Correlation Between Apparent Diffusion Coefficient and IDH-1/1p19q Genotype of Glioma / 肿瘤防治研究

Objective To investigate the correlation between ADC value and glioma IDH-1/1p19q genotype. Methods The MRI features and molecular pathological results of 69 patients with pathologically confirmed diagnosis of WHO grade Ⅱ/Ⅲ glioma between March 2013 and December 2020 were retrospectively analyzed. The diagnostic performance of ADC values on glioma genotypes (IDH-1, 1p19q) was evaluated using the ROC curve of the subjects' working characteristics. Results The ADCmean, ADCmin, rADCmean, and rADCmin in the IDH-1 mutation group were significantly higher than those in the IDH-1 wild group (P < 0.05, P < 0.01, P < 0.05, P < 0.01). The use of the rADCmin threshold (0.979×103mm2/s) had the highest efficacy (AUC=0.770) for diagnosis of IDH-1 mutant and IDH-1 wild-type gliomas as well as sensitivity and specificity of 84.61% and 59.09%, respectively. Conclusion ADC can be used as an imaging biomarker for noninvasive prediction of IDH-1 mutant and wild-type Ⅱ /Ⅲ gliomas.

Advances in Combined Immunotherapy for Triple Negative Breast Cancer / 肿瘤防治研究

The triple-negative breast cancer has a relatively poor prognosis with limited therapeutic options. This subtype is highly immunogenetic and exhibits rich tumor infiltrated lymphocytes in the tumor microenvironment. However, immunotherapy alone is less effective as compared with the doublet of chemotherapy and immunotherapy in TNBC. The efficacy in early recurrence settings of mTNBC exceeds that in heavily treated subgroups. Meanwhile, other combinations including anti-angiogenesis, immune modulators, and PARPi elicit a promising effect. Herein, this paper reviews the progress of efficacy, safety, and the outlook in the immunotherapy of TNBC disease.

Target-responsive subcellular catabolism analysis for early-stage antibody-drug conjugates screening and assessment

Events including antibody‒antigen affinity, internalization, trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody-drug conjugate (ADC) catabolism and hence the toxicity. Nevertheless, an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking. Considering the plethora of ADC candidates under development, we developed a target-responsive subcellular catabolism (TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest. We firstly applied TARSC to study the commercial T-DM1 and the biosimilar. We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences. Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further

The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems

As one of the most important components of caveolae, caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways, and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction. In recent years, the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored. In addition, the interplay between caveolin-1 and nano-drugs is bidirectional. Caveolin-1 could determine the intracellular biofate of specific nano-drugs, preventing from lysosomal degradation, and facilitate them penetrate into deeper site of tumors by transcytosis; while some nanocarriers could also affect caveolin-1 levels in tumor cells, thereby changing certain biophysical function of cells. This article reviews the role of caveolin-1 in tumor prognosis, chemotherapeutic drug resistance, antibody drug sensitivity, and nano-drug delivery, providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

Role of diffusion: weighted magnetic resonance imaging in evaluation of renal masses

Background: Diffusion-weighted magnetic resonance imaging (DWI) is a valuable tool to narrow down the differential diagnosis of renal masses. Studies have shown that benign renal masses have higher Apparent diffusion coefficient (ADC) value than malignant renal masses. Aim of study was to evaluate the role of diffusion-weighted magnetic resonance imaging in the characterization of renal masses.Methods: The study was conducted in department of Radio diagnosis at ABVIMS and Dr. RML Hospital, New Delhi between June 2017 to March 2019. This was a cross-sectional observational study comprising of 28 patients. Patients found to have renal mass on ultrasound and computed tomography (CT) were evaluated further on 3T siemens Magnetic resonance imaging (MRI) scanner. In addition to routine sequences, DWI using b value of 0,500,1000 s/mm2 sequence was used to study to differentiate benign and malignant renal masses.Results: Of a total of 28 cases, the most common malignant mass was renal cell carcinoma (RCC). Angiomyolipoma (AML) was the most common benign masses. DWI showed low ADC values in most of the malignant masses and high ADC values in most of the benign masses. The cut-off level of ADC value for differentiation among benign and malignant renal masses was 1.08×10-3 mm2/s. DWI-MR findings were correlated with histopathological diagnosis.Conclusion: DWI with ADC measurements are a non-invasive, problem solving tool for characterization of renal masses helping to differentiate malignant from benign masses.

Use of MRI Apparent Diffusion Coefficient to Noninvasively Differentiate between the Histologic Grades of Meningioma.

It is well known in the literature that Apparent Diffusion Coefficient (ADC) obtained during diffusion-weighted MRI of brain is sensitive in detecting and differentiating low-grade and aggressive meningiomas. However, other studies establish no correlation between mean-ADC and ultimate classification as benign, atypical or malignant. We wanted to assess the correlation between, A. mean of MRI Apparent Diffusion Coefficient (mean-ADC) and B. meningioma biomarker Ki-67 proliferation index, in cases of both low-grade and aggressive meningioma. We also wanted to assess the sensitivity of mean-ADC for diagnosing an aggressive meningioma.METHODSWe analysed 66 surgically treated meningioma patients with complete histopathology report (HPR) in Government Medical College, Kozhikode during the period of study (Nov-2017-Oct-2018), also having a pre-operative mean-ADC value during Diffusion Weighted Imaging (DWI) investigation at the same centre. For the latter, a standard MRI brain protocol including diffusion imaging was conducted and ADC map was generated. Regions of interest (ROIs) were manually drawn within the tumour on ADC map and mean-ADC values were measured.RESULTSUsing Pearson correlation coefficient, we found a significant negative correlation between Ki-67 proliferation index and mean-ADC in meningioma cases. We also calculate 0.79 x 10-3 mm2/s being a reasonable mean-ADC cut-off value due to its sensitivity of 84% and specificity of 77% in differentiating between typical and atypical meningiomas.CONCLUSIONSThe non-invasive calculation of mean-ADC is a valid diagnostic tool. Further, mean ADC can be used as a good test to differentiate typical and atypical meningiomas. The latter is a particularly valid conclusion, since there were few results from conventional MRI studies to differentiate between various typical and atypical meningiomas.

Evaluation and prediction of therapeutic response to neoadjuvant androgen deprivation therapy for prostate cancer by diffusion weighted imaging / 中华泌尿外科杂志

Objective To evaluate the effect of neoadjuvant androgen deprivation therapy (ADT) for prostate cancer on diffusion weighted imaging base on the pathological results after radical prostatectomy.Methods Medical records of 33 patients diagnosed with prostate cancer and treated with neoadjuvant androgen deprivation therapy and radical prostatectomy between January 2016 and September 2019 at Peking University First Hospital were retrospectively reviewed.Average age of patients was 67.7 (49-81) years old.All of the patients underwent prostate MRI examination before and after neoadjuvant ADT.Results Mean prostate volume after neoadjuvant ADT is 28.5 (6.25-113.76) em3,which decreased significantly by therapy (Z =-4.458,P ＜ 0.05).Apparent diffusion coefficient (ADC) values increased significantly in tumor (1.070 ± 0.325) vs.(0.828 ± 0.291) × 10-3 mm2/s (P ＜ 0.001) and decreased in benign prostatic tissue (P ＜ 0.05).Relative changes in ADC differed significantly between low-median level ISUP group and high level ISUP group (0.315 ± 0.173) vs.(0.164 ± 0.224) × 10-3 mm2/s (P ＜ 0.05),as well as obvious reaction group and focal reaction group(0.278 ± 0.21) vs.(0.094 ± 0.119) × 10-3 mm2/s (P ＜ 0.05).Conclusions There were significant,quantitative measurable changes of ADC value in prostate cancer after neoadjuvant ADT.DWI can be used to assess the efficacy of neoadjuvant ADT for prostate cancer as well as predicting pathological features.

Current LC-MS-based strategies for characterization and quantification of antibody-drug conjugates / 药物分析学报

The past few years have witnessed enormous progresses in the development of antibody-drug conju-gates (ADCs). Consequently, comprehensive analysis of ADCs in biological systems is critical in sup-porting discovery, development and evaluation of these agents. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a promising and versatile tool for ADC analysis across a wide range of scenarios, owing to its multiplexing ability, rapid method development, as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high, molecular resolution. However, despite this tremendous potential, challenges persist due to the high complexity in both the ADC molecules and the related biological systems. This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.

Coeficiente de difusión aparente en tejido encefálico: valores de normalidad en población colombiana clínicamente sana / Apparent diffusion coefficient in brain tissue: values of normality in clinically healthy colombian population

Resumen Introducción: Las secuencias de difusión en resonancia magnética, incluido el coeficiente de difusión aparente (ADC), representan una herramienta fundamental para el radiólogo en el diagnóstico clínico. Sin embargo, no existe estandarización para las medidas entre los límites normales o un rango de valores normales del ADC. Objetivo: Determinar valores normales del ADC en el tejido encefálico para la población clínica y radiológicamente sana. Métodos: Estudio de corte transversal sobre datos retrospectivos, se midieron valores del ADC para 21 regiones encefálicas (sustancia gris frontal, parietal y temporal, sustancia blanca frontal y parietal, núcleo caudado, putamen, tálamo, cápsula interna, hemisferios cerebelosos bilateralmente y puente del tallo cerebral) en 90 sujetos clínica y radiológicamente sanos, en dos clínicas privadas de Bogotá. Resultados: Valores normales del ADC, en población clínica y radiológicamente sana, en 21 territorios encefálicos, análisis comparativo de los resultados según el sexo y edad de los pacientes, y correlación entre las mediciones realizadas por dos investigadores. Conclusiones: Los hallazgos sirven como referencia para la población colombiana y latinoamericana normal, establecen un punto de comparación para la evaluación de patologías intracraneanas, y abre la posibilidad a desarrollar nuevos proyectos de investigación que busquen determinar valores de ADC en población enferma.

Abstract Introduction: The diffusion sequences in magnetic resonance, including the apparent diffusion coefficient (ADC), represent a fundamental tool for the radiologist in the clinical diagnosis. However, there is no standardization for measurements between normal limits or a range of normal ADC values. Objective: To determine normal ADC values ​​in the brain tissue for the clinical and radiologically healthy population. Methods: Cross-sectional study on retrospective data, ADC values ​​were measured for 21 encephalic regions (frontal gray, parietal and temporal substance, frontal and parietal white matter, caudate nucleus, putamen, thalamus, internal capsule, cerebellar hemispheres bilaterally and bridge of the brainstem) in 90 clinically and radiologically healthy subjects, in two private clinics in Bogotá. Results: Normal ADC values, in a clinical and radiologically healthy population, in 21 encephalic territories, comparative analysis of the results according to the sex and age of the patients, and correlation between the measurements made by two researchers. Conclusions: The findings serve as a reference for the Colombian and normal Latin American population, establish a point of comparison for the evaluation of intracranial pathologies, and open the possibility to develop new research projects that seek to determine ADC values ​​in sick population.

Discursos sobre educação física escolar e o protagonismo da midiatização esportiva / Discourses on school physical education and the protagonism of sports mediatization / Discursos sobre educación física escolar y el protagonismo de la mediatización deportiva

A pesquisa desenvolve reflexões sobre sentidos enunciados em reportagens exibidas no programa televisivo Esporte Espetacular durante o mês de janeiro de 2017. O conjunto enunciativo investigado apresentou como as aulas de educação física escolar são desenvolvidas em quatro países: Brasil, Inglaterra, Estados Unidos e Japão. Metodologicamente, a Análise de Discurso Crítica (ADC) proporcionou a identificação das representações relacionais entre esporte e educação, e as estratégias discursivas construídas nessas reportagens. A reflexão sobre o texto/imagem como discurso social e a potência das representações esportivas como fenômeno discursivo e ideológico, torna a enunciação esportiva o currículo majoritário no ambiente educacional relativo às aulas de educação física escolar.

The research develops reflections on the meanings expressed in reports presented in the television program Esporte Espetacular during the month of January, 2017. The enunciative set investigated presented how the school physical education classes are developed in four countries: Brazil, England, United States and Japan. Methodologically, the Critical Discourse Analysis (ADC) provided the identification of the relational representations between sport and education, and the discursive strategies constructed in these reports. The reflection on the text/image as a social discourse and the power of sports representations as a discursive and ideological phenomenon, makes sports enunciation the main curriculum in the educational environment related to school physical education classes.

La investigación desarrolla reflexiones sobre sentidos enunciados en reportajes exhibidos en el programa televisivo Esporte Espectacular durante el mes de enero de 2017. El conjunto enunciativo investigado presentó cómo las clases de educación física escolar se desarrollan en cuatro países: Brasil, Inglaterra, Estados Unidos y Japón. Metodológicamente, el Análisis de Discurso Crítico (ADC) proporcionó la identificación de las representaciones relacionales entre deporte y educación, y las estrategias discursivas construidas en esos reportajes. La reflexión sobre el texto/imagen como discurso social y la potencia de las representaciones deportivas como fenómeno discursivo e ideológico, hace la enunciación deportiva el currículo mayoritario en el ambiente educativo relativo a las clases de educación física escolar.