Honokiol suppresses the aberrant interactions between renal resident macrophages and tubular epithelial cells in lupus nephritis through the NLRP3/IL-33/ST2 axis.

Lupus nephritis (LN) is a type of immune-complex nephritis caused by systemic lupus erythematosus and is a major contributor to mortality and morbidity. Honokiol (HNK) has been found to have a therapeutic effect on LN, but its action mechanism remains unclear. In this study, we first demonstrated that HNK attenuates kidney injury in MRL/lpr mice. Results from RNA sequencing combined with ingenuity pathway analysis suggested that HNK plays an anti-LN role through inhibition of the NLRP3 inflammasome and IL33. GEO chip data, single-cell data, and clinical samples from LN patients demonstrated that the pyroptosis and IL-33/ST2 pathways are abnormally activated during the stage of LN. In vivo, similar to the results of the AAV-mediated NLRP3 shRNA MRL/lpr model, HNK downregulated serum and renal IL-33 levels, and suppressed NLRP3 inflammasome and the IL-33/ST2 axis in the kidney. In vitro, co-culturing NLRP3-overexpressing or IL-33 knocked-down rat renal macrophages with NRK-52E cells confirmed that NLRP3 activation in resident macrophages directly upregulates IL-33, which in turn mediates the IL-33/ST2/NF-κB pathway to promote the inflammatory response of renal tubular epithelial cells. Furthermore, a molecular docking model and surface plasmon resonance analysis were utilized to demonstrate a direct interaction between HNK and NLRP3. In conclusion, this study provides a novel anti-LN treatment strategy in which HNK plays a preventive and therapeutic role against LN by suppressing the abnormal crosstalk between renal resident macrophages and renal tubular epithelial cells by inhibiting the activation of the NLRP3/IL-33/ST2 axis.

Association between anlotinib trough plasma concentration and treatment outcomes in advanced non-small-cell lung cancer.

Background: Efficacy and toxicities of anlotinib (ANL) show large inter-patient variation, which may partly be explained by differences in ANL exposure. Exposure-response/toxicities relationship have not been investigated for ANL. Therefore, the aim of the present study was to explore the association between the trough plasma concentration (Ctrough) of ANL and treatment outcomes in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with advanced NSCLC who started third-line or further ANL alone therapy between January 2021 and October 2022. This study examined the ANL Ctrough and clinical response evaluation at day 43 after initiation of ANL treatment. We evaluated the association between the ANL Ctrough and clinical efficacy and toxicities. Additionally, this study defined patients with complete response (CR), partial response (PR) and stable disease (SD) as responder. The receiver-operating characteristic (ROC) curve combined with Youden index was identify the potential threshold value of ANL Ctrough for the responder. Results: 52 patients were evaluated for analyses. The median ANL Ctrough was 11.45ng/ml (range, 3.69-26.36 ng/ml). The ANL Ctrough values in the PR group (n=6, 15.51 ng/ml (range, 8.19-17.37 ng/ml)) was significantly higher than in the PD group (n=8, 7.44 ng/ml (range, 5.41-14.69 ng/ml), p=0.001). The area under the ROC curve (AUCROC) was 0.76 (95% confidence interval (CI), 0.58-0.93; p=0.022) and threshold value of ANL Ctrough predicting responder was 10.29 ng/ml (sensitivity 65.9% and specificity 87.5%, the best Youden index was 0.53). The disease control rate (DCR) was 84.6%, and DCR was significantly higher in the high-exposure group (≥10.29ng/ml) than low-exposure group (<10.29ng/ml) (96.67% vs 68.18%, p=0.005). Although there was no significant difference in ANL Ctrough between grade ≥ 3 and grade ≤2 toxicities, the incidence of any grade hand-foot syndrome (70.0% vs 36.36%, p=0.016) and thyroid-stimulating hormone elevation (53.33% vs 22.73%, p =0.026) was significantly higher in the high-exposure group compared with the low-exposure group. Conclusions: Considering these results, we propose that maintaining ANL Ctrough ≥ 10.29ng/ml was important for achieving the response in advanced NSCLC patients treated with ANL.

Degradable collagen/sodium alginate/polyvinyl butyral high barrier coating with water/oil-resistant in a facile and effective approach.

Degradable bio-based materials have been widely considered as functional coatings, however, it is a great challenge to fabricate biodegradable coatings with high barrier, water- and oil- resistance. In this work, such coatings were fabricated by using collagen fibers (CF), sodium alginate (SA), and polyvinyl butyral (PVB). CF and SA were mixed evenly and coated on Ca2+ pretreated filter paper. It was mainly due to the electrostatic adsorption between collagen fibers and sodium alginate, and the crosslinking between the adsorption products and Ca2+. By coating PVB solution, the barrier performance was further improved. Notably, the composite exhibited excellent water vapor resistance (48 g/m2·24 h), water resistance (31 g/m2), oil resistance (kit rating: 12/12) and good mechanical properties. This degradable, environmentally friendly, and simple composite paper method has excellent barrier properties, mechanical properties and fluorine-free properties, and will have many applications in the food and packaging fields.

In vitro gastrointestinal digestibility of corn oil-in-water Pickering emulsions stabilized by three types of nanocellulose.

The effect of three nanocellulose (various in crystalline allomorph and morphology) on lipid in vitro gastrointestinal digestibility was investigated. Corn oil-in-water emulsions were prepared by CNCs-I, CNCs-II and CNFs respectively. The variations of droplets diameter D[4,3], zeta potential, and microstructure were measured during gastrointestinal digestion (mouth, stomach and small intestine), and the free fatty acid (FFA) released in the small intestine phase were examined. The FFA-released test results indicated that both crystalline allomorph and morphology of nanocellulose affected the degree of lipid digestion, especially the morphology. FFA released amount was ranked in the order of CNCs-I (56.60%), CNCs-II (48.67%) and CNFs (28.21%). This is mainly due to the difference in the self-assembly behavior of nanocellulose at the interface. Our findings provide an innovative solution that using nanocellulose as food-grade particle stabilizer to modulate the digestion of Pickering emulsified lipids, which would benefit the development of given functional foods.

LncRNA MEG8 plays an oncogenic role in hepatocellular carcinoma progression through miR-367-3p/14-3-3ζ/TGFßR1 axis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it carries a poor prognosis. Clarifying the pathologic mechanisms of this disease will be beneficial for the diagnosis and treatment of HCC. LncRNA MEG8 is involved in several tumors but its role in HCC progression remains unknown. This study was designed to explore the role and regulatory mechanisms of MEG8 in HCC progression. MTT, EdU, wound-healing, and transwell assays were employed to analyze the proliferation, migration, and invasion of HCC cells. A luciferase assay was utilized to confirm the predicted binding site. RNA immunoprecipitation and co-immunoprecipitation were employed to verify the binding between MEG8 and miR-367-3p as well as 14-3-3ζ and TGFßR1. Real-time PCR and western blot were employed to detect the expression of interesting genes. Results revealed that MEG8 was increased in HCC tissues and cells, and was correlated with the poor prognosis of HCC patients. Inhibiting MEG8 significantly repressed the HCC cells' ability to proliferate, migrate, and invade. Moreover, MEG8 sponged miR-367-3p to upregulate 14-3-3ζ, the binding of which suppressed TGFßR1 degradation, thereby enhancing TGFß signaling. In conclusion, this work exposed a novel role and regulatory mechanism of MEG8 in HCC and provided new insight into the treatment of HCC.

Iron-Catalyzed Oxidative C-H Functionalization of Internal Olefins for the Synthesis of Tetrasubstituted Furans.

Tetrasubstituted furans were efficiently synthesized from Fe(OAc)2-catalyzed C-H/C-H cross-dehydrogenative-coupling (CDC) reactions of activated carbonyl methylenes with S,S-functionalized internal olefins, that is, α-oxo ketene dithioacetals and analogues, under oxidative conditions. ß-Ketoesters, 1,3-dicarbonyls, ß-keto nitrile, and amide derivatives were used as the coupling partners. The resultant alkylthio- and carbonyl-functionalized furans could be further transformed to diverse arylated furan derivatives and furan-fused N-heterocycles, respectively. The control experiments have revealed a radical reaction pathway.

[Employing DNA Damage Response Inhibitors to Enhance Chemosensitivity of Ovarian Carcinoma Cells].

OBJECTIVE: To assess the sensitisation effects of DDR inhibitors combined with conventional chemotherapeutics agents (cisplatin et al) in a drug-resistant ovarian cancer cell line(OVCAR-8). METHODS: Inhibitors of DDR regulators with cisplatin were applied to challenge OVCAR-8, and evaluated the DNA damage response (DDR) and cytotoxic effects of different combination of chemicals. Inhibition of proliferation to OVCAR-8 of different drugs was evaluated by MTT assay. The activation of phosphorylation of histone family 2A variant (yH2AX) and p53 binding protein 1 (53BP1) in OVCAR-8 were evaluated by immunofluorescence to observe their ability of recruitment and forming foci at DNA damage site. RESULTS: We observed that combined treatment of ataxia-telangiectasia mutated (ATM)/ATM and Rad 3-related (ATR) inhibitor and cisplatin can suppress the activation of damage repair mechanisms and weakened the proliferative activity of OVCAR-8 cells (P<0. 01) ; ATR pathway was suppressed and the signal of γH2AX weakened and cell survival rate significantly reduced when combination therapy of HU and Wortmannin (P < 0.05); poly ADP-ribose polymerase (PARP) inhibitor could not enhance chemosensitivity in OVCAR-8 cells when combined with cisplatin (P > 0.05). CONCLUSION: We substantiated that appropriate inhibitors of DNA damage response may have a potential to improve the anti-tumor effect of conventional chemotherapy drugs and prevent drug resistances.

Safety and Efficacy of Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Radical Surgery Alone in Locally Advanced Cervical Cancer Patients.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) among patients with locally advanced cervical cancer (LACC). METHODS: Eight hundred patients with LACC received either NACT followed by RS (NACT-RS) or RS alone. The primary outcome measures assessed the efficacy and adverse effects of NACT. Secondary outcome measures compared the preoperative clinical stage to the postoperative pathologic stage in NACT-RS and RS patients, assessed intraoperative and postoperative complications, including the adverse effects of postoperative radiotherapy and radiochemotherapy, and estimated the 5-year progression-free survival and 5-year overall survival. RESULTS: The clinical response to NACT was 89.54%. Patients in the NACT-RS group had lower preoperative hemoglobin levels (115.20 vs 122.04 g/L, P < 0.001), a longer operative time (mean, 233.66 vs 224.37 minutes, P = 0.008), more intraoperative bleeding (750.34 vs 684.41 mL, P = 0.011), a shorter duration of catheter use (mean, 29.84 vs 32.14 days, P = 0.036), and a lower incidence of postoperative complications (7.30% vs 13.62%, P = 0.002) and postoperative radiotherapeutic and radiochemotherapeutic adverse effects (3.16% vs 4.63%, P < 0.001) compared to patients in the RS group. The 5-year progression-free survival and 5-year overall survival were 80.30% and 81.10% in the NACT-RS group and 81.00% and 78.50% in the RS group (P > 0.05). Pathological poor differentiation, nonsquamous cell carcinoma, parametrial invasion, positive pelvic lymph node, and lymphovascular invasion (P < 0.05) were independent risk factors for recurrence. CONCLUSIONS: Neoadjuvant chemotherapy may reduce RS-associated complications and postoperative radiotherapeutic and radiochemotherapeutic adverse effects in Chinese patients with LACC.

[Functional Analysis of DNA Damage Repair Factor WDR70 and Its Mutation in Ovarian Cancer].

OBJECTIVES: To analyze the cellular function of the newly discovered DNA damage repair factor WDR70, and investigate the mutation in ovarian cancer to verify if function loss of the WDR70gene was associated with ovarian cancer. METHODS: The WDR70 gene was silenced by using siRNA technique or overexpressed its wild and mutation type by with lentivirus and plasmid in hunman cells. The subcellular localization and biochemical function of WDR70 was analyzes by indirect immunofluorescence and immunoblotting. The expression level of WDR70 and the mutations of its cDNA was checked with RT-PCR sequencing for 1 normal ovarian tissue and 16 ovarian cancer specimen. RESULTS: We found gene silencing of WDR70 or overexpression of WDR70 mutation type disrupts the phosphorylation level of homologous recombination functional protein RPA32 and the ability of recruitment at DNA damage site of recombinase RAD51, the loss of function of WDR70 also causes the elevation of the chromosome breakage in metaphase. Meanwhile, we also noticed that the existence of multiple mutations in genomic WDR70 in ovarian cancer specimen. CONCLUSIONS: Our results defined that in vitro system, WDR70 is a DNA damage repair gene, silencing of WDR70 or overexpression of WDR70 mutation type disrupts homologous recombination and chromosomal instability; the frequent mutations of WDR70 gene in genome of ovarian cancer specimens could also lead to DNA repair defeat and gene instability. Consequently WDR70 gene could represent an anti-cancer mechanism for ovarian cancer.

[HPV E7 Function in DNA Damage Response of Cervical Intraepithelial Neoplasia.]

OBJECTIVES: To determine the function of human papillomavirus (HPV) E7 in DNA damage response of cervical intraepithelial neoplasia (CIN) 3 cells. METHODS: Samples of CIN 3 and child foreskin tissues were collected,with pathologically confirmed HPV positive and negative,respectively.Collagenase A was used for digesting tissues prior to primary culture.The HPV negative cells were infected with lentivirus E7 and pLV.Proteins(53BP1,NBS1,BRCA1 and RPA32) responsive to DNA double break damages were detected by indirect immunofluorescent staining after 0-8 h treatment with X-ray (2 or 5 Gy). RESULTS: After treatment with 2 or 5 Gy X-ray,53BP1,NBS1,BRCA1 and RPA32 foci in HPV+ cells increased compared with HPV- cells (P<0.05).Less 53BP1,RPA32,BRCA1 and NBS1 foci positive cells (foci>5) were found in E7 infected cells than in pLV infected cells(P<0.05).Both of them reached the peak at 6 h (2 Gy) or 4 h (5 Gy). CONCLUSIONS: We have successfully established a model to detect the function of HPV E7 in DNA damage response using primary culture of CIN fibroblasts.With the progression of CIN,HPV E7 can inhibit DNA double break repair.

[DNA damage response of epithelial ovarian cancer cells (primary culture) to chemo-radiotherapy].

OBJECTIVE: To detect protein dynamic changes of cellular localization and the DNA damage response of epithelial ovarian cancer cells to chemo-radiotherapy. METHODS: 28 specimens of epithelial ovarian cancer were collected, with 6 cases diagnosed as borderline serous cystadenoma, 5 as highly differentiated, 6 as medium differentiated and 11 as poorly differentiated cystadenocarcinoma. Collagenase A was used for digesting tissues before primary culture. We compared the characteristics of cells cultured in different mediums (MCDB/M199 medium, primary culture medium, and DMEM medium) supplemented with multiple growth-promoting factors. The characteristics of cells were examined in terms of the maintenance of normal cell morphology, proliferation potential, and cell fibrosis proteins (53BP1 and gamma-H2AX) responsive to DNA damage [those in the ATM checkpoint pathway determined by indirect immunofluorescent staining after treatment with camptothecin (CPT) and X-ray]. RESULTS: Normal morphology was maintained relatively well in the cells cultured in MCDB/M199 medium and its cell fibrosis was slow compared with the cells cultured in other media. Gradually increased endogenous damage was demonstrated by the expression of 53BP1 and gamma-H2AX foci (P < 0.05) in all of the ovarian primary cells. After treatment with CPT and ionizing radiation, increased levels of DNA double-strand breaks were observed indicating a classic DNA damage response. CONCLUSION: We have successfully established a protocol for the primary culture of epithelial ovarian cancer cells, which provides an important platform for characterizing DNA damage responses of the cells. With the progression of epithelial ovarian cancers, the ATM checkpoint pathway is activated by endogenous DNA lesions. This signaling pathway can be further activated by CPT or X-ray irradiation, hampering the growth of tumor cells and further progression of cancers.

Decreased histone H2B monoubiquitination in malignant gastric carcinoma.

AIM: To investigate H2B monoubiquitination (uH2B) and H3K4 di- and tri-methylation (H3K4-2me, H3K4-3me) levels and their clinical significance in gastric cancer (GC). METHODS: Immunohistochemistry (IGC) was used to detect the differential levels of uH2B, H3K4-2me and H3K4-3me modifications in GC specimens from chemo/radiotherapy-naïve patients who underwent potentially curative surgical resection (n = 159) and in a random sampling of non-tumor gastric epithelium specimens (normal controls, n = 20). The immunohistochemistry (IHC)-detected modifications were classified as negative, low-level, or high-level using a dual-rated (staining intensity and percentage of positively-stained cells) semi-quantitative method. The relationships between uH2B modification levels and clinicopathological parameters of GC were assessed by a Wilcoxon rank sum test (pairwise comparisons) and the Kruskal-Wallis H test (multiple comparisons). The correlation between uH2B modification and survival was estimated by Kaplan-Meier analysis, and the role of uH2B as an independent prognostic factor for survival was assessed by multivariate Cox regression analysis. RESULTS: The presence and level of H3K4-2me and H3K4-3me IHC staining was similar between the normal controls and GC specimens. In contrast, the level of uH2B was significantly lower in the malignant gastric tissues (vs normal control tissues) and decreased along with increases in dedifferentiation (well differentiated > moderately differentiated > poorly differentiated). The level of uH2B correlated with tumor differentiation (P < 0.001), Lauren's diffuse- and intestinal-type classification (P < 0.001), lymph node metastasis (P = 0.049) and tumor-node-metastasis stage (P = 0.005). Patients with uH2B+ staining had higher 5-year survival rates than patients with uH2B-staining (52.692 ± 2.452 vs 23.739 ± 5.207, P < 0.001). The uH2B level was an independent prognostic factor for cancer-specific survival (95%CI: 0.237-0.677, P = 0.001). CONCLUSION: uH2B displays differential IHC staining patterns corresponding to progressive stages of GC. uH2B may contribute to tumorigenesis and could be a potential therapeutic target.

Giant cell-rich osteosarcoma in long bones: clinical, radiological and pathological features.

PURPOSE: The purpose of this study was to review the clinical presentation, imaging, pathology and outcome of patients with giant cell-rich osteosarcoma (GCRO) of long bones. MATERIALS AND METHODS: Radiography (n=9), magnetic resonance imaging (MRI) (n=6), computed tomography (CT) (n=3) and clinical course of nine patients (five males and four females; mean age, 26 years) with pathologically confirmed GCRO were retrospectively reviewed. Specific imaging findings, including size, eccentricity, ossification, lysis, cystic change, expansile growth, periosteal reaction, cortical destruction, soft tissue extension and joint involvement were documented. RESULTS: Presenting symptoms were pain in six patients and pain and palpable mass in three. An ill-defined margin surrounding a predominantly osteolytic lesion was detected at the proximal tibia (n=7) or femur (n=2) on imaging studies. Seven cases showed limited ossification. Three cases had tumours in the metaphysis and six in the metaepiphysis. The average maximum tumour dimension was 4.7 cm×5.2 cm×7.8 cm. Microscopically, tumours were composed of atypical cells with scanty osteoid formation and multinucleated giant cells. All patients received chemotherapy, and surgery was performed in eight patients. Three patients were dead and six were alive at the last follow-up. CONCLUSIONS: GCRO is a rarer variant that has very close resemblance to giant cell tumour. Patients usually present nonspecific symptoms of pain and palpable mass. It usually shows an osteolytic lesion with locally spared new bone formation in the metaphysis and/or metaepiphysis on imaging. Histologically, the atypical tumour cells with osteoid formation and multinucleated giant cells are the key factor in the diagnosis and differential diagnosis.

Recurrence in giant cell tumour of bone: imaging features and risk factors.

PURPOSE: This study was done to investigate X-ray, computed tomography (CT) and magnetic resonance (MR) imaging features of recurrence in giant cell tumour of bone (GCTB) and to evaluate risk factors. MATERIALS AND METHODS: Medical records and imaging data were reviewed for 55 cases of recurrent GCTB. All images were reviewed retrospectively and independently by two radiologists experienced in skeletal musculature. The common radiological findings; factors related to tumour recurrence such as gender, age, location; pathological fracture, Campanacci grading and surgical procedure were analysed by nonparametric test (Mann-Whitney U test for two independent samples test and Kruskal-Wallis H test for multiple independent samples test). p values <0.05 were considered to indicate a statistically significant difference. RESULTS: The imaging features of recurrent GCTB were as follows: osteolytic destruction or bone resorption of graft bone or around the polymethylmethacrylate (PMMA), soft tissue mass formation and expansile change. Tumour parenchyma showed markedly heterogeneous enhancement, except for necrotic cystic cavities, on contrast-enhanced MR images. Wide resection had a smaller (p=0.031) risk of local recurrence than did intralesional curettage. There was no statistical significance in gender, age, location, pathological fracture and Campanacci staging (p>0.05). CONCLUSIONS: The risk of recurrence in GCTB was influenced by the type of surgery and adjuvants. Bone transformaresorption, soft tissue mass formation and aggravated expansile change are reliable signs of recurrence on imaging.

[DNA damage response in ovarian clear cell adenocarcinoma].

OBJECTIVE: To study the relationship between ovarian clear cell adenocarcinoma and DNA damage. METHODS: 14 samples were selected from clinical ovarian cases including 3 cases with normal ovarian tissue, 6 cases with poorly differentiated ovarian tumor, 5 cases with ovarian clear cell adenocarcinoma, treated by X-ray irradiation and frozen sections respectively. DNA damage response was analyzed by immunofluorescence and Western blot. RESULTS: Before X-ray irradiation, compared to normal ovarian tissue, a large number of endogenous damage existed in ovarian clear cell adenocarcinoma, and phosphorylation of histone family 2A variant (H2AX) was abnormally enhanced 1 hour after irradiation treatment, however, DNA repair was normal in ovarian clear cell adenocarcinoma. Phosphorylation of H2AX was dispensable for p53 binding protein 1 (53BP1) activation and couldn't be colocalized in clear-type ovarian cancer tissues. CONCLUSION: The abnormal DNA damage activation implies that the network of DNA damage signaling pathway may be defective.

Primary diaphyseal osteosarcoma in long bones: imaging features and tumor characteristics.

OBJECTIVE: This study aims to assess retrospectively the imaging features of diaphyseal osteosarcoma and compare its characteristics with that of metaphyseal osteosarcoma. MATERIALS AND METHODS: Eighteen pathologically confirmed diaphyseal osteosarcomas were reviewed. Images of X-ray (n=18), CT (n=12) and MRI (n=15) were evaluated by two radiologists. Differences among common radiologic findings of X-ray, CT and MRI, and between diaphyseal osteosarcomas and metaphyseal osteosarcomas in terms of tumor characteristics were compared. RESULTS: The common imaging features of diaphyseal osteosarcoma were bone destruction, lamellar periosteal reaction with/without Codman triangle, massive soft tissue mass/swelling, neoplastic bone and/or calcification. CT and MRI had a higher detection rate in detecting bone destruction (P=0.001) as compared with that of X-ray. X-ray and CT resulted in a higher percentage in detecting periosteal reaction (P=0.018) and neoplastic bone and/or calcification (P=0.043) as compared with that of MRI. There was no difference (P=0.179) in detecting soft tissue mass among three imaging modalities. When comparing metaphyseal osteosarcoma to diaphyseal osteosarcoma, the latter had the following characteristics: a higher age of onset (P=0.022), a larger extent of tumor (P=0.018), a more osteolytic radiographic pattern (P=0.043). CONCLUSION: As compared with metaphyseal osteosarcoma, diaphysial osteosarcoma is a special location of osteosarcoma with a lower incidence, a higher age of onset, a larger extent of tumor, a more osteolytic radiographic pattern. The osteoblastic and mixed types are diagnosed easily, but the osteolytic lesion should be differentiated from Ewing sarcoma. X-ray, CT and MRI can show imaging features from different aspects with different detection rates.

[Clinicopathologic features of 234 cases with borderline ovarian tumors].

OBJECTIVE: To determine the clinicopathologic characteristics and prognostic factors that may be used to predict the poor outcome of patients with borderline ovarian tumors. METHODS: All cases with borderline ovarian tumors treated in the West China Second University Hospital from January 2001 to June 2007 were analyzed retrospectively for clinicopathologic features, treatment parameters and outcome of treatment. Univariate and multivariate analyses were used to assess independent prognostic factors using the logistic regression model. RESULTS: The median age of 234 patients was 40.1 years with a range of 14 to 80 years. There were 101 (43.2%), 94 (40.2%), 19 (8.1%), 12 (5.1%), 8 (3.4%) cases of serous, mucinous, mixed, endometrioid and clear cell tumors, respectively. Out of 234 cases, 182 (77.8%) underwent laparotomy and 45 (19.2%) underwent laparoscopy. Seven women underwent laparoconversion. Fertility sparing surgery was performed on 119 cases (50.9%) and radical surgery was performed on 115 cases (49.1%). Totally 161 (68.8%) patients had stage I, 19 (8.1%) had stage II, 54 (23.1%) had stage III, and none had stage IV disease. Sixty-four women received postoperative chemotherapy. The median follow-up was 40 months with a range of 8 to 78 months. Recurrence was found in 26 cases (11.1%) during follow-up, and no tumor-related death was reported. The logistic regression model showed that surgery procedure (OR = 2.304, P = 0.024), cyst rupture (OR = 2.213, P = 0.038), stage (OR = 4.114, P < 0.01), microinvasion (OR = 2.291, P = 0.046) and peritoneal implants (OR = 2.101, P = 0.016) were the five independent prognostic factors affecting recurrence. CONCLUSIONS: Although patients with borderline ovarian tumors have an excellent prognosis, the risk of recurrence remains in some patients. Emphasis should be put on these patients with high risk factors and preventive strategies should be taken to prevent their progression.

[Improve the chemosensitivity of resistant ovarian cancer cell by small RNA interference].

OBJECTIVE: To investigate the effects of siRNA on the drug resistance reversal of ovarian cancer cell. METHODS: The siRNA was transfected into human ovarian cancer cell line OVCAR8/TR by liposome. ATP-bioluminence assay was applied to measure the drug sensitivity to four chemotherapeutic agents before and after transfection. RESULTS: ATP-bioluminence assay showed that OVCAR8/TR cells were resistant to cDDP, ADM and Taxol. After siRNA transfection, OVCAR8/TR cells were sensitive to ADM and Taxol which are tansported by P-gp. The inhibition rate of ADM was improved from 37% to 58%, and that of Taxol was improved from 26% to 78%. However, the resistance of OVCAR8/TR cells to cDDP was not reversed. CONCLUSION: siRNA can effectively improve the drug resistance to chemotherapeutic agents which are transfered by P-gp. The RNA interference can reverse MDR1-mediated drug resistance in ovarian cancer cell.

[Research on human ovarian cancer cell MDR1 gene silenced by siRNA].

OBJECTIVE: To evaluate the effects of siRNA on the inhibitions of mRNA and P-gp expression of ovarian cancer cell with high expression of multidrug resistance gene (MDR1). METHODS: The siRNA was transferred into ovarian cancer cell line OVCAR8/TR. The real time RT-PCR and flow cytometry were used respectively to determine the expression of mRNA or P-gp of MDR1. RESULTS: The inhibition of mRNA-84% expression occurred at 48 h after cell transfection, and the inhibition of P-gp-85.23% expression occurred at 72 h after cell transfection. Afterward the inhibitions to mRNA and P-gp expressions gradually returned to the normal levels. The amounts of mRNA and P-gp expression had no difference between negative control and untransfected cells. CONCLUSION: RNA interference presents in the human ovarian cancer cell, siRNA can effectively inhibit the expression of mRNA and P-gp of MDR1. The RNAi may represent a new approach for the treatment of MDR1-mediated drug resistance.