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At least 289 records · Page 16Linked to original sources

p53 immunostaining as a marker for oral cancer in diagnostic cytopathology--preliminary report.

The expression of p53 in oral mucosal disorders is strongly associated with malignant disease. Smears from normal and malignant oral mucosa were investigated for the presence of p53 using CM1 polyclonal antibody against p53 protein. The expression of p53 in smears was compared with the expression of the marker in biopsies from these oral carcinomas. p53 was identified in eight smears from 12 biopsy positive oral cancers. It was not seen in smears from eight p53-negative oral cancers and 40 smears from normal oral mucosa. It is suggested that expression of p53 in smears from a clinically suspicious lesion may be of value in the diagnosis of oral carcinoma.

Biomarkers, Tumor↗

Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications.

Carcinogenesis is a multistep process characterized by genetic alterations that influence key cellular pathways involved in growth and development. Oncogenes refer to those genes whose alterations cause gain-of-function effects, while tumor suppressor genes cause loss-of-function effects that contribute to the malignant phenotype. The effects of these alterations are complex due to the high number of changes in a typical case of breast cancer and the interactions of the biological pathways involved. This review focuses on the more common abnormalities in oncogenes and tumor suppressor genes in human breast cancer and their known associations with clinical outcome in terms of tumor classification, prognosis, and response to specific therapies. A better understanding of these relationships has led to new therapeutic applications. Agents that target oncogenes and their associated pathways are now in clinical use, with many more undergoing preclinical and clinical testing. The availability of antibodies, small synthetic molecules, cyotokines, gene therapy techniques, and even natural compounds that are screened for specific biological properties has greatly increased the number of candidate drugs. Nevertheless, clinical successes have been limited because of the redundancy of many cancer-related pathways as well as the high degree of variability in genotype and phenotype among individual tumors. Likewise, strategies to replace tumor suppressor gene functions face numerous technical hurdles. This review summarizes the current achievements and future prospects for the therapeutic targeting of oncogenes and tumor suppressor genes and new technology to better classify tumors and accurately predict responses to standard and novel agents.

Breast Neoplasms↗

Mechanism-Driven Diagnostic Development: A Specimen-Aware Framework Illustrated by Colorectal Cancer and Solid Tumours.

Translational oncology has moved rapidly from histopathology and single-analyte biomarkers toward multi-dimensional molecular profiling. Yet many clinically deployed tests still use reductionist biomarker strategies that under-represent cancer complexity. This review examines whether a mechanistic, multi-layered, and specimen-aware approach can improve cancer detection, classification, prognosis, minimal residual disease (MRD) assessment, and therapeutic selection. Evidence across solid tumours shows that genomic alterations alone incompletely explain tumour state, metastatic behaviour, immune evasion, or therapeutic vulnerability. Integrated genome and transcriptome analyses, proteogenomics, single-cell atlases, fragmentomic, methylation based cell-free DNA assays, metabolomics and microbiome assessments reveal clinically relevant biology that single modality tests cannot determine. Minimally invasive collected specimens can extend access to screening, diagnosis and longitudinal monitoring, but the choice of specimen should be matched to disease biology and analytes that represent mechanisms of oncogenesis. However, translation remains constrained by pre-analytical variability, contamination, differences in tumour shedding behaviour, clonal haematopoiesis, translation of generated models, incomplete external validation and uncertain downstream clinical utility for emerging platforms. This review provides a commentary on the future of cancer diagnostics, the considerations and barriers to clinical translation, the relationship between utility and dimensionality of biomarkers assessed and the emerging rationale towards mechanistically grounded integrated models.

biomarkers↗

Full-field direct digital telemammography: technical components, study protocols, and preliminary results.

The early detection of breast cancer increases the survival rate in women. Today, film-screen mammography is the most common and effective technique for the detection of breast cancer. However, the film-screen image recording system of current mammography has several technical limitations that can reduce the breast cancer diagnostic accuracy. A state-of-the-art technology, full-field direct digital mammography (FFDDM) has the potential to increase the sensitivity of clinical and screening examinations and emerge as a film-screen mammography replacement. It is believed that efficiently delivering the superior image quality of FFDDM to expert mammographers will significantly increase the breast cancer diagnostic accuracy. This concept motivates the studies of FFDDM telemammography. In this paper, we will report the FFDDM telemammography project that is being conducted in our facility. The fundamental technology of the FFDDM system and the characteristics of FFDDM images are described. Our research approach is through three protocols: telediagnosis, teleconsultation, and telemanagement. Each of these study protocols is defined. To conduct this FFDDM telemammography project, an asynchronous transfer-mode-network-based telemammography system is developed across two remote campuses in our facility. The architecture of this system is detailed. Unlike other medical imaging modalities, the matrix of an FFDDM image is huge. How to present the image information to mammographers via currently available display media is a challenging task. Our display approaches for the FFDDM images are described. Some preliminary study results from the current phase of this study are reported.

Breast Neoplasms↗

Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial.

There is a need to quantify the benefits and harms of colorectal cancer (CRC) screening using primary colonoscopy or fecal immunochemical testing (FIT) compared with usual care with no screening. Guidelines recommend screening in individuals aged 50-75 years using colonoscopy or FIT, and many screening programs use one-sample biennial FIT. Here we compare incidence of diagnosed CRCs and gastrointestinal and cardiovascular events between screening and usual care during the diagnostic phase of the SCREESCO trial. A randomized block method (no masking) assigned 278,280 individuals aged 60 years to once-only colonoscopy, 2 rounds of two-stool FIT with a low cutoff (10 μg g-1 feces) or usual care (control group) in a ratio of 1:6 for colonoscopy versus control and 1:2 for FIT versus control. In the analysis, 31,113 individuals were in the primary colonoscopy arm and 60,267 were in the FIT arm, and there were 186,671 primary colonoscopy controls, of whom 120,521 were also controls for comparison with the FIT arm. After a median follow-up of 4.8 years, the incidence rate of CRC was 107.9 in the colonoscopy arm and 99.9 in controls per 100,000 person-years (incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 0.91-1.28) and 96.0 in the FIT arm and 103.9 in controls (IRR: 0.92, 95% CI: 0.81-1.05). Rates of stage I-II CRC were higher in the colonoscopy arm (IRR: 1.38, 95% CI: 1.09-1.74) and in the FIT arm (IRR: 1.19, 95% CI: 0.99-1.43) versus controls. Rates of cardiovascular and gastrointestinal events were slightly higher in the intervention arms during the first year and were subsequently more similar to controls. Our findings of an increase in CRC detection implies a benefit of screening while the increase in adverse events suggests some initial harm. ClinicalTrials.gov: NCT02078804 .

Humans↗

Molecular diagnostics of cancer predisposition: hereditary non-polyposis colorectal carcinoma and mismatch repair defects.

Hereditary non-polyposis colorectal carcinoma accounts for 5-13% of all colorectal carcinomas and is inherited in a dominant fashion. Two different forms can be distinguished. Type I is restricted to colorectal cancers, whereas type II patients acquire acolorectal, endometrial, gastric, small intestinal and transitional carcinomas of the upper urinary tract. Germline mutations in the human mismatch repair genes (hMSH2, hMSH6, hMLH1, hPMS2) account for the majority of hereditary non-polyposis colorectal carcinoma. As a result of the mismatch repair deficiency, replication errors are not repaired, resulting in a mutator phenotype. Simple repetitive sequences (microsatellites) are especially prone to replication errors and analysis of their stability combined with immunohistochemical analysis of mismatch repair protein expression provides a rapid diagnostic strategy. For patients either (1) fulfilling the Amsterdam criteria for HNPCC, (2) with synchronous or metachronous hereditary non-polyposis colorectal carcinoma-related tumors, (3) with hereditary non-polyposis colorectal carcinoma-related tumors before the age of 45 and/or (4) with right sided CRC and mucinous, solid, or cribriform growth patterns, screening for mismatch repair deficiencies should be performed. The identification of colorectal cancers displaying a mutator phenotype has implications for both treatment and prognosis.

Adaptor Proteins, Signal Transducing↗

Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents.

The use of near-infrared (NIR) light to interrogate deep tissues has enormous potential for molecular-based imaging when coupled with NIR excitable dyes. More than a decade has now passed since the initial proposals for NIR optical tomography for breast cancer screening using time-dependent measurements of light propagation in the breast. Much accomplishment in the development of optical mammography has been demonstrated, most recently in the application of time-domain, frequency-domain, and continuous-wave measurements that depend on endogenous contrast owing to angiogenesis and increased hemoglobin absorbance for contrast. Although exciting and promising, the necessity of angiogenesis-mediated absorption contrast for diagnostic optical mammography minimizes the potential for using NIR techniques to assess sentinel lymph node staging, metastatic spread, and multifocality of breast disease, among other applications. In this review, we summarize the progress made in the development of optical mammography, and focus on the emerging work underway in the use of diagnostic contrast agents for the molecular-based, diagnostic imaging of breast.

Absorption↗

Epigenetic diagnostics of cancer--the application of DNA methylation markers.

In recent years it has become apparent that epigenetic events are potentially equally responsible for cancer initiation and progression as genetic abnormalities. DNA methylation is the main epigenetic modification in humans. Two DNA methylation lesions coexist in human neoplasms: hypermethylation of promoter regions of specific genes within a context of genomic hypomethylation. Aberrant methylation is found at early stages of carcinogenesis and distinct types of cancer exhibit specific patterns of methylation changes. Tumor specific DNA is readily obtainable from different clinical samples and methylation status analysis often permits sensitive disease detection. Methylation markers may also serve for prognostic and predictive purposes as they often reflect the metastatic potential and sensitivity to therapy. As current findings show a great potential of recently characterised methylation markers, more studies in the field are needed in the future. Large clinical studies of newly developed markers are especially needed. The review describes the diagnostic potential of DNA methylation markers.

Biomarkers, Tumor↗

[Early stomach cancer: new diagnostic and therapeutic aspects].

Gastroscopy is the diagnostic measure of choice in early recognition of gastric carcinoma, offering an accuracy rate of 96-99. However, this goal can only be achieved when biopsies are taken with forceps and snare from all circumscribed lesions which may hide a carcinoma. The common association with hyperplasiogenic polyps (15/86), adenoma and borderline lesion (7/86) and synchronous gastric carcinoma (8/86) request a subtle preoperative diagnosis if one does not perform gastrectomy in principle. Endoscopic resection (5/86) or local excision (6/86) should be debated in carcinomas located close to the cardia, and in high-risk patients. 5-year-survival rates of the "Erlangen early gastric cancer registry", are in accordance with the excellent results reported in the Japanese literature.

Adenoma↗