RESUMEN
A case of poorly differentiated tubular gastric adenocarcinoma with tumor-associated tissue eosinophilia (TATE) is studied by light and electron microscopy, focusing on membrane interactions between eosinophils and tumor cells. 29.2% of the eosinophils in contact with tumor cells showed intact granules, 28.3% exhibited piecemeal degranulation (PMD), 40% were characterized by coexistence of PMD and compound exocytosis in the same granulocyte, whereas classical exocytosis was found in 2.5% of the eosinophils with PMD. Eosinophil Sombrero Vesicles (EoSVs), important tubulovesicular carriers for delivery of cytotoxic proteins from the specific granules during PMD, were also studied at the ultrastructural level. In activated eosinophils, EoSVs and specific granules with ultrastructural signs of degranulation were polarized toward tumor cells. Ultrastructural changes in paraptosis-like cell death, such as mitochondrial swelling, dilation of the nuclear envelope, cytoplasmic vacuoles, and nuclear chromatin condensation, but without margination of the chromatin, were observed in these tumor cells. Our data support the notion that eosinophils may exert an antitumoral role in gastric cancer. Finally, the case reported provides, for the first time, ultrastructural evidence of classical and compound exocytosis of eosinophils in the tumor stroma of human adenocarcinoma.
Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/ultraestructura , Gránulos Citoplasmáticos/patología , Gránulos Citoplasmáticos/ultraestructura , Eosinófilos/metabolismo , Eosinófilos/ultraestructura , Exocitosis , Humanos , Microscopía Electrónica , Neoplasias Gástricas/patologíaRESUMEN
AIMS: Although evaluation of nuclear morphology is important for the diagnosis and categorisation of breast lesions, the criteria used to assess nuclear atypia rely upon the subjective evaluation of several features that may result in inter- and intraobserver variation. This study aims to refine the definitions of cytonuclear features in various breast lesions. METHODS AND RESULTS: ImageJ was used to assess the nuclear morphological features including nuclear diameter, axis length, perimeter, area, circularity and roundness in 160 breast lesions comprising ductal carcinoma in situ (DCIS), invasive breast carcinoma of no special type (IBC-NST), tubular carcinoma, usual ductal hyperplasia (UDH), columnar cell change (CCC) and flat epithelial atypia (FEA). Reference cells included normal epithelial cells, red blood cells (RBCs) and lymphocytes. Reference cells showed size differences not only between normal epithelial cells and RBCs but also between RBCs in varied-sized blood vessels. Nottingham grade nuclear pleomorphism scores 1 and 3 cut-offs in IBC-NST, compared to normal epithelial cells, were < ×1.2 and > ×1.4 that of mean maximum Feret's diameter and < ×1.6 and > ×2.4 that of mean nuclear area, respectively. Nuclear morphometrics were significantly different in low-grade IBC-NST versus tubular carcinoma, low-grade DCIS versus UDH and CCC versus FEA. No differences in the nuclear features between grade-matched DCIS and IBC-NST were identified. CONCLUSION: This study provides a guide for the assessment of nuclear atypia in breast lesions, refines the comparison with reference cells and highlights the potential diagnostic value of image analysis tools in the era of digital pathology.
Asunto(s)
Adenocarcinoma , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Núcleo Celular/patología , Variaciones Dependientes del Observador , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Biopsia , Neoplasias de la Mama/patología , Neoplasias de la Mama/ultraestructura , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/ultraestructura , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/ultraestructura , Células Epiteliales/patología , Células Epiteliales/ultraestructura , Femenino , Humanos , Hiperplasia/patologíaRESUMEN
FLO-1 cell line represents an important tool in esophageal adenocarcinoma (EAC) research as a verified and authentic cell line to study the disease pathophysiology and antitumor drug screenings. Since in vitro characteristics of cells depend on the microenvironment and culturing conditions, we performed a thorough characterization of the FLO-1 cell line under different culturing conditions with the aim of (1) examining the effect of serum-free growth medium and air-liquid interface (A-L) culturing, which better reflect physiological conditions in vivo and (2) investigating the differentiation potential of FLO-1 cells to mimic the properties of the in vivo esophageal epithelium. Our study shows that the composition of the media influenced the morphological, ultrastructural and molecular characteristics of FLO-1 cells, such as the expression of junctional proteins. Importantly, FLO-1 cells formed spheres at the A-L interface, recapitulating key elements of tumors in the esophageal tube, i.e., direct contact with the gas phase and three-dimensional architecture. On the other hand, FLO-1 models exhibited high permeability to model drugs and zero permeability markers, and low transepithelial resistance, and therefore poorly mimicked normal esophageal epithelium. In conclusion, the identified effect of culture conditions on the characteristics of FLO-1 cells should be considered for standardization, data reproducibility and validity of the in vitro EAC model. Moreover, the sphere-forming ability of FLO-1 cells at the A-L interface should be considered in EAC tumor biology and anticancer drug studies as a reliable and straightforward model with the potential to increase the predictive efficiency of the current in vitro approaches.
Asunto(s)
Adenocarcinoma/ultraestructura , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula , Ensayos de Selección de Medicamentos Antitumorales/métodos , Ensayos de Selección de Medicamentos Antitumorales/normas , Neoplasias Esofágicas/ultraestructura , Adenocarcinoma/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo , Descubrimiento de Drogas/métodos , Neoplasias Esofágicas/patología , Humanos , Inmunohistoquímica , Uniones Intercelulares/ultraestructuraRESUMEN
Mini-abstract: Application of a three-dimensional culture system with air exposure facilitates the formation of large cell spheres possessing cribriform glands and producing mucin in the collagen gel. Transmission electron microscopy revealed the formation of microvilli and junctional complexes at the apical side of the cell. This study aimed to reproduce the characteristics of original adenocarcinoma tumors in vitro. The pancreatic cell line, SUIT-58, derived from a moderately differentiated adenocarcinoma of metastatic pancreatic cancer was used. The cells have a sheet structure in conventional cell culture without forming glands or exhibiting mucin production in the lumen. First, the necessity of scaffolds to create an adenocarcinoma-like microenvironment for SUIT-58 pancreatic cancer cells was assessed. Compared with conventional culture plates, the use of type I collagen as a scaffold played an important role in the formation of densely congested microvilli, as observed through scanning electron microscopy. As gland formation is one of the features of adenocarcinoma, we also assessed gland formation. Use of a recently developed three-dimensional culture system with air exposure resulted in the formation of large cell spheres possessing cribriform glands, which released mucin into the lumen. Transmission electron microscopy also revealed the formation of microvilli in the lumen of the glands and junctional complex at the intercellular part, which were similar to those observed in xenografts. These findings indicate that an in vitro three-dimensional culture system with air exposure reflects the intrinsic features of the original tumor, suggesting that this culture system could be useful for preliminary research of certain cancers.
Asunto(s)
Adenocarcinoma/ultraestructura , Técnicas de Cultivo de Célula , Microscopía Electrónica de Rastreo/métodos , Microscopía Electrónica de Transmisión/métodos , Neoplasias Pancreáticas/ultraestructura , Adenocarcinoma/patología , Humanos , Neoplasias Pancreáticas/patología , Esferoides Celulares , Andamios del Tejido , Células Tumorales Cultivadas , Microambiente Tumoral , Neoplasias PancreáticasRESUMEN
Current conventional mono and combination therapeutic strategies often fail to target breast cancer tissue effectively due to tumor heterogeneity comprising cancer stem cells (CSCs) and bulk tumor cells. This is further associated with drug toxicity and resistivity in the long run. A nanomedicine platform incorporating combination anti-cancer treatment might overcome these challenges and generate synergistic anti-cancer effects and also reduce drug toxicity. GANT61 and curcumin were co-delivered via polymeric nanoparticles (NPs) for the first time to elicit enhanced anti-tumor activity against heterogeneous breast cancer cell line MCF-7. We adopted the single-emulsion-solvent evaporation method for the preparation of the therapeutic NPs. The GANT61-curcumin PLGA NPs were characterized for their size, shape and chemical properties, and anti-cancer cell studies were undertaken for the plausible explanation of our hypothesis. The synthesized GANT61-curcumin PLGA NPs had a spherical, smooth surface morphology, and an average size of 347.4 d. nm. The NPs induced cytotoxic effects in breast cancer cells at a mid-minimal dosage followed by cell death via autophagy and apoptosis, reduction in their target protein expression along with compromising the self-renewal property of CSCs as revealed by their in vitro cell studies. The dual-drug NPs thus provide a novel perspective on aiding existing anti-cancer nanomedicine therapies to target a heterogeneous tumor mass effectively.
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Neoplasias de la Mama/tratamiento farmacológico , Curcumina/uso terapéutico , Nanopartículas/química , Fosfatidilinositol 3-Quinasas/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Proteína con Dedos de Zinc GLI1/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias de la Mama/patología , Neoplasias de la Mama/ultraestructura , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcumina/farmacología , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Femenino , Humanos , Células MCF-7 , Ratones , Nanopartículas/ultraestructura , Tamaño de la Partícula , Espectroscopía de Fotoelectrones , Piridinas/farmacología , Pirimidinas/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/patología , Electricidad EstáticaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Given that macroautophagy/autophagy activation is prevalent in PDAC, the dual roles of autophagy could be involved in PDAC heterogeneity. In this work, we demonstrated that TGFB1 induced autophagic flux through SMAD4-dependent or SMAD4-independent pathways based on a distinct genetic context. In SMAD4-positive PDAC cells, TGFB1-induced autophagy promoted proliferation and inhibited migration by decreasing the nuclear translocation of SMAD4. Conversely, TGFB1-induced autophagy inhibited proliferation and promoted migration in SMAD4-negative cells through the regulation of MAPK/ERK activation. TGFB1 expression also positively correlated with LC3B expression in PDAC specimens. A high level of LC3B was associated with unfavorable overall survival (OS) and disease-free survival (DFS) in SMAD4-negative PDAC patients, although LC3B could not predict OS and DFS for the 110 PDAC patients. Thus, TGFB1-induced autophagy contributed to the different patterns of PDAC progression. This knowledge can aid in improving our understanding of the molecular classification of PDAC and might guide the development of therapeutic strategies for PDAC, especially for SMAD4-negative PDAC.Abbreviations: CDH1: cadherin 1; CDH2: cadherin 2; CI: combination index; CQ: chloroquine; DFS: disease-free survival; EMT: epithelial-to-mesenchymal transition; ERK: extracellular signal-regulated protein kinase; GFP: green fluorescent protein; IHC: immunohistochemistry; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPK: mitogen-activated protein kinase; OS: overall survival; PBS: phosphate-buffered saline; PDAC: pancreatic ductal adenocarcinoma; RAP: rapamycin; RFP: red fluorescent protein; RT: room temperature; shRNA: short-hairpin RNA; SQSTM1: sequestosome 1; TCGA: The Cancer Genome Atlas; TEM: transmission electron microscopy; TGFB1: transforming growth factor beta 1; TMA: tissue microarray.
Asunto(s)
Autofagia , Progresión de la Enfermedad , Neoplasias Pancreáticas/patología , Proteína Smad4/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/ultraestructura , Línea Celular Tumoral , Núcleo Celular/metabolismo , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/ultraestructura , Pronóstico , Proteína Sequestosoma-1/metabolismo , Neoplasias PancreáticasRESUMEN
The origin of blood and lymphatic vessels in high-grade serous adenocarcinoma of ovary (HGSOC) is uncertain. We evaluated the potential of cancer stem cells (CSCs) in HGSOC to contribute to their formation. Using spheroids as an in vitro model for CSCs, we have evaluated their role in primary malignant cells (PMCs) in ascites from previously untreated patients with HGSOC and cell lines. Spheroids from PMCs grown under specific conditions showed significantly higher expression of endothelial, pericyte and lymphatic endothelial markers. These endothelial and lymphatic cells formed tube-like structures, showed uptake of Dil-ac-LDL and expressed endothelial nitric oxide synthase confirming their endothelial phenotype. Electron microscopy demonstrated classical Weibel-Palade bodies in differentiated cells. Genetically, CSCs and the differentiated cells had a similar identity. Lineage tracking using green fluorescent protein transfected cancer cells in nude mice confirmed that spheroids grown in stem cell conditions can give rise to all three cells. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor inhibited the differentiation of spheroids to endothelial cells in vitro. These results suggest that CSCs contribute to angiogenesis and lymphangiogenesis in serous adenocarcinoma of the ovary, which can be inhibited.
Asunto(s)
Adenocarcinoma/patología , Linfangiogénesis , Neoplasias Quísticas, Mucinosas y Serosas/patología , Células Madre Neoplásicas/patología , Neovascularización Patológica/patología , Neoplasias Ováricas/patología , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/ultraestructura , Ascitis/metabolismo , Ascitis/patología , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Biomarcadores de Tumor/metabolismo , Vasos Sanguíneos/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Células Endoteliales/metabolismo , Femenino , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias Quísticas, Mucinosas y Serosas/irrigación sanguínea , Neoplasias Quísticas, Mucinosas y Serosas/ultraestructura , Células Madre Neoplásicas/ultraestructura , Neoplasias Ováricas/irrigación sanguínea , Neoplasias Ováricas/ultraestructura , Pericitos/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Rhabdoid colorectal carcinoma (RC) is a rare lesion localized to the proximal colon of patients with a mean age at diagnosis of around 70 years. This tumor shows an aggressive behavior with an overall survival period shorter than 12 months. The diagnostic hallmark is the presence of rhabdoid cells. Alterations in chromatin remodeling (SMARCB1) and in the centrosome structure (CROCC) are reported in RC usually BRAFmut and MSI-H. RKO intestinal neoplastic cells culture (BRAFmut, SMARCB1wt, MSI-H) with CROCC knockdown exhibit rhabdoid features and develop prominent projections from the edge of the cell. METHODS: Here, we investigated two cases of CROCCmutSMARCB1wt RC by scanning and transmission electron microscopy (SEM, TEM). RESULTS: TEM confirmed the diagnostic presence of intermediate cytoplasmic filaments and nucleolar margination. SEM showed cellular protrusions (lamellipodia) in the intercellular spaces not evident at light microscopy. CONCLUSIONS: These protrusions CROCC-related might represent the pathogenetic mechanism underlying the rhabdoid aggressive behavior, independently of tumor staging. To our knowledge, the SEM technique was applied in the study of this neoplasm for the first time.
Asunto(s)
Adenocarcinoma/ultraestructura , Neoplasias Colorrectales/ultraestructura , Proteínas del Citoesqueleto/genética , Tumor Rabdoide/ultraestructura , Adenocarcinoma/genética , Adenocarcinoma/patología , Anciano , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Humanos , Microscopía Electrónica , Seudópodos/patología , Seudópodos/ultraestructura , Tumor Rabdoide/genética , Tumor Rabdoide/patologíaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is a destructive cancer with poor prognosis. Both novel therapeutic targets and approaches are needed to improve the overall survival of PDAC patients. MicroRNA-212 (miR-212) has been reported as a tumor suppressor in multiple cancers, but its definitive role and exact mechanism in the progression of pancreatic cancer is unclear. In this study, we developed a new chimeric peptide (PL-1) composed of plectin-1-targeted PDAC-specific and arginine-rich RNA-binding motifs which could condense miRNA to self-assemble supramolecular nanoparticles. These nanoparticles could deliver miR-212 into PDAC cells specifically and efficiently which also showed good stability in RNase and serum. Moreover, we demonstrated that PL-1/miR-212 nanoparticles could dramatically enhance the chemotherapeutic effect of doxorubicin for PDAC both in vitro and in vivo. In terms of mechanism, combined miR-212 intervention by PL-1/miR-212 nanoparticles resulted in obvious decrease of USP9X expression (ubiquitin specific peptidase 9, X-linked, USP9X) and eventually enhanced the doxorubicin induced apoptosis and autophagy of PDAC cells. These findings provide a new promising anti-cancer strategy via PL-1/miR-212 nanoparticles and identify miR-212/USP9X as a new potential target for future systemic therapy against human PDAC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Doxorrubicina/uso terapéutico , MicroARNs/administración & dosificación , Nanopartículas/química , Neoplasias Pancreáticas/tratamiento farmacológico , Péptidos/química , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Secuencia de Aminoácidos , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Secuencia de Bases , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/ultraestructura , Línea Celular Tumoral , Doxorrubicina/farmacología , Humanos , Masculino , Ratones Desnudos , MicroARNs/genética , Nanopartículas/ultraestructura , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/ultraestructura , Ubiquitina Tiolesterasa/metabolismoRESUMEN
Invadopodia, cancer cell protrusions with proteolytic activity, are functionally associated with active remodeling of the extracellular matrix. Here, we show that the invadopodia-related protein TKS5 is expressed in human pancreatic adenocarcinoma lines, and demonstrate that pancreatic cancer cells depend on TKS5 for invadopodia formation and function. Immunofluorescence staining of human pancreatic cancer cells reveals that TKS5 is a marker of mature and immature invadopodia. We also analyze the co-staining patterns of TKS5 and the commonly used invadopodia marker Cortactin, and find only partial co-localization of these two proteins at invadopodia, with a large fraction of TKS5-positive invadopodia lacking detectable levels of Cortactin. Whereas compelling evidence exist on the role of invadopodia as mediators of invasive migration in cultured cells and in animal models of cancer, these structures have never been detected inside human tumors. Here, using antibodies against TKS5 and Cortactin, we describe for the first time structures strongly resembling invadopodia in various paraffin-embedded human tumor surgical specimens from pancreas and other organs. Our results strongly suggest that invadopodia are present inside human tumors, and warrants further investigation on their regulation and occurrence in surgical specimens, and on the value of TKS5 antibodies as pathological research and diagnostic tools.
Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/fisiología , Adenocarcinoma/patología , Proteínas de Neoplasias/fisiología , Neoplasias Pancreáticas/patología , Podosomas/fisiología , Adenocarcinoma/química , Adenocarcinoma/cirugía , Adenocarcinoma/ultraestructura , Adulto , Anciano , Línea Celular Tumoral , Cortactina/análisis , Femenino , Técnica del Anticuerpo Fluorescente Directa , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias/química , Neoplasias/patología , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/ultraestructura , Adhesión en Parafina , Podosomas/química , Podosomas/ultraestructura , Interferencia de ARN , ARN Interferente Pequeño/genéticaRESUMEN
BACKGROUND/AIM: Gastric cancer is the third leading cause of cancer mortality worldwide. Human epidermal growth factor (Her-2/neu) has shown strong therapeutic implication in breast cancer. Although the prevalence of Her-2/neu over-expression in gastric cancer has been reported across the world, it is still unknown from South Asia. The aim of this study is to evaluate Her-2/neu expression in gastric adenocarcinomas and to correlate with various clinicopathological variables. PATIENTS AND METHODS: A total of 95 consecutive patients undergoing endoscopic biopsy or gastrectomy were recruited in this study. Clinicopathological parameters of all patients were recorded and hematoxylin and eosin (H and E) staining was performed. Over-expression of Her-2/neu was investigated by immunohistochemistry using α-Her-2 antibody. To quantify Her-2/neu over-expression, the Hofmann validation scoring system was used and further its association was seen with age, gender, histopathological type, grade, and stage of the tumor. Data were entered and analyzed using SPSS version 21. A P value of <0.05 was considered as significant. RESULTS: Overall, 21 (22.1%) cases were positive for Her-2/neu overexpression from the total of 95 gastric adenocarcinomas. Her-2/neu was significantly expressed in low-grade gastric cancer (grade I = 50%, grade II = 34.5%, grade III = 14.5%; P = 0.030). Although there was insignificant difference between Her-2/neu over expression and other variables, Her-2/neu score 3+ was predominantly seen in females, age >60 years, Laurens intestinal type, and IIIC stage tumors. CONCLUSION: Her-2/neu is over-expressed in a limited group of gastric cancer patients in our population and indicates a significant strong association with low grades of gastric cancer.
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Adenocarcinoma/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Estómago/patología , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Endoscopía/métodos , Femenino , Gastrectomía/métodos , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Pakistán/epidemiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/ultraestructuraRESUMEN
AIMS: Gut-associated lymphoid tissue (GALT) carcinoma is a rare colorectal tumour that arises in the epithelium covering GALT. GALT carcinoma is a differentiated tubular adenocarcinoma with dense lymphoid tissue with a characteristically well-demarcated margin. To date, 26 cases of GALT carcinoma, including the three cases discussed here, have been reported. Most (24 of 26) were discovered at early stages and none of the cases have documented any metastases. This suggests that GALT carcinoma may have a favourable prognosis. It is hypothesised that GALT carcinoma originates from M cells in specialised epithelia covering GALT. However, this hypothesis has yet to be confirmed. METHODS AND RESULTS: In this study, we examined three cases of GALT carcinoma by immunohistochemistry detection of glycoprotein 2, a specific marker for M cells, and electron microscopy. Our findings showed that the tumour cells of GALT carcinoma in all three cases were negative for M cells. We thus concluded that GALT carcinoma may be a tubular adenocarcinoma arising by chance in the GALT. This unique carcinoma is a diferentiated adenocarcinoma that grows slowly with the development of GALT. CONCLUSIONS: We propose that GALT carcinoma should be classified separately because of its histological setting and good prognosis.
Asunto(s)
Adenocarcinoma/patología , Neoplasias Colorrectales/patología , Mucosa Intestinal/patología , Adenocarcinoma/ultraestructura , Anciano , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/ultraestructura , Femenino , Humanos , Inmunohistoquímica , Mucosa Intestinal/ultraestructura , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana EdadRESUMEN
In this study, we describe, compare, and discuss several subcellular alterations found in Colorectal Adenocarcinoma and peritumoral tissue using transmission electron microscopy, morphometry, and statistical analysis. Tissue samples from anterior resections were collected from patients diagnosed with Colorectal Adenocarcinoma in the University Hospital of Caracas. Samples were processed according to the typical protocol for their observation through transmission electron microscopy. The resulting images were analyzed using specialized software for the collection of morphometric data. Several anomalies were common for both tissues, including but not limited to, rough endoplasmic reticulum and mitochondrial swelling, nuclear invagination, nuclear enlargement, and cellular swelling. In general, alterations within the tumor were more frequent and intense. Extensive organellar degradation and other evidences of cellular damage seemed to extend past the edge of the tumor into the peritumoral tissue. There seems to be a clear process of lateral cancerization present in the peritumoral area. The tissue layers composed of smooth muscle cells, probably due to their structural features, may allow greater diffusion of harmful substances produced by the tumor. A more in-depth analysis of peritumoral tissue considering organellar damage and morphometric data may provide relevant insight about the changing microenvironment promoted by the close proximity of a tumor.
Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/ultraestructura , Anciano , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Microscopía Electrónica de Transmisión/métodos , Persona de Mediana EdadRESUMEN
Vaginal and vulvar tumors are uncommon in dogs. Knowledge of canine primary clitoral neoplasia is restricted to a few case reports, and only carcinomas have been reported. Cytologic and histologic features reported in the literature seem to overlap with those of canine apocrine gland anal sac adenocarcinoma (AGASA). Clinical features also recall those of canine AGASA, such as locoregional metastases and hypercalcemia of malignancy (HM). In this study, 6 cases of primary canine clitoral carcinomas (CCCs), with and without HM, were investigated by means of cytology, histopathology, electron microscopy, and immunohistochemistry for neuroendocrine markers including chromogranin A (CGA), synaptophysin (SYN), neuron-specific enolase (NSE), and S-100. In all 6 tumors, cytologic findings were consistent with malignant epithelial neoplasia of apocrine gland origin. The tumors examined were classified into 3 different histological patterns representing different degrees of differentiation: tubular, solid, and rosette type. Both CGA and SYN were mildly expressed in 2 of 6 tumors, while NSE was consistently expressed in all 6 cases. None of the tumors were S-100 positive. Transmission electron microscopy revealed electron-dense cytoplasmic granules compatible with neuroendocrine granules in all 6 cases. CCCs presented clinicopathologic features resembling AGASAs with neuroendocrine characteristics, and 2 of 6 neoplasms were considered as carcinomas with neuroendocrine differentiation and were positive for 3 neuroendocrine markers. CCCs can often present with HM, and long-term outcome is likely poor. Our study concludes that CCC seems to be a rare tumor, but it might be underestimated because of the overlapping features with AGASA. Further studies should aim to define the true incidence of this disease.
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Adenocarcinoma/patología , Biomarcadores de Tumor/análisis , Carcinoma/veterinaria , Enfermedades de los Perros/patología , Hipercalcemia/veterinaria , Síndromes Paraneoplásicos/veterinaria , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Adenocarcinoma/ultraestructura , Animales , Carcinoma/diagnóstico , Carcinoma/patología , Carcinoma/ultraestructura , Cromogranina A/análisis , Clítoris/patología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/cirugía , Perros , Femenino , Hipercalcemia/diagnóstico , Hipercalcemia/patología , Inmunohistoquímica/veterinaria , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/patología , Sinaptofisina/análisis , Vulva/patologíaRESUMEN
INTRODUCTION: It have been found previously that colorectal cancer (CRC) is accompanied by atrophy of myenteric plexuses (MPs) localized close to the tumor. The aim of the study was to compare ultrastructure of MPs localized in the unchanged part of the colon wall distant to CRC tumor with the ultrastructure of MPs in the vicinity of CRC tumor. MATERIAL AND METHODS: The present study was conducted using post-operative material derived from 11 patients with CRC. Samples of colon wall were taken from the margin of cancer invasion and from a macroscopically unchanged segment of the large intestine, immediately fixed and processed according to the standard protocol for transmission electron microscopy studies. RESULTS: In the MPs localized in the control part of colon wall the presence of numerous unmyelinated axons and cell bodies of neurons, interstitial cells of Cajal and enteroglial cells were observed. As compared to control samples, in the MPs located close to the tumor invasion, expansion of the extracellular matrix and myelin-like structures accompanying some nerve fibers were found. The appearance of mast and plasma cells was observed within MPs in the vicinity of CRC tumor. Sporadically, apoptotic cells were present inside the MPs. CONCLUSIONS: The presence of myelin-like structures and apoptotic cells within MPs located close to tumor invasion suggests that atrophy of MPs may be caused by factors released from CRC tumor.
Asunto(s)
Adenocarcinoma/patología , Colon/ultraestructura , Neoplasias Colorrectales/patología , Plexo Mientérico/ultraestructura , Adenocarcinoma/ultraestructura , Anciano , Neoplasias Colorrectales/ultraestructura , Femenino , Humanos , Masculino , Plexo Mientérico/patologíaRESUMEN
Objective: To investigate the clinicopathologic features of microcystic, elongated and fragmented (MELF) pattern invasion of endometrial adenocarcinoma. Methods: HE and immunohistochemistry staining method were used to analysis morphologic features and immunophenotype of 72 patients of endometrial adenocarcinoma with MELF pattern invasion, and chi-square test was used to analysis the clinicopathologic features. Results: The mean age of 72 patients was 54 years (40 to 70 years). Thirty-two patients were pre-menopausal and 40 were post-menopausal. According to the FIGO staging system (2014), 32 cases(44.4%)were at stage â , 22 cases(30.6%)at stage â ¡, 17 cases(23.6%)at stage â ¢ and 1 case(1.4%) at stage â £. Microscopically, MELF invasion showed microcystic, elongated slit-like or fragmented glands in myometrium and their lining cells usually were cube or flat, as well as the single or clusters of eosinophilic tumor cells mimicking histocytes. In addition, a fibromyxoid or inflammatory stromal response was often present.Immunohistochemical staining showed that MELF invasion was positive for p16, CA125 and CA19-9, but negative for ER, PR and p53.Compared with non-MELF pattern invasion, significant differences were noted in menopause pausimenia, FIGO stages, deep invasion into myometrium, lymph metastasis, lymphovascular space invasion (LVSL), serum CA125 and CA19-9 in patients with MELF pattern invasion (all P<0.05). Conclusions: MELF pattern invasion of endometrial adenocarcinoma is characterized by advanced FIGO stage, deep myoinvasion, high metastasis rate to lymph node and LVSL. Pathologists should recognize the MELF invasion and evaluate the depth of myometrium of infiltration and LVSL with special attention to the presence of MELF invasion with necessary immunohistochemistry for more accurate pathological diagnosis.
Asunto(s)
Adenocarcinoma/patología , Neoplasias Endometriales/patología , Adenocarcinoma/sangre , Adenocarcinoma/química , Adenocarcinoma/ultraestructura , Adulto , Anciano , Distribución de Chi-Cuadrado , Neoplasias Endometriales/sangre , Neoplasias Endometriales/química , Neoplasias Endometriales/ultraestructura , Femenino , Histiocitos/patología , Humanos , Inmunohistoquímica , Inmunofenotipificación , Ganglios Linfáticos , Metástasis Linfática , Persona de Mediana Edad , Miometrio/química , Miometrio/patología , Invasividad NeoplásicaRESUMEN
The cancer drug gemcitabine (GEM) is a key drug for treating pancreatic ductal adenocarcinoma (PDAC), but PDAC cells develop chemoresistance after long-term administration. Since the tolerance was immediately spread to every PDAC tissue in a patient, it is assumed that some certain efficient mechanisms underlay in the development of chemoresistance. Changes in the levels of particular microRNAs or alterations in intercellular communication play a dominant role in chemoresistance development, and recent data also suggest that exosomes play an important role in this process. In this study, we revealed that the loop conferred chemoresistance in PDAC cells. The loop was as follows; 1, The long-term exposure of GEM increased miR-155 expression in PDAC cells. 2, The increase of miR-155 induced two different functions; exosome secretion and chemoresistance ability via facilitating the anti-apoptotic activity. 3, Exosome deliver the miR-155 into the other PDAC cells and induce the following function. The target therapy to miR-155 or the exosome secretion effectively attenuated the chemoresistance, and these results were validated with both clinical samples and in vivo experiments. This mechanism represents a novel therapeutic target in GEM treatment to PDAC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos , Exosomas/metabolismo , MicroARNs/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/ultraestructura , Línea Celular Tumoral , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Exosomas/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , MicroARNs/genética , Microdisección , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/ultraestructura , Pronóstico , Factores de Tiempo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Gemcitabina , Neoplasias PancreáticasRESUMEN
Minimal-deviation endometrioid adenocarcinoma (MDEA) of the uterine cervix is a rare tumor that may be confused histologically with a number of benign lesions as well as other types of endocervical neoplasia. The histologic and immunohistochemical features of MDEA have been described in case reports and in small series, but correlation of these findings with ultrastructural examination has not been documented. Herein we report a 51-yr-old patient who underwent hysterectomy for menorrhagia and was found to have a clinically unsuspected, stage IB cervical MDEA. The light microscopic, immunohistochemical, and electron microscopic features of the tumor are described, with the most significant ultrastructural abnormality being the presence of abnormal cilia and ciliogenesis.
Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma Endometrioide/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adenocarcinoma/patología , Adenocarcinoma/ultraestructura , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/ultraestructura , Cuello del Útero/patología , Cuello del Útero/ultraestructura , Diagnóstico Diferencial , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/ultraestructuraRESUMEN
Metastasis is a great challenge in lung adenocarcinoma (ADC) therapy. Cholesterol has been implicated in ADC metastasis. 4-cholesten-3-one, as cholesterol metabolite and analog, can substitute membrane cholesterol and increase membrane fluidity. In this study, we explored the possibility that 4-cholesten-3-one inhibited ADC metastasis. Low-dose 4-cholesten-3-one significantly restrained ADC cells migration and invasion with little effects on cells viabilities. Further investigation showed that 4-cholesten-3-one promoted ROS generation, which transiently activated AMPKα1, increased HIF1α expression, reduced Bcl-2 expression and caused autophagy. AMPKα1 knockdown partly suppressed 4-cholesten-3-one-induced autophagy but, neither prevented 4-cholesten-3-one-induced upregulation of HIF1α or downregulation of Bcl-2. 4-cholesten-3-one-induced autophagy facilitated the release of HMGB1 from nuclei to cytoplasm, blocking nuclear translocation of HIF1α and activation of MMP2 and MMP9. Also, 4-cholesten-3-one induced time-dependent phosphorylation of caveolin-1, Akt and NF-κB. With increasing treatment time, 4-cholesten-3-one accelerated caveolin-1 internalization, but reduced the phosphorylation of Akt and NF-κB, and inhibited the expression of snail and twist. These data suggested that 4-cholesten-3-one could be a potential candidate for anti-metastasis of lung adenocarcinoma.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Caveolina 1/metabolismo , Colestenonas/uso terapéutico , Proteína HMGB1/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/ultraestructura , Adenocarcinoma del Pulmón , Animales , Autofagia/efectos de los fármacos , Neoplasias Encefálicas/secundario , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colestenonas/farmacología , Colesterol/metabolismo , Endocitosis/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/ultraestructura , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Biológicos , Invasividad Neoplásica , Fosforilación/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
RATIONALE: Hepatoid adenocarcinoma (HAC) is a rare malignant lung tumor that histologically resembles typical hepatocellular carcinoma (HCC) when it is metastatic to the lung. To date, this clinical entity has not been highlighted in the pulmonary literature. OBJECTIVE: We present a review of all known cases of HAC, including the relevant clinical and histopathological features important for pulmonologists. MEASUREMENTS AND MAIN RESULTS: The purpose of this report is to present a new case of HAC, with typical clinical and histologic features of this malignancy, and to summarize findings of previously reported cases. A systematic literature search of the electronic database PUBMED was conducted to identify all cases of hepatoid adenocarcinoma reported in the English literature, between January 1980 and June 2015. HAC and HCC can be distinguished by immunohistochemical staining. HAC usually presents as a large bulky solitary mass in the upper lobe; there is an exceedingly high prevalence in males and most patients with this tumor are smokers. Serum alpha-fetoprotein (AFP) in very high levels has been a distinguishing feature of this tumor. Nodal and distant metastases are common at initial presentation and, as a result, the prognosis is very poor. Resection and long-term survival, however, have been reported. CONCLUSION: Hepatoid adenocarcinoma, first described as a gastric tumor, has also been described in the lung. It morphologically resembles and must be distinguished from metastatic HCC of the lung. While most tumors produce AFP, the case we present demonstrates that this should not be a criterion for diagnosis.