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Objective: To construct a remote screening network for breast cancer based on automated breast ultrasound (ABUS) and explore the value of ABUS with remote reading for breast cancer screening. Methods: We constructed a remote breast cancer screening network including one remote reading center and 48 image-acquisition centers. We recruited women to participate in breast cancer screening at one of these image-acquisition centers from January 2021 to January 2023. The technicians collected the whole breast images using the ABUS. The images were then sent to the reading center through the PVBUS System and interpreted independently by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). BI-RADS categories 1 and 2 indicate negative screening results, and women diagnosed with these categories were recommended for annual breast ultrasound screening. BI-RADS categories 3, 4, and 5 indicate positive results. Women with BI-RADS category 3 lesions were recommended for follow-up examinations every 6 months using ABUS or handheld ultrasound, while those with BI-RADS 4 and 5 lesions were suggested to undergo pathological examinations. Results: In our study, we enrolled 10 344 women who completed the ABUS screening and were followed up for more than 12 months. After remote reading, 6 164 women were diagnosed with BI-RADS category 1 and 2 626 woman were within BI-RADS category 2. In contrast, 1 404 women were within BI-RADS category 3, a total of 135 women were within BI-RADS category 4, and 15 women were within BI-RADS category 5. The positive screening rate of ABUS was 15.0% (1 554/10 344). The ABUS with remote reading had a detection rate of 3.7/1 000 (38/10 344) for breast cancer screening, with a sensitivity of 97.4% (38/39) and a specificity of 85.3% (8 789/10 305). Among the 38 breast cancer cases detected, 92.1% (35/38) were invasive carcinomas, and 63.2% (24/38) were stage 0 or â breast cancers. Conclusions: Breast cancer screening based on ABUS with remote reading provided an efficient and feasible solution to the problem of unevenly distributed medical resources and medical staff levels in various regions of China, enabling the decentralization of high-quality medical resources and improving the accessibility of high-quality screening services. It has provided an alternative for breast cancer screening in China.
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Neoplasias da Mama , Detecção Precoce de Câncer , Ultrassonografia Mamária , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico , Feminino , Ultrassonografia Mamária/métodos , Detecção Precoce de Câncer/métodos , Estudos Prospectivos , Estudos de Coortes , Pessoa de Meia-Idade , Adulto , Mama/diagnóstico por imagemRESUMO
Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering ß-emitting 177Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of 177Lu-DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumors longitudinally through positron emission tomography (PET) using a SSTR2-specific positron-emitting radiotracer,18F-NOTA-Octreotide. In animals receiving CAR T cells and a low-dose (2.5 Gy) of TRT following the administration of 177Lu-DOTATATE, we observed a rapid regression of large subcutaneous tumors, which coincided with a dramatic increase in serum proinflammatory cytokines. Tumor burden was also reduced when a higher radiation dose (6 Gy) was delivered to the tumor. However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.
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Neoplasias , Animais , Neoplasias/tratamento farmacológico , Octreotida/uso terapêutico , Linfócitos T , Imunoterapia , Radioisótopos/uso terapêuticoRESUMO
Objective: To improve the awareness of hemophagocytic syndrome(HPS) secondary to COVID-19 (COVID-sHPS). Methods: We reported an adult case of COVID-sHPS, including clinical presentation, laboratory examinations, histopathological findings, treatment strategy, and outcome. We also conducted literature research in PubMed database and Wanfang database using the keywords "COVID-19" and "hemophagocytic syndrome" and subsequently summarized relevant literature. Results: A 49-year-old man was admitted to our hospital after 4 weeks of recurrent fever. Prior to this hospitalization, he had received an empiric combination therapy with antibiotics and antiviral drugs against SARS-CoV-2. His vital signs were within the normal range and no abnormalities were found on physical examination on admission. After admission, throat swab nucleic acid tests were weakly positive for SARS-CoV-2, and negative for influenza and respiratory syncytial virus. Blood nucleic acid tests for cytomegalovirus and EB virus were negative, as was blood mNGS. Laboratory tests showed a series of abnormalities, including leukopenia, thrombocytopenia, low fibrinogen, elevated serum ferritin, elevated transaminase, decreased NK cell activity, and hemophagocytosis in bone marrow. According to the HPS-2004 diagnostic criteria, he was diagnosed with hemophagocytic syndrome, which was high likely to be caused by COVID-19 infection due to the lack of evidence of genetic risk factors and other clear triggers. He was initially treated with dexamethasone at a dose of 10 mg·m-2·d-1 and his condition improved rapidly. The literature search identified twenty-three articles on COVID-sHPS, 22 of which were in English. A total of 89 patients had COVID-sHPS and 55 (61.7%) were male. COVID-sHPS could occur at any age, but mainly in adults (86/89, 96%). Fever was reported in the literature with a clear description of the course of the disease. Most HPS occurred during the acute phase of COVID-19, but 3 patients developed HPS during the convalescent phase. Almost all reported cases presented with increased ferritin, elevated transaminases, elevated triglycerides, and cytopenia, mainly anemia and thrombocytopenia. In the retrieved literature, HS-score≥169 was frequently used to diagnose COVID-sHPS, and glucocorticoid in combination with immunoglobulin was the most common treatment strategy. COVID-sHPS had a poor prognosis and a high mortality rate (84.2%, 75/89). Conclusions: The prognosis of COVID-sHPS is poor, so clinicians should raise their awareness of the disease, identify high-risk suspected populations, and arrange reasonable relevant examinations for definite diagnosis and early initial treatment to improve their outcome.
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COVID-19 , Linfo-Histiocitose Hemofagocítica , Trombocitopenia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , COVID-19/complicações , SARS-CoV-2 , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/complicações , Prognóstico , Trombocitopenia/complicaçõesRESUMO
Objective: To analyze the clinical and imaging features of patients with sudden sensorineural deafness and acute cerebral infarction in order to provide evidence for early recognition of such diseases. Methods: This was a case series reporting study. A retrospective analysis was performed on the clinical and imaging data of 29 patients with sudden hearing loss (SHL) who admitted to the Otolaryngology Head and Neck Surgery Department of Beijing Tiantan Hospital from January 2017 to December 2021 and diagnosed with acute cerebral infarction using MRI-DWI. Results: The patients were aged 31-71 years, with an average age of 56±12 years, and 82.8% (24/29) were men. In total, 82.8% (24/29) of the patients had three or more atherosclerotic risk factors, and 24.1% (7/29) had a history of SHL. The hearing types were flat and total deafness: 86.2% (25/29) of the patients had severe hearing loss, 27.6% (8/29) had bilateral SHL, 17.2% (5/29) had further hearing loss during hospitalization, and 82.8% (24/29) had dizziness or vertigo at the onset. The signs of central nervous system involvement mainly included speech impairment, diplopia, dysphagia, central facial paralysis, facial and limb hypoesthesia, ataxia, and decreased muscle strength. Imaging evaluation showed that 21 cases were located in the posterior circulation supply area and 8 cases in the anterior circulation supply area. Additionally, 82.8% (24/29) patients had vertebrobasilar artery stenosis, and 58.6% (17/29) patients had severe vertebrobasilar artery stenosis or occlusion. Conclusions: Patients with SHL who progress to cerebral infarction often have multiple atherosclerotic risk factors and SHL. Most of the patients are middle-aged and older men who often complain of dizziness or dizziness accompanied by severe flat and total deafness with unilateral or bilateral SHL. Imaging findings suggest that most patients have posterior circulation infarction, often accompanied by severe stenosis or occlusion of the vertebrobasilar artery.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Acidente Vascular Cerebral , Masculino , Pessoa de Meia-Idade , Humanos , Idoso , Adulto , Feminino , Perda Auditiva Súbita/complicações , Perda Auditiva Súbita/diagnóstico , Tontura , Estudos Retrospectivos , Constrição Patológica/complicações , Surdez/complicações , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/diagnóstico , Acidente Vascular Cerebral/complicações , Vertigem/diagnóstico , Doença Aguda , Infarto Cerebral/complicaçõesRESUMO
The passion fruit peel (PFP) is the by-product of juice processing and is rich in phenolic compounds and dietary fibers. As the high ADF content in PFP (34.20%), we proceeded to treat PFP with cellulase. The ADF decreased to 16.70% after enzymatic processing, and we supposed that enzymolytic passion fruit peel (EPF) should have a greater growth performance than PFP to broilers. Two trials were conducted to evaluate the effects of dietary PFP or EPF supplementation on growth performance, serum biochemical indices, meat quality, and cecal short-chain fatty acids, microbiota, and metabolites in broilers. In Exp. 1, 180 1-day-old Sanhuang broilers (male, 36.17 ± 2.47 g) were randomly allocated into 3 treatments, with 6 replicates in each treatment. The 3 experimental diets included 1 basal diet (control) and 2 PFP-added diets supplemented with 1 and 2% PFP, respectively. The trial lasted for 42 d. In Exp. 2, 144 Sanhuang broilers (male, 112-day-old, 1.62 ± 0.21 kg) were randomly allocated to 3 treatments. Each treatment was distributed among 6 pens, and each pen contained 8 broilers. The 3 treatment diets included: a control diet, a positive control diet supplementing 75 mg/kg chlortetracycline, and the experimental diet supplementing 3% EPF. The trial lasted for 56 d. Results showed that dietary 1 and 2% PFP addition did not affect growth performance in Exp. 1, and the 3% EPF supplementation had a negative effect on ADFI (P < 0.05) in Exp. 2. A decreased serum triglyceride (P < 0.05) in broilers was observed in Exp. 1. Broilers fed EPF had a higher glutathione peroxidase (GSH-Px) (P < 0.05), and lower levels of tumor necrosis factor-α (TNF-α) (P < 0.05) and glucose (P < 0.05) in Exp. 2. We also found that broilers from PFP or EPF-treated treatments had an increased butyrate content and higher microbial diversity in the cecum. The effects of antioxidation, anti-inflammatory function, and elevated SCFAs were confirmed after the microbe and untargeted metabolomic analysis. Dietary EPF supplementation significantly increased the SCFA-generating bacteria, anti-inflammatory-related bacteria, the antioxidant-related and anti-inflammatory-related metabolites. Moreover, dietary 3% EPF addition positively affects the biosynthesis of phenylpropanoids, which strongly correlate with the antioxidant and anti-inflammatory properties. In conclusion, the proper addition level did not affect the growth performance, and the PFP and EPF could improve the antioxidation state, anti-inflammatory activity, and intestinal functions of Sanhuang broilers to some extent.
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Antioxidantes , Passiflora , Masculino , Animais , Antioxidantes/metabolismo , Galinhas , Citocinas/metabolismo , Passiflora/metabolismo , Frutas , Suplementos Nutricionais/análise , Dieta/veterinária , Ácidos Graxos Voláteis/metabolismo , Ração Animal/análiseRESUMO
Wound healing involves complex pathophysiological mechanism, among which angiogenesis is considered as one of the key steps in wound healing, and promoting wound angiogenesis can accelerate wound healing. In recent years, mesenchymal stem cell-derived extracellular vesicles have been proven to produce equivalent effects of wound healing promotion comparable to stem cell therapy, with the advantages of low antigenicity and high biocompatibility. The specific mechanism by which extracellular vesicles facilitate wound healing is still not fully understood and is thought to involve all stages of wound healing. This article focuses on the possible mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis, so as to provide ideas for further study on the mechanism of extracellular vesicles to promote wound healing.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Cicatrização/fisiologia , Transplante de Células-TroncoRESUMO
BACKGROUND: The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. AIM: This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. DESIGN: This was a 5-year retrospective study on the antibiotic resistance of cancer patients. METHODS: In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. FINDINGS: Between 2016 and 2020, 216â219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. CONCLUSIONS: The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.
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Staphylococcus aureus Resistente à Meticilina , Neoplasias , Humanos , Staphylococcus aureus , Escherichia coli , Estudos Retrospectivos , Pacientes Internados , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Farmacorresistência Bacteriana , Pseudomonas aeruginosa , Imipenem , China/epidemiologia , Klebsiella pneumoniae , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate the expression and gene function of methyltransferase-like protein 27 (METTL27) in colon cancer, its association with immune infiltration and its prognostic significance. METHODS: We analyzed the expression levels of METTL27 in 33 cancers using R language and identified METTL27 as a differential gene in colon cancer. The related signaling pathways of METTL27 were analyzed by gene functional annotation and enrichment. SsGSEA algorithm was used to analyze immune infiltration, and logistic analysis was used to evaluate the correlation between METTL27 expression and clinicopathological features of the patients. Kaplan-meier analysis, univariate and multivariate Cox regression analysis were performed to construct a nomogram for evaluating the correlation between METTL27 expression and clinical prognosis. The expression level of METTL27 was further verified in colorectal cancer cell lines and 16 clinical specimens of colorectal cancer tissues using qPCR and Western blotting. RESULTS: METTL27 was highly expressed in 21 cancers, and its expression was significantly higher in colon cancer than in adjacent tissues (P < 0.001). METTL27-related genes were identified by differential analysis, and functional annotation revealed that METTL27 was significantly enriched in transmembrane transport and lipid metabolism, and 5 related signaling pathways were identified by GSEA. METTL27 expression was negatively correlated with different T helper cells and central memory T cells (P < 0.001). The patients with a high METTL27 mRNA expression had a poor survival outcome. Cox regression analysis showed that METTL27 expression was an independent prognostic factor of the overall survival. The expression level of METTL27 was significantly higher in the colorectal cancer cell line than in normal cells (P < 0.05). CONCLUSION: METTL27 is overexpressed in colon cancer and is associated with a poor prognosis of the patients. A high expression of METTL27 showed is associated less T cell immune infiltration, suggesting the potential of METTL27 as a prognostic marker of colon cancer.
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Neoplasias do Colo , Neoplasias do Colo/patologia , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA MensageiroRESUMO
BACKGROUND: Atopic dermatitis (AD) is a common, chronic, severely pruritic, eczematous skin disease that seriously deteriorates the quality of life of patients. Scratching is a cardinal symptom of AD. Although the vicious itch-scratch cycle continues and aggravates skin barrier dysfunction in AD, how scratching induces skin barrier dysfunction through tight junctions remains unclear. AIM: To study the effect of scratching on tight junctions in the itch-scratch cycle. METHODS: Scratching behaviour and skin barrier dysfunction on the neck and back in an AD mouse model were assessed. The expression of tight junction proteins was compared between the neck and back mice, and the mechanisms underlying the involvement of Akt/CLDN1 pathways in this process were explored. RESULTS: We used oxazolone to induce AD on the neck or back of mice. There was significantly more scratching behaviour and more pronounced skin barrier dysfunction with the neck than with the back. Downregulation of claudin-1 (CLDN1) and upregulation of Akt phosphorylation in skin were well correlated with scratching behaviour in this AD model. Furthermore, SC79, an agonist of Akt phosphorylation, could downregulate CLDN1 expression in HaCaT cells. An antagonist of Akt phosphorylation (LY294002) was used to treat the AD mice; this treatment rescued CLDN1 expression through inhibiting Akt phosphorylation in skin, and importantly, also inhibited the scratching behaviour induced by AD. CONCLUSION: The results reveal the underlying mechanism of tight junction damage promoted by scratching in the itch-scratch cycle of AD, and opens a new avenue to pruritus management in AD, through Akt antagonists.
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Claudina-1/metabolismo , Dermatite Atópica/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pele/metabolismo , Junções Íntimas/metabolismo , Animais , Comportamento Animal , Dermatite Atópica/patologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prurido/metabolismo , Pele/patologiaRESUMO
We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.
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Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Receptor Proteína Tirosina Quinase ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Carga Tumoral , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Objective: To analyze the clinical,imaging and pathological features of Pleuroparenehymal fibroelastosis (PPFE). Methods: The clinieal data of a patient diagnosed as PPFE admitted in department of Respiratory and Critical Care Medicine,Beijing Hospital in April 2017 were reported and the related literatures were reviewed.With "pleuroparenehymal fibroelastosis" as the search terms, and the search time before October 1st 2017 for Wanfangdata, China National Knowledge Infrastructure(CNKI), and PubMed. Results: The patient was a 46-year-old male presented with cough, shortness of breath after exercise.A CT scan of the chest revealed bilateral, irregular pleural thickening with upper lobe predominance.After 3 years of antituberculosis treatment,the disease progressed. A diagnosis of pleuroparenehymal fibroelastosis (PPFE) was confirmed by CT guided lung biopsy. A total of 132 cases were reported (including 1 case in Chinese). 88 of them were confirmed by pathology with detailed data.Clinical data of 89 reported cases with PPFE including 48 males and 41 females aged 13 to 85 years were enrolled and analyzed in the study.The common symptoms were dyspnea(62%, 55 cases),cough(58%, 52 cases),recurrent respiratory tract infection(17%, 15 cases).The main CT features are reported:pleural thickening(87%,77 cases), recurrent pneumothorax(52%,46 cases), traction bronchiectasis(30%, 27 cases),subpleural comsolidation(20%, 18 cases). All patients were proven PPFE by biopsy.34 cases received corticosteroid, 5 cases received lung transplant operation.40 cases died during the follow-up from 4 month to 84 month. Conclusions: Pleuroparenehymal fibroelastosis is a rare disease.The imaging findings were dominated by both upper lobes. Lung biopsy might be necessary. PPFE is often misdiagnosed as pulmonary tuberculosis/obsolete pulmonary tuberculosis,asbestosis,connective tissues disease and Drug-induced pneumonitis.There was no consensus on the treatment.
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Pulmão/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Pleura/patologia , Doenças Pleurais/patologia , Fibrose Pulmonar/patologia , Biópsia , China , Tosse/etiologia , Dispneia/etiologia , Feminino , Humanos , Pulmão/patologia , Pulmão/cirurgia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/diagnóstico por imagem , Pleura/diagnóstico por imagem , Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/cirurgia , Fibrose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
N6-methyladenosine (m6A) is one of the most common and abundant modifications in RNA, which is related to many biological processes in humans. Abnormal RNA modifications are often associated with a series of diseases, including tumors, neurogenic diseases, and embryonic retardation. Therefore, identifying m6A sites is of paramount importance in the post-genomic age. Although many lab-based methods have been proposed to annotate m6A sites, they are time consuming and cost ineffective. In view of the drawbacks of the intrinsic methods in RNA sequence recognition, computational methods are suggested as a supplement to identify m6A sites. In this study, we develop a novel feature extraction algorithm based on the frequent gapped k-mer pattern (FGKP) and apply the linear regression to construct the prediction model. The new predictor is used to identify m6A sites in the Saccharomyces cerevisiae database. It has been shown by the 10-fold cross-validation that the performance is better than that of recent methods. Comparative results indicate that our model has great potential to become a useful and effective tool for genome analysis and gain more insights for locating m6A sites.
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AIMS: Polymorphous adenocarcinoma (PAC) usually follows an indolent course, but some cases may show recurrences and high-grade features. The genetic events associated with recurrences and high-grade versions are yet to be defined. Our aim was to determine the genetic underpinning of recurrent PACs of the salivary gland and the repertoire of somatic genetic alterations in cases with high-grade histology. METHODS AND RESULTS: Four PACs from three patients, including one case with matching primary and recurrent tumours, one de-novo high-grade PAC, and a PAC that transformed to a high-grade tumour following multiple recurrences, were subjected to targeted sequencing (Memorial Sloan Kettering Mutation Profiling of Actionable Cancer Targets assay) or whole-exome sequencing. Both matching primary and recurrent tumours, and the de-novo high-grade PAC, harboured clonal PRKD1 E710D hotspot mutations, whereas the PAC that underwent high-grade transformation upon recurrence, which was wild-type for PRKD1, harboured a PRKD2 rearrangement. The PACs analysed here also harboured mutations targeting cancer genes such as PIK3CA, SETD2, ARID1A, and NOTCH2. A clonal decomposition analysis of the matching primary and recurrent PACs revealed that a minor subclone from the primary tumour became dominant in the recurrent tumour following a clonal selection evolutionary pattern. CONCLUSIONS: Our findings demonstrate that recurrent and high-grade PACs are underpinned by PRKD1 E710D hotspot mutations or PRKD2 rearrangements, and that recurrences of PACs may stem from the selection of pre-existing subclones in the primary tumour.
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Adenocarcinoma/genética , Recidiva Local de Neoplasia/genética , Proteína Quinase C/genética , Proteínas Quinases/genética , Neoplasias das Glândulas Salivares/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Rearranjo Gênico , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Proteína Quinase D2 , Neoplasias das Glândulas Salivares/patologiaRESUMO
Inflammation is a response that protects the body from pathogens. Through several inflammatory signaling pathways mediated by various families of transcription factors, such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1), interferon regulatory factors (IRFs), and signal transducers and activators of transcription (STATs), various inflammatory cytokines and chemokines are induced and inflammatory responses are boosted. Simultaneously, inhibitory systems are activated and provide negative feedback. A typical mechanism by which this process occurs is that inflammatory signaling molecules upregulate mitogen-activated protein kinase phosphatase-1 (MKP1) expression. Here, we investigated how kinases regulate MKP1 expression in lipopolysaccharide-triggered cascades. We found that p38 and c-Jun N-terminal kinase (JNK) inhibitors decreased MKP1 expression. Using specific inhibitors, gene knockouts, and gene knockdowns, we also found that tumor necrosis factor receptor-associated factor family member-associated nuclear factor κB activator (TANK)-binding kinase 1 (TBK1) and Janus kinase 2 (JAK2) are involved in the induction of MKP1 expression. By analyzing JAK2-induced activation of STATs, STAT3-specific inhibitors, promoter binding sites, and STAT3-/- cells, we found that STAT3 is directly linked to TBK1-mediated and JAK2-mediated induction of MKP1 expression. Our data suggest that MKP1 expression can be differentially regulated by p38, JNK, and the TBK1-JAK2-STAT3 pathway after activation of toll-like receptor 4 (TLR4). These data also imply crosstalk between the AP-1 pathway and the IRF3 and STAT3 pathways.
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Inflamação/genética , Janus Quinase 2/genética , Proteínas Serina-Treonina Quinases/genética , Fator de Transcrição STAT3/genética , Animais , Fosfatase 1 de Especificidade Dupla/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Fator Regulador 3 de Interferon/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Lipopolissacarídeos/toxicidade , MAP Quinase Quinase 4/genética , Camundongos , NF-kappa B/genética , Células RAW 264.7 , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Fator de Transcrição AP-1/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
BACKGROUND: The erythrocyte sedimentation rate (ESR) as measured using the Westergren method is extremely elevated in patients with monoclonal gammopathy (MG) owing to the abundance of positively charged paraproteins. However, it has not been determined if the ESR is likewise high in patients with MG when measured using alternate ESR methods. METHODS: The ESR was measured using both the modified Westergren and microhemagglutination method (TEST1) in 36 patients with MG and in 159 individuals with other diseases. RESULTS: Erythrocyte sedimentation rates measured by the Westergren vs microhemagglutination methods showed substantial, but not remarkably high correlation. ESR measured using the Westergren method was higher in MG than in non-MG patients; however, ESR measured using microhemagglutination was not different in the 2 groups, resulting in a larger ΔESR (microhemagglutination ESR-Westergren ESR) in MG patients. When considered as continuous variables, none of the tested interfering plasma proteins (C-reactive protein, globulin, or fibrinogen) showed substantial correlations with Westergren or microhemagglutination ESRs. MG and low hematocrit were the only factors independently associated with ΔESR on multivariate analysis. CONCLUSION: We demonstrated, for the first time, that the ESR as measured by microhemagglutination is not elevated in patients with MG compared with those without. The ESR does not correlate with a particular plasma protein, showing that its measurement is multifactorial. The presence of MG is an independent factor for ΔESR.
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Sedimentação Sanguínea , Hemaglutinação , Paraproteinemias/sangue , Adulto , Estudos de Casos e Controles , Feminino , Hematócrito , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The effect of magnesium sulfate on brain tissue of SD rats irradiated by 6MeV electron was investigated. METHODS: SD rats were divided into three groups: control group, irradiation (IR group) and irradiation treated with magnesium sulfate (IR+M group). After being anesthetized, the whole brains of IR group and IR+M group were exposed to 6 MeV electron radiation. IR+M group was i.p. injected with 10% magnesium sulfate (400 mg/kg) one day before radiation and three days and five days after radiation. And on the 1st, 3rd, 7th and 14th day after radiation, SD rats were euthanatized to take brain tissue for the detection of calcium, redox status and cell apoptosis, as well as the expression of NF-κB and ICAM-1. RESULTS: The results indicated that magnesium treatment may alleviate the elevation of calcium and enhance redox status through increasing the activities of superoxide dimutase (SOD) and myeloperodase (MPO), and decreasing the concentration of malondialdehyde (MDA). Tunnel and immunohistochemistry assay suggested that treatment with magnesium decreased the apoptosis rate of brain cells and the expressions of caspase-3, respectively. Decline of the expression of NF-κB and ICAM-1 protein was observed after the treatment of magnesium. CONCLUSION: All the results demonstrated that magnesium may elicit protective effect against radiationinduced brain injury by reducing calcium overload, improving redox and inhibiting cell apoptosis. Moreover, magnesium significantly down-regulated the protein or mRNA levels of NF-κB and ICAM- 1. The findings may provide references for the application of magnesium in clinic for brain injury induced by radiation.
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Lesões Encefálicas/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Cálcio/metabolismo , Caspase 3/metabolismo , Feminino , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Magnésio/metabolismo , Sulfato de Magnésio/farmacologia , Masculino , Malondialdeído/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Lesões por Radiação/metabolismo , Protetores contra Radiação/farmacologia , Ratos Sprague-DawleyRESUMO
Talimogene laherparepvec (TVEC) is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing granulocyte macrophage-colony stimulating factor (GM-CSF) and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB-IV M1a melanoma. However, clinical response assessment can be problematic due to immune-related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients. Over 5 months, TVEC injections were administrated in a median of 20 tumors per patient for 9 median doses prior to biopsy of persistent, indurated nodules. Granulomatous dermatitis with melanophages and melanin pigment incontinence was observed in all samples without evidence of melanoma cells in 4 patients. The fifth patient was rendered melanoma-free by resection of the 1 nodule out of 4 with persistent tumor. Repetitive administration of TVEC or other oncolytic viral immunotherapies mimicking unresolved infection can produce granulomatous inflammation confounding assessment of the degree of tumor response and need for additional TVEC therapy. Tumor biopsies are encouraged after 4 to 6 months of TVEC administration to differentiate melanoma from granulomatous inflammation. Patients with confirmed granulomatous dermatitis replace continued with remained in remission after treatment discontinuation. Inflammatory nodules typically regress spontaneously.
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Dermatite/etiologia , Toxidermias/patologia , Melanoma/tratamento farmacológico , Terapia Viral Oncolítica/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Doença Crônica , Dermatite/patologia , Granuloma/induzido quimicamente , Granuloma/patologia , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Cutâneas/secundário , Melanoma Maligno CutâneoRESUMO
BACKGROUND: We assessed the nutritional risks among children hospitalised with acute burn injuries and their associated clinical outcomes using three nutritional risk screening (NRS) tools: Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGKIDS ), Pediatric Yorkhill Malnutrition Score (PYMS) and Screening Tool for the Assessment for Malnutrition in Pediatrics (STAMP). METHODS: This prospective cross-sectional study was conducted from October 2015 to November 2016, in a regional burn centre. Patients were screened by two independent observers, using the three NRS tools. RESULTS: A total of 100 children aged 3 months to 16.5 years were included. STRONGKIDS identified 16% of patients as having high risk, with being identified 45% by PYMS and 44% by STAMP. After adjustment for confounding factors in multivariate regression analysis, patients in the high-risk group had significantly longer median (SD) lengths of stay [medium versus high risk: STRONGKIDS , 9.5 (6.6) versus 15.0 (24.2) days; PYMS, 8.5 (4.4) versus 13.0 (16.1) days; STAMP, 9.0 (5.7) versus 11.0 (17.4) days] and greater median (SD) weight loss [medium versus high risk: STRONGKIDS, 0.15 (0.8) versus -0.35 (0.8) kg; STAMP, 0.5 (0.7) versus 0 (0.1) kg] than patients in the medium-risk group (P < 0.05). The strengths of agreement in the nutritional risk classification between the two observers were good (κ for STRONGKIDS = 0.61; PYMS = 0.79; STAMP = 0.75) (P < 0.01). CONCLUSIONS: The STRONGKIDS , PYMS and STAMP tools could be useful and practical for determining which hospitalised children with acute burn injuries will need additional nutritional intervention.
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Queimaduras/complicações , Hospitalização/estatística & dados numéricos , Desnutrição/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Avaliação Nutricional , Doença Aguda , Adolescente , Criança , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Desnutrição/etiologia , Programas de Rastreamento/métodos , Estado Nutricional , Estudos Prospectivos , Fatores de RiscoRESUMO
Objective: To analyze the clinical features, diagnosis, and treatment of desquamative interstitial pneumonia(DIP). Methods: The clinical manifestation, radiology, and pathology were analyzed in one patient with DIP in Beijing Hospital following review of the literatures. Results: The patient was a 55-year-old male presented with cough, shortness of breath and hypoxemia.Previous history of smoking and exposure to a variety of metals. A CT scan of the chest revealed diffuse ground-glass densities. A diagnosis of desquamative interstitial pneumonia (DIP) was confirmed by a thoracoscopic open lung biopsy. After treatment with hormone, the condition improved.A total of 66 cases were included in this study, the smoking groupof 20 cases, non-smokers of 46 cases.The smoking group was older than the non-smoking group [(47.5±12.1)years vs (26.1±22.5) years]; the present of chest pain, shortness of breath(4/20 vs 0/46; 8/20 vs 3/46) was higher in smoking group than in non-smoking group, and ground glass opacity in the chest image(15/20 vs 20/46) was also higher in smoking group than in non-smoking group.Pulmonary function showed more diffuse dysfunction(12/14 vs 6/13) in smoking group than in non-smoking group. Conclusions: As a rare disorder, DIP is associated with current or former cigarette smoking and many other risk factors. The clinical presents of non-smoker is atypical.DIP is curable to glucocorticoid and has a good prognosis.There is a possible of recurrence.
Assuntos
Doenças Genéticas Inatas , Doenças Pulmonares Intersticiais , Biópsia , Brônquios , Bronquiolite , Dor no Peito , Tosse , Glucocorticoides , Humanos , Influenza Humana , Pulmão , Masculino , Pessoa de Meia-Idade , Pneumonia por Mycoplasma , Recidiva , Fatores de Risco , Tórax , Tomografia Computadorizada por Raios XRESUMO
Small cell lung cancer (SCLC) is characterized by rapid growth rate and a tendency to metastasize to distinct sites of patients' bodies. The human serine/threonine kinase 33 (STK33) gene has shown its potency as a therapeutic target for prevention of lung carcinomas including non-small cell lung cancer (NSCLC), but its function in the oncogenesis and development of SCLC remains unrevealed. In the current study, it was hypothesized that STK33 played a key role in the proliferation, survival, and invasion of SCLC cells. The expression of STK33 in human SCLC cell lines NCI-H466 and DMS153 was inhibited by specific shRNA. The cell proliferation, cell apoptosis, and cell invasion of the cells were assessed with a series of in vitro assays. To explore the mechanism through which STK33 gene exerted its function in the carcinogenesis of SCLC cells, the effect of STK33 knockdown on the activity of S6K1/RPS6/BAD signaling was detected. Then the results were further confirmed with STK33 inhibitor ML281 and in vivo assays. The results demonstrated that inhibition of STK33 in SCLC cells suppressed the cell proliferation and invasion while induced cell apoptosis. Associated with the change in the phenotypic features, knockdown of STK33 also decreased the phosphorylation of RPS6 and BAD while increased the expression of cleaved caspase 9, indicating that apoptosis induced by STK33 suppression was mediated via mitochondrial pathway. Similar to the results of STK33 knockdown, incubating NCI-H466 cells with STK33 inhibitor also reduced the cell viability by suppressing RPS6/BAD pathways. Additionally, STK33 knockdown also inhibited tumor growth and RPS6/BAD activity in mice models. Findings outlined in our study were different from that in NSCLC to some extent: knockdown of STK33 in SCLC cells induced the apoptosis through mitochondrial pathway but independent of S6K1 function, inferring that the function of STK33 might be cancer type specific.