食管癌体外照射加腔内~（192）铱治疗疗效分析

食管癌外照射加腔内后装治疗４０例与单纯外照射６０例。腔内治疗在外照射肿瘤量５０－６０Ｇｙ后进行，４－６Ｇｙ／次周，治疗２－３次，总量６０－６５Ｇｙ。单纯外照射总量也达６０－６５Ｇｙ／６－７周。外照射加腔内组ＣＲ７５％、ＰＲ２２．５％、ＮＲ２．５％，一年生存率８０％。单纯外照射组分别为４３％，５２％，５％，５６．７％。提示外照射加腔内治疗能提高食管癌的生存率及生存质量。腔内治疗在食管癌的根治性放疗中成为不可缺少的手段。     

内外照射加化疗联合治疗食管癌临床分析

目的 分析外照射、腔内近距离治疗及化疗治疗食管癌的疗效及其与外照射比较。方法 １２０例食管癌随机分成４组,每组３０例。Ⅰ组为外照射,Ⅱ组为外照射加腔内照射,Ⅲ组为外照射加化疗,Ⅳ组为内照射加化疗。外照射采用＾６０Ｃｏ治疗,２Ｇｙ／次,５次／周,总剂量６０－７４Ｇｙ;腔内照射６－８Ｇｙ／次,１次／周,总量１８～２４Ｇｙ;化疗用卡铂,１００ｍｇ／ｄ,５次／周,总量１０００ｍｇ。结果 Ⅱ～Ⅳ组的１,２,３年生存率高于Ⅰ组（Ｐ〈０．０５）。Ⅰ～Ⅳ组的３年生存率分别为１３．３％、３６．７％、４０．０％和４６．７％,死于肿瘤复发及未控分别为７２．２％、４０．０％、４３．７％和３８．４％（Ｐ〈０．０５）,远处转移率无明显差异。结论 外照射与近距离治疗和化疗的综合治疗可提高食管癌局部控制率和１,２,３年生存率。     

Ⅰ、Ⅱ期鼻咽癌外照射联合高剂量率腔内后装治疗

目的探讨高剂量率腔内后装治疗在鼻咽癌放疗中的作用。材料与方法从１９９２年１月至１９９３年６月，１１０例Ⅰ、Ⅱ期鼻咽癌患者随机分为外照射加高剂量率腔内后装治疗组（综合放疗组）和单纯外照射组（对照组）。综合放疗组外照射鼻咽剂量５６～６０Ｇｙ／２８～３０次／５、６～６周，腔内治疗鼻咽顶壁粘膜下０．３ｃｍ给量８Ｇｙ３次／１．５～２周。对照组外照射鼻咽剂量６６～７２Ｇｙ／３３～３６次／６．６～７．２周。结果治疗后３６个月局部控制率综合放疗组优于对照组（９８，２％对８５．５％，Ｐ＜０．０５）；张口困难发生率，综合放疗组低于对照组（７．３％对４７．３％，Ｐ＜０．００５）。结论外照射加高剂量率腔内后装治疗可提高早期（Ⅰ、Ⅱ期）鼻咽癌的局部控制率。     

食管癌超分割放疗剂量的临床研究

为探索食管癌超分割放疗适宜的剂量，１９８７年３～９月我们对８０例中段食管鳞癌患者随机分为３组进行对照研究：Ａ组总量为６０～７０Ｇｙ／６～７周，每天１次２Ｇｙ，每周５次；Ｂ组总量为５１Ｇｙ／２３天，每天２次，每；１．５Ｇｙ；Ｃ组总量为５０Ｇｙ／２３天，每天３次，每次１Ｇｙ。所有病人随诊超过５年，５年生存率Ａ、Ｂ、ＣＭ组分别为１１．１％、３７％和２３．１％。Ｂ组与Ａ组比较Ｐ＜０．０５。结果表明，总量为５１Ｇｙ的每天２次超分割放疗，具有疗程短、经济负担轻、生存率高等优点，治疗食管癌是可行的。     

鼻咽癌原发灶复发联合外照射和腔内后装治疗

从１９９１年１月至１９９２年１２月，收集我院鼻咽癌首程放疗后鼻咽原发灶复发，再分期Ｔ１和Ｔ２的８０例，随机分为外照射加腔内后装治疗组（综合放疗组）和单纯外照射组（对照组）各４０例。综合放疗组外照射鼻咽剂量３０￣６０Ｇｙ／１５￣３０次，３￣６周（中位剂量４４Ｇｙ），腔内后装鼻咽顶粘膜下０．３ｃｍ剂量１０￣３６Ｇｙ／２￣６次，１￣３周（中位剂量３０Ｇｙ）；对照组外照射鼻咽剂量６０￣７０Ｇｙ／３０￣３６     

热疗加放射治疗局部晚期宫颈癌

观察热疗加放射在治疗局部晚期宫颈癌的作用。从１９９４年１月－１９９６年１２月收治局部晚期宫颈癌６０例，分为两组。热放组３０例，外照射平均剂量５０．３Ｇｙ（全盆腔），腔内放疗平均剂量３９．４Ｇｙ／Ａ点，腔内热疗４３℃～４５℃／４０ｍｉｎ～４５ｍｉｎ，每周一次，共４次。单放组３０例，外照射平均剂量４９．５Ｇｙ／全盆腔，腔内放疗平均剂量３６．１３Ｇｙ／Ａ点。肿瘤Ⅲ期完全消退率，热放组和单放组各为８０％和１３．３％，Ｐ＜０．０１。热疗加放疗治疗局部晚期宫颈癌近期疗效好。     

经导管^192lr近距离放射治疗局部晚期肝门部胆管癌

目的：观察局部晚期肝门部胆管癌姑息性引流术后＾１９２ｌｒ腔内放疗的疗效。方法：先行手术探查尽可能刮除肿瘤并放置Ｕ型管引流，术后再经导管腔内放疗。参考点距离放射源中心轴１０ｍｍ，总量２４－３０Ｇｙ／３次，３例配合肝动脉区域性灌注化疗，１例配合外照射ＤＴ４５Ｇｙ／４．５周。结果：生存期６－２６个月，中位生存期１１．５月。１５例死亡，１例目前存活８个月。全组１年生存率３７．５％，２年生存率６．０％，结论     

高剂量率腔内放射治疗原发性支气管肺癌合并肺不张

目的研究高剂量率（ＨＤＲ）腔内放疗加外照射治疗原发性支气管肺癌合并肺不张的肺复张和近期疗效。方法原发性支气管肺癌９５例，Ｋａｒｎｏｆｓｋｙ评分２０～５０分。治疗分两组：Ａ组５７例，先用ＨＤＲＩｒ－１９２腔内照射，７～１０Ｇｙ，每周１次，共２～３次，总剂量为２０～３０Ｇｙ，而后常规外照射，剂量与Ｂ组相同。Ｂ组３８例，单纯外照射，先大野每次２Ｇｙ，总剂量为４０Ｇｙ／４Ｗ，后缩野每次２Ｇｙ，总剂量为２０～３０Ｇｙ／２～３Ｗ。结果Ａ组肺复张率较Ｂ组为高（Ｐ＜０．０５）。肺不张时间超过６个月者复张困难。一年生存率分别为４２％（２４／５７）和３９．５％（１５／３８），无明显差异。结论高剂量率腔内放射结合外照射可改善原发性支气管肺癌合并肺不张的症状。     

前程加卡铂后程野中野加速超分割放射治疗食管癌90例临床观察

目的探讨前程加卡铂后程野中野加速超分割放射治疗食管癌的疗效。材料与方法自１９９１年１０月至１９９３年６月对９０例食管癌病人随机分常规放射治疗组（常规组）和前程加卡铂后程野中野加速超分割放疗组（前化后超组）各４５例。两组临床资料相近，具备可比性。常规组每周照５次，每次２Ｇｙ，总量６０～７０Ｇｙ；前化后超组前３周放疗同常规组，配合卡铂每周两次，每次１００ｍｇ，总量６００ｍｇ。第４，５周在原照射野中设小野（同病变长度），每次１．５Ｇｙ，每周５次，上午照大野，下午照小野，总量５周６５Ｇｙ，其中大野５周５０Ｇｙ，小野后两周１５Ｇｙ。结果放疗结束时Ｘ线改善前化后超组病灶全消和消失１／２以上８６．７％（３９／４５），常规组５７．８％（２６／４５）（Ｐ＜０．０１）。１，２，３，４年生存率分别为７５．６％、５３．３％、４２．２％、３３．３％和５５．６％、３１．１％、２０．０％、１５．６％。前化后超组明显好于常规组（Ｐ＜０．０５）。结论前程配合卡铂后程大野套小野加速超分割放射治疗能显著提高食管癌１，２，３，４年生存率，病人能顺利完成疗程。     

经导管~(192)Ir近距离放射治疗局部晚期肝门部胆管癌

目的：观察局部晚期肝门部胆管癌姑息性引流术后１９２Ｉｒ腔内放疗的疗效。方法：先行手术探查尽可能刮除肿瘤并放置Ｕ型管引流，术后再经导管腔内放疗。参考点距离放射源中心轴１０ｍｍ，总量２４～３０Ｇｙ／３次。３例配合肝动脉区域性灌注化疗，１例配合外照射ＤＴ４５Ｇｙ／４．５周。结果：生存期６～２６个月，中位生存期１１．５月。１５例死亡，１例目前存活８个月。全组１年生存率３７．５％，２年生存率６．０％，结论：局部晚期肝门部胆管癌姑息性引流术后腔内放疗可提高生存期及生活质量     

Role of acidosis-sensitive microRNAs in gene expression and functional parameters of tumors in vitro and in vivo

Background: The acidic extracellular environment of tumors has been shown to affect the malignant progression of tumor cells by modulating proliferation, cell death or metastatic potential. The aim of the study was to analyze whether acidosis-dependent miRNAs play a role in the signaling cascade from low pH through changes in gene expression to functional properties of tumors in vitro and in vivo.Methods: In two experimental tumor lines the expression of 13 genes was tested under acidic conditions in combination with overexpression or downregulation of 4 pH-sensitive miRNAs (miR-7, 183, 203, 215). Additionally, the impact on proliferation, cell cycle distribution, apoptosis, necrosis, migration and cell adhesion were measured.Results: Most of the genes showed a pH-dependent expression, but only a few of them were additionally regulated by miRNAs in vitro (Brip1, Clspn, Rif1) or in vivo (Fstl, Tlr5, Txnip). Especially miR-215 overexpression was able to counteract the acidosis effect in some genes. The impact on proliferation was cell line-dependent and most pronounced with overexpression of miR-183 and miR-203, whereas apoptosis and necrosis were pH-dependent but not influenced by miRNAs. The tumor growth was markedly regulated by miR-183 and miR-7. In addition, acidosis had a strong effect on cell adhesion, which could be modulated by miR-7, miR-203 and miR-215.Conclusions: The results indicate that the acidosis effect on gene expression and functional properties of tumor cells could be mediated by pH-dependent miRNAs. Many effects were cell line dependent and therefore do not reflect universal intracellular signaling cascades. However, the role of miRNAs in the adaptation to an acidic environment may open new therapeutic strategies.     

Expression of thrombomodulin in astrocytomas of various malignancy and in gliotic and normal brains

Summary A total of 22 surgical specimens, 16 astrocytomas with various malignancy, 3 brains adjacent to tumor and 3 brains with non-neoplastic lesion, was investigated immunohistochemically for the expression of thrombomodulin (TM). This membrane protein is localized on the vascular endothelium of nearly every human tissue and plays a crucial role in the maintenance of antithrombotic property of the endothelial cells. Although the normal cerebral vessels were negative for TM, the tumor vessels were positive for TM. The increased expression of TM was, however, demonstrated not only in glioblastomas but also in low-grade astrocytomas. Furthermore, the vessels in the brains adjacent to tumor and gliotic brains were also positive for TM. Those observations suggested that the tendency of intratumoral bleeding, which is rather characteristic of glioblastomas, is not simply explained by the altered expression of vascular endothelial TM. In two cases of glioblastoma, not only the blood vessels but also the tumor cells were positive. Considering the mitogenic activity of thrombin, a ligand for TM, the increased expression of TM might be related to the tumor neovascularization and also the tumor growth.     

The role of alcohol in oral and pharyngeal cancer in non-smokers, and of tobacco in non-drinkers

Data from a hospital-based case-control study of oral and pharyngeal cancer conducted in Northern Italy were used to analyse the risk associated with alcohol in non-smokers and with tobacco in non-drinkers. Out of a total of 336 cases (291 males and 45 females) and 1,652 controls (1,272 males and 380 females) 27 cases and 572 controls described themselves as lifelong non-smokers. Odds ratios (ORs) were 1.5 for 14-55 vs. 0-13 alcoholic drinks per week and 2.2 for 56 or over; the trend in risk was statistically significant. Among 19 cases and 213 controls who described themselves as non-drinkers, the ORs were 3.8 and 12.9 for smokers of less than 15 and greater than or equal to 15 cigarettes per day, with a highly significant trend. This study therefore confirms that tobacco has an independent role in the aetiology of oral and pharyngeal cancer, and suggests that alcohol may have an independent role as well, even where, as in Northern Italy, wine is its predominant source. Indeed, ORs were similar to those for tobacco and alcohol individually, each adjusted for the other factor, in the overall data-set.     

Nitrate and nitrite in saliva and urine of inhabitants of areas of low and high incidence of cholangiocarcinoma in Thailand

Cholangiocarcinoma is one of the main liver diseases in northeast Thailand. Associations with exposure to liver fluke and N-nitrosodimethylamine in formation of the tumour have been demonstrated in animals. This study was carried out to compare possible endogenous formation of N-nitroso compounds in inhabitants of areas with low and high incidences of cholangiocarcinoma by examining the levels of nitrate and nitrite in their saliva and urine. Thirty-two subjects (16 males and 16 females) living in the north-east (high incidence) and 12 volunteers (6 males and 6 females) in Bangkok (low incidence) were allowed to take regular meals, and their saliva and urine were collected before, and 30, 60 and 120 min after each meal. Nitrate and nitrite concentrations in saliva of the group in the high-incidence area were significantly higher than those of the group in Bangkok: salivary nitrate was 2-2.8 times higher and nitrite 2-5.6 times higher in the north-eastern group when compared with levels at each corresponding time interval in the low-incidence group. Nitrate levels in urine were also significantly higher in the north-eastern group at some time intervals, but urinary nitrite levels were similar and very low in both groups throughout the day. This finding may indicate a greater possibility of in-vivo formation of N-nitroso compounds in the north-east area than in Bangkok and might be associated with the occurrence of cholangiocarcinoma in north-east Thailand.     

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

Background:

The clinical use of immunotoxins (ITs) has been hampered by hepatotoxicity, and the induction of a strong human-anti-IT response. The human-anti-IT response results in neutralisation of the immunoconjugates, rendering repetitive treatment inefficacious.

Methods:

We evaluated the combination of cyclosporin A (CsA) with various Pseudomonas exotoxin A-based ITs in human breast, cervical, and prostate cancer cell lines measured by protein synthesis, cell viability, and TUNEL assay. Furthermore, expression of essential proteins were analysed by western blot. We used cervical cancer model in nude rats to evaluate the anti-metastatic effect of the combination. The anti-immunogenic response by the CsA treatment was investigated in immunocompetent rats.

Results:

The combination of CsA with ITs caused remarkable synergistic cytotoxicity, in several cancer cell lines, characterised by protein synthesis inhibition, decreased cell viability, and an increased apoptotic index. Furthermore, the combination strongly inhibited formation of metastases in a cervical cancer model in nude rats with a statistically significant increase in median survival time of the combination-treated animals, as compared with those receiving a suboptimal dose of IT alone. Notably, we found in immunocompetent rats that the anti-IT immunoresponse elicited by repeated administration of IT was efficiently abrogated by CsA; notably the antibody responds towards the highly immunogenic PE was shown to be prevented.

Conclusion:

The combination of ITs and CsA might constitute a significant improvement in the clinical potential of systemic IT treatment of cancer patients.