[Molecular diagnosis of neoplasms].
Based on general biological features of cancer cells, different aspects of cancer diagnostics are discussed.
Biomarkers, Tumor↗
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Cancer gene discovery using digital differential display.
The Cancer Gene Anatomy Project database of the National Cancer Institute has thousands of expressed sequences, both known and novel, in the form of expressed sequence tags (ESTs). These ESTs, derived from diverse normal and tumor cDNA libraries, offer an attractive starting point for cancer gene discovery. Using a data-mining tool called Digital Differential Display (DDD) from the Cancer Gene Anatomy Project database, ESTs from six different solid tumor types (breast, colon, lung, ovary, pancreas, and prostate) were analyzed for differential expression. An electronic expression profile and chromosomal map position of these hits were generated from the Unigene database. The hits were categorized into major classes of genes including ribosomal proteins, enzymes, cell surface molecules, secretory proteins, adhesion molecules, and immunoglobulins and were found to be differentially expressed in these tumorderived libraries. Genes known to be up-regulated in prostate, breast, and pancreatic carcinomas were discovered by DDD, demonstrating the utility of this technique. Two hundred known genes and 500 novel sequences were discovered to be differentially expressed in these select tumor-derived libraries. Test genes were validated for expression specificity by reverse transcription-PCR, providing a proof of concept for gene discovery by DDD. A comprehensive database of hits can be accessed at http:// www.fau.edu/cmbb/publications/cancergenes. htm. This solid tumor DDD database should facilitate target identification for cancer diagnostics and therapeutics.
Biological Specimen Banks↗
A practical approach to fibromyalgia.
The term fibromyalgia refers to a collection of symptoms with no clear physiologic cause, but the symptoms together constitute a clearly recognizable and distinct pathologic entity. The diagnosis is made through the examiner's clinical observations. The differential diagnosis must include other somatic syndromes as well as disease entities, including hepatitis, hypothyroidism, diabetes mellitus, electrolyte imbalance, multiple sclerosis, and cancer. Diagnostic criteria serve as guidelines for diagnosis, not as absolute requirements. Treatment of fibromyalgia, which is an ongoing process, remains individualized, relying on a good physician-patient relationship. It is goal-oriented, directed at helping patients get restorative sleep, alleviating the somatic pains, keeping patients productive, and regulating schedules. It can be achieved through a goal-oriented agreement between patient and provider. Because fibromyalgia is chronic and may affect all areas of an individual's functioning, the physician needs to also evaluate the social support systems of patients with fibromyalgia. The approach to treatment should integrate patient education as well as non-pharmacologic and pharmacologic modalities. To keep patients well educated and involved in their healthcare, physicians should provide patients with adequate sources for reliable information.
Analgesics↗
[Oncologic diseases incidence in flying and ground maintenance personnel].
Incidence of oncologic disease and oncologic death rate among the flying and ground maintenance personnel in the period from 1996 to 2000 were reviewed. Death rate was found to be below the expectation in both categories. The standard risk for the flying and maintenance personnel made up 0.68 and 0.61, respectively. The flying personnel had a higher risk of cancer of the rectum, large intestine, and prostate. The authors propose to validate USI or analysis for the specific prostate antigen as screening methods of early prostate cancer diagnostics as part of the flyer's medical certification.
Adult↗
A practical approach to fibromyalgia.
Fibromyalgia is the name given to a collection of symptoms with no clear physiologic cause, The constellation of symptoms are clearly recognizable as a distinct pathologic entity. The diagnosis is made through clinical observations made by the examiner. Differential diagnosis must include other somatic syndromes as well as disease entities like hepatitis, hypothyroidism, diabetes mellitus, electrolyte imbalance, multiple sclerosis, and cancer. Diagnostic criteria are given as guidelines for the diagnosis, not as absolute requirements. Treatment of this condition remains individualized and relies heavily on having a therapeutic relationship with a provider. Treatment of this syndrome needs to be looked at as an ongoing process. Goal oriented treatment aimed at maintaining specific functions can be directed at helping a patient get restorative sleep, alleviating the somatic pains that ail the patient, keeping a person productive, regulating schedules or through goal oriented agreements made with the patient. Since this syndrome is chronic and may effect all areas of a persons functioning the family and social support system of the person being treated need to be evaluated. Patients often seek alternative medical treatments for this problem including diet therapy, acupuncture, and herbal therapy. Treatment must involve more than just the symptoms presented and the patient can only be treated successfully if they are willing to work at changing their own perceptions, and ways of relating to stressors in their world.
Adaptation, Psychological↗
Androgen receptor in prostate carcinoma: immunohistochemical and ligand saturation analyses.
Status of androgen receptor (AR) in prostate carcinoma is biologically important. Therefore, more methods assessing AR abnormalities are warranted. Immunohistochemical (IHC) and ligand saturation (LSA) assays were not compared in details. AR in 53 cases were tested by monoclonal antibody (Ab) F39.4.1 (Biogenex), polyclonal Ab N-20 (Santa Cruz) and by ligand saturation analysis with (3)H-methyltrienolon. Statistical analyses were performed with Spearman's nonparametric rank test including neoadjuvant therapy subgroups treated by antiandrogens, combined androgen blockade (22 cases; flutamide with gosereline) or without therapy. By using monoclonal Ab we found AR positive tumor nuclei in 46 cases. Mean of positives was 64%, median 75%. The polyclonal Ab was not sufficiently specific. With LSA AR were found in 43 cases. Mean level was 6.6 fmol/mg, median 5.5 fmol/mg. Comparing IHC with LSA, we noted correlation trend only for the monoclonal Ab (r=0.35; p=0.02). With thresholds 70% positive nuclei for IHC and 6 fmol/mg for LSA, there were 66% and 43% cases positive with IHC and LSA, respectively. The LSA and IHC positives did not show significant agreement, concordance level being 58% only. We found significant IHC-LSA correlation (r=0.68; p=0.004) solely in combined androgen blockade subgroup with 82% level concordance. Our study has demonstrated that AR IHC and LSA are independent complementary methods. Significant correlation between LSA and IHC show only cases treated with combined androgen blockade. An explanation hypothesis is discussed concerning LH-RH influence on free AR capable of ligand binding. IHC as well as LSA have specific biologic significance and may be useful for prostate cancer diagnostic and therapy.
Adenocarcinoma↗
[The modern role of stomach cancer radiodiagnostics].
The authors' main purpose was to assess the role of stomach cancer radiodiagnostics, considering the changes in the morphology of the disease within the last decades of the 20th century. The results of radiodiagnostic and morphological study of 1258 cases of verified stomach cancer were compared. This methodical approach allowed correction of radiodiagnostic methods and stomach cancer semiotics, directed towards detection of endophytic tumors. The radiologic examination included conventional radiologic imaging, ultrasonography, computed tomography, and magnetic resonance imaging of the stomach. The morphologic examination included a method of studying endophytic stomach cancer, specially designed for this research. According to the authors of the article, the prevalence of diffuse and mixed stomach cancer has increased substantially within the last 34 years; the incidence of the stomach upper part involvement has increased 2.4 times. The modem radiodiagnostics and semiotics of stomach cancer are based on the principles of endophytic tumor detection. The authors conclude that modern radiodiagnostics and endoscopy are two main methods of stomach cancer diagnostics.
Adult↗
[Limit investigation in cancer of unknown primary site].
Cancer of unknown primary (CUP) is relatively common, approximately 3-5% of all cancers. Diagnostic evaluation must include adequate tumor biopsies for pathology evaluation (PAD) as well as abdominal and chest CT. Prognosis is generally poor, but subgroups occur where long-term survival is possible, and a few patients can even be cured. If patients do not belong to any of these subgroups, diagnostic evaluation and treatment should be considered in relation to possible benefits. CUP diagnosed patients should, if possible, be cared for by experienced hospital units with access to a multi-disciplinary network. New radiological methods, such as PET and whole-body MRI, may in certain cases provide important information for diagnosis.
Aged↗
Biomarker profiling for cancer diagnosis, prognosis and therapeutic management.
The basis of cancer treatment has come a long way since the days of the the classical TNM staging. Identification of novel biomarkers for various cancers and their specific correlations with prognosis have increased our understanding of carcinogenesis and tumour progression on the molecular level. Recent advances in technologies for simultaneous detection of multiple biomarkers have opened up new avenues for multimarker profiling on a more individual scale. We summarize the key molecular determinants and their prognostic role in various cancers, and examine the available techniques for analysing biomarker panels that can have a major impact on cancer diagnostics and therapeutics.
Biomarkers, Tumor↗
[An axillary metastasis as the first sign of the breast carcinoma--a case review].
BACKGROUND: Carcinoma of the breast is the most commonly diagnosed women cancer. Less than 1% of the patients diagnosed with breast cancer initially present with axillary metastases as their only clinical manifestation. CASUISTIC: We report case of 58 years old woman with occult breast carcinoma in which extensive axillary node metastasis was the first manifestation. DISCUSSION: Breast cancer presenting with axillary metastases and no clinical apparent primary tumour in the breast is an uncommon form of stage II or IV of this disease. Ultrasonography, mammography, MRI and excisional biopsy are indicated for detecting occult primary tumours. The appropriate treatment of the breast after an axillary presentation of occult breast carcinoma continues to be a controversial issue. Complete axillary lymph node dissection is indicated in all patients. As a local treatment of the breast is indicated irradiation of the breast or total mastectomy or subcutaneus mastectomy with application of the breast prothesis. CONCLUSION: Axillary metastasis is rare first sign of breast cancer. Diagnostics of the occult breast carcinoma is difficult. The treatment of occult breast carcinoma is still controversial.
Axilla↗
The extracellular domain of p185/neu is released from the surface of human breast carcinoma cells, SK-BR-3.
The human breast carcinoma cell line SK-BR-3, expresses the neu oncogene product, p185, which is a receptor tyrosine kinase. Using a double monoclonal antibody capture enzyme-linked immunosorbent assay for p185, activity was detected in conditioned media from cultures of SK-BR-3 cells. Two monoclonal antibodies specific for the extracellular domain of p185/neu immunoprecipitated a protein with a molecular mass of approximately 105 kDa. p105 was further shown to compete with p185 for binding to monoclonal antibodies and pulse-chase experiments indicate that it was generated by post-translational processing. Peptide maps showed that p105 and p185 are related polypeptides. Since p105 is close to the predicted size for the extracellular domain of p185/neu, we propose that SK-BR-3 cells specifically process and release this portion of the receptor into the medium. The release of the extracellular domain may have implications in oncogenesis and its detection could prove useful as a cancer diagnostic.
Adenocarcinoma↗
The role of DNA methylation in cancer development.
Epigenetic modifications include DNA methylation and covalent modification of histones. These alterations are reversible but very stable and exert a significant impact on the regulation of gene expression. Changes in methylation of promoter or first exon may mimic the effect of mutations of various tumor suppressor genes (TSGs) or protooncogenes. Carcinogenesis can also result from aberrations in genomic DNA methylation that include hypermethylation and hypomethylation of promoter or first exon of cancer-related genes. Hypermethylation of promoter of various TSGs causes their transcriptional silencing. However, hypomethylation of regulatory DNA sequences activates transcription of protooncogenes, retrotransposons, as well as genes encoding proteins involved in genomic instability and malignant cell metastasis. The methylation of genomic DNA in malignant cells is catalyzed by DNA methyltransferases DNMT1 and DNMT3B, revealing significantly elevated expression in different types of cancers. The reversibility of hypermethylation can be used as target of therapeutic treatment in cancer. DNMT 1 and DNMT3B inhibitors including 5-Aza-2'-deoxycytidine and antisense oligonucleotides have been applied in clinical trials of such treatment. Identification of aberrations of DNA methylation in cancer cells is a new field of investigation in carcinogenesis. We believe that epigenetic cancer diagnostic and therapy will be achieved in the next decades.
Acetylation↗
In vitro ultrastructural localization of the catalytic activity of adenosine deaminase in murine C-1300 neuroblastoma.
Adenosine deaminase (ADA) activity was localized at the surface membrane of the mouse C-1300 neuroblastoma by incubation of a confluent tissue culture monolayer grown on Lux-Permanox cultureware with 6-chloropurine ribonucleoside (CPR). This substrate is dechlorinated by ADA to form Cl-. At loci of ADA activity, Cl- is precipitated with added silver ion (Ag+), and electron dense metallic silver (Ag degree) is formed upon exposure to light. The incubation was conducted in 0.2 M HEPES buffer (277 mOs) at 37 degrees C, pH 7.4, which contained 1 mM CPR, for 5 min (in this buffer, this is four times the Km); the control lacked the substrate. After completion of the incubation, the monolayer was briefly rinsed with 0.2 M HEPES and 2.5% glutaraldehyde in 0.2 M HEPES containing AgNO3 at a final concentration of 2 mM. Dehydration was accomplished in a graded series of ethanol followed by embedment in the L. R. White resin at 60 degrees C overnight. Thin sections (80 to 100 mm), cut parallel to the monolayer, showed ADA activity at the cells' surface membrane with a smaller amount of activity evenly distributed in the subadjacent ectoplasmic zone. The control lacked any silver grain localization. Since in preliminary studies of neuronal tissue the ADA activity was minimal, these findings may contribute to developing a diagnostic cancer screening test.
Adenosine Deaminase↗
[The clinical x-ray diagnosis of pulmonary hamartomas].
A clinico-roentgenologic study of 67 patients with hamartoma of the lung was carried out. Hamartoma could not be even suggested unless X-ray examination was performed but even this procedure sometimes failed to identify the disease. It was far from being each case that typical roentgenologic features of hamartoma were observed. Transthoracic needle biopsy may be helpful in identifying the nature of a roentgenologically detected tumor. Roentgenologically, hamartoma should be first of all distinguished from peripheral lung cancer. When clinico-roentgenologic and needle biopsy data are inconclusive with respect to lung cancer diagnostic thoracotomy should be performed.
Adult↗
[25 years of the study of alpha-fetoprotein].
alpha-Fetoprotein (AFP) is an embryonic serum protein. Only traces of AFP are present in blood of adult man or animal, but its level substantially increases during liver regeneration and in cases of primary liver carcinoma or embryonic carcinomas. Different aspects of AFP studies (localization of its synthesis, structure and functions, genetic control of its synthesis and its use for cancer diagnostics) are reviewed. The main consideration is given to the cellular mechanisms of regulation of AFP synthesis. Hypothesis of "structural repression of AFP" is substantiated. According to it formation of liver trabeculae leads to suppression of AFP synthesis in hepatocytes, whereas escape of hepatocyte from trabecula results in activation of AFP synthesis. A new experimental model is described: AFP synthesis is activated in primary hepatocyte culture and is suppressed during three-dimensional growth of hepatocytes in collagen gel or mixed culture with nonparenchymal liver cells.
Animals↗
Cytophotometric study of premalignant and malignant cells of the cervix in an approach towards automated cytology.
Based on a cytophotometric procedure in combination with Feulgen reactive DNA and Pap-1 labeled specimens, the DNA values and hematoxylin-dense substances were examined in individual cells from 62 cases of premalignant and malignant lesions of the cervix, in contrast to normal squamous epithelia of 40 cases and 500 normal lyphocytes. The range of DNA values for the cells from benign proliferation and mild dysplasia cases was within a normal diploid-tetraploidy. In contrast, cases with carcinoma in situ and microinvasive carcinoma exhibited a DNA range which extended beyond hypertetraploidy with many cellspossessing a DNA value in excess of hexaploidy. Marked dysplasia from 11 cases also showed the same DNA range as carcinoma in situ. Our decision criteria derived from thresholding DNA value may be useful in an automatic cancer diagnostic test. In an aid to the manual measurement, an automatic glass fibrooptic system is now in preparation in an approach towards automation of uterine cytology for scanning of malignant cells.
Carcinoma in Situ↗
[Osteosarcoma of the urinary bladder with a prostatic cancer as a 2d primary tumor].
Osteosarcomas of the urinary bladder are exceedingly rare neoplasms. Post mortem findings of such a tumor are described in a 78 year old man who also had a primary prostate cancer. Diagnostic principles as well as differential diagnosis are discussed and the literature concerning this tumor is reviewed.
Adenocarcinoma↗
[Investigation of cancer with unicellular algae].
The Euglena alga culture modifications allow to distinguish between tumor serum and control serum. The modifications with ascites tumor AH 13R rat serum were also significatively different from healthy rat. These results suggest that this assay model could be applied for early cancer diagnostics. This communication is a summary of the 50 years work described on the bellow cited literature.
Animals↗