Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that soluble extracts from human colonic carcinoma (SCE) were potent inhibitors of the PHA-induced DNA synthesis of normal allogeneic peripheral lymphocytes. From the present study, SCE appeared to have a broad and nonspecific range of activity. The SCE-suppressive effect was observed whatever the lymphoid organ or the animal species used as a source of stimulated lymphocytes. Moreover, we always obtained a complete inhibition of the lymphoproliferative response to all tested mitogens including PHA, Con A, PWM, and, for animal lymphocytes, LPS. In addition to the suppressive activity on lymphocytes, SCE also inhibited proliferation of cultured human CCL6 embryonic intestine cells and HT29 colonic carcinoma cells, and of cultured rat fibrosarcoma cells. Soluble extracts from HT29 cells (SCCE) were able to mimic the nonspecific suppressive and cytostatic activities of SCE. The suppressive activity was also found in extracts from hepatic metastases (SHME) of a primary colonic tumor. In contrast, soluble extracts from normal liver or nonmalignant colonic mucosa did not interfere with cell proliferation. These data suggest that both SCE and SCCE contain molecular components(s) that can inhibit a wide variety of proliferating cells, including stimulated lymphocytes.
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PMID:Nonspecific suppressive and cytostatic activities mediated by human colonic carcinoma tissue or cultured cell extract. 67 Jul 7

A radioimmunoassay for ng quantities of DNA was developed. [125l]lododeoxyuridine-labeled DNA was used as the antigen, and the serum of a lupus erythematosus patient served as the source of antibody. The level of free DNA in the serum of 173 patients with various types of cancer and in 55 healthy individuals was determined by this radioimmunoassay. DNA concentration in the normal controls had a range of 0 to 100 ng/ml with a mean of 13 +/- 3 ng/ml (S.E.). For comparison purposes, the range of 0 to 50 ng/ml was designated as normal, and 93% of controls were found in this range. In the cancer patients, the DNA concentration ranged from zero to mug levels with a mean of 180 +/- 38 ng/ml. Fifty % of the patients values were found in the range of 0 to 50 ng/ml; the other 50% were between 50 and 5000 ng/ml. No correlation could be seen between DNA levels and the size or location of the primary tumor. Significantly higher DNA levels, however, were found in the serum of patients with metastatic disease (mean of 209 +/- 39 ng/ml), as compared to nonmetastatic patients (mean 100 +/- 30, p less than 0.02). After radiation therapy in lymphoma, lung, ovary, uterus, and cervical tumors, the levels decreased in 66 to 90% of the patients, whereas in glioma, breast, colon, and rectal tumors, the DNA levels decreased only in 16 to 33% of the patients. Generally, the decrease in DNA concene of tumor size and reduction of pain. Conversely, when DNA levels either increased or remained unchanged, a lack of response to the treatment was noted. Of 17 patients who died within a year, 13 showed DNA levels that remained high or unchanged, whereas only 4 showed lower levels during treatment. Persistent high or increasing DNA levels in the circulation, therefore, may signal a relapse and are probably a poor prognostic sign. The relatively high percentage (50%) of cancer patients with apparently normal DNA levels would suggest that this test may have low diagnostic value. It should be pointed out, however, that all these patients represent a selected group considered for radiation therapy, usually after surgery and/or chemotherapy. It is possible that a better correlation between DNA levels and cancer will be obtained prior to the initiation of treatment. On the other hand, DNA in the serum may be an important tool for the evaluation of therapy or the comparison of different regimens.
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PMID:Free DNA in the serum of cancer patients and the effect of therapy. 83 66

The content of DNA was investigated by the method of pulsed cytophotometry in cells of the following neoplasms: pulmonary cancer, benign lesions and cancer of the stomach, melanomas of the skin, malignant lymphomas and metastases of cancer into the lymphatic node. In the normal tissues and benign tumours the number of proliferating cells (DNA value of 3p, 4p) was not significant--from 2.0 to 5.0%. Polyploid cells were absent. In tumours the number of cells varied broadly--proliferating cells from 5.0 to 27,0%, polyploid cells from 9.0 to 40.0%. The use of the method of pulsed cytophotometry in prophylactic examinations is not effective, since in many cases changes could be detected only in single cells not identifiable on DNA-cytograms. Investigation of DNA content by the method of pulsed cytophotometry in a great number of tumour cells makes it possible to determine more accurately the character of the tumoral process, the level of differentiation of the tumoral tissue.
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PMID:[Cytophotometric method of determination of DNA content of neoplastic cells]. 84 36

The Madison 109 (M109) tumor was discovered in 1964 in the lung of a BALB/c mouse. This experimental carcinoma is maintained in vivo by sc passage in the right axillary region. When implanted im (5 X 10(5) cells) into the right hind leg of BALB/c mice for testing, the primary progresses with metastases to the lung, spleen, and liver. The metastases to the lung are visible within 3 weeks and result in the death of the host in about 35 days after tumor implant. Implantation of a lung nodule is tumorigenic and lethal. Pyran polymer therapy delayed the appearance of lung metastases, inhibited the growth of the primary tumor, and significantly increased the lifespan of BALB/c mice inoculated with the M109 tumor. No spontaneous regression has been observed and very few "no takes" have occurred in untreated BALB/c mice inoculated with at least 500 M109 cells. Of the 82 agents tested so far, the M109 model has selected active agents such as actinomycin D, adriamycin, daunorubicin, DNA, procarbazine, and pyran polymer. It has not shown sensitivity as tested to several standard therapeutic agents including cytosine arabinoside, BCNU, hydroxyurea, mechlorethamine, melphalan, triethylenemelamine, and vincristine.
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PMID:Characterization and responsiveness of the Madison 109 lung carcinoma to various antitumor agents. 92 51

Soluble extracts from human colonic tumors (STE) and from their hepatic metastases (SHME) were found to be unable to induce a proliferative response among normal allogenic lymphocytes. However, addition of these tissue extracts to cultures stimulated with various mitogens resulted in an almost complete inhibition of lymphocyte DNA synthesis. Nevertheless, they did not reduce the unstimulated lymphocyte spontaneous proliferation. Control experiments have shown that normal or nonmalignant tissues do not affect the lymphocyte reactivity to mitogens. The specific immunosuppressive evvect was found to be irreversible and to block lymphocyte activation at an early stage. The inhibitor was soluble (not sedimented at 220,000 times G for 2 hr) and not nonspecifically cytotoxic. STE was slso found to induce morphologic alterations resulting in blastlike cell production. However, no mitotic figures were seen, even after colchicin treatment. It is suggested that STE might contain molecular component(s) which would exert a double effect: 1) trigger metabolic alterations responsible for the blast-like cell induction, and 2) inhibit the lymphoproliferative response. The significance of such a mechanism is discussed in conection with the nonspecific immunosuppression caused by a tumor and the immune unresponsiveness against the tumor itself. A preliminiary characterization of this tumor material has shown that its molecular weight was about 70,000 and that it is not related to carcinoembryonic antigen or alpha-fetoprotein.
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PMID:Inhibition of normal allogenic lymphocyte mitogenesis by a soluble inhibitor extracted from human colonic carcinoma. 97 47

Melanomas developed in both sexes of a strain of Tuxedo variety of the swordtail (Xiphophorus helleri) at a relative frequency of 10-15%. They did not metastasize. However, the tumor margin had infiltratitive growth and subsequently ulcerated. This feature, together with the histologic and cytologic features and apparent heteroploidy of the tumors, as revealed by their DNA content, indicated that the tumors were indeed neoplastic. Electron microscopic findings on the melanosomes in these melanomas at various stages of development were comparable with those on the Harding-Passey mouse melanoma, which contains granular premelanosomes.
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PMID:Morphologic and microspectrophotometric studies on spontaneous melanomas in Xiphophorus helleri. 113 50

In-vitro sensitivity to cystostatic agents was tested in 137 cases of breast carcinoma, with 125 tests being analysable. Inhibition of in-vitro incorporation of 3H-uridine or 3H-thymidine into RNA or DNA of the original tumour cells after incubation with antineoplastic substances was used as the index for the in-vivo sensitivity of the tumour. 30% of the carcinoma cells were sensitive in-vitro, 70% resistant. About 75% of sensitive cancers were sensitive against several agents. Cyclophosphamide proved to be most effective in-vitro: it was tested via 4-hydroxycyclophosphamide or 4-hydroperoxycyclophosphamide. There was a correlation between histological type and in-vitro sensitivity of the cancer, as well as between proliferative activity and in-vitro sensitivity in that proliferation-active tumours were more frequently sensitive in-vitro than proliferation-poor ones. Primary tumours and metastases of the same patient frequently showed different sensitivity. In some cases the development of resistance against cytostatic drugs was demonstrated during treatment. Testing tumours against combinations of cytostatic drugs demonstrated an additive effect of the antineoplastic substances in-vitro.
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PMID:[In-vitro testing of the sensitivity of mammary carcinoma cells to cytostatic drugs (author's transl)]. 115 20

The quantitative ratios of RNA:DNA were followed in a developing transplanted fibrosarcoma in C3H mice and in its lung metastases. There was a significant increase in these ratios in developing tumors originating from cell suspensions (P smaller than 0.001) and a single implanted piece (P smaller than 0.05). No significant change was demonstrated in developing fibrosarcoma originating from two pieces of this tumor (P greater than 0.05) which were implanted simultaneously. When comparing the ratios of RNA and DNA of developing lung metastases to the primary tumors, we found a significantly higher ratio in the metastases (P smaller than 0.001). No significant changes in RNA:DNA ratios were demonstrated in normal proliferating tissues either in physiologic hyperplasia or embryo tissue culture (P greater than 0.05).
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PMID:RNA:DNA ratios in a developing fibrosarcoma and its lung metastases in C3H mice. 117 91

By labelling dermal infiltrate cells with H3-thymidine, two types of skin tumours can be distinguished: one type with many labelled cells in the infiltrate (H3-thymidine labelling index, H3-I), the other with few labelled cells. Type I includes malignant melanoma (H3-I = 2.2%) and hemangioendothelioma (2.8%). Type II includes metastases of malignant melanoma (1%), squamous cell carcinoma (1.1%), basel cell epithelioma (0.5%), nevus cell nevus (0.6%), and nevoid lentigo (0.4). The number of labelled cells in the cellular reaction of Type II tumours does not differ significantly from that in normal human corium (0.75%), though there may be a dense cellular reaction. DNA-synthesizing cells were classified with the aid of characteristical stainings and histochemical methods. A vast majority of them were found to be lymphocytes. Our research underlines the special importance of cellular inflammatory reaction, i.e. cellular immunity, im malignant melanoma and probably in hemangioendothelioma.
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PMID:Lymphocyte stimulation in the cellular inflammatory reaction of some human skin tumours. 120 Jul 1

We investigated 24 patients with melanotic tumours (under them 22 malignant melanoms). The tumour material (31 x by biopsy, 2 x by autopsy) was homogenized and stained with Ethidium bromide after pepsination. The distribution of the DNA content of the tumour cell nuclei was measured by impulse cytophotometry. The criterion for the curves was the height of the 4-c-peak in percentage of the diploid peak. Our material was divided in 3 groups: I. Without metastases. II. Metastases, slowly progressive. III. Metastases, rapidly progressive. Between the groups there were significant differences: the higher the 4-c-peak, the greater the malignancy. In the group III we mostly had tetraploid populations with the maximal peak at 4-c. The course of the disease (as seen by metastasis, effect of chemotherapy, growing in cell culture) runs parallel to the findings of impulse cytophotometry. In one case of melanosis praeblastomatosa circumscripta Dubreuilh we found a pure diploid cell population without peaks at 4-c. For prognosis (not for diagnosis) the impulse cytophotometric investigation of malignant melanoma is more suitable than the histology. In the discussion we expose the connections between proliferation and DNS distribution of cell nuclei in a tetraploid population. The terminology of cell cycle phases is extended to tetraploid populations with new terms (G', S'). In some cases we found stem lines. As shown by repeated impulse cytophotometric investigations a changing of stem lines in the DNA distribution curve is possible (change from hyperdiploid to tetraploid). The impulse cytophotometry is suitable for such investigations on melanomas.
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PMID:[Impulse cytophotometric investigations on melanoblastoma (author's transl)]. 120 Jul 81


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