恶性肿瘤精准热疗的部分研究进展

21世纪以来,随着人们生活习惯的改变及生活环境污染的增加,肿瘤的发病率日益升高,成为人类疾病死亡的主要原因。目前除了常规治疗肿瘤的三大手段之外,热疗的出现为肿瘤的防治提供了更为安全有效的方案。机械制造、计算机技术及分子生物学、材料学等学科的高速发展,尤其是以MRI无创测温技术引导下的射频和超声聚焦热疗技术以及分子水平靶向热疗手段为代表的精准热疗,为肿瘤治疗提供了更为广阔的前景。为更好地了解目前肿瘤精准热疗的大体情况,本文就其部分研究进展进行了综述。     

基于磁纳米材料的磁热疗抗肿瘤研究进展北大核心CSCD

肿瘤热疗是继手术、放化疗、靶向治疗等治疗之后又一重要的肿瘤治疗手段。磁热治疗(MH)是一种新兴的热疗方法,因具有无创/微创性、高效性和良好的组织穿透性等优点而受到广泛关注,为恶性肿瘤实现高效、低不良反应精准医疗分子水平治疗提供了新手段,成为目前肿瘤治疗新的研究方向。实现MH需要磁性材料和适宜磁场,其中氧化铁纳米颗粒(IONs)由于其较高的生物相容性和加热能力而被广泛研究为MH剂。本文就磁性纳米氧化铁材料的研究进展及目前基于磁性纳米颗粒的磁性热疗协同抗肿瘤治疗的研究进展进行分析,综述磁热治疗这一前沿技术在肿瘤治疗中的潜在应用。     

功能型复合生物材料用于肿瘤局部热疗的研究进展

肿瘤热疗不但具有杀伤广谱恶性肿瘤的能力,还可与化疗、放疗在临床治疗上相结合产生协同增敏的效果。同时又能减轻放、化疗治疗的毒副作用,因而被国际医学界称为“绿色疗法”。当前新型的热疗手段与传统的热疗手段相比较而言,能够提高治疗的适形性、有效性和靶向性,并且能够极大的减小热疗的毒副作用。但是新型的热疗手段需要借助于外界的能量源和热疗介质,即由安全、高效的热疗介质将外源的能量转化为热量并在肿瘤区域实现能量的“聚焦”,从而达到对肿瘤组织精确、高效的杀伤。所以,对基于功能型生物材料的热疗介质的开发和选择就成为了决定新型热疗治疗效果的关键因素。目前,针对肿瘤局部热疗的功能型复合生物材料的综述鲜有报道,因此,本文就目前肿瘤热疗领域中光热治疗、磁感应热疗和微波热疗的相关复合介质材料进行总结阐述,为功能型复合生物材料在未来肿瘤热疗领域提供借鉴。     

中国肿瘤热疗临床应用指南(2017.V1.1)

热疗是继手术、放疗、化疗及生物治疗之后的第五种肿瘤治疗手段,亦是重要的肿瘤辅助治疗方法之一,临床应用无毒、安全,也称为绿色治疗。近年来,肿瘤的热疗越来越受到人们的重视,全国许多地市级医院甚至县级医院都普遍开展了肿瘤的热疗,并取得了很好的治疗效果。目前国内外尚无肿瘤热疗的指南和规范,为了指导和规范肿瘤热疗的临床应用,更好地为肿瘤患者服务,特制定中国肿瘤热疗临床应用指南,就浅部热疗、深部热疗、全身热疗及体腔灌注热疗的适应证、禁忌证、操作程序与方法、注意事项、热疗的疗效评价及随访等进行了全面详细地阐述,供肿瘤热疗治疗领域同仁们参考。     

放热疗联用的临床研究进展

1989年被美国FDA认证为第五大肿瘤治疗手段以来,热疗一直是肿瘤治疗方法中的一研究热点。已有临床前期及临床研究充分肯定了热疗的放疗增敏作用,本文基于临床证据就放热疗联用的研究进展做出综述,着重从治疗温度、热疗的次数及间隔时间、放热疗之间的间隔时间与时序等角度,分析讨论了热疗和放疗联用过程中的各类问题。该综述介绍了放热疗结合应用的进展与展望,为进一步进行放热疗联用的临床探索提供了参考。     

放热疗联用的临床研究进展

1989年被美国FDA认证为第五大肿瘤治疗手段以来,热疗一直是肿瘤治疗方法中的一研究热点。已有临床前期及临床研究充分肯定了热疗的放疗增敏作用,本文基于临床证据就放热疗联用的研究进展做出综述,着重从治疗温度、热疗的次数及间隔时间、放热疗之间的间隔时间与时序等角度,分析讨论了热疗和放疗联用过程中的各类问题。该综述介绍了放热疗结合应用的进展与展望,为进一步进行放热疗联用的临床探索提供了参考。     

肿瘤热化疗研究进展

热疗是一种理想的辅助治疗手段,对放疗和化疗都有增敏作用。近年来,肿瘤热化疗的分子生物学以及细胞和动物实验研究方面进展很快,为进一步开展热疗联合化疗的临床试验提供了理论基础和指导。就热化疗治疗肿瘤机制、辅助化疗的不同的热疗方式及热化疗常用药物的研究进行综述。     

食管癌腔内热疗进展

热疗是癌症综合治疗的手段之一。本文综述近年来食管癌腔内热疗的临床研究结果及现存主要问题。 1.加温技术 食管癌热疗属深部肿瘤加温疗法。目前主要用腔内辐射器加温。方     

肿瘤热化疗研究进展

热疗是一种理想的辅助治疗手段,对放疗和化疗都有增敏作用.近年来,肿瘤热化疗的分子生物学以及细胞和动物实验研究方面进展很快,为进一步开展热疗联合化疗的临床试验提供了理论基础和指导.就热化疗治疗肿瘤机制、辅助化疗的不同的热疗方式及热化疗常用药物的研究进行综述.     

肿瘤热化疗研究进展

热疗是一种理想的辅助治疗手段,对放疗和化疗都有增敏作用.近年来,肿瘤热化疗的分子生物学以及细胞和动物实验研究方面进展很快,为进一步开展热疗联合化疗的临床试验提供了理论基础和指导.就热化疗治疗肿瘤机制、辅助化疗的不同的热疗方式及热化疗常用药物的研究进行综述.     

Interstitial hyperthermia (MINERVE) for perineal local recurrence of rectal cancer

Interstitial hyperthermia (MINERVE) was performed for 2 patients with perineal local recurrence of rectal cancer. The MINERVE was a 20 W generator of 550-610 kHz with 4 pairs of probes creating an electromagnetic field (Odam Co., France). The basic regimen was five irradiation treatments of 2 Gy per week, with two hyperthermia treatments (for 60 minutes at more than 43.5 degrees C) a week, 500 mg of 5-FU or 25 mg of CDDP per hyperthermia treatment, and 3 g/day of PSK. The radiation therapy was performed prior to hyperthermia, the chemotherapy at the same time. Perineal tumors and symptoms disappeared completely in 1 patient and were reduced in 1 patient. This treatment is expected to be clinically as a part of multidisciplinary treatment for superficial malignant tumors.     

Immunotherapy and whole-body hyperthermia as combined modality treatment of a subcutaneous murine sarcoma

Interleukin–2 and hyperthermia have been used individually to treat a variety of tumors in both experimental and human trials. Combined adoptive immunotherapy and hyperthermia is an exciting new line of investigation. Previous work in our laboratory has shown that combined local hyperthermia and rIL-2 therapy can significantly decrease the rate of tumor growth. In this study, we investigated the effect of combined whole-body hyperthermia (WBHT) and rIL-2 on the growth of subcutaneous MCA-105 murine tumors in C57BL/6 mice. Treatment of both microscopic (day 3) and macroscopic (day 10) tumors was evaluated. In the treatment of microscopic tumors, animals received either no treatment; rIL-2 (3 × 10⁵ IU ip tid) on days 3–7; plus WBHT(41°C for 30 min) on days 3, 5, and 7; or WBHT only on days 3, 5, and 7. In treating macroscopic tumors, animals received either no treatment; rIL-2 on days 10–14; plus WBHT on days 10, 12, and 14; or WBHT only on days 10, 12, and 14. While combined treatment and WBHT alone had no significant effect on the growth of microscopic tumors, combined IL-2 and WBHT significantly reduced the rate of tumor growth of macroscopic tumors. These results suggest that the tumor microenvironment plays a critical role in combined WBHT and rIL-2 therapy, and may be due to effects of WBHT on the tumor vasculature. © 1993 Wiley-Liss, Inc.     

Effects of tumor necrosis factor-alpha on tumor blood flow and hyperthermic treatment

The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha), given alone or in combination with local hyperthermia, on perfusion and growth of a moderately rhTNF-alpha-sensitive rat tumor (DS-carcinosarcoma) was investigated. DS-carcinosarcomas were implanted into the hind foot dorsum of Sprague-Dawley rats. Tumor blood flow (TBF) was measured with the krypton-85 clearance technique. Treatment with either tumor necrosis factor-alpha (0.1-1.0 mg/kg) or hyperthermia (43.3 and 44.3 degrees C, 40 min) can decrease the perfusion of malignant tumors. The TBF reduction was fully established 2 h after rhTNF-alpha injection and lasted for at least 4 h. The application of local hyperthermia (T greater than 42 degrees C) 3 h after rhTNF-alpha administration further diminished tumor blood flow. Volume growth of the tumors was monitored during repeated treatment. rhTNF-alpha (0.2 and 1.0 mg/kg i.v.) combined with hyperthermia (43.3 and 44.3 degrees C, 40 min, starting 3 h after rhTNF-alpha injection) were given every third day from the fifth to the 20th day after tumor implantation. Monotherapies retarded tumor growth in a dose-dependent manner. Combined treatment was superior to either monotherapy leading to local tumor control in 40-50% of the animals treated. It is concluded that local hyperthermia can enhance the efficacy of rhTNF-alpha treatment by further reducing tumor perfusion.     

Influence of ultrasound-induced hyperthermia and X-irradiation on the incidence of metastases from a solid tumor

The KHT sarcoma transplanted into mouse legs was treated by X-irradiation, hyperthermia or a combination of X-irradiation plus hyperthermia. Neither 20 Gy of X-irradiation or hyperthermia for 60 min were effective in controlling the local tumors when used alone. Simultaneous treatments, however, resulted in 22% of the tumors being locally controlled corresponding to a TER of 2.0. Local control was increased when irradiation was given 1 h before or after hyperthermia, TER 2.8 and was maximum, TER 2.9, when the hyperthermia was 0.1 h after irradiation. When the local tumor was controlled by irradiation alone or by irradiation delivered 1 h before or after hyperthermia, all of the metastases that subsequently occurred arose before or during treatment. When tumors were locally controlled by radiation given during or immediately after hyperthermia, metastases developed that must have occurred as a consequence of the treatment. The treatment sequence that resulted in a maximum TER for tumor control did not correlate with the risk of metastatic spread. The timing of the irradiation in relation to hyperthermia may explain some contradictory findings regarding the influence of heat on the incidence of metastases. Hyperthermia did not affect the distribution of anatomic sites involved with metastases or the ratio of lymphatic to hematogenously spread metastases.     

Current status of lasers in neurosurgical oncology.

During the past decade and a half, the photothermal and photochemical effects of several medical lasers have been studied for the clinical treatment of benign and malignant, primary and secondary central nervous system tumors. Increased precision and hemostasis during tumor excision while limiting manipulation and retraction of nervous tissues are possible with the microsurgical carbon dioxide, argon, and frequency doubled neodymium:YAG lasers. Computerized tomography and magnetic resonance imaging-directed volumetric tumor removal by laser is feasible with computer-generated visual displays referenced to the patient's anatomy using stereotactic instrumentation. Photodynamic therapy with hematoporphyrin derivative as the photosensitizer and neodymium:YAG laser hyperthermia are currently under evaluation for the treatment of residual and recurrent malignant tumors. Encouraging results have been reported for each of these nonablative forms of laser use.     

Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles

We investigated the effect and feasibility of hyperthermia treatment on subcutaneous pancreatic cancer in female Kunming mice, using a murine pancreatic cancer cell line (MPC-83) established by us and found in this study to originate from epithelial pancreatic acinus. Magnetic fluid (MF) with ferromagnetic particles of about 20?nm in size was used as a heating mediator. MF was injected into the subcutaneous nodules with subaxillary regions of mice 10 days after tumor transplantation; homogeneous distribution of magnetic nanoparticles in nodules was easily detected by X-ray 24?h later. Mice were allocated to four groups as follows: no treatment (control); MF injection alone; alternating magnetic field (AMF) irradiation alone; and MF injection and hyperthermia generated by applying AMF (300?kHz, 110?Gs). The two hyperthermia-treated subgroup tumors reached central temperatures of 47 and 51?C, respectively, for 30?min; while rectal temperature in both subgroups remained below 36?C. Tumor growth was inhibited and survival significantly prolonged in the hyperthermia group compared with other groups (P<0.05). Tumor cells near the MF in the hyperthermia group apoptosed or necrosed immediately after hyperthermia. By day 14, there were no subcutaneous nodules; and residual magnetic nanoparticles were ingested by phagocytes. Nuclear proliferating cell nuclear antigen (PCNA) decreased in hyperthermia group tumor cells compared to the other groups; cytoplasmic heat shock protein?70 (HSP?70) was conspicuously higher immediately after hyperthermia (P<0.05). This technique had therapeutic potential and provided a new idea in the treatment of pancreatic cancer.     

Radiofrequency hyperthermia as adjuvant therapy following surgical resection of an experimental malignant neoplasm

Local recurrence after radical surgery is a major problem with many primary solid cancers. The use of radiofrequency hyperthermia (RFHT) as adjuvant therapy to surgery was explored in the Fischer bladder carcinoma (FBCa)/F344 rat tumor system. After subcutaneous innoculation of 34 rats with 10(6) FBCa cells in suspension, RFHT was administered to 17 animals on days 1, 5, 8, and 12. The development of palpable tumors was delayed but not prevented, and tumor growth was retarded in RFHT-treated animals. In another experiment 40 rats were innoculated by subcutaneous trocar injection with a 1 mm3 piece of FBCa. After tumor excision on day 17, adjuvant therapy (untreated control, mitomycin C, RFHT, or RFHT plus mitomycin C) was started on day 20 (10 rats/treatment). The 20 RFHT-treated rats had only 1 incisional recurrence as compared to 9 recurrences in sham-heated rats (P less than 0.005). The authors conclude that RFHT has considerable value as adjuvant therapy to surgery in these tumors. Additional studies of RFHT as adjuvant treatment after surgical excision of tumors are planned.     

Inhibition of heat shock protein 90 sensitizes melanoma cells to thermosensitive ferromagnetic particle-mediated hyperthermia with low Curie temperature

Heat shock protein (Hsp) 90 is a key regulator of a variety of oncogene products and cell-signaling molecules, and the therapeutic benefit of its inhibition in combination with radiation or chemotherapy has been investigated. In addition, hyperthermia has been used for many years to treat various malignant tumors. We previously described a system in which hyperthermia was induced using thermosensitive ferromagnetic particles (FMP) with a Curie temperature (Tc = 43˚C) low enough to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, we examined the antitumor effects of combining a Hsp90 inhibitor (geldanamycin; GA) with FMP-mediated hyperthermia. In cultured B16 melanoma cells, GA exerted an antitumor effect by increasing the cells' susceptibility to hyperthermia and reducing expression of Akt. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMP were then injected into the resultant tumors, and the mice were divided into four groups: group I, no treatment (control); group II, one hyperthermia treatment; group III, GA alone; and group IV, GA with hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMP increased and stabilized at the Tc. In group IV, complete regression of tumors was observed in five of nine mice (56%), whereas no tumor regression was seen in groups I–III. Our findings suggest that inhibition of Hsp90 with hyperthermia increases its antitumor effect. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90 inhibition has important implications for the treatment of cancer. ( Cancer Sci 2009; 100: 558–564)     

Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas.

The effect of localized hyperthermia on blood flow and cis-diamminedichloroplatinum(II) (CDDP) pharmacokinetics in 7,12-dimethylbenz[a]anthracene-induced mammary adenocarcinomas was studied. Blood flow was determined in rat tumors and normal tissue immediately and 1, 2, and 3 h after local hyperthermia treatment (43 degrees C, 1 h) as well as in unheated tumors of rats. The rate of blood flow in the tumor was increased 1.9 times at the end of treatment relative to control values and returned to the control values by 3 h after hyperthermia. Similarly, the rate of blood flow in the peripheral skin around the tumor immediately after hyperthermia was 2.2 times greater than that of unheated skin and returned to near normal values by 3 h after heating. Tumor-bearing rats received CDDP 1 h before, at the beginning of, at the end of, and 1 h after hyperthermia administration. The CDDP plasma concentration versus time profiles for rats did not vary statistically between treatment groups. Two h after CDDP administration, the mean tumor CDDP concentration of the rats which received drug at the beginning of hyperthermia was statistically greater (P less than 0.05) than tumor CDDP concentrations in rats which received drug at the end of heat treatment. The latter group was given CDDP when tumor blood flow was the greatest; however, mean tumor drug concentration was lowest of all the groups. The mean drug concentration in tumor tissues of rats which received drug 1 h after hyperthermia was comparable to rats which received drug at the beginning of hyperthermia. This suggests that drug delivery or uptake in tumors may be altered when local hyperthermia is administered concurrently or sequentially.