A Scoring System to Select the Candidates for Adjuvant Chemotherapy Alone in High-Risk Early-Stage Cervical Cancer Patients With Pelvic Lymph Node Metastases After Surgery.

BACKGROUND: The aim was to build a risk scoring system to guide the adjuvant treatment for early-stage cervical cancer patients with pelvic lymph node (LN) metastases after surgery. METHODS: A cohort of 1213 early-stage cervical cancer patients with pelvic LN metastases (T1-2aN1M0) were selected from the NCI SEER database, of which 1040 patients received adjuvant external beam radiotherapy concurrent with chemotherapy (EBRT+Chemo) and 173 patients received adjuvant chemotherapy alone. The Cox regression analysis was applied to identify the risk factors associated with worse survival. The exp (ß) of each independent risk factors from multivariate analysis was assigned to develop the risk scoring system. The total cohort was divided into different risk subgroups accordingly and the efficacy of different adjuvant modalities in each risk subgroups was compared. RESULTS: The patients were divided into 3 risk subgroups (Low-risk: total score <7.20, Middle-risk:7.20≤ total score≤ 8.40, High-risk: total score<8.40) based on the scoring system incorporating 5 independent risk factors. The survival analysis suggested that low-risk (hazard ratio [HR]=1.046, 95% CI: 0.586-1.867; P= 0.879) and middle-risk patients (HR=0.709, 95% CI: 0.459-1.096; P =0.122) could not benefit more from EBRT+Chemo than Chemo alone. However, EBRT+Chemo remained the superiority to Chemo alone in the high-risk subgroup (HR=0.482, 95% CI: 0.294-0.791; P =0.003). CONCLUSION: A risk scoring system has been built to direct the adjuvant treatment for early-stage cervical cancer patients with pelvic LN metastases after surgery, where Chemo alone was totally enough for low-risk and middle-risk patients stratified by the model while EBRT+Chemo was still recommended for patients in the high-risk subgroup.

A population-based risk scoring system to individualize adjuvant treatment for stage IIIC endometrial cancer patients after surgery.

BACKGROUND: To develop a risk scoring system to tailor the adjuvant treatment for stage IIIC EC patients after surgery. METHODS: Data source was from the Surveillance, Epidemiology, and End Results (SEER) registry, where 3251 post-operative stage IIIC EC patients with different adjuvant treatment were included. Cox regression analysis was used to identify risk factors. The exp (ß) of each independent risk factors generating from the cox analysis was used to construct the risk scoring system, which was further utilized to divide the patients into different risk subgroups and the efficacy of different adjuvant modalities in each risk subgroups would be compared accordingly. RESULTS: Six independent risk factors were identified to develop the scoring system, which further divided the patients into three risk subgroups based on the total risk score (Low-risk≤8.46, 8.47 ≤ Middle-risk≤9.94, High-risk≥9.95). This study revealed that CRT was not superior to RT alone (HR:1.208, 95%CI: 0.852-1.741; P = 0.289) or CT alone (HR:1.260, 95%CI: 0.750-2.116; P = 0.382) in Low-risk subgroup. We also observed that CRT had a survival advantage over other treatment modalities in the Middle-risk subgroup (All P < 0.001), but CRT and CT alone to be superimposable in the High-risk subgroup (HR: 1.395, 95%CI: 0.878-2.216; P = 0.159). CONCLUSION: A risk scoring system has been developed to tailor the adjuvant treatment for stage IIIC EC patients after surgery, where RT or CT alone could be a substitute for CRT in Low-risk patients and CT alone was a potential alternative for High-risk patients while CRT remained to be the optimal choice for the Middle-risk patients.

Prognostic model for the exemption of adjuvant chemotherapy in stage IIIC endometrial cancer patients.

Background: This study aimed to develop a nomogram to predict the survival for stage IIIC endometrial cancer (EC) patients with adjuvant radiotherapy (ART) alone and personalize recommendations for the following adjuvant chemotherapy (ACT). Methods: In total, 746 stage IIIC EC patients with ART alone were selected from the Surveillance, Epidemiology, and End Results (SEER) registry. Cox regression analysis was performed to identify independent risk factors. A nomogram was developed accordingly, and the area under the receiver operating characteristic curve (AUC) and C-index were implemented to assess the predictive power. The patients were divided into different risk strata based on the total points derived from the nomogram, and survival probability was compared between each risk stratus and another SEER-based cohort of stage IIIC EC patients receiving ART+ACT (cohort ART+ACT). Results: Five independent predictors were included in the model, which had favorable discriminative power both in the training (C-index: 0.732; 95% CI: 0.704-0.760) and validation cohorts (C-index: 0.731; 95% CI: 0.709-0.753). The patients were divided into three risk strata (low risk <135, 135 ≤ middle risk ≤205, and high risk >205), where low-risk patients had survival advantages over patients from cohort ART+ACT (HR: 0.45, 95% CI: 0.33-0.61, P < 0.001). However, the middle- and high-risk patients were inferior to patients from cohort ART+ACT in survival (P < 0.001). Conclusion: A nomogram was developed to exclusively predict the survival for stage IIIC EC patients with ART alone, based on which the low-risk patients might be perfect candidates to omit the following ACT. However, the middle- and high-risk patients would benefit from the following ACT.

Construction and validation of a prognostic model for stage IIIC endometrial cancer patients after surgery.

BACKGROUND: To explore the most predictive lymph node (LN) scheme for stage IIIC endometrial cancer (EC) patients after hysterectomy and develop a scheme-based nomogram. METHODS: Data from 2626 stage IIIC EC patients, diagnosed between 2010 and 2014, were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry. The predictive ability of four LN schemes was assessed using C-index and Akaike information criterion (AIC). A nomogram based on the most predictive LN scheme was constructed and validated. The comparison of the predictive ability between nomogram and FIGO stage was conducted using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: FIGO stage (stage IIIC1/stage IIIC2) was not an independent risk factor for OS in stage IIIC EC patients (P = 0.672) and log odds of positive lymph nodes (LODDS) had the best predictive ability (C-index: 0.742; AIC: 8228.95). A nomogram based on LODDS was constructed and validated, which had a decent C-index of 0.742 (0.723-0.762). The nomogram showed a better predictive ability than that of the FIGO staging system. CONCLUSION: FIGO IIIC1/FIGO IIIC2 could not differentiate the prognosis for stage IIIC EC patients. We developed and validated a nomogram based on LODDS to predict OS for post-operative patients with stage IIIC EC.

A real-world, population-based study of the trends for incidence and prognosis in high-grade neuroendocrine tumor of cervix.

To explore the incidence and prognosis trends for high-grade cervical neuroendocrine tumor (HGCNET) and construct a nomogram to predict prognosis for HGCNET. Annual age-adjusted incidence of HGCNET from 1975 to 2015 was retrieved from the Surveillance, Epidemiology, and End Results program, the linear regression, poisson regression and annual percentage changes were used to assess the incidence trend. Also, trends for relative survival (RS) and overall survival (OS) in HGCNET patients from 1975 to 2015 were evaluated. From 1988 to 1975, 514 HGCNET patients were selected and divided into two cohorts with a ratio of 7:3. Nomogram to predict OS for these patients was constructed and validated. The incidence trend for HGCNET was unchanged in the past four decades (P = 0.734), but the proportion of HGCNET in diagnosed cervical cancer slightly increased from 0.9% in 1975 to 1.9% in 2015 (P < 0.001). The 5-year RS and OS for HGCNET in the study periods decreased steadily (RS: P = 0.009; OS: P = 0.008). Nomogram incorporating age, T stage, lymph-node positive, distant metastasis and surgery was constructed. The C-index of the nomogram was 0.716 (0.680-0.752), which was higher than the FIGO staging system. The incidence of HGCNET remained unchanged in the past four decades but the proportion of HGCNET has slightly increased. Besides, a steadily decreasing survival for HGCNET was observed in the study periods. A nomogram was constructed to better predict prognosis for HGCNET.

Anti-Diabetic and Anti-Nephritic Activities of Grifola frondosa Mycelium Polysaccharides in Diet-Streptozotocin-Induced Diabetic Rats Via Modulation on Oxidative Stress.

Grifola frondosa is an edible fungus with a variety of potential pharmacological activities. This study investigates the hypoglycemic, anti-diabetic nephritic, and antioxidant properties of G. frondosa polysaccharides in diet-streptozotocin-induced diabetic rats. After a 4-week treatment with 100 mg/kg of metformin and 200 mg/kg of one of four different G. frondosa polysaccharide mixtures (especially GFPS3 and GFPS4), diabetic rats had enhanced body weight and suppressed plasma glucose, indicating the hypoglycemic activities of the G. frondosa polysaccharides. G. frondosa polysaccharides regulated the level of serum creatinine, blood urea nitrogen, N-acetyl-ß-D-glucosaminidase, and albuminuria; inhibited the serum levels of interleukin (IL)-2, IL-6, and TNF-α; and enhanced the serum levels of matrix metalloproteinase 9 and interferon-α, confirming their anti-diabetic nephritic activities. G. frondosa polysaccharides ameliorated the pathological alterations in the kidneys of diabetic rats. Moreover, G. frondosa polysaccharides modulated the serum levels of oxidant factors such as superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, and reactive oxygen species, revealing their antioxidant properties. Furthermore, the administration of G. frondosa polysaccharides inhibited nuclear factor kappa B activities in the serum and kidneys. All of the data revealed that the activation of nuclear factor kappa B plays a central role in G. frondosa polysaccharide-mediated anti-diabetic and anti-nephritic activities.

Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis.

Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an L­glutamic acid (L­Glu)­damaged HT22 cell apoptosis model and an aluminum chloride plus D­galactose­induced AD mouse model. In L­Glu­damaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase­3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase­3 activity assay kit, and propidium iodide and Annexin V staining. Furthermore, SC suppressed the accumulation of intracellular reactive oxygen species (ROS), restored the dissipation of mitochondrial membrane potential, enhanced the expression of antiapoptotic proteins and reduced the expression of pro­apoptotic proteins, as determined by immunofluorescence assays and western blotting. In AD mice, SC enhanced vertical and horizontal movements in an autonomic activity test, and reduced the escape latency time in the water maze test. SC reduced the deposition of amyloid ß1­42 (Aß1­42) and the expression of phosphorylated­Tau in the hippocampus as determined by immunohistochemistry analysis, but enhanced the serum levels of Aß1­42 of AD mice as determined by ELISA. ELISA analyses also revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of AD mice. The present study confirmed that the protective effects of SC in AD in vitro and in vivo are associated with its antioxidant and antiapoptotic properties.

The anti-fatigue activities of Tuber melanosporum in a mouse model.

Tuber melanosporum (TM) is an edible fungus that exhibits antioxidant and anti-tumor activity via its unique bioactive metabolites. The present study analyzed the anti-fatigue effects of TM using a BALB/c mouse model. The anti-fatigue properties of TM were evaluated by assessing the endurance of mice by performing forced swimming, rotary rod and running tests. Following 2 weeks TM treatment, hepatic and muscular ATP, and glycogen levels were increased in mice subjected to 30 min swimming, compared with controls. Similarly, levels of serum lactic acid and lactic dehydrogenase were decreased in the same group, compared with the control. Additionally, TM treatment reduced reactive oxygen species and malondialdehyde levels, and increased superoxide dismutase and glutathione peroxidase levels in the muscle, liver and/or serum. The effect of TM on hormone levels was also investigated in the present study, as different efficacies of TM were observed in male and female mice. TM treatment increased serum levels of progesterone, estradiol and testosterone in female and male mice, whereas a decrease in serum luteinizing hormone levels was only observed in females. A decrease in serum follicle-stimulating hormone levels was identified in females, whereas an increase was observed in males. The current study demonstrated that the anti-fatigue effects of TM occur via the regulation of oxidative stress, energy metabolism and hormone levels.

Polysaccharide purified from Lycium barbarum protects differentiated PC12 cells against L­Glu­induced toxicity via the mitochondria­associated pathway.

The present study successfully demonstrated the neuroprotective effects of purified Lycium barbarum polysaccharide (LBPS02) against glutamate (L­Glu)­induced differentiated PC12 (DPC12) cell apoptosis. Purified polysaccharide was obtained by using a diethylaminoethyl­52 cellulose anion exchange column and a Sepharose G­100 column. During identification and characterization, LBPS02 was validated to be a fraction with 68 kDa molecular weight, and with a structure containing 1→3, 1→4 and 1→6 linkages. Data further revealed that LBPS02 pretreatment effectively improved cell viability, reduced apoptosis rate, and restored the mitochondrial dysfunction in L­Glu­exposed cells. LBPS02 suppressed L­Glu­induced reactive oxygen species (ROS accumulation in DPC12 cells. N­acetylcysteine, a ROS inhibitor, strongly enhanced the efficacy of LBPS02. Furthermore, LBPS02 normalized the levels of anti­apoptotic proteins, and regulated the phosphorylation of extracellular signal­regulated kinases (ERKs) and protein kinase B (Akt) in L­Glu­explored DPC12 cells. In conclusion, LBPS02­mediated neuroprotective effects are at least partially associated with the modulation of Akt and ERKs, and the subsequent inhibition of the mitochondrial apoptotic pathway. LBPS02 may be a candidate for neurodegenerative disease treatment.

The Hypoglycemic, Hypolipidemic, and Anti-Diabetic Nephritic Activities of Zeaxanthin in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats.

Zeaxanthin (ZA), an important compound found in Lycium barbarum, shows various pharmacodynamic effects. In our present study, a high-fat, high-sucrose diet and streptozotocin (STZ)-induced diabetic rat model was used to investigate the antidiabetic activities of ZA. After a 4-week administration of 200 and 400 mg/kg of ZA and 100 mg/kg of metformin hydrochloride, various blood biochemical indexes were detected. ZA strongly normalized the reduced bodyweight and enhanced fasting blood glucose in diabetic rats. The positive data obtained from the oral glucose tolerance test further confirmed its antidiabetic effects. ZA displayed significant hypolipidemic activities indicated by its modulation of serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. The antidiabetic nephropathy of ZA was confirmed by its regulation of pathological kidney structures, urine levels of n-acetyl-ß-d-glucosaminidase and albuminuria, and serum levels of urea nitrogen. ZA inhibited the serum levels of inflammatory factors including interleukin-2 (IL-2), IL-6, tumor necrosis factor-α, and nuclear factor kappa B, further confirming its renal protection. Moreover, the serum imbalances in superoxide dismutase, glutathione peroxidase, methane dicarboxylic aldehyde, and catalase were normalized by ZA, suggesting its antioxidant properties. Altogether, ZA produced hypoglycemic, hypolipidemic, and antidiabetic nephritic effects in a diet-STZ-induced diabetic rat model.

Lycium barbarum Polysaccharide Mediated the Antidiabetic and Antinephritic Effects in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats via Regulation of NF-κB.

Lycium barbarum, extensively utilized as a medicinal plant in China for years, exhibits antitumor, immunoregulative, hepatoprotective, and neuroprotective properties. The present study aims to investigate the hyperglycemic and antidiabetic nephritic effects of polysaccharide which is separated from Lycium barbarum (LBPS) in high-fat diet-streptozotocin- (STZ-) induced rat models. The reduced bodyweight and enhanced blood glucose concentration in serum were observed in diabetic rats, and they were significantly normalized to the healthy level by 100 mg/kg of metformin (Met) and LBPS at doses of 100, 250, and 500 mg/kg. LBPS inhibited albuminuria and blood urea nitrogen concentration and serum levels of inflammatory factors including IL-2, IL-6, TNF-α, IFN-α, MCP-1, and ICAM-1 compared with diabetic rats, and it indicates the protection on renal damage. Furthermore, the activities of SOD and GSH-Px in serum were enhanced strikingly by LBPS which suggests its antioxidation effects. LBPS, compared with nontreated diabetic rats, inhibited the expression of phosphor-nuclear factors kappa B (NF-κB) and inhibitor kappa B alpha in kidney tissues. Collectively, LBPS possesses antidiabetic and antinephritic effects related to NF-κB-mediated antioxidant and antiinflammatory activities.

Water-soluble chitosan regulates vascular remodeling in hypertension via NFATc1.

OBJECTIVE: Hypertension is a public health problem in the world, and the disability and mortality rate is extremely high. Its important pathology foundation is vascular remodeling. Water-soluble chitosan (WSC) is the degradation product of chitosan, and have a role to control hypertension. The present study aims to investigate the regulatory effects of WSC on vascular remodeling in hypertension, and further to confirm the roles of nuclear factor c1 of activatied T cells (NFATc1) during this effect. METHODS: Primary cultured rat abdominal aortic smooth muscle cells were incubated with PBS, AngII, and AngІІ + WSC (0.1 mg/L) for 24 h. MTT and western blot methods were applied to analyzed the cell proliferation and c-myc protein expression, respectively, among all experimental groups. Successfully established spontaneously hypertensive Wistar-kyoto rats (SHR) were divided into two groups randomly: SHR group (n = 30) and SHR + WSC group (n = 30,WSC150 mg/kg/d). Another 15 Wistar-kyoto rats treated with PBS were served as control group. At the end of the experiments, the hemodynamic changes were analyzed using rat tail arterial pressure measuring instrument. H&E staining was performed to observe the morphological changes of abdominal aorta. Furthermore, immunohistochemical method, western blot and real-time quantitative PCR were applied to detected the expression of NAFTc1 protein and mRNA. RESULTS: WSC significantly reduced the cell viability in primary cultured rat abdominal aortic smooth muscle cells compare with PBS and AngІІ-treated cells. Compared with PBS group, the enhanced expression level of c-myc protein was observed in AngІІ-treated cells, which was significantly blocked by WSC incubation. Compared with control rats, the abnormally high blood pressure and membrane thickness/lumen diameter ratio of abdominal aorta were noted in SHR model rats, which strongly reduced after WSC administration. Hypertension resulted in an increment on expression of both NFATc1 protein and mRNA in abdominal aorta of Wistar-kyoto rats compared with control groups. Encouragingly, WSC strikingly suppressed the high levels of NFATc1 protein and even mRNA. CONCLUSION: In both cell and animal experiments, we succefully confirmed the regulatory effects of WSC on vascular remodeling in hypertension. Based on the present results, WSC-inhibited vascular remodeling may be related to the modulation on NFATc1 expression. Our experiment provides a solid basis for the clinical application of WSC on hypertension.