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1.
J Am Chem Soc ; 146(15): 10857-10867, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38587540

RESUMO

The asymmetric cross-coupling of unsaturated bonds, hampered by their comparable polarity and reactivity, as well as the scarcity of efficient catalytic systems capable of diastereo- and enantiocontrol, presents a significant hurdle in organic synthesis. In this study, we introduce a highly adaptable photochemical cobalt catalysis framework that facilitates chemo- and stereoselective reductive cross-couplings between common aldehydes with a broad array of carbonyl and iminyl compounds, including N-acylhydrazones, aryl ketones, aldehydes, and α-keto esters. Our methodology hinges on a synergistic mechanism driven by photoredox-induced single-electron reduction and subsequent radical-radical coupling, all precisely guided by a chiral cobalt catalyst. Various optically enriched ß-amino alcohols and unsymmetrical 1,2-diol derivatives (80 examples) have been synthesized with good yields (up to 90% yield) and high stereoselectivities (up to >20:1 dr, 99% ee). Of particular note, this approach accomplishes unattainable photochemical asymmetric transformations of aldehydes with disparate carbonyl partners without reliance on any external photosensitizer, thereby further emphasizing its versatility and cost-efficiency.

2.
Cardiovasc Res ; 120(2): 203-214, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38252891

RESUMO

AIMS: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known. METHODS AND RESULTS: In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and P21-activated kinase 1/AKT/Runx2 pathways. CONCLUSION: IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.


Assuntos
Exossomos , Hipertensão Pulmonar , Células-Tronco Pluripotentes Induzidas , Hipertensão Arterial Pulmonar , Ratos , Animais , Camundongos , Hipertensão Arterial Pulmonar/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Remodelação Vascular , Exossomos/metabolismo , Fibroblastos/metabolismo , Hipertensão Pulmonar Primária Familiar/metabolismo , Artéria Pulmonar , Monocrotalina/efeitos adversos , Monocrotalina/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
3.
J Formos Med Assoc ; 123(2): 238-247, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37586970

RESUMO

BACKGROUND: The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. METHODS: Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. RESULTS: Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. CONCLUSION: In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.


Assuntos
Esôfago de Barrett , Gastroenteropatias , Humanos , Azul Alciano , Amarelo de Eosina-(YS) , Seguimentos , Hematoxilina , Estudos Retrospectivos , Viés de Seleção , Endoscopia , Inibidores da Bomba de Prótons/uso terapêutico , Metaplasia
4.
J Cancer ; 14(13): 2552-2561, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37670969

RESUMO

Genes of the homeobox (HOX) family encode transcription factors, which play a role in cancer progression. However, their role in gastric cancer has not been adequately evaluated. Herein, we evaluated the genetic changes and mRNA of target genes of the HOX family in gastric cancer patients using publicly available online datasets. We found that HOXC8 was amplified in gastric cancer tissues, and mRNA expression levels were significantly associated with tumor status (P=0.044) and poor overall survival (P<0.01). HOXC8 knockdown significantly reduced the viability of gastric cancer cell lines. HOXC8 modulated the expression of secreted phosphoprotein 1 (SPP1, osteopontin) and phosphorylation of AKT/ERK in gastric cancer cells. Survival analysis demonstrated a decrease in overall survival rates among the high HOXC8/high SPP1 expression group compared with the low HOXC8/low SPP1 expression group. In conclusion, HOXC8 may be an independent prognostic factor and serve as a useful predictive biomarker for gastric cancer.

5.
J Cell Physiol ; 238(10): 2316-2334, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37724600

RESUMO

Vibrio vulnificus, a gram-negative bacterium, causes serious wound infections and septicemia. Once it develops into early phase sepsis, hyperinflammatory immune responses result in poor prognosis in patients. The present study aimed to examine the possible underlying pathogenic mechanism and explore potential agents that could protect against V. vulnificus cytotoxicity. Here, we report that infection of mouse macrophages with V. vulnificus triggers antiphagocytic effects and pyroptotic inflammation via ATP-mediated purinergic P2X7 receptor (P2X7R) signaling. V. vulnificus promoted P2X7-dependent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 translocation, modulating the expression of the inflammasome sensor NLR family pyrin domain containing 3 (NLRP3), adaptor apoptosis-associated speck-like protein containing a card (ASC), and pyroptotic protein gasdermin D (GSDMD) in mouse macrophages. V. vulnificus induced the NLRP3/caspase-1 inflammasome signaling complex expression that drives GSDMD transmembrane pore formation and secretion of interleukin (IL)-1ß, IL-18, and macrophage inflammatory protein-2 (MIP-2). This effect was blocked by P2X7R antagonists, indicating that the P2X7R mediates GSDMD-related pyroptotic inflammation in macrophages through the NF-κB/NLRP3/caspase-1 signaling pathway. Furthermore, blockade of P2X7R reduced V. vulnificus-colony-forming units in the spleen, immune cell infiltration into the skin and lung tissues, and serum concentrations of IL-1ß, IL-18, and MIP-2 in mice. These results indicate that P2X7R plays a vital role in mediating phagocytosis by macrophages and pyroptotic inflammation during V. vulnificus infection and provides new opportunities for therapeutic intervention in bacterial infections.

6.
Org Lett ; 25(35): 6566-6570, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37646425

RESUMO

A highly effective approach based on an organophotocatalytic α-C(sp3)-H functionalization/radical cyclization cascade has been developed. This method enables the synthesis of various tricyclic heterocycles containing S, O, and N atoms with excellent site selectivity and diastereoselectivity. Mechanistic investigations have confirmed that the reaction involves photoredox-triggered C(sp3)-H cleavage followed by a radical cyclization and aromatization process. These findings are expected to pave the way for developing cost-effective tandem radical reactions and synthesizing heterocyclic drugs.

7.
J Cancer ; 14(10): 1689-1706, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476181

RESUMO

Background: Previous investigations have demonstrated the role of Aldehyde Dehydrogenase 2 (ALDH2) levels in the cancer initiation and progression, prognosis, and treatment response in kinds of malignancies. However, its significance in the head and neck squamous cell carcinoma (HNSC) by different human papillomavirus (HPV) statuses remains unclear. Methods: We conducted an in-depth analysis of ALDH2 in HNSC using various bioinformatics tools, investigating its expression, alteration, differential levels, prognostic significance, molecular interactions, immune characteristics, and conducting experimental validation through immunohistochemistry (IHC) arrays and Western blot to compare expression levels between tumor and normal tissues, analyze the associations with clinicopathological features, and investigate its responses to chemotherapies. Results: ALDH2 levels are downregulated in HNSC tissues and associated with higher American Joint Committee on Cancer (AJCC) T classification and worse overall survival in HPV-unrelated HNSC, yet not in HPV-related HNSC. ALDH2 is positively regulated by copy-number variation and negatively regulated by DNA methylation. The association of ALDH2 with prognosis may be due to its interaction with ALDH6A1, and its co-expressed genes are predictive biomarkers of HNSC. We also found high ALDH2 levels in bulk tumors are associated with increased immune surveillance cells, such as naïve B cells and M1 macrophages in HPV-unrelated HNSC. IHC and western blot showed that ALDH2 is downregulated in the oral cavity, hypopharyngeal cancers, and well-differentiated carcinoma. In vitro, low ALDH2 levels showed reduced response to 5-fluorouracil in HNSC-derived cell lines. Conclusion: Our analyses revealed the genetic and cellular targets and drug response of ALDH2 in HNSC. We also found ALDH2 is involved in regulating the immune response of the tumor microenvironment, and high levels of ALDH2 in bulk HNSC may enhance antitumor immunity, which could improve prognosis. These findings suggest that ALDH2 could be a potential biomarker in improving risk stratification and tailoring treatment strategies in HNSC patients, especially in the HPV-unrelated subgroup.

8.
Am J Dermatopathol ; 45(6): 391-396, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36939126

RESUMO

ABSTRACT: Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement on chromosome 6p25.3 is a newly identified subtype of LyP. It is characterized by an older age of onset, localized skin lesions, with good prognosis, and it resembles a hybrid of LyP types B and C in histopathology. A limited number of cases have been reported so far. In this article, we reported a case of a 72-year-old man with recurrent episodes of widespread multiple discrete papular or vesicular eruptions on a region of the head, trunk, and 4 extremities for about 3 years. Histopathological examination of a vesicle revealed a subepidermal blister with abundant atypical lymphocytes in the vesicular space, band-like infiltrates in the papillary dermis, along with epidermotropism and pilosebaceous structure involvement. Fluorescence in situ hybridization analysis further demonstrated DUSP22-IRF4 rearrangement on chromosome 6p25.3. A diagnosis of vesicular LyP with this rare subtype was made according to the clinical and pathological findings.


Assuntos
Papulose Linfomatoide , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Papulose Linfomatoide/genética , Papulose Linfomatoide/patologia , Hibridização in Situ Fluorescente , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Vesícula , Cromossomos , Fosfatases de Especificidade Dupla/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética
9.
Asia Pac J Clin Oncol ; 19(1): 27-34, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35509196

RESUMO

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a rare cutaneous T cell lymphoma, which is indolent in nature but could claim life if not correctly diagnosed and promptly treated. SPTCL is usually presented clinically as painless subcutaneous and erythematous nodules over the trunk or extremities. Active clinical vigilance for these subcutaneous nodules or panniculitis-like lesions is warranted. A biopsy must be performed in order to make a correct diagnosis. Positron emission tomography scan is utilized for disease staging and treatment follow-up. Due to the rarity of this lymphoma, a standard treatment protocol is not established yet. However, most cases of SPTCL could be treated well under immunosuppressive or polychemotherapeutic drugs except in cases with hemophagocytic syndrome. Hematopoietic stem cell transplantation may be used in refractory or relapse cases. In this review, we presented a case of SPTCL with long-term complete remission. Meanwhile, since most clinical evidences and experiences of SPTCL are based mostly on case reports or small case series, and the understanding of the SPTCL pathophysiology is limited, we reviewed and updated the pathophysiology and treatments of SPTCL.


Assuntos
Linfoma de Células T , Paniculite , Neoplasias Cutâneas , Humanos , Recidiva Local de Neoplasia , Paniculite/diagnóstico , Paniculite/tratamento farmacológico , Linfoma de Células T/diagnóstico por imagem , Linfoma de Células T/tratamento farmacológico , Neoplasias Cutâneas/patologia
10.
Clin Pathol ; 15: 2632010X221123539, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119438

RESUMO

Mastocytosis is a rare disorder affecting both children and adults by gathering of functionally defective mast cells in the body's tissues. The World Health Organization (WHO) classified mastocytosis into cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma (MCS). We hereby present a case of retroperitoneal MCS with concurrent systemic mastocytosis and an undisclosed associated hematological neoplasm (SM-undisclosed AHN). The diagnosis of MCS and SM was made after the second biopsy over retroperitoneal mass, lymph node, and ovary for rapidly progressive disease with the presentation of unexplained recurrent flushing, palpitation, and shock, in addition to abdominal pain. A clonal myeloid neoplasm was also suspected by the karyotype and hemogram data. Unfortunately, the patient succumbed to the disease quickly. Apart from this unique case, the previously reported cases of SM with MCS in the literature were also reviewed.

11.
Artif Intell Med ; 125: 102244, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241257

RESUMO

The detection of the most common type of liver tumor, that is, hepatocellular carcinoma (HCC), is one essential step to liver pathology image analysis. In liver tissue, common cell change phenomena such as apoptosis, necrosis, and steatosis are similar in tumor and benign tissue. Hence, the detection of HCC may fail when the patches covered only limited tissue region without enough neighboring cell structure information. To address this problem, a Feature Aligned Multi-Scale Convolutional Network (FA-MSCN) architecture is proposed in this paper for automatic liver tumor detection based on whole slide images (WSI). The proposed network integrates the features obtained at different magnification levels to improve the detection performance by referencing more neighboring information. The FA-MSCN consists of two parallel convolutional networks in which one would extract high-resolution features and the other would extract low-resolution features by atrous convolution. The low-resolution features then go through central cropping, upsampling, and concatenation with high-resolution features for final classification. The experimental results demonstrated that Multi-Scale Convolutional Network (MSCN) improves the detection performance compared to Single-Scale Convolutional Network (SSCN), and that the FA-MSCN is superior to both SSCN and MSCN, demonstrating on HCC detection.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Redes Neurais de Computação
12.
Sci Rep ; 12(1): 1496, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087173

RESUMO

Tight junction proteins 1-3 (TJP1-3) are components of tight junctions that can link transmembrane proteins to the actin cytoskeleton, and their incidence directly correlates to metastasis. However, the role of the TJP family in bladder cancer has not been adequately evaluated. In this study, we evaluated the genetic changes, mRNA and protein expressions of the target genes of the TJP family in bladder cancer patients using online database and immunohistochemistry, respectively. We found that TJP1 was amplified in bladder cancer tissue and that the protein expression levels were significantly associated with age (p = 0.03), grade (p = 0.007), and stage (p = 0.011). We also examined the correlation between TJP1 and other high-frequency mutation genes using TIMER. TJP1 mRNA levels were positively correlated with TTN and RYR3 mRNA levels in bladder cancer tissue. Taken together, TJP1 expression is associated with poor clinical outcomes in patients with bladder cancer and can be a useful predictive biomarker for bladder cancer staging.


Assuntos
Proteína da Zônula de Oclusão-1
13.
Ear Nose Throat J ; 101(9): NP392-NP396, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33215532

RESUMO

Oncocytic tumors comprise a group of rare benign neoplasm of salivary glands, accounting for less than 1% of all salivary gland tumors. Nodular oncocytic hyperplasia characterized by multiple unencapsulated oncocytic nodules in the salivary glands is an extremely rare condition. We report a case of bilateral nodular oncocytic hyperplasia of parotid glands with parapharyngeal space extension in an 80-year-old woman whose initial presentation was recurrent parotitis. Our case may be the first report of nodular oncocytic hyperplasia in the parapharyngeal space, arising from the parotid gland. The patient underwent total parotidectomy and excision of parapharyngeal tumors using a transparotid transcervical approach, and at the 2-year follow-up, no evidence of recurrence was found.


Assuntos
Adenoma Oxífilo , Neoplasias Parotídeas , Doenças das Glândulas Salivares , Adenoma Oxífilo/patologia , Adenoma Oxífilo/cirurgia , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperplasia/patologia , Hiperplasia/cirurgia , Espaço Parafaríngeo , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia
14.
Pathol Res Pract ; 229: 153700, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929603

RESUMO

AIMS: Intracranial myxoid mesenchymal tumors (IMMTs) with fusions between EWSR1/FUS and CREB transcription factors have morphologic overlap with myxoid angiomatoid fibrous histiocytoma (mAFH) and myoepithelial tumor/carcinoma (MET/MEC). We aimed to study the clinicopathologic and genetic spectrum of extracranial IMMT-like tumors and their relationships with mAFH and MET/MEC. METHODS: Twelve extracranial tumors harboring EWSR1/FUS-CREB fusions across different histologic groups were characterized using RNA sequencing, FISH and/or RT-PCR. RESULTS: There were 4 IMMT-like neoplasms, 3 MET/MECs, and 5 mAFHs from the tibia (n=1), oral cavity (n=2), and soft tissues (n=9; 5 in the extremities), harboring EWSR1-ATF1 in 4 cases, FUS-CREM and EWSR1-CREM in 3 each, and EWSR1-CREB1 in 2. Multinodular growth, reticular/cording/trabecular arrangements, myxocollagenous matrix, and lymphocytic infiltrates variably prevailed among the 3 groups. mAFHs were characterized by cells with syncytial cytoplasm. IMMT-like neoplasms and MET/MECs shared cells with distinct boundaries, but only MET/MECs expressed GFAP and/or S100. MUC4 and ALK were expressed in some IMMT-like neoplasms (2/4; 2/4) and mAFH (2/5; 1/5). Pan-TRK reactivity was observed in two IMMT-like neoplasms with upregulated NTRK3 mRNA and one MEC. Local recurrences, typically ≥ 12 months postoperatively, developed in 2/3 IMMT-like neoplasms, 1/2 MET/MECs, and 0/4 mAFHs with follow-up. No definite associations were found between fusion types and histology, immunoprofile or outcome. CONCLUSIONS: We demonstrated the similarities and differences among 3 extracranial myxocollagenous tumor groups sharing EWSR1/FUS-CREB fusions. Oral IMMT-like neoplasms harboring FUS-CREM or EWSR1-ATF1 and FUS-CREM-positive.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etiologia , Proteína de Ligação a CREB/fisiologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/etiologia , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Adulto Jovem
15.
Diagnostics (Basel) ; 11(10)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34679626

RESUMO

Recent studies have reported that SERPINE2 contributes to the development of various cancers. However, its association with urothelial carcinoma (UC) remains unclear. In this study, data on urinary bladder UC (UBUC) cases from The Cancer Genome Atlas (TCGA) database were used to investigate the prognostic value of SERPINE2 mRNA expression. Then, SERPINE2 expression was analyzed with tissue microarrays constructed from 117 upper tract UC (UTUC) and 84 UBUC tissue specimens using immunohistochemical staining. Results were compared to clinicopathologic data by multivariate analysis. In the TCGA database, high SERPINE2 mRNA expression indicated a poor prognosis in patients with UBUC. Furthermore, Mann-Whitney U test showed that high SERPINE2 immunoexpression was significantly associated with adverse pathologic parameters including invasion, high grade, coexistence of UC in situ, and advanced pT stage (all p < 0.05, except for a marginal association with high-grade UBUC, p = 0.066). Kaplan-Meier analysis revealed that high SERPINE2 expression was associated with worse overall survival (OS; UTUC, p = 0.003; UBUC, p = 0.014) and disease-free survival (UTUC, p = 0.031; UBUC, p = 0.033). Moreover, multivariate analysis identified high SERPINE2 expression as an independent prognostic factor for OS (UTUC, p = 0.002; UBUC, p = 0.024). Taken together, our findings demonstrated that increased SERPINE2 expression is associated with adverse pathologic features and may serve as a prognostic biomarker for UC.

16.
Biology (Basel) ; 10(5)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063325

RESUMO

BACKGROUND: Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in histiocytic proliferative disorders, it provides a novel perspective on the pathomechanism of cutaneous RDD. We aim to investigate the genomic mutations in MAPK/ERK pathway in cutaneous RDD. METHODS: We retrospectively recruited all cases of cutaneous RDD from two hospitals in Taiwan from January 2010 to March 2020 with the clinicopathologic features, immunohistochemistry, and treatment. Mutations of neuroblastoma RAS viral oncogene homolog (NRAS), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in MAPK/ERK pathway were investigated by the highly sensitive polymerase chain reaction with Sanger sequencing. RESULTS: Seven patients with cutaneous RDD were recruited with nine biopsy specimens. The median age was 46 years (range: 17-62 years). Four of seven patients (57.1%) received tumor excision, while the other three chose oral and/or topical or intralesional steroids. NRAS mutation was detected in 4 of 7 cases (4/7; 51.7%), and NRAS A146T was the most common mutant point (n = 4/7), followed by NRAS G13S (n = 2/7). There is no KRAS or BRAF mutation detected. CONCLUSIONS: We report the NRAS mutation is common in cutaneous RDD, and NRAS A146T was the most frequent mutation in this cohort. Mutations in the NRAS gene can activate the RAS/MAPK signaling and have been reported to be associated with various cancers. It indicates that NRAS mutation in MAPK/ERK pathway may involve the pathogenesis of cutaneous RDD.

17.
Org Lett ; 23(10): 4067-4071, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33970648

RESUMO

A cobalt-catalyzed aminofluorination reaction of styrenes with N-fluorosulfonamides serving as both the amination and fluorination agents has been developed. The switch of selectivity in this catalytic reaction from aminofluorination to diamination could be easily achieved by the addition of 1.0 equiv of PPh3. Both transformations tolerated a wide array of substrates under mild reaction conditions.

18.
J Cutan Pathol ; 48(1): 140-146, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32954567

RESUMO

Adult-onset inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon cutaneous disease compared to childhood-onset ILVEN. The typical histopathologic features are alternating parakeratosis and orthokeratosis with an absent granular layer underneath parakeratosis, in contrast to a thickened granular layer below the foci of orthokeratosis in psoriasiform epidermal hyperplasia. Herein, we present a 49-year-old woman with typical clinical and histopathologic characteristics of adult-onset ILVEN, including linear arrangement of thick scaly papules and plaques localized on the medial side of her right leg, ankle, and foot. Immunohistochemical studies included involucrin, Ki-67, and keratin-10. Compared to the staining pattern in psoriasis, the expression of involucrin in this case was of lower intensity and localized to upper epidermal layers with relatively less extensive staining beneath regions of parakeratosis as compared to orthokeratosis; Ki-67 showed lower basal layer proliferative activity; and keratin-10 showed a greater intensity of staining within suprabasal epidermis.


Assuntos
Nevo Sebáceo de Jadassohn/patologia , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
19.
Org Biomol Chem ; 18(39): 7740-7750, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32940308

RESUMO

Unlike many other state-of-the-art transition-metal-catalyzed allylic substitutions, cobalt-catalyzed allylic substitution has received much less attention from synthetic chemists for a long time despite the fact that cobalt is an earth-abundant, low-cost and thus much more sustainable option as either a reagent or a catalyst in organic synthesis. Recently, there has been an upsurge in the use of cobalt catalysis in allylic functionalization reactions, including allylic substitution, nucleophilic allylation, and Heck-type allylic functionalization, to construct synthetically significant building blocks featuring a double bond available for diverse downstream synthetic manipulations. This review highlights the current development of cobalt catalysis in allylic functionalization with an in-depth discussion of the reaction scope and mechanistic insights.

20.
Int J Colorectal Dis ; 35(11): 1979-1987, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32556459

RESUMO

PURPOSE: The sessile serrated adenoma/polyp detection rate (SSA/PDR) among different colonoscopy indications from daily practice has not been fully understood. This study aimed to evaluate the detection and clinical characteristics of serrated polyps and conventional adenomas between outpatient department (OPD) and physical checkup unit (PCU) patients receiving colonoscopy. METHODS: The data for this retrospective study were collected between 2016 and 2017 at Kaohsiung Veterans General Hospital in Taiwan. A total of 7047 individuals were included, and information on polyp and adenoma detection was extracted from the colonoscopy reports. RESULTS: The adenoma detection rate, the SSA/PDR, and the detection rate of traditional serrated adenoma (TSA) were 32.2%, 0.60%, and 0.50%, respectively. Risk analysis revealed no significant difference (p = 0.095) in SSA/PDR between individuals < 50 years and ≥ 50 years, and no trend of increased SSA/PDR as age increased was observed (p = 0.320). SSA/P and TSA had higher risks for synchronous advanced neoplasia than conventional adenoma, but with proximal hyperplastic polyps lower (p < 0.001, respectively). No significant difference of SSA/PDR between OPD and PCU patients was observed (p = 1.000); however, the age of SSA/P was significantly older in OPD than in PCU patients (p = 0.048). CONCLUSION: The detection rates of CA and TSA were associated with age groups; however, SSA/PDR was insignificantly higher among individuals aged < 50 years than those with other age groups. In addition, SSA/PDR between OPD and PCU patients was not significantly found in daily practice of colonoscopies.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Adenoma/diagnóstico , Adenoma/epidemiologia , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Colonoscopia , Humanos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Retrospectivos , Taiwan
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