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1.
Cell ; 161(7): 1494-6, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-26091030

RESUMO

In mouse intestinal tumors induced by the inhibition of APC, the restoration of APC function causes complete tumor regression with normal differentiation and return of stem cell function irrespective of whether tumors also carried mutations in Kras and p53. These findings by Dow et al. validate the Wnt pathway as an exquisite target for intervention.


Assuntos
Proteína da Polipose Adenomatosa do Colo/metabolismo , Neoplasias Colorretais/genética , Modelos Animais de Doenças , Intestino Grosso/patologia , Intestino Delgado/patologia , Animais
2.
Cell ; 161(7): 1539-1552, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-26091037

RESUMO

The adenomatous polyposis coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally suppressed using a doxycycline-regulated shRNA. Apc suppression produces adenomas in both the small intestine and colon that, in the presence of Kras and p53 mutations, can progress to invasive carcinoma. In established tumors, Apc restoration drives rapid and widespread tumor-cell differentiation and sustained regression without relapse. Tumor regression is accompanied by the re-establishment of normal crypt-villus homeostasis, such that once aberrantly proliferating cells reacquire self-renewal and multi-lineage differentiation capability. Our study reveals that CRC cells can revert to functioning normal cells given appropriate signals and provide compelling in vivo validation of the Wnt pathway as a therapeutic target for treatment of CRC.


Assuntos
Proteína da Polipose Adenomatosa do Colo/metabolismo , Neoplasias Colorretais/genética , Modelos Animais de Doenças , Intestino Grosso/patologia , Intestino Delgado/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Proliferação de Células , Neoplasias Colorretais/patologia , Doxiciclina/administração & dosagem , Genes p53 , Pólipos Intestinais/metabolismo , Pólipos Intestinais/patologia , Intestino Grosso/metabolismo , Intestino Delgado/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas p21(ras)/genética , Interferência de RNA , Via de Sinalização Wnt
3.
Mol Cell ; 81(2): 370-385.e7, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33271062

RESUMO

The mechanisms of cellular energy sensing and AMPK-mediated mTORC1 inhibition are not fully delineated. Here, we discover that RIPK1 promotes mTORC1 inhibition during energetic stress. RIPK1 is involved in mediating the interaction between AMPK and TSC2 and facilitate TSC2 phosphorylation at Ser1387. RIPK1 loss results in a high basal mTORC1 activity that drives defective lysosomes in cells and mice, leading to accumulation of RIPK3 and CASP8 and sensitization to cell death. RIPK1-deficient cells are unable to cope with energetic stress and are vulnerable to low glucose levels and metformin. Inhibition of mTORC1 rescues the lysosomal defects and vulnerability to energetic stress and prolongs the survival of RIPK1-deficient neonatal mice. Thus, RIPK1 plays an important role in the cellular response to low energy levels and mediates AMPK-mTORC1 signaling. These findings shed light on the regulation of mTORC1 during energetic stress and unveil a point of crosstalk between pro-survival and pro-death pathways.


Assuntos
Proteína 5 Relacionada à Autofagia/genética , Proteína de Domínio de Morte Associada a Fas/genética , Intestino Grosso/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Animais Recém-Nascidos , Proteína 5 Relacionada à Autofagia/deficiência , Caspase 8/genética , Caspase 8/metabolismo , Morte Celular/genética , Proteína de Domínio de Morte Associada a Fas/deficiência , Regulação da Expressão Gênica , Glucose/antagonistas & inibidores , Glucose/farmacologia , Células HEK293 , Células HT29 , Humanos , Intestino Grosso/efeitos dos fármacos , Intestino Grosso/patologia , Células Jurkat , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Lisossomos/patologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metformina/antagonistas & inibidores , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Proteína Serina-Treonina Quinases de Interação com Receptores/deficiência , Transdução de Sinais , Sirolimo/farmacologia , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo
4.
Digestion ; 105(5): 373-379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38857573

RESUMO

INTRODUCTION: Patients with Crohn's disease (CD) require an assessment of small bowel lesions, while difficulties exist in performing small intestinal examinations, especially in small-sized medical offices. Small bowel capsule endoscopy (SBCE) is handy and can be performed in most clinical settings. The only drawback of SBCE is a requirement of patency testing prior to the exam because it sometimes requires CT scanning to localize the ingested patency capsule (PC), which may be a substantial burden for the patient. We have developed a novel PC detection system named PICS (patency capsule, ileocolonoscopy, and small bowel capsule endoscopy) method by which we can avoid CT scanning. In the PICS method, ileocolonoscopy (ICS) is performed after 30-33 h of PC ingestion and the PC can be localized by ICS in patients who have not excreted the PC, and the entire intestine can be examined in combination with subsequent SBCE without additional bowel preparation. The aim of this study was to assess the usefulness and safety of the PICS method for CD patients. METHODS: CD patients who underwent PICS method from April 2021 to March 2023 were reviewed for clinical data, outcome of PICS method including the rates of PC detection by ICS, the number of patients underwent SBCE, and adverse events. Lewis score was used to assess SBCE results. RESULTS: The PICS method was performed in 54 patients. The median age of patients was 28.5 years old, and 64.8% of them were ileocolic type. The median disease duration was 10.5 months and 24.1% had history of small bowel resection. Five cases (9.3%) confirmed gastrointestinal patency by ICS, and none of the cases required CT scanning. One patient who could not be confirmed patency by ICS, and the other patient who excreted PC but was found ileal stenosis by ICS did not undergo SBCE. Remaining 52 patients received SBCE, and the median Lewis score of them was 0 (IQR 0, 450). There were no adverse events including small bowel obstruction by PC and SBCE retention in this series. CONCLUSION: The PICS method is not only feasible and safe but also convenient to assess disease extent in patients with CD. By localizing PC with ICS, additional CT scanning could be unnecessary for SBCE, which benefits both physicians and CD patients.


Assuntos
Endoscopia por Cápsula , Colonoscopia , Doença de Crohn , Intestino Delgado , Humanos , Doença de Crohn/diagnóstico por imagem , Endoscopia por Cápsula/métodos , Masculino , Feminino , Adulto , Intestino Delgado/diagnóstico por imagem , Pessoa de Meia-Idade , Colonoscopia/métodos , Adulto Jovem , Estudos Retrospectivos , Intestino Grosso/diagnóstico por imagem , Intestino Grosso/patologia , Adolescente , Idoso , Tomografia Computadorizada por Raios X/métodos
5.
Gut ; 71(3): 479-486, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33952604

RESUMO

OBJECTIVE: Effective medical therapy and validated trial outcomes are lacking for small bowel Crohn's disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion. DESIGN: Modified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures. RESULTS: In this exercise, diagnosis of naïve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials. CONCLUSION: Standardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.


Assuntos
Doença de Crohn/patologia , Obstrução Intestinal/patologia , Intestino Grosso/patologia , Consenso , Constrição Patológica , Doença de Crohn/complicações , Humanos , Obstrução Intestinal/etiologia , Índice de Gravidade de Doença , Inquéritos e Questionários
6.
J Intern Med ; 291(2): 224-231, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34437741

RESUMO

BACKGROUND: Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab. METHODS: Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed. RESULTS: All tested samples were strongly positive for SARS-CoV-2. CONCLUSIONS: This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.


Assuntos
COVID-19 , Intestino Grosso/patologia , Isquemia , COVID-19/patologia , Humanos , Isquemia/diagnóstico , Isquemia/virologia , Necrose , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Trombose
7.
Cytokine ; 152: 155826, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35158258

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the newly emerging lung disease pandemic COVID-19. This viral infection causes a series of respiratory disorders, and although this virus mainly infects respiratory cells, the small intestine can also be an important site of entry or interaction, as enterocytes highly express in angiotensin-2 converting enzyme (ACE) receptors. There are countless reports pointing to the importance of interferons (IFNs) with regard to the mediation of the immune system in viral infection by SARS-CoV-2. Thus, this review will focus on the main cells that make up the large intestine, their specific immunology, as well as the function of IFNs in the intestinal mucosa after the invasion of coronavirus-2.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Mucosa Intestinal/metabolismo , Intestino Grosso/metabolismo , SARS-CoV-2/metabolismo , COVID-19/patologia , Humanos , Mucosa Intestinal/lesões , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Intestino Grosso/lesões , Intestino Grosso/patologia , Intestino Grosso/virologia
8.
Georgian Med News ; (327): 18-26, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35959928

RESUMO

The main purpose of the study is to determine peculiar morphological characteristics of structural changes of alimentary system organs in the case of experimental undifferentiated dysplasia of connective tissue (UDCT). Intranatal antigen introduction was conducted as an experimental model of UDCT. Objects of investigation - pharynx, duodenum, ileum, caecum, ascendant colon of white rats from the first up to the 60th day of postnatal life. Animals were contained in standard conditions of vivarium according to Law of Ukraine № 1759-VI (15.12.2009) On the Protection of Animals from Cruelty. Morphological structure of organs were examined at days 1st, 7th, 14th, 21th, 45th, 60th after birth. Morphometric, histological, histochemical, lectinistochemical, immunehistochemic and statistic methods were used. Analysis of the obtained results was conducted by means of statistical methods with the use of computer license program «Statistica for Windows 13¼ (StatSoft Inc., № JPZ804I382130ARCN10-J). The compared results considered such, that for certain differ at р<0,05 that is generally accepted for biological and medical researches. On the background of experimental syndrome of UDCT, developed by intranatal antigen loading, it is settled that the number of intraepithelial lymphocytes, number of lymphocytes of submucose layer of alimentary tract increases. Ratio between cells of mucosa (including epithelial layer and submucosal layer) changes. Interrelation between layers of alimentary tube changes resulting in the thickening of mucosa (including epithelial layer and submucosal layer) and thinning of muscular layer. These inflections result in elongation of duodenum, small and large intestines. Throughout the first month after birth in rats with experimental syndrome of UDCT lymphocyte/epitheliocyte, lymphocyte/ fibroblast and lymphocyte/mitosis indexes change in proximal and distal parts of digestive tract.


Assuntos
Tecido Conjuntivo , Duodeno , Intestino Grosso , Animais , Colo , Tecido Conjuntivo/patologia , Duodeno/patologia , Íleo , Mucosa Intestinal/patologia , Intestino Grosso/patologia
9.
Artigo em Russo | MEDLINE | ID: mdl-35439392

RESUMO

The colorectal cancer remains one of leading problems of modern coloproctology and oncology. The polyps are one of pathology of colon widespread in population and predictor of colorectal cancer. Their timely detection and removal is considered as only effective measure of prevention of colon malignant neoplasms. The morbidity of colon malignant neoplasms in the Perm Kray was monitored in 2004-2018. Its structure and dynamics were evaluated. The software is described that allows both physicians and patients to evaluate probability of detecting colon neoplasms that contributes to expansion of the research database of coloproctologic studies. The ways of increasing effectiveness of predicting incidence of colorectal cancer and colon polyps were proposed on the basis of neural networks, that permit to increase detection of corresponding pathology by personalizing screening.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Pólipos do Colo/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Incidência , Intestino Grosso/patologia , Programas de Rastreamento
10.
J Gastroenterol Hepatol ; 36(2): 362-366, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32483847

RESUMO

BACKGROUND AND AIM: Paralytic ileus is a common intestinal dysfunction in critically ill patients, which results in complications and poor hospital outcomes. There are still no established effective medications, except correcting the primary causes and prokinetics trial, which have limited efficacy and potential adverse events. This study aims to evaluate the efficacy of prucalopride on paralytic ileus in critically ill patients. METHODS: A randomized, double-blind, placebo-controlled trial of five consecutive days treatment periods was conducted. Critically ill patients with paralytic ileus were included. The primary endpoint was the improvement of bowel dilatation on plain abdominal radiography. The secondary endpoint was the change of abdominal circumference. RESULTS: Twenty patients were consecutively enrolled in the study. There was no significant difference in baseline characteristics of patients. The common causes of hospitalization were infection and respiratory problems. The maximum large bowel diameters dramatically decreased in prucalopride group and reached maximum point on the third day after intervention when compared with placebo (-2.1 [± 1.8] vs 0.3 [± 1.5] cm, P = 0.01). The maximum small bowel diameters were noticeably less decreased and were not significantly different when compared with placebo. The abdominal circumferences notably decreased and significantly diverged from placebo on the third day. CONCLUSIONS: Prucalopride was an effective enterokinetic agent to improve non-severe inflammatory/ischemic bowel conditions related paralytic ileus in critically ill patients. Its effect was predominant on large intestine but could not be well demonstrated on small bowel in this study. Future study or concomitant other prokinetics for upper gut motility should be further evaluated.


Assuntos
Benzofuranos/uso terapêutico , Estado Terminal , Pseudo-Obstrução Intestinal/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Pseudo-Obstrução Intestinal/patologia , Intestino Grosso/patologia , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Agonistas do Receptor 5-HT4 de Serotonina/uso terapêutico , Resultado do Tratamento
11.
Mol Cell Proteomics ; 18(4): 657-668, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30617156

RESUMO

Bacteria can circumvent the effect of antibiotics by transitioning to a poorly understood physiological state that does not involve conventional genetic elements of resistance. Here we examine antibiotic susceptibility with a Class A ß-lactamase+ invasive strain of Klebsiella pneumoniae that was isolated from a lethal outbreak within laboratory colonies of Chlorocebus aethiops sabaeus monkeys. Bacterial responses to the ribosomal synthesis inhibitors streptomycin and doxycycline resulted in distinct proteomic adjustments that facilitated decreased susceptibility to each antibiotic. Drug-specific changes to proteomes included proteins for receptor-mediated membrane transport and sugar utilization, central metabolism, and capsule production, whereas mechanisms common to both antibiotics included elevated scavenging of reactive oxygen species and turnover of misfolded proteins. Resistance to combined antibiotics presented integrated adjustments to protein levels as well as unique drug-specific proteomic features. Our results demonstrate that dampening of Klebsiella pneumoniae susceptibility involves global remodeling of the bacterial proteome to counter the effects of antibiotics and stabilize growth.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Klebsiella pneumoniae/metabolismo , Proteoma/metabolismo , Animais , Antibacterianos/uso terapêutico , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Chlorocebus aethiops , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Intestino Grosso/microbiologia , Intestino Grosso/patologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Proteômica , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo
12.
BMC Cancer ; 20(1): 133, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075595

RESUMO

BACKGROUND: The importance of ACF is not fully explained, however, their number may be a good predictor of synchronous and metachronic adenoma or other polyps whose removal reduces the risk of CRC. Due to the epidemiological and genetic association of ACF with pre-cancer lesions, they may be a potential CRC biomarker. The aim of our study was to show that the number and type of rectal ACF may be a good predictive factor for the presence of polyps located proximally from the splenic flexure and that the type and number of ACF can correlate with the number and specific types of polyps in the large intestine. METHODS: The study included 131 patients who underwent colonoscopy combined with rectal mucosa staining with 0.25% methylene blue. The number of rectal ACF was determined and bioptats were sampled for histopathological examination to assess the type of ACF. Endoscopic ACF assessment criteria given by L. Roncucci were used. The obtained material was subjected to statistical analysis using probability distribution, U-test, t-student test, and chi 2 as well as the Statistica 7.1 software package. RESULTS: The study population was divided into three subgroups according to the number of ACF observed, i.e. ACF < 5, 5-10 and > 10. ACF < 5 were found in 35 patients (29.41%), 5-10 ACF in 70 (58.82%) and ACF > 10 in 14 individuals (11.76%). The study revealed the presence of normal ACF (p = 0.49), hyperplastic ACF (p = 0.34), dysplastic ACF (p = 0.11), and mixed ACF (p = 0.06). A single type of ACF was most commonly observed (n = 88, p = 0.74). In the researched group a larger number of ACF is concurrent with adenomas and hyperplastic polyps. The number of ACF clearly correlates with the dysplasia advancement in the adenoma and the number of polyps found. CONCLUSIONS: Rectal ACF are a useful marker for the presence of cancerous lesions in the proximal and distal sections of the large intestine.


Assuntos
Focos de Criptas Aberrantes/patologia , Adenoma/patologia , Biomarcadores Tumorais/análise , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Intestino Grosso/patologia , Lesões Pré-Cancerosas/patologia , Adenoma/cirurgia , Idoso , Pólipos do Colo/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/cirurgia , Fatores de Risco
13.
Cell Biol Int ; 44(11): 2284-2292, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32749739

RESUMO

Radiotherapy is an important adjuvant treatment for large intestine cancer even though it does not cause any response in many patients. The present study aimed to investigate the effects of the TTN antisense RNA 1 (TTN-AS1) long noncoding RNA (lncRNA) on radiotherapy dynamics of large intestine cancer cells and to explore the underlying molecular mechanisms. TTN-AS1 expression was evaluated by reverse-transcription quantitative polymerase chain reaction, western blot, and cellular immunofluorescence, and flow cytometry analysis was used to measure apoptosis. Radiotherapy was simulated in vitro by exposing cancer cells to X-ray. TTN-AS1 was highly expressed in large intestine cancer cells after an X-ray exposition for 24 hr. TTN-AS1 knockdown improved the radiosensitivity of large intestine cancer cells and promoted apoptosis by increasing Bax/Bcl2 protein expression and the active-caspase 3/caspase 3 ratios following X-ray treatment. In addition, TTN-AS1 negatively regulated miR-134-5p expression, and miR-134-5p-mimic transfection decreased PAK3 protein expression in large intestine cancer cells. Importantly, TTN-AS1 promoted PAK3 and P21 protein expression in HT29 cells after X-ray treatment. Moreover, the knockdown of P21 protein expression improved radiosensitivity and promoted X-ray-induced apoptosis of HT29 cells. Finally, PAK3 knockdown expression decreased the p-AKT/AKT and p-GSK-3ß/GSK-3ß ratios and promoted the ß-catenin transfer from the nucleus to the cytoplasm. These data suggest that the TTN-AS1 lncRNA promoted resistance to radiotherapy of large intestine cancer cells by increasing PAK3 expression via miR-134-5p inhibition, and this may be related to the P21 and AKT/GSK-3ß/ß-catenin pathway.


Assuntos
Neoplasias Intestinais/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Conectina/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Intestinais/metabolismo , Intestino Grosso/metabolismo , Intestino Grosso/patologia , MicroRNAs/metabolismo , Oligorribonucleotídeos Antissenso/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Tolerância a Radiação/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , beta Catenina/metabolismo , Quinases Ativadas por p21/genética
14.
Dig Dis Sci ; 65(1): 269-275, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31300994

RESUMO

BACKGROUND AND AIMS: Prior studies have shown that about 90% of all carcinoid tumors occur in the GI tract. However, epidemiological studies of these tumors have been limited by small sample size. Our aim was to obtain a more robust epidemiologic survey of large bowel carcinoids (LBC), using population-based data in order to more accurately identify risk factors for these tumors. METHODS: We used a commercial database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients aged 18 and older who were diagnosed with LBC, excluding appendiceal carcinoids, between 1999 and 2018 based on Systematized Nomenclature Of Medicine-Clinical Terms (SNOMED-CT) and evaluated the prevalence of LBC. We also performed univariate analysis to describe age-, race-, and gender-based distributions and to identify potential risk factors. RESULTS: Of the 62,817,650 individuals in the database, 4530 were identified to have LBC with an overall prevalence of 7.21/100,000. Individuals with LBC were more likely to be elderly (age > 65) [OR 2.17, CI 2.05-2.31, p < 0.0001], smokers [OR 3.25; 95% CI 3.00-3.53, p < 0.0001], have a history of alcohol use [OR 3.75; 95% CI 3.52-3.99, p < 0.0001], diabetes mellitus (DM) [OR 4.42; 95% CI 4.14-4.72, p < 0.0001], obesity [OR 1.58; 95% CI 1.43-1.74, p < 0.0001], family history of cancer [OR 8.06; 95% CI 7.47-8.71, p < 0.0001], and personal history of ulcerative colitis [OR 6.93; 95% CI 5.55-8.64, p < 0.0001] or Crohn's disease [OR 6.45; 95% CI 5.24-7.95, p < 0.0001]. The prevalence of LBC was less among Caucasians compared to African-Americans [OR 0.57; 95% CI 0.53-0.61, p < 0.0001]. There was no statistically significant gender-based difference; men versus women [OR 1.02; 95% CI 0.96-1.08, p = 0.47]. The most common presenting symptoms included flushing, diarrhea, nausea, weight loss, and abdominal pain, while the most common GI associations included perforation, obstruction, hemorrhage, intussusception, and volvulus. CONCLUSION: This is the largest epidemiological study evaluating the prevalence of LBC. We estimated the prevalence rate of LBC to be 7.21/100,000. The presence of significant risk factors with the clinical picture suspicious for a LBC should warrant thorough evaluation as these tumors can lead to life-threatening complications. Further studies are needed to better understand the mechanism of association between these risk factors and LBC.


Assuntos
Tumor Carcinoide/epidemiologia , Neoplasias Intestinais/epidemiologia , Intestino Grosso , Adolescente , Adulto , Fatores Etários , Idoso , Tumor Carcinoide/patologia , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Intestinais/patologia , Intestino Grosso/patologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Raciais , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
15.
Int J Mol Sci ; 21(22)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33228092

RESUMO

The enteric nervous system (ENS), located in the wall of the gastrointestinal (GI) tract, is characterized by complex organization and a high degree of neurochemical diversity of neurons. One of the less known active neuronal substances found in the enteric neurons is neuregulin 1 (NRG1), a factor known to be involved in the assurance of normal development of the nervous system. During the study, made up using the double immunofluorescence technique, the presence of NRG1 in the ENS of the selected segment of porcine large intestine (caecum, ascending and descending colon) was observed in physiological conditions, as well as under the impact of low and high doses of bisphenol A (BPA) which is commonly used in the production of plastics. In control animals in all types of the enteric plexuses, the percentage of NRG1-positive neurons oscillated around 20% of all neurons. The administration of BPA caused an increase in the number of NRG1-positive neurons in all types of the enteric plexuses and in all segments of the large intestine studied. The most visible changes were noted in the inner submucous plexus of the ascending colon, where in animals treated with high doses of BPA, the percentage of NRG1-positive neurons amounted to above 45% of all neuronal cells. The mechanisms of observed changes are not entirely clear, but probably result from neurotoxic, neurodegenerative and/or proinflammatory activity of BPA and are protective and adaptive in nature.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Sistema Nervoso Entérico/efeitos dos fármacos , Intestino Grosso/efeitos dos fármacos , Neuregulina-1/genética , Fenóis/toxicidade , Administração Oral , Animais , Esquema de Medicação , Sistema Nervoso Entérico/metabolismo , Sistema Nervoso Entérico/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Intestino Grosso/inervação , Intestino Grosso/metabolismo , Intestino Grosso/patologia , Neuregulina-1/agonistas , Neuregulina-1/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Plexo Submucoso/efeitos dos fármacos , Plexo Submucoso/metabolismo , Plexo Submucoso/patologia , Suínos
17.
Ann Diagn Pathol ; 39: 1-14, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30597401

RESUMO

Premalignant polyps of the large intestine are common specimens in surgical pathology. They consist of several different subtypes identifiable by histological criteria that are associated with different molecular characteristics and with the development of different types of colorectal carcinoma. The most common of these is the conventional adenoma, which most commonly leads to carcinomas with a low degree of methylation (CIMP-L) that are microsatellite stable. In Lynch syndrome patients these polyps lead to CIMP-L carcinomas that are microsatellite instable. The second most common is the sessile serrated adenoma, which leads to carcinomas with a high degree of methylation (CIMP-H) that may be either microsatellite stable or instable. The least common premalignant polyp is the traditional serrated adenoma, which can lead to either CIMP-L or CIMP-H carcinomas, most often microsatellite stable. This paper will review the histological features of these lesions, discuss problems in diagnosis and discuss the role of histology in management.


Assuntos
Pólipos do Colo/diagnóstico , Intestino Grosso/patologia , Lesões Pré-Cancerosas/diagnóstico , Pólipos do Colo/patologia , Metilação de DNA , Progressão da Doença , Humanos , Instabilidade de Microssatélites , Lesões Pré-Cancerosas/patologia , Sensibilidade e Especificidade
18.
Lupus ; 27(10): 1661-1669, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30028259

RESUMO

This study was performed to investigate the clinical characteristics of lupus enteritis in Japanese patients with systemic lupus erythematosus (SLE). A total of 481 patients with SLE admitted to our hospital between 2001 and 2015 were retrospectively reviewed. Diagnosis of lupus enteritis was based on the following three criteria: (1) abdominal symptoms, (2) diffuse long-segment bowel thickening and (3) a requirement for glucocorticoid therapy. Lupus enteritis was identified in 17 patients (3.5%) and there were two distinct types: small intestine-dominant and large intestine-dominant. Significant differences between the two types were noted with respect to the age, frequency of biopsy-proven lupus nephritis, frequency of rectal involvement, maximum bowel wall thickness, and requirement for steroid pulse therapy. Among patients with large intestine-dominant lupus enteritis, 60% had extra-intestinal symptoms (hydroureter, bladder wall thickening, and bile duct dilatation) that are known complications of intestinal pseudo-obstruction. Two patients with large intestine-dominant lupus enteritis developed intestinal pseudo-obstruction either before or after diagnosis of lupus enteritis. Five patients (29%) developed recurrence during a median observation period of 7.2 years (1.4-14.4 years). In conclusion, large intestine-dominant lupus enteritis resembles intestinal pseudo-obstruction and these two diseases may have a common pathogenesis.


Assuntos
Enterite/diagnóstico , Pseudo-Obstrução Intestinal/diagnóstico , Intestino Grosso/patologia , Intestino Delgado/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Adulto , Povo Asiático , Biópsia , Enterite/tratamento farmacológico , Enterite/epidemiologia , Enterite/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Incidência , Pseudo-Obstrução Intestinal/tratamento farmacológico , Pseudo-Obstrução Intestinal/epidemiologia , Pseudo-Obstrução Intestinal/patologia , Intestino Grosso/diagnóstico por imagem , Intestino Grosso/efeitos dos fármacos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/efeitos dos fármacos , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
19.
Scand J Gastroenterol ; 53(8): 1013-1017, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30041551

RESUMO

PURPOSE: To examine the usefulness of non-magnified close observation with blue laser imaging (BLI) using a colonoscope with close observation capability in determining indications for cold polypectomy. METHODS: We conducted an image evaluation study on 100 consecutive colorectal lesions of 10 mm or less which were observed endoscopically without magnification using BLI mode prior to treatment. Two experts and two non-experts reviewed the images using the Japan NBI expert team (JNET) classification and the diagnostic accuracy was analyzed. RESULTS: The final pathological diagnoses of the 100 lesions were hyperplastic/sessile serrated polyp (HP/SSP), low grade dysplasia (LGD), high grade dysplasia (HGD) and deep submucosal invasive cancer (dSM), respectively, in 12, 79, 9 and 0 lesions. When JNET classification type 1 corresponds to HP/SSP; 2A to LGD; 2B to HGD; and 3 to dSM; the overall diagnostic accuracy was 84.3%. Accuracy was 90.5% for experts and 78.0% for non-experts. High confidence rate was 67.5% for experts and 48.0% for non-experts. In diagnostic accuracy for HGD, the sensitivity, specificity, PPV and NPV were, respectively, 77.8%, 98.9%, 87.5% and 97.8% for experts; and 66.6%, 92.3%, 46.2% and 96.6% for non-experts. CONCLUSIONS: The diagnostic accuracy of unmagnified close observation with BLI using a colonoscope with close observation capability is similar to that reported for magnifying endoscopy and is useful in predicting the histological diagnosis of colorectal polyps of 10 mm or less although the effectiveness may be limited for non-experts. This modality is a potentially useful tool in deciding indications for cold polypectomy.


Assuntos
Pólipos do Colo/diagnóstico por imagem , Colonoscopia/métodos , Intestino Grosso/diagnóstico por imagem , Lasers , Imagem de Banda Estreita/instrumentação , Biópsia , Crioterapia , Diagnóstico Diferencial , Desenho de Equipamento , Humanos , Intestino Grosso/patologia , Japão , Sensibilidade e Especificidade
20.
Scand J Gastroenterol ; 53(8): 1008-1012, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29979091

RESUMO

BACKGROUND: Mechanical obstruction of the appendiceal lumen is proposed as a possible factor in the pathogenesis of acute appendicitis. Hence, patients over the age of 40 are often referred to a follow-up colonoscopy after admission for acute appendicitis. The use of CT scans question whether routine colonoscopy still has a place in follow-up for these patients. METHODS: All patients aged over 40 years with confirmed acute appendicitis admitted to St. Olav's Hospital in the period from 2010 to 2015 were included in this retrospective study. Findings and distribution of significant colorectal neoplasms (cancer and advanced adenomas) within three years after the admission were evaluated. RESULTS: Fifty-four (7.4%) of the 731 patients were found to have colonic neoplasms; 9 patients (1.2%) were found to have colorectal cancer of which 7 were located on the right side, 22 patients (3.0%) were found to have advanced adenomas and 23 patients (3.1%) were found to have non-advanced adenomas. The sensitivity and specificity for CT to discover cancer was 0.25 and 0.97, respectively. A total of 316 patients (43.2%) had colonoscopy within three years after admission. CONCLUSION: There may be an increased risk of colorectal neoplasms in patients over the age of 40 admitted with acute appendicitis. There seems to be an increased proportion of right-sided cancer relatively to other colonic locations. The sensitivity for CT scans to discover colorectal cancer in this group is low. Further studies are needed to decide whether routine colonoscopy is indicated after acute appendicitis in patients over 40 years.


Assuntos
Adenoma/patologia , Apendicite/complicações , Colonoscopia , Neoplasias Colorretais/patologia , Intestino Grosso/patologia , Doença Aguda , Adenoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
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