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Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
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Humanos , Femenino , Plaquetas/patología , Biomarcadores de Tumor/genética , Neoplasias Ováricas/patología , ChinaRESUMEN
Endometriosis is a common, benign, oestrogen-dependent, chronic gynaecological disorder associated with pelvic pain and infertility. Some researchers have identified nerve fibers in endometriotic lesions in women with endometriosis. Mesenchymal stem cells [MSCs] have attracted interest for their possible use for both cell and gene therapies because of their capacity for self-renewal and multipotentiality of differentiation. We investigated how human umbilical cord-MSCs [hUC-MSCs] could affect nerve fibers density in endometriosis. In this experimental study, hUC-MSCs were isolated from fresh human umbilical cord, characterized by flow cytometry, and then transplanted into surgically induced endometriosis in a rat model. Ectopic endometrial implants were collected four weeks later. The specimens were sectioned and stained immunohistochemically with antibodies against neurofilament [NF], nerve growth factor [NGF], NGF receptor p75 [NGFRp75], tyrosine kinase receptor-A [Trk-A], calcitonin gene-related peptide [CGRP] and substance P [SP] to compare the presence of different types of nerve fibers between the treatment group with the transplantation of hUC-MSCs and the control group without the transplantation of hUC-MSCs. There were significantly less nerve fibers stained with specific markers we used in the treatment group than in the control group [p<0.05]. MSC from human umbilical cord reduced nerve fiber density in the treatment group with the transplantation of hUC-MSCs
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Cordón Umbilical , Células Madre Mesenquimatosas , Fibras Nerviosas , Ratas Wistar , Endometriosis , Modelos Animales , InmunohistoquímicaRESUMEN
Objective To investigate the possible origin of ovarian epithelial inclusions and its relationship with the low-grade ovarian serous carcinoma.Methods By comparatively evaluating the morphologic (secretory and ciliated cell distribution ) and immunophenotypic [using paired box gene 8 (PAX8),tubulin,calretinin,and Ki-67 as first antibodies] attributes of ovarian epithelial inclusions,the normal tubal epithelium,and the ovarian tumors,all adnexal tissues from a total of 198 patients were studied,including 116 adnexae removed for non-neoplastic indications,53 serous cystadenomas,44 serous borderline tumors,and 41 low-grade serous carcinomas,which were collected from Qilu Hospital of Shandong University and University of Arizona in USA.Immunohistochemical single staining was used to detect the expressions of PAX8,tubulin,calretinin,and Ki-67 in the two groups,while immunohistochemical double staining of PAX8/calretinin was used to figure out the immunophenotype of various ovarian epithelial inclusions in a more intuitive way.Results With immunohistochemical single staining of PAX8 and calretinin,the vast majority (90%,54/60) of ovarian surface epithelia displayed a mesothelial phenotype [calretinin(+),PAX8 (-)],whereas 10% (6/60)of the cases displayed foci with tubal phenotype [calretinin(-),PAX8 (+)].In contrast,most (79%,728/921 ) of the ovarian epithelial inclusions displayed a tubal phenotype,though 21% (193/921) of the ovarian epithelial inclusions showed a mesothelial phenotype.It was further proved by immunohistochemical double staining of PAX8/ calretinin.Secretory and ciliated cells were found in the ovarian epithelial inclusions with tubal phenotype.There was a progressive increase in the secretory/ciliated cells ratio and proliferative index,from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma,according to the expression of tubulin and Ki-67.Conclusions The findings make a strong argument that the ovarian epithelial inclusions displaying a tubal phenotype with PAX8 (+),calretinin (-) is likely derived from fallopian tube rather than through Mullerian metaplasia from ovarian surface epithelium.The increasing trend of secretory/ciliated cells ratio and proliferative index from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma indicates that the latter is a clonal expansion of secretory cells.Genetic and molecular studies are needed to further confirm these findings.
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<p><b>OBJECTIVE</b>To observe the effects of angiostatin gene combined with chemotherapy on implanted human ovarian carcinoma of nude mouse.</p><p><b>METHODS</b>The mice were randomly divided into four groups after 7 days of the intraperitoneal injection of tumor cells (4 x 10(6)), and injected respectively with empty plasmid pcDNA3.0, angiostatin plasmid, cisplatin, and angiostatin plasmid + cisplatin. For combinational treatment, reagents were delivered in a timed fashion, where angiostatin plasmid was injected first, followed by cisplatin 24h later. The tumor samples were prepared to be used in the examinations of the expression of angiostatin with immunohistochemistry, of MVD in the tumor with immunohistochemistry, and of cell apoptosis with TUNEL staining.</p><p><b>RESULTS</b>Tumor growth and ascites formation were inhibited in all 3 groups except for the control group. The therapeutic effectiveness in the combined group was more significant than in the other two groups. In this group, MVD (32.5 +/- 4.3) was the lowest and apoptosis index (5.12 +/- 0.63) was the highest (P < 0.01).</p><p><b>CONCLUSIONS</b>Angiostatin gene therapy combined with chemotherapy has a synergistic effect on the inhibition of ovarian cancer angiogenesis and ascites formation. Combining multiple therapies to treat ovarian cancer is an effective strategy.</p>
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Animales , Femenino , Humanos , Ratones , Angiostatinas , Genética , Antineoplásicos , Usos Terapéuticos , Cisplatino , Usos Terapéuticos , Terapia Combinada , Inyecciones Intraperitoneales , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Ováricas , Patología , Terapéutica , Peritoneo , Distribución Aleatoria , Trasplante HeterólogoRESUMEN
<p><b>BACKGROUND</b>BAFF, the B cell activation factor, is a member of the tumor necrosis factor (TNF) ligand family that binds to BCMA, TACI, and BAFF-R. Previous studies have shown that members of the TNF family are detected in human placental trophoblast cells, but the expression patterns of BAFF involved in human decidua and the differential expression of BAFF between normal pregnancy and miscarriage are still incompletely documented or unknown. This study was designed to investigate the expression of BAFF and BAFF-R in the trophoblast and decidua of normal early pregnant women and recurrent spontaneous abortion (RSA) patients.</p><p><b>METHODS</b>Forty-five patients with RSA and 45 normal pregnant women were included in this study. By reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical experiments, we explored the expression of BAFF and BAFF-R in the maternal-fetal interface of normal early pregnant women and RSA patients.</p><p><b>RESULTS</b>Analysis by RT-PCR and Western blotting revealed that BAFF was detected in both trophoblast and decidua of all the samples, and the expression level was higher in the tissues of normal early pregnant women (P<0.05) than that of recurrent spontaneous abortion patients under the same gestational weeks. Messages for BAFF-R were absent. Immunohistochemical experiments showed that expression of BAFF was cell-specific which was localized to villous cytotrophoblast and syncytiotrophoblast cells in trophoblast and to stromal cells in decidua. Whereas BAFF was prominent on the trophoblast and decidua of normal early pregnant women, it was decreased in the tissues of RSA patients.</p><p><b>CONCLUSIONS</b>BAFF might steer maternal leukocytes away from a harmful immune response and toward a favorable one and play a potentially vital role for successful pregnancy.</p>
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Femenino , Humanos , Embarazo , Aborto Habitual , Metabolismo , Factor Activador de Células B , Genética , Fisiología , Decidua , Química , Metabolismo , Inmunohistoquímica , Interleucina-10 , Genética , ARN Mensajero , Células TH1 , Alergia e Inmunología , Células Th2 , Alergia e Inmunología , Trofoblastos , Química , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the in vitro effect of HSV-tk/GCV using a hTERT promoter-driven vector system on Skov3 ovarian cancer cells.</p><p><b>METHODS</b>An expression vector (pBTdel-279-tk) containing tk gene under the hTERT promoter was constructed by molecular biological methods, and then was transfected into Skov3 ovarian cancer cells, normal ovarian epithelial cells (NOEC) and human embryonic lung fibroblast by cationic liposome. Following the transfection with tk, GCV was added, and MTT and flow cytometry methods were applied to investigate its antitumor effect. RT-PCR was used to detect the tk gene in ovarian cancer cells and normal cells after the transfection of pcDNA3-tk or pBTdel-279-tk.</p><p><b>RESULTS</b>pBTdel-279-tk/GCV system induced apoptosis in hTERT-positive ovarian cancer cells, but not in hTERT-negative normal ovarian epithelial cells and fibroblasts. The hTERT promoter system was almost as efficient in inducing cancer cell death as the CMV promoter. tk gene was expressed in Skov3 cells and NOEC after pcDNA3-tk transfection, while positive was only in ovarian cancer cells after pBTdel-279-tk transfection.</p><p><b>CONCLUSION</b>The telomerasespecific transfer of the tk gene under the hTERT promoter is a novel targeting approach for the treatment of ovarian cancer and may lead to an effective and specific gene therapy.</p>
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Femenino , Humanos , Apoptosis , Genética , Cistadenocarcinoma Seroso , Genética , Patología , Proteínas de Unión al ADN , Ganciclovir , Farmacología , Terapia Genética , Neoplasias Ováricas , Genética , Patología , Regiones Promotoras Genéticas , Genética , Simplexvirus , Genética , Telomerasa , Genética , Timidina Quinasa , Genética , Transfección , Células Tumorales CultivadasRESUMEN
0.05).The ultramicrostructure of cells detected by electron microscope showed that GJIC function in transfected group was higher than that in the other two groups.While in migration assay,the numbers of cells in lower chamber passing through the membrane in transfected group,blank control group and negative control group were 112?23,306?49 and 322?91, respectively;with significant differences among 3 groups(P
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AIM: To investigate the expression of NKG2A,NKG2D and their ligands in pregnancy uterine micro-environment and to probe the function of NKG2A and NKG2D imbalance expression during the immunotolerance at the fetal-maternal boundary.METHODS: Decidual lymphocytes and peripheral lymphocytes were obtained from 30 women during 6-9 weeks of pregnancy who were undergoing selective termination.FACS technology was used to detect NK cells number and NKG2A,NKG2D expression.RT-PCR was used to investigate HLA-E and MICA mRNA in trophoblast tissue.RESULTS: Natural killer cells predominate,accounting for 70% of pregnancy endometrial lymphocytes.FACS results indicated that NKG2A was significantly increased in decidual NK cells as compared with that in peripheral NK cells,accounting for 97.86%?1.75% and 33.35%?10.92%.The difference between them in NKG2A expression was significant(P
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Objective To evaluate the feasibility and effectiveness of combination chemotherapy with etoposide and cisplatin(EP)regimen on the patients with high-risk,chemorefractory and recurrent gestational trophoblastic neoplasia(GTN).Methods Thirty-nine patients with gestational trophoblastic tumors were analyzed retrospectively,25 of 39 patients were of high-risk,9 patients were chemorefractory and 5 patients were recurrent.All 39 patients were administrated with EP regimen,and 10 patients were assisted with surgery.All the patients were followed up.Clinical response,toxicity,the occurrence of secondary tumors of all patients,and the fertility of 30 patients whose fertility function was preserved were investigated. Results Thirty-nine GTN patients underwent a total of 221 cycles of the EP regimen.The average number of courses for each patient was 5.7.The total complete remission rate of the regimen was 74%(29/39). Twenty-five patients with high-risk GTN received a total of 139 cycles and the average number of courses was 5.6.Nineteen patients achieved complete remission and 6 patients showed drug-resistant.The complete remission rate of the high-risk group was 76%(19/25).Nine patients with chemorefractory GTN obtained a total of 55 cycles and the average number of courses was 6.1.Six patients achieved complete remission and 3 patients showed drug-resistant again.The complete remission rate of the chemorefractory group was 6/9. Five patients with recurrent GTN received 27 cycles and the average number of courses was 5.4.Four patients achieved complete remission,1 patient showed drug-resistance and died.Bone marrow toxicity, gastrointestinal reaction and alopecia were the main side effects of the EP regimen,but the bone marrow toxicity was slight and no grade Ⅳ side effect occurred.No fatal effect was found.Eight of 30 patients whose fertility faction was preserved had become pregnant after recovery,with a total of 8 pregnancies.Among them,2 were terminated by induced abortion,and 6 underwent normal term delivery and gained 6 infants who had no congenital malformation.All the 6 children had normal growth and development after childbirth. None of the women developed secondary tumors.Conclusion The EP regimen is effective and safe for the treatment of high-risk,chemorefractory and recurrent GTN.
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0.05).(4) Toxicity:Grade Ⅲ-Ⅳ myelosuppression was 60%(18/30)in Tp group,26%(8/31)in TC group and 30%(10/33)in PC group.The TP regimen had the greatest hematologic toxicity(P0.05). Conclusions As first line chemotherapy in epithelial ovarian cancer,TP regimen comparable to the standard chemotherapy regimen.