Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A technique of passive hemagglutination inhibition (PHI) has been used to monitor levels of carcinoembryonic antigen (CEA) in human sera following surgical therapy. CEA was coupled to human type O-negative erythrocytes in the presence of bis-diazotized benzidine. Pre-operative and post-operative sera from 11 patients with primary adenocarcinomas of the gastrointestinal tract and from one patient with ulcerative colitis were then tested for their capacity to inhibit the agglutination of the sensitized cells in the presence of a predetermined amount of goat anti-CEA serum. Positive sera were defined as those which inhibited agglutination at dilutions of greater than 1:8. The pre-operative sera from 11 of the 12 patients inhibited agglutination at dilutions of 1:16 or greater. The one negative serum was from a patient with primary adenocarcinoma of the colon in the stage of Dukes' C. At one month post-resection, the PHI titer of six patients with colon cancer and of the patient with ulcerative colitis was less than or equal to 1:8. However, by 4 months post-resection, all but 3 of the patients had PHI titers in the positive range. These elevated titers were accompanied by recurrence of tumor growth and/or metastatic dissemination. A radioimmunoassay was used to quantitate CEA in 22 of the sera which had been tested by PHI. When positive sera were defined as those which inhibited agglutination at dilutions of greater than 1:8 and contained CEA in excess of 5 ng per ml, the results of the two procedures were in agreement for 17 of the 22 specimens. Five sera, representative of 2 patients with colon cancer, were false negative by PHI.
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PMID:Use of a passive hemagglutination inhibition test for monitoring levels of serum carcinoembryonic antigen following surgical therapy. 94 51

From 1977 to 1984, 56 patients with colon cancer adherent to other organs were operated upon. Twenty-three (41 percent) underwent palliative treatment without resection. The mean survival in this group was 6 months. The results of en bloc resection were evaluated in 33 patients (59 percent) with colon carcinoma and tumor growth in adjacent organs. Pathologic staging was based on Dukes' (Astler and Coller) classification. Dukes' B carcinoma was shown in 15 patients. Dukes' C in 14 patients, and Dukes' D in four patients. The 4-year survival rate was as follows: Dukes' B, 47 percent; Dukes' C, 29 percent; and Dukes' D, 0 percent. The 4-year survival rate for the whole group was 33 percent. The postoperative morbidity and mortality were 6 percent and 3 percent, respectively. Colon cancer with involvement of adjacent structures should not be regarded as an incurable Dukes' D carcinoma; en bloc resection is indicated and can be performed with acceptable morbidity and mortality.
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PMID:En bloc resection of colon carcinoma adherent to other organs: an efficacious treatment? 171 11

Gastrin stimulates the growth of some human colon adenocarcinomas grown in vitro or as xenografts in nude mice. To evaluate the possibility of elevated plasma gastrin levels in patients with adenomatous polyps or colorectal cancer, we carried out a radioimmunoassay in subjects fasting overnight and undergoing colonoscopy. The study included 190 patients who were divided into three groups: controls (n = 65), those with benign adenomas (n = 63), and those with adenocarcinomas (n = 62). The mean values of plasma gastrin in the cancer group (112.71 +/- 16.65 pg/ml) were significantly higher than those of the control group (40.41 +/- 1.88 pg/ml) as well as those of the polyp group. Mean plasma gastrin values in the polyp group (54.27 +/- 5.29 pg/ml) were also significantly higher than those of the control group. In the cancer group, 32 of 62 patients (51.6%) had gastrin levels greater than the control mean +2 SD, as opposed to only 10 of 63 (15.9%) in the polyp group. The number, size, histologic type, and presence of dysplasia in the polyp group and the location or Dukes' stage in the cancer group had no significant influence on gastrin levels in this study. Preliminary results in cancer patients with elevated preoperative gastrin levels show a postoperative reduction in six of seven patients. The exact cause and role of hypergastrinemia in tumor growth in such patients remains to be determined. Measurements taken both before and after colectomy coupled with a systematic search for specific gastrin receptors would be useful.
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PMID:Elevated serum gastrin levels in patients with colorectal neoplasia. 174 82

To further understand the molecular mechanisms and the biological indicators of colonic tumorigenesis, the authors examined tyrosine kinase activity in the cytosol and in the particulate fraction of the homogenates of specimens from 20 human colonic carcinomas and compared them with the adjacent normal mucosal tissues. Total protein tyrosine kinase activity could be precisely detected using miniphosphocellulose column purification and a synthetic peptide, Glu-asparagine (Asp)-alanine (Ala)-Glu-tyrosine (Tyr)-Ala-Ala-arginine (Arg)-Arg-Arg-glycine (Gly) (E11-G1), as an artificial substrate. Tyrosine kinase activity of colonic carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity in the particulate fraction was elevated with respect to protein concentration. The average specific activity ratios were 1.95 +/- 0.27 (normal cytosolic/carcinoma cytosolic) and 0.57 +/- 0.01 (normal particulate/carcinoma particulate) for tyrosine kinase activity. Cellular distribution (% cytosol) of tyrosine kinase activity in normal mucosa and in carcinoma varied from 21.0% to 91.2% and from 7.0% to 61.4%, respectively. In nearly all cases the percentage of cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal tissues. There was no difference due to histologic type or the presence of adenomatous components. A significant decrease of cytosolic tyrosine kinases was correlated with Dukes' Stage A. With advancing Dukes' stage, the average specific activity ratios (normal cytosol/carcinoma cytosol) were decreased. This study indicates that colonic carcinogenesis might be associated with alterations in cellular levels of tyrosine kinase activity and that the average specific activity ratio (normal cytosol/carcinoma cytosol) had a possible correlation with colonic tumor growth.
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PMID:Altered protein tyrosine kinase levels in human colon carcinoma. 198 53

Cecal carcinoma has been associated with a poorer prognosis than other colon carcinomas because of the presumed longstanding obscure symptoms. In a combined study of three Dutch hospitals, a total of 166 patients with cecal carcinoma were evaluated after right hemicolectomy. Special emphasis was placed on clinical symptoms related to advanced tumor growth, e.g., pain, anemia, and palpable mass. These factors and clinicopathological staging were evaluated with aid of the Cox regression model. Ninety percent of the resected specimens contained a Dukes' B or C carcinoma. Only 5% were found to have widespread metastatic disease. Overall 5 year survival rate was found to be 0.57. No statistically significant relation to pain or palpable mass was found. Anemia, however, was related to a better survival, especially in patients with a Dukes' B carcinoma. Clinicopathological staging according to Dukes' is closely related to survival. It is concluded that carcinoma of the cecum behaves similarly to other colon malignancies.
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PMID:Cecal carcinoma: a different colon malignancy? 237 Aug

Primary cultures of resected human colon carcinoma were used to study differentiation agents directly on the biologically relevant cancer cells rather than on highly selected established cell lines. To achieve primary cultures which remained viable and replicating for several days, carcinomas were partly digested to epithelial organoids, which were selectively plated with high efficiency on collagen I-bovine serum albumin films in specially formulated serum-free medium. A monoclonal antibody, 29-15, was identified which binds to a cell surface epitope expressed on 16 of 21 invasive colon carcinomas of the Dukes' B2, C, or D histopathology classes, but not expressed on any of 11 noninvasive benign tumors (adenomas) at identical antibody titer. Noncytotoxic concentrations of the differentiation agent, hexamethylene bisacetamide (HMBA), induced the loss of the 29-15 epitope from HT29 colon carcinoma cells. HMBA also induced HT29 cells to lose the capacity for anchorage-independent growth with a similar dose-response curve and time course to the loss of 29-15 epitope. Twelve primary cultured human colon carcinomas exhibited differential responses when exposed to 1 to 7 mM HMBA for 7 days. Four moderately to well-differentiated carcinomas lost expression of the 29-15 epitope at each HMBA concentration. The tumor growth fraction was decreased in each tumor, with a mean decrease of 76% at 5 mM HMBA. A dose-dependent induction of nonproliferating tumor colonies, lacking [3H]thymidine labeling, occurred in three of the four carcinomas. In six other tumors, including those at less differentiated stages, HMBA induced the opposite effect: a two- to threefold increase in the tumor growth fraction at the optimal value of 5 mM HMBA, an increase in mean colony size, and no loss of the 29-15 malignancy epitope. No effects were observed in the two other carcinomas tested. Thus HMBA was able to induce growth arrest and loss of the malignancy epitope 29-15 in those carcinomas already at an advanced stage of differentiation, and to exert a growth stimulating effect on those carcinomas apparently at more immature stages.
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PMID:Heterogeneous responses of human colon carcinomas to hexamethylene bisacetamide. 245 79

Blood group antigen content of human carcinomas located in the distal large bowel (descending colon, sigmoid colon, and rectum) was determined by the specific red cell adherence reaction and was compared to several morphologic features of prognostic significance, e.g., differentiation, extent of tumor spread, peritumoral lymphoplasmocytic infiltration, and growth patterns. About 50% of the carcinomas expressed blood group antigens in either diffuse or patchy distribution. Classification of tumors according to the extent of local spread revealed that 60% of Dukes stage A tumors were blood group antigen-negative, whereas 58% of those in Dukes stage B were positive. Dukes stage C lesions had an intermediate position, and this limits the prognostic usefulness of blood group antigen determinations. No significant correlations were found between blood group antigenicity and the degree of histologic differentiation, the degree of peritumoral lymphoplasmocytic infiltration, and the mode of tumor growth.
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PMID:Epithelial blood group antigens in human carcinomas of the distal colon: further studies on their pathologic significance. 692 8

A retrospective review of all the 951 patients less than 40 years of age with colorectal cancer in Denmark 1943-67 is described. The annual incidence in Denmark of colorectal cancer in this age group is 1.4/100,000. These patients do not differ from other patients with colorectal cancer with regard to sex ratio, tumor localization, extent of tumor growth, histologic type, frequency of intestinal obstruction and perforation. Of these patients 53 per cent were subjected to radical operation. The five-year crude survival rate was 32 per cent for all patients and 65 per cent in cases of radical operation. The operative mortality was 9 per cent. The extent of tumor growth according to Dukes' classification and the presence of intestinal obstruction and/or perforation were the only factors found to influence the prognosis. The survival rates correspond to rate given in the literature in respect of colorectal cancer, regardless of age. It is concluded that colorectal cancer in young patients differs in no respect from the disease in older patients.
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PMID:Colorectal cancer in patients less than 40 years of age in Denmark, 1943-1967. 739 7

Expression of the CD44 molecule has been linked to tumor growth and metastases in both human and rodent cancers. Alternatively spliced variants expressed in rat and mouse tumors have been shown to confer metastatic potential to non-metastatic carcinoma cell lines, and human homologues of rat variant mRNA sequences are expressed in human tumors. In the present study matched sets of RNA from adenocarcinomas of the colon and distant normal mucosa were assayed for CD44 expression by quantitative RT-PCR. Retrospective analysis revealed that colonic tumor cells had both quantitative and qualitative differences in CD44 expression when compared to normal mucosa. These were: 1) an increase in levels of CD44 transcripts, 2) an increase in levels of alternatively spliced transcripts, 3) the presence of larger alternatively spliced transcripts with inserts > 400 bases and 4) the primary alternatively spliced CD44 isoform in colonic adenocarcinomas in all cases is CD44R. Interestingly, two patterns of CD44 isoform expression termed "variant dominant" or "balanced" patterns of expression, based on the ratio of variant to standard CD44 transcripts (R+V's/H), could be differentiated. An unfavorable prognosis was suggested for tumors expressing increased levels of CD44 variant exons previously associated with tumor metastasis. Specifically, patients with tumors expressing the "variant dominant" pattern of expression irregardless of Dukes classification and Dukes C and D staged tumors of both patterns exhibited a poorer prognosis.
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PMID:Alternative splicing of CD44 pre-mRNA in human colorectal tumors. 751 91

The therapeutic effects of the low and high affinity mAbs 17-1A and 323/A3 were investigated in nude mice xenografted with LS 180 human colorectal carcinoma cells. Treatment of mice grafted with dispersed tumor cells, before formation of a tumor nodule, was started 1 day after s.c. injection of tumor cells and consisted of a single i.p. injection of murine 17-1A or 323/A3 mAb. Tumor appearance after a single injection of either 17-1A or 323/A3 was delayed as compared to injection of an irrelevant mAb. Both 17-1A and 323/A3 reduced the tumor growth rate, and both mAbs decreased the total number of mice that eventually developed a tumor. In all experiments, 323/A3 showed consistently better treatment effects on xenografted mice than mAb 17-1A. For treatment of established tumors with mAb 17-1A or 323/A3 therapy was delayed until a tumor nodule was macroscopically detectable. One single i.p. injection of mAb 17-1A had no effect on further tumor growth and mean tumor size as compared to the control group injected with irrelevant mAb. One single i.p. injection with mAb 323/A3 reduced the tumor growth rate in some mice with established tumors and resulted in a significant difference of mean tumor size of this group as compared to the 17-1A treated mice and the control groups. Multiple injections with mAb 17-1A also had no effects on established tumors, in contrast to mAb 323/A3, where serial injections resulted in tumor growth reduction and, eventually, in some mice reduction in tumor size. In summary, we showed that in nude mice mAb 323/A3 (Ka = 2 x 10(9) M-1) is much more potent than mAb 17-1A (Ka = 5 x 10(7) M-1) in eradication of nonestablished tumor cells and treatment of small established tumors. These results suggest that high affinity mAbs like 323/A3 might dramatically improve the clinical results obtained thus far with the low affinity mAb 17-1A in the adjuvant treatment of surgically resected Dukes C colorectal cancer patients with minimal residual disease.
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PMID:Immunotherapy with low and high affinity monoclonal antibodies 17-1A and 323/A3 in a nude mouse xenograft carcinoma model. 767 Dec 52


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