• Brassica oleracea
• Cytolethal distending toxins (CDTs)
• DFT
• E. coli
• Gallbladder cancer
• In vitro antibacterial activity
• Molecular docking
• Molecular dynamics

• Environmental Exposure
• Epidemiology
• Gallbladder Neoplasms
• Prevention and Control
• Risk Factors

• ecotoxicology
• environmental change
• neoplasm
• pollution
• selective pressure

• Cholangiocarcinoma
• Gallbladder cancer
• Microbiome

• Humans
• Dysbiosis/complications
• Biliary Tract Neoplasms/diagnosis
• Biliary Tract Neoplasms/etiology
• Biliary Tract
• Gallbladder Diseases
• Microbiota

• biliary tract cancer
• cholangiocarcinoma
• metabolite
• microbiome

• 82260555 the National Natural Science Foundation of China
• ldyyyn2021-78 the First Hospital of Lanzhou University Intra-Hospital Fund Youth Fund
• 2022B-027 the Education Department of Gansu Province: Innovation Fund Project

Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms, including gallbladder cancer. In this regard, data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products (RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu, thus supporting tumor growth and development. AGEs are formed in biological systems or foods, and food-derived AGEs, also known as dietary AGEs are known to contribute to the systemic pool of AGEs. Once they bind to RAGE, the activation of multiple and crucial signaling pathways are triggered, thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration. In the present review, we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer, and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.

• Gallbladder cancer
• Advanced glycation end-products
• Receptor of advanced glycation end-products
• Chronic inflammation
• Nutrition

• Humans
• Receptor for Advanced Glycation End Products/metabolism
• Glycation End Products, Advanced/metabolism
• Gallbladder Neoplasms/etiology
• Inflammation
• Cytokines

Microbiotas are the range of microorganisms (mainly bacteria and fungi) colonizing multicellular, macroscopic organisms. They are crucial for several metabolic functions affecting the health of the host. However, difficulties hamper the investigation of microbiota composition in cultivating microorganisms in standard growth media. For this reason, our knowledge of microbiota can benefit from the analysis of microbial macromolecules (DNA, transcripts, proteins, or by-products) present in various samples collected from the host. Various omics technologies are used to obtain different data. Metagenomics provides a taxonomical profile of the sample. It can also be used to obtain potential functional information. At the same time, metatranscriptomics can characterize members of a microbiome responsible for specific functions and elucidate genes that drive the microbiotas relationship with its host. Thus, while microbiota refers to microorganisms living in a determined environment (taxonomy of microorganisms identified), microbiome refers to the microorganisms and their genes living in a determined environment and, of course, metagenomics focuses on the genes and collective functions of identified microorganisms. Metabolomics completes this framework by determining the metabolite fluxes and the products released into the environment. The gallbladder is a sac localized under the liver in the human body and is difficult to access for bile and tissue sampling. It concentrates the bile produced in the hepatocytes, which drains into bile canaliculi. Bile promotes fat digestion and is released from the gallbladder into the upper small intestine in response to food. Considered sterile originally, recent data indicate that bile microbiota is associated with the biliary tract’s inflammation and carcinogenesis. The sample size is relevant for omic studies of rare diseases, such as gallbladder carcinoma. Although in its infancy, the study of the biliary microbiota has begun taking advantage of several omics strategies, mainly based on metagenomics, metabolomics, and mouse models. Here, we show that omics analyses from the literature may provide a more comprehensive image of the biliary microbiota. We review studies performed in this environmental niche and focus on network-based approaches for integrative studies.

• DNA repair
• Staphylococcus aureus
• actinic keratosis
• cancer-promoting toxins
• genotoxicity
• keratinocytes
• oxidative stress
• phenol soluble modulins
• proteomics
• squamous cell carcinoma
• transcriptomics

• LP160100731 Australian Research Council
• APP1071822 National Health and Medical Research Council
• APP1059012 National Health and Medical Research Council
• none Merchant foundation
• APP1137127 Medical Research Futures Fund

• Mutagen
• carcinogen
• environmental factors
• human health

Co-infection with the cagA strain of Helicobacter pylori exacerbates the pathology of human liver fluke Opisthorchis viverrini (OV) infection leading to cholangiocarcinoma. However, underlying mechanisms remain unclear. We report a significant increase in cagA-positive and cagA-negative H. pylori in the stomach, blood, bile, and in the OV worms of co-infected Syrian golden hamsters at one hour, three hours, and one month, post-infection, compared to hamsters infected with either OV or H. pylori alone. Except in the worms, H. pylori numbers declined at three months post-infection, particularly in the bile fluid of co-infected animals. Both strains of H. pylori were immunohistochemically detected in the tegument of the worm, as well as in the bile duct epithelium when co-infected with O. viverrine, but not in H. pylori infection alone. Interestingly, only the cagA-positive strain was detected in the gut of the worm. Co-infection between cagA-positive H. pylori and O. viverrini resulted in a more severe biliary pathology and decreased E-cadherin expression in vivo and in vitro than those of the cagA-negative strain. These data suggest that O. viverrini acts as a carrier of cagA-positive H. pylori and co-migrates to the bile ducts, whereas O. viverrini facilitates H. pylori colonization and enhances the biliary pathogenesis and carcinogenesis.

• Helicobacter pylori
• Opisthorchis viverrini
• co-infection
• colonization
• migration
• pathogenesis

The human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.

• Cancer treatment
• Future research
• Gut microbiome
• Intratumour microbiota
• Locally resident microbiome
• Mechanism

• Bile
• Chronic Cholecystitis
• Gallbladder Diseases
• Gallbladder Neoplasms
• Microbiota

• Adult
• Bacteria/classification
• Bacteria/isolation & purification
• Bile/metabolism
• Bile/microbiology
• Case-Control Studies
• Cholecystitis/microbiology
• Cholecystitis/pathology
• Dysbiosis/microbiology
• Gallbladder/microbiology
• Gallbladder Diseases/microbiology
• Gallbladder Neoplasms/microbiology
• Humans
• Metagenomics
• Microbiota
• Middle Aged
• Phylogeny

• NRF-2014R1A1A1005144 National Research Foundation of Korea
• NRF-2021M3E5D1A01015177 National Research Foundation of Korea

• Cyclomodulins
• carcinomas
• cell cycle modulation
• hyperplasia

• Bacterial peptide
• Colon cancer
• HPRP-A1
• iRGD

• Gall bladder cancer
• Gall stone
• Modified Widal test
• Salmonella paratyphi
• Salmonella typhi

• CTLA-4
• cancer progression and microbes
• immuno-oncology
• immunotherapy
• microbiome
• physiological responses

• Humans
• Immunotherapy
• Microbiota/immunology
• Neoplasms/immunology
• Neoplasms/microbiology
• Neoplasms/therapy

• Colorectal cancer
• Inflammatory bowel disease
• Iran
• Streptococcus gallolyticus

Bacterial infections are increasingly being recognized as risk factors for the development of adenocarcinomas. The strong epidemiological evidence linking Helicobacter pylori infection to stomach cancer has paved the way to the demonstration that bacterial infections cause DNA damage in the host cells, initiating transformation. In this regard, the role of bacterial genotoxins has become more relevant. Salmonella enterica serovars Typhi and Paratyphi A have been clinically associated with gallbladder cancer. By harnessing the stem cell potential of cells from healthy human gallbladder explant, we regenerated and propagated the epithelium of this organ in vitro and used these cultures to model S. Paratyphi A infection. This study demonstrates the importance of the typhoid toxin, encoded only by these specific serovars, in causing genomic instability in healthy gallbladder cells, posing intoxicated cells at risk of malignant transformation.

Carcinoma of the gallbladder (GBC) is the most frequent tumor of the biliary tract. Despite epidemiological studies showing a correlation between chronic infection with Salmonella enterica Typhi/Paratyphi A and GBC, the underlying molecular mechanisms of this fatal connection are still uncertain. The murine serovar Salmonella Typhimurium has been shown to promote transformation of genetically predisposed cells by driving mitogenic signaling. However, insights from this strain remain limited as it lacks the typhoid toxin produced by the human serovars Typhi and Paratyphi A. In particular, the CdtB subunit of the typhoid toxin directly induces DNA breaks in host cells, likely promoting transformation. To assess the underlying principles of transformation, we used gallbladder organoids as an infection model for Salmonella Paratyphi A. In this model, bacteria can invade epithelial cells, and we observed host cell DNA damage. The induction of DNA double-strand breaks after infection depended on the typhoid toxin CdtB subunit and extended to neighboring, non-infected cells. By cultivating the organoid derived cells into polarized monolayers in air-liquid interphase, we could extend the duration of the infection, and we observed an initial arrest of the cell cycle that does not depend on the typhoid toxin. Non-infected intoxicated cells instead continued to proliferate despite the DNA damage. Our study highlights the importance of the typhoid toxin in causing genomic instability and corroborates the epidemiological link between Salmonella infection and GBC.

• DNA damage
• Salmonella
• gallbladder
• gallbladder cancer
• mucosoid cultures
• organoid cultures
• typhoid toxin

• bacteremia
• cancer
• staphylococcus aureus

• Adolescent
• Adult
• Aged
• Bacteremia/blood
• Bacteremia/epidemiology
• Bacteremia/etiology
• Child
• Child, Preschool
• Cohort Studies
• Denmark/epidemiology
• Female
• Humans
• Incidental Findings
• Infant
• Male
• Middle Aged
• Neoplasms/diagnosis
• Neoplasms/epidemiology
• Poisson Distribution
• Risk Factors
• Staphylococcus aureus/drug effects
• Staphylococcus aureus/pathogenicity

The Gram-negative Campylobacter jejuni is a major cause of foodborne gastroenteritis in humans worldwide. The cytotoxic effects of Campylobacter have been mainly ascribed to the actions of the cytolethal distending toxin (CDT): it is mandatory to put in evidence risk factors for sequela development, such as reactive arthritis (ReA) and Guillain–Barré syndrome (GBS). Several researches are directed to managing symptom severity and the possible onset of sequelae. We found for the first time that rapamycin (RM) is able to largely inhibit the action of C. jejuni lysate CDT in U937 cells, and to partially avoid the activation of specific sub-lethal effects. In fact, we observed that the ability of this drug to redirect lysosomal compartment, stimulate ER-remodeling (highlighted by ER–lysosome and ER–mitochondria contacts), protect mitochondria network, and downregulate CD317/tetherin, is an important component of membrane microdomains. In particular, lysosomes are involved in the process of the reduction of intoxication, until the final step of lysosome exocytosis. Our results indicate that rapamycin confers protection against C. jejuni bacterial lysate insults to myeloid cells.

• CD317/tetherin
• Campylobacter jejuni
• ER-remodeling
• lysosome positioning and exocytosis
• rapamycin

• Epstein Barr
• cancer
• cytomegalovirus
• infection
• oncogenesis
• viruses

• bacterial peptide
• bacteriocins
• bacteriotherapy
• breast cancer
• toxin

• Animals
• Bacteria/metabolism
• Bacteriocins/metabolism
• Breast Neoplasms/metabolism
• Breast Neoplasms/therapy
• Colicins/metabolism
• Humans
• Nisin/metabolism
• Peptides, Cyclic/metabolism

A great number of researches over the last years are allocated to know cancer reasons, prevention and treatment strategies. Bacterial infections are one of the promoting factors in cancer development. The present study was carried out to study effects of heat-killed bacteria on cancer cell lines MCF7 and HT-29. To this purpose, four bacterial strains including Salmonella typhi, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa were assayed. Thermal inactivation method was used to kill the bacteria and preserve the bacterial surface proteins unchangeable. The concentrations of 0.01, 0.1, 0.5 and 1 mg/ml of inactivated bacteria were prepared to evaluate the effects of heat-inactivated bacterial solutions on MCF7 and HT-29 cell lines. MTT assay was used to measure the cell viability of cancer cells treated with different concentration of inactivated bacterial solutions.The MTT assay results after 48 hours showed that the heat-killed bacterial solutions were able to induce the proliferation of both cancer cell lines. In addition, the most cell viability in MCF-7 cell line was seen in samples treated with S. epidermidis, while in HT29 cells, the most one was seen in S. typhi treated samples. It was concluded that bacterial infections are cancer-deteriorating agents, and any species of bacteria is specific to certain cancerous tissue.

• Breast cancer
• Chronic infections
• Colon cancer
• Heat inactivation
• Inflammatory responses
• MTT-assay

• Animals
• China
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/parasitology
• Humans
• Schistosoma japonicum
• Schistosomiasis japonica/complications
• Schistosomiasis japonica/epidemiology

• Genetic predisposition
• Mycobacterium tuberculosis
• lung cancer risk
• microRNA
• sRNA

Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy.

• Chronic Inflammation
• Gallbladder Cancer
• Gallstones
• HER2/Neu
• Heavy Metals
• New Mexico
• Personalized medicine

Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention.

• DNA Damage Response
• Salmonella Typhi
• biofilm
• gallbladder cancer
• gallstone
• infection
• inflammation
• skin manifestations
• toxin

• Animals
• Biofilms/growth & development
• Gallbladder Neoplasms/metabolism
• Gallbladder Neoplasms/microbiology
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/prevention & control
• Humans
• Salmonella typhi/physiology
• Typhoid Fever/metabolism
• Typhoid Fever/pathology
• Typhoid Fever/therapy

Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.

• Gallbladder cancer
• Epidemiology
• Molecular genetics
• Pathogenesis

• Biomarkers, Tumor/genetics
• DNA Methylation
• Epigenesis, Genetic
• Gallbladder Neoplasms/epidemiology
• Gallbladder Neoplasms/genetics
• Gallbladder Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease
• Humans
• Loss of Heterozygosity
• Microsatellite Instability
• Molecular Epidemiology
• Mutation
• Phenotype
• Risk Factors

• Chile
• Salmonella enterica serovar Typhi
• Vi antibodies
• epidemiology
• gallbladder cancer
• meta-analysis

• Case-Control Studies
• Female
• Gallbladder Neoplasms/diagnosis
• Gallbladder Neoplasms/epidemiology
• Gallbladder Neoplasms/etiology
• Humans
• Male
• Risk Assessment
• Salmonella typhi/immunology
• Typhoid Fever/complications
• Typhoid Fever/epidemiology
• Typhoid Fever/microbiology

• cancer
• infection
• malignant
• neoplasia
• oncogenesis
• viruses

• Hormesis
• Lipid peroxidation
• Microbiome
• Oncogenesis
• Tumor microenvironment

• Animals
• Bacteria
• Carcinogenesis
• Hormesis
• Humans
• Microbiota
• Neoplasms/drug therapy
• Neoplasms/microbiology
• Reactive Oxygen Species
• Tumor Microenvironment

Gallbladder cancer (GBC) shows a marked geographical variation in its incidence. Middle-aged and elderly women are more commonly affected. Risk factors for its development include the presence of gallstones, chronic infection and pancreaticobiliary maljunction. Controversy remains in regard to the theory of carcinogenesis from adenomyomatosis, porcelain gallbladder and adenoma of the gallbladder. The surgical strategy and prognosis after surgery for GBC differ strikingly according to T-stage. Discrimination of favorable cases, particularly T2 or T3 lesions, is useful for the selection of surgical strategies for individual patients. Although many candidate factors predicting disease progression, such as depth of subserosal invasion, horizontal tumor spread, tumor budding, dedifferentiation, Ki-67 labeling index, p53 nuclear expression, CD8+ tumor-infiltrating lymphocytes, mitotic counts, Laminin-5-gamma-2 chain, hypoxia-inducible factor-1a, cyclooxygenase-2 and the Hedgehog signaling pathway have been investigated, useful prognostic makers or factors have not been established. As GBC is often discovered incidentally after routine cholecystectomy and accurate preoperative diagnosis is difficult, close mutual cooperation between surgeons and pathologists is essential for developing a rational surgical strategy for GBC.

• Gallbladder cancer
• Surgical strategy
• Pathology
• Prognostic factors

• Colorectal cancer
• Streptococcus bovis
• colon cancer
• meta-analysis
• rectal cancer
• risk factor

• Barriers
• Cancer
• Coinfection
• Evolution
• Infection
• Oncogenesis
• Prevention
• Vaccination

Metaplastic features of the gallbladder epithelium are considered to be the precursors of gallbladder cancer. Considering the possible role of chronic inflammatory changes in the development of these lesions and the rationale for performing an early prophylactic cholecystectomy, we performed a retrospective study to assess the prevalence of gallbladder metaplasia in patients who underwent cholecystectomy due to underlying cholelithiasis.

We reviewed the routine histopathology reports of 86 patients with chronic cholecystitis, who underwent elective cholecystectomy, to assess the prevalence of gallbladder metaplasia in the course of chronic cholecystitis. We further attempted to evaluate the existence of any correlations between the presence of the gallbladder metaplasia and the type of lithiasis, as well as the gallbladder wall thickness.

The overall prevalence of metaplastic features in the resected specimens was 25.6%. Dysplastic changes were more frequent in gallbladder specimens with concurrent metaplasia. Moreover, in presence of metaplastic changes, we observed an increase of the average gallbladder wall thickness. Finally, metaplastic and dysplastic changes were associated with the presence of micro-lithiasis rather than macro-lithiasis.

Gallbladder metaplastic changes appear to be more frequent in cases of micro-lithiasis and seem to be associated with a chronic thickening of the gallbladder wall. Taking into account the usually sub-clinical course of this group of patients, when compared to patients with macro-lithiasis, further studies are needed to evaluate a possible role of prophylactic cholecystectomy in this population to prevent the long term evolution of these early changes to cancerous lesions.

• Cancer
• Cholecystectomy
• Gallbladder
• Metaplasia

• Adenocarcinoma/complications
• Carcinoid Tumor/complications
• Female
• Humans
• Intestinal Neoplasms/complications
• Male
• Sepsis/complications
• Streptococcal Infections/complications
• Streptococcus bovis

• Aetiology
• Chronic inflammation
• Gallbladder cancer
• Pathogenesis