Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.

Real-Life Experience with Neo-Adjuvant Chemotherapy in Muscle Invasive Bladder Cancer and Its Outcome

Objectives: Muscle-invasive bladder cancer (MIBC) has a poor prognosis with a 5-year overall survival rate of 50%. Current guidelines recommend the use of neoadjuvant chemotherapy (NAC) followed by radical cystectomy in these patients. However, its application remains limited and underutilized in clinical practice. This study aims to delineate, in real-life practice, the clinical characteristics and outcomes of patients with muscle-invasive bladder cancer (MIBC) who received NAC and were subsequently candidates for cystectomy. Methods: This study is a retrospective observational analysis of patients with muscle-invasive bladder cancer (stages T2-T4aN0M0 and T1-T4aN1M0) who received neoadjuvant chemotherapy prior to total cystectomy. The data, collected over a six-year period from 2018 to 2024, originates from Hotel Dieu de France University Hospital in Beirut. Various factors were analyzed, including age, sex, history of smoking, stage of disease at diagnosis, presence of carcinoma in situ (CIS), and any prior history of Bacillus Calmette-Guérin (BCG) treatment or T1 or Ta disease. Additionally, the study evaluates renal function prior to neoadjuvant chemotherapy (NAC), specifies the type and number of chemotherapy cycles administered, the pathological complete response (pCR) following cystectomy and calculate both overall survival and disease-free survival rates. Results: A total of 36 patients were analyzed, with a median age of 71.6 years. 77.7% were male, 22.2% were female, and 77.8% were smokers. 55.6% of the patients presented with de novo muscle-invasive bladder cancer (MIBC), 44.4% had a history of Ta or T1 stage tumors and 100% had urothelial histology and lower tract location. Among these 36 patients, 27.8% had received intravesical Bacillus Calmette-Guérin (BCG) treatment, while 72.2% did not. 86.1% of patients had a creatinine clearance greater than 60, whereas 13.9% had a clearance below 60 but still above 50. At the time of diagnosis, 61.1% were at stage II, 13.9% were at stage IIIa, and 25.0% were at stage IIIb. All the patients received the combination of gemcitabine and cisplatin with a median number of 3.9 cycles per patient. Out of the 36 patients, 5 experienced disease progression and did not undergo radical cystectomy, while another 5 opted for trimodal therapy (TMT) after evaluation by cystoscopy showing no residual lesion. The remaining 26 patients proceeded with radical cystectomy. Among these 26 cystectomized, 30.8% demonstrated a complete pathological response. During the follow-up period, 75% of these 36 patients did not experience disease progression, with a median disease-free survival of 9.5 months and a mean disease-free survival of 19.72 months. No deaths were recorded in this study, and overall survival data could not be determined. Conclusion: In our real-world experience, approximately one-third of patients who received gemcitabine and cisplatin NAC followed by radical cystectomy achieved a pathological complete response. Extended follow-up is necessary to assess long-term outcomes, including median overall survival. Future research should focus on investigating and comparing between triple modality therapy and cystectomy, both after neoadjuvant chemotherapy.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Potential clinical application of microRNAs in bladder cancer

Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

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

TM9SF1 promotes bladder cancer cell growth and infiltration

BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Effect of internal iliac artery chemotherapy after transurethral resection of bladder tumor for muscle invasive bladder cancer

Objective： To evaluate the clinical effect of transurethral resection of bladder tumor（TUR-BT） combined with internal iliac artery chemotherapy and intravesical instillation therapy for muscle invasive bladder cancer（MIBC）.Methods： From February 2007 to April 2014, 62 patients with MIBC were treated with TUR-BT combined with intravesical instillation therapy, with or without internal iliac artery chemotherapy, and the chemotherapy regimen is gemcitabine and cisplatin（GC）. The bladder preservation and survival rate as well as cancer-specific survival（CSS） rate and overall survival（OS） rate of the two groups were compared.Results： Sixty-two patients were followed-up for 26-102 months with an average of 58.4±3.1 months. Recurrence-free survival（RFS） at 2-year for TUR ＋ GC group and TUR group were 77.8% and 53.8%, respectively. Bladder preserved rate（BPR） at 3-year for TUR ＋ GC group and TUR group were 94.4% and 80.8%. CSS rate at 2-year for TUR ＋ GC group and TUR group were 94.4% and 84.6%. The diseasefree survival（DFS） at 1-year for TUR ＋ GC group and TUR group were 83.3% and 61.5%, and 77.8% and 53.8% for the 2nd year. OS at 2-year for TUR ＋ GC group and TUR group were 88.9% and 92.3%.Conclusions： TUR-BT and intravesical instillation therapy combined with internal iliac artery chemotherapy for MIBC had a better outcome at RFS, BPR and DFS than the treatment without internal iliac artery chemotherapy, and no difference in OS and CSS.

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer

Objective:Conservative approaches in muscle-invasive bladder cancer(MIBC)have been evolved to avoid aggressive surgery,but are limited to elderly,frail,and patients medically unfit for surgery.Our study aimed to assess the response rate of neoadjuvant chemotherapy(NACT)before radiotherapy(RT)in MIBC patients.Methods:Forty patients with urothelial carcinoma of stage T2-T4a,N0,M0 were enrolled between November 2013 and November 2015,and treated with three cycles of NACT with gemcitabine-cisplatin.Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors(RECIST)criteria.Patients who achieved complete response(CR)and partial response(PR)>50%were treated with radical RT,and those who had PR<50%,stable disease(SD),and progressive disease(PD)underwent radical cystectomy(RC).Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model.Results:After NACT,35(87.5%)patients achieved either PR>50%or CR,and were treated with RT.Five(12.5%)patients who had PR<50%,SD,or PD underwent RC.All patients who received radiation showed CR after 6 weeks.Median follow-up was 43 months(range:10-66 months)and median overall survival(OS)was not reached.Three-year OS,local control,and disease-free survival were 70.1%,60.9%,50.6%,respectively,and 50%of patients preserved their functioning bladder.Three-year OS rate was 88.9%in patients who achieved CR to NACT,73.1%in patients with PR≥50%and 40%in patients with PR<50%.Conclusion:NACT followed by RT provides a high probability of local response with bladder preservation in CR patients.Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.

A multi-institutional retrospective study of hyperthermic plus intravesical chemotherapy versus intravesical chemotherapy treatment alone in intermediate and high risk nonmuscle-invasive bladder cancer

Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after transurethral resection.Methods:We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers.We matched 364 intermediate or high risk cases and divided them into 2 groups:the HIVEC+IVEC group[chemohyperthermia(CHT)composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia]and the IVEC group(intravesical instillation without hyperthermia).The data were recorded in the database.The primary endpoint was 2-year recurrence-free survival(RFS)in all NMIBC patients(n=364),whereas the secondary endpoints were the assessment of radical cystectomy(RC)and 5-year overall survival(OS).Results:There was a significant difference in the 2-year RFS between the two groups in all patients(n=364;HIVEC+IVEC:82.42%vs.IVEC:74.18%,P=0.038).Compared with the IVEC group,the HIVEC+IVEC group had a lower incidence of RC(P=0.0274).However,the 5-year OS was the same between the 2 groups(P=0.1434).Adverse events(AEs)occurred in 32.7%of all patients,but none of the events was serious(grades 3–4).No difference in the incidence or severity of AEs between each treatment modality was observed.Conclusions:This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients.Both treatments were well-tolerated in a similar manner.

Metabolomics for the diagnosis of bladder cancer: A systematic review

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.Methods: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.Results: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.Conclusion: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.

Prediction of recurrence risk in patients with non-muscle-invasive bladder cancer

ObjectiveNon-muscle-invasive bladder cancer (NMIBC) remains a common challenge in uro-oncology with conflicting reports on recurrence risk. This study aimed to elucidate the recurrence rate of NMIBC in the Cancer Clinic of Shahid Beheshti Hospital in Iran and to investigate related parameters affecting recurrence risk.MethodsThe data of 143 patients with NMIBC, who underwent treatment between January 2017 and January 2020 and were followed up from the initial transurethral resection of bladder tumor until November 30, 2020 in our institution, were retrospectively assessed. The Cox regression analysis and Kaplan–Meier plot of recurrence-free survival were used to determine independent contributing factors for tumor recurrence.ResultsAmong patients with NMIBC, 83.9% were male, and 16.1% were female, with a mean age of 64.4 (standard deviation [SD] 12.9) years. During the follow-up, 71 (49.7%) patients showed tumor recurrence, with a mean recurrence time of 11.5 (SD 6.9) months. In the Chi-square test or Fisher's exact test, the age (≥65 years) (p=0.037), obesity (body mass index ≥30 kg/m^(2)) (p=0.004), no diabetes mellitus (p=0.005), smoking (current or former smoker) (p=0.001), immediate perfusion therapy (p=0.035), number of tumors (>3) (p<0.001), and tumor stage (Ta, T1, and Tis) (p=0.001) had independent significant effects on the recurrence of NMIBC. The multivariate Cox regression analysis indicated that preoperative obesity (hazards ratio [HR] 7.90;95% confidential interval [CI] 4.01–15.55;p<0.001), current or former smoking (HR 1.85;95% CI 1.07–3.20;p=0.027), and a high-grade tumor (HR 4.03;95% CI 1.59–10.25;p=0.003) were significant predictors of tumor recurrence. The Kaplan–Meier plot of recurrence-free survival showed that obesity (log-rank p<0.001), current or former smoking (log-rank p=0.001), and a high-grade tumor (log-rank p=0.006) were associated with a shorter time interval until the first tumor recurrence.ConclusionThe study found a high recurrence rate of NMIBC in Iran from January 2017 to January 2020, with the obesity, smoking history, and the high-grade tumor as contributing factors.

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

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

Uncovering the epidemiology of bladder cancer in the Arab world: A review of risk factors, molecular mechanisms, and clinical features

Objective:Bladder cancer(BC)is a significant public health concern in the Middle East and North Africa,but the epidemiology and clinicopathology of the disease and contributors to high mortality in this region remain poorly understood.The aim of this systematic review was to investigate the epidemiological features of BC in the Arab world and compare them to those in Western countries in order to improve the management of this disease.Methods:An extensive electronic search of the PubMed/PMC and Cochrane Library databases was conducted to identify all articles published until May 2022,following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.A total of 95 articles were included in the final analysis after title,abstract,and full-text screening,with additional data obtained from the GLOBOCAN and WHO 2020 databases.

Current and Potential Roles of Ferroptosis in Bladder Cancer

Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

LncRNA MEG3 Inhibits the Epithelial-mesenchymal Transition of Bladder Cancer Cells through the Snail/E-cadherin Axis

Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Methods Cell invasion,migration,and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells.The expression levels of E-cadherin were measured using Western blotting,RT-qPCR,and dual luciferase reporter assays.RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets.Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin.The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin.Additionally,MEG3 suppressed the phosphorylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinase(JNK),and P38,thereby decreasing the expression of Snail and stimulating the expression of E-cadherin.Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells,indicating its potential as a promising therapeutic target for the treatment of bladder cancer.

Inhibition of proliferation,migration,and invasiveness of bladder cancer cells through SAPCD2 knockdown

Introduction:Bladder cancer(BC)has a high incidence and mortality rate worldwide.Suppressor anaphasepromoting complex domain containing 2(SAPCDC2)is over-expressed in a variety of tumors.Objectives:This study investigated the effects of SAPCD2 knockdown on BC cells.Methods:T24 and UMUC3 cell models and the xenografted BC tumor model with SAPCD2 knockdown were established to observe the malignant phenotype of BC cells by cell counting kit-8 assay,colony formation test,wound healing,and Transwell assay,mRNA and proteins expressions were measured with quantitative real-time polymerase chain reaction,western blotting,and tissue immunohistochemistry.Lithium chloride agonist on the Wnt/β-catenin pathway was used to clarify the molecular mechanism of SAPCD2 knockdown.Results:SAPCD2 expression was significantly higher in BC cell lines than in SVHUC-1 cells.SAPCD2 knockdown inhibited viability and cloning,hindered the G0/G1 phase of the cell cycle in UMUC3 and T24 cells,and decreased the migration and invasiveness of BC cells.SAPCD2 knockdown inhibited expression levels of cyclin D1,cyclin B1,N-cadherin,vimentin,Snail,β-catenin,c-Myc,and cyclin-dependent kinase 4,while the P21 and E-cadherin were raised by SAPCD2 knockdown.Furthermore,lithium chloride reversed the effects of SAPCD2 knockdown on the expression levels of the above proteins in UMUC3 and T24 cells.In vivo,SAPCD2 knockdown inhibited the volume,weight,and expression of Ki-67 andβ-catenin in tumors and increased the E-cadherin expression.Conclusion:SAPCD2 knockdown inhibits the malignant phenotype of BC via a pathway involvingβ-catenin.

Targeting the organelle for radiosensitization in cancer radiotherapy

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.