Jinyu Huang

Comparison Different Methods of Intraoperative and Intraperitoneal Chemotherapy for Patients with Gastric Cancer: A Meta-analysis

PURPOSE To investigate the efficacy and safety of intraperitoneal chemotherapy (IPC) for patients with gastric cancer and to compare effects between different regimens of IPC. METHOD Randomized controlled trials comparing the effects of surgery plus intraperitoneal chemotherapy with surgery alone or comparing the efficacy between different regimens of intraperitoneal chemotherapy were searched for in Medline, Embase, Pubmed, the Cochrane Library and the Chinese BioMedical Disc and so on by two independent reviewers. After quality assessment and data extraction, data were pooled for meta-analysis using RevMan5.16 software. Tests of interaction were used to test for differences of effects among subgroups grouped according to different IPC regimens. RESULTS Fifteen RCTs with a total of 1713 patients with gastric cancer were included for quality assessment and data extraction. Ten studies were judged to be of fair quality and entered into meta-analysis. Hyperthermic intraoperative intraperitoneal chemotherapy (HR=0.60, P<0.01), hyperthermic intraoperative intraperitoneal chemotherapy plus postoperative intraperitoneal chemotherapy (HR=0.47, P<0.01) and normothermic intraoperative intraperitoneal chemotherapy (HR=0.70, P=0.01) were associated with a significant improvement in overall survival. Tests of interaction showed that hyperthermia and additional postoperative intraperitoneal chemotherapy did not impact on its effect. Further analysis revealed that intraperitoneal chemotherapy remarkably decrease the rate of postoperative hepatic metastasis by 73% (OR=0.27, 95% CI=0.12 to 0.67, P<0.01). However, intraperitoneal chemotherapy increased risks of marrow depression (OR=5.74, P<0.01), fever (OR=3.67, P=0.02) and intra-abdominal abscess (OR=3.57, P<0.01). CONCLUSION The present meta-analysis demonstrates that hyperthermic intraoperative intraperitoneal chemotherapy and normothermic intraoperative intraperitoneal chemotherapy should be recommended to treat patients with gastric cancer because of improvement in overall survival. However, it is noteworthy that intraperitoneal chemotherapy can increase the risks of marrow depression, intra-abdominal abscesses, and fever.

Low junctional adhesion molecule A expression correlates with poor prognosis in gastric cancer

BACKGROUND The aberrant expression of junctional adhesion molecule A (JAM-A), which has a close correlation with the development, progression, metastasis, and prognosis of cancer, has been frequently reported. However, neither JAM-A expression nor its correlation with clinicopathologic variables and patient survival has been defined in gastric cancers. Moreover, little is known about the role of JAM-A in gastric cancer progression. We carried out the present study to investigate the prognostic value of JAM-A expression in gastric cancer patients. Furthermore, the biological roles of JAM-A in gastric cancer progression were also investigated. METHODS We determined JAM-A expression in 167 primary gastric cancer tissues and 94 matched adjacent non-tumor tissues by immunohistochemistry. Transwell migration assays and matrigel invasion assays were used to explore the role of JAM-A in gastric cancer cells migration and invasion. CCK-8 assays were used to examine the effect of JAM-A on the proliferation of gastric cancer cells. RESULTS JAM-A was downregulated in gastric cancer tissues. Low JAM-A expression was significantly associated with tumor size, lymphatic vessel invasion, lymph node metastasis, and TNM stage. Low JAM-A expression was also significantly associated with poor disease-specific survival in gastric cancer patients. Multivariate analysis demonstrated low JAM-A expression as an independent factor predicting poor survival. In addition, JAM-A had the effect on inhibition of gastric cancer cells migration and invasion. However, JAM-A had no significant effects on proliferation of gastric cancer cells. CONCLUSIONS Low JAM-A expression correlates with poor clinical outcome and promotes cell migration and invasion in gastric cancer.

The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis

Objective Comprehensive studies have investigated the prognostic and clinicopathological value of tumor-associated macrophages (TAMs) in gastric cancer patients, yet results remain controversial. Therefore, we performed a meta-analysis to clarify this issue. Methods PubMed, Embase, and the Cochrane Library databases were searched to identify eligible studies. We extracted hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) to estimate the effect sizes. In addition, subgroup analysis and sensitivity analysis were also conducted. Results A total of 19 studies involving 2242 patients were included. High generalised TAMs density was significantly associated with poor overall survival (OS) (HR 1.49, 95% CI 1.15–1.95). Subgroup analysis revealed that CD68+ TAMs had no significant effect on OS (HR 1.38, 95% CI 1.00–1.91). High M1 TAMs density was correlated with better OS (HR 0.45, 95% CI 0.32–0.65). By contrast, high density of M2 TAMs was correlated with a poor prognosis for OS (HR 1.48, 95% CI 1.25–1.75). Furthermore, high M2 TAMs density was correlated with larger tumor size, diffuse Lauren type, poor histologic differentiation, deeper tumor invasion, lymph node metastasis, and advanced TNM stage. Conclusions Overall, this meta-analysis reveal that although CD68+ TAMs infiltration has the neutral prognostic effects on OS, the M1/M2 polarization of TAMs are predicative factor of prognosis in gastric cancer patients.

The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature

BackgroundHuman epidermal growth factor receptor-2 (HER2) is regarded as an important and promising target in the treatment of HER2-positive breast cancers. However, the correlation of clinicopathological characteristics and prognostic significance of HER2 overexpression in gastric cancer patients remains unclear. Our aim was to clarify this issue.MethodsEmbase, PubMed, and the Cochrane Library were searched for relevant articles published up to May 2016. Outcomes of interest contained sex, age, tumor size, tumor site, tumor node metastasis (TNM) stage, distant metastasis, lymph node metastasis, Lauren’s classification, differentiation grade, lymphovascular invasion, neural invasion, and multivariate analysis data for overall survival.ResultsA total of 41 studies of 17,494 gastric cancer patients were identified with HER2 test. HER2 positive rate was 19.07% (95% CI = 9.16, 28.98). There existed statistical significance between HER2 overexpression and patients’ prognosis (RR = 1.47, 95% CI = 1.09, 1.98). Male patients (OR = 1.48, 95% CI = 1.34, 1.65), proximal tumors (OR = 1.25, 95% CI = 1.07, 1.47), intestinal-type tumors (OR = 3.37, 95% CI = 2.54, 4.47), advanced stage cancers (OR = 1.35, 95% CI = 1.10, 1.66), lymph node metastasis (OR = 1.26, 95% CI = 1.14, 1.41), well-differentiated cancers (OR = 1.79, 95% CI = 1.15, 2.76), and distant metastasis (OR = 1.91, 95% CI = 1.08, 3.38) were correlated with higher HER2 expression rates. However, no statistical differences existed in age, tumor size, lymphovascular invasion, or neural invasion. Subgroup analysis revealed that HER2 expression rates reported in articles from Asian (19.52%) countries were quantitatively higher than those from European (16.91%) areas. Results were consistent with those reports that define HER2 status according to trastuzumab for gastric cancer (ToGA) criteria.ConclusionThis study showed that HER2 overexpression was associated with poor prognosis in gastric cancer patients. HER2 positive rates may be associated with sex, tumor site, TNM staging system, distant metastasis, lymph node metastasis, Lauren’s classification, and differentiation grade in gastric cancer patients. The HER2 expression rate in Asians may be higher than that in Europeans. This study offers a convenient way for doctors to select patients for relevant HER2 detection and following treatment.

Borrmann type IV gastric cancer should be classified as pT4b disease

BACKGROUND The impact of macroscopic pathologic features of primary tumor that could be obtained preoperatively on pT classification has not been reported so far. The aim of this study was to investigate the feasibility of incorporation of Borrmann type IV gastric cancer into the pT classification. MATERIALS AND METHODS Clinicopathologic and prognostic data of 1622 patients with advanced gastric cancer who underwent radical surgery were retrospectively studied. RESULTS Of 1622 patients, 135 (8.32%) patients were classified as having Borrmann type IV gastric cancer. We first confirmed that Borrmann type IV gastric cancer was one of the independent prognostic factors for patients with advanced gastric cancer who underwent radical surgery. Interestingly, we found that overall survival of patients with Borrmann type IV gastric cancer could be clearly distinguished by pN classification and pathological TNM stage but not by pT classification. Importantly, further analysis demonstrated that the prognosis of Borrmann type IV gastric cancers was homogeneous with that of pT4b cancers but poorer than pT2, pT3, pT4a cancers. Therefore, we proposed a novel pT classification in which pT4b disease was defined as cancers that were Borrmann type IV or those that had invaded adjacent structures. Two-step multivariate analysis demonstrated that the novel pT classification was more suitable for prognostic assessment than the original classification. CONCLUSIONS Classifying Borrmann type IV gastric cancer as pT4b disease improves pT classification prediction of prognosis in patients with advanced gastric cancer after radical surgery.

Lung cancer cells induce senescence and apoptosis of pleural mesothelial cells via transforming growth factor-beta1.

Pleural dissemination is commonly associated with metastatic advanced lung cancer. The injury of pleural mesothelial cells (PMCs) by soluble factors, such as transforming growth factor-beta1 (TGF-β1), is a major driver of lung cancer pleural dissemination (LCPD). In this study, we examine the effects of TGF-β1 on PMC injury and the ability of TGF-β1 inhibition to alleviate this effect both in vitro and in vivo. PMCs were co-cultured with the high TGF-β1-expressing lung cancer cell line A549 and with various TGF-β1 signaling inhibitors. Expression of cleaved-caspase 3, cleaved-caspase 9, p21, and p16 were evaluated by Western blot and immunofluorescent confocal imaging. Apoptosis was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltrazoliumbromide assay and AnnexinV-propidium iodide (PI) staining. PMC senescence was assessed by staining for senescence-associated β-galactosidase (SA-β-Gal). The ability of lung cancer cells (LCCs) to adhere to injured PMCs was investigated using an LCC-PMC adhesion assay. In our mouse model, PMC injury status was monitored by hematoxylin–eosin (H&E) and Masson’s trichrome staining. LCCs expressing high levels of TGF-β1 induce apoptosis and senescence of PMCs in a co-culture system. Injured PMCs adhere to LCCs, which may further promote LCPD. Importantly, PMC monolayer injury could be reversed with TGF-β1 inhibitors. This was consistent with our in vivo data showing that the TGF-β1 inhibitor SB-431542 attenuated PMC barrier injury induced by A549 culture medium in our mouse model. Our study highlights the importance of TGF-β1 signaling in LCPD and establishes this signaling pathway as a potential therapeutic target in the disease.

Effect of neoadjuvant chemotherapy in patients with gastric cancer: a PRISMA-compliant systematic review and meta-analysis

BackgroundNeoadjuvant chemotherapy (NAC) is extensively used in the treatment of patients with gastric cancer (GC), particularly in high risk, advanced gastric cancer. Previous trials testing the efficacy of NAC have reported inconsistent results.MethodsThis study compares the combined use of NAC and surgery with surgery alone for GC by using a meta-analytic approach. We performed an electronic search of PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials (RCTs) on NAC published before Oct 2015. The primary outcome of the studies was data on survival rates for patients with GC. The summary results were pooled using the random-effects model. We included 12 prospective RCTs reporting data on 1538 GC patients.ResultsPatients who received NAC were associated with significant improvement of OS (P = 0.001) and PFS (P < 0.001). Furthermore, NAC therapy significantly increased the incidence of 1-year survival rate (SR) (P = 0.020), 3-year SR (P = 0.011), and 4-year SR (P = 0.001). Similarly, NAC therapy was associated with a lower incidence of 1-year (P < 0.001), 2-year (P < 0.001), 3-year (P < 0.001), 4-year (P = 0.001), and 5-year recurrence rate (P = 0.002). Conversely, patients who received NAC also experienced a significantly increased risk of lymphocytopenia (P = 0.003), and hemoglobinopathy (P = 0.021).ConclusionsThe findings of this study suggested that NAC is associated with significant improvement in the outcomes of survival and disease progression for GC patients while also increasing some toxicity.

HCRP1 downregulation confers poor prognosis and induces chemoresistance through regulation of EGFR-AKT pathway in human gastric cancer.

The current study aims to investigate the biological roles and clinical significance of HCRP1 in human gastric cancer. The expression pattern of HCRP1 in gastric cancer tissue and adjacent non-cancerous tissue was detected by immunohistochemistry. HCRP1 downregulation was found in 57 of 137 human gastric cancer samples and correlated with advanced TNM stage, positive nodal status, and relapse. Log-rank test showed that HCRP1 downregulation also correlated with poor overall survival and reduced relapse-free survival. In addition, we found that HCRP1 overexpression inhibited proliferation, colony formation, and invasion in HGC-27 cells. On the other hand, HCRP1 depletion by small interfering RNA promoted proliferation, colony formation, and invasion in SGC-7901 cells. We also treated gastric cancer cells with cisplatin. MTT and Annexin V/PI analysis were carried out to examine change of chemoresistance. We found that HCRP1 overexpression sensitized HGC-27 cells to cisplatin while its depletion reduced sensitivity in SGC-7901 cells. Moreover, we found that HCRP1 overexpression negatively regulated cyclin D1, MMP-2, p-EGFR, p-ERK, and p-AKT. HCRP1 depletion showed the opposite effects. In conclusion, our results suggest that HCRP1 downregulation might serve as an indicator for poor prognosis in gastric cancer patients. HCRP1 reduces drug resistance through regulation of EGFR-AKT signaling.

Prognostic value and clinicopathological significance of proliferating cell nuclear antigen expression in gastric cancer: a systematic review and meta-analysis

Background The prognostic significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer has long been assessed, yet results remain controversial. Therefore, we performed a meta-analysis to assess the prognostic value and clinicopathological significance of PCNA in gastric cancer. Methods A systematic literature search of PubMed, EMBASE, and the Cochrane Library databases was conducted. Summary odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate the correlations between PCNA expression and clinicopathological features, overall survival (OS), and disease-free survival (DFS). Results A total of 19 studies involving 2,852 participants were included in our analysis. The pooled HR indicated that high PCNA expression was significantly associated with poor OS (HR 1.66, 95% CI 1.32–2.08) and DFS (HR 1.81, 95% CI 1.40–2.36). Subgroup analysis revealed that the association between PCNA and OS was also significant in Asian and European patients. In addition, the pooled ORs showed that high PCNA expression was significantly associated with deeper tumor invasion (OR 2.37, 95% CI 1.71–3.27), lymph node metastasis (OR 2.49, 95% CI 1.85–3.35), and advanced stage cancer (OR 1.89, 95% CI 1.36–2.63). Conclusion Our meta-analysis indicates that high PCNA expression might be a prognosticator of poor survival and a promising therapeutic target for gastric cancer patients.

Long-Term Sleep Duration as a Risk Factor for Breast Cancer: Evidence from a Systematic Review and Dose-Response Meta-Analysis

Sleep patterns have been associated with the development of cancers, although the association between sleep duration and breast cancer remains controversial. The purpose of our study was to explore the relationship between sleep duration and breast cancer risk. The PubMed and Web of Science databases were searched, and restricted cubic splines were used to explore the dose-response relationship. Data from 415,865 participants were derived from 10 studies. A J-shaped nonlinear trend was found between sleep duration and breast cancer incidence (Pnon-linear = 0.012); compared with the reference hours (6 h or 7 h), with increasing sleep hours, the risk of breast cancer increased (Ptrend = 0.028). Moreover, a nonlinear relationship was found between sleep duration and estrogen receptor-positive breast cancer (Pnon-linear = 0.013); the risk of estrogen receptor-positive breast cancer increased with increasing sleep hours compared to the reference hours (Ptrend = 0.024). However, no nonlinear relationship was found between sleep duration and estrogen receptor-negative breast cancer; the risk of estrogen receptor-negative breast cancer was 1.035 for every additional sleep hour. Compared to women with the reference number of sleep hours, women with a longer sleep duration might have a significantly increased risk of breast cancer, especially estrogen receptor-positive breast cancer.