RESUMO
BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignant tumor. The standard treatment for CCOC is surgical resection and adjuvant radiotherapy (RT). Radiotherapy is generally considered in inoperable cases. However, there are no reports on definitive RT for CCOC, and the role of RT in patients with inoperable CCOC remains unknown. Therefore, in this report, we present two cases of carbon-ion (C-ion) RT for CCOC. CASE PRESENTATION: In case 1, a 73-year-old man with mandibular CCOC presented with recurrence in the inferior temporal fossa after two tumor resections. The tumor was considered inoperable, and C-ion RT (57.6 Gy in 16 fractions) was administered. The tumor remained controlled even after 20 months of C-ion RT; however, the patient died of other causes. In case 2, a 34-year-old man with maxillary CCOC presented with recurrence in the left sinonasal region after two tumor resections. The tumor was considered inoperable, and C-ion RT (64 Gy in 16 fractions) was administered. However, recurrence was observed in the irradiated field 19 months after the treatment. Subsequently, C-ion RT (64 Gy in 16 fractions) was repeated for the recurrent tumors. Seven years and 6 months after the initial irradiation, the tumor remains controlled, and the patient is alive without any unexpected serious adverse events. CONCLUSION: C-ion RT may be an effective treatment option for patients with inoperable CCOC.
Assuntos
Radioterapia com Íons Pesados , Recidiva Local de Neoplasia , Tumores Odontogênicos , Humanos , Masculino , Idoso , Tumores Odontogênicos/radioterapia , Tumores Odontogênicos/patologia , Tumores Odontogênicos/cirurgia , Radioterapia com Íons Pesados/métodos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/patologia , Adulto , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Prognóstico , Neoplasias Mandibulares/radioterapia , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/cirurgia , Evolução FatalRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant neoplasm with various morphologies. Recognition of histological patterns that can predict prognosis is important in pathological examination. Recently, the complex glandular pattern was defined as a morphology associating the poor prognosis in lung adenocarcinoma. We investigated the significance of the complex glandular pattern in PDAC by performing a retrospective analysis. Among 240 consecutive cases of conventional PDACs, 21 cases in which complex glandular pattern constituted >50 % of the total tumor volume (CG-PDACs) were identified. The prevalence of CG-PDAC was 8.8 % among all preoperative therapy-naïve and surgically resected conventional PDACs. Compared to the control PDACs (n = 95), the CG-PDACs were characterized by significantly higher prevalence of small- to medium-sized artery invasion (71.4 % vs. 14.7 %, p < 0.0001), intratumoral necrosis (59.1 % vs. 16.8 %, p < 0.0001), tumor budding (mean: 15.5 vs. 12.5 per 0.785 mm2, p = 0.04), significantly higher Ki67 proliferative index (mean: 75.0 % vs. 54.7 %, p < 0.0001), and the HNF1α-/KRT81+ (quasi-mesenchymal) immunophenotype (42.9 % vs. 19.0 %, p = 0.004). In Kaplan-Meier analyses, the CG-PDAC patients achieved significantly worse disease-free survival (DFS) and overall survival (OS) compared to the control PDAC patients; the respective median DFS and OS were 6.3 and 17.7 months for CG-PDACs, and 22.6 and 52.8 months for control PDACs. A multivariate Cox regression analysis showed that predominance of complex glandular pattern was an independent prognostic factor (hazard ratio: 2.95; 95 % confidence interval: 1.46-5.98; p = 0.003). Our results provide new insights into the complex glandular pattern in conventional PDACs as a novel and potentially useful prognostic factor.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Prognóstico , Neoplasias PancreáticasRESUMO
A 34-year-old man visited our hospital complaining of a small painless left scrotal mass. His serum alpha-fetoprotein and human chorionic gonadotropin-beta levels were normal. Ultrasonography revealed a solitary 14 mm mass. Magnetic resonance imaging revealed a mass with high intensity on T2-weighted imaging. Computed tomography revealed a heterogeneous tumor in the left scrotum. Left high orchiectomy was performed. The histopathological diagnosis was a teratoma without germ cell neoplasia in situ (GCNIS). Fluorescence in situ hybridization analysis showed no appearance of i(12p). The patient was clinically diagnosed as having a prepubertal-type testicular teratoma. Adult teratomas contain GCNIS and are aggressively treated as malignant germ cell tumors. However, a prepubertal-type teratoma is benign and does not relapse. It is essential to validate the appearance of i(12p) to differentiate prepubertal and postpubertal-type teratoma.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Adulto , Humanos , Hibridização in Situ Fluorescente , Masculino , Recidiva Local de Neoplasia , Orquiectomia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia , Neoplasias Testiculares/cirurgiaRESUMO
PURPOSE: Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) strongly contrasts cancerous tissue against background healthy tissues. Positron emission tomography/computed tomography (PET/CT) applies the uptake of 18-fluorodeoxyglucose in the diagnosis of cancer. Our aim was to compare DWIBS/T2 and PET/CT in patients with upper gastrointestinal cancers. METHODS: Patient records, including imaging results from July 2012 to March 2015, were analyzed retrospectively. Four men (age, 72.5 ± 5.3 years) and ten women (age, 71.6 ± 4.0 years) were enrolled in this study. The numbers of patients with esophageal cancer, gastric cancer, gastrointestinal stromal tumor, and duodenal cancer were one, eight, three, and two, respectively. RESULTS: Six out of eight patients with gastric cancer had positive results on both DWIBS/T2 and PET/CT. The diameter and depth of invasion of gastric cancer was larger in patients with positive DWIBS/T2 and PET/CT findings than those with negative findings. These results suggested that patients with gastric cancer with larger pixel numbers might tend to show positive results with DWIBS/T2. CONCLUSIONS: DWIBS/T2 and PET/CT have similar sensitivity for the diagnosis of upper gastrointestinal cancer. The diameter and depth of invasion affected the detectability of gastric cancer.
Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias Gastrointestinais/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Imagem Corporal Total , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Trato Gastrointestinal Superior/diagnóstico por imagem , Trato Gastrointestinal Superior/patologiaRESUMO
BACKGROUND/AIMS: The aim of this study was to identify factors affecting the detection of colorectal cancer (CRC) and colon polyps (CPs) using abdominal ultrasonography (US). METHODOLOGY: Patient records were analyzed retrospectively. Those diagnosed as having either CRC or CPs by colonoscopy performed after screening abdominal US were enrolled. The diagnostic criterion for CRC was an irregularly thickened wall or mass. CPs were diagnosed as spherical or ovoid hypoechoic lesions arising within the colonic lumen as seen on abdominal US. RESULTS: Sixteen patients had a total of 16 CRC lesions and 11 patients had a total of 17 CPs. All CRC lesions invaded deeper than the subserosa. Cancer cell invasion limited to the submucosa was noted in the two 1.5-cm CPs. Detection of these lesions was not associated with invasion to lymph or blood vessels. These results suggest that wall thickening might be the consequence of cancer cells invading below the subserosa, thereby resulting in the lesions becoming detectable on abdominal US. CONCLUSIONS: Detection of CRC and CPs on abdominal US was associated with lesion size and depth of invasion.
Assuntos
Colo/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Mucosa Intestinal/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Colo/patologia , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Invasividade Neoplásica , Valor Preditivo dos Testes , Estudos Retrospectivos , Carga Tumoral , UltrassonografiaRESUMO
Dendritic epidermal T cells (DETCs) found in mouse skin are NKG2D-positive γδ T cells involved in immune surveillance and wound repair. It is assumed that the interaction of an NKG2D receptor on DETCs and an MHC class I-like NKG2D ligand on keratinocytes activates DETCs, which then secrete cytokines promoting wound repair. However, direct evidence that DETC activation through NKG2D signaling promotes wound repair is not available. In the present study, we generated mAbs for an NKG2D ligand H60c previously suggested to be expressed specifically on skin keratinocytes. Local administration of H60c-specific mAb inhibited activation of DETCs and significantly delayed wound repair. Likewise, administration of NKG2D-specific mAb impaired wound repair to a similar extent. The delay in wound closure resulting from the blockade of the NKG2D pathway was comparable to that observed in γδ T cell-deficient mice. These results indicate that H60c/NKG2D interactions play a critical role in wound repair. Reassessment of binding affinities showed that H60c monomers bind to NKG2D with affinity (K(d) = 26 ± 3.2 nM) comparable to those of other high-affinity NKG2D ligands. H60c is transcribed not only in skin but also in tissues such as tongue and female reproductive tract known to contain epithelium-resident γδ T cells expressing invariant TCRs, suggesting a more general role for H60c in the maintenance of epithelial integrity.
Assuntos
Queratinócitos/imunologia , Células de Langerhans/imunologia , Antígenos de Histocompatibilidade Menor/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Linfócitos T/imunologia , Cicatrização/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Comunicação Celular , Citocinas/biossíntese , Citocinas/imunologia , Epiderme , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Queratinócitos/metabolismo , Células de Langerhans/metabolismo , Camundongos , Camundongos Knockout , Antígenos de Histocompatibilidade Menor/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/antagonistas & inibidores , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Ligação Proteica , Transdução de Sinais , Linfócitos T/metabolismoRESUMO
Jawless vertebrates such as lamprey and hagfish lack T-cell and B-cell receptors; instead, they have unique antigen receptors known as variable lymphocyte receptors (VLRs). VLRs generate diversity by recombining highly diverse leucine-rich repeat modules and are expressed clonally on lymphocyte-like cells (LLCs). Thus far, two types of receptors, VLRA and VLRB, have been identified in lampreys and hagfish. Recent evidence indicates that VLRA and VLRB are expressed on distinct populations of LLCs that resemble T cells and B cells of jawed vertebrates, respectively. Here we identified a third VLR, designated VLRC, in the lamprey. None of the approximately 100 VLRC cDNA clones subjected to sequencing had an identical sequence, indicating that VLRC can generate sufficient diversity to function as antigen receptors. Notably, the C-terminal cap of VLRC exhibits only limited diversity and has important structural differences relative to VLRA and VLRB. Single-cell PCR analysis identified LLCs that rearranged VLRC but not VLRA or VLRB, suggesting the presence of a unique population of LLCs that express only VLRC.
Assuntos
Petromyzon/imunologia , Receptores de Antígenos/genética , Animais , DNA Complementar , Rearranjo Gênico , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
BACKGROUND/AIMS: To clarify the usefulness of screening ultrasonography (US) to diagnose gastric and colorectal cancer, patient records were analyzed retrospectively. METHODOLOGY: Ultrasonography was performed for patients with abdominal symptoms. They were then subjected to computed tomography (CT) when diagnosed with gastric cancer, colorectal cancer, or bowel obstruction. Patient records were analyzed retrospectively after final diagnosis of gastric cancer or colorectal cancer by endoscopy, surgery or necropsy. RESULTS: Twelve patients were diagnosed with colorectal cancer and six with gastric cancer. The detailed structure of colorectal cancer was visible as wall thickening with US, while cancer was often illustrated as a mass by CT. Loss of stratification was clear with US in 11 patients. US demonstrated wall thickening in 10 patients and a mass in 1 patient, while CT demonstrated wall thickening in 3 patients and a mass in 8 patients. The structure of colorectal cancer was more obvious when using US than when using CT. One patient demonstrated focal wall thickening with US, but this was not detected by CT. CONCLUSIONS: US is useful for diagnosis of gastric cancer and colorectal cancer. US produces more detailed findings in colorectal cancer than CT.
Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Programas de Rastreamento/métodos , Neoplasias Gástricas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias Colorretais/patologia , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
It has been established that nuclear pseudostratification of the neural epithelium in vertebral embryos is caused by interkinetic nuclear migration, a cell cycle-dependent regulation of nuclear movement, during which the G2/M-phase nuclei move apically before returning basally in the G1/S phase. Here we demonstrate the cell cycle-related nuclear location characteristic of interkinetic nuclear migration in human neoplastic and non-neoplastic pseudostratified glands. Immunohistochemical analysis with phosphohistone H3 (a G2/M-phase marker) and Ki67 was performed on fetal tissues, proliferative-phase endometrium (5 cases), and colonic adenomas (12 cases). In all cases, G2/M nuclei were significantly located apically, whereas Ki67-positive nuclei were widely distributed along the basal-apical axis. In the proliferating zone of the normal colon mucosa, elongated nuclei in the G2/M phase were occasionally found on the apical side of the cells. These results suggest that the interkinetic nuclear migration occurs in association with cell proliferation in both neoplastic and non-neoplastic glands.
Assuntos
Adenocarcinoma/patologia , Adenoma/patologia , Núcleo Celular/fisiologia , Neoplasias do Colo/patologia , Proliferação de Células , Colo/patologia , Endométrio/citologia , Epitélio/patologia , Feminino , Feto/citologia , Pontos de Checagem da Fase G2 do Ciclo Celular , Histonas/metabolismo , Humanos , Fosforilação , Processamento de Proteína Pós-TraducionalRESUMO
As coronavirus disease 2019 (COVID-19) vaccine booster campaigns progress worldwide, new reports of complications following COVID-19 vaccination have emerged. We herein report a case of new-onset anti-glomerular basement membrane (GBM) disease concomitant with myeloperoxidase-antineutrophil cytoplasmic antibody positivity concurrent with high levels of interleukin (IL)-26 following the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal association with vaccination in this case suggests that an enhanced neutrophilic immune response through IL-26 may have triggered necrotizing glomerulonephritis and a T-cell-mediated immune response to GBMs, leading to the development of anti-GBM antibodies, with an enhanced B-cell response after the vaccination triggering anti-GBM IgG and the onset of anti-GBM disease.
Assuntos
Doença Antimembrana Basal Glomerular , COVID-19 , Glomerulonefrite , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Peroxidase , Vacinas contra COVID-19/efeitos adversos , Vacina BNT162 , COVID-19/complicações , Autoanticorpos , InterleucinasRESUMO
The ubiquitin-proteasome pathway, which degrades intracellular proteins, is involved in numerous cellular processes, including the supply of immunocompetent peptides to the antigen presenting machinery. Proteolysis by proteasomes is conducted by three beta subunits, beta1, beta2, and beta5, of the 20S proteasome. Recently, a novel beta subunit expressed exclusively in cortical thymic epithelial cells was discovered in mice. This subunit, designated beta5t, is a component of the thymoproteasome, a specialized type of proteasomes implicated in thymic positive selection. In this study, we show that, like its mouse counterpart, human beta5t is expressed exclusively in the thymic cortex. Human beta5t was expressed in approximately 80% of cortical thymic epithelial cells and some cortical dendritic cells. Human beta5t was incorporated into proteasomes with two other catalytically active beta subunits beta1i and beta2i, forming 20S proteasomes with subunit compositions characteristic of thymoproteasomes. The present study demonstrates, for the first time, the existence of thymoproteasomes in the human thymic cortex, indicating that thymoproteasome function is likely conserved between humans and mice.
Assuntos
Complexo de Endopeptidases do Proteassoma/análise , Timo/enzimologia , Células Dendríticas/enzimologia , Células Epiteliais/enzimologia , Humanos , Especificidade de Órgãos , Distribuição TecidualRESUMO
We report on the onset of minimal change disease (MCD) presenting with anasarca after a second dose of the messenger RNA (mRNA)-based Pfizer-BioNTech vaccine against coronavirus disease 2019 (COVID-19). A 75-year-old previously healthy male was admitted with rapidly progressive anasarca and proteinuria of 7.7 g/day following the second dose. A kidney biopsy revealed MCD with nephrotic syndrome. He was treated with intravenous methylprednisolone followed by prednisolone, leading to complete remission after 35 days in the hospital. Since definite causality between the vaccine and MCD remains unclear, awareness of this potential adverse effect of mRNA vaccines is important to determine its true incidence and frequency.
RESUMO
NKG2D is a major activating receptor of natural killer cells. Its ligands are major histocompatibility complex (MHC) class I-like molecules whose expression is induced by cellular stresses such as infections and tumorigenesis. Humans have two families of NKG2D ligands (NKG2DL): MHC class I-related chains (MIC) encoded in the MHC and UL16-binding proteins (ULBP) encoded outside the MHC. By contrast, mice have only the latter family of ligands; instead, they have non-MHC-encoded MILL molecules that are closely related to MIC, but do not function as NKG2DL. To gain insights into the origin and evolution of MIC, ULBP, and MILL gene families, we conducted comparative genomic analysis of NKG2DL family genes in five mammalian species. In the opossum MHC, we identified a ULBP-like gene adjacent to a previously described MIC-like gene, suggesting that ULBP genes were originally encoded in the MHC. The opossum genome also contained a transcribed MILL-like gene in a region syntenic to the rodent regions encoding MILL molecules. These observations indicate that MIC-, ULBP-, and MILL-like genes emerged before the divergence of placental and marsupial mammals. Comparison of the human, cattle, rat, mouse, and opossum genomes indicates that after emigration from the MHC, ULBP genes underwent extensive duplications in each species. In mice, some of the ULBP genes appear to have been translocated telomerically on the same chromosome, forming a major cluster of existent NKG2DL genes.
Assuntos
Evolução Molecular , Genoma , Mamíferos/genética , Subfamília D de Receptores Semelhantes a Lectina de Células NK/genética , Sequência de Aminoácidos , Animais , Bovinos , Biologia Computacional , Proteínas Ligadas por GPI , Fator 15 de Diferenciação de Crescimento/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Ligantes , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Gambás/genética , Filogenia , RatosRESUMO
Undifferentiated thymic carcinoma is a rare tumor of the thymus. Due to the extreme rarity of undifferentiated thymic carcinoma, very limited information about its characteristics is available. We encountered an autopsy case of a 33-year-old woman diagnosed as having an undifferentiated thymic carcinoma with a high inflammatory response. The patient's serum interleukin-6 (IL-6) was elevated to 1930 pg/ml, and immunohistochemical staining of the carcinoma cells was positive for neuroendocrine markers and IL-6. To the best of our knowledge, this is the first report of an IL-6-producing undifferentiated thymic carcinoma with neuroendocrine features that shows a novel potential to produce IL-6.
Assuntos
Proteína C-Reativa/metabolismo , Carcinoma/metabolismo , Interleucina-6/biossíntese , Fragmentos de Peptídeos/metabolismo , Neoplasias do Timo/metabolismo , Adulto , Biomarcadores Tumorais , Biópsia , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Interleucina-6/sangue , Estadiamento de Neoplasias , Proteínas Recombinantes/metabolismo , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Tomografia Computadorizada por Raios XRESUMO
Forkhead box (Fox)/winged-helix transcription factors regulate multiple aspects of immune responsiveness and Foxp3 is recognized as an essential functional marker of regulatory T cells. Herein we describe downstream signaling pathways targeted by Foxp3 that may negatively impact retroviral pathogenesis. Overexpression of Foxp3 in HEK 293T and purified CD4+ T cells resulted in a dose-dependent and time-dependent decrease in basal levels of nuclear factor-kappaB (NF-kappaB) activation. Deletion of the carboxyl-terminal forkhead (FKH) domain, critical for nuclear localization and DNA-binding activity, abrogated the ability of Foxp3 to suppress NF-kappaB activity in HEK 293T cells, but not in Jurkat or primary human CD4+ T cells. We further demonstrate that Foxp3 suppressed the transcription of two human retroviral promoters (HIV-1 and human T cell lymphotropic virus type I [HTLV-I]) utilizing NF-kappaB-dependent and NF-kappaB-independent mechanisms. Examination of the latter identified the cAMP-responsive element binding protein (CREB) pathway as a target of Foxp3. Finally, comparison of the percent Foxp3+CD4+CD25+ T cells to the HTLV-I proviral load in HTLV-I-infected asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis suggested that high Foxp3 expression is associated with low proviral load and absence of disease. These results suggest an expanded role for Foxp3 in regulating NF-kappaB- and CREB-dependent cellular and viral gene expression.
Assuntos
Proteína de Ligação a CREB/genética , Fatores de Transcrição Forkhead/genética , NF-kappa B/genética , Retroviridae/genética , Transcrição Gênica , Linfócitos T CD4-Positivos/metabolismo , Proteína de Ligação a CREB/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação Viral da Expressão Gênica , Marcação de Genes , Humanos , Células Jurkat/citologia , Células Jurkat/metabolismo , Rim/citologia , Rim/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/análise , Retroviridae/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: To show our unique strategy of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma larger than the subcircumference. METHODS: From April 2011, we used a mucosal preservation method called the log bridge (LB) method for the lesion larger than the subcircumference. The patients in whom the circumference of the mucosal defect was 5/6 to <1 were classified into the LB group; those who underwent whole circumferential ESD were classified into the non-LB group. The data were collected retrospectively and were compared between the two groups. RESULTS: Eighteen patients into the LB group and 7 into the non-LB group were classified. The median number of endoscopic balloon dilation sessions after ESD in the LB group tended to be lower than that in the non-LB group. The mean period until complete epithelialization after ESD was significantly shorter in the LB group. The rates of curative resection were 100% (7/7) in the non-LB group and 61.1% (11/18) in the LB group. However, there was no local recurrence in either group for approximately two years. CONCLUSION: In cases involving subcircumferential esophageal lesions, the LB method is useful for achieving rapid healing and might be related to a reduced degree of esophageal stricture.
RESUMO
Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1ß were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas.
Assuntos
Adenocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Fator 3-beta Nuclear de Hepatócito/metabolismo , alfa-Fetoproteínas/biossíntese , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/metabolismo , Fenótipo , Neoplasias Gástricas/metabolismoRESUMO
Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary gland. Albeit common, histologic variants have rarely been noted in MEC. Here, we report a 49-year-old man with a sublingual gland tumor. Histologically, the tumor was composed of spindle cells arranged in interlacing fascicules or globular nests. A few bland small glands containing mucous cells were also scattered. The spindle tumor cells completely lacked immunoreactivity for cytokeratin, and exhibited immunoreactivity for vimentin, S-100, HMB-45, Melan A, and SOX10. The tumor was initially suspected to be clear cell sarcoma, malignant melanoma, or perivascular epithelioid cell tumor with a few entrapped nonneoplastic duct epitheliums. However, reverse-transcription polymerase chain reaction revealed the CRTC3-MAML2 fusion gene product diagnostic of MEC. In fact, a very minor component of the epithelial cells was reminiscent of conventional MEC, whereas major spindled tumor cells possessed markedly altered differentiation. This is the first case report of MEC with extensive spindled morphology and melanocytic marker expression.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Mucoepidermoide/química , Melaninas/análise , Melanócitos/química , Neoplasias das Glândulas Salivares/química , Biomarcadores Tumorais/genética , Biópsia , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgia , Proteínas de Ligação a DNA/genética , Fusão Gênica , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Melanócitos/patologia , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Transativadores , Fatores de Transcrição/genética , Resultado do TratamentoRESUMO
Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.
RESUMO
Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) is useful for the diagnosis of cancer as it presents a clear contrast between cancerous and non-cancerous tissue. The present study investigated the limitations and advantages of DWIBS/T2 with regards to the diagnosis of colorectal polyp (CP) or cancer (CRC). The current study included patients diagnosed with CP or CRC following colonoscopy, who were subjected to DWIBS/T2 between July 2012 and March 2015. Patient records were analyzed retrospectively. Patients were subjected to DWIBS/T2 when they presented with abdominal cancers or inflammation. Colonoscopy was performed as part of screening, or if patients had suspected colon cancer or inflammatory bowel disease. A total of 8 male and 7 female patients were enrolled in the present study. All patients, with the exception of one who had been diagnosed with CRC following colonoscopy, had positive results and all patients diagnosed with CP following a colonoscopy, with the exception of one, had negative results on DWIBS/T2. Thus, CRC was detected by DWIBS/T2, while CP was not (P=0.0028). The diameter of CRC lesions was significantly larger than that of CP (P<0.0001) and that of lesions positive on DWIBS/T2 was significantly larger than that of negative lesions (P=0.0004). The depth of invasion tended to be greater for lesions positive on DWIBS/T2 compared with that of negative ones. This indicated that DWIBS/T2 may be suitable for the detection of CRC but not for detection of CP. The results of DWIBS/T2 may also be affected by lesion diameter and depth of invasion.