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Biomedical subjects

Rajiv Kumar

Publications and source records attributed to Rajiv Kumar.

At least 19 recordsLinked to original sources
PubMed2026

Epigenetic Profiling for Early Detection and Treatment Response Monitoring in Non-Small Cell Lung Cancer: Protocol for a Prospective Translational Biomarker Study.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide and continues to have poor survival outcomes, with most patients diagnosed at advanced stages of disease. In New Zealand, NSCLC contributes substantially to cancer inequities, with Māori communities experiencing disproportionately high incidence and mortality rates. Although low-dose computed tomography screening can improve early detection, major limitations remain, including false-positive findings, overdiagnosis, high infrastructure costs, and limited accessibility for rural and underserved populations. Liquid biopsy approaches using circulating tumor DNA (ctDNA), particularly DNA methylation profiling, have emerged as promising, minimally invasive strategies for improving cancer detection, treatment monitoring, and precision oncology. OBJECTIVE: This study aims to establish integrated genomic and epigenomic predictive and prognostic biomarkers using ctDNA, tumor tissue, and transcriptomic profiling to improve early detection, risk stratification, treatment selection and response prediction, and longitudinal monitoring, with particular emphasis on identifying molecular mechanisms associated with treatment resistance and disease progression. METHODS: This prospective observational translational biomarker study is being conducted through the University of Otago and associated respiratory and oncology services in New Zealand. The study will recruit participants with NSCLC (including squamous and nonsquamous subtypes), individuals referred to fast-track lung nodule assessment clinics, and nonmalignant respiratory controls. Serial peripheral blood sampling will be performed in selected participants at predefined clinical follow-up time points to evaluate treatment response and disease progression. The availability of formalin-fixed paraffin-embedded archival tissues will be recorded, but will not be mandatory for enrollment. Genome-scale DNA methylation profiling will be performed using cell-free reduced representation bisulfite sequencing (cfRRBS), while targeted genomic profiling and transcriptomic analyses will be conducted using targeted sequencing panels and RNA sequencing. Integrative bioinformatic analyses will be used to identify molecular biomarkers associated with early-stage disease, advanced disease, treatment response, and therapeutic resistance. RESULTS: Ethics approval for the study has been obtained from the New Zealand Health and Disability Ethics Committee (2022 EXP 12566). This study commenced in 2022, and recruitment and biospecimen collection are ongoing. The study aims to recruit approximately 450 participants, including patients with NSCLC, individuals referred through respiratory diagnostic pathways, and nonmalignant controls. As of July 31, 2026, 205 participants have been recruited, with recruitment continuing until the target sample size is reached. Molecular and data analyses are ongoing, with additional publications expected as the cohort matures. CONCLUSIONS: This study will generate one of the first integrated genomic, epigenomic, and transcriptomic liquid biopsy datasets for NSCLC in New Zealand. The findings are expected to support the development of sensitive, accessible, and equitable blood-based biomarkers for NSCLC detection and treatment monitoring while also contributing to improved precision oncology approaches and reducing NSCLC inequities among Māori populations.

Humans↗
PubMed2007

The phosphatonins and the regulation of phosphate transport and vitamin D metabolism.

Phosphate homeostasis is preserved during variations in phosphate intake by short-term intrinsic renal and intestinal adaptations in transport processes, and by more long-term hormonal mechanisms, which regulate the efficiency of phosphate transport in the kidney and intestine. Recently, several phosphaturic peptides such as fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein-4 (sFRP-4), extracellular phosphoglycoprotein (MEPE) and fibroblast growth factor 7 (FGF-7) have been shown to play a pathogenic role in several hypophosphatemic disorders such as tumor-induced osteomalacia (TIO), autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), the McCune-Albright syndrome (MAS) and fibrous dysplasia (FD). These proteins induce phosphaturia and hypophosphatemia in vivo, and inhibit sodium-dependent renal phosphate transport in cultured renal epithelial cells. Interestingly, despite the induction of hypophosphatemia by FGF-23 and sFRP-4 in vivo, serum 1, 25-dihydroxyvitamin D (1alpha,25(OH)(2)D) concentrations are decreased or remain inappropriately normal, suggesting an inhibitory effect of these proteins on 25-hydroxyvitamin D 1alpha-hydroxylase activity. In FGF-23 knockout mice, 25-hydroxyvitamin D 1alpha-hydroxylase expression is increased and elevated serum 1alpha,25(OH)(2)D levels cause significant hypercalcemia and hyperphosphatemia. MEPE, however, increases circulating 1alpha,25(OH)(2)D. Circulating or local concentrations of these peptides/proteins may regulate 25-hydroxyvitamin D 1alpha-hydroxylase activity in renal tissues under physiologic circumstances.

Animals↗
PubMed2007

Phosphatonins and the regulation of phosphate homeostasis.

Inorganic phosphate (P(i)) is required for energy metabolism, nucleic acid synthesis, bone mineralization, and cell signaling. The activity of cell-surface sodium-phosphate (Na(+)-P(i)) cotransporters mediates the uptake of P(i) from the extracellular environment. Na(+)-P(i) cotransporters and organ-specific P(i) absorptive processes are regulated by peptide and sterol hormones, such as parathyroid hormone (PTH) and 1alpha,25-dihydroxyvitamin D (1alpha,25(OH)(2)D(3)), which interact in a coordinated fashion to regulate P(i) homeostasis. Recently, several phosphaturic peptides such as fibroblast growth factor-23 (FGF-23), secreted frizzled related protein-4 (sFRP-4), matrix extracellular phosphoglycoprotein, and fibroblast growth factor-7 have been demonstrated to play a pathogenic role in several hypophosphatemic disorders. By inhibiting Na(+)-P(i) transporters in renal epithelial cells, these proteins increase renal P(i) excretion, resulting in hypophosphatemia. FGF-23 and sFRP-4 inhibit 25-hydroxyvitamin D 1alpha-hydroxylase activity, reducing 1alpha,25(OH)(2)D(3) synthesis and thus intestinal P(i) absorption. This review examines the role of these factors in P(i) homeostasis in health and disease.

Animals↗
PubMed2006

Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never- and ever-smokers.

This case-control study examines the association between lung cancer and genetic polymorphisms in two base excision repair (BER) genes, XRCC1 and APEX1 and two genes involved in homologous recombination repair (HR), XRCC3 and NBS1. Never-smoking lung cancer patients were recruited, and also the next diagnosed ever-smoking case of the same gender and age group. Controls were recruited from the regional population register, frequency matched to cases by hospital catchment area, gender, age group and smoking category. As a result more than 70% of the study population were women. A total of 331 individuals were analysed. Presence of the XRCC1 399Gln allele was associated with a significantly decreased risk for lung cancer among non-smoking women (odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9). No significant effect was seen with the APEX1 polymorphism. Women smokers carrying the XRCC3 241Met allele showed a significantly decreased risk for lung cancer (OR 0.3, CI 0.2-0.7). The NBS1 185Gln allele was significantly associated with an increased risk for lung cancer among non-smoking women (OR 2.2, CI 1.0-4.8) and low-dose smoking women (OR 4.8, CI 1.5-15.7). The protective effect of the variant XRCC3 241Met allele was strengthened when combined with the low-risk Glu185 allele of the NBS1 gene. Smokers (OR 0.38, CI 0.16-0.90) and women (OR 0.42, CI 0.21-0.85) with at least three low-risk alleles in these two HR genes showed a significantly decreased risk for lung cancer. Thus, in spite of a relatively small study population, this study, including a comparatively large number of never-smokers and women, presents several novel aspects on genetic susceptibility to lung cancer. Our results show that the genetic variation in XRCC1, XRCC3 and NBS1 influence lung cancer susceptibility among women, and that combinations of risk alleles in the two HR genes can enhance the effects.

Adult↗
PubMed2006

Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects.

We investigated association between polymorphisms in DNA repair genes and the capacity to repair DNA damage induced by gamma-irradiation and by base oxidation in a healthy population. Irradiation-specific DNA repair rates were significantly decreased in individuals with XRCC1 Arg399Gln homozygous variant genotype (0.45 +/- 0.47 SSB/10(9) Da) than in those with wild-type genotype (1.10 +/- 0.70 SSB/10(9) Da, P=0.0006, Mann-Witney U-test). The capacity to repair oxidative DNA damage was significantly decreased among individuals with hOGG1 Ser326Cys homozygous variant genotype (0.37 +/- 0.28 SSB/10(9) Da) compared to those with wild-type genotype (0.83 +/- 0.79 SSB/10(9) Da, P=0.008, Mann-Witney U-test). Investigation of genotype combinations showed that the increasing number of variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms resulted in a significant decrease of irradiation-specific repair rates (P=0.008, Kruskal-Wallis test). Irradiation-specific DNA repair rates also decreased with increasing number of variant alleles in XRCC1 Arg399Gln in combination with variant alleles for two other XRCC1 polymorphisms, Arg194Trp and Arg280His (P=0.002 and P=0.005, respectively; Kruskal-Wallis test). In a binary combination variant alleles of hOGG1 Ser326Cys and APE1 Asn148Glu polymorphisms were associated with a significant decrease in the capacity to repair DNA oxidative damage (P=0.018, Kruskal-Wallis test). In summary, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms seem to exert the predominant modulating effect on irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative damage, respectively.

Adult↗
PubMed2006

ARLTS1 variants and melanoma risk.

Variants in the tumor suppressor gene ARLTS1 (ADP-ribosylation factor-like tumor-suppressor gene 1) have been shown to influence familial cancer risk. Both Cys148Arg and Trp149Stop were associated with an increased risk of familial or high-risk familial breast cancer, respectively. We studied the impact of these gene variants on melanoma risk, investigating 351 melanoma patients and 804 control subjects. While ARLTS1 Trp149Stop did not influence melanoma risk (OR = 0.83, 95% CI = 0.37-1.88, p = 0.65), Cys148Arg revealed a statistically significant association with an increased risk for heterozygous carriers (OR = 1.43, 95% CI = 1.05-1.95, p = 0.02). An additional risk enhancement, though statistically non-significant, was observed in individuals with multiple melanomas (OR = 2.33, 95% CI = 0.87-6.26, p = 0.08).

ADP-Ribosylation Factors↗
PubMed2006

Gene expression profiling of human endometrial-trophoblast interaction in a coculture model.

Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture system of endometrial stromal cells with first-trimester trophoblast explants was established. Trophoblast and endometrial stromal cells were separated after 24 h. Gene expression of endometrial stromal cells after coculture was compared with the gene expression of endometrial stromal cells cultured alone by microarray analysis. We confirmed the expression of distinct genes using real-time PCR. Genes up-regulated included those for inflammatory response, immune response, and chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL-18 receptor, IL-15, IL-15 receptor, TNF-alpha-induced protein 6, and IL-6 signal transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal transduction. Also up-regulated were genes for growth and development, glucose metabolism, and lipid metabolism: DKK-1, WISP, IGF-II, hydroxysteroid 11beta-dehydrogenase 1, hydroxyprostaglandin dehydrogenase 15, prostaglandin E synthase, prostaglandin F receptor, aldehyde dehydrogenase 1 family, member A3 and phosphatidic acid phosphatase type 2B. Other genes included genes for cell-cell signaling (pre-B-cell colony-enhancing factor 1), proteolysis, calcium ion binding, regulation of transcription, and others. Down-regulated genes included genes for proteolysis (MMP-11 and mitochondrial intermediate peptidase), genes for cell death (caspase 6, death-associated protein kinase 1, and histone deacetylase 5), transcription factors (sex determining region Y-box 4, dachshund homolog 1, ets variant gene 1, and zinc finger protein 84 and 435), and genes for humoral immune response (CD24 antigen). Trophoblast has a significant impact on endometrial stromal cell gene expression. Some of the genes regulated by trophoblast in endometrial stromal cells are already known to be regulated by progesterone and show the endocrine function of trophoblast during pregnancy. Others are genes so far unknown to play a role in endometrial-trophoblast interaction and open a wide field of investigation.

Adult↗
PubMed2006

Biophysical properties of the extra-cellular domain of the calcium-sensing receptor.

The Calcium-Sensing Receptor (CaSR) is a G-protein-coupled receptor that regulates calcium homeostasis by altering parathyroid hormone release, and which binds divalent and trivalent cations, amino acids, polyamines, and polycationic ligands. To obtain information about the structural properties of the CaSR, we expressed milligram quantities of a pure, homogeneous, and functional fragment of the human CaSR extracellular domain (residues 20-535). The expressed and purified protein is folded and binds both neomycin and calcium. It forms dimers in the absence of reducing agents such as beta-mercaptoethanol. Thermal denaturation studies show it has enthalpy and entropy values of unfolding equal to DeltaH=-178+/-4 kJ/mol and DeltaS=-535+/-13 J/mol/K. The protein has significant secondary structure with alpha-helical, beta-sheet, beta-turns, and disordered content of 36.6+/-6.7%, 13.3+/-5.3%, 20.2+/-3.3%, and 29.4+/-4.0%, respectively. The described method for the expression and purification of CaSR should prove useful for further structural studies of this physiologically important protein.

Animals↗
PubMed2006

Spectroscopic techniques and cyclic voltammetry with synthesis: manganese(II) coordination stability and its ligand field parameters effect on macrocyclic ligands.

Manganese(II) macrocyclic complexes are prepared with different macrocyclic ligands, containing cyclic skeleton bearing organic components which have different chromospheres like N, O and S donor atoms and stereochemistry. Thus, six macrocyclic ligands, were prepared and their capacity to retain the manganese(II) ion in solid as well as in aqueous solution was determined and characterized by elemental analyses, molar conductance measurements, magnetic susceptibility measurements, mass, (1)H NMR, IR, electronic spectral and cyclic voltammetric studies. The electronic spectrum of this system showed a dependence that may be consistent with the formation of stable complexes and coordination behaviour of the ions. ESR spectra of all the complexes are recorded in solid as well as solution, which show the oxidation state of the manganese(II). Spin Hamiltonian manganese(II), which can be defined as the magnetic field vector (H): H = gBeta(e)HS + D[S(2)(z) - 35/12] + E[S(2)(z) - S(2)(y)] + ASI + (1/6)a [S(4)(x) + S(4)(y) + S(4)(z) - 707/16] + (1/180)F[(35S(2)(z) - 475)/(2S(2)(z) + 3255/10)] Significant distortion of the manganese(II) ion in observed geometry is evident from the angle subtended by the different membered chelate rings and the angles spanned by trans donor atoms octahedral geometry. Cyclic voltammetric studies indicate that complexes with all ligands undergoes one electron oxidation from manganese(II) to manganese(III) followed by a further oxidation to manganese(IV) at a significantly more positive potential.

Anions↗
PubMed2006

Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D(28K).

Calbindin-D(28K) is a Ca2+-binding protein, performing roles as both a calcium buffer and calcium sensor. The NMR solution structure of Ca2+-loaded calbindin-D(28K) reveals a single, globular fold consisting of six distinct EF-hand subdomains, which coordinate Ca2+ in loops on EF1, EF3, EF4 and EF5. Target peptides from Ran-binding protein M and myo-inositol monophosphatase, along with a new target from procaspase-3, are shown to interact with the protein on a surface comprised of alpha5 (EF3), alpha8 (EF4) and the EF2-EF3 and EF4-EF5 loops. Fluorescence experiments reveal that calbindin-D(28K) adopts discrete hydrophobic states as it binds Ca2+. The structure, binding interface and hydrophobic characteristics of Ca2+-loaded calbindin-D(28K) provide the first detailed insights into how this essential protein may function. This structure is one of the largest high-resolution NMR structures and the largest monomeric EF-hand protein to be solved to date.

Amino Acid Sequence↗
PubMed2006

Metal-binding properties of human centrin-2 determined by micro-electrospray ionization mass spectrometry and UV spectroscopy.

We analyzed the metal-binding properties of human centrin-2 (HsCen-2) and followed the changes in HsCen-2 structure upon metal-binding using micro-electrospray ionization mass spectrometry (muESI-MS). Apo-HsCen-2 is mostly monomeric. The ESI spectra of HsCen-2 show two charge-state distributions, representing two conformations of the protein. HsCen-2 binds four moles calcium/mol protein: one mol of calcium with high affinity, one additional mol of calcium with lower affinity, and two moles of calcium at low affinity sites. HsCen-2 binds four moles of magnesium/mol protein. The conformation giving the lower charge-state HsCen-2 by ESI, binds calcium and magnesium more readily than does the higher charge-state HsCen-2. Both conformations of HsCen-2 bind calcium more readily than magnesium. Calcium was more effective in displacing magnesium bound to HsCen-2 than vice versa. Binding of a peptide from a known binding partner, the xeroderma pigmentosum complementation group protein C (XPC), to apo-HsCen-2, occurs in the presence or the absence of calcium. Near and far-UV CD spectra of HsCen-2 show little difference with addition of calcium or magnesium. Minor changes in secondary structure are noted. Melting curves derived from temperature dependence of molar ellipticity at 222 nm for HsCen-2 show that calcium increases protein stability whereas magnesium does not. Delta 25 HsCen-2 behaves similarly to HsCen-2. We conclude that HsCen-2 binds calcium and magnesium and that calcium modulates HsCen-2 structure and function by increasing its stability without undergoing significant changes in secondary or tertiary structure.

Binding Sites↗
PubMed2006

FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation.

BACKGROUND: The phosphatonins fibroblast growth factor-23 (FGF-23) and FRP-4 are inhibitors of tubular phosphate reabsorption that may play a role in the hyperphosphatemia associated with chronic kidney disease (CKD) or in the hypophosphatemia associated with renal transplants. METHODS: Plasma FGF-23, FRP-4, phosphorus and parathyroid hormone were measured in patients at all stages of CKD. Phosphate regulation of FGF-23 and secreted frizzled related protein-4 (sFRP-4) was examined in end-stage renal disease patients in the presence and absence of therapeutic phosphate binder usage. In renal transplant patients, plasma FGF-23, sFRP-4 and phosphorus concentrations were determined before and 4-5 days after transplantation. RESULTS: Plasma FGF-23 correlated with creatinine clearance (r2 = -0.584, p < 0.0001) and plasma phosphorus (r2 = 0.347, p < 0.001) in CKD patients and with plasma phosphorus (r2 = 0.448, p < 0.001) in end-stage renal disease patients. Phosphate binder withdrawal increased FGF-23 levels. In kidney transplant patients, dramatic decreases in FGF-23 (-88.8 +/- 5.4%) and phosphorus (-64 +/- 10.2%) were observed by 4-5 days post-transplantation. In patients with post-transplant hypophosphatemia, FGF-23 levels correlated inversely with plasma phosphorus (r2 = 0.661, p < 0.05). sFRP-4 levels did not change with creatinine clearance or hyperphosphatemia in CKD or end-stage renal disease patients, and no relation was noted between post-transplant sFRP-4 levels and hypophosphatemia. CONCLUSIONS: In CKD, FGF-23 levels rose with decreasing creatinine clearance rates and increasing plasma phosphorus levels, and rapidly decreased post-transplantation suggesting FGF-23 is cleared by the kidney. Residual FGF-23 may contribute to the hypophosphatemia in post-transplant patients.

Female↗
PubMed2006

Coordination stability between metal/ligands interaction by modern spectroscopic studies: IR, electronic, EPR and cyclic voltammetry of cobalt(II) complexes with organic skeleton containing cyclic ligands.

A comparative investigation of the interaction of two pyrrole-substituted, mixed oxygen and nitrogen donor, macrocycles ligands have been designed and their coordination interaction with cobalt(II) is studied. Cobalt(II) salts combine with a tetradentate and hexadentate macrocyclic nitrogen/oxygen donor ligands and formed novel cobalt(II) complexes which are characterized by elemental analysis, molar conductance, magnetic moments, mass, (1)H NMR, IR, electronic and EPR spectral studies. At the room temperature magnetic moment for cobalt(II) complexes lie in the range 4.70-5.01BM, which is higher than the spin-only value. All the complexes are high-spin type and have three unpaired electrons. Therefore, the electronic confutation and the splitting of the orbital will be t(2g)(5)eg(2). The electrochemical behaviour of the cobalt(II) complexes, the Co(III)/Co(II) couple are observed. Their positive potential indicates that metal in lower oxidation state is strongly bound to these ligands. The difference between the potential of the anodic peak and cathodic peak remains constant in all complexes. Also, the ratio between the cathodic peak current and square root of the scan rate is practically constant for the studied complexes.

Cobalt↗
PubMed2006

The structure of the human centrin 2-xeroderma pigmentosum group C protein complex.

Human centrin-2 plays a key role in centrosome function and stimulates nucleotide excision repair by binding to the xeroderma pigmentosum group C protein. To determine the structure of human centrin-2 and to develop an understanding of molecular interactions between centrin and xeroderma pigmentosum group C protein, we characterized the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide. Our structure shows that the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium atoms, whereas the amino-terminal lobe is in a closed conformation positioned distantly by an ordered alpha-helical linker. A stretch of the amino-terminal domain unique to centrins appears disordered. Two xeroderma pigmentosum group C peptides both bound to centrin-2 also interact to form an alpha-helical coiled-coil. The interface between centrin-2 and each peptide is predominantly nonpolar, and key hydrophobic residues of XPC have been identified that lead us to propose a novel binding motif for centrin.

Amino Acid Motifs↗
PubMed2006

Ala228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia, mantle cell lymphoma, prostate cancer, head and neck squamous cell carcinoma and bladder cancer.

Allelic loss of chromosome 8p21-22 is a frequent event in various human cancers including mantle cell lymphoma (MCL), prostate cancer, head and neck squamous cell carcinoma (HNSCC) and bladder cancer. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors, including TNFRSF10A and TNFRSF10B, are located within this chromosomal region. Since recent studies demonstrate that chronic lymphocytic leukemia (CLL) and prostate cells are TRAIL induced apoptosis, TRAIL-receptors are strong tumor suppressor candidate genes in human cancers exhibiting loss of chromosomal material in 8p21.3. However, no mutation of the TRAIL receptor genes has been reported in CLL, MCL, prostate cancer, HNSCC so far. In this study we analyzed the complete coding region of TNFRSF10A and TNFRSF10B in a series of 32 MCL and 101 CLL samples and detected a single nucleotide polymorphism (SNP) in TNFRSF10A (A683C) with tumor specific allele distribution. We examined allele distribution in 395 samples of different tumor entities (prostate cancer, n = 43; HNSCC, n = 40; bladder cancer, n = 179) and compared them to 137 samples from healthy probands. We found the rare allele of TNFRSF10A is more frequent in CLL, MCL, prostate cancer, bladder cancer and HNSCC. The A683C polymorphism did not cosegregate with other TNFRSF10A polymorphisms previously described. Thus screening for 683A-->C nucleotide exchanges may become important in diagnosis and/or treatment of these malignancies.

Binding Sites↗
PubMed2006

The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case-control study in Sweden.

Mechanisms behind the strong associations of esophageal adenocarcinoma risk with gastroesophageal reflux (GOR) and body mass remain to be defined. In a nationwide population-based case-control study, we examined associations of polymorphisms in the DNA repair genes XPD, XPC, XRCC1 and XRCC3 with risk of esophageal adenocarcinoma, squamous-cell carcinoma (SCC) and gastric cardia adenocarcinoma, and paid special attention to possible interactions with symptomatic reflux or body mass. We collected blood samples from 96, 81 and 126 interviewed incident cases of esophageal adenocarcinoma, esophageal SCC and gastric cardia adenocarcinoma, respectively, and 472 randomly selected controls, frequency-matched with regard to age and sex. DNA was extracted and polymorphisms in XPD codon 751 (Lys-->Gln), codon 312 (Asp-->Asn), C insertion in intron 10 of XPD, XPC codon 939 (Lys-->Gln), XRCC1 codon 399 (Arg-->Gln) and XRCC3 codon 241 (Thr-->Met) were examined using PCR-RFLP. Odds ratios (ORs) derived from multivariate logistic regression with adjustments for potential confounding factors estimated relative risks. XPD codon 751 Lys/Gln and Gln/Gln genotypes, compared with Lys/Lys genotype, were both associated with a more than doubled risk for esophageal adenocarcinoma (OR=2.4; 95% CI=1.4-4.4; OR=2.7, 95% CI=1.3-5.9). The combined effects of these genotypes and symptomatic GOR or body mass showed borderline significant deviation from additivity. Excess risks for esophageal SCC were also noted for XPD 751Gln variant genotypes. Other studied variants were not found to be related to the three tumors. Our study suggests that XPD 751Gln allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Spectral studies with coordination behaviour of (NO3) and (NCS) anions and EPR parameters of chromium(III) complexes which have different chromospheres macrocyclic ligands: synthesis and electronic spectroscopy.

New macrocyclic ligands were prepared and chromium(III) stability in the marcrocyclic cavities are reported. Two of them have four-coordinate [N2O2]:[N4], third one has five-coordinate [N2O2S] and the last one has six-coordinate [N4O2] donor macrocyclic cavities. These macrocyclic ligands have been synthesized with their chromium(III) complexes which have mononuclear nature and their structural features have been discussed on the basis of: elemental analysis, magnetic moment, electronic, IR, 1H NMR, and EPR spectral studies. All the chromium(III) complexes show magnetic moments in the range of 3.74-3.80 B.M. corresponding to high-spin configuration. However, the interaction of oxygen to the chromium ion in complexes is much weaker than that of other donor atoms. The spin-orbit coupling parameter, z, gives no significance because the splitting of doublet transition lines are too large to be explained by spin-orbit coupling. The beta values (0.75-0.79) indicate the covalent character, which is due to the presence of sigma bond between the metal/ligand. lambda values indicate that the complexes under study have substantial covalent character and their g-values have also been calculated by using spin-orbital coupling constant (lambda).

Anions↗