A 62-year-old male presented with pain and haematuria starting 3 months before. The computed tomography showed focal and mural bladder thickening with ureteropelvic dilatation. The following transurethral bladder resection revealed a high-grade muscle-invasive urothelial carcinoma. In the subsequent cystoprostatectomy we found the same tumour, but adding focal tumour-associated stromal osseous metaplasia. Ossifying metaplasia is an extremely rare feature in urothelial carcinoma, with a few reported cases and represents a diagnostic challenge, mimicking radiotherapy-induced sarcoma or sarcomatoid carcinoma. (AU)
Varón de 62 años que consulta por dolor y hematuria desde hace 3 meses. En la tomografía computarizada se observó un engrosamiento focal y mural de la vejiga con dilatación ureteropélvica. La resección vesical transuretral reveló un carcinoma urotelial infiltrante de alto grado músculo-invasivo. En la cistoprostatectomía posterior encontramos el mismo tumor, pero añadiendo focos de metaplasia ósea estromal asociada al tumor. La metaplasia osificante es una característica extremadamente rara en el carcinoma urotelial, con algunos casos informados, y representa un desafío diagnóstico, ya que simula un sarcoma inducido por radioterapia o un carcinoma sarcomatoide. (AU)
Humans , Male , Middle Aged , Osteoma, Osteoid , Carcinoma, Transitional Cell , Urinary Bladder , Metaplasia , Tomography, X-Ray Computed
Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.
Adenocarcinoma, Mucinous , Fallopian Tube Neoplasms , Fallopian Tubes , Metaplasia , Tumor Suppressor Protein p53 , Humans , Female , Fallopian Tube Neoplasms/pathology , Fallopian Tube Neoplasms/metabolism , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/metabolism , Aged , Middle Aged , Retrospective Studies , Fallopian Tubes/pathology , Aged, 80 and over , Tumor Suppressor Protein p53/metabolism , Metaplasia/pathology , Keratin-7/metabolism , CDX2 Transcription Factor/metabolism , CDX2 Transcription Factor/genetics , Mucin-6/metabolism , Matrix Attachment Region Binding Proteins/metabolism , Matrix Attachment Region Binding Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Carcinoma in Situ/pathology , Immunohistochemistry
BACKGROUND: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies. METHOD: The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells. RESULT: Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway. CONCLUSION: The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions.
Metaplasia , Humans , Air , Models, Biological , Gastric Mucosa/pathology , Gastric Mucosa/metabolism , Stomach/pathology , Organoids/pathology , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Transcriptome/genetics , Intestines/pathology
BACKGROUND: Metaplastic breast carcinomas are a rare variant group of breast carcinomas. They are usually high-grade and triple-negative tumors. They often present with large primary tumor sizes. However, the involvement of axillary lymph nodes is infrequent at the time of diagnosis. Metaplastic breast carcinomas are associated with a worse prognosis and a poorer response to chemotherapy in comparison with other non-metaplastic triple-negative breast cancers. Up until this point, there are no specific treatment recommendations for metaplastic breast carcinomas beyond those intended for invasive breast cancer in general. CASE PRESENTATION: A 40-year-old woman complained of a palpable mass in her left axilla. On ultrasonography, the mass was solid, spindle-shaped, hypoechoic with regular borders, and exhibited decreased vascularity. At first, the mass appeared to be of a muscular origin. There was not any clinical nor ultrasonic evidence of a primary breast tumor. On magnetic resonance imaging, the axillary mass was a well-defined with regular borders, measuring 24 × 35 mm. Needle biopsy showed a spindle cell tumor with mild to moderate atypia. The subsequent surgical resection revealed a spindle cell neoplasm within a lymph node, favoring a metastatic origin of the tumor. The tumor cells lacked expression of estrogen, progesterone, and HER2 receptors. PET-CT scan indicated pathological uptake in the left breast. Accordingly, the patient was diagnosed with metaplastic breast cancer that had metastasized to the axillary lymph node. She commenced a combined chemotherapy regimen of doxorubicin and cyclophosphamide. After six treatment cycles, she underwent left modified radical mastectomy with axillary lymph node dissection. Pathological examination of the specimens revealed a total burn-out tumor in the breast due to excellent treatment response. There were no residual tumor cells. All dissected lymph nodes were free of tumor. At the one-year follow-up, the patient showed no signs of tumor recurrence. CONCLUSION: This report sheds light on a distinctive presentation of metaplastic breast carcinoma, emphasizing the need for vigilance in diagnosing this rare and aggressive breast cancer variant. In addition, the patient's remarkable response to chemotherapy highlights potential treatment avenues for metaplastic breast cancer.
Breast Neoplasms , Humans , Female , Adult , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/diagnosis , Axilla , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphatic Metastasis , Metaplasia , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology
BACKGROUND AND AIMS: Gastric intestinal metaplasia is a precancerous disease, and a timely diagnosis is essential to delay or halt cancer progression. Artificial intelligence (AI) has found widespread application in the field of disease diagnosis. This study aimed to conduct a comprehensive evaluation of AI's diagnostic accuracy in detecting gastric intestinal metaplasia in endoscopy, compare it to endoscopists' ability, and explore the main factors affecting AI's performance. METHODS: The study followed the PRISMA-DTA guidelines, and the PubMed, Embase, Web of Science, Cochrane, and IEEE Xplore databases were searched to include relevant studies published by October 2023. We extracted the key features and experimental data of each study and combined the sensitivity and specificity metrics by meta-analysis. We then compared the diagnostic ability of the AI versus the endoscopists using the same test data. RESULTS: Twelve studies with 11,173 patients were included, demonstrating AI models' efficacy in diagnosing gastric intestinal metaplasia. The meta-analysis yielded a pooled sensitivity of 94% (95% confidence interval: 0.92-0.96) and specificity of 93% (95% confidence interval: 0.89-0.95). The combined area under the receiver operating characteristics curve was 0.97. The results of meta-regression and subgroup analysis showed that factors such as study design, endoscopy type, number of training images, and algorithm had a significant effect on the diagnostic performance of AI. The AI exhibited a higher diagnostic capacity than endoscopists (sensitivity: 95% vs. 79%). CONCLUSIONS: AI-aided diagnosis of gastric intestinal metaplasia using endoscopy showed high performance and clinical diagnostic value. However, further prospective studies are required to validate these findings.
Artificial Intelligence , Metaplasia , Humans , Metaplasia/diagnosis , Metaplasia/pathology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Sensitivity and Specificity , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , ROC Curve , Stomach/pathology
PURPOSE: To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors. METHODS: A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated. RESULTS: SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38 months) was significantly longer than that in patients without SM (9 months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90 days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18). CONCLUSIONS: Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest.
Metaplasia , Urethra , Urethral Stricture , Urologic Surgical Procedures, Male , Humans , Urethral Stricture/epidemiology , Urethral Stricture/pathology , Urethral Stricture/surgery , Male , Retrospective Studies , Middle Aged , Aged , Urethra/pathology , Adult , Urologic Surgical Procedures, Male/methods , Time-to-Treatment
Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation.
Metaplasia , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Male , Female , Middle Aged , Aged , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Biomarkers, Tumor , Gastric Mucosa/pathology , Gastric Mucosa/metabolism , Adenocarcinoma/pathology , Cell Line, Tumor
Background: Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy, leading to a poorly-controlled disease state, necessitating the development of novel therapies. Bronchom is a calcio-herbal formulation, which is purported to treat chronic asthma. The objective of the current study was to examine the in-vivo efficacy of Bronchom in mouse model of allergic asthma. Methods: Ultra high performance liquid chromatography was utilized to analyze the phytocompounds in Bronchom. Further, the in-vivo efficacy of Bronchom was evaluated in House dust mite (HDM)-induced allergic asthma in mice. Mice were challenged with aerosolized methacholine to assess airway hyperresponsiveness. Subsequently, inflammatory cell influx was evaluated in bronchoalveolar lavage fluid (BALF) followed by lung histology, wherein airway remodeling features were studied. Simultaneously, the levels of Th2 cytokines and chemokines in the BALF was also evaluated. Additionally, the mRNA expression of pro-inflammatory and Th2 cytokines was also assessed in the lung along with the oxidative stress markers. Results: Phytocompounds present in Bronchom included, gallic acid, protocatechuic acid, methyl gallate, rosmarinic acid, glycyrrhizin, eugenol, 6-gingerol and piperine. Bronchom effectively suppressed HDM-induced airway hyperresponsiveness along with the influx of leukocytes in the BALF. Additionally, Bronchom reduced the infiltration of inflammatory cells in the lung and it also ameliorated goblet cell metaplasia, sub-epithelial fibrosis and increase in α-smooth muscle actin. Bronchom decreased Th2 cytokines (IL-4 and IL-5) and chemokines (Eotaxin and IP-10) in the BALF. Likewise, it could also suppress the mRNA expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6 and IL-33), and IL-13. Moreover, Bronchom restored the HDM-induced diminution of endogenous anti-oxidants (GSH and SOD) and the increase in pro-oxidants (GSSG and MDA). Furthermore, Bronchom could also decrease the nitrosative stress by lowering the observed increase in nitrite levels. Conclusion: Taken together, the results of the present study data convincingly demonstrate that Bronchom exhibits pharmacological effects in an animal model of allergic asthma. Bronchom mitigated airway hyperresponsiveness, inflammation and airway remodeling evoked by a clinically relevant allergen and accordingly it possesses therapeutic potential for the treatment of asthma.
Asthma , Chemokines , Cytokines , Disease Models, Animal , Goblet Cells , Metaplasia , Pyroglyphidae , Th2 Cells , Animals , Asthma/drug therapy , Asthma/immunology , Mice , Cytokines/metabolism , Goblet Cells/pathology , Goblet Cells/immunology , Goblet Cells/drug effects , Pyroglyphidae/immunology , Th2 Cells/immunology , Chemokines/metabolism , Fibrosis , Mice, Inbred BALB C , Airway Remodeling/drug effects , Female , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Lung/pathology , Lung/immunology , Lung/drug effects
Pancreatic ductal adenocarcinoma (PDAC) can originate from acinar-to-ductal metaplasia (ADM). Pancreatic acini harboring oncogenic Kras mutations are transdifferentiated to a duct-like phenotype that further progresses to become pancreatic intraepithelial neoplasia (PanIN) lesions, giving rise to PDAC. Although ADM formation is frequently observed in KrasG12D transgenic mouse models of PDAC, the exact mechanisms of how oncogenic KrasG12D regulates this process remain an enigma. Herein, we revealed a new downstream target of oncogenic Kras, cytokine CCL9, during ADM formation. Higher levels of CCL9 and its receptors, CCR1 and CCR3, were detected in ADM regions of the pancreas in p48cre:KrasG12D mice and human PDAC patients. Knockdown of CCL9 in KrasG12D-expressed pancreatic acini reduced KrasG12D-induced ADM in a 3D organoid culture system. Moreover, exogenously added recombinant CCL9 and overexpression of CCL9 in primary pancreatic acini induced pancreatic ADM. We also showed that, functioning as a downstream target of KrasG12D, CCL9 promoted pancreatic ADM through upregulation of the intracellular levels of reactive oxygen species (ROS) and metalloproteinases (MMPs), including MMP14, MMP3 and MMP2. Blockade of MMPs via its generic inhibitor GM6001 or knockdown of specific MMP such as MMP14 and MMP3 decreased CCL9-induced pancreatic ADM. In p48cre:KrasG12D transgenic mice, blockade of CCL9 through its specific neutralizing antibody attenuated pancreatic ADM structures and PanIN lesion formation. Furthermore, it also diminished infiltrating macrophages and expression of MMP14, MMP3 and MMP2 in the ADM areas. Altogether, our results provide novel mechanistic insight into how oncogenic Kras enhances pancreatic ADM through its new downstream target molecule, CCL9, to initiate PDAC.
Acinar Cells , Carcinoma, Pancreatic Ductal , Metaplasia , Pancreatic Neoplasms , Proto-Oncogene Proteins p21(ras) , Reactive Oxygen Species , Animals , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Mice , Reactive Oxygen Species/metabolism , Humans , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/genetics , Metaplasia/metabolism , Metaplasia/genetics , Acinar Cells/metabolism , Acinar Cells/pathology , Mice, Transgenic , Chemokines, CC/metabolism , Chemokines, CC/genetics , Macrophage Inflammatory Proteins/metabolism , Macrophage Inflammatory Proteins/genetics , Pancreas/metabolism , Pancreas/pathology
Airway hillocks are stratified epithelial structures of unknown function1. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia2,3. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer.
Cell Plasticity , Epithelial Cells , Regeneration , Respiratory Mucosa , Stem Cells , Animals , Female , Humans , Male , Mice , Epithelial Cells/cytology , Epithelial Cells/pathology , Metaplasia/etiology , Metaplasia/pathology , Respiratory Mucosa/cytology , Respiratory Mucosa/injuries , Respiratory Mucosa/pathology , Stem Cells/cytology , Tretinoin/metabolism , Tretinoin/pharmacology , Vitamin A/metabolism , Vitamin A/pharmacology , Lung Neoplasms/etiology , Lung Neoplasms/pathology , Mice, Inbred C57BL
A 62-year-old male presented with pain and haematuria starting 3 months before. The computed tomography showed focal and mural bladder thickening with ureteropelvic dilatation. The following transurethral bladder resection revealed a high-grade muscle-invasive urothelial carcinoma. In the subsequent cystoprostatectomy we found the same tumour, but adding focal tumour-associated stromal osseous metaplasia. Ossifying metaplasia is an extremely rare feature in urothelial carcinoma, with a few reported cases and represents a diagnostic challenge, mimicking radiotherapy-induced sarcoma or sarcomatoid carcinoma.
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Male , Humans , Middle Aged , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/pathology , Urinary Bladder/pathology , Cystectomy , Metaplasia/pathology
Methylation and hydroxymethylation of cytosine moieties in CpG islands of specific genes are epigenetic processes shown to be involved in the development of cervical (pre)neoplastic lesions. We studied global (hydroxy)methylation during the subsequent steps in the carcinogenic process of the uterine cervix by using immunohistochemical protocols for the detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in paraffin-embedded tissues of the normal epithelia and (pre)malignant lesions. This approach allowed obtaining spatially resolved information of (epi)genetic alterations for individual cell populations in morphologically heterogeneous tissue samples. The normal ectocervical squamous epithelium showed a high degree of heterogeneity for both modifications, with a major positivity for 5-mC in the basal and parabasal layers in the ectocervical region, while 5-hmC immunostaining was even more restricted to the cells in the basal layer. Immature squamous metaplasia, characterized by expression of SOX17, surprisingly showed a decrease of 5-hmC in the basal compartments and an increase in the more superficial layers of the epithelium. The normal endocervical glandular epithelium showed a strong immunostaining reactivity for both modifications. At the squamocolumnar junctions, a specific 5-hmC pattern was observed in the squamous epithelium, resembling that of metaplasia, with the typical weak to negative reaction for 5-hmC in the basal cell compartment. The reserve cells underlying the glandular epithelium were also largely negative for 5-hmC but showed immunostaining for 5-mC. While the overall methylation status remained relatively constant, about 20% of the high-grade squamous lesions showed a very low immunostaining reactivity for 5-hmC. The (pre)malignant glandular lesions, including adenocarcinoma in situ (AIS) and adenocarcinoma showed a progressive decrease of hydroxymethylation with advancement of the lesion, resulting in cases with regions that were negative for 5-hmC immunostaining. These data indicate that inhibition of demethylation, which normally follows cytosine hydroxymethylation, is an important epigenetic switch in the development of cervical cancer.
Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Female , Humans , Cytosine/metabolism , Uterine Cervical Neoplasms/pathology , Cervix Uteri/pathology , 5-Methylcytosine/metabolism , DNA Methylation , Carcinoma, Squamous Cell/pathology , Metaplasia/pathology
BACKGROUND/AIM: H. pylori infection can promote a systemic inflammatory syndrome, eventually leading to intestinal metaplasia and gastric cancer. The aim of our study was to investigate the possible association between dyslipidemia and histopathological features of H. pylori gastritis. PATIENTS AND METHODS: An observational, retrospective study was conducted over the period 2017-2022 on symptomatic patients with a positive rapid urease test. A total of 121 patients who underwent upper gastrointestinal endoscopy with stomach biopsy were enrolled in this study. Based on the updated Sydney System, we investigated the association between neutrophils, mononuclear cells, intestinal metaplasia, or gastric atrophy and altered lipid profiles. RESULTS: A high prevalence of H. pylori infection was noticed in the studied group upon the application of the rapid urease test, being associated with dyslipidemia regardless of patient sex. All the endoscopic diagnoses (acute, chronic, or atrophic chronic gastritis, metaplasia) correlated with the histopathological features. Mononuclear cells and metaplasia were more likely to be found in H. pylori-positive patients with dyslipidemia, which is consistent with acute and chronic inflammation caused by H. pylori in the gastric mucosa. CONCLUSION: Although our study was conducted on a small scale, it offers new insights and details regarding H. pylori infection and histopathological features. Mononuclear cells and metaplasia were associated with an altered lipid profile in H. pylori-positive patients. These findings warrant future investigation, such as the evolution of gastric biopsies and lipid profiles before and after eradication.
Gastric Mucosa , Gastritis , Helicobacter Infections , Helicobacter pylori , Tertiary Care Centers , Humans , Helicobacter Infections/pathology , Helicobacter Infections/complications , Helicobacter Infections/microbiology , Male , Female , Romania/epidemiology , Helicobacter pylori/isolation & purification , Middle Aged , Gastritis/pathology , Gastritis/microbiology , Gastric Mucosa/pathology , Gastric Mucosa/microbiology , Adult , Lipids/blood , Lipids/analysis , Retrospective Studies , Aged , Metaplasia/pathology , Biopsy , Dyslipidemias/pathology , Dyslipidemias/blood
Goblet cell hyperplasia and increased mucus production are features of airway diseases, including asthma, and excess airway mucus often worsens these conditions. Even steroids are not uniformly effective in mucus production in severe asthma, and new therapeutic options are needed. Seihaito is a Japanese traditional medicine that is used clinically as an antitussive and expectorant. In the present study, we examined the effect of Seihaito on goblet cell differentiation and mucus production. In in vitro studies, using air-liquid interface culture of guinea-pig tracheal epithelial cells, Seihaito inhibited IL-13-induced proliferation of goblet cells and MUC5AC, a major component of mucus production. Seihaito suppressed goblet cell-specific gene expression, without changing ciliary cell-specific genes, suggesting that it inhibits goblet cell differentiation. In addition, Seihaito suppressed MUC5AC expression in cells transfected with SPDEF, a transcription factor activated by IL-13. Furthermore, Seihaito attenuated in vivo goblet cell proliferation and MUC5AC mRNA expression in IL-13-treated mouse lungs. Collectively, these findings demonstrated that Seihaito has an inhibitory effect on goblet cell differentiation and mucus production, which is at least partly due to the inhibition of SPDEF.
Cell Differentiation , Cell Proliferation , Goblet Cells , Interleukin-13 , Medicine, Kampo , Metaplasia , Mucin 5AC , Mucus , Animals , Goblet Cells/drug effects , Goblet Cells/pathology , Goblet Cells/metabolism , Interleukin-13/metabolism , Mucin 5AC/genetics , Mucin 5AC/metabolism , Mucus/metabolism , Cell Differentiation/drug effects , Guinea Pigs , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , Cells, Cultured , Proto-Oncogene Proteins c-ets/genetics , Proto-Oncogene Proteins c-ets/metabolism , Male , Gene Expression/drug effects , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Mice , Trachea/cytology , Trachea/drug effects , Trachea/pathology , Trachea/metabolism
Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria Helicobacter pylori (HP) is associated with approximately 75% of gastric cancer cases. HP infection induces chronic gastric inflammation, damaging the stomach and fostering carcinogenesis. Most mechanistic studies on gastric cancer initiation are performed in mice and utilize either mouse-adapted strains of HP or the natural mouse pathogen Helicobacter felis (HF). Here, we identified the differences in gastric inflammation, atrophy, and metaplasia associated with HP and HF infection in mice. PMSS1 HP strain or the CS1 HF strain were co-cultured with mouse peritoneal macrophages to assess their immunostimulatory effects. HP and HF induced similar cytokine production from cultured mouse peritoneal macrophages revealing that both bacteria exhibit similar immunostimulatory effects in vitro. Next, C57BL/6J mice were infected with HP or HF and were assessed 2 months post-infection. HP-infected mice caused modest inflammation within both the gastric corpus and antrum, and did not induce significant atrophy within the gastric corpus. In contrast, HF induced significant inflammation throughout the gastric corpus and antrum. Moreover, HF infection was associated with significant atrophy of the chief and parietal cell compartments and induced the expression of pyloric metaplasia (PM) markers. HP is poorly immunogenic compared to HF. HF induces dramatic CD4+ T cell activation, which is associated with increased gastric cancer risk in humans. Thus, HP studies in mice are better suited for studies on colonization, while HF is more strongly suited for studies on the effects of gastric inflammation on tumorigenesis. . IMPORTANCE: Mouse infection models with Helicobacter species are widely used to study Helicobacter pathogenesis and gastric cancer initiation. However, Helicobacter pylori is not a natural mouse pathogen, and mouse-adapted H. pylori strains are poorly immunogenic. In contrast, Helicobacter felis is a natural mouse pathogen that induces robust gastric inflammation and is often used in mice to investigate gastric cancer initiation. Although both bacterial strains are widely used, their disease pathogenesis in mice differs dramatically. However, few studies have directly compared the pathogenesis of these bacterial species in mice, and the contrasting features of these two models are not clearly defined. This study directly compares the gastric inflammation, atrophy, and metaplasia development triggered by the widely used PMSS1 H. pylori and CS1 H. felis strains in mice. It serves as a useful resource for researchers to select the experimental model best suited for their studies.
Gastric Mucosa , Helicobacter Infections , Helicobacter felis , Helicobacter pylori , Metaplasia , Mice, Inbred C57BL , Animals , Helicobacter pylori/immunology , Helicobacter pylori/pathogenicity , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter Infections/immunology , Mice , Helicobacter felis/pathogenicity , Metaplasia/microbiology , Metaplasia/pathology , Gastric Mucosa/pathology , Gastric Mucosa/microbiology , Gastric Mucosa/immunology , Gastritis/microbiology , Gastritis/pathology , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology , Inflammation/microbiology , Inflammation/pathology , Female , Cytokines/metabolism , Disease Models, Animal , Stomach/pathology , Stomach/microbiology
Currently, the diagnostic strategy for chronic gastritis (CG) is aimed not just at fixing the presence of gastric mucosal inflammation, but also at gastric cancer (GC) risk stratification in a particular patient. Modern classification approach with the definition of the stage of gastritis determines the need, activities and frequency of dynamic monitoring of a patient. However, this attitude to the patient suffering from CG was far from always. The present publication is a literature review describing the key milestones in the history of CG research, from the description of the first observations of inflammation of the gastric mucosa, assessment of gastritis as a predominantly functional disease, to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy, assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy, intestinal metaplasia, dysplasia and GC.
Gastric Mucosa , Gastritis , Helicobacter Infections , Helicobacter pylori , Humans , Gastritis/diagnosis , Gastritis/history , Gastritis/microbiology , Gastritis/pathology , Chronic Disease , Gastric Mucosa/pathology , Gastric Mucosa/microbiology , History, 20th Century , Helicobacter Infections/history , Helicobacter Infections/microbiology , Helicobacter Infections/diagnosis , Helicobacter Infections/epidemiology , History, 21st Century , Helicobacter pylori/isolation & purification , Biopsy , Stomach Neoplasms/pathology , Stomach Neoplasms/history , Stomach Neoplasms/diagnosis , History, 19th Century , Disease Progression , Metaplasia , Predictive Value of Tests
The conjunctiva is a non-keratinized, stratified columnar epithelium with characteristics different from the cornea and eyelid epidermis. From development to adulthood, a distinguishing feature of ocular versus epidermal epithelia is the expression of the master regulator PAX6. A conditionally immortalized conjunctival epithelial cell line (iHCjEC) devoid of stromal or immune cells established in our laboratory spontaneously manifested epidermal metaplasia and upregulated expression of the keratinization-related genes SPRR1A/B and the epidermal cytokeratins KRT1 and KRT10 at the expense of the conjunctival trait. In addition, iHCjEC indicated a significant decrease in PAX6 expression. Dry eye syndrome (DES) and severe ocular surface diseases, such as Sjögren's syndrome and Stevens-Johnson syndrome, cause the keratinization of the entire ocular surface epithelia. We used iHCjECs as a conjunctiva epidermal metaplasia model to test PAX6, serum, and glucocorticoid interventions. Reintroducing PAX6 to iHCjECs resulted in upregulating genes related to cell adhesion and tight junctions, including MIR200CHG and CLDN1. The administration of glucocorticoids or serum resulted in the downregulation of epidermal genes (DSG1, SPRR1A/B, and KRT1) and partially corrected epidermal metaplasia. Our results using an isolated conjunctival epidermal metaplasia model point toward the possibility of rationally "repurposing" clinical interventions, such as glucocorticoid, serum, or PAX6 administration, for treating epidermal metaplasia of the conjunctiva.
Conjunctiva , Metaplasia , Conjunctiva/pathology , Conjunctiva/metabolism , PAX6 Transcription Factor/genetics , PAX6 Transcription Factor/metabolism , Humans , Epithelial Cells/metabolism , Epithelial Cells/pathology , Glucocorticoids/therapeutic use , Gene Expression Regulation , Epidermis/pathology , Epidermis/metabolism , Animals , Real-Time Polymerase Chain Reaction , Cell Line
Introducción. El cáncer de vesícula biliar es el más común en el tracto biliopancreático y una importante causa de mortalidad. La metaplasia y la displasia han sido mencionados como probables precursores relacionados con la secuencia metaplasia-displasia-cáncer. El objetivo de este estudio fue establecer las posibles asociaciones entre estas alteraciones histopatológicas y su relación con la edad y el sexo de los pacientes. Métodos. Estudio observacional retrospectivo descriptivo, con un componente analítico de corte transversal. Se incluyeron los informes de patología de pacientes llevados a colecistectomía laparoscópica electiva y ambulatoria, entre enero de 2015 y diciembre de 2020, con colecistitis crónica, colelitiasis o pólipos vesiculares, mayores de 18 años. Se describieron las características demográficas por sexo y edad utilizando medias, desviaciones estándar y porcentajes. Se emplearon la prueba de chi cuadrado y la prueba exacta de Fisher para evaluar la asociación entre las variables cualitativas. Resultados. Se incluyeron 4871 informes de patología. En esta cohorte se encontró asociación estadísticamente significativa entre metaplasia, displasia y cáncer de vesícula (p<0,05), al igual que con el sexo y la edad de los pacientes. Conclusiones. Los resultados sugieren una asociación entre metaplasia, displasia y cáncer de vesícula biliar en la población estudiada. Se recomienda la realización de investigaciones complementarias para definir la posible causalidad entre metaplasia, displasia y cáncer de vesícula biliar en una población más heterogénea.
Introduction. Gallbladder cancer is the most common cancer in the biliopancreatic tract and an important cause of mortality. Metaplasia and dysplasia have been mentioned as probable precursors related to the metaplasia-dysplasia-cancer sequence. The objective of this study was to establish the possible associations between these histopathological alterations and their relationship with the age and sex of the patients. Methods. Descriptive retrospective observational study, with a cross-sectional analytical component. Pathology reports of patients undergoing elective and outpatient laparoscopic cholecystectomy were included between January 2015 and December 2020, with chronic cholecystitis, cholelithiasis, or gallbladder polyps, over 18 years of age. Demographic characteristics by sex and age was performed using means, standard deviations, and percentages. The chi2 test and Fisher's exact test were used to evaluate the association between the qualitative variables. Results. 4871 pathology reports were included. In this cohort, a statistically significant association was found between metaplasia, dysplasia, and gallbladder cancer (p<0.05), as well as with the sex and age of the patients. Conclusions. The results suggest an association between metaplasia, dysplasia and gallbladder cancer in the study population. Additional research is recommended to define the possible causality between metaplasia, dysplasia, and gallbladder cancer in a more heterogeneous population.
Humans , Cholecystectomy , Gallbladder Neoplasms , Disease Progression , Gallbladder , Metaplasia , Neoplasms