have been reported to produce proinflammatory cytokines IL-1alpha, IL-6, GM-CSF, and IL-8 or KC. Production of individual members of the proinflammatory cytokine family has been associated with increased tumor growth or metastasis in a variety of neoplasms. In this study, we determined whether the expression of these cytokines occurs as a result of the events of cellular transformation or culture, or is promoted by interaction of neoplastic cells with factors or cells in the host environment. We compared the expression of proinflammatory cytokines following the spontaneous transformation of murine keratinocytes in vitro, and following the formation of tumors and metastases from these transformed keratinocytes in syngeneic recipients in vivo. Using sensitive ELISA assays, we found that cultures of the in vitro transformed Balb/c SCC line Pam 212 do not produce elevated levels of proinflammatory cytokines IL-1alpha, IL-6, GM-CSF and KC, indicating that transformation or culture alone is insufficient to account for the level of cytokine expression detected in patient and experimental tumors. In contrast, Pam reisolates from primary and metastatic tumors were obtained which constitutively produce markedly elevated levels of cytokines IL-1alpha, IL-6, KC and GM-CSF. The increase in the expression of these cytokines by SCC in vivo occurred independent of T and B lymphocyte-mediated immunity, since increases in expression of the cytokines was observed in lines reisolated from immunodeficient athymic nude and SCID Balb/c congenic mice. The increased expression of cytokines appeared to result from additional events in vivo, rather than due to selection of a pre-existing cytokine-producing subpopulation, since clones of the parental cell line expressed lower cytokine levels than cloned reisolates, and clones of the non-secreting parental cell line that formed tumors in vivo secreted elevated levels of cytokines following reisolation. We conclude that the development of SCC that express proinflammatory cytokines is promoted by tumor-host interaction(s) that are independent of specific T and B cell immunity.
Clin Exp Metastasis 1998 Oct
PMID:The host environment promotes the development of primary and metastatic squamous cell carcinomas that constitutively express proinflammatory cytokines IL-1alpha, IL-6, GM-CSF, and KC. 993 12

We reported previously that tumor cells isolated from metastases of the in vitro transformed squamous cell carcinoma line Pam 212 exhibit an elevation in constitutive production of proinflmmatory cytokines interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor, and KC (the murine homologue of chemokine Gro-alpha). The basis for constitutive expression of these cytokines after tumor progression in vivo is unknown. Regulation of the expression of these proinflammatory cytokines involves transcription factor nuclear factor kappaB (NF-kappaB), which can be activated by cytokines such as tumor necrosis factor (TNF)-alpha. In this study, we compared the constitutive and TNF-alpha-induced expression of proinflammatory cytokines in parental Pam 212 and metastatic LY-2 and LY-8 cell lines and determined the relationship of cytokine expression to activation of NF-kappaB. We found that the metastatic cell lines exhibited an increase in constitutive and TNF-alpha-inducible expression of proinflammatory cytokines when compared with parental Pam 212 cells. The increased cytokine expression was associated with an increase in constitutive and TNF-alpha-inducible activation of NF-kappaB as demonstrated by electrophoretic mobility shift assay and luciferase-reporter gene assay. Constitutive nuclear localization of NF-kappaB p65 was observed in LY-2 and LY-8 cells in culture and in tumor specimens but rarely in Pam 212 cells, consistent with the constitutive activation of NF-kappaB in tumor cels after selection in vivo. Induction of NF-kappaB by TNF-alpha was inhibited by the addition of protease inhibitors calpain inhibitor I and N-tosyl-phechloromethyl ketone and antioxidant 1-pyrrolidinecarbodithioic acid, whereas constitutive activation of NF-kappaB and cytokine KC mRNA expression was inhibited by N-tosyl-phechloromethyl ketone alone. Overexpression of a human Ikappa(B)alpha dominant suppresser in Pam 212 cells inhibited TNF-alpha-induced NF-kappaB binding activity and KC expression. These data indicate that activation of NF-kappaB contributes to increased expression of proinflammatory cytokines during metastatic tumor progression of squamous cell carcinoma, and that distinct mechanisms may be involved in the regulation of constitutive and TNF-alpha-induced activation of NF-kappaB in squamous cell carcinoma.
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PMID:The host environment promotes the constitutive activation of nuclear factor-kappaB and proinflammatory cytokine expression during metastatic tumor progression of murine squamous cell carcinoma. 1041 16

Growth Regulated Oncogene-alpha (GRO-alpha) is an autocrine growth factor in melanoma and is a member of the C-X-C family of chemokines which promote chemotaxis of granulocytes and endothelia through binding to CXC Receptor 2. We found previously that variants of murine squamous cell carcinoma PAM 212 which grow and metastasize more rapidly in vivo constitutively express increased levels of murine GRO-alpha, designated mGRO-alpha, or KC. We have examined the possible role of mGRO-alpha expression in malignant progression of squamous cell carcinoma PAM 212 in homologous BALB/c and BALB CXC Receptor-2 deficient mice. Transfection of the PAM 212 cell line which exhibits low expression of GRO-alpha and malignant potential with a pActin-KC vector encoding mGRO-alpha enabled isolation of PAM-KC expressing cell lines. These PAM-KC transfectants displayed an increased rate of growth and metastasis in BALB/c mice, similar to the highly malignant phenotype observed in spontaneously occurring metastatic variants. Furthermore, the PAM-KC tumors showed an increase in infiltration of host leukocytes and CD31+ blood vessels, consistent with increased CXC chemokine activity. The increased growth of PAM-KC cells was attenuated in CXCR-2 deficient mice, indicating that the increased growth was dependent in part upon host cells responsive to the CXC chemokine. Together, these results show that a CXC chemokine such as GRO-alpha can promote malignant growth of murine squamous cell carcinoma by a host CXCR-2 dependent pathway. Oncogene (2000) 19, 3477 - 3486
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PMID:Growth regulated oncogene-alpha expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC receptor-2 dependent mechanism. 1091 6


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