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

Patients with stage II melanoma were vaccinated with vaccinia virus-induced melanoma cell lysates (VMCL). The vaccine contained viable vaccinia virus, membranous fragments and no intact nuclei. A number of antigens defined by monoclonal antibodies were detected in the vaccine including the ganglioside GD3 and DR antigens. Administration of the vaccine was associated with depression of natural killer cell activity against melanoma and K562 target cells in the first 3-6 months of treatment. Leucocyte dependent antibody (LDA) activity against melanoma cells was induced or increased in titre in approximately half of the patients studied. Continued vaccination was associated in a number of patients with a decrease in LDA titres. Studies on a small sample of patients revealed that this was associated with the development of serum factors which inhibited LDA activity. LDA activity appeared directed to non-MHC antigens on melanoma cells which were of at least two specificities. One specificity which was shared with antigens on a number of non-melanoma carcinoma cells was removed by absorption on fetal brain and may be similar to oncofetal antigens described by other workers. Reactivity against melanocytes was induced in some patients and may underline the development of vitiligo in several patients. These results suggest that vaccines prepared from VMCL may be a favourable method for increasing immune responses against melanoma.
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PMID:Phase II study of vaccinia melanoma cell lysates (VMCL) as adjuvant to surgical treatment of stage II melanoma. II. Effects on cell mediated cytotoxicity and leucocyte dependent antibody activity: immunological effects of VMCL in melanoma patients. 346 Jul 2

Interleukin-2 (IL2) is essential for the expansion of antigen-triggered lymphocytes and cytotoxic T-cells, processes necessary for tumor control that are frequently depressed in malignancy. The authors measured certain aspects of IL2 function in cancer patients and controls and correlated the findings with the general immune response as indicated by the proliferative response to phytohemagglutinin (PHA) in peripheral blood lymphocytes (PBL). The major questions focused on the capacity of PBL to produce IL2, the correlation of this with the proliferative response to PHA, and whether exogenous IL2 could restore T-cell responses and natural killer cell activity in immunodepressed cancer patients. IL2 production was measured by the 3H-thymidine-labeled CT6 assay on the supernatants of the PBL of cancer patients and normal controls after 24 hours of stimulation with PHA. There were 115 cancer patients (70 head and neck, 13 melanoma, 12 breast, 10 colorectal, and 6 other) and 52 controls. IL2 production was essentially normal in the head and neck cancer patients as a group, although their PHA response was depressed. The mean IL2 generated per 3 X 10(6) PBL over 24 hours were 129 mu/ml in the head and neck patients and 132 mu/ml in the breast patients, similar to the 129 mu/ml generated in the controls. There was modest but not significant depression in the melanoma (78 mu/ml) and colorectal cancer patients (81 mu/ml). Although subsets of patients showed depressed IL2 production, there was no significant correlation of IL2 production with the PHA response. Depressed IL2 production showed only limited correlation with depressed lymphocyte responses (r = -0.25), which suggested a dissociation of these functions. Of interest was the finding that indomethacin did augment IL2 production in both cancer patients and controls, suggesting that prostaglandin-mediated regulation is involved. Addition of exogenous IL2 of recombinant origin (Biogen) produced significant augmentation in more than three fourths of the cancer patients and controls. Adding indomethacin further increased this response. Addition of IL2 also significantly increased natural killer activity in both groups. It was concluded that PBL in cancer patients generally have a normal capacity to generate IL2, and this capacity is not related to the proliferative response, which is frequently depressed in these patients. Exogenous IL2 can significantly augment lymphoproliferative and natural killer responses in cancer patients, suggesting that there is merit in exploring the potential therapeutic role of IL2 in these patients.
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PMID:Production of and response to interleukin-2 in peripheral blood lymphocytes of cancer patients. 348 60

Twenty patients with disseminated melanoma were treated with interferon alfa-2a, given by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 X 10(6) U/m2. Of 18 patients considered evaluable, two had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa-2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa-2a on days 3, 10, and 31) consisted of neutropenia, thrombocytopenia, and a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatment, returning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen-stimulated interleukin-2 (IL2) production, and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune system, such as depression of IL2 and immunoglobulin production in vitro, and the differences noted in clinical responses during the present study compared with those observed with interferon alfa-2b given by intravenous (IV) injection in 5-day cycles. These results suggest that interferon alfa-2a has antitumor activity in certain melanoma patients, in particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa-2a and help to optimize treatment regimens.
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PMID:Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma. 348 11

This article examines contraception in adolescents with hematologic, oncologic, dermatologic, and psychiatric disorders, connective tissue diseases, and renal disease and transplants. Teens with iron-deficiency anemia or heavy menstrual flow who need contraception could benefit from oral contraceptives. The IUD is contraindicated for these teens. The IUD is also contraindicated in females with hemorrhagic disease, and hormonal contraceptives are a more appropriate choice for these females. Teens with sickle cell hemoglobinpathies should not use the IUD. Safe use of oral contraceptives (OCs) is questionnable for these teens. The best choice would be barrier methods. Concerns regarding contraception in teens with tumors are mainly 2-fold: effects of pregnancy or contraception on the tumor, and effects of the tumor or tumor therapy on pregnancy and fertility. Therapy including drugs and radiation can have profound effects on the fetus and future fertility. There seems to be no indication that pregnancy has adverse effects on nonhormonal-dependent tumors common in young adults. Malignant melanoma has a strong positive relationship with the use of OCs. OCs have been reported to be helpful in some chronic skin disorders. OCs may not be appropriate for teens who are taking antidepressants or who have a history of depression, although there are contradictory reports in the literature on the effect of the pill on depression. It is helpful for contraceptive services for mentally ill women to be provided by specially trained individuals who are able to obtain informed consent, while taking into account the specific needs of the psychiatrically impaired individual. There are special concerns in prescribing contraception to the mentally retarded teen. Combinations OCs should probably be avoided in adolescents with systemic lupus erythematosus. Because teens with severe chronic renal failure or those on hemodialysis are usually infertile, contraception is less of an issue than for other teens. A barrier method woudl be the msot appropriate method for such teens if they need contraception.
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PMID:Contraceptive use in the chronically ill adolescent female. Part II. 353 Nov 20

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

Thirty-three patients with malignant melanoma and regional lymph node metastases who underwent lymph node dissection were additionally given polychemotherapy with carmustine, hydroxycarbamide and dacarbazine immediately before surgery and up to five times postoperatively. Twenty-nine patients were only treated surgically. These two groups were comparable as regards prognostic criteria, in particular tumour size, ulceration and the number of lymph nodes affected, although the individual follow-up periods varied considerably. The group given chemotherapy showed better results than the control group undergoing surgery alone. The log rank test yielded a significant difference (P less than 0.05) with respect to the probability of relapse-free survival but not as regards probability of survival time. Patients with ulcerated primary melanomas and with a large number of affected lymph nodes had a less favourable prognosis. The major side effects of chemotherapy were transient nausea and bone marrow depression.
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PMID:[Adjuvant chemotherapy in addition to radical surgical treatment of regional lymph node metastases in malignant melanoma]. 369 50

BMY-25282, 7-N-(dimethylamino methylene)mitomycin C, is one of a novel series of amidino mitomycin derivatives. Some of these were discovered as intermediates in a synthetic program being conducted to find improved procedures for modifying the structure of mitomycin C (MMC). Markedly superior in vivo antitumor effects have been observed with BMY-25282 compared to MMC in initial tests against i.p.-implanted P388 leukemia and B16 melanoma. When administered i.v. to mice bearing s.c. B16 melanoma, BMY-25282 was also superior to MMC. The derivative was fully active against a line of L1210 leukemia which was partially resistant to MMC treatment but had little or no activity against a line of L1210 fully resistant to MMC. It is also 2 to 4 times more potent than MMC based on a comparison of doses required to achieve optimum antitumor effects. The superior antitumor efficacy of BMY-25282 over MMC against both i.p. and s.c. B16 melanoma was maintained when the drug was given in pluronic acid formulation. Against P-388 leukemia, however, the efficacy of the drugs was equivalent when BMY-25282 was administered in the pluronic vehicle. In an in vitro clonogenic assay involving freshly explanted human tumors, BMY-25282 was consistently more potent in cytotoxic effects than MMC. With human colorectal carcinoma samples, BMY-25282 was 13.8 times more potent than MMC. The i.v. 50% lethal dose values of BMY-25282 and MMC in C57BL/6 X DBA/2 F1 mice were 2.1 mg/kg and 8.6 mg/kg, respectively. Leukopenic effects of the drugs in mice were comparable at doses up to their respective 50% lethal dose values. Hematology studies in ferrets revealed a similar pattern of depression and recovery of lymphocytes, neutrophils, and platelets for BMY-25282 and MMC; however, with BMY-25282 there was earlier recovery of platelet counts. BMY-25282 is being further developed toward possible clinical trial.
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PMID:Antitumor activity and toxicity in animals of BMY-25282, a new mitomycin derivative. 393 26

This investigation evaluated the prevalence of depression in female patients who had cancer in any of five predesignated sites. Five hundred five women aged 17 to 80 (190 with breast cancer, 143 with gynecologic malignancies, 111 with melanoma, 37 with bowel cancer, and 24 with lymphoma) were randomly screened. Assessment included the Hamilton rating scale for depression, the Zung self-rating depression scale, the Karnofsky performance scale, and a 10-cm visual pain analogue line. The results revealed a mean Hamilton of 10.2 (range, 0 to 41; SD, 7.5), a mean Zung score of 35.3 (range, 11 to 68; SD, 9.6), a Karnofsky median score of 80, and a median pain score of 0. Scores on the Zung scale were highly correlated with those of the Hamilton scale (r = .75). Based on cutoff scores accepted as indicating depression (Hamilton greater than or equal to 20 and Zung greater than or equal to 50), patients were depressed. The depressed subgroup was in significantly more pain, experienced greater physical disability, and was more likely to have had prior episodes of depression as compared to the non-depressed women. The two best predictors of current depression were performance status (Karnofsky) and history of depression. No relationship was found between depression and other demographic variables or disease parameters (diagnosis, time since diagnosis, stage or phase of illness, and current treatment). Our findings indicate that the prevalence of major depression in cancer patients is lower than many previous studies have indicated and falls within the range seen in the general population.
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PMID:Absence of major depressive disorder in female cancer patients. 405 46

The pharmacological effects and metabolism of tiazofurin have been compared in the six transplantable tumors comprising the NCI rodent tumor panel, viz. the P388 leukemia (S); the L1210 leukemia (S); the Lewis lung carcinoma (S); the B16 melanoma (R); the colon 38 carcinoma (R); and the M5076 sarcoma (R), where (S) denotes sensitivity and (R) resistance to tiazofurin. In addition, a variant of the P388 leukemia rendered resistant to the drug in vitro, and maintaining stable resistance in vivo, P388/TR, was also studied. Intraperitoneal administration of tiazofurin (100 mg/kg) resulted in a 3- to 30-fold greater accumulation of thiazole-4-carboxamide adenine dinucleotide (TAD), the proposed active metabolite of the drug in S versus R lines. In general, levels of TAD, percent inhibition of IMP dehydrogenase (mean 40% in S versus 10% in R), depression in the concentration of guanosine nucleotides, (50% in S versus 20% in R) and percent elevation of levels of IMP (500% in S versus 60% in R) correlated well with sensitivity or resistance. However, the B16 melanoma, although resistant to tiazofurin treatment, showed certain biochemical features characteristic of an S line. The sensitive and resistant tumors displayed comparable abilities to phosphorylate tiazofurin, but there was significant depression only in the R lines of the pyrophosphorylase which converts tiazofurin-5'-monophosphate to TAD (mean 78 nmoles/mg protein/hr in S versus 22 nmoles/mg protein/hr in R). The naturally resistant tumors were also found to exhibit a greater ability to degrade synthetic TAD than the sensitive lines (mean 102 nmoles/mg protein/hr in R versus 29 nmoles/mg protein/hr in S lines). The state of sensitivity or resistance could not be attributed to the basal levels of IMP dehydrogenase, to the specific activities of the enzymes of purine salvage, or to the basal concentration of purine and pyrimidine nucleotides. Moreover, treatment with tiazofurin did not influence the enzymes of TAD synthesis or of purine salvage.
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PMID:Studies on the mechanism of action of 2-beta-D-ribofuranosylthiazole-4-carboxamide--V. Factors governing the response of murine tumors to tiazofurin. 614 62


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