Suvemcitug plus chemotherapy for platinum-resistant epithelial ovarian, fallopian tube and primary peritoneal cancer: A phase 1b dose-escalation trial.

OBJECTIVE: The use of bevacizumab has been hampered by safety concerns despite demonstrable progression-free survival (PFS) benefit in subjects with platinum-resistant ovarian cancer, highlighting the need for novel effective and safe antiangiogenic agents. This study aimed to characterize the tolerability, safety, and antitumor activities of escalating doses of anti-VEGF antibody suvemcitug plus chemotherapy in platinum-resistant ovarian cancer patients. METHODS: This open-label, dose-escalation trial enrolled adult patients (≥18 years) with platinum-resistant histologically or cytologically-confirmed epithelial ovarian, fallopian tube and primary peritoneal cancer. Eligible patients received paclitaxel or topotecan plus escalating doses of suvemcitug 0.5, 1, 1.5, or 2 mg/kg once every two weeks. The primary endpoints were safety and tolerability, and antitumor activities of suvemcitug. RESULTS: Twenty-nine subjects received paclitaxel (n = 11) or topotecan (n = 18). No dose-limiting toxicities occurred. The most common adverse events of special interest were proteinuria (41.4%), hypertension (20.7%) and epistaxis (10.3%). No gastrointestinal perforations occurred. Nine subjects (31.0%, 95% CI 15.3-50.8) demonstrated investigators-confirmed objective response, including complete response in 1 and partial response in 8. The median PFS was 5.4 months (95% CI 2.2-7.4). CONCLUSIONS: Suvemcitug demonstrated an acceptable safety profile and promising antitumor activities in platinum-resistant ovarian cancer patients, supporting its further clinical development.

Immune Subtypes and Immune Landscape Analysis of Endometrial Carcinoma.

Some patients with endometrial cancer (EC) suffer from limited survival benefits after immunotherapy, suggesting that there may be a specific pattern associated with immunotherapy. Immune-related genes were extracted from The Cancer Genome Atlas databases. We analyzed the differences among immune subtypes (ISs) in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, immune checkpoint-related genes, immunotherapy, and chemotherapy. We applied dimensionality reduction and defined the immune landscape of EC. Then, we used the Weighted Gene Co-Expression Network Analysis package to identify the coexpression modules of these immune genes. Finally, hub genes were selected and detected by quantitative PCR and immunohistochemistry. We obtained three ISs. There were differences in the distribution of the tumor mutational burden, chemotherapy-induced immune response markers, and immune checkpoint-related genes among the ISs. Regarding immunotherapy and chemotherapy, the IS2 subtypes were more sensitive to programmed cell death protein 1 inhibitors. In addition, different positions in the immune landscape map exhibited different prognostic characteristics, providing further evidence of the ISs. The IS2 subtypes were significantly positively correlated with yellow module gene list, indicating a good prognosis with high score. SIRPG and SLAMF1 were identified as the final characteristic genes. The quantitative PCR and immunohistochemistry results showed that the expression levels of SIRPG and SLAMF1 were low in human EC tissue. In this study, we identified three reproducible ISs of EC. The immune landscape analysis further revealed the intraclass heterogeneity of the ISs. SIRPG and SLAMF1 were identified to be associated with progression, suggesting that they may be novel immune-related biomarkers of EC.

CircNUP50 is a novel therapeutic target that promotes cisplatin resistance in ovarian cancer by modulating p53 ubiquitination.

BACKGROUND: Most patients with ovarian cancer (OC) treated with platinum-based chemotherapy have a dismal prognosis owing to drug resistance. However, the regulatory mechanisms of circular RNA (circRNA) and p53 ubiquitination are unknown in platinum-resistant OC. We aimed to identify circRNAs associated with platinum-resistant OC to develop a novel treatment strategy. METHODS: Platinum-resistant circRNAs were screened through circRNA sequencing and validated using quantitative reverse-transcription PCR in OC cells and tissues. The characteristics of circNUP50 were analysed using Sanger sequencing, oligo (dT) primers, ribonuclease R and fluorescence in situ hybridisation assays. Functional experimental studies were performed in vitro and in vivo. The mechanism underlying circNUP50-mediated P53 ubiquitination was investigated through circRNA pull-down analysis and mass spectrometry, luciferase reporters, RNA binding protein immunoprecipitation, immunofluorescence assays, cycloheximide chase assays, and ubiquitination experiments. Finally, a platinum and si-circNUP50 co-delivery nanosystem (Psc@DPP) was constructed to treat platinum-resistant OC in an orthotopic animal model. RESULTS: We found that circNUP50 contributes to platinum-resistant conditions in OC by promoting cell proliferation, affecting the cell cycle, and reducing apoptosis. The si-circNUP50 mRNA sequencing and circRNA pull-down analysis showed that circNUP50 mediates platinum resistance in OC by binding p53 and UBE2T, accelerating p53 ubiquitination. By contrast, miRNA sequencing and circRNA pull-down experiments indicated that circNUP50 could serve as a sponge for miR-197-3p, thereby upregulating G3BP1 to mediate p53 ubiquitination, promoting OC platinum resistance. Psc@DPP effectively overcame platinum resistance in an OC tumour model and provided a novel idea for treating platinum-resistant OC using si-circNUP50. CONCLUSIONS: This study reveals a novel molecular mechanism by which circNUP50 mediates platinum resistance in OC by modulating p53 ubiquitination and provides new insights for developing effective therapeutic strategies for platinum resistance in OC.

The prognosis of patients with small cell carcinoma of the cervix: a retrospective study of the SEER database and a Chinese multicentre registry.

BACKGROUND: Small cell carcinoma of the cervix is a rare but poor prognosis pathological type of cervical cancer, for which advice in clinical guidelines is unspecific. We therefore aimed to investigate the factors and treatment methods that affect the prognosis of patients with small cell carcinoma of the cervix. METHODS: In this retrospective study, we collected data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries cohort and a Chinese multi-institutional registry. The SEER cohort included females diagnosed with small cell carcinoma of the cervix between Jan 1, 2000, and Dec 31, 2018, whereas the Chinese cohort included women diagnosed between Jun 1, 2006, and April 30, 2022. In both cohorts, eligibility was limited to female patients older than 20 years with a confirmed diagnosis of small cell carcinoma of the cervix. Participants who were lost to follow-up or those for whom small cell carcinoma of the cervix was not the primary malignant tumour were excluded from the multi-institutional registry, and those with an unknown surgery status (in addition to those for whom small cell carcinoma of the cervix was not the primary malignant tumour) were excluded from the SEER data. The primary outcome of this study was overall survival (length of time from the date of first diagnosis until the date of death from any cause, or the last follow-up). Kaplan-Meier analysis, propensity score matching, and Cox-regression analyses were used to assess treatment outcomes and risk factors. FINDINGS: 1288 participants were included in the study; 610 in the SEER cohort and 678 in the Chinese cohort. Both univariable and multivariable Cox regression analysis (SEER hazard ratio [HR] 0·65 [95% CI 0·48-0·88], p=0·0058; China HR 0·53 [0·37-0·76], p=0·0005) showed that surgery was associated with a better prognosis. In subgroup analyses, surgery remained a protective factor for patients with locally advanced disease in both cohorts (SEER HR 0·61 [95% CI 0·39-0·94], p=0·024; China HR 0·59 [0·37-0·95]; p=0·029). Furthermore, the protective effect of surgery was observed among patients with locally advanced disease after propensity score matching in the SEER cohort (HR 0·52 [95% CI 0·32-0·84]; p=0·0077). In the China registry, surgery was associated with better outcomes in patients with stage IB3-IIA2 cancer (HR 0·17 [95% CI 0·05-0·50]; p=0·0015). INTERPRETATION: This study provides evidence that surgery improves outcomes of patients with small cell carcinoma of the cervix. Although guidelines recommend non-surgical methods as first-line treatment, patients with locally advanced disease or stage IB3-IIA2 cancer might benefit from surgery. FUNDING: The National Key R&D Program of China and the National Natural Science Foundation of China.

Clinical analysis of 312 patients with stage IB1-IIA2 cervical squamous cell carcinoma and research on the influencing factors of postoperative recurrence.

OBJECTIVE: To investigate the influencing factors of the recurrence of IB1-IIA2 cervical squamous cell carcinoma after surgical treatment, and to explore the relationship between high-risk human papillomavirus (HR-HPV) infection and postoperative cervical squamous cell carcinoma recurrence. METHODS: Patients (n = 312) diagnosed with stage IB1-IIA2 cervical cancer and treated by radical hysterectomy and lymphadenectomy at this hospital were accrued between January 2014 and December 2016. The clinical data of these patients were analysed, and the association among clinicopathological factors, the association among clinicopathological factors, HPV infection and recurrences was investigated through Cox regression. RESULTS: The median follow-up time was 59.2 months (with a range of 14-77.9 months). The pre-operative HPV infection rate was 85.3% (266/312), and 74 patients had a high level of HPV-DNA (> 5 × 106 copy number / 104 cells). Twenty-nine patients had a postoperative persistent high level of HPV-DNA (9.3%). On multivariate analysis, deep 1/3 stromal invasion (hazard ratio [HR] 114.79, 95% confidence interval [CI] 2.821-4670.111, p = 0.012*) and postoperative persistence of high HPV-DNA levels within 12 months (HR 269.044, 95% CI 14.437-5013.754, p < 0.001*) and 24 months (HR 31.299, 95% CI 1.191-822.215, p = 0.039*) were associated with a higher local recurrence rate. CONCLUSION: Continuous high HPV-DNA levels within 24 months of an operation and deep 1/3 interstitial infiltration were independent risk factors for local recurrences of cervical cancer.

Upregulation of NOD1 and NOD2 contribute to cancer progression through the positive regulation of tumorigenicity and metastasis in human squamous cervical cancer.

BACKGROUND: Metastatic cervical squamous cell carcinoma (CSCC) has poor prognosis and is recalcitrant to the current treatment strategies, which warrants the necessity to identify novel prognostic markers and therapeutic targets. Given that CSCC is a virus-induced malignancy, we hypothesized that the pattern recognition receptors (PRRs) involved in the innate immune response likely play a critical role in tumor development. METHODS: A bioinformatics analysis, qPCR, IHC, immunofluorescence, and WB were performed to determine the expression of NOD1/NOD2. The biological characteristics of overexpression NOD1 or NOD2 CSCC cells were compared to parental cells: proliferation, migration/invasion and cytokines secretion were examined in vitro through CCK8/colony formation/cell cycle profiling/cell counting, wound healing/transwell, and ELISA assays, respectively. The proliferative and metastatic capacity of overexpression NOD1 or NOD2 CSCC cells were also evaluated in vivo. FCM, mRNA and protein arrays, ELISA, and WB were used to identify the mechanisms involved, while novel pharmacological treatment were evaluated in vitro and in vivo. Quantitative variables between two groups were compared by Student's t test (normal distribution) or Mann-Whitney U test (non-normal distribution), and one-way or two-way ANOVA was used for comparing multiple groups. Pearson χ2 test or Fisher's exact test was used to compare qualitative variables. Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. P values of < 0.05 were considered statistically significant. RESULTS: NOD1 was highly expressed in CSCC with lymph-vascular space invasion (LVSI, P < 0.01) and lymph node metastasis (LM, P < 0.01) and related to worse overall survival (OS, P = 0.016). In vitro and in vivo functional assays revealed that the upregulation of NOD1 or NOD2 in CSCC cells promoted proliferation, invasion, and migration. Mechanistically, NOD1 and NOD2 exerted their oncogenic effects by activating NF-κb and ERK signaling pathways and enhancing IL-8 secretion. Inhibition of the IL-8 receptor partially abrogated the effects of NOD1/2 on CSCC cells. CONCLUSIONS: NOD1/2-NF-κb/ERK and IL-8 axis may be involved in the progression of CSCC; the NOD1 significantly enhanced the progression of proliferation and metastasis, which leads to a poor prognosis. Anti-IL-8 was identified as a potential therapeutic target for patients with NOD1high tumor.

Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is an invasive gynaecologic cancer with a high cancer-related death rate. The purpose of this study was to establish an invasion-related multigene signature to predict the prognostic risk of OC. METHODS: We extracted 97 invasion-related genes from The Cancer Genome Atlas (TCGA) database. Then, the ConsensusClusterPlus and limma packages were used to calculate differentially expressed genes (DEGs). To calculate the immune scores of the molecular subtypes, we used ESTIMATE to evaluate the stromal score, immune score and ESTIMATE score. MCP-counter and the GSVA package ssgsea were used to evaluate the types of infiltrating immune cells. Survival and nomogram analyses were performed to explore the prognostic value of the signature. Finally, qPCR, immunohistochemistry staining and functional assays were used to evaluate the expression and biological abilities of the signature genes in OC. RESULTS: Based on the consistent clustering of invasion-related genes, cases in the OC datasets were divided into two subtypes. A significant difference was observed in prognosis between the two subtypes. Most genes were highly expressed in the C1 group. Based on the C1 group genes, we constructed an invasion-related 6-gene prognostic risk model. Furthermore, to verify the signature, we used the TCGA-test and GSE32062 and GSE17260 chip datasets for testing and finally obtained a good risk prediction effect in those datasets. Moreover, the results of the qPCR and immunohistochemistry staining assays revealed that KIF26B, VSIG4 and COL6A6 were upregulated and that FOXJ1, MXRA5 and CXCL9 were downregulated in OC tissues. The functional study showed that the expression of KIF26B, VSIG4, COL6A6, FOXJ1, MXRA5 and CXCL9 can regulate the migration and invasion abilities of OC cells. CONCLUSION: We developed a 6-gene prognostic stratification system (FOXJ1, MXRA5, KIF26B, VSIG4, CXCL9 and COL6A6) that is independent of clinical features. These results suggest that the signature could potentially be used to evaluate the prognostic risk of OC patients.

Diagnostic value of circN4BP2L2 in type I and type II epithelial ovarian cancer.

BACKGROUND: CircN4BP2L2 was previously identified to be significantly decreased in epithelial ovarian cancer (EOC) and was associated with disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 using the unifying model of type I and type II EOC. METHODS: A total of 540 plasma samples were obtained from 180 EOC patients, 180 benign ovarian cyst patients, and 180 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. RESULTS: Low level of circN4BP2L2 was associated with advanced tumor stage (p < 0.01) in type I EOC. Decreased circN4BP2L2 was associated with lymph node metastasis (LNM) (p = 0.04) in type II EOC. The expression level of circN4BP2L2 in type I was similar to that in type II. CircN4BP2L2 could significantly separate type I or type II from benign or normal cohort (p < 0.01). Early-stage type I or type II EOC vs. benign or normal cohort could also be distinguished by circN4BP2L2 (p < 0.01). CONCLUSION: CircN4BP2L2 might serve as a promising diagnostic biomarker for both type I and type II EOC. The diagnostic safety for circN4BP2L2 in early-stage type I or type II EOC is also acceptable. Further large-scale well-designed studies are warranted to investigate whether circN4BP2L2 is specific for all histologic subgroups.

Plasma circN4BP2L2 is a promising novel diagnostic biomarker for epithelial ovarian cancer.

BACKGROUND: Circular RNAs (circRNAs) are more stable than linear RNA molecules, which makes them promising diagnostic biomarkers for diseases. By circRNA-sequencing analysis, we previously found that circN4BP2L2 was significantly decreased in epithelial ovarian cancer (EOC) tissues, and was predictive of disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 in EOC. METHODS: Three hundred seventy-eight plasma samples were acquired prior to surgery. Samples were obtained from 126 EOC patients, 126 benign ovarian cyst patients, and 126 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). EOC cells were transfected with small interference RNAs (siRNAs) and cell proliferation, migration, invasion, cell cycle and cell apoptosis were performed to assess the effect of circN4BP2L2 in EOC. Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. RESULTS: Plasma circN4BP2L2 was significantly downregulated in EOC patients. Decreased circN4BP2L2 was significantly associated with advanced tumor stage, worse histological grade, lymph node metastasis and distant metastasis in EOC. CircN4BP2L2 inhibited tumor cell migration and invasion in vitro. CircN4BP2L2 could significantly separate EOC from benign (AUC = 0.82, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort. Early stage EOC vs benign (AUC = 0.81, P <  0.01) or normal (AUC = 0.90, P <  0.01) cohort could also be distinguished by circN4BP2L2. In discrimination between EOC cohort and benign or normal cohort, circN4BP2L2 performed equally well in both pre- and post-menopausal women. The combination of circN4BP2L2, CA125 and HE4 showed high sensitivity and specificity in detecting EOC cases. CONCLUSIONS: Plasma circN4BP2L2 is significantly downregulated in EOC and might serve as a promising novel diagnostic biomarker for EOC patients, especially in early stage EOC cases. CircN4BP2L2 might act as an adjunct to CA125 and HE4 in detecting EOC. Further large-scale studies are warranted to verify our results.

Concurrent definitive chemoradiation incorporating intensity-modulated radiotherapy followed by adjuvant chemotherapy in high risk locally advanced cervical squamous cancer: a phase II study.

BACKGROUND: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. OBJECTIVES: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. STUDY DESIGN: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0-65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). RESULTS: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3-4 leukopenia and thrombocytopenia, respectively. Grade 3-4 late toxicities were reported in 3 patients. CONCLUSIONS: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

Blood-based DNA methylation profiling for the detection of ovarian cancer.

OBJECTIVES: Ovarian cancer is a fatal gynecological cancer due to the lack of effective screening strategies at early stage. This study explored the utility of DNA methylation profiling of blood samples for the detection of ovarian cancer. METHODS: Targeted bisulfite sequencing was performed on tissue (n = 152) and blood samples (n = 373) obtained from healthy women, women with benign ovarian tumors, or malignant epithelial ovarian tumors. Based on the tissue-derived differentially-methylated regions, a supervised machine learning algorithm was implemented and cross-validated using the blood-derived DNA methylation profiles of the training cohort (n = 178) to predict and classify each blood sample as malignant or non-malignant. The model was further evaluated using an independent test cohort (n = 184). RESULTS: Comparison of the DNA methylation profiles of normal/benign and malignant tumor samples identified 1272 differentially-methylated regions, with 49.4% hypermethylated regions and 50.6% hypomethylated regions. Five-fold cross-validation of the model using the training dataset yielded an area under the curve of 0.94. Using the test dataset, the model accurately predicted non-malignancy in 96.2% of healthy women (n = 53) and 93.5% of women with benign tumors (n = 46). For patients with malignant tumors, the model accurately predicted malignancy in 44.4% of stage I-II (n = 9), 86.4% of stage III (n = 59), 100.0% of stage IV tumors (n = 6), and 81.8% of tumors with unknown stage (n = 11). Overall, the model yielded a predictive accuracy of 89.5%. CONCLUSIONS: Our study demonstrates the potential clinical application of blood-based DNA methylation profiling for the detection of ovarian cancer.

A feasibility study of a modified treatment strategy combined external beam radiation therapy and brachytherapy for cervical cancer.

PURPOSE: To evaluate the feasibility of a modified treatment strategy combined external beam radiation therapy (EBRT) and brachytherapy (BT) for cervical cancer through a dosimetry analysis. MATERIAL AND METHODS: This study retrospectively selected 12 cervical cancer patients treated with the conventional treatment strategy, which consisted of 45─50 Gy/25 fractions of EBRT using volumetric-modulated arc therapy (VMAT) and image-guided BT with a fraction dose of 5─7 Gy. The modified treatment strategy decreased the central EBRT dose while increasing the number of BT fractions. New target volumes were additionally contoured, and new VMAT EBRT plans were generated for the modified treatment strategy. The dosimetric parameters for evaluation included the doses to the most irradiated 2 cc (D2cc) of the organs at risk (OARs) and doses to at least 90% (D90) of the gross tumor volume (GTV) and high-risk clinical target volume (HR-CTV). The total doses to OARs and targets obtained by adding the equivalent doses in 2 Gy fraction (EQD2) from the EBRT and BT plans were used for quantitative comparison between the modified and conventional treatment strategies. RESULTS: Comparison to the conventional treatment strategy, the modified treatment strategy resulted in a higher bladder D2cc, a slightly lower rectal D2cc and a similar HR-CTV D90, all with no significant differences (p > 0.05). The GTV D90 of the modified treatment strategy was significantly higher than that of the conventional treatment strategy (p < 0.01). CONCLUSION: The modified treatment strategy can significantly increase the BT dose while remaining the total doses to the bladder and rectum basically unchanged, demonstrating its feasibility and promising prospect in clinical use.

Dietary addition of fermented sorghum distiller's dried grains with soluble improves carcass traits and meat quality in growing-finishing pigs.

The fermented sorghum distiller's dried grain with soluble (FS-DDGS) contains numerous nutrients, yet its nutritional effects on growing-finishing pigs remain unclear. The present study evaluated the effects of dietary FS-DDGS addition on growth performance, carcass traits, and meat quality in growing-finishing pigs. A total of 48 healthy male crossbred (Large White × Landrace × Duroc) barrows with initial body weight (BW) of 39.95 ± 2.15 kg were allocated to one of four dietary treatments (12 pigs per treatment). The dietary treatments were as follows: basal diet without (FS-DDGS0 group) or with 50 g/kg (FS-DDGS50 group), 100 g/kg (FS-DDGS100 group), or 150 g/kg (FS-DDGS150 group) FS-DDGS, respectively. Results showed that there were no significant differences in the final BW, average daily gain, average daily feed intake, and feed to gain ratio among these four groups. However, dietary FS-DDGS addition increased (linear, P < 0.05) the pH24h value, contents of ash, crude protein, and proline in Longissimus dorsi muscle, and alanine, arginine, aspartic acid, glutamic acid, isoleucine, leucine, lysine, serine, and tyrosine in Biceps femoris (BF) muscle, when compared with the control group. In addition, dietary FS-DDGS addition decreased (linear, P < 0.05) the drip loss, yellowness (b*) value, and lightness (L*) value, while quadratically improved (P < 0.05) the total bone percentage and glycine and proline contents in BF muscle compared with the control group. Collectively, these findings suggested that dietary FS-DDGS addition could improve the carcass traits and meat quality in growing-finishing pigs although further research is needed to explore the underlying mechanisms.

Identification and validation of a novel glycolysis-related gene signature for predicting the prognosis in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynaecological tumor. Changes in glycolysis have been proven to play an important role in OC progression. We aimed to identify a novel glycolysis-related gene signature to better predict the prognosis of patients with OC. METHODS: mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Genotype Tissue Expression (GTEx) database. The "limma" R package was used to identify glycolysis-related differentially expressed genes (DEGs). Then, a multivariate Cox proportional regression model and survival analysis were used to develop a glycolysis-related gene signature. Furthermore, the TCGA training set was divided into two internal test sets for validation, while the ICGC dataset was used as an external test set. A nomogram was constructed in the training set, and the relative proportions of 22 types of tumor-infiltrating immune cells were evaluated using the "CIBERSORT" R package. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined by single-sample gene set enrichment analysis (ssGSEA) with the "GSVA" R package. Finally, the expression and function of the unreported signature genes ISG20 and SEH1L were explored using immunohistochemistry, western blotting, qRT-PCR, proliferation, migration, invasion and xenograft tumor assays. RESULTS: A five-gene signature comprising ANGPTL4, PYGB, ISG20, SEH1L and IRS2 was constructed. This signature could predict prognosis independent of clinical factors. A nomogram incorporating the signature and three clinical features was constructed, and the calibration plot suggested that the nomogram could accurately predict the survival rate. According to ssGSEA, the signature was associated with KEGG pathways related to axon guidance, mTOR signalling, tight junctions, etc. The proportions of tumor-infiltrating immune cells differed significantly between the high-risk group and the low-risk group. The expression levels of ISG20 and SEH1L were lower in tumor tissues than in normal tissues. Overexpression of ISG20 or SEH1L suppressed the proliferation, migration and invasion of Caov3 cells in vitro and the growth of xenograft tumors in vivo. CONCLUSION: Five glycolysis-related genes were identified and incorporated into a novel risk signature that can effectively assess the prognosis and guide the treatment of OC patients.

Olaparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation: SOLO1 China cohort.

PURPOSE: Maintenance therapy with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib provided a substantial progression-free survival (PFS) benefit compared with placebo in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (BRCAm) who were in clinical complete or partial response following platinum-based chemotherapy in the Phase III SOLO1 global study. This led to the approval of maintenance olaparib in China, USA, EU, Japan and other countries, in the newly diagnosed setting. This separate China cohort of the SOLO1 study investigated the efficacy and safety of maintenance olaparib within the Chinese population. PATIENTS AND METHODS: In this double-blind, multicentre study, patients were randomized 2:1 to receive oral olaparib tablets (300 mg twice daily) or placebo. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). RESULTS: Of the 64 randomized patients, 44 received olaparib and 20 placebo. Olaparib reduced the risk of disease progression or death by 54% compared with placebo (HR 0.46, 95% Cl 0.23-0.97; median PFS was not reached in the olaparib arm vs 9.3 months in the placebo arm). The most common AEs in the olaparib arm were nausea (63.6 vs 25.0% with placebo), anaemia (59.1 vs 15.0%) and leukopenia (54.5 vs 20.0%). Grade ≥3 AEs were experienced by 56.8% of olaparib patients and 30.0% of placebo patients. CONCLUSIONS: Results in the SOLO1 China cohort support the use of olaparib as maintenance treatment for Chinese patients with newly diagnosed advanced ovarian cancer who have a BRCAm and are in complete or partial response after platinum-based chemotherapy.

Evaluation of the sexual quality of life and sexual function of cervical cancer survivors after cancer treatment: a retrospective trial.

OBJECTIVE: The purpose of this study was to explore the factors influencing the sexual quality of life of patients with cervical cancer who underwent radical hysterectomy. METHODS: This multicenter retrospective cohort study was conducted from June 2013 to June 2018 at nine hospitals in China. In total, 204 women diagnosed with stage IA to stage IIB cervical cancer who underwent radical hysterectomy completed the questionnaire. Sexual function was measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). All analyses were performed with R version 3.4.3 statistical software packages. A two-sided significance level of 0.05 was used to evaluate the statistical significance. RESULTS: The mean sexual quality of life score was 37.21 ± 17.28, where a higher PISQ score indicates a better sexual quality of life, and we identified the factors associated with sexual dysfunction. The average follow-up time was 29.0 ± 16.0 months. In addition to radical hysterectomy, 182 (89.2%) patients underwent ovarian suspension, 93 (45.6%) underwent chemotherapy, and 74 (36.3%) underwent concurrent radiotherapy. The univariate analysis confirmed that age represents a protective factor for sexual function (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.1-10.8, p = 0.017). The patients who underwent ovarian suspension were more likely to experience a good sexual quality of life (OR - 7.2, 95% CI [- 14.8, - 0.4], p = 0.035) compared to those who did not undergo ovarian suspension. A significant negative association was observed between radiotherapy and the behavioral-emotive, physical and partner-related domains of the PISQ (behavioral-emotive, OR - 1.5, 95% CI [- 2.6, - 0.4], p = 0.011; physical, OR - 0.9, 95% CI [- 1.5, - 0.3], p = 0.006; partner-related, OR - 0.7, 95% CI [- 1.3, 0.0], p = 0.043). Chemotherapy and radiotherapy were common risk factors for sexual dysfunction, and radiotherapy exerted a stronger effect than chemotherapy. CONCLUSIONS: This study shows that the sexual function of cervical cancer patients tends to be related to age, radiotherapy, and chemotherapy. However, across these factors, patients with preserved ovaries tend to return to a satisfactory sexual quality of life after recovering from surgery.

Long-term impact of lymphadenectomies in patients with low-grade, early-stage uterine endometrial stroma sarcoma.

AIM: The aim of our study was to investigate the lymph node metastasis (LNM) rate and effect of lymph node dissection (LND) in patients with stage I, low-grade endometrial stromal sarcoma (LGESS). METHODS: Patients with stage I LGESS (n = 119) that underwent surgery from July 1969 to July 2017, following up over 48 years at the China National Cancer Center were retrospectively analyzed in this study. RESULTS: Surgical records and consulting data for patients with LGESS were analyzed to find that 47 patients received systematic pelvic LND. The number of patients with menopause in the LND(+) group were significantly lower than those in LND(-) group (2.1% vs 22.2%, P = 0.005), meanwhile, patients received bilateral salpingo-oophorectomy procedure in LND(+) group were significantly higher than LND(-) (97.9% vs 58.3%, P < 0.001). Neither progression-free survival nor overall survival was significantly improved in the LND(+) group even after propensity score matching although the progression-free survival has a stronger trend in LND(+) population. CONCLUSION: A systematic LND was not significantly associated with prognosis for patients with early-stage LGESS. There is no sufficient indication for a systematic LND for patients with early-stage LGESS. A systematic LND might be necessary if enlarged lymph nodes were detected by image graphology or observation during surgery.

Nasogastric tube decompression is unnecessary in patients undergoing laparoscopic nephroureterectomy for localized upper tract urothelial carcinoma.

BACKGROUND/PURPOSE: This study investigates the safety and feasibility to perform laparoscopic nephroureterectomy (LNU) for upper tract urothelial carcinoma (UTUC) without routine nasogastric tube (NGT) decompression. METHODS: The hospital-based samples comprised of 100 consecutive UTUC patients receiving elective LNU performed by two experienced surgeons. The nationwide data was based on LHID2005 composed of one million beneficiaries randomly selected from the Taiwan National Health Insurance Research Database to identify patients with the diagnoses of UTUCs receiving LNUs. We then compared baseline characteristics, peri-operative data, convalescence parameters and complications between two groups stratified by use of NGT tube. RESULTS: The hospital-based samples composed of 50 subjects with NGT and 50 without. There were no significant differences in baseline characteristics between two groups. Peri-operative and convalescence parameters were similar when comparing no NGT versus NGT: blood loss of 206 vs. 165 mL; operative time of 180.5 vs.181.1 min; days to intake was 2.1 vs.1.7 days; and hospital stay of 7.8 vs. 7.5 days (all p > 0.05). The nationwide study samples comprised 140 subjects, of which 72 were with NGT and 68 were with no NGT. The baseline data, complications and length of hospital stay were similar between two groups. CONCLUSION: Surgery-naïve patients with localized UTUC received LNU without peri-operative NGT is safe and feasible.

Artemisia pollen allergy in China: Component-resolved diagnosis reveals allergic asthma patients have significant multiple allergen sensitization.

BACKGROUND: Artemisia pollen allergy is a major cause of asthma in Northern China. Possible associations between IgE responses to Artemisia allergen components and clinical phenotypes have not yet been evaluated. This study was to establish sensitization patterns of four Artemisia allergens and possible associations with demographic characteristics and clinical phenotypes in three areas of China. METHODS: Two hundred and forty patients allergic to Artemisia pollen were examined, 178 from Shanxi and 30 from Shandong Provinces in Northern China, and 32 from Yunnan Province in Southwestern China. Allergic asthma, rhinitis, conjunctivitis, and eczema symptoms were diagnosed. All patients' sera were tested by ImmunoCAP with mugwort pollen extract and the natural components nArt v 1, nArt ar 2, nArt v 3, and nArt an 7. RESULTS: The frequency of sensitization and the IgE levels of the four components in Artemisia allergic patients from Southwestern China were significantly lower than in those from the North. Art v 1 and Art an 7 were the most frequently recognized allergens (84% and 87%, respectively), followed by Art v 3 (66%) and Art ar 2 (48%). Patients from Northern China were more likely to have allergic asthma (50%) than patients from Southwestern China (3%), and being sensitized to more than two allergens increased the risk of allergic asthma, in which co-sensitization to three major allergens Art v 1, Art v 3, and Art an 7 is prominent. CONCLUSIONS: Component-resolved diagnosis of Chinese Artemisia pollen-allergic patients helps assess the potential risk of mugwort-associated allergic asthma.

2,4-Dinitrotoluene (DNT) Perturbs Yolk Absorption, Liver Development and Lipid Metabolism/Oxygen Transport Gene Expression in Zebrafish Embryos and Larvae.

2,4-dinitrotoluene (2,4-DNT) is a common environmental pollutant, and was classified as a group 2B human carcinogenic compound by the International Agency for Research on Cancer. This study determined the toxic effects of 2,4-DNT exposure on zebrafish at the embryo-larvae stage, in terms of organ morphogenesis and the expression pattern of selected target genes related to lipid metabolism and oxygen transportation. The results showed that the 120-h post-fertilization LC50 of 2,4-DNT was 9.59 mg/L with a 95% confidence interval of 8.89-10.44 mg/L. The larvae treated with 2,4-DNT showed toxic symptoms including smaller body, less skin pigment production, yolk malabsorption, and disordered liver development. Further studies on the expression of genes related to lipid transport and metabolism, and respiration indicated that they were significantly affected by 2,4-DNT. It is concluded that 2,4-DNT exposure perturbed liver development and yolk absorption in early-life zebrafish, and disturbed the lipid metabolism /oxygen transport gene expression.