Experimental study was done to investigate the effect of suramin on the in vitro and in vivo proliferation and metastasis of penile squamous carcinoma cell line(CUPE-1), morphological changes of CUPE-1 cells induced by suramin and mechanism of action of suramin. Suramin inhibited in vitro proliferation of CUPE-1 significantly with 1C50 of 100 microgram/ml media. In vitro antiproliferative effect of suramin on CUPE-1 was reversible after stopping administration of the drug. Weekly intraperitoneal administration of 200 mg/kg of suramin to nude mouse inhibited the proliferation and metastasis of intraperitoneally implanted CUPE-1 cells significantly. but did not show significant effect on the proliferation of subcutaneously implanted CUPE-1 cells. Suramin induced senile changes on ultrastructure of CUPE-1 cells. Suramin of 300 microgram/ml inhibited the prolireration-stimulating effect of EGF significantly, whereas, suramin of 100 microgram/ml did not inhibit the effect of EGF significantly. Suramin did not show significant cytotoxicity on 3H-thymidine release assay. These results suggest that suramin is a promising drug for the treatment of advanced penile squamous cell carcinoma and blood level of suramin in clinical trial should be continuously maintained in about 300 microgram/ml, and that the main machanism of suramin against CUPE-1 is cytostatic. by antagonizing the action of EGF and inducing growth arrest and senile change.
Animals ; Carcinoma, Squamous Cell* ; Epidermal Growth Factor ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Robenidine ; Suramin

Hydroxyurea is a cytostatic agent that has recently become the drug of choice in the treatment of various myeloproliferative diseases. The cutaneous side effects of hydroxyurea include xerosis, hyperpigmentation, nail discoloration, and scaling. Leg ulcers have only rarely been reported in association with hydroxyurea treatment. A 75-year-old woman presented with leg ulcers, nail discoloration, and xerosis. The leg ulcers were refractory to conventional treatment. She had been taking oral hydroxyurea since being diagnosed with essential thrombocytosis in 2002. Hence, we suspected hydroxyurea-induced leg ulcers and discontinued her hydroxyurea treatment; the ulcers gradually healed thereafter. We present a rare case of hydroxyurea-induced leg ulcers in Korea.
Aged ; Female ; Humans ; Hydroxyurea ; Hyperpigmentation ; Korea ; Leg ; Leg Ulcer ; Nails ; Robenidine ; Thrombocytosis ; Ulcer

Mesna has been used with ifosfamide to prevent urotoxicity in the treatment of testicular cancers. This drug also protected the toxicities of adriamycin without compromising cytostatic activity. With n idea of radioprotective role of sulfhydryl group of radioprotectors and of mesna decreasing the toxic effect of adriamycin which produces free radicals, mesna and radiation were administered to mice to study the protective effect of this drug and to identify the difference in regenerative capacity of the germ cells in the testis between radiation-treated and both mesna- and radiation-treated groups. The shape and numbers of spermatogenic cells in the seminiferous tubules were examined every week after irradiation. In both groups, initial reduction and later recovery in germ seel numbers and shape was observed. The lowest germ cell number was found around three weeks after irradiation. Mean germ cell number of the mesna-treated group was significantly higher than radiation-treated group at all observed periods (p<0.05). More competent regeneration was present in mesna-treated group. These results suggest that mesna protect the testis from radiation injury. Further study will be necessary to identify whether mesna protects other tissues from radiation and it does not hamper tumor control.
Animals ; Doxorubicin ; Free Radicals ; Germ Cells ; Ifosfamide ; Mesna* ; Mice* ; Radiation Injuries ; Regeneration ; Robenidine ; Seminiferous Tubules ; Testicular Neoplasms ; Testis*

A total or 56 patients who underwent TUR-BT for superficial (stages O and A) bladder tumors received various chemoprophylactic treatment to prevent recurrence. 16 patients underwent resection only (Group I). Of the 56 patients treated with chemoprophylactic agents 18 patients were given thio-tepa at weekly interval for 8 weeks (Group 2). 20 patients were given adriamycin. weekly one time for 6 weeks (Group 3). 16 patients were given mitomycin C, weekly one time for 8 weeks (Group 4). All chemoprophylactic groups were followed by monthly one time for 1 year and the dosages of the used agents (thio-tepa, adriamycin and mitomycin C) were 60 mg/l dosage, 50 mg/l dosage and 30 ml/l dosage, respectively. During follow-up period (mean duration; 19.8-25. 2 months), 1umor recurred 56.2 % of group 1 patients, 27.7 % of group 2 patients, 25.0% of group 3 patients, 18.9 % of group 4 patients and 22.2% of total patients. Therefore three drugs were effective to decrease the recurrence rate of superficial bladder tumor and no significant differences in recurrence rate were noticed among drugs. Toxicity of the three agents were negligibly minimal except 2 patients who developed severe gross hematuria after adriamycin instillation.
Administration, Intravesical* ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Hematuria ; Humans ; Mitomycin ; Recurrence ; Robenidine* ; Thiotepa ; Urinary Bladder Neoplasms* ; Urinary Bladder*

This experiment was performed to evaluate the morphological responses of the appendicular mucosa of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG or CP-2 (Coptis chinensis-Croton tiglium extracts). Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (experimental control, BCG or CP-2 treated group). Each experimental group mouse was inoculated with 1 x 10(7) Ehrlich carcinoma cells subcutaneously in the inguinal area. From the next day after inoculations, 0.2 mL of saline, BCG (0.5 mL/25 g B.W.: 0.03 x 10(8) ~ 0.32 x 10(8) CFU) or CP-2 (30 mg/kg) were injected subcutaneously to the animals every other day, respectively. The day following the 7 th injection of BCG or CP-2, each mouse was injected with a single dose of 0.7 microCi/gm of methyl-3H-thymidine (25 Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the tritiated thymidine injection, animals were sacrificed. The number of the labeled epithelial cells of the appendicular mucosae were observed and evaluated. On histological studies of the experimental control, BCG or CP-2 treated mice, general morphologies of the appendicular mucosae were similar. On autoradiographic study, number of the labeled cells of normal control, experimental control, BCG treated or CP-2 treated groups were 362.2+/-56.12, 350.7+/-42.65, 265.8+/-27.08 and 241.3+/-53.29, respectively. Above results show that BCG and CP-2 suppress the DNA synthetic activity of the epithelial cells of the appendix, but did not show any remarkable morphological alterations on the mucosae. These results suggest that BCG and CP-2 are ones of effective anticancer drugs for the cytostatic therapy.
Adult ; Animals ; Appendix* ; DNA* ; Epithelial Cells* ; Humans ; Mice* ; Mice, Inbred ICR ; Mucous Membrane ; Mycobacterium bovis* ; Robenidine ; Thymidine ; Veins

Investigations of the anti-tumor activity of recombinant mouse TNF and etoposide(VP-16) in a nude mouse subcutaneous implantation xenograft model utilizing the CURC-1 human renal cell carcinoma cell line were performed. Recombinant mouse tumor necrosis factor-alpha(rTNF-alpha) and VP-16. both well known cytotoxic and cytostatic anticancer agents were evaluated singly and in combination against subcutaneously growing CURC-1. The results were as follows : 1. In the absence of treatment(Group I). subcutaneously growing CURC-1 tumor nodules demonstrated continued rapid growth. 2. Administration of rTNF(Group II) induced significant tumor regression in the subcutaneous nodules. 3. Administration of rTNF and Etoposide(Group III) demonstrated significant tumor growth inhibition. On histopathological findings, Group I (control) shows rare leukocyte infiltration and no tumor necrosis. In contrast, Group II shows tumor necrosis and more leukocyte infiltration than Group I . Group III demonstrates tumor necrosis. tumor cell degeneration and more leukocyte infiltration than Group II. These results suggest that TNF have antineoplastic effect against subcutaneous human renal cell carcinoma nodule but the synergistic effect of TNF with VP-l6 is uncertain.
Animals ; Antineoplastic Agents ; Carcinoma, Renal Cell* ; Cell Line ; Etoposide* ; Heterografts* ; Humans ; Leukocytes ; Mice ; Mice, Nude* ; Necrosis ; Robenidine ; Tumor Necrosis Factor-alpha*

Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor with broad tissue distribution that plays critical roles during embryonic development, normal tissue homeostasis, and cancer. While its cytostatic activity on normal epithelial cells initially defined TGF-beta signaling as a tumor suppressor pathway, there is ample evidence indicating that TGF-beta is a potent pro-tumorigenic agent, acting via autocrine and paracrine mechanisms to promote peri-tumoral angiogenesis, together with tumor cell migration, immune escape, and dissemination to metastatic sites. This review summarizes the current knowledge on the implication of TGF-beta signaling in melanoma.
Cell Movement ; Embryonic Development ; Epithelial Cells ; Female ; Homeostasis ; Melanoma ; Neoplasm Metastasis ; Pregnancy ; Robenidine ; Tissue Distribution ; Transforming Growth Factor beta ; United Nations

PURPOSE: Verapamil is one of the most extensively characterized modulators of P-glyco- protein (P-gp) mediated multi-drug resistance (MDR), but its plasma concentration required to reverse MDR can cause cardiovascular toxicity. KR-30035 is a newly synthesized verapamil analogue with more potent cytostatic effects, but has lower cardiovascular effects than verapamil. We have assessed the MDR reversing effects of KR-30035 by measuring Tc-99m MIBI uptake in cultured tumor cells and in nude mice bearing human tumor xenografts. MATERIALS AND METHODS: In-vitro uptake of Tc-99m MIBI was measured in murine leukemia cells (L-1210) and those MDR-positive variants after incubation with different concentrations of KR-30035. Results were compared to those with verapamil. Organ and tumoral uptake of Tc-99m MIBI was compared between P-gp (+) human colon cancer (HCT15 cells) and P-gp (-) lung cancer (A549 cells) in nude mice, treated with either KR-30035 or verapamil. RESULTS: There was no significant difference in in-vitro uptake of Tc-99m MIBI between verapamil and KR-30035 group at any concentrations. MIBI uptake in P-gp (+) cells continuously increased either with verapamil or KR-30035 in a dose-dependent manner. Tc-99m MIBI uptake ratios of the tumor [P-gp (+' tumor uptake divided by P-gp (-) uptake] were significantly higher with KR-30035 than with verapamil in tumor bearing nude mice. Washout rate of Tc-99m MIBI from P-gp (+) HCT15 cells was lower in verapamil or KR-30035 groups than in the control group, which was 0.19, 0.19 and 0.27 respectively. CONCLUSION: These studies revealed that KR-30035 can potentially be used as an active modulator of MDR, with its significantly lesser cardiovascular toxicity than verapamil. Our results warrants further evaluation of this novel agent.
Animals ; Colonic Neoplasms ; Drug Resistance, Multiple ; Heterografts ; Humans ; Leukemia ; Lung Neoplasms ; Mice ; Mice, Nude ; P-Glycoprotein ; Plasma ; Robenidine ; Tumor Cells, Cultured ; Verapamil

This experiment was performed to evaluate the morphological responses of the mucosa of the mouse appendix, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of Acriflavine-Guanosine Composition (AG60). Healthy adult ICR mice weighing 25 gm each were divided into normal, experimental control and AG60 treated group. Experimental control and AG60 treated groups, mice were subcutaneously inoculated with 1 x 10(7) Ehrlich carcinoma cells in the inguinal area. From next day after the carcinoma cell inoculations, 0.2 mL of saline or AG60 (5 mg/kg/0.2 mL) were injected subcutaneously to the animals every other day, respectively. The day following the 7 th injection of saline or AG60, each mouse was injected with a single dose of 0.7 microCi/gm of methyl-3H-thymidine (25 Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the 3H-thymidine injection, animals were sacrificed, and appendix tissues were fixed in 10% formalin solution for light microscopy. The number of the labeled mucosal epithelial cells of the appendix were observed and evaluated. For the electron microscopic study, the tissues were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. Ultrathin sections were counter stained with uranyl acetate-lead citrate solutions, and observed. On light microscopic observation of experimental control and AG60 treated mice, did not show any remarkable morphological alterations on the mucosae. On autoradiographic study, number of the labeled cells within 3.5 mm width mucosae of normal control, experimental control, AG60 treated mice were 362.2+/-56.12, 350.7+/-42.65 and 90.7+/-33.48, respectively. On ultrastructural observation of the experimental control and AG60 treated mice, general morphologies of the epithelial cells of appendix were similar. But intranuclear filamentous structures, intramitochondrial dense granules, and myelin figures were occasionally observed in the absorptive cells of AG60 treated mice than control ones. Above results show that AG60 suppress the DNA synthetic activity of the mucosal epithelial cells of mouse appendix, but did show slight ultrastructural alterations in the absortive cells. These results suggest that AG60 is one of effective anticancer drug for the cytostatic therapy.
Adult ; Animals ; Appendix* ; Citric Acid ; DNA* ; Epithelial Cells* ; Formaldehyde ; Humans ; Mice* ; Mice, Inbred ICR ; Microscopy ; Mucous Membrane ; Myelin Sheath ; Osmium Tetroxide ; Robenidine ; Veins

PURPOSE: Mammalian tumor cells differ in their response to ionizing radiation to a degree that some patients are readily curable with conventional doses of radiation, while others are rarely controlled. In experimental systems, it is possible to demonstrate differences between cell lines both in intrinsic radiosensitivity and in the apparent capacity to repair damage. Retinoic acid is a substance that has previously been reported to increase radiosensitivity, but at concentrations likely to have cytostatic effects or induce cellular differentiation. We chose several head and neck cancer cell lines to investigate radiation sensitivity and synergism in combination with retinoic acid. Material and Methods: Seventeen head and neck cancer cell lines (MDA886, P1, P13, A-431, PCI-50, UMSCC-10A, UMSCC-10B, UMSCC-11A, UMSCC-11B, UMSCC-17A, UMSCC-17B, UMSCC-19, UMSCC-22B, UMSCC-30, UMSCC-38, 1YA, 1YB) are irradiated with variable dose of radiation (1 Gy, 5 Gy, 9 Gy) for determination of radiosensitivity of each cell lines. The less radiosensitive cell lines are treated with retinoic acid for evaluation of the effects of retinoic acid on cellular X-ray sensitivity and recovery from X ray-induced potentially lethal damage. RESULTS: Lowest growth inhibition rates are seen UMSCC-11A and 1YA cell lines in 1 Gy, so that we treated with retinoic acid such cell lines. We obtained the following RESULTS: 1) two cell lines appear not inhibitory effect on recovery from X-ray induced potentially lethal damage but growth inhibition synergism when irradiated with retinoic acid in 1 Gy of radiation dose. 2) two cell lines were little effect on radiosensitivity and inhibitory effect on recovery from X-ray damage in 0.5 Gy radiation dose. CONCLUSION: We found that direct radiosensitizing effects of retinoic acid on 1 Gy of radiation dose may act synergistically for cell growth inhibition in vitro study(three cell lines: UMSCC-11A, 1YA, UMSCC-11B). Further in vitro and in vivo experiments are now necessary to evaluate retinoic acid as radiosensitizer for head and neck cancer radiation therapy.
Carcinoma, Squamous Cell* ; Cell Line* ; Head and Neck Neoplasms ; Head* ; Humans* ; Neck* ; Radiation Dosage ; Radiation Tolerance ; Radiation, Ionizing ; Radiation-Sensitizing Agents ; Robenidine ; Tretinoin*