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1.
Front Neurol ; 12: 718032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630289

RESUMO

Intracerebral hemorrhage (ICH) accounts for ~15% of all strokes and is associated with high mortality and disability rates. The systemic inflammation response index (SIRI) is a novel systemic inflammatory marker based on peripheral neutrophil, monocyte, and lymphocyte counts. This study aimed to evaluate the prognostic significance of admission SIRI in patients with spontaneous ICH and compare its predictive ability with that of the neutrophil-to-lymphocyte ratio (NLR). This retrospective study was conducted based on a prospectively collected database of patients with ICH between June 2016 and January 2019. Propensity score matching (PSM) was conducted to adjust for potential imbalances in the clinical parameters. A total of 403 patients were included in the original cohort. The optimal SIRI cut-off value was 2.76. After 1:1 PSM based on potential confounding variables, a new cohort containing 262 patients was established for further analysis. In the original cohort, SIRI served as an independent predictor of 3-month functional outcome [odds ratio (OR), 1.302; 95% CI, 1.120-1.512; p = 0.001] and 1-month mortality (OR, 1.072; 95% CI, 1.020-1.126; p = 0.006), while NLR was independently associated with only 3-month functional outcomes (OR, 1.051; 95% CI, 1.004-1.100; p = 0.031) and not 1-month mortality. The same applied to the PSM cohort. Receiver operating characteristic analyses and predictive models indicated that in most instances, SIRI was superior to NLR and their components in predicting the outcomes of patients with ICH. Our study found that SIRI is determined to be an independent predictive indicator for ICH patients in 3-month functional outcomes and 1-month mortality. The prognostic predictive ability of SIRI was stronger than that of NLR.

2.
J Clin Invest ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591791

RESUMO

Emerging evidence has shown that open reading frames inside lncRNA could encode micropeptides. However, their roles in cellular energy metabolism and tumor progression remain largely unknown. Here, we identified a 94-amino acid-length micropeptide encoded by lncRNA LINC00467 in colorectal cancer. We also characterized its conservation across higher mammals, localization to mitochondria, and the concerted local functions. This peptide enhanced the ATP synthase construction by interacting with the subunit α and γ (ATP5A and ATP5C), increased ATP synthase activity and mitochondrial oxygen consumption rate, and thereby promoted colorectal cancer cell proliferation. Hence, this micropeptide was termed as "ATP synthase associated peptide" (ASAP). Furthermore, loss of ASAP suppressed patient-derived xenograft growth with attenuated ATP synthase activity and mitochondrial ATP production. Clinically, high expression of ASAP and LINC00467 predicted poor prognosis of colorectal cancer patients. Taken together, our findings revealed a colorectal cancer-associated micropeptide as a vital player in mitochondrial metabolism and provided a therapeutic target for colorectal cancer.

3.
Indian J Ophthalmol ; 69(10): 2678-2686, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34571614

RESUMO

Purpose: To describe a practical, self-assembled continuous curvilinear capsulorhexis (CCC) self-training system to facilitate resident self-training and shorten the CCC learning curve. Methods: This was a prospective experimental study that included a total of 600 capsulorhexis cases. A device for CCC practice was self-assembled and used for training and testing. Based on capsulorhexis manipulation experience, three main groups of residents (A, capsulorhexis experience with <50 cases; B, capsulorhexis experience with 400-500 cases; and C, capsulorhexis experience with >1000 cases) were created. Furthermore, based on different capsulorhexis conditions, each main group was divided into four subgroups (1, CCC without an anterior chamber cover and capsulorhexis marker; 2, CCC with an anterior chamber cover without a capsulorhexis marker; 3, CCC with an anterior chamber cover and a capsulorhexis marker; and 4, CCC with an anterior chamber cover and a capsulorhexis marker under 2.5 times magnification). Three CCC-related parameters, including acircularity index (AI), axis ratio (AR), and capsulorhexis time, were statistically evaluated. Results: We compared the differences in study parameters among 50 consecutively completed capsulorhexis cases by one trainee with different capsulorhexis experience in each subgroup. The CCC-related parameter values in subgroups 1 and 4 were significantly different among the three groups (P < 0.001). The capsulorhexis time in subgroup 2 was significantly different among the three groups (P < 0.001). The capsulorhexis time and AI in subgroup 3 were significantly different among the three groups (P < 0.001). Moreover, with increasing manipulation experience (from group A-C), the capsulorhexis time, the AI, and AR tended to decrease. With the help of the CCC marker, in subgroups 3 and 4, the AI and AR were closer to 1.0. Conclusion: This self-assembled CCC self-training system is practical. The CCC marker seems helpful for size specification and centration during self-training.

4.
Cancer Med ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559476

RESUMO

BACKGROUND: A universally acknowledged cancer staging system considering all aspects of the T-, N-, and M-classifications for middle ear squamous cell carcinoma (MESCC) remains absent, limiting the clinical management of MESCC patients. MATERIALS AND METHODS: A total of 214 MESCC patients were extracted from the SEER (the Surveillance, Epidemiology, and End Results) database between 1973 and 2016. The relationships between patient's characteristics and prognoses were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Novel staging schemes for MESCC were designed by adjusted hazard ratio (AHR) modeling method according to the combinations of Stell's T-classification and the eighth AJCC N- and M-classifications, of which performances were evaluated based on five criteria: hazard consistency, hazard discrimination, explained variation, likelihood difference, and balance. RESULTS: T-classification was the most significant prognostic factor for MESCC patients in multivariable analysis (p = 0.021). The N- and M-classifications also had obvious prognostic effect but were not statistically significant by multivariate analysis due to the limited metastasis events. Three novel staging schemes (AHR-Ⅰ-Ⅲ models, different combination of T- and N-classifications) and ST (solely derived from Stell's T-classification) were developed, among which the AHR-Ⅰ staging scheme performed best. CONCLUSIONS: Tumor extension, quantified by Stell's T-classification, is the most significant prognostic factor for MESCC patients. However, our AHR-Ⅰ staging scheme, a comprehensive staging scheme that integrating T-, N-, and M-classifications, might be an optimal option for clinical practitioners to predict MESCC patients' prognosis and make proper clinical decisions.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34477345

RESUMO

BACKGROUND: To determine the thyroid uptake rate by correcting the background and analyse its clinical significance. METHODS: The study included 161 patients with hyperthyroidism. The thyroid uptake rate was calculated by drawing a 100 pixels ROI (Region of Interest) background, above and below the thyroid and correcting the thyroid ROI for background counting. At the same time, the clinical baseline characteristic parameters such as age and thyroid volume etc. of patients with hyperthyroidism were collected. The consistency of 9mTcO4uptake rate before treatment and 131I-uptake rate after treatment, and the correlation between uptake rate of thyroid and baseline characteristic parameters were also analysed. RESULTS: The uptake rate of 99mTcO4 was found positively correlated with 3 h-RAIU, 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity FT3 and FT4, and showed negative correlation with age, effective half-life. (P<0.05). The uptake rate of 131I was found positively correlated with 3 h-RAIU, 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity, FT3, FT4. (P<0.05). In patients with positive thyrotrophin receptor antibody (TRAb), a significant positive correlation between uptake rate of 99mTcO4 and 131I (P<0.05) was observed. There was a high consistency between pre-treatment uptake rate of 99mTcO4 and post-treatment uptake rate of 131I (P = 0.009; W = 0.7). CONCLUSIONS: The corrected thyroid uptake rate is remarkably correlated with clinical characteristic parameters of patients, which can be used to comprehensively evaluate the comprehensive condition of patients with hyperthyroidism.

6.
J Cancer ; 12(19): 5950-5959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476009

RESUMO

Objective: To explore the prognostic value of preoperative albumin to alkaline phosphatase ratio (AAPR) in patients with newly-diagnosed glioblastoma (GBM) and its association with clinical characteristics. Patients and methods: A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2016 to December 31st 2018. X-tile software was applied to determine the optimal cut-off values for AAPR, neutrophil to lymphocyte ratio (NLR), and albumin. Cox regression analyses were applied to evaluate the prognostic value of AAPR in GBM. PSM analysis was conducted to verify the results. Results: A total of 197 and 154 GBM patients were included in original cohort and PSM cohort respectively. The optimal cut-off value for AAPR, NLR, and albumin were 0.56, 4.55 and 42.2 g/L respectively. High AAPR was only significantly related to longer overall survival (OS) (p=0.010) in original cohort. In PSM cohort, no clinical variable was evidently related to the level of AAPR. AAPR was determined to be an independent prognostic indicator in both original cohort (HR=0.599, 95%CI 0.437-0.822, p=0.001) and PSM cohort (HR=0.649, 95%CI 0.459-0.918, p=0.015). Prognostic models including AAPR had better prognostic accuracy than that including albumin. Conclusion: Preoperative AAPR was determined to be an independent risk factor of prognosis in newly-diagnosed GBM patients, and its prognostic ability was stronger than albumin. And PSM analysis also validated the results.

7.
Cancer Cell Int ; 21(1): 430, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399732

RESUMO

BACKGROUND: DDX52 is a type of DEAD/H box RNA helicase that was identified as a novel prostate cancer (PCa) genetic locus and possible causal gene in a European large-scale transcriptome-wide association study. However, the functions of DDX52 in PCa remain undetermined. The c-Myc oncogene plays a crucial role in the development of PCa, but the factors that regulate the activity of c-Myc in PCa are still unknown. METHODS: We determined DDX52 protein levels in PCa tissues using immunohistochemistry (IHC). DDX52 expression and survival outcomes in other PCa cohorts were examined using bioinformatics analysis. The inhibition of DDX52 via RNA interference with shRNA was used to clarify the effects of DDX52 on PCa cell growth in vitro and in vivo. Gene set enrichment analysis and RNA sequencing were used to explore the signaling regulated by DDX52 in PCa. Western blotting and IHC were used to determine the possible DDX52 signaling mechanism in PCa. RESULTS: DDX52 expression was upregulated in PCa tissues. Bioinformatics analysis showed that the level of DDX52 further increased in advanced PCa, with a high DDX52 level indicating a poor outcome. In vitro and in vivo experiments showed that downregulating DDX52 impeded the growth of PCa cells. High DDX52 levels contributed to activating c-Myc signaling in PCa patients and PCa cells. Furthermore, DDX52 expression was regulated by c-Myc and positively correlated with c-Myc expression in PCa. CONCLUSION: DDX52 was overexpressed in PCa tissues in contrast to normal prostate tissues. DDX52 knockdown repressed the growth of PCa cells in vitro and in vivo. Deleting c-Myc inhibited DDX52 expression, which affected the activation of c-Myc signaling.

8.
Cell Res ; 31(10): 1088-1105, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34267352

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

9.
Neurosurg Rev ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241729

RESUMO

This study assesses the effect of extent of resection (EOR) on the longer-term survival and early mortality of elderly patients (≥ 75 years old) with glioblastoma. We used the Surveillance, Epidemiology, and End Results (SEER) database and data from our center to evaluate the effect of EOR on the long-term survival and early mortality of patients with glioblastoma. We included 50 elderly patients (≥ 75 years old) with glioblastoma visiting our hospital. The median overall survival of the patients who underwent a gross total resection, a subtotal resection, and a partial resection were 278, 200, and 83 days, respectively. The multivariate analysis showed that gross total resection (HR: 0.100; 95% CI: 0.015-0.671, p < 0.001) and subtotal reresection (HR: 0.134, 95% CI: 0.022-0.831, p < 0.001) were independent predictors of favorable prognosis when compared with partial resection. The data extracted from the SEER database also indicated that EOR was an independent predictor of OS, CCS, and early mortality. The stratification analysis revealed that gross total resection was the best protective factor of OS, early mortality, and CCS. Radical resection may improve the OS and CCS of glioblastoma patients aged ≥ 75 years and decrease early mortality.

10.
J Stroke Cerebrovasc Dis ; 30(9): 105950, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34214962

RESUMO

BACKGROUND: Redefined hematoma expansion (rHE) including intraventricular hematoma expansion (IVHE) is a new concept in intracerebral hemorrhage (ICH), with better prognostic ability compared to the conventional hematoma expansion. Ultraearly hematoma growth (uHG) and computed tomography angiography (CTA) spot sign are both useful indictors to predict HE and poor clinical outcome. This study aims to explore the clinical characteristics of rHE in retrospective cohort and evaluate the predictive ability of uHG and spot sign in rHE. MATERIALS AND METHODS: This study included nontraumatic spontaneous ICH patients from June 1st 2013 and January 1st 2018 in West China Hospital. Multivariate logistic regression was used to determine risk factors for HE/IVHE/rHE and primary outcomes of ICH patients. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of uHG and spot sign for predicting HE/IVHE/rHE. RESULTS: This retrospective cohort included 469 consecutive patients with ICH. rHE was significantly associated with clinical variables including Glasgow coma scale (GCS), time to initial CT, presence of IVH, hematoma volume, presence of spot sign, and uHG. uHG and spot sign were independent risk factors for rHE. ROC analysis indicated that both uHG (AUC 0.726, 95%CI 0.680-0.773) and spot sign (AUC 0.735, 95%CI 0.686-0.785) possessed high predictive accuracy for rHE. HE and rHE were independent risk factors for 1-month mortality and 3-month functional outcome. CONCLUSIONS: Both uHG and the spot sign were considered to be good predictors for rHE, and the spot sign appeared to have a better predictive accuracy.


Assuntos
Angiografia Cerebral , Hemorragia Cerebral/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Hematoma/diagnóstico por imagem , Idoso , Bases de Dados Factuais , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
11.
Clin Nucl Med ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34132680

RESUMO

ABSTRACT: A 46-year-old asymptomatic woman with a newly detected large pulmonary mass was admitted to our hospital. An ultrasonography-guided needle biopsy was performed based on a suspicion of malignancy, and an ectopic goiter was confirmed pathologically. Laboratory findings were unremarkable, except that thyroid function tests suggested subclinical hyperthyroidism. A 131I whole-body scintigraphy and SPECT/CT were further performed and revealed intense radioiodine uptake in the pulmonary mass, the mediastinal nodule, and thyroid gland. A diagnosis of ectopic pulmonary goiter with normally located thyroid was finally made.

12.
Nat Commun ; 12(1): 3519, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112781

RESUMO

TLR4 signaling plays key roles in the innate immune response to microbial infection. Innate immune cells encounter different mechanical cues in both health and disease to adapt their behaviors. However, the impact of mechanical sensing signals on TLR4 signal-mediated innate immune response remains unclear. Here we show that TLR4 signalling augments macrophage bactericidal activity through the mechanical sensor Piezo1. Bacterial infection or LPS stimulation triggers assembly of the complex of Piezo1 and TLR4 to remodel F-actin organization and augment phagocytosis, mitochondrion-phagosomal ROS production and bacterial clearance and genetic deficiency of Piezo1 results in abrogation of these responses. Mechanistically, LPS stimulates TLR4 to induce Piezo1-mediated calcium influx and consequently activates CaMKII-Mst1/2-Rac axis for pathogen ingestion and killing. Inhibition of CaMKII or knockout of either Mst1/2 or Rac1 results in reduced macrophage bactericidal activity, phenocopying the Piezo1 deficiency. Thus, we conclude that TLR4 drives the innate immune response via Piezo1 providing critical insight for understanding macrophage mechanophysiology and the host response.


Assuntos
Infecções Bacterianas/imunologia , Imunidade Inata , Canais Iônicos/metabolismo , Macrófagos/imunologia , Fagossomos/metabolismo , Receptor 4 Toll-Like/metabolismo , Actinas/metabolismo , Animais , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Citoesqueleto/genética , Citoesqueleto/metabolismo , Infecções por Escherichia coli/imunologia , Transferência Ressonante de Energia de Fluorescência , Células HEK293 , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Canais Iônicos/genética , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Fagocitose/imunologia , Fagossomos/imunologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/imunologia , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
13.
Cancer Gene Ther ; 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059782

RESUMO

Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.

14.
Small ; 17(25): e2100045, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34031977

RESUMO

Luminescence imaging is one of the most effective noninvasive strategies for detection and stratification of inflammation and oxidative stress that are closely related to the pathogenesis of numerous acute and chronic diseases. Herein biocompatible nanoparticles based on a peroxalate ester derived from vitamin E (defined as OVE) are developed. In combination with different fluorophores, OVE can generate luminescence systems with emission wavelengths varying from blue to the near-infrared light in its native and nanoparticle forms, in the presence of hydrogen peroxide (H2 O2 ). The OVE-based nanoprobes exhibit high luminescence signals with extremely long lifetime, upon triggering by inflammatory conditions with abnormally elevated H2 O2 . Activated neutrophils and macrophages can be illuminated by this type of luminescent nanoprobes, with luminescence intensities positively correlated with inflammatory cell counts. In mouse models of peritonitis, alcoholic liver injury, drug-induced acute liver injury, and acute lung injury, the developed luminescence nanoprobes enable precision imaging of inflammation and disease progression. Moreover, tumors expressing a high level of H2 O2 can be shined. Importantly, the OVE-based nanoplatform shows excellent in vitro and in vivo biocompatibility.


Assuntos
Nanopartículas , Neoplasias , Animais , Inflamação , Luminescência , Camundongos , Neoplasias/diagnóstico por imagem , Vitamina E
15.
Cancer Manag Res ; 13: 3259-3269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883939

RESUMO

Objective: To explore the prognostic value of preoperative fibrinogen to albumin ratio (FAR) in patients with glioblastoma (GBM) and its association with clinical characteristics. Patients and Methods: A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2015 to June 31st 2018. Receiver operating characteristic (ROC) curves were performed to determine the optimal cut-off values for fibrinogen, albumin, neutrophil to lymphocyte ratio (NLR), and FAR by calculating the maximum Youden index. Kaplan-Meier curves and Cox regression analyses were applied to evaluate the prognostic value of FAR in GBM. Harrell concordance index (C-index) and Akaike information criterion (AIC) were calculated to compare different prognostic models. Results: A total of 206 GBM patients were included in this research. The optimal cut-off value for fibrinogen, albumin, NLR, and FAR were 2.57, 42.4, 2.28, and 0.068 respectively. High FAR was significantly related to older age, KPS≤80, IDH-1 wildtype, presence of preoperative seizures, higher NLR, and tumor location. In Cox regression analyses, high FAR was significantly associated with poor prognosis. Prognostic models including FAR had the largest C-index and lowest AIC. Conclusion: FAR was determined to be an independent risk factor of prognosis in patients with newly-diagnosed GBM. And the prognostic predictive ability of FAR is stronger than fibrinogen and albumin.

16.
ISA Trans ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33814264

RESUMO

This paper deals with the parameter estimation of Hammerstein-Wiener (H-W) nonlinear systems which have unknown time delay. The linear variable weight particle swarm method is formulated for such time delay systems. This algorithm transforms the nonlinear system identification issue into a function optimization issue in the parameter space, then utilizes the parallel searching ability of the particle swarm optimization and the iterative identification technique to realize the simultaneous estimation of all parameters and the unknown time delay. Finally, parameters in the linear submodule, nonlinear submodule and the time delay are separated from the optimum parameter. Moreover, two illustrative examples are exhibited to evaluate the effectiveness of the proposed method. The simulation results demonstrate that the derived method has fast convergence speed and high estimation accuracy for estimating H-W systems with unknown time delay, and it is applied to the identification of the bed temperature systems.

17.
Chin Neurosurg J ; 7(1): 20, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33795020

RESUMO

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. METHODS: We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. RESULTS: Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0-44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). CONCLUSIONS: These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.

19.
Comput Methods Programs Biomed ; 204: 106047, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33789213

RESUMO

BACKGROUND AND OBJECTIVE: Colon cancer is a fatal disease, and a comprehensive understanding of the tumor microenvironment (TME) could lead to better risk stratification, prognosis prediction, and therapy management. In this paper, we focused on the automatic evaluation of TME in giga-pixel digital histopathology whole-slide images. METHODS: A convolutional neural network is used to recognize nine different content presented in colon cancer whole-slide images. Several implementation details, including the foreground filtering and stain normalization are discussed. Based on the whole-slide segmentation, several TME descriptors are quantified and correlated with the clinical outcome by Kaplan-Meier analysis and Cox regression. Specifically, the stroma, tumor, necrosis, and lymphocyte components are discussed. RESULTS: We validated the method on colon adenocarcinoma cases from The Cancer Genome Atlas project. The result shows that the stroma is an independent predictor of progression-free interval (PFI) after corrected by age and pathological stage, with a hazard ratio of 1.665 (95%CI: 1.110~2.495, p = 0.014). High-level necrosis component and lymphocytes component tend to be correlated with poor PFI, with a hazard ratio of 1.552 (95%CI: 0.943~2.554, p = 0.084) and 1.512 (95%CI: 0.979~2.336, p = 0.062), respectively. CONCLUSIONS: The result reveals the complex role of the tumor microenvironment in colon adenocarcinoma, and the quantified descriptors are potential predictors of disease progression. The method could be considered for risk stratification and targeted therapy and extend to other types of cancer, leading to a better understanding of the tumor microenvironment.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Aprendizado Profundo , Adenocarcinoma/diagnóstico por imagem , Humanos , Microambiente Tumoral
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