BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk...BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.展开更多
Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is a...Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.展开更多
The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in over...The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.展开更多
Objective:Open retroperitoneal lymph node dissection(RPLND)is the gold-standard surgical approach for the management of metastatic testicular cancer,but robotic RPLND is becoming increasingly popular.There is limited ...Objective:Open retroperitoneal lymph node dissection(RPLND)is the gold-standard surgical approach for the management of metastatic testicular cancer,but robotic RPLND is becoming increasingly popular.There is limited research directly comparing open and robotic RPLND.The objective of this systematic review is to identify all the literature with direct comparisons between the open and robotic techniques for RPLND and to compare the two techniques.The primary outcome was peri-operative outcomes,and the secondary outcomes included oncological outcomes and patient demographics.Methods:This systematic review was prospectively registered and was conducted in accordance with the PRISMA statement.The PubMed,Embase and MEDLINE databases were searched for relevant publication from January 2006 to August 2024.Results:Eight studies,totaling 3995 patients,are included in this systematic review,with 3521 patients who underwent open RPLND and 474 who underwent robotic RPLND.For open RPLND,the mean operative duration,blood loss and length of stay were 267.8 min,475 mL and 7.3 d,respectively.For robotic RPLND,the mean operative duration,blood loss and length of stay were 334.5 min,94.6 mL and 3.7 d,respectively.Teratoma was the most common RPLND specimen pathology from both open and robotic surgeries.For open RPLND,the specimens have 13–23 nodes(26–32 mm),whereas the robotic RPLND specimens have 13–28 nodes(18–20 mm).Conclusion:This systematic review suggests that the benefitsof robotic RPLND may be associated with reduced blood loss,shorter hospitalisation and an overall lower risk of minor and major complications while maintaining oncological safety.展开更多
Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing can...Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.展开更多
BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector compu...BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector computed tomography(MDCT)and gastrointestinal endoscopy for GC screening,preoperative staging,and lymph node metastasis detection,thereby providing a reference for clinical diagnosis and treatment.METHODS In this retrospective study clinical and imaging data of 134 patients with suspected GC who were admitted between January 2023 and October 2024 were initially reviewed.According to the inclusion and exclusion criteria,102 patients were finally enrolled in the analysis.All enrolled patients had undergone both MDCT and gastrointestinal endoscopy examinations prior to surgical intervention.Preoperative clinical staging and lymph node metastasis findings were compared with pathological results.RESULTS The combined use of MDCT and gastrointestinal endoscopy demonstrated a sensitivity of 98.53%,specificity of 97.06%,accuracy of 98.04%,positive predictive value of 98.53%,and negative predictive value of 97.06%for diagnosing GC.These factors were all significantly higher than those of MDCT or endoscopy alone(P<0.05).The accuracy rates of the combined approach for detecting clinical T and N stages were 97.06%and 92.65%,respectively,outperforming MDCT alone(86.76% and 79.41%)and endoscopy alone(85.29% and 70.59%)(P<0.05).Among 68 patients with confirmed GC,50(73.53%)were pathologically diagnosed with lymph node metastasis.The accuracy for detecting lymph node metastasis was 66.00%with endoscopy,76.00%with MDCT,and 92.00% with the combined approach,all with statistically significant differences(P<0.05).CONCLUSION The combined application of MDCT and gastrointestinal endoscopy enhanced diagnostic accuracy for GC,provided greater consistency in preoperative staging,and improved the detection of lymph node metastasis,thereby demonstrating significant clinical utility.展开更多
Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a...Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.展开更多
Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. T...Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.展开更多
Summary:Cancer testis(CT)antigens have received particular attention in cancer immunotherapy.OY-TES-1 is a member of CT antigens.This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carci...Summary:Cancer testis(CT)antigens have received particular attention in cancer immunotherapy.OY-TES-1 is a member of CT antigens.This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma(HCC).OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR(RT-PCR).Of the 56 cases of HCC tissues tested,37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR.OY-TES-1 protein was subsequently observed on a panel of tissue microarrays.Sera from patients were tested for OY-TES-1 antibody by ELISA.To identify OY-TES-1 capable of inducing cellular immune response,OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro.The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56(73.21%)HCC tissues,whereas none in 5 normal liver tissues.OY-TES-1 mRNA was frequently expressed not only in HCC tissues(72.97%,27/37),but also in paired adjacent non-cancer tissues(64.86%,24/37).But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues(0.76854 vs.0.09834,P=0.021).Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues,and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues.Seropositivity was detected in 10 of the 45 HCC patients,but not detected in 17 cirrhosis patients and 76 healthy donors.The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2^+HCC cell line which expressed OY-TES-1.The target lysis was mainly HLA class I-dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule.In summary,OY-TES-1 expression is upregulated in HCC tissues and can be recognized by humoral and cellular responses,which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.展开更多
AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this stu...AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.展开更多
MicroRNAs(miRNAs)are small noncoding RNAs involved in the regulation of mRNA transcription and translation,and possess all desirable features of an ideal tumor marker.Of almost 31 different miRNA clusters identified i...MicroRNAs(miRNAs)are small noncoding RNAs involved in the regulation of mRNA transcription and translation,and possess all desirable features of an ideal tumor marker.Of almost 31 different miRNA clusters identified in germ cell tumors(GCTs),miR-371a-3p has shown exceptionally high sensitivity and specificity for both seminomatous and nonseminomatous GCTs.It is easily obtainable and correlates well with tumor burden.Recent multiinstitutional prospective studies have shown promising test characteristics for miR-371a-3p as a diagnostic blood-based biomarker for GCT prior to orchiectomy including 80%e100%sensitivity and 90%e100%specificity.This accuracy may address other unmet needs in the management of patients with GCT.Early studies have suggested the utility of miR-371a-3p in detecting occult nodal metastasis in high-risk clinical stage I and early stage II disease.Ongoing clinical trials including SWOG 1823 and AGCT1531 are specifically designed to confirm the utility of miR-371a-3p in clinical stage I GCT.Despite its strong association with viable GCT after treatment with chemotherapy,miR-371a-3p does not seem to accurately predict the presence of teratoma in residual lesions.Also,standardization of extraction and interpretation methods is a necessary step to assure uniform results across different institutions.展开更多
AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC bef...AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP) in these patients was also determined.RESULTS:The positive rate of MAGE-1,SSX-1 and CTp11 transcripts was 37.7%,34.4%,31.1% in PBMC samples,and 74.4%,73.3%,62.2% in their resected tumor samples,respectively.The positive rate for at least one of the transcripts of three CTA genes was 66.7% in PBMC samples and 91.1% in their resected tumor samples.MAGE-1,SSX-1 and/or CTp11 mRNA were not detected in the PBMC of those patients from whom the resected tumor samples were MAGE-1,SSX-1 and/or CTp11 mRNA negative,nor in the PBMC samples from 20 healthy donors and 10 cirrhotic patients.Among the 90 patients,the serum AFP in 44 patients met the general diagnostic standard(AFP > 400 μg/L) for HCC,and was negative(AFP ≤ 20 μg/L) or positive with a low concentration(20 μg/L < AFP ≤ 400 μg/L) in the other patients.The positive rate for at least one of the transcripts of three CTA genes in PBMC samples from the AFP negative or positive patients with a low concentration was 69.2% and 45.0%,respectively.Of the 90 patients,71(78.9%) were diagnosed as HCC by nested RT-PCR and serum AFP.Although the positive rate for at least one of the transcripts of three CTA genes in PBMC samples from 53 patients at TNM stage or was obviously higher than that in PBMC samples from 37 patients at stage or(77.9% vs 51.4%,P = 0.010),the CTA mRNA was detected in 41.7% and 56.0% of PBMC samples from HCC patients at stages andrespectively.CONCLUSION:Detecting MAGE-1,SSX-1 and CTp11 mRNA in PBMC improves the total diagnostic rate of HCC.展开更多
Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a ...Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.In this review,we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.展开更多
Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely int...Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.展开更多
Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesi...Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.展开更多
BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple pri...BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.展开更多
Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the car...Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.展开更多
Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality wor...Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality worldwide.Many studies have identified the gastrointestinal microbiota,or gut microbiota,as an important contributor to both the pathogenesis and treatment of GPL and GC,thus understanding its role in this transition is crucial.The purpose of this literature review is to introduce the current landscape of microbiota research associated with GPL and GC,with an emphasis on Helicobacter pylori(H.pylori)driven microbial dysbiosis and its modulation through Western medicine and traditional Chinese medicine(TCM)approaches.By elucidating the underlying mechanisms of H.pylori colonization,patterns,and interactions among microbiota,as well as the influence of microbial metabolites,this review highlights crucial driving factors of gastric carcinogenesis.The role of microbiota in conventional interventions,including H.pylori eradication,immunotherapy,as well as TCM herbal decoctions,is also discussed to provide a detailed understanding of the complex interactions between therapy and microbiota and how it could be potentially targeted for effective management of GPL and GC.Ultimately,microbiota-targeting therapeutics may represent a new path toward early detection,targeted treatment,improved prognosis,and potentially reduced incidence of GPL and GC.展开更多
Breast cancer resistance protein （Bcrp） is an ATP-dependent efflux drug transporter. It has a diverse spectrum of hydrophilic and hydrophobic substrates ranging from anticancer, antiviral and antihypertensive drugs,...Breast cancer resistance protein （Bcrp） is an ATP-dependent efflux drug transporter. It has a diverse spectrum of hydrophilic and hydrophobic substrates ranging from anticancer, antiviral and antihypertensive drugs, to organic anions, antibiotics, phytoestrogens （e.g., genistein, daidzein, coumestrol）, xenoestrogens and steroids （e.g., dehydroepiandrosterone sulfate）. Bcrp is an integral membrane protein in cancer and normal cells within multiple organs （e.g., brain, placenta, intestine and testis） that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component of the blood- brain barrier located on endothelial cells near tight junctions （TJs）. However, Bcrp is absent at the Sertoli cell blood-testis barrier （BTB）; instead, it is localized almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation （ES） in stage VI-early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F （filamentous）-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII-VIII tubules. These findings will be carefully evaluated in this brief review.展开更多
Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The d...Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.展开更多
基金Supported by Grant-in-Aid for research by the Kitasato University Medical Center,No.H26-008the JSPS KAKENHI,No.17K16578+3 种基金the JSPS KAKENHI,No.26670609Takeda Science FoundationKitasato University Research Grant for Young ResearchersGrant-in-Aid for research from the Kitasato University Medical Center,No.H25-0006
文摘BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.
文摘Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.
文摘The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.
文摘Objective:Open retroperitoneal lymph node dissection(RPLND)is the gold-standard surgical approach for the management of metastatic testicular cancer,but robotic RPLND is becoming increasingly popular.There is limited research directly comparing open and robotic RPLND.The objective of this systematic review is to identify all the literature with direct comparisons between the open and robotic techniques for RPLND and to compare the two techniques.The primary outcome was peri-operative outcomes,and the secondary outcomes included oncological outcomes and patient demographics.Methods:This systematic review was prospectively registered and was conducted in accordance with the PRISMA statement.The PubMed,Embase and MEDLINE databases were searched for relevant publication from January 2006 to August 2024.Results:Eight studies,totaling 3995 patients,are included in this systematic review,with 3521 patients who underwent open RPLND and 474 who underwent robotic RPLND.For open RPLND,the mean operative duration,blood loss and length of stay were 267.8 min,475 mL and 7.3 d,respectively.For robotic RPLND,the mean operative duration,blood loss and length of stay were 334.5 min,94.6 mL and 3.7 d,respectively.Teratoma was the most common RPLND specimen pathology from both open and robotic surgeries.For open RPLND,the specimens have 13–23 nodes(26–32 mm),whereas the robotic RPLND specimens have 13–28 nodes(18–20 mm).Conclusion:This systematic review suggests that the benefitsof robotic RPLND may be associated with reduced blood loss,shorter hospitalisation and an overall lower risk of minor and major complications while maintaining oncological safety.
文摘Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.
文摘BACKGROUND Early screening,preoperative staging,and diagnosis of lymph node metastasis are crucial for improving the prognosis of gastric cancer(GC).AIM To evaluate the diagnostic value of combined multidetector computed tomography(MDCT)and gastrointestinal endoscopy for GC screening,preoperative staging,and lymph node metastasis detection,thereby providing a reference for clinical diagnosis and treatment.METHODS In this retrospective study clinical and imaging data of 134 patients with suspected GC who were admitted between January 2023 and October 2024 were initially reviewed.According to the inclusion and exclusion criteria,102 patients were finally enrolled in the analysis.All enrolled patients had undergone both MDCT and gastrointestinal endoscopy examinations prior to surgical intervention.Preoperative clinical staging and lymph node metastasis findings were compared with pathological results.RESULTS The combined use of MDCT and gastrointestinal endoscopy demonstrated a sensitivity of 98.53%,specificity of 97.06%,accuracy of 98.04%,positive predictive value of 98.53%,and negative predictive value of 97.06%for diagnosing GC.These factors were all significantly higher than those of MDCT or endoscopy alone(P<0.05).The accuracy rates of the combined approach for detecting clinical T and N stages were 97.06%and 92.65%,respectively,outperforming MDCT alone(86.76% and 79.41%)and endoscopy alone(85.29% and 70.59%)(P<0.05).Among 68 patients with confirmed GC,50(73.53%)were pathologically diagnosed with lymph node metastasis.The accuracy for detecting lymph node metastasis was 66.00%with endoscopy,76.00%with MDCT,and 92.00% with the combined approach,all with statistically significant differences(P<0.05).CONCLUSION The combined application of MDCT and gastrointestinal endoscopy enhanced diagnostic accuracy for GC,provided greater consistency in preoperative staging,and improved the detection of lymph node metastasis,thereby demonstrating significant clinical utility.
文摘Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.
基金Indo-UK Cancer Research ProgramNo.BT/IN/UK/NII/2006+3 种基金Centre for Molecular MedicineNo.BT/PR/14549/MED/14/1291NII-core funding,Department of BiotechnologyGovernment of India
文摘Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81860445,No.81960453,No.81560408,and No.81660429)Natural Science Foundation of Guangxi Province(No.2016GXNSFBA380159,No.2018GXNSFAA281251,No.2018GXNSFAA050151,No.2017GXNSFAA198001,No.2018GXNSFAA281050,and No.2018GXNSFBA281187)+2 种基金Key Laboratory ofEarly Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry ofEducation(No.GK2018-09,No.GKE 2019-08,and No.K2015-TKF03)Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi Province(No.2018KY0109).
文摘Summary:Cancer testis(CT)antigens have received particular attention in cancer immunotherapy.OY-TES-1 is a member of CT antigens.This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma(HCC).OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR(RT-PCR).Of the 56 cases of HCC tissues tested,37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR.OY-TES-1 protein was subsequently observed on a panel of tissue microarrays.Sera from patients were tested for OY-TES-1 antibody by ELISA.To identify OY-TES-1 capable of inducing cellular immune response,OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro.The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56(73.21%)HCC tissues,whereas none in 5 normal liver tissues.OY-TES-1 mRNA was frequently expressed not only in HCC tissues(72.97%,27/37),but also in paired adjacent non-cancer tissues(64.86%,24/37).But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues(0.76854 vs.0.09834,P=0.021).Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues,and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues.Seropositivity was detected in 10 of the 45 HCC patients,but not detected in 17 cirrhosis patients and 76 healthy donors.The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2^+HCC cell line which expressed OY-TES-1.The target lysis was mainly HLA class I-dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule.In summary,OY-TES-1 expression is upregulated in HCC tissues and can be recognized by humoral and cellular responses,which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.
基金Supported by Grant-in-Aid for research by Kitasato University Medical Center,No.H25-0006 and the JSPS,KAKENHI,No.26670609 to Futawatari Nthe JSPS,KAKENHI,No.21700510 and No.17K16578,Takeda Science Foundation and Kitasato University Research Grant for Young Researchers to Fukuyama T
文摘AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.
文摘MicroRNAs(miRNAs)are small noncoding RNAs involved in the regulation of mRNA transcription and translation,and possess all desirable features of an ideal tumor marker.Of almost 31 different miRNA clusters identified in germ cell tumors(GCTs),miR-371a-3p has shown exceptionally high sensitivity and specificity for both seminomatous and nonseminomatous GCTs.It is easily obtainable and correlates well with tumor burden.Recent multiinstitutional prospective studies have shown promising test characteristics for miR-371a-3p as a diagnostic blood-based biomarker for GCT prior to orchiectomy including 80%e100%sensitivity and 90%e100%specificity.This accuracy may address other unmet needs in the management of patients with GCT.Early studies have suggested the utility of miR-371a-3p in detecting occult nodal metastasis in high-risk clinical stage I and early stage II disease.Ongoing clinical trials including SWOG 1823 and AGCT1531 are specifically designed to confirm the utility of miR-371a-3p in clinical stage I GCT.Despite its strong association with viable GCT after treatment with chemotherapy,miR-371a-3p does not seem to accurately predict the presence of teratoma in residual lesions.Also,standardization of extraction and interpretation methods is a necessary step to assure uniform results across different institutions.
基金Supported by National Natural Science Foundation of China,No 30200271
文摘AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP) in these patients was also determined.RESULTS:The positive rate of MAGE-1,SSX-1 and CTp11 transcripts was 37.7%,34.4%,31.1% in PBMC samples,and 74.4%,73.3%,62.2% in their resected tumor samples,respectively.The positive rate for at least one of the transcripts of three CTA genes was 66.7% in PBMC samples and 91.1% in their resected tumor samples.MAGE-1,SSX-1 and/or CTp11 mRNA were not detected in the PBMC of those patients from whom the resected tumor samples were MAGE-1,SSX-1 and/or CTp11 mRNA negative,nor in the PBMC samples from 20 healthy donors and 10 cirrhotic patients.Among the 90 patients,the serum AFP in 44 patients met the general diagnostic standard(AFP > 400 μg/L) for HCC,and was negative(AFP ≤ 20 μg/L) or positive with a low concentration(20 μg/L < AFP ≤ 400 μg/L) in the other patients.The positive rate for at least one of the transcripts of three CTA genes in PBMC samples from the AFP negative or positive patients with a low concentration was 69.2% and 45.0%,respectively.Of the 90 patients,71(78.9%) were diagnosed as HCC by nested RT-PCR and serum AFP.Although the positive rate for at least one of the transcripts of three CTA genes in PBMC samples from 53 patients at TNM stage or was obviously higher than that in PBMC samples from 37 patients at stage or(77.9% vs 51.4%,P = 0.010),the CTA mRNA was detected in 41.7% and 56.0% of PBMC samples from HCC patients at stages andrespectively.CONCLUSION:Detecting MAGE-1,SSX-1 and CTp11 mRNA in PBMC improves the total diagnostic rate of HCC.
基金supported by grants from National Natural Science Foundation of China(No.81460382,No.81560408,No.81360371,and No.81360374)Natural Science Foundation of Guangxi(No.2016GXNSFAA380257,No.2016GXNSFBA380159,and No.2017GXNSFAA198001)+1 种基金Guangxi Key Laboratory of Biological Targeting Diagnosis and Treatment(No.GXSWBX201505)Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)and Ministry of Education(No.GJZ201603 and No.K2015-TKF03)
文摘Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.In this review,we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.
基金support by grants from Capital’s Funds for Health Improvement and Research(Grant No.2024-2-1024)Beijing Natural Science Foundation(Grant No.7232018).
文摘Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.
基金supported by the National Natural Science Foundation of China(No.82360238,82071245)。
文摘Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.
基金Supported by Gansu Provincial Natural Science Foundation,No.21JR1RA010In-Hospital Research Fund of Gansu Provincial Hospital,No.23GSSYD-5.
文摘BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.
基金supported by the National Natural Science Foundation of China(Grant Nos.81902836 and 81572602)the China Postdoctoral Science Foundation(Grant Nos.2017M610339 and 2018M630584)。
文摘Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.
文摘Gastric precancerous lesions(GPL)represent a crucial stage in the complex process of gastric carcinogenesis that leads to gastric cancer(GC),one of the most prevalent cancers and a major source of cancer mortality worldwide.Many studies have identified the gastrointestinal microbiota,or gut microbiota,as an important contributor to both the pathogenesis and treatment of GPL and GC,thus understanding its role in this transition is crucial.The purpose of this literature review is to introduce the current landscape of microbiota research associated with GPL and GC,with an emphasis on Helicobacter pylori(H.pylori)driven microbial dysbiosis and its modulation through Western medicine and traditional Chinese medicine(TCM)approaches.By elucidating the underlying mechanisms of H.pylori colonization,patterns,and interactions among microbiota,as well as the influence of microbial metabolites,this review highlights crucial driving factors of gastric carcinogenesis.The role of microbiota in conventional interventions,including H.pylori eradication,immunotherapy,as well as TCM herbal decoctions,is also discussed to provide a detailed understanding of the complex interactions between therapy and microbiota and how it could be potentially targeted for effective management of GPL and GC.Ultimately,microbiota-targeting therapeutics may represent a new path toward early detection,targeted treatment,improved prognosis,and potentially reduced incidence of GPL and GC.
文摘Breast cancer resistance protein （Bcrp） is an ATP-dependent efflux drug transporter. It has a diverse spectrum of hydrophilic and hydrophobic substrates ranging from anticancer, antiviral and antihypertensive drugs, to organic anions, antibiotics, phytoestrogens （e.g., genistein, daidzein, coumestrol）, xenoestrogens and steroids （e.g., dehydroepiandrosterone sulfate）. Bcrp is an integral membrane protein in cancer and normal cells within multiple organs （e.g., brain, placenta, intestine and testis） that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component of the blood- brain barrier located on endothelial cells near tight junctions （TJs）. However, Bcrp is absent at the Sertoli cell blood-testis barrier （BTB）; instead, it is localized almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation （ES） in stage VI-early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F （filamentous）-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII-VIII tubules. These findings will be carefully evaluated in this brief review.
基金supported in part by the National Natural Science Foundation of China(Nos.32270555 and 32072954).
文摘Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.
