Ultraviolet (UV) radiation is a major environmental risk factor for melanoma, particularly among Caucasians. However, studies have generated conflicting results on the role of UV exposure in the development of acral melanoma, the most prevalent subtype of melanoma in non-Caucasians. In this review, we analyzed studies that have examined the relationship between acral melanoma and UV and show that acral melanoma has specific epidemiological and genetic characteristics, with a lower frequency or absence of UV-induced features. Therefore, we postulate that UV is probably not involved in the etiology of acral melanoma. However, further epidemiological and laboratory studies are required to fully address this controversial issue, which may lead to a better understanding of the pathogenesis and prevention of acral melanoma.

Aberrant methylation of DNA is a common event in the development of cancers, including squamous cell carcinoma (SCC) of the human esophagus. In the present study, we determined: (a) whether aberrant DNA methylation also occurs in the development of N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus, a model of human esophageal SCC; and (b) if so, whether dietary black raspberries (BRBs) are capable of preventing this aberrant DNA methylation. A diet containing 5% BRBs inhibited the development of NMBA-induced tumors in the rat esophagus. This inhibition was associated with reduced mRNA levels of the DNA methyltransferases, Dnmt1 and Dnmt3b, in both dysplastic lesions and in papillomas of the esophagus. In addition, promoter methylation of Sfrp4, a WNT pathway antagonist, was significantly reduced by the berry diet, and this was associated with decreased nuclear localization of β-CATENIN and reduced expression of c-MYC protein in NMBA-treated esophagi. Decreased promoter methylation of Sfrp4 correlated with decreased expression of Dmnt3b and, ultimately, with increased Sfrp4 mRNA expression. This suggests that epigenetic alterations in NMBA-induced rat esophageal tumorigenesis recapitulate epigenetic events in human esophageal SCC, and that BRBs could be useful in preventing the aberrant DNA methylation involved in the development of human esophageal SCC. © 2015 Wiley Periodicals, Inc.

Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and mortality rates and poor survival. Efficacious preventive and treatment options are urgently needed. An increasing number of pharmacologic agents targeting cancer cell death via autophagy mechanisms are being evaluated in hopes of circumventing apoptotic and therapeutic resistance. We report for the first time, loss of Beclin-1, a key mediator of autophagy, was significantly linked to prognostic factors in EAC. Specifically, Beclin-1 expression loss occurred in 49.0% of EAC patients versus 4.8% of controls. There was a significant inverse correlation between loss of Beclin-1 with histologic grade and tumor stage supporting a tumor suppressive role for Beclin-1. Autophagy modulation linked to cell death was examined in EAC cell lines following treatment with a proanthocyanidin-rich cranberry extract, C-PAC, and the commonly used autophagy inducer, rapamycin. C-PAC induced Beclin-1-independent autophagy in EAC cells characterized by reduced phosphorylation at serine 15 and 93, and significant cell death induction. In contrast, rapamycin-induced autophagy resulted in concomitant, increases in total Beclin-1 levels as well as Beclin-1-phosphorylation in a cell line specific manner, leading to long-term cell survival. Furthermore, autophagic LC3-II was induced by C-PAC following siRNA suppression of Beclin-1 in EAC cells. Together these data support a prognostic role of Beclin-1 in EAC with evidence that Beclin-dependent autophagy induction is agent specific. Future studies are necessary to fully interrogate the role autophagy plays in the progression of normal tissue to EAC and how specific agents targeting autophagic mechanisms can be efficaciously applied for cancer prevention or treatment. © 2015 Wiley Periodicals, Inc.

The epidermal growth factor receptor 2 (HER2) has been established as an important target of HER2-positive lung cancer, but somatic mutations in HER2 kinase domain are frequently observed that may cause drug resistance and sensitivity for tyrosine kinase inhibitors (TKIs). In this study, the response profile of 14 small-molecule TKIs upon 11 clinical HER2 mutations was investigated systematically using a synthetic strategy that integrated in silico analysis and in vitro assay to explore the structural basis, energetic property and biological implication underlying the intermolecular interactions of TKIs with wild-type and variant HER2. It is found that most clinical mutations are far away from HER2 active site and thus can only address modest or moderate effect on inhibitor binding. However, few single-point substations such as D769H and D769Y as well as the gatekeeper mutation T798 M were predicted to cause strong resistance for an array of TKIs by reshaping the geometric feature and physiochemical property of the active site. Furthermore, inhibitor response to the most common insertion mutation in HER2 exion 20 (HER2(YVMA) ) was examined in detail; the response can be grouped into three classes: sensitization, resistance and insusceptibility. The Bcr-Abl inhibitor bosutinib and EGFR inhibitor gefitinib were selected as the representatives of, respectively, sensitization and insusceptibility to perform kinase assay against the GST-tagged, recombinant kinase domains of wild-type HER2(WT) and HER2(YVMA) variant. As expected, the biological activity of bosutinib was improved by ∼160-fold due to the insertion, while gefitinib exhibited low inhibitory potency on both HER2(WT) and HER2(YVMA) (IC50 >100 μM). Structural analysis revealed an intensive network of hydrogen bonds and hydrophobic interactions in HER2(YVMA) bosutinib complex, whereas only few nonspecific van der Waals contacts were observed at the complex interface of HER2(YVMA) with gefitinib.

We studied the peculiarity of the expression of several key genes related to dysregulation of cell proliferation and surviving processes in pediatric glioma (glioblastoma multiforme) tissue from five children with age from 5 to 8 years as well a sin corresponding nonmalignant tissue counterparts as control from the same patients. RNA was isolated from glioma tissue and corresponding non-malignant tissue counterparts and PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 gene expressions were studied by quantitative polymerase chain reaction. It was shown that the expression level of genes PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 is increased in pediatric gliomas as compared to corresponding non-malignant tissue counterparts, but in different grade. More significant changes were demonstrated for PFKFB3, PFKFB4 HK2, NAMPT, TSPAN13, and HSPB8 genes. Thus, the changes in pediatric glioma tissues of the expression of PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 genes, which control cell proliferation and apoptosis, possibly contribute to enhance the tumor growth, because these genes control cell proliferation and surviving.

Long noncoding ribonucleic acids (RNAs) nowadays emerge as important biomarkers or potential therapeutic targets discussed in human cancers. Among them, maternally expressed gene 3 (MEG3) is known to be decreased in a variety of malignancies.

MicroRNAs (miRNAs) were popularly investigated in many cancers. The aim of this study was to evaluate the expression, role, and mechanism of microRNA-618 (miR-618) in human thyroid cancer (TC) cells.

The deregulation of microRNA-185 (miR-185) has been showed to be associated with many cancers and act as a tumor suppressor in many types of human malignancies. We hence tried to find out its role in human colorectal cancer (CRC).

The aim of this retrospective study was to evaluate the programmed cell death 1 (PD-1) expression in esophageal squamous cell carcinoma (ESCC) and association with clinical characteristics.

Nuclear factor-kB (NF-kB) activity is crucial for survival and proliferation of many kinds of malignancies, including gastric cancer (GC). The receptor for activated protein kinase C 1 (RACK1) is known to regulate tumor development, whereas the underlined mechanism has not been described clearly.

MicroRNAs are important modulators of the cellular epithelial-mesenchymal transition (EMT) process and are associated with metastasis in human nonsmall cell lung cancer (NSCLC). In this study, we tried to investigate the role of miR-338-3p in NSCLC cells.

The function of long noncoding RNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) has been showed in the former studies. The purpose of this study was to further analyze the underlined mechanisms responsible for its role in ESCC cells.

Introduction of tyrosine kinase inhibitors (TKI) dramatically improves the treatment and survival of the patients with chronic myeloid leukemia (CML) in the last decade. Imatinib (IM) and other TKI induce larger percentage of complete cytogenetic response (CCyR) and major molecular response (MMR). Treatment resistance to TKIs still remains an important problem in the treatment of CML. The aim of our study was to analyze the molecular response (MR) in CML patients treated with Imatinib in our institution. We have analyzed 53 CML patients (pts), 28 females and 25 males, treated with IM as a front or second line treatment. Only 15 pts were treated with IM as a front-line therapy, while 38 pts were pretreated with hydroxyurea or/and interferon. Median duration of CML was 6 years (range: 1 year- 17 years). Median duration of IM treatment was 3 years (range: 1 year-10 years). MR was analyzed in one up to 8 time points with Real Time Quantitative RT-PCR method. Forty six pts (87%) had complete hematological response and 55% of pts had MMR, 13/53(24.5%) pts had MMR at 4.0-4.5 log and 16/53(30.2%) pts had MMR at 3.0-4.0 log. MMR was not achieved in 24/53(45.3%). Our results have shown smaller percentage of patients (55%) with MMR, mostly due to the fact that larger proportion of patients (38/53) were heavily pretreated with HU or/and Interferon for a prolonged period of time, before the IM treatment. This is a major risk factor for acquisition of additional molecular and cytogenetic abnormalities responsible for IM resistance and poor treatment response.

Oncogenetics is the medical care of families with hereditary cancer risk. Bioethics laws strictly control this activity. Taking into account the medical benefit and lives saved through oncogenetics when a constitutional mutation in hereditary cancer risk gene is found, the law requires that information is disseminated to the relatives. If the consultant cannot or will not provide this information, this is the geneticist who will contact the family. This is an unprecedented situation where the doctor encourages medical advices not requested by patients. The Clermont experience is shown on the application of the law and its practical difficulties. Currently the technology of molecular genetic diagnosis is changing rapidly and allows new diagnostics whether at the level of cancerous tumors or in the genome with the perspective that everyone can soon have the sequence of the entire genome with the interpretation of personal risk of cancer diseases or other kinds. It is necessary to better anticipate emerging ethical issues already raised by the first medical practices of these technologies.

Non-homologous end joining (NHEJ) is one of the pathways used to repair the DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as lung cancer susceptibility genes such as the LIG1. However, some studies have generated conflicting results. The aim of this review and meta-analysis was to investigate the association between the LIG1 gene polymorphism and lung cancer risk. Studies focusing on the relationship between the LIG1 gene polymorphisms and susceptibility to lung cancer were selected from several electronic databases, with the last search up to October 25, 2014. Data were extracted by two independent reviewers, and the meta-analysis was performed with STATA version 12.0 software, calculating odds ratios (ORs) with 95 % confidence intervals (95 % CIs). According to the inclusion criteria, we included ten studies with a total of 4012 lung cancer cases and 5629 healthy controls in the meta-analysis. The results showed that the rs156641 polymorphism was significantly associated with lung cancer risk (dominant model: OR 0.694, 95 % CI 0.549-0.878; homozygote model: OR 0.677, 95 % CI 0.526-0.871; heterozygote model: OR 0.712, 95 % CI 0.556-0.913; additive model: OR 0.859, 95 % CI 0.767-0.962), whereas no association was found between rs3730931/rs439132/rs20579 polymorphisms and lung cancer. Our meta-analysis suggested that the rs156641 polymorphism in the LIG1 gene might be associated with an increased risk of lung cancer.

The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder cancer need further research.

Gastric cancer has high morbidity and mortality. Identification of patients with high gastric cancer risk at early stage will improve patient prognosis. In this study, we examined two single nucleotide polymorphism (SNP) sites of COX-2 gene in gastric cancer patients and explored the effect of the SNPs on the morbidity of gastric cancer. We found that the SNPs COX-2-1195G/A and COX-2-8473T/C are correlated with the occurrence of gastric cancer, and the patients with variants A and C of the SNPs are liable to have gastric cancer. Our study provides a potential method for screening of susceptible population of gastric cancer for early-stage intervention in patients.

Our objective is to explore the tumor-specific mutated genes by transcriptome sequencing of patients with acute myeloblastic leukemia. 96 patients with subtype M2 acute myeloid leukemia (AML), admitted during January 2007 to January 2012, were selected. Bone marrow and peripheral blood samples from the patients after the first visit and the patients who were improved or alleviated, were subjected to high-throughput sequencing to compare the gene expression. The single nucleotide mutation related to subtype M2 AML was detected. Meanwhile, real-time fluorescent quantitation RT-PCR was used to detect the AML1/ETO fusion gene and its correlation with prognosis after treatment. Among 96 patients, AML1-ETO fusion gene was positive in 52 cases, the positive rate was 54.17 %. The complete relief (CR) rate of AML1-ETO fusion gene positive patients was 84.62 %, and the CR rate of AML1/ETO fusion gene negative patients was 77.27 %; the CR rate of AML1-ETO positive patients was higher than that of patients without the fusion gene, however there was no statistical difference. In the analysis of recurrent gene mutation in AML-M2 patients, IDH2, ASXL1, TET2, JAK1 and JAK2 gene expressions were not significantly different before treatment and after CR, however, IDHI, JAK3, ABL1 and BCR gene expressions were significantly different. In the study of transcriptome in AML-M2 patients, high-throughput sequencing could effectively detect the difference of the gene expression before treatment and after CR. Furthermore, positive expression of AML1-ETO fusion gene had effect on the prognosis of patients.

To analyze the correlation between the concentration of plasma cell free DNA (cfDNA) of patients with lung cancer or esophageal cancer and clinical features, and to assess the coincidence rate of the EGFR/KRAS mutations between the cfDNA and tumor tissue DNA.