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PubMed1994

The general mammography screening program in Stockholm. Organisation and first-round results.

This presentation describes the organization and first-round results of the Stockholm mass mammography screening program, and discusses ways of checking the quality of an ongoing screening program. The Stockholm mammography screening program started in 1989 at five independent screening units, and comprises more than 150,000 women aged 50 to 69 years. The first round was completed in June 1991. Compliance during the studied period was 70.6%, and the recall rate was 3.0% of the attending women. Breast cancer was diagnosed in 676 women, of whom 90 (13.3%) had a cancer in situ. The cancer prevalence rate was thus 6.3 cancers per 1,000 screened women. Surgery was performed on 925 women, of whom 249 had benign lesions, giving a benign/malignant ratio of 0.37 to 1. Fifty-two per cent of the cancer patients were operated with breast conserving surgery. The median size of the invasive cancers was 12 mm; almost 80% were node-negative. Experience from the first two years of this mass mammography screening program shows that it meets the major quality requirements. One of the main future goals is to maintain the high quality of the program. Another important goal is a further increase in compliance.

Aged↗
PubMed2000

Mutation profile of the p53, fhit, p16INK4a/p19ARF and H-ras genes in Indian breast carcinomas.

Breast cancer is the second most prevalent cancer affecting Indian women. Genetic alterations of oncogenes and tumor suppressor genes were attributed to the development of breast carcinomas. In the present study, human breast tumor DNAs from untreated, non-familial, Indian patients were analysed for the presence of mutations in p53, fhit, p16INK4a/p19ARF and H-ras genes. Polymerase chain reaction-single strand conformation polymorphism and sequencing analysis were used to detect point mutations. Exons 5-8 of p53, exons 1-2 of p16INK4a, exon 2 of p19ARF, exons 5-9 of fhit gene and exons 1-2 of H-ras genes were amplified and analysed individually using exon-flanking primers. Only 12% of the tumors had mutation in p53, 8% had mutation in fhit gene and none of the tumors showed evidence for mutation in p16INK4a/p19ARF and H-ras genes. Tumor B18 exhibited two novel mutations in the p53 gene, ATGright curved arrow GTG (Metright curved arrow Val) at codon 237 and AATright curved arrow GAT (Asnright curved arrow Asp) at codon 263. Both of these mutations are hitherto unreported in breast carcinomas. Tumor B20 had a non-sense mutation CGAright curved arrow TGA (Argright curved arrow Stop) at codon 306 of p53 gene. In fhit gene, tumor B1 exhibited TTCTright curved arrow TACT mutation at intron 8 and tumor B15 had a silent mutation GAGright curved arrow GAA (Gluright curved arrow Glu) at codon 123. Our results indicate that, among the genes analysed, the p53 gene was more frequently mutated than fhit, p16INK4a/p19ARF and H-ras genes in Indian mammary tumors. Transcribable point mutations of fhit gene were found to be extremely uncommon in these tumors. Mutations in the above genes are mutually exclusive and are infrequent in fhit, p16INK4a/p19ARF and H-ras genes suggesting that these genes may not play a major role in Indian breast carcinomas. However, the significant frequency of mutations in the p53 gene suggest that p53 could be one of the genes involved in the genesis of sporadic breast carcinomas in Indian women.

Acid Anhydride Hydrolases↗
PubMed2001

[Usefulness of CT colonography in the preoperative evaluation of patients with distal occlusive colorectal carcinoma].

PURPOSE: To evaluate the role of preoperative virtual colonoscopy to study the proximal colon in patients with distal occlusive carcinomas, diagnosed by conventional colonoscopy. MATERIAL AND METHODS: We examined 19 patients aged 46 to 83 years (13 men and 6 women) with distal occlusive colorectal carcinomas diagnosed by conventional colonoscopy, who were preoperatively studied with virtual colonoscopy. Patients with acute bowel obstruction were excluded. Results were compared with the findings of preoperative conventional colonoscopy and barium enema examination, intraoperative colon palpation, histopathologic outcome, postoperative conventional colonoscopy and barium enema examination. RESULTS: Virtual colonoscopy identified all 19 distal occlusive colon carcinomas and 22 synchronous lesions, 2 cancers (prevalence 10,6%) and 20 polyps (prevalence 68,4%). Both synchronous cancers were confirmed intraoperatively by direct palpation. Postoperative conventional colonoscopy, which was performed in 18 patients, confirmed the presence of 15 polyps in 12 patients. Three subcentimeter polyps were removed during conventional colonoscopy and were missed at virtual colonoscopy. Two polyps shown by virtual colonoscopy were not found at conventional colonoscopy. Postoperative barium enema was performed in three patients and confirmed three polyps identified at virtual colonoscopy. Preoperative barium enema was performed in five patients and failed to adequately demonstrate the proximal colon. Virtual colonoscopy showed a sensitivity of 87% and a specificity of 75%. CONCLUSIONS: Virtual CT colonoscopy can be considered an important diagnostic technique to evaluate preoperatively the proximal colon in patients with distal occlusive carcinomas,as it gives better results than barium enema or conventional colonoscopy, as well as being well tolerated and less invasive.

Adenocarcinoma↗
PubMed2002

Bcl-2 immunohistochemical detection in prostate cancer.

Prostate cancer (Pca) is the most prevalent cancer diagnosed and the second leading cause of cancer-related deaths among men in the Poland. The present study was designed to analyse the relationship between expression of Bcl-2 protein in prostate cancer (PCa) following radical prostatectomy to chosen anatomoclinical and morfological parameters of the tumours. Tumours from 28 patients were assessed by immunohistochemistry. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the anti-human Bcl-2 antibody (Dako/Clon124). The immunolocalization of Bcl-2 was performed using the Labelled Streptavidin Biotin (LSAB) method. No correlation was found between Bcl-2 protein expression and pT stage, lymph node metastases, Gleason score, seminal vesicles invasion, positive or negative resection margins as well as capsular penetration and preoperative PSA serum level.

Adenocarcinoma↗
PubMedDate not supplied

Arg tyrosine kinase expression in human gastric adenocarcinoma is associated with vessel invasion.

BACKGROUND: Gastric cancer is one of the prevalent cancer types in the Far East region. In order to discover new prognostic and diagnostic biomarkers for gastric cancer progression, we have used degenerated PCR primers designed to amplify all expressed protein tyrosine kinase molecules from human cancer tissues. In previous studies, we have shown the clinical significance of arg tyrosine kinases in a colorectal cancer progression model. MATERIALS AND METHODS: We further investigated the protein expression of arg tyrosine kinase by immunohistochemistry and analyzed the clinicopathological association with human cancers. RESULTS AND CONCLUSION: Specimens from 79 patients were examined and this demonstrated that the expression of arg kinase showed no statistically significant correlation with the patients' overall survival. However, higher levels of arg kinase immunoreactivity did show a statistically significant association with vessel invasion in gastric cancer tissues examined. This indicates a potential involvement of arg in gastric cancer invasion and progression.

Adenocarcinoma↗
PubMed2003

Advances in the development of ribozymes and antisense oligodeoxynucleotides as antiviral agents for human papillomaviruses.

Urogenital human papillomavirus (HPV) infections are the most common viral sexually transmitted disease in women. On a worldwide basis cervical cancer is the second most prevalent cancer of women. Although HPV infection is not sufficient to induce cancer, the causal relation between high-risk HPV infection and cervical cancer is well established. Over 99% of cervical cancers are positive for high-risk HPV. Therefore, there is a need for newer approaches to treat HPV infection. Two novel approaches for inactivating gene expression involve ribozymes and oligonucleotides. Methods for identification of target genes involved in neoplastic transformation and tumour growth have been established, and these will lead to therapeutic approaches without any damage to normal cellular RNA molecules, which is often associated with conventional therapeutics. Ribozymes and oligonucleotides represent rational antiviral approaches for inhibiting the growth of cervical lesions and carcinomas by interfering with E6/E7 RNA production. The E6 and E7 genes of high-risk HPVs cooperate to immortalize primary epithelial cells and because they are found in cervical cancer are considered the hallmark of cervical cancer. The use and modification of ribozymes and antisense oligodeoxynucleotides can inhibit the growth of HPV-16 and HPV-18 immortalized cells, and tumour cells by eliminating E6/E7 transcript. Hammerhead and hairpin ribozymes have been widely studied because of their potential use for gene therapy and their place as therapeutic tools for cervical cancer is being evaluated. Although antiviral ribozymes and antisense molecules have been effective as in vitro or in vivo inhibitors of high-risk HPV-positive cells, none is currently in clinical trial. There are, however, a number of other antisense therapies in Phase I-III clinical trial for several oncogenes.

Antiviral Agents↗
PubMed2002

Oncological complications of excess GH in acromegaly.

Around fifteen percent of the deaths reported in acromegaly are attributable to malignancy (SM Melmed, J Clin Endocrinol Metab 2001;86:2929-2934; A Mestrón, SM Webb, In: Endocrine Society, San Francisco, June 2002 (abstract)), uncontrolled disease is associated with a growth advantage for concurrent neoplasms, which are more likely to be aggressive; however, there is no clear evidence of de novo cancer initiation in acromegaly and no proven causal relationship of acromegaly with malignant disease. Overall and cancer mortality in acromegaly have been shown to correlate with the degree of GH control; if post therapy GH is controlled, both the overall and cancer mortality do not appear to differ from that of the normal population (SM Orme et al., J Clin Endocrinol Metab 1998;83:2730-2734; JD Nabarro, Clin Endocrinol 1987;26:481-512). However, no long-term prospective evaluation of cancer prevalence or its relation to biochemical or clinical disease activity is available. IGF-1 appears to exert a permissive effect on tumorigenesis; there is no clear evidence that tumor initiation is triggered by IGF-1 in acromegaly; nevertheless, since IGF-1 may be higher in neoplasms, aggressive treatment aimed at controlling the disease activity will theoretically be advantageous for acromegalic patients with cancer. The prevalence of colon polyps and colon cancer appear to be incresed in acromegaly as is mortality for colon cancer (Orme et al., 1998), so regular colonoscopy screening and polypectomy would seem advisable, especially in older patients with active acromegaly. Surveillance for prostate cancer in elderly males with high IGF-1, especially if also receiving testosterone replacement therapy, is recommendable, by measurement of serum PSA, rectal examination and/or prostatic ultrasound. In women, mammography should be offered, especially after the age of 50 years, as in the normal population. Neither prostate nor breast cancer have been consistently shown to have an increased prevalence in acromegaly, but larger prospective epidemiological studies are required to study this further.

Acromegaly↗
PubMed2007

Screening HIV-infected women for cervical cancer in Thailand: findings from a demonstration project.

OBJECTIVES: Although cervical cancer is an AIDS-defining illness, few HIV-infected women are routinely screened for cervical cancer in Thailand. We screened HIV-infected women for cervical cancer as a component of HIV care and assessed high-risk human papillomavirus (HPV) and cervical cancer prevalence. METHODS: From July 2003 through February 2004, HIV-infected women attending either an infectious disease clinic or a sexually transmitted infection (STI) clinic in Bangkok were tested for high-risk HPV types by Hybrid Capture 2 and screened for cervical cancer by Pap test; those with abnormal cervical cytology were referred for diagnosis and treatment. RESULTS: Two hundred ten HIV-infected women at an infectious disease clinic (n = 150) and an STI clinic (n = 60) received cervical cancer screening. The high-risk HPV prevalence was 38.6% and the prevalence of abnormal cervical cytology was 20.4%. Abnormal cervical cytology and high-risk HPV detection were associated (P < 0.001). We received pathology reports for 23 (53.5%) of 43 women, including all those with a Pap test showing high-grade squamous intraepithelial lesions; the cervical cancer prevalence was 1.9% (4 of 210; 95% confidence interval, 0.5-4.8%). CONCLUSION: The estimated prevalence of high-risk HPV and cervical cancer among HIV-infected women in Thailand was high. This emphasizes the need to integrate cervical cancer screening into HIV care.

Adult↗
PubMed2003

Estimating the prevalence of breast cancer using a disease model: data problems and trends.

BACKGROUND: Health policy and planning depend on quantitative data of disease epidemiology. However, empirical data are often incomplete or are of questionable validity. Disease models describing the relationship between incidence, prevalence and mortality are used to detect data problems or supplement missing data. Because time trends in the data affect their outcome, we compared the extent to which trends and known data problems affected model outcome for breast cancer. METHODS: We calculated breast cancer prevalence from Dutch incidence and mortality data (the Netherlands Cancer Registry and Statistics Netherlands) and compared this to regionally available prevalence data (Eindhoven Cancer Registry, IKZ). Subsequently, we recalculated the model adjusting for 1) limitations of the prevalence data, 2) a trend in incidence, 3) secondary primaries, and 4) excess mortality due to non-breast cancer deaths. RESULTS: There was a large discrepancy between calculated and IKZ prevalence, which could be explained for 60% by the limitations of the prevalence data plus the trend in incidence. Secondary primaries and excess mortality had relatively small effects only (explaining 17% and 6%, respectively), leaving a smaller part of the difference unexplained. CONCLUSION: IPM models can be useful both for checking data inconsistencies and for supplementing incomplete data, but their results should be interpreted with caution. Unknown data problems and trends may affect the outcome and in the absence of additional data, expert opinion is the only available judge.

Journal Article↗
PubMed1990

Cross-sectional versus longitudinal investigations of the diet-cancer relation.

Within a prospective cohort study on diet and cancer, information was collected on cancer prevalence and baseline meat consumption. A nested case-control study on meat and cancer was conducted with 656 prevalent colorectal cases, 1,894 breast cancer cases, and 4,701 controls. When analyzed cross-sectionally, prevalence odds ratios for eating meat rarely versus regularly were 2.08 for female colorectal and 1.75 for breast cancer. In the longitudinal analysis, cases who started consuming meat rarely after diagnosis were excluded, resulting in odds ratios of 0.51 for female colorectal and 1.17 for breast cancer. These opposite findings highlight the problem of cross-sectional designs.

Aged↗
PubMedDate not supplied

The prevalence of colorectal cancer in Italy.

AIMS: To analyze the prevalence of colorectal cancer (CRC) in different areas of Italy by age, interval since diagnosis and disease stage at diagnosis, and to estimate the prevalence of CRC. These data provide estimates of patient demand on health resources. PATIENTS AND METHODS: Eleven Italian cancer registries (CRs) provided data on 33,740 patients observed for up to 15 years. For the 1,829 cases from the specialized colorectal cancer registry of Modena we analyzed prevalence by Dukes' stage and family history. PREVAL software produced observed prevalence figures by time from diagnosis; to determine the total prevalence, correction factors were applied to the observed data. RESULTS: At the end of 1992, five-year CRC prevalence was high (close to 200 per 100,000) in Genova, Parma, Romagna and Firenze, and low (around 75 per 100,000) in the southern areas of Latina and Ragusa. For all CRs, 86 patients per 100,000 population were alive up to 2 years from diagnosis and 77 per 100,000 between 2 and 5 years from diagnosis. The 5-year prevalence of patients diagnosed with Dukes' B or C (high risk of recurrence and requiring postoperative surveillance) was 152 per 100,000; that of Dukes' A patients 36 per 100,000 (considered cured after surgery and not requiring intensive follow-up or care); that of unstaged patients plus those with distant metastasis at diagnosis was 28 per 100,000 at 5 years (requiring palliative care but not follow-up). The 12-year prevalence of HNPCC was 23 per 100,000, or about 7% of the total; for such patients knowledge of the long-term prevalence is important because they are diagnosed young and are at high risk of multiple tumor development. CONCLUSIONS: 70% of the prevalent patients diagnosed within 5 years prior to the prevalence date were likely to require care for cancer recurrence, while 13% of the prevalent cases required care for distant metastases.

Adolescent↗
PubMed2026

The bioinformatics approach to identifying pathogenic variants for colorectal cancer (CRC).

Colorectal cancer (CRC) is the third most prevalent cancer globally, accounting for 9.6% of newly diagnosed cases and 9.3% of cancer-related deaths. It develops from the uncontrolled proliferation of glandular cells in the colon and rectum and is categorized into three primary types: sporadic, hereditary, and colitis-associated. While genetic susceptibility is a key factor in CRC pathogenesis, identifying high-impact pathogenic variants remains a significant challenge. This study integrates bioinformatics and population genetics approaches to identify CRC-associated single-nucleotide polymorphisms (SNPs) with potential clinical significance. CRC-associated SNPs were extracted from the Genome-Wide Association Studies (GWAS) Catalog, functionally annotated via HaploReg, and validated via Ensembl. In addition, expression quantitative trait locus (eQTL) data from the GTEx database were used to assess the effects of these variants on gene expression across human tissues. Our analysis identified three high-priority SNPs (rs9379084, rs3184504, and rs11557154) associated with the RREB1, ATXN2, SH2B3, and DCAF12 genes, which exhibited marked allele frequency differences among populations. These findings suggest potential biomarkers for CRC risk assessment and highlight the importance of genetic screening across diverse populations.

Bioinformatics↗
PubMed2025

Deep Learning on Histologic Slides Accurately Predicts Consensus Molecular Subtypes and Spatial Heterogeneity in Colon Cancer.

Colon cancer (CC) is the third most prevalent cancer type. It is highly heterogeneous, particularly in terms of molecular profiles, which have both prognostic and predictive impacts on the treatment efficacy. However, CC treatment in adjuvant situations is currently guided solely by T and N staging. In this context, consensus molecular subtypes (CMSs) were introduced to stratify patients with CC based on molecular profiles. Recent studies have shown that CMS can be heterogeneous in CC, leading to a worse prognosis. This study focused on predicting CMS and its heterogeneity in CC using deep learning on digitized hematoxylin and eosin &#xb1; saffron-stained whole-slide images. Data and whole-slide images of 1996 patients from the PETACC-8, The Cancer Genome Atlas-COAD, and PRODIGE-13 cohorts were used. The model is trained to predict a 4-dimensional CMS vector, reflecting intratumor heterogeneity (ITH). It comprises a self-supervised model for embedding image patches into vectors and a weakly supervised model predicting CMS calls. Ground-truth CMS scores are obtained with the CMSclassifier package. Interpretability analyses are performed at the slide and patch levels. For homogeneous tumors, the model trained on PETACC-8 achieves 93.0% (&#xb1;1.4%) macroaverage area under the curve in internal cross-validation and 94.4% macroaverage area under the curve in external validation over PRODIGE-13, whereas the The Cancer Genome Atlas-COAD model reaches 85.4% (&#xb1;3.0%) in cross-validation and 92.4% over PRODIGE-13. The trained models also provide spatial distributions of CMS across tumor slides and associate specific histologic features with each CMS. Finally, the models are able to predict ITH. The results show that a deep learning model trained on routine histology slides is capable of providing an efficient and robust method for predicting CMS and characterizing a patient's ITH, paving the way for the routine consideration of CMS/ITH in clinical decision making in the adjuvant setting.

Humans↗
PubMed2025

Identification of key genes related to bone metastasis of breast cancer using bioinformatics methods and construction of a prognostic model.

Breast cancer (BC) ranks among the most prevalent cancers in females, with bone metastasis significantly compromising patients' quality of life and survival rates. Enhancing our comprehension of BC bone metastasis mechanisms at the molecular level holds promise for improving BC treatment and prognosis. Leveraging bioinformatics tools, we integrated multiple datasets, conducted comprehensive analyses across various databases, identified biomarkers associated with BC bone metastasis, and constructed a prognostic model. Firstly, 3 BC bone metastasis-related datasets were downloaded from gene expression omnibus, the data were merged, and batch effects were removed, followed by identification of differentially expressed genes (DEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed using the STRING database to screen hub genes. Then, survival analysis of hub genes was performed using the Cancer Genome Atlas (TCGA) database. A prognostic model was constructed using key genes with survival differences, and the model was evaluated. Two hundred ninety-two DEGs were identified. Gene ontology and KEGG pathway enrichment analysis yielded 769 biological processes (BPs), 78 cellular components, 43 molecular functions, and 50 KEGG pathways. Fifteen hub genes were selected from the protein-protein interaction network. Survival analysis revealed 6 genes related to BC survival. The prognostic model identified 4 genes with important predictive value for BC prognosis. Our study utilized bioinformatics analysis to identify a series of DEGs related to BC bone metastasis. Based on further selection of hub genes, we constructed a relatively ideal prognostic model for BC, and identified 4 genes (DLGAP5, TPX2, PLK1, and CENPN) with valuable predictive value for BC prognosis.

Humans↗
PubMed2006

Cervical cancer and human papillomaviruses: inactivation of retinoblastoma and other tumor suppressor pathways.

Infection with human papillomaviruses (HPVs) is a major public health burden worldwide and is associated with benign and malignant lesions of the skin and genital tract. HPV causes cervical cancer, which represents the second most prevalent cancer in women worldwide. Functions of the viral oncogenes E6 and E7 are essential for carcinogenesis and for support of the viral life cycle. We will begin by discussing the relationship between HPV infection and disease, followed by a review of E6 and E7 activities and their respective cellular targets. Particular emphasis will be placed on established and newly discovered mechanisms by which E7 inhibits members of the cellular retinoblastoma protein family. We will then describe how current research links the above molecular interactions to malignant transformation as well as to aspects of the viral life cycle in vitro and in vivo. As a result of decades of intense HPV research, promising therapies to prevent infection and to treat HPV associated cancers are now on the horizon. We will conclude our review by a description of potential gene therapeutic and hormonal approaches and of new developments in the design of effective vaccines.

Animals↗
PubMed2006

Knowledge of epigenetic influence for prostate cancer therapy.

Prostate cancer is one of the most prevalent cancers in men in many countries, increasing in frequency with age through the most advanced years. The standard treatment for newly diagnosed metastatic tumors is androgen ablation. However, advanced prostate cancer nevertheless often develops in many cases. Although hormonal manipulation and chemotherapy have uncertain value for advanced lesions, especially androgen-independent, recent studies of docetaxel-based chemotherapy in men with androgen-independent prostate cancer have shown a survival benefit. Intensive investigations have shown that aberrant epigenetic features. including aberrant DNA methylation, make an important contribution to carcinogenesis as well as genetic alterations. Hypermethylation of CpG islands in promoter regions can lead to silencing of tumor-suppressor genes, while hypomethylation of the genome leads to instability. This review attempts to provide up-to-date information regarding the significance of epigenetics for human prostate cancer, with aberrations offering dues to therapy and possibly also providing targets for anticancer drugs.

Animals↗
PubMed1999

Inhibitors of 17alpha-hydroxylase/17,20-lyase (CYP17): potential agents for the treatment of prostate cancer.

Prostate cancer (PCa) is now the most prevalent cancer in men in the U.S.A. and Europe. At present the major treatment options include surgical or medical castration. These strategies depend on the abolition of the production of testosterone by the testes. However, as these procedures do not affect adrenal androgen production, they are frequently combined with androgen receptor antagonist to block their action. Inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17alpha-hydroxylase/17,20-lyase (hereafter referred to as CYP17 ) could prevent androgen biosynthesis from both sources. Thus total blockade of androgen production by CYP17 inhibitors may provide effective treatment of prostate cancer patients. Indeed, this strategy is now an area of intense interest within research institutions and the pharmaceutical industry. This review highlights development in the design and evaluation of both steroidal and non-steroidal CYP17 inhibitors since 1965. Major emphasis is given to the potent CYP17 inhibitors and those which may show clinical promise. The review could function as a comprehensive working reference of research accomplishment in the field and what problems remain to be tackled in the future.

Affinity Labels↗