Biomedical subjects

H Tsuchiya

Publications and source records attributed to H Tsuchiya.

329 records · Page 19Linked to original sources

PubMedDate not supplied

Plasminogen activator inhibitor-1 accelerates lung metastasis formation of human fibrosarcoma cells.

We have studied the effects of PAI-1 on the formation of metastasis using human fibrosarcoma cells and DNA transfection. A clone (1-3C), which shows low constitutive expression of PAI-1 and low metastatic potential to the lung, was selected from human fibrosarcoma cell line HT-1080. Newly-derived clones transfected with human PAI-1 cDNA showed a 3-5 fold increase in the antigen level of PAI-1. Further, these clones demonstrated a significant increase in both the number and incidence of lung metastases when inoculated into the tail vein of athymic mice. PAI-1 could be a prognostic marker and a target for understanding the physiology of metastasis, as well as for the treatment and prevention of hematogenous lung metastasis.

Animals↗

PubMedDate not supplied

Disappearance of Ewing's sarcoma following bacterial infection: a case report.

We report a patient with multiple metastases of Ewing's sarcoma in whom the tumor vanished after a bacterial infection. To the best of our knowledge, no comparable case with Ewing's sarcoma has been reported in the literature. The patient was a 17-year-old male who had an irregular destructive lesion of the left pelvis on radiologic examination. Pathologic examination of a biopsy specimen revealed Ewing's sarcoma. After the operation, a roentgenogram showed multiple spinal metastases with paraplegia. Despite initiation of chemotherapy, a subsequent bone scan showed several areas of increased uptake indicating multiple metastatic lesions. A fistula with purulent discharge opened at the operative site. While being treated with antibiotics and fistula irrigation, the fistula narrowed and his high fever subsided. During this period, radiologic examinations indicated that the multiple bone metastases had nearly disappeared. Nine years after the operation, the patient is alive without any evidence of tumor. We postulate that the antitumor activity in this patient resulted from the bacterial infection, and believe that this case supports continued consideration of immunotherapy for cancer.

Adolescent↗

PubMedDate not supplied

Caffeine-assisted chemotherapy and minimized tumor excision for nonmetastatic osteosarcoma.

Osteosarcoma is usually treated with intensive preoperative and postoperative chemotherapy and wide tumor resection, resulting in a 60% to 70% 5-year survival rate. Caffeine has a DNA-repair inhibiting effect. We therefore investigated the impact of caffeine given in conjunction with chemotherapy and limb-sparing surgery on survival and local tumor control in patients with nonmetastatic, high-grade osteosarcoma. Twenty-two patients were given 3 to 5 preoperative courses of intra-arterial cisplatin (120 mg/m2, 1 to 2 hours) and caffeine (1.5 g/m2/day x 3 days) with or without doxorubicin (30 mg/m2/day x 2 days). Following this treatment, limb-sparing surgery was performed by means of intentional marginal excision aiming at preservation of important structures such as major neurovascular bundles, tendons, ligaments and the epiphysis. Three courses of cisplatin and doxorubicin combined with caffeine, and high-dose methotrexate with vincristine and citrovorum factor rescue were given intravenously as postoperative chemotherapy for 21 patients and three courses of high-dose methotrexate and combination of ifosfamide, etoposide and methotrexate for 1 patient. Following the preoperative chemotherapy, there were no viable tumor cells in 19 patients, only scattered foci of viable cells in 2 patients, and some areas of viable tumor cells in 1. The 21 patients with a good chemotherapeutic response on radiographs underwent minimized marginal excision. Functional evaluation of the affected limbs was excellent for 17 patients, good for 3, fair for 1, and poor for 1. No local tumor recurrence was seen in this series. Eighteen patients remain disease-free with a mean follow-up of 61 months. Two patients died of metastatic disease, 1 died of chemotherapy-related complications, and 1 died of unknown causes. The overall 5-year cumulative survival rate was 90%, and the 5-year event-free survival rate was 75%. Chemotherapeutic caffeine enhanced tumor necrosis and improved the success rate of limb-sparing surgery using marginal procedure without any adverse impact on survival. The results of our limited clinical trial appear to justify further prospective, multicenter randomized trials of the benefits of caffeine combined with chemotherapy for nonmetastatic osteosarcoma and other malignant neoplasms.

Adolescent↗

PubMedDate not supplied

Establishment and characterization of an acquired cisplatin-resistant subline in a human osteosarcoma cell line.

A cisplatin (CDDP)-resistant human osteosarcoma cell line (OST/R) was established by continuous exposure to CDDP. OST/R cells proved to be 6.73 times more resistant to CDDP compared with parental OST cells, and showed cross-resistance to carboplatin (CBDCA). The mechanism of CDDP resistance was a significant decrease of intracellular platinum accumulation which was 40% of that in OST cells. OST/R cells were exposed to CDDP for 6 hours, the platinum was released from the cytoplasm of OST/R cells without reaching a state of equilibrium. DNA synthesis in OST/R cells was not inhibited by CDDP exposure, while in OST cells it was reduced by 50%. These data provide the first evidence that the increased efflux of platinum may play an important role in CDDP-resistance.

Antineoplastic Agents↗

PubMedDate not supplied

Caffeine-potentiated chemotherapy and conservative surgery for high-grade soft-tissue sarcoma.

We report here the results of preoperative and postoperative caffeine-potentiated chemotherapy and limb-sparing surgery for soft-tissue sarcomas. Thirty-six patients with histologically high-grade soft-tissue sarcomas were treated with caffeine-potentiated chemotherapy and conservative surgery (25 cases of limb-sparing surgery and 11 of local tumor excision). There were 13 patients with malignant fibrous histiocytoma (MFH), eight with synovial sarcoma, five with liposarcoma, four with malignant schwannoma, four with epithelioid sarcoma, one with leiomyosarcoma and one with extraskeletal chondrosarcoma. Nine patients were at stage III with lung metastasis and the other 27 at stage IIB without metastasis; 22 were male and 14 female with a mean age of 48 years, ranging from 16 to 77. For intra-arterial preoperative chemotherapy, we administered 2-5 courses of cisplatin (120 mg/m2), doxorubicin (30 mg/m2 x 2 days), and caffeine (1.5 g/m2 x 3 days) to 18 patients, and cisplatin and caffeine to the other 18. Although 15 patients had already undergone unplanned tumor excision at other hospitals before preoperative chemotherapy, all patients underwent definitive limb-sparing surgery after the preoperative chemotherapy. Surgical margins were wide for 28 patients, marginal for three and intralesional for five. Local tumor recurrence was seen in one patient with MFH and one with epithelioid sarcoma. Of the 27 stage IIB patients, lung metastasis newly developed in one with MFH, three with synovial sarcoma, two with malignant schwannoma and one with leiomyosarcoma. As for the effects of preoperative chemotherapy in the 33 eligible cases, radiographically confirmed complete response was seen in two patients, partial response in 20 and no response in 11. Histological response to this preoperative chemotherapy consisted of grade I (no response) in 14, grade II (50-90% necrosis) in four, grade III (> 90% necrosis) in eight, and grade IV (no viable cells) in seven cases. An overall objective response rate of 73% was obtained. With the mean follow-up period of 58 months (5-101 months), the overall 5-year cumulative survival rate ascertained with the Kaplan-Meier method was 63% and that of stage II patients 81%. Eight of the nine stage III patients died of metastatic disease within two and a half years from the beginning of the treatment. In conclusion, caffeine-potentiated chemotherapy and limb-sparing surgery brought good results for stage II nonmetastatic soft-tissue sarcomas. The problem of treatment for stage III metastatic soft-tissue sarcomas, however, remains unsolved.

Adolescent↗