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1.
Bioengineered ; 13(1): 1931-1941, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35001804

RESUMO

Most patients with ovarian cancer (OC) get remission after undergoing cytoreductive surgery and platinum-based standard chemotherapy, but more than 50% of patients with advanced OC relapse within the first 5 years after treatment and develop resistance to standard chemotherapy. The production of medicinal properties is the main reason for the poor prognosis and high mortality of OC patients. Cisplatin (DDP) resistance is a major cause for poor prognosis of OC patients. PTPRZ1 can regulate the growth and apoptosis of ovarian cancer cells, while the molecular mechanism remains unknown. This study was designed to investigate the roles of PTPRZ1 in DDP-resistant OC cells and possible mechanism. PTPRZ1 expression in OC tissues and normal tissues was analyzed by GEPIA database and verified by Real-time Quantitative Reverse Transcription PCR (RT-PCR) assay. PTPRZ1 expression in normal ovarian cancer cells and DDP-resistant OC cells was also analyzed. Subsequently, RT-PCR, Western blot, MTT experiment and flow cytometry were used to assess the effects of PTPRZ1-PI3K/AKT/mTOR regulating axis on DDP resistance of OC. PTPRZ1 expression was abnormally low in OC tissues, and notably reduced in DDP-resistant OC cells. MTT experiment and flow cytometer indicated that overexpression of PTPRZ1 enhanced the DDP sensitivity of OC cells and promoted the cell apoptosis. Moreover, the results of our research showed that PTPRZ1 might exert its biological effects through blocking PI3K/AKT/mTOR pathway. PTPRZ1 overexpression inhibitied OC tumor growth and resistance to DDP in vivo. Overall, PTPRZ1 might suppress the DDP resistance of OC and induce the cytotoxicity by blocking PI3K/AKT/mTOR pathway.

2.
Cell Death Dis ; 12(12): 1135, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876569

RESUMO

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. However, the molecular mechanisms underlying HGSOC development, progression, chemotherapy insensitivity and resistance remain unclear. Two independent GEO datasets, including the gene expression profile of primary ovarian carcinoma and normal controls, were analyzed to identify genes related to HGSOC development and progression. A KEGG pathway analysis of the differentially expressed genes (DEGs) revealed that the cell cycle pathway was the most enriched pathway, among which TTK protein kinase (TTK) was the only gene with a clinical-grade inhibitor that has been investigated in a clinical trial but had not been studied in HGSOC. TTK was also upregulated in cisplatin-resistant ovarian cancer cells from two other datasets. TTK is a regulator of spindle assembly checkpoint signaling, playing an important role in cell cycle control and tumorigenesis in various cancers. However, the function and regulatory mechanism of TTK in HGSOC remain to be determined. In this study, we observed TTK upregulation in patients with HGSOC. High TTK expression was related to a poor prognosis. Genetic and pharmacological inhibition of TTK impeded the proliferation of ovarian cancer cells by disturbing cell cycle progression and increasing apoptosis. TTK silencing increased cisplatin sensitivity by activating the mammalian target of rapamycin (mTOR) complex to further suppress cisplatin-induced autophagy in vitro. In addition, the enhanced sensitivity was partially diminished by rapamycin-mediated inhibition of mTOR in TTK knockdown cells. Furthermore, TTK knockdown increased the toxicity of cisplatin in vivo by decreasing autophagy. These findings suggest that the administration of TTK inhibitors in combination with cisplatin may lead to improved response rates to cisplatin in patients with HGSOC presenting high TTK expression. In summary, our study may provide a theoretical foundation for using the combination therapy of cisplatin and TTK inhibitors as a treatment for HGSOC in the future.

3.
Front Oncol ; 11: 749144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966670

RESUMO

Ovarian carcinoma remains the most lethal gynecological carcinoma. Abnormal expression of splicing factors is closely related to the occurrence and development of tumors. The DEAD-box RNA helicases are important members of the splicing factor family. However, their role in the occurrence and progression of ovarian cancer is still unclear. In this study, we identified DEAD-box helicase 23 (DDX23) as a key DEAD-box RNA helicase in ovarian cancer using bioinformatics methods. We determined that DDX23 was upregulated in ovarian cancer and its high expression predicted poor prognosis. Functional assays indicated that DDX23 silencing significantly impeded cell proliferation/invasion in vitro and tumor growth in vivo. Mechanistically, transcriptomic analysis showed that DDX23 was involved in mRNA processing in ovarian cancer cells. Specifically, DDX23 regulated the mRNA processing of FOXM1. DDX23 silencing reduced the production of FOXM1C, the major oncogenic transcript of FOXM1 in ovarian cancer, thereby decreasing the FOXM1 protein expression and attenuating the malignant progression of ovarian cancer. Rescue assays indicated that FOXM1 was a key executor in DDX23-induced malignant phenotype of ovarian cancer. Furthermore, we confirmed that DDX23 was transcriptionally activated by the transcription factor (TF) E2F1 in ovarian cancer using luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. In conclusion, our study demonstrates that high DDX23 expression is involved in malignant behavior of ovarian cancer and DDX23 may become a potential target for precision therapy of ovarian cancer.

4.
Clin Cancer Res ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844979

RESUMO

BACKGROUND: Phase I results of this phase I/II study showed that pamiparib 60 mg BID had antitumor activity and an acceptable safety profile in Chinese patients with advanced cancer, including epithelial ovarian cancer (OC). METHODS: This open-label phase II study was conducted in China and enrolled adult ({greater than or equal to}18 years) patients with platinum-sensitive OC (PSOC, disease progression occurring {greater than or equal to}6 months after last platinum treatment) or platinum-resistant OC (PROC, disease progression occurring <6 months after last platinum treatment). Eligible patients had known or suspected deleterious germline BRCA mutation (gBRCA mut) and had previously received {greater than or equal to}2 lines of therapy. Pamiparib 60 mg PO BID was administered until disease progression, toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST version 1.1. RESULTS: In the total patient population (N=113; PSOC, n=90; PROC, n=23), median age was 54 years (range, 34-79) and 25.6% of patients received {greater than or equal to}4 prior systemic chemotherapy lines. Median study follow-up was 12.2 months (range, 0.2-21.5). Eighty-two PSOC patients and 19 PROC patients were evaluable for efficacy. In PSOC patients, 8 achieved a complete response (CR) and 45 achieved a partial response (PR); ORR was 64.6% (95% CI, 53.3-74.9). In PROC patients, 6 achieved a PR; ORR was 31.6% (95% CI, 12.6-56.6). Frequently reported grade {greater than or equal to}3 adverse events (AEs) were hematologic toxicities, including anemia and decreased neutrophil count. CONCLUSIONS: Pamiparib 60 mg BID showed antitumor activity with durable responses in patients with PSOC or PROC with gBRCA mut, and had a manageable safety profile.

5.
J Cell Mol Med ; 25(23): 10961-10972, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34734468

RESUMO

Rad50 is a component of MRN (Mre11-Rad50-Nbs1), which participates in DNA double-strand break repair and DNA-damage checkpoint activation. Here, we sought to investigate the clinical and functional significance of Rad50 in high-grade serous ovarian cancer (HGSOC). We found that Rad50 was frequently upregulated in HGSOCs and enhanced Rad50 expression inversely correlated with patient survival. In addition, ectopic expression of Rad50 promoted proliferation/invasion and induced EMT of ovarian cancer cells, whereas knockdown of Rad50 led to decreased aggressive behaviors. Mechanistic investigations revealed that Rad50 induced aggressiveness in HGSOC via activation of NF-κB signaling pathway. Moreover, we identified CARD9 as an interacting protein of Rad50 in ovarian cancer cells and the activation of NF-κB pathway by Rad50 is CARD9 dependent. Our findings provide evidence that Rad50 exhibits oncogenic property via NF-κB activation in HGSOC.

6.
Front Med (Lausanne) ; 8: 754890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746191

RESUMO

Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy. Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated. Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6-59.9], 74.2 95% CI: 65.6-81.4), and 45.8% (95% CI: 38.7-53.2), respectively. Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.

7.
Am J Surg Pathol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34753864

RESUMO

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P<0.0001) and TR (odds ratio for TNG1=0.225, 95% CI: 0.051-0.987, P=0.0479; for NTD=0.367, 95% CI: 0.171-0.786, P=0.0099) independent of depth of stromal invasion, lymphovascular invasion, tumor size, FIGO stage, and Silva pattern. Overall, 73/379 (19%) cases were both TNG1 and NTD-negative on the biopsy, and none of these 73 cases showed NM (0%), but a single case (1.4%) showed TR. In contrast, among the 324 biopsies with TNG2/3 and/or presence of NTD, 62 (19.1%) had NM, and 41 (12.9%) had TR. In summary, 2 variables in combination (ie, TNG1 and NTD-negative) identified a subset of HPVA EAC patients-∼19%-with a 0% frequency of nodal metastases and only 1.4% frequency of recurrence. Biopsies highly but imperfectly predicted these features. Nonetheless, these findings may potentially be of clinical utility in the risk stratification of patients with HPVA EACs. This may allow some patients with a minimal risk of nodal metastases and TR to be identified at the biopsy phase, thereby facilitating more personalized, possibly less aggressive treatment.

8.
Cancer Commun (Lond) ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738326

RESUMO

BACKGROUND: To date, there is no approved blood-based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. METHODS: We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre-treatment serum SEMA4C levels, measured using optimized in-house enzyme-linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. RESULTS: We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900-0.941) and 0.932 (95%CI: 0.911-0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early-stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916-0.946) and 0.879 (95%CI: 0.832-0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. CONCLUSIONS: Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

9.
J Transl Med ; 19(1): 415, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620163

RESUMO

BACKGROUND: Immune checkpoint blockades (ICBs) therapy showed limited efficacy in ovarian cancer management. Increasing evidence indicated that conventional and targeted therapies could affect tumor-associated immune responses and increase the effectiveness of immunotherapy. However, the effects of Niraparib, one of the poly (ADP) ribose polymerase (PARP) inhibitors, on the immune response remains unclear. Delineating the crosstalk between cytotoxic anticancer agents and cancer-associated immunity may lead to more efficient combinatorial strategies. METHODS: Programmed death ligand 1 (PD-L1) expression in human ovarian cancer cells after PARP inhibitors treatment was examined by western blotting (WB) and flow cytometry. The expression of poly ADP-ribose polymerase (PARP1), PD-L1, and CD8 in human ovarian cancer tissues was detected by immunohistochemistry(IHC). The effect of Niraparib and PD-L1 blockade in ovarian cancer progression was investigated in vivo. The changes of immune cells and cytokines in vitro and in vivo were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Changes of cGAS/STING signal pathway after Niraparib treatment were determined by WB, ELISA. RESULTS: Niraparib upregulated membrane PD-L1 and total PD-L1 expression in ovarian cancer cells and had a synergistic effect with PD-L1 blockade in vivo. In clinical patient samples, Niraparib augmented cytotoxic CD8+T cell proportion and function. In vivo and vitro, Niraparib can also increase the proportion of T cells and combined with PD-L1 blockade could further enhance the effect. Besides, Niraparib activated the cGAS-STING pathway, increasing the levels of cytokines such as CCL5 and CXCL10, which played a vital role in augmenting the infiltration and activation of cytotoxic T cells. CONCLUSIONS: Niraparib could modulate the immune response via the activation of the cGAS/STING pathway, and combination with PD-L1 blockade could further enhance the effect. These results provide a sound theoretical basis for clinical treatment.


Assuntos
Antígeno B7-H1 , Neoplasias Ovarianas , Feminino , Humanos , Imunidade , Indazóis/farmacologia , Indazóis/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Piperidinas
10.
Oncologist ; 26(12): e2217-e2226, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34427018

RESUMO

BACKGROUND: Adjuvant therapy for patients with cervical cancer (CC) with intermediate-risk factors remains controversial. The objectives of the present study are to assess the prognoses of patients with early-stage CC with pathological intermediate-risk factors and to provide a reference for adjuvant therapy choice. MATERIALS AND METHODS: This retrospective study included 481 patients with stage IB-IIA CC. Cox proportional hazards regression analysis, machine learning (ML) algorithms, Kaplan-Meier analysis, and the area under the receiver operating characteristic curve (AUC) were used to develop and validate prediction models for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 35 (7.3%) patients experienced recurrence, and 20 (4.2%) patients died. Two prediction models were built for DFS and OS using clinical information, including age, lymphovascular space invasion, stromal invasion, tumor size, and adjuvant treatment. Patients were divided into high-risk or low-risk groups according to the risk score cutoff value. The Kaplan-Meier analysis showed significant differences in DFS (p = .001) and OS (p = .011) between the two risk groups. In the traditional Sedlis criteria groups, there were no significant differences in DFS or OS (p > .05). In the ML-based validation, the best AUCs of DFS at 2 and 5 years were 0.69/0.69, and the best AUCs of OS at 2 and 5 years were 0.88/0.63. CONCLUSION: Two prognostic assessment models were successfully established, and risk grouping stratified the prognostic risk of patients with CC with pathological intermediate-risk factors. Evaluation of long-term survival will be needed to corroborate these findings. IMPLICATIONS FOR PRACTICE: The Sedlis criteria are intermediate-risk factors used to guide postoperative adjuvant treatment in patients with cervical cancer. However, for patients meeting the Sedlis criteria, the choice of adjuvant therapy remains controversial. This study developed two prognostic models based on pathological intermediate-risk factors. According to the risk score obtained by the prediction model, patients can be further divided into groups with high or low risk of recurrence and death. The prognostic models developed in this study can be used in clinical practice to stratify prognostic risk and provide more individualized adjuvant therapy choices to patients with early-stage cervical cancer.

11.
Indian J Gynecol Oncol ; 19(3): 51, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222614

RESUMO

Objective: Cervical cancers present major threats to women's health in China. Eliminating cervical cancer in China is a huge challenge, with application of the HPV vaccine, which is an important part. Methods: There are currently four HPV vaccines available in China: E-coli bv-HPV (Wantai, China), bv-HPV, qv-HPV (GSK, UK), and 9v-HPV (MSD, USA). To observe the immunogenicity, efficacy, and safety of these four vaccines in China, we formed the "Chinese Expert Consensus on the Clinical Application of HPV Vaccine." Results: At 7 months after vaccination, all vaccinated subjects had the same immunogenic response to either HPV16 or HPV18, ranging from 96 to 100%, and antibody production in girls aged 9-14 years was 2-3 times higher than that in adult women. Efficacy of the four vaccines against CIN2 + ranged from 87.3% to 100%, with prevention of HPV-associated infection reaching 96% ~ 97% at 12 months. Clinical trials showed bv-HPV and qv-HPV vaccine were also safe in women aged 18-45 years. Clinical trials of the 9v-HPV vaccine are underway. HPV vaccination is currently voluntary and self-paid in China. The "Chinese Expert Consensus on the Clinical Application of HPV Vaccine" will work to promote the application of HPV vaccine in China. Conclusions: In clinical studies, the available HPV vaccines showed excellent efficacy, safety, and immunogenicity in Chinese women. We will continue strengthening screening and encouraging HPV vaccination.

12.
Am J Transl Res ; 13(6): 7148-7155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306475

RESUMO

BACKGROUND: To investigate the associations between Vaginal Pathogenic Community with Bacterial vaginosis, Candida vaginitis, and Trichomonas vaginalis in Chinese women. METHOD: In this experiment, ten BV, nine VVC, eight TV patients, and four non-infected healthy women were recruited. The vaginal samples were collected from the vaginal orifice, the middle of the vagina, and vaginal fornix from every participant and conducted with next-generation sequencing (NGS). The NGS was based upon the analysis of bacterial 16S rRNA genes by using the Illumina Miseq system. RESULTS: No significant difference in microbiome community structures was observed for the three sampling sites from the same subject. Compared with the healthy population, patients with BV and TV showed more diverse symptoms and had a lower amount of Lactobacillus but a higher number of BV-related bacteria like Atopobium, Dialister, Sneathia, Mobiluncus, and Prevotella. On the contrary, the species composition of the VVC group is relatively simple, which has a significantly high abundance of Lactobacillus. Eight genera, including Arcanobacterium, Clostridium, Moryella, Mobiluncus, Shuttleworthia, Dialister, Bulleidia, and Megasphaera, were closely correlated with BV. Among vaginal pathogenic bacteria, Anaerococcus, Lysobacter, Mycoplasma, Peptoniphilus, Sneathia, and Prevotella were more common, with higher copy numbers in the TV group. CONCLUSIONS: The data outlined the overall structure of vaginal communities, indicating that BV and TV were touching related to a sharp increase in the rich taxonomy and diversity of vaginal microbiota. VVC group presented a lower variety, with a significantly high abundance of Lactobacillus.

13.
Front Med ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181195

RESUMO

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

14.
Biomark Res ; 9(1): 49, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134781

RESUMO

Tumor immunotherapy has attracted more and more attention nowadays, and multiple clinical trials have confirmed its effect in a variety of solid tumors. Immune checkpoint inhibitors (ICIs), cancer vaccines, adoptive cell transfer (ACT), and lymphocyte-promoting cytokines are the main immunotherapy methods. Endometrial cancer (EC) is one of the most frequent tumors in women and the prognosis of recurrent or metastatic EC is poor. Since molecular classification has been applied to EC, immunotherapy for different EC subtypes (especially POLE and MSI-H) has gradually attracted attention. In this review, we focus on the expression and molecular basis of the main biomarkers in the immunotherapy of EC firstly, as well as their clinical application significance and limitations. Blocking tumor immune checkpoints is one of the most effective strategies for cancer treatment in recent years, and has now become the focus in the field of tumor research and treatment. We summarized clinical date of planned and ongoing clinical trials and introduced other common immunotherapy methods in EC, such as cancer vaccine and ACT. Hormone aberrations, metabolic syndrome (MetS) and p53 mutant and that affect the immunotherapy of endometrial cancer will also be discussed in this review.

15.
Mol Cell Endocrinol ; 534: 111367, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34146645

RESUMO

High-grade serous ovarian cancer (HGSOC) is characterized by TP53 mutation and somatic copy number alterations (SCNAs). Here we show that the oncogenic transcription factor EVI1 (ecotropic viral integration site-1) is amplified and overexpressed up to 30% of 1640 HGSOC cases in The Cancer Genome Atlas (TCGA). Functionally, EVI1 promotes proliferation/invasion in vitro and tumor growth of xenograft model in vivo. Importantly, we discover that EVI1 regulates estrogen signaling by directly activating ESR1 (estrogen receptor 1) transcription determined by the ChIP and luciferase assay. Interestingly, EVI1 and ESR1 share common regulatory targets as indicated by the analysis of ChIP-Seq data. EVI1 and ESR1 collaborate in the regulation of some estrogen receptor-regulated genes. Furthermore, EVI1 drives tumor aggressiveness partially by regulating estrogen signaling. Estrogen enhances the proliferation, invasion and xenograft growth of ovarian cancer cells. Importantly, estrogen can rescue the inhibition of proliferation, invasion and xenograft growth induced by silencing EVI1. These findings suggest that EVI1 functions as a novel regulator of the estrogen signaling network in ovarian cancer.

16.
Cancer Manag Res ; 13: 4383-4392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103993

RESUMO

Objective: Enhanced recovery after surgery (ERAS) protocol has widely gained acceptance in gynecological surgery. Its safety and efficacy should be evaluated fully via well-designed, randomized, control trials. The main objective of our study is to compare the ERAS protocol with the conventional perioperative care program after gynecological oncology. Furthermore, the secondary objectives of our study are the identification of markers that allow us to evaluate the effectiveness of the application of ERAS elements in the modulation of the body's response to surgical stress. Methods: Patients with gynecological tumors indicated for surgery were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, reduced opioid consumption and immediate mobilization after surgery. The primary endpoint was the reduction of hospital stay in the ERAS group. The day of first flatus, postoperative nausea and vomiting (PONV), maximum pain score by the visual analogue scale (VAS) and complication, readmission rate, reoperation rate, postoperative mortality, total hospital cost and systemic inflammatory response (SIR) were secondary endpoints. Results: A total of 130 patients in gynecological tumor surgery were enrolled (ERAS = 65, conventional = 65). The ERAS group had faster bowel function recovery, significantly less pain, less PONV, shorter hospital stay, and less total hospital costs. SIR markers were estimated and screened out that postoperative platelet, neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) were significantly lower in ERAS groups compared to conventional groups. Conclusion: The implementation of ERAS protocol is safe and enhances postoperative recovery after gynecological oncology surgery. We firstly reveal the beneficial effect of ERAS protocols on the alleviation of postoperative SIR, which is a reflection of the magnitude of surgical trauma. Postoperative platelet, NLR or PLR could be the novel and inexpensive markers to assess how ERAS protocols modulate gynecological oncology surgery. Trial Registration: The trial was registered in ClinicalTrials.gov (NCT03629626).

17.
BMC Pregnancy Childbirth ; 21(1): 366, 2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-33966630

RESUMO

BACKGROUND: Hyperemesis gravidarum (HG) is a common complication during pregnancy, however, HG associated simultaneous onset of blood cell destruction due to electrolyte abnormalities is rare. In this case, a woman with refeeding syndrome (RFS) secondary to electrolyte abnormalities caused by severe HG was diagnosed and managed in our hospital. CASE PRESENTATION: A 29-year old woman was sent to the local hospitals because of severe HG with appetite loss, weight reduction, general fatigue, and she was identified to have severe electrolyte abnormalities. However, the electrolyte abnormalities were not corrected promptly, and then she had the symptoms of stillbirth, altered mental status, visual hallucination, hemolytic anemia and thrombocytopenia. After transferred to our hospital, we continued to correct the electrolyte abnormalities and the labor induction was performed as soon as possible. The symptoms of blood cell destruction were relieved obviously, and the patient discharged four days later. The electrolyte disturbances and physio-metabolic abnormalities caused by HG helped us diagnose this case as RFS. CONCLUSIONS: This case emphasizes that patients with RFS should be diagnosed appropriately and intervened promptly in order to prevent electrolyte imbalance induced blood cell destruction.


Assuntos
Anemia Hemolítica/etiologia , Hiperêmese Gravídica/complicações , Síndrome da Realimentação/etiologia , Adulto , Feminino , Hemólise , Humanos , Hipofosfatemia/etiologia , Trabalho de Parto Induzido , Gravidez , Síndrome da Realimentação/diagnóstico , Desequilíbrio Hidroeletrolítico/etiologia
18.
Acta Obstet Gynecol Scand ; 100(10): 1771-1778, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34027996

RESUMO

Ovarian granulosa cell tumor (GCT) is a rare, low-grade malignant tumor that accounts for 70% of the sex cord-stromal tumors. It has two histopathologic types with different clinical and biologic features: adult GCT and juvenile GCT. Most women diagnosed with the adult GCT have a favorable prognosis, with a 5-year survival rate of 97%-98%, but adult GCT has a feature of late relapse; the recurrence time could be more than 20 years after diagnosis. Juvenile GCT has a survival rate of 97% in stage I and a 5-year survival rate of 0%-22% in advanced stage with earlier recurrence than adult GCT. Consequently, the scenario emphasizes the need for early diagnosis, standardized treatment protocols, and long-term follow up. However, there is a lack of consensus regarding accurate diagnosis of GCT and adjuvant treatment. Furthermore, GCT tends to occur in young women, which emphasizes the viability of fertility-sparing surgery. The current review performed a systematic literature review of 60 articles to summarize the latest advances in GCT, with an emphasis on the molecular pathogenesis and survival after fertility-sparing surgery. We found that young women with fertility-sparing surgery had a desirable reproductive and survival outcome compared with those undergoing radical surgery.


Assuntos
Preservação da Fertilidade , Tumor de Células da Granulosa/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Feminino , Tumor de Células da Granulosa/mortalidade , Humanos , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Análise de Sobrevida
19.
Cell Mol Biol Lett ; 26(1): 20, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022794

RESUMO

BACKGROUND: Several studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers. However, the function and expression of miR-501 in endometrial cancer (EC) remain obscure. METHODS: The expression of miR-501 was determined using quantitative real-time PCR. MTT assay, colony formation assay and cell cycle analysis were used to evaluate the proliferation ability. Migration and invasion were assessed using transwell assay. Tumor formation in nude mice was used to observe the effects of miR-501 on cell proliferation and migration in vivo. Luciferase assay, quantitative real-time PCR and western blot were applied to determine that HOXD10 was the target gene of miR-501. RESULTS: In this study, we observed significantly up-regulated expression of miR-501 in endometrial cancer, which correlated with higher pelvic lymph node metastasis and shorter overall survival in high-grade endometrial cancer. High expression of miR-501 was also found in the copy-number-high group than other groups. Moreover, in vitro and in vivo assay showed that overexpression of miR-501 can promote proliferation and metastasis. Mechanistically, we found that miR-501 promotes tumor progression by directly targeting HOXD10. Further study also indicated that miR-501 overexpression can activate the AKT/mTOR pathway. CONCLUSIONS: MiR-501, which functions as an oncomir in endometrial cancer, might be a potential therapeutic target in high grade endometrial cancer.


Assuntos
Proliferação de Células , Neoplasias do Endométrio/patologia , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Animais , Antagomirs/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Taxa de Sobrevida , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Regulação para Cima
20.
Cytometry A ; 99(6): 610-621, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33840152

RESUMO

Cervical cancer is a major gynecological malignant tumor that threatens women's health. Current cytological methods have certain limitations for cervical cancer early screening. Light scattering patterns can reflect small differences in the internal structure of cells. In this study, we develop a light scattering pattern specific convolutional network (LSPS-net) based on deep learning algorithm and integrate it into a 2D light scattering static cytometry for automatic, label-free analysis of single cervical cells. An accuracy rate of 95.46% for the classification of normal cervical cells and cancerous ones (mixed C-33A and CaSki cells) is obtained. When applied for the subtyping of label-free cervical cell lines, we obtain an accuracy rate of 93.31% with our LSPS-net cytometric technique. Furthermore, the three-way classification of the above different types of cells has an overall accuracy rate of 90.90%, and comparisons with other feature descriptors and classification algorithms show the superiority of deep learning for automatic feature extraction. The LSPS-net static cytometry may potentially be used for cervical cancer early screening, which is rapid, automatic and label-free.


Assuntos
Algoritmos , Neoplasias do Colo do Útero , Detecção Precoce de Câncer , Feminino , Humanos
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