Case Report: Niraparib as Maintenance Therapy in A Patient With Ovarian Carcinosarcoma.

Ovarian carcinosarcoma (OCS) is a rare, highly aggressive and rapidly progressing malignant tumor with an extremely poor prognosis. So far, due to the low incidence of OCS, there are no large-scale prospective studies exploring the standard care of OCS patients. There is no uniform and effective treatment for OCS. Within the development of precision medicine, targeted therapies (such as PARP inhibitors) have been widely used in epithelial ovarian cancer and various other solid tumors. Here, we report a BRCAwt patient with advanced OCS who experienced a second and a third cytoreductive surgery in June 2017 and October 2019 and has been on niraparib maintenance therapy for more than 20 months after receiving second-line and third-line chemotherapy.

Optimizing inhalation therapy in the aspect of peak inhalation flow rate in patients with chronic obstructive pulmonary disease or asthma.

BACKGROUND: Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are commonly used drug-delivering devices for patients with chronic airway diseases. Appropriate peak inhalation flow rate (PIFR) and inhaler technique is essential for effective therapy. We aimed at optimizing inhalation therapy through the analysis of PIFRs in patients with chronic obstructive pulmonary disease (COPD) or asthma as well as the effect of technique training using In-Check DIAL® to help patients to achieve their optimal inspiratory flow rates. METHODS: The study continuously enrolled patients who were diagnosed as COPD or asthma from respiratory clinics. PIFRs were described and analyzed between the newly-diagnosed and follow-up patients, and the stable and acute exacerbation patients, respectively. Every participant was trained inhaler technique using In-Check DIAL®. PIFRs before and after training was compared by self-control analysis. RESULTS: Among a total of 209 patients, the average age was 56.9 years. For DPIs users, 10.8% patients had a PIFR < 30 L/min and 44.1% patients had a PIFR ≥ 60 L/min before technique training. After technique training, scarcely patient (1.5%) had a PIFR < 30 L/min, and 60.5% patients had a PIFR ≥ 60 L/min. The patient's average PIFR increased by 5.6L/min after training. The increase in PIFR before and after training was significant (p < 0.001) for most patients, but no significant variation was found in patients with acute exacerbation (p = 0.822). CONCLUSIONS: A considerable number of patients with COPD or asthma were not able to achieve the minimum or optimal PIFR for DPIs. Inhaler training can increase patients' PIFRs and improve their ability to use DPIs. Trail registration The study has registered in chictr.org.cn (ChiCTR1900024707) and been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142).

The Validity of Using Human Squamous Cell Carcinoma Associated Antigen and Cytokeratin 19 Fragment Antigen 21-1 to Predict Postoperative Adjuvant Radiotherapy for Nonbulky Early-Stage Squamous Cell Carcinoma of the Cervix.

OBJECTIVE: There are no generally accepted biomarkers for the optimal selection of radiotherapy-based or surgical-based treatment options for nonbulky early-stage squamous cell carcinoma of the cervix (IA1-IB1 and IIA1). The objective of this study was to assess the value of human squamous cell carcinoma-associated antigen (SCC-Ag) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in evaluation of patients with nonbulky early-stage squamous cell carcinoma of the cervix to determine if radiotherapy is warranted after radical surgery. METHODS: Patients with stage IA1-IB1 and IIA1 squamous cell carcinoma of the cervix who were treated at the Department of Gynecological Oncology, Affiliated Tumor Hospital of Guangxi Medical University, from March 2012 to August 2014 (n = 308) were treated with radical hysterectomy and pelvic lymphadenectomy. The levels of SCC-Ag and CYFRA21-1 were detected by enzyme-linked immunosorbent assay before surgery. The relationship between the concentrations of SCC-Ag and CYFRA21-1 and risk factors was estimated through logistic regression and analysis of variance t test. The cutoff values of these 2 markers to evaluate the need for postoperative radiotherapy were identified and validated by receiver operating characteristic curve and κ consistency test, respectively. RESULTS: Serum SCC-Ag and CYFRA21-1 levels are significantly increased in patients who require postoperative radiotherapy with a risk factor score of at least 2 (n = 162). Logistic regression analysis revealed that deep stromal invasion and lymph node metastasis are independent risk factors for serum SCC-Ag value, and deep stromal invasion is an independent risk factor for the serum CYFRA21-1 value. Receiver operating characteristic curve revealed that the best predictive cutoff points of SCC-Ag and CYFRA21-1 values were 1.425 and 3.210 ng/mL, respectively. These results were validated by the κ consistency test applied to a validation group of patients. The results suggest that most patients with SCC-Ag and CYFRA21-1 values of at least 1.425 and 3.210 ng/mL, respectively, require postoperative radiotherapy. CONCLUSIONS: Detection of the levels of SCC-Ag and CYFRA21-1 may help guide an individual primary treatment plan for patients with nonbulky early-stage squamous cell carcinoma of the cervix.

[Clinicopathologic analysis of small cell neuroendocrine carcinoma of the cervix].

OBJECTIVE: To analyse the clinico-pathologic characteristics, diagnosis, therapy and prognostic of small cell neuroendocrine carcinoma of the cervix (SCNCC). METHODS: The clinic-pathological features of 12 patients with SCNCC treated in Tumor Hospital of Guangxi Medical University, admitted during March 2006 to July 2010, were analyzed retrospectively. RESULTS: Of 12 patients, the mean age was 38.7 years (rang 28 - 57 years), 6 had stages Ib1-IIa, 6 had stages IIb-IV. Among 8 patients (Ib1-IIIb) underwent surgery, 4 of them received neoadjuvant chemotherapy, 8 of them received adjuvant chemotherapy and(or) radiotherapy. All had greater than one-half stromal invasion, 4 patients had positive pelvic lymph nodes metastases. The positive ratio of the chromogranin (CgA), synaptophysin, neuronspecific enolase (NSE), cytokeratins (CK), CD(56) tested by immunohistochemical staining were 8/12, 9/10, 4/4, 4/4, 4/4, respectively. Median follow-up period was 3 months (1 - 22 months). Among 8 patients underwent surgery, 2 patients developed lung metastases, 1 patient developed liver and lung metastases, 1 patient developed liver metastases concurrently with bone metastases, disease-free survival (DFS) were 3 months (Ib2 with positive lymph nodes), 4.6 months (IIa), 7 months (Ib1), 17 months (Ib2); 2 patient died (8.5 and 11.3 months, respectively) after surgery; 4 patients are alive and show no evidence of disease. Among 4 patients untreated, 1 patients received concurrent chemoradiation and are alive for 10.1 months. Two patient untreated (IIIb, IV) died after 0.6 and 1.3 months final diagnosis, respectively. One patient was lost follow-up. CONCLUSIONS: SCNCC is a highly malignant tumor with rare morbility, propensity for distant spread and dismal prognosis. Final diagnosis of SCNCC depends on pathomorphology and immunohistochemical analysis. Combined therapeutic modalities may in favor of survival in some patients.

[Clinical study of autoantibody spectrum against ovarian cancer associated antigens combined with CA(125) in detecting and monitoring ovarian cancer].

OBJECTIVE: To evaluate the clinical value of autoantibody spectrum against ovarian cancer associated antigens combine CA(125) in detecting and monitoring ovarian cancer. METHODS: Circulating IgG, IgM autoantibodies against ovarian cancer associated antigens which included TM4SF1, C1D, TIZ, OV-142, FXR1 and OV-189 were measured by indirect ELISA in serum from 126 patients with ovarian cancer (prior treatment), 42 patients with benign ovarian masses, 142 healthy women. Cut off value of IgG, IgM autoantibodies were determined by receive operating characteristic (ROC) curve. CA(125) was measured in serum by immunoradiometric assay (IRMA). We evaluated the clinical value of combining multiple autoantibodies (autoantibody spectrum), combining autoantibody spectrum with CA(125) by binary logistic regresion. The positive ratio of autoantibody spectrum in serum (prior and post treatment) of 24 synchronization patients with ovarian cancer was analyzed to evaluate the value in monitoring state of illness. RESULTS: Our data indicated that serum contains IgG, IgM autoantibodies against ovarian cancer associated antigens. The positive ratio of IgG autoantibodies in serum from ovarian cancer patients and cancer-free patients were 34.1% - 47.6% and 13.0% - 19.0%, respectively (P < 0.05). The positive ratio of IgM autoantibodies in serum from ovarian cancer patients and cancer-free patients were 39.7% - 53.2% and 12.0% - 33.2%, respectively (P < 0.05). The positive ratio of IgG autoantibodies against FXR1 and IgM autoantibodies against TIZ, FXR1 and OV-189 in early stage (I-II) ovarian cancer (55.3%, 63.8%, 61.7% and 66.0%) were significantly higher than those in advanced (III-IV) ovarian cancer (34.2%, 39.2%, 26.6%, 45.6%; all P < 0.05). Combining five autoantibodies (TM4SF1 IgG, TM4SF1 IgM, C1D IgG, FXR1 IgG and TIZ IgM) showed significantly improved sensitivity (75.4%, P < 0.05), lower specificity (78.3%, P < 0.05) and similar accuracy (77.1%, P > 0.05) in detecting ovarian cancer compared to those of CA(125) (61.1%, 88.0%, 77.1%). But the autoantibody spectrum showed significantly improved sensitivity in classifying early stage (76.6%), compared to those of CA(125) (51.1%, P < 0.05). Combining autoantibody spectrum with CA(125) showed significantly improved sensitivity (85.7%), specificity (90.8%)and accuracy (88.7%) in detecting ovarian cancer compared to those of autoantibody spectrum alone (all P < 0.05), while CA(125) (61.1%, P < 0.05; 88.0%, P > 0.05; 77.1%, P < 0.05). The positive ratio of combine the autoantibody spectrum with CA(125) was significantly lower in 24 post-treatment serum (42%) compared to the pairing prior treatment serum (88%, P < 0.05). CONCLUSION: Combining the autoantibody spectrum against ovarian cancer associated antigens with CA(125) can improve sensitivity, specificity and accuracy in detecting early ovarian cancer and may be used to monitoring state of illness.

[Impact on survival and quality of life of laparoscopic radical hysterectomy and pelvic lymphadenectomy to patients with early-stage cervical cancer].

OBJECTIVE: To compare intraoperative, pathologic, postoperative outcomes and quality of life of laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH + LPL) with abdominal radical hysterectomy and pelvic lymphadenectomy (ARH + APL) for patients with early-stage cervical cancer. METHODS: The consecutive cases with International Federation of Gynecology and Obstetrics (FIGO) stages Ia2-IIa cervical cancer who underwent surgery from Jan. 1, 2002 to Jan. 1, 2011 were documented, including 85 patients underwent LRH + LPL, and 85 patients underwent ARH + APL as control group. The clinical data of intraoperative, pathologic, postoperative outcomes and quality of life were compared between two groups. Survival data were estimated using Kaplan-Meier survival curves and compared with the log-rank test. Cox proportional hazards model was used for multivariate analysis. RESULTS: All but 2 surgical procedures were completed laparoscopically because of right common iliac vein vessel injuries. Mean operative time, it was longer for LRH + LPL than that for ARH + APL [(242 ± 74) minutes vs. (190 ± 61) minutes, P = 0.000]. Mean recovery time of intestines function was less for LRH + LPL than that for ARH + APL [(45 ± 7) hours vs. (63 ± 11) hours, P = 0.000]. Mean estimated blood loss was less for LRH + LPL than that for ARH + APL [(367 ± 252) ml vs. (460 ± 220) ml, P = 0.006]. Mean recovery time of urinary function was less that for LRH + LPL than that for ARH + APL [(19 ± 4) days vs. (21 ± 4) days, P = 0.000]. There were no significant difference in numbers of the pelvic lymph nodes resected, the extent of parametrial tissue, vaginal cuff, negative margins obtained and complications. The median follow-up was 32 months (range 4 to 105 months), there was no significant difference in the recurrence rate (7% vs. 5%, P = 0.540) and mortality rate (7% vs. 5%, P = 0.540), 5 years disease-free survival (90% vs. 94%, P = 0.812), 5 years over survival (90% vs. 95%, P = 0.532). There were not significant difference in quality of life between ARH + APL group and LRH + LPL group (P > 0.05). Only lympho-vascular space invasion was an independent prognostic factor by multivariate analysis (P = 0.016). CONCLUSIONS: For early-stage cervical cancer, LRH + LPL has similar outcomes compared with ARH + APL. Laparoscopic treatment by experienced surgeons should be an ideal alternative.

[Effects of WWOX on ovarian cancer cell attachment in vitro].

OBJECTIVE: To observe the effects of WWOX on cell attachment in ovarian cancer, and to explore its mechanisms of action. METHODS: Attachment assay was used to assess the adhesion of wwox-transfected PEO1 cells and vector-transfected PEO1 cells that were constructed, as well as PEO1 parent cells. Alpha/beta integrin-mediated cell adhesion assays were designed to identify cells surface integrins in PEO1 clone cells. Integrin function blocking experiments were designed to further determine integrins in PEO1 clone cells according to the integrin that was selected in integrin expression profiling. FACS analysis was used to further detect the level of integrin alpha3 on the cell membrane. RESULTS: Attachment assay showed that adhesion of WWOX-transfected PEO1 cells to fibronectin was significantly slower than that in vector-transfected controls or PEO1 parent cells, cultured on the pre-coated fibronectin for 2 hours (P<0.01). The level of membranous integrins alpha2 and alpha3 in the WWOX-transfected PEO1 cells was significantly decreased, as compared with that in vector-transfected controls (P<0.05), but there was no association with the level of functioning integrins betal or beta2 in clone cells (P>0.05). The attachment assays were repeated after pre-incubating the cells with integrin alpha2 or alpha3 function-blocking antibodies. These results showed that blocking integrin alpha3 significantly reduced the binding to fibronectin of all the PEO1 clonal lines, as compared with cells pre-incubated with a non-specific IgG antibody (P<0.05). In contrast, preincubation with alpha2 blocking antibody had very little effect on fibronectin binding in these cells (P>0.05). FACS analysis showed that membranous integrin alpha3 expression revealed a marked reduction in WWOX-transfected cells than that in vector-transfected cells. CONCLUSION: WWOX acts as an ovarian tumor suppressor by modulating the interaction between tumor cells and the extracellular matrix, decreasing integrin activity and adhesion of tumor cells to fibronectin. This suggests an important role for loss of WWOX tumor suppressor in promoting attachment and adhesion of ovarian cancer cells on locoregional peritoneum, and further resulting in enhancing locoregional peritoneal tumor spread.

[Effect of WWOX gene on the attachment and adhesion of ovarian cancer cells].

OBJECTIVE: To explore the relationship between WWOX gene and attachment and adhesion of ovarian cancer. METHODS: The expression of WWOX mRNA was detected by RT-PCR, the expression of the WWOX protein was evaluated by western blot in WWOX-transfected PEO1 cells (H6, H7, H8 cell) and vector-transfected control cells (vec-1, vec-2 cell). Attachment assay was used to assess the adhesion of the transfection in PEO1 cells via culturing the cells on the pre-coated fibronectin wells. RNA interference (RNAi) was used to knockdown the endogenous expression of WWOX in the A2780 ovarian cancer cell line by liposome. Attachment assay was detected the adhesion to fibronectin after gene silencing. RESULTS: RT-PCR showed that expression of mRNA WWOX in exon9 was in all transfection cells (H6, H7, H8, vec-1, vec-2 cell). Western blot showed that expression of WWOX protein was in the WWOX-transfected cells (H6, H7, H8 cell), but not in the vector-transfected cells (vec-1, vec-2 cell). Attachment assay showed that H6, H7, H8 cell (0.098 +/-0. 003, 0.091 +/- 0.004, 0.099 +/- 0.003) adhered more slowly to fibronectin than vec-1, vec-2 cell (0.185 +/- 0.003, 0.175 +/- 0.006) and non-transfected PEO1 cell (0.211 +/- 0.007), and demonstrated significantly reduced adhesion after 2 hours (P < 0.01). A2780 adhesive cells that WWOX gene be knockdown was 0.059 +/- 0.005, adhered more significantly rapid than those untreated cells that was 0.029 +/- 0.003 after treated 30 minutes (P < 0.05). CONCLUSIONS: WWOX gene can suppress adhesion to fibronectin in ovarian cancer cells. This suggests an important role for loss of WWOX gene in promoting attachment and adhesion of ovarian cancer cells on loco-regional peritoneum, and further resulting in enhancing loco-regional peritoneal tumor invasiveness and spread.

[Clinical evaluation of autoantibody of splice variant of BARD1 in detection of ovarian cancer].

OBJECTIVE: To investigate the value of autoantibody of breast cancer susceptibility 1-associated RING domain (BARD1) splice variant (OV-142) in detection of ovarian cancer. METHODS: We cloned OV-142 gene into plasmid pET-30b(+). The recombinant protein of OV-142 was expressed in pET-30b(+) system and purified. The autoantibody of OV-142 was detected by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: We successfully constructed the recombinant plasmid of OV-142. The recombinant protein was expressed in pET-30b(+) system and purified. The purification rate of the recombinant protein was up to 90%. The relative amount of autoantibody of OV-142 detected by indirect ELISA was analyzed by receiver operating characteristic curve (ROC) and the cutoff value was determined. Combination of the autoantibody IgG of OV-142 and CA(125) was analyzed by logistic regression. The sensitivity, specificity and accuracy was 71.4%, 89.1%, and 81.9%, respectively, which were higher than IgG (41.3%, 84.2%, 66.8%) and CA(125) (61.1%, 88.0%, 77.1%) when used alone each. CONCLUSIONS: OV-142 is a splice variant of BARD1. It may be a potential immunotherapy target of ovarian cancer. Detection of autoantibody of OV-142 is a potent complementary tool of CA(125) in ovarian cancer diagnosis.

[Screening and sero-immunoscreening of ovarian epithelial cancer associative antigens].

OBJECTIVE: To explore epithelial ovarian cancer (EOC) antigens that are potentially useful for cancer early detection and therapy. METHODS: A high quality cDNA library derived from ascites tumor cells of EOC patients (3 cases of serous EOC, 1 case of mucinous EOC, and 1 case of endometrial carcinoma of ovary) was constructed, and the method of combining serological analysis of recombinant cDNA expression libraries (SEREX) and suppression subtractive hybridization (SSH) was used for screening cDNA library. All of the positive clones were sequenced and bioinformatics analysis with BLAST software in GenBank was performed. Serological mini-arrays of recombinant tumor antigens (SMARTA) was used to investigate the prevalence of autoantibodies to these antigens in both 96 ovarian cancer patients and 96 cancer-free controls. RESULTS: Fifty-five positive clones encoding different antigenic genes of EOC recognized by IgG and (or) IgM were obtained. It showed that these 55 clones derived from 45 distinct genes and these genes could be grouped into 6 classes as following according to homology with known expressed sequence tag (EST): (1) known ovarian carcinoma related genes: BARD1, et al; (2) homologous genes with other tumors: TM4SF1, et al; (3) homologous genes with special tissues: ILF3, FXR1, et al; (4) homologous genes with special function: TIZ, C1D, et al; (5) embryo originating genes: PKHD1, et al; (6) novel genes: OV-189, et al. SMARTA results showed that the positive ratio of five EOC antigens TM4SF1 (28% vs. 9%), C1D (21% vs. 6%), BARD1 (23% vs. 5%), FXR1 (23% vs. 8%), OV-189 (31% vs. 13%) which reacting with their IgG autoantibodies, three antigens TIZ (26% vs. 8%), FXR1 (28% vs. 11%), and OV-189 (18% vs. 7%) which reacting with their IgM autoantibodies in patients was higher than in controls (P < 0.05). The positive ratio of EOC antigens FXR1 (34% vs. 16%), and OV-189 (46% vs. 23%) reacting with their IgG autoantibodies and TIZ (40% vs. 18%), FXR1 (46% vs. 18%) which reacting with their IgM autoantibodies in stage I-II patients was higher than that in stage III-IV (P < 0.05). The positive ratio of OV-189 (67% vs. 26%) which reacting with its IgG autoantibodies in well differentiated cases was higher than in moderately-poorly differentiated cases (P < 0.01). Combination of the above antigens showed a 66% sensitivity and 73% accuracy in discriminating EOC. Combination of the autoantibody profile of TM4SF1, C1D, TIZ, BARD1, FXR1, OV-189 with CA125 showed an 83% sensitivity and 80% accuracy in discriminating EOC. CONCLUSIONS: The strategy of combination of SEREX and SSH is a potent tool in isolating tumor-associated antigen genes. Autoantibody profile of TM4SF1, C1D, TIZ, BARD1, FXR1, OV-189 are potential tumor markers in EOC detection.

[Identification of serum biomarkers for ovarian cancer using protein chips and time of flight mass spectrometry technology].

OBJECTIVE: To screen relatively specific biomarkers in serum of ovarian cancer patients using surface-enhanced laser desorption and ionization time of flight mass spectrometry and protein chip technology. METHODS: Serum samples from 99 ovarian cancer patients, 87 healthy volunteers and 21 patients with other ovarian diseases were analyzed using metal affinity chromatography protein chip IMAC3 and cation exchange protein chip WCX2, which can specifically bind the metal-combining-proteins. Proteomic spectra were generated by mass spectrometry. The peaks were detected and filtrated by Ciphergen proteinchip software 3.2.0. Using the Biomarker Pattern 5.0 software, a diagnostic system was developed for separating ovarian cancer from the healthy group. RESULTS: Thirty-one protein peaks were significantly different between ovarian cancer patients and healthy controls (P < 0.05). A diagnostic model consisting of protein peaks from IMAC3 and WCX2 was established. Large scale blind test generated a sensitivity of 100% and specificity of 98% respectively. A differentially expressed protein with a mass-to-charge rate of 7769 was identified as potential biomarkers to distinguish ovarian cancer from other ovarian diseases. CONCLUSIONS: Time of flight mass spectrometry is a useful tool for the detection and identification of new protein markers in serum. It will provide a highly accurate and innovative approach for the diagnosis of ovarian cancer.

[Study on the expression and mutation of cadherin 6 gene in human ovarian carcinoma].

OBJECTIVE: To study expression and mutation of cadherin 6 gene in human ovarian tumor tissues and its clinical significance and to explore new molecular biomarker of ovarian tumors. METHODS: The expression and mutation of cadherin 6 in 41 cases of malignant ovarian tumors, 15 cases of benign ovarian tumors and borderline ovarian tumors and 17 cases of normal tissues were detected by RT-PCR and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique respectively. RESULTS: The positive expression rates of cadherin 6 were 71% in normal group, 53% in benign ovarian tumors, 24% in malignant ovarian tumors, being significantly higher in the former two groups than in malignant tumor group (P < 0.05). Statistical analysis revealed a significant correlation between cadherin 6 gene expression and clinical stages and histological subtype of malignant ovarian tumors. Lower expression rate of cadherin 6 gene was found in cancer tissues at stages III approximately IV than at stages I approximately II (P < 0.01). No mutation was found in normal group and benign tumor tissues and it was observed in 2 out of 41 malignant ovarian tumor tissues. CONCLUSIONS: These results suggest that expression of cadherin 6 gene tends to lack in advanced ovarian carcinoma with lymph node metastases, as well as in poorly differentiated carcinomas. It may be a prognostic marker of ovarian carcinoma.

[Expression of matrix metalloproteinases-9,2,7,and tissue inhibitor of metalloproteinases-1,2,3 mRNA in ovarian tumors and their clinical significance].

BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs)play an important role in cancer cell invasion,and metastasis by degrading the extracellular matrix (ECM). The activities of MMPs are regulated by tissue inhibitor of metalloproteinases (TIMPs). This study was to detect mRNA expression of MMP-9, 2, 7, and TIMP-1, 2, 3 in ovarian tumor tissues,and explore their correlations with clinicopathologic characteristics,and prognosis of patients with ovarian cancer. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR)was used to assay the positive rates,and half-quantity values of MMP-9, 2, 7, and TIMP-1, 2, 3 mRNA in 48 cases of malignant ovarian tumor tissues, 21 cases of benign ovarian tumor tissues, and 22 cases of normal ovarian tissues. RESULTS: The positive rate of MMP-9 mRNA, and the half-quantity values of MMP-9,MMP-2 were significantly higher in malignant tumor tissues than those in normal ovarian tissues (P< 0.05). The positive rates and half-quantity values of TIMP-2,MMP-7,TIMP-3 mRNA were significantly higher in malignant and benign ovarian tumor tissues than those in normal ovarian tissues (P< 0.05). The ratio of MMP-9/TIMP-1 was higher in malignant ovarian tumor tissues(0.91+/-0.67) than that in normal ovarian tissues (0.14+/-0.33)(P< 0.05). The expression level of MMP-9 mRNA was higher in ovarian cancer tissues of stage III-IV(1.13+/-0.66) than those of stage I-II(0.60+/-0.54)(P< 0.05). The mean survival time of MMP-9 positive patients was (43.00+/-17.12) months,and cumulate survival rate was 47.37%,significantly lower than that of MMP-9 negative patients (100%). CONCLUSIONS: MMP-9, MMP-2, MMP-7, TIMP-2, TIMP-3 are over-expressed in ovarian malignant tissues. The over-expression of MMP-9, and the imbalance between MMP-9 and TIMP-1 play important roles in the progress of advanced ovarian cancer. MMP-9 may be a useful prognostic marker for patients with advanced ovarian cancer.

[Relationship of expression of C-erbB2, C-erbB3, and C-erbB4 with ovarian carcinoma].

BACKGROUND & OBJECTIVE: C-erbB2, C-erbB3, and C-erbB4 are numbers of epidermal growth factor family. It has been confirmed that C-erbB2 was related to ovarian carcinoma, but the relationship of C-erbB3 and C-erbB4 with ovarian carcinoma is unclear. The objective of this study was to explore the relationship of expression of C-erbB2, C-erbB3, and C-erbB4 with ovarian carcinoma. METHODS: Streptavidin-peroxidase immunohistochemistry method was used to determine the expression of C-erbB2, C-erbB3, and C-erbB4 in 49 cases of ovarian malignant neoplasms, 21 cases of ovarian benign neoplasms, and 19 cases of normal ovarian tissues (control), then the relationship of expression of C-erbB2, C-erbB3, C-erbB4 and clinicopathologic parameters in ovarian neoplasm was analyzed. RESULTS: (1) The positive expression rates of C-erbB2, C-erbB3, and C-erbB4 in ovarian malignant neoplasms were 75.51%, 69.39%, and 65.31%, respectively, and they were higher than that in ovarian benign neoplasms (19.05%, 23.81%, and 23.81%, respectively) and control (21.05%, 15.79%, and 21.05%, respectively)(P< 0.05). (2) There was not significant difference between the expression of C-erbB2, C-erbB3, and C-erbB4 in ovarian malignant neoplasms and its pathologic type and grade (P >0.05). (3) The positive expression rates of C-erbB2, C-erbB3, and C-erbB4 in the patients with late stage or large amount of ascetic volume ( >500 ml) were 90.0% and 91.3%, respectively, and those also were higher than that in early stage or ascetic volume< 500 ml (P< 0.05). (4) The cumulative survival time of the patients with positive expression of C-erbB2 or C-erbB4 was longer than that without expression (P< 0.01). The analysis of Cox model showed that expressions of C-erbB2 and C-erbB4 in ovarian malignant were also independent prognosis factors for ovarian cancer. CONCLUSION: The C-erbB family would play an importation role in ovarian malignant neoplasms, and also was related to poor prognosis in ovarian cancer.

[Early recurrent factors of ovarian cancer after treatment].

BACKGROUND & OBJECTIVE: Recurrence of ovarian cancer is an important factor that leads to therapeutic failure. At present, the treatment in ovarian cancer is not sufficiently effective. This study was designed to investigate the factors of early recurrence after treatment in ovarian cancer in order to reduce its recurrence. METHODS: The clinical data of the ovarian cancer patients admitted to Affiliated Hospital of Guangxi Medical University during January 1986 to May 1996 who recurred within one year after treatment were analyzed retrospectively. The recurrent rates were compared according to their different clinical stages, pathological types, and residual volumes of the disease as well as the number of courses of pre and postoperative chemotherapy received. Chi-square test was used for statistic analysis. RESULTS: Eighty-two of 373 cases recurred within one year after treatment; the overall recurrent rate was 22.0%. The 1-year recurrent rate in stage I-II patients was lower than that in stage III-IV patients (2.7% versus 30.3%, P< 0.01). The recurrent rate in the patients with undifferentiated adenocarcinoma was higher than that with other pathological type. The recurrent rate in the patients with residuals >or=2 cm was higher than that with residuals < 2 cm (33.8% versus 13.7%, P< 0.01). The recurrent rate in the patients with preoperative chemotherapy was lower than that without it. The recurrent rate in the patients who had received only 1-3 courses of postoperative chemotherapy was higher than that having received 4-6 or >6 courses (67.0% versus 7.7%, 67.0% versus 7.0%, respectively, P< 0.01). CONCLUSION: Early (1-year) recurrence in the patients with ovarian cancer seems to be closely related to late stage of the disease, incomplete surgery, and insufficient chemotherapy courses.

[Study on serum vascular endothelial growth factor level in ovarian malignant tumors].

OBJECTIVE: To explore the diagnostic value of serum vascular endothelial growth factor (VEGF) level in patients with ovarian carcinomas, and to evaluate the correlation between serum VEGF level and prognosis of ovarian cancer. METHOD: Serum VEGF level in patients with ovarian neoplasms (120 cases of ovarian carcinomas, 25 cases of benign tumors) and 90 healthy women as controls was determined by enzyme linked immunosorbent assay (ELISA), also the change of preoperative and postoperative serum VEGF level of 25 cases of epithelial ovarian cancer was observed. RESULTS: (1)The preoperative serum VEGF levels were (766 +/- 1237) mg/L in malignant groups, and there was a significant difference compared with normal controls (55 +/- 19) mg/L or patients with benign tumor (56 +/- 23) mg/L (P < 0.05). As a cut-off at 100 mg/L, sensitivity and specificity of preoperative serum VEGF levels for diagnosing ovarian cancer was 77% and 87% respectively. (2) Serum VEGF level were significantly elevated in advanced stage (955 +/- 1716) mg/L and poorly differentiated (991 +/- 1349) mg/L compared with early stage (198 +/- 287) mg/L and well differentiated (280 +/- 552) mg/L (P < 0.05), but there is no significant difference between the VEGF level and pathological types (P > 0.05). (3) The postoperative serum VEGF levels (118 +/- 110) mg/L were significantly lower than that in preoperative (1074 +/- 1211) mg/L. (4) The average total survival-time in patients with VEGF(+) was 28 months, but it in patients with VEGF(-) was 35 months (P < 0.05). CONCLUSION: Serum VEGF values were higher in malignant tumors and preoperative serum VEGF level has a potential as a marker for diagnosing and monitoring in ovarian neoplasms.