Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.
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PMID:Interferon therapy in multiple myeloma. 10 25

Malignant carcinoid tumors with the carcinoid syndrome has over the years presented a therapeutic challenge. Surgery is the treatment of choice in local disease but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little benefit, whereas a new somatostatin analogue octreotide gives a good control of clinical symptoms but not of tumor progression. Interferon treatment was introduced in 1982 by our group and we are now presenting results of medical treatment in 130 patients with histologically verified malignant carcinoid tumors and liver metastases. One hundred and eleven patients were treated with alpha-interferon, whereas 19 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with alpha-interferon demonstrated a significant biochemical response and 15% also more than 50% reduction of tumor size. In another 43 (39%) patients stabilization of the carcinoid disease was noted whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective response with improvement of diarrheas, flush and/or bronchoconstriction was noticed in 76 patients (68%). Among the 19 patients treated with conventional chemotherapy only 2 showed biochemical response and it lasted only for 3-5 months. The patients treated with chemotherapy had a median survival of only 8 months compared with 80+ months in the group treated with alpha-interferon. The adverse reactions of alpha-interferon are manageable and consist mainly of fatigue, weight reduction and reduction of blood cell counts. Neutralizing interferon antibodies might occur in patients treated with recombinant alpha-interferons (5-15%).
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PMID:The role of interferons in the management of carcinoid tumors. 185 9

Patients with refractory ovarian cancer were treated intra-peritoneally with interferon-gamma. The maximum tolerated dose was achieved at 2 mg/m2. The substance was administered 3 times per week every second week. Interferon-gamma treatment activated locally the macrophages and induced a rise in neopterin urine, serum, and ascites levels. The tumor marker CA-125 showed marked fluctuations of more than 100% during interferon treatment and this was not correlated with neopterin. A flu-like syndrome and especially fatigue were the dose limiting side effects. Two of 3 evaluable patients died on tumor progression whereas one is now 18 months clinically free of disease.
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PMID:[The intraperitoneal installation of gamma interferon for the treatment of refractory ovarian carcinoma]. 251 Oct 58

Fifteen patients with advanced metastatic adenocarcinomas were treated in a phase-I study with continuous intravenous 24 h infusion of recombinant tumor necrosis factor alpha (TNF-alpha) in order to determine the maximum tolerated dose (MTD) and associated side-effects. Patients received 40-400 micrograms/m2 TNF-alpha once (arm A) or twice (arm B) weekly for a scheduled treatment period of 2 months. The observed systemic side-effects resembled those reported for interferons and included fever, chills, fatigue, headaches, myalgias, thrombocytopenia, prostration, and malaise. Dose-limiting toxicities, resulting in a median MTD of 200 micrograms/m2 for 24 h, were fever, chills, fatigue, myalgias, and thrombocytopenia. Out of 15 patients, 11 showed tumor progression, and 3 sustained in no change for over 2 months of treatment. A minor response was seen in 1 patient with a colorectal carcinoma and liver metastases. To reduce side-effects, patients were treated either with paracetamol or indomethacin. Higher MTDs were observed in patients treated with indomethacin. No detectable plasma TNF-alpha levels or TNF antibodies were measured under therapy (plasma TNF-alpha less than 20 pg/ml). We conclude that TNF-alpha appears to have some antineoplastic activity in patients with adenocarcinomas since 4 patients remained in no change or showed a minor response.
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PMID:Phase-I trial of intravenous continuous infusion of tumor necrosis factor in advanced metastatic carcinomas. 265 35

Progressive weight loss and anorexia are frequent phenomena in cancer patients. Although cachexia is an expected occurrence in the terminal stages of nearly all malignancies, it may be a presenting sign when the tumor burden is quite small. Lipid depletion occurs out of proportion to the protein loss and accounts for most of the weight loss in cancer. Lipids, more specifically fatty acids, are the major source of fuel in mammals and may also be used in the synthesis of new cell products. Lipolysis and lipogenesis are under the influence of several important enzymes and peptide hormones that may be modulated by a variety of exogenous factors. There is evidence that cancer patients have lost the normal homeostatic responses to decreased energy intake or starvation that allow a decrease in oxygen consumption and protein sparing. An increase in Cori cycle activity or futile recycling of metabolic products occurs with a net energy expenditure rather than energy production. Clinical studies have shown that the body lipid depletion accompanying tumor progression is not solely secondary to decreased food intake and may be reproduced by the transplantation of certain noninvasive tumors to normal hosts. Elevated basal lipolysis has occasionally been seen early in tumor growth. Such findings suggest the presence of a tumor-associated factor responsible for this increase in lipid mobilization. Some of the potential mechanisms for the altered lipid metabolism seen in cancer have been discussed. Metabolic substrates may be remodeled and directed away from fuel-efficient into energy-requiring pathways. An increased energy expenditure may occur as a result of the energy costs of tumor synthesis, an uncoupling of oxidative phosphorylation, or energy-requiring futile cycling. An overall depletion of lipid may be the final outcome of the inhibition of lipid deposition. TNF/cachectin has recently been found to suppress the activity and synthesis of several key lipogenic enzymes, including lipoprotein lipase. Abnormalities in insulin secretion or sensitivity may be involved in the decrease of fat storage in malignancy. Insulin also exerts a significant antilipolytic effect by its antagonism of hormone-sensitive lipase. Mediators of lipolysis and abnormal lipid metabolism may occur in a number of clinical conditions and include ectopic hormone production, growth factors, and tumor-associated lipolytic factors (lipid mobilizing factor, toxohormone).
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PMID:Fat metabolism and cancer. 353 75

A total of 21 patients with advanced metastatic malignant melanoma were treated in this efficacy study of recombinant leukocyte A interferon (interferon alpha-2a). Patients received 18 X 10(6) units interferon alpha-2a by i.m. injection daily for the first 10 weeks and then three times weekly for a further 4 months. The symptoms of toxicity observed in this study resembled those previously reported for alpha interferons and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, dose-dependent reversible leukopenia, and hepatic transaminase elevations. Of the 21 patients, 12 had evidence of tumor progression, 6 had stable disease for at least 2 months, and complete remission was seen in 3 patients with stage III melanoma. We conclude that interferon alpha-2a appears to have some antiproliferative effect in metastatic malignant melanoma. While its use in stage IV patients with big tumor masses is doubtful, there seems to be therapeutic benefit in earlier stages.
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PMID:Phase II trial of recombinant leukocyte A interferon in advanced malignant melanoma. 358 16

Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule.
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PMID:Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial. 634 90

Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients (n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 +/- 28 days to 510 +/- 28 days (P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.
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PMID:Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. 792 4

To evaluate the clinical efficacy of interferon-alpha in hepatocellular carcinoma, 71 adult Chinese patients with histologically proven inoperable hepatocellular carcinoma were randomized to receive recombinant interferon-alpha 2a (50 x 10(6) IU/m2) intramuscularly three times a week (n = 35) or no antitumor therapy (n = 36). The survival of interferon-alpha-treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.0471); median lengths of survival were 14.5 and 7.5 wk, respectively. Objective tumor regression greater than 50% was observed in 31.4% (11 of 35) of patients receiving interferon-alpha. Interferon-alpha induced tumor regression greater than 50% in 11 (31.4%) patients. Compared with the group receiving no antitumor therapy, the interferon-alpha therapy group had more tumor regression (p < 0.0001) and less tumor progression (p = 0.001). This high-dose interferon-alpha therapy was relatively well tolerated; only 34.3% of patients required reduction of dosage by one third or one half because of persistent fatigue. Two patients with diabetes mellitus (one also had tabes dorsalis) exhibited mental deterioration that might have been partially attributable to interferon-alpha therapy. We conclude that interferon-alpha is useful in a proportion of Chinese patients with inoperable hepatocellular carcinoma, both in prolonging survival and in inducing tumor regression.
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PMID:Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. 838 88

The purpose of this study was to describe disruptions in quality of life (QOL) in women suffering from lung cancer, the leading cause of cancer-related death in the United States. QOL was measured with the CARES-SF. Symptom distress was measured with the modified Symptom Distress Scale, and functional status was measured with the Karnofsky Performance Status Scale. Sixty-nine women with lung cancer participated in a one-time data collection. The typical subject was under 65 years of age, married, has had primary or recurrent non-small cell lung cancer for over 12 months, had limited disease, and was not currently receiving treatment. Subjects had greater disruptions in global QOL and its dimensions compared to a normative heterogeneous female cancer sample. The most prevalent serious disruptions were fatigue, difficulty with household chores, worry about ability to care for self, and worry about cancer progression. The global CARES-SF score was moderately correlated to functional status (r = 0.69, p = < 0.001), and to symptom distress (r = 0.72, p = < 0.001). Symptom distress was associated strongly with the physical subscale of QOL (r = 0.80, p = 0.001) and significantly but less strongly with all other dimensions of QOL. Significantly greater differences in disruptions of quality of life occurred in women younger than 65 years (p = 0.04), women with recurrent disease (p = 0.003), and women with low income (p = 0.008). In stepwise regression, symptom distress predicted 53% of the variance followed by functional status (59%) and recurrence (63%) when QOL was the outcome variable.
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PMID:Women with lung cancer: impact on quality of life. 838 54


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