510.6nm绿色铜蒸气激光加血卟淋衍生物（HpD）对动物移植瘤杀伤…

本文报告５１０．６ｎｍ绿色铜蒸气激光与ＨｐＤ对动物移植瘤的杀伤作用。给带Ｓ１８０和Ｂ１６－ＭＢ小鼠腹腔注射ＨｐＤ５０ｍｇ／ｋｇ，注后７２小时，用５１０．６ｍｍ铜蒸气激光照射肿瘤，照后肿瘤体积和重量，均明显减少（Ｐ＜０．０１和＜０．０５），病理检查照区肿瘤均有坏死，深度为５．５－８．８ｍｍ，平均约７ｍｍ，单纯铜激光照射，肿瘤坏死深度最大达５ｍｍ，ＨｐＤ组和非激光非ＨｐＤ组无上述变化。ＨｐＤ对小鼠Ｂ１     

光敏剂e4光动力学治疗小鼠S-180肉瘤的实验研究

目的:利用激光激活e4,研究对在体小鼠S180肉瘤的杀伤作用,证明e4是可以选用的新型光敏剂之一.方法:荷瘤小鼠腹腔注射e4(40mg/kg)1次,6小时后用强度为24W/cm2的激光照射肿瘤区域1次,时间为20分钟(PDT组).以空白对照组(C),光照组(Light)(激光强度为20W/cm2),光敏剂组(e4)为对照组,每两天测量肿瘤的大小,12天后剥离肉瘤并称重比较.结果:e4在小鼠体内经激光激活后可明显抑制肿瘤生长.PDT组肿瘤的平均重量较空白对照组肿瘤的平均重量要轻,两者比较有统计学意义,P=0.0000,光敏剂组肿瘤的平均重量较空白对照组肿瘤的平均重量要轻,两者比较有统计学意义,P=0.0068.结论:e4光动力治疗对小鼠S-180肉瘤有明显杀伤或抑制作用,e4自身对小鼠S-180肉瘤有一定杀伤或抑制作用.     

竹红菌乙素-PDT与血卟啉衍生物-PDT对食管癌细胞杀伤效应的比较研究

目的：探讨竹红菌素-光动力疗法（hypocrellins B-photodynamic therapy, HB-PDT）对食管癌细胞的杀伤效应,同时与第1代光敏剂血卟啉衍生物（hematoporphyrin derivative, HpD）作对比研究,初步揭示HB-PDT在食管癌治疗方面的优势和前景.方法：以不同浓度的竹红菌乙素（HB）及HpD孵育食管癌细胞,然后分别在铜蒸汽激光混合光饱和光剂量条件下进行照光处理,照光后置于37℃含5% CO2的孵箱中继续孵育24 h,然后用MTT法分别测定不同光敏剂浓度下的存活率,绘制杀伤曲线并拟合曲线方程,根据方程求出不同光敏剂对细胞的半数杀伤浓度 （50% inhibition concentration, IC50）.结果：HB-PDT对食管癌细胞具有很强的杀伤效应,对食管癌细胞杀伤的IC50为34.15 ng/mL;HpD对食管癌细胞杀伤的IC50为1 526.03 ng/mL.两种方法之间差异有统计学意义,P=0.000 1.结论：HB-PDT对食管癌细胞具有很强的杀伤作用;HB-PDT对食管癌细胞株的杀伤效应明显优于HpD-PDT;竹红菌素是比第1代光敏剂HpD更为高效的光敏剂.     

Polyporus sp.MO5多糖的抗肿瘤作用

目的研究真菌Polyporus sp.M05多糖PSM-a体内对荷瘤小鼠S180的抑瘤作用及其机制.方法 MTT法检测PSM-a体外对S180细胞株的增殖抑制作用.建立S180小鼠模型,灌胃治疗,每日检测肿瘤体积并计算瘤体比和抑瘤率.实验结束后处死小鼠,MTT比色法测定小鼠自然杀伤(NK)细胞及淋巴因子活化杀伤细胞(LAK)的杀伤活性.HE染色检测肿瘤组织细胞坏死情况.结果 PSM-a在体外能抑制S180细胞生长;在体内能显著降低荷瘤小鼠的瘤重和瘤体比,250μg/ml的PSM-a对肿瘤抑制率高达80%以上;PSM-a能促进NK细胞及LAK细胞的杀伤活性;病理切片显示PSM-a作用后引起肿瘤组织坏死.结论 PSM-a对S180荷瘤小鼠肿瘤的生长有明显的抑制作用,其机制可能与提高机体免疫细胞对肿瘤细胞的杀伤活性有关.     

竹红菌乙素-PDT与血卟啉衍生物-PDT对食管癌细胞杀伤效应的比较研究

目的探讨竹红菌素-光动力疗法(hypocrellins B-photodynamic therapy,HB-PDT)对食管癌细胞的杀伤效应,同时与第1代光敏剂血卟啉衍生物(hematoporphyrin derivative,HpD)作对比研究,初步揭示HB-PDT在食管癌治疗方面的优势和前景。方法以不同浓度的竹红菌乙素(HB)及HpD孵育食管癌细胞,然后分别在铜蒸汽激光混合光饱和光剂量条件下进行照光处理,照光后置于37℃含5%CO2的孵箱中继续孵育24h,然后用MTT法分别测定不同光敏剂浓度下的存活率,绘制杀伤曲线并拟合曲线方程,根据方程求出不同光敏剂对细胞的半数杀伤浓度(50%inhibition concen-tration,IC50)。结果HB-PDT对食管癌细胞具有很强的杀伤效应,对食管癌细胞杀伤的IC50为34.15ng/mL;HpD对食管癌细胞杀伤的IC50为1526.03ng/mL。两种方法之间差异有统计学意义,P=0.0001。结论HB-PDT对食管癌细胞具有很强的杀伤作用;HB-PDT对食管癌细胞株的杀伤效应明显优于HpD-PDT;竹红菌素是比第1代光敏剂HpD更为高效的光敏剂。     

光动力疗法在骨肉瘤治疗中的初步实验探讨

目的观察光敏剂BCPD-17对小鼠骨肉瘤细胞株LM-8及小鼠皮下移植骨肉瘤的光动力效应。方法将不同浓度的光敏剂BCPD-17(0.5、1.0、2.0、4.0、8.0μg/mL)与小鼠骨肉瘤细胞株LM-8共同孵育4 h,再采用不同激光剂量照射LM-8细胞(激光波长为630 nm,光照能量分别为1.5、3.0、6.0、9.0 J/cm~2),与空白对照组(不加光敏剂,不接受激光照射)、暗毒性组(只加光敏剂,不接受激光照射)、激光组(不加光敏剂,只接受激光照射)比较,24 h后采用MTT法测定其光密度值(OD_(540)),计算抑制率,并于光镜下观察光动力疗法(photo dynamictherapy,PDT)后24 h细胞形态的变化。30只C3H小鼠左侧腰骶部接种LM-8小鼠骨肉瘤细胞,待皮下瘤块直径约10~12 mm时,随机分成空白对照组、低能量密度及高能量密度光动力治疗组,观察4周后有无复发。结果单独光照或光敏剂孵育均无杀伤效应,光敏剂浓度及激光剂量是影响杀伤效应的重要因素。BCPD-17浓度为4μg/mL,光照能量为3 J/cm~2时,对LM-8细胞有明显的光动力杀伤效果,抑制率为57.0%。光镜下可见细胞形态发生明显的变化,呈坏死或凋亡样改变。动物模型实验中,光动力治疗4周后,对照组中10只没有联合PDT的小鼠,仅1只小鼠没有复发,在手术联合PDT治疗的低剂量激光组(240 J/cm~2)小鼠中,4只小鼠出现肿瘤局部复发,在高剂量激光组(360 J//cm~2)小鼠中,只有2只局部复发。结论 BCPD-17对小鼠骨肉瘤LM-8细胞株具有明显的光动力杀伤作用,也能够降低小鼠移植骨肉瘤的局部复发率,PDT是很有前景的治疗骨肉瘤的新方法。     

复发性乳癌用血卟啉激光的局部治疗

血卟啉诱导体(HpD)对肿瘤有亲和性,用特殊光线照射,可治疗鼠肿瘤、狗中心型肺癌。HpD 被450 nm 的紫光激发,在630、690 nm 出现高峰,发红色萤光。处于激发状态的HpD 恢复原来的状态时能产生单氧。前者用于诊断,后者用于治疗。HpD 在体内停滞时间长,从肝、消化道排泄。治疗设备用630～640 nm 波长的激光,能把514.5 nm 的绿光变成波长630～640 nm 的红光。光线经水晶纤维诱导,在纤维顶端引出的功率最大为1600mW。14例乳癌术后皮肤转移的患者试用本法治疗。共87处病灶,其中皮肤浸润病灶71个、皮下病灶16个。14例中12例合并有其他脏器转移,仅2例是单纯皮肤转移。     

激光对荷瘤小鼠免疫系统影响的实验研究

 目的: 借助于低能量的He-Ne激光激活免疫机制, 抑制肿瘤的生长。方法: 采用双抗体夹心ELISA法及MTT法对荷瘤小鼠激光照射前后细胞因子（TL-1、IL-6、IL-8）的含量进行检测, 并对其抑制肿瘤作用进行研究。结果: 激光照射瘤鼠脾区具有促进IL-1、IL-8产生, 抑制IL-6及瘤细胞增殖的作用。与对照组相比有非常显著差异(P<0.01)。结论: 低能量激光照射具有调节患瘤鼠白细胞介素产生及抗肿瘤作用。     

光敏剂e4光动力学治疗小鼠S-180肉瘤的实验研究

目的：利用激光激活e4,研究对在体小鼠S180肉瘤的杀伤作用,证明e4是可以选用的新型光敏剂之一。方法：荷瘤小鼠腹腔注射e4（40mg/kg）1次,6小时后用强度为24W/cm2的激光照射肿瘤区域1次,时间为20分钟（PDT组）。以空白对照组（C）,光照组（Light）（激光强度为20W/cm^2）,光敏剂组（e4）为对照组,每两天测量肿瘤的大小,12天后剥离肉瘤并称重比较。结果：e4在小鼠体内经激光激活后可明显抑制肿瘤生长,PDT组肿瘤的平均重量较空白对照组肿瘤的平均重量要轻,两者比较有统计学意义,P=0.0000,光敏剂组肿瘤的平均重量较空白对照组肿瘤的平均重量要轻,两者比较有统计学意义,P=0.0068。结论：e4光动力治疗对小鼠S-180肉瘤有明显杀伤或抑制作用,e4自身对小鼠S-180肉瘤有一定杀伤或抑制作用。     

恶性黑色素瘤细胞光免疫治疗的研究

目的:探讨光免疫治疗(PIT)能否选择性提高人眼黑色素瘤细胞的光毒作用.方法:单克隆抗体IG12连结光敏物质CMA,形成免疫连结物(McAb-CMA),以评价其对体外人眼黑色素瘤培养细胞OCM431的光免疫治疗作用,RPMI1846黑色素瘤细胞与单克隆抗体IG12无交叉反应,作为对照组.氩离子-染料激光波长654nm,连结1mm光导纤维,光斑大小35mm.靶细胞和对照细胞的存活率用MTT法测定.结果:靶细胞OCM431预先与McAb-CMA培养,激光照射剂量5～40J/cm2显示靶细胞存活率随着激光剂量增加而明显降低.在相同激光照射剂量下,增加McAb-CMA的剂量,细胞存活曲线亦随着降低,当McAb-CMA的量增加超过6.7μmol/L时,肿瘤的光免疫杀伤作用趋平缓.对照细胞(RPMI1846)给予相同的照射条件,在激光剂量40J//cm2时仍有74%±2.6%细胞存活.结论:这一结果显示单克隆抗体IG12 PIT可选择性提高人眼黑色素瘤的光杀伤作用.     

Photodynamic cell killing effects and acute skin photosensitivity of aluminum-chloro-tetrasulfonated phthalocyanine and hematoporphyrin derivative

Aluminum-chloro-tetrasulfonated phthalocyanine (PC) showing an absorption peak at 678 nm was compared to hematoporphyrin derivative (HpD), a photosensitizer commonly used in the photodynamic therapy (PDT) of cancers. In vitro studies: KK-47 cells were exposed to long-wavelength ultraviolet (UVA) or red light (greater than 600 nm, greater than 640 nm and greater than 660 nm) after drug sensitization. With UVA irradiation, a higher photodynamic cell killing effect was observed in the cells treated with HpD than with PC. However, with red light irradiation (both greater than 640 nm and greater than 660 nm) PC resulted in greater cell damage. PC was less toxic to KK-47 cells in the dark. In vivo studies: Using a gold vapor laser (GVL: 627.8 nm, 200 mW/cm2, 200 J/cm2), the photodynamic tumor response was determined in C3H/He mice bearing transplantable squamous cell carcinoma. No significant difference was observed in the tumor volume between the PC and HpD groups, except that the PC group (10.0 mg/kg body weight) showed a significantly higher remission rate (3/6) than the control group (0/10, P less than 0.05). Skin photosensitivity test: Skin photosensitivity was estimated by measuring changes in back skin thickness due to photosensitization. With UVA irradiation, a stronger skin reaction was observed in the HpD group, while with visible light irradiation there was no significant difference between the HpD and PC groups. Based on the superior cell killing effect with red light, reduced toxicity to the cells in the dark and mild skin reaction with UVA, PC may be a more promising photosensitizer for PDT.     

Photodynamic Cell Killing Effects and Acute Skin Photosensitivity of Aluminum-chloro-tetrasulfonated Phthalocyanine and Hematoporphyrin Derivative

Aluminum-chloro-tetrasulfonated phthalocyanine (PC) showing an absorption peak at 678 nm was compared to hematoporphyrin derivative (MpD), a photosensitizer commonly used in the photodynamic therapy (PDT) of cancers. In vitro studies: KK-47 cells were exposed to long-wavelength ultraviolet (UVA) or red light (>600 nm, >640 nm and >660 nm) after drug sensitization. With UVA irradiation, a higher photodynamic cell killing effect was observed in the cells treated with HpD than with PC. However, with red light irradiation (both > 640 nm and >660 nm) PC resulted in greater cell damage. PC was less toxic to KK-47 cells in the dark. In vivo studies: Using a gold vapor laser (GVL: 627.8 nm, 200 mW/cm², 200 J/cm²), the photodynamic tumor response was determined in C3H/He mice bearing transplantable squamous cell carcinoma. No significant difference was observed in the tumor volume between the PC and HpD groups, except that the PC group (10.0 mg/kg body weight) showed a significantly higher remission rate (3/6) than the control group (0/10, P<0.05). Skin Photosensitivity test: Skin photosensitivity was estimated by measuring changes in back skin thickness due to photosensitization. With UVA irradiation, a stronger skin reaction was observed in the HpD group, while with visible light irradiation there was no significant difference between the HpD and PC groups. Based on the superior cell killing effect with red light, reduced toxicity to the cells in the dark and mild skin reaction with UVA, PC may be a more promising photosensitizer for PDT.     

Hyperthermal effects in phototherapy with hematoporphyrin derivative sensitization

Although the photochemical reaction of hematoporphyrin derivative (HpD) appears to play a major role in cytotoxic activity, the hyperthermal contribution to tumor destruction has not yet been clarified. We investigated its role in the effectiveness of laser photoradiation therapy using MS-2 sarcoma transplanted into the hind pad of BALB/c mice as the experimental model. Mice received HpD i.v., 25 mg/kg - 24 h before exposure to light delivered from a dye laser or Nd-YAG laser, or before warming in a thermostated bath. Since our aim was not to cure the tumor, the treatment response was evaluated only as inhibition of tumor growth at different days after treatment. Our results support the view that in laser photochemotherapy the hyperthermia produced by irradiation and the photodynamic effect mediated by HpD could contribute to tumor destruction. Moreover, a synergistic interaction between the photodynamic effect and heat was observed in this experimental model.     

Phthalocyanine: a new photosensitizer in photodynamic therapy

Photodynamic therapy (PDT) with hematoporphyrin derivative (HpD) combined with laser irradiation has been introduced as a new promising clinical method for the treatment of various malignancies. Recently, sulphonated aluminum chloro phthalocyanine (A1PC) has attracted a great deal of attention as a new photosensitizer. Tissue concentrations and photodynamic effects of A1PC and HpD, that has been using clinically in PDT, were determined in nude mice transplanted bladder tumors. According to the tissue distribution of A1PC and HpD at various times after administration, the ratios of tumoral concentration to muscular concentration of A1PC were higher than those of HpD, and skin concentration of A1PC at 24 to 168 hrs. after administration was lower than that of HpD. These results suggest that more A1PC localizes in malignant tumor than HpD, and there is a possibility of reducing skin photosensitivity with A1PC as compared with HpD. The regression of tumor volume after PDT was higher with A1PC and laser light at 670 nm than with HpD and laser light at 630 nm.     

Indocyanine green enhanced near-infrared laser treatment of murine mammary carcinoma

It is well accepted that near-infrared (NIR) lasers are appropriate to ablate benign lesions and induce irreversible thermal injury in deeply seated blood vessels. At this wavelength, the laser light penetrates deep (3-5 mm) into the skin. However, many researchers have reported noticeable pain, extending from mild to severe, during and immediately after NIR laser treatment. Intravenous administration of an exogenous chromophore [indocyanine green (ICG), dye] can effectively convert NIR laser light into heat. In this approach, the presence of ICG has shown to enhance thermal injury of blood vessels in the treatment of healthy tissues. However, the effectiveness of thermal injury on the regression of cutaneous carcinomas during ICG/NIR laser therapy has not been assessed. The purpose of our study was to evaluate the potential benefit of using ICG/NIR laser therapy to regress superficial carcinoma with thermal injury. Two groups of A/J mice with subcutaneous mammary adenocarcinoma tumors (7-9 mm) were irradiated with a 808-nm NIR laser preceded by tail vein injection of ICG dye or sterile saline. Histological evaluation of the subcutaneous tissue revealed minor thermal damage and necrosis in the laser/saline group and substantial damage (up to 100% necrosis) in the laser/ICG group. The laser/ICG-treated group showed a steady reduction in tumor volume compared to the laser/saline group: 48% by day 5 (p = 0.045) and 69-70% by days 8, 9 and 10 (p values 0.0005 or less). The vascular-targeted ICG-NIR laser therapy appears to have potential for treating superficial tumors.     

Effect of 514.5-nm argon ion laser radiation on hematoporphyrin derivative-treated bladder tumor cells in vitro and in vivo

The therapeutic effect of hematoporphyrin derivative (HpD) plus 514.5-nm argon ion laser radiation was compared to HpD plus 630-nm argon ion laser-pumped dye laser radiation in experimental urinary bladder transitional cell carcinoma models. Cultured human bladder cancer cells (EJ) containing HpD were 2.8-fold more sensitive to 514.5-nm radiation than to 630-nm radiation as measured by clonogenic capacity. The relative effectiveness of 514.5-nm versus 630-nm light was approximately proportional to the spectral absorbance for cell-bound HpD at these wavelengths. HpD-sensitized photoirradiation was studied in solid tumors produced by a) the subcutaneous inoculation of cells from murine bladder tumors induced by N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide (CAS: 24554-26-5) into female C3H mice (MBT-2 tumor) and b) the intravesical instillation of N-methyl-N-nitrosourea (CAS: 684-93-5) into the urinary bladders of female Wistar rats. The tumors were exposed to 144 J/cm2 laser light 24-48 hours following ip injection of 20 mg HpD/kg body weight. By 24-48 hours, animals that received HpD and light of either wavelength had partially or completely necrosed tumors. Control groups showed no necrotic changes. Regression of MBT-2 tumors was also investigated. Seven of 14 and 6 of 12 animals had nonpalpable tumors 1 week after treatment with 514.5-nm and 630-nm light, respectively. Tumors in control groups demonstrated no regression. Spectral transmittance from 630 nm to 514.5 nm decreased by about 4% for 130- to 160-micron-thick sections of canine urothelium and bladder submucosa-muscularis. The results of this study indicate that HpD plus 514.5-nm laser radiation may be an effective treatment for small or superficial malignant lesions of the urinary bladder.     

Photo-chemistry therapy of gastrointestinal tumor--analysis of hematoporphyrin derivative (HpD) plus laser photodynamic therapy of 50 cases

This paper reports 50 cases of gastrointestinal tumors treated by photodynamic therapy. The dose of HpD was 5 mg/kg. Fourty-eight to 72 hours after HpD injection, laser (wavelength 630 nm, power density 100-250 J/cm2), transmitted through a quartz fiber, was given. The criteria of therapeutic effectiveness were: complete remission (CR), significant remission (SR), minor remission (MR) and no remission (NR). All patients received endoscopic examination 4 weeks after treatment. No severe complication was observed. Thirty-eight of 50 cases gave CR, SR or MR (76%). The factors effecting treatment are discussed.     

A comparison between argon-dye and excimer-dye laser for photodynamic effect in transplanted mouse tumor.

Photodynamic therapy (PDT) utilizing a hematoporphyrin derivative (HpD) as a sensitizer has become a viable option for the local treatment of neoplastic disease. The argon-dye laser system is commonly used as a light source in this treatment modality. The excimer-dye laser, on the other hand, delivers high-energy red light in a pulsatile fashion. In this investigation, we treated BALB/c mice bearing mouse kidney sarcoma cell tumors with PDT using HpD at the dose of 5 mg/kg body weight as a photosensitizer and either a standard argon-dye laser or the pulsatile excimer-dye laser as the light source. At equal light energy doses (50 J/cm2), necrotic changes at depths averaging 4 mm from the tumor surface were obtained with the argon-dye laser (200 mW power output) while tumor necrosis at depths exceeding 15 mm from the tumor surface was obtained using the excimer-dye laser (6 mJ/pulse, 5 Hz). To determine the best conditions for photoirradiation with the excimer-dye laser, tumor-bearing mice were treated with different total light doses (10, 30 and 50 J/cm2), dose rates (1, 3 and 6 mJ/cm2), and frequencies (5, 15 and 50 Hz) of light exposure. Our results indicate that the optimal effects obtained with the excimer-dye laser are related to the total light dose used and the dose rate, but not to the frequency of light exposure.     

Chemiluminescence and hematoporphyrin derivative: a novel therapy for mammary adenocarcinomas in mice

A Chemiluminescent System (CLS), using a Peroxyoxalate chemiluminescent solution (PCs), together with Hematoporphyrin derivative (HpD) Photofrin II., were utilized in the treatment of transplanted mammary adenocarcinomas in C3H/HeJ female mice. Tumor bearing animals aged 2-4 months were divided into five groups; Group I was the control. Groups 2 and 4 compared the effectiveness of both reagents HpD and PCs which were administered by intratumor injections fractionated over a 96 hour period. Groups 3 and 5 compared the effectiveness of PCs alone. Tests of the PCs were conducted with and without the presence of luminescence. Fifty-three percent of the animals in Group 4 and 47% of the animals in Group 2 remained tumor free 120 days after the completion of treatment. Thirty percent of the animals in Groups 2 and 4 survived one year without tumor recurrence. The results of this study suggest that a chemical light system can be a viable alternative in Photodynamic Therapy (PDT) to laser light for the activation of HpD and treatment of cancer.