An in vitro study of the effect of photodynamic therapy on human meningiomas.

Despite being benign CNS tumours, meningiomas are not always curable and the likelihood of recurrence depends upon the completeness of initial removal. Adjuvant therapy for incompletely resected meningiomas is generally unsatisfactory and such lesions continue to pose difficult management problems. Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas but its activity against meningiomas has not been specifically studied. An in vitro study of the effects of PDT against a variety of meningiomas was therefore conducted. It was found that PDT using haematoporphyrin derivative as a photosensitizing drug showed dose-dependent activity against a variety of histological subtypes of meningioma. The activity of PDT against meningiomas should be investigated further and may eventually provide a useful form of adjuvant therapy for incompletely resected lesions.     

5-氨基乙酰丙酸介导的光动力学对裸鼠人胃癌移植瘤的治疗作用

目的观察5-氨基乙酰丙酸（5-ALA）介导的光动力学治疗对裸鼠人胃癌移植瘤的治疗作用。探索5-ALA介导的光动力学（PDT）治疗胃癌的可能机制。方法以MGC-803人胃癌细胞制备裸鼠人胃癌移植瘤模型：整体荧光成像系统下观察动物瘤体发出的荧光信号：测量荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天的裸鼠肿瘤大小并计算肿瘤体积：末次测量后切除肿瘤行病理检查和透射电镜观察，TUNEL法检测组织细胞凋亡。结果常规方法培养MGC一803人胃癌细胞并接种裸鼠．可以成功制备出裸鼠人胃癌移植瘤的模型：荷瘤裸鼠肿瘤组织在特定波长的荧光激发下可发出特有的红色荧光。荷瘤对照组、单纯激光组、单纯5-ALA组和5-ALA介导的PDT治疗组治疗后第1、3、7、14、21天4组间的肿瘤体积差异有统计学意义（肚1003．086，P=0．000），PDT治疗组明显小于其他3组；病理检查提示．PDT治疗后肿瘤细胞大片凝固性坏死；透射电镜观察提示，PDT治疗组肿瘤组织存在大量死亡细胞及部分凋亡细胞：TUNEL法检测发现，PDT治疗组的肿瘤组织凋亡指数显著高于其他3组（χ^2=18．237．P=0．000）。结论5-ALA介导的PDT对于裸鼠人胃癌移植瘤具有明显的治疗效果．而单纯给予5-ALA或激光辐射对肿瘤无明显抑制作用；肿瘤细胞的坏死及凋亡是5-ALA介导的PDT产生细胞毒作用的重要机制。     

光动力疗法对裸鼠实验性胰腺癌治疗机制的研究

目的 研究光动力疗法（photodynamic therapy,PDT)对裸鼠胰腺移植癌的治疗效果及血管损伤在其中的作用，为临床应用PDT治疗胰腺癌提供依据。方法 将人胰腺癌细胞株SW1990接种于裸鼠皮下，建立移植癌模型。以血卟啉衍生物作为光敏剂，研究PDT治疗胰腺癌的效果，并以第Ⅷ因子为标记，采用免疫组化LSAB法，观察肿瘤血管损伤的情况。结果 PDT对肿瘤有杀伤作用，使肿瘤生长速度明显减慢；PDT可引起血管内皮细胞的损伤和血管结构的破坏。结论 PDT对胰腺癌有治疗作用，血管损伤是其杀伤肿瘤的重要途径。     

细胞毒药物(Gemcitabine)治疗人胰腺癌裸鼠胰腺原位移植癌的实验研究

目的 探讨细胞毒药物（Gemcitabine)对胰腺癌裸鼠原位移植模型（SOI）生长，转移的抑制作用。方法　SOI模型分为Ⅰ组（Gemcitabine 100mg/kg),Ⅱ组（Gemcitabine50mg/kg)和对照组。Gemcitabine于术后第2，3，6，9天给药，ip，术后第10周处死裸鼠；并对肿瘤组织的增殖指数（PI），凋亡指数（AI）以及PI/AI进行分析。结果 （1）Ⅰ组能显著抑制胰腺癌生长，Ⅱ组则无显著的肿瘤抑制作用，但两者对胰腺癌转移和预后均无显著疗效；（2）Ⅰ组可显著降低肿瘤增殖指数（PI），增大凋亡指数（AI），PI/AI显著降低。结论 Gemcitabine单用能有效抑制胰腺癌生长，但对肿瘤转移无显著抑制作用。     

光动力治疗人胆管癌细胞荷瘤裸鼠的实验研究

目的研究光动力疗法(photodynamic therapy,PDT)对人胆管癌荷瘤裸鼠的治疗效果,探讨其抗肿瘤性、安全性及腹腔注射和瘤内注射光敏剂两种不同给药途径疗效的差异。方法人胆管癌细胞QBC939接种于Balb/c裸小鼠皮下,建立荷瘤动物模型。以血卟啉衍生物(HpD)作光敏剂,采用腹腔内和瘤内注射2种不同给药方式,后以波长630 nm的激光照射肿瘤组织,观察PDT后肿瘤体积变化和病理改变。结果接受光动力治疗的两组肿瘤生长速度明显减慢,瘤内局部注射给药组疗效与腹腔给药组差异无统计学意义(P>0.05);组织学检查见肿瘤组织有广泛坏死,各组裸鼠心、肝、肺、肾组织切片未见病理性结构改变。结论HpD,PDT对人胆管癌荷瘤裸鼠的肿瘤组织有杀伤作用,使肿瘤生长减慢;HpD-PDT杀伤胆管癌移植瘤的深度可达0.8cm;在本实验光照条件下的PDT治疗是安全的。     

Potential anti-inflammatory effect of low-level laser therapy on the experimental reflux laryngitis: a preliminary study

The most common cause of laryngitis is the laryngopharyngeal reflux disease. The symptoms of laryngitis can be hoarseness, globus, chronic cough, voice fatigue, throat pain, and dysphagia. Low-level laser therapy (LLLT) is beneficial to reduce the pain and inflammatory response without side effects. Therefore, LLLT may be a useful tool for the treatment of laryngitis. This study proposes to analyze the effect of laser therapy in a model of reflux-induced laryngitis. The animals were randomly put into three groups: control—non-intubated; nasogastric intubation—intubated; and nasogastric intubation with laser therapy—intubated treated with 105-J/cm² laser irradiation. For the induction of laryngitis, the animals were anesthetized and a nasogastric tube was inserted through the nasopharynx until it reached the stomach, for 1 week. Thereafter, measurement of myeloperoxidase activity and the histopathological procedures were performed. In conclusion, we observed in this study that 105-J/cm² infrared laser reduced the influx of neutrophils in rats, and it improved the reparative collagenization of the laryngeal tissues.     

Endoscopic therapy and curative effect in pituitary adenoma patients complicated by acromegalic cardiomyopathy

The study aimed to retrospectively analyze the clinical characteristics of patients with pituitary adenomas complicated by acromegalic cardiomyopathy and to evaluate the effect of endoscopic surgery. Eighty-six pituitary adenoma patients complicated by acromegalic cardiomyopathy who were treated with endoscopic surgery in the First Affiliated Hospital of Soochow University from January 2010 to December 2016 were enrolled. We noted patient clinical characteristics and explored the relationships with surgical treatment. Before and after surgery, all patients underwent an examination of pituitary endocrinology, brain magnetic resonance (MR), and echocardiography. The serum levels of growth hormone (GH), left ventricular end-diastolic diameter (LVIDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular ejection fraction (EF), and mitral valve (E/A ratio) were examined with non-invasive methods, and the results were compared. Of the 86 patients, there were 23 with microadenomas, 27 with large adenomas, and 36 with giant adenomas. There were 28 patients with invasive adenomas and 58 with non-invasive adenomas. The pre-operative mean GH level was 71.23?±?3.29 μg/L, which was positively correlated with tumor volume (r?=?0.751, P?<?0.01). Via trans-sphenoidal endoscopic pituitary adenoma resection, 51 patients underwent total tumor resections, 25 underwent subtotal resections, 8 underwent major part resections, and 2 underwent partial resections. After surgery, the GH mean level was 3.81?±?1.03 μg/L, which was significantly different (t?=?3.72, P?<?0.01) from the pre-operative level. Cardiac function indices, including LVIDd, IVST, LVPWT, E/A, and EF, were significantly improved. The long-term curative rate was 39.17% and the remission rate was 77.29%. For pituitary adenoma patients complicated by acromegalic cardiomyopathy, endoscopic surgery resulted in a good curative effect and the growth hormone levels were maintained, which can significantly improve cardiac structure and function.     

内源性光动力疗法抑制人结肠癌裸鼠种植瘤的实验研究

目的　探讨基于 5 氨基乙酰丙酸 (ALA)的光动力疗法 (PDT)对结肠癌的生长抑制作用。方法　建立人结肠癌SW 480细胞裸鼠种植瘤模型 ,经尾静脉注入ALA液 (2 5 0mg/kg体重 ) ,光敏化 3h后半导体激光仪垂直照射肿瘤 3 0min(能量密度 9J/cm2 ) ,照射后连续观察肿瘤体积 ,瘤体HE染色病理分析。结果　ALA PDT在治疗后早期产生明显的抑制肿瘤增殖作用 ,瘤体组织坏死 ,腺腔样结构解离破坏 ,延命率 40 .2 % ,体积抑瘤率达 64 .1% ,治疗后期 ,肿瘤体积仍会缓慢增长 ,但增长速度明显小于对照组。结论　SALA PDT治疗可明显抑制裸鼠结肠种植瘤生长 ,延长荷瘤裸鼠生存期 ,但仍不能完全抑制肿瘤生长。     

光动力治疗裸小鼠胰腺移植癌的实验研究

目的 研究光动力治疗（ＰＤＴ）对胰腺癌的治疗效果,为胰腺癌寻找有效的治疗手段。方法 接种人胰腺癌细胞ＳＷ１９９０于裸小鼠皮下,建立移植癌模型,以血卟淋衍生物（ＨｐＤ）作为光敏剂,采用腹腔和瘤内局部注射两种不同方式给药,继以波长６３２．８ｎｍ的Ｈｅ－Ｎｅ激光照射肿瘤局部,观察光动力治疗后肿瘤的生长速度和组织形态学变化,并测定了肿瘤组织内脂质过氧化产物丙二醛（ＭＤＡ）的含量,对其治疗机制进行了初步探讨     

纳米微粒光敏剂光动力治疗结肠癌的实验研究

目的探讨普通光敏剂profrinⅡ纳米化后光动力疗法（PDT）对结肠癌的生长抑制作用。方法超声乳化法构建profrinⅡ纳米微粒，建立人结肠癌LOVO细胞裸鼠种植瘤模型，把荷瘤裸鼠分为对照组：不注射光敏剂，不用激光照射；纳米微粒光敏剂组：注射profrinⅡ纳米微粒悬液，不用激光照射；普通光敏剂PDT组：注射profrinⅡ后3h，激光照射30min；纳米微粒光敏剂PDT组：profrinⅡ纳米微粒悬液注射后3h，激光照射30min。经小鼠尾静脉注入profrinⅡ纳米微粒（30mg／kg体重），光敏化3h后用半导体激光仪垂直照射肿瘤30min（能量密度9J／cm^2）。然后连续观察肿瘤体积的变化及荷瘤裸鼠生存时间，瘤体苏木精-伊红染色病理分析。结果纳米微粒光敏剂PDT组在治疗后早期产生明显的抑制肿瘤增殖作用，瘤体组织坏死，腺腔样结构解离破坏，微血管坏死，血栓形成。纳米微粒光敏剂PDT组与对照组和纳米微粒光敏剂组相比，延命率提高65．2％和58．3％（P〈0．05），抑瘤率增加87．9％和87．5％（P〈0．05）；与普通光敏剂PDT组相比，延命率提高18．8％（P〈0．05），抑瘤率增加56．0％（P〈0．05）。结论纳米微粒光敏剂PDT可明显抑制裸鼠结肠种植瘤生长，延长荷瘤裸鼠生存期。     

The effect of photodynamic therapy on the microcirculation

Photodynamic therapy (PDT) is a new form of cancer therapy involving tumor localization by photosensitizing drugs such as dihematoporphyrin ether (DHE). Light irradiation of drug-sensitized tissue results in photoactivation of DHE and tumor necrosis. The mechanism of action is incompletely understood but involves the generation of singlet oxygen which produces cytotoxic effects on tissues containing the compound. In addition, microcirculatory aberrations have been described during PDT. We have studied the acute effects of PDT on the microcirculation using in vivo television microscopy of the rat cremaster. This has enabled us to observe the effects of PDT on both paired and unpaired arterioles and venules using two different wavelengths of activating light (blue, 450-490 nm, and green, 530-560 nm). For both wavelengths of activating light, significant reduction in blood flow of all vessels was seen during PDT. This, in combination with the formation and embolization of platelet thrombi, resulted in stasis of blood flow in 80% of arterioles and 90% of venules. Observation for 2 hr after the completion of photoactivation revealed reperfusion in 20% of the arterioles but none of the venules. Blood flow was reduced by a combination of vasoconstriction and platelet thrombus formation. Reducing the total activating energy from 120J/cm2 to 24J/cm2 significantly reduced the response in venules and the incidence of stasis in both arterioles and venules. We conclude that the photoactivation of DHE results in significant vasoconstriction and thrombosis of normal vessels and that if these effects are seen at later times after DHE administration and in tumor neovasculature they may contribute to the mechanism by which PDT results in tumor necrosis.     

Hypericin and photodynamic therapy decreases human pancreatic cancer in vitro and in vivo

BACKGROUND: The treatment of pancreatic cancer has remained dismal despite advances in medical and surgical care. Recent preclinical data have revealed that hypericin, a photochemical dye, is activated by green light and generates toxic radical species in tumors. We hypothesized that interstitial hypericin and laser phototherapy would decrease pancreatic cancer growth. METHODS: MiaPaCa-2 and PANC-1 cells were grown in tissue culture. In vitro experiments were performed with addition of 10 microg of hypericin/500,000 cancer cells. Cells were incubated with hypericin for 2 h. Cells were then exposed to KTP532 green laser light for 1 min at 0.6 W using a cylindrical diffuser tip. Cell growth was measured by MTT assay 24 h after laser treatment, N = 12. MiaPaCa-2 cells were implanted subcutaneously and orthotopically in pancreas of nude mice. After 5 weeks, both tumors were injected with 100 microg of hypericin followed by insertion of a cylindrical diffuser tip into the tumor center. Mice received 200J KTP laser light at 1.0 W in two sites. Tumors were measured before and 4 weeks after laser treatment. RESULTS: Both in vitro and in vivo mice data showed a significant decrease in growth of pancreatic cancer. Pancreatic cancer cell growth was suppressed by 66.1 +/- 0.2%, n = 12, P < 0.01, ANOVA. Subcutaneous shoulder tumors were suppressed by 91.2 +/- 2.3%, n = 12, P < 0.001, and orthotopically grown pancreatic tumors were suppressed by 42.2 +/- 8.1%, n = 12, P < 0.05, compared to pretreatment sizes. Data expressed as percentage reduction vs paired controls in the MTT assay and vs pre-photodynamic therapy in mice experiments. Paired Student's t tests were performed vs pretreatment sizes. CONCLUSION: Both in vitro and in vivo results revealed a significant decrease in pancreatic cancer cell growth. Laser or dye alone had no effect, indicating that intratumor hypericin and laser therapy may prove useful in unresectable pancreatic cancer.     

Adjuvant therapy for pituitary adenomas: the possible role of photodynamic therapy.

Although benign, pituitary adenomas may not always be curable by surgery alone. This is usually owing to dural infiltration and the technical problems of removal of involved dura in the sellar region. In such circumstances, some form of adjuvant therapy may be needed to address residual tumour and forestall recurrence. Radiotherapy and drugs, such as bromocriptine or octreotide, although effective are far from ideal adjuvant therapies and this has led to the study of the effects of photodynamic therapy on pituitary adenomas. It has been shown that photodynamic therapy using the photosensitising drugs haematoporphyrin derivative and aluminium phthalocyanine is active experimentally against these tumours. This could provide another useful weapon to use against these challenging lesions.     

Peri-operative glucocorticoid replacement therapy in transsphenoidal pituitary adenoma surgery: a prospective controlled study

Summary Background. We set out to prospectively study the peri-operative changes of the hypothalamic-pituitary-adrenal axis (HPA), and to test the hypothesis that the peri-operative corticoid replacement regimen used at the authors’ institution in patients with impaired HPA undergoing transsphenoidal pituitary adenoma surgery is adequate. Method. Thirty seven patients (21 females, 16 males, mean age 50.6 years) underwent transsphenoidal pituitary adenoma surgery (mean tumour diameter 20.6 mm, 13 tumours hormone-secreting). The HPA functions of these patients were classified as impaired (group A, n = 15) or preserved (group B, n = 22) according to the results of a pre-operative corticotrophin releasing-hormone test (CRHT). Eleven patients (9 female, 2 male, mean age 53.6 years) without pituitary adenomas and with a preserved HPA (as assessed by medical history and morning serum cortisol (MSC) measurements), undergoing decompressive surgery for degenerative lumbar disc disease, were also studied (group C). On the day of surgery, the patients of group A received 100 mg hydrocortisone (HC) replacement therapy, which was thereafter gradually tapered off in a standardised fashion. The patients of groups B and C were not treated with corticoids. Pre-operative, intra-operative and post-operative variables of these three patient groups were compared. Findings. The urinary free cortisol excretion (UFC) in group A declined from 6732 ± 7683 μg/d on the day of surgery to 305 ± 358 μg/d on the 10^th post-operative day. In group B, the respective UFC values were 12851 ± 16278 μg/d and 223 ± 235 μg/d. In both of these groups, the mean UFC did not fall into the normal range during the first ten post-operative days. On none of the post-operative days, was there a significant difference between the UFC of groups A and B. The UFC values of group C dropped from 177 ± 157 μg/d on the day of surgery to 87 ± 61 μg/d on post-operative day six, reaching the normal range from the 2^nd post-operative day onwards. All UFC values of group C were significantly lower than those of group A and B. None of the evaluated clinical, laboratory and MRI parameters, as disclosed by uni- and multivariate analysis, showed any significant influence on the peri-operative UFC values. Conclusions. The peri-operative UFC of pituitary adenoma patients with preserved HPA was very high, as compared to patients with degenerative lumbar disc disease. The present study showed for the first time, that the proposed regimen of peri-operative corticoid replacement therapy used in patients with pituitary adenomas and impaired HPA raised cortisol levels to match the physiological increase of UFC in patients with pituitary adenoma surgery and preserved HPA. However, although statistically not significant, the UFC of patients with pituitary adenomas and preserved HPA seemed considerably higher on the day of surgery than in patients with pituitary adenomas and HPA impairment. Although there is no evidence to make it mandatory, administration of 150 mg instead of 100 mg HC substitution on the day of pituitary adenoma surgery in patients with HPA impairment may be prudent. Correspondence: Rudolf A. Kristof, M.D., Universit?tsklinikum Bonn, Klinik und Poliklinik für Neurochirurgie, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.     

去甲斑蝥素对荷瘤裸鼠胆囊癌移植瘤的抗癌作用机制

目的 探讨去甲斑蝥素（NCTD）对荷瘤裸鼠胆囊癌移植瘤的抗癌作用机制。方法 在建立裸鼠胆囊癌移植瘤动物模型的基础上进行肿瘤增殖、侵袭、转移体内干预实验,实验分空白对照、氟尿嘧啶、NCTD、NCTD＋氟尿嘧啶4组。6周末应用链霉素亲和生物素复合物（SABC）法检测移植瘤增殖细胞核抗原（PCNA）、Ki-67、细胞周期素D1（cyclin D1）、p27、Bcl-2蛋白,逆转录PCR（RT-PCR）检测PCNA、cyclin D1、p27、Bcl-2、Bax、存活素（Survivin）基因mRNA。HE染色观察瘤周癌细胞浸润、侵袭,解剖显微镜下观察肺组织转移瘤结节,并采用SABC和RT-PCR检测nm23、金属蛋白酶2（MMP2）及其组织抑制剂（TIMP2）蛋白和mRNA。结果 NCTD组增殖相关PCNA、Ki-67、cyclin D1蛋白表达下降,p27蛋白表达上升;PCNA mRNA、cyclin D1 mRNA表达下降,p27 mRNA表达增高。NCTD组凋亡相关Bcl-2蛋白表达下降;Bcl-2 mRNA、Survivin mRNA表达下降,Bax mRNA表达增高。NCTD显著减少荷瘤鼠移植瘤的瘤周癌细胞浸润和肺转移结节（P〈0．01）;NCTD组转移相关MMP2蛋白表达下降,nm23、TIMP2蛋白表达上升;nm23-H,mRNA、TIMP2 mRNA表达增高。结论 NCTD抑制荷瘤裸鼠胆囊癌移植瘤增殖、侵袭和转移的机制可能与NCTD干扰胆囊癌移植瘤细胞周期,抑制细胞增殖,诱导细胞凋亡,阻止细胞迁移运动,以及影响细胞增殖、细胞周期调控、细胞凋亡、细胞基质溶解和转移相关基因蛋白表达有关。     

Effect of photodynamic therapy on urinary bladder function: an experimental study with rats

Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. The problems with laser light dosimetry and complications relating to bladder function appear to be important limiting factors of PDT in urology. Photodynamic therapy on urinary bladder with normal epithelium of rats was performed using an argon ion laser as an energy source, with aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photosensitizer. Four hours after ALA intravenous administration, the bladders were intravesically radiated with light doses 20, 40, or 80 J/cm². Animals in the control group did not receive ALA and were radiated with 20 J/cm² light dose. Three weeks prior to PDT, the bladder capacity and pressure changes during filling cystometry were assessed. Cystometrics were repeated 1, 3, 7, or 21 days after laser therapy. The light dose 20 J/cm² and 40 J/cm² together with the used ALA dose caused no reduction in bladder capacity, whereas 80 J/cm² light dose produced up to 50% reduction in the capacity at 3 weeks postoperatively. In control group without ALA, the animals did not regain more than 34% of the capacity of their control values at 3 weeks. The light dose of 20 J/cm² and 40 J/cm² with ALA induced functional changes that subsided after day 1. Our results indicate that with proper dosing of photosensitizing drug and light energy, the functional impairment of urinary bladder may be reduced as transient. These findings support the use of PDT as safe therapy of superficial bladder cancer. Received: 10 April 2000 / Accepted: 16 November 2000