peplomycin and Disease-Models--Animal

The presence or absence of metastasis bears an important influence on the prognosis of head and neck cancer patients. Neoadjuvant chemotherapy has become widely employed as an initial treatment. However, the actual effectiveness of neoadjuvant chemotherapy on metastasis is still unestablished. Therefore, using an orthotopic implantation model in which cervical lymph node metastasis of oral squamous cell carcinoma can be reproduced, we investigated the inhibitory effect of neoadjuvant chemotherapy on metastasis. A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19 cells, was implanted into the tongues of nude mice. After implantation, the mice were divided into four groups: S (surgery), C+S (preoperative chemotherapy+surgery), S+C (surgery+postoperative chemotherapy), and a control (nontreatment) groups. The treatment (tumor resection or chemotherapy) was started 7 days postimplantation. The effects of each treatment on cervical lymph node metastasis were investigated by examining the rate of lymph node metastasis formation at 28 days postimplantation. In the control group, five of the 11 mice died of cachexia before the end of the experiment. However, all mice in the S, C+S, and S+C groups survived until 28 days after implantation. The cervical lymph node metastasis rates were 81.8% in S, 18.1% in C+S, 63.6% in S+C, and 100% in control groups. Thus, metastasis to the cervical lymph node was markedly inhibited by the combination of neoadjuvant chemotherapy and tumor resection. The findings of this study indicate that neoadjuvant chemotherapy is effective for inhibiting metastasis, and that it is necessary to begin chemotherapy as early as possible to achieve an inhibitory effect on metastasis. Considering these effects, if anticancer drugs are used, better therapeutic results can be expected.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Disease Models, Animal; Female; Humans; Lymphatic Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neck; Neoadjuvant Therapy; Peplomycin; Tongue Neoplasms; Treatment Outcome

The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to achieve successful remission of the lesion. We evaluated the effects of systemic administration and topical application of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound healing of ulcers in the rabbit gingiva.. Almost uniform round ulcers could be created on the gingiva of the rabbits by chemical injury with acetic acid. When the submandibular glands were removed or i.v. injection of cisplatin (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of the ulcers took longer than in untreated rabbits. To ascertain whether or not human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and bFGF on the proliferation of the cells derived from rabbit gingiva. We then applied EGF or bFGF in these impaired healing models.. EGF and bFGF promoted proliferation of the fibroblasts, and EGF also promoted proliferation of the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic injections of EGF and bFGF in rabbits, which had their submandibular glands removed, and topical application of bFGF accelerated healing of ulcers created in rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote the healing of ulcers was much greater than that of EGF.. Basic FGF may be effective for refractory oral mucosal lesions.

Topics: Administration, Topical; Animals; Cell Division; Cisplatin; Disease Models, Animal; DNA; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Gingiva; Humans; Injections, Intravenous; Mouth Mucosa; Oral Ulcer; Peplomycin; Rabbits; Submandibular Gland; Wound Healing

Using an orthotopic implantation model in which oral cancer invasion and metastasis can be reproduced, we investigated the inhibitory effects of anticancer agents on invasion and metastasis.. A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19, was implanted into the oral floor of nude mice, and cisplatin or peplomycin was administered to the mice 7 or 14 days after implantation. The effects of each anticancer drug and different administration timings on cancer invasion and metastasis were investigated.. Tumor size and the ratio of proliferating cell nuclear antigen-positive cells was significantly reduced. In the control group, the tumors showed grade 4C mode of invasion, whereas in the groups treated with anticancer drugs, grade 3 was observed in 77.3% of the mice, with an inhibitory effect on tumor invasion being observed. The rate of metastasis in the cervical lymph node was significantly decreased in the groups treated with the cisplatin or peplomycin on day 7 after implantation. The tumor stage progression in the metastatic lymph nodes was also inhibited.. Chemotherapy is effective not only for tumor diminution but also for inhibiting invasion and metastasis. In light of these effects, administration of anticancer drugs may be clinically useful in this regard.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line; Cisplatin; Disease Models, Animal; Drug Administration Schedule; Lymphatic Metastasis; Mice; Mice, Nude; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Metastasis; Peplomycin

In an attempt to improve the combined effects of hyperthermia and anti-cancer drugs, an intratumorous (i.t.) injection of the drugs was performed and its effect compared with that obtained by intraperitoneal (i.p.) injection. Using Lewis lung carcinoma growing in the legs of BDF1 mice, weakly toxic drug derivatives, Aclarubicin (ACR), a new platinum complex (DWA2114R), or Peplomycin (PEP) were injected either into the center of the tumors, or intraperitoneally, before or after usual hyperthemia in a 43.5-43.7 degrees C water bath for 45 min. The effects on tumor growth delay and the number of lung metastases were assessed, and the enhancement ratios (ERs) due to the combination were calculated. Tumor growth inhibition by i.t. injection was enhanced additively with ACR (ER; 1.2) and synergistically with DWA2114R (ER; 3.49) and PEP (ER; 2.4) plus hyperthermia. Hyperthermia after i.t. injections of DWA2114R (ER; 3.4) was more effective than either i.t. or i.p. injections after hyperthermia (ER; 2.4). Lung metastases were also inhibited significantly by the combination of hyperthermia and drugs, except when emulsified PEP was injected three times. It was concluded that the i.t. injection of DWA2114R was of value when used in combination with hyperthermia.

Topics: Aclarubicin; Animals; Antineoplastic Agents; Carboplatin; Carcinoma, Lewis Lung; Combined Modality Therapy; Disease Models, Animal; Female; Hyperthermia, Induced; Injections, Intralesional; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Peplomycin

A new animal model for intravesical chemotherapy of bladder cancer was prepared by transplanting BC-47 cells into the bladder wall of syngenic ACI/N rat and later transurethral cauterization of the urothelium covering the developed solid tumor, and compared with two common models. One of the models was prepared by similarly transplanting the tumor cells without further treatment and another by transurethral instillation of the tumor cells into cauterized bladder. Tumor transplantation and denudation were both 100% successful in the new model and was superior to those in two common models. The new model was more sensitive to peplomycin than the common model prepared by transplanting the tumor cells into bladder wall without cauterization of the urothelium, while the sensitivity to adriamycin were practically the same as that of the common model. This difference may be due to presence of the urothelium, which seemed to inhibit a contact of intravesically administered peplomycin with tumor. It could be considered that the new model with denuded tumor has a high predictivity on the clinical effect for drug candidates.

Topics: Administration, Intravesical; Animals; Bleomycin; Disease Models, Animal; Doxorubicin; Female; Neoplasm Transplantation; Peplomycin; Rats; Rats, Inbred ACI; Urinary Bladder; Urinary Bladder Neoplasms