卵巢透明细胞癌临床治疗效果研究

背景与目的:卵巢透明细胞癌相比于其他卵巢上皮性癌,其预后较差,本文对本院卵巢透明细胞癌患者生存率作分析比较,探讨CAP[表柔比星(E-ADM)、顺铂(DDP)加环磷酰胺(CTX)]方案加用丝裂霉素(MMC)后的治疗效果。方法:对本院于1999年1月1日至2002年12月31日接受治疗的卵巢透明细胞癌共33例(A组),同时随机取37例卵巢其他上皮性癌的患者作对照(B组)。Ⅰ期患者行全子宫 双附件 大网膜切除 阑尾切除 淋巴结分期术),2例患者需要生育的卵巢癌患者行患侧附件切除 对侧卵巢活检 大网膜切除 阑尾切除术术。Ⅱ期以上的患者行肿瘤减灭术(tumor reductive surgery,TRS)尽可能使残余灶<1cm,2组患者均在术后化疗均采用CAP方案(静脉应用),但A组患者CAP方案中加用了丝裂霉素。A组患者与仅用CAP方案的透明细胞癌患者(C组)Ⅰ/Ⅱ期15例及Ⅲ/Ⅳ期9例相比较。结果:术前A组与B组Ⅰ/Ⅱ血清CA125差异有显著性,卵巢透明细胞癌血清CA125水平值较低,Ⅲ/Ⅳ期血清CA125差异无显著性。在3次及6次化疗后与化疗前Ⅰ/Ⅱ期A组及B组血清CA125差异有显著性,而Ⅲ/Ⅳ期血清CA125下降水平差异无显著性。A组卵巢透明细胞癌患者中有11例有子宫内膜异位症(33.33%),有7例患者出现深静脉血栓(21.21%),有深静脉血栓的患者与生存率无直接关系(P=0.26)。Ⅰ/Ⅱ期患者的平均生存时间分别为:A组38.3±2.4个月,B组38.3±2.7个月,Ⅰ/Ⅱ期患者A组与B组用Log Rank检验相比较4年生存率差异无显著性(P=0.471),Ⅲ/Ⅳ期患者的平均生存时间分别为:A组20±3个月,B组34±4个月,Ⅲ/Ⅳ期患者A组与B组相比较用Log Rank检验4年生存率差异有显著性(P<0.05)。C组患者Ⅰ/Ⅱ期15例,平均生存时间为:30±3个月,与A组用MMC的透明细胞癌患者Ⅰ/Ⅱ期23例比较生存率差异有显著性(P<0.05)。C组患者Ⅲ/Ⅳ期9例,均死亡。平均生存时间为18±3个月。与A组用MMC的透明细胞癌患者Ⅲ/Ⅳ期10例比较生存率差异无显著性(P=0.430)。结论:卵巢透明细胞癌术前及化疗后血清CA125水平值较低,用CAP加丝裂霉素的规则化疗治疗透明细胞癌对Ⅰ/Ⅱ期患者有一定的治疗效果,对Ⅲ/Ⅳ期患者治疗效果不佳。卵巢透明细胞癌疾病的复发率及死亡率仍然较高。     

Strategies for the development of recombinant vaccines for the immunotherapy of breast cancer

Summary The development of recombinant vaccines for specific immunotherapy of carcinoma represents a novel approach for the treatment of breast cancer and other tumor types. This article reviews the various parameters that should be considered in the development of recombinant vaccines. Several breast cancer associated antigens are also discussed which may provide potential target molecules. The human carcinoembryonic antigen (CEA), which is expressed on approximately 50% of breast cancers, represents one such target for immunotherapy. To enhance the immunogenicity of this antigen, a recombinant CEA-vaccinia vaccine, designated rV-CEA, was produced. To study the effects of this vaccine in an animal model, a murine colon carcinoma cell line was transduced with CEA and transplanted into immunocompetent mice for protection and therapy studies. Pre-clinical toxicity studies were also conducted in non-human primates. The results of these studies showed the rV-CEA vaccine to be immunogenic and safe in both rodents and primates, and to elicit good anti-tumor responses in the rodent model. In a Phase I clinical trial in metastatic breast, lung, and colorectal cancer patients involving three immunizations of rV-CEA, at three dose levels, enhancement of T-cell and antibody responses to vaccinia virus proteins were observed with no toxicity. Specific T-cell responses were studied via stimulation of peripheral blood lymphocytes with specific peptide epitopes from the CEA molecule. These studies demonstrated clear cut differences in establishment of T-cell lines pre- versus post-immunization. The T-cell lines were shown to be CD8⁺ and/or CD4⁺/CD8⁺, to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive carcinoma cells in a HLA restricted manner. Thus, in a Phase I clinical trial the rV-CEA vaccine has been shown to stimulate a CTL response specific for CEA defined epitopes in cancer patients.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Canter, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Guidance for peptide vaccines for the treatment of cancer

Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system – a mechanism of action that clearly differs from anticancer drugs that exert a direct effect. Thus, the clinical development of cancer peptide vaccines should be planned and implemented based on the mechanism of action, which differs significantly from conventional anticancer drug research. The Japanese Society for Biological Therapy has created and published Guidance for peptide vaccines for the treatment of cancer as part of its mission and responsibilities towards cancer peptide vaccine development, which is now pursued globally. We welcome comments from regulators and business people as well as researchers in this area.     

Searching for targets for the systemic therapy of mesothelioma

Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma.     

Experience and outlook for the work of the All-Union Center for the Early Detection of Breast Cancer

The results of studies conducted by the Center's staff for early detection of breast cancer are discussed. About 5,000 females are examined at the Center yearly, with clinical, mammographic and thermographic procedures being used. During five screenings, breast cancer was detected in 56 cases (8.9%-by thermography alone, 16%-clinical examination, 26.8%-mammography alone and 48.2%-mammography plus clinical examination). "Minimal" breast cancer (less than 1 cm in dia.) was detected in 19 cases (33.9%). 76.5% of "minimal" cancers were detected with the aid of mammography.     

Biochemical test for the presence of pepsinogen-pepsin for the diagnosis of stomach cancer metastases]

In metastases and malignant tumors arising from gastric mucous membrane irrespective of their localization the method of electrophoresis and enzyme-electroporesis in agar gel demonstrates the presence of rapidly moving anode fractions I, II, and III corresponding to pepsinogen-pepsin isoforms of normal gastric mucosa but lacking proteolytic activity.     

Criteria for the selection of radionuclides for targeting nuclear antigens for cancer radioimmunotherapy

The potential of utilizing immunoconjugates to selectively deliver radionuclides for the destruction of tumors has stimulated much research activity. From dosimetric and other considerations, the choice of radiolabel is an important factor that needs to be optimized for maximum effectiveness of radioimmunotherapy (RIT). This paper reviews and assesses a number of present and future radionuclides that are particularly suitable for RIT based on the various physical, chemical, and biological considerations. Although intermediate to high-energy beta emitters (with and without gamma photons in their emission) possess a number of advantages for most RIT, the use of alpha, Auger, and short range conversion electron emitters could be attractive for targeting nuclear antigens when the radioimmunoconjugate is internalized into tumor cells. Factors relating to the production and availability of candidate radionuclides as well as their stable chemical attachment to monoclonal antibodies are discussed.     

Nonattendance is still the main limitation for the effectiveness of screening for cervical cancer in the Netherlands

Although mass screening for cervical cancer has been operational for more than 2 decades in the Netherlands, 700 women are still diagnosed with this cancer each year (9 per 100,000). We investigated these cases, in order to evaluate opportunities to further increase the effectiveness of the programme. We analyzed the screening history of women diagnosed with cervical cancer between 1994-1997 using the Dutch national pathology file that includes cervical cytology and histological results. More than half of the cases did not have previous preventive cervical smears, and another 30% had never been invited to the programme because of their age. In the future, we estimate that two thirds of all Dutch women with invasive cervical cancer will be unscreened or under-screened, based on current screening participation of more than 70%. We conclude that increasing screening participation has much more potential for further reducing cervical cancer incidence than reducing the screening interval, increasing the age range or having a screening test with higher sensitivity.     

脊柱关节炎分类标准的演变

脊柱关节炎（ spodyloarthritis，SPA ）是一组互相关联的，通常侵犯脊柱、外周关节、关节周围结构的多系统炎性疾病，包括强直性脊柱炎（ ankylosing spondylitis， AS ）、银屑病关节炎（ psoriatic arthritis，PSA ）、反应性关节炎（ reactive arthritis，REA ）、赖特综合征（ Reiter＇s syndrome，RS ）、炎性肠病关节炎（ inflammatory bowel disease arthritis ）、幼年发病的脊柱关节病以及分类未定的脊柱关节病。     

Radiotherapy for cystadenoma of the trachea

Radiation as a method of treatment was carried out in 16 (25.0%) out of 64 patients with tracheal adenocystoma (radical dosage of 50-70 Gy (12) and palliative--40-48 Gy (4). The dosimetric profile consisted of the cervical, cervico-thoracic, thoracic and bifurcation sections of the trachea. Complete resorption of tumor was registered in 12, partial--3, no effect in 1 cases. Three-, five- and ten-year survival was 65.2 +/- 12.6; 55.9 +/- 13.5 and 10.4 +/- 13.1%, respectively.     

A predictive test for the selection of cancer chemotherapeutic agents for the treatment of human cancer

The use of animals for the screening of chemotherapeutic agents effective against cancer is not always satisfactory. In addition to the problems of cost, space, and care, the results obtained by animal screening do not always parallel those obtained by the clinical use of the agents. With the advent of more refined in vitro technics which can be applied directly to the patient's own tumor tissue, additional information may permit a more critical evaluation of the laboratory findings. The critical index of sensitivity probably lies in the combined evaluation of biochemical analysis and observed morphological damage. From this investigation it would appear that tissue culture of human tumors may serve as a valuable adjunctive method for the screening of chemicals in order to find drugs valuable in the treatment of cancer in man and to serve as a method in the selection of the most effective therapeutic agent for a given tumor in a given patient.