Yi Torng Tee

Significant elevation and correlation of plasma neutrophil gelatinase associated lipocalin and its complex with matrix metalloproteinase-9 in patients with pelvic inflammatory disease.

BACKGROUNDS To detect the expression of plasma neutrophil gelatinase associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) in patients with pelvic inflammatory disease (PID). METHODS Enzyme-linked immunosorbent assay was used to measure the levels of plasma NGAL and NGAL/MMP-9 complex. RESULTS The levels of plasma NGAL or NGAL/MMP-9 complex were increased in patients with PID compared with those in normal controls and decreased significantly after treatment. Pre-treatment plasma level of NGAL was significantly correlated with WBC and neutrophil counts. In patients with PID, plasma level of NGAL/MMP-9 complex was correlated with plasma level of NGAL or MMP-9 significantly. In predicting PID, the sensitivities of NGAL and NGAL/MMP-9 complex were 76.6% and 78.1%; the negative predictive values, 72.7% and 74.5%. CONCLUSIONS Plasma NGAL and NGAL/MMP-9 complex may act as diagnostic adjuvant biomarkers for PID. In patients with PID, about 80% have plasma levels of NGAL or NGAL/MMP-9 complex level >10.04 ng/ml or 2.33 ng/ml, respectively.

Plasma interleukin-1β, -6, -8 and tumor necrosis factor-α as highly informative markers of pelvic inflammatory disease

Abstract Background: The role of proinflammatory cytokines in pelvic inflammatory disease (PID) is unclear. We therefore determined whether plasma proinflammatory cytokines, interleukin-1β (IL-1β), IL-6, IL-8 and tumor necrosis factor-α (TNF-α) were useful plasma markers in PID patients. Methods: Multiplex bead array analysis was used to measure the plasma levels of proinflammatory cytokines in 50 healthy controls as well as in 41 PID patients before and after routine protocol treatments. Results: IL-1β, IL-6, IL-8 and TNF-α were significantly elevated in PID patients before antibiotic treatment than after treatment. However, IL-8 was not significantly different between healthy controls and PID patients. The relative increase in ratio of IL-6 was significantly correlated with white blood cell count (r=0.448, p=0.003), neutrophil count (r=0.472, p=0.002) and C-reactive protein level (r=0.412, p=0.008). Conclusions: IL-1β, IL-6, IL-8 and TNF-α may play an important role in the pathogenesis of PID. These biomarkers, particularly IL-6, could be useful adjuncts for the clinical diagnosis of PID. Clin Chem Lab Med 2008;46:997–1003.

Imbalanced serum concentration between cathepsin B and cystatin C in patients with pelvic inflammatory disease

OBJECTIVE To detect the serum expression of cathepsin B and cystatin C and the ratio of cathepsin B to cystatin C in patients with pelvic inflammatory disease (PID) and speculate whether those are helpful indicators for the diagnosis of PID. DESIGN A random consecutive study. SETTING University hospital. PATIENT(S) Forty-four women who were diagnosed with PID. INTERVENTION(S) Collected blood specimens of patients before and after they received treatment. MAIN OUTCOME MEASURE(S) ELISA analysis was used to measure the serum levels of cathepsin B and cystatin C. RESULT(S) A significantly increased expression of cathepsin B but decreased expression of cystatin C and significant correlations between neutrophils and cathepsin B, as well as between C-reactive protein (CRP) and cathepsin B, were found in patients with PID. Consistently, the ratio of cathepsin B to cystatin C correlated significantly with neutrophils and with CRP in patients with PID. CONCLUSION(S) Increased expression of cathepsin B but a decreased level of cystatin C and an imbalance between cathepsin B and cystatin C may contribute to the progression of PID. Detection of cathepsin B and cystatin C can provide useful clinical information for PID.

Genetic polymorphism of urokinase-type plasminogen activator is interacting with plasminogen activator inhibitor-1 to raise risk of cervical neoplasia.

To evaluate the impact of plasminogen activator (PA) system genes, including urokinase plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor‐1 (PAI‐1) gene polymorphisms in patients with the cervical neoplasia.

Elevated plasma osteopontin level is associated with pelvic inflammatory disease.

Our purpose here was to detect the association among plasma osteopontin concentration, single nucleotide polymorphisms (SNPs) of osteopontin gene, and pelvic inflammatory disease (PID). The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) were respectively used to measure the plasma osteopontin level and its gene polymorphisms. The level of plasma osteopontin was elevated in patients with PID as compared to that of healthy women and decreased significantly after treatment. Plasma osteopontin concentration was significantly correlated with white blood cell (WBC) and neutrophil counts and plasma C-reactive protein (CRP) level in patients with PID. No significant difference was found in the genotypes or alleles distribution of osteopontin SNPs, rs1126616 or rs9138, between patients with PID and normal controls. Plasma osteopontin concentration was not associated with osteopontin polymorphism. When the cutoff level of the plasma osteopontin concentration was set to be 58.53 ng/mL, the adjusted odds ratio of plasma osteopontin for PID risk was 3.87 (95% confident interval: 1.30-11.51). Plasma osteopontin level may act as a prediction marker for PID.

Significant association of genetic polymorphism of human nonmetastatic clone 23 type 1 gene with an increased risk of endometrial cancer

OBJECTIVE To investigate the association of single nucleotide polymorphisms (SNPs) of nonmetastatic clone 23 type 1 (nm23-H1) gene with endometrial cancer and their implication in clinicopathologic characteristics of women in Taiwan. METHODS Three hundred and fifty-nine blood samples were collected from 268 healthy women and 91 patients with endometrial cancer to analyze SNPs rs16949649 and rs2302254 of nm23-H1 promoter using real time polymerase chain reaction and genotyping. The association of genotype and allele differences of nm23-H1 SNPs with endometrial cancer and their implication in some clinicopathologic variables were analyzed using Pearsons Chi-square or Fisher exact tests. RESULTS Women with heterozygous genotypes TC in rs16949649 or CT in rs2302254 exhibited higher risk to develop endometrial cancer as compared to those with their wild-type or homozygous genotypes (odds ratio 3.30 and 1.86; 1.84 and 1.90 for respective SNP). Individuals with CC genotype were at less risk (OR: 0.08; P=0.037) to have non-endometrioid type as compared to those with TT genotype in rs16949649. However, a trend of increased risk (OR: 26.67; P=0.01) of advanced stage endometrial cancer (stage III-IV) was observed in patients with TT genotype as compared to those with CC genotype in rs2302254. CONCLUSIONS Heterozygous genotypes TC in rs16949649 and CT in rs2302254 of nm23-H1 promoter are potential susceptibility factors for endometrial cancer in Taiwan women. Once having the endometrial cancer, Taiwan women with variant homozygote CC in rs1694964 were at less risk to have non-endometrioid type, while women with variant homozygote TT in rs2302254 tended to have advanced stage cancer.

Significant elevation of plasma matrix metalloproteinase-9 level and its ratio to matrix metalloproteinase-2 in patients with pelvic inflammatory disease

OBJECTIVE To detect the expression of plasma matrix metalloproteinase-2 (MMP-2) and MMP-9, and MMP-9:MMP-2 ratio in patients with pelvic inflammatory disease (PID). DESIGN A consecutive study with approximate 1:2 case-to-control ratio. SETTING University hospital. PATIENT(S) Forty-seven patients with PID and 80 healthy women. INTERVENTION(S) Collected blood specimens of patients with PID before and after treatment. MAIN OUTCOME MEASURE(S) ELISA and gelatin zymography were used to measure the expression of plasma MMP-2 and MMP-9. RESULT(S) The level of plasma MMP-9 or MMP-9:MMP-2 ratio was elevated in patients with PID compared with healthy controls and decreased significantly after treatment. The activity of MMP-9, but not MMP-2, tended to be higher in 47 patients with PID before the treatment compared with that after the treatment. Pretreatment plasma MMP-9 or MMP-9:MMP-2 ratio was significantly correlated with white blood cell (WBC) and neutrophil counts. As prediction markers for PID, the sensitivities of MMP-9 and MMP-9:MMP-2 ratio were 76.6% and 76.6%, whereas the negative predictive values were 82.5% and 83.3%. CONCLUSION(S) Level of plasma MMP-9 and MMP-9:MMP-2 ratio may act as prediction markers for PID. In patients with PID, 80% have a plasma MMP-9 level higher than 115 ng/mL or a MMP-9:MMP-2 ratio higher than 2.15.

G801A polymorphism of human stromal cell-derived factor 1 gene raises no susceptibility to neoplastic lesions of uterine cervix.

Objective This study aimed to investigate the association of stromal cell–derived factor 1 (SDF-1) gene polymorphisms with the neoplastic lesions of uterine cervix in Mid-Taiwan women. Materials and Methods Four hundred ninety-eight blood samples were collected from 161 patients with neoplasia of uterine cervix, including 76 cancer patients, 61 patients with high-grade dysplasia, and 24 with low-grade dysplasia, and 337 healthy controls who lived in Mid-Taiwan. Polymorphism of the SDF-1 gene was examined using polymerase chain reaction–restriction fragment length polymorphism. Results For SDF-1 gene polymorphisms, the wild-type homozygous alleles (G/G) yielded 100- and 193-bp products, the heterozygous alleles (G/A) yielded 100-, 193- and 293-bp products, whereas the mutated-type homozygous alleles (A/A) yielded a 293-bp product. We found no significant difference in genotypes or alleles distribution of SDF-1 polymorphisms between patients with cervical neoplasia and healthy women (P = 0.530). Compared with the homozygous GG subgroup, GA and AA subgroups do not increase the risk of cervical neoplasia. Conclusions Although the expression of SDF-1 was reported to be significantly increased in cervical carcinogenesis in previous studies, our results, however, show that SDF-1 gene polymorphism could not be considered as a factor related to an increased susceptibility to cervical neoplasia.

Polymorphisms of Human Nonmetastatic Clone 23 Type 1 Gene and Neoplastic Lesions of Uterine Cervix

Hypothesis: Single-nucleotide polymorphisms (SNP) in promoter of human nonmetastatic clone 23 type 1 (nm23-H1) may affect their binding with transcription factors and affect promoter activity as well as gene transcription. Therefore, we investigated the impact of the nm23-H1 gene polymorphisms on the neoplastic lesions of uterine cervix in mid-Taiwan women (women who live in the central area of Taiwan). We expected that women with different genotypes in nm23-H1 polymorphisms, such as rs34214448, rs16949649, or rs2302254, may have different incidences of cervical neoplasia. Materials and Methods: In total, 366 blood samples were collected from 244 healthy women and 122 patients with cervical neoplasia to analyze 3 nm23-H1 gene single-nucleotide polymorphisms (rs34214448, rs16949649, and rs2302254). Results: The heterozygous genotypes, TG in rs34214448 or TC in rs16949649, were differentially distributed between patients with cervical neoplasia and normal women (Hommel adjusted P = .0440 and .0435, respectively) as compared to their homozygotes. Moreover, compared to those with wild-type homozygotes and heterozygotes, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exert different distributions between patients with cervical neoplasia and normal women (P = .058 and .058). Interestingly, we found the genotype distribution of rs34214448 has significant association with that of rs16949649 with high consistency. Conclusions: Mid-Taiwan women with the polymorphic heterozygotes TG in rs34214448 or TC in rs16949649 of human nonmetastatic clone 23 type 1 promoter have the tendency to develop cervical neoplasia while compared to their homozygous counterparts. However, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exhibit less tendency as compared to those with wild-type homozygotes and heterozygotes.

Primary treatment and prognostic factors of carcinosarcoma of the ovary, fallopian tube, and peritoneum: A Taiwanese Gynecologic Oncology Group study

Objective This study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum. Materials and Methods This retrospective study was undertaken by the Taiwanese Gynecologic Oncology Group. The retrieved clinical data included demographic characteristics, medical disease, tumor status, extent of surgery, and adjuvant chemotherapy. Results In total, 63 patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum were identified. Sixty-one patients with complete data were enrolled for further data analysis. The mean follow-up period was 1.0 year, and the mean overall survival was 15.4 months. By log-rank tests, age, menopausal status, parity, hypertension, diabetes, primary tumor size, para-aortic lymph node metastasis, pretreatment CA-125, preceding diagnostic surgery, hysterectomy, lymphadenectomy, other surgeries, and paclitaxel use were not predictive of overall survival. Omentectomy, no gross residual implants after surgery, platinum treatment, and no pelvic lymph node metastasis had a trend toward better survival. Early diagnosis at stage I and cisplatin/ifosfamide regimen were significant associated with a better overall survival in log-rank and simple Cox regression tests. Bilateral ovarian tumors and metastatic tumors larger than 2 cm were significantly associated with a poorer overall survival. Conclusions Early diagnosis at stage I, unilateral ovarian tumor, metastatic tumors less than 2 cm, and cisplatin/ifosfamide regimen were predictive of a better survival. Omentectomy and complete debulking surgery also showed a trend toward better survival. Thus, these treatment strategies should be applied in patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum.