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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.
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PMID:Immunohistopathological characterizatin of spontaneous metastases in a human lung mucoepidermoid adenocarcinoma (HLMC) xenograft. 988 55

The development of aneuploid clones from diploid progenitor cells is a regular characteristic of head and neck squamous cell carcinoma progression. While the significance of aneuploidy formation for the acquisition of invasive and metastatic behavior is well documented, little is known about the contribution of diploid tumor cells after aneuploid clones have emerged. To distinguish diploid cells of epithelial origin from benign cellular components, we applied multiparameter flow cytometry of DNA content and cytokeratin (CK) expression to 36 primary tumors. Twenty-seven carcinomas accommodated aneuploid cell lines that stained positive for CK. All diploid cell populations obtained from aneuploid carcinomas contained CK-positive subpopulations as did all of nine tumors that consisted exclusively of diploid cells. The proportions of CK-positive diploid cells ranged between 6% and 80%, independent of whether they were achieved from entirely diploid or from aneuploid carcinomas. CK-gated diploid and aneuploid cell populations showed largely identical S-phase fractions. These results emphasize that diploid tumor cells regularly persist after the development of aneuploid clones and significantly contribute to local tumor progression. Despite the presence of diploid epithelial cells in aneuploid primary tumors, exclusively the aneuploid clones of eight corresponding lymph node metastases were CK-positive. This provides further evidence of a largely reduced metastatic potential of diploid tumor cells.
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PMID:Progression of diploid tumor cells in aneuploid head and neck squamous cell carcinomas. 1040 43

A new transitional cell carcinoma cell line, BCCA-1, derived from a primary urinary bladder carcinoma, was characterized with respect to the growth patterns of in vitro culture, xenotransplantability in SCID mice and immunophenotypic profile. The most unusual finding was a strong tendency of forming many aggregates (multicell spheroids) in the first few days of flask cultures, followed by the attachment of spheroids to monolayer fibroblasts, which came along from stroma of the same tumor. Unlike those reported tumor spheroids whose peripheral layers contained proliferative cells, BCCA-1 spheroids rarely contained mitotic cells. The three-dimensional architecture of BCCA-1 spheroids drastically changed by the attachment of spheroids to fibroblasts, from which epithelial tumor cells spread; this was accompanied by pseudopodia formation and highly aggressive growth of tumor cells. As the fibroblasts degenerated due to overgrowth, tumor cells started to aggregate by retracting their pseudopods and forming many semi-attached spheroids, which eventually detached from the sheet of degenerated fibroblasts. BCCA-1 produced solid tumors as xenografts in SCID mice by subcutaneous injection with as low as 5 x 10(6) cells, suggesting malignant nature of these cells. Immunostaining revealed the expression of MHC-class I, S100 protein, cytokeratin CK7 and CK20, beta-HCG, CEA, epithelial membrane antigen, Le(y) and folate-binding protein by this tumor. While the biological significance of spheroid formation of this kind by BCCA-1 cells remains unclear, it may represent a protection mechanism, by which TCC cells could sustain their viability under unfavorable culture conditions, but proliferate when the conditions became improved, such as the presence of fibroblasts. Our results point to the importance of tumor-associated stromal fibroblasts in TCC tumor progression. Further mechanistic studies to elucidate the mechanism involved in the stromal cell contact mediated-activation of TCC cells in this model system are warranted.
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PMID:Human bladder carcinoma cells with an unusual pattern of in vitro growth: transition from nonproliferative spheroids to active monolayer growth upon interaction with tumor-derived fibroblasts. 1081 Mar 50

Sarcomatoid carcinoma is a rare biphasic tumor characterized by a combination of malignant epithelial and mesenchymal cells. We report a rare case of sarcomatoid carcinoma of the colon. A 41-yr-old woman was hospitalized with a history of melena. Total colectomy was performed under the impression of colonic carcinoma. Histologically, the tumor was composed of differentiated adenocarcinoma in superficial portion and sarcomatoid spindle cells in deeper portion with a transitional area between the two portions. The sarcomatous areas revealed polygonal and spindle-shaped anaplastic malignant cells arranged in sheet, short fascicular or haphazard pattern. Immunohistochemically, tumor cells showed a positive immunoreaction for cytokeratin, epithelial membrane antigen, and vimentin. The histopathological and immunohistochemical transitions between the adenocarcinoma area and the spindle cell area suggested that the sarcomatous elements originated from the adenocarcinoma during tumor progression.
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PMID:Sarcomatoid carcinoma of the colon: a case report. 1164 39

Existing prostate cancer cell lines have been derived from late stages of human prostate cancer. In this paper, we present two cell lines generated from prostatic intraepithelial neoplasia (PIN), the precursor lesion for prostate adenocarcinoma. Pr-111 and Pr-117 were established from PIN lesions that developed in the C3(1)/Tag transgenic model of prostate cancer. Pr-111 and Pr-117 cells express simian virus 40 large T antigen (SV40 Tag) and are immortalized in culture, distinguishing them from normal prostate cells. The growth rates of these two cell lines are quite different; with Pr-111 cells growing much more slowly (doubling time approximately 40 hours) compared to Pr-117 cells (doubling time approximately 22 hours), and also show significantly different growth rates in different media. Both prostate cell lines express cytokeratin and androgen receptor (AR) with Pr-111 cells demonstrating androgen-dependent growth and Pr-117 cells exhibiting androgen-responsive growth characteristics. Athymic nude mice injected with Pr-111 cells either do not develop tumors or develop tumors after a long latency period of 14 weeks. Pr-117 cells, however, develop tumors by 3 to 6 weeks, suggesting that Pr-117 cells represent a later stage of tumor progression. These two novel cell lines will be useful for studying early stages of prostate tumor development and androgen responsiveness.
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PMID:Development of PIN and prostate adenocarcinoma cell lines: a model system for multistage tumor progression. 1189 66

BACKGROUND: Detection of micrometastasis is an important problem of clinical significance for a better understanding and control of tumor progression, which will improve patients' survival time.METHODS: To identify micrometastases in bone marrow, an immunocytochemical assay for epithelial cytokeratin protein was performed in 106 patients with primary gastric cancer. Also, in 40 of the 106 patients, vascular endothelial growth factor (VEGF) expression and intratumoral vessel density were examined by an immunohistochemical staining method.RESULTS: Of the 106 patients, 22 (20.8%) presented with cytokeratin-positive cells in bone marrow at the time of primary surgery. The positive findings were related to depth of invasion, peritoneal dissemination, and liver metastasis. Patients with cytokeratin-positivity in bone marrow had a higher VEGF positive rate (73%; 8/11) than did cytokeratin-negative patients (48%; 14/29). Intratumoral vessel density in VEGF-positive patients was 26.9 +/- 10.3, which was significantly higher than that in VEGF-negative patients (13.2 +/- 8.7, P < 0.05). Thus, the presence of cytokeratin-positive cells in bone marrow was closely related to angiogenesis in the primary tumor.CONCLUSIONS: Cytokeratin staining can be useful for identifying patients at high risk for metastasis. Prophylactic lymph node dissection, adjuvant chemotherapy, and antiangiogenic treatment may be necessary for patients with micrometastasis.
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PMID:Clinical significance of micrometastasis in bone marrow of patients with gastric cancer and its relation to angiogenesis. 1195 70

We describe a new human tumor xenotransplant animal model that is highly efficient for engraftment, does not need host conditioning and is suitable for in vivo studies of human tumors. Pieces of 61 freshly operated primary breast tumors were implanted into 172 irradiated and 228 nonconditioned NOD/Scid mice. A high mortality was observed in irradiated but not in nonconditioned recipients. More than 90% of analyzed implanted breast cancer specimens engrafted in the NOD/Scid mice irrespective of pretreatment. The tumors were vascularized within 3 days of implantation and maintained original histomorphology as well as expression patterns of tumor markers (cytokeratin and MUC1) and cytokines (tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4) and IL-10) released by adjacent stromal cells. A majority of tumors grew slowly, locally infiltrating host tissue, whereas some grew aggressively, developing large, fatal tumor masses and metastases within regional lymph nodes. Tumor progression in mice correlated with stage, grade, proliferation index and hormone receptor status of primary tumors. The reproducible growth behavior and preservation of characteristic features suggest that this new xenotransplant model is relevant and can be recommended for testing new anticancer therapies.
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PMID:Efficient engraftment of human primary breast cancer transplants in nonconditioned NOD/Scid mice. 1271 33

Cytokeratins, belonging to the intermediate filament (IF) protein family, are particularly useful tools in oncology diagnostics. At present, more than 20 different cytokeratins have been identified, of which cytokeratins 8, 18, and 19 are the most abundant in simple epithelial cells. Upon release from proliferating or apoptotic cells, cytokeratins provide useful markers for epithelial malignancies, distinctly reflecting ongoing cell activity. It appears that motifs in certain cytokeratins make them likely substrates for caspase degradation, and their subsequent release occurs during the intermediate events in apoptosis. The clinical value of determining soluble cytokeratin protein fragments in body fluids lies in the early detection of recurrence and the fast assessment of the efficacy of therapy response in epithelial cell carcinomas. The three most applied cytokeratin markers used in the clinic are tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), and CYFRA 21-1. TPA is a broad spectrum test that measures cytokeratins 8, 18, and 19. TPS and CYFRA 21-1 assays are more specific and measure cytokeratin 18 and cytokeratin 19, respectively. By following patients with repeated testing during management, the oncologist may obtain critical information regarding the growth activity in symptomatic patients. Although their main use is to monitor treatment and evaluate response to therapy, early prognostic information particularly on tumor progression and metastasis formation is also provided for several types of cancers. Cytokeratin tumor markers can accurately predict disease status before conventional methods and offer a simple, noninvasive, cheap, and reliable tool for more efficient management.
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PMID:Clinical utility of cytokeratins as tumor markers. 1523 34

This is the first report in the English literature of a composite endometrial tumor composed of papillary serous carcinoma and small cell carcinoma. A 79-year-old woman underwent total abdominal hysterectomy and left salpingo-oophorectomy due to endometrial carcinoma. Grossly, the uterus was enlarged with an irregular and nodular serosal surface, thickened myometrium, and irregular endometrium. Microscopic examination revealed an endometrial carcinoma composed of papillary serous carcinoma and small cell carcinoma. There was a differential immunoreactivity between the two components: the cells of the papillary serous carcinoma were positive for cytokeratin, CA-125, CEA, and HER-2/Neu, whereas these markers were negative in the small cell carcinoma. Various neuroendocrine markers were positive in the small cell carcinoma and negative in the papillary serous carcinoma. Fluorescence in situ hybridization analysis using 4, 8, and 10 centromeric probes revealed hyperploidy (6-8 signals) in the small cell carcinoma cells. Most of the serous carcinoma cells were euploid, with scattered trisomies and tetrasomies of these chromosomes. The patient died of progressive disease 5 months after surgery. We suggest that the small cell carcinoma may have arisen from the endometrial papillary serous carcinoma undergoing tumor progression with neuroendocrine differentiation.
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PMID:An unusual composite endometrial tumor combining papillary serous carcinoma and small cell carcinoma. 1525 20

In order to evaluate the significance of altered expression of mucin and cytokeratin during gallbladder carcinogenesis, we characterized the expressional profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31 adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1 expression was absent. However, in adenomas, dysplasias and carcinomas, the expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently associated with carcinomas and showed a higher grade of atypia than those without these antigens. In carcinomas, MUC1 expression was related to invasive growth, lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was related to non-invasive growth. CK7 was diffusely expressed in almost all lesions, but carcinomas with a loss of CK7 expression showed poor survival. In conclusion, normal gallbladder mucosa has a gastric phenotype, but during carcinogenesis and tumor progression, the gastric phenotype is gradually lost and the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in the gallbladder.
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PMID:Phenotypic alterations of mucins and cytokeratins during gallbladder carcinogenesis. 1526 Aug 48


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