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Special Issue "Molecular Classification of Human Cancer and Its Role in Tailored Cancer Therapy"

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

Deadline for manuscript submissions: closed (31 January 2015)

Special Issue Editor

Guest Editor
Dr. William Chi-shing Cho

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
E-Mail
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,

Human cancer has an increasing incidence and high mortality worldwide. The traditional diagnostic practice for this disease is based on histological patterns. Recent researches support the notion that cancer is not a single malignant disorder but rather a group of distinct molecular diseases. In the era of precision medicine with targeted therapies, there is an imperative need to overcome the limitations of the conventional classification system to accurately stratify patients to achieve maximum therapeutic efficacy. As such, many molecular diagnostic tests have been developed to identify the underlying genetic signatures and incorporate them into the conventional histopathological classification of cancer. Profiling of cancer has yielded a number of genetic, microRNA and proteomic markers for molecular classification. Newer approaches include, but are not limited to, cancer stem cells analysis and next-generation sequencing. Indeed, molecular classification has already been extensively applied to some types of cancer, such as the subtypes of luminal A and lumina B estrogen receptor-positive breast cancer, the subtypes of ALK- and EGFR-positive non-small cell lung cancer, the subtypes of WNT pathway and Sonic Hedgehog pathway medulloblastoma, etc. This special issue discusses the significance of molecular classification and its impact on the clinical setting for directing rational cancer therapy.

Dr. William Chi-shing Cho
Guest Editor

Submission

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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.

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Keywords

  • cancer biomarker
  • cancer stem cells
  • clinical trial
  • copy number variation
  • cytogenetics
  • diagnostic imaging
  • digital PCR
  • epigenomics
  • fluorescence in situ hybridization
  • genome-wide association studies
  • genomic database
  • genomics
  • immunohistochemistry
  • metabolomics
  • methylation
  • microarray
  • microfluidics, nanofluidics
  • microRNA
  • molecular classification
  • molecular diagnostics
  • molecular tumor pathology
  • next-generation sequencing
  • non-coding RNAs
  • omics
  • PCR array
  • personalized medicine
  • post-translational modifications
  • precision medicine
  • proteomics
  • single nucleotide polymorphism
  • targeted therapy
  • theranostics
  • translational cancer research

Published Papers (14 papers)

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Research

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Open AccessArticle Knockdown of UbcH10 Enhances the Chemosensitivity of Dual Drug Resistant Breast Cancer Cells to Epirubicin and Docetaxel
Int. J. Mol. Sci. 2015, 16(3), 4698-4712; doi:10.3390/ijms16034698
Received: 15 October 2014 / Revised: 5 February 2015 / Accepted: 13 February 2015 / Published: 2 March 2015
Cited by 2 | PDF Full-text (2697 KB) | HTML Full-text | XML Full-text
Abstract
Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10), may also play some roles in the genesis and development of breast cancer. In the
[...] Read more.
Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10), may also play some roles in the genesis and development of breast cancer. In the current study, we found that the expression of UbcH10 was up-regulated in some breast cancer tissues and five cell lines. We established a dual drug resistant cell line MCF-7/EPB (epirubicin)/TXT (docetaxel) and a lentiviral system expressing UbcH10 shRNA to investigate the effects of UbcH10 knockdown on the chemosensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel. The knockdown of UbcH10 inhibited the proliferation of both MCF-7 and MCF-7/EPB/TXT cells, due to the G1 phase arrest in cell cycle. Furthermore, UbcH10 knockdown increased the sensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel and promoted the apoptosis induced by these two drugs. Protein detection showed that, in addition to inhibiting the expression of Ki67 and cyclin D1, UbcH10 RNAi also impaired the increased BCL-2 and MDR-1 expression levels in MCF-7/EPB/TXT cells, which may contribute to abating the drug resistance in the breast cancer cells. Our research in the current study demonstrated that up-regulation of UbcH10 was involved in breast cancer and its knockdown can inhibit the growth of cancer cells and increase the chemosensitivity of the dual drug resistant breast cancer cells to epirubicin and docetaxel, suggesting that UbcH10 may be a promising target for the therapy of breast cancer. Full article
Open AccessArticle Expression and Diagnostic Value of HE4 in Pancreatic Adenocarcinoma
Int. J. Mol. Sci. 2015, 16(2), 2956-2970; doi:10.3390/ijms16022956
Received: 1 December 2014 / Revised: 24 December 2014 / Accepted: 12 January 2015 / Published: 29 January 2015
Cited by 5 | PDF Full-text (1265 KB) | HTML Full-text | XML Full-text
Abstract
Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4
[...] Read more.
Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4 mRNA level in tumor adjacent tissues and pancreatic adenocarcinoma tissues were tested by real time-PCR. Tissue microarray containing normal, adenocarcinoma, and adjacent pancreatic tissue was tested by immunohistochemistry (IHC). Serum level of HE4, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3) and carbohydrate antigen 125 (CA125) were detected by ELISA assay in control and tumor patients. Further we compared the sensitivity and specificity of determining HE4, CA19-9, CA15-3, and CA125 for diagnosis of pancreatic adenocarcinoma and assessed the complementary diagnostic value of HE4, CA19-9, CA15-3 and CA125. Real time PCR showed significantly increased HE4 mRNA level in pancreatic adenocarcinoma compared with control. Result of IHC showed that HE4 significantly higher expressed in the human pancreatic carcinoma tissues than in both normal and adjacent non-tumorous pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 was highly expressed in early stage of pancreatic adenocarcinoma. Serum HE4 level is higher in cases with pancreatic adenocarcinoma than in the controls. Serum HE4 levels could research to a sensitivity of 45.83% and specificity of 93.75% when the Cutoff was set at 4.59 ng/mL. The Combined HE4 and CA19-9 increased the sensitivity to 83.33%; and interestingly, the combination of HE4 with CA15-3 led to the most powerful sensitivity of 87.5%. Combined with CA19-9 and CA15-3, HE4 could be a potential biomarker to improve the diagnostic power for pancreatic adenocarcinoma. Full article
Open AccessArticle Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells
Int. J. Mol. Sci. 2015, 16(1), 1266-1292; doi:10.3390/ijms16011266
Received: 15 October 2014 / Accepted: 29 December 2014 / Published: 7 January 2015
Cited by 6 | PDF Full-text (5626 KB) | HTML Full-text | XML Full-text
Abstract
Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment
[...] Read more.
Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined. Full article
Open AccessArticle Gene Mutation Analysis in EGFR Wild Type NSCLC Responsive to Erlotinib: Are There Features to Guide Patient Selection?
Int. J. Mol. Sci. 2015, 16(1), 747-757; doi:10.3390/ijms16010747
Received: 17 October 2014 / Accepted: 23 December 2014 / Published: 31 December 2014
Cited by 11 | PDF Full-text (677 KB) | HTML Full-text | XML Full-text
Abstract
Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered
[...] Read more.
Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity. Full article
Open AccessArticle Modulation of Selectin-Mediated Adhesion of Flowing Lymphoma and Bone Marrow Cells by Immobilized SDF-1
Int. J. Mol. Sci. 2014, 15(9), 15061-15072; doi:10.3390/ijms150915061
Received: 27 June 2014 / Revised: 14 August 2014 / Accepted: 19 August 2014 / Published: 27 August 2014
Cited by 1 | PDF Full-text (1148 KB) | HTML Full-text | XML Full-text
Abstract
The α-chemokine, stromal-derived factor-1 (SDF-1), has been linked to the homing of circulating tumor cells to bone. SDF-1 is expressed by bone microvascular cells and osteoblasts and normally functions to attract blood-borne hematopoietic stem and progenitor cells to marrow. It has been shown
[...] Read more.
The α-chemokine, stromal-derived factor-1 (SDF-1), has been linked to the homing of circulating tumor cells to bone. SDF-1 is expressed by bone microvascular cells and osteoblasts and normally functions to attract blood-borne hematopoietic stem and progenitor cells to marrow. It has been shown that treatment of cancer cells with soluble SDF-1 results in a more aggressive phenotype; however, the relevance of the administration of the soluble protein is unclear. As such, a flow device was functionalized with P-selectin and SDF-1 to mimic the bone marrow microvasculature and the initial steps of cell adhesion. The introduction of SDF-1 onto the adhesive surface was found to significantly enhance the adhesion of lymphoma cells, as well as low-density bone marrow cells (LDBMC), both in terms of the number of adherent cells and the strength of cell adhesion. Thus, SDF-1 has a synergistic effect with P-selectin on cancer cell adhesion and may be sufficient to promote preferential metastasis to bone. Full article
Open AccessArticle Clinical Significance of POU5F1P1 rs10505477 Polymorphism in Chinese Gastric Cancer Patients Receving Cisplatin-Based Chemotherapy after Surgical Resection
Int. J. Mol. Sci. 2014, 15(7), 12764-12777; doi:10.3390/ijms150712764
Received: 26 April 2014 / Revised: 30 June 2014 / Accepted: 9 July 2014 / Published: 18 July 2014
Cited by 6 | PDF Full-text (731 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method
[...] Read more.
This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023). Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations. Full article
Open AccessArticle The REST Gene Signature Predicts Drug Sensitivity in Neuroblastoma Cell Lines and Is Significantly Associated with Neuroblastoma Tumor Stage
Int. J. Mol. Sci. 2014, 15(7), 11220-11233; doi:10.3390/ijms150711220
Received: 23 April 2014 / Revised: 30 May 2014 / Accepted: 3 June 2014 / Published: 25 June 2014
Cited by 4 | PDF Full-text (786 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Neuroblastoma is the most common and deadly solid tumor in children, and there is currently no effective treatment available for neuroblastoma patients. The repressor element-1 silencing transcription (REST) factor has been found to play important roles in the regulation of neural differentiation and
[...] Read more.
Neuroblastoma is the most common and deadly solid tumor in children, and there is currently no effective treatment available for neuroblastoma patients. The repressor element-1 silencing transcription (REST) factor has been found to play important roles in the regulation of neural differentiation and tumorigenesis. Recently, a REST signature consisting of downstream targets of REST has been reported to have clinical relevance in both breast cancer and glioblastoma. However it remains unclear how the REST signature works in neuroblastoma. Publicly available datasets were mined and bioinformatic approaches were used to investigate the utility of the REST signature in neuroblastoma with both preclinical and real patient data. The REST signature was found to be associated with drug sensitivity in neuroblastoma cell lines. Further, neuroblastoma patients with enhanced REST activity are significantly associated with higher clinical stages. Loss of heterozygosity on chromosome 11q23, which occurs in a large subset of high-risk neuroblastomas, tends to be correlated with high REST activity, with marginal significance. In conclusion, the REST signature has important implications for targeted therapy, and it is a prognostic factor in neuroblastoma patients. Full article
Open AccessArticle Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer
Int. J. Mol. Sci. 2014, 15(5), 8699-8712; doi:10.3390/ijms15058699
Received: 28 January 2014 / Revised: 4 May 2014 / Accepted: 5 May 2014 / Published: 15 May 2014
Cited by 11 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text
Abstract
We investigated the significance of high- mobility group box1 (HMGB1) and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3), IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial
[...] Read more.
We investigated the significance of high- mobility group box1 (HMGB1) and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3), IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag) was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05). In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05). HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05). HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05). Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment. Full article
Open AccessArticle Role of miR-191/425 Cluster in Tumorigenesis and Diagnosis of Gastric Cancer
Int. J. Mol. Sci. 2014, 15(3), 4031-4048; doi:10.3390/ijms15034031
Received: 17 January 2014 / Revised: 18 February 2014 / Accepted: 19 February 2014 / Published: 5 March 2014
Cited by 21 | PDF Full-text (1838 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gastric cancer (GC) is among the most frequent types of cancer worldwide. Therefore, understanding the biology of GC tumorigenesis is important for appropriate diagnosis and patient surveillance. The miR-191/425 cluster has been reported to be overexpressed in various human cancers, but the tumorigenic
[...] Read more.
Gastric cancer (GC) is among the most frequent types of cancer worldwide. Therefore, understanding the biology of GC tumorigenesis is important for appropriate diagnosis and patient surveillance. The miR-191/425 cluster has been reported to be overexpressed in various human cancers, but the tumorigenic role and clinical significance of miR-191/425 overexpression in gastric carcinogenesis is currently undefined. In this study, the expression of miR-191 and miR-425 in GC tissue and serum was assessed, and the relationship between miRNA expression and clinicopathological data was analyzed. We found that miR-191 and miR-425 were both significantly increased in human GC tissues relative to adjacent normal controls. In addition, miR-191 levels correlated with GC tumor stage and metastatic state. Furthermore, the level of serum miR-191 was significantly higher in the GC group than in the control group when using serum miR-16 as an endogenous control. Finally, inhibition of miR-191 or miR-425 in the GC cell lines HGC-27 not only reduced cell proliferation and cell cycle progression but also impaired cell migration and invasion. Taken together, our results revealed the oncogenic roles of miR-191 and miR-425 in gastric carcinogenesis, and indicated the potential use of serum miR-191 as a novel and stable biomarker for GC diagnosis. Full article
Open AccessArticle Casein Kinase 1 Epsilon Expression Predicts Poorer Prognosis in Low T-Stage Oral Cancer Patients
Int. J. Mol. Sci. 2014, 15(2), 2876-2891; doi:10.3390/ijms15022876
Received: 24 December 2013 / Revised: 13 February 2014 / Accepted: 17 February 2014 / Published: 19 February 2014
Cited by 12 | PDF Full-text (707 KB) | HTML Full-text | XML Full-text
Abstract
Casein kinase 1 is a group of ubiquitous serine/threonine kinases that are involved in normal cellular functions and several pathological conditions, such as DNA repair, cell cycle progression, cytokinesis, differentiation, and apoptosis. Recent studies have indicated that casein kinase 1-epsilon (CK1ε) and casein
[...] Read more.
Casein kinase 1 is a group of ubiquitous serine/threonine kinases that are involved in normal cellular functions and several pathological conditions, such as DNA repair, cell cycle progression, cytokinesis, differentiation, and apoptosis. Recent studies have indicated that casein kinase 1-epsilon (CK1ε) and casein kinase 1-delta (CK1δ) expression has a role in human cancers. We investigated the associations between CK1ε and CK1δ expression and the clinical parameters of oral cancer using immunohistochemical study methods on oral squamous cell carcinoma specimens. The results of our immunohistochemical analysis showed that the loss of CK1ε expression was greatly associated with a poor four-year survival rate in oral cancer patients (p = 0.002). A Kaplan-Meier analysis showed that patients who had a loss of CK1ε expression had a considerably poorer overall survival rate than patients who had positive CK1ε expressions (p = 0.022). A univariate analysis revealed that patients who had a loss of CK1ε expression had considerably poorer overall survival (OS) than patients who had positive expression (p = 0.024, hazard ratio (HR) = 1.7). In conclusion, our data indicated that the loss of cytoplasmic CK1ε expression is greatly associated with poor survival and might be an adverse survival factor. Full article

Review

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Open AccessReview Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach
Int. J. Mol. Sci. 2015, 16(6), 13610-13632; doi:10.3390/ijms160613610
Received: 19 February 2015 / Accepted: 4 June 2015 / Published: 15 June 2015
Cited by 8 | PDF Full-text (1068 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we
[...] Read more.
Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice. Full article
Open AccessReview Cancer Stratification by Molecular Imaging
Int. J. Mol. Sci. 2015, 16(3), 4918-4946; doi:10.3390/ijms16034918
Received: 15 October 2014 / Revised: 13 February 2015 / Accepted: 17 February 2015 / Published: 4 March 2015
Cited by 4 | PDF Full-text (1745 KB) | HTML Full-text | XML Full-text
Abstract
The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor
[...] Read more.
The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2). Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter), as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers. Full article
Figures

Open AccessReview Microenvironment of Tumor-Draining Lymph Nodes: Opportunities for Liposome-Based Targeted Therapy
Int. J. Mol. Sci. 2014, 15(11), 20209-20239; doi:10.3390/ijms151120209
Received: 15 July 2014 / Revised: 20 October 2014 / Accepted: 24 October 2014 / Published: 5 November 2014
Cited by 9 | PDF Full-text (6701 KB) | HTML Full-text | XML Full-text
Abstract
The World Health Organization (WHO) recently reported that the total number of global cancer cases in 2013 reached 14 million, a 10% rise since 2008, while the total number of cancer deaths reached 8.2 million, a 5.2% increase since 2008. Metastasis is the
[...] Read more.
The World Health Organization (WHO) recently reported that the total number of global cancer cases in 2013 reached 14 million, a 10% rise since 2008, while the total number of cancer deaths reached 8.2 million, a 5.2% increase since 2008. Metastasis is the major cause of death from cancer, accounting for 90% of all cancer related deaths. Tumor-draining lymph nodes (TDLN), the sentinel nodes, are the first organs of metastasis in several types of cancers. The extent of metastasis in the TDLN is often used in disease staging and prognosis evaluation in cancer patients. Here, we describe the microenvironment of the TDLN and review the recent literature on liposome-based therapies directed to immune cells within the TDLN with the intent to target cancer cells. Full article
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Other

Jump to: Research, Review

Open AccessCase Report Coexistence of Granular Cell Tumor and Invasive Ductal Breast Cancer in Contralateral Breasts: A Case Report
Int. J. Mol. Sci. 2014, 15(8), 13166-13171; doi:10.3390/ijms150813166
Received: 25 March 2014 / Revised: 16 July 2014 / Accepted: 21 July 2014 / Published: 25 July 2014
PDF Full-text (5016 KB) | HTML Full-text | XML Full-text
Abstract
Granular cell tumor (GCT) is a benign tumor of the breast that can mimic, on breast imaging, invasive carcinomas. Biological evolution of mammary GCT is unknown, especially if it is associated with an invasive carcinoma in the same or contralateral breast. This report
[...] Read more.
Granular cell tumor (GCT) is a benign tumor of the breast that can mimic, on breast imaging, invasive carcinomas. Biological evolution of mammary GCT is unknown, especially if it is associated with an invasive carcinoma in the same or contralateral breast. This report details the morphological features of these synchronous lesions highlighting their biological characteristics and suggesting an appropriate follow up. Full article
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