Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes the detection of a paraprotein in blood or urine in 12 of 260 patients with 'idiopathic' proteinuria, most of whom presented with the nephrotic syndrome. None had myeloma at presentation and only two have developed it. Initial clinical and biochemical findings did not suggest paraprotein-associated disease, total serum globulins and individual immunoglobulin levels usually being in the normal range. In seven of the 12 cases the paraprotein was detected only after repeated analysis of serum and urine specimens over months or years. Renal histopathology varied from case to case and is described in detail; amyloid deposition did not occur in patients who excreted kappa chain Bence Jones protein and was extensive in only three. One of these eventually developed myeloma. Patients were aged 27--69 years at onset and were observed without specific therapy for up to 56 months. Glomerular filtration rate tended to decline and proteinuria persisted. All patients have now been treated by a chemotherapeutic regimen consisting of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, melphalan, and prednisolone, in repeated short courses. In some patients, particularly those who had kappa Bence Jones protein, there was striking improvement. Overall survival is good, eight patients being alive 17--90 months after the onset of symptoms. The importance of repeated search for paraprotein in apparently idiopathic renal disease in adults is emphasized.
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PMID:Detection, significance and treatment of paraprotein in patients presenting with 'idiopathic' proteinuria without myeloma. 68 53

Data are presented indicating marked antineoplastic activity for cis-dichlorodiammineplatinum(II) in MOPC 104E myeloma. One-eighteenth of the dose that produced 100% cures can be combined with noncurative, low doses of cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea to produce antineoplastic activity of the same degree as that produced by much higher dose regimens which regularly produce cures. Since, in the past, results of therapeutic trials in plasma cell tumors in humans have paralleled results in this animal model, clinical trials of cis-dichlorodiammineplatinum in multiple myeloma appear warranted.
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PMID:cis-dichlorodiammineplatinum(II) chemotherapy in experimental murine myeloma MOPC 104E. 85 80

The elderly patient with malignancy is often considered a poor risk for treatment. To assess the effect of age on the treatment of one such disease, multiple myeloma (a disease with increased incidence in the elderly), a study was made of 280 patients treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide and prednisone on a Southeastern Cancer Study Group protocol. Initial response rates after six months of treatment were equivalent for the older compared with the younger age groups, with a slightly longer remission duration for those over 70. Likewise, survival was equivalent for the older patients. This was not the result of selection of older patients with less advanced disease, since the proportion with both good and poor risk factors are not significantly different in the various age groups. Moreover, for patients with each of the prognostic factors, older patients responded at least as well as younger patients. There were no significant differences among the age groups in gastrointestinal, skin, hair, or hematologic toxicity, although there was a slightly higher incidence of mild granulocyte and platelet toxicity in patients over 60. These findings are in contrast to the widely held belief that older patients cannot tolerate chemotherapy. On the contrary, they suggest that the elderly patient with myeloma may be expected to respond and survive, without excessive toxicity, at least as well as a younger counterpart with similar prognostic factors.
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PMID:Effects of age on responses to treatment and survival of patients with multiple myeloma. 684 55

MOPC 104E myeloma cells are brought under host regulation after treatment with cyclophosphamide, 1,3-bis(2-chloroethyl)-1-nitrosourea, or cis-dichlorodiammineplatinum(II). The first indication of this phenomenon is the plateau level of immunoglobulin M(lambda) [IgM(lambda)]. The myeloma recurs more frequently in animals with high plateau levels of IgM(lambda) even when remission is maintained for greater than 200 days. The growth rate of the recurring tumor is altered when compared with the original tumor in the same individual. Different drugs and dosages produce stable myeloma of different sizes. Treatment with cyclophosphamide (10 to 200 mg/kg), or 1,3-bis(2-chloroethyl)-1-nitrosourea (25 mg/kg) gives stable myeloma that produces low plateau levels of IgM(lambda). This myeloma does not show late recurrence. Combination of 1,3-bis(2-chloroethyl)-1-nitrosourea, cyclophosphamide, and cis-dichlorodiammineplatinum(II) in low doses or cis-dichlorodiammineplatinum(II) alone gives a stable myeloma clone(s) which produces IgM(lambda) which plateaus at higher levels, and the myeloma clone recurs relatively late in the life of the animal. These results show that treatment does not lead to the elimination of the dominant myeloma clone. Clonal dominance is, however, broken when the proliferative potential is interrupted by drug treatment. The resulting long stable phase supports the view that the proliferation, the expression of the plasma cell maturation sequences, and the secretion of IgM(lambda) are under normal host regulation. Aging presumably causes a loss of regulatory control permitting clonal expansion and recurrence of the myeloma in animals with high plateau levels of the IgM(lambda). The MOPC 104E myeloma model demonstrates for the first time a conversion of the malignant form to the indolent form as seen for humans.
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PMID:Maintenance of MOPC 104E myeloma in plateau phase. 719 63

We performed a multicenter comparative analysis of autologous peripheral blood stem cell transplantation (PBSCT) and allogeneic bone marrow transplantation (alloBMT) in multiple myeloma. Forty-eight consecutive patients received either PBSCT (24 patients) or alloBMT (24 patients) at one of three institutions in the study group. Preparatory regimens consisted of melphalan and total body irradiation (TBI) or melphalan alone in the PBSCT group. The alloBMT group received one of four regimens: cyclophosphamide and TBI; cyclophosphamide, VP-16 and 1,3-bis(2-chloroethyl)-1-nitrosourea (CVB); busulfan and cyclophosphamide (BU/CY) and total marrow irradiation (TMI); or melphalan and TBI. Procedure-related mortality was 12.5% for the PBSCT group and 25% for the alloBMT group. With a median follow-up for survivors in the PBSCT and alloBMT groups of 11 months (range, 4-46) and 15 months (range, 2-84 months), respectively, there was no significant difference in median overall survival (33.5 versus 38.6 months, p = 0.7637) or event-free survival (16.7 versus 31 months, p = 0.8450). There was, however, a plateau in survival at 40% in the alloBMT group. No plateau in survival was seen in the PBSCT group. Clinical relapses occurred as late as 39 months posttransplant. Patients have survived up to 28 months postrelapse.
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PMID:Transplantation in patients with multiple myeloma: a multicenter comparative analysis of peripheral blood stem cell and allogeneic transplant. 934 28

Nitrogen mustards (NMs) are useful chemotherapeutic agents in the treatment of lymphoma, leukemia, multiple myeloma, and ovarian carcinoma. The antitumor activity of NMs has been attributed to their ability to cross-link the twin strands of DNA. The resulting bifunctional lesions, if not repaired, can inhibit DNA replication and transcription, eventually leading to cell cycle arrest, apoptosis, and the inhibition of tumor growth. The predominant bifunctional DNA lesions of NM have been reported to involve the distal guanine bases in the opposite strands of 5'-GNC sequences. In the present work, the formation of guanine-adenine and adenine-adenine adducts of N,N-bis(2-chloroethyl)methylamine (mechlorethamine) in double-stranded DNA is demonstrated. Guanine-adenine cross-links of mechlorethamine were identified as N-(2-[N3-adenyl]ethyl)-N-(2-[N7-guanyl]ethyl)methylamine (N3A-N7G-EMA), N-(2-[N1-adenyl]ethyl)-N-(2-[N7-guanyl]ethyl)methylamine, and N-(2-[N(6)-adenyl]ethyl)-N-(2-[N7-guanyl]ethyl)methylamine. All three adducts were produced interstrand, while N3A-N7G-EMA was the dominant intrastrand G-A cross-link. The prevalent adenine-adenine mechlorethamine lesions have the structure of N,N-bis(2-[N3-adenyl]ethyl)methylamine (bis-N3A-EMA). DNA-derived lesions have the same HPLC retention times, UV spectra, and MS/MS fragmentation patterns as the authentic standards prepared independently. bis-N3A-EMA lesions were produced in a concentration-dependent manner in calf thymus DNA treated with increasing amounts of mechlorethamine. Furthermore, HPLC-ESI-MS/MS analysis was used to demonstrate the formation of analogous N3-N3 adenine lesions in DNA treated with aromatic nitrogen mustards, N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid and L-phenylalanine mustard. The presence of cross-linked adenine-adenine lesions may explain the enhanced cytotoxicity and mutagenicity of NMs in cells deficient in N3-alkyladenine glycosylase.
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PMID:Adenine-containing DNA-DNA cross-links of antitumor nitrogen mustards. 1525 21