Objective:To investigated the strength of adenosine diphosphate ribosylation factor-like protein 14(ARL14)expression in colorectal cancer(CRC)and its relationship with major infiltrating cells in the tumor microenvironment.Methods:Data from the 607 CRC cases and 51 normal tissues in the TCGA-CRC dataset were analyzed.ARL14 mRNA expression levels were retrospectively collected and the relationship between ARL14 expression and CRC patient prognosis was analyzed.Transcription factors and miRNAs involved upstream in reg-ulating ARL14 expression were predicted.Bioinformatics methods were used to analyze the relationship between ARL14 expression and cell infiltration into the tumor microenvironment.Tumor and normal tissues from 45 CRC patients who underwent surgery in Tianjin Medical University Cancer Institute&Hospital from January 2020 to January 2021 were collected,and expression levels of ARL14,smooth muscle actin-α(α-SMA),and fibroblast-activated protein(FAP)were detected by immunohistochemical staining to verify the relationship between ARL14 expression and fibroblast activation.Results:Differential analysis showed that the ARL14 expression level was significantly lower in CRC tissues than in normal tissues(P<0.001).Patients with low ARL14 expression had worse prognosis than patients with high expression(Log-rank P=0.025).MCP-counter analysis showed that ARL14 expression correlated negatively with fibroblast infiltration(P<0.0001).Im-munohistochemical staining results showed that ARL14 expression was significantly lower in tumors than in normal tissues(P<0.01).ARL14 expression also correlated negatively with α-SMA and FAP expression levels in the interstitium.Conclusions:ARL14 may play a tumor sup-pressor role in CRC and inhibit fibroblast activation.

Objective:To investigate the efficacy and safety of separated R-CHOP in older patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:A total of 137 patients aged 65-80 years newly diagnosed with DLBCL between April 2013 and September 2022 at The First Affiliated Hospital of Zhengzhou University were enrolled.The patients were assigned into separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups based on their different chemotherapy regimens.All individuals were treated in 21-day cycles for 4-8 cycles.The short-term and long-term efficacies and adverse reactions of the treatments were compared among the three groups,and factors influencing progression-free survival(PFS)and overall survival(OS)were analyzed.Results:The overall response rates(ORR)of patients in the separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups were 89.7%,90.3%,and 86.1%,respectively,with no significant differences among them.The complete respond rate(CRR)of the separated R-CHOP group(64.1%)was significantly higher than that of the reduced R-CHOP-like group(33.3%)(P=0.008)but not significantly different from that of the full-dose R-CHOP group(66.1%).Survival curve analysis revealed no significant differences in PFS and OS between the separated and full-dose R-CHOP groups.Although the separated R-CHOP group showed improved PFS compared with the reduced R-CHOP-like group(P=0.036),there was no statistical difference in OS between these two groups.Multivariate analysis revealed that the international prognostic index(IPI)and separated R-CHOP had significant effects on PFS in patients with DLBCL(all P<0.05),whereas only IPI had a significant effect on OS(P<0.001).The incidence of leukopenia and grade 3-4 leukopenia in the separated R-CHOP group was significantly lower than that in the full-dose R-CHOP group(P=0.007,P=0.012),but there was no significant difference with the reduced R-CHOP-like group in this regard.Conclusions:In older patients with newly diagnosed DLBCL,separated R-CHOP showed good efficacy both in the short and long terms and had acceptable safety and tolerability profiles.

Objective:To investigate the expression of the novel immune checkpoint SIGLEC9 and SIGLEC9+T cells in cervical cancer and its clinical correlation.Methods:A total of 132 paraffin-embedded specimens of cervical tissue from patients with cervical cancer who under-went surgical treatment or pathological biopsy at The First Affiliated Hospital of Xinjiang Medical University from May 2022 to October 2023 were included for study.In addition,58 paraffin-embedded specimens of normal cervical tissue from patients with benign uterine leiomyomas who underwent total uterine excision during the same period were selected as normal controls.Furthermore,108 peripheral blood samples from patients with cervical cancer who underwent surgical treatment or pathological biopsy were collected for study,and 86 peripheral blood samples from healthy individuals during the same time period were selected as controls.Bioinformatics technology,im-munohistochemical(IHC)staining,flow cytometry,and double immunofluorescence(IF)staining were used to assess the expression of SIGLEC9 and SIGLEC9+T cells in cervical cancer,followed by correlation analysis with clinical indicators.Results:The bioinformatics,IHC,and double IF staining results showed that SIGLEC9 and SIGLEC9+T cells were highly expressed in cervical cancer tissues(P<0.05).The flow cyto-metry results showed that SIGLEC9+CD4+T and SIGLEC9+CD8+T cells were increased in the peripheral blood of patients with cervical cancer(P<0.05).SIGLEC9 expression correlated with tumor size,FIGO stage,lymph node metastasis,and human papillomavirus(HPV)infection(P<0.05).Conclusions:The novel immune checkpoint SIGLEC9 was highly expressed in cervical cancer tissues,and SIGLEC9+T cells infiltrated cervical cancer tissues.In vitro cell experiments showed that SIGLEC9 affects T cell function.In summary,SIGLEC9 provides a novel research direction for understanding the immune escape mechanism of cervical cancer and a novel therapeutic target for cervical cancer immuno-therapy.

Objective:To investigate the efficacy of sacubitril/valsartan in the treatment of cancer therapy-related cardiac dysfunction(CTRCD).Methods:A comprehensive analysis of all the literature on sacubitril/valsartan therapy for CTRCD published in Pubmed,Web of Science,Cochrane Library,Medline,and Embase from the inception of the database up to March 2023 was conducted,summarizing the tim-ing of drug administration,dosage,and efficacy,and further systematically summarizing the clinical studies on the use of the drug for the prevention of CTRCD.Results:After 3-12 months of treatment with sacubitril/valsartan for CTRCD,NYHA in cancer patients improved from grade Ⅱ-Ⅳ to grade Ⅰ-Ⅱ,LVEF increased by 3.0%to 37.0%,and NT-proBNP decreased by 280.0-65 498.0 pg/mL.Conclusions:The sacu-bitril/valsartan demonstrates efficacy in managing CTRCD and holds significant clinical utility in enhancing LVEF,GLS,and other patient indic-ators,thereby enabling the continuation of anti-tumor therapy and prolonging survival for cancer patients.

Objective:To elucidate the cytopathological characteristics,molecular subtypes,and clinical prognoses of metastatic breast car-cinoma with serosal effusions.Methods:Seventeen cases that included effusion cytology and clinical data were retrospectively analyzed.Two patients were diagnosed between April 2016 and September 2023 at the Suzhou Ninth Hospital Affiliated to Soochow University,and 15 patients were diagnosed at The First Affiliated Hospital of Soochow University.Cytopathological characteristics,molecular subtypes,and prognoses were analyzed.Results:The cytopathological features of metastatic breast carcinoma in serosal effusions were as follows:1)In-vasive ductal carcinoma:one cell type was relatively densely arranged in nests or colored spheres,which displayed an elevated nuclear/cyto-plasmic ratio,irregular nuclear membrane,and cytoplasmic mucin vacuoles.The other cell type was tiled,single scattered,and varied in size and shape,with enlarged nuclei and elevated nuclear/cytoplasmic ratio.2)Invasive lobular carcinoma:cells were scattered and uniform in size and shape.The nuclei had a relatively regular shape,but displayed an elevated nuclear-to-cytoplasmic ratio.Among the 17 breast can-cer cases,6 had transitioned in molecular subtyping,including 1 case from Luminal A to triple-negative type,1 case from Luminal B to hu-man epidermal growth factor receptor 2(HER-2)-overexpressing type,and 4 cases from Luminal B to triple-negative type.Conclusions:The cytopathological characteristics of serous effusion cells combined with immunocytochemical staining and fluorescence in situ hybridization(FISH)suggest that it is important to determine the origin and molecular typing of tumor cells.This provides an important basis for precise clinical treatment and prognosis.

Understanding mechanism of imatinib resistance in gastrointestinal stromal tumors(GIST)and developing new therapeutic tar-gets and schemes to address this resistance exhibit great potential to improve the long-term prognosis of patients with GIST.This review summarizes exiting research into the molecular characteristics of GIST and mechanisms of imatinib resistance acting via non-coding RNA,lysosomes,key protein molecules,fibroblast growth factor-2(FGF-2),and other modulators.Research shows that different drug resistance mechanism networks are closely connected and interrelated.Combining imatinib therapy with multiple drugs that inhibit the resistance mechanism shall present new options treating GIST thereby improving prognosis.Identification and implementation of individualized treat-ment strategies based on drug resistance mechanisms will provide new adjuvant treatment options for patients with GIST resistant to imat-inib,thus delaying progression of GIST.

With the progression of research on extrachromosomal DNA(ecDNA),it has been shown that ecDNA exists mainly in tumor cells and plays a crucial role in tumor heterogeneity and drug resistance.ecDNA is observed in several cancer types,but rarely in normal cells.Due to their strong oncogene amplification and dynamic alteration capabilities,patients with ecDNA-containing tumor cells often have negative clinical prognoses.Research has confirmed the presence of ecDNA in the cancer cells of patients with small cell lung cancer(SCLC).This re-view provides a comprehensive summary of the formation mechanism of ecDNA,the processes through which it is amplified in cancer cells,the mechanisms through which ecDNA promotes tumor growth,recurrence,and metastasis,and its relationship with high drug resistance in SCLC.Finally,we generalize the treatment direction for ecDNA-enriched SCLCs,thereby guiding future research.

Approximately 8%to 15%of patients with metastatic colorectal cancer(mCRC)harbor BRAF mutation,and the V600E mutation is the most common form of BRAF mutation.The prognosis of patients with metastatic colorectal cancer harboring BRAF V600E mutation is poor.Initial standard chemotherapy is often ineffective,necessitating an intensive follow-up treatment,which usually provides limited effic-acy.Consequently,the disease becomes notably difficult to treat and progresses rapidly,resulting in a decreased overall patient survival rate.This review details the research advancements in treatment of BRAF V600E-mutant metastatic colorectal cancer.

Objective:To explore whether cytoplasmic linker protein 170(CLIP170)affects papillary thyroid cancer(PTC)cell metastasis and invasion and clarify the underlying mechanisms.Methods:We analyzed CLIP170 expression levels in PTC using GEO and TCGA data and con-structed CLIP170 knockdown(CLIP170KD)cells using lentiviral transfection.Then,we evaluated their functions through Transwell transfer and invasion assays.We assessed how CLIP170 affected the cellular actin structure via immunofluorescence analysis.We detected transforming growth factor-β 1(TGF-β1)release in the cell culture medium using enzyme-linked immunosorbent assay(ELISA).We also assessed epithelial-mesenchymal transition(EMT)and TGF-β signaling pathway molecule expression using immunoblotting and reverse-transcription quantitat-ive fluorescence PCR and validated the results in a nude mouse lung metastasis model.Results:CLIP170 expression level in PTC was lower than that in normal thyroid tissue.Regarding the function,CLIP170KD significantly enhanced PTC cell metastasis both in vitro and in vivo.Re-garding the underlying mechanism,CLIP170KD triggered TGF-β pathway activation,subsequently promoted tumor cell migration and invasion.The inhibitor of TGF-β effectively inhibited TGF-β activation,and this inhibition significantly reversed the CLIP170KD-induced tumor metastasis.Conclusions:CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.

Objective:To examined the role of copper starvation in oral squamous cell carcinoma(OSCC),along with the molecular functions and mechanisms of SLC31A1 in these cells.Methods:Initially,SLC31A1 was silenced to induce a copper starvation environment.Sub-sequently,we evaluated the effects of copper starvation on oral squamous cell carcinoma cells using the CCK-8 assay,cell scratch assay,and subcutaneous tumor formation in nude mice.In addition,changes in autophagy and EZH2 expression levels in oral squamous cell carcinoma cells were detected after SLC31A1 silencing.Lactate dehydrogenase activity was assayed to determine its impact on natural killer(NK)cell cytotoxicity after SLC31A1 silencing.Results:Silencing of SLC31A1 significantly inhibited the proliferation,migration,and subcutaneous tu-mor formation ability of oral squamous cell carcinoma cells.Furthermore,silencing SLC31A1 mediated EZH2 degradation and increased NK cell infiltration.Conclusions:Copper starvation can regulate the proliferation,migration,and subcutaneous tumor formation ability of oral squamous cell carcinoma and increase NK cell infiltration by modulating EZH2 expression.