中国人尿路斑块蛋白Ib组织特异性及其启动子的克隆与鉴定

目的:研究中国人尿路斑块蛋白Ib的组织特异性并克隆与鉴定其启动子。方法:RT-PCR检测32例膀胱癌、16例正常膀胱粘膜、15例正常小肠粘膜、16例正常食道粘膜、19例正常肾实质、20例正常肝实质、8例正常皮肤及8例正常心肌标本中尿路斑块蛋白Ib的表达。以人正常膀胱粘膜为材料提取基因组DNA,克隆尿路斑块蛋白Ib启动子片段,并凝胶电泳和测序鉴定。结果:所有正常膀胱粘膜标本、16例分化Ⅰ级膀胱癌中有15例(93.8%)、9例分化Ⅱ级膀胱癌中有7例(77.8%)、7例分化Ⅲ级膀胱癌中有4例(57.1%)检测到尿路斑块蛋白Ib表达,而正常食道粘膜、小肠粘膜、肾实质、肝实质、皮肤、心肌标本均未检测到尿路斑块蛋白Ib表达。中国人尿路斑块蛋白Ib234bp的启动子被克隆并完成鉴定。结论:中国人尿路斑块蛋白Ib具有高度尿路移行上皮特异性,加上其启动子短小,尿路斑块蛋白Ib启动子非常适合膀胱癌的靶向基因治疗研究。我们成功克隆出中国人尿路斑块蛋白Ib启动子片段,为后续研究奠定了基础。     

Role of the antioxidant system and redox-dependent regulation of transcription factors bcl-2 and p53 in forming resistance of human K562 erythroleukemia cells to doxorubicin]

Prooxidant effect of chemotherapeutic agents is of significant interest in connection with activation of oxidative stress in cancer cells. Role of development of adaptive antioxidant response to the rise of resistance to cytotoxical effect of doxorubicin (DOX) has been studied in human erythroleukemia K562 cells. Growth of resistance to DOX caused enhancement of antioxidant enzymes (Cu, Zn-SOD, Mn-SOD, catalase) elevation of Mn-SOD activity being predominant. Additional increasing of antioxidant level was elevation of GSH maintenance and level of GST-related enzymes (glutathione peroxidase, glutathione S-transferase, glutathione reductase) in resistance K562/DOX cells. The enhancement of antioxidant system prevented activation of lipid peroxidation. Furthermore, the antioxidant growth caused decrease of level of proteintyrosine kinases, thioredoxin, thioredoxin reductase in contrary to elevation of glutaredoxin activity. Increasing of Bcl-2 and suppression of p53 levels was found to be caused by the change of redox state of K562DOX cells. The data support the suggestion that adaptive antioxidant response to prooxidant effect of DOX promotes the development of cellular drug resistance.     

Radiographic characteristics of nodular cancers of the breast with delimited forms of growth

The results of examination of 1,080 patients operated for carcinoma tuberosum of the breast at the clinic of the Institute in 1968-1978 are discussed. Distinct boundary of tumor growth was established in 281 cases by gross examination of tissue obtained by mastectomy. The results of X-ray examination were improved by means of histotopographic sections of tissue specimens in 100 cases. It was shown that distinct boundary of the growth of carcinoma tuberosum of the breast may be adequately identified in most cases on the basis of mammographic evidence (even, undulate or polycyclic contour of malignancy). Also, it was established that mammography offers a more adequate means of preoperative identification of the actual size of tumor than palpation does. An analysis of the mammographic picture contributes to the choice of the most efficient scheme of treatment of breast cancer patients.     

膝部肿瘤切除后关节功能重建的方法分析

目的 探讨膝部肿瘤切除后关节功能重建的方法选择和疗效。方法 54例膝关节周围肿瘤中，骨巨细胞瘤25例，非骨化性纤维瘤2例，成纤维性纤维瘤2例，动脉瘤样骨囊肿1例，软骨黏液性纤维瘤2例，骨肉瘤15例，软骨肉瘤2例，恶性纤维组织细胞瘤5例。23例采用瘤体切除，吻合血管的自体髂骨、腓骨联合移植术，12例瘤段切除灭活再植术，19例瘤段切除人工假体置换术。结果 54例平均随访5年6个月，成活病例术后功能评价优良率为76％。结论 膝部肿瘤切除后关节功能的重建，应根据肿瘤的大小、包壳的完整性、软组织的侵及情况，以及肿瘤的病理组织学性质，选择适当的手术方法。瘤体切除，吻合血管的自体髂骨、腓骨联合移植术，是治疗膝关节周围良性侵袭性肿瘤或低度恶性肿瘤较为理想的方法。     

Potent inhibitory effects of suicide inhibitors of P450 isozymes on 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene initiated skin tumors

A single dose of 1-ethynylpyrene (EP), 1-vinylpyrene (VP) or 2-ethynylnaphthalene (EN) was applied to the skin of SENCAR mice 5 min before an initiating dose of 7,12-dimethylbenz[a]anthracene (DMBA) or benzo[a]pyrene (B[a]P) and the development of skin tumors then promoted with biweekly topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). The application of EP strongly inhibited the formation of skin tumors initiated by either DMBA or B[a]P in a dose-dependent manner. Application of 44 pmol of EP inhibited tumor initiation by 10 nmol of DMBA approximately 25%; application of 440 nmol of EP inhibited tumor initiation by 200 nmol of B[a]P approximately 51%. A high single dose of EP (4.4-44 mumol) nearly eliminated skin tumor initiation by either 10 nmol of DMBA or 200 nmol of B[a]P. Application of VP also inhibited the formation of skin tumors initiated by either DMBA or B[a]P in a dose-dependent manner, but higher doses of VP than of EP were required to produce comparable inhibitions. Application of 44 nmol of VP inhibited tumor initiation by 10 nmol of DMBA approximately 30%; application of 4.4 mumol of VP inhibited tumor initiation by 200 nmol of B[a]P approximately 56%. Application of EN yielded contrasting results. EN inhibited the formation of skin tumors initiated by 10 nmol of DMBA, but the observed dose-dependence was minimal; tumors were decreased about 40% by 3.3 mumol of EN and only about 65% by 132 mumol of EN. A high single dose of EN (132 mumol) increased both the mean number of tumors per mouse and the percentage of mice that developed tumors after initiation by 200 nmol of B[a]P. Topical application of 4.4 mumol of EP, 22 mumol of VP or 33 mumol of EN to the skin of SENCAR mice 5 min before a single initiation dose of 2.5 mumol of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) had a minimal inhibitory effect (14-28%) on the development of skin tumors produced by subsequent biweekly promotion with TPA. A single dose of 44 mumol of EP or 132 mumol of EN followed by biweekly applications of TPA did not produce skin tumors; however, a dose of 44 mumol of VP followed by promotion with TPA produced a low but significant number of skin tumors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Rearrangement of human T cell receptor beta and gamma chain genes in adult T cell leukemia/lymphoma

We studied rearrangement of human T cell receptor genes (TCR) of C beta, C gamma, V gamma and J gamma in 34 cases of adult T cell leukemia/lymphoma (ATLL), consisting of 29 cases with monoclonally integrated HTLV-I proviral DNA (ATLL-W) and five without monoclonal integration (ATLL-O), in comparison with 12 cases of other peripheral T cell lymphomas (non-ATLL). All cases of both ATLL and non-ATLL showed some rearrangement of T cell receptor genes (TCRs) of C beta, C gamma, V gamma, or J gamma. Rearrangement of TCR beta was found in 28 of 29 cases of ATLL-W, all cases of ATLL-O, and eight of 12 cases of non-ATLL. Rearrangement of TCR gamma was observed in 21 of 22 cases of ATLL-W, and in all cases of ATLL-O and non-ATLL. In TCR gamma, rearrangement of C gamma was seen in six of 20 cases of ATLL-W, none of three ATLL-O cases and three of six cases of non-ATLL. V gamma rearrangement occurred in 14 of 18 cases of ATLL-W, one of two cases of ATLL-O, and three of six cases of non-ATLL. Rearrangement of J gamma was found in 16 of 22 cases of ATLL-W, two of five ATLL-O cases, and six of seven non-ATLL cases. Rearrangement was more frequent in ATLL-W than in ATLL-O and non-ATLL. The incidence rate of rearrangement of V gamma families of V gamma 1, V gamma 2, and V gamma 3 was nearly the same in each group, except for deletion of V gamma 3, which was often observed in ATLL but was absent in non-ATLL. These results indicate the usefulness of detection of TCR and HTLV-I proviral DNA to differentiate ATLL from other T cell malignancies.     

Differential diagnosis of malignant forms of hormonally-active tumors of the ovary

Case histories of 427 patients with main histotypes of hormone-producing tumors of the ovaries (201--theca-cell, 177--granulosa-cell, 28--mixed theca-granulosa-cell and 21--virilizing) were analyzed. The problem of differential diagnosis of malignant forms of these tumors by methods of clinical examination was studied. Major statistically significant clinical signs of malignancy of hormone-producing tumors of the ovaries--extension of abdomen and abdominal pain, relatively short duration of case history, bilateral lesions, large size of sessile tuberculous tumors, high level of ascites, especially hemorrhagic one, and comparatively young age of patients--were established.     

Regulation of cell growth by retinoids and gene expression

Retinoids are compounds that can elicit specific biological responses by virtue of their binding to and activating a specific receptor or a set of receptors. Retinoids produce various specific biological effects, including induction of terminal differentiation, regulation of cell proliferation, regulation of gene expression and regulation of the activity of specific enzymes in cells. In this article, the effects of retinoids on gene expression are reviewed. Among these effects suppression of myc expression and induction of EGF-receptor mRNA expression are considered to be closely related to regulation of cell proliferation. The effects of retinoids on cell growth are discussed on the basis of these two actions: myc mRNA suppression and EGFR mRNA induction. The mode of retinoidal action seems to be similar to that of steroids, as many investigators suggest. The molecular mechanism of retinoidal action is considered to be the formation of a retinoid-receptor complex and its interaction with regulatory elements of DNA. The possibility of application of the methodology used in the investigation of steroidal action to the study of retinoidal action is also discussed.     

The Radiology of Cyanotic Congenital Heart Disease

A consideration of the radiological contribution to the diagnosis and management of the three common forms of cyanotic congenital heart disease is presented. The infant with tetralogy of Fallot or pulmonary atresia with ventricular septal defect is usually studied before palliative surgery is undertaken. The site of obstruction to pulmonary blood flow and the presence of suitable pulmonary arteries to receive an anastomosis must be established. In the older patient presenting for repair detailed assessment of the intracardiac anatomy as well as the sites of obstruction and routes of filling of the pulmonary arteries is desiiable. Some variations of the anatomy of ventricular septal defect in tetralogy of Fallot are described. Following a brief consideration of the relationship of straightforward transposition of the great vessels to the normal state and to the partial transposition complexes, the radiological assessment of the neonatal infant with transposition is presented. The diagnosis of transposition, the state of the interventricular septum, and the state of the ductus arteriosus must be established and sometimes pulmonary stenosis excluded to assist in the selection of the most suitable palliation. Before correction, a complete anatomical assessment of intracardiac anatomy, including detail of the outflow tracts, is necessary.     

Biosynthesis of soluble proteins and pepsinogen of the mucus membrane and cancer of the stomach in man]

Thyrosine-I-C14 and serine-3-C14 show a higher level of incorporation into total soluble proteins of human gastric blastoma hemogenates than those of the mucous membrane. Moreover, a low radioactivity of pepsinogen was detected in the tumors. Also, there was a different rate of incorporation of these aminoacids both into separate fractions of soluble protein and pepsinogen of the mucous membrane and cancer of the stomach. These differences seem to be conditioned by alterations of the process of regulation of protein biosynthesis in the tumors. Simultaneously, there is a direct dependence of the proteolytic activity of pepsin isoforms on the rate of incorporation of the mucous membrane and cancer of human stomach.     

Parametric analysis of the survival of cancer patients based on the results of radiation therapy of cervical cancer patients

An approach based on the parametric distribution of the life span of tumor-bearing individuals was suggested for the analysis of cancer patients survival. Two groups of patients with cancer of the cervix uteri were identified on the basis of the pre-treatment data (before radiation therapy) on rates of tumor growth. Kinetic curves for tumor growth were constructed using the said distribution procedure as well as the data on survival in each study group. Mean values of the coefficient of critical increase of tumor cells were obtained. The interpretation of clinical data in terms of kinetic characteristics of tumor process provides a better understanding of the causes underlying differences in survival of various groups of cancer patients.     

Molecular mechanisms of initiation and promotion of multistage chemical carcinogenesis

Multistage carcinogenesis is the process of development of neoplastic changes, including the successive stages of initiation and promotion which occur in a strict order. This process is subject to the application of a similarly strict sequence of exo-and/or endogenous carcinogenic factors, either of which alone is incapable of tumor induction. Initiation includes the phases of metabolic activation, interaction of reactive metabolites with DNA and fixation of induced lesion. It is the stage of development of such primary mutation lesions of genotype of target-cells as the irreversible transition of these cells to an "initiated" status (predisposition to transformation). Promotion is the stage of quantitative and quantitative-qualitative changes including secondary epigenomic reversible lesions of the phenotype (gene expression) of initiated cells. This process culminates in irreversible transformation of cells.     

Photodynamic therapy for treatment of solid tumors--potential and technical challenges

Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors.     

Design of automatic radiotherapy of locally spread cancer of the urinary bladder

How to apply information obtained with modern methods of visualization of urinary bladder (UB) primary cancer and regional metastatic zones (ultrasound investigation, computer tomography, NMR-tomography, urography, cystoscopy) in design of radiotherapy is demonstrated as well as contribution of each of these methods to design of individual regimens of computer gamma-therapy. This advanced method of radiotherapy makes use of computer design and programs of multicenter and multiposition static and dynamic techniques of calculation of total dose distributions which comply with topographic anatomy of the tumor and radiobiological programs of radiotherapy of UB cancer.     

C-erbB-2表达对宫颈癌预后的价值及放疗对其表达的影响

目的前瞻性探讨C-erbB-2表达与宫颈癌病理学分级、肿瘤浸润深度及复发等相关性，以及放疗对C-erbB-2表达的影响。方法采用免疫组化法检测77例宫颈癌以及其中21例术前放疗前的病理标本C-erbB-2表达，并长期随访。结果C-erbB-2表达程度与宫颈癌病理学分级、肿瘤浸润深度及复发等差异有统计学意义（P〈0．05）。术前放疗可以降低C—erbB-2在宫颈癌组织中的表达（P〈0．01）。C—erbB-2在宫颈癌组织中表达显著高于在正常宫颈组织中表达（P〈0．05）。结论C-erbB-2表达与宫颈癌病理学分级呈负相关，与宫颈癌浸润深度、复发呈正相关。C—erbB-2表达可作为宫颈癌患者预后的重要生物学标志。术前放疗可以降低C—erbB-2在宫颈癌组织中的表达。     

Endocrine function in small cell undifferentiated carcinoma of the lung

The endocrine status of 106 patients with undifferentiated small cell carcinoma of the lung was evaluated before treatment was begun. Almost one half of the patients had evidence of abnormal control of the secretion of adrenal cortical steroids, manifested by loss of diurnal rhythmicity or dexamethasone suppressibility. Only two had the clinical syndrome of ectopic ACTH secretion. Evidence of inappropriate secretion of vasopressin was found in 38% of the patients, most of whom also had abnormalities of corticosteroid secretory pattern. About one half of the patients had evidence of abnormal glucose tolerance, and many also had a paradoxical rise of plasma growth hormone concentration after glucose administration. The levels of the other hormones studies were normal. The pattern of hormone abnormality observed in these patients appears to be relatively specific for small cell undifferentiated carcinoma, and is different from that observed in other pulmonary tumors. Patients with abnormal control of plasma cortisol had a worse prognosis than those with normal adrenal function, largely because of decreased response rates to chemotherapy. Other endocrine abnormalities were of no prognostic significance.     

胰头癌和壶腹癌的淋巴结转移及病理特点分析

目的:探讨胰头癌和壶腹癌的淋巴结转移及病理特点.方法:回顾性分析201例胰头癌和壶腹癌根治手术后的淋巴结转移及病理特点,χ2检验分析淋巴结转移与病理因素的相关性.结果:201例胰头癌和壶腹癌行胰十二指肠切除术,淋巴结转移率分别为32.65%(16/49),30.92%(47/152),其转移淋巴结累及部位基本相同,其中88.89%(32/36)单个淋巴结转移位于胰十二指肠周围.x2检验显示壶腹癌淋巴结转移相关的病理因素有:肿瘤直径(P=0.002),肿瘤分化程度(P=0.012),十二指肠壁浸润(P=0.008),T分期(P=0.000),胰腺受侵(P=0.005),胰头癌与上述病理因素无关,但神经浸润比例高.结论:胰头癌的淋巴结转移及病理特点与壶腹癌有所不同,手术方式的应有所区别,胰头癌应行扩大根治性手术切除.     

No major tumorigenic role for beta-catenin in serrated as opposed to conventional colorectal adenomas

Intracellular redistribution of beta-catenin through mutation of the adenomatous polyposis coli (APC) gene has been proposed as an early tumorigenic event in most colorectal tumours. In serrated adenoma (SA), a newly recognised subtype of colorectal adenoma, APC mutations are uncommon, and the contribution of beta-catenin to tumorigenesis remains unclear. We compared intracellular localisation of beta-catenin and presence of mutations in exon 3 of beta-catenin between 45 SAs, with 71 conventional adenomas (CADs), and eight carcinomas invading the submucosa (SCAs). Widespread or focal nuclear beta-catenin expression was demonstrated in 7% of SAs (three out of 45), 61% of CADs (43 out of 71), and 88% of SCAs (seven out of eight). Cytoplasmic immunostaining for beta-catenin was demonstrated in 16% of SAs (seven out of 45), 77% of CADs (55 out of 71), and 88% of SCAs (seven out of eight). No mutation in exon 3 of beta-catenin was found in SAs or SCAs, while 7% of CADs (five out of 71) had beta-catenin mutations. No nuclear or cytoplasmic expression of beta-catenin was observed in the hyperplastic or conventionally adenomatous epithelium of mixed-type SAs. These findings suggest that beta-catenin mutation is unlikely to contribute to the tumorigenesis in SA, and that intracellular localisation of beta-catenin may not be associated with an early event of the tumour progression in most SAs.     

The influence of the anaesthetic on survival rates of breast cancer patients after surgery

The end results of therapy of 1,358 breast cancer patients were studied. Anaesthesia was performed by ether-nitrogen-oxygen (554 cases) or halothane-nitrogen-oxygen (804 cases) mixture with addition of oxygen. The method of Holstead was employed in all cases. A comparison of groups of patients on the basis of such parameters as the anaesthetic used, age and degree of tumour progression (according to the TNM classification and results of postoperative histological assays) showed them to be identical. The study showed that the type of anaesthesia influenced the end results of therapy of cancer patients: the survival rates of patients receiving halothane anaesthesia were much higher than those of the ether-anaesthetized patients. The differences were most pronounced among patients who received pre-operative radiation therapy and post-operative chemotherapy as well as in cases of metastasis spread into regional lymph nodes. The mechanism of the effect of the anaesthetic on the survival rates of cancer patients may be explained on the basis of the data available on the varying influences of anaesthetics on the pituitary-adrenal cortex system and carcinemia development during operation as well as the role of immunity in tumour cell implantation and growth of metastases.     

Causes of death of blue-collar workers at a Dublin brewery, 1954--73.

The suggested association between high consumption of beer and an increased risk of death from cancer of the colon and rectum was investigated among blue-collar workers at a Dublin brewery, who consume more than average amounts of beer, usually in the form of stout. A study of their mortality between 1954 and 1973 showed that they had as good an expectation of life as all Dublin males, with no increased risk of death from cancer of the oesophagus, pharynx, liver or of cirrhosis of the liver, accidents or suicide, conditions normally associated with the high consumption of alcohol. They had significantly increased risk of death from cancer of the rectum and also from diabetes mellitus. Twenty per cent of the workers, differentiated by their place of work within the brewery, had a much higher risk of death from cancer of the rectum.