Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

Endobronchial metastasis secondary to renal clear cell carcinoma:A case report

BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.

Rare primary squamous cell carcinoma of the intrahepatic bile duct: A case report and review of literature

BACKGROUND Cholangiocarcinoma is the most common malignancy of the biliary tree and has a poor prognosis.Adenocarcinoma is the most common pathological type of cho-langiocarcinomas,but rare squamous,adenosquamous,and mucinous variants have been reported without adequate clinical data.CASE SUMMARY This report describes a rare case of primary squamous cell carcinoma(SCC)of the intrahepatic bile duct.The patient was admitted with a tumor in the hepatic caudate lobe with no obvious clinical symptoms.Examination revealed hepatitis B surface antigen positivity,a slight increase in alfa-fetoprotein to 16.34 ng/mL,and an irregular slightly heterogeneous enhancing lesion in the hepatic caudate lobe,which was initially thought to be hepatocellular carcinoma.Laparoscopic re-section was performed,and the final pathology suggested a rare primary SCC of the intrahepatic bile duct.Immunohistochemistry indicated positivity for villin,partial positivity for p63,and negativity for hepatocyte,CK7,CK8,CK19,and CK20.The Ki-67 index was approximately 60%.The patient received six cycles of Tegio chemotherapy.A new lesion was detected in the liver after 15 months.The surgery was performed,and the patient was followed-up at a local hospital.To date,no new lesions have been observed.CONCLUSION Surgery is the first choice for resectable lesions,and combined chemotherapy based on pathology is essential for increasing overall survival.

TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways

Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.

Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

MicroRNAs in hepatocellular carcinoma treatment:Charting the path forward

MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.

Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.

3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

Hydrangea serrata extract exerts tumor inhibitory activity against hepatocellular carcinoma HepG2 cells via inducing p27/CDK2-mediated cell cycle arrest and apoptosis

Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.

Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis

Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

Primary acinic cell carcinoma of the breast: A case report and review of literature

BACKGROUND In the current World Health Organization classification,acinic cell carcinoma(AcCC)of the breast is considered a rare histological subtype of triple-negative breast cancer.Because of the few reports in the literature,data concerning clinical outcomes are limited.Here,we report a case of AcCC of the breast in a 48-year-old woman.A 48-year-old woman with a mass in her right breast came to our hospital for further diagnosis.Mammography and an ultrasound(US)scan showed a mass in the upper inner side of the right breast.She then underwent surgery to resect the mass in her right breast.Postoperative pathological examination revealed that the tumor had abundant acinar-like structures formed by tumor cells with prominent eosinophilic granules in the cytoplasm,consistent with acinar cell carcinoma.The results of immunohistochemical analysis supported the diagnosis of breast acinar cell carcinoma.Two months later,she underwent breast-conserving surgery and sentinel lymph node biopsy.The pTNM stage was T2N0M0.After surgery,the patient received 30 radiotherapy sessions.The patient was followed up for a period of one year,and no recurrence was found.AcCC of the breast is a rare type of malignant tumor.Because it is usually asym-ptomatic and can be detected by imaging studies,routine breast US or mamm-ograms are important.However,there are no characteristic diagnostic imaging findings or clinical manifestations,so immunohistochemical examination is critical for an accurate diagnosis of AcCC of the breast.

Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P<0.001).The 3-year CSS rate in the A/P≤0.5 group was significantly greater than that in the A/P>0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.