Gastric cancer derived exosomes mediate the delivery of circRNA to promote angiogenesis by targeting miR-29a/VEGF axis in endothelial cells.

Accumulating evidence has been found that circular RNA (circRNA) plays a critical role in the initiation and development of various diseases by modulating gene expression in the cytoplasm. However, the role of circ_0044366 (termed circ29) in gastric cancer (GC) has yet to be elusive. We detected that exosomal circ29 was confirmed to be highly expressed in GC and can significantly impair the proliferation, migration, tube formation of HUVEC by exosomal communication. Interestingly, this effect could be blocked by the effect of miR-29a. In brief, we confirmed that circ29, as a sponge of miR-29a, plays a responsible role in the occurrence and development of GC by regulating the VEGF pathway. Therefore, it may be used as a potential target for the treatment of GC.

Exosomal miRNAs as circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.

Exosomes secreted by living cancer cells can regulate metastasis. Exosomal miRNAs can reflect pathological conditions of the original cancer cells. Therefore, we aim to identify exosomal miRNAs as circulating biomarkers for haematogenous metastasis of gastric cancer. Pre-treatment serum samples of eighty-nine patients with stage II/III gastric cancer were collected. Thirty-four of them developed haematogenous metastasis after surgery and the other fifty-five did not. Extraction of exosomes was validated by western blot, transmission electron microscopy and nanoparticle tracking analysis. MiRNA qPCR array was performed in three matched pairs of samples. Internal control was selected from PCR array and validated in the remaining samples. Expressions of exosomal miRNAs were evaluated in the remaining samples by RT-qPCR, as well as in gastric cancer tissue samples and cell culture medium. Expression levels of exosomal miRNAs were analysed with clinical characteristics. The results indicated thirteen up-regulated and six down-regulated miRNAs were found after normalization. MiR-379-5p and miR-410-3p were significantly up-regulated in metastatic patients (P < .01). Higher expression of exosomal miR-379-5p or miR-410-3p showed shorter progression-free survival of the patients (P < .05). It was also found that miR-379-5p and miR-410-3p were down-regulated in gastric cancer tissue samples, while they were significantly up-regulated in gastric cancer cell culture medium compared with cancer cells. In conclusion, exosomal miRNAs are promising circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.

DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 pathway.

Gastric cancer is a common malignancy worldwide. The occurrence of multidrug resistance (MDR) is the major obstacle for effective gastric cancer chemotherapy. In this study, the in-depth molecular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated. The results showed that DJ-1 expression level was higher in MDR variant SGC7901/VCR cells than that in its parental SGC7901 cells. Moreover, DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells, while DJ-1 knockdown in SGC7901/VCR cells induced re-sensitization to adriamycin, vincristine, cisplatin, and 5-fluorouracil. These results suggested that DJ-1 mediated the development of MDR in SGC7901 gastric cancer cells. Importantly, further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells. Meanwhile, we found that PI3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN, consequently resulting in Nrf2 phosphorylation and activation, and thereby inducing Nrf2-dependent P-glycoprotein (P-gp) and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells. Overall, these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells. The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells, prompting its further investigation as a molecular target to overcome MDR.

Complete histopathologic examination of risk reduction gastrectomy specimens for CDH1 germline mutation: Is it warranted in routine clinical practice?

AIMS: CDH1 germline mutation is associated with high penetrance of hereditary diffuse gastric cancer (HDGC). Due to the lack of endoscopically identifiable lesions, routine surveillance is ineffective in the early detection of gastric cancer, and risk-reduction gastrectomy is often recommended. Many academic pathology departments elect to submit the entire gastrectomy specimen for histological examination, which is associated with significantly increased cost, technical and professional time, and turnaround time. METHODS: We present our experience with 5 completely submitted and 2 representatively submitted prophylactic total gastrectomy cases in HDGC patients. RESULTS: Multifocal intramucosal signet ring cell carcinoma was identified in all cases except one, in which only in situ carcinoma was identified. The tumoral foci (2 to 35 per case; average 14.4) were concentrated in proximal stomach. No submucosal invasion or nodal metastases was seen in any case. The final stage was either stage 0 (pTisN0cM0) or stage 1a (pT1aN0cM0). CONCLUSIONS: Our findings are in line with that reported in the literature. Considering that deeply invasive carcinoma is very rare in this situation, and no further treatment is indicated for the vast majority of those patients, complete submission and pathologic examination of the entire stomach provides little additional value for routine clinical management. We propose a two-step approach with targeted submission of the proximal stomach, and subsequent entire submission of the remaining stomach if no intramucosal carcinoma is identified during the initial targeted examination.

N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo.

Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca2+-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.

Exosome-mediated transfer of CLIC1 contributes to the vincristine-resistance in gastric cancer.

Our previous study shows that high Chloride intracellular channel 1 (CLIC1) expression can efficiently enhance invasion and migration of gastric cancer (GC) cells in vitro. Growing evidences have found that exosomes are involved in chemotherapy resistance in several cancers including GC. We aimed to evaluate the effect of the exosome-mediated transfer of CLIC1 in the vincristine-resistance of GC. The effect of exosome-mediated transfer of CLIC1 on the development of resistance to vincristine in GC cell line SGC-7901 and the potential underlying mechanisms were investigated by Cell Counting Kit-8 (CCK8), RT-PCR, and Western blotting. Exosomes were isolated from cell supernatants by differential ultracentrifugation. Comparing with SGC-7901, the expression level of CLIC1 is higher in vincristine­resistant cell line SGC-7901/VCR (P < 0.05). After silencing the expression of CLIC1 by RNA interference, the half inhibition concentration (IC50) to vincristine decreased significantly in SGC-7901/VCR, and the expression of CLIC1 decreased significantly in exosomes from SGC-7901/VCR. After 48 h co-culturing with exosomes from SGC-7901/VCR, the IC50 to vincristine in SGC-7901 increased significantly, and the expression of CLIC1, P-gp, and Bcl-2 were significantly up-regulated. CLIC1 was closely associated with the resistance to vincristine in GC, and exosome-mediated transfer of CLIC1 could induce the development of resistance to vincristine in vitro. The possible mechanism was related to up-regulated P-gp and Bcl-2. However, in vivo study was needed to confirm the results in future.

Bufalin induces protective autophagy by Cbl-b regulating mTOR and ERK signaling pathways in gastric cancer cells.

Bufalin, a natural small-molecule compound derived from the traditional Chinese medicine Chan su, has shown promising anti-cancer effects against a broad variety of cancer cells through different mechanisms. It has been reported to induce autophagy in gastric cancer cells. However, the molecular mechanism involved is not fully elucidated. In the present study, we aimed to investigate the molecular mechanism by which bufalin induce autophagy in human gastric cancer cells. We found that bufalin induced apoptosis and autophagy in gastric cancer cells, and autophagy prevented human gastric cancer cells from undergoing apoptosis. Bufalin treatment changed the expression of autophagy-related proteins. Moreover, phosphorylated Akt, mTOR, and p70S6K were all significantly decreased, while phosphorylated ERK1/2 was increased by bufalin. Pretreatment of MGC803 cells with the ERK1/2-specific inhibitor PD98059 led to the down-regulation of LC3 II. Further study showed that Cbl-b positively regulated autophagy by suppressing mTOR and enhancing ERK1/2 activation. Therefore, our data provide evidence that bufalin induces autophagy in MGC803 cells via both Akt/mTOR/p70S6K and ERK signaling pathways, and Cbl-b-mediated suppression of mTOR and activation of ERK1/2 might play an important role.

Analysis of Extracellular Vesicles in Gastric Juice from Gastric Cancer Patients.

Extracellular vesicles (EVs) are secretory membrane vesicles containing lipids, proteins, and nucleic acids; they function in intercellular transport by delivering their components to recipient cells. EVs are observed in various body fluids, i.e., blood, saliva, urine, amniotic fluid, and ascites. EVs secreted from cancer cells play important roles in the formation of their environment, including fibrosis, angiogenesis, evasion of immune surveillance, and even metastasis. However, EVs in gastric juice (GJ-EVs) have been largely unexplored. In this study, we sought to clarify the existence of GJ-EVs derived from gastric cancer patients. GJ-EVs were isolated by the ultracentrifuge method combined with our own preprocessing from gastric cancer (GC) patients. We verified GJ-EVs by morphological experiments, i.e., nanoparticle tracking system analysis and electron microscopy. In addition, protein and microRNA markers of EVs were examined by Western blotting analysis, Bioanalyzer, or quantitative reverse transcription polymerase chain reaction. GJ-EVs were found to promote the proliferation of normal fibroblast cells. Our findings suggest that isolates from the GJ of GC patients contain EVs and imply that GJ-EVs partially affect their microenvironments and that analysis using GJ-EVs from GC patients will help to clarify the pathophysiology of GC.

Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling.

In this study, we aimed to investigate the effects of curcumin on cell activities of gastric cancer (GC), and the connection between curcumin and P53, as well as, PI3K signaling. This study was conducted with two cell lines SGC-7901 and BGC-823, both were exposed to curcumin at the concentrations of 0, 10, 20, and 40 µm. MTT assay, flow cytometry (FCM) assay, transmission electron microscopy (TEM) were used to study the underlying mechanisms of curcumin in respective of proliferation, apoptosis, and autophagy. Western blot assay was also employed to detect impacts of curcumin on tophosphatidylinositol-3 kinase (PI3K) and P53 signaling pathways-related proteins. MTT assay displayed that curcumin inhibited GC cell proliferation. FCM results indicated that curcumin induced the apoptosis of GC cells. TEM revealed that curcumin induced autophagy in GC cells. Western blot results showed that curcumin activated P53 signaling pathway and inhibited PI3K signaling pathway. Curcumin may inhibit proliferation and induce the autophagy and apoptosis in GC cells. Additionally, curcumin activated the P53 signaling pathway by up-regulating P53 and P21, which also inhibited PI3K pathway through down-regulating PI3K, p-Akt, and p-mTOR.

Lymph nodes around the posterior gastric artery: their existence, frequency, and clinical implications.

PURPOSE: The lymphatic flow along the posterior gastric artery (PGA) is considered of possible clinical importance in terms of lymphatic metastasis; however, little is known about the lymph nodes (LNs) around this artery. The purpose of this study was to establish if LNs exist around the PGA and to evaluate their clinical implications. METHODS: We examined the tissues surrounding the PGA from 21 cadavers to search for LNs. We also investigated the patterns of lymphatic metastases in patients who underwent surgery for gastric neoplasms at our institute to detect their presence along the PGA. RESULTS: The PGA was identified in 11 cadavers, and LNs around the PGA were detected microscopically in 2 of these. Lymphatic metastasis directly to the LNs at the splenic artery without any metastases was regarded as skip metastasis along the PGA. Skip metastasis was found in two of ten patients who underwent surgery for remnant gastric cancer. CONCLUSIONS: The existence of LNs around the PGA was confirmed, and based on our findings, lymphatic metastasis through the PGA is possible in patients with remnant gastric cancer.

Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging.

Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, here, the Lasso method (which stands for least absolute shrinkage and selection operator and which is a multiclass logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The methodology developed with 28 frozen training samples of clear histopathologic diagnosis showed an overall accuracy value of 98% for the 12,480 pixels evaluated in cross-validation (CV), and 97% when a completely independent set of samples was tested. By applying an additional spatial smoothing technique, the accuracy for both CV and the independent set of samples was 99% compared with histological diagnoses. To test our method for clinical use, we applied it to a total of 21 tissue-margin samples prospectively obtained from nine gastric-cancer patients. The results obtained suggest that DESI-MSI/Lasso may be valuable for routine intraoperative assessment of the specimen margins during gastric-cancer surgery.

Real Time Metastatic Route Tracking of Orthotopic PC-3-GFP Human Prostate Cancer Using Intravital Imaging.

The cellular basis of metastasis is poorly understood. An important step to understanding this process is to be able to visualize the routes by which cancer cells migrate from the primary tumor to various distant sites to eventually form metastasis. Our laboratory previously developed single-cell in vivo imaging using fluorescent proteins to label cancer cells. In the present study, using PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) and orthotopic tumor transplantation, we have imaged in live mice various highly diverse routes by which PC-3 cells metastasize superiorly and inferiorly to distant sites, including in the portal area, stomach area, and urogenital system. Imaging began at day 9, at which time distant metastasis had already occurred, and increased at each imaging point at days 10, 13, 14, and 16. Metastatic cells were observed migrating superiorly and inferiorly from the primary tumor as well as in lymphatic channels and trafficking in various organ systems demonstrating that PC-3 has multiple metastatic routes similar to hormone-independent advanced-stage prostate cancer in the clinic.

A flavonoid compound from Chrysosplenium nudicaule inhibits growth and induces apoptosis of the human stomach cancer cell line SGC-7901.

CONTEXT: Gastric cancer remains highly prevalent, but treatment options are limited. Natural products have proved to be a rich source of anticancer drugs. Chrysosplenium nudicaule Ledeb. (Saxifragaceae) is a perennial herb that grows in the highlands of China. It has been used as a traditional Chinese medicine to treat digestive diseases for hundreds of years. Recent studies revealed that this herb had anticancer activity, and the flavonoids were speculated to be the effective components. 6,7,3'-Trimethoxy-3,5,4'-trihydroxy flavone (TTF) and 5,4'-dihydroxy-3,6,3'trimethoxy-flavone-7-O-ß-d-glucoside (DTFG) are flavonoid compounds isolated from Chrysosplenium nudicaule. OBJECTIVE: This study examined the effect of TTF and DTFG on SGC-7901 human stomach cancer cell in vitro to determine the anticancer and induction of apoptosis properties of TTF. MATERIALS AND METHODS: The proliferation of cells treated with 32, 16, 8, 4, and 2 µg/mL of TTF or DTFG for 24, 48, and 72 h was assessed by the MTT assay. After being treated with TTF, the apoptosis of SGC-7901 cells was assessed by acridine orange staining, ultrastructure, electrophoresis of DNA fragmentation, and flow cytometry. RESULTS: Results indicated that TTF inhibited the growth of cancer cells with an IC50 value of 8.33 µg/mL after 72 h incubation. However, DTFG showed no inhibitory effect on the growth of the cancer cell. Further studies on TTF also confirmed that it was able to induce apoptosis of SGC-7901 cells at a concentration as low as 4 µg/mL. DISCUSSION AND CONCLUSION: The apoptotic effect of TTF makes it a promising candidate for future chemotherapeutic application in treating stomach cancer.

Evaluation of Fibroblast Growth Factor Receptor 2 Expression, Heterogeneity and Clinical Significance in Gastric Cancer.

BACKGROUND: We aimed to evaluate the protein and mRNA expression of fibroblast growth factor receptor 2 (FGFR2) by immunohistochemistry (IHC) and mRNA in situ hybridization (ISH), respectively, and to assess the heterogeneity of FGFR2 expression in gastric cancer (GC). METHODS: A tissue microarray containing 362 surgically resected GC tissues and 135 matched metastatic lymph nodes was evaluated using FGFR2b IHC and FGFR2 ISH. FGFR2 fluorescence ISH was also performed in 188 cases. RESULTS: All FGFR2-amplified cases (5 of 188) showed FGFR2b protein and FGFR2 mRNA overexpression (p < 0.001), and FGFR2 amplification was not identified in FGFR2b IHC- and FGFR2 mRNA ISH-negative cases. Kaplan-Meier survival analysis revealed that FGFR2b protein and FGFR2 mRNA overexpression was significantly associated with a poor overall survival (p < 0.001 and p = 0.012, respectively), and multivariate analyses showed that FGFR2 mRNA overexpression was an independent biomarker of a poor overall survival. Intratumoral heterogeneity of FGFR2b protein and FGFR2 mRNA overexpression was observed in 5 of 9 (55.5%) and 18 of 21 (85.7%) cases, respectively. Discordant FGFR2b and FGFR2 expression results between primary and matched metastatic lymph nodes were observed in 5 of 9 (55.5%) and 4 of 14 (28.6%) cases, respectively. CONCLUSIONS: Intratumoral heterogeneity and discordant FGFR2b expression in primary tumors and metastatic lymph nodes are common in GC.

Eosinophil-Specific Granules in Tumor Cell Cytoplasm: Unusual Ultrastructural Findings in a Case of Diffuse-Type Gastric Carcinoma.

A case of desmoplastic variant of diffuse-type gastric carcinoma in a 72-year-old woman is reported. Microscopic findings included poorly cohesive tumor cells, resembling mononuclear inflammatory cells, prominent diffuse desmoplasia, and tumor-associated tissue eosinophilia. Electron microscopy confirmed the undifferentiated phenotype of tumor cells and disclosed activated eosinophils in the tumor stroma. Eosinophil-specific granules were found either free in the tumor stroma or within the cytoplasm of some tumor cells. Electron microscopy provided also circumstantial evidence of phagocytosis of apoptotic eosinophils by tumor cells. Extracellular, membrane-bound, eosinophil-specific granules have been long recognized in tissues associated with eosinophilia, including allergic diseases, inflammatory responses to helminths, and in stroma of some neoplasms. Our ultrastructural study now extends these findings and provides additional morphological evidence of eosinophil-specific granules within the cytoplasm of gastric carcinoma cells.

Photodynamic therapy using nanoparticle loaded with indocyanine green for experimental peritoneal dissemination of gastric cancer.

Although there have been multiple advances in the development of novel anticancer agents and operative procedures, prognosis of patients with advanced gastric cancer remains poor, especially in patients with peritoneal metastasis. In this study, we established nanoparticles loaded with indocyanine green (ICG) derivatives: ICG loaded lactosomes (ICGm) and investigated the diagnostic and therapeutic value of photodynamic therapy (PDT) using ICGm for experimental peritoneal dissemination of gastric cancer. Experimental peritoneal disseminated xenografts of human gastric cancer were established in nude mice. Three weeks after intraperitoneal injection of the cancer cells, either ICGm (ICGm-treated mice) or ICG solution (ICG-treated mice) was injected through the tail vein. Forty-eight hours after injection of the photosensitizer, in vivo and ex vivo imaging was carried out. For PDT, 48 h after injection of the photosensitizer, other mice were irradiated through the abdominal wall, and the body weight and survival rate were monitored. In vivo imaging revealed that peritoneal tumors were visualized through the abdominal wall in ICGm-treated mice, whereas only non-specific fluorescence was observed in ICG-treated mice. The PDT reduced the total weight of the disseminated nodules and significantly improved weight loss and survival rate in ICGm-treated mice. In conclusion, ICGm can be used as a novel diagnostic and therapeutic nanodevice in peritoneal dissemination of gastric cancer.

Naturally occurring phenethyl isothiocyanate-induced inhibition of gastric cancer cell growth by disruption of microtubules.

BACKGROUND AND AIM: Phenethyl isothiocyanate (PEITC) derives from vegetables commonly consumed by man and has been demonstrated as a promising chemopreventive agent against several types of cancer. However, the potential in preventing gastric cancer as well as the underlying mechanisms are to date not fully understood. The present study aimed at elucidating the cellular effects induced by PEITC in gastric cancer cells leading to apoptosis. METHODS: The human gastric cancer cell lines Kato-III and MKN74 were employed. Cell proliferation was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Morphology and migration were investigated through a contrast microscope. Cell cycle distribution was analyzed using flow cytometry of PI-stained cells. Microtubules were studied by confocal detection of Kato-III cells transfected to express GFP-tagged microtubules. Commercial kits were employed to study the effect of PEITC on apoptosis, caspase-3 activity, and glutathione content in MKN74 cells. RESULTS: Kato-III and MKN74 cells responded, with different sensitivity, dose- and time-dependently in inhibition of cell proliferation to PEITC treatment. Further, PEITC induced aberrated cell morphologies and inhibited migration of MKN74 cells. Kato-III cells treated with PEITC accumulated in G2 /M phase and displayed a loss of microtubuli with the subsequent formation of apoptotic bodies. Although weak responses, MKN74 cells also accumulated in G2 /M phase, became apoptotic, increased caspase-3 activity, and suffered a reduction of glutathione pool. CONCLUSION: Our findings demonstrate that PEITC induces disintegration of microtubules in human gastric cancer cells contributing to cell cycle arrest and ultimately apoptosis, contributing to an increased understanding of PEITC-induced inhibition of gastric cancer cell growth.

Evaluating the diagnoses of gastric antral lesions using magnifying endoscopy with narrow-band imaging in a Chinese population.

AIM: To evaluate the accuracy of diagnosing gastric antral lesions in routine clinical practice using magnifying endoscopy with narrow-band imaging (M-NBI) as a real-time diagnosing technique. METHODS: Consecutive patients undergoing upper endoscopy were selected for the study. In each patient, the mucosa of the gastric antrum was observed by M-NBI, and the gastric microstructure was categorized into five types (A-E). Based on these patterns, histological types were predicted in a real-time manner. The accuracy of these predictions was evaluated based on histological findings. Inter-observer agreement was also assessed. RESULTS: A total of 207 sites in 90 patients were examined by M-NBI. Compared with type A gastric microstructure, types B and C gastric microstructure showed a significantly higher degree of inflammation (P < 0.001). The sensitivity, specificity and accuracy of types B + C microstructure as a predictor of gastric inflammation were 85.4, 81.7 and 83.1 %, respectively. Similarly, the sensitivity, specificity and accuracy of type D microstructure as a predictor of gastric intestinal metaplasia were 71.8, 95.2 and 90.8 %, respectively, and those of type E microstructure as a predictor of early gastric cancer were 80.0, 98.9 and 97.6 %, respectively. The sensitivity and specificity of type B alone, type C alone and types B + C combined for the detection of Helicobacter pylori infection were 52.2 and 87.0 %, 22.8 and 92.2 %, 75.0 and 79.1 %, respectively. The kappa value for the inter-observer agreement was 0.715 (95 % confidence interval 0.655-0.895). CONCLUSIONS: In conclusion, M-NBI can significantly improve the accuracy of the prediction of histopathology of gastric antral lesions in vivo, implying the possibility of using M-NBI as an effective diagnosis technique.

Antioxidant activity and ultrastructural changes in gastric cancer cell lines induced by Northeastern Thai edible folk plant extracts.

BACKGROUND: Phytochemical products have a critical role in the drug discovery process. This promising possibility, however, necessitates the need to confirm their scientific verification before use. Hence, this study aims to evaluate (1) the antioxidant activity, (2) cytotoxicity potential, and (3) the effect on ultrastructural alteration in gastric cancer cell lines through exposure to fractions of three local Northeastern Thai edible plants. METHODS: Plants, Syzygium gratum, Justicia gangetica and Limnocharis flava were extracted with ethyl acetate, and each crude extract analysed for their total phenolics content by Folin-Ciocalteu method. Their antioxidant activity was assessed using the ABTS system. The extracts were then assayed for cytotoxicity on two gastric cancer cell lines Kato-III and NUGC-4, and compared with Hs27 fibroblasts as a control using the MTT assay. The cell viability (%), IC50 values, as well as the ultrastructural alterations were evaluated after treatment with one way analysis of variance (ANOVA). RESULTS: The total phenolic values of the ethyl acetate extracts were well correlated with the antioxidant capacity, with extracted product of S. gratum displaying the highest level of antioxidant activity (a 10-fold greater response) over J. gangetica and L. flava respectively. Exposure of S. gratum and J. gangetica extracts to normal cell lines (Hs27) resulted in marginal cytotoxicity effects. However, through a dose-dependent assay S. gratum and J. gangetica extracts produced cytotoxicological effects in just over 75 percent of Kato-III and NUGC-4 cell lines. In addition, apoptotic characteristic was shown under TEM in both cancer cell lines with these two extracts, whereas characteristics of autophagy was found in cell lines after post exposure to extracts from L. flava. CONCLUSIONS: From these three plants, S. gratum had the highest contents of phenolic compounds and antioxidant capacity. All of them found to contain compound(s) with cytotoxicity in vitro on cancer cells but not on normal cell lines as resolved in tissue culture and ultrastructural analysis. This is the first report to show the effect on cellular alteration as apoptosis of an ethyl acetate extract of S. gratum and J. gangetica. Further studies are now focused on individual isolates and their function, prioritizing on S. gratum and J. gangetica for the development of novel therapeutics and combatants against cancer.