Biomedical subjects

S Jo

Publications and source records attributed to S Jo.

At least 19 recordsLinked to original sources

PubMed2006

Long-term release of fluocinolone acetonide using biodegradable fumarate-based polymers.

Intraocular drug delivery systems made from biodegradable polymers hold great potential to effectively treat chronic diseases of the posterior segment of the eye. This study is based on the hypothesis that crosslinked poly(propylene fumarate) (PPF)-based matrices are suitable long-term delivery devices for the sustained release of the anti-inflammatory drug fluocinolone acetonide (FA) due to their hydrophobicity and network density. FA-loaded rods of 10 mm length and 0.6 mm diameter were fabricated by photo-crosslinking PPF with N-vinyl pyrrolidone (NVP). The released amounts of FA and NVP were determined by HPLC analysis. The effects of drug loading and the ratio of PPF to NVP on the release kinetics were investigated using a 2(3-1) factorial design. Overall, FA release was sustained in vitro over almost 400 days by all tested formulations. Low burst release was followed by a dual modality release controlled by diffusion and bulk erosion with release rates up to 1.7 microg/day. The extent of the burst effect and the release kinetics were controlled by the drug loading and the matrix composition. Matrix water content and degradation were determined gravimetrically. Micro-computed tomography was used to image structural and dimensional changes of the devices. The results show that photo-crosslinked PPF-based matrices are promising long-term delivery devices for intraocular drug delivery.

Chemistry, Pharmaceutical↗

PubMed2001

Modification of oligo(poly(ethylene glycol) fumarate) macromer with a GRGD peptide for the preparation of functionalized polymer networks.

A novel macromer, oligo(poly(ethylene glycol) fumarate) (OPF), was synthesized by the reaction between poly(ethylene glycol) (PEG) of molecular weight 1000 (PEG 1.0K) and fumaryl chloride. The oligo(PEG fumarate) (OPF 1.0K) was modified with a peptide known to modulate cellular functions, Gly-Arg-Gly-Asp (GRGD), after being activated with 4-nitrophenyl chloroformate (NPC). The determined yield of the GRGD modification in 0.1 M sodium bicarbonate buffer of pH 8.3 was 83% as determined by NMR measurements. The OPF 1.0K and the OPF 1.0K modified with GRGD were cross-linked with an unsaturated biodegradable polyester, poly(propylene fumarate) (PPF), by photopolymerization. The cross-linked PPF was characterized by Fourier transform infrared (FT-IR) spectroscopy and contact angle measurements. The equilibrium contact angle of water on the cross-linked PPF surface decreased with the incorporation of OPF 1.0K and the OPF 1.0K modified with GRGD. The results suggest that the OPF macromer can be used for the preparation of functionalized networks incorporating cell adhesion specific sequences.

Biopolymers↗

PubMed2000

RNase P ribozymes selected in vitro to cleave a viral mRNA effectively inhibit its expression in cell culture.

An in vitro selection procedure was used to select RNase P ribozyme variants that efficiently cleaved the sequence of the mRNA encoding thymidine kinase of herpes simplex virus 1. Of the 45 selected variants sequenced, 25 ribozymes carried a common mutation at nucleotides 224 and 225 of RNase P catalytic RNA from Escherichia coli (G(224)G(225) --> AA). These selected ribozymes exhibited at least 10 times higher cleavage efficiency (k(cat)/K(m)) than that derived from the wild type ribozyme. Our results suggest that the mutated A(224)A(225) are in close proximity to the substrate and enhance substrate binding of the ribozyme. When these ribozyme variants were expressed in herpes simplex virus 1-infected cells, the levels of thymidine kinase mRNA and protein were reduced by 95-99%. Our study provides the first direct evidence that RNase P ribozyme variants isolated by the selection procedure can be used for the construction of gene-targeting ribozymes that are highly effective in tissue culture. These results demonstrate the potential for using RNase P ribozymes as gene-targeting agents against any mRNA sequences, and using the selection procedure as a general approach for the engineering of RNase P ribozymes.

Animals↗

PubMed2000

Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience.

PURPOSE: To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS: During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS: The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION: External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.

Aged↗

PubMed2000

Surface modification using silanated poly(ethylene glycol)s.

Surface-grafted poly(ethylene glycol) (PEG) molecules are known to prevent protein adsorption to the surface. The protein-repulsive property of PEG molecules are maximized by covalent grafting. We have synthesized silanated monomethoxy-PEG (m-PEG) for covalent grafting of PEG to surfaces with oxide layers. Two different trialkoxysilylated PEGs were synthesized and characterized. The first trialkoxysilylated PEG was prepared by direct coupling of m-PEG with 3-isocyanatopropyltriethoxysilane through a urethane bond (silanated PEG I). The other silanated PEG (silanated PEG II) containing a long hydrophobic domain between PEG and a silane domain was prepared by reacting m-PEG with 1,6-diisocyanatohexane and 10-undecen-1-ol in sequence before silylation with 3-mercaptopropyl trimethoxysilane. Silanated PEGs I and II were grafted onto glass, a model surface used in our study. The PEG-grafted glass surfaces were characterized by contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Although contact angle did not change much as the bulk concentration of silanated PEG used for grafting increased from 0.1 to 20 mg/ml for both PEGs I and II, the surface atomic concentrations from XPS measurements showed successful PEG grafting. Surface PEG grafting increased concentration of surface carbon but decreased silicone concentration. The high resolution C1s spectra showed higher ether carbon with lower hydrocarbon compositions for the PEG-grafted surfaces compared to the control surface. AFM images showed that more PEG molecules were grafted onto the surface as the bulk concentration used for grafting was increased. AFM images of the dried surfaces showed that the surfaces were not completely covered by PEG molecules. After hydration, however, the surface appears to be covered completely probably due to the hydration of the grafted PEG chains. Glass surfaces modified with silanated PEGs reduced fibrinogen adsorption by more than 95% as compared with the control surface. Silanated PEGs provides a simple method for PEG grafting to the surface containing oxide layers.

Adsorption↗

PubMed2000

Reduced frequencies of peripheral interferon-gamma-producing CD4+ and CD4- cells during acute Kawasaki disease.

BACKGROUND: This study was performed to analyze the frequencies of peripheral interferon (IFN)-gamma-producing cells at the single-cell level and to determine concentrations of circulating IFN-gamma in the acute and subacute phases of Kawasaki disease (KD). METHODS: Ten patients with KD were studied and seven healthy children were selected as control subjects. Using immunofluorescent detection of intracellular IFN-gamma in CD4-positive and CD4-negative cells, the frequencies of IFN-gamma-producing cells in peripheral blood mononuclear cells were studied. Circulating IFN-gamma levels were measured by enzyme-linked immunosorbent assay. RESULTS: The frequencies of peripheral blood CD4+ and CD4- IFN-gamma-producing cells in acute-phase KD patients were significantly lower than in subacute-phase KD patients and control children (p < 0.05). CD4- cells, thought to be mainly composed of CD8+ cells, appeared to be more responsible for the reduced frequencies of total IFN-gamma-producing cells than CD4+ cells. There were, however, no differences in the frequencies of IFN-gamma-producing cells between KD patients in the subacute phase and control children. In contrast, serum IFN-gamma levels were higher in KD patients in the acute phase than in the subacute phase (p < 0.05). CONCLUSIONS: The above results show increased levels of circulating IFN-gamma and decreased emergence of peripheral IFN-gamma-producing cells in acute KD patients, suggesting transient infiltration of activated IFN-gamma-producing cells into the inflammatory sites during acute KD. These findings also support the hypothesis that IFN-gamma plays an important role in the pathogenesis of KD-related vasculitis.

CD4-Positive T-Lymphocytes↗

PubMed1999

Surface modification with PEO-containing triblock copolymer for improved biocompatibility: in vitro and ex vivo studies.

Poly(ethylene oxide) (PEO) has been frequently used to modify biomaterial surfaces for improved biocompatibility. We have used PEO-polybutadiene-PEO triblock copolymer to graft PEO to biomaterials by gamma-irradiation for a total radiation dose of 1 Mrad. The molecular weight of PEO in the block copolymer was 5000. In vitro study showed that fibrinogen adsorption to Silastic, polyethylene, and glass was reduced by 70 to approximately 95% by PEO grafting. On the other hand, the reduction of fibrinogen adsorption was only 30% on expanded polytetrafluoroethylene (e-PTFE). In vitro platelet adhesion study showed that almost no platelets could adhere to PEO-coated Silastic, polyethylene, and glass, while numerous platelet aggregates were found on the ePTFE. The platelet adhesion in vitro corresponded to the fibrinogen adsorption. When the PEO-grafted surfaces were tested ex vivo using a series shunt in a canine model, the effect of the grafted PEO was not noticeable. Platelet deposition on ePTFE was reduced by PEO grafting from 8170 +/- 1030 to 5100 +/- 460 platelets 10(-3) microm2, but numerous thrombi were still present on the PEO-grafted surface. The numbers of platelets cumulated on Silastic, polyethylene, and glass were 100 +/- 80, 169 +/- 35, and 24 +/- 22 platelets 10(-3) microm2, respectively. This is about 35% reduction in platelet deposition by PEO grafting. While the numbers of deposited platelets were small, the decreases were not as large as those expected from the in vitro study. This may be due to a number of reasons which have to be clarified in future studies, but it appears that in vitro platelet adhesion and fibrinogen adsorption studies may not be a valuable predictor for the in vivo or ex vivo behavior of the PEO-grafted surfaces.

Adsorption↗

PubMed1996

Clinical usefulness of determining the rate of thermal clearance within heated tumors.

Between June 1987 and June 1988, 28 patients (28 tumors) with liver, retroperitoneal, intrapelvic, or superficial tumors were treated with hyperthermia combined with radiotherapy and/or chemotherapy. Hyperthermia was administered once or twice a week for 30-60 min per session, up to a total of 2-11 sessions, with an 8-MHz RF capacitive heating device. Blood flow in the tumors was evaluated from the rate of thermal clearance (TCR) using the bio-heat transfer equation. The TCR was measured in the middle of the first heating session and at the end of the last heating session by turning off the output power of the heating device. For 9 patients, contrast-enhanced CT scans were taken and CT numbers at the centers of tumors were measured before and after the entire course of hyperthermia. Changes in TCR were closely related to average tumor center temperature, changes in CT number, and tumor response. When smaller and more superficial tumors were treated by hyperthermia combined with radiotherapy and/or chemotherapy that consisted of many heating sessions and during which a high average tumor center temperature was achieved, a better tumor response was obtained. The better the tumor response, the higher the local control rate became. The cause-specific survival rate of patients who achieved good tumor responses was higher than that of patients who showed poor tumor responses. Changes in TCR and CT number in heated tumors were useful and important indicators of tumor response to hyperthermia.

Adolescent↗

PubMed1992

Hyperthermia combined with radiation therapy for primarily unresectable and recurrent colorectal cancer.

The value of adjuvant hyperthermia to radiotherapy in the treatment of locally advanced colorectal cancers was investigated. Between 1981 and 1989, 71 primarily unresectable or recurrent colorectal tumors were treated with radiotherapy at the Department of Radiology, Kyoto University Hospital. Of the 71 tumors, 35 were treated with radiotherapy plus hyperthermia (group I), while 36 tumors (group II) were unsuitable for hyperthermia mainly because of difficulties with the insertion of temperature probes or the thickness of the patient's subcutaneous fat (greater than 2 cm). The mean total radiation dose was 58 Gy and 57 Gy for groups I and II, respectively. Thirty deep-seated pelvic tumors were treated with an 8 MHz radiofrequency capacitive heating device, and five subsurface tumors were treated with a 430 MHz microwave hyperthermia system. Hyperthermia was given following radiotherapy for 30-60 min for a total of 2-14 sessions (mean 5.7). In 32 of the 35 tumors heated, direct measurement of tumor temperature was performed. For the five tumors treated with the microwave heating device, the means of the mean maximum, average, and minimum measured intratumoral temperatures were 45.4 degrees C, 43.3 degrees C, and 40.6 degrees C, respectively. The corresponding values were 42.2 degrees C, 41.3 degrees C, and 40.3 degrees C for the 27 tumors treated with the capacitive heating device. Effective heating of deep-seated pelvic tumors was more difficult than heating of abdominal wall or perineal tumors. The local control rate at 6 months after the treatment, which was defined as absence of local progression of the tumors, was 59% (17/29) and 37% (11/30) for groups I and II, respectively. The objective tumor response rate (complete regression plus partial response) evaluated by computed tomography was 54% (19/35) in group I, whereas it was 36% (10/28) in group II. A better response rate of 67% was obtained in the 15 tumors with a mean average tumor temperature of greater than 42 degrees C. Although limitation of our current heating devices exist, the combination of hyperthermia with radiotherapy is a promising treatment modality in the treatment of locally advanced colorectal cancer.

Adenocarcinoma↗

PubMed1992

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

[Clinical results of hyperthermia alone in the treatment of refractory human tumors].

Retrospective analysis of patients with refractory tumors which were treated with hyperthermia alone in five institutions was performed. Hyperthermia was applied to 30 refractory tumors including 19 deep-seated tumors for a total of 427 sessions by 8 MHz or 13.56 MHz radiofrequency capacitive heating devices. Of the 30 tumors treated, 3 (10%) showed complete regression and 2 (7%) more than 50% regression. Although tumor regression was observed in small tumors, large deep-seated tumors did not respond to heat alone. Thus, response rate of hyperthermia alone was lower than expected, although subjective improvement by hyperthermia was noted in 53% patients. We consider that hyperthermia should be combined with radiation or chemotherapy whenever possible.

Adult↗

PubMed1989

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↗

PubMed1989

[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↗

PubMed1989

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↗

PubMed1989

Histopathological changes of human tumors following thermoradiotherapy.

Twenty human malignant tumors treated with thermoradiotherapy were examined histopathologically. Hyperthermia was administered regionally with a 13.56-MHz or 8-MHz RF heating device, once or twice a week after irradiation, 2 to 12 sessions in total. Fifteen tumors received a total radiation dose of 26 to 70 Gy in fractions of 1.8 Gy to 2.0 Gy a day, 5 days a week, whereas five tumors received a total dose of 20 to 60 Gy in fractions of 4 Gy each, twice a week. Microscopic examination of 4 of the 20 tumors revealed complete necrosis throughout the cross-section of the entire tumor. All the four tumors had received a total dose of over 60 Gy and a tumor center temperature of over 42 degrees C. In 10 tumors, more than 50% but less than 99% of the cross-section of the entire tumor had massive coagulation necrosis. The remaining six tumors showed relatively little change; the area of intratumor necrosis was less than 50%. The grade of tumor necrosis was dependent on both the temperatures of tumor center and periphery, and a total radiation dose. The small blood vessels and capillaries in the tumor parenchyma were markedly damaged in 16 of the 20 tumors, while the blood vessels in the tumor stroma were damaged in only 2 tumors. Condensation of the destroyed nucleus observed in 15 tumors was considered to be a typical change induced by thermoradiotherapy. Viable tumor cells remained in the tumor central area in only four tumors and around the blood vessels in only three tumors. However, in the tumor peripheral area, viable tumor cells were observed in 16 out of the 20 tumors. These results indicate that histopathological changes induced by thermoradiotherapy are greater in the tumor central area than in the tumor peripheral area, and provide strong rationale for utilizing full dose radiation therapy in combination with hyperthermia as opposed to lower doses for cancer therapy.

Adult↗

PubMed1989

Suppression of contact sensitivity by local hyperthermia treatment due to reduced Langerhans cell population in mice.

The effects of local hyperthermia treatment on contact sensitivity (CS) and on the number of Langerhans cells (LCs) were studied in mice. CS was significantly suppressed when mice were sensitized in the hyperthermia treated skin I, 2 or 4 days after treatment (43 degrees C for 45 min). This suppressive effect was not observed 7 or 14 days after the treatment. CS was also suppressed when mice were sensitized in non-treated skin I day after the treatment. The density of LCs detected as ATPase-positive cells also decreased significantly 1, 2, 4 and 7 days after the treatment. There appeared to be a positive correlation between the number of LCs and the extent of CS when mice were sensitized at hyperthermia treated skin. It was observed that this suppressive effect on CS was dose- and temperature-dependent. It could be transferred by spleen cells from the hyperthermia treated and DNFB-sensitized donors, and was antigen specific when spleen cells were transferred before sensitization of the recipient mice. This indicated it was, in part, associated with the induction of suppressor cells. These findings suggest that local hyperthermia treatment reduces the number of LCs with subsequent suppression of the induction phase of delayed-type hypersensitivity by the generation of antigen-specific suppressor cells.

Animals↗