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.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

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.

Using multi-omics analysis to explore diagnostic tool and optimize drug therapy selection for patients with glioma based on cross-talk gene signature

Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.

Computationally guided design and synthesis of dual-drug loaded polymeric nanoparticles for combination therapy

Single-drug therapies or monotherapies are often inadequate,particularly in the case of life-threatening diseases like cancer.Consequently,combination therapies emerge as an attractive strategy.Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs,such as low water solubility and bioavailability,high toxicity,etc.However,it remains a significant challenge in encapsulating two drugs in a nanoparticle.To address this issue,computational methodologies are employed to guide the rational design and synthesis of dual-drug-loaded polymer nanoparticles while achieving precise control over drug loading.Based on the sequential nanoprecipitation technology,five factors are identified that affect the formulation of drug candidates into dual-drug loaded nanoparticles,and then screened 176 formulations under different experimental conditions.Based on these experimental data,machine learning methods are applied to pin down the key factors.The implementation of this methodology holds the potential to signif-icantly mitigate the complexities associated with the synthesis of dual-drug loaded nanoparticles,and the co-assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy.This approach provides a new strategy for enabling the streamlined,high-throughput screening and synthesis of new nanoscale drug-loaded entities.

Fe(Ⅲ)-juglone nanoscale coordination polymers for cascade chemodynamic therapy through synergistic ferroptosis and apoptosis strategy

Chemodynamic therapy(CDT)relying on the transformation of endogenous hydrogen peroxide(H_(2)O_(2))into cytotoxic hydroxyl radicals(·OH)based on the catalysis of Fenton/Fenton-type reactions exhibits great potentiality for cancer treatment.However,the inadequate H_(2)O_(2)supply and intricate redox homeostasis in tumor microenvironment(TME)severely impair the efficacy of CDT.Herein,we design selfassembled 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated polyethylene glycol(DSPE-PEG)-modified Fe(Ⅲ)-juglone nanoscale coordination polymers(FJP NCPs)as redox homeostasis disruptors for juglone-enhanced CDT.Responding to glutathione(GSH)-rich and acidic TME,the Fe^(2+)/Fe^(3+)-guided CDT and GSH consumption by Fe^(3+)are activated,resulting in·OH downstream and up-regulation of lipid peroxidation(LPO).In addition,the released juglone not only depletes GSH through Michael addition,but also elevates intracellular H_(2)O_(2)level for achieving·OH further bursting.With the impressive efficiency of GSH exhaustion and reactive oxygen species(ROS)storm generation,ferroptosis and apoptosis are significantly enhanced by FJP NCPs in vivo.In brief,this facile and efficient design for versatile nanoscale coordination polymers presents a novel paradigm for effectively elevating CDT efficiency and tumor synergistic therapy.

Smart multi-functional aggregates reoxygenate tumor microenvironment through a two-pronged strategy to revitalize cancer immunotherapy

PD-1/PD-L1 inhibitors have emerged as standard treatments for advanced solid tumors;however,challenges such as a low overall response rate and systemic side effects impede their implementation.Hypoxia drives the remodeling of the tumor microenvironment,which is a leading reason for the failure of immunotherapies.Despite some reported strategies to alleviate hypoxia,their individual limitations constrain further improvements.Herein,a novel two-pronged strategy is pre-sented to efficiently address hypoxia by simultaneously adopting atovaquone(ATO,inhibiting oxygen consumption)and oxyhemoglobin(HbO2,directly supplement-ing oxygen)within a multifunctional aggregate termed NPs-aPD-1/HbO2/ATO.In addition to eliminating hypoxia with these two components,this smart aggre-gate also includes albumin and an ROS-responsive cross-linker as a controlled release scaffold,along with PD-1 antibody(aPD-1)for immunotherapy.Intriguingly,NPs-aPD-1/HbO2/ATO demonstrates exceptional tumor targeting in vivo,exhibit-ing≈4.2 fold higher accumulation in tumors than in the liver.Consequently,this aggregate not only effectively mitigates hypoxia and significantly assists aPD-1 immunotherapy but also simultaneously resolves the targeting and systemic toxicity issues associated with individual administration of each component.This study pro-poses substantial implications for drug-targeted delivery,addressing tumor hypoxia and advancing immunotherapy,providing valuable insights for advancing cancer treatment strategies.

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.

Hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma:A case report

BACKGROUND Liver cancer treatment is characterized by multidisciplinary participation and coexistence of multiple treatment methods.Hypofractionated and intensity-modulated radiotherapy is a new precise radiotherapy technique applied to the treatment of systemic malignant tumors.There is a lack of understanding of hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma(HCC).CASE SUMMARY We report a case of metastatic HCC treated with hypofractionated and intensity-modulated radiotherapy combined with systemic therapy.A 41-year-old man was diagnosed with metastatic HCC(T3N1M1 stage IVB).Because it was found to be in the late stage of cancer and had already metastasized,it was impossible to undergo surgical treatment.In addition to aggressive comprehensive treatment for the primary lesion,local treatment for metastatic cancer can improve the patient's survival potential.Hypofractionated and intensity-modulated radiotherapy can provide a larger single treatment dose within a shorter overall treatment time,and improve the local control rate of the tumor.Follow-up examination demonstrated that the tumor and metastatic lesions had shrunk after therapy.The treatment has showed good efficacy.The patient survived for 18 months without disease progression and stable disease persisted for>38 months.CONCLUSION Targeted therapy and immunotherapy followed by hypofractionated and intensity-modulated radiotherapy are also effective for advanced metastatic HCC.

New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

Efficacy evaluation and survival analysis of the combination of oxaliplatin plus Teysuno (SOX) with immune checkpoint inhibitors in the conversion therapy of locally advanced gastric cancer

Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.

Study on the Effect of Self-Help Mindfulness Therapy on Rumination in Patients with Depression

Objective:To evaluate the nursing effect of self-help mindfulness therapy for patients with depression.Methods:120 cases of depression patients admitted to the Department of Psychosomatic Disorders of our hospital between January 2020 and January 2023 were selected.After being grouped by the random draw method,60 cases in the observation group adopted self-help mindfulness therapy and 60 cases in the control group adopted conventional nursing care,the nursing effects were subsequently compared.Results:Before nursing,there was no difference in the comparison of clinical symptom scores,rumination scores,positive psychological scores,and self-esteem scores between the two groups(P>0.05).After nursing,the clinical symptom scores of the observation group were lower than those of the control group;the rumination scores were lower than those of the control group;the positive psychological scores were higher than those of the control group;and the self-esteem scores were higher than those of the control group,and all of them were statistically significant(P<0.05).Conclusion:Self-help mindfulness therapy can improve the clinical symptoms of patients with depression and their rumination,and enhance their positive psychological state and self-esteem level,which has high nursing advantages.

Suggestions on Improving China’s Breakthrough Therapy Designation System

Objective To analyze the characteristics of breakthrough therapy designation(BTD)and its implementation in China,and to provide reference for the optimization of BTD system.Methods A comparative research method was used to study the content and implementation effect of BTD system in China and the relevant policies and implementation of the same procedures of drug regulatory authorities in the United States,Japan and the European Union.Then,the differences in policies and implementation results among these countries were analyzed to provide suggestions for the implementation and optimization of this system in China.Results and Conclusion China’s BTD system is implemented late and a small number of drugs has been approved.At the same time,there are problems such as insufficient guidance and communication from the agency to applicants,a broad application condition,single review mode,and lack of full-time personnel.Both the agencies and the applicants have limited experience due to the short implementation time of BTD system in China.There are still some problems despite we have learned a lot from the experience of other drug regulatory agencies.Therefore,based on our national conditions,we should strengthen the guidance of evaluation agency to applicants,optimize the eligibility criteria of BTD system,introduce the rolling review,and increase the number of professional liaisons,which can accelerate the development and marketing process of drugs with obvious clinical value,and finally to address unmet medical need.

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。

Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor

Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsive multifunctional nanoplatform(Bi2S3@Bi@PDA-HA/Art NRs)was presented for synergistic photothermal therapy(PTT),chemodynamic therapy(CDT),and photodynamic therapy(PDT)to achieve better therapeutic outcomes.The Z-scheme heterostructured bismuth sulfide@bismuth nanorods(Bi2S3@Bi NRs)guaranteed excellent photothermal performance of the nanoplatform.Moreover,its ability to produce O2 and reactive oxygen species(ROS)synchronously could relieve tumor hypoxia and improve PDT outcomes.The densely coated polydopamine/ammonium bicarbonate(PDA/ABC)and hyaluronic acid(HA)layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ“bomb-like”release of Art.The CDT treatment was achieved by activating the released Art through intracellular Fe2+ions in an H2O2-independent manner.Furthermore,decreasing the glutathione peroxidase 4(GPX4)levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs.Owing to the synergistic effect,this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo.Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

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.