PLGA‐PEG‐c(RGDfK)‐ Kushenol E micelles (PPCKM) with a therapeutic potential for targeting ovarian cancer

Background: As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from Sophora flavescens, which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor-targeting nanoparticle system modified with tumor-homing c(RGDfK) peptides. Materials and Methods: In the current study, poly(lactic-co-glycolic acid)-poly(ethylene glycol)-modified with cyclic RGDfK peptide (PLGA-PEG-c(RGDfK))-KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor-active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV-3 cells and xenograft models in BALB/c nude mice. Results: The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV-3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration-dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site. Conclusion: The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.

The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) recently reported a reduction in the average overall mortality among ovarian cancer patients screened with an annual sequential, multimodal strategy that tracked biomarker CA125 over time, where increasing serum CA125 levels prompted ultrasound. However, multiple cases were documented wherein serum CA125 levels were rising, but ultrasound screens were normal, thus delaying surgical intervention. A significant factor which could contribute to false negatives is that many aggressive ovarian cancers are believed to arise from epithelial cells on the fimbriae of the fallopian tubes, which are not readily imaged. Moreover, because only a fraction of metastatic tumors may reach a sonographically-detectable size before they metastasize, annual screening with ultrasound may fail to detect a large fraction of early-stage ovarian cancers. The ability to detect ovarian carcinomas before they metastasize is critical and future efforts towards improving screening should focus on identifying unique features specific to aggressive, early-stage tumors, as well as improving imaging sensitivity to allow for detection of tubal lesions. Implementation of a three-stage multimodal screening strategy in which a third modality is employed in cases where the first-line blood-based assay is positive and the second-line ultrasound exam is negative may also prove fruitful in detecting early-stage cases missed by ultrasound.

Ovarian cancer: role of ultrasound in preoperative diagnosis and population screening

Carrier Cell–mediated Delivery of a Replication-competent Adenovirus for Cancer Gene Therapy

Objective To investigate the diagnosis significance of serum HE4 ,CYFRA21-1 , CA125 levels for the benign and malignant varian tumor,and evaluate the value of single detection and combined detection on judging the high risks of ovarian cancer. Methods A total of 45 patients with primary ovarian cancer and 56 patients with benign varian tumor and 50 healthy subjects admitted in Wendeng central hospital whose serum levels of HE4 ,CYFRA21-1 and CA125 were detected by electro-chemiluminescence（ ECL）,any index above the normal limit was setting for positive,the positive rate and coincidence rate of the three indexes in diagnosis of ovarian cancer was analyzed,and the diagnosis values of three indexes in the benign and malignant varian tumors were compared. Results HE4 and CYFRA21-1 levels of ovarian cancer group were significantly higher,compared with the benign tumor group,and healthy contol group and the differences were statistically significant（ P ﹤0. 05 ）,however there was no significant difference between benign tumor group and control group（ P﹥0. 05 ）,for the ma-lignant tumors the specificity and positive predictive value were very high[ HE4（ 100%,100%）,CY-FRA21-1（98. 2%,96. 7%）]and the diagnostic accuracy was relatively high（90. 1%,83. 2%）,com-pared with CA125 the difference was significant（ P﹤0. 05 ）,but both of them the sensitivity was lower than CA125. The CA125 levels were all increased in benign and malignant tumor,only the extent was different,there was significant difference between them（P﹤0. 05）and the difference was also statistical-ly significant in benign and control group（ P﹤0. 05 ）,which can simply distinguish benign and malignant tumors, however the specificity for the diagnosis of ovarian cancer is not very high （75%）and the positive predictive value and diagnostic accuracy was also relatively low（ 72%, 77. 2%）,The sensitivity and accuracy of diagnosis was improved by combining the three indexes and the clinical diagnosis was optimized. Conclusions HE4 ,CYFRA21-1 levels are only increased in malig-nant tumors,and they are mainly used for the diagnosis of ovarian cancer,CA125 levels are all in-creased in benign and malignant tumors,only the extent is different and it can be used for distinguis-hing and diagnosing of benign and malignant tumors. Combining the three indexes can improve the sensitivity and accuracy of the diagnosis of ovarian cancer,and it has important significance for the early diagnosis and treatment of ovarian cancer. Key words: Human epididymis protein 4 Cytokeratin 19 fragment antigen 21-1 CA125 Ovarian cancer Electrochemiluminescence

Ovarian cancer (OC) is a major gynecological malignancy with an annually increasing morbidity that poses a significant threat to the health of women worldwide. Most OC patients are diagnosed at an advanced stage. It is an urgent task to search for biomarkers for the diagnosis and treatment of OC. The lncRNA HCP5 (HCP5) was recently identified as an oncogene in several malignant tumors. However, the function of HCP5 in OC has rarely been reported. Herein, the levels of HCP5 and PTBP1 were found to be markedly increased in malignant OC tumor tissues and OC cell lines. In HCP5-silenced SKOV-3 and HEY cells, cell viability was markedly decreased, and the apoptosis rate was significantly increased, with more cells exhibiting G0/G1 arrest and increased expression of cleaved caspase-3 and cleaved caspase-9. Furthermore, the number of migrated cells, number of invaded cells, and migration distance were notably decreased by the knockdown of HCP5 in SKOV-3 cells and HEY cells. In the xenograft model established with SKOV-3 cells, the number of lung metastases, tumor growth, and Ki67 expression in tumor tissues were markedly decreased by the knockdown of HCP5, accompanied by an increased percentage of TUNEL-positive cells. HCP5 was found to be localized in the nucleus, and the interaction between HCP5 and PTBP1 was verified by RNA pull-down and RNA immunoprecipitation assays. Furthermore, in HCP5-overexpressing OC cells, the impacts of HCP5 on cell proliferation and apoptosis were significantly attenuated by the knockdown of PTBP1. Collectively, these results indicate that HCP5 facilitates the progression of OC by interacting with the PTBP1 protein.

Objective: To look for the association of raised CA 125/ CEA ratio and positive ascitic fluid cytology with the diagnosis of epithelial ovarian cancer in patients with an adnexal mass. Study Design: Comparative Cross-sectional study. Setting: Department of Oncology and Gynecology, Sheikh Zayed Hospital Rahimyarkhan. Period: September 2021 to February 2022. Material & Methods: A total of three hundred patients presenting with adnexal mass were recruited for the study. All patients underwent detailed evaluation, including CA 125 levels, CEA levels and ascitic fluid cytology. After complete staging workup, they underwent surgery and histopathological analysis of adnexal mass. A consultant histopathologist made the diagnosis of ovarian cancer. Association of various factors, including raised CA 125/ CEA ratio and positive ascitic fluid cytology with the diagnosis of ovarian cancer, was established. Results: Out of 350 patients of adnexal mass included in analysis, 273 (88%) were diagnosed with ovarian carcinoma, while 77 (22%) were not diagnosed with ovarian cancer after the surgery and had a diagnosis other than ovarian cancer. 179 (51.2%) patients were post-menopausal whereas 171 (48.8%) were pre-menopausal. It was revealed that raised CA-125/CEA ratio and positive ascitic fluid cytology had a statistically significant association with the diagnosis of ovarian carcinoma on histopathology (p-value<0.001). Conclusion: Most patients who presented with adnexal mass were diagnosed with ovarian carcinoma in our study. Raised CA 125/ CEA ratio and positive ascitic fluid cytology at baseline predicted a histopathological diagnosis of ovarian cancer in our study participants.

Objective To investigate the diagnosis significance of human epididymis (HE4), cytokeratin-19-fragment (CYFRA21-1), carbohydrate antigen 199 (CA199) on the malignant ovarian tumor, and to evaluate the value of individual and combined detection in judging high risk ovarian cancer. Methods The serum HE4, CYFRA21-1, CA199 levels of 45 patients with primary ovarian cancer, 56 patients with benign ovarian tumor and 50 healthy check-up women in our hospital were detected by electrochemiluminescence immunoassay (ECL). The positive rates and coincidence rates of them were analyzed and the diagnostic value of them were compared. Results HE4 and CYFRA21-1 levels of ovarian cancer group were significantly higher compared with the benign tumor group and healthy control group and the differences were statistically significant (Z=-8.61, P<0.001; Z=-8.39, P<0.001; Z=-8.60, P<0.001; Z=-8.39, P<0.001), however there is no difference between benign tumor group andcontrol group(Z=-1.31, P=0.189; Z=-1.29, P=0.191). The difference of CA199 between benign tumor group and control group was statistically significant (Z=-8.79, P<0.001). For the malignant tumors, the specificity and positive predictive value of HE4 (99.8%, 99.7%), CYFRA21-1 (99.0%, 96.7%) were very high and the diagnostic accordance rates were relatively high (93.4%, 88.7%), but the sensibilities of them were lower compared with CA199.CA199 was increased both in benign and malignant ovarian tumors with different degrees, but the specificity was not very high (85.8%), and the positive predictive value and the diagnosis accordance rate were low (70.6%, 84.1%). The combined detection of HE4, CYFRA 21-1 and CA199 could improve the sensitivity and of the diagnosis of ovarian cancer (100%) and accuracy (89.4%). Conclusions HE4 and CYFRA21-1 only increas in malignant ovarian tumors, and they are mainly used for the diagnosis of ovarian cancer; CA199 level is increased both in benign and malignant ovarian tumors, but the extent is different and it can be used for distinguishing and diagnosing of benign and malignant ovarian tumors. Combining the three indexes can improve the sensitivity and accuracy of the diagnosis of ovarian cancer, and has an important significance for the early diagnosis and treatment of ovarian cancer. Key words: Ovarian neoplasms; Keratins; Antigens, tumor-associated, carbohydrate; human epididymis protein 4

The aim of this study was to detect the expressions of serum micro-ribonucleic acid (miR)-26b and miR-21 in ovarian cancer patients, and to explore their associations with the diagnosis, clinicopathological parameters and prognosis of ovarian cancer. A total of 86 patients diagnosed with ovarian cancer in our hospital from January 2014 to January 2015 were enrolled in the observation group. Meanwhile, another 86 subjects receiving physical examination in our hospital during the same period were enrolled in the control group. The expressions of serum miR-26b and miR-21 in both groups were detected via Real Time fluorescence-quantitative Polymerase Chain Reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were plotted. Later, the clinical diagnostic value of combined detection of miR-26b and miR-21 in ovarian cancer was analyzed. Moreover, the associations of serum miR-26b and miR-21 expressions with clinicopathological characteristics and prognosis of ovarian cancer patients were explored. The expression of serum miR-26b in ovarian cancer patients was significantly lower than that of healthy subjects, while miR-21 expression was markedly higher in ovarian cancer patients (p<0.05). The area under the ROC curve (AUC), the sensitivity and specificity of miR-26b detection, miR-21 detection and combined detection in the diagnosis of ovarian cancer were 0.753 vs. 0.826 vs. 0.916, 47.2 vs. 76.3 vs. 87.6 and 78.5 vs. 85.6 vs. 90.4, respectively. Therefore, it could be observed that both the sensitivity and specificity of combined detection were remarkably higher than those of single detection (p<0.05). In addition, the expressions of serum miR-26b and miR-21 were associated with clinical stage and lymph node metastasis of ovarian cancer patients, whereas it was not correlated with age and histological type. The 3-year survival rate of patients with high expression of serum miR-26b was significantly higher than that in those with low expression of serum miR-26b. However, the 3-year survival rate of patients with low expression of serum miR-21 was higher than that in those with high expression. MiR-21 is highly expressed, while miR-26b is lowly expressed in the serum of ovarian cancer patients. Both of them may be involved in the incidence and development of ovarian cancer. Furthermore, combined monitoring of serum miR-26b and miR-21 has a certain value in the clinical diagnosis and treatment of ovarian cancer.

Diet and survival after a diagnosis of ovarian cancer: a pooled analysis from the Ovarian Cancer Association Consortium.

Non-epithelial ovarian cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up

Comparison of CA125, HE4, and ROMA index for ovarian cancer diagnosis

IntroductionMutations in Breast Cancer Susceptibility Genes (BRCA) are associated with an increased risk of both breast and ovarian cancer. In previous studies, about 20% of ovarian cancer patients reported a...

BackgroundCentrosome amplification is recognized as a hallmark of cancer. Kinesin family member C1 (KIFC1), a centrosome-clustering molecule, is essential for the viability of extra centrosome-bearing cancer cells and may be the basis for the progression of ovarian cancer. However, its biological function and mechanism in ovarian cancer have not yet been studied.Material/MethodsQuantitative reverse-transcription polymerase chain reaction was performed to detect the levels of KIFC1 and centrosome protein E (CENPE). Further, cell viability was analyzed with CCK-8 assay, and immunofluorescence was used to measure the expression of Ki67 and PCNA. Cell migration was analyzed with wound healing and transwell assays. Western blot analysis was performed to measure the expression of proteins in ovarian cancer cells. The relationship between KIFC1 and CENPE was investigated by performing co-immunoprecipitation.ResultsKIFC1 was upregulated in ovarian cancer cells, especially in SKOV3 cells. Additionally, we found that KIFC1 silencing in SKOV3 cells inhibited cell proliferation and downregulated the expression of Ki67 and PCNA. Further, the knockdown of KIFC1 suppressed cell migration and epithelial-mesenchymal transition (EMT) and regulated the expression of matrix metalloproteinase (MMP)2, MMP9, E-cadherin, N-cadherin, Snail, and ZEB1. Next, we found that KIFC1 bound to and positively regulated CENPE, a tumor promoter in certain human cancers. All the suppressive effects triggered by KIFC1 inhibition were reversed by CENPE overexpression.ConclusionsKIFC1 contributed to cell proliferation, migration, and EMT via interacting with CENPE in ovarian cancer. KIFC1 might be a potential biomarker and therapeutic target in ovarian cancer patients.

Objective To prepare monoclonal antibodies and immunoradiometric assay kit against human epididymis protein 4 (HE4) and study its clinical value in diagnosis of ovarian cancer. Methods BALB/c mice were immunized with recombinant HE4 antigen, 2 paired monoclonal antibodies were generated through splenic cell and myeloma cell fusion and screening. The detection antibody was labeled with 125 Iodine and immunoradiometric assay kit for HE4 was developed. The detect sensitivity of the kit was determined, and its clinical sensitivity and specificity in diagnosis of ovarian cancer was evaluated. Results Two paired monoclonal antibodies with high affinity and specialty were generated. The detect sensitivity of this immunoradiometric assay was 3.65 pmol/L, and the clinical sensitivity and specificity in diagnosis of ovarian cancer was 90.83% and 99.17% respectively. Conclusions This study was prepared by a high affinity monoclonal antibodies against HE4, and the technical indexes of HE4 immunoradiometric assay kit were rather good. So it could be used in early diagnosis and curative effect observation of ovarian cancer, and reduce its lethality rate. Key words: Human epididymis protein-4; Ovarian neoplasm, antibodies Monoclonal; Immunoradiometric assay