Therapeutic perspectives for adult soft tissue sarcoma—updates from the 2022 ASCO annual meeting

At the recent 2022 American Society of Clinical Oncology(ASCO)annual meeting,the latest progress was presented in clinical trials of various therapeutic modalities for adult soft tissue sarcoma(STS),including chemotherapy,targeted therapy,anti-immune checkpoint immunotherapy,and multiple combination treatments(Table 1).Generally,the development of clinical treatments for STS is relatively slow,owing to the complex pathological subtypes of sarcoma and their heterogeneous biological behaviors.Here,we briefly summarize updates from this year’s ASCO meeting and discuss the future therapeutic perspectives for unspecific STS.

The prognostic significance of non-sentinel lymph node metastasis in cutaneous and acral melanoma patients—A multicenter retrospective study

Background:Whether non-sentinel lymph node(SLN)-positive melanoma patients can benefit from completion lymph node dissection(CLND)is still unclear.The current study was performed to identify the prognostic role of nonSLN status in SLN-positive melanoma and to investigate the predictive factors of non-SLN metastasis in acral and cutaneous melanoma patients.Methods:The records of 328 SLN-positive melanoma patients who underwent radical surgery at four cancer centers from September 2009 to August 2017 were reviewed.Clinicopathological data including age,gender,Clark level,Breslow index,ulceration,the number of positive SLNs,non-SLN status,and adjuvant therapy were included for survival analyses.Patients were followed up until death or June 30,2019.Multivariable logistic regression modeling was performed to identify factors associated with non-SLN positivity.Log-rank analysis and Cox regression analysis were used to identify the prognostic factors for disease-free survival(DFS)and overall survival(OS).Results:Among all enrolled patients,220(67.1%)had acral melanoma and 108(32.9%)had cutaneous melanoma.The 5-year DFS and OS rate of the entire cohort was 31.5%and 54.1%,respectively.More than 1 positive SLNs were found in 123(37.5%)patients.Positive non-SLNs were found in 99(30.2%)patients.Patients with positive non-SLNs had significantly worse DFS and OS(log-rank P<0.001).Non-SLN status(P=0.003),number of positive SLNs(P=0.016),and adjuvant therapy(P=0.025)were independent prognostic factors for DFS,while non-SLN status(P=0.002),the Breslow index(P=0.027),Clark level(P=0.006),ulceration(P=0.004),number of positive SLNs(P=0.001),and adjuvant therapy(P=0.007)were independent prognostic factors for OS.The Breslow index(P=0.020),Clark level(P=0.012),and number of positive SLNs(P=0.031)were independently related to positive non-SLNs and could be used to develop more personalized surgical strategy.Conclusions:Non-SLN-positive melanoma patients had worse DFS and OS even after immediate CLND than those with non-SLN-negative melanoma.The Breslow index,Clark level,and number of positive SLNs were independent predictive factors for non-SLN status.

Multi-omics characterization and therapeutic liability of ferroptosis in melanoma

Dear Editor,Ferroptosis,an iron-dependent form of programmed cell deathdriven by excessive lipid peroxidation,1has emerged as,apromising andeffective strategy fortrigering cancer celldeath.2,3Insufficient understanding of the role of ferroptosis in melanomaprogression and the tumor microenvironment(TME)has limitedthe development of ferroptosis-targeted therapy and combina-tions with other therapeutic strategies.

Spatially asymmetric cascade nanocatalysts for enhanced chemodynamic therapy

Chemodynamic therapy(CDT)based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy.However,most of the reported cascade catalytic systems are designed based on symmetric-or co-assembly of multiple catalytic active sites,in which their functions are difficult to perform independently and may interfere with each other.Especially in cascade catalytic system that involves fragile natural-enzymes,the strong oxidation of free-radicals toward natural-enzymes should be carefully considered,and the spatial distribution of the multiple catalytic active sites should be carefully organized to avoid the degradation of the enzyme catalytic activity.Herein,a spatially-asymmetric cascade nanocatalyst is developed for enhanced CDT,which is composed by a Fe_(3)O_(4)head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase(mSiO_(2)-GOx).The mSiO_(2)-GOx subunit could effectively deplete glucose in tumor cells,and meanwhile produce a considerable amount of H_(2)O_(2)for subsequent Fenton reaction under the catalysis of Fe_(3)O_(4)subunit in the tumor microenvironment.Taking the advantage of the spatial isolation of mSiO_(2)-GOx and Fe_(3)O_(4)subunits,the catalysis of GOx and freeradicals generation occur at different domains of the asymmetric nanocomposite,minimizing the strong oxidation of free-radicals toward the activity of GOx at the other side.In addition,direct exposure of Fe_(3)O_(4)subunit without any shelter could further enhance the strong oxidation of free-radicals toward objectives.So,compared with traditional core@shell structure,the long-term stability and efficiency of the asymmetric cascade catalytic for CDT is greatly increased by 138%,thus realizing improved cancer cell killing and tumor restrain efficiency.

COVID-19-associated gastrointestinal and liver injury:clinical features and potential mechanisms

Coronavirus disease-2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The infection is spreading globally and poses a huge threat to human health.Besides common respiratory symptoms,some patients with COVID-19 experience gastrointestinal symptoms,such as diarrhea,nausea,vomiting,and loss of appetite.SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2(ACE2)and there is increasing evidence of a possible fecal–oral transmission route.In addition,there exist multiple abnormalities in liver enzymes.COVID-19-related liver injury may be due to drug-induced liver injury,systemic inflammatory reaction,and hypoxia–ischemia reperfusion injury.The direct toxic attack of SARS-CoV-2 on the liver is still questionable.This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.

下肢急性筋膜室综合征 筋膜切开术必须早做,良好的外科技术非常重要

肢体的急性筋膜室综合征是以无弹性的骨筋膜室室内压升高为特征的外科急症。持续增高的组织内压使毛细血管灌注压低于能够维持组织生存的水平,于是在数小时内就可以发生不可逆转的肌肉和神经损伤。