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

The calcium channel antagonists (CCAs) amlodipine, diltiazem, and verapamil inhibited HT-39 human breast cancer cell proliferation in a concentration-dependent manner. The apparent 50% inhibitory dose values were 1.5 microM for the dihydropyridine amlodipine, 5 microM for the benzothiazapine diltiazem, and 10 microM for the phenylalkylamine verapamil. Amlodipine treatment caused a rapid concentration-dependent decrease of intracellular calcium concentration in the HT-39 cell line. Addition of 1 microM amlodipine had no effect on intracellular calcium levels, 3 microM amlodipine lowered intracellular calcium levels in the HT-39 cells by 13.7%, and 10 microM amlodipine lowered intracellular calcium levels by 33.2%. Also, lowering medium calcium levels from 2.0 mM to 0.5 microM resulted in a rapid 41.3% decrease in intracellular calcium and a concomitant 60% inhibition of HT-39 cell DNA synthesis. When HT-39 cells were transplanted into athymic mice, marked hypercalcemia developed. Serum calcium levels from control mice were 8.3 +/- 0.6 mg/dl (mean +/- SE; n = 4); those from tumor-bearing mice were 11.3 +/- 0.08 mg/dl (mean +/- SE; n = 17). Blood calcium levels correlated directly with tumor size (r = 0.91, P less than 0.01). We examined the capacity of three CCAs to specifically inhibit HT-39 tumor growth in vivo. One week after inoculation of HT-39 cells, mice were acclimated to vehicle or 0.1 mg/day amlodipine, 1.0 mg/day diltiazem, or 1.0 mg/day verpamil, in their drinking water, for 7 days. Oral administration of the dihydropyridine amlodipine (0.35 mg/day) for 10 days inhibited HT-39 breast tumor growth by 83.5 +/- 20.1% (mean +/- SE). Oral administration of diltiazem (3.5 mg/day) inhibited HT-39 breast tumor growth rate by 46.5 +/- 6.6% over a 2-week measurement period, and verapamil (3.5 mg/day) inhibited tumor growth rate by 68.2 +/- 9.7% (mean +/- SE). The CCAs had no effect on mouse body weight or gross organ morphology at the concentrations used. Lack of depolarization-induced calcium fluxes in the HT-39 cell line suggests that these cells do not express voltage-operated calcium channels. Thus, our study correlates an effect of amlodipine to lower intracellular calcium levels, by a mechanism not known at present, with its effect to inhibit HT-39 cell proliferation. These findings are important since they demonstrate that amlodipine and other CCAs with known pharmacodynamics and side effects act to blunt breast tumor progression in vivo.
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PMID:Inhibition of cancer cell growth by calcium channel antagonists in the athymic mouse. 153 73

The effects of 7 days' chemotherapy with penicillin G, piperacillin, mezlocillin, cephalothin, cefamandole, cefotaxime, gentamicin, amikacin, streptomycin, rifampicin, doxycycline, and clindamycin on local tumor growth and metastatic lung colonization were studied in an experimental tumor model (BALB/c-mouse-sarcoma L-1). The antibiotic dosages administered to mice were calculated on a body weight basis from doses recommended for human therapy. Except for mezlocillin, piperacillin, rifampicin and doxycycline, antibiotic treatment did not significantly influence local tumor growth, lung colonization and immune functions. Whereas mezlocillin exerted positive (tumor suppressive) or negative (tumor promoting) effects depending on the chemotherapy schedule, tumor growth and spread were significantly increased independent of the timing scheme after rifampicin or doxycycline treatment. Since certain immune functions (delayed type hypersensitivity; proliferation of spleen lymphocytes) were significantly suppressed after administration of mezlocillin, rifampicin and doxycycline, a correlation between antimicrobial chemotherapy and tumor progression may be possible.
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PMID:Influence of 12 antibiotics on antitumor immunity in BALB/c-mice. 155 13

We have shown in previous studies that metastatically-competent variant subpopulations (B5, C1) derived from a non-metastatic murine mammary adenocarcinoma (SP1) have a pronounced growth advantage over their non-metastatic tumor cell counterparts in primary tumors. As a result, primary tumors can be progressively overgrown by cells having the competence to spread elsewhere in the body. This occurs despite any evidence to indicate an intrinsic in vivo growth rate advantage of the metastatic cells when grown as isolated populations. This suggested that cell-cell interactions between metastatic and non-metastatic tumor populations may be involved in the metastatic cell growth dominance process. Evidence was therefore sought for growth factors released by SP1 cells which could preferentially stimulate the B5 or C1 variants and thereby mediate this cell-cell interaction process. We found that cocultures of SP1 and C1 or B5 cells with irradiated C1, B5, or SP1 "feeder" cells showed significant stimulation of C1 and B5 by SP1 "feeder" cells. Cell growth stimulation in response to EGF, TGF-alpha, TGF-beta 1, bFGF, PDGF, NGF, IGF-1, or IGF-2 demonstrated that only TGF-beta 1 could duplicate this effect. A repeat of the coculture experiment in the presence of specific neutralizing anti-TGF-beta antibodies was therefore undertaken and this was found to markedly reduce the stimulation of C1 or B5 cells by irradiated SP1 cells. Conditioned media from the SP1 and C1 cell lines was quantitated for TGF-beta activity and contained 4.5 ng/ml and 2.0 ng/ml, respectively. However, the majority of the TGF-beta released by SP1 cells was found to be spontaneously active, whereas 70% of the TGF-beta released by C1 cells was in its latent form. Scatchard analysis revealed approximately four times the number of TGF-beta receptors, of similar type and affinity, present on C1 as compared with SP1 cells. The in vitro results support the hypothesis that active TGF-beta released by SP1 cells may stimulate the proliferation of metastatic variant cells in a paracrine like fashion. In vivo evidence for this was obtained by showing that coinjection of irradiated SP1 cells could selectively stimulate tumor growth of viable C1 cells and this effect was markedly diminished by neutralizing polyclonal anti-TGF-beta antibodies. Taken together, the results suggest a novel role for TGF-beta in clonal evolution of malignant tumor growth and as a molecular mediator of tumor cell-tumor cell interactions involved in facilitating tumor progression.
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PMID:Reduction of TGF-beta activity abrogates growth promoting tumor cell-cell interactions in vivo. 165 15

Long-term results were assessed in 173 bladder cancer patients subjected to cystectomy. Twenty-eight (16.2%) patients died postoperatively. End results were evaluated in 142 patients. The patients were followed up for 1-17 years. Within that period, 50 patients (35.2%) died of tumor progression whereas 20--from renal failure (14.1%). Overall three- and five-year survival was 54.8 +/- 5.1 and 50.0 +/- 5.6%, respectively. Treatment results were studied versus stage, histologic pattern, type of treatment, tumor growth pattern and age. A significant correlation was established for stage and effectiveness of cystectomy only.
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PMID:[The results of cystectomy in bladder cancer]. 166 4

Tumor cell progression and parenchymal infiltration play important roles in the pathogenesis of gliomas. Using retrovirally marked rat 9L gliosarcoma cells, which when injected in the CDF rat brain form noninfiltrating tumors which grow only surrounding existing blood vessels, we were able to investigate elements of tumor growth and progression within the substance of the brain. Transfection of 9L by oncogenes associated with tumor progression and expressed in gliomas resulted in alterations in the in vivo phenotype of these cells, with the production of faster growing, well-vascularized, large solid tumors. However, diffuse infiltration was not seen. Moreover, coinjection of 9L or its transfectants together with the infiltrative C6 cell line resulted in a mixed tumor of noninfiltrating 9L cells in an environment of infiltrating C6 cells, suggesting that the infiltrative ability of C6 cells is controlled on the individual cell level.
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PMID:Overexpression of oncogene products can cause tumor progression without parenchymal infiltration in the rat brain. 167 34

Clonal cell lines were derived from rat liver epithelial cells following their transformation with either v-raf or v-raf/v-myc. Cells transformed with v-raf alone showed reduced tumor incidence and tumor growth rates when implanted into nude mice, compared to cells also expressing the v-myc oncogene. A series of additional clones isolated from a tumor obtained following inoculation of an athymic nude mouse with the v-raf-transformed rat liver epithelial cells displayed an intermediate range of tumor aggressiveness. These findings indicate that unknown genotypic and/or phenotypic changes occur during tumor formation in vivo, which are required in addition to raf activation for complete expression of the malignant phenotype. This in vitro model of tumor progression was used to examine alterations in the expression of genes related to the growth control of liver epithelial cells, which may be involved in the malignant conversion of the preneoplastic cells. A close association was observed between the increased level of expression of the transforming growth factors alpha and beta 1, the decreased expression of extracellular matrix proteins fibronectin and collagen I, and the tumor aggressiveness (latency/growth rate), suggesting a causal role for these factors in the progression of v-raf-transformed rat liver epithelial cells to the fully malignant phenotype.
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PMID:Expression of growth-related genes during tumor progression in v-raf-transformed rat liver epithelial cells. 170 45

Reliable predictors of response for prostate cancer patients undergoing hormonal therapy are lacking. This study investigates the possibility that tumor proliferation rates might predict tumor behavior for these patients. The growth fraction of metastatic prostate cancer biopsy specimens obtained before androgen withdrawal therapy was evaluated by Ki-67 antibody immunohistochemical study to determine whether a higher tumor growth fraction was associated with a shorter time to tumor progression after therapy. The percentage of Ki-67-positive malignant epithelial nuclei in the primary tumors of 17 patients ranged from 1.7% to 7.5% (median, 2.5%). When patients were divided into two response groups according to the median time to progression, poor responders (time to progression less than 20 months) and good responders (greater than or equal to 20 months) had similar growth fractions (3.5 +/- 0.5% versus 3.1 +/- 0.6% Ki-67-positive nuclei, respectively). However, when patients were divided into two groups based on the median growth fraction, patients with a high growth fraction (greater than 2.5% Ki-67-positive nuclei) tended to have a shorter time to progression (median, 10 months) than patients with a low (less than 2.5%) growth fraction (median time to progression, 25 months), although statistical significance was not reached. Despite this interesting trend, Ki-67 immunostaining was not accurate to predict the time to progression in individual patients undergoing hormonal therapy. Reliable prediction of growth rates may require measurement of both cell proliferation and cell death rates.
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PMID:Determination of growth fraction in advanced prostate cancer by Ki-67 immunostaining and its relationship to the time to tumor progression after hormonal therapy. 171 May 38

The cancer stroma is made of cellular and non cellular formations which grow along with cancer cells to build up a tumor. It comes from inflammatory cells and mesenchymal tissue which are mobilized and modified by factors released by cancer cells which bring about inflammatory cell accumulation, angiogenesis, fibroblast mitosis and extracellular matrix production. The extracellular matrix is altogether a barrier against and supporting to cancer cells. The extracellular matrix is also involved in the storage of growth factors which are bound to glycosaminoglycans. Although they are antinomic in vitro, peptidic factors released by tumor cells seem to have an enhancing effect on tumor growth in vivo. The cancer invasion is mediated through diverse enzyme activities, particularly proteases, which degrade the matrix whose degradation products can facilitate the tumor progression. The anti-cancer activity which is exhibited in vitro by macrophages and lymphocytes is expressed at a low level by tumor-macrophages and lymphocytes in vivo. The cancer associated inflammation has no particular feature which could help to screening or to follow up patients. Several elements of the cancer stroma could be selected as targets for investigative cancer therapy.
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PMID:[Cancer stroma]. 176 34

In order to clarify cell proliferation kinetics of human colorectal cancer, 91 cases were investigated by cytofluorometry and clinicopathological findings. The results showed colorectal cancers could be divided into 3 groups according to the ploidy pattern. Group I was the diploid cell population, group II the polyploid cell populations and group II' the aneuploid cell populations. These ploidy patterns were found not to be related both to the histological types and the gross pathological classification. Most of the intramucosal cancers were found in group I, and the cancers of more advanced growth mainly in groups II and II'. The fraction of diploid cells in the groups I and II' did not show the remarkable change, but in the group II decreased with tumor progression. These results indicate the ploidy patterns appear to change with the submucosal invasion, and also that while the ploidy patterns in the groups I and II' are stable, those in the group II increase the extent of polyploidization with the tumor growth. Lymphatic metastases were found to be more frequent in the group II than in the groups I and II'. It is suggested that the mechanism of lymphatic metastasis would be related to the cell polyploidization.
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PMID:[Cytofluorometric analysis of cell proliferation kinetics of the human colorectal cancer]. 177 Sep 32

To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.
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PMID:Estradiol induced changes in tumor growth and steroid receptor content in a heterotransplanted human endometrial adenocarcinoma. 181 Apr 29


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