Abstract Title: Positive response of a primary leiomyosarcoma of the breast following salvage hyperthermia and pazopanib. Abstract Source: Korean J Intern Med. 2016 Apr 15. Epub 2016 Apr 15. PMID: 27079325 Abstract Author(s): Sun Young Lee, Na-Ri Lee Article Affiliation: Sun Young Lee Abstract: No Abstract Available Article Published Date : Apr 14, 2016

Abstract Title: Hyperthermia synergizes with chemotherapy by inhibiting PARP1-dependent DNA replication arrest. Abstract Source: Cancer Res. 2016 Mar 24. Epub 2016 Mar 24. PMID: 27013194 Abstract Author(s): Lea Schaaf, Matthias Schwab, Christoph Ulmer, Simon Heine, Thomas E Mürdter, Jens O Schmid, Georg Sauer, Walter E Aulitzky, Heiko van der Kuip Article Affiliation: Lea Schaaf Abstract: Although hyperthermia offers clinical appeal to sensitize cells to chemotherapy, this approach has been limited in terms of long-term outcome as well as economic and technical burden. Thus, a more detailed knowledge about how hyperthermia exerts its effects on chemotherapy may illuminate ways to improve the approach. Here we asked whether hyperthermia alters the response to chemotherapy-induced DNA damage and if this mechanism is involved in its sensitizing effect, in BRCA-competent models of ovarian and colon cancer. Notably, we found that hyperthermia delayed the repair of DNA damage caused by cisplatin or doxorubicin, acting upstream of different repair pathways to block histone polyADP-ribosylation (PARylation), a known effect of chemotherapy. Further, hyperthermia blocked this histone modification as efficiently as pharmacological inhibitors of polyADP-ribosyl polymerase (PARPi), producing comparable delay in DNA repair, induction of double strand breaks (DSB) and cell cytotoxicity after chemotherapy. Mechanistic investigations indicated that inhibiting PARylation by either hyperthermia or PARPi induced lethal DSB upon chemotherapy treatment, not only by reducing DNA repair but also by preventing replication fork slowings. Overall, our work reveals how PARP blockade - either by hyperthermia or small molecule inhibition - can increase chemotherapy-induced damage in BRCA-competent cells. Article Published Date : Mar 23, 2016

Abstract Title: Antiproliferative and Proapoptotic Effects of Crocin Combined with Hyperthermia on Human Breast Cancer Cells. Abstract Source: DNA Cell Biol. 2016 Mar 22. Epub 2016 Mar 22. PMID: 27003728 Abstract Author(s): Seyedeh Elham Mostafavinia, Mohsen Khorashadizadeh, Reyhane Hoshyar Article Affiliation: Seyedeh Elham Mostafavinia Abstract: We investigated the suppressive effects of crocin alone and in combination with hyperthermia (HT) on proliferation of breast cancer cells. Cell viability, colony formation ability, and apoptosis were assessed by 3-(4,5-dimetylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), soft agar, Hoechst 33258 staining, and percentage of lactate dehydrogenase (LDH) release methods, respectively. The mRNA levels Hsp27, Hsp70, Hsp90, Bax, and Bcl-2 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hsp70 and Hsp90 proteins were determined using enzyme-linked immunosorbent assay (ELISA) technique. Crocin in combination with HT significantly inhibited the proliferation of cancer cells in a dose- and time-dependent manner. There was a degree of synergism in the combined treatment. However, crocin did not show the high cytotoxic effect on normal cells. This treatment decreased colony formation of cancer cells up to 94%. Changed nuclear morphology and increased LDH indicated that crocin combined with HT has a more apoptotic effect than crocin alone. Furthermore, in treated cells Bax/Bcl-2 ratio markedly increased, whereas expression of heat-induced genes decreased. Also, the Hsp70 and Hsp90 proteins decreased in the treated cells. Our study indicated that combination of crocin and HT has strong antiproliferative and apoptotic activities against breast cancer cells. Hence, it is suggested that more studies are warranted to apply crocin as a possible, safe, and promising anticancer agent in cancer. Article Published Date : Mar 21, 2016

Abstract Title: Targeted near infrared hyperthermia combined with immune stimulation for optimized therapeutic efficacy in thyroid cancer treatment. Abstract Source: Oncotarget. 2016 Feb 9 ;7(6):6878-90. PMID: 26769848 Abstract Author(s): Le Zhou, Mengchao Zhang, Qingfeng Fu, Jingting Li, Hui Sun Article Affiliation: Le Zhou Abstract: Treatment of thyroid cancer has incurred much focus because of its high prevalency. As a new strategy treating thyroid cancer, hyperthermia takes several advantages compared with surgery or chemotherapy, including minimal invasion, low systematic toxicity and the ability to enhance the immunogenicity of cancer cells with the expression Hsp70 which serves as Toll-like receptors-4 (TLR-4 agonist). However, Hsp70 as a molecular chaperone can protect cells from heat induced apoptosis and therefore compromise the tumor killing effect of hyperthermia. In this study, to solve this problem, a combined hyperthermia therapy was employed to treat thyroid cancer. We prepared a probe with the tumor targeting agent AG to monitor thyroid tumor issue and generate heat to kill tumor cells in vivo. At the same time Quercetin (inhibitor of HSP70) and lipopolysaccharide (LPS) (agonist of TLR-4) were used for the combined hyperthermia therapy. The results showed that compared with free IR820, AG modification facilitated much enhanced cellular uptake and greatly pronounced tumor targeting ability. The combined therapy exhibited the most remarkable tumor inhibition compared with the single treatments both in vitro and in vivo. These findings verified that the new therapeutic combination could significantly improve the effect of hyperthermia and shed light on a novel clinical strategy in thyroid cancer treatment. Article Published Date : Feb 08, 2016

Abstract Title: Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma. Abstract Source: Tumour Biol. 2015 Dec 1. Epub 2015 Dec 1. PMID: 26628295 Abstract Author(s): Wei Dai, Quangen Gao, Jianping Qiu, Jianmao Yuan, Guoliang Wu, Genhai Shen Article Affiliation: Wei Dai Abstract: Quercetin (Q), a flavonoid compound, which is obtained in variety of fruits, seeds, and vegetables, has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, studies on the anticancer effects and underlying mechanisms of Q in human hepatocellular carcinoma (HCC) are still limited. The present study is conducted to investigate the anticancer efficacy and adjuvant chemotherapy action of Q in HCC. HCC cell lines HepG2 and SMCC-7721 were treated with different concentrations of Q. The antiproliferative effects of Q were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the apoptosis and cell cycle dynamics were assessed by flow cytometry; the expression of apoptosis-associated proteins were evaluated by Western blot and immunohistochemistry staining; the tumor growth in vivo was evaluated in a xenograft mouse model. Our results showed that Q effectively inhibited human HCC cell proliferation and induced apoptosis by upregulating the expression of Bad and Bax and downregulating the expression of Bcl-2 and Survivin in vitro. Furthermore, Q obviously inhibited the tumor growth and enhanced the 5-fluorouracil (5-FU) therapeutic efficacy in vitro and in vivo. Taken together, our findings highlight that Q effectively inhibited the growth of tumor and enhanced the sensitivity to thermotherapy, indicating Q is a potential treatment option for HCC. Article Published Date : Nov 30, 2015

Abstract Title: Efficacy of hyperbaric oxygen therapy combined with mild hyperthermia for improving the anti-tumour effects of carboplatin. Abstract Source: Int J Hyperthermia. 2015 ;31(6):643-8. Epub 2015 Jul 9. PMID: 26156211 Abstract Author(s): Takayuki Ohguri, Naoki Kunugita, Katsuya Yahara, Hajime Imada, Hidehiko Uemura, Nadayoshi Shinya, Gotou Youjirou, Chijiwa Takashi, Ryuji Okazaki, Akira Ootsuyama, Yukunori Korogi Article Affiliation: Takayuki Ohguri Abstract: PURPOSE: The aim of this study was to evaluate the effects of hyperbaric oxygen therapy (HBO) on the enhancement of hyperthermic chemosensitisation to carboplatin at mild temperatures in experimental tumours. METHODS: SCCVII carcinoma in C3H/He mice was used to assess tumour growth delay. The mice received intraperitoneal injections of carboplatin. For HBO treatment, the mice were exposed to HBO at 2.0 atmospheres of absolute oxygen for 60 min. For mild hyperthermia (HT), treatment at 41.5 °C for 30 min was performed. The tumour tissue pO2 levels were measured with a digital pO2 monitor during and immediately after treatment. RESULTS: The average time taken to reach a threefold relative tumour size was significantly longer after treatment with carboplatin combined with mild HT and HBO than after treatment with carboplatin and mild HT. The relative sizes of the tumours after the combined treatment were smallest when the treatment sequence was carboplatin, mild HT, and HBO. The tumour tissue pO2 values were significantly higher immediately after mild HT followed by HBO than immediately after HBO followed by mild HT. The tumour tissue pO2 levels during mild HT and HBO generally increased, although the patterns of the increases varied. CONCLUSION: The administration of HBO increased the effects of hyperthermic chemosensitisation to carboplatin at mild temperatures on experimental tumours, particularly when given in the sequence of carboplatin, mild HT, and HBO, a finding that supports previous clinical outcomes for a novel combined therapy using carboplatin plus HT and HBO. Article Published Date : Dec 31, 2014

Abstract Title: Hyperthermia combined with 5-fluorouracil promoted apoptosis and enhanced thermotolerance in human gastric cancer cell line SGC-7901. Abstract Source: Onco Targets Ther. 2015 ;8:1265-70. Epub 2015 May 27. PMID: 26064061 Abstract Author(s): Tao Liu, Yan-Wei Ye, A-Li Zhu, Zhen Yang, Yang Fu, Chong-Qing Wei, Qi Liu, Chun-Lin Zhao, Guo-Jun Wang, Xie-Fu Zhang Article Affiliation: Tao Liu Abstract: This study was designed to investigate the proliferation inhibition and apoptosis-promoting effect under hyperthermia and chemotherapy treatment, at cellular level. Human gastric cancer cell line SGC-7901 was cultivated with 5-fluorouracil at different temperatures. Cell proliferation and apoptosis were determined, and expression of Bcl-2 and HSP70 was measured at different treatments. Cell survival rates and inhibition rates in chemotherapy group, thermotherapy group, and thermo-chemotherapy group were drastically lower than the control group (P<0.05). For tumor cells in the thermo-chemotherapy group, survival rates and inhibition rates at three different temperatures were all significantly lower than those in chemotherapy group and thermotherapy group (P<0.05). 5-Fluorouracil induced apoptosis of SGC-7901 cells with a strong temperature dependence, which increased gradually with increase in temperature. At 37°C and 43°C there were significant differences between the thermotherapy group and chemotherapy group and between the thermo-chemotherapy group and thermotherapy group (P<0.01). The expression of Bcl-2 was downregulated and HSP70 was upregulated, with increase in temperature in all groups. Cell apoptosis was not significant at 46°C (P>0.05), which was probably due to thermotolerance caused by HSP70 accumulation. These results suggested that hyperthermia combined with 5-fluorouracil had a synergistic effect in promoting apoptosis and enhancing thermotolerance in gastric cancer cell line SGC-7901. Article Published Date : Dec 31, 2014

Abstract Title: Inhibitory effects of mild hyperthermia plus docetaxel therapy on ER(+/-) breast cancer cells and action mechanisms. Abstract Source: J Huazhong Univ Sci Technolog Med Sci. 2013 Dec ;33(6):870-6. Epub 2013 Dec 13. PMID: 24337851 Abstract Author(s): Feng Lv, Yang Yu, Bin Zhang, Dong Liang, Zhao-ming Li, Wei You Article Affiliation: Feng Lv Abstract: The purpose of this study was to verify that a combination of mild hyperthermia and docetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach. The effects of docetaxel on the proliferation of cells from the estrogen receptor (ER)-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and effective experimental concentrations of docetaxel were determined. The effects of mild hyperthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The effects of these combined treatments on cell cycle progression in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cytometry. The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase (MAPK) pathways were analyzed by using Western blotting. The effects of these combined treatments on the expression of the heat shock protein 70 (HSP70) and the multi-drug resistance (MDR) gene product P-glycoprotein (Pgp) were examined by using Western blotting. The results showed that the half-maximal inhibitory concentration (IC50) of docetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31 μmol/L respectively. Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453 cells. Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from (23.66±3.59)% and (18.51±3.17)% in docetaxel treatment group to (47.12±6.73)% and(55.16±7.42)% in mild hyperthermia plus docetaxel group, indicating that the mild hyperthermia and docetaxel therapeutic approaches exhibited significant synergistic antitumor effects. Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells. Western blotting demonstrated that proteins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone. As compared with blank control group, cells from the mild hyperthermia plus docetaxel group exhibitedsignificantly decreased B-cell lymphoma 2 (Bcl-2) protein expression but slightly increased Bcl-2-associated X protein (Bax) expression. Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia. It was concluded that treatments of mild hyperthermia plus docetaxel inhibited the proliferation of human breast cancer cells, promoted apoptosis of breast cancer cells, and produced synergistic antitumor effects. Article Published Date : Nov 30, 2013

Abstract Title: [Synergistic effect of thermotherapy in combination with chemotherapy on lung tumor A549 cells growth through activation of c-Jun N-terminal kinase and inhibition of heat shock protein70 expression]. Abstract Source: Wei Sheng Yan Jiu. 2008 Sep ;37(5):529-32. PMID: 19069644 Abstract Author(s): Shan Gao, Lin Wang, Weidong Wu, Fang Zhou Article Affiliation: Shan Gao Abstract: OBJECTIVE: To study the synergistic effect of thermotherapy and chemotherapy with chemotherapy on lung tumor cell growth in order to explore its underlying mechanisms. METHODS: A549 cells were treated by combination of 43 degrees C and 50 microg/L Paclitaxel, and 43 degrees C or 50 microg/L Paclitaxel alone. MTU assay and Wound-healing assay were used to measure the survival and the invasive capacity. Phosphorylation of JNK and expression of HSP70 were determined with Western Blotting. Cells without treatment were used as controls. RESULTS: In comparison with cells treated with 43 degrees C and 50 microg/L Paclitaxel alone, or with combination of 43 degrees C and 50 microg/L Paclitaxel and SP600125, the proliferation rate of cells subjected to combination treatment of 43 degrees C and 50 microg/L Paclitaxel decreased significantly (P>0.05). There were no significant differences in cell proliferation between untreated cells and the cells treated with 43 degrees C heat, 50 microg/L Paclitaxel and SP600125 (P>0.05). The invasive capacities of the cells treated combination of 43 degrees C heat and 50 microg/L Paclitaxel were markedly reduced in comparison to other treatment groups. Also phosphorylations of JNK were significantly elevated in comparison to untreated cells or the cells only underwent chemotherapy (P<0.05). The expression levels of HSP70 on thermotherapy in combination with chemotherapy were more lower than those in thermotherapy group (P<0.05). CONCLUSION: Thermotherapy in combination with chemotherapy showed more strong inhibitory effect than those of thermotherapy or chemotherapy alone on lung tumor cell growth. The resultant phosphorylation of JNK and inhibition of HSP70 expression could be responsible for this effect. Article Published Date : Aug 31, 2008

Abstract Title: Effects of deep and superficial heating in the management of frozen shoulder. Abstract Source: J Rehabil Med. 2008 Feb;40(2):145-50. PMID: 18509580 Abstract Author(s): May S F Leung, Gladys L Y Cheing Article Affiliation: Physiotherapy Department, Our Lady of Maryknoll Hospital, Hong Kong. Abstract: OBJECTIVES: To determine whether the addition of deep or superficial heating to stretching produces better clinical outcomes than stretching alone in the management of frozen shoulder. DESIGN: A single-blinded, randomized controlled study. SUBJECTS: Thirty subjects suffering from the stiffness phase of frozen shoulder. METHODS: Subjects were randomly allocated to receive: (i) deep heating plus stretching; (ii) superficial heating plus stretching; or (iii) stretching alone. Both heating groups received the respective treatments 3 times per week for 4 weeks. All groups received a standard set of shoulder stretching exercises. The American Shoulder and Elbow Surgeons assessment form was recorded at the baseline, sessions 6 and 12, and at the 4-week follow-up session. RESULTS: A significant improvement was seen in all groups in all outcome measures except for that of shoulder flexion range. The improvement in the shoulder score index and in the range of motion was significantly better in the deep heating group than in the superficial heating group. CONCLUSION: The addition of deep heating to stretching exercises produced a greater improvement in pain relief, and resulted in better performance in the activities of daily living and in range of motion than did superficial heating. Article Published Date : Feb 01, 2008