The cascade of gastric cancer, a leading cause of cancer incidence and mortality, is multifactorial. Helicobacter pylori (HP) infection plays a major role in gastric cancer (GC), and there has been ...an accumulation of data regarding the chemopreventive effect of HP eradication. However, it remains unclear how HP infection causes GC and how HP eradication prevents GC. To clarify this issue, the following approaches were performed in this review article. First, how HP‐induced atrophic gastritis (AG) and intestinal metaplasia (IM) provoke the development of GC is shown, followed by how long HP eradication takes to induce a reversible change in AG and IM. Second, epigenetic studies of PTPN6, MOS, DCC, CRK, and VAV1 were performed in noncancerous gastric specimens in terms of HP status. Among these genes, MOS was found to be a possible surrogate marker for GC development. HP eradication decreased aberrant DNA methylation in a gene‐specific manner, and MOS played a role in metachronous gastric neoplasms. Third, transforming growth factor‐β1 (TGF‐β1) and TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) markers were investigated in gastric mucosa. HP infection triggered the TGF‐β1‐induced EMT pathway and caused the emergence of GC stem cells, such as CD44v8‐10. When HP was eradicated, these two pathways were inhibited. Finally, a 2222 cohort study showed that HP eradication significantly decreased the risk of noncardiac GC. Taken together, HP eradication is effective as a primary GC prevention method, and its underlying mechanism includes reversibility of AG and IM, methylation, EMT, and stem cells.
CDH23 mutations have mostly been associated with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic or nonsyndromic SNHL (DFNB12). Herein, we demonstrate the ...contribution of CDH23 mutations to postlingual nonsyndromic SNHL (NS-SNHL). We screened 32 Korean adult probands with postlingual NS-SNHL sporadically or in autosomal recessive fashion using targeted panel or whole exome sequencing. We identified four (12.5%, 4/32) potential postlingual DFNB12 families that segregated the recessive CDH23 variants, qualifying for our criteria along with rapidly progressive SNHL. Three of the four families carried one definite pathogenic CDH23 variant previously known as the prelingual DFNB12 variant in a trans configuration with rare CDH23 variants. To determine the contribution of rare CDH23 variants to the postlingual NS-SNHL, we checked the minor allele frequency (MAF) of CDH23 variants detected from our postlingual NS-SNHL cohort and prelingual NS-SNHL cohort, among the 2040 normal control chromosomes. The allele frequency of these CDH23 variants in our postlingual cohort was 12.5%, which was significantly higher than that of the 2040 control chromosomes (5.53%), confirming the contribution of these rare CDH23 variants to postlingual NS-SNHL. Furthermore, MAF of rare CDH23 variants from the postlingual NS-SNHL group was significantly higher than that from the prelingual NS-SNHL group. This study demonstrates an important contribution of CDH23 mutations to poslingual NS-SNHL and shows that the phenotypic spectrum of DFNB12 can be broadened even into the presbycusis, depending on the pathogenic potential of variants. We also propose that pathogenic potential of CDH23 variants and the clinical fate of DFNB12 may be predicted by MAF.
The distribution of gut microbiota varies according to age (childhood, puberty, pregnancy, menopause, and old age) and sex. Gut microbiota are known to contribute to gastrointestinal (GI) diseases ...such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer; however, the exact etiology remains elusive. Recently, sex and gender differences in GI diseases and their relation to gut microbiota has been suggested. Furthermore, the metabolism of estrogen and androgen was reported to be related to the gut microbiome. As gut microbiome is involved in the excretion and circulation process of sex hormones, the concept of "microgenderome" indicating the role of sex hormone on the gut microbiota has been suggested. However, further research is needed for this concept to be universally accepted. In this review, we summarize sex- and gender-differences in gut microbiota and the interplay of microbiota and GI diseases, focusing on sex hormones. We also describe the metabolic role of the microbiota in this regard. Finally, current subjects, such as medication including probiotics, are briefly discussed.
Because of the sex-gender differences that are shown in a diversity of physiological and psychological factors, it can be speculated that the clinical presentation of symptoms as well as treatment ...strategies in women and men with irritable bowel syndrome (IBS) may differ. Studies have revealed that IBS is more common in women than men. As for the IBS subtype, IBS with constipation is significantly more prevalent among women than men. Sex hormones and gender differences may play important roles in the pathophysiology of IBS. However, its pathophysiologic mechanisms still remain largely unknown, and therapeutic implications are limited. Moreover, women IBS patients have been reported to feel more fatigue, depression, anxiety, and lower quality of life than men IBS patients. Furthermore, there has been evidence of differences in the appropriate treatment efficacy to IBS in men and women, although relatively few men are enrolled in most relevant clinical trials. A more sex-gender-oriented approach in the medical care setting could improve understanding of heterogeneous patients suffering from IBS. An individualized and multicomponent approach including sex and gender issues might help improve the treatment of IBS.
In addition to the main chromosome, approximately one in ten bacterial genomes have a ‘second chromosome’ or ‘megaplasmid’. Here, we propose that these represent a single class of elements that have ...a distinct and consistent set of properties, and suggest the term ‘chromid’ to distinguish them from both chromosomes and plasmids. Chromids carry some core genes, and their nucleotide composition and codon usage are very similar to those of the chromosomes they are associated with. By contrast, they have plasmid replication and partitioning systems and the majority of their genes confer accessory functions. Chromids seem particularly rich in genus-specific genes and appear to be ‘reinvented’ at the origin of a new genus.
Among the most promising therapeutic modalities for cancer treatment is the blockade of immune checkpoint pathways, which are frequently co-opted by tumors as a major mechanism of immune escape. ...CTLA-4 and PD-1 are the representative examples, and their blockade by therapeutic antibodies leads to enhanced anti-tumor immunity with durable clinical responses, but only in a minority of patients. This has highlighted the need to identify and target additional immune checkpoints that can be exploited to further enhance immune responses to refractory cancers. These emerging targets include natural killer (NK) cell-directed checkpoint receptors (KIR and CD94/NKG2A) as well as the NK- and T cell-expressed checkpoints TIM-3, TIGIT, CD96, and LAG-3. Interestingly, the potentiation of anti-tumor immunity by checkpoint blockade relies not only on T cells but also on other components of the innate immune system, including NK cells. NK cells are innate lymphoid cells that efficiently kill tumor cells without MHC specificity, which is complementary to the MHC-restricted tumor lysis mediated by cytotoxic T cells. However, the role of these immune checkpoints in modulating the function of NK cells remains unclear and somewhat controversial. Unraveling the mechanisms by which these immune checkpoints function in NK cells and other immune cells will pave the way to developing new therapeutic strategies to optimize anti-tumor immunity while limiting cancer immune escape. Here, we focus on recent findings regarding the roles of immune checkpoints in regulating NK cell function and their potential application in cancer immunotherapy.
Intratumor heterogeneity within individual cancer tissues underlies the numerous phenotypes of cancer. Tumor subclones ultimately affect therapeutic outcomes due to their distinct molecular features. ...Drug-resistant subclones are present at a low frequency in tissues at the time of biopsy, but can also arise as a result of acquired somatic mutations. A number of different approaches have been utilized to understand the nature of intratumor heterogeneity. Clonal analysis using whole exome or genome sequencing data can help monitor subclones in the context of tumor progression. Multiregional biopsies permit the molecular characterization of subclones within tumors. Deep sequencing has also provided researchers with the ability to measure the low allele fraction variant within a small number of cells. Ultimately, single-cell sequencing will enable the identification of every minor population within a tumor microenvironment. In the clinical context, the ability to identify and monitor the subclonal architecture of a tumor is valuable for the development of precise cancer therapeutic methods.
The sex/gender of gastroenterologists impact patients' satisfaction, compliance, and clinical outcomes. For instance, female gastrointestinal (GI) endoscopist-patient gender concordance improves ...health-related outcomes. This finding suggests that it is important to increase the number of female GI endoscopists. While the number of women in the field of gastroenterology is increasing in the United States and Korea by over 28.3%, it is not enough to account for the gender preferences of female patients. GI endoscopists are at a high risk of endoscopy-related injuries. However, there is a different distribution of muscle and fat; male endoscopists are more affected in their back, while females are more affected in the upper extremities. Women are more susceptible to endoscopy-related injuries than men. There is a correlation between the number of colonoscopies performed and musculoskeletal pain. Job satisfaction is lower in young female gastroenterologists (30' and 40') than in the opposite gender and other ages. Thus, it is important to address these issues in the development of GI endoscopy.
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