Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimetastatic effect of cepharanthin with or without 5-fluorouracil (5-FU) was examined in an experimental model of lung metastasis induced by Lewis lung carcinoma (3LL) in C57BL/6crSlc mice. Injection of cepharanthin i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination therapy with cepharanthin plus 5-FU inhibited significantly the lung metastases. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with cepharanthin. Cepharanthin depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of cepharanthin. A possible mechanism of the inhibition of lung metastases by treatment with cepharanthin may be that this drug acts through macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that combination therapy with cepharanthin plus 5-FU may have clinical value in the prevention of cancer metastasis.
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PMID:Inhibitory effect of a biscoclaurine alkaloid, cepharanthin, on lung metastasis of Lewis lung carcinoma. 188 Sep 98

Retrospective studies have provided indirect evidence that allogeneic blood transfusion may adversely influence the prognosis of cancer patients. This effect may be prevented by using autologous blood transfusions. However, this involves preoperative donation of blood, the consequences of which are still unknown. The aim of the present study was to investigate the possible effects of blood loss on tumour growth and on NK-cell activity. An artificial lung metastasis model was used in the BN rat from which 20 per cent of the blood volume was taken at different time intervals. The results showed that blood loss, one day prior to tumour challenge, had a profound stimulating effect on tumour growth. After blood loss, the number of lung metastases was doubled as compared to controls. This tumour-promoting effect could be prevented by an immediate plasma transfusion, but not by evoking a normal haemoglobin level after blood loss by pretreatment with recombinant erythropoietin (rEpo). The NK-cell activity of spleen cells was significantly depressed, 24 hours after blood loss. At a 50:1-lymphocyte-to-target cell ratio, the NK-cell activity dropped from 25.3 per cent in controls to 9.3 per cent in experimental animals. Since NK-cells are assumed to play a role in the clearance of tumour cells from the circulation, the enhanced tumour growth observed after blood loss might be caused by this depression.
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PMID:The influence of blood loss on tumour growth: effect and mechanism in an experimental model. 194 94

The question of increased tumor cell dissemination after surgical stress was addressed in the model system of the spontaneously metastasizing rat adenocarcinoma BSp73ASML, wherein amputation of the hind leg 7 days after intrafootpad implantation of tumor cells cured the animals, while surgical stress by laparotomy 2 days prior to amputation resulted in lung metastases in 80% of rats. A detailed in vitro analysis of natural killer (NK) and macrophage (Mo) activity in different lymphatic compartments revealed the following impacts of surgery: splenic NK cells displayed unaltered activity. Yet, there was a considerable decrease in the number of lymphoid cells during the first 4 days after surgery, being followed by an overshooting repopulation. In the peripheral blood, activity levels of NK cells dropped significantly during the first 24 h after surgery; later on, NK cells appeared activated with an over 2-fold increase in lytic units (LU), 4 days after surgery, NK activity had returned towards normal levels. Most dramatic changes were observed in the peritoneal cavity, being directly involved in the surgical intervention. Six hours after surgery the peritoneal cavity was nearly depleted of NK cells and Mo, the few remaining cells being highly activated. Within 2 days the peritoneal cavity was repopulated with a 3-4 fold excess of lymphoid cells and Mo, but the repopulating cells were extremely low in lytic activity. It is concluded that depression of nonadaptive immunity after surgical stress is mainly due to traffic and repopulation with immature cells, i.e. there was no indication of suppressor cell activity. This was confirmed by a combined treatment consisting in a systemic application of Corynebacterium parvum 2 days before surgery and a local application of C. parvum after surgery, which counter-balanced the stress-induced depression of NK and Mo activity. Accelerated and increased metastatic spread could be prevented concomitantly.
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PMID:Depression of nonadaptive immunity after surgical stress: influence on metastatic spread. 270

A phase II trial with mitozolomide was carried out in patients with malignant melanoma, since in preclinical studies this new imidazotetrazine had shown promising effects against human melanoma xenografts. Twenty-one evaluable patients with advanced malignant melanoma were treated with 115 mg m-2 of mitozolomide, given orally every 6 weeks. None of the patients had received prior chemotherapy. Two partial responses (10 and 7+ months) were observed. The responding patients had lung metastases, and one of them had, in addition, a huge (17 X 14 cm) lymph node metastasis in the groin. Also, one patient had a 48% tumour volume reduction of lung metastases. The dose limiting side effect of the treatment was bone marrow depression, with delayed leukopenia and thrombocytopenia. The median white blood cell counts and platelet nadirs were 2.5 X 10(9) 1(-1) (range 1.1-3.8) and 59 X 10(9) 1(-1) (range 14-95), respectively. Non-haematological adverse reactions were limited to mild or moderate nausea. It is concluded that orally administered mitozolomide is active against malignant melanoma and seems to have a response rate comparable to those of the most active established drugs.
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PMID:Mitozolomide (NSC 353451), a new active drug in the treatment of malignant melanoma. Phase II trial in patients with advanced disease. 358 Feb 66

The optimum treatment of malignant choroidal melanoma remains controversial. Some authors have hypothesized that enucleation promotes metastatic disease. This hypothesis has been demonstrated in the B16F10 melanoma mouse model. The present study used this model to examine the effect of external beam irradiation as a means of reducing metastases induced by enucleation. The results show a dose-dependent reduction in the DNA synthesis of irradiated melanoma cells. Administration of 800 cGy (800 rad) of radiation produced a 90% reduction in DNA synthesis; however, higher levels of radiation failed to produce further depression of cell proliferation. Irradiation of melanoma cells before intravenous injection resulted in a significant dose-dependent reduction in the number of lung metastases. While there was no effect with 100 cGy (100 rad) of radiation, 1000 cGy (1000 rad) produced a 95% reduction in metastases. In the animal model of enucleation-induced metastasis, 2000 cGy (2000 rad) delivered to the orbit either before or after enucleation produced a significant reduction in the number of lung tumors, compared with animals that did not undergo irradiation; 1000 cGy (1000 rad) delivered before enucleation did not have such an effect. These studies provide evidence that periorbital external beam irradiation is useful in reducing metastases following enucleation of a malignant melanoma in this animal model.
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PMID:Reduction of enucleation-induced metastasis in intraocular melanoma by periorbital irradiation. 363 44

The differential effects of the i.v. administration of egg-white lysozyme on primary tumor growth and on the formation of spontaneous and artificial lung metastases have been determined in mice bearing two rodent metastasizing tumors: Lewis lung carcinoma and MCa mammary carcinoma. The depression of metastasis formation was particularly pronounced at 50 and 100 mg/kg/day given on days 1,5,10,15 after tumor transplantation, causing a correspondent prolongation of the life-span of the animals carrying artificial induced lung metastases. Contact between tumor cells and egg-white lysozyme seems at least partially responsible for the observed antitumor effects, although no direct cytotoxicity for tumor cells has been detected yet.
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PMID:Antineoplastic effects of egg-white lysozyme in mice bearing solid metastasizing tumors. 370 53

We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.
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PMID:Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes. 387 51

The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an experimental model of lung metastases induced by Lewis lung carcinoma in mice. Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination treatment with GIV-A and 5-FU inhibited significantly the lung metastases. The number of peritoneal macrophages, total cells and macrophages in the lung increased in mice treated with GIV-A. Binding of the third component of complement (C3) cleavage products (C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A was enhanced, as shown by the fluorescent antibody technique. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A. GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of GIV-A. The picryl chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was depressed after the implantation of tumor and treatment with 5-FU. GIV-A restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of normal mice. GIV-A not only enhanced the degree of spleen cell-mediated sheep red blood cell (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of the spleen and thymus and the number of spleen cells, but also restored the suppressive effect of 5-FU. In the group receiving GIV-A, the percentages of splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly increased as compared with the tumor-bearing mice treated with saline. Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the Lyt2+/Thy1.2+ ratio was decreased. These results suggest that the antitumor effect of GIV-A may be correlated with the changing pattern of the Thy1.2-, L3T4- and asialo GM1-positive cells, C3 activation, macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that GIV-A may have clinical value in the prevention of cancer metastasis.
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PMID:Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A) prepared from brown seaweed Sargassum thunbergii. 857 81

T lymphocytes from tumor-draining lymph nodes (TDLN), after activation and expansion in vitro, can mediate regression of metastatic tumor in animal models. We have shown that TDLNs are subject to tumor-induced suppression that is tumor specific, T-cell mediated, and dependent on the duration of tumor growth, but the mechanism of this suppression remains largely unknown. Recently, in other model systems, tumor-bearer T cells have been shown to have decreased expression of T-cell receptor-zeta (TCR zeta), a key component in antigen-driven activation pathways. We sought to investigate whether the suppression of TDLN reactivity that accompanies prolonged tumor growth was associated with decreased expression of TCR zeta in fresh and in vitro activated lymph node lymphocytes. Mice bearing subcutaneous tumor deposits of MCA 205 had TDLN cells harvested after various durations of tumor growth, then activated in vitro with anti-CD3 for 2 days (activation phase), followed by expansion with interleukin-2 (IL-2) (10 U/ml) for 3 days (expansion phase). Two-color flow cytometry was used to determine TCR zeta expression in fresh and activated TDLN cells. Antitumor reactivity was assessed by the ability of activated TDLN to mediate regression of lung metastases. There was a time-dependent suppression of the antitumor reactivity of the activated TDLN; activated TDLN from mice bearing tumors 14 days or less were able to mediate the regression of established lung metastases, whereas activated TDLN from animals bearing tumors 21 days or more were ineffective. In addition, TCR zeta expression on T lymphocytes from fresh and activated TDLN was also depressed in a time-dependent manner. Because tumor-induced immunosuppression in our model is known to be T cell mediated, we examined whether the Th2 cytokine IL-4, when added in vitro during activation or expansion, could suppress antitumor reactivity and lead to a depression in TCR zeta expression of TDLN cells in a fashion similar to prolonged tumor growth. The addition of 10 U/ml of IL-4 in vitro had a marked suppressive effect on the antitumor activity of day 14 TDLN; the effect was most pronounced when IL-4 was present during the expansion phase. Fluorescence-activated cell sorter analysis of day 14 TDLN exposed to IL-4 in vitro demonstrated a marked decrease in TCR zeta expression, comparable to that seen in late tumor-bearer TDLN. Thus, TDLN from late tumor-bearers show a consistent decrease in TCR zeta expression that is associated with suppressed antitumor reactivity, and exposure to IL-4 in vitro results in qualitatively and quantitatively similar changes. Our observations suggest a mechanism whereby Th2 cells could mediate immunosuppression by downregulating a critical component of the T-cell-receptor signal transduction machinery.
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PMID:Tumor-induced suppression of antitumor reactivity and depression of TCRzeta expression in tumor-draining lymph node lymphocytes: possible relationship to the Th2 pathway. 908 83

A 2-year-old intact female Golden Retriever presented due to rapidly progressing depression, ascites, dysuria, abdominal pain, and severe vaginal bleeding. At necropsy, the retroperitoneal space was expanded by multiple coalescing neoplastic nodules and the uterine wall was thickened with poorly defined neoplastic infiltrates. The urinary bladder was markedly thickened due to botryoid nodules exhibiting exophytic growth into the lumen. Metastases to lung, liver, kidney, and abdominal and thoracic lymph nodes were also noted. Microscopically, the genital tract and retroperitoneal masses were consistent with the alveolar subtype of rhabdomysarcoma, while the urinary bladder mass had characteristics of the embryonal subtype. Immunohistochemically, the neoplastic cells in all these tissue sites were intensely positive for desmin, sacromeric actin, and vimentin, while they were uniformly negative for cytokeratin and smooth muscle actin. Phosphotungstic acid hematoxylin stain revealed cross-striations in the cytoplasm of scattered neoplastic cells. Based on the gross findings, histopathology, and immunohistochemistry, genitourinary rhabdomyosarcoma with multisystemic metastases was made.
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PMID:Genitourinary rhabdomyosarcoma with systemic metastasis in a young dog. 1760 14


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