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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

450 records · Page 25Linked to original sources
PubMedDate not supplied

Attenuation of live E. coli-induced acute lung injury by X-ray irradiation in guinea pigs.

Irradiation is suspected to injure inflammatory cells, such as neutrophils and mononuclear phagocytes, cells known to contribute to the development of acute lung injury (ALI). This study examined whether preexposure to x-ray irradiation modifies ALI induced by E. coli injected intravenously in guinea pig. Thirty animals were divided into two control and two irradiated subgroups: the first control group received saline only (n = 8), and the second control group received E. coli, 2 x 10(9)/kg body weight, suspended in saline (n = 6), IV. The first irradiated group received a single 12-Gy dose + saline (n = 6), and the second irradiated group received a single 12-Gy dose + E. coli (n = 10). The lung wet-to-dry-weight ratio (W/D) and 125I-albumin lung tissue/plasma ratio (T/P) were measured as markers of lung injury. W/D was significantly higher in the control E. coli group than in the other groups. T/P in the control E. coli group was also increased compared with T/P measured in the other groups. In the control E. coli group, a marked increase in bronchoalveolar lavage (BAL) neutrophils was observed compared with the control saline group. However, no significant difference in BAL neutrophil counts was observed between the control and irradiated E. coli groups. In contrast, BAL macrophages were significantly reduced in the irradiated E. coli groups compared with the control E. coli group. These findings suggest that x-ray irradiation attenuates E. coli-induced ALI in guinea pigs, an effect explained, at least in part, by a reduction in the number of alveolar macrophages.

Analysis of Variance↗
PubMedDate not supplied

Evidence of antisense tumor targeting in mice.

Even though increased accumulations of radiolabeled antisense DNAs compared to control DNAs are becoming a routine observation in cultured tumor cells, trustworthy evidence of tumor targeting in vivo by an antisense mechanism remains elusive. The goal of this study was to obtain convincing evidence of antisense tumor targeting in nude mice by using two different tumors and both intratumoral (i.t.) and intravenous (i.v.) administration of radiolabeled antisense and control sense DNAs. Both the MDR++ cell line KB-G2 and its parent MDR+ cell line KB-31 were used in this study. The antisense (AS) DNA was directed against the AUG start codon of the MDR1 mRNA and, along with the sense (S) control DNA, was a uniform phosphorothioate administered naked. In previous cell culture studies from our laboratories, the accumulation of this AS DNA was strikingly high in KB-G2 cells and only average in KB-31 cells, a fact we attribute to the 1000-fold higher expression by RT-PCR of MDR1 mRNA in the former cell line. In this study, both DNAs were radiolabeled with (99m)Tc via MAG3 and administered i.t. or i.v. at 1 microg (100 microCi) per animal 24 h prior to sacrifice and dissection in mice bearing thigh tumors of about 1 g. Following i.t. administration, no statistically significant differences (Student's t test, p < 0.05, N = 4) between the AS and S DNA biodistributions in normal tissues were observed except in the KB-G2 mice in which muscle levels were lower for the S control. In contrast, tumor levels in the KB-G2 animals were significantly higher for the AS DNA vs S DNA (14.7 vs 8.5% ID/g) while this difference (8.6 vs 4.3% ID/g) was insignificant in the KB-31 animals. The whole body images obtained just prior to sacrifice clearly show improved targeting of AS DNA vs S DNA in the KB-G2 but not the KB-31 animals. Calculations based on these results show that about 60 000 AS DNAs accumulated specifically (i.e. AS DNA - S DNA) per KB-G2 tumor cell following i.t. administration. When administered i.v. rather than i.t., higher tumor levels in KB-G2 animals compared to KB-31 were not observed, most likely because of the lower dosage reaching the tumors. When the KB-G2 and KB-31 results are combined, no statistically significant differences between the AS and S DNA biodistributions in normal tissues were observed except in blood in which S DNA levels were higher and in spleen in which they were lower. In contrast, tumor levels were significantly higher for the AS DNA vs S DNA (0.100 vs 0.063% ID/g). Calculations based on these results show that about 400 AS DNAs accumulated specifically per tumor cell following i.v. administration. Therefore evidence for tumor targeting in vivo by an antisense mechanism has been obtained in that statistically higher tumor accumulations of the (99m)Tc-AS DNA were observed compared to the control (99m)Tc-S DNA both following i.t. and i.v. administrations. The successful localization of AS DNA in tumor demonstrates that in vivo AS targeting of tumor is feasible although improvements in tumor delivery and normal tissue clearance are needed for practical antisense imaging.

Animals↗
PubMedDate not supplied

Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the uterine cervix.

Patients with cervical cancer are subject to postoperative adjuvant therapy if the histopathologic examination reveals parametrial involvement. This study evaluated the patterns of failure in patients with pathologic parametrial invasion (pT2b) treated with adjuvant pelvic irradiation. Between April 1985 and March 1997, 45 patients with pT2b cervical cancer were treated with postoperative pelvic irradiation. The median age was 52 years. Preoperative clinical stages were stage Ib in 8 patients, IIa in 4, and IIb in 33. Twenty-three patients had lymph node metastasis. The median total dose of whole pelvic radiation therapy was 50 Gy. Occurrence of pelvic failure or distant metastasis according to the nodal status was examined. None of the 22 patients without lymph node metastasis developed distant metastasis. Among the 23 node-positive patients, 6 developed distant metastasis as an initial failure site. The 5-year overall survival of the entire group was 78%. The actuarial distant metastasis-free rates at 5 years were 73% and 100% for those with and without pelvic lymph node metastasis, respectively (P = 0.016). Results support previous evidence for chemoradiation in patients with pelvic lymph node metastasis. However, it appears that the role of systemic chemotherapy for node-negative pT2b patients is yet to be established.

Adult↗
PubMedDate not supplied

Breast-conserving therapy for ductal carcinoma in situ.

This retrospective analysis evaluates the treatment results and prognostic factors of 114 patients with ductal carcinoma in situ (DCIS) undergoing breast conserving therapy (BCT) at Keio University Hospital Department of Radiology, between 1988 and 1997. A total of 132 patients with DCIS of the breast came to our hospital between 1988 and 1997, and 114 cases were suitable candidates for BCT. All of the patients were female and ranged in age from 26 to 81 years (median 46). Ninety-one patients were premenopausal, and 23 were postmenopausal. Median clinical tumor size was 2.0 cm (0-8.0 cm). Postoperatively 48 cases received 50 Gy/25 fractions of external irradiation to the whole breast via tangential ports. The follow-up period after treatment ranged from 11 to 162 months (median 46.7). The local relapse-free rate and overall survival rate of the 114 patients were 89.5% and 100%, respectively. Local failure and regional nodal failure occurred in 12 and 1 patient, respectively. Radiotherapy was a significant risk factor for local failure (p=0.05). No postmenopausal patients developed local failure, but the difference did not reach statistical significance (p=0.103). The 12 recurrent cases underwent additional surgery and all remain alive without recurrence, to date, i.e., at least 16 months. Breast-conserving surgery plus irradiation is appropriate treatment for DCIS patients.

Adult↗
PubMedDate not supplied

Postoperative radiation therapy for stage IB-IIB carcinoma of the cervix with poor prognostic factors.

BACKGROUND: To investigate failure pattern and to evaluate the prognostic impact of lymph node metastasis in patients with cervical cancer treated with postoperative adjuvant pelvic irradiation. MATERIALS AND METHODS: Ninety-eight patients with FIGO IB to IIB cervical cancer were treated with radical hysterectomy, bilateral pelvic lymphadenectomy and postoperative radiation therapy. All the patients had at least one of the following pathologic risk factors for pelvic recurrence; 1) positive margins, 2) positive pelvic lymph nodes other than common iliac node, 3) deep stromal invasion more than 50% or parametrial invasion. RESULTS: The 5-year overall survival (OAS) rate for the entire patient group was 82%. Causes of the first failure were pelvic recurrence in 5 cases and distant metastasis in 15 cases. Fifteen of the 47 patients with positive pelvic lymph nodes developed distant metastasis, whereas distant metastasis was noted in only 1 of 51 patients without lymph node metastasis. The 5-year OAS rates for patients with and without pelvic lymph node metastasis were 76% and 89%, respectively (p = 0.018). CONCLUSION: Despite receiving postoperative pelvic irradiation, apparently lower survival was observed for node positive patients.

Adult↗
PubMedDate not supplied

Effect of combined treatment with radiation and low dose etoposide on cell survival.

BACKGROUND: To improve the radiotherapy results, we evaluated etoposide as an effective radiosensitizer by using cultured cell-lines. MATERIALS AND METHODS: Four cell lines having different doubling times (DT) were used: V79 (Chinese hamster fibroblasts, DT = 9 hours), (1), T24 (human bladder cancer, DT = 19 hours) (2), MDA-MB231 (human breast cancer, DT = 25-30 hours) (3) and RMG1 (human ovarian cancer, DT = 50 hours) (4). Cell survival was determined by colony assay and cell cycle analysis was performed by flow-cytometry. RESULTS: The survival curves showed RMG1 to be the most radiosensitive, followed by MDA-MB231, T24, and V79. V79 was most chemosensitive to etoposide, followed by T24, MDA-MB231 and RMG1. Neither 24-hours exposure to etoposide (< or = 0.05 microgram/ml) or 0.5-h exposure (< or = 1.0 microgram/ml) had any cell killing effect on any of the cell lines used. When the cells were irradiated after exposure to 1 microgram/ml of etoposide for 0.5 hours, no radiosensitization was observed in any of the cell lines except V79. Enhanced radiosensitivity was observed in V79 and T24 cells (which have a relatively short DT) when they were incubated with 0.05 microgram/ml etoposide for 24 hours but no enhanced effect was seen in MDA-MB231 or RMG1 cells (which have a relatively long DT). CONCLUSION: It is suggested that a combination of radiation and etoposide may be useful in the treatment of rapidly growing cancer.

Animals↗
PubMedDate not supplied

The role of low-dose hemithoracic radiotherapy for thoracic dissemination of thymoma.

We retrospectively reviewed the records of 11 thymoma patients to clarify the role of hemithoracic irradiation and chemotherapy for patients with thoracic dissemination at the initial presentation. Radiotherapy was administered postoperatively in all but two patients who were not candidates for surgical treatment. Radiotherapy doses ranged from 10 to 17 Gy for the entire hemithorax of the disseminated site and from 30 to 55 Gy to the primary tumor bed. Chemotherapy of various protocols was also employed preceding radiotherapy in seven cases. Cumulative 5- and 10-year survival rates were 80% and 64%, respectively. Regrowth-free 5- and 10-year survival rates were 55% and 37%, respectively. Six of the 11 patients were free from regrowth at a median follow-up interval of 60 months. The role of chemotherapy remained unclear. Acute or late sequelae were modest and acceptable. In conclusion, entire hemithoracic irradiation is justified as postoperative or definitive radiotherapy treatment for disseminated thymoma unless there is a risk of radiation pneumonitis. Further evaluation should be conducted.

Adult↗
PubMedDate not supplied

99mTc-MIBI scintigraphy as an indicator of the chemosensitivity of anthracyclines in patients with breast cancer.

BACKGROUND: Chemoresistance of tumor cells is involved with many factors, one of which is the P-glycoprotein function to pump anthracyclines out of cells. 99mTc-MIBI accumulates in several tumors, and some of these cells wash out 99mTc-MIBI through P-glycoprotein. MATERIALS AND METHODS: We investigated if the wash-out of 99mTc-MIBI from the tumor in fifteen female patients with breast cancer could be related with the chemosensitivity of anticancer agents; doxorubicin (DOX), epirubicin (FAM), pinorubicin (PINO), mitomycin (MMC), cisplatin (CDDP), and 5-fluorouracil (5-FU), in each tumor tissues. The wash-out of 99mTc-MIBI, defined as retention index, was quantified from an early and delayed 99mTc-MIBI imaging. The chemosensitivity of the anticancer agent, and inhibition ratio, was determined in vitro assay by using surgical specimens obtained from patients who underwent 99mTc-MIBI imaging. P-glycoprotein in the surgical specimen was studied by immunohistochemical staining on its paraffin section using a monoclonal antibody. RESULTS: Inhibition ratio of anthracycline agent, DOX, FAM or PINO, was well correlated with retention index of 99mTc-MIBI with coefficient of 0.75, 0.60, or 0.62, respectively, whereas a poor relationship was observed for MMC and CDDP. The retention indices of 99mTc-MIBI were remarkably small for patients in the P-glycoprotein positive group. CONCLUSION: 99mTc-MIBI retention index quantified from its early and delayed scintigraphy is a good indicator to predict the chemosensitivity of anthracyclines in untreated breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗