RESUMEN
BACKGROUND: Inflammatory cancer-associated fibroblasts (iCAFs) was first identified by co-culture of pancreatic stellate cells and tumor organoids. The key feature of iCAFs is IL-6high/αSMAlow. We examine this phenomenon in gastric cancer using two cell lines of gastric fibroblasts (HGF and YS-1). METHODS AND RESULTS: HGF or YS-1 were co-cultured with MKN7 (a gastric adenocarcinoma cell line) in Matrigel. IL-6 protein levels in the culture supernatant were measured by ELISA. The increased production of IL-6 was not observed in any of the combinations. Instead, the supernatant of YS-1 exhibited the higher levels of IL-6. YS-1 showed IL-6high/αSMA (ACTA2)low in real-time PCR, mRNA-seq and immunohistochemistry. In mRNA-seq, iCAFs-associated genes and signaling pathways were up-regulated in YS-1. No transition to myofibroblastic phenotype was observed by monolayer culture, or the exposure to sonic hedgehog (SHH) or TGF-ß. YS-1 conditioned medium induced changes of morphology and stem-ness/differentiation in NUGC-3 (a human gastric adenocarcinoma cell line) and UBE6T-15 (a human bone marrow-derived mesenchymal stem cell line). CONCLUSIONS: YS-1 is a stable cell line of gastric iCAFs. This discovery will promote further research on iCAFs for many researchers.
Asunto(s)
Adenocarcinoma , Fibroblastos Asociados al Cáncer , Neoplasias Gástricas , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteínas Hedgehog/metabolismo , Línea Celular Tumoral , Neoplasias Gástricas/metabolismo , Fibroblastos/metabolismo , Adenocarcinoma/metabolismo , ARN Mensajero/metabolismoRESUMEN
BACKGROUND/AIM: "Stromal high expression" of Nicotinamide N-methyltransferase (NNMT), previously reported as a poor prognostic factor of gastric cancer, was based on immunohistochemical H-score. However, this could simply indicate an increase in cancer-associated fibroblasts (CAFs) because NNMT is positive for fibroblasts. To verify this, the proportion and staining intensity of stromal NNMT-positive stellate/spindle cells were evaluated separately and examined for its association with related proteins (H3K4me3, H3K27me3, and LOXL2). PATIENTS AND METHODS: Immunohistochemistry for NNMT, H3K4me3, H3K27me3, and LOXL2 was performed on 521 tissue microarrays of gastric cancer. Cancer stromal stellate/spindle cells were evaluated according to morphology, proportion, and stain intensity of NNMT, loss of H3K4me3 and H3K27me3, and stain intensity of LOXL2. Their associations with clinicopathological characteristics and overall survival were examined. RESULTS: Higher staining intensity of NNMT was not related to a poorer prognosis. However, higher proportion of NNMT-positive stellate/spindle cells indirectly contributed to a poor prognosis. It was associated with CAF-like morphology and a global decrease in H3K4me3/H3K27me3, which were both associated with high LOXL2 expression. These three factors were independent poor prognostic factors. In addition, in the LOXL2-high group, prognosis significantly deteriorated with the presence of a global decrease in H3K4me3/H3K27me3. CONCLUSION: The higher proportion of NNMT-positive cancer stromal cells in gastric cancer serves as an indicator for identifying unfavorable prognostic CAFs that show a global decrease in H3K4me3/H3K27me3. This facilitates research on the nature of these cells and their characteristics.
Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Gástricas , Humanos , Histonas , Nicotinamida N-Metiltransferasa/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Pronóstico , Células del Estroma/metabolismoRESUMEN
INTRODUCTION: Chondromyxoid fibroma (CMF) is a rare, benign bone tumor that occurs predominantly in the second and third decades of life, more frequently in males. Overexpression of GRM1 as a consequence of tumor-specific gene rearrangement of GRM1 has recently been reported as a useful immunohistochemical marker for histopathological diagnosis of CMF. However, the usefulness of GRM1 staining of cytology specimens has not yet been evaluated. In this report, the cytological findings and GRM1 immunocytochemistry of two cases of CMF are described. CASE PRESENTATIONS: Case 1 was a 15-year-old girl with a rib tumor. Imaging findings suggested a benign neurogenic tumor such as schwannoma. The tumor had increased in size over a 2-year period and was resected. Case 2 was a 14-year-old boy with a metatarsal tumor involving his left first toe. Imaging findings were suspicious of a benign neoplastic lesion. Biopsy findings suggested a benign tumor, and the patient underwent tumor resection. Cytologically, in both cases the tumor cells were predominantly spindle-shaped or stellate, with a myxoid to chondromyxoid background matrix and multinucleated giant cells, and these matrices were metachromatic with Giemsa staining. Cellular atypia was more accentuated in case 2 than in case 1. Immunocytochemical staining for GRM1 was positive in both cases. CONCLUSION: Due to the overlap in cytological findings, it is often difficult to differentiate CMF from chondroblastoma and chondrosarcoma grade 2. Immunocytochemical staining for GRM1 may support the diagnosis of CMF, and the reuse of Papanicolaou-stained specimens is applicable. The present cases further demonstrated the difficulty of differentiating CMF from other mimicking tumors such as chondroblastoma and chondrosarcoma grade 2. In such instances, immunocytochemistry for GRM1 is applicable to the diagnostic process, the value of which is strengthened by reusing Papanicolaou-stained specimens.
Asunto(s)
Neoplasias Óseas , Condroblastoma , Condrosarcoma , Fibroma , Adolescente , Femenino , Humanos , Masculino , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Condroblastoma/diagnóstico , Condroblastoma/cirugía , Condroblastoma/metabolismo , Condrosarcoma/patología , Citología , Fibroma/diagnóstico , Fibroma/cirugía , Fibroma/patología , Receptores de Glutamato Metabotrópico/inmunología , Receptores de Glutamato Metabotrópico/metabolismoRESUMEN
Fungal rhinosinusitis (FRS) presents as various phenotypes ranging from asymptomatic colonization to life-threatening infections. Here, we report an atypical case of FRS of the left maxillary sinus that extended to the contralateral maxillary sinus through the nasal septum. An 80-year-old woman with a history of osteoporosis was referred to our hospital for further management of headaches and chronic rhinosinusitis. Computed tomography (CT) of the sinus revealed a mass lesion with calcification in the left maxillary sinus, extending to the contralateral maxillary sinus through the nasal septum. T1-weighted and T2-weighted magnetic resonance imaging revealed a mass lesion with low-intensity signals. Endoscopic sinus surgery was performed for the diagnosis and treatment. Histopathological examination revealed fungal elements in the caseous material of the left maxillary sinus. However, no tissue-invasive fungal forms were found. Additionally, eosinophilic mucin was not observed. Based on these findings, the patient was diagnosed with fungus ball (FB). To the best of our knowledge, there are no reports of a FB extending contralaterally through the nasal septum. This report serves as a reminder that FB can extend into contralateral paranasal sinuses through the nasal septum and the possibility that osteoporosis is a cause of extensive bone destruction.
RESUMEN
Pulmonary involvement in vascular Behçet's disease (BD) (VBD) is a serious manifestation. Among the pulmonary manifestations, pulmonary embolism is considered a rare manifestation because deep vein thrombosis (DVT) has been thought to detach from the vessel wall, whereas pulmonary thrombus has been suggested to result from in situ pulmonary arteritis.In this case report, we present histopathological evidence of pulmonary embolism derived from DVT in an autopsy case of VBD. This observation emphasises that DVT causes pulmonary embolism in BD, indicating that anticoagulants are required for its prevention.
Asunto(s)
Síndrome de Behçet , Embolia Pulmonar , Trombosis , Anticoagulantes/uso terapéutico , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Humanos , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/etiología , Trombosis/etiologíaRESUMEN
Myxoid leiomyosarcoma (MLS) is a rare variant of leiomyosarcoma, with most cases occurring in the uterus. A case of MLS arising in the periosteal region of the tibia, mimicking extraskeletal myxoid chondrosarcoma (EMC), is described. The evaluation included histological and cytological comparison with EMC. The patient was a 77-year-old man with a palpable mass at the anterior aspect of the right lower leg. After diagnosis by cytopathology and biopsy examination, a wide resection was performed. The resulting cytological smears were composed primarily of spindle-shaped tumor cells in a myxoid and hemorrhagic background. Histologically, the tumor showed abundant myxoid matrix and tumor cells proliferating in a cord-like to reticular pattern, exhibiting a lace-like arrangement that mimicked EMC. Although immunohistochemical findings suggested leiomyosarcoma, a diagnosis of EMC eventually was excluded by the lack of a split signal when assessed for a rearrangement of NR4A3 by chromogenic in situ hybridization. Despite histological similarity to EMC, characteristic cytological findings of EMC such as epithelioid structures with a cord-like pattern and chondroblast-like lacunar structures were not observed in the smears of this patient's MLS. We propose that cytopathological examination of bone and soft tissue lesions is useful as a diagnostic tool in similar cases. A total diagnostic workup, including clinical, radiographic, cytopathological, histopathological, and molecular findings, is needed to ensure an accurate final diagnosis and to reduce diagnostic error.
Asunto(s)
Neoplasias Óseas/patología , Condrosarcoma/patología , Leiomiosarcoma/patología , Neoplasias de los Tejidos Conjuntivo y Blando/patología , Tibia/patología , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Óseas/química , Neoplasias Óseas/genética , Neoplasias Óseas/cirugía , Condrosarcoma/química , Condrosarcoma/genética , Proteínas de Unión al ADN/genética , Diagnóstico Diferencial , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación in Situ , Leiomiosarcoma/química , Leiomiosarcoma/genética , Leiomiosarcoma/cirugía , Masculino , Neoplasias de los Tejidos Conjuntivo y Blando/química , Neoplasias de los Tejidos Conjuntivo y Blando/genética , Valor Predictivo de las Pruebas , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea/genética , Tibia/química , Tibia/cirugíaRESUMEN
BACKGROUND: Currently, there is an unwavering consensus that the standard surgery for congenital biliary dilation (CBD) is extrahepatic bile duct resection and choledochojejunostomy. However, decades prior, choledochocyst-gastrointestinal anastomosis without extrahepatic bile duct resection (internal drainage surgery, IDS) was preferred for CBD because of its simplicity. Currently, there is almost no chance of a surgeon encountering a patient who has undergone old-fashioned IDS, which has been completely obsolete due to the risk of carcinogenesis from the remaining bile duct. Moreover, the pathological condition long after IDS is unclear. Herein, we report a case of life-threatening bile duct bleeding as well as carcinoma of the bile duct 62 years after IDS in a patient with CBD. CASE PRESENTATION: An 82-year-old Japanese woman with hemorrhagic shock due to gastrointestinal bleeding was transferred to our hospital. She had a medical history of unspecified surgery for CBD at the age of 20. Based on imaging findings and an understanding of the historical transition of the surgical procedure for CBD, the cause of gastrointestinal bleeding was determined to be rupture of the pseudoaneurysm of the dilated bile duct that remained after IDS. Hemostasis was successfully performed by transcatheter arterial embolization (TAE) in an emergency setting. Then, elective surgery for extrahepatic bile duct resection and choledochojejunostomy was performed to prevent rebleeding. Pathological examination revealed severely and chronically inflamed mucosa of the bile duct. Additionally, cholangiocarcinoma (Tis, N0, M0, pStage 0) was incidentally revealed. CONCLUSION: It has been indicated that not only carcinogenesis, but also a risk of life-threatening bleeding exists due to long-lasting chronic inflammation to the remnant bile duct after IDS for CBD. Additionally, both knowledge of which CBD operation was performed, and an accurate clinical history are important for the diagnosis of hemobilia.
RESUMEN
INTRODUCTION: BCOR-CCNB3 sarcoma (BCS) is one of the histological types classified as an undifferentiated small round cell sarcoma of bone and soft tissue. This sarcoma frequently develops in males under 20 years of age. Histologically, a delicate capillary network has been reported as a conspicuous finding. In this study, the cytological findings of BCS were observed in two cases of primary lesions and one case of a lung metastatic lesion. The cytological findings of BCS were compared with its histological mimics, and the characteristic findings of BCS were examined. METHODS: Three cases of BCS were studied, and a cytological comparison was performed with 8 cases of Ewing sarcoma (ES) and 10 cases of synovial sarcoma (SS; monophasic type: 7 cases, biphasic type: 2 cases, poorly differentiated: 1 case). RESULTS: In all BCS cases, small clusters with thin and delicate vascular cores and tiny vascular fragments were conspicuous. In ES and SS cases, although small clusters with vascular cores were observed, the vascular cores were thicker than in BCS, and no tiny vascular fragments appeared in most cases. Cytomorphological differences of tumour cells were also observed among BCS, ES, and SS. Predominantly rounded nuclei with fine chromatin and inconspicuous nucleoli can be cytological clues for BCS. CONCLUSIONS: BCS shows characteristic cytological findings that make the diagnosis of BCS more likely than that of ES and SS. Cytological evaluation is a useful tool for appropriate differential diagnosis that leads to a more accurate final diagnosis and rapid treatment.
Asunto(s)
Sarcoma de Ewing , Sarcoma Sinovial , Sarcoma , Adolescente , Adulto , Biomarcadores de Tumor/análisis , Nalgas/diagnóstico por imagen , Nalgas/patología , Ciclina B/análisis , Diagnóstico Diferencial , Fémur/diagnóstico por imagen , Fémur/patología , Talón/diagnóstico por imagen , Talón/patología , Humanos , Inmunohistoquímica , Masculino , Proteínas Proto-Oncogénicas/análisis , Proteínas Represoras/análisis , Sarcoma/diagnóstico , Sarcoma/patología , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/patología , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/patología , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
INTRODUCTION: Diagnosing renal pathologies is important for performing treatments. However, classifying every glomerulus is difficult for clinicians; thus, a support system, such as a computer, is required. This paper describes the automatic classification of glomerular images using a convolutional neural network (CNN). METHOD: To generate appropriate labeled data, annotation criteria including 12 features (e.g., "fibrous crescent") were defined. The concordance among 5 clinicians was evaluated for 100 images using the kappa (κ) coefficient for each feature. Using the annotation criteria, 1 clinician annotated 10,102 images. We trained the CNNs to classify the features with an average κ ≥0.4 and evaluated their performance using the receiver operating characteristic-area under the curve (ROC-AUC). An error analysis was conducted and the gradient-weighted class activation mapping (Grad-CAM) was also applied; it expresses the CNN's focusing point with a heat map when the CNN classifies the glomerular image for a feature. RESULTS: The average κ coefficient of the features ranged from 0.28 to 0.50. The ROC-AUC of the CNNs for test data varied from 0.65 to 0.98. Among the features, "capillary collapse" and "fibrous crescent" had high ROC-AUC values of 0.98 and 0.91, respectively. The error analysis and the Grad-CAM visually showed that the CNN could not distinguish between 2 different features that had similar visual structures or that occurred simultaneously. CONCLUSION: The differences in the texture or frequency of the co-occurrence between the different features affected the CNN performance; thus, to improve the classification accuracy, methods such as segmentation are required.
RESUMEN
Epithelioid hemangioma is a rare benign vascular tumor that consists of capillary-sized vessels lined by epithelioid endothelial cells. Diffuse cavernous hemangioma is a congenital benign vascular neoplasm consisting of increased dilated vessels. We report a case of epithelioid hemangioma and diffuse cavernous hemangioma that co-occurred in the rectum. To our knowledge, this is the first report in which two rare vascular lesions coexisted. Because both epithelioid hemangioma and diffuse cavernous hemangioma are often clinically confounded by malignant tumors, differentiating these benign lesions from other possible malignant tumors is significant.
Asunto(s)
Hemangioma Cavernoso/patología , Hemangioma/patología , Recto/patología , Anciano , Células Endoteliales/patología , Hemangioma/diagnóstico , Hemangioma Cavernoso/diagnóstico , Humanos , MasculinoRESUMEN
BACKGROUND/AIM: Myeloid/lymphoid or mixed lineage leukemia 2 (MLL2) gene is mutated in gastric cancer, with most resulting in inactivated proteins. In this study, we examined the expression of MLL2 protein in gastric cancers. PATIENTS AND METHODS: The expression of MLL2 protein in cancer cell nuclei was studied by immunohistochemistry in tissue microarrays of 529 human gastric cancers. MLL2 expression was classified into low and high expression from the point of zygosity, and its relationships with mismatch repair protein expression and clinicopathological features were examined. RESULTS: Low expression of MLL2 was associated with younger age, MSH6, and early cancers. MLL2-low pT1a cancers were associated with fibrosis, especially ulcer scars, and in 62.5% of them there was no direct contact between carcinoma and fibrosis. CONCLUSION: There is potentially an association between low expression of MLL2 protein and gastric malignancy from chronic fibrosis.
Asunto(s)
Proteína de la Leucemia Mieloide-Linfoide , Neoplasias Gástricas , Proteínas de Unión al ADN , Detección Precoz del Cáncer , Fibrosis , Humanos , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Neoplasias , Neoplasias Gástricas/genéticaAsunto(s)
Bronquiolitis Obliterante/etiología , Enfermedad de Castleman/diagnóstico , Pénfigo/etiología , Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/patología , Enfermedad de Castleman/complicaciones , Enfermedad de Castleman/patología , Resultado Fatal , Femenino , Humanos , Pénfigo/diagnóstico , Pénfigo/patología , Adulto JovenRESUMEN
BACKGROUND: Pulmonary NUT carcinoma is rare, but lethal, thus, must not be overlooked. The definitive diagnosis is made by a NUT monoclonal antibody or gene analysis, but these are not always routinely available. Therefore, the diagnosis depends on this rare disease being suspected from the clinical and pathological findings. Generally, NUT carcinoma of the lung occurs near the hilum in younger adults with severe subjective symptoms. Histologically, it is characterized by the monomorphic growth of small cells which showed positivity of p63 immunohistochemistry. CASE PRESENTATION: An 82-year-old man was referred for an incidental finding of an abnormal shadow at the peripheral apex of the right lung on computed tomography for a regular follow-up examination of renal cancer. Microscopically, small cell carcinoma was initially suspected; however, immunohistochemistry was not typical. NUT carcinoma with BRD4-NUT fusion was ultimately diagnosed using a NUT monoclonal antibody, fluorescence in situ hybridization, and RNA-seq. p63 and p40 protein expression was not detected. CONCLUSIONS: This is the first case of pulmonary NUT carcinoma to show negativity for p63 and is the oldest among previously reported cases. The present case suggests that NUT carcinoma should be suspected when the morphology of monomorphic growth of small cells without lineage-specific differentiation, regardless of age, clinical symptoms, the tumor location, or p63 expression.
Asunto(s)
Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales , Humanos , Neoplasias Renales , Masculino , Proteínas de la Membrana , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/patologíaRESUMEN
Cancer stem cells (CSCs) play a decisive role in the development and progression of cancer. To investigate CSCs in Epstein-Barr virus (EBV)-associated carcinoma (EBVaGC), we screened previously reported stem cell markers of gastric cancer in EBV-infected gastric cancer cell lines (TMK1 and NUGC3) and identified CD44v6v9 double positive cells as candidate CSCs. CD44v6/v9+/+ cells were sorted from EBVaGC cell line (SNU719) cells and EBV-infected TMK1 cells and these cell populations showed high spheroid-forming ability and tumor formation in SCID mice compared with the respective CD44v6/v9-/- cells. Sphere-forming ability was dependent on the nuclear factor-κB (NF-κB) signaling pathway, which was confirmed by decrease of sphere formation ability under BAY 11-7082. Small interfering RNA knockdown of latent membrane protein 2A (LMP2A), one of the latent gene products of EBV infection, decreased spheroid formation in SNU719 cells. Transfection of the LMP2A gene increased the sphere-forming ability of TMK1 cells, which was mediated through NF-κB signaling. Together, these results indicate that CD44v6v9+/+ cells are CSCs in EBVaGC that are maintained through the LMP2A/NF-κB pathway. Future studies should investigate CD44v6/v9+/+ cells in normal and neoplastic gastric epithelium to prevent and treat this specific subtype of gastric cancer infected with EBV.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/fisiología , Células Madre Neoplásicas/metabolismo , Neoplasias Gástricas/etiología , Animales , Biomarcadores , Línea Celular Tumoral , Modelos Animales de Enfermedad , Humanos , Inmunofenotipificación , Ratones , FN-kappa B/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Pre-resection pleural lavage cytology is useful to predict tumor recurrence and the prognosis of lung cancer patients. Recently, extracellular vesicles (EVs) isolated from effusion specimens have come under the spotlight, and several studies showed that microRNA in EVs is associated with prognosis. MicroRNA-21 (miR-21) is a representative onco-microRNA, and miR-21 in EVs (EV-miR-21) promotes cancer dissemination by inducing mesothelial to mesenchymal transition (MMT) in the peritoneal cavity. In this study, we isolated EVs from pleural lavage fluid and focused on EV-miR-21 as a diagnostic factor with a relationship to pleural dissemination. METHODS: The Cancer Genome Atlas dataset comprising of 448 cases of lung adenocarcinoma, tissue microarray of 144 cases of lung adenocarcinoma, and pleural lavage fluid of 41 cases was used to examine miR-21 expression levels. The function of EV-miR-21 was investigated in vitro. RESULTS: The miR-21 expression level in primary sites was associated with a poor prognosis and correlated with pleural invasion of adenocarcinoma. EV-miR-21 levels in pleural lavage fluid were associated with positive cytology and pleural invasion in the primary sites, even in cytology-negative cases. In vitro studies demonstrated that EV-miR-21 induces the MMT. Mesothelial cells in the MMT showed functions similar to cancer-associated fibroblasts, which are an important stromal component in primary sites and disseminated pleural lesions. CONCLUSIONS: EV-miR-21 in pleural lavage fluid is important as a diagnostic and prognostic factor. Moreover, EV-miR-21 induces the MMT, which can form premetastatic niches of dissemination in the pleural cavity.
Asunto(s)
Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/metabolismo , Vesículas Extracelulares/patología , Regulación Neoplásica de la Expresión Génica , Mesodermo/patología , MicroARNs/genética , Derrame Pleural Maligno/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular , Transición Epitelial-Mesenquimal , Vesículas Extracelulares/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Mesodermo/metabolismo , Persona de Mediana Edad , Derrame Pleural Maligno/metabolismo , Pronóstico , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
Fat injections aid in the healing of radiation-induced skin damage. We hypothesized that the direct application of fat grafts to the surfaces of radiation-induced ulcers is also effective. Here, we aimed to evaluate the effectiveness of a combination treatment comprising fat injections around ulcers and fat grafts on ulcer surfaces. The dorsal skin of inbred rats was irradiated at a single dose of 20 Gy before producing ulcers. After the inguinal fat was harvested using the Coleman technique, the rats were divided into four groups: Group 1, ulcer wounds were covered using dressing materials and staples only; Group 2, fat was injected around the ulcers using a cannula; Group 3, fat was grafted onto ulcer surfaces; and Group 4, a combination of fat injection around the ulcers and fat grafts onto ulcer surfaces was employed. The mean healing time (± standard deviation) of each group was as follows: Group 1, 16.0 ± 2.2 days; Group 2, 14.5 ± 2.0 days; Group 3, 15.2 ± 1.7 days; and Group 4, 13.4 ± 1.0 days. The healing time of Group 4 was significantly shorter than that of Group 1 (p = .0005) and Group 3 (p = .023). In both groups that received fat grafts, fat tissue was observed in the dermis on hematoxylin-eosin-stained slides at 4 and 8 weeks after the ulcers were created. In conclusion, the combination treatment of fat grafted onto ulcer surfaces and injected around ulcers was effective in accelerating the epithelization of radiation-induced ulcers.
Asunto(s)
Grasa Abdominal/trasplante , Inyecciones , Úlcera Cutánea/terapia , Colgajos Quirúrgicos , Cicatrización de Heridas , Animales , Modelos Animales de Enfermedad , Epidermis/patología , Traumatismos Experimentales por Radiación , Ratas Endogámicas F344 , Úlcera Cutánea/etiología , Factores de TiempoRESUMEN
BACKGROUND/AIM: CD10 function in urothelial carcinoma (UC) remains controversial. We previously reported that miR-21 in UC may be a prognostic marker for cancer progression. The aim of this study was to examine the clinicopathological significance of CD10 expression in UC and its relationship with miR-21 expression. MATERIALS AND METHODS: Immunohistochemistry for CD10 was performed on 232 UCs. CD10 expression in TCs and stroma was evaluated respectively, and its association with carcinogenesis and survival was analyzed. RESULTS: High tumorous CD10 was significantly associated with higher tumor stage, histological grade and vessel infiltration, and poorer prognosis, whereas stromal CD10 was significantly associated with younger age, higher tumor stage, and vessel infiltration. On multivariable analysis, CD10 expression in TCs, miR-21 expression in TCs and TS, and tumor stage were independent prognostic factors. CONCLUSION: Tumorous CD10 is more strongly related to progression of UC than stromal CD10 and is an independent factor for UC prognosis.
Asunto(s)
Carcinoma/metabolismo , Neprilisina/metabolismo , Células del Estroma/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Urotelio/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinogénesis , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Células del Estroma/patología , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Spindle-shaped stromal cells of tumors are derived from various cellular origins, including mesenchymal stem cells (MSCs). MSCs express CD73, CD90 and CD105 antigens. Herein, the aim was to investigate the association between the expression of specific MSC markers in gastric cancer stromal cells and the clinicopathological features of the disease. MATERIALS AND METHODS: The expression of CD73, CD90 and CD105 in spindle-shaped cancer stromal cells was studied by immunohistochemistry in tissue arrays containing 546 gastric cancer cases. Univariate and multivariate analyses were performed to evaluate the association of MSC marker expression with clinicopathological variables. RESULTS: Spindle-shaped cancer stromal cells expressing the MSC markers CD73, CD90 or CD105 were associated with larger tumor size, advanced cancer, venous infiltration, lymphatic infiltration, and lymph node metastasis. Statistical analysis demonstrated that the presence of CD105-positive spindle cells was an independent prognostic factor of advanced cancer, lymph node metastasis and EBV infection in multivariate analysis. CONCLUSION: Spindle-shaped gastric cancer stromal cells expressing CD73, CD90 or CD105 are involved in disease progression, and among them, CD105-positive cells are strongly associated with poor prognosis.
Asunto(s)
5'-Nucleotidasa/genética , Endoglina/genética , Neoplasias Gástricas/genética , Antígenos Thy-1/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Femenino , Proteínas Ligadas a GPI/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Células del Estroma/metabolismo , Células del Estroma/patologíaRESUMEN
Thus far, only 23 cases of the ectopic production of parathyroid hormone (PTH) have been reported. We have characterized the genome-wide transcription profile of an ectopic PTH-producing tumor originating from a retroperitoneal histiocytoma. We found that the calcium-sensing receptor (CaSR) was barely expressed in the tumor. Lack of CaSR, a crucial braking apparatus in the presence of both intraparathyroid and, probably, serendipitous PTH expression, might contribute strongly to the establishment and maintenance of the ectopic transcriptional activation of the PTH gene in nonparathyroid cells. Along with candidate drivers with a crucial frameshift mutation or copy number variation at specific chromosomal areas obtained from whole exome sequencing, we identified robust tumor-specific cytochrome P450 family 24 subfamily A member 1 (CYP24A1) overproduction, which was not observed in other non-PTH-expressing retroperitoneal histiocytoma and parathyroid adenoma samples. We then found a 2.5-kb noncoding RNA in the PTH 3'-downstream region that was exclusively present in the parathyroid adenoma and our tumor. Such a co-occurrence might act as another driver of ectopic PTH-producing tumorigenesis; both might release the control of PTH gene expression by shutting down the other branches of the safety system (e.g., CaSR and the vitamin D3-vitamin D receptor axis).