Genetic Variations of and Genes Are Associated With Increased Susceptibility and Clinical Outcome of Non-Small-Cell Carcinoma Patients.

Background: Immune system-related receptors CD40 (tumor necrosis factor receptor superfamily member 5), BAFFR (tumor necrosis factor receptor superfamily member 13C), and LTβR (tumor necrosis factor receptor superfamily member 3) play a pivotal role in non-small-cell lung cancer (NSCLC). To further evaluate their role in NSCLC, rs1883832 (T>C), rs7290134 (A>G), and rs10849448 (A>G) single-nucleotide polymorphisms (SNPs) were investigated regarding their impact in risk and clinical outcome of NSCLC patients.

Methods: The three selected SNPs were evaluated in 229 NSCLC patients and 299 healthy controls, while CD40, BAFFR, and LTβR protein expression was assessed by immunohistochemistry in 96 tumor specimens from NSCLC patients.

Differentially Methylated Ultra-Conserved Regions Uc160 and Uc283 in Adenomas and Adenocarcinomas Are Associated with Overall Survival of Colorectal Cancer Patients.

Deregulation of the transcribed ultra-conserved regions (T-UCRs) Uc160, Uc283, and Uc346 has been reported in colorectal cancer (CRC) recently. Here, we investigated promoter methylation of these T-UCRs during the adenoma-carcinoma sequence and their clinical significance in CRC patients. Methylation levels were assessed in CRC, adenomas, infiltrated lymph nodes, and metastatic tissue specimens.

Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients.

A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-κΒ2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection.

Liability of the voltage-gated potassium channel KCNN3 repeat polymorphism to acute oxaliplatin-induced peripheral neurotoxicity.

Thus far, there are conflicting results on the causal role of K+ channels in the pathogenesis of acute oxaliplatin-induced peripheral neurotoxicity (OXAIPN). As such, we tested the hypothesis that the voltage-gated K+ channel KCNN3 repeat polymorphism confers liability to acute OXAIPN. DNA from 151 oxaliplatin-treated patients for colorectal cancer was extracted and genotyped.

Expression of Immune System-Related Membrane Receptors CD40, RANK, BAFFR and LTβR is Associated with Clinical Outcome of Operated Non-Small-Cell Lung Cancer Patients.

An increasing number of studies implicates the NF-κB (Nuclear Factor of kappa light chain gene enhancer in B cells) alternative pathway in non-small-cell lung cancer (NSCLC). We assessed the clinical significance of CD40 (Tumor necrosis factor receptor superfamily member 5, TNFRSF5), BAFFR (B-cell activating factor receptor), RANK (Receptor activator of NF-κB) and LTβR (lymphotoxin β receptor) receptors, which activate the alternative pathway of NF-κB, in NSCLC. Evaluation of CD40, BAFFR, RANK and LTβR expression was performed based on the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets, while protein expression was assessed by immunohistochemistry in specimens from 119 operated NSCLC patients.

NF-kB2 Genetic Variations are Significantly Associated with Non-Small Cell Lung Cancer Risk and Overall Survival.

During the last decade, a growing number of publications implicate NF-kB2 in NSCLC pathogenesis. Here, we investigated the clinical relevance of NF-kB2 single nucleotide polymorphisms (SNPs) rs7897947, rs11574852 and rs12769316 in NSCLC and their association with NF-kB2 protein and mRNA levels. Our data show that TT (rs7897947T >G) and AA (rs12769316G >A) genotypes were strongly associated with an increased risk for NSCLC (P = 0.

Follicle-Stimulating Hormone Receptor (FSHR): A Promising Tool in Oncology?

The cellular pathway of follicle-stimulating hormone (FSH) and its receptor (FSHR) is typically involved in reproduction in mammals. In humans, the FSHR is normally found in cells of the testis and the ovary, while it is scarcely expressed in other normal tissues. The expression of FSH/FSHR is studied in prostate, thyroid, and ovarian cancer tissues.

Lack of association of the M129V polymorphism of the PRNP gene with pseudoexfoliation syndrome.

Purpose: In this study we aimed to evaluate the polymorphism at codon 129 (M129V) of the PRNP gene as a secondary risk factor for pseudoexfoliation syndrome (PEX).

Methods: Two hundred and seventy-five unrelated subjects, including 156 patients with PEX and 119 unrelated control subjects, were recruited from the University Hospital of Patras, Greece. All patients and controls were of Caucasian or European ancestry.

Early-Stage Breast Cancer in the Elderly: Confronting an Old Clinical Problem.

Breast cancer generally develops in older women and its incidence is continuing to increase with increasing age of the population. The pathology and biology of breast cancer seem to be different in the elderly, often resulting in the undertreatment of elderly patients and thus in higher rates of recurrence and mortal-ity. The aim of this review is to describe the differences in the biology and treatment of early breast cancer in the elderly as well as the use of geriatric assessment methods that aid decision-making.

Variant of BCL3 gene is strongly associated with five-year survival of non-small-cell lung cancer patients.

Objectives: BCL3, a known atypical IκB family member, has been documented to be upregulated in hematological malignancies and in some solid tumors, functioning as a crucial player in tumor development. Recently, rs8100239, a tag-Single Nucleotide Polymorphism (SNP) in BCL3 (T>A) has been identified, but there are no data regarding its involvement in non-small-cell lung cancer (NSCLC) initiation and progression.

Materials And Methods: To study the possible association of BCL3 with NSCLC, 268 patients and 279 healthy controls were genotyped for rs8100239.

Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: a genome-wide study replication and meta-analysis.

We aimed at validating the role of genetic variants identified by a recent genome-wide association study (GWAS) as determinants of chronic oxaliplatin-induced peripheral neurotoxicity (OXAIPN). Eight polymorphisms (rs10486003, rs2338, rs843748, rs797519, rs4936453, rs12023000, rs17140129, and rs6924717) were genotyped in a total of 150 colorectal cancer patients of Caucasian origin receiving oxaliplatin-based chemotherapy. The severity grade of chronic OXAIPN was assessed by NCI-CTC criteria and the clinical version of the Total Neuropathy Score(©) (TNSc(©) ).

NSCLC and the alternative pathway of NF-κB: uncovering an unknown relation.

Lung cancer is the leading cause of cancer-related deaths worldwide. Although our knowledge on the pathobiology of the disease has increased in the last decades, the prognosis of lung cancer patients has hardly changed. Many signaling pathways are implicated in lung carcinogenesis, but the role of the alternative pathway of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lung cancer pathogenesis and progression has not been investigated.

Altered expression of NFY-C and RORA in colorectal adenocarcinomas.

NFY-C, a subunit of the transcription factor NFY, binds to the promoters of several eukaryotic genes, including cell cycle-related genes. RORA is a steroid hormone receptor implicated in a range of important cellular processes. We evaluated the expression of NFY-C and RORA in colorectal adenocarcinomas and normal colonic tissue.

Enhancement of TGF-β signaling responses by the E3 ubiquitin ligase Arkadia provides tumor suppression in colorectal cancer.

TGF-β signaling provides tumor protection against colorectal cancer (CRC). Mechanisms that support its tumor-suppressive properties remain unclear. The ubiquitin ligase Arkadia/RNF111 enhances TGF-β signaling responses by targeting repressors of the pathway for degradation.

Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas.

The pathogenesis of colorectal carcinoma (CRC) is a complex process that involves the recruitment of both genetic and epigenetic mechanisms. Recent studies underline the cardinal role of small, noncoding RNA molecules, called microRNAs (miRs), in the pathobiology of numerous physiological and pathological processes, including oncogenesis. MiR biogenesis and maturation is mainly regulated by the nuclear ribonuclease Drosha and the cytoplasmic ribonucleases Dicer and Ago2.

Association of FOXP3 expression with non-small cell lung cancer.

Background/aim: Lung cancer is rarely cured by current therapeutic approaches. Although numerous studies have implicated FOXP3 positive regulatory T-cells in cancer pathogenesis, the role of FOXP3 in lung cancer pathogenesis remains unkown.

Materials And Methods: Using immunohistochemistry FOXP3 expression was determined in 44 NSCLC tissue specimens, 20 samples from adjacent non neoplastic lung parenchyma and 5 normal lung tissue specimens.

The survivin -31 snp in human colorectal cancer correlates with survivin splice variant expression and improved overall survival.

Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue.

VEGF polymorphisms may be associated with susceptibility to colorectal cancer: a case-control study.

The vascular endothelial growth factor (VEGF) has a pivotal role in angiogenesis. VEGF levels appear to be influenced by single nucleotide polymorphisms (SNPs) of the VEGF gene. The aim of this study was to assess the importance of four VEGF SNPs in modulating susceptibility to colorectal cancer.

The survivin -31 snp in human colorectal cancer correlates with survivin splice variant expression and improved overall survival.

Background: survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue.

Prion protein expression and the M129V polymorphism of the PRNP gene in patients with colorectal cancer.

The prion protein, PrP(C), is known mostly for its involvement in neurodegenerative spongiform encephalopathies. However, a role for this molecule in cancer is becoming increasingly recognized partly because it promotes cell proliferation and inhibits apoptosis. Moreover, the codon 129 polymorphism (M129V) of the PRNP gene (the PrP(C)-encoding gene) has been associated with neurodegenerative disease development and severity, while no information is available regarding its role in colorectal cancer (CRC) incidence and disease progression.

Liability of the voltage-gated sodium channel gene SCN2A R19K polymorphism to oxaliplatin-induced peripheral neuropathy.

Aim: It was the aim of this study to test the hypothesis that the voltage-gated sodium channel gene SCN2A R19K polymorphism confers liability to oxaliplatin-induced peripheral neuropathy (OXLIPN).

Methods: Sixty-two patients with advanced colorectal cancer were genotyped, using allele-specific primers and SYBR green in real-time polymerase chain reaction. All patients had received adjuvant oxalipla-tin-based chemotherapy.

POLR2F, ATP6V0A1 and PRNP expression in colorectal cancer: new molecules with prognostic significance?

Background: DNA-directed RNA polymerase II subunit F (POLR2F), a subunit of the V0 domain of the vacuolar ATPase (ATP6V0A1) and the prion protein (PRNP) are molecules of potential importance in carcinogenesis and targeted cancer therapy. However, their expression has not been studied in colorectal carcinomas.

Patients And Methods: Expression microarray data were analyzed using a novel computational tool to reveal elevated levels of POLR2F, ATP6V0A1 and PRNP in relapsed colorectal carcinoma patients.