[Show abstract][Hide abstract] ABSTRACT: Purpose: Despite advances in cancer therapy, treating pancreatic cancer remains one of the major challenges in the field of medical oncology. We conducted this phase II study to evaluate the efficacy and safety of regional hyperthermia combined with gemcitabine for the treatment of unresectable advanced pancreatic cancer. Methods: Eligibility criteria included histologically proven, locally advanced or metastatic pancreatic cancer. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15 every 4 weeks. Regional hyperthermia was performed once weekly, 1 day preceding or following gemcitabine administration. The primary end point was the 1-year survival rate. Secondary objectives were determination of tumour response and safety. Results: We enrolled 18 patients with advanced pancreatic cancer between November 2008 and May 2010. The major grade 3-4 adverse events were neutropenia and anaemia; however, there were no episodes of infection. The objective response rate (ORR) and disease control rate (ORR + stable disease) were 11.1% and 61.1%, respectively. Median overall survival (OS) was 8 months, and the 1-year survival rate was 33.3%. Median OS of patients with locally advanced pancreatic cancer was 17.7 months. Conclusions: Regional hyperthermia combined with gemcitabine is well tolerated and active in patients with locally advanced pancreatic cancer.
International Journal of Hyperthermia 07/2012; 28(7):597-604. DOI:10.3109/02656736.2012.695428 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previously we have demonstrated that whole body hyperthermia (WBH) improves insulin resistance in diabetic mice. The aim of the present study was to perform a gene expression analysis of the liver and adipose tissue of obesity-induced insulin resistant diabetic mice (db/db mice) after WBH and to define the molecules that play the important role in improvement of insulin resistance by WBH. Male db/db mice were treated with WBH 3 times per week for 12 weeks. Total RNA was extracted from the liver and adipose tissue of db/db mice, and differences in the gene expression profiles among db/+ mice, untreated db/db mice, and WBH-treated db/db mice were investigated using a high-density DNA microarray. WBH directly targets liver and adipose tissue, resulting in modifications in NF-kappaB and IL-6 signalling pathways, as well as lipid metabolism. Although the mechanisms have not yet been completely investigated, we can conclude that WBH may provide a new therapeutic or preventive modality against type 2 diabetes mellitus and metabolic or insulin resistance syndrome through the modification of several signalling pathways.
International Journal of Hyperthermia 01/2010; 26(2):101-7. DOI:10.3109/02656730903272917 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 64-year-old man was admitted to our hospital with anal pain on evacuation. MRI revealed a large rectal submucosal tumor, more than 6 cm in diameter. Fine needle histological diagnosis indicated GIST with moderate risk. The patient was treated with imatinib mesylate in order to preserve the anus. The anal pain and tumor size decreased. Trans-anal local excision was performed. This case suggests that imatinib mesylate can make it possible to treat large rectal GIST cases by preserving anus, if neoadjuvant chemotherapy can be effective.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 12/2009; 106(12):1751-7.
[Show abstract][Hide abstract] ABSTRACT: We examined whether hyperthermia attenuated the metastatic potential of colon cancer through the induction of heat shock protein 70 (Hsp70).
Colon26 cells were separated into four groups: (1) no pretreatment, (2) hyperthermia at 42 degrees C for 1 hour, (3) pretreatment with geranylgeranylacetone (GGA) 10(-6) M for 2 hours, and (4) hyperthermia after GGA treatment. We measured cell viabilities and the contents of Hsp70. We assessed nuclear factor-kappa-B (NF-kappa-B) status with and without tumor necrosis factor-alpha (TNF-alpha) stimulation. For in vivo study, colon26 cells were injected via the tail vein or into a subcutaneous area of mice and the numbers of lung metastatic nodules or the volumes of subcutaneous tumors were assessed. Untreated cells were incubated with PKH26. Experimental metastasis models were then generated and used to assess the fixed cancer cells.
Tumor development in the subcutaneous tumor models and cell viabilities were similar among the four groups. However, the GGA plus hyperthermia group had fewer lung metastatic nodules in the experimental lung metastasis model and higher Hsp70 induction than the other cell groups. The GGA plus hyperthermia pretreatment group also showed a lower number of fixed cells in lungs and lower activation of NF-kappa-B by TNF-alpha than the other cell groups.
It is suggested the metastatic potential but not the proliferation potency of cancer cells is inhibited by the transient induction of Hsp70.
International Journal of Hyperthermia 04/2009; 25(2):141-9. DOI:10.1080/02656730802631783 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Whole body hyperthermia (WBH) has been used clinically as an adjunct to radio- and chemotherapy in patients with various cancers. Recently, it has been reported that an activation of the immune system has recently been reported as a possible contributor to the therapeutic effects of WBH. Conversely, the glycolipid alpha-galactosylceramide (alpha-GalCer) is recognized by natural killer (NK) T cells together with the monomorphic MHC-like antigen, CD1d, in mice and humans. This study investigated the antitumor effects of WBH combined with alpha-GalCer in a mouse subcutaneous tumor model of colon cancer.
Colon26 cells were inoculated subcutaneously into male BALB/c mice to establish subcutaneous tumor. Colon26-bearing mice were treated with WBH using far infrared rays three times/week. Rectal temperature was maintained for 60 min at 41 degrees C. In some experimental groups, alpha-GalCer was intraperitoneally injected before WBH. We investigated the therapeutic effects of WBH, alpha-GalCer and combined therapy.
(1) Compared with controls, WBH alone resulted in significant inhibition of tumor growth. (2) No inhibitory effect on tumor growth was seen with alpha-GalCer. (3) The combination of WBH and alpha-GalCer showed significant inhibition of tumor growth and prolongation of survival. (4) Serum IFN-gamma increased after 3 h and returned to basal levels by 24 h after alpha-GalCer administration. (5) CTL activity was enhanced following combination therapy with WBH and alpha-GalCer.
WBH showed antitumor effects in a mouse subcutaneous tumor model of colon cancer. Addition of alpha-GalCer increased the efficacy of WBH, probably via enhancement of immune response.
International Journal of Hyperthermia 12/2007; 23(7):591-8. DOI:10.1080/02656730701708328 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we examined the efficacy of whole body hyperthermia (WBH) on obesity-induced insulin resistance in diabetic mice.
Male db/db mice were treated with WBH 3 times per week for 12 weeks. The rectal temperature of mice reached 38.0 degrees C 5 min after heating, and was kept at 38.0 degrees C for 30 min. At the end of each week, tail snip glucose levels were determined under fasting conditions. The GLUT-4 gene expression of muscle tissue was analyzed by real-time PCR.
(1) WBH-treated db/db mice showed a significant decrease in fasting blood glucose level as compared with untreated db/db mice (p < 0.01). (2) Plasma insulin levels in untreated db/db mice at the age of 10 weeks were significantly increased compared with those of db/+ mice (p < 0.0001). On the other hand, the reduction (31%) in insulin levels in WBH-treated mice indicated improved insulin sensitivity. (3) The ability of WBH to increase insulin sensitivity was further established in glucose tolerance tests and insulin tolerance tests. (4) Urine albumin of db/db mice significantly increased compared with those of db/+ mice at 18 weeks of age (p < 0.001). This increase in urinary albumin was significantly inhibited by WBH (p < 0.01). (5) WBH up-regulated the expression of GLUT4 mRNA in skeletal muscle.
Although the mechanisms have not yet been completely investigated, WBH may provide a new therapeutic or preventive modality against obesity-related diseases such as T2DM and metabolic or insulin resistance syndrome.
International Journal of Hyperthermia 06/2007; 23(3):259-65. DOI:10.1080/02656730601176824 · 2.65 Impact Factor