Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

RADIOIMMUNOTHERAPY IN TREATMENT OF UNRESECTABLE HEPATOMA－A REPORT OF 43 CASES

Forty-three patients with surgically verified unresectable hepatoma had been treated by radioimmunotherapy(RIT)using￣(131)I antiferritin antibidy as a part of multimodality treatment during 1985 - 1990.The shortand long-term responses were compared with those in control group of 39 patients with unresectable hepatoma receiving conventional multimodality treatment in the same period.The rates of the tumor shrinkage,serum AFP decline and sequence resction were 67. 4% (29/43),69.6%(16/23)and 30.2%(13/43)respectively,which were significantly higher than those in contrul group[23.1%(15/39),40.0%(8/20)and 10.3%(4/39),respectively].The 1-,3- and 5-year survival rates were 61.5%,40.4%and 35.4%,respectively,for the RIT group,and 51.2%,20.1% and 15.5% ,respectrely,for the control group.The tumor size,dose of RIT and sequence resection were identified as significant factors (P=0.005,0.025 and 0.006,respectively, with Cox analysis model in 13 influencing factors.The results indicate that RIT was an effective one in multimodality treatment,particularly in the conversion of unresectable to resectable tumor.

Characterization of cancer genomic heterogeneity by next-generation sequencing advances precision medicine in cancer treatment

Cancer is a heterogeneous disease with unique genomic and phenotypic features that differ between individual patients and even among individual tumor regions.In recent years,large-scale genomic studies and new next-generation sequencing technologies have uncovered more scientifc details about tumor heterogeneity,with significant implications for the choice of specific molecular biomarkers and clinical decision making Genomic heterogeneity signifcantly contributes to the generation of a diverse cell population during tumor development and progression,representing a determining factor for variation in tumor treatment response.It has been considered a prominent contributor to therapeutic failure,and increases the likelihood of resistance to future therapies in most common cancers.The understanding of molecular heterogeneity in cancer is a fundamental component of precision oncology,enabling the identification of genomic alteration of key genes and pathways that can be targeted therapeutically.Here,we review the emerging knowledge of tumor genomics and heterogeneity,as well as potential implications for precision medicine in cancer treatment and new therapeutic discoveries.An analysis and interpretation of the TCGA database was included.

Effect of post-bond heat treatment on the microstructure and high temperature mechanical property of a TLP bonded γ'-strengthened co-based single crystal superalloy

Post-bond heat treatment(PBHT) applied to a transient liquid phase(TLP) bonding joint is an effective approach to remove the brittle borides and improve its properties.Herein,we proposed two types of PBHT strategies to obtain a TLP bonded γ'-strengthened Co-based single crystal superalloy,and the microstructural characteristics and tensile properties of the two heat treated joints were compared to identify the optimal PBHT strategy.The evolution of the brittle boride in the joint after the PBHT was studied by using in-situ microscopy.The experimental results allowed to provide a theoretic model to quantitatively evaluate the distribution of the brittle phase after the optimal PBHT and analyze the joint fractures to understand the failure mechanisms.The obtained results revealed that a post-bond solid solution treatment performed to the joint at a high temperature(over 1275℃) could decrease the area fraction of the boride from 7.2 % to 1.4 % and increase the elongation from 1.9 % to 7.8 %.This work emphasizes the relevance of solid solution temperature when a PBHT strategy is applied.