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)

In an effort to increase the efficacy of several antineoplastic alkylating agents (CDDP, L-PAM, CTX, or BCNU), we examined the effect of the modulator Fluosol-DA/carbogen in combination with a second modulator, either lonidamine or pentoxifylline, on the survival of FSaIIC tumor cells and of bone marrow CFU-GM from tumor-bearing C3H mice. Fluosol-DA/carbogen increased the tumor-cell killing activity of each alkylating agent by about 10 times. In contrast, lonidamine alone did not significantly increase the cytocidal activity of any of the alkylating agents tested. However, in combination with Fluosol-DA/carbogen, the use of lonidamine produced about a 100-fold increase in the tumor cell kill achieved with CDDP as compared with CDDP alone. No increase in tumor cell kill over that produced with the single modulator Fluosol-DA/carbogen was seen following the addition of lonidamine to the combination treatment with L-PAM, CTX, or BCNU. Unfortunately, although neither lonidamine nor Fluosol-DA/carbogen alone significantly increased alkylator toxicity to bone marrow CFU-GM, the combination of modulators increased the toxicity of each alkylating agent to bone marrow by about 10 times. Pentoxifylline caused an increase in alkylator activity against the FSaIIC fibrosarcoma only when used with BCNU; this effect was further augmented by the addition of Fluosol-DA/carbogen. The combination of modulators pentoxifylline plus Fluosol-DA/carbogen was more effective than Fluosol-DA/carbogen alone only when the former was used with BCNU, whereas only minimal increases in tumor-cell killing activity were obtained with this modulator combination and CDDP, L-PAM, or CTX. Pentoxifylline increased the bone marrow CFU-GM toxicity of L-PAM by about 10 times. The bone marrow CFU-GM toxicity was further increased by Fluosol-DA/carbogen, as was the toxicity of each of the other alkylating agents. Lonidamine plus Fluosol-DA/carbogen may be useful in increasing the therapeutic efficacy of CDDP, and the combination of pentoxifylline plus Fluosol-DA/carbogen might improve the antitumor activity of BCNU.
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PMID:Fluosol-DA/carbogen with lonidamine or pentoxifylline as modulators of alkylating agents in the FSaIIC fibrosarcoma. 190 12

Preparative regimens for bone marrow transplantation (BMT) use a sequence of drugs, such as cyclophosphamide, in combination with radiation. However, the optimum sequencing of the two agents that will maximize tumor cell kill and minimize normal tissue damage is unknown and controversial. The studies presented here were done in order to determine the effect of cyclophosphamide on bone marrow and lung damage in mice when given 24 h before or after total body irradiation (TBI). A range of single doses of TBI was given before or after a single sublethal dose of 180 mg/kg of cyclophosphamide. The bone marrow of all mice intended for lung damage assessment was reconstituted with 5 x 10(6) syngeneic bone marrow cells. Lung damage was assessed by breathing rate and lethality; bone marrow damage by lethality at 30 days. LD50 values for pneumonitis were obtained between 30 and 84 days after cyclophosphamide and radiation and between 80 and 180 days after radiation alone. Dose modifying factors were obtained as the ratio of LD50s for mice given only TBI compared to those for mice given cyclophosphamide and TBI. Cyclophosphamide enhanced radiation pneumonitis when given before or after TBI, giving DMFs of 1.4 and 1.2 (1.1-1.4, 95% c.l.) respectively. The effect of cyclophosphamide on radiation pneumonitis was drug dose-dependent. The LD50 for death from bone marrow damage was reduced when cyclophosphamide was given either before or after TBI but the effect was greater, i.e. the LD50 was lower when cyclophosphamide was given after TBI. These data show that cyclophosphamide given 24 h after TBI causes less lung damage but more bone marrow damage in this mouse model.
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PMID:Cyclophosphamide 24 hours before or after total body irradiation: effects on lung and bone marrow. 192 49

An attempt has been made to simplify and to provide an understanding of some of the new modalities for evaluation of head and neck pathology. Both CT and MRI are complementary to each other: MRI being superior to CT in evaluating soft tissue, and CT being superior to MRI in assessing fine bony details and in identifying microcalcifications. MRI is the modality of choice for tumor evaluation because it has several advantages over CT in assessing the location, spread, and staging of the disease. HRCT scanning remains the procedure of choice in the evaluation of middle ear and base of the skull, and in the evaluation of benign sinonasal disease. CPA and IAC lesions are best evaluated by MRI. Three-dimensional surface reformations of axial CT scans enable the surgeon to plan the operative approach needed to reduce facial fractures and to repair cranial deformities.
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PMID:Computed tomography versus magnetic resonance imaging and three-dimensional applications. 194 24

Five patients with high risk multiple myeloma not responsive to standard chemotherapy were treated by high-dose chemotherapy (Melphalan, Cyclophosphamide) (HDC) and total body irradiation (TBI) followed by autografting with blood stem cells. These cells were previously collected by leukaphereses from eight to twelve occasions during hematopoietic recovery following profound aplasia induced by each course of intensive chemotherapy (Vincristine, Adriamycin, Cyclosphosphamide, Prednisone) when the patient reached a neutrophil count of 1,000/microliters and a platelet count of 100,000/microliters. No patients had evidence of tumor plasmacells in leukaphereses products using cytology, immunocytochemistry and immunofluorescence. At this time the patient 5 is not evaluable because of the short follow-up. One died at day 30 from heart failure. All living patients achieved a complete remission which persisted at a follow-up of 300, 261 and 136 days. Autologous blood derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. Our results indicate the feasibility of this therapeutic approach over allogenic or autologous bone marrow transplantation in selected patients with high tumour mass multiple myeloma.
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PMID:Blood stem cells autografts in patients with high risk multiple myeloma. 197 31

Previous studies demonstrated that single doses of systemic cyclophosphamide (CY) as low as 0.5 mg/kg are effective in preventing bladder tumor implantation in a rat model. In an effort to determine if the urinary bladder represents a unique site of CY activity, a series of experiments were performed to define the mechanism by which low-dose CY prevents bladder tumor implantation. Potential sites for CY antitumor activity include direct tumor cytotoxicity resulting from serum delivery of drug to the tumor; tumor cytotoxicity resulting from tissue drug levels at the site of implantation; altered tumor cell adherence to the urothelial injury site; nonspecific urothelial cytotoxicity resulting from urinary excretion of the CY metabolites; tumor cell-specific cytotoxicity resulting from urinary excretion of the CY metabolite acrolein; and second-pass cytotoxicity resulting from urinary excretion of the active form of CY. Experiments were performed to determine if a single predominant site of activity could be defined. Cyclophosphamide levels at the site of tumor implantation appeared to be the most important determinant of antiimplantation activity. Only tumor recipients pretreated with CY had a significant decrease in bladder tumor implantation. In vivo and in vitro assays measuring the effect of blood-borne drug delivery directly to the tumor failed to demonstrate cytotoxic activity. Tumor cell adherence assays measuring in vitro adherence of CY-treated tumor cells and in vivo adherence of tumor cells in CY-treated recipients showed no difference in comparison to control groups. Interval histological comparison of CY-treated and control bladders failed to demonstrate any difference. Urinary levels of acrolein did not contribute to antiimplantation activity. Preimplantation CY doses prevented tumor development in a s.c. implantation model, thereby excluding a second-pass effect resulting from urinary drug excretion. These data suggest that the bladder is not unique in its response to systemic low-dose CY administered for the prevention of implantation-mediated tumor recurrence. Low-dose, perioperative chemoprophylaxis may be applicable to other tumor systems in which intraoperative tumor dissemination is felt to contribute to recurrence risk.
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PMID:Single-dose cyclophosphamide for the prevention of bladder tumor implantation in F344 rats: site of drug activity. 199 76

Since 1986, attempts have been made to improve the anti-cancer effect of Cisplatin (CDDP) in malignant ovarian tumor patients and their quality of life (QOL), by increasing single and total dose of CDDP and by short-stay cyclic treatment at our institution. In this study, the side effects of CDDP at high and low doses were compared and the effect on the QOL was analysed. Twenty ovarian malignant tumor patients who underwent adjuvant chemotherapy (CDDP 70 mg/m2, Adriamycin (ADR) 20 mg/m2, Cyclophosphamide (CPM) 200 mg/m2 given every 4 weeks for a total of 5 times and every 8-12 weeks thereafter for 5 times) after initial surgery were compared with non randomized control patients who received the old regimen of of our institution (CDDP 35 mg/m2, ADR 20 mg/m2, CRP 200 mg/m2, 5-FU 150 mg/m2 for 5 days given every 4 weeks for a total of 5 times without discharge from hospital). There was no significant difference between the groups in the white blood cell (WBC) count and creatinine clearance (Ccr) throughout the treatment, although a slight drop was observed after the second course in both groups. The QOL was examined by interviewing the patients on their physical and mental condition. Although the total amount of CDDP was increased from 175 mg/m2 to as much as 700 mg/m2, no severe nephrotoxicity or myelosuppression was seen and patients felt better and preserved a good QOL during a short hospital stay. These results clearly indicate the efficacy of our new regimen.
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PMID:[Cyclic high dose CAP therapy by short-stay admission for ovarian malignancies--to increase total dose of CDDP and to improve quality of life of patients]. 199 12

A murine plasmacytoma MOPC 104E (MOPC) is highly sensitive to chemotherapeutic agents such as cyclophosphamide and mitomycin C as well as to immunotherapy (OK-432-combined adoptive immunotherapy using interleukin-2-cultured killer cells). In the present study, we prepared cyclophosphamide-resistant MOPC cells (MOPC-CPA/R) by serial in vivo passage of tumor cells following cyclophosphamide treatment. The in vivo sensitivity of MOPC-CPA/R to mitomycin C or to immunotherapy (OK-432-combined adoptive immunotherapy) was significantly decreased compared to the parent MOPC. In vitro experiments showed that MOPC-CPA/R were more resistant (five-fold) to lysis by cultured immune spleen cells than MOPC. Inhibition of the lytic activity of cultured immune spleen cells against MOPC was significantly increased (P less than 0.05) by the addition of unlabeled MOPC compared to unlabeled MOPC-CPA/R. These results suggest that MOPC-CPA/R express weaker antigenicity than MOPC. However, the transfer of immune spleen cells cultured with tumor extract derived from MOPC-CPA/R significantly prolonged the survival of MOPC-CPA/R-inoculated mice. Thus, by repeated cyclophosphamide treatment, tumor cells with low-antigenicity were selected. These tumor cells had lower sensitivity to another chemotherapeutic agent and immunotherapy. Such an immunological response may play an important role in cancer therapy.
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PMID:A murine plasmacytoma MOPC 104E resistant to cyclophosphamide is resistant to immunotherapy. 199 69

The object of the present investigations was delineation of the exclusive effects of cyclophosphamide (Cytoxan) on host humoral response to tumor, as evaluated by the level of circulating antigen/antibody complexes (AACs), which may reflect the chemo-responsiveness of hosts and provide a rationale for new therapeutic strategies. Our data, recorded in Copenhagen X Fischer rats bearing Dunning's R-3327 Mat Ly-Lu adenocarcinoma of the prostate, show no modulatory effect of cyclophosphamide at 10 mg/kg, a nonspecific immunosuppressive effect at 30 mg/kg, and a definite immunostimulatory effect on host humoral immunity at 100 mg/kg. Sequential determination of AAC levels at different stages of tumor growth, i.e. from the primary to the metastatic stage, performed with the original purpose of demonstrating that any disturbance in the immunoregulatory mechanism of the host was due to cyclophosphamide rather than to changes in tumor load, revealed that levels of AACs parallel disease progression in the initial stages of primary tumor growth but rapidly decrease to near-normal levels in the presence of heavy tumor burden.
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PMID:Immunomodulatory effect of cyclophosphamide on host humoral immunity in Dunning's R-3327 adenocarcinoma of the prostate. 202 60

The total dosage and therapeutic value of Cyclophosphamide (CPA) administered as adjuvant chemotherapy for breast cancer were studied. The subjects were those under 65 years of age who were diagnosed as Stage II breast cancer and underwent curative operation at any of 10 national hospitals from May, 1978 to April, 1981. CPA at dose of 100mg was administered orally every day. Comparison was made between the long-term administration group (L) of patients receiving a total of 25 g/m2 over 18 months and the short-term administration group (S) receiving a total of 6 g/m2 over 6 months, in terms of survival rate (SV) and disease-free survival rate (DFV). Cases selected as the subjects were randomly allotted to the two groups by means of the envelope method. The number of cases registered was 316. Of them, 308 cases were eligible for the study. Thirty-eight cases (23.6%) in L and 15 cases (10.2%) in S dropped out due to side effects and other reasons. No difference was observed between the two groups in background factors such as age, menopausal status, type of operation, histological diameter of tumor, histological type and metastasis to lymph nodes. Results of a 10-year follow-up revealed no difference in SV and DFV between the two groups. Excluding the drop-out cases, however, DFV was significantly high in L. There was no difference in DFV between the two group in terms of menopausal status. DFV was significantly high in L, if one includes cases with metastasis to lymph nodes. DFV was high in L, even when a group with no more than 3 metastatic lymph nodes and the group with not less than 4 were included. It is of little value to administer CPA to all Stage II cases for a long period of time. CPA may be indicated for cases showing metastasis to lymph nodes.
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PMID:[Adjuvant chemotherapy using cyclophosphamide for breast cancer. National Hospital Collaborative Group for Study of Breast Cancer Treatment]. 202 1

In 1990, the first gamma unit in Asia was installed at Tokyo University Hospital. This article describes the radiosurgical techniques used and clinical experiences during treatment of 70 cases at the unit. Stereotactic radiosurgery using a gamma knife for the treatment of AVM, CPA tumor and meningioma has been used for more than 20 years. With this form of therapy, a high dose of radiation is delivered from multi-directional beams to deep lesions of the brain, incurring only minimal radiation exposure at the periphery. When a large dose of radiation is applied to a small area, there may be certain side effects especially if care is not taken. Accordingly, treatment of brain lesions using a gamma knife requires teamwork, even though it appears to be a safe procedure at the present time.
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PMID:[The development of radiosurgery--introduction of the gamma knife for brain lesions]. 203 May 28


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