Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indirect mammo-lymphography with serial radiograms was made on rats bearing three established rat mammary carcinomas (SMT-2A, TMT-50, MT-W9B), with the water-soluble contrast medium, Iotasul. In the lymphogenously metastasizing SMT-2A, fine lymphatic sprouts from the tumor were seen converging into an afferent lymph vessel that was extending toward a metastatic regional lymph node, in 15-30 min. For 45 min, the dye remained localized in the primary tumor with no other vascular structures or viscera visible until it emerged in the urinary bladder, indicating that Iotasul was absorbed slowly into the systemic circulation via lymphatics and diluted beyond recognition by lymph and blood, and then reconcentrated in urine. In contrast, in the hematogenously metastasizing TMT-50, Iotasul was rapidly diffused into the blood stream, revealing the inferior caval vein within 5 min, and by 15 min the heart, aorta, common carotid arteries, kidney and ureter were all clearly revealed. In the non-metastasizing MT-W9B host, several small vascular markings around the tumor were seen by 10 min and the outline of kidneys and urinary bladder in 15 min, suggesting that the dye was also absorbed through blood capillaries but somewhat slowly. Thus, the differential vascular permeability in rat mammary tumors revealed by Iotasul has not only helped to distinguish lymphatics from blood vessels, but also to correlate it with their metastatic potential.
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PMID:Differential permeability of lymphatic and blood vessels in determining the route of metastasis as demonstrated by indirect lymphography. 335 12

The antimetastatic effect of a new water-soluble derivative of camptothecin, 7-ethyl-10-(4-(1-piperidino)-1-piperidino) carbonyloxy-camptothecin (CPT-11), were examined in several metastatic murine tumor systems. Intravenous (i.v.) injection of CPT-11 into BALB/c mice inhibited lung metastasis by i.v. inoculated, metastatic colonic adenocarcinoma 26 (C26) cells, C26NL-17, in BALB/c mice. This treatment was also effective in C57BL/6 mice against lung metastasis by i.v. inoculated B16-F10 and B16-BL6 cells, highly metastatic variants of the B16 melanoma. Furthermore, intraperitoneal (i.p.) injection of CPT-11 significantly inhibited the growth of C26NL-22 cells, a highly metastatic variant of C26, inoculated subcutaneously (s.c.) into the left front footpads of BALB/c mice. Also, i.p. or i.v. injection of CPT-11 effectively inhibited the growth of 3LL tumors inoculated s.c. into the hind footpads of C57BL/6 mice. Moreover, following s.c. inoculation of either C26NL-22 or 3LL cells, combined surgical excision of the primary tumor and either i.p. or i.v. CPT-11 injections given before or after surgery markedly inhibited the formation of pulmonary metastases. These results show that a new derivative of camptothecin, CPT-11, has a potent inhibitory effect against both spontaneous and experimental lung metastasis.
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PMID:Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. 337 Jul 38

To study the effects of total-body hyperthermia (TBH) on metastases from malignant tumors, Lewis lung carcinoma (LLC)-bearing C57BL/6 mice and mouse ascites hepatoma 134-bearing C3H/He mice were immersed in a heated water bath. Rectal temperature was maintained for 30 min at 40 degrees C or 42 degrees C. After treatment, the incidence of lung metastasis was analyzed in LLC-inoculated mice, and the presence or absence of metastasis in affiliated lymph nodes was determined in mouse ascites hepatoma 134-inoculated mice. A significant inhibition in primary tumor growth in LLC- and mouse ascites hepatoma 134-bearing mice treated with 42 degrees C TBH was noted. The incidence of lung metastasis was increased from the control level of 1.6 +/- 0.63 (SD) to 2.4 +/- 0.98 in the 42 degrees C TBH (P less than 0.01) groups but not in the 40 degrees C TBH group. Metastasis to affiliated lymph nodes was similar for the controls and the 40 degrees C and 42 degrees C TBH groups. The increase in lung metastasis in LLC-treated mice subjected to 42 degrees C TBH could be prevented by the combined use of anticancer drugs such as cis-diamminedichloroplatinum(II) (1.0, 3.0 mg/kg) or mitomycin C (0.3, 1.0 mg/kg). Furthermore, the combined use of 42 degrees C TBH and anticancer drugs showed the inhibition of primary tumor growth to a greater degree than did 42 degrees C TBH alone or anticancer drugs alone. Since 42 degrees C TBH may induce tumor metastasis, especially hematogenous metastasis, it seems advisable to use anticancer drugs in combination with clinical thermal applications.
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PMID:Effects of total-body hyperthermia on metastases from experimental mouse tumors. 391 41

Epidemiological and experimental investigations have led to the hypothesis that the growth of malignant melanoma is induced by hormones. The demonstration of free-hormone binding sites in melanoma tissue may help to determine the validity of this hypothesis, as receptors are necessary for the transformation of hormonal action. The DCC assay with subsequent saturation analysis was used for the demonstration of specific cytoplasmatic binding sites of steroid hormones. The presence of free-cytosolic estrogen-, progesterone- and glucocorticosteroid receptors was investigated in 50 melanoma samples from 46 patients. In 20 of the 50 specimens, free estrogen and progesterone receptors were found. Free-glucocorticosteroid receptors we found in 10 cases. The use of four fold-labeled estradiol (2,4,6,7-[3]-17 beta-estradiol) in the DCC assay produced a false-positive demonstration of free-estrogen receptors. Tyrosinase hydroxylates estradiol at the C2 level of the steroid. Using fourfold labeled estradiol, tritium is separated at the C2 position, thus forming radioactive water in the cytosol which mimics high, free-estrogen binding sites. The use of twofold-labeled estradiol or L-dopa in the experiments with fourfold labeled estradiol produced no false-positive determinations of estrogen receptors. The demonstration of receptors in malignant melanomas was unaffected by the sex of the patient. Also, the type of malignant melanoma, the invasion level, and the prognostic index did not show a correlation with the presence of the various hormone receptors. In metastases, free steroid hormone receptors were detected less often than in the primary tumor.
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PMID:[Steroid receptors in malignant melanomas]. 393 Apr 22

We investigated the mechanism of metastatic spread in Lewis lung carcinoma-bearing C57BL/6 mice exposed to 42 degrees C total-body hyperthermia (TBH) by water immersion. When the mice were treated with 42 degrees C TBH 24 h after resection of the primary tumor, the spread of lung metastasis was inhibited (P less than 0.01). When tumor-bearing mice were exposed to 42 degrees C TBH followed by resection of the primary tumors 24 h later, the spread of lung metastasis was greater than in the control group from which tumors were removed 6 days after inoculation (P less than 0.05). When normal mice were subjected to 42 degrees C TBH and Lewis lung carcinoma cells were subsequently injected i.v., lung metastasis increased significantly in those mice that had received tumor cell injection between immediately after and 48 h after TBH treatment (P less than 0.02-0.001). Tumor-bearing mice were subjected to 42 degrees C TBH, and changes in the lung tissues were examined. Between 12 and 48 h after TBH, alveolar collapse, edema, and cellular infiltration into the alveolar walls were seen. Tumor-bearing mice were exposed to 42 degrees C TBH and blood was taken from the inferior vena cava. The number of tumor cells in the blood increased significantly 12 h after TBH exposure (P less than 0.05). We suggest that TBH promotes the intravascular invasion of tumor cells and that histological changes in the host lung facilitate the implantation of tumor cells.
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PMID:Mechanism of metastatic spread by 42 degrees C total-body hyperthermia in Lewis lung carcinoma. 394 87

Accompanying surgical resection of the primary tumor is removal of its drainage lymph nodes. However, all of the minute regional lymph nodes cannot be identified and some may be left behind. If a certain anticancer agent in the form of an emulsion is injected topically into the lymph nodes, it may suppress the lymphatic metastases. Domestic rabbits were used as experimental animals, because transplantable VX2 tumors are available. The vermiform appendix was selected as the transplantation site because of its rich supply of lymph follicles, simulating lymph nodes histologically, and because the path of lymph drainage is very simple. The drainage lymph node, which is located at the root of the appendix, was selected for study. The rate of transfer of bleomycin into lymph nodes and of its sustained release from the nodes was extremely enhanced by the use of a sphere-in-oil-type emulsion--more than two times higher than in the use of a W/O emulsion. Although prolongation of survival time did not take place in animals receiving the bleomycin solution topically or intravenously, five of the seven rabbits receiving the local administration of bleomycin as a sphere-in-oil or a water-in-oil emulsion, between which differences were not found in tumor effects, survived with complete reduction of the lymph node metastases.
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PMID:Surgical chemotherapy against lymph node metastases: an experimental study. 615 74

This study describes a comparison of 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) and imidazole-4-carboxamide,5-(3,3-dimethyl-1-triazeno) (DTIC) with reference to antitumor activity on different murine tumors and hematological toxicity. DM-COOK appeared comparably or slightly more effective in L1210, P388, and M5 tumors in the mouse. However, when the treatment of mice bearing M5 with DM-COOK was combined with surgical removal of the primary tumor, the host's life-span was highly significantly prolonged. The two drugs showed similar activity in an M5 variant selected for resistance to cyclophosphamide. In L1210 Ha, a leukemia that is spontaneously resistant to DTIC, DM-COOK was not effective. Both DM-COOK and DTIC caused transient leukopenia with a maximum WBC fall of 57% and 71% compared with control values. DM-COOK's greater chemical stability might be an advantage, as the decomposition of DTIC is thought to lead to products responsible for some toxic effects in humans. Like other phenyldimethyltriazenes DM-COOK, is a good candidate for clinical trials because its water solubility eliminates formulation problems.
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PMID:Comparison of the antitumor activity of DTIC and 1-p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt on murine transplantable tumors and their hematological toxicity. 646 99

The antitumor and antimetastatic activities of the water-soluble peptidoglycan monomer GlnNAc-Mur-NAc-L-Ala-D-iso-Gln-meso-diamminopimelic acid (omega-NH2)-D-Ala-D-Ala (PGM), which has immunostimulant effects, have been evaluated in CBA mice bearing MCa mammary carcinoma. The antineoplastic effects of PGM depend strictly on the dosage and treatment schedule used. Though a significant inhibition of the primary tumor growth is observed over a wide range of dosage, only the IV administration of daily doses of 50 mg/kg/day on days 1, 5, 10, 15 inhibits spontaneous lung metastasis formation and in parallel prolongs the survival time of the treated mice. The magnitude of the antimetastatic effects of PGM depends on the degree of dissemination of the tumor, and is greater when the number of metastatic foci is low. Examination of the therapeutic potential of PGM in combination with surgery has further indicated that the timing of administration plays an important role in the overall effectiveness of this substance. A 5-day interval is necessary between two consecutive injections for the induction of significant increases of the survival times.
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PMID:Antitumor and antimetastatic activity of the immunoadjuvant peptidoglycan monomer PGM in mice bearing MCa mammary carcinoma. 656 78

A newly synthesized platinum analogue, cis-1,1-diaminomethylcyclohexaneplatinum(II) sulfate (TNO-6), was compared with cis-diamminedichloroplatinum(II) (cis-DDP) for antitumor activity and nephrotoxicity. Antitumor activity was determined in an IgM immunocytoma model in the LOU/M rat. Tumor cells were inoculated on the left flank, and therapy was started when a tumor diameter of 10 to 30 mm was reached. At the start of the therapy, the primary tumor had already metastasized to the draining lymph node and liver. Both platinum compounds, dissolved in 5% glucose water, induced an almost complete tumor regression within 10 to 14 days (average, 84% tumor load reduction) and prolonged survival, compared to that of nontreated animals. The antitumor activity induced by repeated i.p. administration of cis-DDP and TNO-6 reached its maximum at a dose of 1.0 mg/kg body weight (twice a week for 7 weeks). This treatment regimen resulted in a highest tolerable dose for cis-DDP of 1.0 mg/kg and for TNO-6 of 2.0 mg/kg. However, when rats were treated with a 2.0-mg/kg dose of TNO-6, no increase in antitumor activity was obtained. For both platinum compounds, tumor recurrence occurred in almost all animals within 2 to 7 days after the maximum tumor load reduction. Tumors that recurred were found to be cross-resistant to both platinum compounds tested but were sensitive to treatment with doxorubicin (Adriamycin). With regard to toxicity, repeated administration of TNO-6 (1.0 mg/kg twice a week for 7 weeks) induced less decrease of body weight than did cis-DDP. For TNO-6, even in the highest dose investigated (2.0 mg/kg twice a week for 7 weeks), no nephrotoxicity was observed on histological examination of kidney and blood urea and creatinine values, whereas for cis-DDP nephrotoxicity was still present in the lowest dose investigated (0.5 mg/kg). From the comparison of the antitumor activity and nephrotoxicity of TNO-6 and cis-DDP, administered i.p. in 5% glucose solution, it is concluded that both drugs have comparable antitumor activity and potency. In contrast to the effects of cis-DDP, no nephrotoxicity was observed with TNO-6; thus, TNO-6 might be a good alternative to cis-DDP in avoiding nephrotoxicity during platinum therapy.
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PMID:Antitumor activity, induction of cross-resistance, and nephrotoxicity of a new platinum analogue, cis-1,1-diaminomethylcyclohexaneplatinum(II) sulfate, and of cis-diamminedichloroplatinum(II) in an immunocytoma model in the LOU/M rat. 668 93

Fresh-brewed regular coffee at concentrations of 25, 50, and 100% was consumed ad libitum as the sole fluid intake of F1 Sprague-Dawley rats (55 male and 55 female/group), derived from P0-treated females which were provided 50% coffee for about 5 weeks prior to copulation and throughout gestation and lactation. P0 males, P0 control females, and two groups of F1 control rats received tap water. Ten rats/sex/level were killed and examined after 1 year; survivors were killed after 2 years. Smaller mean body weights (50 and 100% coffee concentrations) occurred with increased feed and liquid consumption. Mean serum alkaline phosphatase, bilirubin, BUN, and calcium values occasionally were elevated. Serum cholesterol levels at 2 years were elevated in males (25 and 100%) and at 1 and 2 years in females (100%). Bone calcium was slightly reduced in females consuming 25 or 100% coffee for 1 year, but not after 2 years. Treatment-related increases in relative weights of lungs, kidneys, liver, and epididymides were recorded. Significantly increased mortality was observed in females receiving 50 or 100% coffee. There also was some evidence of a relationship between coffee consumption and the number of primary tumor-bearing animals; however, this finding appeared ambiguous, dependent on the assumption that tumors were the probable cause of death.
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PMID:Two-year toxicity/carcinogenicity study of fresh-brewed coffee in rats initially exposed in utero. 674 Jun 85


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