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)

Mutations of p53 as a tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported to occur with varying frequency in different geographic regions, which might be different etiology for HCC. Overexpressions of p53 (well known for its implications in mutations of the p53 gene), PCNA and alpha-fetoprotein (AFP) have been reported to be associated with carcinogenesis and/or tumor progression and poor prognosis in various types of cancer. To estimate the geographical difference of the p53 gene, PCNA and AFP in HCC, we examined 14 Japanese HCC cases, 8 Indonesian HCC cases, and 27 Indonesian chronic active hepatitis (CAH) or liver cirrhosis cases, using immunohistochemical approaches. Overexpression of p53 was identified in 37.5% of Japanese HCC, in 62.5% of Indonesian HCC and none in CAH. The mean PCNA Labeling Index of Japanese HCC, Indonesian HCC and CAH was detected in 48.6%, 30.4%, and 43.5%, respectively. AFP was detected in 35.7% of Japanese and 25% of Indonesian HCC. The rate of p53 overexpression in Indonesian HCC was as high as in HCC of southern part of China, which might share the similar etiology in both regions.
 ...
PMID:Immunohistochemical study of P53, PCNA and AFP in hepatocellular carcinoma, a comparison between Indonesian and Japanese cases. 1141 97

Zinc-alpha(2)-glycoprotein (Znalpha(2)gp) is widely distributed in body fluids and epithelia. Its expression in stratified epithelia increases with differentiation. We previously showed that Zn alpha(2)gp has ribonuclease activity, and that squamous tumor cells grown on a matrix of Znalpha(2)gp were growth-inhibited. Here we demonstrate, both by adding Znalpha(2)gp to the culture medium and, more unequivocally, by stably transfecting SiHa cells with Znalpha(2)gp cDNA, that the introduction of Znalpha(2)gp into SiHa tumor cells reduces proliferation. In response to Znalpha(2)gp, we find an accumulation of the cell population in G(2)/M by flow cytometry, paralleling the reduction of proliferation. In order to distinguish growth inhibition by cell cycle arrest from that produced by apoptosis or differentiation, we examine by RT-PCR how Znalpha(2)gp affects the expression of genes commonly used as markers of these properties. No changes are observed for PCNA, p53, c-myc, or bcl-2. Only cdc2 expression responds to Znalpha(2)gp, with a reduction of up to over a factor of two. Cdc2 is the only cyclin-dependent kinase regulating the G(2)/M transition without redundancy and is required as a rate-limiting step in the cell cycle. Its increased expression has been directly linked to increased proliferation and decreased differentiation of advanced tumors; conversely, its downregulation by Znalpha(2)gp might hinder tumor progression. J. Cell. Biochem. Suppl. 36: 162-169, 2001.
 ...
PMID:Zinc-alpha(2)-glycoprotein hinders cell proliferation and reduces cdc2 expression. 1145 81

PC SPES (BotanicLab, Brea, California) an herbal supplement for patients with prostate cancer, is composed of 7 highly concentrated Chinese herbs and 1 US herb. It was developed in seeking positive attributes of Chinese and Western medicine for cancer treatment. Chemical standardization of this composition showed that baicalin is the most abundant active compound. Several reports on phase 2 clinical studies of PC SPES suggest that it is a well-tolerated active treatment for androgen-independent prostate cancer. In this report, data obtained from various laboratory experiments will be presented to elucidate the in vitro mechanism. Profound biologic effects of PC SPES on prostate cancer cells were observed on both androgen-dependent (LNCap) and androgen-independent (DU-145) cell lines. These effects include the following: (1) induction of cell apoptosis and cell cycle modulation; (2) inhibition of cell proliferation; (3) downregulation of bcl-2, bcl-6, proliferating cell nuclear antigen, and prostate-specific antigen proteins; (4) downregulation of androgen receptor (AR); and (5) upregulation of p53, bax, and p21 proteins. Concurrent animal studies using 2 different models, Copenhagen rats and nude mice, confirmed a dose-dependent suppressive effect of PC SPES on tumor volumes and tumor progression. Our results show that the cytotoxic and cytostatic properties of PC SPES are not entirely dependent on the presence of AR. The antitumor mechanism of PC SPES is complex. It involves multiple metabolic pathways, such that the whole extract acts on redundant mechanisms, which otherwise will permit cell survival if a single-target agent is used.
 ...
PMID:In vitro mechanism of PC SPES. 1150 43

The study was concerned with growth of sarcoma M-1 and basic morphological characteristics of proliferative activity of cells of this strain as well as apoptosis of cells at different stages of tumor progression in rats before and after a single gamma irradiation at 30 Gy. At the parenchymal periphery which determines tumor growth, the PCNA index of proliferating cells was 76.5%; spontaneous cell death--0.28%. During post-irradiation period, the sarcoma PCNA index fell to 62.3% while the apoptotic index rose five-fold. These findings support the concept of radiation-induced apoptosis being a major pathogenetic factor responsible for effectiveness of radiotherapy of tumors. Indirect evidence on PCNA immunostaining suggested that synthesis of this cyclin is sensitive to the level of oxygen input in the cell, yet it offers sufficient resistance to gamma-radiation.
 ...
PMID:[Growth kinetics and functional morphology of M-1 sarcoma in rats before and after gamma-irradiation]. 1154 33

The thiol N-acetyl-L-cysteine (NAC), an analogue and precursor of reduced glutathione, has cancer chemopreventive properties attributable to its nucleophilicity, antioxidant activity, and a variety of other mechanisms. We demonstrated recently that NAC has anti-invasive, antimetastatic, and antiangiogenic effects in in vitro and in vivo test systems. In the present study, s.c. transplantation of KS-Imm cells in (CD-1)BR nude mice resulted in the local growth of Kaposi's sarcoma, a highly vascularized human tumor. The daily administration of NAC with drinking water, initiated after the tumor mass had become established and detectable, produced a sharp inhibition of tumor growth, with regression of tumors in half of the treated mice along with a markedly prolonged median survival time. The production of vascular endothelial growth factor (VEGF) and certain proliferation markers (proliferating cell nuclear antigen and Ki-67) were significantly lower in Kaposi's sarcomas from NAC-treated mice than from control mice. Treatment of KS-Imm cells with NAC in vitro resulted in a dose-dependent inhibition of chemotaxis and invasion through inhibition of gelatinase-A (matrix metalloproteinase-2, MMP-2) activity without altering MMP-2 or MMP-9 mRNA levels. NAC also significantly inhibited VEGF production but did not affect proliferation markers in vitro. Reverse transcription-PCR analysis indicated that total VEGF mRNAs were reduced by 10 mM NAC. Taken together, these findings provide evidence that NAC, the safety of which even at high doses has been established in almost 40 years of clinical use, in addition to its chemopreventive action, has a strong antiangiogenic potential that could be exploited for preventing cancer progression as well as used in cancer adjuvant therapy.
 ...
PMID:Inhibition of angiogenesis-driven Kaposi's sarcoma tumor growth in nude mice by oral N-acetylcysteine. 1171 47

Immunocytochemical studies of the expression of PCNA, Ki67 and p53 protein have been done by different groups on sporadic keratocysts (OKCs) and OKCs associated with the naevoid basal cell carcinoma syndrome (NBCCS). These 'markers' have in common that they are all expressed in actively proliferating cells, particularly in neoplasms. The findings were compared with their expression in dentigerous and radicular cysts. While there was some variability in the reported results, probably because of technical inconsistencies and the use of different antibodies, a definite trend emerged. In general PCNA, Ki67 and p53 positivity occurred more frequently and more intensely in the OKCs, and in the syndrome-related more than the solitary, compared with the other cyst types. In the OKCs the positivity was expressed mostly in the suprabasal layers of epithelium whereas in the other cysts types it was mainly in the basal layer that positivity was observed. Other studies showed that the gene for the NBCCS (PTCH), a tumour suppressor gene, mapped to chromosome 9q22.3. PTCH gene mutation has been shown to be an important step in the pathogenesis of the OKC and was thought to have a role in the development of the sporadic as well as the syndrome-related OKCs. The 'two-hits' hypothesis was invoked in support of the view that syndrome-related basal cell carcinomas (BCCs) and OKCs probably arise from precursor cells that contain an inherited 'first hit'. Only a single mutation was then required in the somatic cell to cause homozygous inactivation and neoplastic progression. Sporadic OKCs might arise from susceptible cells in which two somatic mutations or 'hits' have occurred, one of which manifests as allelic loss. The loss of tumour suppressor genes supports the view that the OKC is a benign neoplasm.
 ...
PMID:The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 2. Proliferation and genetic studies. 1207 94

Cathepsin-D is an independent marker of poor prognosis in human breast cancer. We previously showed that human wild-type cathepsin-D, as well as its mutated form devoid of proteolytic activity stably transfected in 3Y1-Ad12 cancer cells, stimulated tumor growth. To investigate the mechanisms by which human cathepsin-D and its catalytically-inactive counterpart promoted tumor growth in vivo, we quantified the expression of proliferating cell nuclear antigen, the number of blood vessels and of apoptotic cells in 3Y1-Ad12 tumor xenografts. We first verified that both human wild-type and mutated cathepsin-D were expressed at a high level in cathepsin-D xenografts, whereas no human cathepsin-D was detected in control xenografts. Our immunohistochemical studies then revealed that both wild-type cathepsin-D and catalytically-inactive cathepsin-D, increased proliferating cell nuclear antigen expression and tumor angiogenesis. Interestingly, wild-type cathepsin-D significantly inhibited tumor apoptosis, whereas catalytically-inactive cathepsin-D did not. We therefore propose that human cathepsin-D stimulates tumor growth by acting-directly or indirectly-as a mitogenic factor on both cancer and endothelial cells independently of its catalytic activity. Our overall results provide the first mechanistic evidences on the essential role of cathepsin-D at multiple tumor progression steps, affecting cell proliferation, angiogenesis and apoptosis.
 ...
PMID:Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis. 1218 97

NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist of HGF but also as an inhibitor of angiogenesis. By studying the antitumor effect of NK4, we evaluated the potential of gene therapy with NK4 as a treatment for pancreatic cancer. Expression vector pcDNA3-NK4 containing NK4 cDNA was used to transfect human pancreatic cancer cell line SUIT-2. Although the established NK4 transfectant continuously expressed NK4 protein, the expression was shown by migration assay to be insufficient to antagonize HGF in vitro. Proliferation of the NK4 transfectant did not differ significantly from that of a mock transfectant. In vivo, we used models of orthotopic implantation and liver metastasis to transplant NK4-transfected clone or mock-transfected clone into nude mice. Cell proliferation in vivo, evaluated by immunohistochemical staining of proliferating cell nuclear antigen, did not differ between NK4 and mock transfectants, and this was also the finding in the in vitro assay. However, the NK4-transfected clone showed significant inhibition of tumor progression in both the orthotopic implantation and liver metastasis models. The number of vessels within tumors was significantly decreased, and the apoptotic tumor cells were increased in number. The results of these experiments show that genetic modification of tumor cells with NK4 cDNA yields a significant antitumor effect and that this effect is mainly obtained by NK4's function as an angiogenesis inhibitor rather than as an HGF antagonist. We conclude that the potent angiogenesis inhibitor NK4 may be a promising molecule for gene therapy of pancreatic cancer.
 ...
PMID:Tumor suppression through angiogenesis inhibition by SUIT-2 pancreatic cancer cells genetically engineered to secrete NK4. 1237 95

Recently, a close relationship between the cell cycle and apoptosis was confirmed in oral squamous cell carcinoma (SCC). To clarify the expression of cell cycle-related proteins and apoptosis in the oral premalignant state, we investigated the expression of p27, cyclin D1 and proliferating cell nuclear antigen (PCNA) using immunohistochemical staining, and apoptotic index (AI) using ApopTag in situ staining. The positive expression-score of p27 was 42.0% in leukoplakia (34.8% in hyperplasia, 55.4% in dysplasia) and 31.1% in SCC (43.3% in the early stage of SCC, 25.9% in the advanced stage of SCC). The level of p27 expression showed a peak in dysplasia and decreased in SCC. The expression of cyclin D1 was almost constant between hyperplasia and SCC. The expression of PCNA increased sequentially with disease progression. The apoptotic index (AI) in the p27-positive leukoplakia group was significantly higher than that in the p27-negative leukoplakia group (3.9 +/- 3.6 vs. 1.5 +/- 1.6, p = 0.026). From these results, we suggest that the abundance of p27 in oral leukoplakia may inhibit cell proliferation and lead premalignant tumor cells to apoptosis, and thus is concerned with prevention of tumor progression.
 ...
PMID:Expression of p27 and apoptosis in oral leukoplakia. 1282 Mar 81

Deregulation of G1 cyclins has been reported in several human and rodent tumors including colon cancer. To investigate the expression pattern of G1 cyclins in 1,2- dimethyl-hydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis, we studied the expression of cyclin D1 and cyclin E by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry (IHC). The mRNA level of cyclin D1 was increased 1.2-fold in adenocarcinomas but not significantly in adenomas, when compared with normal rat colonic mucosa (p<0.05). The cyclin E mRNA level was increased 2.7-fold in adenomas and 3.3-fold in adenocarcinomas (p<0.05). The PCNA mRNA level was also increased 1.9-fold in adenomas and 1.8-fold in adenocarcinomas (p<0.05). Immunohistochemical staining revealed exclusive nuclear staining of the neoplastic cells for cyclin D1, cyclin E and PCNA. Cyclin D1 expression was detected in 56.3% of the adenomas and in 61.5% of the adenocarcinomas examined, whereas cyclin E expression was detected in 87.5% of the adenomas and in 92.3% of the adenocarcinomas. Overall, cyclin D1, cyclin E and PCNA expression was significantly increased at both the mRNA and protein levels in normal colonic mucosa, adenomas and adenocarcinomas, but there was no significant difference in the degree of expression of these genes in adenomas and adenocarcinomas. Our results indicate that the overexpression of cyclin D1 and cyclin E may play an important role during the multistage process of rat colon carcinogenesis, at a relatively early stage, and may disturb cell-cycle control in benign adenomas, and thereafter, participate in tumor progression.
 ...
PMID:Overexpression of cyclin D1 and cyclin E in 1,2-dimethylhydrazine dihydrochloride-induced rat colon carcinogenesis. 1461 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>