Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.19
Toshikazu Tsuji
{"title":"Measurement of Intracellular Temperature by Fluorescent Polymeric Thermometers","authors":"Toshikazu Tsuji","doi":"10.3191/THERMALMED.33.19","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.19","url":null,"abstract":"","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73395262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.129
K. M. Z. Rahman, S. Kose, N. Imamoto
Hikeshi is a protein that mediates the heat stress-induced nuclear import of heat shock protein 70 (HSP70: HSPA1 and HSPA8). Dysfunction of Hikeshi in humans can cause serious hereditary diseases, but the cellular function of Hikeshi is not fully understood. Previously, we reported that depletion of Hikeshi resulted in different effects in two human cell lines following proteotoxic stress. Depletion of Hikeshi reduced the survival of HeLa cancer cells after proteotoxic stress. However, Hikeshi-knockout (KO) hTERTRPE1 cells, immortalized with telomerase reverse transcriptase, acquired resistance against proteotoxic stress, which was accompanied by increased p21 (WAF1/CIP1, CDKN1A) expression. p21 is a cell-cycle inhibitor and a direct p53-regulated target gene. Here, we investigated the effect of Hikeshi depletion and inhibition of HSP70 molecular chaperone function on cellular signaling in HeLa and hTERT-RPE1 cells. Functional modulation of HSP70 with the inhibitor YM-1 caused cell death in the HeLa cells but resulted in growth arrest of the hTERT-RPE1 cells. Further, YM-1 treatment dramatically up-regulated p53 and p21 proteins in hTERT-RPE1 cells and down-regulated FoxM1 and survivin, which are regulators of cell cycle progression, in both hTERT-RPE1 cells and HeLa cells. Our results showed that regardless of the presence or absence of Hikeshi, the p53-p21 pathway becomes active when hTERT-RPE1 non-cancer cells are treated with YM-1, which contributes to protection against cell death. Hikeshi might function as an upstream regulator of HSP70, which affects activation of the p53-p21 pathway, especially during and after proteotoxic stress.
{"title":"Effect of an Inhibitor of HSP70, YM-1, on Hikeshi Knockout Cells","authors":"K. M. Z. Rahman, S. Kose, N. Imamoto","doi":"10.3191/THERMALMED.33.129","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.129","url":null,"abstract":"Hikeshi is a protein that mediates the heat stress-induced nuclear import of heat shock protein 70 (HSP70: HSPA1 and HSPA8). Dysfunction of Hikeshi in humans can cause serious hereditary diseases, but the cellular function of Hikeshi is not fully understood. Previously, we reported that depletion of Hikeshi resulted in different effects in two human cell lines following proteotoxic stress. Depletion of Hikeshi reduced the survival of HeLa cancer cells after proteotoxic stress. However, Hikeshi-knockout (KO) hTERTRPE1 cells, immortalized with telomerase reverse transcriptase, acquired resistance against proteotoxic stress, which was accompanied by increased p21 (WAF1/CIP1, CDKN1A) expression. p21 is a cell-cycle inhibitor and a direct p53-regulated target gene. Here, we investigated the effect of Hikeshi depletion and inhibition of HSP70 molecular chaperone function on cellular signaling in HeLa and hTERT-RPE1 cells. Functional modulation of HSP70 with the inhibitor YM-1 caused cell death in the HeLa cells but resulted in growth arrest of the hTERT-RPE1 cells. Further, YM-1 treatment dramatically up-regulated p53 and p21 proteins in hTERT-RPE1 cells and down-regulated FoxM1 and survivin, which are regulators of cell cycle progression, in both hTERT-RPE1 cells and HeLa cells. Our results showed that regardless of the presence or absence of Hikeshi, the p53-p21 pathway becomes active when hTERT-RPE1 non-cancer cells are treated with YM-1, which contributes to protection against cell death. Hikeshi might function as an upstream regulator of HSP70, which affects activation of the p53-p21 pathway, especially during and after proteotoxic stress.","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74884177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.103
I. Tohnai
: Dysfunctions and cosmetic disturbance after surgery for oral cancer are major problem. I focused hyperthermia as non-invasive therapy for oral cancer. Magnetic induction interstitial hyperthermia using ferromagnetic implant needle (Implant heating system : IHS) has been developed, and the antitumor effectiveness was studied experimentally and clinically for tongue cancer. The effectiveness of hyperthermia tended to extend gradually toward the peripheral side of the tongue tumor inoculated VX7. Eight patients with primary cancer of the oral cavity were treated using hyperthermia combined with chemotherapy. As a result, the thermal distribution was good, and complete response was observed in all patients. The antitumor effectiveness of interstitial hyperthermia using magnetic liposomes was studied experimentally. The primary tongue tumor was disappeared due to good thermal distribution. Magnetic liposomes were delivered selectively to the cervical lymph node metastasis. Then, necrosis and apoptosis were observed in the cervical lymph node metastasis under alternating magnetic field. Ferucarbotran of existing drugs was heated under alternating magnetic field. Combination of cisplatin with ferucarbotran under alternating magnetic field induced apoptosis of cancer cells more effectively than cisplatin alone with significant differences. A new anti-cancer agent for magnet-guided delivery with anti-cancer activity (Fe (Salen)) was studied experimentally in terms of antitumor effectiveness. Fe (Salen) alone inhibited the growth of tongue tumor. The heat was confirmed in Fe (Salen) under alternating magnetic field, and tongue tumor was disappeared with interstitial hyperthermia using Fe (Salen). The combined therapy with superselective intra-arterial chemoradiotherapy and RF hyperthermia was effective therapy for advanced oral cancer with cervical lymph node metastasis (N3). This therapy is promising as a new strategy of non-invasive therapy for advanced oral cancer.
{"title":"Hyperthermia for Oral Cancer","authors":"I. Tohnai","doi":"10.3191/THERMALMED.33.103","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.103","url":null,"abstract":": Dysfunctions and cosmetic disturbance after surgery for oral cancer are major problem. I focused hyperthermia as non-invasive therapy for oral cancer. Magnetic induction interstitial hyperthermia using ferromagnetic implant needle (Implant heating system : IHS) has been developed, and the antitumor effectiveness was studied experimentally and clinically for tongue cancer. The effectiveness of hyperthermia tended to extend gradually toward the peripheral side of the tongue tumor inoculated VX7. Eight patients with primary cancer of the oral cavity were treated using hyperthermia combined with chemotherapy. As a result, the thermal distribution was good, and complete response was observed in all patients. The antitumor effectiveness of interstitial hyperthermia using magnetic liposomes was studied experimentally. The primary tongue tumor was disappeared due to good thermal distribution. Magnetic liposomes were delivered selectively to the cervical lymph node metastasis. Then, necrosis and apoptosis were observed in the cervical lymph node metastasis under alternating magnetic field. Ferucarbotran of existing drugs was heated under alternating magnetic field. Combination of cisplatin with ferucarbotran under alternating magnetic field induced apoptosis of cancer cells more effectively than cisplatin alone with significant differences. A new anti-cancer agent for magnet-guided delivery with anti-cancer activity (Fe (Salen)) was studied experimentally in terms of antitumor effectiveness. Fe (Salen) alone inhibited the growth of tongue tumor. The heat was confirmed in Fe (Salen) under alternating magnetic field, and tongue tumor was disappeared with interstitial hyperthermia using Fe (Salen). The combined therapy with superselective intra-arterial chemoradiotherapy and RF hyperthermia was effective therapy for advanced oral cancer with cervical lymph node metastasis (N3). This therapy is promising as a new strategy of non-invasive therapy for advanced oral cancer.","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86990064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.29
K. Ohnishi
Cancer stem cells (CSCs) or tumor-initiating cells (TICs) have been identified in a variety of cancers and are defined as a small population of cancer cells that have stem cell-like phenotypes. CSCs are resistant to current chemotherapy and radiotherapy and have high ability of tumorigenesis. It is likely that CSCs contribute to cancer metastases and tumor recurrence, which cause a poor prognosis. Thus, targeting strategy of CSCs is extremely important for advancement of cancer therapies. However, CSC itself is not well understood. This review refers to key points to be noticed in CSC research and considers effectiveness of hyperthermia for CSC-targeting. It has been reported that heating has an inhibitory influence on some extraand intra-cellular factors that are related to the survival of CSCs. In this review, the potentiality of hyperthermia for CSC-targeted cancer therapy is discussed with relation to those survival factors.
{"title":"Effectiveness of Hyperthermia on Cancer Stem Cells","authors":"K. Ohnishi","doi":"10.3191/THERMALMED.33.29","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.29","url":null,"abstract":"Cancer stem cells (CSCs) or tumor-initiating cells (TICs) have been identified in a variety of cancers and are defined as a small population of cancer cells that have stem cell-like phenotypes. CSCs are resistant to current chemotherapy and radiotherapy and have high ability of tumorigenesis. It is likely that CSCs contribute to cancer metastases and tumor recurrence, which cause a poor prognosis. Thus, targeting strategy of CSCs is extremely important for advancement of cancer therapies. However, CSC itself is not well understood. This review refers to key points to be noticed in CSC research and considers effectiveness of hyperthermia for CSC-targeting. It has been reported that heating has an inhibitory influence on some extraand intra-cellular factors that are related to the survival of CSCs. In this review, the potentiality of hyperthermia for CSC-targeted cancer therapy is discussed with relation to those survival factors.","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75421301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.63
M. Morita, M. Ikebe, Masaki Kagawa, Y. Nakaji, M. Sugiyama, D. Yoshida, M. Ota, T. Iguchi, K. Sugimachi, N. Kunitake, H. Saeki, E. Oki, S. Ohga, Y. Toh, Y. Maehara
Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.53
Oiendrila B. Debnath, K. Saito, K. Ito, M. Uesaka
{"title":"Interstitial Hyperthermia in Combination with Radiation Brachytherapy for Treatment of Breast Tumor","authors":"Oiendrila B. Debnath, K. Saito, K. Ito, M. Uesaka","doi":"10.3191/THERMALMED.33.53","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.53","url":null,"abstract":"","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87521353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.75
H. Shoji, Kazuki Jinbo, K. Sugawara, S. Suda, M. Motegi, H. Murata, K. Ogoshi, Takeo Takahashi, T. Asao, H. Kuwano
: To avoid colostomy, we try to improve local control, i e . to perform pathological complete response (pCR) by the neoadjuvant chemoradiation (NACR) with concurrent thermal therapy, falling into a so-called “ wait-and-see policy ” . The aim of this study is examined whether the treatment response of NACR with concurrent thermal therapy for rectal cancer can be predicted after the treatment completion and we showed the changing history of our treatment protocol, current results of our study and a new perspective and potential role of thermal therapeutic approaches in patients with rectal cancer. In this study, 81 patients with rectal cancers (54 resected, M : F ＝ 61 : difference RO ≥ 0 Watt group (p ＜ 0.05), but not in the difference RO ＜ 0 Watt group. These data suggest that patients with a small tumor ( GTV ≤ 32 cm 3 ) and a difference RO ＜ 0 Watt are enough to treat by NACR only and those with a large tumor ( GTV ≥ 80 cm 3 ) and a RO difference ≥ 0 Watt by NACR with concurrent with thermal therapy.
为了避免结肠造口，我们尝试改善局部控制，如:通过新辅助放化疗(NACR)同时进行热疗来实现病理完全缓解(pCR)，陷入所谓的“观望政策”。本研究的目的是探讨NACR联合热疗在直肠癌治疗完成后的治疗反应是否可以预测，我们展示了我们治疗方案的变化历史、目前的研究结果以及热疗方法在直肠癌患者中的新视角和潜在作用。本研究中81例直肠癌患者(切除54例，M: F = 61例):差异RO≥0瓦特组(p < 0.05)，差异RO < 0瓦特组无差异。这些数据表明，小肿瘤(GTV≤32 cm 3)且RO差< 0瓦特的患者仅采用NACR治疗就足够了，大肿瘤(GTV≥80 cm 3)且RO差≥0瓦特的患者采用NACR联合热疗治疗。
{"title":"Thermal Therapy as Multidisciplinary Therapy Applied to Rectal Cancer:: A New Perspective and Potential Role of This Treatment","authors":"H. Shoji, Kazuki Jinbo, K. Sugawara, S. Suda, M. Motegi, H. Murata, K. Ogoshi, Takeo Takahashi, T. Asao, H. Kuwano","doi":"10.3191/THERMALMED.33.75","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.75","url":null,"abstract":": To avoid colostomy, we try to improve local control, i e . to perform pathological complete response (pCR) by the neoadjuvant chemoradiation (NACR) with concurrent thermal therapy, falling into a so-called “ wait-and-see policy ” . The aim of this study is examined whether the treatment response of NACR with concurrent thermal therapy for rectal cancer can be predicted after the treatment completion and we showed the changing history of our treatment protocol, current results of our study and a new perspective and potential role of thermal therapeutic approaches in patients with rectal cancer. In this study, 81 patients with rectal cancers (54 resected, M : F ＝ 61 : difference RO ≥ 0 Watt group (p ＜ 0.05), but not in the difference RO ＜ 0 Watt group. These data suggest that patients with a small tumor ( GTV ≤ 32 cm 3 ) and a difference RO ＜ 0 Watt are enough to treat by NACR only and those with a large tumor ( GTV ≥ 80 cm 3 ) and a RO difference ≥ 0 Watt by NACR with concurrent with thermal therapy.","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81002094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It has been known that major heat shock proteins, such as Hsp90 and Hsp70, and their transcription factor HSF1 are overexpressed in a wide range of cancer cells. Its biological significance, however, remains unclear. Recently, it has been recognized that HSF1 and HSPs are cell survival factors and essential for cancer cell development and progression, and the HSF1-HSPs system seems to be co-opted by cancer cells for their own survival under stressful conditions (low oxygen concentration, low nutrient, low pH). According to this conception, targeting HSF1 and HSPs with a specific inhibitor has been suggested for cancer therapy. Hsp90 inhibitors have long been studied from 1990ʼ not only in a basic research but also in clinical phase I, phase II, even phase III trials. Recently, several inhibitors of Hsp70 and HSF1 for the purpose of cancer therapy have been reported. In this review, basic researches aimed for cancer therapy targeting these survival factors (HSF1 and HSPs) with a specific inhibitor are summarized.
{"title":"Targeting Cell Survival Factors, HSF1 and HSPs, with a Specific Inhibitor for Cancer Therapy","authors":"K. Ohtsuka","doi":"10.3191/THERMALMED.33.1","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.1","url":null,"abstract":"It has been known that major heat shock proteins, such as Hsp90 and Hsp70, and their transcription factor HSF1 are overexpressed in a wide range of cancer cells. Its biological significance, however, remains unclear. Recently, it has been recognized that HSF1 and HSPs are cell survival factors and essential for cancer cell development and progression, and the HSF1-HSPs system seems to be co-opted by cancer cells for their own survival under stressful conditions (low oxygen concentration, low nutrient, low pH). According to this conception, targeting HSF1 and HSPs with a specific inhibitor has been suggested for cancer therapy. Hsp90 inhibitors have long been studied from 1990ʼ not only in a basic research but also in clinical phase I, phase II, even phase III trials. Recently, several inhibitors of Hsp70 and HSF1 for the purpose of cancer therapy have been reported. In this review, basic researches aimed for cancer therapy targeting these survival factors (HSF1 and HSPs) with a specific inhibitor are summarized.","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75265666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.3191/THERMALMED.33.117
Hisaki Aiba, Satoshi Yamada, S. Miwa, T. Otsuka
: Radio-hyperthermo-chemotherapy (RHC), which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft-tissue tumors was introduced with the aim of decreasing local recurrence after surgery. We performed various experiments to apply this trimodal therapy to soft-tissue sarcomas, and herein review progress at our institution. In vitro application of hyperthermia (42-43 ℃ ) resulted in apoptosis and selectively decreased the number of cells in the G1 phase, which are thought to exhibit radioresistance. Moreover, simultaneous administration of hyperthermia (42 ℃ ) with cisplatin increased the concentration of the anti-tumor agent within the cells, resulting in significant inhibition of DNA synthesis. These findings reinforced the synergic effects of hyperthermia and chemotherapy / radiotherapy. 87.1% in the RHC and database groups, respectively ; p ＝ 0.04), despite patients in the RHC group undergoing surgery with closer margins. Thus, RHC neoadjuvant therapy inhibits local recurrence, demonstrating a new strategy for treating soft-tissue sarcoma following less invasive surgery, potentially resulting in limb preservation and averting amputation.
{"title":"Clinical Application of Hyperthermia to Soft Tissue Sarcoma; Result of Single Institution","authors":"Hisaki Aiba, Satoshi Yamada, S. Miwa, T. Otsuka","doi":"10.3191/THERMALMED.33.117","DOIUrl":"https://doi.org/10.3191/THERMALMED.33.117","url":null,"abstract":": Radio-hyperthermo-chemotherapy (RHC), which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft-tissue tumors was introduced with the aim of decreasing local recurrence after surgery. We performed various experiments to apply this trimodal therapy to soft-tissue sarcomas, and herein review progress at our institution. In vitro application of hyperthermia (42-43 ℃ ) resulted in apoptosis and selectively decreased the number of cells in the G1 phase, which are thought to exhibit radioresistance. Moreover, simultaneous administration of hyperthermia (42 ℃ ) with cisplatin increased the concentration of the anti-tumor agent within the cells, resulting in significant inhibition of DNA synthesis. These findings reinforced the synergic effects of hyperthermia and chemotherapy / radiotherapy. 87.1% in the RHC and database groups, respectively ; p ＝ 0.04), despite patients in the RHC group undergoing surgery with closer margins. Thus, RHC neoadjuvant therapy inhibits local recurrence, demonstrating a new strategy for treating soft-tissue sarcoma following less invasive surgery, potentially resulting in limb preservation and averting amputation.","PeriodicalId":23299,"journal":{"name":"Thermal Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82103778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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