RESUMO
Intraductal papillary mucinous neoplasm (IPMN) is a precancerous lesion of pancreatic cancer. Although there are 4 types of IPMN, among which intestinal-type IPMN is likely to progress into invasive cancer known as colloid carcinoma, no information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study was conducted to explore how the intestinal differentiation system is maintained during the tumor progression of intestinal-type IPMN using surgical resection specimens. Results showed that Atoh1, a critical transcriptional factor for intestinal differentiation toward the secretory lineages of intestinal epithelial cells, was expressed in an invasive-grade IPMN. To determine the function of Atoh1 in pancreatic cancer, we generated a pancreatic ductal adenocarcinoma (PDAC) cell line overexpressing Atoh1. In a xenograft model, we successfully induced an IPMN phenotype in PDAC cells via Atoh1 induction. Finally, for the first time, we discovered that GPA33 is expressed in intestinal-type IPMN, thereby suggesting a novel target for cancer therapy. In conclusion, the intestinal differentiation system might be maintained during tumor progression of intestinal-type IPMN. Further analysis of the function of Atoh1 in IPMN might be useful for understanding the molecular mechanism underlying the malignant potential during the tumor progression of IPMN.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular/fisiologia , Neoplasias Intraductais Pancreáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Intestinos/patologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Pessoa de Meia-Idade , Neoplasias Intraductais Pancreáticas/metabolismo , FenótipoRESUMO
Satoyoshi syndrome is a rare multisystemic disorder of unknown etiology characterized by progressive muscle spasms, alopecia and diarrhea. Multiple protruding lesions with cystic glands, namely gastroenterocolitis cystica polyposa, manifest in the gastrointestinal tract. Since the first report of these lesions in 1977, which was unique to Satoyoshi syndrome, few studies have focused on their role, and the associated clinicopathological features are not well understood. Here, we report a 64-year-old Japanese woman with Satoyoshi syndrome who presented with multiple polypoid lesions in the stomach, duodenum, jejunum, ileum and colon. Histologically, the polypoid lesions in the intestine comprised multiple heterotopic submucosal glands containing cystically dilated glands and smooth muscle fibers in the lamina propria mucosa and/or submucosa. Additionally, we observed stromal changes, such as fibrosis, discontinuous and thinning muscularis mucosae, and diffuse neural fiber proliferation in the entire intestinal tract. Furthermore, multiple foci of adenocarcinomas were identified within several heterotopic submucosal glands. We hypothesized that multiple heterotopic submucosal glands in the present case corresponded to previously reported gastroenterocolitis cystica polyposa, suggesting that these lesions are essential in the histopathology and are a unique manifestation of Satoyoshi syndrome.
Assuntos
Adenocarcinoma/diagnóstico , Alopecia/patologia , Osso e Ossos/anormalidades , Coristoma/patologia , Diarreia/patologia , Mucosa Intestinal , Neoplasias Intestinais/diagnóstico , Espasmo/patologia , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Alopecia/complicações , Osso e Ossos/patologia , Coristoma/diagnóstico , Coristoma/etiologia , Diarreia/complicações , Feminino , Humanos , Enteropatias/diagnóstico , Enteropatias/etiologia , Enteropatias/patologia , Neoplasias Intestinais/etiologia , Neoplasias Intestinais/patologia , Pessoa de Meia-Idade , Espasmo/complicaçõesRESUMO
Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30-100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40-100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial-myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1-30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut-off value of the percentage of En1-expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1-positive and the others were En1-negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Adenoide Cístico/diagnóstico , Proteínas de Homeodomínio/metabolismo , Neoplasias das Glândulas Salivares/diagnóstico , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Adenoma Pleomorfo/diagnóstico , Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Curva ROC , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To predict metachronous liver metastasis after pancreatectomy for pancreatic neuroendocrine neoplasms (Pan-NENs). SUMMARY OF BACKGROUND DATA: Liver metastasis determines the prognosis of patients with Pan-NENs, but no index exists in the WHO 2017 classification for this prediction. METHODS: Between April 2014 and March 2018, resected primary tumors from 20 patients with or without simultaneous liver metastasis were examined using genome-wide gene expression analysis. For validation analysis, resected primary tumors from 62 patients without simultaneous liver metastasis were examined for PAX6 expression. RESULTS: Gene expression profiling revealed pancreatic beta cell genes (NES, -2.0; P < 0.001) as the most downregulated set in patients with simultaneous liver metastasis. In the test study, PAX6 was the most valuable index for liver metastasis (log FC, -3.683; P = 0.0096). Multivariate analysis identified PAX6 expression (hazard ratio, 0.2; P = 0.03) as an independent risk factor for metachronous liver metastasis-free survival (mLM-FS). The 5-year mLM-FS of patients with high versus low PAX6 expression was significantly better (95% vs 66%, respectively; P < 0.0001). The 5-year overall survival rate of was also better than in those with high versus low PAX6 expression (100% vs 87%, respectively). Patients with low PAX 6 expression were significantly younger and leaner, had a higher Ki-67 index (P = 0.01, 0.007, 0.008, respectively), and showed a higher mitotic rate than patients with high PAX6 expression. CONCLUSIONS: Downregulated pancreatic beta cell genes involving PAX6 in primary tumors may predict mLM and poor overall survival after primary tumor resection in Pan-NEN patients.
Assuntos
Células Secretoras de Insulina/metabolismo , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/cirurgia , Fator de Transcrição PAX6/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Biomarcadores Tumorais/metabolismo , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Hepatectomia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/secundário , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Fatores de Risco , Análise de SobrevidaRESUMO
AIMS: Lymph node metastasis (LNM) has not been found in more than 85% of patients with early invasive colorectal adenocarcinoma (T1-CRAC) who undergo surgery after therapeutic endoscopy due to the risk for LNM. Better histological risk assessment for LNM of endoscopically resected T1-CRAC is important to avoid unnecessary additional surgery. METHODS AND RESULTS: We evaluated cancer gland rupture (CGR), i.e. cancer glands with a discontinuous epithelial lining, at the invasive front, as a potential risk factor for LNM by histological examination of differentiated T1-CRAC from 217 patients who underwent surgery with or without therapeutic endoscopy. CGR was represented by C-shaped neoplastic glands with a variable inflammatory or stromal reaction, and was occasionally accompanied by mucus lake or abscess formation. CGR was observed in 168 (77%) cases, including all 20 cases with LNM, and the odds ratio of LNM was higher for CGR than for deep invasion (depth of submucosal invasion ≥1000 µm). All cases with LNM were found among 148 cases with deep invasion and positive CGR, whereas no LNM was detected in 29 cases with deep invasion and negative CGR, regardless of vascular invasion or tumour budding. In the 148 cases, LNM was detected in 18 (19%) of 93 cases with positive vascular invasion or high-grade tumour budding, and in two (4%) of 55 cases without either. CONCLUSIONS: Our findings suggest that CGR is an easily applied and objective histological finding for predicting LNM that could be useful for assessing the risk for LNM of endoscopically resected T1-CRAC with deep invasion.
Assuntos
Adenocarcinoma/patologia , Algoritmos , Neoplasias Colorretais/patologia , Metástase Linfática/patologia , Invasividade Neoplásica/patologia , Adenocarcinoma/cirurgia , Idoso , Neoplasias Colorretais/cirurgia , Endoscopia do Sistema Digestório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
AIMS: A number of homeobox transcriptional factors are utilised as organ-specific markers in the histopathological diagnosis of neoplasms. We have screened a homeobox gene that is expressed specifically in normal sweat gland cells and is useful for the histopathological diagnosis of sweat gland neoplasms. METHODS AND RESULTS: By screening an open database resource of The Human Protein Atlas, 37 genes among the 235 homeobox transcriptional factors were found to be expressed specifically in the skin. Among those 37 genes, the engrailed homeobox 1 (En1) was expressed in normal eccrine glands but not in the epidermal keratinocytes. Expression of En1 was found throughout the eccrine glands, but not in the apocrine secretory coils, sebaceous glands or hair follicles. Expression of En1 was examined immunohistochemically in 111 cases of cutaneous epithelial neoplasms. All nine cases of poroma, seven cases of spiradenoma and six cases of syringoma, which are considered to differentiate towards eccrine glands, showed positive nuclear staining in most of the tumour cells. Sebaceous gland and hair follicle tumours were immunonegative. En1 was expressed focally in the epidermal neoplasms of seborrheic keratosis and squamous cell carcinoma. CONCLUSION: Engrailed homeobox 1 was expressed specifically in normal eccrine glands and was expressed in most of the tumour cells of sweat gland neoplasms with eccrine gland differentiation. En1 was expressed focally in epidermal neoplasms; however, it was absent in sebaceous or hair follicle neoplasms. These findings will help in the histopathological diagnosis as well as understanding of the histogenesis of sweat gland neoplasms.
Assuntos
Glândulas Écrinas/metabolismo , Proteínas de Homeodomínio/genética , Neoplasias das Glândulas Sudoríparas/genética , Fatores de Transcrição/genética , Glândulas Écrinas/patologia , Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Sistema de Registros , Neoplasias das Glândulas Sudoríparas/metabolismo , Neoplasias das Glândulas Sudoríparas/patologia , Fatores de Transcrição/metabolismoRESUMO
Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous group of cancers of the intrahepatic biliary tract. However, few studies have evaluated integrin expression according to an ICC subgroup. We immunohistochemically investigated α6ß4 (ß4) and αvß6 (ß6) integrin expressions in 48 ICCs, and evaluated their relationship with clinical and pathological parameters and ligand expression, as well as transforming growth factor (TGF)-ß1. ß4 and ß6 expressions were detected in 46 (96%) and 35 (73%) ICC cases, respectively. We classified ICC into negative, low (ß4, 29 cases; ß6, 36 cases), or high (ß4, 19 cases; ß6, 12 cases) integrin expression groups. ß4 and ß6 integrin levels were higher in the non-peripheral central localization type ICC than in the peripheral localization type; they were also higher in the periductal-infiltrating or intraductal-growth types than in the mass-forming type ICC; lastly, they were higher in the well-differentiated type than in the poorly-differentiated type ICC. High expression was related to bile duct invasion. In addition, ß4 and ß6 expressions were associated with mucin production and the expression of cytoplasmic epithelial membrane antigen, laminin-5, and tenascin-C. TGF-ß1 was correlated with ß6 expression and poor overall survival. These results suggest that integrin expression is associated with subclassification and clinicopathological features of ICC through the coincident expression of their ligands and TGF-ß1.
Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Regulação para Baixo , Integrina alfa6beta4/metabolismo , Integrinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/metabolismo , Colangiocarcinoma/classificação , Colangiocarcinoma/metabolismo , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
A man in his 60's with interstitial pneumonitis who was previously admitted to another hospital was transferred to our hospital for further investigations 6 years prior to an acute exacerbation. Given his history of avian contact, the presence of antibodies specific to avian antigen, and a positive result of the inhalation provocation test using pigeon dropping extracts, he was diagnosed with bird-related hypersensitivity pneumonitis (BRHP). As such, we instructed the patient to avoid exposure to avian antigen, and regularly measured the level of avian antigen in dust samples collected from his household environment. Despite avoiding the stimulus, corticosteroids and immunosuppressants were needed in view of progression of dyspnea after approximately five to six years. Four months after immunosuppressant therapy began, the patient suffered an acute exacerbation of BRHP and died. At this time, we found that the level of avian antigen was much higher than baseline. We suggest that exposure to high level of avian antigen is one cause of an acute exacerbation of BRHP.
Assuntos
Alveolite Alérgica Extrínseca , Pulmão do Criador de Aves , Animais , Antígenos , Columbidae , Poeira , Humanos , MasculinoRESUMO
Occult breast cancer, which develops as a metastatic lesion with no primary tumor detected in the breast, is a rare breast cancer. A 68-year-old female patient particularly complained of the presence of a right axillary mass. The mass in the right axilla was palpable, but no tumor was found in both the breasts on palpation, ultrasound examination, or MRI. Partial breast resection and axillary lymph node dissection were performed following a diagnosis of invasive ductal carcinoma by core needle biopsy. There was no mammary gland tissue present around the tumor due to the pathology of the disease, and the tumor was diagnosed as occult breast cancer. As the cancer was ER negative and HER2 positive, treatment with a combination of FEC, docetaxel, and trastuzumab was initiated. Radiotherapy, which irradiated the right supraclavicular fossa and the right mammary gland, was administered. No disease recurrence and mammary tumor has been reported in the patient till date. Treatment of occult breast cancer generally includes local therapy such as radiation and surgery. However, in the present case, we did not operate upon the breast; instead we treated the right breast and the right supraclavicular fossa with radiation therapy. As the tumor was HER2 positive, we reasoned that local control of disease would be likely if treatment with chemotherapy and trastuzumab was performed effectively.
Assuntos
Neoplasias da Mama/diagnóstico , Diagnóstico Diferencial , Linfonodos/patologia , Idoso , Axila , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Linfonodos/cirurgia , Receptor ErbB-2/análise , Resultado do TratamentoRESUMO
OBJECTIVES: Cortical actin is a thin layer of filamentous (F-)actin that lies beneath the plasma membrane, and its role in pathophysiology remains unclear. We investigated the subcellular localization of cortical actin by the histopathological and experimental studies of lung adenocarcinomas. MATERIALS AND METHODS: The subcellular localization of cortical actin was studied in surgically resected lung adenocarcinomas tissues and in 3-dimensionally cultured lung adenocarcinoma A549 cells. RESULTS: In normal type II alveolar cells and the bronchiolar epithelium, cortical actin was localized to the apical-side cytoplasm. In invasive adenocarcinoma cells, cortical actin was frequently localized to the matrix side. The degree of cortical actin localized to the matrix side was associated with the loss of basement membrane and a poor prognosis. In A549 cell spheroids cultured in a type I collagen and basement membrane extract Matrigel™ mixed gel, cortical F-actin was localized to the matrix side with phosphorylated myosin light chain. Super-resolution and electron microscopy results suggest that compact wrinkling of the plasma membrane by myosin-mediated F-actin contraction is an explanation for cortical actin accumulation at the matrix side. The myosin II inhibitor blebbistatin suppressed the 3-dimensional collective migration of A549 cells induced by constitutively active Cdc42 and MT1-MMP. CONCLUSION: Cortical actin accumulation at the matrix-side cytoplasm of cancer cells occurs in invasive lung adenocarcinomas and it possibly participates in the migration of cancer cells through myosin-mediated contraction.
Assuntos
Actinas/metabolismo , Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Células A549 , Adenocarcinoma/diagnóstico , Adenocarcinoma de Pulmão , Membrana Celular/metabolismo , Movimento Celular , Citoplasma/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Miosinas/efeitos dos fármacos , Invasividade Neoplásica , Metástase Neoplásica , PrognósticoRESUMO
BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. Although the goal of UC therapy has recently been to target mucosal healing, the molecular mechanism of mucosal healing remains unknown. In this study, we aimed to elucidate the molecular dynamics related to the proliferation and differentiation of intestinal epithelial cells during cytapheresis therapy in a short duration. METHODS: Endoscopy was performed in 26 patients with UC in multicentre hospitals, and biopsy specimens were collected from the rectum before and within two weeks after leukocytapheresis (LCAP). The expression of representative proteins in intestinal epithelial cells and pathological findings was compared before and after LCAP. RESULTS: The expression of caudal type homeobox 2 (CDX2) and a hes family bHLH transcription factor 1(HES1) markedly increased after LCAP. Patients with endoscopic improvement after LCAP showed the expression of CDX2 before LCAP. Moreover, the number of goblet cells significantly increased after LCAP. Patients without endoscopic improvement after LCAP did not show the expression of CDX2 before LCAP. However, the expression of CDX2 markedly increased after LCAP. CONCLUSION: This study suggests that cytapheresis might induce CDX2 expression without affecting the cell proliferation, thus resulting in mucosal healing with goblet cell restoration.
Assuntos
Fator de Transcrição CDX2/metabolismo , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/terapia , Expressão Gênica , Mucosa Intestinal/fisiologia , Leucaférese , Regeneração/genética , Adulto , Biomarcadores/metabolismo , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Feminino , Células Caliciformes/fisiologia , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Coriocarcinoma/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Adulto , Coriocarcinoma/patologia , Coriocarcinoma/cirurgia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND OBJECTIVE: Lobar and temporal histological variability in chronic bird-related hypersensitivity pneumonitis (BRHP) has not been clearly elucidated. This study was designed to evaluate the spatio-temporal histopathological variability in chronic BRHP. METHODS: Fifty-two patients with chronic BRHP who underwent a surgical lung biopsy (SLB) between 1992 and 2008 were evaluated. The histopathological characteristics of the lung biopsy specimens were classified by the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS) consensus classification of idiopathic interstitial pneumonias (IIPs). Autopsy specimens from seven patients were also evaluated to examine the serial changes from SLB to autopsy. RESULTS: In a study of lobar histological variability based on the findings of SLB, 7 patients were diagnosed with cellular nonspecific interstitial pneumonia (NSIP) pattern, 16 with fibrotic NSIP pattern, 20 with fibrotic NSIP pattern and usual interstitial pneumonia (UIP) (discordant UIP) pattern and 9 with UIP (concordant UIP) pattern. In a study of sequential changes, specimens of SLBs with fibrotic NSIP pattern changed to a bronchiolocentric interstitial pneumonia (BIP) pattern or UIP pattern. CONCLUSION: Interlobar and intralobar histological variability is present in chronic BRHP. In several patients with chronic BRHP, a fibrotic NSIP pattern may be an early lesion that progresses to a UIP pattern.
Assuntos
Pulmão do Criador de Aves/patologia , Pneumonias Intersticiais Idiopáticas/patologia , Exposição por Inalação/efeitos adversos , Pulmão/patologia , Idoso , Animais , Autopsia , Biópsia , Pulmão do Criador de Aves/imunologia , Aves , Lavagem Broncoalveolar , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/imunologia , Masculino , PrognósticoRESUMO
BACKGROUND: Pulmonary granulomas are sometimes resected because they resemble lung cancer and false-positive findings come through from positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG). Mycobacterial infection is a common cause of granulomas. OBJECTIVE: The purpose of this study was to evaluate the radiopathological features and the methods for identifying mycobacterial infections in granulomatous nodules resected from the lung. METHODS: Thirty-five solitary lesions resected because of suspected lung cancer were enrolled, including 22 nonfungal granulomatous lesions and 13 benign lesions as controls. The radiological, microbiological, and histological findings were reviewed. To identify mycobacterial infection, immunohistochemical (IHC) staining, IS6110 polymerase chain reaction (PCR), and real-time PCR for the detection of Mycobacterium tuberculosis (TB) were performed using formalin-fixed and paraffin-embedded tissue specimens. The correlations between the radiopathological features and the median maximum standardized uptake value (SUVmax) of 18F-FDG PET were also evaluated. RESULTS: Mycobacteria were isolated from the cultures of 10 of the granulomatous lesions, including TB from 2 and Mycobacterium avium complex from 8. The mean size of the nodules in the culture-positive group was significantly larger than that of those in the culture-negative group (30.5 ± 13.1 vs. 15.1 ± 6.3 mm, p = 0.003). IHC stainings were positive in 15 granulomas. Eight granulomas were positive in IS6110 PCR, and 7 of them were also positive in real-time PCR. SUVmax was ≥2.5 in all of the PCR-positive granulomas. CONCLUSION: The most frequent cause of granulomatous lesions was mycobacterial infection. It seemed that the culture result was associated with nodule size and that the results of IS6110 were associated with 18F-FDG-uptake.
Assuntos
Granuloma/microbiologia , Infecções por Mycobacterium/diagnóstico , Nódulo Pulmonar Solitário/microbiologia , Idoso , Feminino , Granuloma/diagnóstico por imagem , Granuloma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium/diagnóstico por imagem , Infecções por Mycobacterium/patologia , Infecções Respiratórias/diagnóstico por imagem , Infecções Respiratórias/microbiologia , Infecções Respiratórias/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologiaRESUMO
Patients with inflammatory bowel disease (IBD) have an increased risk of developing colitis-associated colorectal cancer (CAC). CAC cells often develop chemoresistance, resulting in a poorer prognosis than that of sporadic colorectal cancer (CRC). The mechanism by which CAC enhances malignant potential remains unknown. We have previously reported that the proteasomal degradation of the transcription factor Atonal homolog 1 (Atoh1) protein results in the non-mucinous form of CRC. It also remains unknown whether Atoh1 protein is expressed in CAC. Therefore, in the present study, we investigated whether Atoh1 protein stabilizes in CAC. Consequently, the treatment with TNF-α stabilized Atoh1 protein through the inactivation of GSK-3ß via Akt, resulting in the mucinous form of CRC cell lines. Atoh1 protein also enriched cancer stem cells with upregulated Lgr5 expression and cells in G0/G1 cell cycle phase, resulting in both the chemoresistance to 5-fluorouracil and oxaliplatin and the promotion of cell migration. Immunofluorescence of the human mucinous CAC specimens showed the accumulation of NF-κB p65 at nuclei with the expression of Atoh1 in mucinous cancer. In conclusion, the inflammation associated with carcinogenesis may preserve the differentiation system of intestinal epithelial cell (IEC), resulting in the acquisition of both the mucinous phenotype and high malignant potential associated with the enrichment of cancer stem cell.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/patologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Western Blotting , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo RealAssuntos
Fusariose/etiologia , Fusarium/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antifúngicos/uso terapêutico , Criança , Síndrome Congênita de Insuficiência da Medula Óssea/complicações , Síndrome Congênita de Insuficiência da Medula Óssea/terapia , Evolução Fatal , Fusariose/tratamento farmacológico , Fusariose/microbiologia , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Hospedeiro Imunocomprometido , Masculino , Insuficiência de Múltiplos Órgãos/microbiologia , Neutropenia/complicações , Neutropenia/congênito , Neutropenia/terapia , Transplante Haploidêntico/efeitos adversosRESUMO
Video 1EUS-guided FNA using a forward-viewing echoendoscope enabled the accurate diagnosis of a hypervascularized retroperitoneal tumor as a hereditary paraganglioma.
RESUMO
Ovarian neuroendocrine carcinoma is a rare and aggressive tumor with a poor prognosis. Ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) are often used for diagnosis. However, no specific features exist, and preoperative diagnosis is often difficult. We present a case in which ovarian neuroendocrine carcinoma was diagnosed postoperatively, with the intention to discuss its imaging features on 18F fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). A 70-year-old woman presented to a local hospital with abdominal pain. CT showed a uterine mass and multiple swollen lymph nodes. The mass expanded from the uterus into the left ovarian vessels on dynamic MRI. The SUVmax of the mass and lymph nodes on 18F-FDG PET/CT were notably elevated to 53.2 and 33.0 respectively. Considering the tumor location and high SUVmax, a malignant uterine tumor was suspected. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omental biopsy, and resection of the left ovarian vessels were performed. Histological examination confirmed that the tumor was a neuroendocrine carcinoma derived from the left ovary. To the best of our knowledge, there are only few reports on the 18F-FDG uptake in ovarian neuroendocrine carcinomas. Conversely, in other organs, the carcinomas frequently exhibit markedly elevated SUVmax on 18F-FDG PET/CT. It is possible that ovarian neuroendocrine carcinomas share similar traits, and elevated SUVmax could indicate the potential presence of this histological type.
RESUMO
BACKGROUND: Recent advances in omics techniques have allowed detailed genetic characterization of aldosterone-producing adenoma (APA). The pathogenesis of APA is characterized by tumorigenesis-associated aldosterone synthesis. The pathophysiological intricacies of APAs have not yet been elucidated at the level of individual cells. Therefore, a single-cell level analysis is speculated to be valuable in studying the differentiation process of APA. METHODS: We conducted single-nucleus RNA sequencing of APAs with KCNJ5 mutation and nonfunctional adenomas obtained from 3 and 2 patients, respectively. RESULTS: The single-nucleus RNA sequencing revealed the intratumoral heterogeneity of APA and identified cell populations consisting of a shared cluster of nonfunctional adenoma and APA. In addition, we extracted 2 cell fates in APA and obtained a cell population specialized in aldosterone synthesis. Genes related to ribosomes and neurodegenerative diseases were upregulated in 1 of these fates, whereas those related to the regulation of glycolysis were upregulated in the other fate. Furthermore, the total RNA reads in the nucleus were higher in hormonally activated clusters, indicating a marked activation of transcription per cell. CONCLUSIONS: The single-nucleus RNA sequencing revealed intratumoral heterogeneity of APA with KCNJ5 mutation. The observation of 2 cell fates in KCNJ5-mutated APAs provides the postulation that a heterogeneous process of cellular differentiation was implicated in the pathophysiological mechanisms underlying APA tumors.