Increased plasma soluble CD40 ligand concentration in pelvic inflammatory disease.

BACKGROUND: The role of soluble CD40 ligand (sCD40L) in pelvic inflammatory disease (PID) remains unclear. We sought to determine whether sCD40L was an efficient serum marker as with WBC and CRP in PID patients. METHODS: Enzyme-linked immunosorbent assay was used to measure the plasma levels of sCD40L before and after routine protocol treatments in sixty-four PID patients and seventy healthy controls. RESULTS: The level of plasma sCD40L (pg/ml) was significantly elevated in PID patients (1632.83±270.91) compared to that in normal controls (700.33±58.77; p=0.001) and decreased significantly as compared to that in the same patients (928.77±177.25; p=0.0001) after they received treatment. The concentration of sCD40L was significantly correlated with the level of plasma C-reactive protein (CRP) in the blood (r=0.202, p=0.01, n=134). When the cutoff level of plasma sCD40L levels was determined to be 1612.26pg/ml based on ROC, the sensitivity, specificity, and the area under the curve of plasma sCD40L level for predicting PID were 0.26, 0.97, and 0.58 (95% confidence interval: 0.48-0.68), respectively, while the adjusted odds ratio (AOR) with their 95% CI of plasma sCD40L for PID risk was 7.09 (95% CI=1.14-43.87, p=0.03). CONCLUSIONS: The expression of plasma sCD40L was increased in patients with PID and detection of plasma sCD40L could be useful for the diagnosis of PID.

Correlation of plasma osteopontin and neutrophil gelatinase-associated lipocalin levels with the severity and clinical outcome of pelvic inflammatory disease.

OBJECTIVE: To investigate the correlation of two important inflammatory biomarkers, plasma osteopontin and neutrophil gelatinase-associated lipocalin (NGAL), with the severity and outcome of pelvic inflammatory disease (PID). MATERIALS AND METHODS: Sixty-one patients with PID, including 25 patients with tubo-ovarian abscess (TOA), were consecutively recruited. Their blood samples were tested for the concentrations of plasma osteopontin and NGAL using enzyme-linked immunosorbent assay. The associations of these biomarkers with TOA, length of hospitalization, and incidence of surgery were also analyzed. RESULTS: Plasma osteopontin level was significantly increased in PID patients with TOA compared to PID patients without TOA (median 107.77 ng/mL vs. 72.39 ng/mL, p = 0.004). However, there was no significant difference for plasma NGAL. If the cutoff level of plasma osteopontin was set at 81.1 ng/mL, there was a 76.0% sensitivity and a 24.0% false negative rate in predicting TOA in PID patients. Plasma osteopontin significantly correlated with length of hospital stay (r = 0.467, p < 0.001), and this correlation was better than that of NGAL. However, neither biomarker was associated with incidence of surgery. CONCLUSION: Plasma osteopontin has a better correlation with TOA and length of hospitalization compared to NGAL. If plasma osteopontin level falls below 81.1 ng/mL, PID patients will have about a 20% chance of developing TOA. Incorporating plasma osteopontin, but not NGAL, will allow for an adjuvant diagnostic biomarker for TOA and predictor of length of hospital stay.

The expression of ribonucleotide reductase M2 in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients.

BACKGROUND: To investigate the implication of ribonucleotide reductase M2 (RRM2) in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients. METHODOLOGY AND PRINCIPAL FINDINGS: The impact of RRM2 on cell viability was investigated in SiHa cervical cancer cells after RRM2 knockdown and the addition of cisplatin, which induces inter- and intra-strand DNA crosslinks. RRM2 immunoreactivity was evaluated by semi-quantitative H score among 29 normal, 30 low-grade dysplasia, 30 high-grade dysplasia and 103 invasive cancer tissue specimens of the uterine cervix, using tissue microarrays. RRM2 was then correlated with the clinicopathological variables of cervical cancer and patient survival. A greater toxic effect on cell viability using cisplatin was reflected by the greater reduction in RRM2 protein expression in SiHa cells. The RRM2 expression in cancer tissues was higher than that in high-grade dysplasia, low-grade dysplasia or normal cervical tissues. RRM2 upregulation was correlated with deep stromal invasion, large tumors and parametrial invasion and predicted poor survival. CONCLUSIONS: RRM2 is a new molecular marker for the diagnosis and clinical outcomes of cervical cancer. It is involved in cervical carcinogenesis and predicts poor survival, and may be a potential therapeutic target including in cisplatin treatment.

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.

Relationships of single nucleotide polymorphisms of monocyte chemoattractant protein 1 and chemokine receptor 2 with susceptibility and clinicopathologic characteristics of neoplasia of uterine cervix in Taiwan women.

Few studies reported the implication of single nucleotide polymorphisms (SNPs) of monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) in clinical significance of cancer of uterine cervix. We hypothesized that SNPs of MCP-1 and CCR-2 may affect the expression of these genes and then proteins. Therefore, we investigated the influence of the gene polymorphisms of MCP-1 and CCR-2 on the susceptibility and clinicopathologic characteristics of cervical neoplasia in Taiwan women. We recruited 86 patients with invasive cancer and 61 with high-grade dysplasia and 253 control women and selected 1 MCP-1 SNP rs1024611 (-2518G/A) and 1 CCR-2 SNP rs1799864 (190G/A; V64I) to determine their genotypes distribution using polymerase chain reaction-restriction fragment length polymorphism. In comparison to normal individuals with homozygotes GG in MCP-2 SNP, women with GA or AA carried a 2.01 odds ratio of developing cervical cancer. Nevertheless, it was not demonstrated in CCR-2 SNP. Furthermore, women with mutant homozygote (AA) of MCP-1 SNP increased the risk of deep stromal invasion, large tumor diameter, and parametrium invasion of cervical cancer, when compared to those with wild homozygote GG or heterozygote GA. However, women with mutant homozygotes (AA) of CCR-2 SNP did not increase the risk of poor clinicopathologic characteristics. In conclusion, MCP-1 SNP may be correlated with the development, deep stromal invasion, large tumor diameter, and parametrium invasion of cervical cancer but not with cancer recurrence or survival of Taiwan women patients with cancer. However, the SNP of its receptor, CCR-2, is not implicated in cervical cancer.

Significantly increased concentration of soluble urokinase-type plasminogen activator receptor in the blood of patients with pelvic inflammatory disease.

BACKGROUND: To determine expression levels of urokinase-type plasminogen activator (uPA), soluble urokinase-type plasminogen activator receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1) in plasma and to identify gene polymorphisms specific to patients with pelvic inflammatory disease (PID) and healthy controls. METHODS: Enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were used to measure plasma levels and polymorphisms in uPA, suPAR, and PAI-1 among seventy healthy controls and 64 PID patients before and after they received routine treatment protocols. RESULTS: The levels of plasma uPA (ng/ml) and soluble suPAR (pg/ml) were significantly increased in PID patients (uPA: 0.57±0.03; suPAR: 1372.04±68.20) when compared to that in normal controls (uPA: 0.55±0.06, p=0.002; suPAR: 1192.46±51.98, p=0.04); moreover, suPAR decreased significantly after treatment when compared to levels noted in the same patients (1220.06±58.14; p=0.003) after they received treatment. The increased expression of suPAR was significantly correlated with WBC counts (r=0.382, p=0.002, n=64) in blood as well as the plasma levels of CRP (r=0.441, p<0.0001, n=64) and uPA (r=0.426, p<0.0001, n=64) of PID patients prior to receiving treatment. CONCLUSIONS: Increased plasma suPAR could be a biological marker for the diagnosis of PID and may reflect a new focus in targeted therapy for pelvic inflammatory disease.

Markedly elevated soluble E-cadherin in plasma of patient with pelvic inflammatory disease.

OBJECTIVE: To estimate the expression of plasma soluble E-cadherin and the gene polymorphism in patients with pelvic inflammatory disease (PID). DESIGN: Hospital-based case-control study. SETTING: University hospital. PATIENT(S): Sixty-four women with PID. INTERVENTION(S): Blood specimen collection from patients before and after they received treatment. MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were respectively used to measure the plasma soluble E-cadherin level and E-cadherin polymorphism. RESULT(S): The level of plasma E-cadherin was significantly elevated in patients with PID as compared with that in normal controls; it decreased significantly after treatment when compared with levels noted in the same patients before they received treatment. When the cutoff level of plasma E-cadherin level was set to 20.22 ng/mL on the basis of receiver-operating characteristic curve (ROC), the sensitivity, specificity, and the area under the curve of plasma E-cadherin level for predicting PID were 0.81, 0.80, and 0.835 (95% confidence interval 0.76-0.90), respectively. The adjusted odds ratio for age, white blood cell count, and C-reactive protein levels was 19.66 (5.48-70.47). CONCLUSION(S): Elevated plasma soluble E-cadherin expression was involved in the pathogenesis of PID and is useful for the diagnosis of PID.

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.

Single-nucleotide polymorphisms and haplotypes of membrane type 1-matrix metalloproteinase in susceptibility and clinical significance of squamous cell neoplasia of uterine cervix in Taiwan women.

Membrane type 1-matrix metalloproteinase (MT1-MMP) participates in the activity of MMP-2, which correlates with cancer of uterine cervix. Single-nucleotide polymorphisms (SNPs) in promoter and exon of MT1-MMP may influence their binding with transcription factors and gene transcription. To date, no study reports the association of the MT1-MMP polymorphisms with cervical neoplasia. Therefore, we investigated the influence of the MT1-MMP gene polymorphisms on the susceptibility and clinicopathological variables of cervical neoplasia for women in Taiwan. We recruited 72 patients with cervical squamous cell carcinoma and 63 with high-grade dysplasia as 1 subgroup. Meanwhile, 280 control women were included as another subgroup. The SNPs rs1003349 (site -165), rs2236307 (+7096), and rs3751489 (+8153) as well as rs2236302 (site +6727) of MT1-MMP gene were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism and real-time PCR genotyping, respectively. Then, we correlated these SNPs and haplotypes with the development of cervical neoplasia and cancer clinicopathological variables. We found that women with CC genotype in rs2236307 SNP exhibited a more risk to develop cervical neoplasia as compared with those with wild genotype TT. Haplotypes -165 T, +6727 C, +7096 C, +8153 G or -165 G, +6727 G, +7096 T, and +8153 G and diplotypes including at least 1 type of these haplotypes of MT1-MMP gene showed a higher risk of cervical neoplasia. However, both haplotypes were not significantly correlated with the clinicopathological characteristics of cervical cancer. In conclusion, Taiwan women with variant homozygote CC (+7096) and haplotypes, TCCG and GGTG, of MT1-MMP exhibit more risk in developing cervical neoplasia.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: In total, 336 blood samples were collected from healthy women and 136 patients with cervical neoplasia to analyze the gene polymorphisms of representative PA system genes. RESULTS: There was no significant association between cervical neoplasia cases and gene polymorphisms of uPA, uPAR and PAI-1 genes as well as to the carcinogenesis of cervical if the cervical neoplasia cases were stratified to HSILs and invasive cancer cases. However, we found a mutual interaction between uPA/PAI-1 genes, which women carrying the uPA/PAI-1 CC/4G4G allele had a 1.70-fold higher risk (OR = 1.70; 95% CI 1.04-2.79) of cervical neoplasia compared with those carrying the CC/4G5G allele. CONCLUSIONS: Individuals with uPA/PAI-1 CC/4G5G allele were in high susceptibility for cervical neoplasia. The combined polymorphism of uPA/PAI-1 might diminish the ability of PAI-1 to inhibiting cervical cancer carcinogenesis when PAI-1 alone as the role of inhibitor.

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.

Significant relation of tissue inhibitor of matrix metalloproteinase-2 and its combination with matrix metalloproteinase-2 to survival of patients with cancer of uterine cervix.

Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) has high affinity for matrix metalloproteinase-2 (MMP-2). Few studies simultaneously investigate their implication in prognosis of patients with cervical cancer. We used reverse transcription-polymerase chain reaction and immunohistochemical method for cervical tissues and microarrays to investigate the association among TIMP-2, MMP-2, clinicopathological parameters, and prognosis of patients with cancer. Our results showed that cancer tissues exhibited less TIMP-2 expression and patients with pelvic lymph node metastasis had less TIMP-2 expression. Positive TIMP-2 constellated with negative MMP-2 indicated lower recurrence probability and better overall survival. The protective effect of TIMP-2 expression may overcome the adverse effect of MMP-2 expression in terms of disease-free interval and overall survival while neither TIMP-2 nor MMP-2 alone can be used to predict outcome. We suggest that following patients other than those with positive TIMP-2 and negative MMP-2 expression more closely and intensely may improve their prognosis.

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.

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.

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 Pearson's 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.

Significantly elevated concentration of plasma monocyte chemotactic protein 1 of patients with pelvic inflammatory disease.

Our goal was to compare the expression of plasma monocyte chemotactic protein 1 (MCP-1) and the gene polymorphism in patients with pelvic inflammatory disease (PID) and healthy controls. The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were, respectively, used to measure the plasma MCP-1 level and MCP-1 polymorphism in 70 healthy controls and in 64 patients with PID before and after they received routine treatment protocols. We found plasma MCP-1 was significantly elevated in patients with PID compared to that in normal controls and decreased significantly compared to that in patients with PID after they received treatment. The increased expression of plasma MCP-1 was significantly correlated with the cell counts of white blood cells (WBCs) in blood and the level of plasma C-reactive protein (CRP) of patients with PID before they received treatment. There was no association between MCP-1 -2518G/A SNP and its gene expression levels and PID susceptibility. Elevated plasma MCP-1 could be a biological marker for the diagnosis and to be a new strategy for target therapy of pelvic inflammatory disease.

L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines.

Multidrug resistance (MDR) of cancer cells to cytotoxic drugs significantly impedes chemotherapeutic treatment. The purpose of this study is to characterize docetaxel (DOC) or vincristine (VCR) selected A549 and H1299 non-small cell lung cancer (NSCLC) sublines that exhibit MDR phenotypes and followed by re-sensitization study. Although all drug resistant sublines showed cross-resistance to DOC, VCR, and doxorubicin (DXR), the expression of ATP-binding cassette (ABC) transporter B1 (ABCB1) gene was found to be strongly induced in DOC but not in VCR resistant A549 sublines by quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR). In DOC and VCR resistant H1299 sublines, moderate expression of ABCB1 was detected. The levels of ABCB1 protein and efflux activities were further examined by immunoblotting and rhodamin-123 staining assay. The results showed that both ABC and non-ABC mediated MDR are existed. Furthermore, verapamil (VER), an inhibitor of ABCB1 and an L-type calcium channel blocker, is capable of reversing the resistance in all drug-resistant sublines independent of ABCB1 expression. Importantly, VER only sensitizes resistant sublines but has no effect on parental cancer cells. Other L-type calcium channel blockers, such as diltiazem (DIL) and nifedipine (NIF), also sensitize MDR sublines without interfering with ABCB1 activity but with lower efficacy than VER. Our data showed that in addition to ABCB1, calcium channel activity may play a crucial role in DOC- and VCR-acquired MDR. Therefore, inhibition of calcium influx may provide a new target to modulate MDR in chemotherapy.

Elevated plasma stromal cell-derived factor 1 protein and its gene polymorphism in patients with pelvic inflammatory disease.

The objective was to compare the expression of plasma stromal cell-derived factor 1 and the gene polymorphism in patients with pelvic inflammatory disease and healthy controls. The enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were, respectively, used to measure the plasma stromal cell-derived factor 1alpha level and stromal cell-derived factor 1 polymorphism in 50 healthy controls and in 44 patients with pelvic inflammatory disease before and after they received routine treatment protocols. The level of plasma stromal cell-derived factor 1alpha was elevated in patients with pelvic inflammatory disease compared to normal controls and decreased significantly after treatment. There were significant correlations between plasma stromal cell-derived factor 1alpha level and neutrophil count as well as between stromal cell-derived factor 1alpha level and white blood cell count in patients with pelvic inflammatory disease. There was no significantly different distribution of stromal cell-derived factor 1 genotypes between patients with pelvic inflammatory disease and normal controls. Patients with pelvic inflammatory disease having stromal cell-derived factor 1-3'A allele were associated with significantly elevated plasma stromal cell-derived factor 1alpha concentration compared to patients with pelvic inflammatory disease having G/G homozygous alleles (P < .02). In normal controls, there was no significant difference in the plasma stromal cell-derived factor 1 level between individuals with and without stromal cell-derived factor 1-3'A allele. When the cutoff level of plasma stromal cell-derived factor 1alpha level was determined to be 2192 pg/mL based on receiver-operating characteristic curve, the sensitivity, specificity, positive predictive value, and negative predictive value as well as accuracy were 77.3%, 88.0%, 85.0%, 81.5%, and 83.0%. In conclusion, when the cutoff level was determined to be 2192 pg/mL, plasma stromal cell-derived factor 1alpha level can be used to predict pelvic inflammatory disease.

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.

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.