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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 725-730, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105464

RESUMO

OBJECTIVE: To investigate the predictive value of methyltransferase EZH2 expression level on the clinical efficacy and long-term prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). METHODS: 161 patients with newly treated PGI-DLBCL in our hospital from August 2013 to July 2019 were selected. The expression level of EZH2 protein was detected by immunohistochemistry, and the short-term efficacy and long-term survival differences of patients with different levels of EZH2 were compared. The predictive values of EZH2 expression level on the short-term efficacy and long-term prognosis of PGI-DLBCL patients were analyzed by Log-rank test and COX risk proportional regression model. Chi-square test and Logistic regression analysis were used to analyze the influencing factors of EZH2 expression level. RESULTS: The complete response (CR) and overal response(OR) rates of those with high EZH2 expression were significantly lower than those with low EZH2 expression (P<0.001). The median OS and PFS of EZH2 high-level and low-level expression group was 37, 31 months and 49, 42 months, respectively. The cumulative OS and PFS rates of the high-level expression group were significantly lower than those of the low-level expression group, and the differences were statistically significant (P<0.05). The high expression levels of H3K27me3, EZH2, BCL-2, BCL-6, c-MYC were closely related to the shortening of OS and PFS, while the high expression level of Ki-67 was closely related to the shortening of OS (P<0.05), of which the high expression levels of H3K27me3, EZH2, BCL-2, and BCL-6 were independent risk factors for shortening of OS and PFS. The expression level of EZH2 was positively correlated with the expression level of H3K27me3, BCL-6, c-MYC and Ki-67 (r=0.741, r=0.837, r=0.809, r=0.772), and the high expression levels of H3K27me3, BCL-6 and Ki-67 were independent factors influencing the high expression of EZH2. CONCLUSION: In patients with PGI-DLBCL, the high expression of EZH2 significantly reduces the short-term CR and OR rates, which is an independent risk factor for the shortening of long-term OS and PFS rates, and it is independently related to the high expression of H3K27me3 and BCL6.


Assuntos
Linfoma Difuso de Grandes Células B , Proteína Potenciadora do Homólogo 2 de Zeste , Humanos , Imuno-Histoquímica , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
2.
Invest Ophthalmol Vis Sci ; 62(7): 6, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34086044

RESUMO

Purpose: To investigate the expression of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 in human retina. Methods: Human post-mortem eyes from 13 non-diabetic control cases and 11 diabetic retinopathy cases were analyzed for the expression of ACE2. To compare the vascular ACE2 expression between different organs that involve in diabetes, the expression of ACE2 was investigated in renal specimens from nondiabetic and diabetic nephropathy patients. Expression of TMPRSS2, a cell-surface protease that facilitates SARS-CoV-2 entry, was also investigated in human nondiabetic retinas. Primary human retinal endothelial cells (HRECs) and primary human retinal pericytes (HRPCs) were further used to confirm the vascular ACE2 expression in human retina. Results: We found that ACE2 was expressed in multiple nonvascular neuroretinal cells, including the retinal ganglion cell layer, inner plexiform layer, inner nuclear layer, and photoreceptor outer segments in both nondiabetic and diabetic retinopathy specimens. Strikingly, we observed significantly more ACE2 positive vessels in the diabetic retinopathy specimens. By contrast, in another end-stage organ affected by diabetes, the kidney, ACE2 in nondiabetic and diabetic nephropathy showed apical expression of ACE2 tubular epithelial cells, but no endothelial expression in glomerular or peritubular capillaries. Western blot analysis of protein lysates from HRECs and HRPCs confirmed expression of ACE2. TMPRSS2 expression was present in multiple retinal neuronal cells, vascular and perivascular cells, and Müller glia. Conclusions: Together, these results indicate that retina expresses ACE2 and TMPRSS2. Moreover, there are increased vascular ACE2 expression in diabetic retinopathy retinas.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Retinopatia Diabética/enzimologia , Receptores Virais/metabolismo , Retina/enzimologia , SARS-CoV-2/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Sítios de Ligação , Western Blotting , Células Cultivadas , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/virologia , Retinopatia Diabética/patologia , Retinopatia Diabética/virologia , Endotélio Vascular/enzimologia , Endotélio Vascular/virologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pericitos/enzimologia , Pericitos/virologia , Vasos Retinianos/enzimologia , Vasos Retinianos/patologia , Vasos Retinianos/virologia , Serina Endopeptidases/metabolismo
3.
BMC Infect Dis ; 21(1): 521, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078297

RESUMO

BACKGROUND: The clinical manifestations of recent syphilis can be variable, with typical and atypical patterns. Several conditions may cause atypical clinical aspects, including human immunodeficiency virus (HIV) co-infection. Besides the clinical features, co-infections may completely alter syphilis serological tests, causing interpretative difficulties and diagnostic delays. Aim of the work is to describe the difficulties encountered during the diagnostic evaluation of atypical skin manifestations and of the serology for syphilis of an HIV-infected patient who had contracted it several times. CASE PRESENTATION: In 2020, a 52-year old HIV-positive bisexual male patient was admitted to our department with a 4-month history of moderately itchy cutaneous lesions localized at his neck, trunk and arms. In 2013, the patient presented with a classic syphilitic roseola of the trunk and a secondary syphilis was diagnosed, with increased levels of rapid plasma reagin (RPR), Treponema pallidum hemagglutination assay (TPHA), anti-Treponema pallidum IgM and IgG Index. A second episode occurred in 2018, as a primary syphilis with multiple ulcerative lesions of the penis, and increased levels of RPR, IgG and IgM. In 2019, a further episode of secondary syphilis was treated with Doxycycline. In 2020, erythematous and papular lesions with vesicular components and urticarial erythema multiforme (EM)-like lesions were present at the neck, trunk and arms. Serological tests and Nucleic Acid Amplification Test (NAAT) for Treponema Pallidum were performed, as well as a cutaneous biopsy with histological and immunohistochemical evaluation of one lesion. NAAT was negative for T. pallidum. Serological test results were discordant with a new syphilis infection, showing only increased levels of RPR and anti-Treponema IgG. The cutaneous biopsy revealed a non specific histological pattern, while the immunohistochemical evaluation with anti-spirochetal antibodies was mandatory for the diagnosis of recent syphilis, showing clusters of rod-shaped elements, some of which with spiral form, focally present at the epidermis and adnexal structures. CONCLUSIONS: Nowadays, syphilis may present with atypical clinical and serological features. Physicians should be aware of these possible alterations and consider syphilis even in case of uncommon clinical aspect and unclear serological tests. Cutaneous biopsy and immunohistochemical exam may be mandatory for the diagnosis.


Assuntos
Sífilis/diagnóstico , Treponema pallidum/isolamento & purificação , Anticorpos Antibacterianos/sangue , Biópsia , Infecções por HIV/complicações , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva , Minorias Sexuais e de Gênero , Sífilis/patologia , Sorodiagnóstico da Sífilis , Treponema pallidum/imunologia
4.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072419

RESUMO

Although endometriosis is a benign disease characterized by the presence of endometrial tissues outside the uterus, ectopic endometrial cells can exhibit malignant biological behaviors. Retinol-binding protein4 (RBP4) is a novel adipocyte-derived cytokine, which has important roles in regulating insulin sensitivity and energy metabolism. RBP4 is a potent modulator of gene transcription, and acts by directly controlling cell growth, invasiveness, proliferation and differentiation. Here, we evaluated the possible role of RBP4 in the pathogenesis of endometriosis. We compared the levels of RBP4 in the tissues and peritoneal fluid (PF) of women with and without endometriosis and evaluated the in vitro effects of RBP4 on the viability, invasiveness, and proliferation of endometrial stromal cells (ESCs). RBP4 levels were significantly higher in the PF of the women in the endometriosis group than in the controls. RBP4 immunoreactivity was significantly higher in the ovarian endometriomas of women with advanced stage endometriosis than those of controls. In vitro treatment with human recombinant-RBP4 significantly increased the viability, bromodeoxyuridine expression, and invasiveness of ESCs. Transfection with RBP4 siRNA significantly reduced ESC viability and invasiveness. These findings suggest that RBP4 partakes in the pathogenesis of endometriosis by increasing the viability, proliferation and invasion of endometrial cells.


Assuntos
Suscetibilidade a Doenças , Endometriose/etiologia , Endometriose/metabolismo , Ovário/patologia , Proteínas Plasmáticas de Ligação ao Retinol/genética , Biomarcadores , Sobrevivência Celular , Endometriose/patologia , Feminino , Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunofenotipagem , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Proteínas Recombinantes/farmacologia , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/farmacologia
5.
Pol J Pathol ; 72(1): 11-22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060284

RESUMO

Discriminating thyroid and parathyroid lesions may sometimes pose a diagnostic difficulty. Medullary thyroid carcinomas (MTCs) display various cytologic and architectural features that resemble other thyroid and even rarely some parathyroid neoplasms. Moreover, some MTCs may have negative serum calcitonin, rendering them difficult to diagnose. Hence, to reach an appropriate diagnosis in problematic cases of these three categories - thyroid lesions, MTC and parathyroid lesions - the use of several immunohistochemical panels has been suggested and applied. However, conventional markers are not always conclusive in problematic cases. Thus, in the current study we aim to evaluate the diagnostic utility of using GATA3 and INSM1 (insulinoma-associated protein 1) as novel nuclear markers to be applied as an adjunct in case of histopathologic suspicion. A retrospective study was carried out on samples of lesions from three groups: group 1: thyroid lesions (27), group 2: medullary thyroid carcinoma (25); 1/25 had negative serum levels of calcitonin, and group 3: parathyroid lesions (36). Biopsies were received at the Pathology Laboratory of Ain Shams University Hospitals. INSM1 showed 98% diagnostic accuracy in diagnosing MTC and differentiating it from other thyroid lesions. The case of MTC with negative serum calcitonin showed positive INSM1 staining. GATA3 showed 96.8% diagnostic accuracy in diagnosing parathyroid lesions and differentiating them from thyroid lesions. Using immunohistochemical staining by GATA3 and INSM1, in the appropriate histopathological setting, significantly aids in the differentiation between thyroid lesions, parathyroid lesions and MTCs. INSM1 could serve as a potential diagnostic marker in the rare cases of non-secretory MTC and in metastatic work up.


Assuntos
Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Carcinoma Neuroendócrino/diagnóstico , Fator de Transcrição GATA3 , Humanos , Imuno-Histoquímica , Proteínas Repressoras , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico
6.
Pol J Pathol ; 72(1): 39-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060286

RESUMO

Colorectal cancer (CRC) is the third most common cancer worldwide and is associated with a high level of mortality and morbidity. In this study we evaluate expression of p-p38 and p-MSK1 in CRC and determine whether there is an association between expression of these markers and any clinicopathologic parameters that could be of prognostic value. Expression of p-p38, p-MSK1 and ki-67 were examined by immunohistochemistry in 135 archival CRC cases and the findings were correlated with the patient clinicopathological data. P-p38 and p-MSK1 were expressed at high level in 58.5 % and 60.7% of CRC cases respectively. A statistically significant negative correlation was found between expression of p-p38 and Ki-67 (p < 0.001, r = -0.63) and between p-MSK1 and Ki-67 expression (p < 0.001, r = -0.61). The majority of CRC cases expressing high levels of p-p38 also expressed high levels of p-MSK1 and this correlation was highly significant (p < 0.001, r = 0.863). The high expression of p-p38 and p-MSK1 was also significantly associated with low Dukes and TNM stage. The elevated expression of p-38 and p-MSK1 in CRC was associated with a good prognosis and prolonged overall survival (p < 0.001, each). Our finding showed that activation of the p38-MSK1 axis determines a good outcome in CRC.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Humanos , Imuno-Histoquímica , Prognóstico , Proteínas Quinases S6 Ribossômicas 90-kDa
7.
Pol J Pathol ; 72(1): 84-86, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060291

RESUMO

Gastrointestinal type of endometrial carcinoma is a newly described entity for which clearly defined diagnostic criteria have only recently been published. Among morphologic criteria, gastrointestinal mucinous adenocarcinoma of endometrium must not show a typical endometrioid component. We present a case with morphologic diversity, with areas showing gastric and intestinal differentiation as well as an endometrioid-like component. However, the endometrioid-like component not only did not show classic squamous metaplasia, but was also MUC6-positive, while the positivity for ER/PR was only focal. The recognition of gastric/gastrointestinal differentiation in endometrial carcinomas is best accomplished using both morphology and immunohistochemistry rather than either alone.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Endométrio , Neoplasias Uterinas , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica
8.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063554

RESUMO

Acute lung injury (ALI) afflicts approximately 200,000 patients annually and has a 40% mortality rate. The COVID-19 pandemic has massively increased the rate of ALI incidence. The pathogenesis of ALI involves tissue damage from invading microbes and, in severe cases, the overexpression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). This study aimed to develop a therapy to normalize the excess production of inflammatory cytokines and promote tissue repair in the lipopolysaccharide (LPS)-induced ALI. Based on our previous studies, we tested the insulin-like growth factor I (IGF-I) and BTP-2 therapies. IGF-I was selected, because we and others have shown that elevated inflammatory cytokines suppress the expression of growth hormone receptors in the liver, leading to a decrease in the circulating IGF-I. IGF-I is a growth factor that increases vascular protection, enhances tissue repair, and decreases pro-inflammatory cytokines. It is also required to produce anti-inflammatory 1,25-dihydroxyvitamin D. BTP-2, an inhibitor of cytosolic calcium, was used to suppress the LPS-induced increase in cytosolic calcium, which otherwise leads to an increase in proinflammatory cytokines. We showed that LPS increased the expression of the primary inflammatory mediators such as toll like receptor-4 (TLR-4), IL-1ß, interleukin-17 (IL-17), TNF-α, and interferon-γ (IFN-γ), which were normalized by the IGF-I + BTP-2 dual therapy in the lungs, along with improved vascular gene expression markers. The histologic lung injury score was markedly elevated by LPS and reduced to normal by the combination therapy. In conclusion, the LPS-induced increases in inflammatory cytokines, vascular injuries, and lung injuries were all improved by IGF-I + BTP-2 combination therapy.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Anilidas/farmacologia , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Tiadiazóis/farmacologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/virologia , Anilidas/uso terapêutico , Animais , COVID-19/complicações , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/genética , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/uso terapêutico , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tiadiazóis/uso terapêutico , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
9.
Zhonghua Bing Li Xue Za Zhi ; 50(6): 615-619, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34078049

RESUMO

Objective: To study the application of cell transfer technology to solve the problem of the limited number of fine needle aspiration cytology (FNAC) smears for various immunocytochemistry (ICC) staining and other auxiliary tests, and to enhance accurate cytological diagnosis. Methods: Thirty-four cases of FNAC smears from January 2020 to April 2020 in the Department of Pathology of Beijing Hospital were collected for investigation of the cell transfer technique. The materials in the most cell smear were divided and transferred to several glass slides. After de-staining, the recipient slides were stained with EnVision ICC. The technique was validated by comparing the consistency of the ICC of transferred cell smears and the corresponding immunohistochemical (IHC) staining on biopsies. Results: There were a total of 180 cell transfer slides from 34 cases, of which 174 had the same cell morphology, size and structure as the original smears, with the success rate of cell transfer of 96.7% (174/180). Totally 174 ICC stains were performed on the successfully transferred cell smears, of which 153 smears had available corresponding IHC staining of histologic specimens. Of these, 148 showed concordance between ICC staining and the IHC staining. Cells were successfully transferred in 96.7 % (148/153) of the cell sheets, keeping the same morphology and structure as compared to their original smears. The diagnosis of all 34 FNAC cases was the same to that of their corresponding pathology on biopsies with 100 % concordance. Conclusions: The cell transfer technique is a simple and effective way to make full use of diagnostic cells on a cell smear, and is valuable for accurate cytological diagnosis.


Assuntos
Citodiagnóstico , Biópsia por Agulha Fina , Imuno-Histoquímica , Coloração e Rotulagem
10.
Zhonghua Bing Li Xue Za Zhi ; 50(6): 626-631, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34078051

RESUMO

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED). Methods: Twelve cases of GAED diagnosed in Fujian Provincial Hospital from August 2019 to August 2020 were collected. HE staining, immunohistochemistry and HER2 gene amplification were evaluated. In addition, 343 cases of gastric adenocarcinoma diagnosed in the same period were used as the control group to compare the clinicopathological differences between them. Results: The 12 cases of GAED included 10 males and 2 females, aged 59-75 years (median 66.5 years). The main clinical manifestations were abdominal pain, melena with hematemesis; nine tumors were ulcerative and three were protuberant. The tumor diameter ranged from 1.5 to 9.5 cm (median 6.0 cm). Histologically, the tumor cells were arranged in tubular, papillary, cribriform, or adenoid structures. The cells were cuboidal to columnar, with relatively distinct cell boundaries and abundant clear or slightly eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for SALL4 (12/12), glypican-3 (9/12), AFP (5/12), CDX2 (8/12), CD10 (3/12), p53 mutated (10/12), HER2 (2/12, 3+), and both cases showed HER2 gene amplification by fluorescence in situ hybridization. Compared with common gastric adenocarcinoma, GAED showed higher rate of vascular invasion and tumor progression (P<0.05), but there were no significant differences in age, sex, degree of differentiation, nerve invasion, lymph node metastasis, pT stage, pN stage and pM stage (P>0.05). Conclusions: GAED is a rare type of gastric adenocarcinoma. Pathologically, GAED has both embryonal and intestinal phenotypes. In terms of biological behavior, it is more invasive. GAED needs to be distinguished from common gastric adenocarcinoma in clinical diagnosis.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Biomarcadores Tumorais/genética , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino
11.
Zhonghua Bing Li Xue Za Zhi ; 50(6): 632-637, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34078052

RESUMO

Objective: To investigate the clinicopathological features, immunohistochemical characteristics, differential diagnosis and prognosis of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinomas. Methods: Two cases of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma were collected at Fudan University Shanghai Cancer Center, Shanghai, China from 2017 to 2018. The clinicopathological characteristics were analyzed. Hematoxylin and eosin, and immunohistochemical stains were performed, and the relevant literatures were reviewed. Results: The two patients were both male, aged 60 and 74 years, respectively. Their symptoms were both abdominal pain. The tumor arose in the esophagogastric junction in case 1, and the cardia to the fundus and the posterior wall of the upper part of gastric body in case 2. Both tumors were present as an ulcerative mass. The patients died of tumor 11 months and 8 months after surgery, respectively. Histologically, the tumor cells arranged in sheets, nests, cords or trabecular patterns, and pseudoavleolar structure. The tumor cells were epithelioid with uniform morphology, while the tumors showed scant stroma and massive necrosis. Variable rhabdoid cells and multinucleated giant cells were seen in both cases. SMARCA4 encoding protein BRG1 was undetectable in both tumors, while SMARCB1 encoding protein INI1 was detected. The tumor cells were diffusely positive for vimentin and negative for epithelial marker (CKpan), gastrointestinal stromal tumor markers (CD117 and DOG1), myogenic markers (desmin and myogenin), melanoma markers (S-100 protein, SOX10 and HMB45), and lymphohematopoietic markers (LCA and CD20). Conclusions: Gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma is a rare and highly aggressive tumor with poor prognosis. The detection of subunits protein expression of SWI/SNF complex is important for diagnosis of the tumor.


Assuntos
Carcinoma , Neoplasias Gástricas , Biomarcadores Tumorais/genética , China , DNA Helicases , Humanos , Imuno-Histoquímica , Masculino , Proteínas Nucleares/genética , Prognóstico , Proteína SMARCB1/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Fatores de Transcrição/genética
12.
Rev Med Liege ; 76(5-6): 489-495, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-34080385

RESUMO

The management of melanoma is a typical example of a pluridisciplinary approach, in order to provide the patient with a rapid and adequate treatment plan after the initial diagnosis. Both in the domains of dermatology, pathology and oncology, enormous progress has been made. Recent advances permit a rapid access to diagnostic techniques using teledermoscopy, an improved diagnostic accuracy using dermoscopy, pre-interventional high-frequency ultrasound and optical coherence tomography, a determination of risk factors using immunohistochemistry and genetic analyses on the pathology samples. Furthermore, the development of immunotherapies, in particular the anti-PD1 antibodies, and the directed therapies, therapies permitting an increased number of patients to experience an increased survival with an acceptable tolerance profile in the event of metastatic lesions. This article describes the patient's care pathway, from the initial diagnosis, staging, to an eventual treatment and follow-up.


Assuntos
Melanoma , Neoplasias Cutâneas , Dermoscopia , Humanos , Imuno-Histoquímica , Imunoterapia , Melanoma/diagnóstico , Melanoma/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia
13.
Nat Commun ; 12(1): 2577, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972551

RESUMO

Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial-fibroblast, epithelial-muscle and epithelial-nerve interactions. The epithelial-fibroblast interface, namely, hair germ-dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for hair cycle regulation and hair germ-dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.


Assuntos
Membrana Basal/citologia , Matriz Extracelular/metabolismo , Folículo Piloso/metabolismo , Laminina/metabolismo , Transcriptoma/genética , Animais , Membrana Basal/metabolismo , Membrana Basal/ultraestrutura , Células Epiteliais/metabolismo , Matriz Extracelular/genética , Feminino , Fibroblastos/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Família Multigênica , Células Musculares/metabolismo , Neurônios/metabolismo , Análise de Célula Única
14.
J Int Med Res ; 49(5): 3000605211016138, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34038217

RESUMO

Acute myeloid leukemia (AML) with T lymphoblastic lymphoma (T-LBL) is a hematologic tumor of two origins, myeloid and lymphoblastic, and is relatively rare in the same patient. We report a rare case of AML with T-LBL. After the patient was diagnosed, he received standard chemotherapy, which decreased the primitive bone marrow cell percentage from 84% to 5%; however, the enlarged superficial lymph nodes showed no obvious change in size. Immunohistochemistry revealed the following: cluster of differentiation (CD)3 (+), CD5 (+), CD7 (+), transmission disequilibrium test (TDT) (+), myeloperoxidase (MPO) (-), and lysozyme (Lys) (-). The lymph node morphology and immunohistochemical results indicated T-LBL. Therefore, the final diagnosis was AML with T-LBL, with both diseases occurring independently and concurrently.


Assuntos
Leucemia Mieloide Aguda , Linfoma não Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Imuno-Histoquímica , Leucemia Mieloide Aguda/tratamento farmacológico , Linfonodos/diagnóstico por imagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
15.
Medicine (Baltimore) ; 100(21): e25993, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032716

RESUMO

ABSTRACT: Guanine nucleotide-binding protein-like-3-like (GNL3L) is required for processing ribosomal pre-rRNA and cell proliferation and is upregulated in many types of cancer. This study is aimed to investigate the clinical significance of GNL3L in esophageal cancer. The mRNA and protein expression levels of GNL3L were determined by using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. GNL3L was localized in both cytoplasm and nucleus. The expression levels of GNL3L in esophageal cancer tissues were significantly higher than those in adjacent nonmalignant tissues. High GNL3L expression was associated with pathologic type and poor differentiation. Patients with high GNL3L expression had shorter overall survival (OS) than those with low GNL3L expression. Multivariate Cox regression analysis revealed that GNL3L expression was an independently predictive factor for the OS of patient with esophageal cancer. The Gene Expression Profiling Interactive Analysis (GEPIA) databases also showed that GNL3L was upregulated in esophageal cancer, which was closely associated with an unfavorable prognosis of patients with esophageal cancer. Taken together, our findings suggest that GNL3L is upregulated in esophageal cancer, which is linked to the progression of the disease. As a result, GNL3L could be used as a biomarker for esophageal cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Proteínas de Ligação ao GTP/metabolismo , Proteínas Nucleares/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Núcleo Celular/patologia , Proliferação de Células , Quimioterapia Adjuvante/métodos , Citoplasma/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia , Esôfago/citologia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Proteínas de Ligação ao GTP/análise , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Prognóstico , Regulação para Cima
16.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946490

RESUMO

The cystic fibrosis transmembrane conductance regulator (CFTR) gene is influenced by the fundamental cellular processes like epithelial differentiation/polarization, regeneration and epithelial-mesenchymal transition. Defects in CFTR protein levels and/or function lead to decreased airway surface liquid layer facilitating microbial colonization and inflammation. The SERPINA1 gene, encoding alpha1-antitrypsin (AAT) protein, is one of the genes implicated in CF, however it remains unknown whether AAT has any influence on CFTR levels. In this study we assessed CFTR protein levels in primary human lung epithelial cells grown at the air-liquid-interface (ALI) alone or pre-incubated with AAT by Western blots and immunohistochemistry. Histological analysis of ALI inserts revealed CFTR- and AAT-positive cells but no AAT-CFTR co-localization. When 0.5 mg/mL of AAT was added to apical or basolateral compartments of pro-inflammatory activated ALI cultures, CFTR levels increased relative to activated ALIs. This finding suggests that AAT is CFTR-modulating protein, albeit its effects may depend on the concentration and the route of administration. Human lung epithelial ALI cultures provide a useful tool for studies in detail how AAT or other pharmaceuticals affect the levels and activity of CFTR.


Assuntos
Barreira Alveolocapilar/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Mucosa Respiratória/metabolismo , alfa 1-Antitripsina/metabolismo , Biomarcadores , Linhagem Celular , Células Cultivadas , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Células Epiteliais/metabolismo , Imunofluorescência , Humanos , Imuno-Histoquímica , alfa 1-Antitripsina/genética
17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 33(2): 148-153, 2021 Apr 16.
Artigo em Chinês | MEDLINE | ID: mdl-34008361

RESUMO

OBJECTIVE: To investigate the expression and clinicopathological significance of Bcl-2 and Bax genes in colorectal cancer (CRC) patients complicated with schistosomiasis. METHODS: The CRC patients receiving surgical treatment in the First Affiliated Hospital of Dali University from June 2016 to June 2020 were recruited as the study subjects, and 30 subjects were randomly sampled from the CRC patients complicated with schistosomiasis (CRC-S group) and 30 subjects were randomly sampled from the CRC patients without schistosomiasis (CRC group) using a random number table method. The cancer specimens were sampled from subjects in the CRC-S and CRC groups, and the peri-cancer specimens were sampled from subjects in the CRC group. The Bcl-2 and Bax expression was quantified in cancer and peri-cancer specimens using a real-time fluorescent quantitative PCR (qPCR) assay and immunohistochemistry at transcriptional and translational levels, and the cell apoptosis was detected in cancer specimens using HE staining. RESULTS: A total of 60 subjects were enrolled, including 30 cases in the CRC group and 30 cases in the CRC-S group. There were no significant differences between the two groups in terms of gender distribution (χ2 = 0.271, P > 0.05), mean age (t = -0.596, P > 0.05), tumor growth pattern (χ2 = 0.275, P > 0.05), tumor location (χ2 = 4.008, P > 0.05), tumor invasion depth (χ2 = 0.608, P > 0.05), degree of tumor differentiation (χ2 = 0.364, P > 0.05), or presence of vascular metastasis (χ2 = 1.111, P > 0.05), while significant differences were seen between the two groups in terms of histological type, presence of lymph node metastasis and TMN staging (χ2 = 5.963, 8.297 and 5.711, all P values < 0.05). qPCR assay and immunohistochemistry quantified significantly higher Bcl-2 and Bax expression in cancer specimens from the CRC and CRC-S groups than in the peri-cancer specimens from the CRC group at both translational and transcriptional levels (all P values < 0.05), and higher Bcl-2 and lower Bax expression were seen in the cancer specimens from the CSC-S group than that from the CRC group (all P values < 0.05). In addition, the cell apoptotic rate was significantly greater in the cancer specimens in the CRC group than in the CRC-S group (42.00% vs. 23.35%; χ2 = 41.500, P = 0.000). CONCLUSION: Schistosomiasis may be involved in the development and progression of CRC through affecting Bcl-2 and Bax gene expression in the apoptosis signaling pathway.


Assuntos
Neoplasias Colorretais , Esquistossomose , Apoptose , Neoplasias Colorretais/complicações , Neoplasias Colorretais/genética , Humanos , Imuno-Histoquímica , Esquistossomose/complicações , Proteína X Associada a bcl-2/genética
18.
BMJ Case Rep ; 14(5)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958358

RESUMO

Inflammatory myofibroblastic tumours (IMTs) are rare benign neoplasms of intermediate malignant potential that are found in the lungs and rarely at extrapulmonary sites common in children and young adults. IMTs tend to be locally invasive and have some amount of metastatic potential as well. We present two cases of IMTs involving the duodenum, pancreas and distal bile duct. The first case presented with extensive involvement of the first three parts of the duodenum and head of the pancreas, while the second presented with a pancreatic and biliary tree involvement. Upon examinations and investigations, these tumours mimicked malignant neoplasms. A Whipple procedure for surgical resection was undertaken in both cases. The histological findings showed fascicles of spindle cells with infiltration of lymphocytes and plasma cells. The inflammatory myofibroblastic tumour was diagnosed based on pathological grounds with immunohistochemistry. Preoperative diagnosis of IMTs is difficult and complete surgical resection is the primary treatment.


Assuntos
Granuloma de Células Plasmáticas , Criança , Duodeno , Granuloma de Células Plasmáticas/diagnóstico por imagem , Granuloma de Células Plasmáticas/cirurgia , Humanos , Imuno-Histoquímica , Pâncreas , Pancreaticoduodenectomia
19.
J Int Med Res ; 49(5): 3000605211013172, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33983064

RESUMO

The patient was a 62-year-old man diagnosed as having prostatic extra-gastrointestinal stromal tumor (EGIST) who was treated with imatinib. No recurrence or metastasis was found after a 6-month follow-up. We identified 14 cases of prostatic primary EGIST in PubMed and summarized these cases with our case. The patients' ages ranged from 31 to 78 years (average: 53.6 years), and most patients' prostate-specific antigen (PSA) concentrations were within normal limits (92.9%, 13/14). All patients underwent imaging examinations; prostatic masses measured 6 to 14.2 cm (mean: 9.43 cm), and imaging excluded secondary prostatic masses from the intestinal tract. By immunohistochemical staining, the tumors were positive for cluster of differentiation (CD)117 (71.4%, 10/14), DOG1 (100%, 7/7), and CD34 (100%, 14/14), and negative for smooth muscle actin (SMA) (71.4%, 10/14), desmin (100%, 11/11), and S100 (100%, 12/12). Treatment depended on the results of the gene mutation detection as well as the risk estimation according to tumor size and microscopic mitotic rates (>5 per 50 high-power fields: 60%, 6/10). Among the 12 patients with reported outcomes, nine achieved good results (no recurrence or metastasis), one achieved reduced mass volume, one experienced recurrence, and one died.


Assuntos
Tumores do Estroma Gastrointestinal , Adulto , Idoso , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Próstata/diagnóstico por imagem , Proteínas Proto-Oncogênicas c-kit/genética
20.
Nat Commun ; 12(1): 2594, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972529

RESUMO

Adult neural stem cells (NSCs) must tightly regulate quiescence and proliferation. Single-cell analysis has suggested a continuum of cell states as NSCs exit quiescence. Here we capture and characterize in vitro primed quiescent NSCs and identify LRIG1 as an important regulator. We show that BMP-4 signaling induces a dormant non-cycling quiescent state (d-qNSCs), whereas combined BMP-4/FGF-2 signaling induces a distinct primed quiescent state poised for cell cycle re-entry. Primed quiescent NSCs (p-qNSCs) are defined by high levels of LRIG1 and CD9, as well as an interferon response signature, and can efficiently engraft into the adult subventricular zone (SVZ) niche. Genetic disruption of Lrig1 in vivo within the SVZ NSCs leads an enhanced proliferation. Mechanistically, LRIG1 primes quiescent NSCs for cell cycle re-entry and EGFR responsiveness by enabling EGFR protein levels to increase but limiting signaling activation. LRIG1 is therefore an important functional regulator of NSC exit from quiescence.


Assuntos
Células-Tronco Adultas/metabolismo , Ventrículos Laterais/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Células-Tronco Adultas/citologia , Células-Tronco Adultas/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 4/farmacologia , Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/genética , Proteínas de Ligação a DNA/metabolismo , Receptores ErbB/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Ontologia Genética , Imuno-Histoquímica , Interferons/farmacologia , Ventrículos Laterais/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Glicoproteínas de Membrana/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Proteômica , RNA-Seq , Regeneração/efeitos dos fármacos , Tetraspanina 29/metabolismo , Regulação para Cima
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