Clinical trajectories preceding incident dementia up to 15 years before diagnosis: a large prospective cohort study.

BACKGROUND: Dementia has a long prodromal stage with various pathophysiological manifestations; however, the progression of pre-diagnostic changes remains unclear. We aimed to determine the evolutional trajectories of multiple-domain clinical assessments and health conditions up to 15 years before the diagnosis of dementia. METHODS: Data was extracted from the UK-Biobank, a longitudinal cohort that recruited over 500,000 participants from March 2006 to October 2010. Each demented subject was matched with 10 healthy controls. We performed logistic regressions on 400 predictors covering a comprehensive range of clinical assessments or health conditions. Their evolutional trajectories were quantified using adjusted odds ratios (ORs) and FDR-corrected p-values under consecutive timeframes preceding the diagnosis of dementia. FINDINGS: During a median follow-up of 13.7 [Interquartile range, IQR 12.9-14.2] years until July 2022, 7620 subjects were diagnosed with dementia. In general, upon approaching the diagnosis, demented subjects witnessed worse functional assessments and a higher prevalence of health conditions. Associations up to 15 years preceding the diagnosis comprised declined physical strength (hand grip strength, OR 0.65 [0.63-0.67]), lung dysfunction (peak expiratory flow, OR 0.78 [0.76-0.81]) and kidney dysfunction (cystatin C, OR 1.13 [1.11-1.16]), comorbidities of coronary heart disease (OR 1.78 [1.67-1.91]), stroke (OR 2.34 [2.1-1.37]), diabetes (OR 2.03 [1.89-2.18]) and a series of mental disorders. Cognitive functions in multiple tests also demonstrate decline over a decade before the diagnosis. Inadequate activity (3-5 year, overall time of activity, OR 0.82 [0.73-0.92]), drowsiness (3-5 year, sleep duration, OR 1.13 [1.04-1.24]) and weight loss (0-5 year, weight, OR 0.9 [0.83-0.98]) only exhibited associations within five years before the diagnosis. In addition, serum biomarkers of enriched endocrine, dysregulations of ketones, deficiency of brand-chain amino acids and polyunsaturated fatty acids were found in a similar prodromal time window and can be witnessed as the last pre-symptomatic conditions before the diagnosis. INTERPRETATION: Our findings present a comprehensive temporal-diagnostic landscape preceding incident dementia, which could improve selection for preventive and early disease-modifying treatment trials.

Phylogenetic and ion-response analyses reveal a relationship between gene expansion and functional divergence in the Ca2+/cation antiporter family in Angiosperms.

KEY MESSAGE: Plant CaCA superfamily genes with higher tendency to retain after WGD are more gene expression and function differentiated in ion-response. Plants and animals face different environmental stresses but share conserved Ca2+ signaling pathways, such as Ca2+/Cation transport. The Ca2+/cation antiporters superfamily (CaCAs) is an ancient and widespread family of ion-coupled cation transporters found in all kingdoms of life. We analyzed the molecular evolution progress of the family through comparative genomics and phylogenetics of CaCAs genes from plants and animals, grouping these genes into several families and clades, and identified multiple gene duplication retention events, particularly in the CAX (H+/cation exchanger), CCX (cation/Ca2+ exchanger), and NCL (Na+/Ca2+ exchanger-like) families. The tendency of duplication retention differs between families and gene clades. The gene duplication events were probably the result of whole-genome duplication (WGD) in plants and might have led to functional divergence. Tissue and ion-response expression analyses revealed that CaCAs genes with more highly differentiated expression patterns are more likely to be retained as duplicates than those with more conserved expression profiles. Phenotype of Arabidopsis thaliana mutants showed that loss of genes with a greater tendency to be retained after duplication resulted in more severe growth deficiency. CaCAs genes in salt-tolerant species tended to inherit the expression characteristics of their most recent common ancestral genes, with conservative ion-response expression. This study indicates a possible evolutionary scheme for cation transport and illustrates distinct fates and a mechanism for the evolution of gene duplicates. The increased copy numbers of genes and divergences in expression might have contributed to the divergent functions of CaCAs protein, allowing plants to cope with environmental stresses and adapt to a larger number of ecological niches.

[Research in rheological properties of four types of ophthalmic preparations].

This study is prepared to provide the basis of rheological parameters for the additional quality standard of ophthalmic gels, the rheological properties of the ophthalmic gels and the other three types of ophthalmic preparations. The medicines were compared through the study of the rheological properties for four types of ophthalmic preparations. The cone-plate rheometer was used to determine the dynamic and steady rheological parameters of four types of ophthalmic preparations. The similarities and differences of the measured results were analyzed to summarize the rheological indexes and parameters which are applied to distinguish the ophthalmic gels and the other types of ophthalmic preparations. 1 The elastic modulus should be greater than the viscous modulus for the ophthalmic gels in the range of the linear viscoelastic region. 2 The ophthalmic gels should be shear thinning non-Newtonian fluid with a certain yield stress and thixotropy. 3 The dynamic viscosity of the ophthalmic gels should be greater than 0.5 Pa·S at the temperature of 25 ℃ with the 50 s-1 shear rate. The typical rheological indexes and parameters of the ophthalmic gels were proposed in this article. The determination methods are simple and feasible. The rheological indexes and parameters have an important significance in the prescription design, production technology and quality control of the ophthalmic gels.

FOXA1 Expression Significantly Predict Response to Chemotherapy in Estrogen Receptor-Positive Breast Cancer Patients.

PURPOSE: Most estrogen receptor (ER)-positive breast cancer responds poorly to chemotherapy and no single cost-effective biomarker capable of selecting chemosensitive ones has been found yet. We investigated FOXA1 for its role in predicting chemosensitivity of this subgroup in neoadjuvant chemotherapy settings. METHODS: We reviewed pathologic slides of 123 patients who were diagnosed with ER-positive breast cancer on core needle biopsy and underwent neoadjuvant chemotherapy at our institution between 2002 and 2012. FOXA1 expression and pathologic response were evaluated. We then statistically analyzed FOXA1 expression and its relationship with chemosensitivity. RESULTS: FOXA1 expression before NAC was correlated with poor chemoresponse in ER-positive as well as luminal A and luminal B breast cancer patients (p = 0.002, 0.001, and 0.049 respectively). Significant association between change of FOXA1 staining position after NAC and chemosensitivity also was observed (p = 0.024). Multivariate analysis identified FOXA1 expression before NAC as an independent predictor of chemosensitivity in ER-positive and luminal A breast cancer patients [p = 0.002; relative risk (RR) 0.163; 95 % confidence interval (CI) 0.053-0.500, and p = 0.002; RR 0.055; 95 % CI 0.008-0.353, respectively]. Additionally, change of FOXA1 staining position after NAC was shown to be an independent predictor of chemoresponse in luminal B subtype breast cancer patients (p = 0.012; RR 0.153; 95 % CI 0.035-0.665). CONCLUSIONS: FOXA1 expression can independently predict chemosensitivity of ER-positive breast cancer patients.

[Studies on terpenoids from Zygophyllum fabago].

This study was to investigate the chemical constituents of the aerial part of Zygophyllumfabago, by phytochemical methods. The compounds were isolated by silica gel and Sephadex LH-20 column chromatographies from the EtOAc extract. Their structures were characterized by various spectroscopic data (1H-NMR, 13C-NMR, MS) and comparison with the literature. As a result, thirteen compounds were isolated and their structures were identified as 1-hydroxyhinesol(1), hinesol(2), atractylenolactam(3), beta-eudesmol (4), 5alpha-hydroperoxy-beta-eudesmol(5), 12-hydroxy-valenc-1(10)-en-2-one(6), pubinernoid A(7), (6S,7E)-6-hydroxy-4,7-megastigmadien-3,9-dione(8), 3-hydroxy-5alpha, 6alpha-epoxy-beta-ionone (9), (3S,5R, 6S, 7E)-3, 5, 6-trihydroxy-7-megastigmen-9-one(10), (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one(11), (S)-3-hydroxy-beta-ionone(12), and blumenol A(13). Compounds 1-7 were sesquiterpenoids and 8-13 were megastigmane type norsesquiterpenoids. All the compounds were obtained from Z. fabago for the first time, and compound 1 was a new natural product.

Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease.

Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.

Plasma proteomic profiles predict individual future health risk.

Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative score markedly stratified the risk for 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, and genitourinary diseases, cancers, and mortality. The discriminations witnessed high accuracies achieved by ProRS for 10 endpoints (e.g., cancer, dementia, and death), with C-indexes exceeding 0.80. Notably, ProRS produced much better or equivalent predictive performance than established clinical indicators for almost all endpoints. Incorporating clinical predictors with ProRS enhanced predictive power for most endpoints, but this combination only exhibited limited improvement when compared to ProRS alone. Some proteins, e.g., GDF15, exhibited important discriminative values for various diseases. We also showed that the good discriminative performance observed could be largely translated into practical clinical utility. Taken together, proteomic profiles may serve as a replacement for complex laboratory tests or clinical measures to refine the comprehensive risk assessments of multiple diseases and mortalities simultaneously. Our models were internally validated in the UK Biobank; thus, further independent external validations are necessary to confirm our findings before application in clinical settings.

Clinicopathologic variables predicting tumor response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND AND OBJECTIVES: To identify clinicopathologic variables that could predict pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: The study enrolled 108 patients who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and December 2010. Tumor responses to neoadjuvant chemotherapy were assessed in terms of tumor regression. Statistical analyses were performed to identify factors associated with pathologic tumor response. RESULTS: Tumor regression was found in 22.2% (24/108) patients, patients with tumor regression observed better overall survival as compared to that of patients without tumor regression. Univariate and multivariate analyses observed that both tumor differentiation and tumor size were independent predictors of tumor regression. CONCLUSIONS: This study suggests that both tumor differentiation and tumor size is the most important clinical predicator of pathologic tumor response, it may be of benefit in the selection of treatment options in locally advanced gastric cancer.

Sentinel lymph node biopsy predicts lymph node metastasis in early gastric cancer: a retrospective analysis.

BACKGROUND/AIMS: Minimally invasive treatments have emerged as the frontline therapy for patients with early gastric cancer (EGC). However, some cT1N0 patients with EGC may have lymph node metastasis because of inadequate evaluation. This study aimed to investigate the diagnostic accuracy of sentinel lymph node (SLN) and tried to find out feasible criteria for SLN-guided minimally invasive surgery for EGC. METHODS: A solitary metastasis lymph node was taken as SLN, the features of lymph node metastasis were analyzed retrospectively in 255 patients with EGC, and the result was then compared with a SLN biopsy in 23 patients with EGC. RESULTS: Depth of invasion and tumor size were independent risk factors for lymph node metastasis in EGC. The lymph node metastasis rate for mucosal carcinoma with a diameter <4 cm was 2.5%, and it was 13.3% when the diameter was ≥ 4 cm (p = 0.040). For submucosal carcinoma, it was 25.4% when the tumor diameter was <3 cm and 50.5% when the diameter was ≥ 3 cm (p = 0.003). The accuracy, sensitivity, and specificity of SLN biopsy in EGC was 100%, respectively. The distribution characteristics of SLN were consistent with those of lymph node metastasis in EGC. CONCLUSIONS: SLN-guided minimally invasive surgery could be safely performed in EGC according to feasible criteria.

[Study on the proficiency testing program of pharmaceutical preparation analysis].

This proficiency testing program is established to evaluate the pharmaceutical preparation analysis capacity of laboratories recommended by 18 countries and economies. It was authorized by Asia Pacific Laboratory Accreditation Cooperation (APLAC), and organized by Shanghai Institute for Food and Drug Control (SIFDC) and China National Accreditation Service for Conformity Assessment (CNAS). The 0.3sigma test is used to evaluate the homogeneity and stability of the proficiency testing sample. The results of the laboratories were assessed by Z-score. The robust average and the robust standard deviation of the participants' results were calculated as assigned value and standard deviation for performance assessment of hydrochlorothiazide and captopril using robust statistics. Thirty-three of 38 laboratories recommended by 18 countries and economies sent their results back. Twenty-four laboratories' results were observed as satisfactory. Five laboratories were identified as having reported at least one questionable result. Four laboratories were identified as having reported at least one unsatisfactory result.

[Prognostic effect of postoperative resection-margin status for intraoperative positive resection margins in patients with advanced gastric cancer].

OBJECTIVES: To investigate prognostic effect of postoperative resection-margin status for intraoperatively positive resection margin in advanced gastric cancer and discuss the treatment choice for intraoperatively positive resection margins. METHODS: A retrospective study was investigated in 64 advanced gastric cancer patients with positive resection margin after potentially curative resection. The survival between 50 patients who was re-excised to a negative resection margin (NR group) and 14 patients who were left with positive resection margin (PR group) was compared. Prognostic factors were analyzed using univariate and multivariate Cox regression model analysis. RESULTS: The median survival in the PR group was 17.0 months (95%CI: 11.6 - 22.4) as compared with 23.0 months (95%CI: 20.5 - 25.5) in the NR group (P = 0.045). However, resection-margin status lost significance on multivariate analysis. In the subgroup of D2 lymphadenectomy, the median survival in the PR group and NR group were 17.0 months (95%CI: 12.0 - 22.0) and 24.0 months (95%CI: 19.8 - 28.1) respectively; multivariate analysis further identified resection margin status as an independent prognostic factor. CONCLUSIONS: Re-excision for intraoperatively positive margin to negative margin improves the prognosis of the patients with advanced gastric cancer, and re-excision is the first choice when intraoperative frozen section detects a positive margin. Routine frozen section of resection margin should be mandatory in all advanced gastric cancer undergoing potentially curative surgery.

Surgical management of monomorphic epitheliotropic intestinal T-cell lymphoma followed by chemotherapy and stem-cell transplant: A case report and review of the literature.

BACKGROUND: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and rapidly progressive intestinal T-cell non-Hodgkin lymphoma associated with a very poor prognosis and a median survival of 7 mo. Advances in the identification of MEITL over the last two decades have led to its recognition as a separate entity. MEITL patients, predominantly male, typically present with vague and nonspecific symptoms and diagnosis is predominantly confirmed at laparotomy. Currently, there are no standardized treatment protocols, and the optimal therapy remains unclear. CASE SUMMARY: We report a case of MEITL that was initially considered to be gastrointestinal stromal tumor (GIST) and Imatinib was administered for one cycle. The 62-year-old man presented with abdominal pain, abdominal distension, and weight loss of 20 pounds. Within 2 wk, the size of the mass considerably increased on computed tomography scans. The patient underwent surgery followed by chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and stem-cell transplant. A correct diagnosis of MEITL was established based on postoperative pathology. Immunophenotypically, the neoplastic cells fulfilled the diagnostic criteria for MEITL as they were CD3+, CD4+, CD8+, CD56+, and TIA-1+. CONCLUSION: Given that MEITL has no predisposing factor and presents with vague symptoms with rapid progression, the concomitant presence of abdominal symptoms and B symptoms (weight loss, fever, and night sweats) with hypoalbuminemia, anemia, low lymphocytic count and endoscopic findings of diffuse infiltrating type lesions should alert physicians to this rare disease, especially when it comes to Asian patients. Immediate laparotomy should then be carried out followed by chemotherapy and stem-cell transplant.

High GP73 Expression Correlates with Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study.

Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.

Low level of serum high-density lipoprotein cholesterol in gastric cancer correlates with cancer progression but not survival.

BACKGROUND: The clinical significance of lipid profile in gastric cancer remains unclear. The aim of the present study was to investigate the correlation between serum lipid profiles and patient clinical parameters as well as prognosis in gastric cancer. METHODS: The preoperative plasma lipid profile levels of 358 gastric cancer patients, who were operated in between 2001 and 2009, were retrospectively evaluated, and the correlation between these factors and patient clinical parameters as well as survival were analyzed. RESULTS: There was a significant association between serum high-density lipoprotein cholesterol level (HDL-C <54.2 mg/dL) and cancer progression, Logistic regression analysis revealed that lower level of serum HDL-C was an independent risk factor for deeper cancer invasion, nodal metastasis as well as late stage in patients with gastric cancer. However, no significant association was reported between other lipid markers [triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL) and apolipoprotein A (apoA)] and lymph node involvement as well as stage of disease. In univariate analysis and multivariate analyses regarding patient's survival, there was no significant association between the groups in terms of TG, TC, HDL-C, LDL-C, VLDL and apoA. CONCLUSIONS: Low level of serum HDL-C in gastric cancer correlates with cancer progression but not patient's survival.

Prediction of recurrence of early gastric cancer after curative resection.

BACKGROUND: Recurrence of early gastric cancer (EGC) after curative resection is rare, and the types of EGC that may recur have not been well studied. We attempted to create a system for predicting recurrence of EGC after R0 resection. METHODS: From January 1987 to April 2005, 2,923 patients with EGC who underwent curative resection were retrospectively studied. Of them, 79 patients (2.7%) experienced recurrence. Logistic regression was performed to identify independent risk factors for overall recurrence and early recurrence (recurred within 24 months after resection) of EGC. A nomogram was developed on the basis of a Cox regression. RESULTS: Median time to recurrence was 20.5 months, and early recurrence accounted for 60.7% of instances. Presence of lymph node metastasis and elevated gross type were independent risk factors for overall recurrence; patients with both identified risk factors had a higher recurrence rate than average level (17.5% vs. 2.7%, P < 0.001). Meanwhile, male gender, elevated gross type, and presence of lymph node metastasis were significantly associated with early recurrence, and in patients with all of the aforementioned identified risk factors, the early recurrence rate was higher (12.2% vs. 1.6%, P < 0.001). A nomogram for predicting the disease-free survival after operation was constructed. Its c-index was 0.79 and it appeared to be accurate. CONCLUSIONS: Recurrence of EGC after curative resection can be predicted by using common clinical characteristics. Patients at high risk of overall and early recurrence could be identified; individual disease-free survival was predictable by the internally validated nomogram.

Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition.

BACKGROUND: Regulatory T (Treg) cells are a major component of the microenvironment of hepatocellular carcinoma (HCC) contributing to immunosuppression. The present study aimed to evaluate the effects of Treg cells on the invasion potential of HCC. METHODS: Infiltrating Treg cells were isolated from fresh HCC tissues by immunomagnetic bead separation and detected by flow cytometry. Circulating tumor cells (CTCs) were detected using the CellSearch platform. The cell migration and invasion potentials were evaluated by Transwell assays. The cell viability was tested by the cell counting kit-8 (CCK8) approach, and the apoptosis rates were determined by flow cytometry. The concentrations of active transforming growth factor-ß1 (TGFß1) were measured by enzyme-linked immunosorbent assay. RESULTS: Infiltrating Treg cells significantly correlated with the number of CTCs and vascular invasion (both P<0.05). Moreover, these cells could greatly promote HCC migration, invasion, and proliferation, and inhibit HCC apoptosis. Polymerase chain reaction and Western blot assays revealed that Treg cells significantly decreased the expression levels of epithelium-related molecules and increased the expression levels of mesenchyme-related molecules. Treg cells could activate Smad2/3 via secreting TGFß1, and these effects could be impaired by knocking down the expression of TGFß1 in Treg cells. CONCLUSIONS: The involvement of infiltrating Treg cells in triggering the TGFß1 signaling pathway and promoting the epithelial-mesenchymal transition (EMT) of cancer cells during tumor hematogenous dissemination is presumably responsible for increasing the invasiveness potential of HCC cells. Targeting Treg cells in microenvironments can be a promising therapeutic strategy to improve the prognosis for patients with HCC undergoing resection.

Clinicopathologic characteristics and prognosis for young gastric adenocarcinoma patients after curative resection.

BACKGROUND: Conflicting results from previous studies on gastric adenocarcinoma (GC) in young patients have led to controversy surrounding the prognosis for young GC patients. METHODS: The authors studied 6954 patients with GC who received curative resections. They were classified into three groups: those aged 40 years or less ("young," 12.7%); those aged 41-65 years ("middle-aged," 66.7%); and those aged more than 65 years ("elderly," 20.6%). Clinicopathologic characteristics and overall survival rates were analyzed. RESULTS: Young patients were predominately female and had tumors that were histologically undifferentiated. However, in regard to T4 invasion, N3 lymph node metastasis, and TNM stage IV, the characteristics of the tumors of young patients were similar to those of middle-aged and elderly patients. Overall survival rate was significantly better in young patients than middle-aged patients (P = .018) and elderly patients (P < .001). Stratified by TNM stage, young patients showed better overall survival at stage I than middle-aged patients, and at stages I, II, and IIIa than elderly patients. Multivariate analysis indicated that age was an independent prognostic factor (as well as gender, operation type, depth of invasion, and lymph node status). CONCLUSIONS: The predominance of female cases and tumors that were histologically undifferentiated were distinctive characteristics in young patients. Young patients could gain a survival benefit after curative resection with stage I disease.

Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer.

AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.

Neoadjuvant chemotherapy versus surgery alone for locally advanced gastric cancer: a retrospective comparative study.

BACKGROUND/AIMS: Preoperative chemotherapy is considered an effective treatment option for patients with gastric cancer. We retrospectively evaluated neoadjuvant chemotherapy with oxaliplatin, leucovorin and 5-flurouracil (OLF) in patients with locally advanced gastric cancer to determine its feasibility, as well as impact on the curative resection rate and patients' survival. METHODOLOGY: A total of 87 patients with locally advanced gastric cancer that underwent preoperative chemotherapy combined with surgery or surgery alone were randomly matched according to the clinical TNM stage. The clinical responses to chemotherapy were assessed. The curative rate, postoperative complications and patients' survival between both groups were compared. RESULTS: The two groups were well matched. Complete or partial response was observed in 51.7% (15/29) of patients in the OLF group, and three (10.3%) of them had complete pathologic response. The curative resection rates were 89.7% in the OLF group and 77.6% in the surgery alone group. The postoperative complications were equal for both groups. The mean survival is 20.6 months in the OLF group vs. 19.9 months in the surgery alone group (p=0.02). CONCLUSIONS: Neoadjuvant chemotherapy using OLF combination is active in gastric cancer and the toxicity level is acceptable. This treatment improves the curative resection rate and patients' survival in locally advanced gastric cancer.

[Effects of hepatocyte growth factor gene transfection on adriamycin-induced apoptosis of gastric cancer cells in vitro].

OBJECTIVE: To investigate the effects of hepatocyte growth factor (HGF) on adriamycin-induced apoptosis of gastric cancer cells in vitro. METHODS: An eukaryotic expression plasmid (pIRES2-EGFP) containing HGF (pIRES2-EGFP-HGF) was constructed. Human gastric cancer cell line MKN-45 cells were transfected in vitro with pIRES2-EGFP containing HGF or not. RT-PCR and Western blot were used to determine the target gene expression. Function of HGF was determined by MDCK cell scattering assay. Cell viability was tested by MTT assay. Apoptosis was evaluated by DNA fragmentation assay as well as flow cytometry using PI staining. RESULTS: The HGF transfected MKN45 cells could stably express HGF mRNA, and secrete HGF protein to the cell culture median which was detected to exhibit normal function. The cell inhibition rate induced by adriamycin in HGF-transfected cells was decreased as compared to that of parental and mock transfected cells. When treated with adriamycin at 0.1 microg/ml, the parental and mock transfected cells present typical apoptotic ladder on DNA electrophoresis while HGF transfected cell did not. The apoptotic rate was decreased in HGF transfected cells as compared with that of parental and mock transfected cells. CONCLUSION: HGF gene transfection may suppress adriamycin-induced apoptosis of gastric cancer cells.