[The Advancement of Attenuated Total Reflection Fourier Transform Infrared Technology in Clinical Application].

The authors systemically reviewed the fast development of attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and its clinical application in the past decades. The advantages of this objective technique include real time scanning, easy manipulation and no harm to the subjects examined. Combined with pattern recognition methodology and further confirmation with the clinical and pathological diagnosis, the goal of fast differentiation of malignancy from benign lesions could be achieved. ATR-FTIR spectroscopy technique has shown high differential capacity for benign and malignant tissues such as thyroid, breast and pulmonary diseases. ATR-FTIR spectroscopy has being applied in investigating the differential value (the sensitivity, specificity, and accuracy) of metastatic lymph nodes in thyroid and breast cancer with encouraging results. ATR-FTIR technique would become a promising tool in tissue diagnosis intra-operatively. ATR-FTIR spectroscopy has also been widely applied in detecting bio-fluid to differentiate diseases. The serum ATR-FTIR spectroscopy has the ability of reflecting disease-related information in a fingerprint manner with little amount of blood. Several published articles have covered diseases such as glioma, chest pain, prostate cancer, renal failure, Alzheimer's disease, and ovarian cancer. The results of these researches have proved the efficacious discriminate value of this method. As ATR-FTIR spectroscopy has the potential of fast analysis, accurate diagnosis, and low cost-effective value. It would become one of the most important assisting diagnosis tools in future. Follow-up study should focus on enhancing sample quality and enlarging sample size to have further prospective clinical application.

Human genetic variants of homologous recombination repair genes first found to be associated with Epstein-Barr virus antibody titers in healthy Cantonese.

Epstein-Barr virus (EBV) infection is a major risk factor for nasopharyngeal carcinoma (NPC). Despite high prevalence of infection among the general population worldwide, only a small proportion of infected individuals presents with seropositivity for EBV-specific IgA antibodies. This seropositive subgroup of EBV carriers has an elevated cumulative risk for NPC during their lifetime. Previous studies reported that the host homologous recombination repair (HRR) system participates in EBV lytic replication, suggesting a potential mechanism to influence EBV reactivation status and thus seropositivity. To investigate whether genetic variants of HRR genes are associated with the serostatus in a healthy population, we investigated the association between seropositivity for anti-VCA-IgA and 156 tagging SNPs in 35 genes connected with HRR in an observational study among 755 healthy Cantonese speakers in southern China. Six variant alleles of MDC1, RAD54L, TP53BP1, RPA1, LIG3 and RFC1 exhibited associations with seropositivity (p(trend) from 0.0085 to 0.00027). Our study provides evidence that genetic variation within the HRR might affect an individual's propensity for EBV seropositive status of anti-VCA IgA antibody.

[Study on the meningoima using FT-mid-IR spectroscopy].

In the present investigation, 24 cases of meningoima tissues (including 12 cases of benign tumor and 12 cases of malignant tumor 12) were detected using FT-mid-IR spectroscopy linked with attenuated total reflectance (ATR) accessory. These FTIR spectra obtained from the above-mentioned meningoima tissues were analyzed and compared. Significant differences were found in the spectral features of different kinds of meningoima tissues for example fibrous type meningoima and endothelioid meningoima; and for the same type of meningoima tissues the significant differences in the spectram features can be also observed with the increase of grade malignancy. The malignant tumor can be distinguished primarily from benign tumor by the changes of position, shape and intensity of infrared absorption bands, particularly in the ranges of 1 000-1 500 cm(-1). The results show that the peak position of the bands (such as 1 160 cm(-1)) can be used to distinguish the characteristic of meningoima which are in agreement with the pathological results. The accuracy is larger than 85%. These results demonstrate that FT-mid-IR spectroscopy exhibits prospect to develop a novel, non-invasive and rapid method for the diagnosis the brain tumors.

Comprehensive pathway-based association study of DNA repair gene variants and the risk of nasopharyngeal carcinoma.

DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China, the ethnic group with the highest risk for NPC. A 2-stage study design was utilized. In the discovery stage, 676 tagging SNPs covering 88 DNA repair genes were genotyped in a matched case-control study (cases/controls = 755/755). Eleven SNPs with P(trend) < 0.01 were identified. Seven of these SNPs were located within 3 genes, RAD51L1, BRCA2, and TP53BP1. In the validation stage, these 11 SNPs were genotyped in a separate Cantonese population (cases/controls = 1,568/1,297). Two of the SNPs (rs927220 and rs11158728), both in RAD51L1, remained strongly associated with NPC. The SNP rs927220 had a significant P(combined) of 5.55 × 10(-5), with OR = 1.20 (95% CI = 1.10-1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong linkage disequilibrium with rs927220 (r(2) = 0.7), had a significant P(combined) of 2.0 × 10(-4), Bonferroni corrected P = 0.1372. Gene-environment interaction analysis suggested that the exposures of salted fish consumption and cigarette smoking had potential interactions with DNA repair gene variations, but need to be further investigated. Our findings support the notion that DNA repair genes, in particular RAD51L1, play a role in NPC etiology and development.

[Association of nasopharyngeal carcinoma risk with cytochrome P450 CYP1A1 gene polymorphisms].

OBJECTIVE: To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. METHODS: A total of 457 Cantonese nuclear families,consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943), were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. RESULTS: FBAT analysis showed that the minor allele frequencies (MAF) of the two SNP were 0.442 (C) and 0.339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification: chi2 = 2.399, P = 0.301; with stratification: low-titer group (VCA-IgA <1:80), MAF = 0.457 (C), chi2 = 1.221, P = 0.543; high-titer group (VCA-IgA > or = 1:80), MAF = 0.427 (C), chi2 =2.832, P = 0.243) . For m2 polymorphism, when VCA-IgA <1:80, the G allele showed decreased transmission under additive and dominant model (MAF = 0.347 (G); Zadditive = -2.120, Padditive = 0.034; Zdominant = - 2.303, Pdominant = 0.021) and a boundary P value was got with global statistic (chi2 = 5.394, P = 0.067) . Haplotype TG (0.057), constructed by m1 and m2, might decrease nasopharyngeal carcinoma risk (Z= -2.002, P=0.045). A boundary P value was also got with global statistic (chi2 =7.067, P=0.070). CONCLUSION: There was no statistical significance between m1 polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.

A case-control and a family-based association study revealing an association between CYP2E1 polymorphisms and nasopharyngeal carcinoma risk in Cantonese.

Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is more prevalent in Southern China, especially in Guangdong. The cytochrome P450 2E1 (CYP2E1) has been recognized as one of the critically important enzymes involved in oxidizing carcinogens and is probably to be associated with NPC carcinogenesis. To systematically investigate the association between genetic variants in CYP2E1 and NPC risk in Cantonese, two independent studies, a family-based association study and a case-control study, were conducted using the haplotype-tagging single-nucleotide polymorphism approach. A total of 2499 individuals from 546 nuclear families were initially genotyped for the family-based association study. Single-nucleotide polymorphisms (SNPs) rs9418990, rs915908, rs8192780, rs1536826, rs3827688 and one haplotype h2 (CGTGTTAA) were revealed to be significantly associated with the NPC phenotype (P = 0.045-0.003 and P = 0.003, respectively). To follow up the initial study, a case-control study including 755 cases and 755 controls was conducted. Similar results were observed in the case-control study in individuals <46 years of age and had a history of cigarette smoking, with odds ratios (ORs) of specific genotypes ranging from 1.88 to 2.99 corresponding to SNP rs9418990, rs3813865, rs915906, rs2249695, rs8192780, rs1536826, rs3827688 and of haplotypes h2 with OR = 1.65 (P = 0.026), h5 (CCCGTTAA) with OR = 2.58 (P = 0.007). The values of false-positive report probability were <0.015 for six SNPs, suggesting that the reported associations are less probably to be false. This study provides robust evidence for associations between genetic variants of CYP2E1 and NPC risk.

[FTIR spectroscopic study on gallbladder carcinoma cell and nucleus].

The aim of the present research is to establish the cell basis for the carcinoma tissue diagnosis by exploring a method to obtain the FTIR (Fourier transform infrared spectra) of the cultured carcinoma cell and nucleus with FTIR spectroscopy, and investigating the special spectral features of the carcinoma cell and nucleus compared with the carcinoma tissues. In this paper, the gallbladder carcinoma tissues confirmed by histology were measured using a Nicolet Magna 5700-II FTIR spectrometer and the corresponding FTIR spectra were obtained. The cultured gallbladder carcinoma cell (GBC-SD) and nucleus were centrifuged to provide a small pellet of cell and nucleus for FTIR analysis. The cell and nucleus pellet was then placed on the OMNIC sampler. Then the infrared spectra were recorded by the same equipment. Based on the previously established criteria, a comparative study was subsequently carried out between the spectra of the cultured carcinoma cell and nucleus (GBC-SD) and that of the corresponding gallbladder tissues. Several infrared spectral features of the carcinoma cell and nucleus were obtained. All the results suggest that the spectral features of the carcinoma cell and nucleus can be well reflected by that of the carcinoma tissue, though the later is more complicated, which might originate from the intrinsic complexity of the tissue. This study shows that the diagnosis of carcinoma tissue by FTIR method exhibits sufficient cell basis.

[Study on malignant and normal rectum tissues using IR and 1H and 31P NMR spectroscopy].

In the present paper, NMR spectroscopy, an effective tool to detect the variation in, molecular structure and changes in chemical composition of metabolites in tissues, was used to study the differences between malignant and normal tissues from rectum. 1H and 31P spectra of seven malignant rectum tissue samples and five normal control tissues were investigated by using a 300 M NMR spectrometers and compared with the results of the infrared spectra of normal and malignant rectum organ tissues. The results indicate that the 1H and 31P spectra of rectum cancer tissues are significantly different from those of the normal controls and most differences present in the form of variation in relative intensities of the characteristic peaks of various metabolites. Systematic differences in the NMR spectra between malignant tissues and normal controls are as follows: in the 1H NMR spectra, differences lie in fatty acids with the concentration of fatty acid decreasing significantly in malignant tissues. In the 31P NMR spectra, differences lie in phospholipid, with the chemical shift of phospholipid decreasing significantly in malignant tissues. This phenomenon may reflect the fact that the activity of protein synthesis is enhanced in cancerous tissues. The difference in the chemical shift of phospholipid between normal rectal tissue and malignant tissue may be considered as a detection criterion. Therefore, the above spectral variations in 31P NMR spectra may be utilized as a potential tool to diagnose rectum cancer.

[FTIR spectroscopic explorations of freshly resected laryngeal carcinoma tissues].

OBJECTIVE: To investigate the characteristics of freshly resected laryngeal carcinoma by Fourier transform infrared spectroscopy (FTIR). METHODS: FTIR was applied to the study of the cancerous tissues and adjacent normal tissues in 32 patients. RESULTS: Compared with pathological diagnosis results, one benign specimen was classified as a malignant, the accuracy was 98.4%. Significant differences were seen in the FTIR spectra between the normal and malignant laryngeal tissues. The peak at 1085 cm(-1) shift to 1114 cm(-1) showed that the relative contents of DNA in laryngeal carcinoma cells was increased. The peak at 1397 cm(-1) was stronger than 1451 cm(-1) in normal tissues, while it was not obvious in cancer tissues. I(2926)/I(2870) in carcinoma cells was lower than that in normal tissues. The wave numbers of the bands of amide I and amide II, symmetric and asymmetric stretching bands of CH(3), stretching vibration bands of C-OH and NH band were shifted to higher number in cancer tissues. CONCLUSION: The study shows that the malignant and normal laryngeal tissues have different FTIR spectra, which are mainly due to changes in protein, nucleic acid and phospholipids. FTIR may become a new method for the diagnosis of laryngeal carcinoma in clinical practice.

[Family-based association study of XRCC1 gene polymorphisms in nasopharyngeal carcinoma].

OBJECTIVE: To test the association between XRCC1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through a family-based association study. METHODS: A total of 2134 study subjects from 457 Cantonese nuclear families were recruited in the study. Each family had two parents and at least one offspring with nasopharyngeal carcinoma. Genotyping for three single nucleotide polymorphisms in XRCC1 gene, including rs1799782 (C > T), rs25489 (G > A) and rs25487 (G > A), were performed with PCR-RFLP assay. The genotype data were analyzed with family-based association test (FBAT) software to check linkage and association between the three genetic markers and susceptibility of nasopharyngeal carcinoma. RESULTS: FBAT analysis showed XRCC1 gene genotypes and haplotypes were not significantly associated with nasopharyngeal carcinoma in our study population (rs1799782: chi(2) = 1.006, P = 0.605; rs25489: chi(2) = 0.470, P = 0.790; rs25487: chi(2) = 2.563, P = 0.278; haplotype: chi(2) = 3.004, P = 0.557, global statistic). For rs25487, the G allele (major allele) showed increased transmission under dominant model (Z = 1.985, P = 0.047). Whereas the C allele (minor allele) exhibited reduced transmission under recessive model (Z = -1.985, P = 0.047). However, no increased/reduced transmission was observed under additive model and with global statistic. CONCLUSION: There is no evidence of an association between polymorphisms in XRCC1 gene and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families is observed in this study.

[Application of fourier transform infrared spectroscopy to non-invasive detection of pleomorphic adenoma of salivary gland in vivo].

In the present work, 20 patients with salivary pleomorphic adenoma were recruited for FTIR spectroscopic measurement. These obtained FTIR spectra were analyzed and compared. It was found that there were significant differences in the spectral features of the skin covering normal salivary gland, pleomorphic adenoma, and carcinoma change of pleomorphic adenoma, such as the changes in peak position, band shape and relative intensity of the bands in the ranges of 1000-1800 cm(-1) and 2800-3000 cm(-1). Pathological diagnosis demonstrated that 2 of the 20 patients suffered actually carcinoma change of pleomorphic adenoma, which is in good agreement with the result of FTIR spectroscopicmeasurement. FTIR spectroscopic m ethodsuggested that pleomorphic adenoma is the intermediate between normal salivary gland and carcinoma change of pleomorphic adenoma.