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.     

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.     

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.     

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.     

STUDY OF DELETION OF P16 GENE IN THE PROGRESSION OF BRAIN ASTROCYTOMAS

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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.     

Translational and functional oncogenomics. From cancer-oriented genomic screenings to new diagnostic tools and improved cancer treatment

We present here an experimental pipeline for the systematic identification and functional characterization of genes with high potential diagnostic and therapeutic value in human cancer. Complementary competences and resources have been brought together in the TRANSFOG Consortium to reach the following integrated research objectives: 1) execution of cancer-oriented genomic screenings on tumor tissues and experimental models and merging of the results to generate a prioritized panel of candidate genes involved in cancer progression and metastasis; 2) setup of systems for high-throughput delivery of full-length cDNAs, for gain-of-function analysis of the prioritized candidate genes; 3) collection of vectors and oligonucleotides for systematic, RNA interference-mediated down-regulation of the candidate genes; 4) adaptation of existing cell-based and model organism assays to a systematic analysis of gain and loss of function of the candidate genes, for identification and preliminary validation of novel potential therapeutic targets; 5) proteomic analysis of signal transduction and protein-protein interaction for better dissection of aberrant cancer signaling pathways; 6) validation of the diagnostic potential of the identified cancer genes towards the clinical use of diagnostic molecular signatures; 7) generation of a shared informatics platform for data handling and gene functional annotation. The results of the first three years of activity of the TRANSFOG Consortium are also briefly presented and discussed.     

Is there still a role for the uniscale assessment of quality of life?

AIMS AND BACKGROUND: To obtain proof of external validity of the visual analogue scale and re-evaluate the use of this instrument in assessing cancer patients' quality of life. METHODS: Consecutive patients attending 79 Italian medical oncology and radiotherapy centers over a period of 1 week were asked to fill out both a questionnaire concerning the presence of 19 problems and a 100-mm linear visual analogue scale evaluating their quality of life. Quality of life was rated as "good" and "bad" when given a score of 70-100 and 0-30, respectively. Multifactorial logistic models were used where good and bad quality of life were correlated with explanatory variables including patient and disease characteristics and the presence or absence of the 19 problems. RESULTS: Gender, level of education, treatment setting, Karnofsky performance status, disease extent, and the presence of 12 out of 19 problems were found to be correlated with good quality of life. A similar pattern of correlations was found with bad quality of life. CONCLUSIONS: Due to the difficulties in attaining reliable assessment of quality of life using psychometric questionnaires, the further proof of validity obtained in this study allows us to propose the re-evaluation of the role of the uniscale in measuring the quality of life of cancer patients.     

Correlation between serum prolactin levels and hepatocellular tumorigenesis induced by 3'-methyl-4-dimethylaminoazobenzene in mice.

Ovariectomy at 1 month of age promotes development of hepatocellular adenomatous nodules in female C57BL/6 x DS-F1 mice treated neonatally with 3''-methyl-4-dimethylaminoazobenzene (3''-Me-DAB). Implantation of oestradiol-17 beta (E2) pellets at 1 month of age suppresses nodule development. Since E2 increases serum levels of prolactin, high serum levels of prolactin in mice that have received implants of E2 pellets may play a role in the suppression of hepatocellular tumorigenesis. Therefore, to investigate the role of prolactin in hepatocellular tumorigenesis, we examined development of adenomatous nodules in female mice that had been treated neonatally with 3''-Me-DAB and had undergone ovariectomy at 1 month of age, under various serum levels of prolactin. Treatment of these mice with perphenazine (dopamine antagonist) from 6 months of age or transplantation of pituitary glands under the renal capsule at 6 months of age markedly increased serum levels of prolactin and significantly suppressed the incidence of adenomatous nodules at 12 months of age. Implantation of E2 pellets at 1 month of age increased serum levels of prolactin to a greater extent and further decreased the incidence of adenomatous nodules. Treatment of mice that had received implants of E2 pellets at 1 month of age with bromocriptine (dopamine agonist) from 6 months of age decreased serum levels of prolactin, and was accompanied by an increase in the incidence of nodules. The present results showed that an increase in serum levels of prolactin was accompanied by a decrease in incidence of liver tumours induced by 3''-Me-DAB in mice, suggesting a suppressive effect of prolactin on liver tumorigenesis in mice. Thus, it is possible that the suppressive effect of oestrogen on liver tumorigenesis in mice is mediated, at least in part, by prolactin.     

Carcinoma of the biliary tract

Six problems were pointed out in General Rules for Surgical Studies on Cancer of Biliary Tract; division of extrahepatic bile duct and papilla of Vater, definition of carcinoma of the bile duct, gallbladder and papilla of Vater, classification of the lymphnodes, macroscopic classification of cancer of the biliary tract, tumor size and staging, pathological rules. Furthermore, in 15 cases of the gallbladder carcinoma and 21 cases of the bile duct carcinoma, the correlation between the prognosis and the histological findings of cancer invasion to the wall or of lymphnode metastasis was evaluated.     

Factor supprossing alpha1 fetoprotein production.

The injection of sera of adult mice or of a 20% extract of small and large intestine, liver, kidney, spleen, thymus, and lungs of adult mice suppressed the alpha1 fetoprotein production in syngeneic newborn recipients. Extracts of the striated muscles of adult mice had a meager inhibitory effect. Extracts of mouse embryonic intestine and those of the while embryo without the gastrointestinal tract had almost negligible amounts of suppressing factor. The possible role of humoral factors regulating the synthesis of embryonic antigens for the control of tumor growth was discussed author...     

Chemosensitivity testing using stem cell assay in urological and other malignancies

We have attempted to grow several kinds of malignant tumors using human tumor stem cell assay. Formation of colonies in vitro was seen in 65 of 132 primary tumors (49%), including 25 of 41 (61%) uroepithelial cancers, 12 of 19 (63%) renal cancers, five of 12 (42%) testicular cancers, five of 21 (24%) gastrointestinal malignancies, five of 12 (42%) lung cancers, five of 11 (45%) hematopoietic malignancies and five of 16 (31%) other malignancies. Growth sufficient for in vitro chemosensitivity tests of CDDP developed from seven cases of uroepithelial cancer, three of them (43%) were sensitive to 2.5 micrograms X hour/ml of CDDP. The specimens from a metastatic testicular tumors that received several courses of PVB chemotherapy resulted in the resistance of the in vitro chemosensitivity test at a higher dosage of CDDP. Nine cases of renal cancer had sufficient growth for an in vitro chemosesitivity test of interferon. One of them was sensitive for alpha 2 type interferon. Three of seven cases were sensitive for alpha type of interferon. To predict clinical correlation, 19 patients were tested with the same drugs used in the in vitro chemosensitivity test. The predictability resulted in more than 60% of true positive, 91% of true negative and 86% of overall predictability.     

盆腔浆液性腺癌输卵管伞端的病理特征

目的 研究盆腔浆液性腺癌合并的输卵管伞端病变病理特点,探讨其在浆液性腺癌发生中的意义.方法 观察43例盆腔浆液性腺癌(31例卵巢癌,12例腹膜癌)的输卵管伞端病理形态,对其中40例(69条输卵管)进行p53免疫组化染色.结果 43例盆腔浆液性腺癌中,31例(44条输卵管)合并伞端癌,14条癌灶≤5 mm,癌累及黏膜达68.3%;20例(28条输卵管)有伞端黏膜上皮内癌.44条伴有伞端癌的输卵管中,23条大体表现为伞端粘连与伞不清.伞端早期病变镜下表现为局部分泌细胞增多,上皮细胞具有一致性,黏膜皱襞走行变直,71.4%伞端上皮内癌黏膜皱襞间散落有明显异型的肿瘤性上皮蕾或单个腺体.伞端癌的p53阳性表达率为86.4%,上皮内癌为60.7%.结论 输卵管伞端癌是盆腔浆液性腺癌的重要组成部分,伞端上皮内癌在盆腔浆液性腺癌中十分常见,伞端是盆腔浆液性腺癌的重要起源地.

Abstract：

Objective To study the serous lesions of the fimbria of the fallopian tube in patients with pelvic serous adenocarcinoma and investigate its significance in the serous carcinogenesis.Methods To observe the morphological features of the fimbria of the fallopian tube in 43 cases of pelvic serous adenocarcinoma (31 cases of ovarian carcinoma and 12 cases of peritoneal carcinoma).Immunohistochemical examination of p53 expression was performed on samples of 69 fallopian robes of 40 cases.Results Fimbria carcinoma was identified in 44 tubes in 31 of 43 cases.Fourteen of the carcinoma foci were ≤5 mm.In 68.3% of the fimbria carcinomas demonstrated involvement of the mucosa.Twenty eight tubes of 20 cases exhibited intraepithelial carcinoma.Twenty three of 44 tubes of the fibria carcinomas showed fimbria adherence and unclear appearance.The early histological changes of the fimbria epithelium included proliferation of local secretory cells, homogeneity, and straightening of the mucous folds.Clusters of tumor epithelial cells or single gland with atypical features floated between mucosal folds were found in 71.4% of the fimbria with intraepithelial carcinoma.The positive expression rate of p53 in the fimbria carcinomas and the fimbria intraepithelial carcinomas were 86.4% and 60.7%, respectively.Conclusions Fimbria carcinomas is an important component in pelvic serous adenocarcinomas.The fimbria intraepithelial carcinoma is also very common among the cases of pelvic serous adenocarcinoma.The fimbria may be an important primary site of pelvic serous adenocarcinomas.