109,286 research outputs found
Role of academic institute in cancer therapy development in National Institute of Cancer Research, NHRI in Taiwan
No full text[[abstract]]National Health Research Institutes (NHRI) is a non-profit organization established by the Taiwan government in 1996. Among the 10 research units, 8 research institutes and two research centers, the National Institute of Cancer Research (NICR) and the Institute of Biotechnology and Pharmaceutical Research (IBPR) are involved in cancer therapy development. NICR aims to ascertain statistically efficacious new drugs and therapy for locally prevalent cancers through clinical trials. Whiles, IBPR is a fully integrated institute with multi-disciplinary technologies cover major aspects of the drug discovery and development. Such an integrated infrastructure facilitates the new drug development within NHRI. For instance, NICR joined in the pre-clinical and clinical development of a vascular-disrupting, anti-microtubular agent, DPRB104.Besides the intramural collaboration, NICR also plays an important role in helping the new drug development for domestic pharmaceutical companies. Regarding investigator-initiated trials, NICR explored the commercial available, off-labeled agents as well as yet approval agents for treating domestic prevalent cancers
Prognosis of non-small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes
No full text[[abstract]]Purpose: Current lung cancer staging and prognosis methods are based on imaging methods, which may not be sensitive enough for early and accurate detection of metastasis. This study aims to validate the use of a panel of markers for circulating cancer cell detection to improve the accuracy of cancer staging, prognosis, and as a rapid assessment of therapeutic response. Experimental Design: We analyzed the National Cancer Institute-Cancer Genome Anatomy Project database to identify potential marker genes for the detection of circulating cancer cells in peripheral blood. Nested real-time quantitative PCR and a scoring method using cancer cell load L-c were employed to correlate the amount of circulating cancer cells with clinical outcomes in 54 non-small cell lung cancer (NSCLC) patients. The Kaplan-Meier method was employed for analysis of prognostic variables. Results: A panel of four marker genes was identified and experimentally validated. With these marker genes, we achieved an overall positive detection rate of 72% for circulating cancer cells in the peripheral blood of NSCLC patients. Patients who had higher L-c values had worse outcomes and shorter survival times. Patients with poor therapeutic response were revealed by positive detection of circulating cancer cells after therapy. The results correlated well with the patients' survival time. Conclusion: Circulating cancer cell detection by a panel of markers and the L-c scoring method can supplement the current tumor, node, metastasis staging method for improved prognosis and for rapid assessment of therapeutic response. Together, they may facilitate the design of better therapeutic strategies for the treatment of NSCLC patients
The association between periodontal disease and pancreatic cancer
No full text[[abstract]]Background: Despite years of research, the causes of pancreatic cancer have remained largely unknown. Periodontal disease (PD) is an emerging risk factor for various systemic diseases, including cancer. The current study investigated the association between PD (periodontitis, gingivitis, and others) and development of pancreatic cancer. Methods: Using data from the National Health Insurance Research Database of Taiwan, 139,805 subjects with PD and 75,085 subjects without PD were identified. The association between PD and pancreatic cancer was assessed using Cox proportional hazards regression model. Results: Having PD was associated with a higher pancreatic cancer risk (hazard ratio (HR) = 1.55, 95% confidence interval (CI): 1.02-2.33). The higher pancreatic cancer risk associated with PD was observed among those aged 65 years or older (HR = 2.17, 95% CI: 1.03-4.57) and but not among those aged younger than 65 years (HR = 0.83, 95% CI: 0.52-1.34). Further analysis showed that PD remained an independent risk factor for pancreatic cancer after adjusting for diabetes, hyperlipidemia, allergies, viral hepatitis, peptic ulcer, pancreatitis, COPD (as a proxy for cigarette smoking) and alcoholic-related conditions (as a proxy for alcohol drinking). Conclusions: Our analysis showed a significantly positive association between PD and pancreatic cancer risk. Further investigation is needed to explain the underlying biological mechanisms for the positive association between PD and pancreatic cancer
Mutation of the STK11 gene predicts recurrence of breast cancer
No full text[[abstract]]Introduction: Breast cancer is the most common cancer in women, and some patients develop recurrence after standard therapy. Effective predictors are urgently needed to detect recurrence earlier. Methods: We conducted a comprehensive study via an experimental and bioinformatics approach to detect mutated genes in breast cancer. Twenty-seven breast cancer patients who developed recurrence within 24 months postoperatively and 22 control cancer patients without recurrence were enrolled from National Cheng Kung University Hospital in Taiwan. Targeted deep sequencing was performed to assess the mutations among individuals with breast cancer using a panel of 143 cancer-associated genes. Bioinformatics and public databases were used to predict the protein functions of the mutated genes. Results: Mutations were identified in 49 breast cancer specimens, and the most frequently mutated genes were BRCA2, TP53, APC, ATM, BRCA1, NOTCH1, TET2, NF1, TSC2, PIK3CA, TSC1, PTEN, MSH2, PTCH1, PIK3R1, STK11, RB1, BAP1, CDH1 and FBXW7. Mutation of these genes was correlated with protein phosphorylation and autophosphorylation. Among these highly mutated genes, mutations of STK11 were associated with poor prognosis and increased recurrence of breast cancer. Knockdown of STK11 in triple negative breast cancer cell lines increases transcription of cytokines and modulates immune response. Conclusion: Our findings suggest that mutation of STK11 is correlated with early recurrence of breast cancer patients and it will become a powerful prognostic marker for recurrence of breast cancer. Suppression of STK11 signaling by gene mutation may contribute to immune escape
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No full textDescription based on: March 2000; title from caption."A newsletter of the Applied Sociocultural Research Branch of the National Cancer Institute"--March 2000.Mode of access: Internet.Issued by: Division of Cancer Control and Population Sciences,
Dicer elicits paclitaxel chemosensitization and suppresses cancer stemness in breast cancer by repressing AXL
No full text[[abstract]]Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here we report that adenovirus type 5 E1A-mediated elevation of the microRNA processing enzyme Dicer is sufficient to enhance paclitaxel sensitization and reduce cancer stem-like cell properties in this setting. Elevating Dicer expression increased levels of the AXL kinase targeting microRNA miR-494, thereby repressing AXL expression to increase paclitaxel sensitivity. We found that Dicer expression was regulated at the transcription level by E1A, through activation of a MAPK14/CEBPalpha pathway. Our findings define a mechanism of E1A-mediated chemosensitization for paclitaxel which is based upon the suppression of breast cancer stem-like cells, with potential implications for the diagnosis and treatment of breast cancer patients
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Cancer studies II
No full textTable of Contents. Cancer etiology / Alfred Taylor (p. 1-12) -- The yolk sac method of cultivating tumor tissue in eggs / Alfred Taylor (p. 13-26) -- The use of embryonated eggs in cancer therapy experiments / Alfred Taylor (p. 27-35) -- The effect of metallic chlorides on the growth of tumor and nontumor tissue / Alfred Taylor and Nell Carmichael (p. 36-79) -- Factors influencing the utilization of glucose by suspensions of living tumor and embryo cells / M. Kendall Young, Jr., and Alfred Taylor (p. 80-98) -- Appendix. Publications on cancer from the University of Texas Biochemical Institute, 1942-1952 (p. 99-101).UT Librarie
TET1-mediated epigenetic reprogramming switches metabolism and promotes malignant phenotypes of ovarian cancer
No full text[[abstract]]Epigenetic dysregulation is one of the mechanisms involved in ovarian cancer carcinogenesis. Recently identified a new epigenetic modulator ten-eleven translocation protein 1 (TET1), a DNA dioxygenase which is believed in DNA demethylation through a 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) conversion, plays an important role in regulating self-renewal and specification in embryonic stem cells. In addition, it works as a tumor suppressor gene by inhibition of cell invasion, migration and tumor growth in breast and prostate cancer. However, the role of TET1 in ovarian cancer remains unknown. Thus we examed the expression level of TET1 in ovarian cancer tissues. We found that TET1 expression level correlated with cancer staging (p = 0.03) in 88 ovarian cancer from our biobank and poor survival (p = 0.012) in TCGA database. High expression of TET1 was observed in advanced stage, high-grade primary tumor specimens in comparison with normal ovarian surface epithelium (OSE) brushings (p = 0.0005) by NCBI database (GSE18520). These results suggested that TET1 may play some roles in ovarian cancer development, which is different from those previously published in other cancers. To study the function of TET1 in ovarian cancer, we generated TET1 over-expressing and knockdown cell lines model, the expression level and enzymatic activities of TET1 were confirmed by real time PCR, western and 5hmC stain. Here we found that TET1 increases the abilities of cell migration, anchorage-independent growth and promotes tumor growth. In addition, TET1 actives cancer stem markers and enhances the abilities of spheroid formation. Ovarian cancer stem cells (OCSCs) from cell line express high level of TET1 while the differentiated progenies suppress TET1 expression. Moreover, seven of eight patient-derived OCSCs revealed high expressing of TET1 in comparison with its parental cancer cells by quantitative PCR. To further examine the TET1 regulation network, we combined the expression array and MethCap-seq to analyze the epigomic changes. We found that a cluster of target genes which were up-regulated through DNA demethylation were enzymes responsible for oxidative phosphorylation. We investigated metabolic status by Extracellular Flux Analyzer (seahourse) on the TET1-overexpressing cells. Compared with control cells, TET1-overexpressing cells revealed 1.7 fold (p = 0.011) increase of oxygen consumption rate (OCR); while the extracellular acidification rate (ECAR) showed no difference (p = 0.856). This bioenergetic metabolism shift may be due to demethylation of subunits of mitochondria complexs. Taken together, TET1 reprograms the epigenome, shifts the metabolism, increases the malignant phenotypes and confers a poor prognosis of ovarian cancer. Targeting mitochondria on TET1-expressing ovarian cancer patients may provide a new way of personalized therapy
Salt-inducible kinase 3 expression identifies long-term survivors of serous ovarian cancer
No full text[[abstract]]Background: Epithelial ovarian cancer (EOC) has a high tumor-associated mortality rate among the gynecological cancers because EOC is usually diagnosed during the advanced stage. Cancer antigen (CA) 125 is the most well-studied biomarker for ovarian cancer screening. However, CA125 is also elevated in numerous conditions, resulting in decreased specificity. Materials and Method: We collected ovarian cancer specimens from 204 patients and examined the SIK3 and CA125 expression levels. The expression percentage of SIK3 or CA125 in the tumor cells, pre-surgery serum CA125 was divided into two groups and compared with patient overall survival, progression-free survival, cancer stage, cancer type and chemotherapeutic resistance. Results: A total of 30.9% of the patients had stage I disease, 7.8% had stage II disease, 52.4% had stage III disease, and 8.9% had stage IV disease. The median OS and PFS were 49.5 months (range 0.25-205 months) and 28.4 months (0.25-182.4), respectively. The mean age of the patients was 52.8 years (range 25-82 years). The histological classification was based on the four main ovarian cancer types: serous (51.5%), endometrioid (14.2%), clear cell (20.6%), and mucinous (9.3%). In all stages of the disease, high expression of SIK3 (SIK3-H) was associated with a markedly better OS, compared with low expression of SIK3 (SIK3-L) (127.0 months and 46.0 months, respectively; hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.41 to 0.86; P=0.005). SIK3-H had a markedly better PFS rate than SIK3-L (66.0 months and 26.0 months, respectively; HR for disease progression or recurrence, 0.68; 95% CI, 0.47 to 0.99; P=0.04). The same results were evident for serous ovarian cancer, where SIK3-H had a better OS rate than SIK3-L (75.0 months and 34.0 months, respectively; HR for death, 0.57; 95% CI, 0.36 to 0.91; P=0.02) and a better PFS rate than SIK3-L (44 and 13 months, respectively; HR, 0.52; 95% CI, 0.32 to 0.83; P=0.006). Notably, for advanced stage serous ovarian cancer, Only SIK3-H had a better OS rate than SIK3-L (48.0 months and 28.0 months, respectively; HR for death, 0.56; 95% CI, 0.33 to 0.96; P=0.03) and PFS rate (32 and 13 months, respectively; HR, 0.57; 95% CI, 0.34 to 0.95; P=0.03). Tissue CA125 expression and the pre-surgery serum CA125 level did not show significant differences in OS and PFS. Our results demonstrated that high SIK3 expression correlated with better OS and PFS rates in ovarian cancer patients, especially in patients with advanced serous ovarian cancer. Conclusion: High expression of SIK3 indicates a better prognosis in primary ovarian cancer and serous disease, especially in advanced serous disease
Tumor-associated antigen L6 and the invasion of human lung cancer cells
No full text[[abstract]]Metastasis is a coordinated process that depends on the interaction of cancer cells with the tumor microenvironment. Members of the transmembrane-4 superfamily (TM4SF) of surface proteins have been implicated in the regulation of cancer cell metastasis, and the expression of several TM4SF members on tumor cells is inversely correlated with patient prognosis. The tumor-associated antigen L6 (TAL6), a distant member of the TM4SF, is expressed on most epithelial cell carcinomas and is a target for antibody-mediated therapy. We examined whether TAL6 may play a role in cancer metastasis by using an established series of human lung carcinoma cell lines (CL1-0 to CL1-5) that exhibit increasing invasiveness in vitro and in vivo. We found that TAL6 expression correlated with the in vitro invasiveness of CL lung carcinoma cells (r(2) = 0.98) and human carcinoma cells (r(2) = 0.69). Forced expression of TAL6 on CL1-0 lung carcinoma cells significantly increased their in vitro invasiveness and decreased the survival of SCID mice in an experimental metastasis model. Specific antibody against TAL6 (monoclonal antibody L6) significantly reduced the migration and invasiveness of CL1-5 lung carcinoma cells. The effects of monoclonal antibody L6 on CL1-5 invasion required clustering of TAL6 on the cell surface. Real-time reverse transcription-PCR of lung cancer specimens showed that increased expression of TAL6 was significantly associated with early postoperative relapse (P = 0.034) and shorter survival (P = 0.025) in squamous cell lung cancer patients. Thus, TAL6 appears to be involved in cancer invasion and metastasis
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