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Measurement of Intracellular Temperature by Fluorescent Polymeric Thermometers 荧光聚合物温度计测定细胞内温度
Pub Date : 2017-01-01 DOI: 10.3191/THERMALMED.33.19
Toshikazu Tsuji
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引用次数: 0
Effect of an Inhibitor of HSP70, YM-1, on Hikeshi Knockout Cells HSP70抑制剂YM-1对Hikeshi敲除细胞的影响
Pub Date : 2017-01-01 DOI: 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.
Hikeshi是一种介导热应激诱导的热休克蛋白70 (HSP70: HSPA1和HSPA8)核输入的蛋白。人类hikishi功能障碍可引起严重的遗传性疾病,但hikishi的细胞功能尚不完全清楚。先前,我们报道了在蛋白质毒性应激后,Hikeshi的消耗对两种人类细胞系产生不同的影响。Hikeshi的耗竭降低了HeLa癌细胞在蛋白毒性应激后的存活率。然而,hikishi基因敲除(KO) hTERTRPE1细胞,端粒酶逆转录酶永生化,获得了对蛋白质毒性应激的抗性,这伴随着p21 (WAF1/CIP1, CDKN1A)表达的增加。P21是一种细胞周期抑制剂,是p53直接调控的靶基因。在这里,我们研究了Hikeshi缺失和抑制HSP70分子伴侣功能对HeLa和hTERT-RPE1细胞信号传导的影响。抑制剂YM-1对HSP70的功能调节导致HeLa细胞死亡,但导致hTERT-RPE1细胞生长停滞。此外,在hTERT-RPE1细胞和HeLa细胞中,m -1处理显著上调hTERT-RPE1细胞中的p53和p21蛋白,下调FoxM1和survivin蛋白,这两种蛋白是细胞周期进程的调节因子。我们的研究结果表明,无论Hikeshi是否存在,当hTERT-RPE1非癌细胞用m -1处理时,p53-p21通路变得活跃,这有助于防止细胞死亡。Hikeshi可能作为HSP70的上游调节剂,影响p53-p21通路的激活,特别是在蛋白毒性应激期间和之后。
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引用次数: 0
Hyperthermia for Oral Cancer 口腔癌的热疗
Pub Date : 2017-01-01 DOI: 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.
口腔癌手术后的功能障碍和美容障碍是主要问题。我专注于热疗作为口腔癌的非侵入性治疗。采用铁磁种植针进行磁感应间质热疗(种植体加热系统:IHS),并对舌癌的抗肿瘤效果进行了实验和临床研究。热疗的效果逐渐向接种VX7的舌肿瘤外周侧延伸。对8例原发性口腔癌患者采用热疗联合化疗治疗。结果,热分布良好,所有患者均获得完全缓解。实验研究了磁性脂质体间质热疗的抗肿瘤效果。原发舌瘤因热分布良好而消失。磁性脂质体选择性递送至颈部淋巴结转移灶。交变磁场作用下颈部淋巴结转移灶出现坏死和细胞凋亡。现有药物的糖铁在交变磁场下加热。交变磁场下顺铂联合阿铁糖素对肿瘤细胞凋亡的诱导效果优于单用顺铂,且差异有统计学意义。实验研究了一种具有抗癌活性的新型磁导传递抗癌剂Fe (Salen)的抗癌效果。单用铁(Salen)可抑制舌肿瘤的生长。在交变磁场作用下,铁(Salen)热证实舌瘤消失,铁(Salen)间质热治疗舌瘤消失。超选择性动脉内放化疗联合射频热疗是晚期口腔癌伴颈淋巴结转移(N3)的有效治疗方法。该疗法有望成为晚期口腔癌无创治疗的新策略。
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引用次数: 0
Effectiveness of Hyperthermia on Cancer Stem Cells 热疗对癌症干细胞的疗效
Pub Date : 2017-01-01 DOI: 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.
癌症干细胞(CSCs)或肿瘤起始细胞(tic)已在多种癌症中被发现,并被定义为具有干细胞样表型的一小群癌细胞。CSCs对当前的化疗和放疗具有耐药性,具有较高的肿瘤发生能力。CSCs可能导致肿瘤转移和肿瘤复发,导致预后不良。因此,CSCs的靶向策略对于癌症治疗的推进具有极其重要的意义。然而,CSC本身并没有得到很好的理解。本文综述了CSC研究中应注意的要点,并考虑了热疗对CSC靶向治疗的有效性。据报道,加热对一些与csc存活相关的细胞外和细胞内因子有抑制作用。在这篇综述中,热疗在csc靶向癌症治疗中的潜力与这些生存因素的关系进行了讨论。
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引用次数: 0
Current Treatment and Application of Hyperthermia for Squamous Cell Carcinoma of the Esophagus 热疗治疗食管鳞状细胞癌的现状及应用
Pub Date : 2017-01-01 DOI: 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
Squamous cell carcinoma of the esophagus (ESCC) is a fairly aggressive disease with a poor prognosis. Surgical resection has been the gold standard of treatment for localized ESCC. However, this carcinoma is fairly sensitive to radiation, as well as chemotherapeutic agents such as cisplatin and 5-fluorouracil. Based on clinical trials conducted mainly by the Japan Clinical Oncology Group (JCOG), preoperative chemotherapy is regarded as the standard treatment for resectable ESCC in Japan. We have applied hyperthermia to ESCC mainly as a preoperative treatment associated with chemoradiotherapy since it has been experimentally proven to enhance the anti-tumor effects of chemotherapeutic agents and irradiation. The long-term survival as well as histological effectiveness was reported to be better in patients who received preoperative hyperthermochemoradiotherapy (HCR) than in those who received preoperative chemoradiotherapy (CRT). Definitive CRT is frequently performed even for resectable ESCC, and salvage treatment for either remnant or recurrent diseases remains an important clinical problem. We have applied hyperthermia simultaneously with chemotherapy as a salvage treatment for such patients, and complete response as well as stable disease was achieved in several patients. Hyperthermia is a promising modality as a salvage treatment and has recently been incorporated into regimens including taxanes. Potential enhancement of hyperthermia with certain drugs should be experimentally evaluated, and the clinical application of Hyperthermia for esophageal cancer ・ M. Morita et al. 63 ― ― Received 6 July, 2017, Accepted 28 August, 2017: This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sport, Science and Technology of Japan and the Fujii Setsuro Memorial Foundation. *Corresponding author: Tel, +81-92-541-3231; Fax, +81-92-542-8503; e-mail, masarum@nk-cc.go.jp doi: 10.3191/thermalmed.33.63 ©2017 Japanese Society for Thermal Medicine hyperthermia may be warranted with other newly-developed regimens.
食管鳞状细胞癌(ESCC)是一种侵袭性很强的疾病,预后较差。手术切除一直是治疗局限性ESCC的金标准。然而,这种癌对放射以及化疗药物如顺铂和5-氟尿嘧啶相当敏感。根据主要由日本临床肿瘤小组(JCOG)开展的临床试验,术前化疗在日本被视为可切除ESCC的标准治疗方法。我们将热疗应用于ESCC,主要是作为术前与放化疗相关的治疗,因为实验证明热疗可以增强化疗药物和放疗的抗肿瘤作用。据报道,术前接受高温放化疗(HCR)的患者的长期生存和组织学疗效优于术前接受放化疗(CRT)的患者。即使对于可切除的ESCC,也经常进行明确的CRT,对于残余或复发疾病的抢救治疗仍然是重要的临床问题。我们将热疗与化疗同时应用于此类患者的抢救治疗,有几例患者达到完全缓解和病情稳定。热疗是一种很有前途的救助性治疗方式,最近已被纳入包括紫杉烷在内的治疗方案。应实验评估某些药物对热疗的潜在增强作用,以及热疗在食管癌中的临床应用·M. Morita等。63 - - 2017年7月6日收到,2017年8月28日接受:这项工作得到了日本教育、文化、体育、科学技术省和藤井Setsuro纪念基金会的部分资助。*通讯作者:电话:+81-92-541-3231;传真+ 81-92-542-8503;e-mail, masarum@nk-cc.go.jp doi: 10.3191/thermalmed.33.63©2017日本热医学学会热疗可能与其他新开发的方案一起得到保证。
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引用次数: 0
Interstitial Hyperthermia in Combination with Radiation Brachytherapy for Treatment of Breast Tumor 间质热疗联合近距离放射治疗乳腺肿瘤
Pub Date : 2017-01-01 DOI: 10.3191/THERMALMED.33.53
Oiendrila B. Debnath, K. Saito, K. Ito, M. Uesaka
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引用次数: 4
Thermal Therapy as Multidisciplinary Therapy Applied to Rectal Cancer:: A New Perspective and Potential Role of This Treatment 热疗法作为多学科治疗在直肠癌中的应用:一个新的视角和潜在的作用
Pub Date : 2017-01-01 DOI: 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。
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引用次数: 0
Targeting Cell Survival Factors, HSF1 and HSPs, with a Specific Inhibitor for Cancer Therapy 靶向细胞生存因子,HSF1和热休克蛋白,用特异性抑制剂治疗癌症
Pub Date : 2017-01-01 DOI: 10.3191/THERMALMED.33.1
K. Ohtsuka
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.
已知主要的热休克蛋白,如Hsp90和Hsp70及其转录因子HSF1在广泛的癌细胞中过表达。然而,其生物学意义尚不清楚。最近,人们已经认识到HSF1和HSPs是细胞生存因子,是癌细胞发育和进展的必要因素,并且HSF1-HSPs系统似乎被癌细胞在应激条件下(低氧浓度、低营养、低pH)的生存所利用。根据这一概念,针对HSF1和热休克蛋白的特异性抑制剂已被建议用于癌症治疗。从1990年开始,Hsp90抑制剂不仅在基础研究中,而且在临床I期、II期甚至III期试验中都得到了广泛的研究。最近,几种Hsp70和HSF1抑制剂被报道用于癌症治疗。本文综述了针对这些生存因子(HSF1和HSPs)的特异性抑制剂治疗癌症的基础研究进展。
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引用次数: 4
Clinical Application of Hyperthermia to Soft Tissue Sarcoma; Result of Single Institution 热疗治疗软组织肉瘤的临床应用单一制度的结果
Pub Date : 2017-01-01 DOI: 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.
:采用放疗、热疗、化疗相结合的放射-高温化疗(RHC)治疗软组织恶性肿瘤,目的是减少术后局部复发。我们进行了各种实验,将这种三模式疗法应用于软组织肉瘤,在此回顾我们机构的进展。体外热疗(42-43℃)导致细胞凋亡,并选择性地减少G1期细胞数量,这被认为表现出辐射抗性。此外,42℃的热疗与顺铂同时施用可增加细胞内抗肿瘤药物的浓度,从而显著抑制DNA合成。这些发现加强了热疗和化疗/放疗的协同作用。RHC组和数据库组分别为87.1%;p = 0.04),尽管RHC组患者的手术缘更近。因此,RHC新辅助治疗可以抑制局部复发,为微创手术后治疗软组织肉瘤提供了一种新的策略,可能导致肢体保留和避免截肢。
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引用次数: 0
温熱・化学・放射線治療および高気圧酸素療法を用いた集学的治療で完全奏効と長期生存が得られた切除不能胆嚢癌の1例 采用温热、化学、放射线治疗和高气压氧疗法的集学治疗,获得完全奏效和长期存活的不可切除胆囊癌1例
Pub Date : 2016-09-30 DOI: 10.3191/THERMALMED.32.13
義士 鞆田, 真 太田, 肇 今田, 宏之 成定, 丈明 森岡
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引用次数: 0
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Thermal Medicine
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