Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4'-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) is a new anthracycline derivative. The antitumor activity of THP-ADM was tested on 51 human tumor samples representing ten different tumor types in in vitro colony assay method. Tested tumors were: 26 cases of ovarian cancer, 8 cases of breast cancer, 6 cases of colorectal cancer, 3 cases of endometrial cancer, 2 cases each with gastric cancer and sarcoma, and another 4 cases. An in vitro colony assay was done in soft agar as described by Hamburger & Salmon. The criteria for in vitro sensitivity was defined as a 70 percent or greater reduction in the number of colonies after a 1-h exposure to drugs. The selected concentrations of THP-ADM for assay were 0.05, 0.5, and 1.0 micrograms/ml. The sensitivity rates for THP-ADM in each dose were: 0.05 micrograms/ml (7/19, 37%), 0.5 micrograms/ml (10/51, 20%), and 1.0 micrograms/ml (12/19, 63%). In vitro sensitivity of adriamycin (0.04 micrograms/ml) was simultaneously tested in 49 cancer patients. Five out of 25 ovarian cancer patients (20%) showed responses to adriamycin and an overall response rate was 12% (6/49). These data indicate that THP-ADM has an antitumor activity against various cancers and it is comparable to that of adriamycin.
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PMID:Activity of 4'-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) in a human tumor cloning system. 668 22

In previous in vitro studies, the authors showed that phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBL) from cancer patients to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. Thus, after IRB approval, a phase I clinical protocol was instituted in cancer patients who had failed all other therapy to determine the toxicity and effects, in vivo, of the infusion of large numbers of such PHA activated autologous PBL. Ten patients were treated on the protocol, six with sarcoma, one with melanoma, and three with colorectal cancer. Up to a total of 1.7 X 10(11) PBL were obtained from 7 to 15 successive leukaphereses, the cells from each leukapheresis being incubated in vitro in medium containing PHA and human AB serum for 2 days and then reinfused following the next leukapheresis 2 days later. Toxicity encountered included fever and chills in 10/10 patients, headaches in 5/10, nausea and vomiting in 3/10, and requirement for erythrocyte transfusion in 8/10. No evidence for autoimmune disease, abnormal serum chemical or coagulation studies, or pulmonary emboli was found. 111Indium trafficing studies showed distribution of infused cells mainly to the spleen and liver, with some accumulation in the lungs and tumor especially after repeated infusions. In 9/10 patients, activated PBL were detected in the peripheral circulation by the sixth leukapheresis. Evidence for this was found by assaying the incorporation of tritiated thymidine (3H-Tdr) into, and lysis of fresh tumor cells by, unstimulated PBL from successive leukaphereses. No tumor regression was seen in these patients with bulk disease. These studies demonstrated that large numbers of PHA-activated PBL can be safely obtained and infused into humans, achieving an increase in the number of circulating activated cells with evidence of migration of cells to tumor, lungs, liver and spleen. Further studies of the use of activated lymphocyte infusion in conjunction with chemotherapy in humans are in progress.
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PMID:Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. 669 92

The growing number of oncological patients subjected to radiogherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecting demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.
CRC Crit Rev Diagn Imaging 1980 Jan
PMID:Postradiation atrophy of mature bone. 698 80

Murine strains which bear constitutive inactivating mutations of either the APC or the p53 tumor suppressor genes are characterised by spontaneous tumors. APC mutated (Min) mice develop large and small bowel adenomas, a small proportion of which, in time, become malignant. p53 deficient mice develop predominantly lymphoma and sarcoma. By interbreeding these strains we have shown that there is co-operativity between these mutations, leading to a shift in phenotype. Most notably, this was characterised by a range of abnormalities of the exocrine pancreas in 83% of animals heterozygous for the APC mutation and constitutively null for functional p53. Dysplasia and preneoplastic foci were seen in 61% of these animals and pancreatic acinar cell adenocarcinoma in 22%. Analysis of these tumors showed them to have lost the remaining wild-type copy of APC. Similar loss of APC was not associated with the development of other extra-intestinal tumors. Surprisingly, given the proposed role for loss of function mutations of the p53 gene in the development of human colorectal cancer, we have found no evidence for either an increase in the rate of adenoma formation in APC +/-, p53 -/- animals, or an increased rate of progression to malignancy compared with APC +/- p53 +/+ mice. These findings highlight striking tissue-specific differences in the tumor suppressor effects of p53.
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PMID:Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy. 747 22

A recently described splice variant of CD44 has been shown to confer metastatic potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Using antibodies raised against a bacterial fusion protein encoded by variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins in human lymphoid cells and tissues, in non-Hodgkin's lymphomas, and in colorectal neoplasia. Normal lymphohematopoietic cells express barely detectable low levels of variant CD44 glycoproteins, while T lymphocytes, upon activation by mitogen or antigen, transiently upregulate expression of specific CD44 variant glycoproteins. The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that in the rat confers metastatic capability. Interestingly, overexpression of v6 was also found in several aggressive, but not in low-grade, non-Hodgkin's lymphomas (NHL). In human colorectal neoplasia we also observed strong overexpression of CD44 splice variants in all invasive carcinomas and carcinoma metastasis. Interestingly, focal expression was already observed in adenomatous polyps, expression being related to areas of dysplasia. The findings establish CD44 variants as tumor progression markers in colorectal cancer.
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PMID:CD44 splice variants: expression during lymphocyte activation and tumor progression. 750 54

Recently, splice variants of CD44 have been described that confer metastatic potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Using antibodies against variant CD44 (CD44v) sequences, we have examined the expression of variant CD44 glycoproteins on human lymphoid cells and tissues and in colorectal neoplasia. Lymphohematopoietic cells express low levels of CD44v glycoproteins. During the process of lymphocyte activation in vitro and in vivo, expression of CD44v glycoproteins is transiently upregulated. The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that confers metastatic capability. In human colorectal neoplasia we observed overexpression of CD44 splice variants in all invasive carcinomas. Already at early stages of colorectal tumor progression exon v5 epitopes were overexpressed. Tumor progression was strongly related to expression of CD44 isoforms containing exon v6 encoded domains. The findings establish CD44 variants as tumor progression markers in colorectal cancer.
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PMID:Expression of CD44 splice variants during lymphocyte activation and tumor progression. 753 Jan 51

Ninety seven patients with metastatic lung tumors were treated surgically in our department. Second pulmonary resections were performed in 13 patients. They consists of 9 males and 4 females, their age ranged from 12 to 75 years old (average 54.4 years old). Tumors originate from sarcoma in 5 cases, laryngeal cancer, colorectal cancer, renal cell cancer in 2 cases respectively, oral cavity cancer and transitional cell cancer in 1 case respectively. No second pulmonary resection was performed in patients with metastatic lung tumors originating from lung cancer or breast cancer, because they metastatize not only lung but also general organs. No second pulmonary resection was required in patients with testicular tumor and choriocarcinoma, because chemotherapy take good effect on them.
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PMID:[Clinical study on reoperation for recurrent pulmonary metastasis]. 819 37

Between 1960 and 1991, 103 consecutive patients underwent pulmonary resection for metastatic lung tumors in our department. Of the 103 cases 52 were males and 51 were females, aged from 21 to 83 years old. The items of the primary origin of them were 23 cases colorectal cancer, 21 of osteogenic sarcoma, 11 of soft part sarcoma, 10 of mammary cancer, 7 of choriocarcinoma, 7 of renal cancer and others. The 5 year survival of the colorectal lung metastases were examined according to the number and size of the tumors, the tumor free interval and operation modalities. The 5 year survival rate was 45%. The recent trends of surgical treatment for metastatic lung tumors show a significant decrease of surgical treatment of choriocarcinoma, however trends show a significant increase of colorectal carcinoma. The surgical treatment of the colorectal cancer metastases, not only solid metastasis and, multiple metastases but also localized liver metastasis have given satisfactory results. With the present state of chemo-therapy and radiation therapy an acceptable survival rate cannot be expected except for only some kinds of metastatic tumor, and so most other tumors should be surgical resected. In particular it is desirable that a lobectomy with lymph node dissection be performed on solid colorectal metastasis.
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PMID:[Surgical treatment for metastatic lung tumors--with special references to colorectal lung metastases]. 821 55

From 1991 to 1995, we initiated cultures of 94 fresh tumor samples of various histologies in an effort to grow tumor-infiltrating lymphocytes (TIL) using flasks and subsequent expansion in semipermeable bags. The five most prevalent tumor types from which TIL were successfully initiated were melanoma (25 successful initiates in 34 tumor samples, 74% success rate), colorectal cancer (12 of 18, 67%), renal cell carcinoma (9 of 12, 75%), breast (4 of 5, 80%), and sarcoma (5 of 7, 71%). The overall success rate for all tumors was 67 of 94 (71%). There were no instances of contamination from the time of culture initiation through harvesting of the final cell product for clinical use. The mean number of days to reach successful initiation (> 5 x 10(8) cells) was 35 +/- 24 days (mean +/- SD). TIL were then expanded from these successful initiates for either a repeated low-dose therapy (TIL reinfusion numbers of 5 x 10(8)-5 x 10(9) or for a repeated high-dose therapy (> 5 x 10(9)-5 x 10(10). The mean number of days to expand a TIL culture from the time of initiation to treatment for a first low-dose TIL was 59 days (range, 27-94 days) compared with 80 days (range, 33-209 days) for high-dose TIL. For patients who received a second or third high-dose TIL treatment, the average number of days needed to expand TIL was 39 days (n = 10) if there was no intervening cryopreservation of TIL, compared with 49 days (n = 10) if the culture had to be reestablished from cryopreserved TIL. For patients who received a second or third low-dose TIL, the mean number of days needed to expand TIL was 23 days (n = 3) if there was no intervening cryopreservation compared with 42 days (n = 17) if cultures had to be reestablished after cryopreservation of TIL. Low-dose TIL displayed predominantly CD4+ phenotype in 76% of 42 cultures, whereas high-dose TIL displayed predominantly CD8+ phenotype in 84% of 44 cultures. Cells bearing the natural killer (NK) phenotype (CD3-, CD56+) and the lymphokine activated killer (LAK) phenotype (CD3+, CD56+) were present in both low- and high-dose TIL cultures, but these phenotypes were never predominant. Cytotoxicity testing consistently demonstrated the persistence of NK and LAK activity in addition to the killing of allogeneic and autologous melanoma tumor targets. This work confirms that TIL cultures from most tumor types can be successfully established and expanded for therapeutic use, and repeated expansion from continuous TIL culture or cryopreserved TIL for repeated treatments is feasible. Such cultures are predominantly T lymphocytes that are phenotypically heterogeneous, and these phenotypes do not remain constant during prolonged time in culture.
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PMID:Characterization of tumor-infiltrating lymphocytes derived from human tumors for use as adoptive immunotherapy of cancer. 933 45

The feasibility of combined studies on a cell-line panel and primary cultures of patient tumor cells in the preclinical evaluation of new anticancer drugs was evaluated in a study of the activity and cross-resistance pattern in vitro of the new semi-synthetic vinca alkaloid vinorelbine (Vrb). The activity of Vrb was investigated in ten cell lines representing different resistance mechanisms and in a total of 256 fresh human tumor samples, using the fluorometric microculture cytotoxicity assay (FMCA). Resistance to Vrb in the cell lines was associated with expression of the multidrug resistance-mediating P-glycoprotein and the multidrug resistance-associated protein (MRP) and by a recently described tubulin-associated mechanism, while the cell lines with topoisomerase II- and glutathion-associated resistance did not show decreased sensitivity to the drug. Cross-resistance to vincristine (Vcr) and other tubulin-active agents was high in cell lines as well as in patient cells. As with most commonly used anti-cancer drugs, Vrb was more active in hematological than in solid tumor samples. Among the solid tumors investigated, the highest in vitro response rates were observed in ovarian cancer (27%), sarcoma (25%), non-small cell lung cancer (21%) and bladder cancer (20%), while no response was observed in renal or colorectal cancer. Compared to Vcr, Vrb appeared to be slightly more active in solid tumors and slightly less active in hematological tumors. The results show that although Vrb displays a high degree of cross-resistance to Vcr and other tubulin-active drugs, some difference in the activity spectrum could be detected and that the drug is sensitive to multiple mechanisms of resistance. The results also suggest that leukemias, ovarian cancer, sarcoma and bladder cancer are possible further targets for Vrb. The combination of studies on a cell-line panel and patient tumor cells from a broad spectrum of diagnoses to evaluate a new drug seems feasible and may give information on the mechanism of action and target diagnoses for phase II trials.
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PMID:In vitro evaluation of new anticancer drugs, exemplified by vinorelbine, using the fluorometric microculture cytotoxicity assay on human tumor cell lines and patient biopsy cells. 941 16


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