[Diagnostic imaging of cancer].
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Diagnostic Imaging↗
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Measuring complete diagnostic evaluation in colorectal cancer screening.
Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.
Barium Sulfate↗
Obesity and subcutaneous fat patterning in relation to breast cancer in postmenopausal women participating in the Diagnostic Investigation of Mammary Cancer Project.
Associations of body fat and body fat distribution with breast cancer were studied in 16,355 postmenopausal women with a natural menopause, aged 49 to 68 years, participating in a breast cancer screening project (the Diagnostic Investigation of Mammary Cancer [DOM] project in Utrecht, The Netherlands). One hundred nineteen women had breast cancer detected at first screening. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness. No relationship between fat distribution and breast cancer was found. After adjustment for age, women in the highest quartile of Quetelet's index (QI) (weight/height2) had an odds ratio of 1.65 (95% confidence interval [CI], 0.97 to 2.81) compared with women in the the lowest quartile (test for trend, P less than 0.05). For subscapular skinfold and triceps skinfold, the odds ratios were 2.23 (95% CI, 1.28 to 3.91) and 2.01 (95% CI, 1.21 to 3.32), respectively, comparing the highest with the lowest quartile. The authors conclude that in postmenopausal women, overall obesity is associated with increased risk of breast cancer, whereas fat distribution, as measured by contrasting groups of subscapular and triceps skinfold thicknesses, is not related to breast cancer.
Adipose Tissue↗
[Colorectal cancer: contribution of new diagnostic tools].
Colorectal cancers profited much from the progress of the imagery, which have occurred since a score of years. The imagery by magnetic resonance, in particular, supplanted the porto-scanner in the evaluation of hepatic metastases of colorectal cancers requiring a surgery. In the field of the assessment of the metastatic disease, like in the event of suspicion of recurrence of a cancer of the rectum, the functional imagery with tomography by emission of positons also represents a major projection whose indications should grow progressively with the equipment of the territory. The echo-endoscopy, whose advent is older, allows a very precise exploration of the loco-regional extension of cancers of the rectum, indication for which it was still threatened by no other examination. Lastly, and whereas its place largely remains to be defined, images obtained by virtual coloscopy, are very impressive. It however will be necessary, in the years to come, to precisely evaluate the interest of this new method of imagery in the diagnosis of colorectal tumors, or in the follow-up of certain patients.
Colonic Neoplasms↗
Simultaneous detection of the tumor suppressor FHIT gene and protein using the multi-functional biochip.
The tumor suppressor gene, fragile histidine triad (FHIT), encompasses the most common human chromosomal fragile site, at 3pl4.2. Detection of FHIT gene is important in cancer diagnostics since its alterations have been associated with several human cancers. A unique multi-functional biochip for simultaneous detection of FHIT DNA and FHIT protein on the same platform was applied. The design of the biochip is based on miniaturization of photodiodes, where functioning of multiple optical sensing elements, amplifiers, discriminators, and logic circuitry are integrated on a single IC board. Performance of biochip is based on biomolecular recognition processes using both DNA and protein bioreceptors, Cy5-labeled probes and laser excitation. Application of biochip for concurrent detection of various immobilized target DNA and protein molecules and multiplex of DNA and protein on the same microarray was accomplished. Linearity of biochip for quantitative measurements was demonstrated. Results demonstrated utility of this multi-functional biochip as a useful detection technology with applications in biological and clinical laboratories.
Acid Anhydride Hydrolases↗
Diagnostic imaging and staging of primary lung cancer.
Improved diagnostic imaging has the potential to guide the surgeon in choice of invasive procedures required for staging and treatment of lung cancer. In the evaluation of a solitary pulmonary nodule, absence of growth for 2 years or certain typical calcifications are strong evidence of benignity, but we do not advocate following indeterminate nodules without a diagnosis because even small nodules may be carcinomas. In assessing chest wall invasion, computed tomography has no greater predictive value than a history of localized pain. The absence of nodes greater than 1.0 cm in short axis diameter on computed tomograms of the thorax is associated with low risk of tumor in mediastinal nodes, but tissue diagnosis is required for certainty. The finding of nodes larger than 1.0 cm may be useful in guiding the surgeon during staging procedures. Currently, there is no advantage of magnetic resonance imaging over computed tomography in evaluation of mediastinal nodes. Complete history and physical examination with routine serum chemistries will identify patients at high risk for metastases and will guide selection of appropriate special studies. It is emphasized that accurate staging requires histologic diagnosis and that CT and thorough surgical evaluation of the mediastinum are complementary procedures in staging of lung cancer.
Diagnostic Imaging↗
Cancer among medical diagnostic x-ray workers in China.
Cancer incidence among 27,011 diagnostic x-ray workers was compared to that of 25,782 other medical specialists employed between 1950 and 1980 in China. X-ray workers had a 50% higher risk of developing cancer than the other specialists [relative risk (RR) = 1.5; 95% CI = 1.3-1.7]. Leukemia was strongly linked to radiation work (RR = 3.5, n = 30). Cancers of the breast (RR = 1.4, n = 11), thyroid (RR = 2.1, n = 7), and skin (RR = 1.5, n = 6) were increased among x-ray workers employed for 10 or more years. High risks of cancers of the esophagus (RR = 3.5, n = 15) and liver (RR = 2.4, n = 48) were not consistent with a radiation effect since risk did not vary by duration of employment. This finding suggested that some differences might exist between groups of hospital workers in social class, alcohol intake, dietary habits, and other risk factors. No excess lung cancer (RR = 0.9, n = 22) or multiple myeloma (n = 0) was observed. Significant excesses of leukemia and cancers of the breast and thyroid occurred among x-ray workers first employed prior to 1960 when radiation exposures in China were high. In fact, it was not uncommon for employees to be given time off from x-ray work because their wbc count was severely depressed. These data indicated that repeated exposure to x-rays over many years can increase the risk of leukemia and several other tumors but apparently not that of lung cancer.
Adult↗
Comparison between fatigue, sleep disturbance, and circadian rhythm in cancer inpatients and healthy volunteers: evaluation of diagnostic criteria for cancer-related fatigue.
The aim of this study was to evaluate whether diagnostic criteria for cancer-related fatigue syndrome (CRFS) could be rigorously applied to cancer inpatients, and to explore the relationship between subjective fatigue and objective measures of physical activity, sleep, and circadian rhythm. Female cancer patients (n=25) and a comparison group of subjects without cancer (n=25) were studied. Study participants completed a structured interview for CRFS and questionnaires relating to fatigue, psychological symptoms, and quality of life (QoL). Wrist actigraphs worn for 72 hours were used as an objective measure of activity, sleep, and circadian rhythm. Compared to controls, cancer patients were more fatigued, had worse sleep quality, more disrupted circadian rhythms, lower daytime activity levels, and worse QoL. After exclusion of subjects with "probable" mood disorders, the prevalence of CRFS was 56%. Fatigue severity among the cancer patients was significantly correlated with low QoL, depression, constipation, and decreased self-reported physical functioning. It can be concluded that the diagnostic criteria for CRFS can be applied to cancer inpatients but strict application requires a rigorous assessment of psychiatric comorbidity. Despite cancer inpatients having greater impairments of sleep and circadian rhythm, it was found that fatigue severity did not appear to be related to these impairments.
Aged↗
microRNAs as oncogenes and tumor suppressors.
microRNAs (miRNAs) are a new class of non-protein-coding, endogenous, small RNAs. They are important regulatory molecules in animals and plants. miRNA regulates gene expression by translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-guided rapid deadenylation. Recent studies show that some miRNAs regulate cell proliferation and apoptosis processes that are important in cancer formation. By using multiple molecular techniques, which include Northern blot analysis, real-time PCR, miRNA microarray, up- or down-expression of specific miRNAs, it was found that several miRNAs were directly involved in human cancers, including lung, breast, brain, liver, colon cancer, and leukemia. In addition, some miRNAs may function as oncogenes or tumor suppressors. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites, suggesting that miRNAs may play a more important role in the pathogenesis of a limited range of human cancers than previously thought. Overexpressed miRNAs in cancers, such as mir-17-92, may function as oncogenes and promote cancer development by negatively regulating tumor suppressor genes and/or genes that control cell differentiation or apoptosis. Underexpressed miRNAs in cancers, such as let-7, function as tumor suppressor genes and may inhibit cancers by regulating oncogenes and/or genes that control cell differentiation or apoptosis. miRNA expression profiles may become useful biomarkers for cancer diagnostics. In addition, miRNA therapy could be a powerful tool for cancer prevention and therapeutics.
Animals↗
Pseudo-Meigs' syndrome caused by secondary ovarian tumors from gastrointestinal cancer. A case report and review of the literature.
BACKGROUND: Pseudo-Meigs' syndrome is a condition characterized by nonmalignant ascites and/or pleural effusion caused by pelvic tumors other than solid benign ovarian tumors. This syndrome has only rarely occurred in association with gastrointestinal cancers. METHOD: We treated a 53-year-old woman who developed this syndrome due to ovarian metastasis from colon cancer. Diagnostic work-up for abdominal distension disclosed a sigmoid colon cancer and bilateral ovarian masses. Ultrasonography demonstrated massive ascites and a right pleural effusion. Repeated cytologic examinations of both effusions revealed no malignant cells. Laparotomy disclosed no peritoneal dissemination. A radical sigmoidectomy and hysterectomy with bilateral salpingo-oophorectomy were performed. RESULTS: Histologic examination confirmed ovarian metastases from the colonic primary tumor. After resection, both effusions disappeared promptly, confirming a diagnosis of pseudo-Meigs' syndrome caused by sigmoid colon cancer. The patient remains alive with disease after 52 months. CONCLUSION: Among 6 reported occurrences with gastrointestinal tumors including our case, the primary site was the colon or rectum in 5 and the stomach in 1. Two cases were due to Krukenberg tumors. Three patients with documented outcomes were alive 108, 52, and 12 months after resection. Clinicians should note that gastrointestinal cancers, especially colorectal tumors, rarely may cause pseudo-Meigs' syndrome and resection may provide long-term palliation.
Adenocarcinoma↗
Emerging interest in the kallikrein gene family for understanding and diagnosing cancer.
Kallikreins are proteolytic enzymes that constitute a subfamily of serine proteases. Novel kallikrein genes were cloned recently, and it was shown that the human kallikrein family contains 15 genes tandemly aligned on chromosomal locus 19q13.3-q13.4. Based on their altered expression in tumor cells, kallikreins may be involved in the pathogenesis and/or progression of cancer. Evidence is presented that certain kallikreins may be exploited as diagnostic cancer biomarkers. Although the function(s) of novel kallikreins is currently unknown, increasing evidence suggests that kallikreins may participate in regulatory enzymatic cascade(s). Elucidation of the function of novel kallikreins largely depends on the availability of active recombinant proteins. Here, the zymogen for kallikrein 13 was overexpressed in Pichia pastoris and biochemically characterized. It was shown that the kallikrein 13 zymogen displays intrinsic catalytic activity leading to autoactivation. A clipped form of kallikrein 13 was identified, indicating autocatalytic cleavage at the internal bond R114-S115. Mature kallikrein 13 displays trypsin-like activity with restricted specificity on synthetic and protein substrates. Combinatorial P1-Lys libraries of tetrapeptide fluorogenic substrates were synthesized and used for the profiling of the P2 specificity of selected kallikreins. Interestingly, it was shown that human kallikrein 13, similarly to PSA, could specifically cleave human plasminogen to generate angiostatin-like fragments, suggesting that specific kallikreins may have antiangiogenic actions. An understanding of the physiology of human kallikreins is emerging with potential clinical applications.
Amino Acid Sequence↗
Specialized DNA arrays for the differentiation of pancreatic tumors.
PURPOSE: Malignant tumors of the pancreas are frequently indistinguishable from inflammatory tumors arising in the context of a chronic pancreatitis with the use of conventional imaging techniques. Thus, cytologic analysis of cells obtained by abdominal ultrasound, computed tomography, or endoscopic ultrasound-guided fine needle aspiration biopsy is required for diagnosis. However, the reliability of cytologic analyses of pancreatic fine needle aspirates remains unsatisfactory, with a diagnostic accuracy of < or =80%. The purpose of the current study was therefore to develop a novel diagnostic approach based on expression profiling of biopsy material using a specialized diagnostic cDNA array. EXPERIMENTAL DESIGN: Previous gene expression profiling studies were reevaluated to design a 558-feature diagnostic array. Minimal amounts of residual material from pancreatic cytology samples as well as surgically resected tumor and control tissue specimens were analyzed using the diagnostic array and a newly developed statistical classification system. RESULTS AND CONCLUSIONS: Our diagnostic approach resulted in 95% accurate differentiation between ductal adenocarcinomas and nonmalignant tumors of the pancreas. The diagnostic array, in conjunction with conventional diagnostic procedures, is thus suitable to significantly improve the reliability of pancreatic cancer diagnostics and can be expected to become a valuable new tool in the routine workup of suspect masses in the pancreas.
Adenocarcinoma↗
EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis.
Telomerase is elevated in >90% of breast carcinomas and therefore has received much attention as a target for breast cancer therapy and cancer diagnostic research. Dietary components that are capable of inhibiting the growth of cancer cells without affecting the growth of normal cells are receiving considerable attention in developing novel cancer-preventive approaches. Studies have shown that (-)-epigallocatechin-3-gallate (EGCG) from green tea imparts a growth inhibitory effect on cancer cells. Here, we show that treatment of EGCG dose-dependently inhibited (20-100%) the reproductive or colony forming potential, and also decreased cell viability at different time points studied ( approximately 80% inhibition) in human breast carcinoma MCF-7 cells but had no adverse effect on the growth of normal mammary cells. Treatment of EGCG for 48 and 72 h markedly increased the percentage of apoptotic cells (32-51%) in MCF-7 cells compared to that of non-EGCG treated cells (8-14%). In order to identify the possible mechanism of decreased cell viability and induction of apoptosis in breast carcinoma cells by EGCG, we found that treatment of MCF-7 cells with EGCG dose-dependently inhibited telomerase activity (40-55%), and also inhibited the mRNA expression (40-55%) of hTERT, a catalytic subunit of telomerase. Additional studies demonstrated that EGCG also inhibited the protein expression of hTERT, which indicated that inhibition of telomerase was associated with down-regulation of hTERT. Together, our results indicate that EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to the suppression of cell viability and induction of apoptosis, thus providing the molecular basis for the development of EGCG as a novel chemopreventive and pharmacologically safe agent against breast cancer.
Antineoplastic Agents, Phytogenic↗
Lymphocyte fluorescence polarization changes after phytohemagglutinin stimulation in the diagnosis of colorectal carcinoma.
A lymphocyte fluorescence polarization test that measures reactivity to phytohemagglutinin (PHA) has permitted discrimination of a majority of patients with colorectal carcinoma from noncancer individuals. The test involves separation of two lymphocyte fractions from 20 ml venous blood on a modified leukocyte separation gradient, incubation with PHA for 45 minutes, addition of fluorescein diacetate, and analysis of change in fluorescence polarization. Of 19 colorectal patients tested preoperatively, 13 had a positive stimulation index, 3 a zero index, and 3 a negative index. Of 7 patients with other malignant neoplasms, a positive value was obtained in 6 and a negative value in 1. Of 14 patients with other diseases, a negative value was obtained in 9, zero in 3, and positive in 2. Of 31 normal donors a negative value was obtained in 27, zero in 2, and weak positive in 2. This rapid test promises to develop into a useful cancer-diagnostic method, and elucidation of its biological basis should identify a new cancer marker.
Adult↗
[Molecular diagnostics of ovarian cancer using proteome techniques].
Ovarian cancer is most common gynecological malignancy which is difficult for early diagnostics. Development of new methods for diagnostics of ovarian cancer, especially, on early stage, is the urgent problem of modern oncology. A general approach to early diagnostics of cancer is a discovery of specific blood disease biomarkers. Ovarian cancer biomarker used in the modern art, CA125, has some drawbacks resulting in extensive research recently directed to this tumor diagnosis. In particular, it was shown the advantage of parallel use of several diagnostic biomarkers instead of the single one. Proteome techniques (two-dimensional electrophoresis, mass-spectrometry methods) in connection to bioinformatics represent a powerful tool for new biomarker discovery. In this respect, the best method of choice is shown to be SELDI-TOF (Surface-enhanced laser desorption/ionization time-of-flight) technique which combines chromatography protein chip application and mass-spectrometry-based detection. In this review, new ovarian biomarker data obtained by proteome methods are summarized.
Biomarkers↗
Validity of self reported diagnoses of cancer in a major Spanish prospective cohort study.
INTRODUCTION: This study aims to assess the validity of self reported diagnoses of cancer by persons recruited for the Spanish EPIC (European prospective investigation into cancer and nutrition) cohort study and to identify variables associated with correctly reporting a diagnosis of cancer. METHODS: 41 440 members of EPIC were asked at the time of recruitment whether they had been diagnosed with cancer and the year of diagnosis and site. The process of validating self reported diagnoses of cancer included comparison of the cohort database with the data from the population based cancer registries. Cancer diagnostic validity tests were calculated. The association between a correct report and certain sociodemographic, tumour related, or health related variables were analysed by logistic regression. RESULTS: The overall sensitivity of self reported diagnoses of cancer is low (57.5%; 95% CI: 51.9 to 63.0), the highest values being shown by persons with a higher level of education or with a family history of cancer and the lowest values by smokers. Breast and thyroid cancers are those with the highest diagnostic validity and uterus, bladder, and colon-rectum those with the lowest. In both sexes the variables showing a significant association with a correct report of cancer are: higher education level, number of previous pathologies, invasive tumour, and, in women, a history of gynaecological surgery. CONCLUSIONS: The overall sensitivity of self reported diagnoses of cancer is comparatively low and it is not recommended in epidemiological studies for identifying tumours. However, self reported diagnoses might be highly valid for certain tumour sites, malignant behaviour, and average to high levels of education.
Adult↗
Detection of HER2 gene amplification by fluorescence in situ hybridization in breast cancer.
Fluorescence in situ hybridization (FISH) is increasingly recognized as the most accurate and predictive test for both HER2 gene amplification or expression and response to Herceptin therapy in breast cancer. Diagnostic procedures for FISH require rigorous quality control, as with all diagnostic procedures, which rely on standardized methodologies. We describe the use of FISH for HER2 in our own laboratory, based on more than 4000 diagnostic assays, and the optimal approaches to scoring HER2 gene amplification in breast cancer.
Breast Neoplasms↗
Diagnostic and therapeutic applications of epigenetics.
Epigenetic abnormalities, such as aberrant methylation of CpG islands, are inherited over cell divisions, and play important roles in carcinogenesis. Aberrant methylation of CpG islands specific to tumor cells can be used as a marker to detect cancer cells or cancer-derived DNA, taking advantage of the high sensitivity of methods to detect aberrant methylation. Methylations of specific genes or methylation patterns of groups of genes were found to be associated with responses to chemotherapeutics and prognosis. Methylation in non-cancerous tissues is now attracting attention as a tumor risk marker, and is emerging as a target for cancer prevention. Epigenetic alterations are potentially reversible. The use of DNA demethylating agents has turned out to be effective for hematological malignancies, and is being tested in solid tumors. Histone deacetylase inhibitors and methods for gene-specific epigenetic modification are being developed. Application of epigenetics to cancer diagnostics and therapeutics, and possibly to cancer prevention, is coming into clinics.
Biomarkers, Tumor↗