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S Masunaga

Publications and source records attributed to S Masunaga.

104 records · Page 6Linked to original sources
PubMedDate not supplied

Clinical results of thermoradiotherapy for locally advanced and/or recurrent breast cancer--comparison of results with radiotherapy alone.

From August 1979 until 1988, 26 breast cancer patients with 30 tumours were treated by hyperthermia in combination with radiotherapy. Of the 30 tumours, 11 were locally advanced primary tumours (group 1), six were locally advanced recurrent tumours after operation (group 2) and 13 were locally recurrent tumours after radiotherapy (group 3). The thermal profiles showed that the capability of an RF capacitive heating device is comparatively high for large breast tumours with a volume of more than 100 cm3, and that of a 430 MHz microwave device with a single-lens applicator is excellent for localized tumours. The response rate of group 1 and 2 tumours was excellent, and superior to that of historically controlled tumours that were treated by radiotherapy alone from July 1962 until August 1979. In group 3 the tumour response to thermoradiotherapy was not different from that to radiotherapy, but the possibility of significantly reducing total irradiation dose was indicated. More than one good heating session led to a significantly high local response, and factors having a tendency to influence local response were average minimum tumour temperature, tumour volume, and number of effective heat treatments.

Adult↗
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Site-specific phase I, II trials of hyperthermia at Kyoto University.

Site-specific phase I, II trials of locoregional hyperthermia undertaken at Kyoto University are briefly reviewed. Thermometry analysis demonstrated the usefulness of RF (radiofrequency) capacitive heating equipment in the treatment of various subsurface or deep-seated tumours including locally advanced breast cancers, soft tissue tumours, lung cancers involving the chest wall, liver tumours, unresectable or recurrent colorectal cancers, and invasive urinary bladder cancers. The difficulty in heating whole tumour volume or hypervascular tumours to therapeutic temperatures was also shown. Non-randomized trials for locally advanced breast cancers, unresectable or recurrent colorectal cancers and invasive urinary bladder cancers demonstrated a higher response rate in thermoradiotherapy than in radiotherapy alone. The complications associated with treatment were not generally serious except for chronic bowel damages in a trial for colorectal cancers. These promising phase I, II trials encourage the future phase III trials.

Breast Neoplasms↗
PubMedDate not supplied

Development of intra-arterial hyperthermia using a dextran-magnetite complex.

Dextran-magnetite complex (DM) is a colloidal sol of subdomain magnetite particles (i.e. a 'magnetic fluid'). The specific absorption rate of DM in an AC magnetic field is much higher than those of multidomain ferrite particles due to its different mechanism of heat generation. We designed two DM-containing embolic materials (a DM/Lipiodol emulsion and a DM/degradable starch microsphere suspension) to heat target tissues with the use of an external AC magnetic field. In vitro experiments showed that the heat-generating capacity of DM was not reduced in these mixtures. When these materials were injected into the renal arteries of Japanese white rabbits, they both achieved embolization of the artery and selective heating of the embolized kidney by exposure to a 100 kHz AC magnetic field of approximately 15,000 A/m. Histological examination showed a homogeneous distribution of DM in the embolized kidney. These results suggest the possibility of using DM-containing embolic materials for inductive hyperthermia.

Animals↗
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Clinical results of thermoradiotherapy for soft tissue tumours.

Thirty-one unresectable and/or recurrent soft tissue tumours in 27 patients underwent hyperthermia in combination with radiation therapy. Locoregional hyperthermia was administered once or twice a week for 40-60 min to a total of 2-14 sessions using RF capacitive or microwave heating equipment. Radiation therapy was given 10-20 min before hyperthermia at doses of 20.8 to 70 Gy. The mean +/- SD of the maximum, average, and minimum intratumour temperatures was 44.0 +/- 2.9 degrees C, 42.3 +/- 1.6 degrees C, 40.1 +/- 1.1 degree C respectively, and that of the percentage of the intratumour points that exceeded 41 and 43 degrees C was 66.0 +/- 33.6, and 31.0 +/- 26.1 respectively. Of the 31 tumours treated, 13 (42%) showed CR (complete regression), 10 (32%) PR (> 50 and < 100% regression) and 8 (26%) NC (< 50% regression). Since intratumour low density areas on post-treatment CT scans have been demonstrated to be a useful parameter for assessing tumour response to thermoradiotherapy, the presence of low density areas was also assessed. Low density areas were classified into the following three categories according to the percent area occupied in the maximal cross-section of the tumour: type I, < 50%, type II, 50-80%; type III, > 80%. Of 20 tumours evaluable, 6 (30%) exhibited type III change, 11 (55%) type II and 3 (15%) type I. All of the type III tumours demonstrated a marked response on follow-up or histopathological examination. The major complication associated with treatment was skin ulcer in two patients. The five-year survival of the total 27 patients and 18 patients who had no distant metastases at the start of treatment was 32 and 48% respectively. These results indicate the clinical benefit of thermoradiotherapy using RF capacitive or microwave equipment for locally advanced and/or recurrent soft tissue tumours.

Adult↗
PubMedDate not supplied

Clinical experiences in the thermoradiotherapy for advanced gastric cancer.

Recurrent and/or inoperable gastric cancer has been treated by thermoradiotherapy at Kyoto University Hospital since 1983. In the present study, the efficacy of hyperthermia (using radiofrequency capacitive heating) plus radiotherapy for gastric cancer was evaluated in 21 patients with local recurrence, abdominal wall metastases, peritonitis carcinomatosis or paraaortic node metastases. The intratumour temperature was measured using a microthermocouple thermometer. The means of the maximum, average, and minimum intratumour temperature were 43.5, 42.1, and 41.1 degrees C respectively. The local tumour response was evaluated using computed tomography (CT). The local response rate (complete regression plus partial regression/all tumours) was 88.9%, which seemed to be higher than that of other reports using thermochemotherapy or radiotherapy alone. The one-year cumulative survival rate was 39.1%.

Adult↗
PubMedDate not supplied

Thermoradiotherapy of superficial and subsurface tumours: analysis of thermal parameters and tumour response.

Between 1988 and 1993, 57 superficial and subsurface tumours of various tumour type were treated with a 430-MHz microwave heating device. Mean (range) tumour depth of the 57 tumours was 3.0 (0.5-6.5) cm. Fifty-four tumours were treated with thermoradiotherapy. Total radiation dose ranged from 20 to 70 Gy with a mean of 53 Gy. For the remaining three tumours, thermochemotherapy was performed. Hyperthermia was given once a week, and a total of 207 heat sessions was administered. Our goal of hyperthermia treatment was to elevate all monitored tumour points > 41 degrees C for > 30 min. The mean (range) number of intratumoral thermometry points was 3.7 (2-6). The goal of hyperthermia treatment was achieved in 49% of the sessions. At the time of maximum tumour regression, complete response was noted in 53% of the tumours treated with thermoradiotherapy. Univariate analysis demonstrated that parameters including tumour type (breast cancer versus others), tumour depth, minimum tumour temperature, average tumour temperature, minimum equivalent time at 43 degrees C, and number of heat sessions achieving the treatment goal significantly affected the tumour response of the combined treatment, while total radiation dose and number of heat sessions were not significant factors for tumour response. Multivariate logistic analysis revealed that only tumour depth (< 3 versus > or = 3 cm) was a significant prognostic factor for tumour response (p = 0.029). Tumour type (breast cancer versus others) and a number of heat sessions achieving the treatment goal (0-1 versus 2-5) were found to be of borderline significance in the multivariate analysis (p = 0.075 and 0.097 respectively). The number of heat sessions achieving a minimum tumour temperature of > 41 degrees C for > 30 min seems a practical thermal parameter that influences tumour response. The present study indicates the importance of quality and quantity of heat session on the treatment outcome of thermoradiotherapy.

Adolescent↗
PubMedDate not supplied

Alteration in the hypoxic fraction of quiescent cell populations by hyperthermia at mild temperatures.

We investigated oxygenation of quiescent (Q) tumour cells in vivo by mild heat treatment. C3H/He mice bearing SCC VII tumours received BrdU continuously for 5 days via implanted mini-osmotic pumps, to label all proliferating (P) cells. The tumours were then irradiated after treatment, and were excised, minced and trypsinized. The tumour cell suspension thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling was determined using immunofluorescence staining for BrdU. This MN frequency was then used to calculate the surviving fraction of unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total (P + Q) tumour cells. Thus, a cell survival curve could be determined for the cells not labelled with BrdU, which can be regarded as the Q cells in a tumour for all practical purposes. The MN frequency in total tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. Assays performed immediately after irradiation of both normally aerated and hypoxic tumours showed that Q cells contained higher hypoxic fractions than the total tumour cell population. Mild heat treatment (40.0 degrees C, 60 min) before irradiation decreased the hypoxic fraction, even when is was combined with nicotinamide administration. In contrast, mild heating did not decrease the hypoxic fraction when the mice were placed in a circulating carbogen (95% O2/5% CO2) chamber. Therefore, mild heat treatment was thought to preferentially oxygenate the chronically hypoxic fraction.

Animals↗
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Potentially lethal damage repair by total and quiescent tumor cells following various DNA-damaging treatments.

After continuous labeling of proliferating (P) cells with 5-bromo-2'-deoxyuridine (BrdU) for 5 days, SCC VII tumor-bearing mice received various kinds of DNA-damaging treatments: gamma-ray irradiation, tirapazamine (TPZ, hypoxia-specific cytotoxin) administration, or cisplatin injection. From 0.5 to 72 hr after treatment, tumors were excised, minced, and trypsinized. Single tumor cell suspensions were incubated for 48 hr with a cytokinesis-blocker, cytochalasin-B. Then, the micronucleus (MN) frequency for BrdU-unlabeled cells, quiescent (Q) cells at treatment, was determined using immunofluorescence staining for BrdU. The MN frequency for total (P+Q) cells was obtained from tumors that were not pretreated with BrdU labeling. The sensitivity to each DNA-damaging treatment was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Treatment with gamma-rays or cisplatin resulted in a larger MN frequency in total cells than in Q cells. In contrast, TPZ treatment produced a smaller MN frequency in total cells than in Q cells. Regardless of the treatment used, Q cells showed greater repair capacities than total cells. However, TPZ caused much smaller repair capacity in both total and Q cells, compared with gamma-rays or cisplatin. Gamma-rays and cisplatin produced similar repair patterns. Differences in sensitivity between total and Q cells and repair patterns of the two cell populations were thought to depend on differences between the two cell populations in the toxicity of the DNA-damaging treatment and distribution pattern of the anticancer agent.

Animals↗
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Sensitizing effect of the phosphatidylinositol 3-kinase inhibitor wortmannin on thermal neutron irradiation with or without boron compound.

Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to be an efficient radiosensitizer. We have investigated the radiosensitizing effect of wortmannin on cell killing against thermal neutrons produced by the Kyoto University Research (KUR) reactor. Wortmannin was added to cells 2 hours before irradiation and removed 16 hours after irradiation. Cells were irradiated by thermal neutrons with or without boron at 0, 10, and 20 ppm. The biological end point of cell survival was measured by colony formation assay. The D0 values of thermal neutrons in different boron concentrations, 0, 10, and 20 ppm were 1.2, 1.1, and 1.0 Gy, respectively. When cells were treated with wortmannin, the D0 values decreased to 0.5, 0.6, and 0.8 Gy at boron concentrations of 0, 10, and 20 ppm, respectively. Wortmannin enhanced cell death against thermal neutron irradiation especially in the absence of boron. Thus, our results suggest that wortmannin may be useful to combine with boron neutron capture therapy (BNCT) treatment when boron uptake by cells is limited.

Androstadienes↗
PubMedDate not supplied

Effect of caffeine on gamma-ray induced G2 arrest in well-synchronized Chinese hamster ovary cells in vitro.

G1-rich cells were separated from exponentially growing asynchronous cultured Chinese hamster ovary (CHO-K1) cells by centrifugal elutriation and a Coulter Counter. The G1-rich cells were incubated in medium that contained hydroxyurea (HU) to kill S phase cells and obtain the purest G1/S boundary cells possible. The HU-treated cells were washed, and were again incubated, in medium without HU, to allow these well-synchronized G1/S boundary cells to progress to S and G2/M phases. At various times after release from G1/S boundary, 4 Gy of gamma-ray and/or caffeine was administered to the cells. Eight hours after the removal of HU, cell-cycle analysis was performed with a flow cytometer. G2 arrest induced by gamma-rays was clearly shown when radiation was given earlier than 6.5 hours after HU removal. G2 arrest induced by radiation given 0.5-6.5 hours after HU removal was reduced by caffeine treatment given 6.0-6.5 hours after HU removal. Caffeine released radiation-induced G2 arrest when the radiation was given before the cultured cells entered G2/M phase and when caffeine was applied to the irradiated cells at the time when G1/S boundary cells not treated by radiation or with caffeine entered G2/M phase. Our method of centrifugal elutriation combined with incubation with HU was useful for isolating pure G1/S boundary cells from in vitro asynchronous cultures.

Animals↗
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Determination and drug modification assessed by micronucleus frequency assay of potentially lethal damage repair in quiescent cell populations within murine solid tumors.

We investigated potentially lethal damage repair (PLDR) by quiescent (Q) tumor cells in vivo. SCC VII tumor-bearing C3H/He mice were irradiated with 60Co gamma-rays after being given 10 injections of 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in their tumors, and the tumors were than excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (Cyt-B, a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling was determined using immunofluorescence staining for BrdU. Thus, the MN frequency was determined for cells not labeled by BrdU; for all practical purposes, such cells can be regarded as the Q cells in a tumor. The MN frequency in the total (P + Q) tumor cell population was determined from irradiated tumors that were not pretreated with BrdU. Assays were performed immediately after irradiation alone, 24 hours after the injection of cis-diaminedichloroplatinum(II) (CDDP), mitomycin C (MMC), misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] (MISO), 3-aminobenzamide (3-AB), camptothecin (CPT) or caffeine (CAF) following irradiation, and 24 hours after irradiation alone. Q cells were more radioresistant and had a greater capacity for PLDR than the tumor cell population as a whole. CDDP and MISO (especially the latter) inhibited PLDR more strongly in Q cells than in the tumor cell population as a whole. However, CPT and CAF exerted similar inhibition of PLDR in Q cells and in the tumor cell population as a whole. This assay method appears to be useful for detecting the responses of Q tumor cells to various chemical agents.

Animals↗
PubMedDate not supplied

Resistance to 195mPt-radiolabeled cis-diaminedichloroplatinum (II) of SHOK cells transfected with various oncogenes.

SHOK (Syrian hamster Osaka-Kanazawa) cells were transfected with activated oncogenes (v-mos, c-myc, N-ras, H-ras, K-ras). These oncogene-transfected cells were treated with 195mPt-cis-diaminedichloroplatinum (II) (CDDP). Clonogenic cell survival assay showed that oncogene-transfected cells exhibited 1.3-4.8 fold (v-mos; 2.4, c-myc; 3.6, N-ras; 1.3, H-ras; 4.8, K-ras; 2.3) increased resistance to cisplatin compared with the parental SHOK cells. The distribution of DNA, RNA, and protein fractions of treated cells was determined using the method of Schneider. The CDDP concentrations binding to DNA, RNA, and protein were measured by counting 195mPt-radioactivity. CDDP uptake was decreased in these oncogene-transfected cells. However, the range of reduction of CDDP uptake in DNA was smaller than the resistance range demonstrated in the cell killing efficiency.

Animals↗
PubMedDate not supplied

Enhancement of cisplatin sensitivity of quiescent cells in solid tumors by combined treatment with tirapazamine and low-temperature hyperthermia.

We examined the enhanced chemosensitivity of quiescent (Q) cells in solid tumors to cis-diamminedichloroplatinum (II) (cisplatin) by combined treatment with tirapazamine (TPZ) and mild heating. C3H/He and Balb/c mice bearing SCC VII and EMT6/KU tumors, respectively, received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. TPZ was administered intraperitoneally 2 h before cisplatin injection and/or tumors were locally heated at 40 degrees C for 60 min immediately after cisplatin injection. Sixty minutes after cisplatin injection, the tumors were excised, minced and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P+Q) tumor cells was determined from the tumors that were not pretreated with BrdU. The sensitivity to cisplatin was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Other groups of tumor-bearing C3H/He and Balb/c mice not given BrdU were injected with 195mPt-radiolabeled cisplatin. In both tumor systems, the MN frequency in Q cells was lower than that in the total cells. TPZ and mild heat treatment elevated the MN frequency in total and Q cells in both tumor systems, and to a higher extent in Q cells. The combination of TPZ and mild heat treatment increased the MN frequency more markedly than treatment with either TPZ or mild heating alone. In total tumor cells, TPZ and mild heat treatment increased the MN frequency in EMT6/KU tumor cells more markedly than in SCC VII tumor cells. 195mPt-labeled cisplatin uptake into total tumor cells was increased by mild heat treatment but not by TPZ. The cisplatin-sensitivity of Q cells was lower than that of total cells in both tumor systems. TPZ was thought to sensitize Q cells by killing the hypoxic cells without influencing tumor blood flow, and mild hyperthermia appeared to sensitize Q cells by distributing more cisplatin with an increase in blood flow in solid tumors.

Animals↗