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Special Issue "Advances in Molecular Oncology 2014"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology".

Deadline for manuscript submissions: closed (31 December 2014)

Special Issue Editor

Guest Editor
Dr. William Chi-shing Cho

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
Interests: cancer biomarker; chinese medicine; diabetes mellitus; evidence-based medicine; genomics; microRNA; molecular diagnostics; nasopharyngeal carcinoma; non-small cell lung cancer; proteomics

Special Issue Information

Dear Colleagues,

The completion of the human genome project and the availability of high-throughput technologies have led a dramatic change in cancer research. In the past few decades, oncological studies are evolving from traditional to molecular oncology. Numerous researches have contributed to our knowledge of the molecular mechanisms underlying cancer progression, defining pathways that influence cancer therapy and response, as well as developing new tools and therapeutics to prevent or manage cancer more effectively. The field of molecular oncology is growing rapidly and it has a great impact on basic science, clinical study, and translational cancer research. This open-access special issue will bring together original research and review articles on molecular oncology. It highlights new discoveries, approaches, and technical developments in molecular cancer research. The main feature of this special issue is to provide an open-source sharing of significant works in the field of molecular oncology that can advance our understanding of cancer development which may lead to the discovery of novel molecular diagnostic technologies and targeted therapeutics.

Topics of this special issue include, but are not limited to:

  • Key biological processes such as: genome instability, checkpoints, cell cycle, DNA repair, apoptosis, autophagy, angiogenesis, invasion and metastasis, signaling pathway, "drivers" versus "passengers"
  • Molecular tumor pathology
  • Tumor microenvironment
  • Cancer epidemiology and prevention
  • Cancer biomarkers: screening, diagnosis, treatment response, prognosis
  • Cancer therapy: target discovery, drug design, resistance, targeted therapy, theranostics, personalized medicine
  • Translational cancer research
  • High-throughput technologies: genomics, epigenomics, proteomics, metabolomics, microarray, next generation sequencing, and other omics technologies
  • Genomic and proteomic databases and applications

Dr. William Chi-shing Cho
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs).


Keywords

  • angiogenesis
  • animal models
  • apoptosis
  • autophagy
  • cancer biomarker
  • cancer epidemiology
  • cancer prevention
  • cancer screening
  • cancer stem cells
  • cell cycle
  • clinical decision-making
  • CLIA (Clinical Laboratory Improvement Amendments)
  • clinical trial
  • copy number variation
  • DNA repair
  • epigenomics
  • gene expression profiling
  • genome instability
  • genomic database
  • genomics
  • invasion
  • metabolomics
  • metastasis
  • methylation
  • microarray
  • microRNA
  • molecular diagnostics
  • molecular tumor pathology
  • next generation sequencing
  • oncogenic driver
  • noncoding RNA
  • omics
  • personalized medicine
  • precision medicine
  • prognosis
  • functional proteomics
  • signaling pathway
  • SNP genotyping
  • targeted therapy
  • theranostics
  • therapeutic targets
  • translational cancer research
  • treatment response
  • tumor microenvironment

Related Special Issues

Published Papers (30 papers)

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Research

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Open AccessArticle Psoralea glandulosa as a Potential Source of Anticancer Agents for Melanoma Treatment
Int. J. Mol. Sci. 2015, 16(4), 7944-7959; doi:10.3390/ijms16047944
Received: 12 March 2015 / Revised: 30 March 2015 / Accepted: 31 March 2015 / Published: 9 April 2015
Cited by 2 | PDF Full-text (1962 KB) | HTML Full-text | XML Full-text
Abstract
With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol ( [...] Read more.
With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol (1), 3-hydroxy-bakuchiol (2) and 12-hydroxy-iso-bakuchiol (3)) against melanoma cells (A2058). In addition, the effect in cancer cells of bakuchiol acetate (4), a semi-synthetic derivative of bakuchiol, was examined. The results obtained show that the resinous exudate inhibited the growth of cancer cells with IC50 value of 10.5 μg/mL after 48 h of treatment, while, for pure compounds, the most active was the semi-synthetic compound 4. Our data also demonstrate that resin is able to induce apoptotic cell death, which could be related to an overall action of the meroterpenes present. In addition, our data seem to indicate that the apoptosis correlated to the tested products appears, at least in part, to be associated with an increase of reactive oxygen species (ROS) production. In summary, our study provides the first evidence that P. glandulosa may be considered a source of useful molecules in the development of analogues with more potent efficacy against melanoma cells. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle In Utero Exposure to Low-Dose Alcohol Induces Reprogramming of Mammary Development and Tumor Risk in MMTV-erbB-2 Transgenic Mice
Int. J. Mol. Sci. 2015, 16(4), 7655-7671; doi:10.3390/ijms16047655
Received: 1 January 2015 / Revised: 30 March 2015 / Accepted: 30 March 2015 / Published: 7 April 2015
Cited by 1 | PDF Full-text (3645 KB) | HTML Full-text | XML Full-text
Abstract
There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were [...] Read more.
There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Exploring Prostate Cancer Genome Reveals Simultaneous Losses of PTEN, FAS and PAPSS2 in Patients with PSA Recurrence after Radical Prostatectomy
Int. J. Mol. Sci. 2015, 16(2), 3856-3869; doi:10.3390/ijms16023856
Received: 18 December 2014 / Accepted: 5 February 2015 / Published: 11 February 2015
Cited by 1 | PDF Full-text (1287 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The multifocal nature of prostate cancer (PCa) creates a challenge to patients’ outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients’ [...] Read more.
The multifocal nature of prostate cancer (PCa) creates a challenge to patients’ outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients’ clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2.0–9.7 (mean 5.4) years, copy number variation (CNV) data was evaluated for association with patients’ PSA status during follow-up. From our results, the loss of unique genes on 10q23.31 and 10q23.2–10q23.31 were identified to be significantly associated to PSA recurrence (p < 0.05). The implication of PTEN and FAS loss (10q23.31) support previous reports due to their critical roles in prostate carcinogenesis. Furthermore, we hypothesize that the PAPSS2 gene (10q23.2–10q23.31) may be functionally relevant in post-operative PSA recurrence because of its reported role in androgen biosynthesis. It is suggestive that the loss of the susceptible region on chromosome 10q, which implicates PTEN, FAS and PAPSS2 may serve as genetic predictors of PSA recurrence after radical prostatectomy. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Expression and Significance of CD44, CD47 and c-met in Ovarian Clear Cell Carcinoma
Int. J. Mol. Sci. 2015, 16(2), 3391-3404; doi:10.3390/ijms16023391
Received: 22 November 2014 / Revised: 9 December 2014 / Accepted: 9 January 2015 / Published: 4 February 2015
Cited by 9 | PDF Full-text (1480 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aims: The aim of the present study is to investigate the differential expression of CD44, CD47 and c-met in ovarian clear cell carcinoma (OCCC), the correlation in their expression and their relationship with the biological behavior of OCCC. Methods: We used immunohistochemistry [...] Read more.
Aims: The aim of the present study is to investigate the differential expression of CD44, CD47 and c-met in ovarian clear cell carcinoma (OCCC), the correlation in their expression and their relationship with the biological behavior of OCCC. Methods: We used immunohistochemistry to examine the expression of CD44, CD47 and c-met in OCCC (86 cases) and investigated the effects of the expression and interaction of these molecules on the development of OCCC. Results: CD44, CD47 and c-met expression was significantly high in OCCC. Expression of CD44 and CD47 correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05), and expression of c-met correlated with chemotherapy resistance and prognosis (all p < 0.05), but did not correlate with lymph node metastasis (all p > 0.05). The surgical stage, CD44, CD47 and c-met expression were independent risk factors for OCCC prognosis (all p < 0.05). Patients with low levels of CD44, CD47 and c-met showed better survival than those with high levels (all p < 0.05). There was a positive correlation between CD44 (or CD47) and c-met, as well as between CD44 and CD47 (the Spearman correlation coefficient rs was 0.783, 0.776 and 0.835, respectively, all p < 0.01). Additionally, pairwise correlation analysis of these three markers shows that the high expression of CD44/CD47, CD44/c-met and CD47/c-met were correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05), but did not correlate with lymph node metastasis (all p > 0.05). Conclusions: Expression of CD44, CD47 and c-met was upregulated in OCCC and pairwise correlation. CD44, CD47 and c-met may have synergistic effects on the development of OCCC and are prognostic factors for ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma
Int. J. Mol. Sci. 2015, 16(2), 2294-2306; doi:10.3390/ijms16022294
Received: 22 November 2014 / Revised: 18 December 2014 / Accepted: 15 January 2015 / Published: 22 January 2015
Cited by 5 | PDF Full-text (2427 KB) | HTML Full-text | XML Full-text
Abstract
F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) [...] Read more.
F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle High Levels of KAP1 Expression Are Associated with Aggressive Clinical Features in Ovarian Cancer
Int. J. Mol. Sci. 2015, 16(1), 363-377; doi:10.3390/ijms16010363
Received: 7 November 2014 / Accepted: 16 December 2014 / Published: 26 December 2014
Cited by 2 | PDF Full-text (10295 KB) | HTML Full-text | XML Full-text
Abstract
KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 [...] Read more.
KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230–0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Connexin 43 Suppresses Tumor Angiogenesis by Down-Regulation of Vascular Endothelial Growth Factor via Hypoxic-Induced Factor-1α
Int. J. Mol. Sci. 2015, 16(1), 439-451; doi:10.3390/ijms16010439
Received: 18 November 2014 / Accepted: 19 December 2014 / Published: 26 December 2014
Cited by 4 | PDF Full-text (2334 KB) | HTML Full-text | XML Full-text
Abstract
Previous work showed that connexin 43 (Cx43) reduced the expression of hypoxic-induced factor-1α (HIF-1α) in astrocytes. HIF-1α is a master transcription factor for angiogenesis in tumor. Angiogenesis is essential for tumor progression. Here, we investigated the role of Cx43 in vascular endothelial [...] Read more.
Previous work showed that connexin 43 (Cx43) reduced the expression of hypoxic-induced factor-1α (HIF-1α) in astrocytes. HIF-1α is a master transcription factor for angiogenesis in tumor. Angiogenesis is essential for tumor progression. Here, we investigated the role of Cx43 in vascular endothelial growth factor (VEGF) production and angiogenesis in murine tumor. In the study, mouse B16F10 and 4T1 cells were overexpressed or knockdown with Cx43. The expression profiles as well as activity of the treated cells were examined. Furthermore, reduced Cx43 expression in B16F10 and 4T1 cells causes increased expression of VEGF and enhanced the proliferation of endothelial cells. On the contrary, the expression of VEGF and the proliferation of endothelial were increased in the conditioned medium of Cx43-knockdown tumor cells. We subcutaneously transplanted Cx43-overexpressing B16F10 cells into mice to evaluate the roles of Cx43 in the tumor angiogenesis. Both tumor size and the number of vessels growing in the tumor were markedly decreased compare with control group. Our findings suggest that Cx43 inhibited tumor growth by reducing angiogenesis. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Twist-1 Up-Regulation in Carcinoma Correlates to Poor Survival
Int. J. Mol. Sci. 2014, 15(12), 21621-21630; doi:10.3390/ijms151221621
Received: 16 August 2014 / Revised: 20 October 2014 / Accepted: 11 November 2014 / Published: 25 November 2014
Cited by 10 | PDF Full-text (1018 KB) | HTML Full-text | XML Full-text
Abstract
Epithelial-to-mesenchymal transition (EMT) facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through E-box-responsive elements. There are two twist-like proteins, Twist-1 and Twist-2, sharing high structural homology in mammals. Twist-1 was found [...] Read more.
Epithelial-to-mesenchymal transition (EMT) facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through E-box-responsive elements. There are two twist-like proteins, Twist-1 and Twist-2, sharing high structural homology in mammals. Twist-1 was found to be a key factor in the promotion of metastasis of cancer cells, and is known to induce EMT. Twist-1 participation in carcinoma progression and metastasis has been reported in a variety of tumors. However, controversy exists concerning the correlation between Twist-1 and prognostic value with respect to carcinoma. A systematic review and meta-analysis were performed to determine whether the expression of Twist-1 was associated with the prognosis of carcinoma patients. This analysis included 17 studies: four studies evaluated lung cancer, three evaluated head and neck cancer, two evaluated breast cancer, two evaluated esophageal cancer, two evaluated liver cancer and one each evaluated osteosarcoma, bladder, cervical and ovarian cancer. A total of 2006 patients were enrolled in these studies, and the median trial sample size was 118 patients. Twist-1 expression was associated with worse overall survival (OS) at both 3 years (hazard ratio “HR” for death = 2.13, 95% CI = 1.86 to 2.45, p < 0.001) and 5 years (HR for death = 2.01, 95% CI = 1.76 to 2.29, p < 0.001). Expression of Twist-1 is associated with worse survival in carcinoma. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Growth Suppression of Colorectal Cancer by Plant-Derived Multiple mAb CO17-1A × BR55 via Inhibition of ERK1/2 Phosphorylation
Int. J. Mol. Sci. 2014, 15(11), 21105-21119; doi:10.3390/ijms151121105
Received: 16 September 2014 / Revised: 31 October 2014 / Accepted: 6 November 2014 / Published: 14 November 2014
Cited by 1 | PDF Full-text (6877 KB) | HTML Full-text | XML Full-text
Abstract
We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal [...] Read more.
We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAbP) CO17-1A and mAbP CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAbP CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAbP CO17-1A × BR55-treated. The mAbP CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAbP CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAbP CO17-1A × BR55. In addition, the mAbP CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAbP CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAbP CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle MicroRNA-130b Promotes Cell Aggressiveness by Inhibiting Peroxisome Proliferator-Activated Receptor Gamma in Human Hepatocellular Carcinoma
Int. J. Mol. Sci. 2014, 15(11), 20486-20499; doi:10.3390/ijms151120486
Received: 25 August 2014 / Revised: 1 November 2014 / Accepted: 4 November 2014 / Published: 7 November 2014
Cited by 21 | PDF Full-text (4460 KB) | HTML Full-text | XML Full-text
Abstract
MircroRNA-130b (miR-130b) is proposed as a novel tumor-related miRNA and has been found to be significantly dysregulated in tumors. In this study, the expression level of miR-130b was found to be obviously higher in hepatocellular carcinoma (HCC) tissues than that in nontumor [...] Read more.
MircroRNA-130b (miR-130b) is proposed as a novel tumor-related miRNA and has been found to be significantly dysregulated in tumors. In this study, the expression level of miR-130b was found to be obviously higher in hepatocellular carcinoma (HCC) tissues than that in nontumor tissues. Further, miR-130b was expressed at significantly higher levels in aggressive and recurrent tumor tissues. Clinical analysis indicated that high-expression of miR-130b was prominently correlated with venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage in HCC. Elevated miR-130b expression was observed in all HCC cell lines (HepG2, SMMC-7721, Huh7, Hep3B and MHCC97H) as compared with that in a nontransformed hepatic cell line (LO2). Furthermore, an inverse correlation between miR-130b and E-cadherin and a positive correlation between miR-130b and Vimentin were observed in HCC tissues. Down-regulation of miR-130b expression reduced invasion and migration in both Hep3B and MHCC97H cells. Peroxisome proliferator-activated receptor gamma (PPAR-γ) was inversely correlated with miR-130b expression in HCC tissues. In addition, down-regulation of miR-130b restored PPAR-γ expression and subsequently suppressed epithelial-mesenchymal transition (EMT) in HCC cells. We identified PPARγ as a direct target of miR-130b in HCC in vitro. Notably, PPAR-γ knockdown abolished down-regulation of miR-130b-inhibited EMT in MHCC97H cells. In conclusion, miR-130b may promote HCC cell migration and invasion by inhibiting PPAR-γ and subsequently inducing EMT. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Validation of Bmi1 as a Therapeutic Target of Hepatocellular Carcinoma in Mice
Int. J. Mol. Sci. 2014, 15(11), 20004-20021; doi:10.3390/ijms151120004
Received: 23 August 2014 / Revised: 12 October 2014 / Accepted: 23 October 2014 / Published: 3 November 2014
Cited by 1 | PDF Full-text (6783 KB) | HTML Full-text | XML Full-text
Abstract
Bmi1 is a member of the polycomb group family of proteins, and it drives the carcinogenesis of various cancers and governs the self-renewal of multiple types of stem cells. Our previous studies have revealed that Bmi1 acts as an oncogene in hepatic [...] Read more.
Bmi1 is a member of the polycomb group family of proteins, and it drives the carcinogenesis of various cancers and governs the self-renewal of multiple types of stem cells. Our previous studies have revealed that Bmi1 acts as an oncogene in hepatic carcinogenesis in an INK4a/ARF locus independent manner. However, whether Bmi1 can be used as a potential target for hepatocellular carcinoma treatment has not been fully confirmed yet. Here, we show that perturbation of Bmi1 expression by using short hairpin RNA can inhibit the tumorigenicity and tumor growth of hepatocellular carcinoma cells both in vitro and in vivo. Importantly, Bmi1 knockdown can block the tumor growth, both in the initiating stages and the fast growing stages. Cellular biology analysis revealed that Bmi1 knockdown induces cell cycle arrest and apoptosis. Our findings verify Bmi1 as a qualified treatment target for hepatocellular carcinoma (HCC) and support Bmi1 targeting treatment with chemotherapeutic agents. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Evaluating the Role of PTH in Promotion of Chondrosarcoma Cell Proliferation and Invasion by Inhibiting Primary Cilia Expression
Int. J. Mol. Sci. 2014, 15(11), 19816-19831; doi:10.3390/ijms151119816
Received: 2 September 2014 / Revised: 15 October 2014 / Accepted: 23 October 2014 / Published: 31 October 2014
PDF Full-text (3051 KB) | HTML Full-text | XML Full-text
Abstract
Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP) has a close relationship with various tumor types. The objectives of this study were to research the [...] Read more.
Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP) has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84), and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Active Transport Can Greatly Enhance Cdc20:Mad2 Formation
Int. J. Mol. Sci. 2014, 15(10), 19074-19091; doi:10.3390/ijms151019074
Received: 28 August 2014 / Revised: 30 September 2014 / Accepted: 11 October 2014 / Published: 21 October 2014
Cited by 5 | PDF Full-text (885 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To guarantee genomic integrity and viability, the cell must ensure proper distribution of the replicated chromosomes among the two daughter cells in mitosis. The mitotic spindle assembly checkpoint (SAC) is a central regulatory mechanism to achieve this goal. A dysfunction of this [...] Read more.
To guarantee genomic integrity and viability, the cell must ensure proper distribution of the replicated chromosomes among the two daughter cells in mitosis. The mitotic spindle assembly checkpoint (SAC) is a central regulatory mechanism to achieve this goal. A dysfunction of this checkpoint may lead to aneuploidy and likely contributes to the development of cancer. Kinetochores of unattached or misaligned chromosomes are thought to generate a diffusible “wait-anaphase” signal, which is the basis for downstream events to inhibit the anaphase promoting complex/cyclosome (APC/C). The rate of Cdc20:C-Mad2 complex formation at the kinetochore is a key regulatory factor in the context of APC/C inhibition. Computer simulations of a quantitative SAC model show that the formation of Cdc20:C-Mad2 is too slow for checkpoint maintenance when cytosolic O-Mad2 has to encounter kinetochores by diffusion alone. Here, we show that an active transport of O-Mad2 towards the spindle mid-zone increases the efficiency of Mad2-activation. Our in-silico data indicate that this mechanism can greatly enhance the formation of Cdc20:Mad2 and furthermore gives an explanation on how the “wait-anaphase” signal can dissolve abruptly within a short time. Our results help to understand parts of the SAC mechanism that remain unclear. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle TPX2 Is a Prognostic Marker and Contributes to Growth and Metastasis of Human Hepatocellular Carcinoma
Int. J. Mol. Sci. 2014, 15(10), 18148-18161; doi:10.3390/ijms151018148
Received: 2 September 2014 / Revised: 16 September 2014 / Accepted: 26 September 2014 / Published: 9 October 2014
Cited by 7 | PDF Full-text (2022 KB) | HTML Full-text | XML Full-text
Abstract
Targeting protein for Xenopus kinesin-like protein 2 (TPX2), a microtubule-associated protein, impacts spindle assembly in human cells. Several studies have demonstrated that TPX2 is overexpressed in different types of human cancers and promotes tumor growth and metastasis. In this study, we found [...] Read more.
Targeting protein for Xenopus kinesin-like protein 2 (TPX2), a microtubule-associated protein, impacts spindle assembly in human cells. Several studies have demonstrated that TPX2 is overexpressed in different types of human cancers and promotes tumor growth and metastasis. In this study, we found that the expression level of TPX2 was obviously higher in hepatocellular carcinoma (HCC) tissues than in matched nontumor tissues. Elevated expressions of TPX2 mRNA were observed in all HCC cell lines (HepG2, Hep3B, SMMC-7721, Bel-7402 and Huh7) as compared with that in a non-transformed hepatic cell line (LO2). Clinical analysis indicated that the positive expression of TPX2 was significantly correlated with venous infiltration, high Edmondson-Steiner grading and advanced TNM tumor stage in HCC. Furthermore, TPX2 was a novel prognostic marker for predicting 5-year overall survival (OS) and disease-free survival (DFS) of HCC patients. In vitro studies found that TPX2 knockdown significantly inhibited cell proliferation and viability in both Hep3B and HepG2 cells. Moreover, TPX2 knockdown obviously slowed down tumor growth in a nude mouse xenograft model. Otherwise, TPX2 knockdown prominently suppressed HCC cell invasion and migration. In conclusion, these results indicate that TPX2 may serve as a prognostic marker and promotes tumorigenesis and metastasis of HCC. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Expression Profiling of Exosomal miRNAs Derived from Human Esophageal Cancer Cells by Solexa High-Throughput Sequencing
Int. J. Mol. Sci. 2014, 15(9), 15530-15551; doi:10.3390/ijms150915530
Received: 10 May 2014 / Revised: 28 July 2014 / Accepted: 19 August 2014 / Published: 2 September 2014
Cited by 14 | PDF Full-text (5289 KB) | HTML Full-text | XML Full-text
Abstract
Cellular genetic materials, such as microRNAs (miRNAs), mRNAs and proteins, are packaged inside exosomes, small membrane vesicles of endocytic origin that are released into the extracellular environment. These cellular genetic materials can be delivered into recipient cells, where they exert their respective [...] Read more.
Cellular genetic materials, such as microRNAs (miRNAs), mRNAs and proteins, are packaged inside exosomes, small membrane vesicles of endocytic origin that are released into the extracellular environment. These cellular genetic materials can be delivered into recipient cells, where they exert their respective biological effects. However, the miRNA profiles and biological functions of exosomes secreted by cancer cells remain unknown. The present study explored the miRNA expression profile and distribution characteristics of exosomes derived from human esophageal cancer cells through Solexa high-throughput sequencing. Results showed that 56,421 (2.94%) unique sequences in cells and 7727 (0.63%) in exosomes matched known miRNAs. A total of 342 and 48 known miRNAs were identified in cells and exosomes, respectively. Moreover, 64 and 32 novel miRNAs were predicted in cells and exosomes, respectively. Significant differences in miRNA expression profiles were found between human esophageal cancer cells and exosomes. These findings provided new insights into the characteristics of miRNAs in exosomes derived from human esophageal cancer cells and the specific roles of miRNAs in intercellular communication mediated by exosomes in esophageal cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle MRC2 Expression Correlates with TGFβ1 and Survival in Hepatocellular Carcinoma
Int. J. Mol. Sci. 2014, 15(9), 15011-15025; doi:10.3390/ijms150915011
Received: 22 April 2014 / Revised: 10 July 2014 / Accepted: 20 August 2014 / Published: 26 August 2014
Cited by 7 | PDF Full-text (3625 KB) | HTML Full-text | XML Full-text
Abstract
MRC2 (Mannose Receptor C Type 2) is a constitutively recycling endocytic receptor belonging to the mannose receptor family, which has been found to be closely involved with cancer metastasis. This study attempted to determine MRC2 expression on hepatocellular carcinoma (HCC) and its [...] Read more.
MRC2 (Mannose Receptor C Type 2) is a constitutively recycling endocytic receptor belonging to the mannose receptor family, which has been found to be closely involved with cancer metastasis. This study attempted to determine MRC2 expression on hepatocellular carcinoma (HCC) and its significance on postsurgical prognosis of HCCs. The expression of both MRC2 and transforming growth factor (TGFβ1) was detected in tumor tissues and adjacent liver tissues from 96 HCCs by immunohistochemistry staining, and it was found that MRC2 expression in HCC tissues was significantly higher than in adjacent liver tissues. HCCs with higher MRC2 expression had worse prognosis after liver resection. Univariate analysis showed that advanced TNM staging of HCC, higher Edmonson-Steiner classification, intrahepatic metastases, portal vein invasion, higher MRC2 and higher TGFβ1 were the poor prognostic factors. Furthermore, multivariate analysis revealed that intrahepatic metastases, higher MRC2 and higher TGFβ1 were the independent prognostic factors. TGFβ1 treatment up-regulated MRC2 expression, cell migration and invasion of Huh7 cells notably. In addition, knockdown of MRC2 repressed the effect of TGFβ1 on cell migration and invasion. These data suggest that MRC2 overexpression predicts poor prognosis of HCCs after liver resection and MRC2 potentially contributed to TGFβ1-driven up-regulation of cell migration and invasion in HCC. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Up-Regulated FASN Expression Promotes Transcoelomic Metastasis of Ovarian Cancer Cell through Epithelial-Mesenchymal Transition
Int. J. Mol. Sci. 2014, 15(7), 11539-11554; doi:10.3390/ijms150711539
Received: 30 April 2014 / Revised: 17 June 2014 / Accepted: 20 June 2014 / Published: 27 June 2014
Cited by 5 | PDF Full-text (1937 KB) | HTML Full-text | XML Full-text
Abstract
Fatty acid synthase (FASN), responsible for the de novo synthesis of fatty acids, has been shown to act as an oncogene in various human cancers. However, the mechanisms by which FASN favors the progression of ovarian carcinoma remain unknown. In this study, [...] Read more.
Fatty acid synthase (FASN), responsible for the de novo synthesis of fatty acids, has been shown to act as an oncogene in various human cancers. However, the mechanisms by which FASN favors the progression of ovarian carcinoma remain unknown. In this study, we evaluated FASN expression in ovarian cancer and investigated how FASN regulates the aggressiveness of ovarian cancer cells. Our results show that increased FASN is associated with the peritoneal metastasis of ovarian cancers. Over-expression of FASN results in a significant increase of tumor burden in peritoneal dissemination, accompanied by augment in cellular colony formation and metastatic ability. Correspondingly, FASN knockdown using RNA interference in ovarian cancer cells inhibits the migration in vitro and experimental peritoneal dissemination in vivo. Mechanistic studies reveal that FASN promotes Epithelial-mesenchymal Transition (EMT) via a transcriptional regulation of E-cadherin and N-cadherin, which is also confirmed by luciferase promoter activity analysis. Taken together, our work demonstrates that FASN promotes the peritoneal dissemination of ovarian cancer cells, at least in part through the induction of EMT. These findings suggest that FASN plays a critical role in the peritoneal metastasis of ovarian cancer. Targeting de novo lipogenesis may have a therapeutic potential for advanced ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Figures

Open AccessArticle Clinical Impact of Tumor-Infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma
Int. J. Mol. Sci. 2014, 15(6), 9718-9734; doi:10.3390/ijms15069718
Received: 1 May 2014 / Revised: 16 May 2014 / Accepted: 22 May 2014 / Published: 30 May 2014
Cited by 2 | PDF Full-text (1616 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Primary small cell esophageal carcinoma is a rare and aggressive type of gastrointestinal cancer with poor prognosis. In the present study, the impact of tumour infiltrating inflammatory cells on clinico-pathological characteristics and the patients’ prognosis were analysed. A total of 36 small [...] Read more.
Primary small cell esophageal carcinoma is a rare and aggressive type of gastrointestinal cancer with poor prognosis. In the present study, the impact of tumour infiltrating inflammatory cells on clinico-pathological characteristics and the patients’ prognosis were analysed. A total of 36 small cell esophageal carcinomas, 19 adjacent normal tissues and 16 esophageal squamous cell carcinoma samples were collected. Qualified pathologists examined eosinophils, neutrophils, lymphocytes and macrophages on histochemical slides. The infiltration of eosinophils and macrophages in small cell esophageal carcinoma was significantly increased as compared with tumor adjacent normal tissues, and was significantly less in esophageal squamous cell carcinoma. Macrophage count was significantly associated with (p = 0.015) lymph node—stage in small cell esophageal carcinoma. When we grouped patients into two groups by counts of infiltrated inflammatory cells, Kaplan-Meier analysis revealed that high macrophage infiltration group (p = 0.004) and high eosinophil infiltration group (p = 0.027) had significantly enhanced survival. In addition, multivariate analysis unveiled that eosinophil count (p = 0.002) and chemotherapy (Yes vs. No, p = 0.001) were independent prognostic indicators. Taken together, infiltration of macrophages and eosinophils into the solid tumor appear to be important in the progression of small cell esophageal carcinoma and patients’ prognosis. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle MicroRNA-103 Promotes Colorectal Cancer by Targeting Tumor Suppressor DICER and PTEN
Int. J. Mol. Sci. 2014, 15(5), 8458-8472; doi:10.3390/ijms15058458
Received: 8 March 2014 / Revised: 17 April 2014 / Accepted: 18 April 2014 / Published: 13 May 2014
Cited by 12 | PDF Full-text (2278 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms for miRNAs in colorectal cancer remain largely unknown. Here, we found that miR-103 is up-regulated in colorectal cancer [...] Read more.
MicroRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms for miRNAs in colorectal cancer remain largely unknown. Here, we found that miR-103 is up-regulated in colorectal cancer and its overexpression is closely associated with tumor proliferation and migration. In addition, repressing the expression of miR-103 apparently inhibits colorectal cancer cell proliferation and migration in vitro and HCT-116 xenograft tumor growth in vivo. Subsequent software analysis and dual-luciferase reporter assay identified two tumor suppressor genes DICER and PTEN as direct targets of miR-103, and up-regulation of DICER and PTEN obtained similar results to that occurred in the silencing of miR-103. In addition, restoration of DICER and PTEN can inhibit miR-103-induced colorectal cancer cell proliferation and migration. Our data collectively demonstrate that miR-103 is an oncogene miRNA that promotes colorectal cancer proliferation and migration through down-regulation of the tumor suppressor genes DICER and PTEN. Thus, miR-103 may represent a new potential diagnostic and therapeutic target for colorectal cancer treatment. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle SREBP-1 Has a Prognostic Role and Contributes to Invasion and Metastasis in Human Hepatocellular Carcinoma
Int. J. Mol. Sci. 2014, 15(5), 7124-7138; doi:10.3390/ijms15057124
Received: 22 February 2014 / Revised: 16 March 2014 / Accepted: 10 April 2014 / Published: 25 April 2014
Cited by 16 | PDF Full-text (3089 KB) | HTML Full-text | XML Full-text
Abstract
Sterol regulatory element-binding protein 1 (SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC), [...] Read more.
Sterol regulatory element-binding protein 1 (SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC), is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05). SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM) stage (p < 0.05). The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05). Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05). In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05). Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05). These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Combined Elevation of microRNA-196a and microRNA-196b in Sera Predicts Unfavorable Prognosis in Patients with Osteosarcomas
Int. J. Mol. Sci. 2014, 15(4), 6544-6555; doi:10.3390/ijms15046544
Received: 13 March 2014 / Revised: 28 March 2014 / Accepted: 9 April 2014 / Published: 17 April 2014
Cited by 14 | PDF Full-text (474 KB) | HTML Full-text | XML Full-text
Abstract
Aim: To investigate whether the aberrant expression of microRNA (miR)-196a and miR-196b can be used as potential prognostic markers of human osteosarcoma. Methods: Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression levels of miR-196a and miR-196b [...] Read more.
Aim: To investigate whether the aberrant expression of microRNA (miR)-196a and miR-196b can be used as potential prognostic markers of human osteosarcoma. Methods: Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression levels of miR-196a and miR-196b in osteosarcoma tissues and patients’ sera. Results: Expression levels of miR-196a and miR-196b in osteosarcoma tissues were both significantly higher than those in noncancerous bone tissues (both p < 0.001), in line with which, the serum levels of the two miRNAs were also markedly upregulated in patients with osteosarcomas compared with healthy controls (both p < 0.001). Then, the elevation of serum miR-196a and miR-196b levels both more frequently occurred in osteosarcoma patients with high tumor grade (p = 0.008 and 0.01, respectively), positive metastasis (p = 0.001 and 0.006, respectively) and recurrence (p = 0.001 and 0.006, respectively). Moreover, high serum miR-196a, high serum miR-196b and conjoined expression of miR-196a/miR-196b were all independent prognostic factors for OS (overall survival) and DFS (disease-free survival) of osteosarcoma patients. Conclusion: Our present data indicate the involvement of miR-196a and miR-196b upregulation in the pathogenesis of osteosarcoma. More importantly, the altered levels of circulating miR-196a and miR-196b might have great potential to serve as novel and non-invasive prognostic factors for this malignancy. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Beclin 1 Expression in Ovarian Tissues and Its Effects on Ovarian Cancer Prognosis
Int. J. Mol. Sci. 2014, 15(4), 5292-5303; doi:10.3390/ijms15045292
Received: 30 December 2013 / Revised: 1 March 2014 / Accepted: 17 March 2014 / Published: 26 March 2014
Cited by 7 | PDF Full-text (439 KB) | HTML Full-text | XML Full-text
Abstract
Beclin 1 is an autophagy-associated protein involved in apoptosis and drug resistance, as well as various malignancies. We investigated the expression of Beclin 1 protein in ovarian epithelial tissues and correlated it with the prognosis of ovarian cancer. Beclin 1 protein expression [...] Read more.
Beclin 1 is an autophagy-associated protein involved in apoptosis and drug resistance, as well as various malignancies. We investigated the expression of Beclin 1 protein in ovarian epithelial tissues and correlated it with the prognosis of ovarian cancer. Beclin 1 protein expression was determined using immunohistochemistry in 148 patients with ovarian epithelial cancer, 26 with ovarian borderline tumor, 25 with benign ovarian tumor, and 30 with normal ovarian tissue. The relationships between Beclin 1 protein expression and ovarian cancer pathological characteristics were analyzed. The risk factors for ovarian cancer prognosis were analyzed using Cox’s regression model. A survival curve was plotted from the follow-up data of 93 patients with ovarian cancer to analyze the effects of Beclin 1 expression on the prognosis of ovarian cancer. The positive rates of Beclin 1 were significantly higher in ovarian epithelial cancer (148) and borderline tumor (26) than in benign ovarian tumor (25) or normal ovarian tissue (30) (all p < 0.001). The surgical stage and Beclin 1 expression were both independent risk factors for ovarian cancer prognosis (both p < 0.05). Patients with high Beclin 1 levels showed better survival than those with low Beclin 1 levels (p = 0.009). Beclin 1 protein is upregulated in ovarian epithelial cancer and is a prognostic factor of ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)

Review

Jump to: Research

Open AccessReview New Therapies for Dedifferentiated Papillary Thyroid Cancer
Int. J. Mol. Sci. 2015, 16(3), 6153-6182; doi:10.3390/ijms16036153
Received: 30 December 2014 / Revised: 14 February 2015 / Accepted: 4 March 2015 / Published: 17 March 2015
Cited by 8 | PDF Full-text (892 KB) | HTML Full-text | XML Full-text
Abstract
The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic [...] Read more.
The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, which fails to respond to RAI, exhibiting a more aggressive behavior. The lack of specific, effective and well-tolerated drugs, the scarcity of data about the association of multi-targeting drugs, and the limited role of radioiodine for dedifferentiated thyroid cancer, call for further efforts in the field of new drugs development. Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF proto-oncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways playing a crucial role in the development of thyroid cancer. Targeted novel compounds have been demonstrated to induce clinical responses and stabilization of disease. Sorafenib has been approved for differentiated thyroid cancer refractory to RAI. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
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Open AccessReview An Epigenetic Regulator: Methyl-CpG-Binding Domain Protein 1 (MBD1)
Int. J. Mol. Sci. 2015, 16(3), 5125-5140; doi:10.3390/ijms16035125
Received: 23 December 2014 / Revised: 13 February 2015 / Accepted: 1 March 2015 / Published: 5 March 2015
Cited by 5 | PDF Full-text (1191 KB) | HTML Full-text | XML Full-text
Abstract
DNA methylation is an important form of epigenetic regulation in both normal development and cancer. Methyl-CpG-binding domain protein 1 (MBD1) is highly related to DNA methylation. Its MBD domain recognizes and binds to methylated CpGs. This binding allows it to trigger methylation [...] Read more.
DNA methylation is an important form of epigenetic regulation in both normal development and cancer. Methyl-CpG-binding domain protein 1 (MBD1) is highly related to DNA methylation. Its MBD domain recognizes and binds to methylated CpGs. This binding allows it to trigger methylation of H3K9 and results in transcriptional repression. The CXXC3 domain of MBD1 makes it a unique member of the MBD family due to its affinity to unmethylated DNA. MBD1 acts as an epigenetic regulator via different mechanisms, such as the formation of the MCAF1/MBD1/SETDB1 complex or the MBD1-HDAC3 complex. As methylation status always changes along with carcinogenesis or neurogenesis, MBD1 with its interacting partners, including proteins and non-coding RNAs, participates in normal or pathological processes and functions in different regulatory systems. Because of the important role of MBD1 in epigenetic regulation, it is a good candidate as a therapeutic target for diseases. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessReview Tumor Progression Locus 2 (Tpl2) Kinase as a Novel Therapeutic Target for Cancer: Double-Sided Effects of Tpl2 on Cancer
Int. J. Mol. Sci. 2015, 16(3), 4471-4491; doi:10.3390/ijms16034471
Received: 29 December 2014 / Revised: 15 February 2015 / Accepted: 15 February 2015 / Published: 25 February 2015
Cited by 1 | PDF Full-text (1373 KB) | HTML Full-text | XML Full-text
Abstract
Tumor progression locus 2 (Tpl2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that conveys various intra- and extra-cellular stimuli to effector proteins of cells provoking adequate adoptive responses. Recent studies have elucidated that Tpl2 is an indispensable signal transducer as [...] Read more.
Tumor progression locus 2 (Tpl2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that conveys various intra- and extra-cellular stimuli to effector proteins of cells provoking adequate adoptive responses. Recent studies have elucidated that Tpl2 is an indispensable signal transducer as an MAP3K family member in diverse signaling pathways that regulate cell proliferation, survival, and death. Since tumorigenesis results from dysregulation of cellular proliferation, differentiation, and apoptosis, Tpl2 participates in many decisive molecular processes of tumor development and progression. Moreover, Tpl2 is closely associated with cytokine release of inflammatory cells, which has crucial effects on not only tumor cells but also tumor microenvironments. These critical roles of Tpl2 in human cancers make it an attractive anti-cancer therapeutic target. However, Tpl2 contradictorily works as a tumor suppressor in some cancers. The double-sided effects of Tpl2 originate from the specific upstream and downstream signaling environment of each tumor, since Tpl2 interacts with various signaling components. This review summarizes recent studies concerning the possible roles of Tpl2 in human cancers and considers its possibility as a therapeutic target, against which novel anti-cancer agents could be developed. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessReview Diverse Roles of SIRT1 in Cancer Biology and Lipid Metabolism
Int. J. Mol. Sci. 2015, 16(1), 950-965; doi:10.3390/ijms16010950
Received: 15 November 2014 / Accepted: 24 December 2014 / Published: 5 January 2015
Cited by 8 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
SIRT1, an NAD+-dependent deacetylase, has been described in the literature as a major player in the regulation of cellular stress responses. Its expression has been shown to be altered in cancer cells, and it targets both histone and non-histone proteins [...] Read more.
SIRT1, an NAD+-dependent deacetylase, has been described in the literature as a major player in the regulation of cellular stress responses. Its expression has been shown to be altered in cancer cells, and it targets both histone and non-histone proteins for deacetylation and thereby alters metabolic programs in response to diverse physiological stress. Interestingly, many of the metabolic pathways that are influenced by SIRT1 are also altered in tumor development. Not only does SIRT1 have the potential to regulate oncogenic factors, it also orchestrates many aspects of metabolism and lipid regulation and recent reports are beginning to connect these areas. SIRT1 influences pathways that provide an alternative means of deriving energy (such as fatty acid oxidation and gluconeogenesis) when a cell encounters nutritive stress, and can therefore lead to altered lipid metabolism in various pathophysiological contexts. This review helps to show the various connections between SIRT1 and major pathways in cellular metabolism and the consequence of SIRT1 deregulation on carcinogenesis and lipid metabolism. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessReview Battle Against Cancer: An Everlasting Saga of p53
Int. J. Mol. Sci. 2014, 15(12), 22109-22127; doi:10.3390/ijms151222109
Received: 20 September 2014 / Revised: 23 October 2014 / Accepted: 25 November 2014 / Published: 1 December 2014
Cited by 8 | PDF Full-text (755 KB) | HTML Full-text | XML Full-text
Abstract
Cancer is one of the most life-threatening diseases characterized by uncontrolled growth and spread of malignant cells. The tumor suppressor p53 is the master regulator of tumor cell growth and proliferation. In response to various stress signals, p53 can be activated and [...] Read more.
Cancer is one of the most life-threatening diseases characterized by uncontrolled growth and spread of malignant cells. The tumor suppressor p53 is the master regulator of tumor cell growth and proliferation. In response to various stress signals, p53 can be activated and transcriptionally induces a myriad of target genes, including both protein-encoding and non-coding genes, controlling cell cycle progression, DNA repair, senescence, apoptosis, autophagy and metabolism of tumor cells. However, around 50% of human cancers harbor mutant p53 and, in the majority of the remaining cancers, p53 is inactivated through multiple mechanisms. Herein, we review the recent progress in understanding the molecular basis of p53 signaling, particularly the newly identified ribosomal stress—p53 pathway, and the development of chemotherapeutics via activating wild-type p53 or restoring mutant p53 functions in cancer. A full understanding of p53 regulation will aid the development of effective cancer treatments. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessReview Large Intervening Non-Coding RNA HOTAIR Is an Indicator of Poor Prognosis and a Therapeutic Target in Human Cancers
Int. J. Mol. Sci. 2014, 15(10), 18985-18999; doi:10.3390/ijms151018985
Received: 25 June 2014 / Revised: 26 September 2014 / Accepted: 1 October 2014 / Published: 20 October 2014
Cited by 14 | PDF Full-text (1018 KB) | HTML Full-text | XML Full-text
Abstract
In the human genome, the fraction of protein-coding genes that are stably transcribed is only up to 2%, with the remaining numerous RNAs having no protein-coding function. These non-coding RNAs (ncRNAs) have received considerable attention in cancer research in recent years. Breakthroughs [...] Read more.
In the human genome, the fraction of protein-coding genes that are stably transcribed is only up to 2%, with the remaining numerous RNAs having no protein-coding function. These non-coding RNAs (ncRNAs) have received considerable attention in cancer research in recent years. Breakthroughs have been made in understanding microRNAs and small interfering RNAs, but larger RNAs such as long ncRNAs (lncRNAs) remain an enigma. One lncRNA, HOX antisense intergenic RNA (HOTAIR), has been shown to be dysregulated in many types of cancer, including breast cancer, colorectal cancer, and hepatoma. HOTAIR functions as a regulatory molecule in a wide variety of biological processes. However, its mechanism of action has not been clearly elucidated. It is widely believed that HOTAIR mediates chromosomal remodeling and coordinates with polycomb repressive complex 2 (PRC2) to regulate gene expression. Further study of HOTAIR-related pathways and the role of HOTAIR in tumorigenesis and tumor progression may identify new treatment targets. In this review, we will focus on the characteristics of HOTAIR, as well as data pertaining to its mechanism and its association with cancers. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
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Open AccessReview Pomegranate and Its Components as Alternative Treatment for Prostate Cancer
Int. J. Mol. Sci. 2014, 15(9), 14949-14966; doi:10.3390/ijms150914949
Received: 23 June 2014 / Revised: 6 August 2014 / Accepted: 18 August 2014 / Published: 25 August 2014
Cited by 12 | PDF Full-text (1590 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used [...] Read more.
Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as “nature’s power fruit”. Recent research has shown that pomegranate juice (PJ) and/or pomegranate extracts (PE) significantly inhibit the growth of prostate cancer cells in culture. In preclinical murine models, PJ and/or PE inhibit growth and angiogenesis of prostate tumors. More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. Results from clinical trials are also promising. PJ and/or PE significantly prolonged the prostate specific antigen (PSA) doubling time in patients with prostate cancer. In this review we discuss data on the effects of PJ and PE on prostate cancer. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessReview Salmonella as an Innovative Therapeutic Antitumor Agent
Int. J. Mol. Sci. 2014, 15(8), 14546-14554; doi:10.3390/ijms150814546
Received: 24 June 2014 / Revised: 28 July 2014 / Accepted: 18 August 2014 / Published: 21 August 2014
Cited by 5 | PDF Full-text (943 KB) | HTML Full-text | XML Full-text
Abstract
Lack of specificity of the therapeutic agent is a primary limitation in the treatment of a tumor. The use of preferentially replicating bacteria as therapeutic agents is an innovative approach to tumor treatment. This is based on the observation that certain obligate [...] Read more.
Lack of specificity of the therapeutic agent is a primary limitation in the treatment of a tumor. The use of preferentially replicating bacteria as therapeutic agents is an innovative approach to tumor treatment. This is based on the observation that certain obligate or facultative anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. Bacteria have been employed as antitumor agents that are capable of preferentially amplifying within tumors and inhibiting their growth. Moreover, bacteria-derived factors have an immune-stimulation effect. Therefore, bacteria are able to transfer therapeutic genes into the tumor cells using their infective ability. Herein, we introduce the application of bacteria for tumor therapy and focus on Salmonella, which have been widely used for tumor therapy. Salmonella have mainly been applied as gene-delivery vectors, antitumor immune activators and tumor cell death inducers. This study will not only evaluate the therapeutic efficacy of Salmonella for the treatment of tumor but will also elucidate the mechanisms underlying the antitumor activities mediated by Salmonella, which involve host immune responses and cellular molecular responses. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)

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