[Effect and mechanism of free total rhubarb anthraquinones on pyroptosis of J774A.1 macrophages].

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.

Type II Abernethy malformation with cystic fibrosis in a 12-year-old girl: A case report.

BACKGROUND: Abernethy malformation, also known as congenital extrahepatic portosystemic shunt, is an uncommon malformation resulting from aberrant development of the portal venous system. Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene. It mainly affects the exocrine glands of the respiratory, digestive and reproductive systems. It is considered extremely rare in the Asian population. We present a clinical case involving a pediatric patient of Asian descent who was diagnosed with Abernethy malformation and CF. CASE SUMMARY: A 12-year-old girl presented with a medical history of recurring respiratory infections and hemoptysis, and chest computed tomography (CT) showed bronchiectasis. Whole exome sequencing was performed for the patient, yielding findings that revealed a compound heterozygous variant of the CFTR gene: c.233_c.234insT/p.Trp79fsTer3 (maternal origin); c.2909G>A/p.Gly970Asp (paternal origin). CF was diagnosed. The physician's attention was drawn to the presence of splenomegaly during disease progression. Abdominal enhanced CT revealed splenomegaly, compression of the left kidney, and multiple tortuous dilated vascular shadows were seen at the splenic hilum, which flowed back into the left renal vein and portal vein, suggesting Abernethy malformation type II. Intraoperatively, the abnormal blood flow was seen to merge into the inferior vena cava through the left renal vein without hepatic processing, and the pathology of liver biopsy showed hypoplastic, dilated or absent portal vein branches, both of which supported the diagnosis of Abernethy malformation type II. This represents the initial documented instance of Abernethy malformation accompanied by a CFTR gene mutation in the existing body of literature. CONCLUSION: Coexisting Abernethy malformation and CF are rare. Detailed medical history information, abdominal enhanced CT, venography and genetic testing contribute to diagnosis as well as differential diagnosis.

Synthesis of Fluorescent Cyclic Peptides via Gold(I)-Catalyzed Macrocyclization.

Rapid and efficient cyclization methods that form structurally novel peptidic macrocycles are of high importance for medicinal chemistry. Herein, we report the first gold(I)-catalyzed macrocyclization of peptide-EBXs (ethynylbenziodoxolones) via C2-Trp C-H activation. This reaction was carried out in the presence of protecting group free peptide sequences and is enabled by a simple commercial gold catalyst (AuCl·Me2S). The method displayed a rapid reaction rate (within 10 min), wide functional group tolerance (27 unprotected peptides were cyclized), and up to 86% isolated yield. The obtained highly conjugated cyclic peptide linker, formed through C-H alkynylation, can be directly applied to live-cell imaging as a fluorescent probe without further attachment of fluorophores.

Eosinophilic granulomatosis with polyangiitis, asthma as the first symptom, and subsequent Loeffler endocarditis: A case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare form of anti-neutrophil cytoplasmic antibody-associated vasculitis characterized by asthma, vasculitis, and eosinophilia. CASE SUMMARY: We report an atypical case of EGPA in a 20-year-old female patient. Unlike previously reported cases of EGPA, this patient's initial symptom was asthma associated with a respiratory infection. This was followed by Loeffler endocarditis and cardiac insufficiency. She received treatment with methylprednisolone sodium succinate, low molecular weight heparin, recombinant human brain natriuretic peptide, furosemide, cefoperazone sodium/sulbactam sodium, and acyclovir. Despite prophylactic anticoagulation, she developed a large right ventricular thrombus. EGPA diagnosis was confirmed based on ancillary test results and specialty consultations. Subsequent treatment included mycophenolate mofetil. Her overall condition improved significantly after treatment, as evidenced by decreased peripheral blood eosinophils and cardiac markers. She was discharged after 17 d. Her most recent follow-up showed normal peripheral blood eosinophil levels, restored cardiac function, and a reduced cardiac mural thrombus size. CONCLUSION: This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.

Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization.

Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents-ethynylbenziodoxolones (EBXs)-onto peptides. These peptide-EBXs can be readily accessed, by both solution- and solid-phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein-protein interaction inhibition.

The regulatory network of the chemokine CCL5 in colorectal cancer.

The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.

A deep learning model based on contrast-enhanced computed tomography for differential diagnosis of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) is highly malignant, and its early diagnosis remains difficult. This study aimed to develop a deep learning model based on contrast-enhanced computed tomography (CT) images to assist radiologists in identifying GBC. METHODS: We retrospectively enrolled 278 patients with gallbladder lesions (> 10 mm) who underwent contrast-enhanced CT and cholecystectomy and divided them into the training (n = 194) and validation (n = 84) datasets. The deep learning model was developed based on ResNet50 network. Radiomics and clinical models were built based on support vector machine (SVM) method. We comprehensively compared the performance of deep learning, radiomics, clinical models, and three radiologists. RESULTS: Three radiomics features including LoG_3.0 gray-level size zone matrix zone variance, HHL first-order kurtosis, and LHL gray-level co-occurrence matrix dependence variance were significantly different between benign gallbladder lesions and GBC, and were selected for developing radiomics model. Multivariate regression analysis revealed that age ≥ 65 years [odds ratios (OR) = 4.4, 95% confidence interval (CI): 2.1-9.1, P < 0.001], lesion size (OR = 2.6, 95% CI: 1.6-4.1, P < 0.001), and CA-19-9 > 37 U/mL (OR = 4.0, 95% CI: 1.6-10.0, P = 0.003) were significant clinical risk factors of GBC. The deep learning model achieved the area under the receiver operating characteristic curve (AUC) values of 0.864 (95% CI: 0.814-0.915) and 0.857 (95% CI: 0.773-0.942) in the training and validation datasets, which were comparable with radiomics, clinical models and three radiologists. The sensitivity of deep learning model was the highest both in the training [90% (95% CI: 82%-96%)] and validation [85% (95% CI: 68%-95%)] datasets. CONCLUSIONS: The deep learning model may be a useful tool for radiologists to distinguish between GBC and benign gallbladder lesions.

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs.

The transcription factor, sterol regulatory element binding protein 1 (SREBP-1), plays important roles in modulating the proliferation, metastasis, or resistance to antitumor agents by promoting cellular lipid metabolism and related cellular glucose-uptake/Warburg Effect. However, the underlying mechanism of SREBP-1 regulating the proliferation or drug-resistance in lung squamous cell carcinoma (LUSC) and the therapeutic strategies targeted to SREBP-1 in LUSC remain unclear. In this study, SREBP-1 was highly expressed in LUSC tissues, compared with the paired non-tumor tissues (the para-tumor tissues). A novel small-molecule inhibitor of SREBP-1, MSI-1 (Ma's inhibitor of SREBP-1), based on natural product monomers, was identified by screening the database of natural products. Treatment with MSI-1 suppressed the activation of SREBP-1-related pathways and the Warburg effect of LUSC cells, as indicated by decreased glucose uptake or glycolysis. Moreover, treatment of MSI-1 enhanced the sensitivity of LUSC cells to antitumor agents. The specificity of MSI-1 on SREBP-1 was confirmed by molecular docking and point-mutation of SPEBP-1. Therefore, MSI-1 improved our understanding of SREBP-1 and provided additional options for the treatment of LUSC.

Nitrogen and sulfur co-doped carbon dots with bright fluorescence for intracellular detection of iron ion and thiol.

Carbon dots (CDs) have been widely used in recent years because of their excellent water solubility and abundant surface functional groups. However, compared with quantum dots or biological probes, the quantum yield of CDs is lower, and the fluorescence mainly concentrated in the blue-green range, which significantly limits the biological applications of CDs. Heteroatoms doping is the most common method to improve the luminescence of CDs. In this work, nitrogen and sulfur co-doped luminescent CDs were successfully synthesized by microwave assisted method using glutathione (GSH) and p-phenylenediamine (PPD) as raw materials. It can emit bright green fluorescence in ethanol solution, and the maximum emission wavelength is 535 nm when excited at 374 nm, and the absolute quantum yield is as high as 63%. Iron ion (Fe3+) can interact with the functional groups on the surface of the CDs to form CDs/Fe3+, which is a non-fluorescence complex, and Fe3+ can be reduced to ferrous ion (Fe2+). In other words, the reaction mechanism of CDs and Fe3+ is a combination of dynamic quenching and static quenching. The fluorescence of CDs quenched by Fe3+ can be restored by thiol, because there is a stronger binding force between sulfhydryl (-SH) on the surface of thiol and Fe3+, which enables CDs to be released. In addition, the CDs has good biocompatibility and stability, indicating that it has excellent potential in bioimaging. This discovery will expand the application of CDs in the fields of biosensing and imaging.

Histone methylation in pancreatic cancer and its clinical implications.

Pancreatic cancer (PC) is an aggressive human cancer. Appropriate methods for the diagnosis and treatment of PC have not been found at the genetic level, thus making epigenetics a promising research path in studies of PC. Histone methylation is one of the most complicated types of epigenetic modifications and has proved crucial in the development of PC. Histone methylation is a reversible process regulated by readers, writers, and erasers. Some writers and erasers can be recognized as potential biomarkers and candidate therapeutic targets in PC because of their unusual expression in PC cells compared with normal pancreatic cells. Based on the impact that writers have on the development of PC, some inhibitors of writers have been developed. However, few inhibitors of erasers have been developed and put to clinical use. Meanwhile, there is not enough research on the reader domains. Therefore, the study of erasers and readers is still a promising area. This review focuses on the regulatory mechanism of histone methylation, and the diagnosis and chemotherapy of PC based on it. The future of epigenetic modification in PC research is also discussed.

Periodontitis Exacerbates and Promotes the Progression of Chronic Kidney Disease Through Oral Flora, Cytokines, and Oxidative Stress.

Periodontitis is a type of systemic immune inflammation that is caused by the complex infection of a variety of microorganisms in the subgingival plaque and the imbalance of the microbial ecological environment in the mouth. Periodontitis and chronic kidney disease (CKD) share many risk factors, such as obesity, smoking, and age. A growing body of data supports a strong correlation between periodontitis and kidney disease. Evidence supports the role of periodontal inflammation and elevated serum inflammatory mediators in renal atherosclerosis, renal deterioration, and end-stage renal disease (ESRD) development. Periodontitis is a risk factor for kidney disease. However, to our knowledge, there are few studies detailing the possible link between periodontitis and CKD. This review summarizes the possible mechanisms underlying periodontitis and CKD. More importantly, it highlights novel and potential pathogenic factors for CKD, including bacteria, pro-inflammatory mediators and oxidative stress. However, most research on the relationship between periodontitis and systemic disease has not determined causality, and these diseases are largely linked by bidirectional associations. Future research will focus on exploring these links to contribute to new treatments for CKD.

Real-Time Imaging of Intracellular Glutathione Levels Based on a Ratiometric Fluorescent Probe with Extremely Fast Response.

Glutathione (GSH), the most abundant nonprotein thiol found in living organisms, are involved in the etiology and progression of many human diseases including cancer. So, monitoring changes of cellular GSH levels has an important guiding significance. To date, however, majority of probes can only qualitatively detect GSH in living cells. Herein, with coumarin as the read-out fluorophore and Michael addition as the sensing mechanism, six fluorescent probes were designed and synthesized. Among them, RP-2 exhibited a reversible and extremely fast response toward GSH (half time: ∼3 s), which endowed RP-2 the capacity of real-time imaging. Among the reversible probes based on Michael addition, RP-2 had both the largest forward and reverse rate constants thus far. The reaction between RP-2 and GSH was studied in detail by density functional theory and fluorescence spectroscopy. Real-time imaging of GSH levels in living cells was achieved with a temporal resolution of seconds. To simplify the processing of images, a program was developed and validated. RP-2 was expected to serve as a new fluorescent imaging tool to understand the function of intracellular GSH in the future.

Nickel(II)-Catalyzed Addition of Aryl-, Alkenyl-, and Alkylboronic Acids to Alkenylazaarenes.

A nickel(II)-catalyzed addition of aryl-, alkenyl-, and alkylboronic acids to alkenylazaarenes was presented. This reaction exhibited high efficiency (up to 93% yield), a broad substrate scope (seven types of heterocycles), and good functional group compatibility. The resulting products can be further transformed to many useful building blocks. Finally, the preliminary studies suggested that the adjacent N atom of the heterocycles was essential for the high reactivity.

One-Pot Preparation of 9,10-Dihydrophenanthrenes Initiated by Rhodium(III)-Catalyzed C-H Activation and Relay Diels-Alder Reaction.

An efficient one-pot synthesis of multisubstituted 9,10-dihydrophenanthrenes from easily available 2-arylazaarenes and cyclohexadienone-tethered terminal alkynes (1,6-enynes) has been successfully achieved. This domino reaction proceeded smoothly through Cp*Rh(III)-catalyzed C-H activation, direct protonation of alkenyl-Rh intermediates, intramolecular Diels-Alder reaction, alkene isomerization, subsequent ring-opening aromatization, and acetylation. This strategy was pot-economical and tolerated a wide range of functional groups. Moreover, the potent anticancer activities against HepG2 cells were observed for these artificial 9,10-dihydrophenanthrene derivatives.

Smoking status and subsequent gastric cancer risk in men compared with women: a meta-analysis of prospective observational studies.

BACKGROUND: Smoking is one of the well-established risk factors for gastric cancer incidence, yet whether men are more or equally susceptible to gastric cancer due to smoking compared with women is a matter of controversy. The aim of this study was to investigate and compare the effect of sex on gastric cancer risk associated with smoking. METHODS: We conducted a systemic literature search in MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify studies published from inception to December 2018. We included prospective observational studies which reported effect estimates with 95% confidence intervals (CIs) for associations of current or former smokers with the incidence of gastric cancer by sex. We calculated the ratio of relative risk (RRR) with corresponding 95% CI based on sex-specific effect estimates for current or former smokers versus non-smokers on the risk of gastric cancer. RESULTS: We included 10 prospective studies with 3,381,345 participants in our analysis. Overall, the summary RRR (male to female) for gastric cancer risk in current smokers was significantly increased compared with non-smokers (RRR: 1.30; 95% CI: 1.05-1.63; P = 0.019). Furthermore, there was no significant sex difference for the association between former smokers and gastric cancer risk (RRR: 1.20; 95% CI: 0.92-1.55; P = 0.178). However, the result of sensitivity analysis indicated the pooled result was not stable, which was altered by excluding a nested case-control study (RRR: 1.31; 95% CI: 1.10-1.57; P = 0.002). CONCLUSION: This systematic review showed a potential sex difference association between current smokers and the risk of gastric cancer. The sex differential in smokers can give important clues for the etiology of gastric cancers and should be examined in further studies.

The role of EGFR mutation as a prognostic factor in survival after diagnosis of brain metastasis in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. METHODS: Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017. RESULTS: 4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method. CONCLUSIONS: This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases.

High-Oxygen-Content Carbon Dots as a High-Efficiency Inhibitor of Human Insulin Aggregation.

Neurodegenerative diseases consist of Alzheimer's disease and type 2 diabetes which pose serious health effects. Carbon dots are widely used in the treatment of these types of diseases with their excellent biocompatibility and low toxicity. Herein, we use l- or d-cysteine to synthesize nontoxic high-oxygen carbon dots with a size around 3 nm and full of highly oxygenic functional groups. Through a ThT fluorescence assay, far-UV CD spectroscopy, and TEM, we find that carbon dots (CDs) can inhibit the nucleation process and elongate the lag phase by a large degree, and the higher-oxygen content one (d-CDs) exhibits a more significant inhibitory effect. When the dose of d-CDs reached 0.5 mg mL-1, it can impede the protofibril formation for nearly 1 week. Through the isothermal titration calorimetry (ITC) experiment, we obtain this result because d-CDs interact with the human insulin (HI) monomer (Ka1 = 2.46 × 104 L mol-1) stronger than l-CDs do (Ka2 = 1.62 × 103 L mol-1). More importantly, these two high-oxygen CDs still have a gorgeous inhibitory effect; even human insulin was nucleated, which has not been reported previously. This is because the association constant of fibril seeds interacting with d-CDs (Ka3 = 2.91 × 104 L mol-1) is large and competes against the interaction with the HI monomer so it can slow the fibrillation rate. Moreover, the interaction is mainly driven by electrostatic force. This is the first time results have been found of highly oxygenic CDs having a great inhibitory effect when they already have the growth sites and are illustrated by ITC experiments, which suggest further protein fibrillation inhibition.

Synthesis and biological evaluation of 2,5-disubstituted furan derivatives as P-glycoprotein inhibitors for Doxorubicin resistance in MCF-7/ADR cell.

Multidrug resistance (MDR) is a tendency in which cells become resistant to structurally and mechanistically unrelated drugs, which is mediated by P-glycoprotein (P-gp). It is one of the noteworthy problems in cancer therapy. As one of the most important drugs in cancer therapy, doxorubicin has not good effectiveness if used independently. So targeting the P-gp protein is one of the key points to solve the MDR. Three series of furan derivatives containing tetrahydroquinoline or tetrahydroisoquinoline were designed and synthesized as P-gp inhibitors in this paper. Compound 5m containing 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline possessed good potency against P-gp (EC50 = 0.89 ±â€¯0.11 µM). The preliminary structure-activity relationship and docking studies demonstrated that compound 5m would be great promise as a lead compound for further study. Most worthy of mention is drug combination of doxorubicin and 5m displayed antiproliferative effect of about 97.8%. This study provides highlighted P-gp inhibitor for withstanding malignant tumor cell with multidrug resistance especially doxorubicin resistance setting the basis for further studies.

The efficacy and safety of targeted therapy with or without chemotherapy in advanced gastric cancer treatment: a network meta-analysis of well-designed randomized controlled trials.

BACKGROUND: Advanced gastric cancer (AGC) is a severe malignant tumor associated with high mortality. Targeted therapy is an important approach for improving the therapeutic effects of AGC treatment. This study evaluates the efficacy and safety of targeted agents for AGC patients. METHODS: PubMed, EmBase, and the Cochrane Library were searched for double-blind randomized controlled trials (RCTs) of AGC treatments published prior to July 2017. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and severe adverse effects (AEs) were evaluated to determine the efficacy and safety of targeted agents. A network meta-analysis with a frequentist framework was performed to assess the effects of various targeted agents for AGC treatment. RESULTS: Our analysis included 16 articles involving 5371 patients and 11 types of agents. The network meta-analysis showed that apatinib (97.5%) was most likely to improve PFS, followed by regorafenib (86.3%) and rilotumumab (65.4%). Apatinib was similarly best for OS outcome, (95.5%) followed by rilotumumab (74.7%) and regorafenib (70%). Apatinib (89.6%) also had the best improvement on ORR, followed by rilotumumab (75.4%) and everolimus (68.4%). Bevacizumab (85.5%) was likely to get the lowest severe AEs, followed by sunitinib (63%). CONCLUSIONS: Apatinib, regorafenib, and rilotumumab improved patient PFS and OS. When combined with chemotherapy, ramucirumab and rilotumumab had high efficacy but low tolerability, and bevacizumab had moderate efficacy and tolerability for PFS. Without chemotherapy, ramucirumab and regorafenib had relatively high therapeutic efficacy tolerability for PFS.

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

BACKGROUND: Neoadjuvant 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. METHODS: This 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. RESULTS: Patients 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). CONCLUSIONS: The 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.