Journal of Carcinogenesis最新文献_第9页

Mapping cancer cell metabolism with(13)C flux analysis: Recent progress and future challenges. 用(13)C通量分析绘制癌细胞代谢图谱:最新进展和未来挑战

Journal of Carcinogenesis Pub Date : 2013-07-24 eCollection Date: 2013-01-01 DOI: 10.4103/1477-3163.115422

Casey Scott Duckwall, Taylor Athanasaw Murphy, Jamey Dale Young

{"title":"Mapping cancer cell metabolism with(13)C flux analysis: Recent progress and future challenges.","authors":"Casey Scott Duckwall, Taylor Athanasaw Murphy, Jamey Dale Young","doi":"10.4103/1477-3163.115422","DOIUrl":"https://doi.org/10.4103/1477-3163.115422","url":null,"abstract":"The reprogramming of energy metabolism is emerging as an important molecular hallmark of cancer cells. Recent discoveries linking specific metabolic alterations to cancer development have strengthened the idea that altered metabolism is more than a side effect of malignant transformation, but may in fact be a functional driver of tumor growth and progression in some cancers. As a result, dysregulated metabolic pathways have become attractive targets for cancer therapeutics. This review highlights the application of(13)C metabolic flux analysis (MFA) to map the flow of carbon through intracellular biochemical pathways of cancer cells. We summarize several recent applications of MFA that have identified novel biosynthetic pathways involved in cancer cell proliferation and shed light on the role of specific oncogenes in regulating these pathways. Through such studies, it has become apparent that the metabolic phenotypes of cancer cells are not as homogeneous as once thought, but instead depend strongly on the molecular alterations and environmental factors at play in each case. ","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.115422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31670875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator. 肿瘤代谢符合系统生物学:丙酮酸激酶异构体PKM2是代谢的主要调节因子。

Journal of Carcinogenesis Pub Date : 2013-07-24 eCollection Date: 2013-01-01 DOI: 10.4103/1477-3163.115423

Fabian V Filipp

{"title":"Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator.","authors":"Fabian V Filipp","doi":"10.4103/1477-3163.115423","DOIUrl":"https://doi.org/10.4103/1477-3163.115423","url":null,"abstract":"Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor activation-induced tumorigenesis. These biochemical activities are controlled by a shift in the oligomeric state of PKM2 that includes acetylation, oxidation, phosphorylation, prolyl hydroxylation and sumoylation. Metabolically active PKM2 tetramer is allosterically regulated and responds to nutritional and stress signals. Metabolically inactive PKM2 dimer is imported into the nucleus and can function as protein kinase stimulating transcription. A systems biology approach to PKM2 at the genome, transcriptome, proteome, metabolome and fluxome level reveals how differences in biomolecular structure translate into a global rewiring of cancer metabolism. Cancer systems biology takes us beyond the Warburg effect, opening unprecedented therapeutic opportunities. ","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.115423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31670877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 50

Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A single center study. 印度肺腺癌中表皮生长因子受体突变:单中心研究。

Journal of Carcinogenesis Pub Date : 2013-07-12 eCollection Date: 2013-01-01 DOI: 10.4103/1477-3163.114970

Dinesh Chandra Doval, Saud Azam, Ullas Batra, Kumardeep Dutta Choudhury, Vineet Talwar, Sunil Kumar Gupta, Anurag Mehta

{"title":"Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A single center study.","authors":"Dinesh Chandra Doval, Saud Azam, Ullas Batra, Kumardeep Dutta Choudhury, Vineet Talwar, Sunil Kumar Gupta, Anurag Mehta","doi":"10.4103/1477-3163.114970","DOIUrl":"https://doi.org/10.4103/1477-3163.114970","url":null,"abstract":"Background: Adenocarcinoma, a subgroup of non-small cell lung cancer, is the most frequent form occurring in the non-smokers. Mutation in tyrosine kinase domain of epidermal growth factor receptor (EGFR) has been a common feature observed in lung adenocarcinoma. The study was carried out to detect the prevalence of EGFR mutation in lung adenocarcinoma.Materials and methods: EGFR mutation status in 166 lung adenocarcinoma patients was obtained retrospectively. Mutation tests were performed on paraffin embedded tissue blocks as a routine diagnostic procedure by polymerase chain reaction followed by direct nucleotide sequencing. Patient's demographics and other clinical details were obtained from the medical records.Results: EGFR mutation was detected in 43/166 (25.9%) patients. Gender wise mutation was observed as 18/55 (32.7%) in females and 25/111 (22.5%) in males. Overall, EGFR mutation was correlated with never smokers and distant metastasis (P < 0.05), but not associated with the gender, disease stage and pleural effusion. Exon 19 deletions were significantly correlated with females, never smokers, pleural effusion and distant metastasis (P < 0.05). However, point mutation on exon 21 did not show any statistical association with the above variables. Median overall survival was 22 months (95% confidence interval, 15.4-28.6). Female sex, EGFR mutation and absence of metastasis are associated with good prognosis.Conclusion: EGFR mutation in lung adenocarcinoma was higher in never smokers, females and patients with distant metastasis. However, it was not linked with tobacco smoking. The prevalence of EGFR mutation observed is in range with the previously published reports from the Asian countries.","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.114970","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31670874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 34

Stage-specific analysis of plasma protein profiles in ovarian cancer: Difference in-gel electrophoresis analysis of pooled clinical samples. 卵巢癌血浆蛋白谱的分期特异性分析:汇集临床样本的凝胶电泳分析差异

Journal of Carcinogenesis Pub Date : 2013-06-29 Print Date: 2013-01-01 DOI: 10.4103/1477-3163.114216

Mark J Bailey, Kristy L Shield-Artin, Karen Oliva, Mustafa Ayhan, Simone Reisman, Gregory E Rice

{"title":"Stage-specific analysis of plasma protein profiles in ovarian cancer: Difference in-gel electrophoresis analysis of pooled clinical samples.","authors":"Mark J Bailey, Kristy L Shield-Artin, Karen Oliva, Mustafa Ayhan, Simone Reisman, Gregory E Rice","doi":"10.4103/1477-3163.114216","DOIUrl":"https://doi.org/10.4103/1477-3163.114216","url":null,"abstract":"Introduction: Ovarian cancer is the leading cause of death from gynecological cancer. Non-specific symptoms early in disease and the lack of specific biomarkers hinder early diagnosis. Multi-marker blood screening tests have shown promise for improving identification of early stage disease; however, available tests lack sensitivity, and specificity.Materials and methods: In this study, pooled deeply-depleted plasma from women with Stage 1, 2 or 3 ovarian cancer and healthy controls were used to compare the 2-dimensional gel electrophoresis (2-DE) protein profiles and identify potential novel markers of ovarian cancer progression.Results/discussion: Stage-specific variation in biomarker expression was observed. For example, apolipoprotein A1 expression is relatively low in control and Stage 1, but shows a substantial increase in Stage 2 and 3, thus, potential of utility for disease confirmation rather than early detection. A better marker for early stage disease was tropomyosin 4 (TPM4). The expression of TPM4 increased by 2-fold in Stage 2 before returning to \"normal\" levels in Stage 3 disease. Multiple isoforms were also identified for some proteins and in some cases, displayed stage-specific expression. An interesting example was fibrinogen alpha, for which 8 isoforms were identified. Four displayed a moderate increase at Stage 1 and a substantial increase for Stages 2 and 3 while the other 4 showed only moderate increases.Conclusion: Herein is provided an improved summary of blood protein profiles for women with ovarian cancer stratified by stage.","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.114216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31582557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Effects of maternal dietary exposure to cadmium during pregnancy on mammary cancer risk among female offspring. 母亲在怀孕期间饮食接触镉对女性后代患乳腺癌风险的影响。

Journal of Carcinogenesis Pub Date : 2013-06-29 Print Date: 2013-01-01 DOI: 10.4103/1477-3163.114219

Jennifer Davis, Galam Khan, Mary Beth Martin, Leena Hilakivi-Clarke

{"title":"Effects of maternal dietary exposure to cadmium during pregnancy on mammary cancer risk among female offspring.","authors":"Jennifer Davis, Galam Khan, Mary Beth Martin, Leena Hilakivi-Clarke","doi":"10.4103/1477-3163.114219","DOIUrl":"https://doi.org/10.4103/1477-3163.114219","url":null,"abstract":"Background: Since heavy metal cadmium is an endocrine disrupting chemical, we investigated whether maternal exposure to cadmium during the pregnancy alters mammary tumorigenesis among female offspring.Methods: From gestation day 10 to day 19, pregnant rat dams were fed modified American Institute of Nutrition (AIN93G) diet containing 39% energy from fat (baseline diet), or the baseline diet containing moderate (75 μg/kg of feed) or high (150 μg/kg) cadmium levels. Some dams were injected with 10 μg 17β-estradiol (E2) daily between gestation days 10 and 19.Results: Rats exposed to a moderate cadmium dose in utero were heavier and exhibited accelerated puberty onset. Both moderate and high cadmium dose led to increased circulating testosterone levels and reduced the expression of androgen receptor in the mammary gland. The moderate cadmium dose mimicked the effects of in utero E2 exposure on mammary gland morphology and increased both the number of terminal end buds and pre-malignant hyperplastic alveolar nodules (HANs), but in contrast to the E2, it did not increase 7, 12-dimethylbenz (a) anthracene-induced mammary tumorigenesis.Conclusions: The effects of in utero cadmium exposure were dependent on the dose given to pregnant dams: Moderate, but not high, cadmium dose mimicked some of the effects seen in the in utero E2 exposed rats, such as increased HANs in the mammary gland.","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.114219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31582558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Applications of metabolomics in cancer research. 代谢组学在癌症研究中的应用。

Journal of Carcinogenesis Pub Date : 2013-06-18 Print Date: 2013-01-01 DOI: 10.4103/1477-3163.113622

Kathleen A Vermeersch, Mark P Styczynski

引用次数: 89

Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of activated T-cells-driven c-MYC expression. 洋地黄素通过抑制活化t细胞驱动的c-MYC表达的核因子诱导癌细胞凋亡。

Journal of Carcinogenesis Pub Date : 2013-05-20 Print Date: 2013-01-01 DOI: 10.4103/1477-3163.112268

Qing Feng Yang, Clifton L Dalgard, Ofer Eidelman, Catherine Jozwik, Bette S Pollard, Meera Srivastava, Harvey B Pollard

{"title":"Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of activated T-cells-driven c-MYC expression.","authors":"Qing Feng Yang, Clifton L Dalgard, Ofer Eidelman, Catherine Jozwik, Bette S Pollard, Meera Srivastava, Harvey B Pollard","doi":"10.4103/1477-3163.112268","DOIUrl":"https://doi.org/10.4103/1477-3163.112268","url":null,"abstract":"Background: Cardiac glycosides such as digitoxin have been shown to directly cause apoptotic death of cancer cells both in vitro, and in vivo. However, the mechanism connecting cardiac glycoside action to apoptosis is not known. It has been reported that compounds resembling digitoxin are able to reduce c-MYC expression. Furthermore, it has been previously shown that the transcription of c-MYC depends on nuclear factor of activated T-cells (NFAT) binding sites in the c-MYC promoter. We have therefore hypothesized that NFAT might mediate digitoxin effects on c-MYC mRNA message.Materials and methods: We have chosen to study this process in HeLa cells where structurally intact c-MYC genes in 8q24 co-localize with human papilloma virus 18 at all integration sites.Results: Here we show that within the 1(st) h following treatment with digitoxin, a significant reduction in c-MYC mRNA occurs. This is followed by a precipitous loss of c-MYC protein, activation of caspase 3, and subsequent apoptotic cell death. To test the NFAT-dependence mechanism, we analyzed the effects of digitoxin on NFAT isoform-dependent auto-activation of a NFAT-luciferase expression system. Drug dependent effects on expression varied according to each of the four canonical NFAT isoforms (1, 2, 3 or 4). The most digitoxin-sensitive NFAT isoform was NFAT1. Using c-MYC chromatin immune precipitation, we find that digitoxin inhibits interaction of NFAT1 with the proximal c-MYC promoter.Conclusions: These results suggest that the carcinotoxic activity of digitoxin includes suppression of NFAT-driven c-MYC expression.","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.112268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31582555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Targeted agents in non-small cell lung cancer therapy: What is there on the horizon? 靶向药物用于非小细胞肺癌治疗:有什么新进展?

Journal of Carcinogenesis Pub Date : 2013-03-18 Print Date: 2013-01-01 DOI: 10.4103/1477-3163.109253

Victoria M Villaflor, Ravi Salgia

引用次数: 13

Human endogenous retroviral K element encodes fusogenic activity in melanoma cells. 人内源性逆转录病毒K元件编码黑色素瘤细胞的促聚变活性。

Journal of Carcinogenesis Pub Date : 2013-03-16 Print Date: 2013-01-01 DOI: 10.4103/1477-3163.109032

Gengming Huang, Zhongwu Li, Xiaohua Wan, Yue Wang, Jianli Dong

{"title":"Human endogenous retroviral K element encodes fusogenic activity in melanoma cells.","authors":"Gengming Huang, Zhongwu Li, Xiaohua Wan, Yue Wang, Jianli Dong","doi":"10.4103/1477-3163.109032","DOIUrl":"https://doi.org/10.4103/1477-3163.109032","url":null,"abstract":"Introduction and hypothesis: Nuclear atypia with features of multi nuclei have been detected in human melanoma specimens. We found that the K type human endogenous retroviral element (HERV K) is expressed in such cells. Since cellular syncytia can form when cells are infected with retroviruses, we hypothesized that HERV K expressed in melanoma cells may contribute to the formation of multinuclear atypia cells in melanoma.Experiments and results: We specifically inhibited HERV K expression using RNA interference (RNAi) and monoclonal antibodies and observed dramatic reduction of intercellular fusion of cultured melanoma cells. Importantly, we identified loss of heterozygosity (LOH)of D19S433 in a cell clone that survived and proliferated after cell fusion.Conclusion: Our results support the notion that proteins encoded by HERV K can mediate intercellular fusion of melanoma cells, which may generate multinuclear cells and drive the evolution of genetic changes that provide growth and survival advantages.","PeriodicalId":52464,"journal":{"name":"Journal of Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4103/1477-3163.109032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31461965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 40

Cell of origin of lung cancer. 肺癌的起源细胞。

Journal of Carcinogenesis Pub Date : 2013-03-16 Print Date: 2013-01-01 DOI: 10.4103/1477-3163.109033

Jennifer M Hanna, Mark W Onaitis

引用次数: 137