Nuclear heat shock protein 110 expression is associated with poor prognosis and hyperthermo-chemotherapy resistance in gastric cancer patients with peritoneal metastasis.

AIM: To investigate the significance of heat shock protein 110 (HSP110) in gastric cancer (GC) patients with peritoneal metastasis undergoing hyperthermo-chemotherapy. METHODS: Primary GC patients (n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermo-chemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS: HSP110 immnohistochemical staining in 14 GC patients showed that five (35.7%) samples belonged to the low expression group, and nine (64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group (P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis (P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 °C in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 °C, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro. CONCLUSION: The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.

In vivo anti-cancer efficacy of magnetite nanocrystal--based system using locoregional hyperthermia combined with 5-fluorouracil chemotherapy.

We present an approach for synchronizing hyperthermia and thermal-responsive local drug release. The targeting probe has a magnetite nanocrystal (Fe3O4@PSMA) core and a polynucleotide shell that carries 5-fluorouracil (5-FU) and anti-human epidermal growth factor receptor 2 (anti-HER2) antibody for cancer cell-specific targeting. The targeting nanocrystals play as an important role to relay the externally delivered radiofrequency energy for tumor hyperthermia. Locoregional heat then triggers a drug release from the oligonucleotide carrier as it directly damages tumor cells. Cell viability assays and pathological examinations show that this synchronization is significantly more efficacious in both in vitro and in vivo models than hyperthermia or chemotherapy alone. Prominent tumor remission in vivo was achieved through radiofrequency synchronization of hyperthermia and chemotherapy after the nanoparticle had been intravenously injected.

Evaluation of the optimal temperature for interventional thermochemotherapy treatment of hepatic carcinoma / 介入放射学杂志

Objective To explore a safe and effective hyperthermia interventional therapy temperature for hepatic carcinoma. Methods Eight swines were divided into four groups according to trans-arterial hyperthermic perfusion temperature, 45 ?C , 50 ?C ,55 ?C , and 60 ?C (catheter flowing temperature) groups. The hepatic and renal functions and blood coagulation function were examined before and after the procedur and then all swines were sacrificed and the livers were pathologically analysed,simultoneously with the evaluation of the safe hyperthermic temperature 35 hepatic carcinomas were carried out under this interventional hyperthermochemotherapy via the arterial catheter (80 cm, 5F) placed into the tumoral artery with the perfusion agents warmed to 60～65 ?C (catheter flowing temperature was 47.55?0.44 ?C ). Results The hyperthermic coagulation necrosis, hepatic dysfunction level and fever were found after 55 ?C and 60 ?C hyperthermic perfusion while those of 45 ?C and 50 ?C groups basically remained normal. The tumor growth rate and total efficacy rate were -(0.35?0.32) and 79.2%, respectively, and 0.5, 1, 1.5 year survival rates were 100%, 80%, 60% respectively after follow-up. The adverse effects of the interventional hyperthermochemotherapy was similar to the routine TACE. Conclusions 45 ?C and 50 ?C (catheter flowing temperature) hyperthermochemotherapy for hepatic carcinoma is safe and effective.