Clinical outcomes and biomarker exploration of first-line PD-1 inhibitors plus chemotherapy in patients with low PD-L1-expressing of gastric or gastroesophageal junction adenocarcinoma.

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.

The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer.

BACKGROUND: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. METHODS: Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 and 2-3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. RESULT: One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. TRG 2-3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P < 0.001). CONCLUSION: TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

Quantification of biomolecules responsible for biomarkers in the surface-enhanced Raman spectra of bacteria using liquid chromatography-mass spectrometry.

Recently, specific biomarkers in the surface-enhanced Raman scattering (SERS) spectra of bacteria have been successfully exploited for rapid bacterial antibiotic susceptibility testing (AST) - dubbed SERS-AST. The biomolecules responsible for these bacterial SERS biomarkers have been identified as several purine derivative metabolites involved in bacterial purine salvage pathways (W. R. Premasiri, J. C. Lee, A. Sauer-Budge, R. Theberge, C. E. Costello and L. D. Ziegler, Anal. Bioanal. Chem., 2016, 408, 4631). Here we quantified these metabolites in the SERS spectra of Staphylococcus aureus and Escherichia coli using ultra-performance liquid chromatography/electrospray ionization-mass spectrometry (UPLC/ESI-MS). The time dependences of the concentrations of these molecules were measured using 13C- or 12C-purine derivatives as internal and external standards respectively in UPLC/ESI-MS measurements. Surprisingly, a single S. aureus and an E. coli cell were found to release millions of adenine and hypoxanthine into a water environment in an hour respectively. Furthermore, simulated SERS spectra of bacterial supernatants based on the mixtures of purine derivatives with measured concentrations also show great similarity with those of the corresponding bacterial samples. Our results not only provide a quantitative foundation for the emerging SERS-AST method but also suggest the potential of exploiting SERS for in situ monitoring the changes in bacterial purine salvage processes in response to different physical and chemical challenges.

Custom-designed arrays of anodic alumina nanochannels with individually tunable pore sizes.

We demonstrate a process to selectively tune the pore size of an individual nanochannel in an array of high-aspect-ratio anodic aluminum oxide (AAO) nanochannels in which the pore sizes were originally uniform. This novel process enables us to fabricate arrays of AAO nanochannels of variable sizes arranged in any custom-designed geometry. The process is based on our ability to selectively close an individual nanochannel in an array by using focused ion beam (FIB) sputtering, which leads to redeposition of the sputtered material and closure of the nanochannel with a capping layer of a thickness depending on the energy of the FIB. When such a partially capped array is etched in acid, the capping layers are dissolved after different time delays due to their different thicknesses, which results in differences in the time required for the following pore-widening etching processes and therefore creates an array of nanochannels with variable pore sizes. The ability to fabricate such AAO templates with high-aspect-ratio nanochannels of tunable sizes arranged in a custom-designed geometry paves the way for the creation of nanophotonic and nanoelectronic devices.

The relationship between brain metastasis and HER2 expression status in gastric cancer.

BACKGROUND: Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis. METHODS: HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021. We collected GC patients diagnosed between 2010 and 2016 from the SEER database. The primary endpoint was survival from the diagnosis of BM. Multivariable logistic regression was used to determine potential risk factors of BM at diagnosis in SEER database. Survival analysis was performed using the Kaplan-Meier method. RESULT: There were 513 HER2-positive GC patients, including 16 (3.1%) with BM. Among 38 brain metastasis GC patients we collected, 16 (42.1%) patients were HER2 positive. We collected 34,199 GC patients from the SEER database and there were 260 (0.76%) patients with BM at diagnosis. GC patients that are male, white, of younger age, with primary lesions located in the proximal stomach or with distant lymph nodes, liver, bone, or lung metastasis are more likely to develop BM. The median overall survival time from diagnosis of BM was 12.73 months, and the survival time from brain metastasis of HER2-positive patients was numerically shorter, though the difference was not significant (5.30 months vs.16.13 months, P = 0.28.) CONCLUSION: The incidence of BM in patients with HER2-positive gastric cancer is 4.08 times higher than that in general patients. The median overall survival time from BM is shorter for HER2-positive patients.

A novel vertical fan-out platform based on an array of curved anodic alumina nanochannels.

Focused ion beam lithography and a two-step anodization have been combined to fabricate a vertical fan-out platform containing an array of unique probes. Each probe comprises three anodic alumina nanochannels with a fan-out arrangement. The lithography is used to pattern an aluminum sheet with a custom-designed array of triangular 'cells' whose apexes are composed of nanoholes. The nanoholes grow into straight nanochannels under proper voltage in the first-step anodization. The second step uses a doubled voltage to induce lateral repulsion among the nanochannels' growth fronts originating in the same cell. Therefore, the fronts fan out. The repulsion roots in the inter-front distance being shorter than the naturally favoured length, which increases with anodization voltage. The fan-out evolution continues until the growth fronts originating in all the cells evolve into a close-packed two-dimensional hexagonal lattice whose spacing is identical to the favoured one. The chemical and physical mechanisms behind the fan-out fabrication are discussed. This novel fan-out platform facilitates probing and handling of many signals from different areas on a sample's surface and is therefore promising for applications in detection and manipulation at the nanoscale level.

Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins.

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC.

Sphingosine kinase 1 enhances colon cancer cell proliferation and invasion by upregulating the production of MMP-2/9 and uPA via MAPK pathways.

PURPOSE: Sphingosine kinase (SphK) 1 is an oncogenic enzyme promoting transformation, proliferation, and survival of a number of human tumor cells. However, its effect on colon cancer cell behavior has not been fully clarified. METHODS: SphK1 plasmid or SphK1 shRNA transfection and N,N-dimethylsphingosine (DMS) was used to regulate the expression and activity of SphK1 in colon cancer line LOVO. Cell proliferation, apoptosis, invasion, and protein expression were detected by MTT, flow cytometry, transwell chambers model, and western blot. The levels of metalloproteinases-2/9 (MMP-2/9) and urokinase plasminogen activator (uPA) were detected by ELISA. RESULTS: Overexpression of SphK1 after plasmid transfection markedly enhanced LOVO cell viability and invasiveness and reduced cell apoptosis. In contrast, inhibition of SphK1 by DMS and shRNA significantly suppressed cell viability and invasiveness but promoted cell apoptosis. SphK1 increased the constitutive expression of extracellular signal-regulated kinase1/2 (ERK1/2) but reduced the constitutive expression of p38 mitogen-activated protein kinase (MAPK). Blocking ERK1/2 pathway inhibited the biological effects induced by overexpression of SphK1. Blocking p38 MAPK pathway reversed the effects of DMS and SphK1 shRNA. Moreover, SphK1 was required for the production of MMP-2/9 and uPA in tumor cells, which was suppressed by ERK1/2 inhibitor U0126, but enhanced by the p38 MAPK inhibitor SB203580. CONCLUSIONS: SphK1 enhances colon cancer cell proliferation and invasiveness, meanwhile suppressing cell apoptosis. SphK1 promoting the secretion of MMP-2/9 and uPA via activation of ERK1/2 and suppression of p38 MAPK pathways maybe the molecular mechanisms for its regulation of the malignant behavior of colon cancer cell.

Efficacy and safety of PD-1 inhibitors combined with chemotherapy as first-line therapy for advanced esophageal cancer: A systematic review and network meta-analysis.

BACKGROUND: Different clinical trials for advanced esophageal cancer have investigated diverse immuno-oncology combinational treatment in first-line setting, but the optimal choice has not been identified. METHODS: We used PubMed, Embase, and Cochrane Library databases for systematic retrieval. The primary endpoint was overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (AEs) between immune checkpoint inhibitors combined with chemotherapy and chemotherapy. RESULTS: A total of five phase-III randomized controlled trials involving 3,163 patients met the inclusion criteria. Significantly improved OS (HR: 0.69, 95% CI: 0.62-0.76, P＜0.001), PFS (HR: 0.62, 95% CI: 0.55-0.70, P < 0.001) and ORR (RR: 1.41, 95% CI: 1.23-1.62, P＜0.001) were observed when programmed death 1 (PD-1) inhibitor was added to chemotherapy. Toripalimab plus chemotherapy achieved the best OS benefit than any other treatment examined (HR: 0.58, 95% CI: 0.43-0.78). The longest PFS was founded in both sintilimab-chemotherapy and camrelizumab-chemotherapy combination (HR: 0.56, 95% CI: 0.46-0.68). Patients treated with nivolumab-chemotherapy got the best ORR improvement as compared to other combinations (RR: 1.73, 95% CI:1.40-2.14). Camrelizumab-chemotherapy and pembrolizumab-chemotherapy caused a relatively lower incidence of grade ≥ 3 AEs than other immunotherapy combination regimens. Subgroup analyses suggested significant OS advantage in programmed death-ligand 1(PD-L1) tumor-positive score (TPS) ≥ 10% groups and obviously longer PFS in PD-L1 combined positive score (CPS) ≥ 10 groups. CONCLUSIONS: In advanced esophageal cancer, PD-1 inhibitors combined with chemotherapy as first-line therapy have better survival outcomes than chemotherapy with greater but manageable toxicity. Toripalimab-chemotherapy showed the best OS benefit over chemotherapy, while sintilimab-chemotherapy and camrelizumab-chemotherapy generated the best PFS. The highest ORR improvement was founded in patients receiving nivolumab plus chemotherapy.

Whole-Exome Sequencing Among Chinese Patients With Hereditary Diffuse Gastric Cancer.

Importance: The E-cadherin gene, CDH1, and the α-E-catenin gene, CTNNA1, were previously identified as hereditary diffuse gastric cancer (HDGC) susceptibility genes, explaining 25% to 50% of HDGC cases. The genetic basis underlying disease susceptibility in the remaining 50% to 75% of patients with HDGC is still unknown. Objective: To assess the incidence rate of CDH1 germline alterations in HDGC, identify new susceptibility genes that can be used for screening of HDGC, and provide a genetic landscape for HDGC. Design, Setting, and Participants: This cohort study conducted retrospective whole-exome and targeted sequencing of 284 leukocyte samples and 186 paired tumor samples from Chinese patients with HDGC over a long follow-up period (median, 21.7 [range, 0.6-185.9] months). Among 10 431 patients diagnosed with gastric cancer between January 1, 2002, and August 31, 2018, 284 patients who met the criteria for HDGC were included. Data were analyzed from August 1 to 30, 2020. Main Outcomes and Measures: Incidence rate of CDH1 germline alterations, identification of new HDGC susceptibility genes, and genetic landscape of HDGC. Results: Among 284 Chinese patients, 161 (56.7%) were female, and the median age was 35 (range, 20-75) years. The frequency of CDH1 germline alterations was 2.8%, whereas the frequency of CDH1 somatic alterations was 25.3%. The genes with the highest incidence (>10%) of private germline alterations (including insertions and deletions) in the HDGC cohort were MUC4, ABCA13, ZNF469, FCGBP, IGFN1, RNF213, and SSPO, whereas previously reported germline alterations of CTNNA1, BRCA2, STK11, PRSS1, ATM, MSR1, PALB2, BRCA1, and RAD51C were observed at low frequencies (median, 4 [range, 1-12] cases). Furthermore, enrichment of the somatic variant signature of exposure to aflatoxin suggested potential interaction between genetics and environment in HDGC. Double-hit events in genes such as CACNA1D were observed, which suggested that these events might serve as important mechanisms for HDGC tumorigenesis. In addition, germline variants of FSIP2, HSPG2, and NCKAP5 and somatic alterations of FGFR3, ASPSCR1, CIC, DGCR8, and LZTR1 were associated with poor overall survival among patients with HDGC. Conclusions and Relevance: This study provided a genetic landscape for HDGC. The study's findings challenged the previously reported high germline alteration rate of CDH1 in HDGC and identified new potential susceptibility genes. Analyses of variant signatures and double-hit events revealed potentially important mechanisms for HDGC tumorigenesis. Findings from the present study may provide helpful information for further investigations of HDGC.

Morphological evolution of porous nanostructures grown from a single isolated anodic alumina nanochannel.

Porous anodic aluminum oxide (AAO) membranes have been widely used as templates for growing nanomaterials because of their ordered nanochannel arrays with high aspect ratio and uniform pore diameter. However, the intrinsic growth behavior of an individual AAO nanochannel has never been carefully studied for the lack of a means to fabricate a single isolated anodic alumina nanochannel (SIAAN). In this study, we develop a lithographic method for fabricating a SIAAN, which grows into a porous hemispherical structure with its pores exhibiting fascinating morphological evolution during anodization. We also discover that the mechanical stress affects the growth rate and pore morphology of AAO porous structures. This study helps reveal the growth mechanism of arrayed AAO nanochannels grown on a flat aluminum surface and provides insights to help pave the way to altering the geometry of nanochannels on AAO templates for the fabrication of advanced nanocomposite materials.

Autocatalytic reaction in hydrolysis of difructose anhydride III.

Hydrolysis of several polysaccharides in neutral and weak acid environment has been shown to exhibit autocatalytic behavior. Because the pH value of the solution decreases during hydrolysis, it has been proposed that proton is the catalyst of the autocatalytic reaction. We monitored the hydrolysis of difructose anhydride III (DFA III) in both strong and weak acid environment using Raman spectroscopy and found that it is also an autocatalytic reaction. Its Raman signatures were analyzed with ab initio method. When the reaction product, fructose, is added in the beginning of the reaction, the speed of hydrolysis increases to a magnitude that cannot be explained by the rate enhancement due to a decrease in the pH value, indicating that proton alone is not an effective catalyst for the reaction. It is the combination of proton and a certain form of reaction product such as monosaccharide or its derivatives that catalyzes the hydrolysis of difructose anhydride III. Similar results are observed in the hydrolysis of cellobiose, suggesting the universality of this autocatalytic reaction. Our findings provide the first clue to a new autocatalytic pathway in the hydrolysis of polysaccharides.

Cronkhite-Canada syndrome with steroid dependency: A case report.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare nonhereditary disease characterized by chronic diarrhoea, diffuse gastrointestinal polyposis and ectodermal manifestations. The lethality of CCS can be up to 50% if it is untreated or if treatment is delayed or inadequate. More than 35% of the patients do not achieve long-term clinical remission after corticosteroid administration, with relapse occurring during or after the cessation of glucocorticoid use. The optimal strategy of maintenance therapy of this disease is controversial. CASE SUMMARY: A 47-year-old man presented to the hospital with a 3-mo history of frequent watery diarrhoea, accompanied by macular skin pigmentation that included the palms and soles, and onychodystrophy of the fingernails and toenails. Gastroscopy and colonoscopy revealed numerous polyps in the stomach and colon. After other possibilities were ruled out by a series of examinations, CCS was diagnosed and treated with prednisone. The patient took prednisone for more than 1 year before achieving complete resolution of his symptoms and endoscopic findings. The patient was then given prednisone 5 mg/d for 6 mo of maintenance therapy. With clinical improvement and polyp regression, prednisone was discontinued. Eight mo after the discontinuation of prednisone, the diarrhoea and gastrointestinal polyps relapsed. Therefore, the patient was given the same dose of prednisone, and complete remission was achieved again. CONCLUSION: It is necessary to extend the duration of prednisone maintenance therapy for CCS. Prednisone is still effective when readministered after relapse. Surveillance endoscopy at intervals of 1 year or less is recommended to assess mucosal disease activity.

Atomically-resolved interlayer charge ordering and its interplay with superconductivity in YBa2Cu3O6.81.

High-temperature superconductive (SC) cuprates exhibit not only a SC phase, but also competing orders, suppressing superconductivity. Charge order (CO) has been recognized as an important competing order, but its microscopic spatial interplay with SC phase as well as the interlayer coupling in CO and SC phases remain elusive, despite being essential for understanding the physical mechanisms of competing orders and hence superconductivity. Here we report the achievement of direct real-space imaging with atomic-scale resolution of cryogenically cleaved YBa2Cu3O6.81 using cross-sectional scanning tunneling microscopy/spectroscopy. CO nanodomains are found embedded in the SC phase with a proximity-like boundary region characterized by mutual suppression of CO and superconductivity. Furthermore, SC coherence as well as CO occur on both CuO chain and plane layers, revealing carrier transport and density of states mixing between layers. The CO antiphase correlation along the c direction suggests a dominance of Coulomb repulsion over Josephson tunneling between adjacent layers.

Identical-length nanowire arrays in anodic alumina templates.

Arrays of nanowires with identical length are fabricated by using ultrasound to remove the length fluctuation among nanowires, which are deliberately grown in burette-shaped nanochannels on an anodic anumina film. The process allows the fabrication of 10 micron Ag-nanowire arrays with length fluctuation as small as 0.09%. By integrating the process with a focused-ion-beam-based lithographic method to grow nanowires into selective nanochannels in an array, we fabricate arrays of uniform-length nanowires that are arranged in a custom-designed lateral geometry. The ability to fabricate such artificial nanomaterials paves the way for the exploitation of their unusual optical, electrical, and thermal properties.

Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480.

AIM: To investigate the effects of aspirin (acetylsalicylic acid) on proliferation and apoptosis of colorectal cancer cell line SW480 and its mechanism. METHODS: Cyclooxygenase (COX)-2 negative colorectal cancer cell line SW480 was treated with aspirin at concentrations of 2.5 mmol/L, 5.0 mmol/L, 10.0 mmol/L for different periods in vitro. Anti-proliferation effect of aspirin on SW480 was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were observed by flow cytometry (FCM). Transmission electron microscope (TEM) was used for morphological study. Apoptosis-associated genes were detected by immunohistochemical staining and Western blotting. RESULTS: Aspirin inhibited SW480 proliferation and induced apoptosis in a dose- and time-dependent manner. Treatment with different concentrations of aspirin significantly increased the proportions of cells at the G(0)/G(1)phase and decreased the proportions of cells at the S- and G(2)/M phases in a concentration-dependent manner. Aspirin not only induced apoptosis but also caused cell necrosis at a high concentration as well. After treatment with aspirin, SW480 cells displayed typically morphological features of apoptosis and necrosis under TEM, and increased the Bcl-2 expression in cells, but the expression of Bax was down regulated. CONCLUSION: Aspirin inhibits proliferation and induces apoptosis of SW480 cells. Its anti-tumor mechanism may arrest cell cycle and shift Bax/Bcl-2 balance in cells.

Timing of Doppler examination for the detection of arteriovenous fistula after percutaneous renal biopsy.

Percutaneous renal biopsy is frequently performed, and postbiopsy arteriovenous fistula (AVF) formation is not uncommon. In most cases, it is asymptomatic and remains undiagnosed, because Doppler examination is not performed routinely. We describe 2 cases of postbiopsy AVF of the kidney that were detected 61 and 17 months after renal biopsy, respectively. The subsequent superselective transcatheter arterial embolization was successful in both cases. An undetected AVF of the kidney can progress and lead to serious consequences. A follow-up Doppler examination of the kidney soon after renal biopsy and 6 months later is recommended for early detection of nonresolving AVFs to prevent further complications.

Bilateral xanthogranulomatous pyelonephritis.

Xanthogranulomatous pyelonephritis is an uncommon form of chronic bacterial pyelonephritis characterized by the destruction of renal parenchyma and the presence of granulomas, abscesses, and collections of lipid-laden macrophages (foam cells) replacing the renal parenchyma. This case report illustrates the clinical course of bilateral diffuse xanthogranulomatous pyelonephritis with a subtle manifestation in contrast to those typically presenting with fever, flank pain or urinary tract infection. The patient therefore received supportive treatment for 18 months without hemodialysis, instead of the curative treatment, bilateral nephrectomy, which would have caused immediate loss of residual renal function and dependence on hemodialysis.

NIK­ and IKKß­binding protein contributes to gastric cancer chemoresistance by promoting epithelial­mesenchymal transition through the NF­κB signaling pathway.

Systematic chemotherapy is indispensable for gastric cancer patients with advanced stage disease, but the occurrence of chemoresistance drastically limits treatment effectiveness. There is a tremendous need for identifying the underlying mechanism of chemoresistance. NIK­ and IKKß­binding protein (NIBP) (also known as TRAPPC9, trafficking protein particle complex 9) is a regulator of the cytokine­induced NF­κB signaling pathway which has been proven to play pivotal roles in the progression of various malignancies. Nevertheless, it is still ambiguous whether NIBP is involved in the chemoresistance of gastric cancer. The aim of the present study was to investigate the effect of NIBP on chemotherapy resistance of gastric cancer (GC) and to research the mechanisms of Ginkgo biloba extract 761 (EGb 761®) on reversing chemoresistence which has been confirmed in our previous study. In the present study, the results of immumohistochemisty revealed that the positive staining rates of NIBP, NF­κB p65 and NF­κB p­p65 in gastric cancer tissues were obviously higher than those in normal tissues. Furthermore, a close correlation was found to exist between the expression of NIBP and NF­κB p65 (p­p65) in gastric cancer tissues. Moreover, the overexpression of NIBP was closely related to tumor differentiation, depth of invasion, clinical stage and lymphatic metastasis in gastric cancer. Western blot analysis, real­time PCR, MTT assay and flow cytometric analysis were performed and the results demonstrated that compared with the gastric cancer SGC­7901 cells, the expression of NIBP, NF­κB p65, NF­κB p­p65 and mesenchymal marker vimentin were significantly increased in gastric cancer multidrug­resistant SGC­7901/CDDP cells, and the epithelial cell marker ZO­1 was significantly decreased. Meanwhile, it was found that SGC­7901/CDDP cells were accompanied by spindle­like mesenchymal appearance and upregulation of stem cell marker CD133 which has been verified to be an upstream regulatory gene of epithelial­mesenchymal transition (EMT). Further research confirmed that downregulation of NIBP by Ginkgo biloba extract (EGb) 761 EGb 761 suppressed the cis­diamminedichloroplatinum(II) (CDDP)­induced NF­κB signaling pathway, EMT and the expression of CD133 in SGC­7901 and SGC­7901/CDDP cells. Altogether, these data indicate that the NIBP­regulated NF­κB signaling pathway plays a pivotal role in the chemoresistance of gastric cancer by promoting CD133­induced EMT.