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Biomedical subjects

S Masunaga

Publications and source records attributed to S Masunaga.

At least 91 records · Page 5Linked to original sources

Regional hyperthermia combined with radiotherapy in the treatment of lung cancers.

Twenty locally advanced lung cancers were treated by hyperthermia in combination with radiotherapy between November 1980 and January 1990. All tumors selected had invaded or were in contact with the chest wall, so that transcutaneous insertion of thermal probes into the tumor was possible. Using an 8 or 13.56 MHZ RF capacitive heating device, hyperthermia was given once or twice a week after irradiation for 30-60 min per session (1-12 sessions in total). Radiotherapy was delivered at dose of 13.6-70 Gy. The thermal parameters analyzed were a) maximum, average, and minimum intratumor temperatures (Tmax, Tav, and Tmin), which were recorded at the termination of each treatment, and b) the percentages of the intratumor points that exceeded 41 C (%T greater than or equal to 41 C). The mean +/- SD for Tmax, Tav, Tmin, and %T greater than or equal to 41 C was 42.9 +/- 1.7 C, 41.6 +/- 1.2 C, 39.7 +/- 1.1 C, and 56.2 +/- 25.8, respectively. Larger tumors showed higher thermal parameters than the smaller tumors. Of the 12 tumors treated by definitive therapy, 2 (17%) achieved CR, 7 (58%) PR, and 3 (25%) NR. Four of 10 tumors that did not achieve CR showed large intratumor low density areas on post-treatment CT, reflecting massive coagulation necrosis. Higher thermal parameters were closely related to the appearance of low-density areas but not to changes in tumor size. Four tumors treated preoperatively were successfully resected 2 weeks after thermoradiotherapy, whereas four palliatively-treated tumors showed no regression. The side effects associated with hyperthermia were pain in 12 patients (60%) and dyspnea in 3 (15%), all of which resolved after termination of treatment. A skin abscess and a pneumothorax attributed to thermal probe insertion were observed in one patient each. These results indicate that regional RF capacitive hyperthermia is clinically feasible for local treatment of selected lung cancers.

Adenocarcinoma↗

A method for the selective measurement of the radiosensitivity of quiescent cells in solid tumors--combination of immunofluorescence staining to BrdU and micronucleus assay.

C3H/He mice bearing the SCC VII tumor were irradiated after being given 10 injections of 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating cells in the tumors, and the tumors were then excised and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (which blocks cytokinesis), and the micronucleus frequency in unlabeled cells was determined using immunofluorescence staining to BrdU. The micronucleus frequency was then used to calculate the surviving fraction of the unlabeled cells, using the regression line relating the micronucleus frequency to the surviving fraction determined separately for the total tumor cell population. Using this technique, a cell survival curve could be determined for the unlabeled cells, which were regarded as the quiescent cells. Assays performed both immediately after and 24 h after irradiation of normally-aerated tumors showed that unlabeled cells were more radioresistant and had a greater capacity for repair of potentially lethal damage than the tumor cell population as a whole. Moreover, when the assay was performed immediately after the irradiation of both normally-aerated and hypoxic tumors, it was found that unlabeled cells had a much higher hypoxic fraction than the tumor cell population as a whole. This appears to be a useful method for determining the responses of quiescent cells in solid tumors to various treatments.

Animals↗

Radiofrequency thermotherapy for malignant liver tumors.

Inoperable malignant liver tumors have been treated by radiofrequency hyperthermia at Kyoto University Hospital since 1983. In this study, clinical hyperthermia for malignant liver tumor was evaluated for 67 tumors in which we could measure intratumor temperatures. Of the 67 tumors, 41 were hepatocellular carcinomas (HCC), six cholangiocarcinomas, and 20 metastatic tumors. Cholangiocarcinoma and metastatic tumors were more susceptible to this treatment than HCC. Of the three types of HCC, higher intratumor temperatures were achieved in the diffuse type than in the nodular or massive types. The minimum tumor temperature of HCC stayed below 40 degrees C in 46% of cases, especially in larger tumors. The local response rates (complete remission plus partial remission/all) were 28% and 11% for HCC and non-HCC, respectively, for thermochemotherapy; 86% and 33%, for thermoradiotherapy; and 33% and 89%, for thermotherapy with embolization. No apparent relationship was observed between the intratumor temperatures and local response rate.

Adenoma, Bile Duct↗

[Clinical results of conventional fractionation radiotherapy for glottic and supraglottic laryngeal cancers--the usefulness of hyperfractionation for these cancers].

Ninety patients with glottic and eighteen patients with supraglottic laryngeal cancer (anyN, M0) were treated by conventional fractionation radiotherapy between July, 1963 and August, 1988. Tumor control and cause specific survival were evaluated according to tumor location (glottic or supraglottic) and tumor size (T1, T2, T3, or T4). As a result, the steepness of dose-response curve for the tumor control in T1-2 glottic and T2 supraglottic tumors was more slanting upwards than that in other laryngeal tumors, and the patients whose tumors were irradiated at larger doses had a tendency to survive longer. These results suggested that T1-2 glottic and T2 supraglottic laryngeal tumors can have a good application for hyperfractionation radiotherapy which is a radiation therapy with multiple fractions per day with a small fraction size and with which tumors can receive larger radiation doses than with conventional fractionation radiotherapy. Five patients with glottic or supraglottic tumors treated by hyperfractionation radiotherapy obtained CR, and now show no recurrence. We are going to investigate the usefulness of hyperfractionation radiotherapy after treating more patients with Twice-A-Day fractionation radiotherapy.

Adult↗

[Clinical results of loco-regional hyperthermia combined with chemotherapy in the treatment of malignant tumors].

From December 1982 through January 1989, 22 patients with 25 tumors were treated by thermochemotherapy. Of the 25 tumors, 13 were locally recurrent tumors after radiotherapy, 10 distant metastases, and 2 peritoneal disseminations. Employing two types of heating devices (8MHz capacitive RF, 430MHz microwave), hyperthermia was administered once or twice weekly, for 30-60 minutes per session, up to total sessions of 2-15 (mean = 6.9). In some sessions, anticancer drugs were administered intravenously or intraarterially immediately before or simultaneously with hyperthermia. Of the 25 tumors treated, 2 (8%) showed CR, 11 (44%) PR, 7 (28%) NC, and 5 (20%) PD. The better the tumor response was, the higher local control rate was achieved. The survival rate of patients who achieved CR or PR was higher than that of patients who showed NC or PD. Tumor volume, depth of tumor, averaged maximum intratumor temperature, the number of effective heat sessions and the number of anticancer drugs used were shown to affect the tumor response by multivariate analysis. On the other hand, averaged minimum intratumor temperature and history of previous treatment did not affect the tumor response. As almost all the tumors treated were considered to be refractory to radiotherapy or chemotherapy, the tumor responses obtained with thermochemotherapy seemed very encouraging. The expanded trials are warranted to reveal the effectiveness of thermochemotherapy.

Adolescent↗

Initial clinical results of a 430 MHz microwave hyperthermia system using a lens applicator.

The applicability of a 430 MHz microwave (MW) hyperthermia system using an electric field converging (lens) applicator was evaluated. Twenty-two tumors with a maximum tumor depth of less than 7 cm (10 chest wall tumors, 8 abdominal and pelvic tumors, 2 extremity tumors, and 2 neck tumors) were treated with the lens applicator heating system for a total of 72 sessions in conjunction with irradiation or chemotherapy. Of the 72 heat sessions, our treatment goal of 30 min of hyperthermia with all monitored tumor temperatures above 42 degrees C was achieved in 31 sessions (43%). The average tumor temperature was 42.5, 43.1, 42.0, and 42.0 degrees C for chest wall, abdominal and pelvic, extremity, and neck tumors, respectively; similarly 88, 83, 64 and 50% of monitored points exceeded 41 degrees C. A lens applicator heating system increased the penetration depth of MW, and tumor temperature of 41 degrees C at 5 cm from the surface was easily achieved with a four-aperture lens applicator. Of the 22 tumors, 10 tumors exhibited complete response (CR), 7 partial response (PR) and 5 no response (NR). These results suggest that the lens applicator heating system is useful for heating localized subsurface tumors with a maximum tumor depth of 5-6 cm.

Adenocarcinoma↗

Use of the micronucleus assay for the selective detection of radiosensitivity in BUdR-unincorporated cells after pulse-labelling of exponentially growing tumour cells.

To determine the radiosensitivity of non-S-phase tumour cells in vitro, survival curves of SCC VII tumour cells were obtained after a short block with hydroxyurea. Dose-response curves of micronucleus (MN) frequency appearing in non-S-phase cells were also determined by excluding S-phase cells with immunofluorescence staining to 5-bromo-2'-deoxyuridine (BUdR). Both the dose-response curves of MN frequency and survival curves were analysed by a linear-quadratic model (surviving fraction = exp (-alpha D-beta D2), MN frequency = aD+bD2+c). A good correlation between the alpha/beta and alpha/beta ratios was observed. In both BUdR-unincorporated and asynchronous cell cultures, the regression lines between the surviving fraction and micronucleus frequency were statistically identical. Therefore, it was shown that cell survival curves, which cannot be obtained directly by the routine colony-formation technique, can be calculated using the micronucleus frequency and the regression line in asynchronous cell cultures. Therefore, it should be possible to detect the response to irradiation of quiescent cells in tumours using the immunofluorescence staining to BUdR and the MN frequency assay.

Bromodeoxyuridine↗

[Hypoxic cell radiosensitizer present status and problems from viewpoint of clinical radiotherapy].

The results of clinical trials of hypoxic cell radiosensitizers were reviewed in order to clarify the present status and problems in this field. Most trials failed to show an effectiveness of the combination, however, some ENT tumors and bladder cancers were improved in local tumor responses and survivals. A selection of the patients suitable for the combination and development of simple method for the selection are indispensable. SERs necessary for clinical radiotherapy are considered to be larger than 1.2 at 2 Gy fraction level. Present hypoxic cell radiosensitizers have no significant effects on alpha values. Since radiation responses at low radiation dose ranges are dominated by alpha values, the chemicals having an effects on alpha values have to be developed.

Cell Hypoxia↗

[Clinical assessment of thermoradiotherapy of breast cancer and cancer of the urinary bladder].

Non-randomized clinical trials of thermoradiotherapy for breast cancer and carcinoma of the urinary bladder were reported. Thermoradiotherapy was useful for breast cancer treatment in term of (1) increased local control for locally advanced tumors and (2) possibility of reducing dose of irradiation for recurrent tumors following radiotherapy. Tumor response to thermoradiotherapy was dependent on tumor volume and maximum or minimum tumor temperature. Thermoradiotherapy was also effective as a preoperative-treatment for urinary bladder cancer. The incidence of down-staging and degeneration of tumors was significantly higher in thermoradiotherapy than in radiotherapy. These effects were temperature dependent. Patients with T 3-4 NOMO or Grade 3 tumors treated with thermoradiotherapy showed a tendency of increased survival compared with those treated with radiotherapy alone.

Adult↗

Treatment of murine SCC VII tumors with localized hyperthermia and temperature-sensitive liposomes containing cisplatin.

The release of cisplatin (CDDP) encapsulated in temperature-sensitive unilamellar liposomes to murine SCC VII carcinoma by localized hyperthermia and the effects of the treatment on tumor growth were studied. A transition temperature of the temperature-sensitive liposomes containing cisplatin (LIP-CDDP) was 41 degrees C. Twenty-four hours after injection of LIP-CDDP, the heated tumors (42 degrees C, 60 min) contained 3.3 times more CDDP than the unheated tumors receiving free CDDP. Although the uptake of liposome-associated CDDP by liver was approximately threefold greater at 1.5 h after injection than uptake of free CDDP, it decreased about 50% over a 24-h period. No difference in uptake of the two forms of CDDP by kidney was observed. The combination of LIP-CDDP and localized heating at 42 or 43 degrees C was more effective relative to the amount of CDDP in delaying tumor growth than that of free CDDP and hyperthermia. Treatment with LIP-CDDP plus local heating resulted in a dose-modifying factor of 5.3 when compared with free CDDP and no hyperthermia. The dose-modifying factor was 2.8 when treatment with LIP-CDDP and heat was compared with treatment with free CDDP and heat. Thus CDDP could be released selectively from the temperature-sensitive liposomes by heat and resulted in both a greater uptake of the drug and a delay in tumor growth.

Animals↗

Histological analysis of the effect of hyperthermia on normal rabbit hepatic vasculature.

The effects of hyperthermia on rabbit hepatic vasculature were studied histologically. To investigate heat-induced vascular damage in the central veins, portal veins, and hepatic arterioles, the left lobes of rabbit liver were heated locally for 30 min in the range of 40-46 degrees C. Hyperthermia was induced by an 8-MHz radiofrequency current heating device using a needle type interstitial applicator. This device allowed application of heat to a central area of 10 x 10 mm no more than 1 degree C below the preset temperature. Within the area of 1 cm2, the percentage of damaged (ruptured or thrombosed) vessels was estimated for each type of hepatic vasculature. Vascular damage following hyperthermia continued up to 24 h after heating for the three types of hepatic vasculature. Central veins were the most thermosensitive followed by portal veins, whereas hepatic arterioles were the most thermoresistant. The temperature causing 50% vascular damage 24 h after heating was 41.5-42.5 degrees C, 42.5-43.5 degrees C, and 44-45 degrees C for central veins, portal veins, and arterioles, respectively. This differential thermal responsiveness of hepatic vasculature may be attributed to the histological structure of the vessels.

Animals↗

[Clinical results of thermoradiotherapy of locally advanced and recurrent breast cancers--comparison of results with radiotherapy alone].

From August 1979 through January 1988, 23 breast cancer patients with 25 tumors supposed to be refractory to conventional treatment were treated by thermoradiotherapy. Of the 25 tumors, 10 were locally advanced primary tumors [Group 1], 4 locally advanced recurrent tumors after operation more than 5 cm in maximum diameter [Group 2], and 11 locally recurrent tumors after radiotherapy [Group 3]. The present study was not a formal randomised-trial, but a historical-controlled study. The results were compared with tumors which were treated by radiation therapy alone between July 1962 and August 1979. The historical control groups comprised 11 tumors for Group 1, 17 for Group 2 and 19 for Group 3. Employing 4 types of heating devices (8, 13.56 MHz capacitive RF, 430, 2450 MHz microwave), hyperthermia was administered once or twice a week after irradiation, for 30-60 minutes per session, up to a total sessions of 2-9. Radiotherapy was delivered in fractions of 180 to 200 cGy per day, 5 days per week, up to 28-74.4 Gy in total, or in fraction of 400 cGy, two times per week, up to 28-60 Gy. Tumor temperatures were measured by inserting thermocouples into the tumors. The tumors that did not recur during follow-up of more than 3 months were regarded as locally controlled tumors, and the local control rate was calculated. The local control rate in Group 2 and the local response rate (CR + PRa) in Group 1 were higher than those of the historically controlled tumors. In Group 3, hyperthermia combined with lower total doses of irradiation showed a high local response rate similar to that by radiation therapy alone. Thus local hyperthermia in combination with radiation therapy seems to be more effective than radiotherapy alone for locally advanced and recurrent breast cancers.

Adult↗

Radiofrequency (RF) capacitive hyperthermia combined with radiotherapy in the treatment of abdominal and pelvic deep-seated tumors.

Thermal parameters and tumor response were determined in 33 abdominal and pelvic deep-seated tumors which were treated with hyperthermia in combination with radiation therapy. Hyperthermia was applied regionally for a total of 3-14 sessions (mean; 6.4 sessions), using an 8 MHz radiofrequency (RF) capacitive heating device. An average tumor temperature (Tav) of more than 42 degrees C was achieved in 17 (52%) tumors, and intratumor temperatures above 42 degrees C could be maintained for more than 20 min (effective heat session) in 103 (52%) of the 198 heat sessions. Of the 33 tumors, 4 tumors exhibited complete regression (CR), 7 PRa (80-99% regression), 7 PRb (50-79% regression) and 15 NR (less than 50% regression). Tumor response (CR + PRa) was apparently dependent on the thermal parameters. Tumors with Tav of more than 42 degrees C or those receiving more than three effective heat sessions showed a significantly higher response rate than those heated less effectively. This trend was also noted in minimum tumor temperature. As to radiation dose, most of the responders received a total of 60-70 Gy irradiation. The two characteristic features in tumor response in effectively heated tumors, were slow tumor regression and appearance of an intratumor low density area on post-treatment computed tomography.

Abdominal Neoplasms↗

[Results of thermoradiotherapy of deep-seated tumors and problems in the evaluating its effects].

The results of thermoradiotherapy for deep-seated tumors indicated that 15% of the affected patients achieved CR and that the response rate (CR plus PR) was 58%. However, in some of the tumors which did not regress sufficiently, no regrowth was observed during follow-up. Furthermore, post-treatment CT scan revealed low-density areas occupying as much as 80% of the tumor area in 4 of 13 PRb tumors and 5 of 15 NRs. The appearance of these remarkable low-density areas on CT might be specific to thermotherapy, since it is uncommon following radiation therapy alone. Fifteen PR or NR tumors were resected and subjected to histopathological examination. It was found that cancer cells remained mainly in the tumor periphery in 12 of the 15 tumors while none were present throughout the entire tumor in the remaining 3 (2 PRbs and one NR). It was concluded from these results that it was possible to achieve local tumor control following thermoradiotherapy not only in CR tumors but also in some PRs or NRs which might remain unchanged in size but show prominent low-density areas on CT scan during follow-up. Accordingly, this suggests that the effects of thermoradiotherapy for deep-seated tumors should be evaluated on the basis of not only tumor regression but also the appearance of these low-density areas on post-treatment CT.

Combined Modality Therapy↗

Hepatic abscess secondary to a fishbone penetrating the gastric wall: CT demonstration.

Preoperative diagnosis of hepatic abscess due to foreign bodies penetrating the gastrointestinal tract is uncommon with conventional imaging methods. This report describes and illustrates a case of hepatic abscess secondary to a fishbone penetrating the gastric antrum wall which was diagnosed preoperatively by CT and confirmed at surgery. The value of CT in the preoperative diagnosis of cases of this kind is emphasized.

Female↗

Origin attribution of polychlorinated dibenzo-p-dioxins and dibenzofurans in sediment and soil from a Japanese freshwater lake area through congener-specific data analysis.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) in sediment and soil from a freshwater lake area were congener-specifically determined. The obtained data were examined to estimate the major origins of these compounds, with the aid of principal component analysis (PCA). Four major principal components (PCs) were obtained, and three of them were attributed to PCDDs/PCDFs in the atmosphere, in a diphenyl ether herbicide and in pentachlorophenol, based on congener-specific comparisons with references. One PC remained unattributed. These four were interpreted as the major origins of PCDDs/PCDFs in the area. The relative influence of the origins was also investigated.

Agriculture↗

Modification of tirapazamine-induced cytotoxicity in combination with mild hyperthermia and/or nicotinamide: reference to effect on quiescent tumour cells.

C3H/He and Balb/c mice bearing SCC VII or EMT6/KU tumours received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days to label all proliferating (P) cells. The tumours were locally heated at 40 degrees C for 60 min and/or the tumour-bearing mice received intraperitoneal injection of nicotinamide, and then tirapazamine (TPZ) was injected intraperitoneally. Sixty minutes after TPZ injection, the tumours were excised, minced and trypsinized. The tumour cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labelling (quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P+Q) tumour cells was determined from the tumours that were not pretreated with BrdU. The cytotoxicity of TPZ was evaluated in terms of the frequency of induced micronuclei in binuclear tumour cells (= MN frequency). In both tumour systems, the MN frequencies of Q cells were greater than those of total tumour cell populations. Mild heat treatment elevated the MN frequency in total and Q cells in both tumour systems, but the effect was more marked in Q cells. In total cells, mild heat treatment increased the MN frequency in EMT6/KU tumour cells more markedly than in SCC VII tumour cells. In contrast, in both tumour systems, nicotinamide decreased the MN frequency in both cell populations, with a greater influence on the total cells. The combination of TPZ and mild heat treatment may be useful for sensitizing tumour cells in vivo, including Q cells.

Animals↗