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Objective: To analyze the risk factors that affect the prognosis of patients with optic neuritis through imaging examinations and clinical data analysis. Methods: 130 patients with optic neuritis admitted to our hospital from February 2018 to February 2022 were selected as the study subjects. They were divided into a poor prognosis group (n = 52) and a good prognosis group (n = 78) based on their prognosis. Imaging examination and clinical data analysis, along with the assessment of the predictive value of statistically significant continuous variables using ROC experiments and risk factors using logistic regression were performed. Results: The results showed that there was no statistically significant difference in general data such as gender and BMI between the two groups (P > .05). Compared with the group with good prognosis, the group with poor prognosis had higher age (34.47 ± 1.58 years vs 35.81 ± 2.60 years), onset to visit interval (1.81 ± 0.40 weeks vs 2.50 ± 0.64 weeks), VCAM-1 (608.70 ± 42.80 ng/mL vs 625.58 ± 35.62 ng/mL), recurrence rate (48.72% vs 69.23%), optic nerve atrophy rate (3.85% vs 15.38%), eye rotation pain rate (28.21% vs 30.77%), and MRI long T2 signal rate (21.79% vs 40.38%). The proportion of MRI T1 enhanced signals was relatively high (17.95% vs 34.62%) (P < .05). Age, the interval between onset and visit time, and AUC of VCAM-1 were 0.657, 0.785, and 0.621, and the optimal cutoff values were 35 years old, 2 weeks old, and 620.29 ng/mL; 95% CI was (0.596 0.738), (0.704 0.852), and (0.532 0.704), P < .05. Conclusion: Age (>35 years old), recurrence (yes), interval between onset and visit (>2 weeks), MRI long T2 signal (yes), and MRI T1 enhanced signal (yes) are all risk factors that affect the prognosis of patients with optic neuritis. Clinical attention should be paid to high-risk populations.
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BACKGROUND: Mesenchymal sarcomas are tumors that originate from mesenchymal tissue. Most mesenchymal sarcomas can be accurately classified, but some are unclassifiable in clinical practice. Molecular detection methods enable patients to benefit from molecular-targeted therapies for many cancers, including lung, breast, and bowel cancers. Further, even unclassified tumors can have therapeutic targets. NTRK gene fusions are sporadic genetic alterations that occur across tumor entities. If NTRK gene fusions are detected, TRK inhibitors can be used regardless of the tumor entity. CASE PRESENTATION: This report describes a case with an unclassifiable mesenchymal sarcoma carrying a neurotrophic tyrosine receptor kinase NTRK1-KHDRBS1 gene fusion that was diagnosed and treated at multiple hospitals. Diagnostic work-up included pathological and immunohistochemical analysis, which excluded angiosarcoma, dendritic cell sarcoma, and pseudomyogenic hemangioendothelioma. The patient achieved a long-term survival without tumor relapse after treatment with crizotinib. CONCLUSIONS: This case will be of significant interest to pathologists because, despite the tumor being unclassified, a molecular target was identified. Although the FDA does not currently approve crizotinib for treatment of patients harboring NTRK gene fusions, this case provides new insights for diagnosis and treatment of mesenchymal sarcomas with NTRK1 gene translocations. Similar to ALKomas, which can be successfully treated using NTRK molecular-targeted therapy, tumors with NTRK gene translocations can be classified as NTRKomas, even when they occur at different organ sites, and with varying histological morphologies, and immunophenotypes.
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Receptor trkA , Sarcoma , Proteínas Adaptadoras de Transdução de Sinal , Crizotinibe/uso terapêutico , Proteínas de Ligação a DNA , Fusão Gênica , Humanos , Recidiva Local de Neoplasia , Proteínas de Fusão Oncogênica/genética , Prognóstico , Proteínas de Ligação a RNA , Receptor trkA/genética , Sarcoma/tratamento farmacológico , Sarcoma/genéticaRESUMO
Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor, typically occurring in middle-aged and elderly individuals. The molecular mutation spectrum of CMPT remains insufficiently explored. Commonly known driver gene alterations include KRAS, BRAF, EGFR, and ALK rearrangement. This report details the clinicopathological features of 2 patients presenting with CMPT as pulmonary nodules during clinical examinations. Microscopic analysis revealed tumors with glandular or papillary structures, consisting of mucinous cells, ciliated columnar cells, and basal cells. Notably, both patients exhibited STRN::ALK fusion, a finding not previously associated with CMPT. STRN::ALK fusion serves as a target for therapy in various tumors, including non-small cell lung cancer, thyroid cancer, and colon cancer. Consequently, we conducted a review of relevant literature, summarizing the clinicopathological and molecular characteristics of CMPT to facilitate further research. Our insights enhance the understanding of this uncommon tumor and contribute to the expansion of its molecular alteration spectrum.
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PURPOSE: IKAROS family zinc finger 3 (IKZF3) is an oncogene involved in different malignancies, particularly in the development and malignant progression of lymphocytes. However, IKZF3 amplification and clinical significance in gastric cancers (GCs) remain unexplored. METHODS: We examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays. RESULTS: IKZF3 amplification was detected in 6.9% (28/404) of all GC patients, with higher rates in intestinal-type gastric cancer (IGC) (11.22%, 22/196) compared to other types (2.88%, 6/208). HER2 amplification was identified in 16.09% (65/404) of all GC patients, with higher rates in IGC (20.92%, 41/196) compared to other types (11.54%, 24/208). Co-amplification of IKZF3 and HER2 was detected in 8.16% (16/196) of IGC patients and in 2.40% (5/208) of other types. IKZF3 amplification showed significant correlation with IGC (P = 0.001) and HER2 amplification (P = 0.0001). IKZF3 amplification exhibited significantly worse disease-free survival (DFS) (P = 0.014) and overall survival (OS) (P = 0.018) in GC patients, particularly in IGC (DFS: P < 0.001; OS: P < 0.001), rather than other types. Cox regression analysis demonstrate IKZF3 amplification as an independent poor prognostic factor in all GCs (P = 0.006, P = 0.004 respectively) and in IGC patients, regardless of stages I-II or III-IV (P = 0.007, P = 0.004 respectively). On the other hand, HER2 amplification was significantly associated with worse DFS (P = 0.008) and OS (P = 0.01) in IGC patients, but not in all GCs and in multivariate analysis. Within the subset of patients with HER2 amplification, those also exhibiting IKZF3 amplification displayed potential poorer prognosis (P = 0.08, P = 0.11 respectively). CONCLUSION: IKZF3 amplification was detected in minority of GC patients, especially in IGC, and was an independent indicator of poor prognosis. Our study, for the first time, found the prognostic value of IKZF3 was superior to HER2 for GC patients.
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Amplificação de Genes , Fator de Transcrição Ikaros , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Fator de Transcrição Ikaros/genética , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Idoso , Adulto , Hibridização in Situ Fluorescente , Idoso de 80 Anos ou mais , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Neoplasias Intestinais/mortalidadeRESUMO
Ribisin A has been shown to have neurotrophic activity. The aim of this study was to evaluate the neuroprotective effect of ribisin A on injured PC12 cells and elucidate its mechanism. In this project, PC12 cells were induced by H2O2 to establish an injury model. After treatment with ribisin A, the neuroprotective mechanism of ribisin A was investigated by methyl tetrazolium (MTT) assay, Enzyme-linked immunosorbent assay (ELISA), flow cytometric analysis, fluorescent probe analysis, and western blot. We found that ribisin A decreased the rate of lactate dehydrogenase (LDH) release, increased cellular superoxide dismutase (SOD) level, decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Ca2+ expression and reactive oxygen species (ROS). Moreover, ribisin A significantly increased mitochondrial membrane potential (MMP) and inhibited apoptosis of PC12 cells. Meanwhile, ribisin A activated the phosphorylation of ERK1/2 and its downstream molecule CREB by upregulating the expression of Trk A and Trk B, the upstream molecules of the ERK signaling pathway.
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Catecóis , Peróxido de Hidrogênio , Fármacos Neuroprotetores , Ratos , Animais , Células PC12 , Peróxido de Hidrogênio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Fármacos Neuroprotetores/farmacologia , Apoptose , Estresse Oxidativo , Sobrevivência CelularRESUMO
Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate biologic potential, which occurs mostly in the lung and abdomen cavity of children and young adults. Uterine IMTs are rare. Herein, we presented clinicopathologic features of 4 uterine IMTs. All four patients were initially diagnosed as leiomyosarcoma by other hospitals and corrected to uterine IMT after pathological consultation. Patient age ranged from 44 to 64 years old. Two cases demonstrated multiple masses. Microscopically, three tumors were composed of fascicular spindled cells with eosinophilic cytoplasm, and the other one was densely composed of spindled and epithelioid cells with bizarre and multinucleated cells. Tumor cells showed variable nuclear atypia, ranging from mild to severe. Prominent inflammatory cell infiltration was found in one case, and necrosis in two tumors. Immunochemistry staining revealed expression of smooth muscle markers in all four tumors, including a-SMA and desmin. Three tumors were positive for ALK protein expression. FISH analysis demonstrated ROS1 rearrangement in one tumor and ALK rearrangement in the other 3 tumors. NGS analysis showed novel NUDCD3-ROS1 and NRP2-ALK fusions in two tumors and TNS1-ALK fusion in the other two tumors. Gene aberrations involving p53 signaling pathway were identified in all four cases. All patients received surgery as primary treatment, and one had neoadjuvant chemotherapy. Three patients recurred within 12 months, and the other one recurred after 7 years. Patients with recurrence were treated with a combination of chemotherapy, targeted therapy, or surgery. In conclusion, the diagnosis of uterine IMTs can be challenging. Ancillary studies including ALK IHC, FISH, and NGS are helpful to establish diagnosis and to discover novel gene rearrangement potentially for targeted therapy.
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Neoplasias , Proteínas Tirosina Quinases , Feminino , Humanos , Quinase do Linfoma Anaplásico/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Útero , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análiseRESUMO
This research aimed to establish the gas chromatography (GC) fingerprints and examine the immunomodulatory activity of the rhizome of Menispermum dauricum polysaccharides. In this study, the preparation conditions were optimized by the response surface method (RSM). GC is an effective and sensitive technique employed to measure the composition of monosaccharides; the GC fingerprints of total polysaccharides from 10 batches of the rhizome of M. dauricum (tMDP) were established, and chemometrics methods were adopted to examine the differences and similarities of tMDP from distinct regions. The similarity evaluation illustrated that the polysaccharides derived from the rhizome of M. dauricum from different origins were highly similar. The results of principal components analysis (PCA) illustrated that all the tMDPs may be integrated into one group within the 95% confidence interval, but the rhizome of M. dauricum from different origins could also be distinguished in the plot of PCA scores. Then, the major bioactive fraction MDP was purified and obtained by column chromatography. Our previous study showed that MDP exhibited significant immunomodulatory activity, but the mechanism of the in vitro immunomodulatory activity of MDP is unclear. The macrophage activation induced by MDP was abolished when Toll-like receptor 4 (TLR4) signaling was knocked down by the TLR4 inhibitor. Furthermore, western blot analysis illustrated that MDP activated RAW264.7 cells through MAPKs and NFκB pathways induced by TLR4. This research offers a theoretical foundation for quality control and additional study as a potential immunomodulator of MDP.
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Alcaloides , Menispermum , Alcaloides/análise , Menispermum/química , Receptor 4 Toll-Like/análise , Rizoma/química , Polissacarídeos/farmacologia , Cromatografia GasosaRESUMO
BACKGROUND: Former single center studies indicated that HER2 assessment with two primary tumor blocks (dual block HER2 assessment) could be an efficient and practical approach to overcome the adverse impact of heterogeneity and acquire a HER2 positive rate in gastric cancer (GC). This multicenter prospective clinical trial (NCT02843412) was launched to verify its value and generality. METHODS: A total of 3806 participants with primary GCs have been enrolled from 8 hospitals in China. Two primary tumor blocks were selected and recorded as block 1 and block 2 after histological evaluation. An HER2 (4B5) rabbit monoclonal antibody was used for the immunohistochemistry (IHC) analysis. RESULTS: In total patients, HER2 IHC positive (3+) rate with dual block assessment (9.4%) was higher than that with single block assessment (block 1: 7.8%, block 2: 7.8%) (P < 0.001). Compared with single-block assessment, dual-block assessment increased the positive rate by approximate 20%. Similarly, HER2 equivocal (2+) rate was increased in dual block assessment (25.8%), which was higher than that in single block assessment (block 1: 20.3%, block 2: 20.9%) (P < 0.001). Conversely, dual block assessment demonstrated a lower HER2 negative (0/1+) rate (64.8%) than single block assessment (block1: 71.9%, block 2: 71.3%) (P < 0.001). These findings were also confirmed in individual hospitals. CONCLUSIONS: Dual block HER2 assessment effectively increased HER2 IHC positive rate in resected specimens of GC. We recommended dual block HER2 assessment be promoted in routine clinical practice in GC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02843412 . Registered 1 July 2016 - Retrospectively registered.
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Neoplasias Gástricas , Biomarcadores Tumorais , China , Humanos , Imuno-Histoquímica , Estudos Prospectivos , Receptor ErbB-2 , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: Familial gastrointestinal stromal tumors (GISTs) is a rare autosomal dominant disorder characterized by an array of clinical manifestations. Only 35 kindreds with germline KIT mutations and six with germline PDGFRA mutations have been reported so far. It is often characterized by a series of manifestations, such as multiple lesions and hyperpigmentation. However, the effect of imatinib treatment in these patients is still uncertain. CASE SUMMARY: Here, we report two patients (father and daughter) in a Chinese family (for the first time) with germline KIT mutation, and described their pathology, genetics and clinical manifestations. A 25-year-old Chinese woman went to hospital because of abdominal pain, and computed tomography showed multiple tumors in the small intestine. Small pigmented spots appeared on the skin within a few months after birth. Her father also had multiple pigmented spots and a history of multifocal GISTs. Multiple GISTs associated with diffuse interstitial Cajal cells (ICCs) hyperplasia were positive for CD117 and DOG-1. Gene sequencing revealed a germline mutation at codon 560 of exon 11 (p.V560G) of KIT gene in these two patients. Imatinib therapy showed the long-lasting disease stability after resection. Remarkably, the hypopigmentation of the skin could also be observed. Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient. CONCLUSION: Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT/PDGFRA mutation, hyperpigmentation and family history.
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AIMS: HER2 and osteopontin (OPN) are both important biomarkers in gastric cancer (GC). The relationships between them remain to be revealed. The purpose of this study is to explore the role of OPN in epithelial-mesenchymal transition (EMT) in HER2 positive GCs. METHODS: Nanostring analysis was used to compare the mRNA levels of 730 cancer related genes between paired HER2 3+ and non-3+ areas in GC patients. Immunohistochemistry (IHC) staining was performed to analyze the expression levels of OPN, as well as EMT markers including E-cad, N-cad, twist and vimentin in both areas. To further verify the role of OPN in EMT, the expression levels of OPN and EMT markers, tumor invasion/migration were analyzed after down-regulating HER2 and OPN in GC cell lines MKN-45 and N-87. RESULTS: Nanostring analysis identified 8 differential expression genes between HER2 3+ and non-3+ areas. Among them, the expression level of OPN was positively correlated with that of HER2. In GC specimens, OPN showed higher expression level in HER2 3+ areas where higher E-cad expression levels and lower N-cad and twist levels were also found. After knocking down OPN and HER2 by siRNA, both cell lines show decreased invasion/migration abilities, along with the down-regulation of the EMT phenotype, supporting by the decrease of E-cad, and the increase of N-cad and twist at both mRNA and protein levels. In addition, HER2 knock-down lead to a dramatic decrease of OPN expression. CONCLUSIONS: These findings indicate that HER2 may promote EMT via the regulation of OPN in GCs.
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Transição Epitelial-Mesenquimal , Osteopontina/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Osteopontina/genética , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
In the present study, we aimed to investigate the clinical and prognostic values of CDK4 amplification and improve the risk stratification in patients with esophageal squamous cell carcinoma. CDK4 amplification was analyzed by fluorescence in situ hybridization using tissue microarray consisting of representative tissues of 520 patients with esophageal squamous cell carcinoma, and its correlation with clinicopathological features and clinical outcomes were evaluated. CDK4 amplification was found in 8.5% (44/520) of patients with esophageal squamous cell carcinoma. CDK4 amplification was negatively correlated with disease progression (P = 0.003) and death (P = 0.006). Patients with CDK4 amplification showed a significantly better disease-free survival (P = 0.016) and overall survival (P = 0.023) compared with those patients without CDK4 amplification. When patients were further stratified into I-II stage groups and III-IV stage groups, CDK4 amplification was significantly associated with both better disease-free survival (P = 0.023) and overall survival (P = 0.025) in the I-II stage group rather than the III-IV stage group. On univariate and multivariate analysis, invasive depth and CDK4 amplification were associated with disease-free survival and overall survival. Taken together, CDK4 amplification was identified as an independent prognostic factor for survival, which could be incorporated into the tumor-node-metastasis staging system to refine risk stratification of patients with esophageal squamous cell carcinoma.
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BACKGROUND: G protein-coupled receptors (GPCRs) are involved in several signaling pathways. However, the roles of many GPCRs in tumor oncogenesis and progression are not fully understood. In our previous study, we concluded that the absence of Gpr110 decelerates the development of liver brosis/cirrhosis into tumorigenesis. In our current study, the role of GPR110 in the oncogenesis and progression of lung cancer was observed. METHODS: After collecting tumor tissues from lung cancer patients, the expression of GPR110 was analyzed by both Western blotting and real-time PCR. Immunofluorescence was used to observe GPR110 expression in human lung cancer cells. A CCK8 kit was used to analyze the proliferation of human lung cancer cells transfected with Gpr110. Changes in cell migration were evaluated with wound healing and Transwell assays. A nude mouse xenograft model was constructed. Lung cancer model was induced in Gpr110-/- mice with urethane. RESULTS: GPR110 mRNA and protein expression was significantly higher in lung cancer tissue. GPR110 was barely expressed in H460, A549, H1299, and SPC-A1 cells, but its expression in PC-9 and QG56 cells was significantly higher. Overexpression of GPR110 promoted the proliferation and cell aggregation of H1299 cells and H1299 cell migration was also enhanced. Overexpression of GPR110 in H1299 cells significantly promoted tumor development in the nude mice tumor xenograft model. There was no statistical significance between the Gpr110+/+ and Gpr110-/- mice despite the lesions in the Gpr110-/- mice group decreasing at 35 and 40 weeks after the initial injection of urethane. CONCLUSIONS: Our findings indicate that GPR110 promotes the progression of lung cancer through accelerating cell proliferation and migration.
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BACKGROUND: Gastric cancer (GC) is the second most frequent cause of cancer deaths worldwide. c-Met, a receptor tyrosine kinase, transduces signals from extracellular growth factors. c-Met-targeted therapeutics hold a great potential in treating gastric and related cancers, and a precise evaluation of c-Met expression is a prerequisite for subsequent treatment. METHODS: We compared the sensitivity between one and two paraffin blocks in evaluating c-Met expression in GC subjects by immunohistochemistry (IHC). A total of 365 GC patients were divided into cohort 1 (n = 206) for the one tumor tissue paraffin block test and cohort 2 (n = 159) for the dual tumor tissue paraffin block test. In the dual blocks group, we investigated the results from two different paraffin blocks, then we used the higher one as the final score. RESULTS: Inconsistent c-Met expression in the dual paraffin blocks group occurred in 29 (18.2%) cases. The pooled data in cohort 1 and cohort 2 indicate that when using results from dual paraffin blocks, the c-Met positive (3+) rate of GC testing could be promoted. CONCLUSION: In GC, using dual tumor tissue paraffin blocks instead of one tumor tissue paraffin block is an efficient, economical and practical method of minimizing the false-negative rate of c-Met status assessment by IHC.
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A 65-year-old man was diagnosed with hepatocellular carcinoma 4 years ago, for which he underwent interventional therapy and radiofrequency ablation after the right lobe partial hepatectomy. He was doing well, and an FDG PET/CT scan performed 1 year earlier did not reveal any hypermetabolic lesions. However, on recent examination, a soft tissue mass inside the oral cavity was found. 18F-FDG PET/CT imaging was performed to evaluate the possible metastasis. The images showed that the oral lesion was hypermetabolic. The pathology after biopsy confirmed oral metastasis from hepatocellular carcinoma.
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Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Bucais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Carcinoma Hepatocelular/patologia , Fluordesoxiglucose F18 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Neoplasias Bucais/secundário , Imagem Multimodal , Compostos RadiofarmacêuticosRESUMO
A 66-year-old woman presented with abdominal pain for 1 month. Ultrasonography displayed multiple hepatic masses that were thought as metastases. FDG PET/CT was performed to assess the nature of these masses and to search primary malignancy. The images showed elevated FDG activity in the partially calcified hypodense lesions in the liver without abnormality elsewhere. The lesions were subsequently confirmed as primary extraosseous osteosarcoma in the liver. The patient received liver transplantation. Six months later, her CA-125 was significantly increased. The follow-up PET/CT scan demonstrated the widespread metastases.
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Neoplasias Hepáticas/diagnóstico por imagem , Osteossarcoma/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Osteossarcoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos RadiofarmacêuticosRESUMO
A 52-year-old man presented with chest distress and low back pain for 1 month. CT examination displayed a thymic tumor with the metastases to bilateral lungs as well as mediastinal and bilateral hilar lymph nodes. To evaluate the involved extent of the disease, F-FDG PET/CT scan was carried out, which showed that in addition to the thymic mass, multiple foci of abnormally increased FDG activity in the bilateral lungs, neck and chest lymph nodes, and bones were observed. Finally, the biopsy of the mass confirmed the diagnosis of thymic small cell neuroendocrine carcinoma.
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Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma de Células Pequenas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Timo/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Compostos RadiofarmacêuticosRESUMO
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by an autoimmune-mediated loss of insulin secreting ß-cells. Each B lymphocyte clone that escapes immune tolerance produces a specific antibody. No specific treatment against autoantibodies is available for autoimmune diseases. We have developed a strategy to produce an antiserum against autoantibodies for the treatment of T1DM. Non-obese diabetic (NOD) but not Balb/c mouse serum contains autoantibodies. Antisera were produced by immunizing Balb/c mice with affinity-purified IgG from NOD or BALB/c mice along with the immune adjuvant (hereafter, NIgG or BIgG, respectively). A bolus administration of NIgG significantly reduced serum autoantibodies, autoantibody-positive B lymphocytes in the spleens of NOD mice, mortality and morbidity of diabetes, blood glucose and islet immune infiltration, whereas it increased islet mass in NOD mice for at least 26 weeks. NIgG antiserum treatment has no significant effect on CD3(+), CD4(+) or CD8(+) T cells and B220(+) or CD19(+) B cells. BIgG also imparted a moderate therapeutic effect, although it was considerably lower than that of NIgG. NIgG did not cross-react with allogeneic serum. NIgG showed no effect on Balb/c mice. The results show the feasibility of producing antiserum against autoantibodies to prevent and treat autoimmune-induced T1DM with a single bolus administration.
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Autoanticorpos/farmacologia , Linfócitos B/imunologia , Diabetes Mellitus Tipo 1/terapia , Imunoglobulina G/farmacologia , Ilhotas Pancreáticas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Linfócitos B/patologia , Glicemia/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Feminino , Humanos , Imunização , Ilhotas Pancreáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Baço/imunologia , Baço/patologia , Análise de Sobrevida , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
BACKGROUND: This study investigated the efficacy and safety of a new treatment strategy of combining panitumumab and bevacizumab, plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) versus FOLFIRI alone as second-line chemotherapy for metastatic colorectal cancer (mCRC) patients with known V-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) mutation status. METHODS: Patients with mCRC who had known KRAS tumor status and unsuccessful previous oxaliplatin-based chemotherapy were included in the study. They were randomly assigned to two groups to receive panitumumab and bevacizumab plus FOLFIRI, or FOLFIRI alone. In panitumumab and bevacizumab plus FOLFIRI group, patients were given 4 mg/kg panitumumab and bevacizumab plus FOLFIRI every 2 weeks. RESULTS: In all, 65 patients were assigned to panitumumab and bevacizumab plus FOLFIRI group, and 77 to FOLFIRI alone group. For WT KRAS patients, the median progression-free survival (PFS) was 5.7 months (95% confidence interval [CI], 2.4-7.5 months) for panitumumab and bevacizumab plus FOLFIRI and 3.8 months (95% CI, 3.0-6.7 months) for FOLFIRI alone; median overall survival (OS) was 15.2 months (95% CI, 8.9-19.7 months) for panitumumab and bevacizumab plus FOLFIRI and 11.0 months (95% CI, 8.2-15.4 months) for FOLFIRI alone. For MU KRAS patients, median PFS was 5.1 months (95% CI, 2.7-10.2 months) for panitumumab and bevacizumab plus FOLFIRI and 4.1 months (95% CI, 2.5-8.4 months) for FOLFIRI alone; median OS was 12.8 months (95% CI, 7.8-15.8 months) for panitumumab and bevacizumab plus FOLFIRI and 10.5 months (95% CI, 6.1-15.3 months) for FOLFIRI alone. Grade 3 and 4 adverse events were associated with panitumumab and bevacizumab plus FOLFIRI but tolerable among patients. CONCLUSION: Patients with mCRC can be safely and efficiently treated with second-line chemotherapy of combining panitumumab and bevacizumab plus FOLFIRI, despite their KRAS mutation status.
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PURPOSE: Both borneol and danshensu are bioactive substances derived from traditional Chinese medicine. In this paper, the effect of borneol on the distribution of danshensu to the eyes in rabbits via oral administration was investigated. METHODS: The rabbits were injected danshensu (1.0 g/kg) into the auris dextra vein 15 min after intragastric administration of borneol and the danshensu concentrations in plasma, aqueous humor, and vitreous humor were measured by high-performance liquid chromatography. Draize test was used to examine the eye irritation. RESULTS: Compared with the administration of danshensu alone, danshensu concentrations co-administrated with borneol in plasma were between 60.99 and 722.90 microg/ml. Peak times (T(max)) in both groups appeared at 0 min; however, compared with the control group, the values were not statistically significant although they differ (P > 0.05). The concentrations of danshensu in aqueous humor and vitreous humor in test group are higher than that in control group. The difference was statistically significant (P < 0.05). T(max) in both groups appeared at 25 min. Neither irritation nor inflammatory reaction was found during the examinations. CONCLUSION: The results suggest that the promoting effect of borneol on the permeability of drugs through the blood-ocular barrier in vivo is obvious, which indicates that borneol has the potential to be used as an ocular penetration enhancer.