Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53R2 gene encodes the ribonucleotide reductase (RR) small subunit 2 homologue, and is induced by several stress signals activating p53, such as DNA-damaging agents. The p53R2 gene product causes an increase in the deoxynucleotide triphosphate (dNTP) pool in the nucleus, which facilitates DNA repair and synthesis. We hypothesized that p53R2 would be a good molecular target for cancer gene therapy. In this study, three human oral cancer cell lines (SAS, HSC-4 and Ca9-22), a human breast cancer cell line MCF-7, and a normal human fibroblast cell line NHDF were tested. We silenced the expression of p53R2 with the highly specific post-transcriptional suppression of RNA interference (RNAi). We investigated p53R2 expression with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The sensitivity to anticancer agents was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of p53R2 showed no association with the mutational status of p53. The cancer cell lines with higher p53R2 expression were more resistant to 5-FU. RNAi-mediated p53R2 reduction selectivity inhibited growth and enhanced chemosensitivity in cancer cell lines but not in normal fibroblasts. These results suggest that basal transcription of p53R2 could be associated with the sensitivity to anticancer agents. Moreover, we assessed the possibility that p53R2 would be a good molecular target, and report that RNAi targeting of p53R2 could be useful for oral cancer gene therapy.
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PMID:Silencing of the p53R2 gene by RNA interference inhibits growth and enhances 5-fluorouracil sensitivity of oral cancer cells. 1589 Feb 38

Cancer is a major morbidity and mortality concern in Malaysia. Based on National Cancer Registry data, the Malaysian population is estimated to bear a cancer burden of about 40,000 new cases per year, and a cumulative lifetime risk of about 1:4. Cancer research in Malaysia has to consider needs relevant to our population, and resources constraints. Hence, funding bodies prioritise cancers of high prevalence, unique to our community and posing specific clinical problems. Cancer diagnosis is crucial to cancer management. While cancer diagnosis research largely aims at improvements in diagnostic information towards more appropriate therapy, it also impacts upon policy development and other areas of cancer management. The scope of cancer diagnosis upon which this paper is based, and their possible impact on other R&D areas, has been broadly categorized into: (1) identification of aetiological agents and their linkages to the development of precancer and cancer (impact on policy development, cancer prevention and treatment), (2) cancer biology and pathogenesis (impact on cancer prevention, treatment strategies and product development), (3) improvements in accuracy, sensitivity and specificity in cancer detection, monitoring and classification (impact on technology development) and (4) prognostic and predictive parameters (impact on treatment strategies). This paper is based on data collected by the Working Group on Cancer Diagnosis Research for the First National Conference on Cancer Research Coordination in April 2004. Data was collated from the databases of Institutions/Universities where the authors are employed, the Ministry of Science, Technology and Innovation (MOSTI) and targeted survey feedback from key cancer researchers. Under the 7th Malaysia Plan, 76 cancer projects were funded through the Intensified Research in Priority Areas (IRPA) scheme of MOSTI, amounting to almost RM15 million of grant money. 47(61.8%) of these projects were substantially in cancer diagnosis, accounting for 65.6% (RM 9.7 million) of cancer project funds. The 8th Malaysia Plan saw a change in research strategy. The IRPA agency fielded several top-down projects which encouraged a multicentre and multidisciplinary approach. This resulted in larger funding per project i.e. RM32 million for 49 projects. There was also a surge of interest in drug development and natural products. Because of this shift in direction, cancer diagnosis projects constituted only 51% of IRPA-funded cancer projects. Nonetheless funding for cancer diagnosis research has exceeded that of the 7th Malaysia Plan, being RM12.5 million by March 2004. The majority of such research is carried out at the Universities, engaging a large number of young scientists and postgraduate students (51 MSc and 21 PhD). A lot of research findings presented at scientific meetings have not yet been published and there is a glaring shortage of patents and commercialization of research findings (such as creation of test kits). Because diagnosis is very much a part of clinical practice, many researchers felt satisfied and confident that their work will be translated into practice and will significantly improve diagnostic services in Malaysia. National guidelines and consensus development on at least three malignancies i.e. breast cancer, oral cancer and lymphoma, have substantial basis in local R&D work. Problems encountered in research included (1) insufficient funding to realize research objectives, (2) lack of local expertise (most research assistants are inexperienced BSc graduates with no or minimal research experience), (3) inadequate technical support from vendors during equipment failure, (4) inexperienced Institutional development units to assist in product development, (5) lack of venture capital for commercialization of findings, and (6) inadequate incentives to undertake research. Researchers pointed out that plans to promote research should include the establishment of (1) regional and national cancer tissue banks, (2) a National Cancer Research Institute, (3) a dedicated cancer research fund, (4) a registry of cancer researchers, (5) national research coordinators, (6) improved coverage by the National Cancer Registry, (7) more international collaboration, (8) a better career structure for researchers, (9) improved Institutional support for product realization, and (10) better recognition for cancer researchers.
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PMID:Research on cancer diagnosis in Malaysia: current status. 1619 Jan 3

The spatial scan statistic is commonly used for geographical disease cluster detection, cluster evaluation and disease surveillance. The most commonly used shape of the scanning window is circular. In this paper we explore an elliptic version of the spatial scan statistic, using a scanning window of variable location, shape (eccentricity), angle and size, and with and without an eccentricity penalty. The method is applied to breast cancer mortality data from Northeastern United States and female oral cancer mortality in the United States. Power comparisons are made with the circular scan statistic.
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PMID:An elliptic spatial scan statistic. 1643 34

A 69-year-old Hispanic woman presented for the evaluation of nodules on the head and back. In the past, she had been treated for basal cell carcinoma (BCC) of the face; the referring physician was concerned that the new lesions might also be BCC. The patient had an extensive past medical history. In addition to BCC, she had been treated for breast cancer, colon cancer, and cervical cancer prior to emigrating to the USA. Her colonic malignancy had been localized proximal to the splenic flexure. She also had a history of colonic polyps and distal colonic villous adenoma. She denied ever being treated with radiation. Further details of her medical history and cancer staging were not available. Her family history was significant for a sister with colon cancer and transitional cell carcinoma of the urinary bladder. In addition, she had a great aunt with oral cancer and a great uncle with lung cancer. Neither the patient or her relatives had any history of tobacco use. On physical examination, in addition to scars from a radical mastectomy and midline abdominal laparotomy, four skin lesions were noted: two on the scalp, one on the tragus, and one on the mid-back. The first lesion on the vertex of the scalp was a yellow-brown waxy papule measuring 0.6 x 0.5 cm. This lesion was similar to that on the mid-back, except in size. The lesion on the back measured 1.2 x 1.0 cm. The second lesion on the frontal scalp measured 0.8 x 0.6 cm and was red-brown with a pearly appearance and some central hyperkeratosis. The tragus lesion was similar in appearance to that on the frontal scalp. Shave biopsies of all lesions were obtained. The lesions on the scalp and mid-back revealed lobules of sebaceous cells in the dermis with a minority of surrounding basaloid cells, consistent with a diagnosis of sebaceous adenoma (Fig. 1). Although the lesion on the frontal scalp also showed sebaceous differentiation, there were a greater number of basaloid cells, some with hyperchromatic nuclei and mitotic figures; this was consistent with a diagnosis of sebaceous epithelioma (Fig. 2). The final lesion (tragus) was histologically consistent with a keratotic BCC. No further treatment was required for these benign sebaceous tumors, but their presence defined our patient's condition as Muir-Torre syndrome. Mohs' micrographic surgery was performed on the tragus BCC and the margins were tumor free in one stage. The patient returned 1 year later with a lesion anterior to the left axilla which was biopsied to rule out BCC (Fig. 3). Histologically, this lesion was also consistent with sebaceous epithelioma.
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PMID:Muir-Torre syndrome: a case of this uncommon entity. 1653 37

Two large-scale, phase III cancer prevention trials, the Breast Cancer Prevention Trial (BCPT) of tamoxifen and Prostate Cancer Prevention Trial (PCPT) of finasteride, concluded with strikingly positive and simultaneously problematic results: reduced cancer risks but a major adverse finding with each agent that prevented its widespread use in the community. For most moderate-risk people, such as those studied in the BCPT and PCPT, the benefit of reduced breast or prostate cancer does not outweigh the major risk of tamoxifen (endometrial cancer in the BCPT) or apparent risk of finasteride (high-grade prostate cancer in the PCPT). Promising interventions with biologically active substances are likely to have adverse, perhaps unforeseen effects, especially with long-term preventive use. Acceptance of such agents will depend heavily on the level of cancer risk of the target population. This article outlines research in molecularly identified high-risk oral intraepithelial neoplasia that creates the clinical opportunity for optimizing the risk-benefit ratio of agents to prevent oral cancer. Two other major research efforts focused on improving preventive agent risk-benefit ratios are molecular-targeted research designed to target away from known adverse signaling pathways and multidisciplinary research based on the PCPT that will develop comprehensive models of prostate cancer risk (especially of aggressive prostate cancer) and pharmacoecogenetic models for identifying high-risk men most likely to benefit from (and not be harmed by) finasteride or similar (5alpha-reductase inhibiting) agents. Defining and targeting high-risk populations, developing molecular-targeted approaches, and developing accurate pharmacoecogenetic models promise to reduce the risk of chemoprevention and ultimately to reduce the risk and burden of major cancers.
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PMID:Reducing the "risk" of chemoprevention: defining and targeting high risk--2005 AACR Cancer Research and Prevention Foundation Award Lecture. 1654 Jun 34

We examine the theoretical basis of screening, followed by an evaluation of screening initiatives from a population health perspective and a discussion of the organisation of mass screening programmes. Evidence for the effectiveness of screening by primary site from both randomised trials and evaluation of service screening is summarised and the existing cancer screening programmes in the European Union are described. Sufficient evidence from several randomised trials to demonstrate mortality reduction exists for breast cancer and colorectal cancer screening. At least one trial has shown efficacy with a mortality end-point in screening for hepatocellular carcinoma and oral cancer. Randomised trials have demonstrated a lack of mortality effect in lung cancer screening based on chest X-ray and sputum cytology. Despite the lack of randomised trials, population screening for cervical cancer with cytological smears has been convincingly shown to reduce cervical cancer incidence and mortality.
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PMID:Cancer screening: evidence and practice in Europe 2008. 1834 53

We assessed the immunological status of stage III and IV head and neck squamous cell carcinoma (HNSCC) patients and age-matched healthy individuals. In HNSCC patients, the total leukocyte count was lower and the proliferating ability of PBMCs against phytohemagglutinin (PHA) was significantly downregulated. These cells showed lower expression of the early activation marker CD69. Within this PBMC population, the proportion of CD4+, CD8+ T cells, CD3- CD56+, CD16+ NK cells and CD3+ CD56+ NK-T cells was seriously downregulated. However, the proportion of CD4+ CD25+ Foxp3+ regulatory T cells having suppressor function was upregulated. Other immune cells, like CD14+ monocytes/macrophages and CD20+ B cells, were also fewer in number, although this difference was not statistically significant. Assessment of the cytokine secretory status of PBMCs revealed suppressed levels of Th1 cytokines (IFN-gamma, IL-12 and TNF-alpha) and elevated secretion of Th2 cytokines (IL-4 and IL-10) for HNSCC PBMCs whereas just the opposite was seen for PBMCs from healthy individuals. Dysregulation in the profile of immunocompetent cells and cytokine secretion was reflected in the suppressed cytotoxic function of HNSCC PBMCs, as tested on KB (oral cancer), MCF7 (breast cancer), COLO205 (colon cancer), Jurkat (T cell leukemia), K562 (erythroleukemia) and U937 (monocytic lymphoma) cell lines. The observed decreased cytotoxicity of HNSCC PBMCs may be due to the downregulated expression of cytotoxic molecules (perforin, granzymeB and FasL) in HNSCC PBMCs. Assessment of the extent of immune dysfunction might help design immunotherapeutic protocols by incorporating any agent having immunomodulatory function.
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PMID:Dysregulation in immune functions is reflected in tumor cell cytotoxicity by peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients. 1854 33

Using tigogenin as starting material, (20S)-20-hydroxycholestane-3,6-dione (1), (16S, 20S)-16,20-dihydroxycholestan-3-one (2), (20S)-20-hydroxycholest-1-ene-3,16-dione (3) and (20S)-20-hydroxycholest-4-ene-3,16-dione (4), natural polyoxygenated steroids from the gorgonian, Leptogorgia sarmentosa, were synthesized in four steps. Antitumor activity against three tumor cell lines (breast cancer, MCF7, lung cancer NCI and oral cancer KB) was evaluated. Two compounds (3 and 4) showed strong activity against NCI (IC(50) 6.16 and 10.51 microM) and moderate activity against MCF7 and KB, the IC(50) being in the range 30.65-47.22 microM. Compound 2 showed moderate activity against NCI (IC(50) 42.68 microM) but was inactive against MCF7 and KB whereas compound 1 showed no activity against all tested cells.
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PMID:First synthesis of 3,16,20-polyoxygenated cholestanes, new cytotoxic steroids from the gorgonian Leptogorgia sarmentosa. 1855 Jan 36

Phosphorylation on certain Ser/Thr-Pro motifs is a major oncogenic mechanism. The conformation and function of phosphorylated Ser/Thr-Pro motifs are further regulated by the prolyl isomerase Pin1. Pin1 has been shown to be prevalently overexpressed in human breast cancer cell lines and cancer tissues and to play a critical role in the transformation of mammary epithelial cells by activating multiple oncogenic pathways. Pin1 expression was found to be an excellent independent prognostic marker in prostate cancer. However, little is known about Pin1 and its downstream targets beta-catenin and cyclin D1 expressions in human oral cancers. In the present study, we quantified Pin1 expression in 74 paired normal/tumor human oral cancer samples as well as oral cancer cell lines. Pin1 was overexpressed in oral squamous cell carcinoma (OSCC) and its level correlated with beta-catenin accumulation and cyclin D1 expression. Moreover, we examined Pin1 mRNA expression in OSCC and cancer cell lines by RT-PCR analysis. The results showed that there is concordance in the relationship between the Pin1 mRNA level and Pin1 protein expression. The up-regulation of Pin1 mRNA expression in tumor part when comparing with that in non-tumor part was in agreement with that of the Pin1 protein overexpressed in OSCC. In addition, we showed that the molecular and immunohistochemical profiles of Pin1 overexpression were associated with progression of OSCC. Taken together, these results indicate that Pin1 is a regulator of cyclin D1 expression in OSCC and might play a role in oral oncogenesis. The overexpression of Pin1 can be used as an indicator for pathological diagnosis of OSCC.
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PMID:Pin1 overexpression is associated with poor differentiation and survival in oral squamous cell carcinoma. 1928 14

Aziridine-containing compounds have been of interest as anticancer agents since late 1970s. The design, synthesis and study of triaziquone (TZQ) analogues with the aim of obtaining compounds with enhanced efficacy and reduced toxicity are an ongoing research effort in our group. A series of bis-type TZQ derivatives has been prepared and their cytotoxic activities were investigated. The cytotoxicity of these bis-type TZQ derivatives were tested on three cancer lines, including breast cancer (BC-M1), oral cancer (OEC-M1), larynx epidermal cancer (Hep2) and one normal skin fibroblast (SF). Most of these synthetic derivatives displayed significant cytotoxic activities against human carcinoma cell lines, but weak activities against SF. Among tested analogues the bis-type TZQ derivative 1a showed lethal effects on larynx epidermal carcinoma cells (Hep2), with an LC(50) value of 2.02 microM, and also weak cytotoxic activity against SF cells with an LC(50) value over 10 microM for 24 hr treatment. Comparing the viability of normal fibroblast cells treated with compound 1a and TZQ, the LC(50) value of the latter was 2.52 microM, indicating more toxicity than compound 1a. This significantly decreased cytotoxicity of compound 1a towards normal SF cells, while still maintaining the anticancer activity towards Hep2 cells is an interesting feature. Among the seven compounds synthesized, compound 1c has similar toxicity effects on the three cancer cell lines and SF normal cells as the TZQ monomer.
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PMID:Synthesis and antitumor evaluation of novel bis-triaziquone derivatives. 1963 5


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