Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with nodular lymphoma initially respond to a number of therapies but relapse is common and inexorable with time, and despite further therapy, most patients will ultimately die of their lymphoma. The recent demonstration of their sensitivity to alpha-interferon is promising. The importance of this human antitumor effect is that it is presumably based on mechanisms different from conventional agents. Phase I trials of various doses and schedules of recombinant alpha-interferon have shown that effective serum levels can be obtained by intramuscular (IM), intravenous (IV), or subcutaneous (SC) routes. Virtually all patients experienced some degree of acute toxicity manifested by fever, chills, myalgia, and headache. Tolerance usually developed to acute adverse effects within the first few weeks of therapy, regardless of dose or schedule. Fatigue and anorexia were the most important adverse reactions, occurring during the first two weeks of treatment and generally persisting for the duration of therapy. Occasional adverse effects relating to the central nervous and cardiovascular systems have been reported. Primary laboratory abnormalities observed during treatment include decreases in hematologic parameters and elevations of liver function tests. The clinical efficacy of alpha-interferon, both natural and recombinant, has been demonstrated in both untreated and heavily pretreated patients with nodular lymphoma. The response rate has approached 50% in recent studies; however, less than half were complete responders. Future directions include combination of interferon with cytotoxic agents or other biological response modifiers and use as adjuvant therapy.
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PMID:Alpha-interferon in the treatment of nodular lymphomas. 354 Dec 18

Natural interferon-alpha preparation "Sumiferon" was recently developed in Japan. This is a human lymphoblastoid interferon (HLBI) preparation. Like other interferon preparations, this preparation showed both direct and indirect antitumor effect and the toxicities were moderate. The phase I-II studies were carried out in 38 major institutions in Japan. In the phase I study in 5 patients with advanced breast cancer, the maximum tolerated dose (MTD) was found to be 12 X 10(6) units/day given for 1 month. In the phase II study, HLBI was given in at 3 approximately 6 X 10(6) units/day. Out of 391 cases, 280 were evaluable. Complete and partial responses (CR and PR) were observed in 40 (14.3%) out of 280 evaluable cases, including 11 (19.6%) out of 56 renal cell cancer, 14 (19.2%) out of 73 multiple myeloma, and 9 (17.3) out of 52 malignant lymphoma among others. Major side effects observed were: fever (69.8%), gastrointestinal disturbances (31.4%), leukopenia (30.7%), thrombocytopenia (27.8%), hepatotoxicities (23.6%) and general fatigue (22.1%). Sumiferon seemed to be one of useful antitumor drugs effective against renal cancer.
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PMID:[Introduction of natural interferon-alpha "Sumiferon"]. 363 77

Forty-nine patients with non-Hodgkin's lymphoma or Hodgkin's disease were entered into a multi-institutional phase II trial to evaluate the antitumor activity of human interferon alpha, prepared from buffy coats. Interferon alpha was administered intramuscularly in doses of 1 X 10(6) u, 3 X 10(6) u or 9 X 10(6) u daily for 30 days. Objective partial responses were seen in 3 of 18 patients with nodular lymphoma, all at the 9 X 10(6) u dose. Interferon alpha was not observed to be of therapeutic benefit in the other subtypes of non-Hodgkin's lymphoma or Hodgkin's disease. The major toxicities consisted of fatigue, fever, myalgias and weight loss. Serum interferon levels obtained 3 to 4 hours after injection varied widely, even among patients treated at the same dose level. Despite the relatively low doses of interferon used and the brief period of administration, this study extends the earlier observations of the antitumor effect of interferon in nodular lymphoma. These results are discussed in relation to the cumulative experience in human lymphoma using alpha interferons induced in human leukocytes and those produced in bacteria by recombinant DNA techniques.
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PMID:Human interferon alpha in malignant lymphoma and Hodgkin's disease. Results of the American Cancer Society trial. 402 69

A case of malignant lymphoma in the skull after head injury associated with whole bone metastasis is reported. The patient was a 66-year-old man who was admitted to Almeida Memorial Hospital because of headache and general fatigue 2 months after head injury. After admission tumors appear in the frontal and occipital region and grew rapidly. Plain craniogram revealed large map-like bone destructions and multiple punched out lesions. Bone scintigram with 99mTc-MDP revealed multiple accumulations of RI in the skull, vertebrae, ribs and pelvis. CT scan revealed destructive, markedly enhancing bone tumor which was compressing the brain as an extradural mass in the left frontal and occipital regions. Pathological examination of the tumor revealed malignant lymphoma of non-Hodgkin type and diffuse pleomorphic type. Though combination chemotherapy with ACNU, FT 207, PSK, CHOP (Cyclophosphamide, Adriamycin, Vincristine and Predonisone) and Acracinomycin A was performed after operation, and brought forth regression of tumor size and improvement of clinical symptoms transiently, he died 6 months after the onset because of recurrence in many bones with pathological fracture and complications such as pneumonia, DIC and acute renal failure. At autopsy the tumors were found to be localized only in the bones, but in none of lymphnode or visceral organs. Malignant lymphoma appearing initially as a skull tumor is rare, and its diagnosis and treatment were discussed.
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PMID:[A case of malignant lymphoma in the skull after head injury associated with multiple bone tumors]. 408 41

Thirty-eight patients with advanced breast cancer, multiple myeloma, and malignant lymphoma were treated with partially purified (about 0.1%) leukocyte interferon. Patients were treated with a remission-induction schedule of 3 million to 9 million antiviral units daily intramuscularly for 4 to 26 weeks. Responding patients were maintained on a schedule of 3 million U three times weekly. Tumor regression was observed in seven of 17 patients with breast cancer. Six of 10 patients with multiple myeloma responded with a decrease of at least 50% in serum myeloma protein levels or Bence Jones protein excretion. Six of the 11 lymphoma patients achieved tumor regression. Complete remissions occurred in two patients. Of the 19 responding patients, five remain on study for 52 to 63 weeks. Toxicity included low-grade fever, fatigue, anorexia, and partial alopecia. Myelosuppression (lowest median leukocyte count, 2500/mm3; granulocytes, 1300/mm3) occurred in most patients. On the basis of this pilot study, we conclude that leukocyte interferon can induce tumor regression in patients with advanced cancer.
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PMID:Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma. 615 12

The topographical distributions and mobilities of the murine histocompatibility antigen H-2Kk and of concanavalin A (Con A) binding sites have been studied on a murine lymphoma cell line. The spatial distribution of H-2Kk antigens, the average distance between H-2Kk antigens and Con A binding sites, and the separation of different determinants on the H-2Kk antigen itself were determined by using fluorescence resonance energy-transfer measurements with a dual-laser flow sorter. From the lack of energy transfer between bound monoclonal anti-H-2Kk antibodies conjugated with fluorescein (donor) and rhodamine (acceptor), we conclude that the H-2Kk antigen exists without appreciable clustering on the cell surface. Substantial energy transfer between appropriately labeled Con A and antibodies bound to the H-2Kk antigen shows that the two populations are interspersed. Donor/acceptor pairs of monoclonal antibodies binding to different determinants on the same H-2Kk antigen exhibited a degree of energy transfer indicative of a mean separation of 8.6 nm between the sites. Time-resolved phosphorescence anisotropy measurements with anti-H-2Kk antibodies labeled with eosin or erythrosin yielded rotational mobility information for the antigen-antibody complexes on the cell membrane. The rotational correlation time of 10-20 mus and the finite residual anisotropy are compatible with an uniaxial mode of rotation of monomeric antigen around its transmembrane portion and, thus, provide additional evidence for an unclustered distribution. Capping by rabbit anti-mouse IgG immobilized the antigen-antibody complex. Fluorescence recovery after photobleaching was used to calculate an apparent lateral diffusion coefficient of 5 +/- 3 X 10(-10) cm2 . s-1 for the H-2Kk antigen labeled with fluoresceinated IgG or its corresponding Fab fragment.
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PMID:Distribution and mobility of murine histocompatibility H-2Kk antigen in the cytoplasmic membrane. 635 Oct 71

Fifty-two patients with advanced cancer received sequentially escalating doses of 3 to 50 million units of recombinant DNA-produced alpha interferon by daily intramuscular injection. There were 23 patients with metastatic breast cancer, 17 patients with nodular poorly differentiated lymphocytic lymphoma, and 12 patients with multiple myeloma. Complete and partial remissions were obtained in 35 percent of patients with nodular poorly differentiated lymphoma, whereas rare activity was found in breast cancer and multiple myeloma. Dose-limiting toxicity occurred in patients receiving 36 million units or more and consisted of fatigue/asthenia, weight loss, and elevation of transaminase levels, requiring frequent interruption, reduction in dose, or cessation of treatment. Hematologic toxicity was rarely a limiting factor, but myelosuppression was severe in some patients with multiple myeloma. All toxicities were reversible on discontinuation of treatment. Antibodies to recombinant leukocyte A interferon were seen infrequently but may adversely affect therapy.
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PMID:Collaborative phase I-II study of recombinant DNA-produced leukocyte interferon (clone A) in metastatic breast cancer, malignant lymphoma, and multiple myeloma. 654 79

A Phase I study was carried out with ricin, a plant toxin acting by inhibiting protein synthesis, on 54 cancer patients with advanced disease. Ricin was given as i.v. bolus injections every two weeks at dose levels ranging from 4.5 to 23 micrograms/sq m of estimated body surface area. Ricin was well tolerated at doses up to 18 to 20 micrograms/sq m. At these levels and at higher levels, flu-like symptoms with fatigue and muscular pain appeared and, in some patients, nausea and vomiting occurred also. No myelo-suppression was seen. Antibodies to ricin were detected in serum after two to three ricin injections. Ricin was eliminated from blood according to first order kinetics. At each dose level, the plasma concentrations, as well as the side effects, showed only minor differences between patients. The highest dose given, 23 micrograms/sq m, gave plasma concentrations twice those found previously to be therapeutically effective in tumor-bearing mice. Of 38 evaluable patients, one patient with lymphoma had a partial response. Stable disease was observed in four patients with renal cancers, in two with soft tissue sarcomas, and in one patient each with mesothelioma, thyroid, and rectal cancer. A dose of 23 micrograms/sq m is recommended for Phase II trials of ricin.
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PMID:Phase I study of the plant protein ricin. 669 85

This paper over-viewed the clinical studies on various interferons including HLBI (human lymphoblastoid interferon), HuIFN-beta (human fibroblast interferon) and r-IFN-alpha A (recombinant leukocyte A interferon) which have been tried widely in Japan. These interferons have shown some antitumor effects on various malignancies such as malignant lymphoma, multiple myeloma, renal cell carcinoma, leukemias, brain tumors, malignant melanoma, mycosis fungoides and others. Adverse reactions included fever, general fatigue, leukopenia and thrombocytopenia, and abnormal liver function tests were experienced.
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PMID:[Effects of interferon on various malignancies]. 669 57

Recent studies have demonstrated that patients receiving cancer chemotherapy are more likely to have a successful treatment outcome if they receive optimal doses of drug continually. The current study was designed as a first step toward discovering factors that are associated with emotional distress during treatment and subsequent decisions by patients to delay, reduce, or terminate treatment. Interviews were conducted with 61 patients receiving chemotherapy for malignant lymphoma. Patients reported on side effects of treatment and their efforts to control them, their knowledge and beliefs about their illness, their strategies for monitoring the effectiveness of treatment, and the extent to which they had been prepared for the experiences of chemotherapy. Ratings of emotional distress were obtained on an 11-point self-report scale, and information about treatment schedules was obtained from medical records. The number of side effects experienced, but not the duration or severity, was positively correlated with distress. Vague, diffuse side effects such as tiredness and pain were more likely to be associated with distress than were acute, specific side effects such as nausea and vomiting. Patients who reported either unsuccessful attempts to cope with side effects or no attempts at all had greater distress than those who were coping successfully. Patients who developed conditioned nausea during treatment reported higher distress than those who did not.
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PMID:Factors contributing to emotional distress during cancer chemotherapy. 709 22


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