[Effectiveness of the Kokonovo test in predicting cancerous diseases].
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Gastric carcinogenesis is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. We analysed the patterns of chromosomal instability in 35 gastric carcinomas and their clinical correlations. With microarray competitive genomic hybridization, genomewide chromosomal copy number changes can be studied with high resolution and sensitivity. A genomewide scanning array with 2275 BAC and P1 clones spotted in triplicate was used. This array provided an average resolution of 1.4 Mb across the genome. Patterns of chromosomal aberrations were analysed by hierarchical cluster analysis of the normalized log(2) tumour to normal fluorescence ratios of all clones, and cluster membership was correlated to clinicopathological data including survival. Hierarchical cluster analysis revealed three groups with different genomic profiles that correlated significantly with lymph node status (P=0.02). Moreover, gastric cancer cases from cluster 3 showed a significantly better prognosis than those from clusters 1 and 2 (P=0.02). Genomic profiling of gastric adenocarcinomas based on microarray analysis of chromosomal copy number changes predicted lymph node status and survival. The possibility to discriminate between patients with a high risk of lymph node metastasis could clinically be helpful for selecting patients for extended lymph node resection.
In a prospective investigation biopsy specimens were obtained of 150 women with primary, untreated endometrial carcinoma for determinination of the content of estrogen and progesterone receptors (E2 and PR). After a varying interval 13 who developed metastases despite routine surgical and radiation therapy received treatment with gestagens. The clinical effect of the hormone was studied for any correlation with the initial content of E2 and PR. Eight of the women (61--71 years) proved E2R positive (greater than 10 fmoles/mg cytosolprotein), 2 had no PR and the remaining 6 had PR in a concentration of 7--892 fmoles/mg cytosolprotein). 7 responded clinically to gestagen therapy (tumors poorly differentiated in 3 and moderately in 4). Five of the women (50--84 years) were E2R negative; they had no PR, they did not respond to gestagen therapy and died after 2--8 months (tumors poorly differentiated in 2 and moderatley in 3). Determination of E2R and PR in endometrial carcinoma appears to be a clinically useful test for predicting whether a patient is likely to respond to treatment with gestagens.
We investigated coexisting autoantibodies in sera of 553 patients with a neurological presentation and one or more paraneoplastic neuronal nuclear or cytoplasmic autoantibodies: antineuronal nuclear autoantibody type 1 (ANNA-1), ANNA-2, ANNA-3; Purkinje cell cytoplasmic autoantibody type 1 (PCA-1), PCA-2; and CRMP-5-immunoglobulin G or amphiphysin-immunoglobulin G. Except for PCA-1, which occurred alone, 31% of sera had more than one of these autoantibodies. In addition, 25% of sera had neuronal calcium channel (P/Q-type or N-type), potassium channel, ganglionic acetylcholine receptor, muscle acetylcholine receptor, or striational antibodies. The autoantibody profiles observed in patients with paraneoplastic disorders imply the targeting of multiple onconeural antigens and predict the patient's neoplasm, but not a specific neurological syndrome.
The aim of this study was to correlate quantitative dynamic contrast-enhanced MRI (DCE MRI) parameters with microvessel density (MVD) in prostate carcinoma. Twenty-eight patients with biopsy-proven prostate carcinoma were examined by endorectal MRI including multiplanar T2- and T1-weighted spin-echo and dynamic T1-weighted turbo-FLASH MRI during and after intravenous Gd-DTPA administration. Microvessels were stained on surgical specimens using a CD31 monoclonal antibody. The MVD was quantified in hot spots by counting (MVC) and determining the area fraction by morphometry (MVAF). The DCE MRI data were analyzed using an open pharmacokinetic two-compartment model. In corresponding anatomic locations the time shift (Deltat) between the beginning of signal enhancement of cancer and adjacent normal prostatic tissue, the degree of contrast enhancement and the contrast exchange rate constant (k21) were calculated. The MVC and MVAF were elevated in carcinoma (p<0.001 and p=0.002, respectively) and correlated to k21 (r=0.62, p<0.001 and r=0.80, p<0.001, respectively). k21-values of carcinoma were significantly higher compared with normal peripheral but not central zone tissue. Deltat was longer in high compared with low-grade tumors (p=0.025). The DCE MRI can provide important information about individual MVD in prostate cancer, which may be helpful for guiding biopsy and assessing individual prognosis.
Use of laboratory animals to identify carcinogenic potential of chemicals, mixtures, and other agents has a modern history of greater than 40 years from which much useful scientific and public health information can be derived. While laboratory animals differ from humans in some respects that may affect responses to hazardous exposures, use of such models is based on experimental evidence indicating that there are more genetic, genomic, physiological, biochemical, and metabolic similarities than differences among mammalian species. Issues of concordance of responses between rodent species and between rodents and humans as well as repeatability and site-specificity are important considerations in evaluating laboratory animal carcinogenicity results. Variables in experimental design such as animal strain, diet, route of exposure, and study, duration as well as single-site versus multisite carcinogenic responses all influence interpretation and intelligent use of study data. Similarities and differences in site-specific laboratory animal and corresponding human cancers should also be considered in study evaluation. Recent attempts to explore genetically engineered mice and to humanize the mouse for more relevant identification of carcinogen hazard identification have yielded mixed results. In the end we are confronted by the realization that virtually all animal cancer models are useful but imperfect surrogates for humans. Assuming the percentage of chemicals currently in commerce that are estimated to be potent animal or human carcinogens is quite low, the task of identifying agents with significant carcinogenic potential is daunting and important. The biological conundrum of scientific debate regarding the relevance of carcinogenicity studies in laboratory animals is likely to continue. Nonetheless public health considerations must take precedence when deciding human safety issues.
Mortality from colon cancer could be reduced with routine screening, yet screening rates are low. Current screening tools are limited by expense and suboptimal acceptance. A retrospective case-control study of all cases of colon cancer diagnosed at our institution over a 5-year period was performed to determine the frequency of blood count abnormalities in these patients upon presentation. One hundred twenty-seven patients had right-sided colon cancer: 107 (84%) had an elevated red cell distribution width (RDW); 87 (69%) had anemia; and 70 (55%) had a low mean corpuscular volume (MCV). Ninety-eight patients had left-sided colon cancer: 49 (50%) had an elevated red cell distribution width; 43 (44%) had anemia; and 22 (22%) had a low mean corpuscular volume. The red cell distribution width was 84% sensitive and 88% specific for right-sided colon cancer. An elevated red cell distribution width may help better identify those patients who should be referred for full colonoscopy.
Several anticancer drugs have been associated with cardiac toxicity, especially the anthracyclines and trastuzumab. The pathogenesis of anthracycline-associated toxicity has been well described, whereas the mechanism of trastuzumab-associated toxicity is unknown. Although routine cardiac imaging studies (e.g. echocardiogram or multiple gated acquisition scans) may identify subclinical evidence of myocardial dysfunction, available data do not support their routine use for monitoring asymptomatic patients undergoing cancer therapy. Other modalities such as nuclear medicine scintigraphy with indium-111-antimyosin antibody and endomyocardial biopsy have been shown to be useful in identifying early cardiac damage, but their routine use is limited by practical considerations such as feasibility and cost. Consequently, there is significant interest in developing simple and reproducible methods for identifying patients at risk for treatment-induced myocardial damage. Available data suggest that circulating markers such as troponins and natriuretic peptides could potentially be useful for this purpose. Measurement of plasma troponin levels are commonly used in clinical practice in order to provide diagnostic and prognostic information in patients with myocardial ischaemia. Elevated levels may likewise correlate with anthracycline-induced cardiac damage, although plasma levels are only minimally elevated (well below that associated with ischaemia), and elevations may persist for weeks or months after anthracycline exposure. Clinical trials are currently evaluating the role of these markers in predicting both early and late, clinical and subclinical damage associated with anthracyclines and trastuzumab.
In a study of 30 months duration, involving 600 male and 600 female Wistar rats fed on 12 different diets/dietary regimes, none of which involved deliberate exposure to any known genotoxic carcinogen, highly significant between-group differences were observed in survival and incidence of various neoplastic and non-neoplastic diseases. A full report of the findings is being prepared. Here we report that, irrespective of diet or dietary regime, there were highly significant correlations of body weight at 29 weeks of age with premature death (P less than 0.0001 in both males and females), with development of benign or malignant neoplasm of any site (P less than 0.0001 in males and P less than 0.01 in females) and with development of malignant neoplasm at any site (P less than 0.0001 for sexes combined). Numerous kinds of neoplasm contributed to these overall correlations. The most significant were pituitary tumour (P less than 0.0001), mammary gland tumour (P less than 0.0001), squamous or anaplastic carcinoma of the jaw (P less than 0.001), and subcutaneous mesodermal tumours (P less than 0.05). The 20% of rats that were heaviest at 29 weeks were more than twice as likely to die prematurely than the lightest 20% (2.56 times--males, and 2.11 times--females), and almost twice as likely to develop a malignant tumour (1.87 times for the sexes combined). These findings have important implications for the design and interpretation of carcinogenicity tests in rodents and of laboratory and human studies of relationships between diet, ageing-related degenerative diseases, and cancer.
Twenty-two patients who previously responded to first-line hormonal therapy were evaluated for factors which would predict for response to second hormonal manipulation. Investigations performed at progression after initial hormone response included immunocytochemical estimation of estrogen and progesterone receptors as well as flow cytometric analysis of tumor ploidy. Approximately 50% of patients were found still to be estrogen receptor positive at relapse from first-line hormone treatment. Progesterone receptor had, however, usually become negative. Nine of the 22 patients responded to second-line hormonal therapy. Second hormone responses occurred with equal frequency among hormone receptor-positive and hormone receptor-negative patients. Tumor ploidy, as determined by flow cytometric study did, however, predict for response. Eight of 12 patients with diploid tumors responded to second-line hormone therapy whereas only one of ten with aneuploid tumors responded. Flow cytometric analysis appears to be a promising technique for prediction of second hormone response after relapse from first-line hormone manipulation.
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We addressed the problem of discriminating between 24 diseased and 17 healthy specimens on the basis of protein mass spectra. To prepare the data, we performed mass to charge ratio (m/z) normalization, baseline elimination, and conversion of absolute peak height measures to height ratios. After preprocessing, the major difficulty encountered was the extremely large number of variables (1676 m/z values) versus the number of examples (41). Dimensionality reduction was treated as an integral part of the classification process; variable selection was coupled with model construction in a single ten-fold cross-validation loop. We explored different experimental setups involving two peak height representations, two variable selection methods, and six induction algorithms, all on both the original 1676-mass data set and on a prescreened 124-mass data set. Highest predictive accuracies (1-2 off-sample misclassifications) were achieved by a multilayer perceptron and Naïve Bayes, with the latter displaying more consistent performance (hence greater reliability) over varying experimental conditions. We attempted to identify the most discriminant peaks (proteins) on the basis of scores assigned by the two variable selection methods and by neural network based sensitivity analysis. These three scoring schemes consistently ranked four peaks as the most relevant discriminators: 11683, 1403, 17350 and 66107.
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Despite our expanding knowledge of prostatic histopathology, several controversies regarding the prediction of a tumor's biologic behavior still exist. Numerous histologic grading schemes specific for prostate carcinomas have been developed, but pathologists and urologists do not agree on which system is most accurate. Unfortunately, the Broders system, which is frequently used, tends to underestimate tumor grade and malignant potential. Recently, computer-assisted nuclear morphometry has added objectivity to the formerly subjective grading process, and improved prognostic accuracy for early and advanced disease. The relationship between tumor volume and grade remains controversial. Although it has been stated that volume and grade are directly related, our examination of radical prostatectomy specimens casts some doubt on this. While it can be shown that tumor volume is proportional to the surface area of capsular penetration by malignant cells, tumor penetration is more closely related to histologic grade.
OBJECTIVE: The rate of normalization of human chorionic gonadotropin or CA 125 in other gynecologic malignancies is highly predictive of response to therapy and recurrence. Serum squamous cell carcinoma antigen (SCC antigen) levels were studied in patients with invasive cervical carcinoma to determine if the rate of normalization was associated with outcome. STUDY DESIGN: One hundred eighty-four patients were studied. A logistic regression of elevated SCC antigen levels was performed. RESULTS: In primary squamous cell carcinoma the SCC antigen level was elevated in stages I, II, III, and IV disease and all stages combined in 24%, 57%, 67%, 71%, and 43% of cases, respectively. Only 27% of patients with nonsquamous carcinoma of the cervix had elevated SCC antigen levels. SCC antigen levels were elevated in 50% of patients with recurrent disease. In both primary and recurrent disease elevated SCC antigen levels decreased with effective therapy. Normalization of elevated SCC levels was associated with a complete response; however, logistic regression of SCC antigen values was not. CONCLUSION: When initially elevated, SCC antigen assays aided in determination of response and detection of recurrences.