Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an effort to improve the treatment of patients with refractory or recurrent lymphoma, we developed a protocol using cis-platinum combined with two other agents of known efficacy in these disorders but with differing side effects: VP-16 and MGBG. Twenty-six eligible patients were treated with this regimen. There were 15 men and 11 women with a median age of 54 years (22-73), and performance status of 1 (0-3). Their diagnoses were Hodgkin's disease 5 and non-Hodgkin's lymphoma [NHL] 21 which included 11 with diffuse histocytic lymphoma [DHL]. The median number of chemotherapy regimens was 2 (1-5); 12 also received radiotherapy. Twenty patients are evaluable for response: 15 NHL and 5 Hodgkin's disease. Three patients, all of whom had DHL entered complete remission (20%) with a median time to treatment failure of 7 1/2 months. Six NHL (40%) and one Hodgkin's disease (20%) patients entered a partial remission. There were three early deaths: one due to progressive disease, one to acute respiratory failure, and one with disease status undocumented. Toxicity included leukopenia, thrombocytopenia, anorexia, nausea, vomiting, stomatitis, alopecia, renal failure, profound peripheral neuropathy, and hypersensitivity vasculitis. Treatment was stopped because of the latter two. These agents are non-crossresistant with doxorubicin-containing regimens. The drugs are possibly synergistic and modestly active with moderate to severe toxicity.
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PMID:Cisplatin, VP-16-213 and MGBG (methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma, a phase II study. 319 89

Patients with advanced lymphoma who relapse from intensive first-line combination chemotherapy generally have a very poor prognosis. The use of investigational drugs which lack cross-resistance to agents commonly used for initial therapy represents an important approach to the management of such patients. Based upon our prior experience, we developed a protocol which employed a combination of three new agents. Mitoguazone (600 mg/m2) was administered on Days 1 and 10; etoposide (100-125 mg/m2) was administered on Days 2, 3, and 4; and gallium nitrate (300 mg/m2/day) was administered as a continuous iv infusion over 24 hours on Days 1-7. Treatment cycles were repeated every 3-4 weeks pending tolerance to toxic reactions. Forty-two patients are evaluable for response (35 with non-Hodgkin's lymphoma and seven with Hodgkin's disease). All patients had received extensive prior treatment (median of two previous chemotherapy regimens). Less than one-half of patients had achieved complete remission (CR) with previous therapy. Twenty-two patients (52%) showed major antitumor responses (five CR, 17 partial). All patients who achieved CR had diffuse large cell lymphoma. Two patients in CR relapsed in the CNS. The median duration of response for patients who achieved partial response was 4 months (range, 1-11+). Major toxic reactions included myelosuppression, optic neuritis, mucositis, and corneal keratitis or conjunctivitis. This combination of experimental agents has major therapeutic activity in patients with advanced, resistant lymphoma. Optimal application of these drugs may be obtained by use as one arm of an intensive program of alternating non-cross-resistant regimens.
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PMID:Salvage chemotherapy of advanced lymphoma with investigational drugs: mitoguazone, gallium nitrate, and etoposide. 379 Dec 68

We treated 45 patients with advanced malignant lymphoma, using a combination of methyl-GAG and teniposide (VM-26). All patients had received extensive prior treatment with combination chemotherapy with or without irradiation. Both methyl-GAG (600 mg/m2) and VM-26 (100 mg/m2) were administered on Days 1 and 8 of the treatment protocol and, in responding patients, every 2 weeks thereafter. Partial responses occurred in six of 12 patients with Hodgkin's disease and in ten of 31 patients with non-Hodgkin's lymphoma. The median duration of response for all patients was 3 1/2 months (range, 1 1/2-11). There were moderate toxic effects, including nausea, myalgia, weakness, and myelosuppression. Relative to our recent experience with methyl-GAG as a single agent, the addition of VM-26 to methyl-GAG did not produce a superior rate or duration of response in similar, heavily pretreated patient populations with malignant lymphoma; however, the combination caused considerably more myelotoxicity. We conclude that the use of VM-26 with methyl-GAG in this dose schedule offers no advantage over single-agent therapy. Methyl-GAG, when administered on a biweekly schedule, is effective and well-tolerated. This agent should be considered for incorporation into chemotherapy protocols for the therapy of previously untreated patients with malignant lymphoma.
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PMID:Combination chemotherapy for patients with relapsed malignant lymphoma using methyl-GAG and teniposide (VM-26). 704 33

Methylglyoxalbisguanylhydrazone or MGBG is an agent with a unique mechanism of action (polyamine biosynthesis inhibition). MGBG was discarded in the 1960s because of severe mucositis and other toxicities. New clinical trials in the late 1970s and early 1980s utilized weekly administration and indicated MGBG had significant activity in patients with chemotherapy-refractory Hodgkin's and non-Hodgkin's lymphoma. In addition, some activity was noted in patients with head and neck, prostate, esophageal, and endometrial cancer. The toxicities on the weekly schedule were minimal and no myelosuppression was noted. Based on MGBG's spectrum of antitumor activity and its activity in severely debilitated patients, we hypothesize that MGBG may have greater antitumor activity in patients who are malnourished (possibly based on polyamine depletion). MGBG is a good candidate for treatment of AIDS-associated NHL because it has proven activity in patients with NHL which is not associated with AIDS, crosses the blood brain barrier, is non-myelosuppressive, and appears to work in patients with inanition (no polyamines available to reverse MGBG's antitumor effects). Clinical trials are ongoing to determine the activity of MGBG in AIDS-associated NHL and other diseases. Based on encouraging initial results, it appears MGBG may become part of our therapeutic armamentarium.
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PMID:MGBG: teaching an old drug new tricks. 791 20

Mitoguazone is a unique chemotherapeutic agent whose activity is believed to result primarily from the competitive inhibition of S-adenosyl-methionine decarboxylase leading to a disruption in polyamine biosynthesis. Initial clinical trials demonstrated that the dose-limiting toxicities (mucositis and myelosuppression) of Mitoguazone were both dose and schedule dependent. Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life. Concurrent with a recent Phase II trial of Mitoguazone in patients with AIDS related non-Hodgkin's lymphoma, the single dose pharmacokinetics of Mitoguazone were characterized. Twelve patients received 600 mg/m2 of intravenous Mitoguazone over 30 minutes on an intermittent every 2 week schedule. Blood, urine, cerebrospinal fluid (CSF), pleural fluid and tissue samples were collected and analyzed by HPLC. Mitoguazone was cleared from the plasma triexponentially with a harmonic mean terminal half-life of 175 hours and a mean residence time of 192 hours. Peak plasma levels occurred immediately post-infusion, ranged from 6.47 to 42.8 micrograms/ml, and remained (for an extended period) well above the reported concentration for inhibition of polyamine biosynthesis. Plasma clearance averaged 4.73 l/hr/m2 with a relatively large apparent volume of distribution at steady-state of 1012 l/m2 indicating tissue sequestration. Renal excretion of unchanged Mitoguazone accounted for an average of 15.8% of the dose within 48 to 72 hours post-administration. Detectable levels of drug were present in random voided samples eight days post-dose. Mitoguazone levels in CSF ranged from 22 to 186 ng/ml post-dose with CSF/plasma ratios ranging from 0.6% to 7%. The pleural fluid/plasma ratio was approximately 1. Tissue levels of Mitoguazone were highest in the liver followed by lymph node, spleen and the brain.
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PMID:Pharmacokinetic profile of Mitoguazone (MGBG) in patients with AIDS related non-Hodgkin's lymphoma. 891 46

Mitoguazone (methylglyoxal bisguanylhydrazone, methyl-GAG or MGBG) is a synthetic polycarbonyl derivative with activity in patients with Hodgkin's and non-Hodgkin's lymphoma, head and neck cancer, prostate cancer, and esophageal cancer. Mitoguazone has also recently been documented to have activity in patients with AIDS-related lymphoma. Among anticancer drugs, mitoguazone has a unique mechanism of action via interference with the polyamine biosynthetic pathway. Polyamines stabilize DNA structure by non-covalent cross-bridging between phosphate groups on opposite strands. In addition, mitoguazone causes uncoupling of oxidative phosphorylation. In this study, the ability of mitoguazone to induce apoptosis by inhibiting the polyamine pathway was assessed in three Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and one prostate carcinoma cell line (MPC 3). Additional evaluations were performed in two human breast cancer cell lines (MCF7 with wild-type p53 and VM4K with mutated p53) to determine whether the p53 tumor suppressor gene was required for efficient apoptosis induction. The present study demonstrated that mitoguazone induces apoptosis in all the different human cancer cell lines tested in a concentration- and time-dependent way, and triggers a p53-independent programmed cell death in the human breast cancer MCF7 cell line.
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PMID:Mitoguazone induces apoptosis via a p53-independent mechanism. 977 8