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Biomedical subjects

Kozo Morita

Publications and source records attributed to Kozo Morita.

8 recordsLinked to original sources

Randomized phase II study of immunomodulator Z-100 in patients with stage IIIB cervical cancer with radiation therapy.

OBJECTIVE: To find the optimal dose of immunomodulator Z-100 in patients with stage IIIB squamous cell carcinoma of the cervix in combination with radiation therapy. METHODS: The patients were randomly assigned to the dosage levels of 2, 20 or 40 mug of Z-100. Z-100 was subcutaneously injected twice a week during radiotherapy and once in two weeks during the maintenance period. The response rate after radiotherapy was evaluated, and the optimal clinical dosage was then determined. Safety of Z-100 was evaluated during the radiation therapy and maintenance therapy. Survival was also evaluated. RESULTS: A total of 116 patients were entered. The adverse reactions were not dose-dependent and no serious toxicities were observed. The response rates were 72.2% (26/36) in the 2 microg group, 84.6% (33/39) in the 20 microg group and 94.3% (33/35) in the 40 microg group (P = 0.006). However, the survival was not significantly different. CONCLUSIONS: The optimal dose of Z-100 was determined to be 40 mug in combination with radiation therapy for stage IIIB cervical cancer. However, impact of Z-100 on survival must be determined by the placebo controlled randomized trial, because survival benefit was not observed in this small population study.

Adolescent↗

Elective neck irradiation on ipsilateral side in patients with early tongue cancer for high-risk group with late cervical lymph node metastasis.

A prospective study was performed to assess the efficacy of elective neck irradiation (ENI) on the ipsilateral side in patients with early tongue cancer among a high-risk group with late cervical lymph node metastasis. Patients in the high-risk group had T2-tumors, excluding superficials or T1-tumors > or =19 mm in maximal diameter with invasion or ulcer. Between February 1989 and October 1997, 70 patients with tongue cancer of Stages I and II were enrolled in the present study (ENI group: 31, non-ENI group: 39). In a combination therapy of external beam irradiation and brachytherapy, the standard dose of interstitial brachytherapy for primary tumors was approximately 60 Gy. Irradiation was initiated with a 9-MeV electron beam at a dose of 50 Gy on the ipsilateral side of the neck only when the day of brachytherapy approached. Three patients (9.7%) in the ENI group had neck lymph node metastasis as did 5 (12.8%) in the non-ENI group (p= 0.684). In patients with ulceration, the incidence of subsequent lymph node metastasis was significantly higher (p=0.029). Neck lymph node metastasis occurred in 2 (16.7%) of 12 patients with ulcers in the ENI group and in 2 (66.7%) of 3 with ulcers in the non-ENI group. Although we could not demonstrate the significant efficacy of ENI in the high-risk group in this study, ENI decreased the neck lymph node metastasis. In addition, our results suggested that ENI particularly inhibits cervical lymph node metastasis in tongue tumor patients with ulcers.

Adult↗

CD24 is expressed specifically in the nucleus pulposus of intervertebral discs.

Intervertebral disc (IVD) consists of a soft gelatinous material in its center, the nucleus pulposus (NP), bounded peripherally by fibrocartilage, annulus fibrosus (AF). Despite the number of patients with IVD degeneration, gene expression analysis has not been undertaken in NP and therefore little is known about the molecular markers expressed in NP. Here, we undertook a microarray screen in NP with the other nine tissues to identify the specific cell surface markers for NP. Five membrane associating molecules out of 10,490 genes were identified as highly expressing genes in NP compared with the other tissues. Among them, we identified CD24, a glycosylphosphatidylinositol (GPI) anchor protein as a cell surface marker for NP. CD24 expression was also detected in the herniated NP and chordoma, a malignant primary tumor derived from notochordal cells, while it was absent in chondrosarcoma. Therefore, CD24 is a molecular marker for NP as well as the diseases of IVD.

Animals↗

DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells.

Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell-specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP-deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes despite normal expression of osteoclast markers and cytoskeletal structure. As osteoclast multinucleation was restored by retroviral introduction of DC-STAMP, loss of cell fusion was directly attributable to a lack of DC-STAMP. Defects in osteoclast multinucleation reduce bone-resorbing activity, leading to osteopetrosis. Similar to osteoclasts, foreign body giant cell formation by macrophage cell fusion was also completely abrogated in DC-STAMP-deficient mice. We have thus identified an essential regulator of osteoclast and macrophage cell fusion, DC-STAMP, and an essential role of osteoclast multinucleation in bone homeostasis.

Animals↗

[Surgical repair of a large isolated internal iliac artery aneurysm presenting with acute renal failure. A case report].

A 71-year-old man was suffering from a large right internal iliac artery aneurysm (rt. IIAA) associated with acute renal failure secondary to bilateral hydronephrosis. Immediately after admission, we performed resection of the rt. IIAA and right common iliac artery-external iliac artery bypass. Postoperative recovery was uneventful and renal function improved. We should consider that a large isolated IIAA may uncommonly cause acute renal failure secondary to hydronephrosis. Expeditious surgical intervention may provide a complete recovery from acute renal failure.

Acute Kidney Injury↗

Radiation therapy for metastatic brain tumors from lung cancer--a review to devise individualized treatment plans.

We retrospectively analyzed patients with brain metastasis from lung cancer to evaluate treatment modalities for metastatic brain tumors and to devise criteria for individualized treatment plans. Between October, 1986 and December, 1994, 90 patients were selected for this study. The majority (67.8%) received whole-brain radiotherapy (WBRT) alone. WBRT following surgical removal was carried out on 14 patients (15.5%). The median dose of radiation therapy was 43.3 Gy for WBRT. The results were as follows: (1) PS (1 and 2 vs. 3 and 4), which showed a significant difference (p < 0.0001) in survival by both univariate analysis and multivariate analysis, (2) brain metastasis alone or concurrent metastases to other sites (p = 0.0001) by univariate analysis, (3) the primary lesion controlled or uncontrolled (p = 0.0006) by univariate analysis, (4) solitary brain metastasis or multiple brain metastases (p = 0.0145) by univariate analysis. Patients were classified into 3 groups, A (PS1, 2, the primary lesion controlled, no distant metastasis and solitary brain metastasis), B (others except for groups A and C), and C (PS 3,4) based on 4 significant factors. The 1-year survival rates and median survival times were, respectively 75% and 1,767 days in Group A, 40.6% and 313 days in Group B, and 7.8% and 121 days in Group C (p < 0.0001). Although the possibility of individualized treatment was suggested, based on 4 factors associated with the patient's condition and disease progression before treatment for brain metastasis, further evaluation by randomized clinical trials is needed.

Adult↗

Continuous infusion low-dose CDDP/5-FU plus radiation in inoperable or recurrent non-small-cell lung cancer: preliminary experience.

The combination therapy of continuous infusion low-dose cisplatin plus 5-fluorouracil (5-FU) with radiation for non-small-cell lung cancer (NSCLC) was performed to assess its effectiveness and any adverse reactions. During the period from April 1994 to December 1998, 18 patients with inoperable or recurrent NSCLC at Aichi Cancer Center Hospital had been treated by chemoradiation with continuous infusion of low-dose cisplatin/5-FU. The median total radiation dose was 66 Gy (range: 60-74.4 Gy). The daily doses of cisplatin and 5-FU ranged from 3 to 6 mg/m2, and from 170 to 250 mg/m2, respectively. In 18 total patients, a complete response was achieved in 4 patients (22%), and a partial response was observed in 12 patients (67%). Grade III toxicity was limited to leukopenia (14.3%). The 1-year and 2-year survival rate in 14 previously untreated patients were 77.4% and 53.1%, respectively. This combination therapy is a well-tolerated regimen. In the future, a study protocol should be designed with a dose-escalation component to further define the optimal doses and schedule for this regimen.

Aged↗

[Three-dimensional conformal radiotherapy with multi-leaf collimator]

In radiation therapy, it is very important to concentrate the high dose to the clinical target volume. For this purpose, S. Takahashi developed the dynamic conformal radiotherapy in 1960. In the first half of 1990' this conformal technique with multi-leaf collimator (MLC) was gradually becoming popular, because the three dimensional extent of the clinical target volume and the surrounding normal tissues was accurately recognized by the use of the serial CT-images, and the 3D-treatment planning was considerably easily obtained by the development of computer-technique. The 3D-CRT (conformal radiation therapy) based on the 3D-treatment planning in a broad sense means the coplanar or non-coplanar irradiation with multi-leaf collimator, and at present it is one of the most reasonable treatment techniques. In order to correspond the high dose region to the clinical target volume as possible, IM (intensity modulation) technique was introduced to the 3D-CRT using MLC in the second half of 1990'. Therefore, the static CRT is routinely used not only in Europe/ USA but also in Japan. But, it is often very difficult to obtain the concave high dose region in static CRT with MLC, even though the IM-technique is applied. At this occasion, the concave high dose region is easily obtained by the use of dynamic CRT such as the hollowed -out technique developed by S. Takahashi in Japan. The dynamic CRT technique is also useful with the static IM-CRT technique. There are two main aims of conformal radiotherapy: First, the protection of the surrounding normal tissues, and second, improvement of the local control rate. Usually the second aim can't be easily achieved, because the tumor control probability curves are often flat. The DVH concept is usually valuable to choose the optimal treatment planning. But, it is difficult to find the optimal dose-distribution, when two DVH-curves cross each other on the middle range of irradiated dose. On that occasion, the NTCP-concept is useful. From the standpoint of the tolerable dose, normal organs are classified into two types: parallel and serial. Therefore, two types of the NTCP-formula should be prepared to apply the NTCP-concept clinically.

Journal Article↗