Acute myeloid leukemia (AML) is often initiated by genetic alterations of machineries that regulate chromatin and transcription, thereby blocking cell differentiation. Such mechanisms may also render leukemia cells vulnerable to perturbations of transcriptional regulators, which includes small molecules targeting the coactivator protein BRD4. Numerous studies have validated BRD4 as a therapeutic target in diverse subtypes of AML; however, the vital function of BRD4 in this disease is only beginning to be understood. Here we discuss the recent progress in elucidating the transcriptional function of BRD4 in AML cells, with an emphasis on the desirable attributes, but also the inherent limitations, of targeting general coactivator proteins as cancer therapy.

Genome-wide association studies (GWAS) have identified multiple common susceptibility loci for pancreatic cancer. Here we report fine-mapping and functional analysis of one such locus residing in a 610 kb gene desert on chr13q22.1 (marked by rs9543325). The closest candidate genes, KLF5, KLF12, PIBF1, DIS3 and BORA, range in distance from 265-586 kb. Sequencing three sub-regions containing the top ranked SNPs by imputation P-value revealed a 30 bp insertion/deletion (indel) variant that was significantly associated with pancreatic cancer risk (rs386772267, P = 2.30 × 10-11, OR = 1.22, 95% CI 1.15-1.28) and highly correlated to rs9543325 (r2 = 0.97 in the 1000 Genomes EUR population). This indel was the most significant cis-eQTL variant in a set of 222 histologically normal pancreatic tissue samples (β = 0.26, P = 0.004), with the insertion (risk-increasing) allele associated with reduced DIS3 expression. DIS3 encodes a catalytic subunit of the nuclear RNA exosome complex that mediates RNA processing and decay, and is mutated in several cancers. Chromosome conformation capture revealed a long range (570 kb) physical interaction between a sub-region of the risk locus, containing rs386772267, and a region ∼6 kb upstream of DIS3 Finally, repressor regulatory activity and allele-specific protein binding by transcription factors of the TCF/LEF family were observed for the risk-increasing allele of rs386772267, indicating that expression regulation at this risk locus may be influenced by the Wnt signaling pathway. In conclusion, we have identified a putative functional indel variant at chr13q22.1 that associates with decreased DIS3 expression in carriers of pancreatic cancer risk-increasing alleles, and could therefore affect nuclear RNA processing and/or decay.

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina’s HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.

Colorectal cancer (CRC) is the fourth most prevalent cancer globally. Several factors have roles in cancer establishment. One of the most important factors is hypoxia that induces hypoxia inducible factor-1 (HIF-1). The HIF-1 alpha overexpressed in hypoxia conditions and plays a pivotal role in carcinogenesis features. In this study, we aimed to examine the efficiency of HIF-1 alpha gene expression at mRNA and protein's level for CRC diagnosing and staging.

Mutations in K-ras codon 12 and 13 of exon 2 are known to affect prognosis and impart resistance to anti-epidermal growth factor monoclonal antibody therapy in colorectal carcinoma (CRC). Our aim was to investigate the utility value of modified mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to detect mutation in K-ras codons of CRC patients and to relate the mutational status to liver metastasis.

Ductal carcinoma in situ (DCIS) is considered a heterogeneous lesion at the molecular level. However, there is a paucity of literature about the existence of molecular subtypes in DCIS which can predict their biological behavior at the preinvasive stage.

Glioblastoma multiforme (GBM) carries a poor prognosis with high recurrence rates. Salvage stereotactic radiosurgery (SRS) may be an effective treatment option.

Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor. Among the evasion strategies developed by tumors, the metalloprotease-dependent shedding of MICA/MICB from tumors (either the free or the exosome form) can contribute to the inhibition of cytolysis by the immune effector cells (all NK cells, most NKT cells; γδ CD8+ T cells and αβ CD8+ T cells, as well as some αβ CD4+ T cells). There are micro-RNA clusters that regulate surface expression and shedding. Polymorphic variants can be used as susceptibility/associative markers and can also possibly be used to correlate with tumor survival as well as staging/grading of tumors. Variations in the expression level require quantification of this marker for diagnostic/prognostic and therapeutic purposes. Mechanism-based studies would provide a better tumor-specific understanding of their relative roles in the processes of tumor cell elimination versus growth and progression. Last but not least, conventional, interlaboratory validated assays (for, e.g., antibody-based methods) should be replaced by robust, reproducible, feasible biophysics-based methods using tumor biopsies. Further, correlative DNA polymorphism-based studies can be done using biological fluids (for, e.g., human saliva) that can be sampled by minimally invasive means.

3-Chloromethylene-6-fluorothiochroman-4-one (CMFT) is a novel thiochromanones derivative that has better anti-tumor activity. In this paper, we will compare the antitumor activity of the cis-trans isomers, and explore their inhibiting effects on human topoisomerase I and topoisomerase II in cell free reaction system. The MTT method was used to study inhibition rates; the AO/EB double staining and TUNEL assay was used to assess proportion of apoptotic cells. The inhibition of CMFT to Topo I and II could be identified by adding CMFT solutions to Topo-DNA reaction mixtures and observing the relative quantities of relaxed strands and supercoils in electrophoresis assay. Results showed that CMFT had dramatic anti-tumor activities at low concentrations and the activity of CMFT trans-isomer is more significant. Use of AO/EB double staining and TUNEL indicated that CMFT induces apoptosis. DNA relaxation assays and DNA cleavage and relegation assays were performed and showed a higher potential to interact with topoisomerase I (Topo I) and topoisomerase II (Topo II) and it was verified that CMFT is a Topo poison which could be one of the mechanisms that induce cell apoptosis. Our results provide preliminary data for further investigation for the mechanism of CMFT of the apoptotic mechanism.

Growing evidence from studies has shown that microRNA-196a (miR-196a) is correlated with treatment response and prognosis in Asian cancer patients. However, the studies reveal that the role of miR-196a is not totally consistent, making it rational to perform a meta-analysis to assess the prognostic value of miR-196a in cancers.

microRNAs are widely involved in a variety of life processes and considered as potential biomarkers of tumor prognosis. A growing number of studies have documented that miRNAs were associated with outcome in NSCLC patients and can act as a prognostic marker. However, existing studies concerning the relationship between miRNAs and outcome in NSCLC patients were contentious and dispersive. Therefore, a systematic metaanalysis to explore the prognostic value of miRNAs on NSCLC patients is urgently needed.

This study was performed to evaluate the surface plasmon resonance-based (SPR) test with the W2600 System of GP Medical Technologies as a screening method for human papillomavirus (HPV) genotyping in China.

Many studies demonstrated that the expression level of HOTTIP in cancerous tissues was significantly higher than that in adjacent normal tissues. Increased expression of HOTTIP was associated with metastasis and a poor prognosis.

The single nucleotide polymorphism (SNP) rs2072408 is located in an intron of the enhancer of zeste homolog 2 (EZH2) gene. Its role in gastric cancer (GC) has not been determined.

Published data on the association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis in the Chinese population was performed.

MDM4 is a negative regulator of the p53 tumor suppression pathway. Recent studies have revealed that the rs4245739 A>C polymorphism of MDM4 in the 3-untranslated region makes it a miR-191 target site which leads to lower MDM4 expression. This study is aimed to detect if rs4245739 single nucleotide polymorphism (SNP) of the MDM4 gene influences the breast cancer development in Iranian-Azeri women.

Breast cancer is the most prevalent cancer and foremost reason of death resulting from malignancy among women worldwide. In recent years, it has been reported that a group of genes named cancer testis genes (CTg) express in adult immune privileged sites and some embryonic tissues. Likewise, it has been demonstrated that CTgs express aberrantly in various tumors and play essential roles in both initiation and development of cancers. In this study, PIWIL2, one member of CTgs, which has an indispensable role in spermatogenesis and tumorigenesis, was examined as an efficient prognostic and diagnostic biomarker in breast cancer. It is worth mentioning that the expression study of PIWIL2 by qPCR on breast cancer samples was performed for the first time, since this approach is much more sensitive than western blot, RT-PCR, and immunohistochemistry.

MicroRNAs (miRNAs) play important roles in cancer development. MiR-222, which is deregulated in multiple types of cancers, shows potential as a prognostic biomarker; however, the association between miR222 expression and cancer prognosis was controversial in previous studies. Here we analyzed the relationship between miR-222 and the survival of cancer patients.