抗膀胱癌单克隆抗体导向的粘附性LAK细胞体外抗膀胱癌作…

为了进一步探索治疗膀胱癌的新途径，用人体脾脏组织制备粘附性淋巴因子激活的杀伤细胞，通过生物素－亲和素系统将抗人膀胱癌单克隆抗体与Ａ－ＬＡＫ细胞偶联构建出ＢＤＩ－１－Ａ－ＬＡＫ细胞偶联物。采用４小时＾５１Ｃｒ释放法测定ＢＤＩ－１－Ａ－ＬＡＫ细胞偶联物体对外人膀胱癌ＢＩＵ－８７细胞的杀伤率。     

超氧阴离子对膀胱癌患者LAK细胞的影响

目的 探讨超氧阴离子（Ｏ２＾－）对膀胱癌患者ＬＡＫ细胞增殖和抗膀胱癌细胞的细胞毒作用的影响。方法 用黄嘌呤（Ｘ）与黄嘌呤氧化酶（ＸＯ）反应产生Ｏ２＾－，用淋巴细胞分离液梯度离心法分离ＬＡＫ细胞，用细胞计数法观察不同浓度的Ｏ２对细胞增殖的影响，培养膀胱癌细胞系ＢＩＵ－８７和ＥＪ作为靶细胞，用ＭＴＴ法测定ＬＡＫ细胞对肿瘤细胞的细胞毒作用。结果 表明一定的浓度的Ｏ２＾－（０．０５Ｕ／ｍｌ ＸＯ和０．５ｍ     

人膀胱癌BIU－87细胞系多重抗药性的形成

应用阿霉素（ＡＤＭ），大剂量短暂冲击结合低浓度持续递增法，逐步诱导人膀胱癌移行上皮细胞系ＢＩＵ－８７，在体外持续培养６个月，获得了具有多重抗药性的ＢＩＵ－８７／ＡＤＭ细胞。该细胞能在浓度为２．０ｇ／Ｌ的ＡＤＭ中持续增殖。通过测定抗癌药物５０％抑制浓度（ＩＣ_（５０））发现，ＢＩＵ－８７／ＡＤＭ细胞对阿霉素的敏感性下降了２１倍，同时对表阿霉素（４－ｅｐｉ）、长春新碱（ＶＣＲ）、足叶乙甙（ＶＰ－１６）也具有显著的交叉抗药性，对顺铂（ＤＤＰ）、丝裂霉素（ＭＭＣ）、５－氟尿嘧啶（５－Ｆｕ）和氨甲喋呤（ＭＴＸ）无抗药性；ＢＩＵ８７／ＡＤＭ细胞在脱离阿霉素诱导第８周时，其抗药性仍保持在９０％以上，结果表明：ＢＩＵ－８７／ＡＤＭ细胞具有多重抗药性（ＭＤＲ）表型，且抗药性较稳定，是研究人膀胱移行细胞癌ＭＤＲ机制和筛选抗药性逆转剂的理想模型。     

免疫毒素导向治疗膀胱癌的实验与临床研究

用抗人膀胱癌单克隆抗体ＢＤＩ－１与苦瓜毒素（ＭＤ）通过化学交联制备的抗人膀胱癌免疫毒素（ＢＤＬ－１－ＭＤ）在体外可以特异地杀伤人膀胱癌细胞；在载瘤裸鼠体内可以明显地抑制人膀胱癌的生长。临床对１８例膀胱癌患者施行膀胱灌注免疫毒素的导向治疗，其中肿瘤Ⅰ级６例，Ⅱ级７例，Ⅲ级５例；首发瘤１４例，复发瘤４例。随访８～２８个月，平均１２．５个月，１７例未复发，１例复发（５．５％）。表明ＢＤＬ－１－ＭＤ在清除膀胱内小于１ｃｍ小瘤灶及防止术后复发方面具有明显效果。     

抗P—糖蛋白单克隆抗体JSB—1和环孢素A协同逆转人膀胱癌MD…

为了证实抗Ｐ－糖蛋白单克隆抗体协同环孢素Ａ逆转入膀胱癌耐药细胞亚株的抗药性以及建立能有效地克服ＭＤＰ的治疗方案对人膀胱移行细胞癌ＢＩＵ－８７细胞系和ＢＩＵ－８７．ＡＤＭ耐药 株经柔红霉素与抗Ｐ－ｇｏ单克 抗 ＪＳＧＢ－１和单独或联合ＣｓＡ；ＪＳＢ－１和单独或联合异搏定自理后，采用Ｍ ＴＴ法评价细胞毒作用荧光光光度计检测细胞民内ＤＮＲ的聚集量。结果ＪＳＢ－１和ＣｓＡ能协同增加ＤＮＲＢＩＵ－８７／ＡＤ     

膀胱癌化疗药物敏感性的实验研究

以膀胱癌细胞株（ＢＩＵ－８７）为靶细胞，采用噻唑蓝（ＭＴＴ）比色法进行了膀胱癌腔内化疗药物敏感试验及条件选择的实验研究。结果发现丝裂霉素Ｃ（ＭＭＣ）、噻替哌（ＴＨＴ）、顺铂（ＤＤＰ）对ＢＩＵ－８７细胞杀伤作用较明显，但在１ｍｇ／ｍｌ、２ｈ作用条件下均未达到５０％抑制率、需增加药物浓度和延长作用时间。认为ＭＭＴ、ＴＨＴ、ＤＤＰ对ＢＩＵ－８７细胞的毒性作用与药物浓度和作用时间有关；为达到最大疗效，药物     

肿瘤坏死因子α和干扰素α对膀胱癌患者LAK细胞增殖和细…

为探讨联合应用白细胞介素２（ＩＬ－２）和干扰素（ＩＦＮ）或肿瘤坏死因子（ＴＮＦ）对膀胱癌患者ＬＡＫ细胞的增殖和细胞毒作用的影响，采用淋巴细胞分离液梯度离心法从２１例膀胱癌患者外周血分离ＬＡＫ细胞并用ＩＬ－２激活培养，细胞于９６孔细胞培养板用细胞计数方法观察了不同浓度ＴＮＦα和ＩＦＮα对细胞增殖的影响，用膀胱癌细胞系ＢＩＵ－８７和ＥＪ细胞作为靶细胞，用ＭＴＴ法测定ＬＡＫ细胞的细胞毒。结果：ＴＮＦα呈     

抗P-糖蛋白单克隆抗体JSB-1和环孢素A协同逆转人膀胱癌MDR的研究

为了证实抗Ｐ糖蛋白（Ｐｇｐ）单克隆抗体协同环孢素Ａ（ＣｓＡ）逆转人膀胱癌耐药细胞亚株的抗药性以及建立能有效地克服ＭＤＲ的治疗方案，对人膀胱移行细胞癌ＢＩＵ８７细胞系和ＢＩＵ８７／ＡＤＭ耐药细胞亚株经柔红霉素（ＤＮＲ）与抗Ｐｇｐ单克隆抗体ＪＳＢ１和单独或联合ＣｓＡ；ＪＳＢ１和单独或联合异搏定（Ｖｅｒ）处理后，采用ＭＴＴ法评价细胞毒作用，荧光分光光度计检测细胞内ＤＮＲ的聚集量。结果：ＪＳＢ１和ＣｓＡ能协同增加ＤＮＲ对ＢＩＵ８７／ＡＤＭ的抗肿瘤作用，但ＪＳＢ１和Ｖｅｒ联合应用却不存在这种协同效应。结果显示：ＪＳＢ１和ＣｓＡ联合应用能增加细胞毒剂对具有Ｐｇｐ表达的ＭＤＲ肿瘤的抗肿瘤效应，是适合于临床应用的多药抗性逆转方案。     

人膀胱癌BIU—87细胞系多重抗药性的形成

应用阿霉素，大剂量短暂冲击结合低浓度持续递增法，逐步诱导人膀胱癌移行上皮细胞系ＢＩＵ－８７，在体外持续培养６个月，获得了具有多重抗药性的ＢＩＵ－８７／ＡＤＭ细胞。该细胞能在浓度为２．０ｇ／Ｌ的ＡＤＭ中持续增殖。通过测定抗癌药物５０％抑制浓度发现，ＢＩＵ－８７／ＡＤＭ细胞对阿霉素的敏感性下降了２１倍同时对表阿霉素，长春新碱，足叶乙甙，也具有显著的交叉抗药性，对顺铂，丝裂霉素，５氟尿嘧啶和氨甲喋呤无抗     

人膀胱癌多重抗药性逆转的实验研究

为探讨膀胱癌多重抗药性逆转机理，应用阿霉素（ＡＤＭ）大剂量短暂冲击结合低浓度持续递增法，获得了具有多重抗药性的ＢＩＵ８７Ｒ／ＡＤＭ细胞。通过测定细胞内ＡＤＭ聚积量和钙离子浓度，发现ＢＩＵ８７Ｒ／ＡＤＭ细胞内ＡＤＭ聚积量显著低于ＢＩＵ８７细胞（Ｐ＜００５）；维拉帕米（ＶＰＬ）、奎宁能使ＢＩＵ８７Ｒ／ＡＤＭ细胞内ＡＤＭ聚积量增加（Ｐ＜００５），两者协同应用基本上可逆转ＢＩＵ８７Ｒ／ＡＤＭ细胞的抗药性。结果表明：（１）细胞内ＡＤＭ聚积量减少是抗药细胞的重要变化，在细胞抗药性发生机理中可能起主导作用，（２）ＶＰＬ、奎宁能逆转ＢＩＵ８７Ｒ／ＡＤＭ细胞的抗药性，可能与增加细胞内ＡＤＭ聚积量有关，与钙通道无关。     

Breast cancer and ovarian cancer genetics

Breast and ovarian cancers are the second and fifth leading causes of cancer death, respectively, among women in the United States. Individuals with breast cancer have a 20--30% chance of having at least one relative with the disease. However, only 5--10% of the cases are a direct result of germline mutations in highly penetrable genes, such as BRCA1 and BRCA2 (BRCA1/2) as well as genes TP53 and PTEN. Since 1996, genetic testing for these mutations has been clinically available. A strategy for the management of women at increased familial risk of breast and ovarian cancers is described, which includes genetic assessment, chemoprevention, radiologic screening, and clinical and self-examination. Genetic testing should occur within a cancer genetic clinic after genetic counseling. A blood sample allows determination of the presence of the BRCA1 and BRCA2 genes, the TP53 gene, the PTEN gene, and the ATM gene. Tumor examination has identified a growth factor receptor gene, human epidermal growth factor receptor (HER-2).With regard to diet and lifestyle, women at increased risk of breast cancer could be advised to reduce dietary fat, avoid obesity, decrease alcohol consumption, and take regular exercise. Although chemoprotection is a valuable consideration, it is important to emphasize that the use of Tamoxifen in BRCA1 and BRCA2 mutation carriers is not established, nor is the optimum duration of benefit. An overview of the main outcomes of the current published studies confirms a 38% decrease in breast cancer incidence with Tamoxifen but recommends its use be restricted to women at high risk of breast cancer and low risk for potential side effects. The role of bilateral risk-reducing mastectomy or prophylactic mastectomy has been controversial for several reasons, including the psychosocial significance of the breast in Western cultures, the wide acceptance of breast conservation in surgery for early breast cancer, and the previous lack of data on its efficacy. The surgical procedure should aim to remove substantially all at-risk breast tissue. However, there is a balance between reduction of cancer risk and cosmetic outcome. Bilateral prophylactic oophorectomy can significantly decrease ovarian cancer risk in women who carry BCRA1 mutations. Oophorectomy lowers the risk of breast cancer, even in women who have previously used hormone replacement therapy. There are no published randomized controlled trials examining the effectiveness of mammographic screening in women under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer. under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer.     

Sequential cancer of concomitant cancer?]

The generally-favoured polyp-cancer sequence hypothesis its probably wrong. The distribution of polyps in large intestine differs from that of cancer. There is evidence that different aetiological factors are involved in the genesis of polyps, their growth rate and the development to invasive cancer. Most polyps are very small (90%). They never develop a cancer. It is a diffusely abnormal state of the large bowel mucosa which renders it more liable to produce often polyps and very rare carcinoma (5%). Polyp-carcinoma concomitance is much nearer to the truth.     

Double cancer observed from bladder cancer]

BACKGROUND: In recent years, despite of the improvement of treatment results for cancer and long life, the occurrence of second primary cancer was increased. In this paper, we analyzed present condition of double cancer observed with bladder cancer in our hospital. METHOD: Last 21 years, we have treated 969 cases (828 male and 141 female) of primary bladder cancer. For those cases, we analyzed in term of frequency, involved organ, age, interval between two cancer occurrence, risk factor and prognosis of double cancer patients. RESULT: Of 969 cases with bladder cancer, 81 cases (8.36%) had double cancer involving 6 cases (0.61%) of triple cancer. In sex, 70 males (9.78%) and 11 females (7.80%) had double cancer. As involved organs, 25 cases (3.02%) had in prostate, 23 cases (2.37%) in stomach, 3 case (2.13%) in breast, 14 cases (1.44%) in colon and rectum. In diagnosis timing of complicated cancer from bladder cancer, 28 cases (34.6%) were diagnosed previously to bladder, 28 cases (34.6%) were simultaneously and 31 cases (38.3%) were secondary. An average interval of diagnosis of two cancer were 49 +/- 42.5 months. An average age of occurrence of second cancer was 70.3 +/- 8.8 years. Actual survival rate from diagnosis of bladder cancer were 90.8%, 68.6%, 53.3% and 30.3%, after 1, 3, 5 and 10 years, respectively. Ten cases were dead by bladder cancer, 21 cases by complicated cancer and 16 cases by another cause. CONCLUSION: The incidence of double cancer with bladder cancer were increased. Prostate cancer, colorectal cancer and breast cancer were gradually increased as complicated organs in Japan. The prognosis of double cancer patients with bladder cancer was poor than single bladder cancer patients.     

Synchronous triple urogenital cancer (renal cancer,bladder cancer,prostatic cancer): a case report

A case of synchronous triple urogenital cancer, which was comprised of renal cell carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder, and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male patient was referred to our outpatient clinic with the complaint of asymptomatic hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml. Cystourethroscopy showed a papillary bladder tumor and coagula through the left urinary orifice. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney. Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the same site. Double cancer, consisting of renal cell carcinoma and transitional cell carcinoma of the urinary bladder, was suspected and we performed left total nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the bladder tumor, one month later. At the same time, we performed a biopsy of the prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma and transitional cell carcinoma of urinary bladder. Histological diagnosis of the prostate biopsy was moderately differentiated adenocarcinoma. Since this case fulfilled the criteria of Warren and Gates, it was classified as synchronous triple urogenital cancer. A review of the literature revealed 17 authentic cases of triple urogenital cancer, of which 14 and 10 cases were reported as a combination of renal cancer, bladder cancer and prostatic cancer, in the world and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the development of the triple cancer.     

Hereditary breast cancer and family cancer syndromes

Hereditary breast cancer (HBC) shows extant clinical and genetic heterogeneity. Clinically one finds the onset of breast cancer at an early age, an excess of bilaterality, and patterns of multiple primary cancer such as combinations of breast and ovarian carcinoma in the hereditary breast-ovarian cancer (HBOC) syndrome. In addition to HBOC, one sees a variety of putative breast cancer-prone genotypes inclusive of hereditary site-specific breast cancer, and the Li-Frameni (SBLA) syndrome that is characterized by cancers involving all three germinal layers including sarcomas, brain tumors, leukemia, lymphoma, and adrenal cortical carcinoma in addition to often markedly early-onset breast cancer. Breast cancer is also associated with autosomal dominantly inherited Cowden's disease and autosomal recessively inherited ataxia-telangiectasia. Examples of pedigrees depicting clincal examples of these several HBC syndromes are presented in order to describe HBC's heterogeneity. The recent identification of the BRCA1 gene in early-onset hereditary sitespecific breast cancer and the HBOC syndrome has led to new challenges for the genetic counselor. We review genetic counseling, which embraces surveillance and management recommendations that are responsive to the natural history of HBC and address the concept for future development of centers of expertise for HBC in the interest of improving cancer control.

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Resumen El cáncer mamario hereditario (CMH) exhibe una gran heterogeneidad clínica y genética. Desde el punto de vista clínico, se observa el comienzo del cáncer mamario en una edad temprana, una tasa considerable de bilateralidad, y patrones de múltiples cánceres primarios, tal como la combinación de carcinomas mamario y ovárico en el síndrome del cáncer de seno-ovario hereditarios (CSOH). Además del CSOH, se puede observar una variedad de genotipos putativos propensos al cáncer, incluyendo el cáncer mamario hereditario de ubicación específica y el síndrome de Li-Fraumeni, que se caracteriza por cánceres que afectan a todas las tres capas germinales, incluyendo sarcomas, tumores cerebrales, leucemia, linfoma y carcinoma adrenocortical, además de un notorio comienzo precoz del cáncer mamario. El cáncer mamario también se asocia con la enfermedad de Cowden hereditaria y autosómica dominante y con la ataxia-telangiectasia autosómicamente recesiva. Se presentan ejemplos de pedigríes que ilustran diversos síndromes de CMH, con el objeto de demostrar la heterogeneidad del CMH. La reciente identificación del gen BRCA1 en el cáncer mamario hereditario, de ubicación específica y de comienzo temprano, y el sindrome CSOH, ha significado nuevos desafíos para el consejero genético. En este artículo hacemos una revisión de la consejería genética que se refiere a la vigilancia y a las recomendaciones sobre manejo que corresponda a la historia natural del CMH, y enfocamos el concepto en cuanto al desarrollo de centros de especializados en CMH, con el propósito de mejorar el control del cáncer.

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Résumé Le cancer du sein héréditaire (CSH) est cliniquement et génétiquement hétérogène. au point de vue clinique, le cancer dbute habituellement à un âge jeune, est souvent bilatéral, et est parfois associé à d'autres cancers primitifs, comme par exemple dans le syndrome de cancer héréditaire du sein et de l'ovaire (SCO). On peut également observer d'autres génotypes présumés susceptibles de donner des cancers du sein héréditaires ainsi que le syndrome Li-Fraumeni (SBLA), caractérisé par l'envahissement des trois couches germinales et comprenant les tumeurs sarcomateuses, les tumeurs du cerveau, les leucémies, les lymphomes, et des cancers des corticosurrénales associées à des cancers du sein à un âge précoce. Le cancer du sein est parfois associé à la maladie de Cowden, une maladie autosomique dominante, et la télangiectasie ataxique, une maladie autosomique récessive. Des exemples de pedigrees de plusieurs types des CSH sont présentés, soulignant l'hétérogénéité de ce syndrome. La plus récente identification du gène BRCA1 et son rôle dans le cancer du sein et le syndrome HBOC est un nouveau challenge pour le généticien d'aujourd'hui. Nous passons en revue nos attitudes de conseil génétique comprenant à la fois les recommandations de surveillance nouveau challenge pour le généticien d'aujourd'hui. Nous passons en revue nos attitudes de conseil génétique comprenant à la fois les recommandations de surveillance et d'attitude thérapeutiques compatibles avec l'histoire naturelle des CSH, et qui ont trait au développement future des Centres spécialisés pour évaluer ces CSH dans le but l'améliorer leur contrôle.

     

Alpha-fetoprotein-producing gastric cancer mimicking extragonadal testicular cancer

A case of alpha-fetoprotein-producing gastric hepatoid adenocarcinoma mimicking an extragonadal testicular cancer in a 28-year-old man is presented. This rare kind of tumor should be included in differential diagnosis in young patients without evidence of primary testicular malignancies.     

Metastasis of thyroid cancer to primary lung cancer

We present a case of a 65-year-old woman whose thyroid cancer metastasized to the lesion of primary lung cancer. Ten years after total thyroidectomy for thyroid cancer, chest radiograph by medical checkup demonstrated three nodular lesions in the bilateral lung fields. Segmental resection of the left S6, partial resection of right S4 and left S10 were performed to remove those lesions. Histologically, small nodules in the right S4 and S10 were diagnosed as a metastatic tumor of thyroid and well differentiated adenocarcinoma, respectively. Left S6 lesion 1.5 cm in diameter was also diagnosed as well-differentiated adenocarcinoma (Noguchi type C), however, small metastatic foci of papillary adenocarcinoma was identified within the lesion which revealed to be “cancer in cancer metastasis”. Metastasis of cancer to another primary cancer is a rare event. We discuss interesting phenomenon of cancer in cancer metastasis with a review of the literature.     

Oesophageal cancer

Oesophageal cancer is one of the most challenging of all tumours to manage. The two main histological types are squamous cell carcinoma and adenocarcinoma. The incidence of adenocarcinoma is increasing secondary to a number of factors including the ageing population, eradication of Helicobacter pylori and increasing gastro-oesophageal reflux disease/Barrett's oesophagus.The most common presentation is dysphagia and at diagnosis (usually by upper gastrointestinal endoscopy) two-thirds of patients are unsuitable for radical treatment due to the early metastatic dissemination of the tumour or poor patient physiological status.Mucosal disease may be treated by endoscopic resection; however, once disease has penetrated the submucosal layer there is a significant chance of lymphatic dissemination and so endoluminal therapy will likely prove inadequate and more radical therapy should be utilized. Tumours with lymph node involvement or invasion of the muscularis propria should be considered for multimodal therapy wherever possible – perioperative chemotherapy (UK) or neoadjuvant chemoradiotherapy (outside UK) and resection, or radical/definitive chemoradiotherapy. Surgery alone or radical radiotherapy are also options for those unfit for multimodal therapy. For patients treated with radical intent the 5-year survival now approaches 50% in some series. Surgery is associated with significant morbidity and a prolonged recovery period to regain preoperative status.     

Pancreatic cancer

Pancreatic cancer accounts for 3% of all cancers in the UK; 7000 new cases are diagnosed annually and a similar number die from the disease each year. It has an insidious onset and, as a result, presentation is usually late, with only about 10–20% of patients having disease amenable to surgical resection. Following resection, the median survival is 11–20 months and the 5-year survival is 7–25%. Patients with unresectable locally advanced disease have a median survival of 6–11 months, and those with metastatic disease have a median survival of 2–6 months. Accurate staging has a vital role in the management of pancreatic tumours now that non-surgical palliative options are available. Computed tomography is currently the imaging modality of choice for diagnosis and staging of pancreatic cancer. With recent advances in magnetic resonance imaging and endoscopic ultrasonography, it is now possible to improve the accuracy of preoperative staging, particularly with respect to local invasion and regional node involvement. Resection is the only treatment that offers the potential of cure; ideally, an R0 resection should be aimed for. Chemotherapy renders a survival advantage in the adjuvant setting, even in patients undergoing R1 resections. Palliative chemotherapy can improve survival by 10–15% and other palliative therapies are aimed at relieving jaundice, controlling pain, treating malabsorption and reversing cancer cachexia.