BACKGROUND Parathyroid carcinoma(PC)is a rare,slow-growing malignant tumor and a rare cause of primary hyperfunctioning of the parathyroid,with a highly variable clinical course,depending on the aggressiveness of the ...BACKGROUND Parathyroid carcinoma(PC)is a rare,slow-growing malignant tumor and a rare cause of primary hyperfunctioning of the parathyroid,with a highly variable clinical course,depending on the aggressiveness of the individual tumor and the degree of hypercalcemia.CASE SUMMARY The aim of this report is to summarize the diagnosis and treatment of three cases of PC and to review and conclude aspects regarding the three collected cases with reference to other relevant cases to explore the value of ultrasound in the diagnosis of PC.All three patients had hypercalcemia,consisting of a high serum calcium level and a high level of parathyroid hormone that was>2-fold(even>30-fold)of the normal upper limit.The ultrasonographic findings of the parathyroid gland showed that the glands were all>30 mm,and the internal echo was uneven.All patients underwent surgery.PC in three cases was confirmed by routine histopathology and immunohistochemistry.CONCLUSION As clinical signs and laboratory results are nonspecific,it is difficult to diagnose PC preoperatively,so imaging examinations are often needed.展开更多
A 24-year-old female patient with parathyroid carcinoma,the rarest endocrine malignancy,had two pregnancies.In the first pregnancy,she had severe nausea and fatigue.Hypercalcemia and hyperparathyroidism were diagnosed...A 24-year-old female patient with parathyroid carcinoma,the rarest endocrine malignancy,had two pregnancies.In the first pregnancy,she had severe nausea and fatigue.Hypercalcemia and hyperparathyroidism were diagnosed in the postpartum period.Hyperemesis gravidarum masked a diagnosis of hypercalcemia.Neck ultrasound and Tc-99 m sestamibi found an enlarged lower right parathyroid gland.The gland was surgically removed,and an initial pathology report described atypical adenoma.Shortly afterward,she became pregnant again.During the second pregnancy,her calcium level was frequently controlled but was always in the normal range.Normocalcemia is explained by the specific physiology of pregnancy accompanied by hemodilution,hypoalbuminemia and maternal hypercalciuria(mediated by increased glomerular filtration).During lactation,calcium levels rose,and a newneck ultrasound showed a solitary mass in the area of prior surgery and an enlarged pretracheal lymph node.Fine needle aspiration of the solitary mass and node showed parathyroid carcinoma cells.The tumor mass was resected en bloc with the contiguous tissues and surrounding lymph nodes(pathology report; parathyroid carcinoma with metastases).Over the next five years,four consecutive surgeries were performed to remove malignant parathyroid tissue,lymph nodes and local metastases.Following the surgical procedures,no hypocalcemia was observed.More serious hypercalcemia recurred; the calcium level was difficult to control with a combination of pamidronate,cinacalcet and loop diuretic.No elements of multiple endocrine neoplasia were present.展开更多
BACKGROUND Pituitary apoplexy represents one of the most serious,life threatening endocrine emergencies that requires immediate management.Gonadotropin-releasing hormone agonist(GnRHa)can induce pituitary apoplexy in ...BACKGROUND Pituitary apoplexy represents one of the most serious,life threatening endocrine emergencies that requires immediate management.Gonadotropin-releasing hormone agonist(GnRHa)can induce pituitary apoplexy in those patients who have insidious pituitary adenoma coincidentally.CASE SUMMARY A 46-year-old woman,with a history of hypertension and menorrhagia was transferred to our hospital from a secondary care hospital after complaints of headache and vomiting,with loss of consciousness 5 min after an injection of GnRHa.The drug was prescribed by her gynecologist due to the presence of uterine myomas.The clinical neurological examination revealed right cranial nerve III palsy,ptosis and movement limitation of the right eye.Our first clinical consideration was a pituitary apoplexy.Blood hormonal analysis revealed mild hyperprolactinemia and high follicle stimulating hormone level;PTH and calcium was high with glomerular filtration rate mildly to moderately decrease.A computed tomography scan,revealed an enlarged pituitary gland(3.5 cm)impinging upon the optic chiasm with bone involvement of the sella.Following contrast media administration,the lesion showed homogeneous enhancement with high-density focus that suggests hemorrhagic infarction of the tumor.Transsphenoidal endoscopic surgery was perfomed and adenomatous tissue was removed.Immunohistochemistry was positive for luteinizing hormone(LH)and follicular-stimulating hormone(FSH).A solid hypoechoic nodule(14 mm x 13 mm x 16 mm)was found in the caudal portion of the right thyroid lobe after a parathyroid ultrasound.A genetic test of Multiple Endocrine Neoplasia type 1(MEN1)was negative.A right lower parathyroidectomy was performed and the pathologic study showed the presence of an encapsulated parathyroid carcinoma of 1.5 cm.A MEN type 4 genetic test was performed result was negative.CONCLUSION This case demonstrates an uncommon complication of GnRH agonist therapy in the setting of a pituitary macroadenoma and the casual finding of parathyroid carcinoma.It also highlights the importance of suspecting the presence of a multiple endocrine neoplasia syndrome and to carry out relevant genetic studies.展开更多
Parathyroid carcinoma is an extremely rare malignant tumor,composed primarily of vacuolated principal cells,but may also be composed of eosinophils.The exact etiology and pathogenesis of parathyroid carcinoma is unkno...Parathyroid carcinoma is an extremely rare malignant tumor,composed primarily of vacuolated principal cells,but may also be composed of eosinophils.The exact etiology and pathogenesis of parathyroid carcinoma is unknown,and head and neck radiation exposure,chronic stimulation from renal failure,and familial syndromes can lead to the development of parathyroid carcinoma.Most parathyroid carcinoma is difficult to distinguish from benign HPT and is often diagnosed only when there is a recurrence of hypercalcemia several years later,which can manifest as weight loss,extreme fatigue,anorexia,and muscle atrophy.At present,surgical resection remains the primary treatment.In this case,the patient underwent initial surgery for primary hyperparathyroidism and was subsequently diagnosed with parathyroid carcinoma.During the 8 years of follow-up,the patient underwent 7 surgeries in combination with radiation therapy,chemotherapy and targeted medications.Although the neck tumor was cured,the patient died of complications related to hypercalcemia.We will review the literature on the combination of surgery,radiotherapy,chemotherapy,and targeted drug therapy in order to improve the diagnosis and treatment of parathyroid carcinoma.展开更多
Parathyroid cancer is an uncommon malignant cancer and is associated with a poor prognosis.The staging of parathyroid cancer represents an important issue both at initial diagnosis and after surgery and medical treatm...Parathyroid cancer is an uncommon malignant cancer and is associated with a poor prognosis.The staging of parathyroid cancer represents an important issue both at initial diagnosis and after surgery and medical treatment.The role of positron emission tomography/computed tomography(PET/CT)with 18F-Fluorodeoxyglucose(18F-FDG)as an imaging tool in parathyroid cancer is not clearly reported in the literature,although its impact in other cancers is well-defined.The aim of the following illustrative clinical cases is to highlight the impact of PET/CT in the management of different phases of parathyroid cancer.We describe five patients with parathyroid malignant lesions,who underwent FDG PET/CT at initial staging,restaging and post-surgery evaluation.In each patient we report the value of PET/CT comparing its findings with other common imaging modalities(e.g.,CT,planar scintigraphy with 99mTcsestamibi,magnetic resonance imaging)thus determining the complementary benefit of FDG PET/CT in parathyroid carcinoma.We hope to provide an insight into the potential role of PET/CT in assessing the extent of disease and response to treatment which are the general principles used to correctly evaluate disease status.展开更多
Background: Neuroendocrine neoplasms are those that develop from a neuroendocrine cell. They most commonly affect the lungs, gastrointestinal tract, and pancreas, being rare conditions in the female genital tract. Whe...Background: Neuroendocrine neoplasms are those that develop from a neuroendocrine cell. They most commonly affect the lungs, gastrointestinal tract, and pancreas, being rare conditions in the female genital tract. When present, these neoplasms often manifest with nonspecific signs and symptoms such as pain, itching, swelling, single-focus lesions, bleeding, and enlargement of inguinal lymph nodes, in addition to the presence of progressively enlarging vulvar nodules. Consequently, the diagnostic investigation involves histopathological examination and confirmation through immunohistochemistry. Objective: To present a comprehensive understanding of this rarely studied pathology. The primary objective is to provide valuable insights that could aid in the future development of universally applicable treatment guidelines. Case Presentation: A 57-year-old female, with no prior comorbidities, menopause at 36, who presented with a left vulvar nodule accompanied by intense pain and swelling, later diagnosed with small cell neuroendocrine carcinoma in the vulva. Conclusion: This case report highlights the importance of enhancing our knowledge regarding small cell neuroendocrine carcinoma in the vulva, given its scarcity in medical literature. The information presented here underscores the need for standardized diagnostic and treatment approaches, paving the way for future consensus on managing this uncommon but challenging neoplasm.展开更多
3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)is a pentacyclic triterpene mainly distributed in food and medicinal plants,which exhibits various pharmacological properties.However,whether these functions are attr...3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)is a pentacyclic triterpene mainly distributed in food and medicinal plants,which exhibits various pharmacological properties.However,whether these functions are attributed to eBAG or additional components in these plants remain unknown.Herein,we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer cells.EBAG induced non-apoptotic cell death in hepatocellular carcinoma cells.The eBAG-induced cell death was inhibited by knock-down of autophagy related gene(ATG)5 and ATG7,by administration of 3-methyladenine,a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase(PI3K),and by chloroquine,a classic autophagy flux inhibitor.We demonstrated that eBAG induced an autophagy-mediated cell death.Application of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP,activation of AMP-activated protein kinase(AMPK),and inhibition of mTOR.Co-treatment with compound C,an AMPK inhibitor,abrogated cell death induced by eBAG.We further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in mice.As a functional food ingredient,eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.展开更多
The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regu...The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regulation and prognosis,particularly those of hepatocellular carcinoma(HCC),remains unclear.To address this knowledge gap,we analyzed expression profiles obtained from The Cancer Genome Atlas(TCGA)database,comparing normal and malignant tumor tissues.We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues.Kaplan-Meier(K-M)analysis revealed the prognostic power of NRAV,wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients.Furthermore,noteworthy associations were observed between NRAV,immune checkpoints,immune cell infiltration,genes related to autophagy,epithelial-mesenchymal transition(EMT),pyroptosis,tumor mutational burden(TMB),and microsatellite instability(MSI)across different cancer types,including HCC.Moreover,NRAV upregulation expression was associated with multiple pathological stages by clinical observations.Furthermore,our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells.The inhibition of NRAV resulted in the inhibition of cell proliferation,migration,and invasion in HCC cells,while also influencing the expression of CD274(PD-L1)and CD44,along with various biomarkers associated with EMT,autophagy,and pyroptosis.The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.展开更多
BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare.AIM To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the ovary.METHODS A retrospective review was conducted on 12 patien...BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare.AIM To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the ovary.METHODS A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary,analyzing clinicopathological characteristics,treatment modalities,and survival status.RESULTS The median age at diagnosis was 34.5 years(range:20 to 62 years).Among the 12 cases,9 were small cell carcinoma of the ovary and 3 were large cell NEC.Five cases were stage I tumors,one case was stage IV,and six cases were stage III.Eleven patients underwent surgery as part of their treatment.All patients received adjuvant chemotherapy.Among the 12 patients,one patient received radiotherapy,and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy.The median progression-free survival was 13 months,and the median overall survival was 19.5 months.Four cases remained disease-free,while eight cases experienced tumor recurrence,including three cases that resulted in death due to disease recurrence.CONCLUSION NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes.Surgical resection remains the mainstay of treatment,with some patients benefiting from adjuvant chemoradiation therapy.展开更多
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...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 cytom-etry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by in-vestigating 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 im-munohistochemistry 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.展开更多
Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progressi...Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.展开更多
Screening for hepatocellular carcinoma in patients at risk is an evidence-based approach;however,adherence to the monitoring protocol recommended by international guidelines is difficult.Hence,there is a need to use t...Screening for hepatocellular carcinoma in patients at risk is an evidence-based approach;however,adherence to the monitoring protocol recommended by international guidelines is difficult.Hence,there is a need to use the best screening options and refine the selection of patients at risk in the future.展开更多
Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors...Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.展开更多
Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal ...Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.展开更多
AIM:To evaluate lacrimal gland adenoid cystic carcinoma(LGACC)of prognosis in patients who underwent different treatment regimens.METHODS:We searched PubMed,EMBASE,and the Cochrane Library for studies done on the trea...AIM:To evaluate lacrimal gland adenoid cystic carcinoma(LGACC)of prognosis in patients who underwent different treatment regimens.METHODS:We searched PubMed,EMBASE,and the Cochrane Library for studies done on the treatment of LGACC,between January 1987 and April 2022.A Metaanalysis was conducted to pool the 5-year overall survival rate(OR),and the 5-year recurrence rate(RR)and 5-year metastasis rate(MR)were assessed.RESULTS:The 30 studies involved 585 patients were included in the Meta-analysis.The pooled 5-year OR with surgery alone was 50%,the 5-year RR was 63%,and the 5-year MR was 34%.The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67%(95%CI 61%,73%),the 5-year RR was 41%,and the 5-year MR was 35%.The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72%(95%CI 59%,84%),the 5-year RR was 48%,and the 5-year MR was 36%.The pooled 5-year OR with surgery,intra-arterial cytoreductive chemotherapy,and adjuvant chemoradiotherapy combined was 78%(95%CI 68%,89%),the 5-year RR was 15%,and the 5-year MR was 27%.CONCLUSION:Comprehensive treatment is more effective than surgery alone.Surgery combined with intraarterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.展开更多
A 64-year-old woman with no particular history presented with chronic pelvic pain since November 2021. The ultrasound performed showed multiple right ovarian cystic ranging from 0.4 to 4 cm on the long axis. She under...A 64-year-old woman with no particular history presented with chronic pelvic pain since November 2021. The ultrasound performed showed multiple right ovarian cystic ranging from 0.4 to 4 cm on the long axis. She underwent a right salpingo-oophorectomy in May 2022. The anatomical pathology result is in favor of a papillary carcinoma developed on stroma ovarii. No adjuvant treatment was necessary since the tumor was well limited, without capsular rupture, stage IA. The thyroid test was normal. The patient is currently being monitored. There is no sign of recurrence 20 months after surgery.展开更多
Musculoskeletal alterations in hepatocellular carcinoma(HCC)are less common than liver-related complications.However,they can significantly impact the quality of life and overall prognosis of patients with HCC.The mai...Musculoskeletal alterations in hepatocellular carcinoma(HCC)are less common than liver-related complications.However,they can significantly impact the quality of life and overall prognosis of patients with HCC.The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asym-ptomatic and unapparent during routine clinical evaluations.This narrative literature review aimed to provide a comprehensive overview of the contem-porary literature related to the changes in the musculoskeletal system in patients with HCC,focusing on its clinical implications and underlying etiopathogenetic mechanisms.Osteolytic bone metastases are the most common skeletal alterations associated with HCC,which could be associated with an increased risk of low-trauma bone fracture.Moreover,previous studies reported that osteopenia,sarcopenia,and myosteatosis are associated with poor clinical outcomes in patients with HCC.Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients,these complications are frequently overlooked in the clinical management of patients with HCC.Taken together,contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis.Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.展开更多
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 ...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.展开更多
Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune ...Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug sensitivity.Methods:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.After classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were screened.Then,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso analysis.The expression of 8 risk genes was verified in vitro.Results:8 risk genes were used to construct the Sphingolipid score model.High-Sphingolipid score predicted poor prognosis of HCC patients.Sphingolipid score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK Cascade.In the High-Sphingolipid score group,a significantly higher proportion of patients with TP53(p53)mutations was significantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs.In vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 significantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 significantly decreased.Silencing TRIM47 reduced the proliferation and promoted apoptosis.The levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis decreased.Conclusion:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk genes.TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.展开更多
Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative res...Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.展开更多
文摘BACKGROUND Parathyroid carcinoma(PC)is a rare,slow-growing malignant tumor and a rare cause of primary hyperfunctioning of the parathyroid,with a highly variable clinical course,depending on the aggressiveness of the individual tumor and the degree of hypercalcemia.CASE SUMMARY The aim of this report is to summarize the diagnosis and treatment of three cases of PC and to review and conclude aspects regarding the three collected cases with reference to other relevant cases to explore the value of ultrasound in the diagnosis of PC.All three patients had hypercalcemia,consisting of a high serum calcium level and a high level of parathyroid hormone that was>2-fold(even>30-fold)of the normal upper limit.The ultrasonographic findings of the parathyroid gland showed that the glands were all>30 mm,and the internal echo was uneven.All patients underwent surgery.PC in three cases was confirmed by routine histopathology and immunohistochemistry.CONCLUSION As clinical signs and laboratory results are nonspecific,it is difficult to diagnose PC preoperatively,so imaging examinations are often needed.
文摘A 24-year-old female patient with parathyroid carcinoma,the rarest endocrine malignancy,had two pregnancies.In the first pregnancy,she had severe nausea and fatigue.Hypercalcemia and hyperparathyroidism were diagnosed in the postpartum period.Hyperemesis gravidarum masked a diagnosis of hypercalcemia.Neck ultrasound and Tc-99 m sestamibi found an enlarged lower right parathyroid gland.The gland was surgically removed,and an initial pathology report described atypical adenoma.Shortly afterward,she became pregnant again.During the second pregnancy,her calcium level was frequently controlled but was always in the normal range.Normocalcemia is explained by the specific physiology of pregnancy accompanied by hemodilution,hypoalbuminemia and maternal hypercalciuria(mediated by increased glomerular filtration).During lactation,calcium levels rose,and a newneck ultrasound showed a solitary mass in the area of prior surgery and an enlarged pretracheal lymph node.Fine needle aspiration of the solitary mass and node showed parathyroid carcinoma cells.The tumor mass was resected en bloc with the contiguous tissues and surrounding lymph nodes(pathology report; parathyroid carcinoma with metastases).Over the next five years,four consecutive surgeries were performed to remove malignant parathyroid tissue,lymph nodes and local metastases.Following the surgical procedures,no hypocalcemia was observed.More serious hypercalcemia recurred; the calcium level was difficult to control with a combination of pamidronate,cinacalcet and loop diuretic.No elements of multiple endocrine neoplasia were present.
基金Supported by FIS del Instituto de Salud Carlos Ⅲ(FEDER from E.U.),Spain,No.PI13/00322 and PI16/00884
文摘BACKGROUND Pituitary apoplexy represents one of the most serious,life threatening endocrine emergencies that requires immediate management.Gonadotropin-releasing hormone agonist(GnRHa)can induce pituitary apoplexy in those patients who have insidious pituitary adenoma coincidentally.CASE SUMMARY A 46-year-old woman,with a history of hypertension and menorrhagia was transferred to our hospital from a secondary care hospital after complaints of headache and vomiting,with loss of consciousness 5 min after an injection of GnRHa.The drug was prescribed by her gynecologist due to the presence of uterine myomas.The clinical neurological examination revealed right cranial nerve III palsy,ptosis and movement limitation of the right eye.Our first clinical consideration was a pituitary apoplexy.Blood hormonal analysis revealed mild hyperprolactinemia and high follicle stimulating hormone level;PTH and calcium was high with glomerular filtration rate mildly to moderately decrease.A computed tomography scan,revealed an enlarged pituitary gland(3.5 cm)impinging upon the optic chiasm with bone involvement of the sella.Following contrast media administration,the lesion showed homogeneous enhancement with high-density focus that suggests hemorrhagic infarction of the tumor.Transsphenoidal endoscopic surgery was perfomed and adenomatous tissue was removed.Immunohistochemistry was positive for luteinizing hormone(LH)and follicular-stimulating hormone(FSH).A solid hypoechoic nodule(14 mm x 13 mm x 16 mm)was found in the caudal portion of the right thyroid lobe after a parathyroid ultrasound.A genetic test of Multiple Endocrine Neoplasia type 1(MEN1)was negative.A right lower parathyroidectomy was performed and the pathologic study showed the presence of an encapsulated parathyroid carcinoma of 1.5 cm.A MEN type 4 genetic test was performed result was negative.CONCLUSION This case demonstrates an uncommon complication of GnRH agonist therapy in the setting of a pituitary macroadenoma and the casual finding of parathyroid carcinoma.It also highlights the importance of suspecting the presence of a multiple endocrine neoplasia syndrome and to carry out relevant genetic studies.
基金This research was funded by National Natural Science Foundation of China(Grant Number:81760142)the High-level Health Talents Project of Yunnan Provincial(Grant Number:H-2017036).
文摘Parathyroid carcinoma is an extremely rare malignant tumor,composed primarily of vacuolated principal cells,but may also be composed of eosinophils.The exact etiology and pathogenesis of parathyroid carcinoma is unknown,and head and neck radiation exposure,chronic stimulation from renal failure,and familial syndromes can lead to the development of parathyroid carcinoma.Most parathyroid carcinoma is difficult to distinguish from benign HPT and is often diagnosed only when there is a recurrence of hypercalcemia several years later,which can manifest as weight loss,extreme fatigue,anorexia,and muscle atrophy.At present,surgical resection remains the primary treatment.In this case,the patient underwent initial surgery for primary hyperparathyroidism and was subsequently diagnosed with parathyroid carcinoma.During the 8 years of follow-up,the patient underwent 7 surgeries in combination with radiation therapy,chemotherapy and targeted medications.Although the neck tumor was cured,the patient died of complications related to hypercalcemia.We will review the literature on the combination of surgery,radiotherapy,chemotherapy,and targeted drug therapy in order to improve the diagnosis and treatment of parathyroid carcinoma.
文摘Parathyroid cancer is an uncommon malignant cancer and is associated with a poor prognosis.The staging of parathyroid cancer represents an important issue both at initial diagnosis and after surgery and medical treatment.The role of positron emission tomography/computed tomography(PET/CT)with 18F-Fluorodeoxyglucose(18F-FDG)as an imaging tool in parathyroid cancer is not clearly reported in the literature,although its impact in other cancers is well-defined.The aim of the following illustrative clinical cases is to highlight the impact of PET/CT in the management of different phases of parathyroid cancer.We describe five patients with parathyroid malignant lesions,who underwent FDG PET/CT at initial staging,restaging and post-surgery evaluation.In each patient we report the value of PET/CT comparing its findings with other common imaging modalities(e.g.,CT,planar scintigraphy with 99mTcsestamibi,magnetic resonance imaging)thus determining the complementary benefit of FDG PET/CT in parathyroid carcinoma.We hope to provide an insight into the potential role of PET/CT in assessing the extent of disease and response to treatment which are the general principles used to correctly evaluate disease status.
文摘Background: Neuroendocrine neoplasms are those that develop from a neuroendocrine cell. They most commonly affect the lungs, gastrointestinal tract, and pancreas, being rare conditions in the female genital tract. When present, these neoplasms often manifest with nonspecific signs and symptoms such as pain, itching, swelling, single-focus lesions, bleeding, and enlargement of inguinal lymph nodes, in addition to the presence of progressively enlarging vulvar nodules. Consequently, the diagnostic investigation involves histopathological examination and confirmation through immunohistochemistry. Objective: To present a comprehensive understanding of this rarely studied pathology. The primary objective is to provide valuable insights that could aid in the future development of universally applicable treatment guidelines. Case Presentation: A 57-year-old female, with no prior comorbidities, menopause at 36, who presented with a left vulvar nodule accompanied by intense pain and swelling, later diagnosed with small cell neuroendocrine carcinoma in the vulva. Conclusion: This case report highlights the importance of enhancing our knowledge regarding small cell neuroendocrine carcinoma in the vulva, given its scarcity in medical literature. The information presented here underscores the need for standardized diagnostic and treatment approaches, paving the way for future consensus on managing this uncommon but challenging neoplasm.
基金supported by Henan Provincial Science and Technology Research Project (212102310355)the National Natural Science Foundation of China (82020108024 and 32161143021)。
文摘3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)is a pentacyclic triterpene mainly distributed in food and medicinal plants,which exhibits various pharmacological properties.However,whether these functions are attributed to eBAG or additional components in these plants remain unknown.Herein,we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer cells.EBAG induced non-apoptotic cell death in hepatocellular carcinoma cells.The eBAG-induced cell death was inhibited by knock-down of autophagy related gene(ATG)5 and ATG7,by administration of 3-methyladenine,a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase(PI3K),and by chloroquine,a classic autophagy flux inhibitor.We demonstrated that eBAG induced an autophagy-mediated cell death.Application of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP,activation of AMP-activated protein kinase(AMPK),and inhibition of mTOR.Co-treatment with compound C,an AMPK inhibitor,abrogated cell death induced by eBAG.We further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in mice.As a functional food ingredient,eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.
基金funded by China National Natural Youth Science Foundation(81802078)Zhejiang Province Public Welfare Research Foundation(GF20H200021)Zhejiang Provincial Department of Medicine and Health Foundation(2019RC315).
文摘The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regulation and prognosis,particularly those of hepatocellular carcinoma(HCC),remains unclear.To address this knowledge gap,we analyzed expression profiles obtained from The Cancer Genome Atlas(TCGA)database,comparing normal and malignant tumor tissues.We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues.Kaplan-Meier(K-M)analysis revealed the prognostic power of NRAV,wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients.Furthermore,noteworthy associations were observed between NRAV,immune checkpoints,immune cell infiltration,genes related to autophagy,epithelial-mesenchymal transition(EMT),pyroptosis,tumor mutational burden(TMB),and microsatellite instability(MSI)across different cancer types,including HCC.Moreover,NRAV upregulation expression was associated with multiple pathological stages by clinical observations.Furthermore,our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells.The inhibition of NRAV resulted in the inhibition of cell proliferation,migration,and invasion in HCC cells,while also influencing the expression of CD274(PD-L1)and CD44,along with various biomarkers associated with EMT,autophagy,and pyroptosis.The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.
文摘BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare.AIM To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the ovary.METHODS A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary,analyzing clinicopathological characteristics,treatment modalities,and survival status.RESULTS The median age at diagnosis was 34.5 years(range:20 to 62 years).Among the 12 cases,9 were small cell carcinoma of the ovary and 3 were large cell NEC.Five cases were stage I tumors,one case was stage IV,and six cases were stage III.Eleven patients underwent surgery as part of their treatment.All patients received adjuvant chemotherapy.Among the 12 patients,one patient received radiotherapy,and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy.The median progression-free survival was 13 months,and the median overall survival was 19.5 months.Four cases remained disease-free,while eight cases experienced tumor recurrence,including three cases that resulted in death due to disease recurrence.CONCLUSION NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes.Surgical resection remains the mainstay of treatment,with some patients benefiting from adjuvant chemoradiation therapy.
基金This work was supported by grants from the National Natural Science Foundation of China(52072005 and 51872279).
文摘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 cytom-etry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by in-vestigating 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 im-munohistochemistry 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.
文摘Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.
文摘Screening for hepatocellular carcinoma in patients at risk is an evidence-based approach;however,adherence to the monitoring protocol recommended by international guidelines is difficult.Hence,there is a need to use the best screening options and refine the selection of patients at risk in the future.
基金This study was supported by Beijing Municipal Science&Technology Commission to Huiguo Ding(Z221100007422002)Beijing Hospitals Authority Youth Programme to Shanshan Wang(QML20211701).
文摘Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,flow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion:In summary,the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.
基金supported by Fujian Provincial Natural Science(2020J01122587)National Natural Science Foundation of China(82103355,82102255,and 82222901)+1 种基金RGC Theme-based Research Scheme(T12-703/19-R)Research grants Council-General Research Fund(14117422 and 14117123)。
文摘Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.
基金Supported by Natural Science Foundation of Beijing(No.7222025)Beijing Hospitals Authority’Ascent Plan(No.DFL20190201)Beijing Science and Technology Rising Star Program.
文摘AIM:To evaluate lacrimal gland adenoid cystic carcinoma(LGACC)of prognosis in patients who underwent different treatment regimens.METHODS:We searched PubMed,EMBASE,and the Cochrane Library for studies done on the treatment of LGACC,between January 1987 and April 2022.A Metaanalysis was conducted to pool the 5-year overall survival rate(OR),and the 5-year recurrence rate(RR)and 5-year metastasis rate(MR)were assessed.RESULTS:The 30 studies involved 585 patients were included in the Meta-analysis.The pooled 5-year OR with surgery alone was 50%,the 5-year RR was 63%,and the 5-year MR was 34%.The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67%(95%CI 61%,73%),the 5-year RR was 41%,and the 5-year MR was 35%.The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72%(95%CI 59%,84%),the 5-year RR was 48%,and the 5-year MR was 36%.The pooled 5-year OR with surgery,intra-arterial cytoreductive chemotherapy,and adjuvant chemoradiotherapy combined was 78%(95%CI 68%,89%),the 5-year RR was 15%,and the 5-year MR was 27%.CONCLUSION:Comprehensive treatment is more effective than surgery alone.Surgery combined with intraarterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.
文摘A 64-year-old woman with no particular history presented with chronic pelvic pain since November 2021. The ultrasound performed showed multiple right ovarian cystic ranging from 0.4 to 4 cm on the long axis. She underwent a right salpingo-oophorectomy in May 2022. The anatomical pathology result is in favor of a papillary carcinoma developed on stroma ovarii. No adjuvant treatment was necessary since the tumor was well limited, without capsular rupture, stage IA. The thyroid test was normal. The patient is currently being monitored. There is no sign of recurrence 20 months after surgery.
基金Supported by the Ministry of Science of the Republic of Serbia,No.451-03-1524/2023-04/18the Science Fund of the Republic of Serbia(IDEAS Program),No.7749444,BoFraM Project.
文摘Musculoskeletal alterations in hepatocellular carcinoma(HCC)are less common than liver-related complications.However,they can significantly impact the quality of life and overall prognosis of patients with HCC.The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asym-ptomatic and unapparent during routine clinical evaluations.This narrative literature review aimed to provide a comprehensive overview of the contem-porary literature related to the changes in the musculoskeletal system in patients with HCC,focusing on its clinical implications and underlying etiopathogenetic mechanisms.Osteolytic bone metastases are the most common skeletal alterations associated with HCC,which could be associated with an increased risk of low-trauma bone fracture.Moreover,previous studies reported that osteopenia,sarcopenia,and myosteatosis are associated with poor clinical outcomes in patients with HCC.Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients,these complications are frequently overlooked in the clinical management of patients with HCC.Taken together,contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis.Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.
基金National Natural Science Foundation of China,No.82173359Basic Research and Frontier Exploration Project of Chongqing and Technology Commission,No.cstc2018jcyjAX0181Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University.
文摘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.
基金The work was supported by funds from The Science and Technology Project of Hangzhou City(Agriculture and Social Development,No.2016007)&(Agriculture and Social Development,No.20201231Y131)&(Social Development,No.20140633B57)The Science and Technology Project of Yuhang District,Hangzhou City(Nos.2017002&2014003)+2 种基金The Health Science and Technology Project of Hangzhou City(No.2015B32)Zhejiang Provincial Natural Science Foundation of China under Grant(No.LTGY23H160006)The Health Science and Technology Project of Zhejiang Province(No.2023XY009).
文摘Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug sensitivity.Methods:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.After classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were screened.Then,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso analysis.The expression of 8 risk genes was verified in vitro.Results:8 risk genes were used to construct the Sphingolipid score model.High-Sphingolipid score predicted poor prognosis of HCC patients.Sphingolipid score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK Cascade.In the High-Sphingolipid score group,a significantly higher proportion of patients with TP53(p53)mutations was significantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs.In vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 significantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 significantly decreased.Silencing TRIM47 reduced the proliferation and promoted apoptosis.The levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis decreased.Conclusion:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk genes.TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.
基金the Specific Research Project of Guangxi for Research Bases and Talents,No.GuiKe AD22035057the National Natural Science Foundation of China,No.82060510 and No.82260569.
文摘Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.
