Advances in extracellular vesicle-based combination therapies for spinal cord injury

Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.

Nanomedicine-based combination therapies for overcoming temozolomide resistance in glioblastomas

Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.

China's foreign aid for global poverty alleviation:artemisinin-based combination therapies against malaria in Togo

From providing funds for the global fight against infectious diseases,to actively participating in global health security actions,to strengthening mutual cooperation in the field of health,and providing medical treatment,training and scholarships to countries in need,China’s foreign aid on global poverty alleviation is increasingly diversified and expanding in scale.Indeed,China is playing an increasingly important leading role in the global health agenda.It is worth mentioning that over the years,artemisinin compound have saved millions of lives all over the world,especially in poverty-stricken areas.China’s work mode of malaria elimination has also been written into WHO’s technical documents and recommended to other countries.Since 2007,Chinese medical staff has carried out the Artemisinin Compound Malaria Control Project in Comoros,bringing Chinese prevention and treatment programs to the local area.By 2014,Comoros had achieved zero deaths from malaria,and the number of cases had dropped by 98%.Now,this program is also extended to Togo,another African country.This article preliminarily summarizes the malaria profile in Togo and introduces China-Togo Cooperative Artemisinin Malaria Control Demonstration Project to provide a reference for better anti-malaria assistance in Togo,and also shows one of the substantive actions of China’s participation in global health governance,which contributes Chinese wisdom and offers Chinese solutions to global poverty alleviation.

Acupuncture, Moxibustion, and Combination Therapies for Insomnia

Insomnia, a common sleep disorder, affects general well-being, hastens the onset of other diseases, and impairs work performance. Hypnotic medications are efficacious in the short term but have obvious side effects. Acupuncture, often used to treat insomnia in traditional Chinese medicine (TCM), is considered to be beneficial in restoring the normal sleep-wake cycle by regulating and restoring the natural flow of qi (energy power). The three main TCM theories for treating insomnia by acupuncture are the tranquilization disturbance, zangfu disturbance (disequilibrium of internal organs), and imbalance of yin and yang theories. Moxibustion, another treatment for insomnia, is usually combined with acupuncture. Acupuncture and moxibustion with tuina (exercise massage), acupuncture with Chinese herbal injection, electroacupuncture, and acupuncture with medication or psychotherapy are other interventions. Some acupuncture-based methods such as needle-rolling acupuncture, auricular acupoint plaster therapy, phlebotomy, and acupoint catgut-embedding therapy are used as well. Although most clinical trials have shown that acupuncture and its combination therapies are significantly effective in insomnia, the beneficial effects may have been overvalued, because of small sample size, nonstrict inclusion and exclusion criteria, flawed methodology, short follow-up, or nonstandardized evaluation. Therefore, clinical studies of high methodological quality are needed to verify the efficacy of acupuncture, moxibustion, and other combination therapies in insomnia.

Combination Therapies for Advanced Biliary Tract Cancer

Biliary tract cancers(BTCs)are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis.Surgery is the only curative therapy.However,most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression.The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy.Nonetheless,many patients develop resistance to this regimen.Over the years,few chemotherapy regimens have managed to improve the overall survival of patients.Accordingly,novel therapies such as targeted therapy have been introduced to treat this patient population.Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways,such as EGFR,VEGF,MEK/ERK,PI3K and mTOR.Moreover,mutational analysis has documented the presence of IDH1,FGFR2,HER2,PRKACA,PRKACB,BRAF,and KRAS gene aberrations.The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies.Cancer vaccines,adoptive cell transfer,and immune checkpoint inhibitors have been extensively investigated in trials of BTC.Therefore,patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes.This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

A Clinical Study to Assess the Effectiveness of Oral Combination Kit Therapy in Syndromic Management of Abnormal Vaginal Discharge (FEMINE Study) in Kinshasa, Democratic Republic of Congo

Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered combination kit, containing 2 g secnidazole, 1 g azithromycin and 150 mg fluconazole (Azimyn FS Kit), has been successfully evaluated in clinical trials and used in several countries for management syndromic vaginal discharge due to infections. Methods: This is a longitudinal study which aimed to verify the clinical efficacy of the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in the syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultations in Kinshasa/DR Congo from March to September 2023. Results: Majority of patients had whitish vaginal discharge (51.6%) of average abundance (56.2%), accompanied by pruritus in 72.1% of cases, and dyspareunia in 23.5% of cases and hypogastralgia in 40.2% of cases. One week after treatment with the Azimyn FS® combined kit, at the greatest majority of patients (97.3%), abnormal vaginal discharge had decreased by more than 50% (84.1%). Two weeks after treatment with the Azimyn FS® combined kit, almost all patients (97.3%) no longer had abnormal vaginal discharge which had completely disappeared. Conclusion: A single dose of secnidazole, azithromycin and fluconazole in the form of an oral combi-kit (Azimyn FS Kit) has shown excellent therapeutic effectiveness in the syndromic treatment of abnormal vaginal discharge wherein patients were treated without diagnostic confirmation.

Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children

Background:In acute falciparum malaria,asexual parasite reduction ratio two days post-treatment initiation(PRRD2)≥10000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives.However,there is little evaluation of alternative measures;for example,parasite reduction ratio one day after treatment initiation(PRRD1)and its relationship with parasite clearance time(PCT)or PRRD2.This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs.Methods:In acutely malarious children treated with artesunate-amodiaquine(AA),artemether-lumefantrine(AL)or dihydroartemisinin-piperaquine(DHP),the relationships between PRRD1 or PRRD2 and PCT,and between PRRD1 and PRRD2 were evaluated using linear regression.Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis.Predictors of PRRD1>5000 per half cycle and PRRD2≥10000 per cycle were evaluated using stepwise multiple logistic regression models.Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase,PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half.Results:In 919 malarious children,PRRD1 was significantly higher in DHP-and AA-treated compared with AL-treated children(P<0.0001).PRRD1 or PRRD2 values correlated significantly negatively with PCT values(P<0.0001 for each)and significantly positively with each other(P<0.0001).PCT estimates from linear regression equations for PRRD1 and PRRD2 showed insignificant bias on the Bland-Altman plot(P=0.7)indicating the estimates can be used interchangeably.At presentation,age>15months,parasitaemia>10000/μl and DHP treatment independently predicted PRRD1>5000 per half cycle,while age>30months,haematocrit≥31%,body temperature>37.4°C,parasitaemia>100000/μl,PRRD1 value>1000 and no gametocytaemia independently predicted PRRD2≥10000 per cycle.Using the linear regression equation generated during the early phase in 166 DHP-treated children,PCT estimates and PCTs determined by microscopy in the 155 children in the later phase were similar in the same patients.Conclusions:PRRD1 and estimates of PCT using PRRD1 linear regression equation of PRRD1 and PCT can be used in therapeutic efficacy studies.Trial registration:Pan African Clinical Trial Registration PACTR201709002064150,1 March 2017,http://www.pactr.org.

Challenges and exploration for immunotherapies targeting cold colorectal cancer

In recent years,immune checkpoint inhibitors(ICIs)have made significant breakthroughs in the treatment of various tumors,greatly improving clinical efficacy.As the fifth most common antitumor treatment strategy for patients with solid tumors after surgery,chemotherapy,radiotherapy and targeted therapy,the therapeutic response to ICIs largely depends on the number and spatial distribution of effector T cells that can effectively identify and kill tumor cells,features that are also important when distinguishing malignant tumors from“cold tumors”or“hot tumors”.At present,only a small proportion of colorectal cancer(CRC)patients with deficient mismatch repair(dMMR)or who are microsatellite instability-high(MSI-H)can benefit from ICI treatments because these patients have the characteristics of a“hot tumor”,with a high tumor mutational burden(TMB)and massive immune cell infiltration,making the tumor more easily recognized by the immune system.In contrast,a majority of CRC patients with proficient MMR(pMMR)or who are microsatellite stable(MSS)have a low TMB,lack immune cell infiltration,and have almost no response to immune monotherapy;thus,these tumors are“cold”.The greatest challenge today is how to improve the immunotherapy response of“cold tumor”patients.With the development of clinical research,immunotherapies combined with other treatment strategies(such as targeted therapy,chemotherapy,and radiotherapy)have now become potentially effective clinical strategies and research hotspots.Therefore,the question of how to promote the transformation of“cold tumors”to“hot tumors”and break through the bottleneck of immunotherapy for cold tumors in CRC patients urgently requires consideration.Only by developing an in-depth understanding of the immunotherapy mechanisms of cold CRCs can we screen out the immunotherapy-dominant groups and explore the most suitable treatment options for individuals to improve therapeutic efficacy.

Combination therapy to overcome ferroptosis resistance by biomimetic self-assembly nano-prodrug

Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer.Herein,we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib(Gefi),ferrocene(Fc)and dihydroartemisinin(DHA)for the combined therapy of both ferroptosis and apoptosis.In the tumor microenvironment,this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH.Interestingly,the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc,further executing tumor cell death with concomitant chemotherapy by Gefi.More importantly,this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis,as well as no noticeable side-effects during treatments.This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.

The progress of combination therapy with immune checkpoint inhibitors in breast cancer

Immunotherapy targets the dysfunctional immune system to induce cancer cell killing by CD8-positive T cells.Immune checkpoint inhibitors(ICIs),specifically anti-PD-1 antibodies,anti-PD-L1 antibodies,and anti-CTLA4 antibodies,have revolutionized the management of many malignancies due to their significant role in generating a durable clinical response.However,clinical data suggest that response rates to ICI monotherapy are low due to the immunologically silent characteristics of breast cancer(BC).Chemotherapy,surgery,radiotherapy,and targeted therapy were recently reported to alter the tumor microenvironment and enhance the ICI response.Some clinical studies supported that ICIs,in combination with other treatment strategies,show superior efficacy in BC control,especially triple-negative breast cancer.Therefore,seeking a reasonable combination therapy is a promising way to improve ICI response.The present review highlights the clinical efficacy of ICIs treatment options in combination with standard-of-care therapies,such as chemotherapy and targeted therapy。

Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?

Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular carcinoma.Its incidence has seen a global upsurge in the past several years.Unfortunately,due to the lack of well-defined risk factors and limited diagnostic tools,iCCA is often diagnosed at an advanced stage,resulting in a poor prognosis.While surgery is the only potentially curative option,it is rarely feasible.Currently,there are ongoing investigations into various treatment approaches for unresectable iCCA,including conventional chemotherapies,targeted therapies,immunotherapies,and locoregional treatments.This study aims to explore the role of transarterial radioembolization(TARE)in the treatment of unresectable iCCA and provide a comprehensive review.The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA,with a median overall survival(OS)of 14.9 months in the study cohort.Studies on TARE for unresectable iCCA,both as a first-line treatment(as a neo-adjuvant down-staging strategy)and as adjuvant therapy,have reported varying median response rates(ranging from 34%to 86%)and median OS(12-16 mo).These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies.Most studies have identified tumor burden,portal vein involvement,and the patient’s performance status as key prognostic factors.Furthermore,a phase 2 trial evaluated the combination of TARE and chemotherapy(cisplatin-gemcitabine)as a first-line therapy for locally advanced unresectable iCCA.The results showed promising outcomes,including a median OS of 22 mo and a 22%achievement in down-staging the tumor.In conclusion,TARE represents a viable treatment option for unresectable iCCA,and its combination with systemic chemotherapy has shown promising results.However,it is important to consider treatment-independent factors that can influence prognosis.Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.

Rationale of Cross-Sectional Descriptive Study on Clinical Effectiveness of Oral Combination Therapy Based on Secnidazole, Azithromycin and Fluconazole in Syndromic Treatment of Abnormal Vaginal Discharge in Kinshasa/DR Congo

Background: Vaginal discharge is one of the most common troubles faced by childbearing age women. About 20% - 25% of women who visit service of gynecology complain of vaginal discharge and leucorrhoea. Management of vaginal discharge in low-income countries generally depends on syndromic approach, which limits the understanding of specific responsible agents. Thus targeted management is based on the identification of causal organism and targeting of therapy against it, while syndromic management is based on presence of high risk factors. Thus the oral combination kit (Azimyn FS Kit®) offers convenience of a one-day treatment compared to other multidose treatments, which will also ensure high patient adherence to treatment, thus increasing chances of desired results. Due to its widespread use, it is proposed to evaluate the effectiveness of this oral association kit therapy in management of vaginal discharge in the population of our milieu in the Democratic Republic of Congo (DRC) particularly those received in outpatient consultation in some medical facilities in city of Kinshasa. Expensive laboratory tests and the associated waiting period for result mean that patient remains without treatment while waiting for test results. Therefore, by adopting a syndromic management approach, patient’s eligibility for treatment will be decided based on abnormal vaginal discharge, their characteristics, severity and other presentations symptomatic. This approach will also avoid losing sight of patients during follow-up and will help to reduce financial burden for patients. Objectives: To determine the efficacy and safety of oral combination kit therapy containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultation in some medical facilities in the city of Kinshasa;to measure rate of recurrence of abnormal vaginal discharge in these patients. And to identify the adverse effects observed in these patients who received treatment with the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in outpatient consultation in some medical facilities in the city of Kinshasa. Methods: It will be a cross-sectional descriptive study. Sample size will be 319 women of childbearing age who consult the gynecology department with complaint of abnormal vaginal discharge and suspicion of vaginal infection, who agree to abstain from sex during treatment and who have given their written consent to use their personal and/or health data in the study. Conclusion: A study on clinical efficacy of oral combination therapy based on secnidazole, azithromycin and fluconazole is beneficial.

Advances in the management of arteriosclerosis of the lower extremity:Integrating Western and Chinese medicine approaches

This editorial provides a commentary on the recent article.The paper reviews current literature and explores innovative treatment strategies for lower extremity arteriosclerosis obliterans(LEASO)through an integrative approach.It highlights the effectiveness of combination therapies that merge traditional Chinese medicine(TCM)with Western medical practices,suggesting that such integrative methods may improve patient compliance and outcomes through personalized care.This paper stresses the importance of rigorous clinical trials to evaluate the efficacy and safety of TCM interventions within LEASO treatment protocols,advocating for evidence-based validation of these combined therapies.Our recommendations emphasize accurate diagnosis,appropriate pharmacological in-terventions,the use of advanced surgical and endovascular techniques,and the inclusion of TCM to address underlying dysfunctions.Additionally,continuous monitoring,patient education,and lifestyle modifications are essential to slow disease progression and achieve optimal patient outcomes.The paper concludes by calling for further research to develop standardized treatment protocols that effectively integrate both Western and Chinese medical approaches in managing LEASO.

Yttrium-90 radioembolization treatment strategies for management of hepatocellular carcinoma

As the third leading cause of cancer-related deaths worldwide,hepatocellular carcinoma(HCC)represents a significant global health challenge.This paper provides an introduction and comprehensive review of transarterial radioembolization(TARE)with Yttrium-90(Y90),a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery.TARE involves the targeted delivery of radioactive microspheres to liver tumors,offering a promising treatment option for managing HCC across various stages of the disease.By evaluating Y90 TARE outcomes across early,intermediate,and advanced stages of HCC,the review aims to present a thorough understanding of its efficacy and safety.Additionally,this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies,as well as personalized treatments.The exploration of these innovative approaches aims to improve treatment outcomes,reduce adverse events,and provide new therapeutic opportunities for HCC patients.The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.