Gastric cancer (GC), which is mainly induced by Helicobacter pylori (H. pylori) infection, is one of the leading causes of cancer-related death in the developing world. Active inflammation initiated by H. pylori infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative recurrence. However, the presence with H. pylori in tumors has been linked to a better prognosis, possibly due to the induction of antitumor immunity. Tumor infiltrations of tumor-associated macrophages, myeloid-derived suppressor cells, neutrophils, Foxp3(+) regulatory T cells are correlated with poor prognosis. Tumor infiltrating CD8(+) cytotoxic T lymphocytes, dendritic cells, and CD45RO T cells are generally associated with good prognosis of GC, although some subsets of these immune cells have inverse prognosis prediction values. High ratios of Foxp3(+)/CD4(+) and Foxp3(+)/CD8(+) in tumors are associated with a poor prognosis; whereas high Th1/Th2 ratio in tumors predicts a good prognosis. High levels of interleukin (IL)-6, IL-10, IL-32, and chemokine C-C motif ligands (CCL)7 and CCL21 in circulation, high expression of CXC chemokine receptor 4, chemokine C-C motif receptor (CCR)3, CCR4, CCR5, CCR7, hypoxia-inducible factor-1α, signal transducer activator of transcription-3, cyclooxygenase-2, and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable prognosis. Increased serum levels of matrix metalloproteinases (MMP)-3, MMP-7, and MMP-11 and increased levels of MMP-9, MMP-12, and MMP-21 in tumors are consistently associated with poor survival of GC. Further emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.

Objective: To assess the efficacy of metformin in megestrol acetate (MA)‐based fertility‐sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC).Design: A randomised, single‐centre, open‐label, controlled trial conducted between October 2013 and December 2017.Setting: Shanghai OBGYN Hospital of Fudan University, China.Population: A total of 150 patients (18–45 years old) with primary AEH or well‐differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76).Methods: Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).Main outcomes and measures: The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w‐CR rate); the secondary efficacy parameters were 30w‐CR rate and adverse events.Results: The 16w‐CR rate was higher in the metformin plus MA group than in the MA‐only group (34.3 versus 20.7%, odds ratio [OR] 2.0, 95% confidence interval [CI] 0.89–4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06–6.21, P = 0.04). This effect of metformin was also significant in non‐obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22–8.84, P = 0.02) and insulin‐sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03–8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints.Conclusion: As a fertility‐sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients.Tweetable For AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve a higher early CR rate compared with MA alone.

Ovarian cancer is a lethal gynecologic tumor and is generally resistant to conventional treatments. Stable cancer-associated fibroblasts (CAFs) are important cellular components in the ovarian cancer tumor microenvironment and may provide novel resources for future treatment strategies. Different subtypes of CAFs display specific functions in tumor pathogenesis and various CAF markers suggest potential treatment targets, such as FAP and GPR77. Both autocrine and paracrine cytokines play important roles in the CAF activation process and regulate tumor progression. Downstream mediators and pathways, including IL-6, TGF-β, NF-κB, mitogen-activated protein kinase (MAPK), and AKT/mTOR/(p70S6K), play important roles in the initiation, proliferation, invasiveness, and metastasis of ovarian cancer cells and also participate in angiogenesis, therapeutic resistance, and other biological processes. Several clinical or preclinical trials have targeted stromal fibroblasts and focused on the properties of CAFs to enhance ovarian cancer treatment outcomes. This review concentrates on the origins, subtypes, and activation of CAFs, as well as specific roles of CAFs in regulating tumor development and drug resistance, and aims to provide potential and prospective targets for improving the therapeutic efficacy of ovarian cancer treatment.

Although the cross-sectional relationship of arterial stiffness with cerebral small vessel disease is consistently shown in middle-aged and young-old adults, it is less clear whether these associations remain significant over time in very old adults. We hypothesize that arterial stiffness is longitudinally associated with white matter characteristics, and associations are stronger within watershed areas. Neuroimaging was obtained in 2006–2008 from 303 elderly (mean age 82.9 years, 59% women, 41% black) with pulse wave velocity (PWV) measures in 1997–1998. Multivariable regression models estimated the coefficients for PWV (cm/sec) in relationship to presence, severity, and spatial distribution of white matter hyperintensities (WMH), gray matter volume, and fractional anisotropy from diffusion tensor, adjusting for demographic, cardiovascular risk factors, and diseases from 1997–1998 to 2006–2008. Higher PWV in 1997–1998 was associated with greater WMH volume in 2006–2008 within the left superior longitudinal fasciculus (age and total brain WMH adjusted, P =0.023), but not with WMH in other tracts or with fractional anisotropy or gray matter volume from total brain ( P >0.2). Associations were stronger in blacks than in whites, remaining significant in fully adjusted models. Elderly with WMH in tracts related to processing speed and memory are more likely to have had higher PWV values 10 years prior, before neuroimaging data being available. Future studies should address whether arterial stiffness can serve as an early biomarker of covert brain structural abnormalities and whether early arterial stiffness control can promote successful brain aging, especially in black elderly.