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)

One of the most exciting areas of molecular oncology is the convergence of two independent lines of evidence suggesting involvement of multiple tumor suppressor genes in a given type of cancer. First, epidemiology and somatic cell genetics indicate the presence of multiple tumor suppressor genes in each of several malignancies. Second, cancers often lose multiple chromosomal regions during tumor progression. We will use two tumors, colorectal cancer and Wilms tumor, to illustrate the questions that multiple tumor suppressor genes raise.
 ...
PMID:Multiple tumor suppressor genes in multistep carcinogenesis. 133 99

Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. Hybrids containing chromosome 18 are morphologically similar to the parental line, whereas those containing chromosome 5 are morphologically distinct from the parental cell line, being small, polygonal, and tightly packed. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Introduction of chromosome 5 had little to no effect on responsiveness, whereas transfer ot chromosome 18 restored responsiveness to some degree. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.
 ...
PMID:Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer. 134 43

Patients with ulcerative colitis carry an increased colorectal cancer risk. The cumulative cancer risk for patients with pancolitis is 0.5-0.7% per patient year. Dysplasia as a histologic marker of a neoplastic transformation is used to identify patients with an increased cancer risk during colonoscopic surveillance. Because the classification of dysplasia is subject to inter- and intraobserver variation new methods for the detection of risk patients have been investigated. DNA analysis by flow cytometry seems to be of value for the detection of DNA aneuploidy and the identification of patients who are at risk for neoplastic progression. The significance of DNA aneuploidy is being evaluated in prospective studies. Surveillance guidelines depend on duration and anatomical extent of the colitis as well as on the detection of dysplasia.
 ...
PMID:[Risk of colorectal cancer in ulcerative colitis--monitoring strategies and identification of risk patients]. 144 7

We examined tissue extracted from 19 gastric, 7 pancreatic, and 23 colorectal carcinoma specimens to determine the comparative incidence of allele loss on chromosomes 5, 17, and 18 and that of KRAS2 point mutations. Chromosome 5 allele loss occurred at the same frequency in all three gastrointestinal tumors (approximately 30%), whereas chromosome 17 and 18 allele losses were seen at a significantly lower frequency in gastric (20%) and pancreatic (0%) malignancies than in colorectal cancer (57%). Point mutations in KRAS2 were seen in 83% of pancreatic and 52% of colon cancers, but not in gastric cancer specimens. In pancreatic tumors, these mutations were always found in the second nucleotide of codon 12. In colorectal cancer, the distribution was more variable, involving the second nucleotide of codon 13 and both the first and second nucleotides of codon 12. These results suggest that inactivation of the adenomatous polyposis coli gene on chromosome 5 may be an initiating step for carcinomas of the stomach and pancreas as well as of the colon, but that the genes involved in tumor progression events may be tissue- or tumor-specific.
 ...
PMID:Evidence for a common molecular pathogenesis in colorectal, gastric, and pancreatic cancer. 166 81

Several recent studies based on restriction fragment length polymorphism analysis have supported the concept that the accumulation of multiple genetic alterations converts a normal cell to a malignant cell. Activation of oncogenes and/or inactivation of tumor suppressor genes have been observed during tumor progression in colorectal cancer, lung cancer, and breast cancer. To investigate the possibility that multiple genes are altered during the progression of renal cell carcinoma, we have used restriction fragment length polymorphism markers throughout the genome to test for loss of heterozygosity in 38 renal cell carcinomas. Nearly 64% of the tumors had lost heterozygosity on the short arm of chromosome 3. We also observed loss of heterozygosity averaging about 30% at informative loci on six other chromosomal arms (chromosomes 5q, 6q, 10q, 11q, 17p, and 19p). These results lead us to suspect the existence of several tumor suppressor genes associated with carcinogenesis of renal cell carcinoma.
 ...
PMID:Allelotype of renal cell carcinoma. 167 Sep 99

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.
 ...
PMID:[Cytofluorometric analysis of cell proliferation kinetics of the human colorectal cancer]. 177 Sep 32

The inherited cancer-inducing disease familial polyposis coli (FPC) provides an excellent model not only for studying tumor progression in colorectal cancer but also for elucidating molecular mechanisms in general oncogenesis. This paper reviewed recent remarkable progresses of molecular mechanisms in colorectal tumorigenesis. This is concerned with the various kinds of genetic alterations that accumulate in the development from normal mucosa to adenoma, and then to adenocarcinoma in comparison with FPC and sporadic cases. This review included also information on the localization of FPC major gene. These observations indicate that in cases of colorectal tumorigenesis several genetic alterations may be involved, including activation of K-ras gene, deregulated expression of c-myc gene or c-fos gene and inactivation of tumor suppressor genes such as p53 and DCC genes, as well as the loss of heterozygosity. The observation suggest that adenomas will have undergone several gene or chromosome mutations before reaching to the fully malignant state. Therefore, DNA diagnosis for colorectal tumors in the clinical level may contribute to more accurate prognosis and better results for further therapy.
 ...
PMID:[Diagnosis of colorectal cancer from DNA level]. 184 82

In a previous study (J Clin Oncol 7:1407-1417, 1989), we identified two dosage administration schedules of fluorouracil (5FU) combined with leucovorin that were superior to single-agent 5FU for the treatment of advanced colorectal cancer. In this same study, a regimen of 5FU plus high-dose methotrexate (MTX) demonstrated a suggestive advantage over 5FU alone. To permit a more definitive comparison, we have extended our evaluation of these three regimens to involve an additional 259 patients. In all, 457 patients with advanced colorectal cancer were randomly assigned to one of the following regimens: 5FU plus low-dose leucovorin, 5FU plus high-dose leucovorin, or 5FU plus high-dose MTX with leucovorin rescue. We have found that each of the 5FU/leucovorin regimens demonstrates a significant (P less than or equal to .01) advantage over 5FU plus high-dose MTX for objective tumor response and interval to tumor progression. Moreover, 5FU plus low-dose leucovorin confers a significant survival benefit (P less than or equal to .01) compared with 5FU plus high-dose MTX. The 5FU plus high-dose leucovorin regimen shows a survival benefit only in unadjusted analyses (P = .04), but this difference is not significant when adjusted for imbalances in prognostic variables (P = .44). Evaluation of the two 5FU/leucovorin regimens rules out a 10% decrease in death rate for the high-dose leucovorin regimen compared with the low-dose leucovorin regimen (P less than .05). The regimen of 5FU plus low-dose leucovorin has now been shown to offer a statistically significant survival advantage versus 5FU alone and versus 5FU plus high-dose MTX, a regimen that had shown promise in earlier trials. These data confirm the efficacy of leucovorin combined with 5FU in patients with advanced colorectal cancer and establish that it is not necessary to use high doses of leucovorin to achieve these results.
 ...
PMID:Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. 156 56

We wished to better understand the role of aneuploidy during the progression of human colorectal cancer. Fresh or frozen multiple samples from 221 human colorectal adenomas, 93 carcinomas, and corresponding control mucosa were investigated using high-resolution DNA flow cytometry. A total number of 164 DNA abnormal clones were observed and characterized by a quantitative index of DNA aneuploidy (DI). In precancerous lesions the vast majority of DNA abnormal clones (almost 3/4 in adenomas with mild to moderate dysplasia) was hypo- and hyper-diploid with DI values from 0.8 to 1.2 (near-diploidy). In moderately to poorly differentiated carcinomas the vast majority of abnormal clones was near-triploid and hypotetraploid with DI values from 1.4 to 1.8 (near hypertriploidy) and only 12% were near-diploid. Adenomas with foci of carcinomas, a group of special interest since they represent a link in colorectal tumor progression, had median triploid DNA content. In addition to an increase in DI values, the carcinomas had a clear increase in the proportion of cells actively synthesizing DNA (S-phase fraction). These results are interpreted as evidence for a ploidy-evolution model according to which near-diploid clones in adenomas at early stages of dysplasia would derive from abnormal mitotic cells that divide their DNA unequally between two daughter cells. Tetrapolidization of these near-diploid cells and successive DNA loss would then lead in later stages of tumor progression to near-hypertriploid clones characterized by a balance of chromosomes bearing growth-promoting and growth-suppressing genes confering a selective proliferative advantage.
 ...
PMID:Tumor progression by DNA flow cytometry in human colorectal cancer. 232 38

Tumor antigens (CEA and AFP) were studied by radioimmunoassay and immunoglobulins A, M and G--after Mancini in blood plasma from 144 cases of colorectal cancer. In most patients, raised levels of CEA, AFP, IgA and IgG were identified. A 5-10-fold increase in CEA and AFP levels matched by a pronounced dysimmunoglobulinemia or IgG deficit (under 10 mg/ml) were prognostically unfavorable. If said shifts persist at days 25-30 after surgery, suspicion of inadequate removal of tumor, its occult dissemination and unfavorable prognosis is justified. Similarly inauspicious are concomitant low antigenic activity in tumor and IgC deficit or a marked dysimmunoglobulinemia. Therefore, a complex assay of tumor-associated antigens (CEA and AFP) and immunoglobulins A, M and G makes a contribution to evaluation of surgery, course of tumor progression and its prognosis.
 ...
PMID:[Possibilities of prognosis in cancer of the transverse colon and rectum using CEA, AFP and immunoglobulins A, M and G]. 243 47


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