A panel of four plasma amino acids is a promising biomarker for newly diagnosed bladder cancer.

BACKGROUND: Metastasis and recurrence are the main causes of death in post-operative bladder cancer (BC), emphasizing the importance of exploring early-stage diagnostic markers. Serum biomarkers constitute a promising diagnostic approach for asymptomatic stage cancer as they are non-invasive, have high accuracy and low cost. AIMS: To correlate concentrations of plasma amino acids with BC progression to assess their utility as an early-stage diagnostic. METHODS: Newly diagnosed BC patients (n = 95) and normal controls (n = 96) were recruited during the period from 1 December 2018 to 30 December 2020. General and food frequency questionnaires established their basic information and dietary intake data. Venous blood samples were collected from fasting subjects and used to detect levels of plasma amino acids by liquid chromatography-mass spectrometry. Verification was performed on the GSE13507 transcriptome gene expression matrix of BC from Gene Expression Omnibus (GEO) database. RESULTS: Eleven amino acids have been identified as altered in the plasma of newly diagnosed BC patients compared to controls (P < 0.05). Adjusted by gender, education, smoking and other factors, plasma ornithine level (OR = 0.256, 95% CI: 0.104-0.630) is a protective factor for BC, plasma levels of methionine (OR = 3.460, 95% CI: 1.384-8.651), arginine (OR = 3.851, 95% CI: 1.542-9.616), and glutamate (OR = 3.813, 95% CI: 1.543-9.419) are all risk factors for BC. ROC analysis demonstrated that the combination of plasma ornithine, methionine, arginine and glutamate could accurately diagnose BC (AUC = 0.84, 95% CI: 0.747-0.833). In addition, the mRNA level of arginase 1 was decreased (P < 0.05), while the inducible nitric oxide synthase was increased significantly, which may be linked with the disturbance of arginine metabolism in BC patients. Further analysis of GEO database confirmed the role of arginine metabolism. CONCLUSION: A biomarker panel containing four amino acids may provide a feasible strategy for the early diagnosis of BC. However, further validation is required through prospective studies.

Gastrodin ameliorates acute pancreatitis by modulating macrophage inflammation cascade via inhibition the p38/NF-κB pathway.

Acute pancreatitis (AP) is a prevalent, destructive, non-infectious pancreatic inflammatory disease, which is usually accompanied with systemic manifestations and poor prognosis. Gastrodin (4-hydroxybenzyl alcohol 4-O-ß-d-glucopyranoside) has ideal anti-inflammatory effects in various inflammatory diseases. However, its potential effects on AP had not been studied. In this study, serum biochemistry, H&E staining, immunohistochemistry, immunofluorescence, western blot, real-time quantitative PCR (RT-qPCR) were performed to investigate the effects of Gastrodin on caerulein-induced AP pancreatic acinar injury model in vivo and lipopolysaccharide (LPS) induced M1 phenotype macrophage model in vitro. Our results showed that Gastrodin treatment could significantly reduce the levels of serum amylase and serum lipase while improving pancreatic pathological morphology. Additionally, it decreased secretion of inflammatory cytokines and chemokines, and inhibited the levels of p-p38/p38, p-IκB/IκB as well as p-NF-κB p-p65/NF-κB p65. Overall our findings suggested that Gastrodin might be a promising therapeutic option for patients with AP by attenuating inflammation through inhibition of the p38/NF-κB pathway mediated macrophage cascade.

Clinical application of molecular residual disease detection by circulation tumor DNA in solid cancers and a comparison of technologies: review article.

Molecular residual disease (MRD), detected by circulating tumor DNA (ctDNA) can be involved in the entire process of solid tumor management, including recurrence prediction, efficacy evaluation, and risk stratification. Currently, the detection technologies are divided into two main categories, as follows: tumor-agnostic and tumor informed. Tumor-informed assay obtains mutation information by sequencing tumor tissue samples before blood MRD monitoring, followed by formulation of a personalized MRD panel. Tumor-agnostic assays are carried out using a fixed panel without the mutation information from primary tumor tissue. The choice of testing strategy may depend on the level of evidence from ongoing randomized clinical trials, investigator preference, cost-effectiveness, patient economics, and availability of tumor tissue. The review describes the difference between tumor informed and tumor agnostic detection. In addition, the clinical application of ctDNA MRD in solid tumors was introduced, with emphasis on lung cancer, colorectal cancer, Urinary system cancer, and breast cancer.

The protective roles of liraglutide on Kawasaki disease via AMPK/mTOR/NF-κB pathway.

Kawasaki disease (KD) is an acute febrile rash illness among children of unknown etiology, with coronary artery injury. The main purpose of this study was to investigate the protective effects of liraglutide on KD, and elucidate the underlying mechanisms. The candida albicans water-soluble fraction (CAWS)-induced coronary arteritis of mouse KD model in vivo and tumor necrosis factor α (TNF-α) induced endothelial cell injury of human umbilical vein endothelial cell (HUVEC) model in vitro were used to explore the anti-inflammation and anti-apoptosis effects of liraglutide on KD. In vivo results showed that liraglutide could significantly alleviate the coronary artery injury of KD mice, as evidenced by the reduction of inflammatory infiltration around the coronary arteries, downregulation of inflammatory cytokines and chemokines expressions, and decrease of TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) positive cell rates. The results in vitro also displayed that liraglutide could markedly relieve the inflammatory of TNF-α induced HUVECs through downregulating the expressions of inflammatory and chemokine indicators as well as inhibit TNF-α induced HUVEC apoptosis by the less ratio of apoptotic cells, the more loss of mitochondrial membrane potential (△Ψm), the lower level of intracellular reactive oxygen species (ROS), and the more ratio of BCL-2/BAX. Further in vivo and in vitro studies demonstrated that liraglutide could rescue endothelial cell injury through AMPK/mTOR/NF-κB pathway. In conclusion, liraglutide could play protective roles on KD through inhibiting endothelial cell inflammation and apoptosis via the activation of AMPK/mTOR/NF-κB pathway.

Comparison of the early clinical efficacy of the SuperPath approach versus the modified Hardinge approach in total hip arthroplasty for femoral neck fractures in elderly patients: a randomized controlled trial.

PURPOSE: To investigate the clinical efficacy and advantages of the SuperPath approach for total hip arthroplasty in the treatment of femoral neck fractures in the elderly population. METHODS: From February 2018 to March 2019, 120 patients were randomly divided into two groups with 60 patients each: the SuperPath group and the conventional group. The results evaluated included the general operation situation, serum markers, blood loss, pain score, hip function and prosthesis location analysis. RESULTS: There was no demographic difference between the two groups. Compared with the conventional group, the SuperPath group had a shorter operation time (78.4 vs. 93.0 min, p = 0.000), a smaller incision length (5.8 vs. 12.5 cm, p = 0.000), less intraoperative blood loss (121.5 vs. 178.8 ml, p = 0.000), a shorter hospitalization time (8.0 vs. 10.8 days, p = 0.000) and less drainage volume (77.8 vs. 141.2 ml, p = 0.000). The creatine kinase level in the SuperPath group was significantly lower than that in the conventional group, while there was no difference in the C-reactive protein level and erythrocyte sedimentation rate level. The visual analog scale score was lower one month postoperatively, and the Harris hip score was higher three months postoperatively in the SuperPath group (p < 0.05). There was no difference in the cup abduction angle or anteversion angle of the two groups. CONCLUSION: We found better clinical efficacy after using the SuperPath approach with less muscle damage, less postoperative pain and better postoperative function than after using the modified Hardinge approach. Trial registration The randomized clinical trial was retrospectively registered at the Chinese Clinical Trial Registry on 31/12/2020 (ChiCTR-2000041583, http://www.chictr.org.cn/showproj.aspx?proj=57008 ).

Global leaders malnutrition initiative-defined malnutrition affects long-term survival of different subgroups of patients with gastric cancer: A propensity score-matched analysis.

As defined by the Global Leaders Malnutrition Initiative (GLIM), malnutrition is strongly associated with a lower quality of life and poor prognosis in gastric cancer patients. However, few studies have precisely explored the predictors of malnutrition, as defined by the GLIM, for overall survival (OS) after gastric cancer surgery in subgroups of patients stratified according to population characteristics. Our research aimed to analyze whether the predictors of malnutrition defined by the GLIM for postoperative OS in gastric cancer patients differ across subgroups. Patients who underwent radical gastric cancer surgery at our center between July 2014 and February 2019 were included in the study. Propensity score matching (PSM) was used to minimize bias. The study population was divided into malnourished and normal groups based on whether they were malnourished as defined by the GLIM. Univariate and multivariate analyses were performed to identify the risk factors affecting OS. The Kaplan-Meier curve and log-rank test were performed to determine the survival rate difference between subgroups. Overall, 1,007 patients were enrolled in the research. Multivariate analysis showed that malnutrition among the patients was 33.47%. Additionally, GLIM-defined malnutrition was an independent risk factor [hazard ratio (HR): 1.429, P = 0.001] for a shorter OS in gastric cancer patients. Furthermore, subgroup analysis showed that the GLIM was more appropriate for predicting OS in older aged patients (≥65 years), females, those with comorbidities (Charlson comorbidity index ≥ 2), and those with advanced gastric cancer (TNM stage = 3). GLIM-defined malnutrition affects the long-term survival of gastric cancer patients, especially older patients, females, patients with comorbidities, and patients with advanced gastric cancer.

Characterization of the tumour microenvironment phenotypes in malignant tissues and pleural effusion from advanced osteoblastic osteosarcoma patients.

PURPOSE: Malignant pleural effusion (MPE) is an adverse prognostic factor in patients with osteoblastic osteosarcoma; however, the cellular contexts of MPE are largely unknown. EXPERIMENTAL DESIGN: We performed single-cell RNA-sequencing (scRNA-seq) on 27 260 cells from seven MPE samples and 91 186 cells from eight osteosarcoma tissues, including one recurrent, one lung metastasis and six primary tumour (PT) samples, to characterize their tumour microenvironment. RESULTS: Thirteen main cell groups were identified in osteosarcoma tumour and MPE samples. Immune cells dominate the cellular contexts in MPE with more T/NK cells and less osteoclasts compared to PT samples. Of T/NK cells, CD8+ GNLY+ , CD8+ KLRC2+ T cells and FCGR3A+ NK cells were enriched in MPE but CD4+ FOXP3+ Tregs were enriched in PT samples. Naïve IGHD+ B and immune regulatory IGHA1+ B cells were largely identified in MPE, whereas bone metabolism-related CLEC11A+ B cells were significantly enriched in osteosarcoma PT. M2-type TAMs, including CLEC11A_TAM, C1QC_TAM and Prolif_TAMs, among myeloid cells were enriched in PT, which may suppress cytotoxicity activities of T cells through multiple ligand-receptor interactions. Mature LAMP3+ DCs were transformed from CD1C+ DC and CLEC9A+ DC sub-clusters when exposure to tumour alloantigens, which may improve T cell cytotoxicity activities on tumour cells under anti-PD-L1 treatments. In further, immune cells from MPE usually present up-regulated glycolysis and down-regulated oxidative phosphorylation and riboflavin metabolism activities compared to those in PT samples. CONCLUSIONS: Our study provided a novel cellular atlas of MPE and PT in patients with advanced osteosarcoma, which may provide potential therapeutic targets in the future.

Controlled release of hydrogen by implantation of magnesium induces P53-mediated tumor cells apoptosis.

Hydrogen has been used to suppress tumor growth with considerable efficacy. Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration. We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials. However, the underlying mechanism of hydrogen's role in cancer treatment remains ambiguous. Here, we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials. We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins, as demonstrated by the in vitro RNA sequencing and protein expression analysis. Then, the P53 proteins disrupt the membrane potential of mitochondria, activate autophagy, suppress the reactive oxygen species in cancer cells, and finally result in tumor suppression. The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse. We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2 µL/mm3 per day, which is much lower than that required for hydrogen inhalation. Taken together, these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway, which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.

Effects of dacomitinib on the pharmacokinetics of poziotinib in vivo and in vitro.

CONTEXT: Dacomitinib and poziotinib, irreversible ErbB family blockers, are often used for treatment of non-small cell lung cancer (NSCLC) in the clinic. OBJECTIVE: This study investigates the effect of dacomitinib on the pharmacokinetics of poziotinib in rats. MATERIALS AND METHODS: Twelve Sprague-Dawley rats were randomly divided into two groups: the test group (20 mg/kg dacomitinib for 14 consecutive days) and the control group (equal amounts of vehicle). Each group was given an oral dose of 10 mg/kg poziotinib 30 min after administration of dacomitinib or vehicle at the end of the 14 day administration. The concentration of poziotinib in plasma was quantified by UPLC-MS/MS. Both in vitro effects of dacomitinib on poziotinib and the mechanism of the observed inhibition were studied in rat liver microsomes and human liver microsomes. RESULTS: When orally administered, dacomitinib increased the AUC, Tmax and decreased CL of poziotinib (p < 0.05). The IC50 values of M1 in RLM, HLM and CYP3A4 were 11.36, 30.49 and 19.57 µM, respectively. The IC50 values of M2 in RLM, HLM and CYP2D6 were 43.69, 0.34 and 0.11 µM, respectively, and dacomitinib inhibited poziotinib by a mixed way in CYP3A4 and CYP2D6. The results of the in vivo experiments were consistent with those of the in vitro experiments. CONCLUSIONS: This research demonstrates that a drug-drug interaction between poziotinib and dacomitinib possibly exists when readministered with poziotinib; thus, clinicians should pay attention to the resulting changes in pharmacokinetic parameters and accordingly, adjust the dose of poziotinib in clinical settings.

Differentiation of human umbilical cord mesenchymal stem cells into Leydig-like cells with defined molecular compounds.

95% of the body's testosterone is produced by the Leydig Cells (LCs) in adult testis, and LC functional degradation can cause testosterone deficiency ultimately leading towards hypogonadism. The transplantation of LCs derived from stem cells is a very promising therapy to overcome the testosterone deficiency. The isolated umbilical cord mesenchymal stem cells (UMSCs) were identified by flow cytometry and adipogenic and osteogenic differentiation. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used for the differentiated Leydig-like cell identification. The comparisons of the testosterone levels, gene expression levels, and cyclic adenosine monophosphate (cAMP) productions were performed through radioimmunoassay, quantitative polymerase chain reaction (qPCR), and cAMP assay kit, respectively. Here, it is stated that our isolated human UMSCs, which could positively express CD29, CD44, CD59, CD90, CD105, and CD166 but negatively express CD34 as well as could be differentiated into adipocytes and osteocytes, could be differentiated into Leydig-like cells (UMSC-LCs) using a novel differentiation method based on molecular compounds. The enrichment UMSC-LCs could secrete testosterone into the medium supernatant and produce considerable cAMP at the stimulation of luteinizing hormone (LH), and positively expressed LC lineage-typical markers LHCGR, SCARB1, SATR, CYP11A1, CYP17A1, HSD3B1, HSD17B3, and SF-1 as well as negatively expressed mesenchymal stem cell typical markers CD29, CD44, and CD105. The expression levels of NR3C4, PDGFRA, and NR3A1 in UMSC-LCs were higher than those of UMSCs and were comparable with LCs. These results illuminated that UMSCs could be differentiated into Leydig-like cells using the defined molecular compounds, which might further support MSC-derived Leydig cell transplantation therapy for testosterone insufficiency.

Integrated analysis of transcriptome-wide m6A methylome of osteosarcoma stem cells enriched by chemotherapy.

Aim: To analyze the m6A methylome of osteosarcoma stem cells (OSCs). Materials & methods: Chemoresistant OSCs were enriched by doxorubicin treatment. Expression of m6A-related enzymes was detected by quantitative real-time-PCR and western blot. MeRIP-seq and RNA-seq were performed to identify differences in m6A methylation and gene expression. Data analysis was conducted to explore the modified genes and their clinical significance. Results: Three m6A-related enzymes were altered in OSCs. Differentially methylated genes were enriched in some pathways regulating pluripotency of stem cells. The expression of several candidate genes were found consistent with that in GSE33458 dataset, and associated with poor prognosis in osteosarcoma patients. Conclusion: m6A may play a role in the emergence and maintaining of OSCs and affect the prognosis.

Differentiation of human adipose derived stem cells into Leydig-like cells with molecular compounds.

Leydig cells (LCs) are the primary source of testosterone in the testis, and testosterone deficiency caused by LC functional degeneration can lead to male reproductive dysfunction. LC replacement transplantation is a very promising approach for this disease therapy. Here, we report that human adipose derived stem cells (ADSCs) can be differentiated into Leydig-like cells using a novel differentiation method based on molecular compounds. The isolated human ADSCs expressed positive CD29, CD44, CD59 and CD105, negative CD34, CD45 and HLA-DR using flow cytometry, and had the capacity of adipogenic and osteogenic differentiation. ADSCs derived Leydig-like cells (ADSC-LCs) acquired testosterone synthesis capabilities, and positively expressed LC lineage-specific markers LHCGR, STAR, SCARB1, SF-1, CYP11A1, CYP17A1, HSD3B1 and HSD17B3 as well as negatively expressed ADSC specific markers CD29, CD44, CD59 and CD105. When ADSC-LCs labelled with lipophilic red dye (PKH26) were injected into rat testes which were selectively eliminated endogenous LCs using ethylene dimethanesulfonate (EDS, 75 mg/kg), the transplanted ADSC-LCs could survive and function in the interstitium of testes, and accelerate the recovery of blood testosterone levels and testis weights. These results demonstrated that ADSCs could be differentiated into Leydig-like cells by few defined molecular compounds, which might lay the foundation for further clinical application of ADSC-LC transplantation therapy.

OCIAD1 promoted pancreatic ductal adenocarcinoma migration by regulating ATM.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplastic disease, characterized with poor outcomes and a 5-year survival rate less than 5%. Dysregulation or dysfunction of immune response factors contribute to cancer development. In this study, we found that OCIAD1 is high expressed in pancreatic cancer gene chip, and verified OCIAD1 associating with cancer malignancy in specimens from patients with PDAC. OCIAD1 down-regulation inhibited PDAC cell lines migration and vice versa. Further analysis of pancreatic cancer gene chip found OCIAD1 high expression was associating with low ATM expression. Then we proved that OCIAD1 regulated ATM to affect the migration of PDAC. Thus we concluded that high OCIAD1 levels in PDAC promoted tumor cells migration. OCIAD1 exerted its effects by regulating ATM.

A residual intra-articular varus after medial opening wedge high tibial osteotomy (HTO) for varus osteoarthritis of the knee.

PURPOSE: Varus deformity of knee osteoarthritis was formed by both intra-articular and extra-articular pathologies. Such intra-articular deformities could not be fully corrected by a medial open-wedge high tibial osteotomy (HTO), which was performed as an extra-articular procedure. Therefore, the purpose of this study was to investigate whether any residual varus was left inside the joint after HTO in the patients with knee osteoarthritis, and a correlation of the residual varus could be traced. METHODS: This study involved 66 patients (66 knees) undergoing HTO for medial knee osteoarthritis. The percentage of mechanical axis (%MA), mechanical femorotibial angle (mFTA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA) and joint line convergence angle (JLCA) were measured on radiographs of the full-length legs preoperatively and 6 months postoperatively. The relationship between changes in the JLCA and alignment correction was assessed. The postoperative residual JLCA was categorized as the optimal (postoperative JLCA ≤ 2°), the acceptable (2° < postoperative JLCA ≤ 5°), and the unacceptable (postoperative JLCA > 5°) to analyze its correlation with pre- or intra-operative factors. RESULTS: Average %MA and mFTA were improved from 5.5 to 60% and from 190.2° to 176.4°, respectively. There was no change in mLDFA, whereas mMPTA changed from 80.3° to 91.8°. JLCA changed from 4.2° to 2.7°. The analyses of multiple linear regression showed that the preoperative JLCA and postoperative changes in mechanical alignment (%MA, mFTA and mMPTA) were two important variables dependently associated with differences in JLCAs postoperatively. However, postoperative JLCAs showed a stronger correlation to preoperative JLCAs than to changes in mechanical alignment postoperatively. A Chi-square analysis showed a significantly higher percentage of patients achieved acceptable postoperative JLCAs in the preoperative JLCA ≤ 6° group (78.8%) compared to the preoperative JLCA > 6° group (6.1%). Therefore, 6° of JLCA was suggested to be a tipping point. CONCLUSIONS: The capability of HTO to correct intra-articular varus deformities, which was represented by JLCAs, is limited. Postoperative residual JLCAs were correlated primarily to preoperative JLCA values and total alignment correction, while the former accounted for most. A preoperative JLCA of 6° was suggested to be a tipping point, and a larger value indicated more than 5° residual JLCA after the HTO.

Enrichment of cancer stem cells by agarose multi-well dishes and 3D spheroid culture.

As the theory of cancer stem cells (CSCs) is maturing, CSC-targeted therapy is emerging as an important therapeutic strategy and seeking the ideal method for rapid enrichment and purification of CSCs has become crucial. So far, based on the known CSC phenotypes and biological characteristics, the methods for enrichment CSCs mainly include low adhesion culture, low oxygen culture, chemotherapy drug stimulation and side population (SP) sorting but these methods cannot realize quick enrichment of the desired CSCs. Herein, we adopt a novel method that efficiently enriches a certain amount of CSCs through agarose multi-well dishes using rubber micro-molds to make cancer cells into cell spheroids (3D). These 3D cancer cell spheroids in the proportions of expression of CSC biomarkers (single stain of CD44, CD44v6 and CD133 or double stain of both CD44 and CD133) were significantly higher than those of the conventional adherent culture (2D) using flow cytometry analysis. In addition, the expression levels of stemness transcription factors such as OCT4, NANOG and SOX2 in 3D were also significantly higher than that in 2D through Western blot (WB) and quantitative polymerase chain reaction (qPCR) assays. In addition, the CSCs in 3D could form colonies with different sizes in soft agar. In conclusion, we developed a new method to enrich some kinds of CSCs, which might be a benefit for future CSC-targeted therapy studies and anti-CSC drug screening applications.

Denosumab versus zoledronic acid for preventing symptomatic skeletal events in Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer: an outcome analyses with a mean follow-up of 3 years.

BACKGROUND: The purpose of this study was to evaluate the efficacy of denosumab or zoledronic acid (ZA) using symptomatic skeletal events (SSEs) as the primary endpoint in Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer. METHODS: Asian postmenopausal women with oestrogen-receptor-positive advanced breast cancer receiving subcutaneous denosumab 120 mg Q4W, or intravenous ZA 4 mg Q4W until the primary analysis cut-off date were retrospectively analysed in the Hong Kong Practice-Based Cancer Research Center(HKCRC) from March 2011 to March 2013. The time to first on-study SSE that was assessed either clinically or through routine radiographic scans was the primary endpoint. RESULTS: 242 patients received denosumab or ZA treatment (n = 120, mean age of 64.9 years (SD 3.01) and n = 122, 65.4 years (3.44), respectively). The median times to first on-study SSE were 14.7 months (12.9-45.6) and 11.7 months (9.9-45.6) for denosumab and ZA, respectively (hazard ratio, HR 0.44, 95% CI 0.71-2.95; p = 0·0002). Compared with the ZA group, denosumab-treated patients had a significantly delayed time to first SSE (HR 0.65 [95% CI 0.29-1.45], p < 0.0001). An increased incidence of SSE was found in the 16-month follow-up with rates of 2.1 and 10.7% for denosumab and ZA, respectively (P = 0.033). The difference persisted with time with rates of 8.3 and 17.2% at the final follow-up, respectively (P < 0.05). CONCLUSION: In postmenopausal women aged ≥60 years with oestrogen-receptor-positive advanced breast cancer, denosumab significantly reduced the risk of developing SSEs compared with ZA. The findings of this pilot trial justify a larger study to determine whether the result is more generally applicable to a broader population.

Enhanced recovery after surgery decreases intestinal recovery time and pain intensity in patients undergoing curative gastrectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) reduces postoperative stress, increases patient satisfaction, and reduces postoperative stay and cost. In this study, we evaluated the feasibility and effectiveness of ERAS protocols compared with conventional perioperative care group and their effect in gastric cancer patients undergoing gastrectomy. METHODS: A cohort of 366 patients were analyzed from a prospectively maintained database. The patients' characteristics, tumor profile, surgical information data and postoperative complications were evaluated. RESULTS: Patients in the ERAS had a faster gastrointestinal function recovery and first flatus (3.26±0.64; P<0.001). Pain intensity of patients in the ERAS group was significantly lower than that of patients in the conventional care group on postoperative days 1 (2.33±0.98; P<0.001) and 3 (1.06±0.63; P<0.001). Postoperative hospital stays were significantly shorter in patients receiving ERAS program (6.66±3.36; P<0.001), than in those patients who received conventional perioperative care (9.02±2.61). CONCLUSION: ERAS can reduce postoperative stress, enhance the recovery of the gut, reduce the pain intensity, and increase satisfaction in gastric cancer patient undergoing curative gastrectomy.

Gait speed predicts post-operative medical complications in elderly gastric cancer patients undergoing gastrectomy.

BACKGROUND: Gait speed is a clinical outcome that can measure the physical performance of elderly gastric patients. The purpose of this study was to determine the importance of gait speed in predicting post-operative morbidities in elderly patients undergoing curative gastrectomy. METHODS: We conducted a prospective study of 357 elderly patients (≥65 years old) undergoing curative gastrectomy. Preoperative gait speed was measured in a 6-m well-lit and unobstructed hallway. Patients were followed up for the post-operative clinical outcomes. Factors contributing to the post-operative morbidities were analysed using univariate and multivariate analyses. RESULTS: Slow gait speed was present in 95 out of 357 patients (26.61%) which was significantly associated with age (P < 0.001), gender (P = 0.016), plasma albumin (P < 0.001), American Society of Anesthesiologists grade (P = 0.012), tumour-node-metastasis grade (P = 0.007), sarcopenia (P < 0.001), handgrip (P < 0.001) and post-operative medical complications (P = 0.022). In univariate analysis, age (P = 0.015) and slow gait speed (P = 0.029) were risk factors of post-operative complications. In multivariate analysis, we found that age (P < 0.001) and slow gait speed (P = 0.029) were independent predictors of post-operative medical complications. CONCLUSION: Slow gait speed is an independent predictor of post-operative medical complications in elderly patients undergoing curative gastrectomy. Those patients should be managed with appropriate perioperative nutritional support and physical exercise which can improve gait speed and reduce the risk of post-operative medical complications.

Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy.

Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran-g-indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer.

Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.