Helicobacter pylori enhances HLA-C expression in the human gastric adenocarcinoma cells AGS and can protect them from the cytotoxicity of natural killer cells.

Helicobacter pylori (H. pylori) seems to play causative roles in gastric cancers. H. pylori has also been detected in established gastric cancers. How the presence of H. pylori modulates immune response to the cancer is unclear. The cytotoxicity of natural killer (NK) cells, toward infected or malignant cells, is controlled by the repertoire of activating and inhibitory receptors expressed on their surface. Here, we studied H. pylori-induced changes in the expression of ligands, of activating and inhibitory receptors of NK cells, in the gastric adenocarcinoma AGS cells, and their impacts on NK cell responses. AGS cells lacked or had low surface expression of the class I major histocompatibility complex (MHC-I) molecules HLA-E and HLA-C-ligands of the major NK cell inhibitory receptors NKG2A and killer-cell Ig-like receptor (KIR), respectively. However, AGS cells had high surface expression of ligands of activating receptors DNAM-1 and CD2, and of the adhesion molecules LFA-1. Consistently, AGS cells were sensitive to killing by NK cells despite the expression of inhibitory KIR on NK cells. Furthermore, H. pylori enhanced HLA-C surface expression on AGS cells. H. pylori infection enhanced HLA-C protein synthesis, which could explain H. pylori-induced HLA-C surface expression. H. pylori infection enhanced HLA-C surface expression also in the hepatoma Huh7 and HepG2 cells. Furthermore, H. pylori-induced HLA-C surface expression on AGS cells promoted inhibition of NK cells by KIR, and thereby protected AGS cells from NK cell cytotoxicity. These results suggest that H. pylori enhances HLA-C expression in host cells and protects them from the cytotoxic attack of NK cells expressing HLA-C-specific inhibitory receptors.

A Multi-Omics Study on the Effect of Helicobacter Pylori-Related Genes in the Tumor Immunity on Stomach Adenocarcinoma.

Background: Helicobacter pylori (HP), a gram-negative spiral-shaped microaerophilic bacterium, colonizes the stomach of approximately 50% of the world's population, which is considered a risk factor for gastritis, peptic ulcers, gastric cancer, and other malignancies. HP is also considered carcinogenic since it involves the mutation and damage of multiple HP-related genes. Stomach adenocarcinoma (STAD) is a common stom5ach cancer with a poor prognosis and high risk of metastasis in the advanced stage. Therefore, an early diagnosis and targeted therapies are needed to ensure a better prognosis. In this study, a scoring system was constructed based on three HP infection-related candidate genes to enable a more accurate prediction of tumor progression and metastasis and response to immunotherapies. Methods: HP infection-induced mutation patterns of STAD samples from six cohorts were comprehensively assessed based on 73 HP-related genes, which were then correlated with the immune cell-infiltrating characteristics of the tumor microenvironment (TME). The risk signature was constructed to quantify the influence of HP infection on individual tumors. Subsequently, an accurate nomogram was generated to improve the clinical applicability of the risk signature. We conducted immunohistochemical experiments and used the Affiliated Hospital of Youjiang Medical University for Nationalities (AHYMUN) cohort data set with survival information to further verify the clinical value of this risk signature. Results: Two distinct HP-related mutation patterns with different immune cell-infiltrating characteristics (ICIC) and survival possibility were identified. We demonstrated that the evaluation of HP infection-induced mutation patterns of tumor could assist the prediction of stages, phenotypes, stromal activity, genetic diversity, and patient prognosis. A low risk score involved an increased mutation burden and activation of immune responses, with a higher 5-year survival rate and enhanced response to anti-PD-1/L1 immunotherapy, while a high risk score involved stromal activation and poorer survival. The efficiency of the risk signature was further evidenced by the nomogram. Conclusions: STAD patients with a low risk score demonstrated significant therapeutic advantages and clinical benefits. HP infection-induced mutations play a nonnegligible role in STAD development. Quantifying the HP-related mutation patterns of individual tumors will contribute to phenotype classification, guide more effective targeted and personalized therapies, and enable more accurate predictions of metastasis and prognosis.

Tumorigenic mechanisms of estrogen and Helicobacter pylori cytotoxin-associated gene A in estrogen receptor α-positive diffuse-type gastric adenocarcinoma.

BACKGROUND: Diffuse-type gastric cancer (DGC), for which Helicobacter pylori infection is a causal factor, is associated with poor prognosis among young women, possibly due to female hormones such as estrogen. We aimed to identify the carcinogenesis induced by estrogen and H. pylori in DGC. METHODS: We screened and selected estrogen receptor alpha (ERα)-positive (MKN45) and ERα-negative (SNU5) DGC cell lines. H. pylori strain 60190 and its isogenic mutant strain lacking cytotoxin-associated gene A (60190ΔCagA) were used to infect MKN45 cells. And the cytotoxin-related gene A (CagA) cDNA which was cloned into pSP65-SR-HA (cagA-pSP65SRa) vector was used to transfect MKN45 cells. Tumor samples were used for DGC organoid culture. RESULTS: In MKN45 cells, we found that estradiol promotes epithelial-mesenchymal transition (EMT) and stemness phenotypes via HOTAIR expression. These effects were further enhanced by the addition of CagA secreted by H. pylori but were reversed by co-treatment with fulvestrant (ICI 182,780), a selective ER degrader. We also validated the effect of estrogen on DGC organoids. ERα expression was associated with tumor invasion and HOTAIR expression in DGC patients with overt H. pylori infection. CONCLUSIONS: These findings may explain the rapid DGC progression in young women with physiologically high levels of estrogen and suggest that fulvestrant with ovarian function suppression could serve as a tumor-suppressive agent in premenopausal patients with DGC.

GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity.

GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Our work for the first time highlights the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of ß -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention.

Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies.

OBJECTIVE: In this study, we determined whether Helicobacter pylori (H. pylori) infection dampens the efficacy of cancer immunotherapies. DESIGN: Using mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of H. pylori-infected mice. In humans, we evaluated the correlation between H. pylori seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC). RESULTS: In mice engrafted with MC38 colon adenocarcinoma or B16-OVA melanoma cells, the tumour volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. We observed a decreased number and activation status of tumour-specific CD8+ T cells in the tumours of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, we observed that dendritic cells of infected mice promote lower tumour-specific CD8+ T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, H. pylori seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for H. pylori seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, H. pylori seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy. CONCLUSION: Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology would be a powerful tool to personalize cancer immunotherapy treatment.

ZAK Gene Expression in Patients with Helicobacter pylori Infection.

BACKGROUND: ZAK protein is a member of the MLK family proteins defined as mediators in the cell cycle. A survey of ZAK gene expression in gastric antral epithelial cells (GAECs) of gastritis and gastric adenocarcinoma patients with Helicobacter pylori genotypes infection can elucidate carcinogenesis of H. pylori genotypes. METHODS: In a case-control study, ZAK gene expression was evaluated in GAECs biopsy samples of gastritis and gastric adenocarcinoma patients with (n 23, 21) and without H. pylori infection (n 27, 32), respectively. Total RNA was extracted from each gastric antral biopsy samples and cDNA synthesized by using Takara kits. H. pylori virulence genes֝ cDNA were detected by traditional PCR and specific primers. The ZAK gene expression was measured using the relative Real-Time RT PCR. RESULTS: The prevalence of gastric adenocarcinoma was the highest in man and 61-85 aged groups (p < .05). There was no significant correlation between the prevalence of H. pylori infection and patients' demographic groups. This study showed that ZAK gene overexpression gradually increases with increasing age and tumor grade among gastric adenocarcinoma patients. The gastric antral biopsy samples with H. pylori vacA s1m2 genotype infection showed a weak correlation with ZAK gene overexpression (p < .1). CONCLUSION: ZAK gene expression was higher in GAECs of gastritis cancer than in gastric adenocarcinoma, indicating the protective effect of ZAK against gastric cancer (p < .005). Reducing ZAK gene expression shows the negative correlations with H. pylori infection and gastric adenocarcinoma.

Helicobacter pylori Targets in AGS Human Gastric Adenocarcinoma: In Situ Proteomic Profiling and Systematic Analysis.

BACKGROUND/AIM: Helicobacter pylori, a gram-negative bacterium, causes chronic stomach diseases in humans. Heat shock proteins (HSPs) are involved in cell integrity, cell growth, and gastric mucosa colonization by H. pylori. This study aimed to investigate HSP expression levels in H. pylori-infected gastric adenocarcinoma AGS cells. MATERIALS AND METHODS: We determined protein expression levels using iTRAQ proteomics analysis. We analyzed the possible network interactions for H. pylori targets in AGS cells using the Ingenuity Pathway Analysis (IPA) software. RESULTS: H. pylori-infected AGS cells potentially targeted EIF2 and BAG2 signaling pathways to regulate cell physiology. In addition, after 3, 6, and 12 h of infection, western blotting revealed significantly decreased HSP70 and HSP105 expression. CONCLUSION: H. pylori decreases HSPs in AGS gastric adenocarcinoma cells, and this is associated with the regulation of EIF2 and BAG2 signaling pathways.

Association of Helicobacter pylori and gastric atrophy with adenocarcinoma of the esophagogastric junction in Taixing, China.

Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ.

Biomarkers CDX2, CK20, CK7 in Schoolchildren with Gastritis in the Realization of Familial Predisposition of Stomach Cancer.

We studied the association of expression of CDX2, CK20, CK7 proteins with familial predisposition to stomach cancer in schoolchildren with gastritis and its activity. Gastroscopy with biopsy of the gastric mucosa was performed in 89 schoolchildren aged 7-17 years with gastrointestinal complaints. The morphological study included the diagnosis of gastritis (Sydney classification) and the presence of Helicobacter pylori. The expression of CDX2, CK20, and CK7 was evaluated immunohistochemically. In children with familial predisposition to stomach cancer, the expression of CK20 in the stomach body was significantly increased (p=0.0225). In addition, the expression of CK20 (p=0.0979) and CDX2 (p=0.0849) tended to insrease in the antral compartment. No significant differences in the expression of CK7 in the gastric antrum and body were found. Some features of the expression of CDX2, CK20, and CK7 proteins in children with family predisposition to stomach cancer were revealed.

Clinicopathological characteristics and prognosis of cervical cancer with different histological types: A population-based cohort study.

OBJECTIVE: The prognostic impact and treatment responses among cervical cancer patients with different histological types remains inconclusive. To determine the prognostic effects of different histologic types, we identified 39,088 patients with a diagnosis of cervical cancer between 2004 and 2016 from the Surveillance, Epidemiology, and End Results program. METHODS: Variables related to the prognosis of cervical cancer were evaluated using log-rank method and univariate/multivariate Cox models before and after propensity score matching. RESULT: Of the 36,310 patients, Squamous cell carcinoma (SCC) was the most common histological type (n = 27,043, 74.5%), followed by adenocarcinoma (AC, n = 7755, 21.4%) and adenosquamous carcinoma (ASC, n = 1512, 4.1%). Compared to SCC patients, patients with AC (HR = 1.14, 95%CI = 1.09-1.20, P < 0.01) and ASC (HR = 1.28, 95%CI = 1.18-1.40, P < 0.01) showed significantly poorer prognosis. Subgroup analyses indicated that the differences in prognosis between AC and SCC were only observed in stage II and III patients (P < 0.01). In patients with concurrent chemoradiotherapy, survival rates of patients with AC were significantly worse compared with similar patients with SCC (HR = 1.14, 95%CI = 1.03-1.27; P < 0.01). CONCLUSION: The prognostic impact of histologic types among patients with cervical cancer depends on tumor stages and therapeutic approaches. Tailored treatment and follow-up planning need to be developed across patients with different histological types and stages.

The Impact of KRAS Mutation in Patients With Sporadic Nonampullary Duodenal Epithelial Tumors.

INTRODUCTION: The genomic characterization of primary nonampullary duodenal adenocarcinoma indicates a genetic resemblance to gastric and colorectal cancers. However, a correlation between the clinical and molecular characteristics of these cancers has not been established. This study aimed to elucidate the clinicopathological features of sporadic nonampullary duodenal epithelial tumors, including their molecular characteristics and prognostic factors. METHODS: One hundred forty-eight patients with sporadic nonampullary duodenal epithelial tumors were examined in this study. Patient sex, age, TNM stage, tumor location, treatment methods, histology, KRAS mutation, BRAF mutation, Fusobacterium nucleatum, mucin phenotype, and programmed death-ligand 1 (PD-L1) status were evaluated. KRAS and BRAF mutations, Fusobacterium nucleatum, mucin phenotype, and PD-L1 status were analyzed by direct sequencing, quantitative polymerase chain reaction, and immunochemical staining. RESULTS: The median follow-up duration was 119.4 months. There were no deaths from duodenal adenoma (the primary disease). Kaplan-Meier analysis for duodenal adenocarcinoma showed a significant effect of TNM stage (P < 0.01). In univariate analysis of primary deaths from duodenal adenocarcinoma, TNM stage II or higher, undifferentiated, KRAS mutations, gastric phenotype, intestinal phenotype, and PD-L1 status were significant factors. In multivariate analysis, TNM stage II or higher (hazard ratio: 1.63 × 1010, 95% confidence interval: 18.66-6.69 × 1036) and KRAS mutation (hazard ratio: 3.49, confidence interval: 1.52-7.91) were significant factors. DISCUSSION: Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered.

Characteristics of pathogenic microbes in lung microenvironment of lung cancer patients without respiratory infection.

PURPOSE: The characteristics of pathogenic microbes are useful for understanding the microbe-driven tumorigenesis. There is a lack of studies on the lung microecology for lung cancer (LC) patients without any respiratory infection. In this work, we aimed to describe the profiles of pathogenic microbes in lung microenvironment of non-small cell lung cancer (NSCLC) patients using pathogen targeted sequencing and 16S rDNA sequencing. METHODS: A total of 22 NSCLC patients (13 adenocarcinomas and 9 squamous cell carcinomas) without any pulmonary infection were enrolled. Among them, we collected 15 pieces of tumor tissues, 5 pieces of peritumoral tissues, 6 blood serum samples, and 5 broncho-alveolar lavage fluid (BALF) samples. Pathogen targeted sequencingand16S rDNA sequencing was performed for microbial classification. RESULTS: The pathogen targeted sequencing results showed that 33, 14, 11, and 27 pathogenic microorganisms were detected in tumor tissues, peritumoral tissues, blood samples, and BALF, respectively. No common microorganisms were shared by four sample types. However, some common elements were shared by three sets: Streptococcus cristatus, Enterococcus, Staphylococcus haemolyticus, Corynebacterium pseudodiphtheria, Acinetobacter jungii, Haemophilus haemolyticus and Haemophilus parainfluenzae. Based on the 16S rDNA sequencing of two BALF samples, there were 104 OTUs found in one BALF sample and 127 OTUs in the other BALF sample; among them, there were 82 common ones, such as OTU1, OTU10, OTU101, OTU105, OTU106, and so on. Based on the above microbial classification and abundance, there might be enriched function in COG terms like COG1132, COG0438 and COG0745, and KEGG terms like K06147, K02029, and K09687. CONCLUSION: This study emphasizes the role of the microbiome in LC patients without respiratory infection. These potential biomarkers of LC based on the taxonomic composition of pathogenic microorganisms might have clinical application.

Tumor microbiome contributes to an aggressive phenotype in the basal-like subtype of pancreatic cancer.

Despite the uniform mortality in pancreatic adenocarcinoma (PDAC), clinical disease heterogeneity exists with limited genomic differences. A highly aggressive tumor subtype termed 'basal-like' was identified to show worse outcomes and higher inflammatory responses. Here, we focus on the microbial effect in PDAC progression and present a comprehensive analysis of the tumor microbiome in different PDAC subtypes with resectable tumors using metagenomic sequencing. We found distinctive microbial communities in basal-like tumors and identified an increasing abundance of Acinetobacter, Pseudomonas and Sphingopyxis to be highly associated with carcinogenesis. Functional characterization of microbial genes suggested the potential to induce pathogen-related inflammation. Host-microbiota interplay analysis provided new insights into the tumorigenic role of specific microbiome compositions and demonstrated the influence of host genetics in shaping the tumor microbiome. Taken together, these findings indicated that the tumor microbiome is closely related to PDAC oncogenesis and the induction of inflammation. Additionally, our data revealed the microbial basis of PDAC heterogeneity and proved the predictive value of the microbiome, which will contribute to the intervention and treatment of disease.

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Despite prior studies, molecular characterization of this disease is not well defined, and little is known regarding Chinese SBA patients. In this study, we conducted multigene next-generation sequencing and 16S ribosomal RNA gene sequencing on samples from 76 Chinese patients with surgically resected primary SBA. Compared with colorectal cancer and Western SBA cohorts, a distinctive genomic profile was revealed in Chinese SBA cohorts. According to the levels of clinical actionability to targetable alterations stratified by OncoKB system, 75% of patients harbored targetable alterations, of which ERBB2, BRCA1/2, and C-KIT mutations were the most common targets of highest-level actionable alterations. In DNA mismatch repair-proficient (pMMR) patients, significant associations between high tumor mutational burden and specific genetic alterations were identified. Moreover, KRAS mutations/TP53 wild-type/nondisruptive mutations (KRASmut /TP53wt/non-dis ) were independently associated with an inferior recurrence-free survival (hazard ratio [HR] = 4.21, 95% confidence interval [CI] = 1.94-9.14, P < .001). The bacterial profile revealed Proteobacteia, Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Cyanobacteria were the most common phyla in SBA. Furthermore, patients were clustered into three subgroups based on the relative abundance of bacterial phyla, and the distributions of the subgroups were significantly associated with the risk of recurrence stratified by TP53 and KRAS mutations. In conclusion, these findings provided a comprehensive molecular basis for understanding SBA, which will be of great significance in improving the treatment strategies and clinical management of this population.

Fungi, host immune response, and tumorigenesis.

Advances in -omics analyses have tremendously enhanced our understanding of the role of the microbiome in human health and disease. Most research is focused on the bacteriome, but scientists have now realized the significance of the virome and microbial dysbiosis as well, particularly in noninfectious diseases such as cancer. In this review, we summarize the role of mycobiome in tumorigenesis, with a dismal prognosis, and attention to pancreatic ductal adenocarcinoma (PDAC). We also discuss bacterial and mycobial interactions to the host's immune response that is prevalently responsible for resistance to cancer therapy, including immunotherapy. We reported that the Malassezia species associated with scalp and skin infections, colonize in human PDAC tumors and accelerate tumorigenesis via activating the C3 complement-mannose-binding lectin (MBL) pathway. PDAC tumors thrive in an immunosuppressive microenvironment with desmoplastic stroma and a dysbiotic microbiome. Host-microbiome interactions in the tumor milieu pose a significant threat in driving the indolent immune behavior of the tumor. Microbial intervention in multimodal cancer therapy is a promising novel approach to modify an immunotolerant ("cold") tumor microenvironment to an immunocompetent ("hot") milieu that is effective in eliminating tumorigenesis.

Outer Membrane Vesicle Production by Helicobacter pylori Represents an Approach for the Delivery of Virulence Factors CagA, VacA and UreA into Human Gastric Adenocarcinoma (AGS) Cells.

Helicobacter pylori infection is the etiology of several gastric-related diseases including gastric cancer. Cytotoxin associated gene A (CagA), vacuolating cytotoxin A (VacA) and α-subunit of urease (UreA) are three major virulence factors of H. pylori, and each of them has a distinct entry pathway and pathogenic mechanism during bacterial infection. H. pylori can shed outer membrane vesicles (OMVs). Therefore, it would be interesting to explore the production kinetics of H. pylori OMVs and its connection with the entry of key virulence factors into host cells. Here, we isolated OMVs from H. pylori 26,695 strain and characterized their properties and interaction kinetics with human gastric adenocarcinoma (AGS) cells. We found that the generation of OMVs and the presence of CagA, VacA and UreA in OMVs were a lasting event throughout different phases of bacterial growth. H. pylori OMVs entered AGS cells mainly through macropinocytosis/phagocytosis. Furthermore, CagA, VacA and UreA could enter AGS cells via OMVs and the treatment with H. pylori OMVs would cause cell death. Comparison of H. pylori 26,695 and clinical strains suggested that the production and characteristics of OMVs are not only limited to laboratory strains commonly in use, but a general phenomenon to most H. pylori strains.

Comprehensive Integration of Genome-Wide Association and Gene Expression Studies Reveals Novel Gene Signatures and Potential Therapeutic Targets for Helicobacter pylori-Induced Gastric Disease.

Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa and can lead to gastric inflammation, ulcers, and stomach cancer. Due to the increase in H. pylori antimicrobial resistance new methods to identify the molecular mechanisms of H. pylori-induced pathology are urgently needed. Here we utilized a computational biology approach, harnessing genome-wide association and gene expression studies to identify genes and pathways determining disease development. We mined gene expression data related to H. pylori-infection and its complications from publicly available databases to identify four human datasets as discovery datasets and used two different multi-cohort analysis pipelines to define a H. pylori-induced gene signature. An initial Helicobacter-signature was curated using the MetaIntegrator pipeline and validated in cell line model datasets. With this approach we identified cell line models that best match gene regulation in human pathology. A second analysis pipeline through NetworkAnalyst was used to refine our initial signature. This approach defined a 55-gene signature that is stably deregulated in disease conditions. The 55-gene signature was validated in datasets from human gastric adenocarcinomas and could separate tumor from normal tissue. As only a small number of H. pylori patients develop cancer, this gene-signature must interact with other host and environmental factors to initiate tumorigenesis. We tested for possible interactions between our curated gene signature and host genomic background mutations and polymorphisms by integrating genome-wide association studies (GWAS) and known oncogenes. We analyzed public databases to identify genes harboring single nucleotide polymorphisms (SNPs) associated with gastric pathologies and driver genes in gastric cancers. Using this approach, we identified 37 genes from GWA studies and 61 oncogenes, which were used with our 55-gene signature to map gene-gene interaction networks. In conclusion, our analysis defines a unique gene signature driven by H. pylori-infection at early phases and that remains relevant through different stages of pathology up to gastric cancer, a stage where H. pylori itself is rarely detectable. Furthermore, this signature elucidates many factors of host gene and pathway regulation in infection and can be used as a target for drug repurposing and testing of infection models suitability to investigate human infection.

Helicobacter pylori and association between its positivity and anatomotopographic settlement in the stomach with the host age range.

Helicobacter pylori (H. pylori) is a Gram-negative, helically shaped flagellated bacterium. Major diseases associated with H. pylori infection include peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The incidence of H. pylori in the anatomotopographic regions of the stomach, such as antrum, corpus, fundus, and incisura angularis, has been investigated. Do the rates of H. pylori in the settlements change over time according to the age ranges of the hosts? Does this change affect the diseases caused by or related to H. pylori? It is estimated that the outcomes, which have been obtained, may provide a new perspective in terms of understanding the etiopathogenesis of H. pylori-induced diseases. A comprehensive literature search of PubMed/MEDLINE databases had been conducted using a combination of terms, "Helicobacter pylori," "Sydney System," "stomach," "pyloric antrum," "gastric corpus," "stomach cancer," and "Helicobacter pylori and age." There are very few articles examining the relationship between the topographic locations of H. pylori and host age range in the English language literature. Therefore, it is also purposed to emphasize the outcomes of our current research about the mentioned topic. In our opinion, similar studies should reveal the settlement and age range in the different geographic locations and societies as in our study. We believe that these findings will contribute to the efforts for understanding overtly of H. pylori-induced disease of the stomach.

Résumé Helicobacter pylori (H. pylori) est une bactérie flagellée à Gram négatif de forme hélicoïdale. Les principales maladies associées à l'infection à H. pylori comprennent l'ulcère gastro-duodénal, l'adénocarcinome gastrique et le lymphome du tissu lymphoïde associé à la muqueuse. L'incidence de H. pylori dans les régions anatomotopographiques de l'estomac, telles que l'antre, le corpus, le fond d'œil et l'incisura angularis, a été étudiée. Les taux de H. pylori dans les colonies changent-ils avec le temps en fonction des tranches d'âge des hôtes? Ce changement affecte-t-il les maladies causées par ou liées à H. pylori? On estime que les résultats obtenus peuvent fournir une nouvelle perspective en termes de compréhension de l'étiopathogenèse des maladies induites par H. pylori. Une recherche documentaire complète des bases de données PubMed/MEDLINE a été effectuée en utilisant une combinaison de termes, "Helicobacter pylori", "Sydney System", "estomac", "antre pylorique", "corpus gastrique", "cancer de l'estomac" et "Helicobacter pylori et l'âge". Il existe très peu d'articles examinant la relation entre les emplacements topographiques de H. pylori et la tranche d'âge de l'hôte dans la littérature de langue Anglaise. Par conséquent, il vise également à souligner les résultats de nos recherches actuelles sur le sujet mentionné. À notre avis, des études similaires devraient révéler l'établissement et la tranche d'âge dans les différentes géographies, les emplacements géographiques et les sociétés, comme dans notre étude. Nous pensons que ces résultats contribueront aux efforts visant à comprendre ouvertement la maladie de l'estomac induite par H. pylori.

Pantoea agglomerans como marcador de cáncer en pacientes inmunodeprimidos / Pantoea agglomerans as a cancer hallmark in immunocompromised patients

Pantoea agglomerans es un bacilo gramnegativo reportado principalmente en heridas penetrantes, infecciones neonatales o como contaminante. La infección relevante por esta bacteria es rara. Nuestra revisión de la literatura sugirió una asociación consistente entre la infección por Pantoea agglomerans en pacientes inmunodeprimidos y una neoplasia maligna previamente diagnosticada. Los autores describen un derrame pleural paraneumónico en el que el aislamiento de Pantoea agglomerans permitió el diagnóstico de novo de cáncer de pulmón

Pantoea agglomerans is a gram-negative rod reported mainly in penetrating wounds, neonatal infections or as a contaminant. Relevant infection by this bacterium is rare. Our review of available literature suggested a consistent association between Pantoea agglomerans infection in immunocompromised patients and previously diagnosed malignancy. The authors describe a parapneumonic pleural effusion in which the isolation of Pantoea agglomerans allowed for de novo diagnosis of lung cancer

Intestinal microbiota and its association with colon cancer and red/processed meat consumption.

The human colon harbors a high number of microorganisms that were reported to play a crucial role in colorectal carcinogenesis. In the recent decade, molecular detection and metabolomic techniques have expanded our knowledge on the role of specific microbial species in promoting tumorigenesis. In this study, we reviewed the association between microbial dysbiosis and colorectal carcinoma (CRC). Various microbial species and their association with colorectal tumorigenesis and red/processed meat consumption have been reviewed. The literature demonstrated a significant abundance of Fusobacterium nucleatum, Streptococcus bovis/gallolyticus, Escherichia coli, and Bacteroides fragilis in patients with adenoma or adenocarcinoma compared to healthy individuals. The mechanisms in which each organism was postulated to promote colon carcinogenesis were collated and summarized in this review. These include the microorganisms' ability to adhere to colon cells; modulate the inhibition of tumor suppressor genes, the activations of oncogenes, and genotoxicity; and activate downstream targets responsible for angiogenesis. The role of these microorganisms in conjugation with meat components including N-nitroso compounds, heterocyclic amines, and heme was also evident in multiple studies. The outcome of this review supports the role of red meat consumption in modulating CRC progression and the possibility of gut microbiome influencing the relationship between CRC and diet. The study also demonstrates that microbiota analysis could potentially complement existing screening methods when detecting colonic lesions.