Publications by authors named "Guiling Li"

100 Publications

Clinical analysis of uterine intravenous leiomyomatosis: A retrospective study of 260 cases.

J Obstet Gynaecol Res 2021 Sep 15. Epub 2021 Sep 15.

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

Methods: We collected the clinical data of 260 patients admitted to the hospital from April 2003 to September 2019 with pathologically confirmed intravenous leiomyomatosis (IVL) and followed up with these patients regularly. Univariate and multivariate logistic regression analyses were carried out on the relevant recurrence factors.

Results: A total of 166 patients were regularly followed up, the median follow-up time was 36 (range 2-168) months, 14 (5.4%) patients eventually relapsed, and the median recurrence time was 8.5 (range 2-42) months. The univariate analysis showed that age (p = 0.003) and surgical type (p < 0.001) were associated with recurrence, and multivariate regression analysis demonstrated that surgical type was the only factor associated with recurrence (p < 0.001, OR 20.01).

Conclusions: The use of gonadotrophin releasing hormone agonist (GnRHa) cannot reduce the postsurgical recurrence rate of patients with UIVL. Compared to total hysterectomy and bilateral salpingo-oophorectomy (TH-BSO), total hysterectomy (TH) does not increase the odds of recurrence, but the chance of recurrence with tumorectomy (TE) is 20 times higher than that of TH-BSO.
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http://dx.doi.org/10.1111/jog.15013DOI Listing
September 2021

Isolation, Purification, Characterization, and Immunomodulatory Activity Analysis of α-Glucans from .

ACS Omega 2021 Aug 12;6(33):21384-21394. Epub 2021 Aug 12.

College of Food and Biological Engineering, Jimei University, Xiamen 361021, P. R. China.

Crude polysaccharides from (SP) were isolated by maceration with a hot alkali solution and further fractionated by DEAE-52 cellulose and Sephadex G-100 chromatography into two purified fractions PSP-1 and PSP-2. The monosaccharide composition analysis indicated that SP was mainly composed of rhamnose and glucose, while PSP-1 and PSP-2 were composed only of glucose. The composition analysis of PSP-1 and PSP-2 by HPLC, FT-IR, and NMR showed that PSP-1 and PSP-2 were branching dextran, and their structures were (1 → 4)-linked-α-D-Glcp as the main chain, and C-6 replaced the single α-D-Glcp as the linear structure of the branch chain. The glucans (SP/PSP-1/PSP-2) can significantly improve the phagocytic ability of macrophages, enhance iNOS activity, promote NO production, and increase IL-6 mRNA expression, so they may possess certain immunomodulatory activity.
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http://dx.doi.org/10.1021/acsomega.1c02175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387993PMC
August 2021

The combination of radiofrequency ablation and vertebroplasty shows advantages over single vertebroplasty in treating vertebral neoplastic lesions.

Skeletal Radiol 2021 Jul 10. Epub 2021 Jul 10.

Department of Interventional Radiology, Subei People's Hospital of Jiangsu Province (Clinical Medical College of Yangzhou University), Yangzhou, JiangSu Province, China.

Objective: To investigate the safety and efficacy of the combination of radiofrequency ablation (RFA) and vertebroplasty versus single vertebroplasty in treating spinal metastases.

Materials And Methods: The data of 35 patients with vertebral neoplastic lesions who received RFA combined with vertebroplasty (group A, 15 patients with 17 lesions) or single vertebroplasty (group B, 20 patients with 24 lesions) from March 2016 to June 2019 were retrospectively compared. The data of patients' Visual Analogue Scale (VAS) scores prior to the treatments, 1 week, 1 month, 3 months, and 6 months after the treatments, injected cement volume, ratios of cement leakage were compared between the two groups.

Results: All procedures were successfully done without severe complications. The VAS scores in group A were decreased more rapidly 1 week after the treatments and remained more stable at 6 months than that in group B (P < 0.05). The cement injected in group A (5.95 ± 1.45 mL, range 4-9.5 mL) was significantly more than that in group B (4.09 ± 0.55 mL, range 3.1-5.5 mL) (P < 0.05). The ratio of vascular cement leakage in group A was significantly lower than that in group B (P < 0.05), while no statistical difference was found in the non-vascular cement leakage (P > 0.05).

Conclusions: Our study shows that the combination of RFA and vertebroplasty has a better analgesic effect with more injected cement and lower rates of venous cement leakage than single vertebroplasty.
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http://dx.doi.org/10.1007/s00256-021-03788-7DOI Listing
July 2021

Analysis of intestinal flora and inflammatory cytokine levels in children with non-infectious diarrhea.

Transl Pediatr 2021 May;10(5):1340-1345

Department of Pediatrics, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, China.

Background: Non-infectious diarrhea is a common symptom in infants and young children. We aimed to analyze the intestinal flora and serum inflammatory cytokine levels of children with non-infectious diarrhea.

Methods: Eighty-nine children with non-infectious diarrhea and 76 healthy children were enrolled from the First Affiliated Hospital of Hainan Medical University between February 2017 and June 2020. Fecal bacterial samples were collected in sterile containers. Following serial dilution, the bacterial samples were cultured in an aerobic medium to cultivate (), , , and . The levels of inflammatory cytokines in the serum, including interleukin (IL)-2, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α), were determined by enzyme-linked immunosorbent assay. Results between the groups were compared using the paired -test. The chi-square test was employed to analyze categorical data, with analysis of variance used for multiple-group comparisons.

Results: No significant differences were observed between the diarrhea and control groups in terms of sex, age, or body mass index distribution. Compared to the control group, the diarrhea group had significantly elevated levels of and but significantly decreased levels of and . In terms of inflammatory cytokines, the levels of IL-2, IL-8, IL-10, and TNF-α were significantly higher in the diarrhea group than in the control group (all P<0.05). In children with non-infectious diarrhea, the levels of IL-2, IL-8, IL-10, and TNF-α were positively correlated with the amount of (r values of 0.412, 0.381, 0.479, and 0.216, respectively) and (r values of 0.257, 0.336, 0.357, and 0.328). Further, the amount of was positively correlated with IL-2 and IL-10 levels (r values of 0.342 and 0.438, respectively), and that of was negatively correlated with IL-2, IL-8, IL-10, and TNF-α levels (r values of -0.252, -0.336, -0.328, and -0.293, respectively). Finally, the level of was also negatively correlated with IL-8 and TNF-α levels (r values -0.301 and -0.464, respectively; both P<0.05).

Conclusions: The abundance and abnormality of , , , and in the intestinal flora of children with non-infectious diarrhea are associated with increased levels of IL-2, IL-8, IL-10, and TNF-α.
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http://dx.doi.org/10.21037/tp-21-168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193003PMC
May 2021

Flow field around bubbles on formation of air embolism in small vessels.

Proc Natl Acad Sci U S A 2021 Jun;118(26)

State Key Laboratory of Tribology, Tsinghua University, 100084 Beijing, China;

An air embolism is induced by intravascular bubbles that block the blood flow in vessels, which causes a high risk of pulmonary hypertension and myocardial and cerebral infarction. However, it is still unclear how a moving bubble is stopped in the blood flow to form an air embolism in small vessels. In this work, microfluidic experiments, in vivo and in vitro, are performed in small vessels, where bubbles are seen to deform and stop gradually in the flow. A clot is always found to originate at the tail of a moving bubble, which is attributed to the special flow field around the bubble. As the clot grows, it breaks the lubrication film between the bubble and the channel wall; thus, the friction force is increased to stop the bubble. This study illustrates the stopping process of elongated bubbles in small vessels and brings insight into the formation of air embolism.
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http://dx.doi.org/10.1073/pnas.2025406118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255810PMC
June 2021

Blood-Repellent Performance of a Controllable Facile-Generated Superhydrophobic Surface.

ACS Appl Mater Interfaces 2021 Jun 9;13(24):29021-29033. Epub 2021 Jun 9.

Key Laboratory of High Efficiency and Clean Mechanical Manufacture of Ministry of Education, School of Mechanical Engineering, Shandong University, Jinan 250061, P. R. China.

Fabrication of a blood-repellent surface is essential for implantable or interventional medical devices to avoid thrombosis which can induce several serious complications. In this research, a novel micropatterned surface was fabricated a facile and cost-effective method, and then, the and blood-repellent performances of the controllable superhydrophobic surface were systematically evaluated. First, a facile and cost-effective strategy was proposed to fabricate a controllable superhydrophobic surface on a medically pure titanium substrate using an ultraviolet laser process, ultrasonic acid treatment, and chemical modification. Second, the superhydrophobicity, durability, stability, and corrosion resistance of the superhydrophobic surface were confirmed with advanced testing techniques, which display a high contact angle, low adhesion to water and blood, and excellent resistant element precipitation. Third, the platelet-rich plasma and whole blood were applied to evaluate the hemocompatibility of the superhydrophobic surface by means of an experiment, and no blood cell activation or aggregation was observed on the superhydrophobic surface. Finally, hollow tubes with an inner superhydrophobic surface were implanted into the left carotid artery of rabbits for 2 weeks to verify the biocompatibility . The superhydrophobic surface could effectively eliminate blood cell adhesion and thrombosis. No obvious inflammation or inordinate proliferation was found by histological analysis. This research provides a facile and cost-effective strategy to prepare a blood-repellent surface, which may have promising applications in implanted biomedical devices.
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http://dx.doi.org/10.1021/acsami.0c21058DOI Listing
June 2021

The Beneficial Effects of Edible Kynurenic Acid from Marine Horseshoe Crab () on Obesity, Hyperlipidemia, and Gut Microbiota in High-Fat Diet-Fed Mice.

Oxid Med Cell Longev 2021 3;2021:8874503. Epub 2021 May 3.

College of Food and Biological Engineering, Jimei University, Xiamen 361021, China.

The marine horseshoe crab () has been considered as food and traditional medicine for many years. Kynurenic acid (KA) was isolated from horseshoe crab in this study for the first time in the world. A previous study in 2018 reported that intraperitoneal administration of KA prevented high-fat diet- (HFD-) induced body weight gain. Now, we investigated the effects of intragastric gavage of KA on HFD mice and found that KA (5 mg/kg/day) inhibited both the body weight gain and the increase of average daily energy intake. KA reduced serum triglyceride and increased serum high-density lipoprotein cholesterol. KA inhibited HFD-induced the increases of serum low-density lipoprotein cholesterol, coronary artery risk index, and atherosclerosis index. KA also suppressed HFD-induced the increase of the ratio of Firmicutes to Bacteroidetes (two dominant gut microbial phyla). KA partially reversed HFD-induced the changes in the composition of gut microbial genera. These overall effects of KA on HFD mice were similar to that of simvastatin (positive control). But the effects of 1.25 mg/kg/day KA on HFD-caused hyperlipidemia were similar to the effects of 5 mg/kg/day simvastatin. The pattern of relative abundance in 40 key genera of gut microbiota from KA group was closer to that from the normal group than that from the simvastatin group. In addition, our results showed the potential antioxidant activity of KA, which suggests that the improvement effects of KA on HFD mice may be partially associated with antioxidant activity of KA. Our findings demonstrate the potential role of KA as a functional food ingredient for the treatment of obesity and hyperlipidemia as well as the modulation of gut microbiota.
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http://dx.doi.org/10.1155/2021/8874503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112934PMC
May 2021

A novel ferroptosis-related gene signature for predicting outcomes in cervical cancer.

Bioengineered 2021 12;12(1):1813-1825

Department of Integration of Western and Traditional Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Ferroptosis, a newly discovered iron-dependent form of cell death, contributes to various pathologies; however, the prognostic value of ferroptosis-related genes (FRGs) in cervical cancer (CC) remains unclear. Herein, we identified 15 differentially expressed FRGs based on data from The Cancer Genome Atlas database. Ten FRGs that correlated with prognosis were screened by univariate Cox regression analysis. The least absolute shrinkage and selection operator regression model was performed to develop a novel prognostic signature. A four-gene model was built to separate samples into high-risk and low-risk groups. Overall survival was lower in the high-risk group than in the low-risk group ( < 0.05). Receiver operating characteristic curve showed a good diagnostic efficiency of the signature. The risk score was identified as an independent prognostic factor via multivariate Cox regression. A functional analysis further revealed a difference in the immune status between the two risk groups. To conclude, we constructed a novel prognostic signature based on FRGs. Targeting ferroptosis may represent a promising approach for the treatment of CC.
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http://dx.doi.org/10.1080/21655979.2021.1925003DOI Listing
December 2021

Mass SARS-CoV-2 molecular and serological screening of medical staff and patients in Hangzhou, China: no evidence of RNA detection, low seroprevalence, and limited exposure risk in the hospital setting.

Ann Transl Med 2021 Apr;9(7):552

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: To assess and limit the SARS-CoV-2 exposure risk from symptomless individuals in the hospital setting, molecular and serological screening of staff and patients attending a tertiary hospital in China was conducted.

Methods: SARS-CoV-2 RNA was tested by quantitative RT-PCR. Anti-SARS-CoV-2 IgM and IgG were screened initially with two lateral flow immunoassays (LFIs) and further confirmed with three chemiluminescence immunoassays (CLIAs). The assay performance was assessed using archived samples from 32 confirmed COVID-19 cases and 80 healthy individuals.

Results: Between April 24 and May 8, 2020, 16,043 subjects (7,392 medical staff, 4,714 inpatients, 1,209 chaperones, 1,705 outpatients, and 1,023 fever clinic patients) were screened. No subject tested positive for viral RNA. Seventy-three (0.46%) tested positive for IgM or IgG on the initial LFI screening, of whom 63 were investigated with CLIAs: 2 (0.01%) were confirmed as seroreactive and 18 (0.11%) were indeterminate. Unconfirmed seroreactivity was significantly more frequent in fever clinic patients. The CLIAs showed similar (95.0-100%) IgM or IgG specificity but higher IgG sensitivity (93.75-96.88% . 31.25-81.25%) than the LFIs. The confirmed seropositive cases included a previously discharged COVID-19 patient and an undiagnosed symptomless patient showing detectable IgM and IgG over 35 days of follow-up. No transmission was evidenced within the corresponding family cluster.

Conclusions: Low SARS-CoV-2 prevalence and limited exposure risk were observed. Seroprevalence varied between 0.012% and 0.12% according to the testing algorithm and the confirmation criteria used, indicating that quality standards for serological tests are needed. Protective immunity in asymptomatic COVID-19 patients who recovered needs to be investigated further, but the associated risk of transmission appeared limited.
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http://dx.doi.org/10.21037/atm-20-7163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105841PMC
April 2021

Novel IMB16-4 Compound Loaded into Silica Nanoparticles Exhibits Enhanced Oral Bioavailability and Increased Anti-Liver Fibrosis In Vitro.

Molecules 2021 Mar 11;26(6). Epub 2021 Mar 11.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.

Background: Liver fibrosis, as a common and refractory disease, is challenging to treat due to the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4), which is expected to have good potential effects against liver fibrosis. However, IMB16-4 is water-insoluble and has very low bioavailability.

Methods: Mesoporous silica nanoparticles (MSNs) were selected as drug carriers for the purpose of increasing the dissolution of IMB16-4, as well as improving its oral bioavailability and inhibiting liver fibrosis. The physical states of IMB16-4 and IMB16-4-MSNs were investigated using nitrogen adsorption, thermogravimetric analysis (TGA), HPLC, UV-Vis, X-ray diffraction (XRD) and differential scanning calorimetry (DSC).

Results: The results show that MSNs enhanced the dissolution rate of IMB16-4 significantly. IMB16-4-MSNs reduced cytotoxicity at high concentrations of IMB16-4 on human hepatic stellate cells LX-2 cells and improved oral bioavailability up to 530% compared with raw IMB16-4 on Sprague-Dawley (SD) rats. In addition, IMB16-4-MSNs repressed hepatic fibrogenesis by decreasing the expression of hepatic fibrogenic markers, including α-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β1) and matrix metalloproteinase-2 (MMP2) in LX-2 cells.

Conclusions: These results provided powerful information on the use of IMB16-4-MSNs for the treatment of liver fibrosis in the future.
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http://dx.doi.org/10.3390/molecules26061545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000840PMC
March 2021

Follow-up study on serum cholesterol profiles and potential sequelae in recovered COVID-19 patients.

BMC Infect Dis 2021 Mar 24;21(1):299. Epub 2021 Mar 24.

Department of Laboratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Background: COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients.

Objective: In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients.

Methods: A 3-6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up.

Results: LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p <  0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p <  0.05). Coagulation and liver functional values were significantly improved at follow-up than at admission for patients (p <  0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p <  0.001) during patients' recovery. With exclusion of the subjects taking traditional Chinese medicines or cholesterol-lowering drugs, LDL-c and HDL-c levels were significantly increased at follow-up than at admission in severe/critical cases (p <  0.05). Residue lesions were observed in CT images in 72% (44 of 61) of follow-up patients.

Conclusions: Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3-6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.
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http://dx.doi.org/10.1186/s12879-021-05984-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989719PMC
March 2021

Solid Tumor Complicated With Venous Thromboembolism: A 10-Year Retrospective Cross-Sectional Study.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:1076029620975484

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) occurs more frequently in cancer patients than in the general population. A retrospective cross-sectional study was carried out in patients with solid tumor complicated with VTE admitted to the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 1st, 2008 and December 31th, 2017. The incidence of VTE in hospitalized cancer patients was 1.8%, twice the incidence of VTE in hospitalized non-cancer patients. The annual incidence of cancer-associated VTE in our center varied between 1.6% in 2015 and 0.4% in 2009 with an overall average incidence of 1.3% over the research decade. BMI values of 549(67.7%) cancer patients were within the normal range, but none of patients had BMI greater than 35 kg/m. 747(92.1%) cancer patients had ECOG PS score ≤ 2 and 481(59.3%) had distant metastasis. Patients with pancreatic, bladder, ovarian and endometrial cancer had the highest incidence of VTE. Upper extremity DVT (47.2%) was more common in cancer patients and might be closely associated with CVC (74.9%), while lower extremities DVT (36.1%) intended to PE development (15.0%). The annual incidence rates showed a fluctuating and upward trend over the research decade. VTE occurrence was closely related to tumor stage, tumor site, catheterization and anti-neoplasm therapy in cancer patients.
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http://dx.doi.org/10.1177/1076029620975484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894580PMC
February 2021

Three Novel Dietary Phenolic Compounds from Pickled Raphanus Sativus L. Inhibit Lipid Accumulation in Obese Mice by Modulating the Gut Microbiota Composition.

Mol Nutr Food Res 2021 03 25;65(6):e2000780. Epub 2021 Feb 25.

Fujian Provincial Engineering Technology Research Center of Marine Functional Food, College of Food and Biological Engineering, Jimei University, Xiamen, 361021, China.

Scope: Although pickled radish is widely consumed worldwide, few studies have investigated the nutritional benefits of bioactive compounds extracted from pickled radish. In this study, the authors investigate the relationship among dietary phenolic compounds, lipid accumulation, and gut microbiota.

Method And Results: Three phenolic compounds 2,6-dihydroxyacetophenone (DHAP), 4-hydroxyphenethyl alcohol (4-HPEA), and 4-hydroxybenzaldehyde (HBA) are extracted from pickled radish. LO2 cells treated with free fatty acid are first used to explore the impact of the above three compounds at different doses on reducing lipid levels. The effects of the three compounds on obesity and the gut microbiota are further investigated in high-fat diet (HFD)-induced KM mice. Results show that three compounds inhibited the lipid accumulation in LO2 cells. The results of animal experiments reveal that three compounds prevented body weight gain and significantly decreased serum lipid levels. Treatment with DHAP, HPEA, and HBA reversed gut microbiome dysbiosis in HFD-induced mice. The three phenolic compounds increase Odoribacter, and decrease Helicobacter and Mucispirillum. Notably, DHAP and HBA reduce the HFD-induced increase in the Firmicutes/Bacteroidetes ratio.

Conclusion: These data suggest that phenolic compounds extracted from pickled radish possess excellent lipid-lowering capacity, providing a theoretical basis for further analysis of the nutritional value of pickled radish.
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http://dx.doi.org/10.1002/mnfr.202000780DOI Listing
March 2021

An Open-label, Multicenter, Single-arm, Phase II Study of Fluzoparib in Patients with Germline Mutation and Platinum-sensitive Recurrent Ovarian Cancer.

Clin Cancer Res 2021 May 8;27(9):2452-2458. Epub 2021 Feb 8.

Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.

Purpose: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline -mutated recurrent ovarian cancer.

Patients And Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1.

Results: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6-78.2] and 70.8% (95% CI, 61.5-79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3-13.9) and 10.3 months (95% CI, 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2-96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred.

Conclusions: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline -mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3546DOI Listing
May 2021

Antioxidant Activity of Docosahexaenoic Acid (DHA) and Its Regulatory Roles in Mitochondria.

J Agric Food Chem 2021 Feb 26;69(5):1647-1655. Epub 2021 Jan 26.

College of Food and Biological Engineering, Jimei University, No. 43 Yindou Road, Jimei District, Xiamen, Fujian 361021, P. R. China.

Reactive oxygen species (ROS) are single-electron-bearing oxidation-reduction products that are mainly produced in mitochondria. Excessive ROS accumulation may lead to oxidative damage. Docosahexaenoic acid (DHA) is an essential component of brain phospholipids and is mainly derived from the diet. Its antioxidant activities have been extensively studied. However, its regulatory roles in mitochondria and the underlying mechanism remain to be elucidated. In this study, the DHA's effect on cellular antioxidant capacity and mitochondrial functions was examined in HepG2 cells. The results showed that 100 μM DHA decreased cellular and mitochondrial ROS levels to 75.2 ± 9.4% ( < 0.05) and 55.1 ± 1.4% ( < 0.01), respectively. It also increased the total antioxidant capacity by 55.6 ± 0.1 and 49.2 ± 1.1% ( < 0.05), based on ABTS and FRAP assay results, respectively. Consistently, it increased the activities and gene expression of major antioxidant enzymes by at least 35 and 40% ( < 0.05), respectively. Furthermore, DHA promoted mitochondrial functions and biogenesis. These data suggested that DHA's antioxidant activity can be attributed to its enhancement of mitochondrial functions and biogenesis. This study may shed light on the molecular mechanisms underlying DHA's function in improving resistance to and relieving the symptoms of chronic disease.
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http://dx.doi.org/10.1021/acs.jafc.0c07751DOI Listing
February 2021

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer.

J Ovarian Res 2021 Jan 11;14(1):12. Epub 2021 Jan 11.

Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Zhejiang, China.

Objective: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy.

Methods: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints.

Results: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2-6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4-46.4%), and the DCR was 65.2% (95% CI, 56.4-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires.

Conclusions: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.
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http://dx.doi.org/10.1186/s13048-020-00736-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798203PMC
January 2021

Ammonium nitrate regulated the color characteristic changes of pigments in Monascus purpureus M9.

AMB Express 2021 Jan 4;11(1). Epub 2021 Jan 4.

Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, Tianjin, 300457, People's Republic of China.

Monascus pigments (MPs) with different color characteristics, produced by submerged fermentation of Monascus purpureus M9, have potential application in food industry. In the present study, the effects and regulatory mechanisms of ammonium nitrate (AN) on the color characteristics of MPs were investigated. The concentration of intracellular pigments was significantly decreased when subjected to AN. The hue and lightness value indicated AN altered the total pigments appearance from original red to orange. The HPLC analysis for six major components of MPs showed that the production of rubropunctatin or monascorubrin, was significantly reduced to the undetectable level, whereas the yields of monascin, ankaflavin, rubropunctamine and monascorubramine, were apparently increased with AN supplement. To be noted, via real-time quantitative PCR strategy, the expression level of mppG, closely relative to orange pigments biosynthesis, was significantly down-regulated. However, the expression of mppE, involved in yellow pigments pathway, was up-regulated. Moreover, the broth pH value was dropped to 2.5-3.5 in the fermentation process resulted from AN treatment, along with the increased extracellular polysaccharide biosynthesis. Taken together, the change of MPs categories and amounts by AN might be the driving force for the color characteristics variation in M. purpureus M9. The present study provided useful data for producing MPs with different compositions and modified color characteristics.
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http://dx.doi.org/10.1186/s13568-020-01165-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782668PMC
January 2021

An Innovative Immune Score-Based Prognostic Nomogram for Patients with Cervical Cancer.

Biomed Res Int 2020 7;2020:8882576. Epub 2020 Nov 7.

Department of Integration of Western and Traditional Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Background: In the past few years, the immune system and tumor immune microenvironment are becoming increasingly popular as more work has been accomplished in this field. However, nomograms based on immune-related characteristics for prognosis prediction of cervical cancer have not been fully explored to our knowledge. We constructed a novel immune score-based nomogram to predict patients with high risk and poor prognosis.

Materials And Methods: 198 patients with cervical cancer from The Cancer Genome Atlas (TCGA) database were included in our study. Immune scores were generated with Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm, and clinic-pathological characteristics were also included for subsequent analysis. Cox proportional hazards regression models were performed for univariate and multivariate analyses to screen the significant factors, and a prognostic nomogram was built. Bootstrap resampling analysis was used for internal validation. The calibration curve and concordance index (C-index) were used to assess the predictive performance of the nomogram.

Results: Patients were split into three subgroups based on immune scores. We found that patients with high immune scores conferred significantly better overall survival (OS) compared with those with medium and low immune scores (hazard ratio (HR), 0.305; 95% confidence interval (CI), 0.108-0.869). A nomogram with a C-index of 0.720 had a favorable performance for predicting survival rate for clinical use by combining immune scores with other clinical features. The calibration curves at 3 and 5 years suggested a good consistency between the predicted OS and the actual OS probability.

Conclusions: Our work highlights the potential clinical application significance of immune score-based nomogram in predicting the OS of cervical cancer patients.
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http://dx.doi.org/10.1155/2020/8882576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669339PMC
April 2021

Enhanced antitumor effects of follicle-stimulating hormone receptor-mediated hexokinase-2 depletion on ovarian cancer mediated by a shift in glucose metabolism.

J Nanobiotechnology 2020 Nov 7;18(1):161. Epub 2020 Nov 7.

Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.

Background: Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity.

Results: HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH β 33-53 or retro-inverso FSH β 33-53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway.

Conclusions: These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.
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http://dx.doi.org/10.1186/s12951-020-00720-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648390PMC
November 2020

Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer.

J Exp Clin Cancer Res 2020 Sep 10;39(1):183. Epub 2020 Sep 10.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: NEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown.

Methods: We detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model. γ-H2AX and Rad51 foci formation, neutral comet assay and clonogenic cell survival assay were applied to determine the radiosensitivity of cervical cancer cells. RNA-seq was performed to identify the downstream effector of NEK2. The gene expression levels were measured by Real-time PCR.

Results: We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer tissues. Furthermore, we provided evidence that depletion of NEK2 impairs oncogenesis and enhances radiosensitivity in cervical cancer. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression.

Conclusions: Our results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.
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http://dx.doi.org/10.1186/s13046-020-01659-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488040PMC
September 2020

Brachytherapy care during the COVID-19 pandemic: Practice statement from a cancer center in Wuhan, China.

Brachytherapy 2021 Jan-Feb;20(1):279-283. Epub 2020 Aug 26.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Purpose: COVID-19 broke out in late 2019 and rapidly spread around the world and became a pandemic. This highly contagious disease affects routine health care services and patients with cancer who are susceptible to it. Delivering brachytherapy on time is critical for patients with cancer to get better prognosis. The purpose of this study is to present workflow and standard for radiation centers to deliver brachytherapy and avoid cross-infection during the COVID-19 pandemic.

Methods And Materials: This study combined previous literature and guidelines of precaution with clinical experience in the COVID-19 pandemic.

Results: A workflow covering patients' screening, health care workers' precaution, training, and other aspects of the whole brachytherapy procedure was established.

Conclusions: From the reopening of radiation center to mid-May in 2020, there is no hospital infection of COVID-19 in patients or health care workers. This recommendation is effective and helpful to other cancer centers.
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http://dx.doi.org/10.1016/j.brachy.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448731PMC
February 2021

Lipidome disturbances in preadipocyte differentiation associated with bisphenol A and replacement bisphenol S exposure.

Sci Total Environ 2021 Jan 25;753:141949. Epub 2020 Aug 25.

Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China. Electronic address:

Bisphenol S (BPS) is the major substitute for the production of bisphenol A (BPA)-free products and detected in both food and environment. Although the relationship between BPA exposure and increased risk of obesity and diabetes has been noted, the potential influence of BPS is not fully understood. Herein, a non-targeted lipidomic study was performed to explore BPA/BPS exposure actions using the 3T3-L1 preadipocyte differentiation model, and revealed the comprehensive lipidome disturbance induced by either BPA or BPS exposure at different doses of 0.01, 1 and 100 μM. BPA was more potent than BPS in disturbance of lipid metabolism. A considerable similarity of BPS exposure to BPA was discovered. The key lipid remodeling in response to exposure was found to involve the cardiolipins, phosphatidylglycerols and fatty acids metabolic pathways, providing novel clues of potential mechanism in which both BPA and BPS exposure could be associated with increased risk of insulin resistance. Our study supplies the perspective into the lipidome response to environmental stress induced by BPA/BPS, and shows that BPA-free products are not necessarily safer. Substitution of BPA by its structural analog BPS should be therefore performed with caution.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141949DOI Listing
January 2021

PAK6 promotes cervical cancer progression through activation of the Wnt/β-catenin signaling pathway.

Oncol Lett 2020 Sep 1;20(3):2387-2395. Epub 2020 Jul 1.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

p21-activated kinase 6 (PAK6), a member of the serine/threonine kinase family, has been reported to be involved in numerous types of cancers. The present study aimed to investigate the role of PAK6 in cervical cancer. In the present study, PAK6 expression was evaluated in tissue microarrays and cell lines by using immunohistochemistry and western blotting. The mRNA level of PAK6 was evaluated by reverse transcription quantitative PCR. The Wnt/β-catenin signaling-related protein expression was detected by western blotting following short hairpin (sh)RNA-mediated PAK6 knockdown or PAK6 overexpression. Cell proliferation was determined using Cell Countink Kit-8. Migration, invasion and colony formation were further assessed following PAK6 knockdown or overexpression. Co-immunoprecipitation (Co-IP) and fluorescence colocalization microscopy were used to detect the interaction between PAK6 and GSK3β. The results from tissue microarray revealed that the expression levels of PAK6 in cervical cancer tissues were upregulated. The downregulation of PAK6 expression levels using shRNA not only decreased cell growth and proliferation, but it also inhibited the migration and invasion of HeLa cells. Conversely, the overexpression of PAK6 promoted the proliferation, migration and invasion of HeLa cells. In addition, the expression levels of proteins involved in the Wnt/β-catenin signaling pathway were modified in the PAK6 knockdown group, including downregulation of GSK3β phosphorylation and Cyclin D1 protein, and upregulation of β-catenin phosphorylation and E-cadherin. In contrast, following the overexpression of PAK6, the Wnt/β-catenin signaling pathway was activated. Further investigation using fluorescence microscopy and Co-IP assays indicated that PAK6 may interact with GSK3β. In conclusion, the findings of the present study suggested that PAK6 may serve a role in promoting cervical cancer through activating the Wnt/β-catenin signaling pathway.
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http://dx.doi.org/10.3892/ol.2020.11797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400107PMC
September 2020

Fabrication of Microspheres from High-Viscosity Bioink Using a Novel Microfluidic-Based 3D Bioprinting Nozzle.

Micromachines (Basel) 2020 Jul 14;11(7). Epub 2020 Jul 14.

Advanced Medical Research Institute, Shandong University, Jinan 250012, China.

Three-dimensional (3D) bioprinting is a novel technology utilizing biocompatible materials, cells, drugs, etc. as basic microcomponents to form 3D artificial structures and is believed as a promising method for regenerative medicine. Droplet-based bioprinting can precisely generate microspheres and manipulate them into organized structures with high fidelity. Biocompatible hydrogels are usually used as bioinks in 3D bioprinting, however, the viscosity of the bioink could be increased due to the additives such as cells, drugs, nutrient factors and other functional polymers in some particular applications, making it difficult to form monodispersed microspheres from high-viscosity bioink at the orifice of the nozzle. In this work, we reported a novel microfluidic-based printing nozzle to prepare monodispersed microspheres from high-viscosity bioink using the phase-inversion method. Different flowing conditions can be achieved by changing the flow rates of the fluids to form monodispersed solid and hollow microspheres using the same nozzle. The diameter of the microspheres can be tuned by changing the flow rate ratio and the size distribution of the microspheres is narrow. The prepared calcium alginate microspheres could also act as micro-carriers in drug delivery.
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http://dx.doi.org/10.3390/mi11070681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408603PMC
July 2020

Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study.

Lancet Oncol 2020 07 29;21(7):904-913. Epub 2020 May 29.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population.

Methods: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ test. Risk factors for mortality were identified by univariable and multivariable logistic regression models.

Findings: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56-70; range 14-96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59-78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56-6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16-10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57-9·50]; p=0·0033) were risk factors for death during admission to hospital.

Interpretation: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes.

Funding: National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S1470-2045(20)30310-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259917PMC
July 2020

Gynecological malignancies with asymptomatic SARS-CoV-2 infection during the convalescence of outbreak.

Gynecol Oncol 2020 07 29;158(1):44-46. Epub 2020 Apr 29.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

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http://dx.doi.org/10.1016/j.ygyno.2020.04.709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188644PMC
July 2020

Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak.

Cancer Discov 2020 06 28;10(6):783-791. Epub 2020 Apr 28.

Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. SIGNIFICANCE: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients..
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http://dx.doi.org/10.1158/2159-8290.CD-20-0422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309152PMC
June 2020

Development and Validation of a Prognostic Nomogram to Guide Decision-Making for High-Grade Digestive Neuroendocrine Neoplasms.

Oncologist 2020 04 29;25(4):e659-e667. Epub 2019 Nov 29.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Background: The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy.

Subjects, Materials, And Methods: We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one.

Results: The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001).

Conclusion: The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials.

Implications For Practice: The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.
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http://dx.doi.org/10.1634/theoncologist.2019-0566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160419PMC
April 2020

A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer.

J Ethnopharmacol 2021 Mar 7;267:112837. Epub 2020 Apr 7.

Department of Integration of Western and Traditional Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200090, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fudan University, Shanghai, 200011, China. Electronic address:

Ethnopharmacological Relevance: Pinellia pedatisecta Schott extract (PE) is generated from Pinellia pedatisecta Schott, a traditional Chinese medicinal plant. PE suppresses cervical tumor growth and exhibits effects on dendritic cells (DCs) that lead to modulation of antitumor CD4 and CD8 responses.

Aims: To explore the underlying mechanisms by which PE modulates tumor-associated dendritic cell (TADC) activation and function.

Methods: DCs and TADCs were generated from murine bone marrow and exposed to PE solutions at different doses, as well as to repeated doses separated at different time intervals. Quantitative PCR, Western blot analysis, flow cytometry, and gene silencing were used to analyze the modulatory effects of PE on the SOCS1/JAK2/STAT pathways. Furthermore, we separated human cervical tumor-infiltrated DCs (TIDCs) and conducted an ex-vivo stimulation model to observe the effect of PE. For phenotypic analysis of cultured DCs and ex vivo human specimens, we used flow cytometry to detect the molecular markers associated with cell function.

Results: In cultured TADCs and human cervical TIDCs, maturation- and functional markers (MHCII, CD80, CD83, CD86, and IL-12) were downregulated, whereas SOCS1 was upregulated. PE enhanced the expression of CD80, CD86, and IL-12 in cervical TIDCs, which induced increased expression of CD107a, GZMB, and perforin in CTLs, and furthermore induced apoptosis in a larger number of tumor cells. In cultured TADCs, PE downregulated SOCS1 expression and activated the phosphorylation of JAK2, STAT1, STAT4, and STAT5 in both dose- and time-dependent manners. The effects of PE upregulating MHCII, CD80, CD86, IL-12 on TADCs were blocked after SOCS1 silencing.

Conclusions: In this study, PE restored the impaired function of cervical TIDCs, thereby eliciting further antitumor CTL responses. The effects of PE on TADCs were mediated through inhibition of SOCS1 and activation of downstream JAK2-STAT1/STAT4/STAT5 pathways. PE may be a potent and effective immunomodulatory drug for antitumor treatment via the blockade of SOCS1 signaling in DCs.
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http://dx.doi.org/10.1016/j.jep.2020.112837DOI Listing
March 2021

Validation and modification of staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma.

BMC Cancer 2020 Mar 6;20(1):188. Epub 2020 Mar 6.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful tumor-node-metastasis (TNM) staging system for poorly differentiated pancreatic neuroendocrine carcinomas (pNECs).

Methods: An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients), and a modified system based on the analysis of the 7th AJCC classification was proposed.

Results: In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI) = 0.73-2.06, P = 0.44; HR for stage III =2.20, 95% CI =1.06-4.56, P = 0.03; HR for stage IV =4.95, 95% CI =3.20-7.65, P < 0.001). The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system.

Conclusions: The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.
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http://dx.doi.org/10.1186/s12885-020-6634-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059325PMC
March 2020
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