1.Evaluation of secondary cytoreduction surgery in platinum-resistant ovarian cancer patients within three-line recurrent: a multicenter, randomized controlled study
Tingting CHEN ; Junfen XU ; Bairong XIA ; Hui WANG ; Yuanming SHEN
Journal of Gynecologic Oncology 2024;35(1):e22-
Background:
Epithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now.
Methods
This multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women’s Hospital, Zhejiang University School of Medicine.Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026.One hundred and forty participants with platinum-resistant ROC who meet the “RSCS criteria” will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life.
2.Evaluation of secondary cytoreduction surgery in platinum-resistant ovarian cancer patients within three-line recurrent: a multicenter, randomized controlled study
Tingting CHEN ; Junfen XU ; Bairong XIA ; Hui WANG ; Yuanming SHEN
Journal of Gynecologic Oncology 2024;35(1):e22-
Background:
Epithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now.
Methods
This multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women’s Hospital, Zhejiang University School of Medicine.Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026.One hundred and forty participants with platinum-resistant ROC who meet the “RSCS criteria” will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life.
3.Evaluation of secondary cytoreduction surgery in platinum-resistant ovarian cancer patients within three-line recurrent: a multicenter, randomized controlled study
Tingting CHEN ; Junfen XU ; Bairong XIA ; Hui WANG ; Yuanming SHEN
Journal of Gynecologic Oncology 2024;35(1):e22-
Background:
Epithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now.
Methods
This multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women’s Hospital, Zhejiang University School of Medicine.Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026.One hundred and forty participants with platinum-resistant ROC who meet the “RSCS criteria” will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life.
4.Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ
Jingjing LIU ; Yu WANG ; Xiaoyun WAN ; Jian ZOU ; Yedan ZHU ; Weiguo LV ; Yuanming SHEN
Journal of Gynecologic Oncology 2023;34(1):e8-
Objective:
To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix.
Methods:
Patients diagnosed with AIS after CC during 2007–2021 were identified by computerized databases at Women’s Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed.
Results:
Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence.
Conclusion
CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.
5.Efficacy of lymph node dissection on stage IIICr of cervical cancer before CCRT: study protocol for a phase III, randomized controlled clinical trial (CQGOG0103)
Misi HE ; Mingfang GUO ; Qi ZHOU ; Ying TANG ; Lin ZHONG ; Qing LIU ; Xiaomei FAN ; Xiwa ZHAO ; Xiang ZHANG ; Gang CHEN ; Yuanming SHEN ; Qin XU ; Xiaojun CHEN ; Yuancheng LI ; Dongling ZOU
Journal of Gynecologic Oncology 2023;34(3):e55-
Background:
Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopical positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. However, there are no prospective study reporting that resecting macroscopic nodes before concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer and no guidelines for surgical resection of bulky lymph nodes. The CQGOG0103 study is a prospective, multicenter and randomized controlled trial (RCT) evaluating lymph node dissection on stage IIICr of cervical cancer.
Methods
Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by computed tomography [CT]/magnetic resonance imaging/positron emission tomography/CT) and the short diameter of image-positive lymph node ≥15 mm. 452 patients will be equally randomized to receive either CCRT (pelvic external-beam radiotherapy [EBRT]/extended-field EBRT + cisplatin [40 mg/m2] or carboplatin [the area under curve=2] every week for 5 cycles + brachytherapy) or open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. A total of 452 patients will be enrolled from multiple hospitals in China within 4 years and followed up for 5 years.
6.Factors affecting long-term survival of advanced high-grade serous ovarian cancer
Yuanming SHEN ; Liqin JIN ; Sangsang TANG ; Yu WANG ; Weiguo LYU ; Zhongbo CHEN ; Xing XIE
Chinese Journal of Obstetrics and Gynecology 2021;56(6):393-400
Objective:To identify the factors associated with long-term survival and guide the decision for primary surgery in patients with advanced high-grade serous ovarian cancer(HGSOC).Methods:In this case-control study, clinical parameters, including surgical and non-surgical associated factors, were collected and compared between the patients with short-term (<2 years) and long-term (>5 years) survival who all underwent primary debulking surgery (PDS) followed by carboplatin and paclitaxel chemotherapy from January 2004 to December 2016. Univariate analysis was examined by chi-square test and multivariate analysis was performed by logistic regression analysis.Results:There were 95 cases long-term survival (LTS group) and 77 cases short-term survival (STS group) in 698 newly diagnosed HGSOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲc and Ⅳ who met include and exclude criteria. (1) Univariate analysis showed that the proportion of complete cytoreduction with no visible residual disease (R0) at PDS and platinum sensitivity in LTS group were significantly higher than those in STS group ( P<0.01). The surgical complexity score (SCS), the preoperative serum CA 125 level and the ascites volume in the LTS group were significantly lower than those of the STS group (all P<0.05). In the LTS group, the preoperative incidence of lesions in retrograde peritoneum of the bladder, serosal and mesangial membrane of the small intestine, upper abdominal peritoneum and liver parenchyma were significantly lower than those in the STS group (all P<0.05). Multivariate logistic regression analysis showed that platinum sensitivity ( OR=0.016, 95% CI: 0.004-0.063, P<0.01), ascites volume >500 ml ( OR=3.193, 95% CI: 1.285-7.930, P=0.012), and SCS ≥8 ( OR=17.433, 95% CI: 2.281-133.25, P=0.003) were independent factors affecting long-term survival ( P>0.05). (2) Totally 37 of 95 in long-term survival and 16 of 77 in short-term survival achieved R0 cytoreduction at PDS. Univariate analysis showed that preoperative serum CA 125 level, preoperative lesion score, preoperative lesion (DS) score, ascites volume, platinum sensitivity,and SCS were significantly correlated with the R0 PDS (all P<0.05). Multivariate analysis showed that ascites volume >500 ml ( OR=5.199, 95% CI: 2.015-13.409, P=0.001), DS >2 ( OR=15.264, 95% CI: 5.843-39.874, P<0.01) and SCS ≥4 ( OR=4.176, 95% CI: 1.618-10.777, P=0.003) were independent factors associated with R0 cytoreduction. In patients with DS ≤2 or SCS <4, but not those with DS >2 or SCS ≥4, R0 cytoreduction was significantly associated with long-term survival. Conclusion:The intrinsic biology of tumor is the factor influencing long-term survival of advanced HGSOC patients, and those who present with wide intraperitoneal metastases and need to remove multiple organs may not benefit from R0 cytoreduction.
7.Role of JAK2-STAT3 signaling pathway in pancreatic injury and systematic inflammatory response in rats with acute necrotizing pancreatitis
Yinfeng SHEN ; Yuanming BA ; Wenyin JIN ; Xia ZHANG ; Qian CHEN ; Junjun TIAN ; Yong ZHU ; Ran TAO
Chinese Journal of Pancreatology 2019;19(3):185-189
Objective To investigate the function of JAK2-STAT3 signaling pathway in pancreatic injury and systematic inflammatory response in rats with acute necrotizing pancreatitis ( ANP) . Methods SD rats were randomly divided into the ANP group (n=48), ANP+JAK2 inhibitor Ruxolitinib group (ANP+R group, n=48), ANP+STAT3 inhibitot Stattic group (ANP+S group, n=48), ANP+Ruxolitinib+Stattic group (ANP+R+S group, n=48), and sham operation group (SO group, n=48). 5% sodium taurocholate injection via retrograde pancreatobiliary duct was used to establish ANP model. Blood samples from abdominal aorta and pancreatic tissue were collected after 3 h, 6 h, 12 h and 18 h after modeling. Serum amylase (AMY) and tumor necrosis factor-α(TNF-α) and interleukin-4 (IL-4) were tested. JAK2 and STAT3 mRNA expression and protein expression of p-JAK2 and p-STAT3 in pancreas were examined by RT qPCR and western blot, respectively. Results AMY, TNF-α and IL-4 in plasma, and JAK2 mRNA, STAT3 mRNA, p-JAK2 protein and p-STAT3 protein at different time points in ANP group were all obviously higher than those in SO group(P<0. 05). Serum AMY, TNF-αand IL-4 in ANP+R group, ANP+S group and ANP+R+S group at different time points were lower than those in ANP group [12 h (5391 ± 1009),(6130 ± 1227),(4818 ± 992)U/L vs (8524 ± 1360) U/L;(147.25 ± 27.85),(156.25 ± 23.17),(127.87 ± 21.39) ng/L vs (187.58 ±20.09)ng/L;(45.89 ±16.95),(50.19 ±15.87),(38.87 ±14.03)ng/L vs (58.85 ±9.34)ng/L] . JAK2 mRNA and p-JAK2 protein,STAT3 mRNA and p-STAT3 protein in ANP+R group and ANP+R+S group at different time points were obviously lower than those in ANP group (12 h 0. 357 ± 0. 091 vs 0. 597 ± 0. 121,1. 115 ± 0. 203 vs 1. 217 ± 0. 213,0. 361 ± 0. 089 vs 0. 489 ± 0. 097,0. 965 ± 0. 189 vs 1. 128 ± 0. 217, 0. 362 ± 0. 092 vs 0. 597 ± 0. 121,1. 107 ± 0. 212 vs 1. 217 ± 0. 213,0. 297 ± 0. 087 vs 0. 489 ± 0. 097,0. 713 ± 0. 184 vs 1. 128 ± 0. 217). STAT3 mRNA and p-STAT3 protein in ANP+S group were obviously lower than those in ANP group(0. 319 ± 0. 107 vs 0. 489 ± 0. 097,0. 849 ± 0. 177 vs 1. 128 ± 0. 217), and the difference was statistically different (P<0.05). Conclusions The activation of JAK2-STAT3 signaling pathway in pancreas may play a key role in the pathogenesis of systematic inflammatory response in ANP.
8.MiR-181a and miR-181b influence proliferation, migration, invasion and angiogenesis via targeting FUT1 in colorectal cancer
Jie ZHOU ; Yuanming ZHENG ; Zongkun SHEN ; Xiaolu MA ; Yanju LI
Chinese Journal of Laboratory Medicine 2018;41(11):841-846
Objective To investigate the correlation of miR-181a and miR-181b with fucosyltransferase FUT1, the functional mechanism was elucidated in a colorectal cancer ( CRC).Methods It collected 32 pairs of tissue samples , 18 males and 14 females in the first affiliated hospital of Dalian Medicinal University, from March 2014 to January 2016.The expression of miR-181a and miR-181b was detected by RT-PCR in CRC tissues , adjacent tissues , serum of colorectal cancer patients and healthy people, and CRC cell lines SW620 and SW480 with differently metastatic ability.The relationship of FUT1 and miR-181a, miR-181b expression were verificated by Pearson's correlation curve.FUT1 was identified the target of miR-181a and miR-181b by Network prediction softwares ( TargetScan Human 7.1, microRNA.org and Starbase v2.0) and luciferase assay.The effects of miR-181a and miR-181b expression on the proliferation, migration, invasion and angiogenesis of SW 480 and SW620 cells were further detected by CCK8, wound healing, transwell and tube foramtion assays.T-test was used for comparison between two independent samples , and one-way anova was used for comparison between multiple samples . Pearson correlation coefficient was used for correlation analysis .Results The levels of miR-181a and 181b in CRC tissues were much lower than in tumor-adjacent tissues (3.12 ±1.88 vs 6.44 ±2.32, t=11.74;3.16 ± 1.77 vs 5.52 ±2.45, t=3.24 ;P<0.05).The levels of miR-181a and 181b in serum of colorectal cancer patients were much lower than in healthy people (1.32 ±0.25,2.57 ±0.48,t=10.26;0.91 ±0.14,1.63 ± 0.29,t=5.19;P<0.05 ) .The levels of miR-181a and miR-181b in SW620, SW480 CRC cells were detected to be much lower than in normal colorectal epithelial cells [(0.65 ±0.10, 0.50 ±0.09) vs 1.0;(0.60 ±0.12,0.42 ±0.03)vs 1.0;t=3.08, P<0.05].FUT1 was highly expressed in CRC tissues and SW620 (t=5.23, P<0.05).Based on the network prediction softwares and luciferase assays , FUT1 was the common target of miR-181a and miR-181b.Over expression of miR-181a or miR-181b inhibited FUT1 level and attenuated the capacity of cell migration , invasion and proliferation in SW 620.Down-regulation of miRNAs in SW480 increased FUT1 expression and promoted the capability of cell migration , invasion and proliferation.Downregulation of the two miRNAs attenuated the capability of cell invasion in SW 480, which was blocked by the reductive FUT1.Conclusion MiR-181a and miR-181b mediated the progression of CRC cells by targeting FUT1.
9.Application of Time-resolved Fluroimmunoassay for Determination of Furaltadone Metabolite 3-Amino-5-morpholinomethyl-2-oxazolidinone
Lihua DENG ; Jinbo DAI ; Zhenlin XU ; Jinyi YANG ; Hong WANG ; Zhili XIAO ; Hongtao LEI ; Yuanming SUN ; Yudong SHEN
Chinese Journal of Analytical Chemistry 2016;(8):1286-1290
To detect furaltadone metabolite 3-amino-5-morpholinomethyl-2-oxazolidinone ( AMOZ ) in fish sample, an Eu3+ labeling time-resolved fluoroimmunoassay ( TRFIA ) was developed. The effects of experimental conditions including AMOZA-OVA concentration, dilution of antibody, and reaction time on the sensitivity of TRFIA were explored. The results showed that the optimized assay conditions were as follows:the AMOZA-OVA concentration was 0. 25 μg/mL; the antibody was diluted 5í104 folds, and the competitive reaction time was 50 min. Under optimal conditions, the method showed a detection limit of 0. 01 ng/mL, an IC50 of 0. 26 ng/mL and a linear range (IC20-IC80) of 0. 025-2. 83 ng/mL. The recoveries of AMOZ in fish at three spiked levels ranged from 78 . 0% to 86 . 0%, and the relative standard deviations were less than 15%. Good correlation between the ic-TRFIA and high performance liquid chromatography-tandem mass spectrometry was obtained for spiked food samples. The proposed ic-TRFIA method was suited for the determination of AMOZ residue in food samples.
10.Indirect Competitive Chemiluminescent Enzyme Immunoassay Method for Determination of Dimethyl Phthalate in Soy Sauce and Liquor
Bin ZHU ; Fan ZHU ; Zhenlin XU ; Jinyi YANG ; Chunhong LIU ; Yuanming SUN ; Hong WANG ; Hongtao LEI ; Yudong SHEN
Chinese Journal of Analytical Chemistry 2015;(7):1027-1032
4-Amino dimethyl phthalate as the hapten was coupled to carrier protein and then used to immunize New Zealand rabbits. Polyclonal antibody which showed specific binding to dimethyl phthalate ( DMP) was thus obtained, and on the basis of this, an indirect competitive chemiluminescent enzyme-linked immunoassay ( icCLEIA ) was developed. The experimental parameters of icCLEIA were optimized as follows: the concentration of coating antigen was 50 μg/L, the primary antibody concentration was 92. 5 μg/L, the secondary antibody concentration was 1μg/mL, distilled water (pH 6. 0) was used as diluent solution and the competitive reaction time was 40 min. Under the optimal conditions, the icCLEIA exhibited a linear working range from 0. 74μg/L to 30. 32μg/L with the limit of detection of 0. 29μg/L. The cross-reactivity of thirteen structural analogues was lower than 5%. The recovery of DMP from spiked liquor and soy sauce samples ranged from 80 . 2% to 116 . 0% and the average RSD was less than 3 . 6%. The detection results of the spiked liquor and soy sauce samples were consistent with those by standard gas chromatography-mass spectrometry method. The developed icCLEIA method exhibited a practical potential for detecting DMP residue in food samples.

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