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
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
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
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 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
Recently, the immunotherapy has been highlighted among cancer treatments. Cancer-testis antigen （CTA） has been studied in a variety of solid tumors because of its specific expression in tumors, and testis, ovary and...Recently, the immunotherapy has been highlighted among cancer treatments. Cancer-testis antigen （CTA） has been studied in a variety of solid tumors because of its specific expression in tumors, and testis, ovary and placenta tissues, but not in other normal tissues. In order to provide a new ap- proach for multiple myeloma （MM） immunotherapy, we examined the CTA expression in MM cell lines, and primary myeloma cells in patients with MM. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the mRNA expression of MAGE-C1/CT7, SSX1, SSX2 and SSX4 in MM cell lines of RPMI-8226 and U266, and bone marrow （BM） Cells of 25 MM patients and 18 healthy vol- unteers. The results showed that the 4 CTAs were expressed in RPMI-8226 and U266 cell lines. The positive expression rate of MAGE-C1/CT7, SSX1, SSX2 and SSX4 in the BM cells of 25 MM patients was 28% （7/25）, 80% （20/25）, 40% （10/25） and 68% （17/25）, respectively. In contrast, the expression of any member of the CTAs was not detected in BM cells of 18 healthy volunteers. The expression of two or more CTAs was detected in 80% （20/25） MM patients, and that of at least one CTA in 88% （22/25）. The mRNA expression levels of SSX1 and SSX4 were significantly higher in patients with MM at stage III than in those at stage I and II （P〈0.05）. No statistically significant differences were observed in the mRNA expression levels of MAGE-C 1/CT7 and SSX2 in further stratified analyses by age, gender, MM types and percentage of MM cells in BM （P〉0.05）. In conclusion, our present study showed that MAGE-C1/CT7, SSX1, SSX2 and SSX4 were co-expressed in MM cell lines and the primary myeloma cells in MM patients, but not expressed in BM cells of healthy subjects. The mRNA levels of SSX1 and SSX4 are associated with MM clinical stage. This work may provide a new insight into MM immuno- therapy in the future.展开更多
Objective:There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen(PSA).There are numerous biomarkers such as prostate health index,4...Objective:There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen(PSA).There are numerous biomarkers such as prostate health index,4Kscore,prostate cancer antigen 3,ExoDX,SelectMDx,and Mi-Prostate Score that may be useful in this decision-making process.However,it is unclear whether any of these tests are accurate and cost-effective enough to warrant being a widespread reflex test following an elevated PSA.Our goal was to report on the clinical utility of these blood and urine biomarkers in prostate cancer screening.Methods:We performed a systematic review of studies published between January 2000 and October 2020 to report the available parameters and cost-effectiveness of the aforementioned diagnostic tests.We focus on the negative predictive value,the area under the curve,and the decision curve analysis in comparing reflexive tests due to their relevance in evaluating diagnostic screening tests.Results:Overall,the biomarkers are roughly equivalent in predictive accuracy.Each test has additional clinical utility to the current diagnostic standard of care,but the added benefit is not substantial to justify using the test reflexively after an elevated PSA.Conclusions:Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors,patient’s ethnicity,cost of the test,patient life-expectancy,and patient goals.There are more recent diagnostic tools such as multi-parametric magnetic resonance imaging,polygenic single-nucleotide panels,IsoPSA,and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening.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
Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already...Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe^(3+),Cu^(2+) reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.展开更多
Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory ...Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.展开更多
BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline ca...BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal.Receiver operating characteristic curve analysis assessed TMI’s prognostic accuracy,and patients were stratified into high-TMI(≥1.39)and low-TMI(<1.39)groups.The primary endpoint was overall survival(OS),with progression-free survival and treatment response as secondary endpoints.RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months.The median OS for high-TMI patients was 29.5 months,significantly lower than the 45.6 months observed in the low-TMI group(P=0.02).The 2-year OS rates for the high-and low-TMI groups were 59.4%and 72.9%,respectively.Median progression-free survival was also shorter for the high-TMI group(14.0 vs 16.0 months,P=0.84).High TMI is an independent prognostic factor for worse OS.CONCLUSION TMI is a simple,cost-effective prognostic tool for mCRC,with high TMI associated with poorer survival outcomes.展开更多
Chimeric antigen receptor T(CAR-T)cell therapy represents a major advance in cancer immunotherapy,offering targeted treatment options,particularly for hematologic malignancies.This review comprehensively explores the ...Chimeric antigen receptor T(CAR-T)cell therapy represents a major advance in cancer immunotherapy,offering targeted treatment options,particularly for hematologic malignancies.This review comprehensively explores the structural evolution,production processes,and cytotoxic mechanisms underlying CAR-T function.Therapy involves engineering autologous T cells with synthetic receptors that allow major histocompatibility complex-independent recognition of tumor-associated antigens.Key structural components such as antigen recognition domains,spacers,transmembrane,and intracellular domains are optimized to enhance specificity,persistence,and cytotoxicity.CAR-T therapy exerts antitumor effects via granzyme-perforin degranulation,Fas/Fas ligand signaling,and cytokine secretion.Over time,the development of second-to fifth-generation CARs has incorporated costimulatory molecules,transcriptional regulation,and logic-gated control to improve efficacy and safety.Additionally,novel engineering strategies such as dual CARs,tandem CARs,SynNotch systems,and universal or inhibitory CARs have expanded antigen targeting and reduced offtumor toxicity.Emerging gene delivery technologies,including viral vectors,transposons,CRISPR/Cas9,and RNA-based electroporation,are improving CART production.Despite notable clinical success,particularly in CD19-and B-cell maturation antigen-targeted therapies,CAR-T applications face challenges,including cell exhaustion,antigen escape,and therapy-induced toxicities,such as cytokine release syndrome and neurotoxicity.Ongoing efforts in engineering innovation,clinical trials,and regulatory support continue to shape CAR-T therapy into a safer,more precise tool for cancer treatment.This review highlights current advances while outlining the barriers and future prospects of CAR-T immunotherapy.展开更多
BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve p...BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve patient survival,adjuvant chemotherapy is commonly administered based on established postoperative guidelines.Despite advancements in chemotherapy delivery,the overall response rate remains below 50%,primarily due to the lack of targeted therapies tailored to specific patient populations.AIM To explore sensitive biomarkers to assess the efficacy of postoperative adjuvant chemotherapy in appropriate patient subgroups.METHODS This study retrospectively analyzed 1628 patients who underwent radical gastrectomy for GC at our hospital in 2017 and 2018,with a subsequent five-year follow-up.Patients were divided based on whether they received postoperative adjuvant chemotherapy.The study aimed to determine optimal cutoff values for various biomarkersneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,carcinoembryonic antigen(CEA),carbohydrate antigen(CA)199,CA724,and CA242-using receiver operating characteristic(ROC)curves.Based on the optimal ROC cut-off,a novel combined metric,NLR-CEA,was developed to assess the efficacy of adjuvant chemotherapy following GC surgery.RESULTS Cox subgroup analysis demonstrated that postoperative adjuvant chemotherapy significantly improved overall survival in the NLR-CEA_Low group with a rate of 0.41(0.26-0.63).In the NLR-CEA_Middle group,the protective effect was observed at 0.69(0.54-0.87),while in the NLR-CEA_High group,it was 0.73(0.53-0.99).Notably,a 32%difference in the efficacy of chemotherapy was observed between the NLR-CEA_Low and NLR-CEA_High groups.CONCLUSION NLR-CEA is an effective biomarker for evaluating the efficacy of postoperative adjuvant chemotherapy in GC.Patients with NLR-CEA_Low exhibit significantly better responses to chemotherapy compared to those with NLRCEA_High.展开更多
BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remain...BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remains limited.AIM To investigate the correlation between baseline MRI features and serum CEA levels in patients diagnosed with primary rectal cancer.METHODS Eighty patients(age:42-78 years)diagnosed with primary rectal cancer were enrolled.Baseline MRI examinations were performed to evaluate tumor size,T stage,circumferential resection margin status,extramural vascular invasion(EMVI),and lymph node metastasis.Serum CEA levels were concurrently measured.Statistical methods were used to analyze correlations.RESULTS Tumor size,T stage,EMVI,and lymph node metastasis were significantly correlated with serum CEA levels(P<0.05).Multivariate analysis identified T stage and lymph node metastasis as independent factors influencing serum CEA levels.CONCLUSION This study confirmed the correlation between baseline MRI features and serum CEA levels in patients with primary rectal cancer,highlighting their potential utility for precise diagnosis,staging,and prognostic evaluation.展开更多
Background:This study aimed to evaluate the prognostic value of the lymphocyte-to-monocyte ratio(LMR)and cancer antigen 724(CA724)in patients with proximal gastric cancer residing in cold climate regions.Methods:A ret...Background:This study aimed to evaluate the prognostic value of the lymphocyte-to-monocyte ratio(LMR)and cancer antigen 724(CA724)in patients with proximal gastric cancer residing in cold climate regions.Methods:A retrospective analysis was conducted on 313 patients diagnosed with proximal gastric cancer in cold climate regions between 2014 and 2017.Preoperative hematological markers,including LMR and CA724,were assessed.Receiver operating characteristic(ROC)curves were used to determine optimal cutoff values,which were then combined to form the LMR+CA724 score.Statistical analyses included Kaplan-Meier survival curves,log-rank tests,and Cox proportional hazards regression.Results:A high preoperative LMR+CA724 score was significantly associated with older age,advanced pTNM stage,vascular invasion,and elevated levels of NMPVR,NMR,and AAR.The LMR+CA724 score demonstrated a higher area under the curve(AUC)compared to LMR or CA724 alone.Multivariate analysis identified pTNM stage,Borrmann type,histological type,and the LMR+CA724 score as independent prognostic factors for overall survival(OS).A nomogram incorporating these four variables achieved an AUC of 0.817,indicating strong predictive performance.Conclusion:The LMR+CA724 score is a reliable and independent prognostic indicator for patients with proximal gastric cancer in cold climate regions.Its integration into clinical practice may support treatment planning and long-term management by enhancing personalized care.Further prospective studies are warranted to validate these findings in broader and more diverse patient populations.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
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.
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 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supported by the Natural Science Foundation of Hubei Province,China(No.2012FK04452)
文摘Recently, the immunotherapy has been highlighted among cancer treatments. Cancer-testis antigen （CTA） has been studied in a variety of solid tumors because of its specific expression in tumors, and testis, ovary and placenta tissues, but not in other normal tissues. In order to provide a new ap- proach for multiple myeloma （MM） immunotherapy, we examined the CTA expression in MM cell lines, and primary myeloma cells in patients with MM. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the mRNA expression of MAGE-C1/CT7, SSX1, SSX2 and SSX4 in MM cell lines of RPMI-8226 and U266, and bone marrow （BM） Cells of 25 MM patients and 18 healthy vol- unteers. The results showed that the 4 CTAs were expressed in RPMI-8226 and U266 cell lines. The positive expression rate of MAGE-C1/CT7, SSX1, SSX2 and SSX4 in the BM cells of 25 MM patients was 28% （7/25）, 80% （20/25）, 40% （10/25） and 68% （17/25）, respectively. In contrast, the expression of any member of the CTAs was not detected in BM cells of 18 healthy volunteers. The expression of two or more CTAs was detected in 80% （20/25） MM patients, and that of at least one CTA in 88% （22/25）. The mRNA expression levels of SSX1 and SSX4 were significantly higher in patients with MM at stage III than in those at stage I and II （P〈0.05）. No statistically significant differences were observed in the mRNA expression levels of MAGE-C 1/CT7 and SSX2 in further stratified analyses by age, gender, MM types and percentage of MM cells in BM （P〉0.05）. In conclusion, our present study showed that MAGE-C1/CT7, SSX1, SSX2 and SSX4 were co-expressed in MM cell lines and the primary myeloma cells in MM patients, but not expressed in BM cells of healthy subjects. The mRNA levels of SSX1 and SSX4 are associated with MM clinical stage. This work may provide a new insight into MM immuno- therapy in the future.
文摘Objective:There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen(PSA).There are numerous biomarkers such as prostate health index,4Kscore,prostate cancer antigen 3,ExoDX,SelectMDx,and Mi-Prostate Score that may be useful in this decision-making process.However,it is unclear whether any of these tests are accurate and cost-effective enough to warrant being a widespread reflex test following an elevated PSA.Our goal was to report on the clinical utility of these blood and urine biomarkers in prostate cancer screening.Methods:We performed a systematic review of studies published between January 2000 and October 2020 to report the available parameters and cost-effectiveness of the aforementioned diagnostic tests.We focus on the negative predictive value,the area under the curve,and the decision curve analysis in comparing reflexive tests due to their relevance in evaluating diagnostic screening tests.Results:Overall,the biomarkers are roughly equivalent in predictive accuracy.Each test has additional clinical utility to the current diagnostic standard of care,but the added benefit is not substantial to justify using the test reflexively after an elevated PSA.Conclusions:Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors,patient’s ethnicity,cost of the test,patient life-expectancy,and patient goals.There are more recent diagnostic tools such as multi-parametric magnetic resonance imaging,polygenic single-nucleotide panels,IsoPSA,and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening.
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.
文摘Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe^(3+),Cu^(2+) reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.
基金the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2021A1515012180,2023A1515012762 and No.2019A1515010962+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.
文摘BACKGROUND Metastatic colorectal cancer(mCRC)is a global health challenge with a poor prognosis.Prognostic markers are critical for survival prediction.METHODS This multicenter,retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal.Receiver operating characteristic curve analysis assessed TMI’s prognostic accuracy,and patients were stratified into high-TMI(≥1.39)and low-TMI(<1.39)groups.The primary endpoint was overall survival(OS),with progression-free survival and treatment response as secondary endpoints.RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months.The median OS for high-TMI patients was 29.5 months,significantly lower than the 45.6 months observed in the low-TMI group(P=0.02).The 2-year OS rates for the high-and low-TMI groups were 59.4%and 72.9%,respectively.Median progression-free survival was also shorter for the high-TMI group(14.0 vs 16.0 months,P=0.84).High TMI is an independent prognostic factor for worse OS.CONCLUSION TMI is a simple,cost-effective prognostic tool for mCRC,with high TMI associated with poorer survival outcomes.
文摘Chimeric antigen receptor T(CAR-T)cell therapy represents a major advance in cancer immunotherapy,offering targeted treatment options,particularly for hematologic malignancies.This review comprehensively explores the structural evolution,production processes,and cytotoxic mechanisms underlying CAR-T function.Therapy involves engineering autologous T cells with synthetic receptors that allow major histocompatibility complex-independent recognition of tumor-associated antigens.Key structural components such as antigen recognition domains,spacers,transmembrane,and intracellular domains are optimized to enhance specificity,persistence,and cytotoxicity.CAR-T therapy exerts antitumor effects via granzyme-perforin degranulation,Fas/Fas ligand signaling,and cytokine secretion.Over time,the development of second-to fifth-generation CARs has incorporated costimulatory molecules,transcriptional regulation,and logic-gated control to improve efficacy and safety.Additionally,novel engineering strategies such as dual CARs,tandem CARs,SynNotch systems,and universal or inhibitory CARs have expanded antigen targeting and reduced offtumor toxicity.Emerging gene delivery technologies,including viral vectors,transposons,CRISPR/Cas9,and RNA-based electroporation,are improving CART production.Despite notable clinical success,particularly in CD19-and B-cell maturation antigen-targeted therapies,CAR-T applications face challenges,including cell exhaustion,antigen escape,and therapy-induced toxicities,such as cytokine release syndrome and neurotoxicity.Ongoing efforts in engineering innovation,clinical trials,and regulatory support continue to shape CAR-T therapy into a safer,more precise tool for cancer treatment.This review highlights current advances while outlining the barriers and future prospects of CAR-T immunotherapy.
文摘BACKGROUND Gastric cancer(GC)is an aggressive malignancy of the gastrointestinal tract characterized by high recurrence rates following radical gastrectomy.To enhance treatment efficacy,reduce recurrence,and improve patient survival,adjuvant chemotherapy is commonly administered based on established postoperative guidelines.Despite advancements in chemotherapy delivery,the overall response rate remains below 50%,primarily due to the lack of targeted therapies tailored to specific patient populations.AIM To explore sensitive biomarkers to assess the efficacy of postoperative adjuvant chemotherapy in appropriate patient subgroups.METHODS This study retrospectively analyzed 1628 patients who underwent radical gastrectomy for GC at our hospital in 2017 and 2018,with a subsequent five-year follow-up.Patients were divided based on whether they received postoperative adjuvant chemotherapy.The study aimed to determine optimal cutoff values for various biomarkersneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio,carcinoembryonic antigen(CEA),carbohydrate antigen(CA)199,CA724,and CA242-using receiver operating characteristic(ROC)curves.Based on the optimal ROC cut-off,a novel combined metric,NLR-CEA,was developed to assess the efficacy of adjuvant chemotherapy following GC surgery.RESULTS Cox subgroup analysis demonstrated that postoperative adjuvant chemotherapy significantly improved overall survival in the NLR-CEA_Low group with a rate of 0.41(0.26-0.63).In the NLR-CEA_Middle group,the protective effect was observed at 0.69(0.54-0.87),while in the NLR-CEA_High group,it was 0.73(0.53-0.99).Notably,a 32%difference in the efficacy of chemotherapy was observed between the NLR-CEA_Low and NLR-CEA_High groups.CONCLUSION NLR-CEA is an effective biomarker for evaluating the efficacy of postoperative adjuvant chemotherapy in GC.Patients with NLR-CEA_Low exhibit significantly better responses to chemotherapy compared to those with NLRCEA_High.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LTGY24H160006Jiaxing Medical Key Discipline,No.2023-ZC-015.
文摘BACKGROUND Serum carcinoembryonic antigen(CEA)levels and magnetic resonance imaging(MRI)findings are widely used for the diagnosis and treatment of rectal cancer;however,research investigating their correlation remains limited.AIM To investigate the correlation between baseline MRI features and serum CEA levels in patients diagnosed with primary rectal cancer.METHODS Eighty patients(age:42-78 years)diagnosed with primary rectal cancer were enrolled.Baseline MRI examinations were performed to evaluate tumor size,T stage,circumferential resection margin status,extramural vascular invasion(EMVI),and lymph node metastasis.Serum CEA levels were concurrently measured.Statistical methods were used to analyze correlations.RESULTS Tumor size,T stage,EMVI,and lymph node metastasis were significantly correlated with serum CEA levels(P<0.05).Multivariate analysis identified T stage and lymph node metastasis as independent factors influencing serum CEA levels.CONCLUSION This study confirmed the correlation between baseline MRI features and serum CEA levels in patients with primary rectal cancer,highlighting their potential utility for precise diagnosis,staging,and prognostic evaluation.
基金supported by the Postdoctoral Scientific Research Development Fund of Heilongjiang Province,2020(Grant No.LBH-Q20157).
文摘Background:This study aimed to evaluate the prognostic value of the lymphocyte-to-monocyte ratio(LMR)and cancer antigen 724(CA724)in patients with proximal gastric cancer residing in cold climate regions.Methods:A retrospective analysis was conducted on 313 patients diagnosed with proximal gastric cancer in cold climate regions between 2014 and 2017.Preoperative hematological markers,including LMR and CA724,were assessed.Receiver operating characteristic(ROC)curves were used to determine optimal cutoff values,which were then combined to form the LMR+CA724 score.Statistical analyses included Kaplan-Meier survival curves,log-rank tests,and Cox proportional hazards regression.Results:A high preoperative LMR+CA724 score was significantly associated with older age,advanced pTNM stage,vascular invasion,and elevated levels of NMPVR,NMR,and AAR.The LMR+CA724 score demonstrated a higher area under the curve(AUC)compared to LMR or CA724 alone.Multivariate analysis identified pTNM stage,Borrmann type,histological type,and the LMR+CA724 score as independent prognostic factors for overall survival(OS).A nomogram incorporating these four variables achieved an AUC of 0.817,indicating strong predictive performance.Conclusion:The LMR+CA724 score is a reliable and independent prognostic indicator for patients with proximal gastric cancer in cold climate regions.Its integration into clinical practice may support treatment planning and long-term management by enhancing personalized care.Further prospective studies are warranted to validate these findings in broader and more diverse patient populations.
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.
