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

The lipophilic antitumor alkaloid acronycine (ACRO) was solubilized in the cosolvent system used for etoposide. ACRO in this etoposide diluent (VPD) was found to be cytotoxic (less than or equal to 50% colony formation in soft agar) in fresh human tumors from patients with renal cell cancer, ovarian cancer, uterine cancer, and metastatic tumors of unknown primary. In P-glycoprotein-positive, multidrug-resistant (MDR) cell lines, ACRO in VPD was active in MDR Chinese hamster ovary cells but not against MDR L1210 murine leukemia cells, 8226 human myeloma cells, or human CCRF-CEM lymphoblasts. In mice, ACRO in VPD was active in two solid tumor models and an i.p. MOPC-315 plasmacytoma model. ACRO i.p. in 10% VPD (v/v%) produced significant tumor growth delays in (a) nude mice bearing human MCF-7 breast cancer xenografts and (b) C57BL mice bearing colon 38 tumor. In MOPC-315-bearing mice, a single i.p. ACRO dose of 25 mg/kg was as effective as melphalan (15 mg/kg) at prolonging life span. Finally, ACRO pharmacokinetics was evaluated in mice given single 25-mg/kg doses i.p. or p.o. The oral bioavailability of an ACRO solution in VPD was only 50% but both i.p. and p.o. regimens achieved plasma levels greater than 1.0 micrograms/ml. The plasma half-life was just under 2 h. These results show that parenteral ACRO in VPD comprises a cytotoxic antitumor agent with improved bioavailability over p.o. administration. ACRO is active in vitro against several human solid tumors but is cross-resistant in 3 of 4 MDR tumor cell lines. The prior clinical activity of p.o. ACRO in myeloma and the new results in MOPC-315 plasmacytomas in mice suggest that ACRO in VPD could have activity against human multiple myeloma.
 ...
PMID:Antitumor activity and murine pharmacokinetics of parenteral acronycine. 291 Apr 53

Fifty-seven patients with advanced malignant tumours were treated with ifosfamide (Holoxan) and mesna (Uromitexan) in our department from November 1979 to December 1984. This series comprised eight cases of soft tissue sarcoma, nine cases of ovarian carcinoma, five cases of non-seminomatous testicular tumour, 11 cases of bronchogenic carcinoma, three cases of renal carcinoma, seven cases of non-Hodgkin's lymphoma, two cases of skeletal fibrosarcoma, two cases of breast carcinoma, one case each of Ewing's tumour, prostatic carcinoma, seminoma, plasma cell tumour, multiple myeloma, malignant teratoma, nasopharyngeal carcinoma, Wilms's tumour, neuroblastoma and mycosis fungoides. Out of these 57 cases, 53 were evaluable. There were five complete remissions and 20 partial remissions, corresponding to a total response rate of 47%. The overall median survival time (MST) of the 53 evaluable patients was 7.5 months. The responders had a longer survival time (MST 10 months) than the non-responders (MST 4.75 months) (p greater than 0.05). Analysis of the results according to sex, age, dosage of ifosfamide and degree of histological differentiation of the tumour cells failed to show any influence of these factors on the therapeutic results. The response rate to ifosfamide found in this study might be related to the histological origin of the tumours and to whether the primary tumours had been resected. The non-seminomatous testicular tumours, non-Hodgkin's lymphomas and ovarian carcinomas showed a high response rate. The response rate was higher in the group in which the primary tumour had been resected (61%) than in the non-resected group (12%) (except the non-Hodgkin's lymphoma). The side-effects of this regimen were moderate. Dyspepsia, nausea, vomiting, myelodepression, dizziness, and alopecia were common. Cystitis could be prevented nearly completely by concomitant administration of mesna, when given correctly, for preventing side-effects of ifosfamide on the urinary system (haemorrhagic cystitis, etc.).
 ...
PMID:Treatment of advanced malignancies with ifosfamide under protection with mesna. 313 Mar 16

A phase I and a phase II study of recombinant gamma-interferon (S 6810) were conducted on a cooperative basis involving 11 and 57 institutions, respectively. In the phase I study, a total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills was observed in approximately 80%. Other toxicities were fatigue (50%), gastrointestinal symptoms (30-40%), changes in hepatic enzymes, and hematological toxicities (20-30%). Dose-limiting factors were judged to be hypotension, leucopenia and CNS toxicity. Since the optimal dose for the phase II study was considered to be 5 X 10(6) U/m2 by daily chronic schedule, a further study was conducted using this dose. Response rates were as follows: 14.3% (renal cell cancer), 11.8% (multiple myeloma) 40.0% (chronic lymphocytic leukemia), 16.7% (non-Hodgkin lymphoma), and 67% (mycosis fungoides). Complete response was obtained in one case each of renal cell cancer, malignant lymphoma and mycosis fungoides. Moreover, intermittent high-dose gamma-interferon against renal cell cancer induced a response rate of 21.4%, significantly higher than the 8.6% obtained by continuous administration. Local injection against cutaneous malignancies resulted in a 55.3% response rate. Anti-viral effect against herpes zoster infection was also preliminarily evaluated. Among 4 cases, 3 responded subjectively well to local injection of gamma-interferon, which is a hopeful result, although a randomized trial is still needed.
 ...
PMID:[Gamma interferon therapy of cancer patients]. 313 83

Interferon-alpha 2b (IFN-alpha) was administered by continuous subcutaneous (s.c.) infusion to 23 patients with hematologic malignancies or metastatic solid tumors: 5 patients with multiple myeloma, 3 with malignant melanoma, 2 with chronic myelogenous leukemia (CML), 10 patients with renal cell cancer, and 3 patients with other solid tumors. Drug was delivered by continuous s.c. infusion for 28 days (1 cycle) at daily dose levels of 0.7, 1.4, 2.5, 3.6, or 5.0 X 10(6) IU/m2 to 3, 3, 3, 8, and 6 patients, respectively. At the highest dose level, a severe flu-like syndrome was seen in 3 patients and severe gastrointestinal toxicity in 2 patients. The maximally tolerated dose (MTD) was 3.6 X 10(6) IU/m2.day and the principal toxicity was a mild to moderate flu-like syndrome. Local skin reactions were occasionally noted at all dose levels if the s.c. needle site was not rotated every 3-4 days. At dose levels of 2.5-3.6 X 10(6) IU/m2.day, IFN-alpha serum levels at steady state ranged from 19 to 61 IU/ml. The time to achieve steady-state conditions ranged from 40 to 72 h and at steady state, 24 h area under the concentration time curve (AUC24 h) ranged from 480 to 1,464 IU/ml.h. Objective responses were seen 3 of 17 evaluable patients: 1/7 in renal cell cancer (14%); 1/2 in CML and in one patient with ependymoma. Remissions lasted 4, 8, and 15 months in renal cell, CML, and ependymoma, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phase I-II trial of interferon-alpha 2b by continuous subcutaneous infusion over 28 days. 323 Mar 30

BALB/c mice were hyperimmunized with ACHN (ATCC CRL 1611, American Type Culture Collection, Rockville, Maryland), a stable in vitro cell line derived from a malignant pleural effusion in a 22-year-old man with renal cell carcinoma. The hyperimmune spleen cells were fused with NS-1 murine myeloma cells using polyethylene glycol. Hybridoma supernatants were screened for the presence of IgG reactive with detergent extracts of ACHN and nonreactive with detergent extracts of normal kidney tissue. A stable, rapidly growing clone named 5F4 was isolated. Supernatant from 5F4 was used as a primary antibody preparation for avidin-biotin complex immunoperoxidase staining of multiple cases of renal cell carcinoma, normal tissues, and other tumors. 5F4 produced IgG which reacted with a cytoplasmic structure in paraffin-embedded sections of all renal cell carcinomas tested. There was occasional, weak, granular, cytoplasmic staining of isolated tubular lining cells in adjacent normal kidney.
 ...
PMID:A renal cell carcinoma neoplastic antigen detectable by immunohistochemistry is defined by a murine monoclonal antibody. 355

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.
 ...
PMID:[Introduction of natural interferon-alpha "Sumiferon"]. 363 77

Serum concentrations of immunoreactive parathyroid hormone (iPTH) measured with a mid-region specific radioimmunoassay and total calcium were correlated in 300 healthy subjects and 158 patients with surgically verified primary hyperparathyroidism (HPT). All the healthy individuals could be separated from the patients by a monoexponential declining curve in which iPTH at concentrations of 0.60 micrograms/l and 0.33 micrograms/l corresponded to calcium concentrations of 2.20 mmol/l and 2.60 mmol/l, respectively. In 22 patients more than one sample was analysed and serum iPTH and calcium were inversely correlated. In contrast, three patients with parathyroid carcinoma showed no reciprocal fluctuations between serum iPTH and calcium. Of 75 patients with hypercalcaemia due to malignant diseases (metastatic mammary carcinoma, bronchial carcinoma, renal carcinoma, myelomatosis), 62 had a normal iPTH/calcium relationship. Two patients with myelomatosis had a temporary elevation of serum iPTH and calcium due to renal impairment. One patient with bronchial carcinoma probably had ectopic production of iPTH. The remaining 10 patients (six mammary carcinomas and four bronchial carcinomas) were found in the pathological iPTH/calcium range. In conclusion, we have demonstrated that an inverse relationship exists between serum iPTH and calcium in patients with non-malignant, primary HPT. Evaluation of iPTH and calcium in the same serum sample gave a correct diagnosis in more than 90% of patients with primary HPT.
 ...
PMID:Improved diagnosis of primary hyperparathyroidism by defining the inverse relationship between serum immunoreactive parathyroid hormone and calcium. 374 90

A hypercalcemia frequency of 1.5% was found in patients with malignant disease attending a large oncological center. Eighty per cent of hypercalcemias were of obvious malignant etiology. Hypercalcemia was most frequent in multiple myeloma, renal carcinoma, squamocellular carcinomas of different sites and breast cancer. Most patients had advanced metastasized disease. In 80% of those with solid tumors malignant hypercalcemia was associated with bone metastases. Serum calcium could almost invariably be reduced by treatment, and active treatment was associated with a more favorable prognosis. One year actuarial survival of patients with malignant hypercalcemia was 31%.
 ...
PMID:Malignant hypercalcemia--a hospital survey. 381 29

We present six patients with associated renal adenocarcinoma and systemic amyloidosis. In five of the patients amyloidosis showed clinical and organ distribution characteristics of reactive (secondary) amyloidosis. The amyloid deposits contained amyloid A protein as defined by potassium permanganate sensitivity and by reactivity with anti-amyloid A antiserum. Four of these patients had suffered from additional inflammatory diseases. In the sixth patient the amyloid disease had different clinicopathologic characteristics and was evidently of an immunoglobulin light-chain-derived type related to a concomitant multiple myeloma. Although renal carcinoma seems to be an effective stimulator of amyloid formation, the possible contributory influence of associated chronic inflammation deserves more careful appraisal.
 ...
PMID:Renal adenocarcinoma and systemic amyloidosis. Immunohistochemical and histochemical studies. 388 41

Alpha interferons are biological response modifiers that regulate immune function, slow cell proliferation, and inhibit virus replication. Large supplies of purified preparations are now available for clinical trials. Common toxicity includes an influenza-like syndrome to which tolerance occurs after several doses, and chronic fatigue and anorexia that may be dose-limiting. Myelosuppression is mild. Alpha interferons have established clinical activity against several human cancers, including melanoma, Kaposi's sarcoma, multiple myeloma, non-Hodgkin's lymphoma, hairy cell leukemia, and renal cell carcinoma. These data and alpha interferon nomenclature are summarized in table form. Intranasal alpha interferon is effective in prophylaxis of common viral upper respiratory tract infections, although toxicity in long-term use is prohibitive. Short-term administration to high risk populations may be most useful. Optimal doses and schedules need to be determined for all indications.
 ...
PMID:The new alpha interferons. 391 Mar 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>