Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectivenes...Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.展开更多
Cancer has long been amajor threat to human health.Recent advancements inmolecular imaging have revolutionized cancer research by enabling early and precise disease localization,essential for effective management.In p...Cancer has long been amajor threat to human health.Recent advancements inmolecular imaging have revolutionized cancer research by enabling early and precise disease localization,essential for effective management.In particular,optical molecular imaging is an invaluable cancer detection tool in preoperative planning,intraoperative guidance,and postoperative monitoring owing to its noninvasive nature,rapid turnover,safety,and ease of use.The tumor microenvironment and cells within it express distinct biomarkers.Optical imaging technology leverages these markers to differentiate tumor tissues from surrounding tissues and capture real-time images with high resolution.Nevertheless,a robust understanding of these cancer-relatedmolecules and their dynamic changes is crucial for effectivelymanaging cancer.Recent advancements in opticalmolecular imaging technologies offer novel approaches for cancer investigation in research and practice.This review investigates themodern opticalmolecular imaging techniques employed in both preclinical and clinical research,including bioluminescence,fluorescence,chemiluminescence,photoacoustic imaging,and Raman spectroscopy.We explore the current paradigm of optical molecular imaging modalities,their current status in preclinical cancer research and clinical applications,and future perspectives in the fields of cancer research and treatment.展开更多
Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph ...Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.展开更多
Background:Previous studies have established the role of 2-oxoglutarate and Fe(II)-dependent oxygenase domain–containing protein 1(OGFOD1)in oncogenesis.The objective of this investigation was to discern the diagnost...Background:Previous studies have established the role of 2-oxoglutarate and Fe(II)-dependent oxygenase domain–containing protein 1(OGFOD1)in oncogenesis.The objective of this investigation was to discern the diagnostic and prognostic relevance of OGFOD1 within the context of bladder cancer(BLCA)using bioinformatics methodologies.Methods:We collected RNA sequencing data from The Cancer Genome Atlas database and verified it using the GSE13507 dataset.Immunohistochemical analysis was based on data from the human protein atlas,and the protein-protein interaction network was constructed using the STRING database.Bioinformatics analysis was performed using the R application,analyzing the correlation between clinical characteristics and OGFOD1 expression,exploring the potential mechanisms of OGFOD1 in BLCA through Kyoto Encyclopedia of Genes and Genomes analysis,and evaluating the diagnostic and prognostic value of OGFOD1 expression in BLCA through receiver operating characteristic curve analysis,Kaplan-Meier analysis,and multivariate Cox analysis.Furthermore,a BLCA prognostic nomogram was constructed.Results:We report higher expression levels of OGFOD1 in BLCA specimens compared with those in noncancerous tissues;this can be used to predict the outcome of the disease.Further,results suggest that OGFOD1 is implicated in the activation of the peroxisome proliferator-activated receptor signaling cascade,potentially interacting with other genes linked to expression in promoting the onset and progression of BLCA.Conclusions:OGFOD1 is a promising candidate as a prognostic indicator in BLCA.展开更多
The increased risk of mucosa-associated lymphoid tissue(MALT)lymphoma is closely associated with chronic antigenic stimulation,with infection being the most common cause of recurrence.Lesions are usually associated wi...The increased risk of mucosa-associated lymphoid tissue(MALT)lymphoma is closely associated with chronic antigenic stimulation,with infection being the most common cause of recurrence.Lesions are usually associated with the gastrointestinal tract,and the involvement of small intestinal is rare.Recent studies have established a close relationship between novel coronavirus 2019(COVID-19)and the occurrence and progression of various diseases.This article presents a rare case of a small intestinal MALT lymphoma.The patient was initially admitted with COVID-19 pneumonia and subsequently developed gastrointestinal bleeding during hospitalization.Medical and endoscopic treatments were ineffective,and an emergency exploratory laparotomy was performed.The affected segment of the small intestine was excised,and a pathological biopsy confirmed the diagnosis of MALT lymphoma.This case underscores the significance of raising clinical awareness of this condition among health care professionals.展开更多
Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of Califor...Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.展开更多
Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular ...Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.展开更多
Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives...Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives.Teamwork with multimodal care is the key to achieving satisfactory outcomes.Advanced imaging modalities have aided in early detection and derivation of optimal treatment plans.Although radical excision of tumors with neoadjuvant or concurrent chemotherapy/radiotherapy has long been the best management option,we have moved froma radical to a conservative approach.In advanced disease,the plan should be to provide supportive care and improve quality of life.Compassion and counseling play important roles.Nutritional support for correcting cancer cachexia is equally important during tumor excision.Newer therapies such as targeted therapy,stem cell therapy,and chemodynamic therapy are all focused on ensuring safe and efficient outcomes;however,the war against cancer continues to oscillate between hope and despair.展开更多
Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes ...Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.展开更多
Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cis...Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.展开更多
MicroRNA-494(miR-494)has emerged as a potential diagnostic biomarker for cancer detection,but conflicting reports have led to uncertainty regarding its clinical utility.This study aims to address these discrepancies b...MicroRNA-494(miR-494)has emerged as a potential diagnostic biomarker for cancer detection,but conflicting reports have led to uncertainty regarding its clinical utility.This study aims to address these discrepancies by conducting a comprehensive metaanalysis of miR-494 diagnostic performance across various cancer types.A comprehensive literature search was performed across multiple databases,including PubMed,Web of Science,Wanfang databases,and CNKI(China National Knowledge Infrastructure),with a cutoff date of April 23,2024.Eligible studies were identified using predefined inclusion criteria and various search strategies to ensure a thorough coverage of the available evidence.To evaluate the diagnostic performance of miR-494 in cancer detection,relevant measures such as sensitivity,specificity,and other diagnostic accuracy indicators were extracted from the included studies.These data were synthesized using bivariate meta-analysis models to generate pooled estimates of miR-494 diagnostic performance.All statistical analyses were conducted using the STATA 16.0 software.This meta-analysis pooled data from 8 studies,comprising a total of 647 cancer cases and 407 healthy controls.The aggregated diagnostic performance of miR-494 was as follows:a sensitivity of 0.67(95%confidence interval[CI],0.52–0.80),a specificity of 0.85(95%CI,0.77–0.91),and an area under the curve of 0.86(95%CI,0.82–0.88),indicating good overall diagnostic accuracy.The diagnostic odds ratio(DOR)was 12.11(95%CI,7–21),suggesting that miR-494 has strong discriminatory power in distinguishing cancer patients from healthy individuals.The positive likelihood ratio of 4.62(95%CI,3.1–6.8)and negative likelihood ratio of 0.38(95%CI,0.26–0.56)further support the diagnostic utility of miR-494.Deeks’funnel plot asymmetry test was employed to assess potential publication bias,yielding a P value of 0.50,which suggests the absence of significant bias in the included studies.The meta-analysis results suggest that miR-494 exhibits promising diagnostic performance in detecting cancer,with moderate accuracy.The pooled sensitivity,specificity,and high area under the receiver operating characteristic curve highlight its potential as a cancer biomarker,indicating its utility in early detection and accurate diagnosis.展开更多
The growth of solid tumors relies on establishing a robust blood supply,with angiogenesis playing a key role in this intricate process.Based on this understanding,therapeutic strategies targeting tumor angiogenesis ha...The growth of solid tumors relies on establishing a robust blood supply,with angiogenesis playing a key role in this intricate process.Based on this understanding,therapeutic strategies targeting tumor angiogenesis have been developed.However,the clinical effectiveness of antiangiogenic therapy(AAT)in treating tumors has not lived up to expectations.In recent years,vasculogenic mimicry(VM)has attracted increasing attention from the academic community as a longstanding but often overlooked mechanism of nonangiogenic tumor vascularization.Within the tumor microenvironment,neoplastic cells can autonomously form vessel-like structures,creating a blood supply that does not rely on endothelial cells.This phenomenon,known as VM,is a critical marker of aggressive tumors and may play a significant role in conferring resistance to AAT.In this review,we thoroughly examine the evidence,clinical characteristics,and mechanisms of VM across various tumor types and explore its potential role and importance in resistance to AAT and the development of new antitumor therapies.展开更多
Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer...Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.展开更多
Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to iden...Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.展开更多
Background:To observe the changes in serum calcitonin levels after application of different surgical methods for primary medullary thyroid microcarcinoma(MTMC)and explore a more reasonable surgical method.Methods:A re...Background:To observe the changes in serum calcitonin levels after application of different surgical methods for primary medullary thyroid microcarcinoma(MTMC)and explore a more reasonable surgical method.Methods:A retrospective analysis of 36 patients with MTMC,16 in group A and 20 in group B,was performed.In group A,tumors were single and confined to the thyroid lobe,and thyroid lobectomy with isthmusectomy was performed.In group B,tumors were in the isthmus or invaded the thyroid gland,or there were multiple foci in bilateral lobes,and patients with primary foci underwent total thyroidectomy.The median follow-up time was 3.6 years.Clinical and pathological characteristics and changes in serum calcitonin(CTn)and carcinoembryonic antigen levels after the surgery were compared between the 2 groups.Results:The difference in the biochemical cure rate after surgery was statistically significant between patients with preoperative serum calcitonin levels<150 pg/mL and≥150 pg/mL(P<0.01).No significant differences in the biochemical cure rates and serum calcitonin levels were noted at different time points after surgery between group A and group B(P>0.05).One recurrence and metastasis were observed in each group after surgery.Conclusions:After performing different surgical methods for the primary foci of MTMC,the changes in serum calcitonin and carcinoembryonic antigen levels are similar.Especially for patients with single foci confined to the thyroid lobe without lateral cervical lymph node metastasis and with serum calcitonin levels<150 pg/mL,the unilateral thyroid lobectomy with isthmectomy can achieve the same therapeutic effect and biochemical cure rate as total thyroidectomy.展开更多
Background:Some observational associations between body weight and breast cancer have attracted attention.However,the causal relationship between these 2 factors remains unclear,and more clinical outcomes are needed f...Background:Some observational associations between body weight and breast cancer have attracted attention.However,the causal relationship between these 2 factors remains unclear,and more clinical outcomes are needed for its validation.Methods:Based on statistical data from a Genome Wide Association Study,we performed a bidirectional Mendelian randomization analysis to assess the bidirectional causal relationship between body weight and breast cancer using 4 methods,with inverse variance weighting as the primarymethod.To verify the robustness and reliability of the causal relationship,we performed a sensitivity analysis using horizontal pleiotropy,outlier,and one-by-one elimination tests.Results:The inverse variance weighting results revealed no significant positive causal relationship between body weight and breast cancer.Similarly,the reverse analysis revealed no causal effect of breast cancer on body weight.Conclusions:The relationship between body weight and breast cancer may be attributed to confounding factors.展开更多
A 44-year-old patient was admitted with tumor rupture in the left hepatic lateral lobe,and he underwent emergent exploratory laparotomy and proceeded for hepatic left lateral lobectomy on September 19,2021.The final d...A 44-year-old patient was admitted with tumor rupture in the left hepatic lateral lobe,and he underwent emergent exploratory laparotomy and proceeded for hepatic left lateral lobectomy on September 19,2021.The final diagnosis of hepatocellular carcinoma was confirmed by histopathological examination of the surgical specimen.Afterward,the patient received hepatic arterial infusion chemotherapy with FOLFOX(oxaliplatin,fluorouracil,and leucovorin)for 5 cycles.Subsequently,recurrence of the hepatocellular carcinoma was diagnosed in the abdominal cavity.The patient was then treated with lenvatinib.Within less than 1 month of the treatment with lenvatinib,the patient was admitted to the emergency room on June 2,2022,because of acute intra-abdominal bleeding(hematomas).Percutaneous intra-abdominal angiography found that the bleeding vessels were the right gastroepiploic artery and left gastric artery.The patient was stabilized after arterial embolization using gelatin sponges.The diagnosis and management of spontaneous intra-abdominal hematomas are discussed.展开更多
Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-der...Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.展开更多
Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be fur...Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.展开更多
Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological...Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.展开更多
基金funded by the Science and Technology Plan of Inner Mongolia Autonomous Region(no.2022YFSH0097)the Medical Research Advancement Fund Project(no.TB212014).
文摘Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.
基金supported by the National Key R&D Program(the 14th Five-Year Plan)(no.2023YFC2706001 and no.2023YFC2706003).
文摘Cancer has long been amajor threat to human health.Recent advancements inmolecular imaging have revolutionized cancer research by enabling early and precise disease localization,essential for effective management.In particular,optical molecular imaging is an invaluable cancer detection tool in preoperative planning,intraoperative guidance,and postoperative monitoring owing to its noninvasive nature,rapid turnover,safety,and ease of use.The tumor microenvironment and cells within it express distinct biomarkers.Optical imaging technology leverages these markers to differentiate tumor tissues from surrounding tissues and capture real-time images with high resolution.Nevertheless,a robust understanding of these cancer-relatedmolecules and their dynamic changes is crucial for effectivelymanaging cancer.Recent advancements in opticalmolecular imaging technologies offer novel approaches for cancer investigation in research and practice.This review investigates themodern opticalmolecular imaging techniques employed in both preclinical and clinical research,including bioluminescence,fluorescence,chemiluminescence,photoacoustic imaging,and Raman spectroscopy.We explore the current paradigm of optical molecular imaging modalities,their current status in preclinical cancer research and clinical applications,and future perspectives in the fields of cancer research and treatment.
基金funded by the National Natural Science Foundation of China(no.82103671).
文摘Background:Luminal A breast cancer has the best prognosis of all malignant breast cancer types.In clinical practice,some patients with luminal A breast cancer present with small tumors(usually<20 mm)but with lymph node metastases or even distant organ metastasis.Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence,there is a significant gap in research on luminal A breast cancer with high invasiveness.This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms.Methods:In this study,we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2(DDHD2).We then evaluated the association between DDHD2 expression and patient prognosis,genetic material changes,and transcriptional,translational,and immune responses in luminal A breast cancer.We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms.Results:The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases.Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration,regulating cell proliferation and apoptosis cycles,and suppressing immune responses.Moreover,a pathway through which DDHD2 inhibited immunity was preliminarily verified.Conclusions:The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer.Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition,DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.
文摘Background:Previous studies have established the role of 2-oxoglutarate and Fe(II)-dependent oxygenase domain–containing protein 1(OGFOD1)in oncogenesis.The objective of this investigation was to discern the diagnostic and prognostic relevance of OGFOD1 within the context of bladder cancer(BLCA)using bioinformatics methodologies.Methods:We collected RNA sequencing data from The Cancer Genome Atlas database and verified it using the GSE13507 dataset.Immunohistochemical analysis was based on data from the human protein atlas,and the protein-protein interaction network was constructed using the STRING database.Bioinformatics analysis was performed using the R application,analyzing the correlation between clinical characteristics and OGFOD1 expression,exploring the potential mechanisms of OGFOD1 in BLCA through Kyoto Encyclopedia of Genes and Genomes analysis,and evaluating the diagnostic and prognostic value of OGFOD1 expression in BLCA through receiver operating characteristic curve analysis,Kaplan-Meier analysis,and multivariate Cox analysis.Furthermore,a BLCA prognostic nomogram was constructed.Results:We report higher expression levels of OGFOD1 in BLCA specimens compared with those in noncancerous tissues;this can be used to predict the outcome of the disease.Further,results suggest that OGFOD1 is implicated in the activation of the peroxisome proliferator-activated receptor signaling cascade,potentially interacting with other genes linked to expression in promoting the onset and progression of BLCA.Conclusions:OGFOD1 is a promising candidate as a prognostic indicator in BLCA.
基金the Wuhan Young and Middle-aged Medical Backbone Personnel Training Project(No.2016(59)).
文摘The increased risk of mucosa-associated lymphoid tissue(MALT)lymphoma is closely associated with chronic antigenic stimulation,with infection being the most common cause of recurrence.Lesions are usually associated with the gastrointestinal tract,and the involvement of small intestinal is rare.Recent studies have established a close relationship between novel coronavirus 2019(COVID-19)and the occurrence and progression of various diseases.This article presents a rare case of a small intestinal MALT lymphoma.The patient was initially admitted with COVID-19 pneumonia and subsequently developed gastrointestinal bleeding during hospitalization.Medical and endoscopic treatments were ineffective,and an emergency exploratory laparotomy was performed.The affected segment of the small intestine was excised,and a pathological biopsy confirmed the diagnosis of MALT lymphoma.This case underscores the significance of raising clinical awareness of this condition among health care professionals.
基金supported by a grant from the Nantong City Science and Technology Bureau Project(no.:HS2020005).
文摘Background:This study investigated the multifaceted role of BRCA2(breast cancer 2)in various cancer types,with a specific focus on thyroid carcinoma(THCA).Methods:Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression,genetic alterations,and clinical implications.Sample filtering criteria were applied,and immunohistochemistry from the Human Protein Atlas was used to validate protein expression.Correlation analyses were used to explore associations between immune-related genes,and immunological signatures were assessed using various tools.Genetic alterations in BRCA2 were analyzed using cBioPortal,and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA.Results:In patients with THCA,differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues.Correlation studies revealed associations between BRCA2 and immune-related genes,emphasizing its potential role in modulating the tumor microenvironment.Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors.Moreover,genetic alterations in BRCA2,particularly the A2738S mutation in exon 18,have been identified in patients with THCA.The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA.Additionally,BRCA2 expression was associated with prognostic factors such as stage and N.Conclusions:This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression,immune modulation,genetic alterations,and clinical prognosis.These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.
基金supported by the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(FBW,grant ZNJC202210)the CAMS Innovation Fund for Medical Sciences(FBW,grant 2022-I2M-C&T-B-118)+1 种基金the National Natural Science Foundation of China(XYM,grant 82303057)the Natural Science Foundation of Hubei Province of China(XYM,grant 2023 AFB521).
文摘Background:The effective management of bladder cancer(BCa)depends on the early diagnosis and surveillance.Previous studies have explored numerous urinary molecules as potential biomarkers of BCa.However,the molecular functions and cell-of-origin profiles of these biomarkers are yet to be elucidated.In this study,we aimed to provide a comprehensive overview of the landscape of urinary biomarker genes for BCa.Methods:We conducted an exhaustive literature search in PubMed,through which 555 biomarker genes were identified.We then analyzed the BCa single-cell atlas to infer the cellular origin of these BCa urine biomarker genes and performed functional enrichment analysis to gain insights into the functional molecular implications of these biomarkers.Results:These genes are involved in tumor proliferation,angiogenesis,cellmigration,and cell death and are predominantly expressed in epithelial and stromal cells.Interestingly,our analysis ofmultiomics tumor data revealed a discordance between tissue and urine in terms of differential methylation and RNA expression,suggesting that biomarker discovery for liquid biopsies should ideally begin with the analysis of bodily fluids rather than relying interest and that test strategies incorporating multiple molecular markers represent an ongoing trend.Conclusions:Collectively,our study has built a landscape of BCa urine biomarker genes,uncovered molecular insights into these biomarkers,and revealed the bibliometric trends in this field,which will contribute to the discovery of novel biomarkers in the future.
文摘Theword“cancer”is associated with terrifying situations,and there is often an aggressive intent to cure.Uncertainty about survival and fear of disfigurement cause major turmoil in the minds of patients and relatives.Teamwork with multimodal care is the key to achieving satisfactory outcomes.Advanced imaging modalities have aided in early detection and derivation of optimal treatment plans.Although radical excision of tumors with neoadjuvant or concurrent chemotherapy/radiotherapy has long been the best management option,we have moved froma radical to a conservative approach.In advanced disease,the plan should be to provide supportive care and improve quality of life.Compassion and counseling play important roles.Nutritional support for correcting cancer cachexia is equally important during tumor excision.Newer therapies such as targeted therapy,stem cell therapy,and chemodynamic therapy are all focused on ensuring safe and efficient outcomes;however,the war against cancer continues to oscillate between hope and despair.
文摘Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.
基金the Beijing Municipal Science and Technology Commission(grant Z211100002921013)the Tongzhou District Science and Technology Committee Project to Tongzhou(grant KJ2020CX010).
文摘Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.
基金supported by grants fromthe National Natural Science Foundation of China(no.82272961)Guangdong Basic and Applied Basic Research Foundation(no.2022A1515011353)the ShenzhenMunicipal Commission of Science and Technology Innovation(no.JCYJ20220530150814033).
文摘MicroRNA-494(miR-494)has emerged as a potential diagnostic biomarker for cancer detection,but conflicting reports have led to uncertainty regarding its clinical utility.This study aims to address these discrepancies by conducting a comprehensive metaanalysis of miR-494 diagnostic performance across various cancer types.A comprehensive literature search was performed across multiple databases,including PubMed,Web of Science,Wanfang databases,and CNKI(China National Knowledge Infrastructure),with a cutoff date of April 23,2024.Eligible studies were identified using predefined inclusion criteria and various search strategies to ensure a thorough coverage of the available evidence.To evaluate the diagnostic performance of miR-494 in cancer detection,relevant measures such as sensitivity,specificity,and other diagnostic accuracy indicators were extracted from the included studies.These data were synthesized using bivariate meta-analysis models to generate pooled estimates of miR-494 diagnostic performance.All statistical analyses were conducted using the STATA 16.0 software.This meta-analysis pooled data from 8 studies,comprising a total of 647 cancer cases and 407 healthy controls.The aggregated diagnostic performance of miR-494 was as follows:a sensitivity of 0.67(95%confidence interval[CI],0.52–0.80),a specificity of 0.85(95%CI,0.77–0.91),and an area under the curve of 0.86(95%CI,0.82–0.88),indicating good overall diagnostic accuracy.The diagnostic odds ratio(DOR)was 12.11(95%CI,7–21),suggesting that miR-494 has strong discriminatory power in distinguishing cancer patients from healthy individuals.The positive likelihood ratio of 4.62(95%CI,3.1–6.8)and negative likelihood ratio of 0.38(95%CI,0.26–0.56)further support the diagnostic utility of miR-494.Deeks’funnel plot asymmetry test was employed to assess potential publication bias,yielding a P value of 0.50,which suggests the absence of significant bias in the included studies.The meta-analysis results suggest that miR-494 exhibits promising diagnostic performance in detecting cancer,with moderate accuracy.The pooled sensitivity,specificity,and high area under the receiver operating characteristic curve highlight its potential as a cancer biomarker,indicating its utility in early detection and accurate diagnosis.
基金supported by grants from the Scientific and Technological Project of Henan Province(grant no.232102311024 and 222102310001)the Henan Provincial Key Projects of Medical Science and Technology Project(grant no.SBGJ202103002 and SBGJ202103010).
文摘The growth of solid tumors relies on establishing a robust blood supply,with angiogenesis playing a key role in this intricate process.Based on this understanding,therapeutic strategies targeting tumor angiogenesis have been developed.However,the clinical effectiveness of antiangiogenic therapy(AAT)in treating tumors has not lived up to expectations.In recent years,vasculogenic mimicry(VM)has attracted increasing attention from the academic community as a longstanding but often overlooked mechanism of nonangiogenic tumor vascularization.Within the tumor microenvironment,neoplastic cells can autonomously form vessel-like structures,creating a blood supply that does not rely on endothelial cells.This phenomenon,known as VM,is a critical marker of aggressive tumors and may play a significant role in conferring resistance to AAT.In this review,we thoroughly examine the evidence,clinical characteristics,and mechanisms of VM across various tumor types and explore its potential role and importance in resistance to AAT and the development of new antitumor therapies.
基金supported by medical science research joint construction project of Henan(71188)Henan Provincial Department of Education under grant no.21B320008.
文摘Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.
文摘Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.
基金supported by a grant from the Gansu Provincial Nature Foundation Project(no.23URRA2346).
文摘Background:To observe the changes in serum calcitonin levels after application of different surgical methods for primary medullary thyroid microcarcinoma(MTMC)and explore a more reasonable surgical method.Methods:A retrospective analysis of 36 patients with MTMC,16 in group A and 20 in group B,was performed.In group A,tumors were single and confined to the thyroid lobe,and thyroid lobectomy with isthmusectomy was performed.In group B,tumors were in the isthmus or invaded the thyroid gland,or there were multiple foci in bilateral lobes,and patients with primary foci underwent total thyroidectomy.The median follow-up time was 3.6 years.Clinical and pathological characteristics and changes in serum calcitonin(CTn)and carcinoembryonic antigen levels after the surgery were compared between the 2 groups.Results:The difference in the biochemical cure rate after surgery was statistically significant between patients with preoperative serum calcitonin levels<150 pg/mL and≥150 pg/mL(P<0.01).No significant differences in the biochemical cure rates and serum calcitonin levels were noted at different time points after surgery between group A and group B(P>0.05).One recurrence and metastasis were observed in each group after surgery.Conclusions:After performing different surgical methods for the primary foci of MTMC,the changes in serum calcitonin and carcinoembryonic antigen levels are similar.Especially for patients with single foci confined to the thyroid lobe without lateral cervical lymph node metastasis and with serum calcitonin levels<150 pg/mL,the unilateral thyroid lobectomy with isthmectomy can achieve the same therapeutic effect and biochemical cure rate as total thyroidectomy.
基金supported by grants from the China Postdoctoral Science Foundation(2021MD703842).
文摘Background:Some observational associations between body weight and breast cancer have attracted attention.However,the causal relationship between these 2 factors remains unclear,and more clinical outcomes are needed for its validation.Methods:Based on statistical data from a Genome Wide Association Study,we performed a bidirectional Mendelian randomization analysis to assess the bidirectional causal relationship between body weight and breast cancer using 4 methods,with inverse variance weighting as the primarymethod.To verify the robustness and reliability of the causal relationship,we performed a sensitivity analysis using horizontal pleiotropy,outlier,and one-by-one elimination tests.Results:The inverse variance weighting results revealed no significant positive causal relationship between body weight and breast cancer.Similarly,the reverse analysis revealed no causal effect of breast cancer on body weight.Conclusions:The relationship between body weight and breast cancer may be attributed to confounding factors.
文摘A 44-year-old patient was admitted with tumor rupture in the left hepatic lateral lobe,and he underwent emergent exploratory laparotomy and proceeded for hepatic left lateral lobectomy on September 19,2021.The final diagnosis of hepatocellular carcinoma was confirmed by histopathological examination of the surgical specimen.Afterward,the patient received hepatic arterial infusion chemotherapy with FOLFOX(oxaliplatin,fluorouracil,and leucovorin)for 5 cycles.Subsequently,recurrence of the hepatocellular carcinoma was diagnosed in the abdominal cavity.The patient was then treated with lenvatinib.Within less than 1 month of the treatment with lenvatinib,the patient was admitted to the emergency room on June 2,2022,because of acute intra-abdominal bleeding(hematomas).Percutaneous intra-abdominal angiography found that the bleeding vessels were the right gastroepiploic artery and left gastric artery.The patient was stabilized after arterial embolization using gelatin sponges.The diagnosis and management of spontaneous intra-abdominal hematomas are discussed.
基金supported by Quzhou City Jiang District Life Oasis Public Welfare Service Center,Health and Health Development Promotion Project(Oncology Research Special Project,no:BJHA-CRP-027).
文摘Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.
基金the Natural Science Foundation of Shaanxi Province(Youth Projectno.2021JQ-423)the foundation of the Second Affiliated Hospital of Xi'an Jiaotong University(no.RC(XM)201706)。
文摘Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is limited.Therefore,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the self-renewal.However,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.Methods:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were used.TIMER database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune cells.GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival rates.Results:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC patients.BMI1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among others.Conclusions:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC.Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.
基金the Natural Science Foundation of Fujian Province(2021 J01539,2023 J011467)Scientific Foundation of the Fuzhou Health Commission(2021-S-wq21,2021-S-wp1).
文摘Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.
