Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Comprehensive Analysis of Cancer Incidence and Mortality Trends in Costa Rica: Implications for Public Health

This commentary delves into the evolving landscape of cancer incidence and mortality in Costa Rica, presenting a comprehensive analysis of the data. Key findings reveal a concerning upward trajectory in cancer incidence rates, placing Costa Rica at the forefront within Central America. While prostate cancer and breast cancer dominate, disparities emerge when scrutinizing gender-specific trends. Notably, stomach and cervical cancers show declines, potentially attributed to targeted interventions. However, colorectal and liver cancers witness mortality increases, necessitating strategic responses. Geographical disparities persist across provinces, highlighting the need for equitable healthcare access. In conclusion, this commentary underscores the urgency of addressing the burgeoning cancer burden in Costa Rica, calling for evidence-based interventions and collaborative efforts on a global scale.

Research Status of Fear of Cancer Recurrence in Breast Cancer Patients

Fear of disease progression is one of the most common psychological problems in the treatment of cancer patients. Early recognition and intervention can effectively control the level of fear of disease progression and improve the quality of life of patients. The present situation and influencing factors of FoP in breast cancer patients were reviewed in this paper, in order to provide reference for clinical research of breast cancer patients.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.

Global, regional, and national burden of early-onset gastric cancer

Objective: The burden of gastric cancer(GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017.Methods: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates(ASIRs) were evaluated using cancer registry data from volumes X±XII of the Cancer Incidence in Five Continents(CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate(ASMR) and the Human Development Index(HDI).Results: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008±2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females.Conclusions: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.

Biological factors driving colorectal cancer metastasis

Approximately 20%of colorectal cancer(CRC)patients present with metastasis at diagnosis.Among Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial treatment.The median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 mo.mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor development.CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations.Different genomic and nongenomic events can induce subclone diversity,which leads to cancer and metastasis.Throughout the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular functions.However,cancer cells presenting neoantigens can be recognized and eliminated by the immune system.In this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle factors.Despite remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains unclear.This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

Surgical treatment of liver cancer and pancreatic cancer under the China Healthcare Security Diagnosis Related Groups payment system

BACKGROUND Data from the World Health Organization’s International Agency for Research on Cancer reported that China had the highest prevalence of cancer and cancer deaths in 2022.Liver and pancreatic cancers accounted for the highest number of new cases.Real-world data(RWD)is now widely preferred to traditional clinical trials in various fields of medicine and healthcare,as the traditional research approach often involves highly selected populations and interventions and controls that are strictly regulated.Additionally,research results from the RWD match global reality better than those from traditional clinical trials.AIM To analyze the cost disparity between surgical treatments for liver and pancreatic cancer under various factors.METHODS This study analyzed RWD 1137 cases within the HB1 group(patients who underwent pancreatectomy,hepatectomy,and/or shunt surgery)in 2023.It distinguished different expenditure categories,including medical,nursing,technical,management,drug,and consumable costs.Additionally,it assessed the contribution of each expenditure category to total hospital costs and performed cross-group comparisons using the non-parametric Kruskal–Wallis test.This study used the Steel–Dwass test for post-hoc multiple comparisons and the Spearman correlation coefficient to examine the relationships between variables.RESULTS The study found that in HB11 and HB13,the total hospitalization costs were significantly higher for pancreaticoduodenectomy than for pancreatectomy and hepatectomy.Although no significant difference was observed in the length of hospital stay between patients who underwent pancreaticoduodenectomy and pancreatectomy,both were significantly longer than those who underwent liver resection.In HB15,no significant difference was observed in the total cost of hospitalization between pancreaticoduodenectomy and pancreatectomy;however,both were significantly higher than those in hepatectomy.Additionally,the length of hospital stay was significantly longer for patients who underwent pancreaticoduodenectomy than for those who underwent pancreatectomy or liver resection.CONCLUSION China Healthcare Security Diagnosis Related Groups payment system positively impacts liver and pancreatic cancer surgeries by improving medical quality and controlling costs.Further research could refine this grouping system and ensure continuous effectiveness and sustainability.

COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway

Objectives:Thyroid cancer(THCA)is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide.And the number of patients dying from THCA has also gradually risen because the incidence continues to increase,so the mechanisms related to effective targets is necessary to improve the survival.This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer(THCA)cell proliferation and the associated pathways.Methods:Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development.COL4A2 expression in THCA tissues was analyzed using immunohistochemistry,and survival information was determined via Kaplan-Meier curves.The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses.Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity,respectively.Downstream of COL4A2 was identified by Gene set enrichment analysis(GSEA).The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model.Results:Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2.THCA patients with high COL4A2 expression had shorter recurrence-free survival.Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity.The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines.The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival.Conclusions:COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

Comparative analysis of breast and lung cancer survival rates and clinical trial enrollments among rural and urban patients in Georgia

Objectives:Rural patients have poor cancer outcomes and clinical trial(CT)enrollment compared to urban patients due to attitudinal,awareness,and healthcare access differential.Knowledge of cancer survival disparities and CT enrollment is important for designing interventions and innovative approaches to address the stated barriers.The study explores the potential disparities in cancer survival rates and clinical trial enrollments in rural and urban breast and lung cancer patients.Our hypotheses are that for both cancer types,urban cancer patients will have longer 5-year survival rates and higher enrollment rates in clinical trials than those in rural counties.Methods:We compared breast and lung cancer patients’survival rates and enrollment ratios in clinical trials between rural(RUCC 4-9)and urban counties in Georgia at a Comprehensive Cancer Center(CCC).To assess these differences,we carried out a series of independent samples t-tests and Chi-Square tests.Results:The outcomes indicate comparable 5-year survival rates across rural and urban counties for breast and lung cancer patients,failing to substantiate our hypothesis.While clinical trial enrollment rates demonstrated a significant difference between breast and lung cancer patients at CCC,no significant variation was observed based on rural or urban classification.Conclusion:These findings underscore the need for further research into the representation of rural patients with diverse cancer types at CCC and other cancer centers.Further,the findings have considerable implications for the initiation of positive social change to improve CT participation and reduce cancer survival disparities.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model

BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.

Cryoablation techniques in bladder cancer: A review

Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldwide.The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer(NMIBC)is transurethral resection of bladder tumors(TURBT).Currently,the standard of care for muscle-invasive bladder cancer(MIBC)is neoadjuvant chemotherapy followed by radical cystectomy.Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue.This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney,prostate gland,lung,liver,and breast,and is particularly effective for unresectable tumors,offering less trauma,quick recovery,good tolerability,and symptom control.However,cryoablation has its limitations.Over the past few years,cryoablation therapy has emerged as a new method for treating early BC.This treatment is minimally invasive,precise,and offers quick recovery,providing patients with a new treatment option.Although randomized studies are still limited,increasing evidence suggests its potential application in bladder cancer combined with transurethral resection(TURBT)or medication.Cryoablation is not standard therapy for bladder cancer.Treatment decisions should be discussed by a multidisciplinary team of urologists,oncologists,and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.

Investigation and analysis of the status of cancer health popularization in China,2023

BACKGROUND Cancer presents a significant public health challenge in China,necessitating broad collaboration across society.The Chinese government has articulated a goal to increase the overall five-year survival rate for cancer by 15%by 2030.Achieving this objective requires not only advances in medical technology,but also an im-provement in the dissemination of knowledge pertaining to cancer prevention and treatment.AIM To provide a comprehensive understanding of the status of cancer prevention and level of popularization in China in 2023.METHODS From January 2023 to May 2023,online questionnaires were distributed to 3000 participants,including medical personnel,patients with cancer,their families,and the general public.There were 2711 valid responses,covering the entire nation.RESULTS A total of 1020 medical personnel and 1691 patients with cancer,their family members,and the general public participated in the survey.Among medical personnel,93.2%had popularized cancer health.Commonly addressed topics included cancer prevention(85.9%)and cancer screening(77.8%).Primary challenges included time constraints(73.9%),insufficient personnel and material support(66.7%),and uncertainty as to where to begin(49.3%).Among patients with cancer,their family members,and the general public,93.4%reported reading or watching cancer science popularization materials and 56.9%expressed a desire for deeper understanding.The most sought-after topics in cancer science popularization included cancer screening(80.2%)and cancer prevention(75.8%).The greatest challenge encountered in accessing cancer health popularization was an abundance of misinformation(67.5%).CONCLUSION Most clinical doctors,patients,family,and the general public wish to participate in cancer education.However,improvement in the quality of content in cancer prevention and treatment education is required.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

The prognostic and immunological impacts of DCX expression:a pan-cancer analysis

Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.

Prostaglandin D2 regulation of autophagy affects stemness of gastric cancer stem cells

Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD44,a stemness marker,was detected by flow cytometry in serum-free cultured 7901-GCSCs;the sphere-forming ability was detected by the sphere-forming assay after stimulation with different concentrations of PGD2(2.5,5,10)μg/mL,and the expression of stemness-related indicators(OCT4,CD44)and autophagyrelated proteins(LC3,Beclin-1)after PGD2 stimulation was detected by the western blot assay in different concentrations.The expression of stemness-related indexes(OCT4,CD44)and autophagy-related proteins(LC3,Beclin-1)were detected by Western blot assay after stimulation with different concentrations of PGD2.The expression of autophagy-related proteins after stimulation with different concentrations of CQ(2.5,5,10)μM was detected by Western blot experiment.The protein expression of autophagy-related proteins(LC3,Beclin-1)and stemness-related indexes(OCT4,CD44)was detected by Western blot experiment after PGD2 as well as PGD2+CQ treatment.Results:Flow cytometry results showed that the expression of CD44 positivity was increased in serum-free cultured 7901-GCSCs compared with gastric cancer cells SGC-7901(P<0.05),which fulfilled the needs of subsequent experiments.The results of stem cell spheroid formation assay showed that the spheroid formation ability of 7901-GCSCs in the PGD2 group was significantly weakened compared with that of the DMSO group(P<0.05).Western blot results showed that the protein expression of stemness-related indexes(OCT4,CD44)was down-regulated in the 7901-GCSCs in the PGD2 group compared with that of the DMSO group(P<0.05),and the expression of autophagy-related proteins(LC3,Beclin-1)expression increased(P<0.05).Compared with the DMSO group,the expression of autophagy-related proteins(LC3,Beclin-1)was decreased in the CQ group(P<0.05).Western blot results also showed that the expression of cellular autophagy-related proteins and stemness-related indexes in the PGD2+CQ group was not significantly changed compared with that of the DMSO group(ns:the difference was not significant),suggesting that the CQ could block the effect of PGD2 on the expression of stemness markers in 7901-GCSCs.7901-GCSCs stemness inhibition.Conclusion:PGD2 may affect the stemness of 7901-GCSCs by regulating autophagy.

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods

In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developing detection and treatment methods should continue.The diagnostic path typically begins with learning the medical history of a patient;this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy.Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization.Thus,there is a need for novel cancer detection methods such as liquid biopsy,elastography,synthetic biosensors,fluorescence imaging,and reflectance confocal microscopy.Conventional therapeutic methods,although still common in clinical practice,pose many limitations and are unsatisfactory.Nowadays,there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy,exosome-based therapy,nanotechnology,dendritic cells,chimeric antigen receptors,immune checkpoint inhibitors,natural product-based therapy,tumor-treating fields,and photodynamic therapy.The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions.As evidenced,modern methods are not without drawbacks;there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity,specificity,safety,and efficacy.Nevertheless,an appropriate route has been taken,as confirmed by the approval of some modern methods by the Food and Drug Administration.

Anti-Cancer Agents Associated Diarrhea:Current Status and Prospects

Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.