A Meaningful Attempt: Applying Dielectric Barrier Discharge Plasma to Induce Polarization of Macrophages.

Macrophage polarization plays an important role in many macrophage-related diseases. This study was designed to preliminarily explore the effects of dielectric barrier discharge (DBD) plasma on the polarization direction and cell activity of macrophages with different phenotypes (ie, M0, M1, and M2). The M1 macrophage marker inducible nitric oxide synthase (iNOS) and M2 macrophage marker cluster of differentiation 206 (CD206) were detected by western blot (WB). The effects of DBD plasma on macrophage viability were analyzed by using a cell counting kit-8 detection kit. M0, M1, and M2 macrophages exhibited a decrease in iNOS expression and an increase in CD206 expression after the DBD plasma intervention. Additionally, the decrease in macrophage viability remained non-significant after initiating the intervention. DBD plasma can promote the transformation of M0 and M1 macrophages to M2 macrophages, and can further enhance the expression of the M2 macrophage phenotype marker CD206. Our study not only demonstrates the potential therapeutic value of DBD plasma for macrophage-related diseases, but it also provides a new direction for research to improve the treatment of macrophage-related diseases. © 2023 Bioelectromagnetics Society.

EM-2, a natural sesquiterpene lactone from Elephantopus mollis H.B.K., enhanced the sensitivity of breast cancer cells to epirubicin by blocking protective autophagy.

BACKGROUND: EM-2, a natural sesquiterpene lactone isolated from Elephantopus mollis H.B.K., showed a good anti-breast cancer effect when combined with epirubicin (EPI). However, its synergistic sensitization mechanism remains unclear. PURPOSE: This study aimed to determine the therapeutic effect and possible synergistic mechanism of EM-2 with EPI in vivo and in vitro and to provide an experimental basis for the treatment of human breast cancer. METHODS: Cell proliferation was measured with MTT and colony formation assays. Apoptosis and reactive oxygen species (ROS) levels were examined through flow cytometry, and the expression levels of proteins related to apoptosis, autophagy, endoplasmic reticulum stress, and DNA damage were detected through Western blot analysis. Moreover, the caspase inhibitor Z-VAD-FMK, autophagy inhibitors bafilomycin A1 and chloroquine, ER stress inhibitor 4-phenylbutyric acid, and ROS scavenger N-acetyl cysteine were applied to verify signaling pathways. Breast cancer cell lines were used to evaluate the antitumor functions of EM-2 and EPI in vitro and in vivo. RESULTS: We demonstrated that in MDA-MB-231 and SKBR3 cells, the IC50 of EPI combined with EM-2 (IC20) was 37.909 and 33.889 times lower than that of EPI alone, respectively. Further study verified that in EPI-resistant lines (MDA-MB-231/EPI), the IC50 of EPI combined with EM-2 (IC20) was 26.305 times lower than that of EPI alone. Mechanistically, EM-2 could reverse the protective effect of EPI against autophagy in SKBR3 and MDA-MB-231 cells. EM-2 and EPI could trigger ER stress. When EM-2 and EPI were used in combination, ER stress was continuously activated, and ER stress-mediated apoptosis was induced. Meanwhile, EM-2 combined with EPI promoted DNA damage then induced apoptosis. In vivo, the volume of breast cancer xenografts in the combination group was smaller than that in the control, EM-2, and EPI groups. Immunohistochemical experiments demonstrated that the combination of EM-2 and EPI could block autophagy and promote ER stress in vivo. CONCLUSION: EM-2 enhances the sensitivity of MDA-MB-231, SKBR3, and EPI-resistant cells to EPI.

The construction of preclinical evidence for the treatment of liver fibrosis with quercetin: A systematic review and meta-analysis.

Quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid, is widely found in fruits and vegetables and exerts broad-spectrum pharmacological effects in the liver. Many studies have explored the bioactivity of quercetin in the treatment of liver fibrosis. Hence, through a systematic review and biological mechanism evaluation, this study aimed to construct a body of preclinical evidence for the treatment of liver fibrosis using quercetin. The literature used in this study was mainly obtained from four databases, and the SYRCLE list (10 items) was used to evaluate the quality of the included literature. A meta-analysis of HA, LN, and other indicators was performed via STATA 15.0 software. Subgroup analyses based on animal species and model protocol were performed to further obtain detailed results. Moreover, the therapeutic mechanism of quercetin was summarized in a directed network form based on a comprehensive search of the literature. After screening, a total of 14 articles (comprising 15 studies) involving 254 animals were included. The results from the analysis showed that the corresponding liver function indexes, such as the levels of HA and LN, were significantly improved in the quercetin group compared with the model group, and liver function, such as the levels of AST and ALT, were also improved in the quercetin group. The species- and model-based subgroup analyses of AST and ALT revealed that quercetin exerts a significant effect. The therapeutic mechanism of quercetin was shown to be related to multiple pathways involving anti-inflammatory and antioxidant activities and lipid accumulation, including regulation of the TGF-ß, α-SMA, ROS, and P-AMPK pathways. The results showed that quercetin exerts an obvious effect on liver fibrosis, and more prominent improvement effects on liver function and liver fibrosis indicators were obtained with a dose of 5-200 mg during a treatment course ranging from 4 to 8 weeks. Quercetin might be a promising therapeutic for liver fibrosis.

Effective dose/duration of natural flavonoid quercetin for treatment of diabetic nephropathy: A systematic review and meta-analysis of rodent data.

BACKGROUND: Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel option with the objective of enhancing curative effect and avoiding adverse reactions. As a representative, Quercetin (Qu) has proved to be of great value in current data. PURPOSE: We aimed to synthetize the evidence regarding the therapeutic effect and specific mechanism of quercetin on DN via systematically reviewing and performing meta-analysis. METHODS: Preclinical literature published prior to August 2021, was systematical retrieval and manually filtrated across four major databases including PubMed, Web of Science, EMBASE and Cochrane library. Pooled overall effect sizes of results were generated by STATA 16.0, and underlying mechanisms were summarized. Three-dimensional dose/time-effect analyses and radar maps were conducted to examine the dosage/time-response relations between Qu and DN. RESULTS: This paper pools all current available evidence in a comprehensive way, and shows the therapeutic benefits as well as potential action mechanisms of Qu in protecting the kidney against damage. A total of 304 potentially relevant citations were identified, of which 18 studies were enrolled into analysis. Methodological quality was calculated, resulting in an average score of 7.06/10. This paper provided the preliminary evidence that consumption of Qu could induce a statistical reduction in mesangial index, Scr, BUN, 24-h urinary protein, serum urea, BG, kidney index, TC, TG, LDL-C, AST, MDA, AGE, TNF-α, TGF-ß1, TGF-ß1 mRNA, CTGF and IL-1ß, whereas HDL-C, SOD, GSH, GSH-Px, CAT and smad-7 were significantly increased. Furthermore, Qu could remarkably improve the renal pathology. In terms of the mechanisms underlying therapy of DN, Qu exerts anti-diabetic nephropathy properties possibly through PI3K/PKB, AMPK-P38 MAPK, SCAP/SREBP2/LDLr, mtROS-TRX/TXNIP/NLRP3/IL-1ß, TGF-ß1/Smad, Nrf2/HO-1, Hippo, mTORC1/p70S6K and SHH pathways. Dose/time-response images predicted a modest association between Qu dosage consumption/administration length and therapeutic efficacy, with the optimal dosage at 90-150 mg/kg/d and administration length ranging from 8 weeks to 12 weeks. CONCLUSIONS: Quercetin exhibit highly pleiotropic actions, which simultaneously contributes to prevent fundamental progression of DN, such as hyperglycemia, dyslipidemia, inflammation, fibrotic lesions and oxidative stress. The therapeutic effect becomes stronger when Qu administration at higher dosages lasts for longer durations. Taken together, quercetin could be used in patients with DN as a promising agent, which has well-established safety profiles and nontoxicity according to existing literature.

The Astragaloside IV Derivative LS-102 Ameliorates Obesity-Related Nephropathy.

Background: Astragaloside IV is the most important bioactive component of Radix Astragali. Previous studies have shown that astragaloside IV plays an important role in the control of early- and mid-stage diabetes and late diabetic nephropathy. However, it is disappointing that the in vivo solubility of astragaloside IV and its bioavailability after oral administration are very low. We recently obtained a new water-soluble derivative of astragaloside IV-astragaloside formic acid (LS-102), which has higher bioavailability than the parent compound. In our previous study, we found that there was a significant inflammatory response in the perirenal adipose tissue of mice with obesity-related nephropathy induced by a high-fat diet (HFD), which was related to macrophage infiltration. We hypothesized that in model mice with obesity-related nephropathy, LS-102 effectively regulated the inflammatory response and pathological changes in obesity-related nephropathy through macrophages in perirenal adipose tissue. If this hypothesis is true, the effects of LS-102 and astragaloside IV on TGF-ß1/Smad signal transduction will be further investigated. Methods: In this study, adipose stem cells and an HFD-induced obesity-related nephropathy mouse model were used to observe the regulatory effect of LS-102 on perirenal fat inflammation and the mechanism. Adipose mesenchymal stem cells were extracted from mice that were fed a normal diet and those with obesity-related nephropathy. The effects of LS-102 on the proliferation of two kinds of cells were measured by the CCK-8 method. The levels of tumor necrosis factor-α (TNF-a) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA. Obesity-related nephropathy mice were randomly divided into five groups: the HFD group, the LAS group (HFD+low concentration of astragaloside IV [10 mg/kg], intragastrically [ig]), the HAS group (HFD+high concentration of astragaloside IV [40 mg/kg], ig), the L102 group (HFD+low concentration of LS-102 [10 mg/kg], ig) and the H102 group (HFD+high concentration of LS-102 [40 mg/kg], ig). Body weight was measured, and the levels of serum glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), serum creatinine (Crea) and blood urea were measured. The kidneys were stained with HE, PAS and Masson's trichrome. Perirenal adipose tissue was harvested to examine the expression of CD68, LCA, CD11C, TNF-a, TGF-ß1, Fn1, Smad2, Smad3, Smad4, and Smad7 by immunohistochemical staining, and F4/80 was examined by immunofluorescence staining. Results: LS-102 significantly inhibited the in vitro secretion of TNF-a and PAI-1 by adipose stem cells in a concentration-dependent manner (P < 0.05). In vivo, the body weights in the LAS group, HAS group, L102 group and H102 group were significantly lower than those in the HFD group (P < 0.05). Except for that in the HFD group, the volume of perirenal adipocytes in the other groups was small and uniform (P < 0.05). Compared with the LAS, HAS, L102 and H102 groups, the HFD group had a larger glomerular cross-sectional area, proliferation of mesangial cells and the mesangial matrix, and increased matrix area/glomerular area (P < 0.05). The effect of LS-102 was better than that of astragaloside IV at the same concentration (P < 0.05). Compared with those in the HFD group, glucose, HDL-C, LDL-C and urea levels in the LAS group, HAS group, L102 group and H102 group were significantly decreased (P < 0.05). The expression of F4/80, CD68, LCA, TNF-a, CD11C, and PAI-1 in perirenal adipose tissue in the HFD group was significantly higher than that in the LAS group, HAS group, L102 group and H102 group (P < 0.05). Compared with those in the HFD group, the expression levels of TGF-ß1 and Fn1 in the HAS group, L102 group and H102 group were significantly increased (P < 0.05). Compared with the HFD group, the HAS group, L102 group and H102 group had decreased immunopositive rates of Smad2, Smad3 and Smad4 (P < 0.05). At the same concentration, the effect of LS-102 was better than that of astragaloside IV (P < 0.05). There was no significant difference in the expression of Smad7 among the different experimental groups (P > 0.05). Conclusion: Astragaloside IV and LS-102 improved the inflammatory reaction in perirenal adipose tissue and renal pathological changes in obesity-related nephropathy model mice and inhibited the TGF-ß1/Smad signaling cascade. At the same concentration, the effect of LS-102 was better than that of astragaloside IV. These results suggest that LS-102 has a better protective effect against obesity-related nephropathy. LS-102 may be a new type of traditional Chinese medicine for the clinical treatment of obesity and its related metabolic diseases.

Hepatic Artery Injection of 131I-Metuximab Combined with Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Prospective Nonrandomized, Multicenter Clinical Trial.

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Electroacupuncture Improves Cerebral Ischemic Injury by Enhancing the EPO-JAK2-STAT5 Pathway in Rats.

OBJECTIVE: Clinically, electroacupuncture (EA) improves cerebral ischemic injury, but its mechanism remains unknown. The aim of this study was to confirm the protective effects of EA on focal cerebral ischemia (FCI)-induced injury and the possible mechanism. METHODS: Sprague-Dawley (SD) rats served as the FCI model and were divided into the sham, model, EA, AG490 and EA+AG490 groups. Rats in the EA and EA+AG490 groups were acupunctured at the Baihui (GV20) and Dazhui (GV14) acupoints, and those in the AG490 and EA+AG490 groups were administered an intracerebroventricular injection of AG490 (a Janus-tyrosine kinase-2 (JAK-2) phosphorylation inhibitor). Neurological deficits and morphological changes in the ischemic cortex were observed through neurological deficit scoring and HE staining, respectively, and neuronal apoptosis was examined using the TUNEL assay. Transmission electron microscopy was used to observe neuronal ultrastructure, and HIF-1α, erythropoietin (EPO), phosphorylated (p)-JAK2, p-STAT5, HSP70, Bax and Bcl-2 expression was measured by RT-PCR and immunohistochemistry. RESULTS: FCI model rats showed obvious neurological deficits and neuronal apoptosis compared with sham rats. EA alleviated FCI-induced neurological deficits, improved neuronal ultrastructure, reduced neuronal apoptosis, and induced HIF-1α, EPO, p-JAK2, p-STAT5, HSP70 and Bcl-2 expression in a time-dependent manner. In contrast, AG490 treatment impaired the effects of EA on neurological deficits, neuronal apoptosis and HIF-1α, EPO, p-JAK2, p-STAT5, HSP70, Bax and Bcl-2 expression. CONCLUSION: EA at GV20 and GV14 could improve neurological deficits and reduce neuronal apoptosis, thereby improving FCI-induced injury, which may be related to enhancing the EPO-JAK2-STAT5 pathway.

The clinical value and usage of inflammatory and nutritional markers in survival prediction for gastric cancer patients with neoadjuvant chemotherapy and D2 lymphadenectomy.

BACKGROUND: The clinical values of inflammatory and nutritional markers remained unclear for gastric cancer with neoadjuvant chemotherapy (NACT). METHODS: The inflammatory, nutritional markers and their changes were analyzed for locally advanced gastric cancer with NACT. The predictive value was evaluated by the Cox proportional hazards regressions under three hypothesized scenarios. The nomograms including independent prognostic factors were plotted for survival prediction. RESULTS: A total of 225 patients were included in the study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index, and hemoglobin (Hgb) were significantly reduced, and the body mass index was significantly increased after NACT (all P < 0.05). The pre-NACT NLR [hazard ratio (HR) = 1.176, P = 0.059] showed a trend to correlate with the overall survival (OS) when only pre-NACT markers available; The post-NACT Hgb (HR = 0.982, P = 0.015) was the independent prognostic factor when only post-NACT markers available; The post-NACT Hgb (HR = 0.984, P = 0.025) and the change value of LMR (HR = 1.183, P = 0.036) were the independent prognostic factors when both pre- and post-NACT markers available. The nomogram had a similar Harrell's C-statistic compared to ypTNM stage (0.719 vs. 0.706). CONCLUSION: For locally advanced gastric cancer, the NACT could significantly decrease some inflammatory markers. The pre-NACT NLR, the post-NACT Hgb and the change value of LMR had some values in survival prediction combined with age, sex, tumor location and the clinical stages under different clinical scenarios. The elevated initial NLR, the preoperative anemia and the greater change value of LMR implied a poor prognosis.

Low frequency pulsed electromagnetic field promotes the recovery of neurological function after spinal cord injury in rats.

Low frequency pulsed electromagnetic field (LFPEMF) has been shown to provide anti-inflammatory and antioxidative effects. However, there are no reports on whether LFPEMF can treat spinal cord injury (SCI) and its therapeutic mechanism. Therefore, this study was conducted to investigate whether LFPEMF can promote the recovery of neurological function after SCI in rats and its therapeutic mechanism. Basso-Beattie-Bresnahan (BBB) score and transcranial magnetic motor-evoked potentials (tcMMEPs) were recorded to assess the recovery of neurological function. Hematoxylin and eosin (HE) staining and luxol fast blue (LFB) staining were performed to assess the severity of SCI. Immunofluorescence (IF) staining and western blotting (WB) were performed to assess the differentiation of oligodendrocyte precursor cells (OPCs) into oligodendrocytes (OLs). Toluidine blue (TB) staining was performed to assess remyelination. WB and enzyme-linked immunosorbent assays (ELISA) were performed to assess the expression of neurotrophins and inflammatory factors. Our results showed that following stimulation by LFPEMF, there were significant improvements in BBB scores, tcMMEP amplitudes, the extent of the damage, and reduced demyelination in rats after SCI. The mature OLs, the number of well-myelinated fibers, and the myelin sheath thickness significantly increased in rats stimulated by LFPEMF after SCI. The expression of neurotrophins significantly increased, and the expression of inflammatory factors significantly decreased in rats stimulated by LFPEMF after SCI. Therefore, we suggest that LFPEMF can promote the recovery of neurological function in rats after SCI by improving the differentiation of OPCs into OLs and promoting remyelination, as well as by inhibiting inflammation and promoting neurotrophic effects. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:449-456, 2019.

The association of garlic with Helicobacter pylori infection and gastric cancer risk: A systematic review and meta-analysis.

BACKGROUND: Garlic may be protective against Helicobacter pylori infection and gastric cancer development. We conducted this study to quantitatively update evidence on garlic intake and gastric cancer with the inclusion of most recent cohort studies and qualitatively summarize epidemiological studies of garlic consumption and Helicobacter pylori infection. MATERIALS AND METHODS: PubMed, Embase, MEDLINE, and Cochrane Library were searched on April 2018. We conducted a meta-analysis to determine whether garlic intake reduced gastric cancer risk using random-effect models and a systematic review to summarize evidence on the association between garlic consumption and Helicobacter pylori infection. Risk of bias was assessed using tools of Cochrane risk of bias and Robins-I for randomized and nonrandomized studies, respectively. RESULTS: Meta-analysis of 18 studies (142 921 subjects) demonstrated high garlic consumption (as comparing the highest category to the lowest) was associated with a reduced gastric cancer risk (OR = 0.51, 95% CI = 0.44-0.57). This association became nonsignificant if only derived from the prospective studies (OR = 0.95, 95% CI = 0.66-1.24). Thirteen studies (4889 participants) were included in the systematic review for garlic consumption and Helicobacter pylori infection; ten of which found no significant results. The majority of these studies were poor in quality given the small sample size and high risk of bias. CONCLUSIONS: Pooled evidence, mainly from case-control studies, suggested a significant inverse association of garlic intake with gastric cancer risk. Given the limitations of included studies, current epidemiological evidence is not sufficient to reach any definite conclusion regarding the association of garlic with Helicobacter pylori infection.

Germline mutations in hereditary diffuse gastric cancer.

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%-3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as hereditary diffuse gastric cancer (HDGC). Studies reported that CDH1 germline mutations are the main cause of HDGC. With the help of rapid development of genetic testing technologies and data analysis tools, more and more researchers focus on seeking candidate susceptibility genes for hereditary cancer syndromes. In addition, National Comprehensive Cancer Network (NCCN) guidelines recommend that the patients of HDGC carrying CDH1 mutations should undergo prophylactic gastrectomy or routine endoscopic surveillances. Therefore, genetic counseling plays a key role in helping individuals with pathogenic mutations make appropriate risk management plans. Moreover, experienced and professional genetic counselors as well as a systematic multidisciplinary team (MDT) are also required to facilitate the development of genetic counseling and benefit pathogenic mutation carriers who are in need of regular and standardized risk management solutions. In this review, we provided an overview about the germline mutations of several genes identified in HDGC, suggesting that these genes may potentially act as susceptibility genes for this malignant cancer syndrome. Furthermore, we introduced information for prevention, diagnosis and risk management of HDGC. Investigations on key factors that may have effect on risk management decision-making and genetic data collection of more cancer syndrome family pedigrees are required for the development of HDGC therapeutic strategies.

Hyperthermic intraperitoneal chemotherapy plus simultaneous versus staged cytoreductive surgery for gastric cancer with occult peritoneal metastasis.

BACKGROUND: Our aim is to evaluate the safety and efficacy of two treatment strategies, hyperthermic intraperitoneal chemotherapy (HIPEC) plus simultaneous versus staged cytoreductive surgery (CRS) in patients with occult peritoneal metastasis of gastric cancer (GC). METHODS: We retrospectively reviewed 26 GC patients who were potential curatively resectable by pre-operative evaluation and found occult peritoneal metastasis by diagnostic laparoscopy. Patients were treated by HIPEC plus either simultaneous CRS (CRS+HIPEC group, n = 11) or staged CRS after systematic chemotherapy (HIPEC+Chemo+CRS group, n = 15). RESULTS: There is no mortality observed in both groups. The treatment complications in two group is comparable (P = 0.683), with 26.7% (4/15) in HIPEC+Chemo+CRS group, and 36.4% (4/11) in CRS+HIPEC group, respectively. The compliance of patients undergoing subsequent chemotherapy is higher in HIPEC+Chemo+CRS group (93.3%, 14/15) than that of CRS+HIPEC group (45.5%, 5/11) (P = 0.021). The mean interval time between CRS and first post-CRS systematic chemotherapy were 42.0 ± 12.0 days in HIPEC+Chemo+CRS group versus 69.8 ± 36.3 in CRS+HIPEC group (P = 0.163), respectively. The median OS in the HIPEC+Chemo+CRS group was 25.0 months, while 28.2 months in the CRS+HIPEC group (P = 0.738). CONCLUSION: For resectable GC patients with laparoscopic findings of occult peritoneal metastasis, HIPEC plus staged CRS is with better tolerance and compliance than simultaneous CRS.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination.

The prognosis for ovarian metastasis of gastric cancer is poor. There is no currently available treatment for this disease. The purpose of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) in female gastric cancer patients with metachronous ovarian metastasis. From January 2000 to December 2010, 62 patients developed ovarian metastasis after undergoing gastrectomy with D2 lymphadenectomy. Thirty-two patients underwent CRS plus HIPEC, and 30 patients underwent CRS alone. The median age of all 62 patients was 44 years (range 19-71 years). Metastatic carcinoma involving bilateral ovaries was observed in 50 patients (80.6 %). The median survival time in the CRS + HIPEC group was 15.5 months (95 % confidence interval [CI] 12.1-18.9 months) but was only 10.4 months (95 % CI 8.5-12.2 months) in the CRS group (P = 0.018). Among the 32 patients with pelvic peritoneal metastasis, a stratified analysis revealed that the median survival period for the 15 patients treated with CRS + HIPEC was significantly higher than that for the patients treated with CRS alone (P = 0.046). Among the 30 patients who suffered from ovarian metastasis alone, the median survival times were similar in both groups (P = 0.141). A multivariate analysis revealed that CRS + HIPEC and a low Peritoneal Cancer Index (PCI) were independent predictors for improved survival. In conclusion, our study indicates that employing the HIPEC procedure after CRS could improve the survival time of patients with ovarian metastasis with few complications; however, we do not recommend HIPEC treatment for ovarian metastasis alone.

Neoadjuvant chemotherapy with FOLFOX: improved outcomes in Chinese patients with locally advanced gastric cancer.

BACKGROUND: Although the role of peri-operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. METHODS: This is a prospective non-randomized study comparing peri-operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan-Meier log rank test was used to calculate and compare survival differences. RESULTS: There were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four-year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P < 0.001) to have improved OS. The most common side effect was grade 1-2 leukopenia. There were no grade 3 neuropathies, grade 4 cytopaenias, or treatment related deaths. CONCLUSION: Peri-operative treatment with FOLFOX shows promise in patients with resectable locally advanced gastric cancer. It warrants further evaluation and should be considered an alternative to peri-operative ECF.

Discovery of covalent inhibitors for MIF tautomerase via cocrystal structures with phantom hits from virtual screening.

Biochemical and X-ray crystallographic studies confirmed that hydroxyquinoline derivatives identified by virtual screening were actually covalent inhibitors of the MIF tautomerase. Adducts were formed by N-alkylation of the Pro-1 at the catalytic site with a loss of an amino group of the inhibitor.