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Animals constantly receive various sensory stimuli, such as odours, sounds, light and touch, from the surrounding environment. These sensory inputs are essential for animals to search for food and avoid predators, but they also affect their physiological status, and may cause diseases such as cancer. Malignant gliomas-the most lethal form of brain tumour1-are known to intimately communicate with neurons at the cellular level2,3. However, it remains unclear whether external sensory stimuli can directly affect the development of malignant glioma under normal living conditions. Here we show that olfaction can directly regulate gliomagenesis. In an autochthonous mouse model that recapitulates adult gliomagenesis4-6 originating in oligodendrocyte precursor cells (OPCs), gliomas preferentially emerge in the olfactory bulb-the first relay of brain olfactory circuitry. Manipulating the activity of olfactory receptor neurons (ORNs) affects the development of glioma. Mechanistically, olfaction excites mitral and tufted (M/T) cells, which receive sensory information from ORNs and release insulin-like growth factor 1 (IGF1) in an activity-dependent manner. Specific knockout of Igf1 in M/T cells suppresses gliomagenesis. In addition, knocking out the IGF1 receptor in pre-cancerous mutant OPCs abolishes the ORN-activity-dependent mitogenic effects. Our findings establish a link between sensory experience and gliomagenesis through their corresponding sensory neuronal circuits.
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Carcinogênese , Glioma , Fator de Crescimento Insulin-Like I , Neurônios Receptores Olfatórios , Olfato , Animais , Glioma/metabolismo , Glioma/patologia , Camundongos , Vias Neurais , Bulbo Olfatório/patologia , Neurônios Receptores Olfatórios/fisiologia , Olfato/fisiologiaRESUMO
The aetiology of inflammatory bowel disease (IBD) is a multifactorial interplay between heredity and environment1,2. Here we report that deficiency in SETDB1, a histone methyltransferase that mediates the trimethylation of histone H3 at lysine 9, participates in the pathogenesis of IBD. We found that levels of SETDB1 are decreased in patients with IBD, and that mice with reduced SETDB1 in intestinal stem cells developed spontaneous terminal ileitis and colitis. SETDB1 safeguards genome stability3, and the loss of SETDB1 in intestinal stem cells released repression of endogenous retroviruses (retrovirus-like elements with long repeats that, in humans, comprise approximately 8% of the genome). Excessive viral mimicry generated by motivated endogenous retroviruses triggered Z-DNA-binding protein 1 (ZBP1)-dependent necroptosis, which irreversibly disrupted homeostasis of the epithelial barrier and promoted bowel inflammation. Genome instability, reactive endogenous retroviruses, upregulation of ZBP1 and necroptosis were all seen in patients with IBD. Pharmaceutical inhibition of RIP3 showed a curative effect in SETDB1-deficient mice, which suggests that targeting necroptosis of intestinal stem cells may represent an approach for the treatment of severe IBD.
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Instabilidade Genômica , Histona-Lisina N-Metiltransferase/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Necroptose , Células-Tronco/metabolismo , Animais , Histona-Lisina N-Metiltransferase/genética , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Camundongos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Células-Tronco/citologiaRESUMO
Immune checkpoint inhibitors (ICIs) plus chemotherapy has demonstrated efficacy in resectable non-small-cell lung cancer (NSCLC), yet the optimal period of neoadjuvant immunochemotherapy is undetermined. In a phase II study (neoSCORE, NCT04459611), more neoadjuvant therapy cycles appeared to provide greater pathological remission, and patients with squamous NSCLC had a better major pathological response rate than those with nonsquamous NSCLC. Sintilimab, a monoclonal anti-PD-1 antibody, has shown encouraging antitumor activity and safety in multiple cancers, including NSCLC. Here, we describe the study design of neoSCORE II (NCT05429463), a randomized, open-label, multicenter phase III trial comparing the efficacy and safety of three cycles with four cycles of neoadjuvant sintilimab plus platinum-based chemotherapy in resectable stage IIA-IIIB squamous NSCLC. Trial registration number: NCT05429463 (ClinicalTrials.gov).
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Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
BACKGROUND: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. METHODS: We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. RESULTS: Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases. CONCLUSIONS: Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.
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BACKGROUND: Mammography (MMG) shows decreased diagnostic accuracy in dense breast tissue, and thus, ultrasonography (US) and breast-specific gamma imaging (BSGI) have gradually been adopted for women with mammographically dense breasts. However, these two adjunct modalities have not been directly compared in previous studies. Hence, we investigated the adjunctive efficacy of US and BSGI in mammographically dense breasts. METHODS: This retrospective, comparative study recruited women with mammographically dense breasts. All enrolled women underwent US and BSGI as adjunctive imaging, and the comparative sensitivity, specificity, and diagnostic accuracy of combined MMG plus BSGI versus MMG plus US were evaluated. McNemar's test was used for paired binary data in this comparative analysis. RESULTS: From April 2013 to April 2016, 364 women with mammographically dense breasts and a final surgical or biopsy pathological diagnosis were recruited, comprising 218 cases of malignant disease (59.9%) and 146 cases of benign disease (40.1%). There was no difference between BSGI and US in enhancing the sensitivity of MMG diagnosis (Se-Difference 3.2%, p = 0.23), but the diagnostic specificity of MMG plus BSGI was superior to that of MMG plus US (Sp-Difference 10.3%, p = 0.003). The area under the ROC curve showed that MMG plus BSGI had better diagnostic accuracy than MMG plus US (0.90 vs. 0.83, p = 0.0019). CONCLUSIONS: For women with mammographically dense breasts, MMG plus BSGI or US can improve the diagnostic accuracy. In addition, BSGI has high specificity and could reduce invasive biopsies and thus may represent a viable diagnostic imaging alternative for mammographically dense breasts. KEY POINTS: ⢠Both BSGI and US can be applied as adjunct imaging diagnostics in women with mammographically dense breasts. ⢠The diagnostic accuracy of MMG plus BSGI was higher than that of MMG plus US. ⢠BSGI has the potential to be used as an adjunct diagnostic modality in women with mammographically dense breasts.
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Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Cintilografia/métodos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Biópsia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Mamografia/métodos , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia , Adulto JovemRESUMO
The availability of a comprehensive tissue library is essential for elucidating the function and pathology of human brains. Considering the irreplaceable status of the formalin-fixation-paraffin-embedding (FFPE) preparation in routine pathology and the advantage of ultra-low temperature to preserve nucleic acids and proteins for multi-omics studies, these methods have become major modalities for the construction of brain tissue libraries. Nevertheless, the use of FFPE and snap-frozen samples is limited in high-resolution histological analyses because the preparation destroys tissue integrity and/or many important cellular markers. To overcome these limitations, we detailed a protocol to prepare and analyze frozen human brain samples that is particularly suitable for high-resolution multiplex immunohistological studies. As an alternative, we offered an optimized procedure to rescue snap-frozen tissues for the same purpose. Importantly, we provided a guideline to construct libraries of frozen tissue with minimal effort, cost and space. Taking advantage of this new tissue preparation modality to nicely preserve the cellular information that was otherwise damaged using conventional methods and to effectively remove tissue autofluorescence, we described the high-resolution landscape of the cellular composition in both lower-grade gliomas and glioblastoma multiforme samples. Our work showcases the great value of fixed frozen tissue in understanding the cellular mechanisms of CNS functions and abnormalities.
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Encéfalo/citologia , Criopreservação/métodos , Imunofluorescência , Animais , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Criopreservação/instrumentação , Glioma/patologia , Glioma/cirurgia , Humanos , Camundongos , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Células-Tronco Neurais/citologia , Células-Tronco Neurais/patologia , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Oligodendroglia/citologia , Oligodendroglia/patologiaRESUMO
PURPOSE: To describe a case of uveal melanoma in the peripheral choroid masquerading as chronic uveitis and to raise awareness about malignant masquerade syndromes. CASE REPORT: A 36-year-old Chinese woman presented from an outside ophthalmologist with a 6-month history of unilateral chronic uveitis unresponsive to medical therapy in the left eye. She was found to have a uveal melanoma in the retinal periphery and underwent successful enucleation of her left eye. The histopathological diagnosis confirmed the clinical diagnosis. CONCLUSIONS: When uveal melanoma presents in an atypical way, the diagnosis is more difficult. This case highlights the uncommon presentations of malignant melanoma of the choroid. It provides valuable information on how peripheral uveal melanoma can present with clinical signs consistent with an anterior uveitis.
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Neoplasias da Coroide/diagnóstico , Melanoma/diagnóstico , Uveíte Posterior/diagnóstico , Adulto , Neoplasias da Coroide/cirurgia , Doença Crônica , Diagnóstico Diferencial , Enucleação Ocular , Feminino , Humanos , Imageamento por Ressonância Magnética , Melanoma/cirurgia , Microscopia Acústica , Uveíte Posterior/cirurgiaRESUMO
Background: Langerhans cell histiocytosis is a rare disease characterized by the abnormal proliferation of Langerhans cells within a single organ or multiple organs. This case report aims to improve the knowledge of the presentation of gastrointestinal Langerhans cell histiocytosis to facilitate the diagnosis and management of this rare disorder. Case presentation: A 19-month-old female presented with repeatedly mucinous bloody stools. The abdominal ultrasound revealed a slightly enlarged spleen. The initial colonoscopy revealed chronic enteritis with a very early onset inflammatory bowel disease. After anti-inflammatory treatment without improvement, an intestinal biopsy was performed at The Forth Affiliated Hospital of Zhejiang University. The final intestinal biopsy and histopathology examination confirmed the presence of Langerhans cell histiocytosis. After diagnosis, additional lung and head imaging examinations revealed no abnormalities. Her condition improved gradually after being treated with chemotherapy (vincristine and prednisone) and molecular-targeted drug(dalafinil) treatment. Conclusion: The clinical symptoms of Langerhans cell histiocytosis involving the gastrointestinal tract are not specific and may resemble symptoms observed in inflammatory bowel disease and other primary gastrointestinal tumors. Therefore, in cases of infants presenting with inflammatory gastrointestinal symptoms that do not resolve after treatment, a biopsy is essential to obtain a differential diagnosis.
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Histiocitose de Células de Langerhans , Doenças Inflamatórias Intestinais , Humanos , Lactente , Feminino , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/patologia , Prednisona/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pulmão/patologia , Doenças RarasRESUMO
Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias da Mama/patologia , Relevância Clínica , Inteligência Artificial , Perfilação da Expressão Gênica , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: In order to improve survival outcomes in resectable non-small cell lung cancer (NSCLC), strategies for neoadjuvant therapy need to be revisited. We evaluated and compared the efficacy of different neoadjuvant therapeutic modalities in a real-world setting. METHODS: A total of 258 patients with clinical stage IIA to IIIB NSCLC was included. All the patients underwent surgical resection after one to four cycles of neoadjuvant treatment consisting of chemotherapy (83), immunotherapy (23), and immunotherapy plus chemotherapy (152). RESULTS: The radiologic response rate in the combined immunochemotherapy group was 67.8%, higher than that of 48.2% in the chemotherapy group and 4.3% in the immunotherapy group (p < 0.001). An improved major pathological response (MPR) was also achieved in the combined therapy group compared with the chemotherapy group and the immunotherapy group (53.9% vs. 10.8% vs. 8.7%, p < 0.001). Patients in the combined therapy group had a significant trend toward longer disease-free survival than those in the chemotherapy alone group (3-year disease-free survival [DFS] of 68.79% vs. 50.81%; hazard ratio [HR] for progression or death, 0.477; p = 0.003). Multivariate Cox analysis identified radical surgery (HR, 0.328; p = 0.033), ypN0-1 stage (HR, 0.591; p = 0.038) and MPR result (HR, 0.362; p = 0.007) to be independent prognostic factors for DFS. CONCLUSIONS: Neoadjuvant treatment with a combination of immunotherapy plus chemotherapy appears to achieve higher radiological and pathological responses than monotherapy for IIA-IIIB NSCLC. Log-rank analysis showed that a better outcome could be expected in patients with the addition of immunotherapy to neoadjuvant chemotherapy if compared with patients with chemotherapy alone in terms of DFS.
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Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Terapia Neoadjuvante/métodos , Masculino , Feminino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Imunoterapia/métodos , Estadiamento de Neoplasias , Resultado do Tratamento , Estudos Retrospectivos , Pneumonectomia/métodos , Intervalo Livre de Doença , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the clinical value of radial endorectal ultrasound (ERUS) in the assessment of preoperative staging of rectal carcinoma. METHODS: One hundred and ten patients with rectal cancer underwent preoperative endorectal ultrasound (ERUS) examination in our hospital from February 2010 to September 2011. ERUS was performed using a Hitachi 900, Hitachi HI Vision Preirus US scanner, with a 5 - 10 MHz rigid rotating radial transducer and a focal length of 2 - 5 cm. The size, shape, echo pattern, infiltration depth, degree of circumferential involvement, extra-rectal invasion of the lesions and lymph node involvement were observed. The results of ERUS staging were compared with histopathological findings of the surgical specimens. RESULTS: The accuracy of ERUS for T staging was 91.4%. The accuracy of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.7%, 88.2%, 88.2% and 96.4%, respectively. The sensitivity of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.3%, 72.7%, 85.4% and 71.4%, respectively. The specificity of ERUS in diagnosing stage T1, T2, T3, T4 cancer was 92.9%, 92.0%, 90.3% and 100.0%, respectively. Comparing the consistency of preoperative T-staging and postoperative pathological results, the Kappa value was 0.75, with a considerable consistency. The sensitivity, specificity, and accuracy of ERUS in the assessment of lymph node metastasis were 74.2%, 89.9% and 85.5%, respectively. Comparing the consistency of preoperative N-staging and postoperative pathological results, the Kappa value was 0.64, with a considerable consistency. CONCLUSIONS: ERUS is a practical and accurate tool in assessment of preoperative staging of rectal tumors in regard to tumor invasion depth (T) and regional lymph node status (N), with advantages of simple operation, less pain, and high accuracy.
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Endossonografia/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Neoplasias Retais/cirurgia , Reto/patologia , Reto/cirurgiaRESUMO
Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.
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Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Variações do Número de Cópias de DNA , Proteínas Nucleares/genética , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Fatores de Transcrição/genética , Prognóstico , Linfoma/genética , Genômica , China , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/genéticaRESUMO
Radiation-induced cerebral necrosis, also known as radiation encephalopathy, is a debilitating condition that significantly impacts the quality of life for affected patients. Secondary central nervous system lymphoma (SCNSL) typically arises from highly aggressive mature B-cell lymphoma, but rarely from extranodal natural killer T-cell lymphoma (ENKTL). Treatment will be guided by differentiation between lymphoma progression from brain necrosis, and is particularly important for critically ill patients in an acute setting. However, differential diagnosis remains challenging because they share similar clinical manifestations and have no specific imaging features. We present the case of a 52-year-old man with ENKTL who suffered an emergency brain herniation secondary to massive radiation necrosis. The diagnosis established by brain biopsy ultimately led to appropriate treatment. The importance of the diagnostic biopsy is highlighted in this case for distinguishing between radiation necrosis and SCNSL.
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BACKGROUND: The density of tumor-infiltrating immunocytes (TICs) has been proposed as an independent predictor of intrahepatic recurrence in patients with hepatocellular carcinoma (HCC). However, the relative roles of TIC density in predicting tumor extrahepatic metastasis remain to be elucidated. METHODS: The densities of CD3(+), CD8(+), granzyme B(+), FoxP3(+), CD45RO(+), CD20(+), CD1a(+), CD83(+), CD57(+), and CD68(+) TICs were assessed by immunohistochemistry in tissue microarrays containing paired intratumoral (IT) and peritumoral (PT) tissues from 206 consecutive HCC patients who underwent liver transplantation. Occurrence of extrahepatic metastasis, recurrence-free survival (RFS), and cancer-specific survival (CSS) were assessed retrospectively in relation to TIC densities. RESULTS: CD45RO(+) memory T cell density was lower in tumor tissue compared with peritumor, whereas CD57(+) senescent T cell density was higher. Univariate analysis revealed that increased CD45RO (IT) (+) and decreased CD57 (PT) (+) densities were statistically significantly associated with favorable RFS and CSS, while other types of TICs, intratumorally or peritumorally, showed no prognostic values. Further, the CD45RO (IT) (+) /CD57 (PT) (+) ratio could stratify patients more accurately in terms of RFS and CSS than either marker used alone. Finally, multivariate analysis indicated that a high CD45RO (IT) (+) /CD57 (PT) (+) ratio was independently associated with better RFS (hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.42 to 0.98; P = 0.040) and CSS (HR = 0.51; 95% CI, 0.31 to 0.83; P = 0.007), but not CD45RO (IT) (+) or CD57 (PT) (+) individually. CONCLUSIONS: These results suggest that the CD45RO (IT) (+) /CD57 (PT) (+) (memory/senescent T cell) ratio is of vital importance in preventing HCC extrahepatic metastasis and in particular demonstrates its independent prognostic value in liver transplant recipients.
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Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Memória Imunológica/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Linfócitos do Interstício Tumoral/imunologia , Carcinoma Hepatocelular/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Linfócitos T/imunologiaRESUMO
Developing green economy has become the focus of governments, scholars, and entrepreneurs all over the world; however, the realization path of green economic efficiency for the regions under the interaction of multiple factors has still been uncertain. This study takes 30 provincial-level regions in China as the empirical object and applies a new method of fuzzy-set qualitative comparative analysis to explore the configuration of conditions for achieving green economic efficiency, which effectively improves the link between theory and practice. This study reveals that the improvement of green economy efficiency is the result of the joint action of multiple factors, and one factor in isolation is not enough for explaining it. Besides, there exist three equivalent paths to achieve high green economic efficiency; therefore, regions can design the most appropriate promotion strategy according to the determined paths. The result shows that high marketization is the core condition for achieving high green economy efficiency. Among the three paths, the combination of environmental regulation, urbanization, marketization, and technological innovation has the highest unique coverage, which alone explains how most regions have achieved high green economic efficiency. Third, four paths for achieving low green economy efficiency have been identified in this study, which provides lessons for regional governments to avoid the decline in green economy efficiency. And specially, the combination of high urbanization, high environment regulation, and high technological innovation can lead to low green economy efficiency because of low marketization. The conclusion improves the theory of green development and provides a practical reference for the regional government to develop green economy.
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Desenvolvimento Econômico , Urbanização , China , Eficiência , Invenções , Governo LocalRESUMO
Background: A high adenosine level is an important characteristic of the tumor microenvironment (TME) in breast cancer. Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. Methods: We performed public database bioinformatics analysis, surgical specimen histological validation, RNA sequencing, and exATP/extracellular adenosine (exADO) assays to reveal the role of PANX1 in regulating the immune microenvironment of basal-like breast cancer. Results: Our results revealed that PANX1 acted as a poor prognostic factor for breast cancer and had high expression in basal-like breast cancer. PANX1 expression was positively correlated with exATP and exADO levels in basal-like breast cancer TME. PANX1 expression was also positively correlated with tumor-associated neutrophil (TAN) infiltration in breast cancer TME and TANs highly expressed ENTPD1 (CD39)/NT5E (CD73). Conclusions: This study suggests that high PANX1 expression is associated with high TAN infiltration and adenosine production to induce local immunosuppression in basal-like breast cancer TME.
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ROS1-rearranged patients account for 1-2% of non-small cell lung cancer (NSCLC) cases. Approximately 10 fusion partners have been discovered, while clinical practice is actively generating knowledge of new ones and their therapeutic responses. Herein, we report a patient with stage IV NSCLC that harbored a novel TPR-ROS1 fusion, which demonstrated a rapid but short partial response to first line crizotinib and primary resistance to subsequent ceritinib. Computed tomography detected a pulmonary nodule in a 53-year-old woman who presented with persistent cough. Histopathologic and molecular examination of the tissue biopsy indicated a poorly differentiated adenocarcinoma staining negative for PD-L1 but harbored a novel translocated promoter region (TPR)-ROS1 (T4:R35) gene fusion. Frontline crizotinib monotherapy elicited a rapid partial response after 1 month, although the disease progressed another 2 months later. After another 3 months of continued crizotinib treatment, the patient manifested newly emerged and enlarged lung and brain lesions. Genomic profiling still identified TPR-ROS1 as the only aberration, while a lymph node biopsy indicated PD-L1 immunopositivity. The patient was then treated with ceritinib and progressed within 1 month. She was started on chemotherapy with pemetrexed plus carboplatin and has achieved rapid partial response as of the latest follow-up. In summary, we provided clinical evidence of a novel TPR-ROS1 fusion and its roles as an oncogenic driver in metastatic NSCLC. To the best of our knowledge, ours is the first case to report this fusion in NSCLC. This case was characterized by a rapid yet short-term response to first line crizotinib and primary resistance to subsequent ceritinib, while no known genetic resistance mechanism was identified and other mechanisms including histologic transformation were unlikely. Future research is needed to unveil the resistance mechanism and formulate effective treatment strategies.
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Background: In this study, a new composite biological mesh named SFP was prepared by combining silk fibroin with polypropylene mesh. The mechanism and clinical application value of the SFP composite mesh were explored. Methods: The fibrous membrane was prepared by electrospinning of silk fibroin. The silk fibrous membrane was adhered to the polypropylene mesh by fibrin hydrogel to make a new composite mesh. The characterizations were verified by structural analysis and in vitro cell experiments. A total of 40 Sprague-Dawley rats were randomly divided into two groups, and 20 rats in each group were implanted with the SFP mesh and pure polypropylene mesh, respectively. The rats were sacrificed in batches on the 3rd, 7th, 14th, and 90th days after surgery. The adhesion degree and adhesion area on the mesh surface were compared, and a histopathological examination was carried out. Results: In vitro cell function experiments confirmed that the SFP mesh had good cell viability. The control group had different degrees of adhesion on the 3rd, 7th, 14th, and 90th days after surgery. However, there was almost no intraperitoneal adhesions on the 3rd and 7th days after surgery, and some rats only had mild adhesions on the 14th and 90th days after surgery in the SFP group. There were statistically significant differences in the postoperative intraperitoneal adhesion area and adhesion degree between the two groups (p < 0.05). Histopathological examination confirmed that the mesenchymal cells were well arranged and continuous, and there were more new capillaries and adipocyte proliferation under the mesenchymal cells in the SFP group. Conclusion: The SFP mesh shows good biocompatibility and biofunction in vitro and in vivo. It can promote the growth of peritoneal mesenchymal cells. The formation of a new mesenchymal cell layer can effectively reduce the extent and scope of adhesion between the mesh and abdominal organs. The SFP mesh will have a good application prospect in the field of abdominal wall hernia repair.
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BACKGROUND: Hepatic solitary fibrous tumor (SFT) is a rare neoplasm. Up to now, only 90 cases have been reported in the English language literature. This report describes a case of SFT of the liver misdiagnosed as hepatocellular carcinoma. CASE SUMMARY: A 42-year-old male had a two-year history of a gradually enlarging intrahepatic nodule. The preoperative imaging revealed a mass with a size of 2.7 cm × 2.3 cm located in the segment IV of the liver. The patient was subjected to the resection of the segment IV, such as the medial segment of the left lobe of the liver. The histological examination of the mass showed various spindled cells irregularly arranged in the stroma. The immunohistochemistry of this mass revealed a positive staining for CD34 and STAT6. The history of intracranial tumor and postoperative pathological results led to the diagnosis of SFT of the liver (SFTL) due to a metastasis from the brain. CONCLUSION: SFTL is an uncommon mesenchymal neoplasm that can be easily overlooked or misdiagnosed. The best treatment choice is the complete surgical resection of the mass. A regular follow-up after the surgery should be performed due to the poor prognosis of metastatic or recurrent SFT.
RESUMO
The aims of this study were to investigate FOXP1 expression in nodal and extranodal diffuse large B-cell lymphoma (DLBCL) and its association with the subclassification and other clinicopathologic parameters of DLBCL. Expression of FOXP1, CD10, Bcl6, MUM1, and Bcl2 was detected by immunohistochemistry on tissue microarray sections. The Kaplan-Meier method was used to estimate the overall survival of patients, and the log-rank test was used to compare survival differences between groups with different FOXP1 protein expressions. Expression of FOXP1 was detected in 67.4% (95/141) of DLBCLs. FOXP1 expression in non-GCB (67/90, 74.4%) was significantly higher than that in GCB (28/51, 54.9%) (p < 0.05). FOXP1 expression in MUM1-positive cases (62/81, 76.5%) was significantly higher than that in MUM1-negative cases (33/60, 55%) (p < 0.01). FOXP1 expression was positively correlated with Bcl2 (p < 0.05) in non-GCB among nodal DLBCL cases. Among the extranodal group, patients with FOXP1 expression had a significantly inferior OS compared to those with negative FOXP1 expression (p < 0.05), which was not seen in nodal group. In conclusion, FOXP1 expression might be involved in the tumorigenesis of both nodal and extranodal DLBCL. The most striking finding of this study was that FOXP1 expression had an adverse effect on survival of patients with extranodal DLBCL, which indicated that FOXP1 function might be mediated by different mechanisms in nodal and extranodal DLBCLs. FOXP1 might play a role in the pathogenesis of nodal non-GCB DLBCL through the pathways in which Bcl2 was involved, and it might be a second important biomarker for non-GCB.