Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flow cytometric analysis was used to study the effect of a calcium influx blocker, nicardipine hydrochloride, on the cytotoxicity of anti-cancer drugs in tumor cells. The parameters used for this study were DNA- and protein-cell distribution histograms. Cells and drugs used for this study were C6 cells from CD Fisher rat glioma and VCR, ADM and ACNU, respectively. The growth inhibitory effect estimated by concentration at ID50 on C6 cells was indicated as follows; VCR showed an 89-fold enhancement, while ACNU showed little enhancement following addition of nicardipine hydrochloride. DNA and protein histograms obtained by flow cytometry revealed almost the same effects as cells which were studied using high concentration of VCR without nicardipine hydrochloride. For the other drugs, ADM showed a small enhancement on histograms, while with ACNU, little enhancement was noted as well as the inhibitory effect of each drug described above. The results indicate that nicardipine hydrochloride greatly affects the cell cytotoxicity of VCR but not so much with ADM and ACNU. From these results, it appears that this drug enhances the action of anti-cancer drugs not only by merely blocking the efflux of drugs from cells but also by other mechanisms which remain to be clarified.
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PMID:[Flow cytometric study of enhanced effect of anti-cancer drugs induced by nicardipine hydrochloride]. 659 5

A case of primary malignant melanoma of the vulva associated with pregnancy in a 31-year-old patient is reported. The primary tumor was first found at week 14 of pregnancy and biopsied on delivery at week 41 of pregnancy. Microscopically, the depth of invasion was Level V. Radical vulvectomy and bilateral inguino-femoral lymphadenectomy were performed and the right inguinal lymph node was positive for metastatic tumor. Chemoimmunotherapy with DTIC, ACNU, VCR and OK432 was undertaken as treatment for this malignant melanoma. Moreover, a comparison of scanning and transmission electron microscopic studies of the original tumor was carried out. This patient is now living 23 months after diagnosis without clinical evidence of recurrence.
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PMID:Primary malignant melanoma of the vulva associated with pregnancy: clinical, light and electron microscopic observations. 666 48

The determinants of intrinsic sensitivity to Vinca alkaloids in vivo were examined in 3 pediatric rhabdomyosarcoma xenografts maintained s.c. in immune-deprived mice. The three lines differed in their sensitivity to VCR and VLB: two lines (Rh12 and Rh28) were extremely sensitive to VCR, whereas Rh18 tumors were less sensitive. Rh28 tumors were also very responsive to VLB, which demonstrated only marginal activity in the other two lines. After administration of equimolar doses (3 mg/kg) of [3H]-VCR and [3H]VLB to tumor-bearing mice, [3H]VCR reached concentrations approaching 1.5 microM in cell water of each tumor line within 4 hr, at which time greater than 93% of the drug was cell-associated. The drug was subsequently retained at this level for at least 72 hr studied. [3H]VLB accumulated to lower maximal concentrations (approximately equal to 1 microM) within 8 hr, but was not retained and, by 72 hr, reached concentrations that were 3- to 4-fold lower than those of [3H]VCR. The extent of drug retention correlated with the antitumor activity except in Rh28 tumors, which were sensitive to VLB, but did not retain the drug. The threshold level for achieving cytotoxicity may, thus, be very low in this line. In normal tissues, maximal concentrations of both [3H]VCR and [3H]VLB were achieved within 1 hr of administration i.p. to tumor-bearing mice. In ileum, liver, and kidney, these were approximately 10-fold higher than the peak levels achieved within tumors or plasma, but declined rapidly to parallel the decrease in plasma reaching concentrations greater than 5-fold lower than the concentration of [3H]VCR in tumors at 72 hr after treatment. Drug concentrations in skeletal muscle also declined rapidly, whereas neither [3H] VCR nor [3H]VLB accumulated to any great extent in brain. The blood volumes of ileum, kidney, and liver were greater than for tumor tissues. Hence, the extent of drug delivery did not necessarily influence therapeutic selectivity. In the case of [3H]VLB, concentrations in tumors approached those of normal tissues at 72 hr after injection. At 24 hr after treatment, 86 to 99% of [3H] VCR and 78 to 90% of [3H]VLB were present in tumors as the parent compound, which also predominated in normal tissues. Metabolites or in vivo degradation products were also identified. Selective retention in tumors appears to be the mechanism by which therapeutic selectivity is achieved with VCR in rhabdomyosarcoma xenografts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Determinants of intrinsic sensitivity to Vinca alkaloids in xenografts of pediatric rhabdomyosarcomas. 669 63

This study, based on a cooperative group project involving 4 major medical institutes in Japan, presents the second survey of malignant melanoma patients (198 cases) where an attempt is made to systemically evaluate the survival rates of these patients with respect to the tumor thickness and location of primary lesions, and the response to chemoimmunotherapy. More than 50% of total collected cases showed the primary lesions on the limbs. The most common type and site of involvement is the acral lentiginous melanomas involving the plantar areas (more than 30). The survival rates affecting the limbs were better than those affecting the non-limb areas. However, the comparison of the survival rates did not reveal any difference between those cases affecting the plantar and non-plantar areas. The difference in the prognosis of melanoma patients appeared to be related to the tumor thickness. By historical comparison, the DAV (DTIC, ACNU, VCR) treated group exhibited a better survival rate than the non-DAV treated group. Furthermore, the DAV group with immunoadjuvant therapy (mainly OK-432) showed a better prognosis than the DAV group without any immunoadjuvant therapy.
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PMID:[Malignant melanoma in Japan: unique distribution and effect of DAV chemoimmunotherapy (part II)]. 670 21

Clomipramine, which is used as antidepressant and possesses calmodulin inhibitory activity, circumvented partly the vincristine resistance in vivo. Although vincristine alone at 30-200 micrograms/kg did not confer a significant therapeutic effect in vincristine resistant P388 leukemia (P388/VCR)-bearing mice, clomipramine at doses of 20 to 50 mg/kg administered daily for 10 d with vincristine enhanced the chemotherapeutic effect of vincristine in P388/VCR-bearing mice. Approximately a 30% increase in life span occurred. Although the circumvention of vincristine resistance was not achieved perfectly, it could be speculated that more than 98-99% of vincristine resistant tumor cells which could not be killed by vincristine alone could be killed by this approach.
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PMID:Potentiation of chemotherapeutic effect of vincristine in vincristine resistant tumor bearing mice by calmodulin inhibitor clomipramine. 686 39

Twenty year's (1959-1979) experience in the treatment of osteosarcoma at the Bone Tumor Center of the Istituto Ortopedico Rizzoli is presented. During this period 433 cases were recorded, but only 266 were considered. All the patients underwent surgery but after 1970 whole-lung irradiation (1971), immunotherapy (1971), and chemotherapy (1972 onward) were added as adjuvant therapies on a nonrandomized basis. In the group treated with surgery alone the prognosis was very poor: 10% survived nine years or more after the diagnosis, an average disease-free interval of 7.7 months and an average survival time of 13 months. Monolateral whole-lung irradiation had negative results and was abandoned after six cases. Adjuvant immunotherapy with irradiated autologous tumor cells gave moderately positive results in 16 patients, but only by delaying the appearance of first metastases, therefore increasing the time of survival. Adjuvant chemotherapy was performed with three different protocols: one protocol with ADM only and two protocols using VCR + MTX (at medium dose) + ADM, administered according to two different schedules. Superimposable results were obtained with these three regimens. With equal follow-up, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly higher than that of patients treated with surgery alone (P less than 0.001). The patients in the chemotherapy group who had relapses showed a prolonged time (mean = 12.3 months) to the onset of the first metastasis. Adjuvant chemotherapy caused virtually no morbidity and no deaths. Reference is made to the advantages of a large and homogeneous caseload deriving from a single institution to avoid preselection bias and evaluate the effectiveness of new therapeutic approaches when patient randomization has not been employed.
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PMID:The treatment of osteosarcoma of the extremities: twenty year's experience at the Istituto Ortopedico Rizzoli. 694 43

PTC, a mixture of oligopeptides of m-L-sarcholysin, acting primarily as an alkylating agent, was utilized as initial therapy following diagnosis in 80 children with nonlocalized neuroblastoma. Of the 67 evaluable patients (21 Stage III, 41 Stage IV and five Stage IV-S), 51 had measurable lesions allowing to evaluate PTC activity; objective tumor responses to the drug were recorded in 45 of these 51 cases (88.2%); 5/5 Stage III, 37/41 Stage IV, 3/5 Stage IV-S. Complete responses were obtained in seven patients (13.7%), partial responses in 32 (62.7%), objective improvement in six (11.8%). Four patients (7.8%) had either no tumor change, or tumor progression. There have been two early drug-related deaths (3.9%). Stage III and IV patients responding to PTC were then treated by irradiation + VCR, followed by cycles of a combination of ADriamycin, vincristine, and cyclophosphamide. Stage IV-S patients received no further therapy. Thirteen of 21 Stage III (61.9%), five of 41 Stage IV (12.2%) and four of five Stage IV-S (80%) are presently alive from 19-48 months (median, 27 months). PTC is an effective agent in advanced neuroblastoma. However, the results of this report do not indicate that its addition to a "standard" treatment, at least in the schedule adopted in this protocol, has improved the final outcome of children with nonlocalized disease.
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PMID:Effect of peptichemio in nonlocalized neuroblastoma. 708 13

The poor 5-year survival rate of patients with malignant colorectal tumors calls for clarification of the question as to whether it is advisable to carry out postoperative adjuvant chemotherapy. In the present study a simple "in vivo" test is described with which the sensitivity of individual human adenocarcinomas of the colon, primary xenotransplanted onto syngeneic "nude"-mice suffering from congenital thymic dysplasia, to cytostatic therapy with 5-FU and VCR could be determined. Five of six primary xenotransplanted tumors showed a significant reduction in size following combined therapy with these drugs in doses comparable to those administered clinically, whereas one of the transplanted tumors remained unresponsive to therapy. On the basis of these results it is absolutely necessary that a comparison be carried out between the rate of tumor remission in groups of patients and animals undergoing the same chemotherapy.
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PMID:Adjuvant chemotherapy of human colorectal adenocarcinoma after growth on mice with congenital thymic dysplasia ("nude"). 2. Tumor remission following treatment with 5-FU and VCR of xenotransplanted primary human colorectal adenocarcinomas. 740 Feb 3

New N-alkylated 1,4-dihydropyridine derivatives were synthesized and their ability to overcome multidrug resistance was examined in vincristine-resistant P388 cells (P388/VCR cells). Compounds that possessed an arylalkyl substituent on the dihydropyridine ring nitrogen were more potent than verapamil in potentiating the cytotoxicity of vincristine against P388/VCR cells. However, neither drug effectively enhanced the antitumor activity of vincristine in tumor-bearing mice. Introduction of basic nitrogen-containing substituents on the side chain of 1,4-dihydropyridines gave improved activity in vitro and in vivo. The piperazine derivative 12c and 12o were more than 10 times as potent as verapamil in vitro. Four compounds selected for in vivo testing showed superior antitumor activity in P388/VCR-bearing mice in combination with vincristine. The structure-activity relationships of the compounds are discussed.
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PMID:N-alkylated 1,4-dihydropyridines: new agents to overcome multidrug resistance. 755 68

Vincristine is used clinically for the treatment of various types of cancer. Recent significant therapeutic improvements obtained by entrapping anthracyclines in sterically stabilized liposomes raised the question whether the therapeutic index of vincristine can be similarly increased by formulation into such long-circulating liposomes. Encapsulation of vincristine in sterically stabilized liposomes (SL-VCR) prolonged the drug's distribution phase plasma half-life in rats from 0.22 to 10.5 hr. There was no significant difference in LD50 (> < or = 2.5 mg/kg, i.v.), but mice given sublethal doses of SL-VCR experienced significantly less weight loss than those given the same dose of free drug. Compared to free drug, SL-VCR was most effective against i.p. or s.c. implanted tumors. However, i.v. tumor inoculation nullified the therapeutic advantage of encapsulation. A single i.v. 2 mg/kg dose of SL-VCR increased the life span of mice bearing i.v. implanted P388 cells by only 44%, while the life span of i.p. P388 implanted mice was increased by 199%. In an s.c. implanted murine colon carcinoma, multiple doses of free drug did little to slow the growth of the tumors, but SL-VCR was able to produce long-term survivors in several dose regimens. These results indicate that prolonged circulation time increases the therapeutic index of VCR entrapped in liposomes against s.c. or i.p. implanted tumors, but does not improve the drug's activity against rapidly growing i.v. disseminated leukemias.
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PMID:Pharmacokinetics and anti-tumor activity of vincristine encapsulated in sterically stabilized liposomes. 762 96


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