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  • 11
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: : Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage. In addition, melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production. On this basis, we have performed a randomized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients (NSCLC) with poor clinical status. The study included 70 consecutive advanced NSCLC patients who were randomized to receive chemotherapy alone with cisplatin (20 mg/m2/day i.v. for 3 days) and etoposide (100 mg/m2/day i.v. for 3 days) or chemotherapy plus melatonin (20 mg/day orally in the evening). Cycles were repeated at 21-day intervals. Clinical response and toxicity were evaluated according to World Health Organization criteria. A complete response (CR) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone. Partial response (PR) occurred in 10/34 and in 6/36 patients treated with or without melatonin, respectively. Thus, the tumor response rate was higher in patients receiving melatonin (11/34 vs. 6/35), without, however, statistically significant differences. The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone (15/34 vs. 7/36, P 〈 0.05). Finally, chemotherapy was well tolerated in patients receiving melatonin, and in particular the frequency of myelosuppression, neuropathy, and cachexia was significantly lower in the melatonin group. This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy, mainly in terms of survival time, and reduce chemotherapeutic toxicity in advanced NSCLC, at least in patients in poor clinical condition.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent studies have shown that the hematopoietic system is under neuroendocrine control. In particular, thrombopoiesis has been proven to be stimulated by melatonin, and the pineal indole has been shown to be effective in the treatment of thrombocytopenia resulting from different causes. At present, however, there are no data concerning the possible thrombopoietic activity of pineal indoles other than melatonin. The present study was carried out to evaluate the effect of a concomitant administration of the pineal indole 5-methoxytryptamine in patients with cancer-related thrombocytopenia who did not respond to melatonin alone. The present study included 30 patients, who were randomized to receive melatonin alone (20 mg/day orally in the evening) or melatonin plus 5-methoxytryptamine (1 mg/day orally in the early afternoon). A normalization of platelet count was achieved in 5/14 (36%) patients treated with melatonin plus 5-methoxytryptamine and in none of the patients treated with melatonin alone (P〈0.05). Moreover, mean platelet number significantly increased only in the patients treated with melatonin plus 5-methoxytryptamine. This preliminary clinical study would suggest that 5-methoxytryptamine, a pineal indole, may also exert thrombopoietic activity. Further studies, however, will be required to establish whether 5-methoxytryptamine may play a direct thrombopoietic activity, or whether it may act by improving melatonin's efficacy.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It is known that the pineal hormone melatonin plays a role in the regulation of several biological functions. In an attempt to investigate interactions between the pineal and the cardiac endocrine activity, in this preliminary study we have evaluated the effect of melatonin on the secretion of the cardiac hormone, atrial natriuretic peptide (ANP). The study included five healthy volunteers, and melatonin was given orally at a dose of 30 mg at 17:00. The results of the study show that the administration of melatonin does not influence ANP plasma concentrations. Further studies will be required to better define the cardiac-pineal interaction.
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Experimental studies have suggested that the pineal hormone melatonin, in addition to its documented antineoplastic action, plays a role in the physiological regulation of blood cell proliferation. Based on these data, we evaluated the clinical effects of melatonin therapy in patients with myelodysplastic syndrome (MDS) secondary to cancer chemotherapy for primary neoplasms. The study was carried out on six patients, and melatonin was given orally at a dose of 20 mg/daily, following a schedule prepared to reproduce the circadian rhythm of the pineal hormone. A transient improvement in platelet and neutrophil count was achieved in two of five patients with thrombocytopenia and in two of four patients with neutropenia before therapy, respectively, while no effect was seen on hemoglobin concentration. Mean survival time was 12.5 months, and a long survival, greater than 30 months, was achieved in two of six patients. These preliminary results seem to suggest that melatonin may have a role in the treatment of MDS induced by previous cancer chemotherapy.
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1435-1463
    Keywords: Opioid system ; melatonin ; pineal gland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent reports point to a link between the pineal gland and the opioid system. In order to investigate this relationship, two separate studies were performed on humans. Beta-endorphin plasma levels were determined after melatonin administration (0.2 mg/kg b.w. i.m. at 2 p.m.). Melatonin serum values were evaluated after administration of FK 33-824, a met-enkephalin analogue (0.3 mg i.v. infusion at 9 a.m.). A significant decrease of beta-endorphin plasma levels was observed 120 minutes after melatonin injection. Melatonin release was stimulated by FK 33-824, with a peak at 30 minutes. The present results provide evidence of the inhibitory effect of melatonin on beta-endorphin secretion and the stimulatory action of the opioid peptides on the pineal gland. However, further studies will be required to clarify the relationship between the opioid system and the pineal gland.
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1433-7339
    Keywords: Interferon-α ; Interferon-β ; Interleukin-2 ; Neoplastic effusions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Preliminary studies have suggested that the intracavitary administration of cytokines may represent a new effective palliative therapy of malignant effusions. To define further the therapeutic role of cytokines in the treatment of neoplastic fluid accumulation, 70 cancer patients with pleural, pericardial or peritoneal cytologically proven neoplastic effusions were randomized to receive intracavitary cycles with interleukin-2 (IL-2; 6x106 IU), interferon (IFNα; 2x107 U) or IFNβ (6x106 U) every week for 2 or 3 weeks. A clinical control of fluid accumulation was obtained in 39/70 (56%) patients. In patients with mesothelioma, the response rate was significantly higher with IL-2 than with IFNα or-β, while there was no difference in patients with tumors other than mesothelioma. Moreover, the duration of the period during which drainage was not required was significantly longer in patients treated with Il-2 than in the other groups. Toxicity was low in all patients. According to preliminary data, this study demonstrates that intracavitary administration of cytokines, including IL-2, IFNα and-β, is a new well-tolerated palliative therapy for malignant effusions, with an efficacy substantially comparable to that described with the most commonly used treatments with tetracyclines or cytostatic agents.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1433-7339
    Keywords: Immunotherapy ; Interleukin-2 ; Melatonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent advances in our knowledge of psychoneuroimmune interactions involved in the control of tumour growth have shown the possibility of manipulating host anticancer defences through a neuroimmunotherapeutic strategy. In particular, our previous studies have demonstrated that the concomitant administration of the pineal neurohormone melatonin may amplify the antitumour efficacy of interleukin-2 (IL-2) in humans. On this basis, a study was planned to investigate the influence of neuroimmunotherapy with low-dose IL-2 plus melatonin on survival time and on performance status in untreatable metastatic cancer patients. The study included 100 patients with metastatic solid tumours, for whom no standard therapy was available. They were randomized to receive IL-2 (3 x 106 IU/day subcutaneously for 4 weeks) plus melatonin (40 mg/day orally) or supportive care alone. Partial tumour regressions were seen in 9/52 (17%) patients treated with the immunotherapy, and in none of the patients treated with supportive care alone. The percentage of survival at 1 year was significantly higher in patients treated with IL-2 and melatonin than in those receiving the supportive care alone (21/52 versus 5/48, P〈0.005). Moreover, the performence status improved in 22/52 patients of the immunotherapy group and in only 8.48 patients treated with supportive care (P〈0.01). This study shows that cancer neuroimmunotherapy with low-dose IL-2 and the pineal hormone melatonin may prolong the survival time and improve the quality of life of patients with metastatic solid tumours who do not respond to conventional therapies.
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 1433-7339
    Keywords: Key words Chemotherapy ; Melatonin ; Myelosuppression ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Experimental data have suggested that the pineal hormone melatonin (MLT) may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, MLT has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy. A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity. The study involved 80 patients with metastatic solid tumors who were in poor clinical condition (lung cancer: 35; breast cancer: 31; gastrointestinal tract tumors: 14). Lung cancer patients were treated with cisplatin and etoposide, breast cancer patients with mitoxantrone, and gastrointestinal tract tumor patients with 5-fluorouracil plus folates. Patients were randomised to receive chemotherapy alone or chemotherapy plus MLT (20 mg/day p.o. in the evening). Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT. Malaise and asthenia were also significantly less frequent in patients receiving MLT. Finally, stomatitis and neuropathy were less frequent in the MLT group, albeit without statistically significant differences. Alopecia and vomiting were not influenced by MLT. This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects, particularly myelosuppression and neuropathy. Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1433-7339
    Keywords: Chemotherapy Melatonin ; Myelosuppression ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experimental data have suggested that the pineal hormone melatonin (MLT) may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, MLT has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy. A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity. The study involved 80 patients with metastatic solid tumors who were in poor clinical condition (lung cancer: 35; breast cancer: 31; gastrointestinal tract tumors: 14). Lung cancer patients were treated with cisplatin and etoposide, breast cancer patients with mitoxantrone, and gastrointestinal tract tumor patients with 5-fluorouracil plus folates. Patients were randomised to receive chemotherapy alone or chemotherapy plus MLT (20 mg/day p.o. in the evening). Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT. Malaise and asthenia were also significantly less frequent in patients receiving MLT. Finally, stomatitis and neuropathy were less frequent in the MLT group, albeit without statistically significant differences. Alopecia and vomiting were not influenced by MLT. This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects, particularly myelosuppression and neuropathy. Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations.
    Type of Medium: Electronic Resource
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