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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the double agar layer method of human tumor clonogenic assay, the anticancer effect of different combinations of anticancer drugs and interferons was tested on 3 lung cancer cell lines, PC-13, PC-14, and Calu-1. The anticancer drugs and the concentrations used in this study were cisplatin (1.0 microgram/mL), adriamycin (1.0 microgram/mL), mitomycin C (0.2 microgram/mL), VP-16 (5.0 micrograms/mL) and 5-FU (5.0 micrograms/mL). Three kinds of interferon, alpha, beta and gamma in 5,000 units/mL, were tested in combination or in sequence with other anticancer drugs on lung cancer cell lines. The results demonstrate an enhanced anticancer effect on PC-14 only with sequential or simultaneous combination of VP-16 with alpha, beta and gamma interferons; and on Calu-1, only with sequential use of adriamycin and beta-interferon. Our results indicate that there is no unique way of combining anticancer drugs and interferons which can obtain an enhanced anticancer effect on all lung cancer cell lines. The best combination of interferon and anticancer drugs seems to be influenced by the biological characteristics of the cancer cells.
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PMID:[Effect of combinations of anticancer drugs with interferons on human lung cancer cell lines evaluated by human tumor clonogenic assay]. 172 Jan 64

The possibility of increasing the activity of etoposide (VP-16) by combining this anti-cancer agent with indomethacin (Indo) was investigated by treating murine and human cultured tumor cells with a combination of Indo and VP-16 and quantitating VP-16 cytotoxicity by the [3H]thymidine incorporation assay. Non-toxic concentrations of Indo were found to enhance the sensitivity to VP-16 in cultured Lewis lung carcinoma (LLC), YAC-1, P815, CCRF-CEM and K562 cells which were all relatively sensitive to VP-16. With the LLC, the Indo effect was dose dependent and near maximal at an Indo concentration of 0.5 micrograms/ml. Indo also increased the response of LLC cells to methotrexate, but not to bleomycin. Ibuprofen was less effective than Indo in enhancing VP-16 sensitivity in LLC cells. The enhanced sensitivity of VP-16 by Indo was not reversed by the prostaglandins PGE2 and PGD2, the analogs carbocyclic thromboxane A2 and carba-prostacyclin or conditioned medium removed after 24 h or 48 h of culture from near confluent LLC cell monolayers. This finding suggests that Indo is not augmenting VP-16 cytotoxicity by inhibiting cyclo-oxygenase activity and prostaglandin production. The lipoxygenase inhibitor, eicosatetraynoic acid (ETYA), was also ineffective in reversing the Indo augmentation of VP-16 sensitivity. This finding indicates that Indo is not acting by inhibiting cyclo-oxygenase and converting larger amounts of arachidonic acid to lipoxygenase products, such as leukotrienes, that could then interact with VP-16 to increase its sensitivity. In other studies, Indo was found to significantly increase the steady state accumulation of [3H]-VP-16 in all five cell lines studied. With the LLC cells, this increased steady state was achieved within 15 min after the addition of Indo to these cells and this enhanced VP-16 uptake was not reversed by the addition of prostaglandin E2 or prostaglandin D2. Thus, taken together, these studies indicate that Indo most likely enhances the cytotoxicity of VP-16 by increasing the cellular accumulation of VP-16. This newly identified function of Indo may be of potential clinical significance in the treatment of cancers in man.
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PMID:Enhancement of etoposide and methotrexate sensitivity by indomethacin in vitro. 172 10

The patient is a 31-year-old man who was suffering from hyperthyroidism and left hemothorax. His serum HCG level was extremely elevated and chest X-ray showed a mass shadow of anterior mediastinum and bilateral multiple intrapulmonary metastasis. Our clinical diagnosis was primary HCG-producing germ cell carcinoma of mediastinum and immediately administered CDDP and VP-16. Chemotherapy was effective and tumor extirpation was carried out for mediastinum and lungs by median sternotomy. All of the resected specimen showed no cancer cells and 4 years have passed with no evidence of recurrence. Aggressive surgical approach is indicated for mediastinal germ cell carcinoma accompanied with intrapulmonary metastasis when chemotherapy is effective.
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PMID:[Surgical therapy of HCG-producing mediastinal tumor accompanied with intrapulmonary metastasis]. 172 89

Mechanisms of resistance to VP-16 in vivo were studied using sensitive and multidrug resistant human breast tumor (MCF-7) cells, implanted bilaterally in nude mice. Administration of VP-16 (40 mg/kg, i.p.) indicated that there were no significant differences in either accumulation and retention of VP-16 or in the drug-induced bulk DNA damage in sensitive or resistant solid xenografts. Furthermore, under these conditions, no differential cytotoxic response to VP-16 was observed in solid tumors.
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PMID:Distribution, DNA damage and cytotoxic effects of etoposide in human tumor xenografts in vivo. 174 94

A 63-year-old man with primary malignant lymphoma of the prostate is presented. The patient underwent total cystoprostatectomy and ileal conduit construction. The specimen revealed malignant lymphoma, diffuse small cleaved cell of the gland. Three months after the operation, local recurrence and enlarged lymph node development were demonstrated by computed tomography. The patient tolerated well a combination chemotherapy of VP-16, doxorubicin, cyclophosphamide and prednisolone for 5 cycles. Tumor recurrence and lymph node spread could never be recognized following this drug treatment. The patient has been asymptomatic after this chemotherapy for over 3 years.
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PMID:Malignant lymphoma of the prostate. Report of a case. 177 10

The combination of biological response modifiers with cytotoxic drugs has proven to be synergistic in several tumor systems. Recombinant human tumor necrosis factor (rhTNF) has been shown to enhance the antitumor efficacy of etoposide (VP-16) in the treatment of C1300 murine neuroblastoma. However, after completion of therapy, tumor growth resumes and results in subsequent death. In an effort to assess the impact of combining surgery with rhTNF/VP-16 therapy, A/J mice bearing the C1300 murine neuroblastoma were treated within adjuvant or neoadjuvant protocols. Adjuvant-treated animals had a longer interval to disease recurrence (P = .01) and smaller average recurrent tumor volumes postexcision (P less than .05) compared with surgical controls. Histological evidence of tumor recurrence and liver metastases was seen in both adjuvant-treated and surgical control animals. Neoadjuvant-treated animals had a longer interval to disease recurrence (P = .03) and smaller average recurrent tumor volumes up to 14 days postexcision (P less than .02) compared with surgical controls. In addition, 30% of the neoadjuvant-treated animals had no microscopic evidence of disease recurrence, and only 14% had histological evidence of liver metastases. The surgical controls in the neoadjuvant experiment all had histological evidence of disease recurrence and liver metastases. Thus, the combination of surgery and rhTNF/VP-16 in the adjuvant or neoadjuvant setting appears to significantly delay the progression of C1300 murine neuroblastoma. Furthermore, administering chemoimmunotherapy prior to surgical excision in a neoadjuvant manner appears to be most beneficial as regards prevention of local disease recurrence and distant metastases.
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PMID:Chemoimmunotherapy in conjunction with surgery: strategies for management of murine neuroblastoma. 177 33

The activity of Etoposide (VP16) in combination chemotherapy against four human transitional cell carcinoma cell lines of bladder (TCCaB) was determined by in vitro colony formation assay. Four anti-tumor agents (methotrexate: MTX, vinblastine: VBL, adriamycin: ADM, cisplatin: DDP) were used for combination chemotherapy with VP16. The ADM + VP16 combination exhibited a strong synergistic antitumor effect against the human TCCaBs compared with other combinations in this study. The combination chemotherapy of ADM + VP16 may be useful as a new chemotherapeutic regimen for advanced bladder cancer.
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PMID:[The activity of etoposide (VP16) in combination chemotherapy against human bladder cancer cells in vitro]. 178 27

A case of recurrent, disseminated retinoblastoma is presented. The primary intraocular tumor, a metastatic mass at recurrence, and the tumor cells infiltrating bone marrow were all positive for the anti-GD2 monoclonal antibody (Mab) 3A7. Indirect immunofluorescence using the monoclonal antibody 3A7 was an effective method of detecting residual disease in the marrow. After remission was achieved by conventional therapy, the patient underwent autologous bone marrow transplantation (ABMT). The preparative regimen consisted of VP-16, cisplatinum, high-dose melphalan, and total body irradiation. The autologous marrow inoculum was clean of tumor cells at the detection level of 1:10,000. The transplant course was uneventful, and the patient is well and disease-free 17 months after ABMT. We conclude that high-dose chemotherapy and total body irradiation in an ABMT setting is feasible and a potentially curative approach to disseminated retinoblastoma.
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PMID:Recurrent disseminated retinoblastoma treated by high-dose chemotherapy, total body irradiation, and autologous bone marrow rescue. 179 58

To investigate the possibility that anticancer drugs combined with cytokines may show increased activity, human tumor cells were treated with combinations of human recombinant interleukin 1 alpha (rIL-1 alpha) and etoposide (VP-16). The cytotoxicity of these combinations was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay using rIL-1 alpha-sensitive A375-C6 melanoma cells and A375-C5 cells, a clonal variant line that is resistant to IL-1 alpha. Data were analyzed for synergism by the median effect principle of T-C. Chou and P. Talalay (J. Biol. Chem., 252: 6438-6442, 1977). At a dose ratio of VP-16 to rIL-1 alpha of 12 nM:1 unit/ml in either simultaneous or sequential exposure (VP-16 first), the calculated combination index values indicated synergistic cytotoxicity toward both A375-C6 cells and A375-C5 cells. IL-1 alpha treatment 24 h prior to VP-16 exposure had no advantage over simultaneous treatment. Surface IL-1 alpha receptors on both A375-C6 and A375-C5 cells were measured using 125I-radiolabeled rIL-1 alpha binding; A375-C6 cells had 701 +/- 128 (SD) receptor molecules/cell and A375-C5 cells only had 58 +/- 33 receptor molecules/cell. The dissociation constants for IL-1 alpha were similar in both cell types (19 +/- 6 pM for A375-C6 and 17 +/- 2 pM for A375-C5). The specific binding of rIL-1 alpha to the surface IL-1 alpha receptors of both sensitive and resistant cells was significantly increased in a dose-dependent fashion by the prior treatment with VP-16 (1.75-fold on A375-C6 cells and 3.5-fold on A375-C5 cells). VP-16 also enhanced the internalization of receptor-bound rIL-1 alpha, suggesting that a possible mechanism of the synergistic cytotoxicity of rIL-1 alpha and VP-16 might be related to the modulation of rIL-1 alpha receptors by VP-16, resulting in increased internalization of rIL-1 alpha.
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PMID:A role for the interleukin 1 receptor in the synergistic antitumor effects of human interleukin 1 alpha and etoposide against human melanoma cells. 182 25

Etoposide is one of the few cancer chemotherapy agents that is schedule-dependent in both preclinical and clinical studies. A randomized trial of etoposide as initial therapy in extensive small cell lung cancer (SCLC) demonstrated the superiority of a 5-day course versus the same total dose administered over 24 hours. The recent availability of oral etoposide capsules has led to further exploration of etoposide's schedule-dependency through the use of daily oral etoposide. Initially, studies at Indiana University and the Hoosier Oncology Group concentrated on refractory germ cell tumors and refractory SCLC. Although both of these tumor types are sensitive to etoposide combination chemotherapy as initial treatment, it is rare to see a response with any single agent in refractory disease. In 25 patients with refractory germ cell tumors, we observed 5 objective responses (20%). In addition, 3 other patients (12%) clearly achieved antitumor effect with a greater than 90% reduction in tumor markers, although radiographic findings remained stable. In refractory SCLC, 1 complete and 5 partial responses were observed in 26 patients, for a 23% response rate. Twenty-five of the 26 had received prior cisplatin/etoposide and 14 also had received prior cyclophosphamide/doxorubicin/vincristine. Daily oral etoposide is capable of producing palliation and objective responses in heavily pretreated patients and may be a preferable method of administration. Future trials are planned using daily oral etoposide as a component of combination chemotherapy as first- and second-line therapy in patients with SCLC.
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PMID:Daily oral etoposide in the treatment of cancer. 184 80


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