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1.
Cell Death Dis ; 15(6): 422, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886389

ABSTRACT

TGF-ß1 plays a pivotal role in the metastatic cascade of malignant neoplasms. N6-methyladenosine (m6A) stands as one of the most abundant modifications on the mRNA transcriptome. However, in the metastasis of gallbladder carcinoma (GBC), the effect of TGF-ß1 with mRNA m6A modification, especially the effect of mRNA translation efficiency associated with m6A modification, remains poorly elucidated. Here we demonstrated a negative correlation between FOXA1 and TGF-ß1 expression in GBC. Overexpression of FOXA1 inhibited TGF-ß1-induced migration and epithelial-mesenchymal transition (EMT) in GBC cells. Mechanistically, we confirmed that TGF-ß1 suppressed the translation efficiency of FOXA1 mRNA through polysome profiling analysis. Importantly, both in vivo and in vitro experiments showed that TGF-ß1 promoted m6A modification on the coding sequence (CDS) region of FOXA1 mRNA, which was responsible for the inhibition of FOXA1 mRNA translation by TGF-ß1. We demonstrated through MeRIP and RIP assays, dual-luciferase reporter assays and site-directed mutagenesis that ALKBH5 promoted FOXA1 protein expression by inhibiting m6A modification on the CDS region of FOXA1 mRNA. Moreover, TGF-ß1 inhibited the binding capacity of ALKBH5 to the FOXA1 CDS region. Lastly, our study confirmed that overexpression of FOXA1 suppressed lung metastasis and EMT in a nude mice lung metastasis model. In summary, our research findings underscore the role of TGF-ß1 in regulating TGF-ß1/FOXA1-induced GBC EMT and metastasis by inhibiting FOXA1 translation efficiency through m6A modification.


Subject(s)
Adenosine , Epithelial-Mesenchymal Transition , Gallbladder Neoplasms , Hepatocyte Nuclear Factor 3-alpha , Mice, Nude , Protein Biosynthesis , Transforming Growth Factor beta1 , Hepatocyte Nuclear Factor 3-alpha/metabolism , Hepatocyte Nuclear Factor 3-alpha/genetics , Humans , Transforming Growth Factor beta1/metabolism , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/metabolism , Animals , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Adenosine/analogs & derivatives , Adenosine/metabolism , Mice , Neoplasm Metastasis , Gene Expression Regulation, Neoplastic , Cell Movement , RNA, Messenger/metabolism , RNA, Messenger/genetics , Mice, Inbred BALB C , Male
2.
BMJ Case Rep ; 17(6)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890111

ABSTRACT

SummarySquamous cell carcinoma (SCC) is an uncommon and frequently aggressive subtype of gallbladder cancer known for its poor outcomes compared with other gallbladder tumours. Gallbladder SCC typically presents as higher grade and more advanced than adenocarcinoma, resulting in lower estimated survival. Early recognition of these tumours is ideal, but infrequently achieved. Herein is a case of a male patient in his 80s with new onset abdominal pain who was initially diagnosed with cholecystitis, but diagnostic imaging revealed a gallbladder mass. Surgical resection and pathology revealed pure SCC of the gallbladder without local organ invasion or metastatic disease. Pure SCC histology of the gallbladder is rare, with limited studies on clinical presentation, natural history, and optimal treatment.


Subject(s)
Carcinoma, Squamous Cell , Gallbladder Neoplasms , Humans , Male , Gallbladder Neoplasms/surgery , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/diagnosis , Aged, 80 and over , Diagnosis, Differential , Tomography, X-Ray Computed , Gallbladder/pathology , Gallbladder/surgery , Gallbladder/diagnostic imaging , Cholecystectomy
3.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 142-146, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836667

ABSTRACT

Gallbladder cancers (GBC) are rare, and they are one of lethal neoplasms of biliary system. The diagnosis is either incidentally during histopathological examinations after cholecystectomy or due to complications of local or systemic spread of the malignancy. The incidence differs ethnically and geographically. The aim was to identify increase risk of cancer in the Kurdistan region by searching for the number of GBC cases among cholecystectomy patients in Sulaymaniyah governorate. This study is laboratory-based retrospective study, including data obtained from 8315 cholecystectomized patients in Sulaymaniyah governorate from 2017- 2021. The information within the questionnaire included: age, sex, clinical notes and histopathological findings; including GBC. The total of 8315 cases; were 2149 males (25.8%) and 6166 females (74.2%). The mean age was (44.67+/-15.18) years. Forty-five cases have been reported as adenocarcinoma of GB and one case of Carcinosarcoma. Among the patients, 875 cases (10.50%) had acute cholecystitis. A significant relationship was found between the findings and the age and gender of the patients. GBC is not common and is mainly diagnosed incidentally after routine post-operative histopathological examination, and mainly affects old ages.


Subject(s)
Cholecystectomy , Gallbladder Neoplasms , Humans , Male , Gallbladder Neoplasms/epidemiology , Gallbladder Neoplasms/pathology , Female , Middle Aged , Adult , Prevalence , Aged , Retrospective Studies , Aged, 80 and over , Young Adult
4.
Nihon Shokakibyo Gakkai Zasshi ; 121(6): 505-513, 2024.
Article in Japanese | MEDLINE | ID: mdl-38853020

ABSTRACT

A 68-year-old female patient was referred to our hospital with acute cholangitis. Computed tomography revealed common bile duct dilatation, gallbladder fundal tumor, and gallbladder wall thickening attached to the tumor. Cholangiography revealed pancreaticobiliary maljunction with biliary dilation. The patient was diagnosed with pancreaticobiliary maljunction with biliary dilation and gallbladder cancer and underwent liver S4b+5 and bile duct resection and reconstruction. Pathological results revealed that the gallbladder fundal tumor included sarcoma, and the gallbladder wall thickening had adenocarcinoma;thus, the patient was diagnosed with gallbladder carcinosarcoma.


Subject(s)
Carcinosarcoma , Gallbladder Neoplasms , Pancreaticobiliary Maljunction , Humans , Female , Gallbladder Neoplasms/diagnostic imaging , Gallbladder Neoplasms/surgery , Aged , Carcinosarcoma/diagnostic imaging , Carcinosarcoma/surgery , Carcinosarcoma/pathology , Pancreaticobiliary Maljunction/diagnostic imaging
5.
Clin Chim Acta ; 560: 119751, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38830523

ABSTRACT

BACKGROUND: The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. METHODS: This study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. RESULTS: The average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. CONCLUSIONS: In gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.


Subject(s)
Fibrinolysis , Gallbladder Neoplasms , Humans , Gallbladder Neoplasms/blood , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/pathology , Female , Male , Cross-Sectional Studies , Middle Aged , Aged , Blood Coagulation , Adult , Biomarkers, Tumor/blood , Diagnosis, Differential , Biomarkers/blood , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism
6.
World J Surg Oncol ; 22(1): 157, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877554

ABSTRACT

OBJECTIVE: This study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). METHODS: Retrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis. RESULTS: Twelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89-30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61-7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67-43.33 months) for Group 3 (n = 4), and 19 months (range 7.89-30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004). CONCLUSION: Surgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.


Subject(s)
Carcinoma, Neuroendocrine , Cholecystectomy , Gallbladder Neoplasms , Humans , Gallbladder Neoplasms/therapy , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/surgery , Gallbladder Neoplasms/diagnosis , Male , Female , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/therapy , Carcinoma, Neuroendocrine/mortality , Carcinoma, Neuroendocrine/surgery , Carcinoma, Neuroendocrine/diagnosis , Middle Aged , Retrospective Studies , Aged , Prognosis , Survival Rate , Adult , Follow-Up Studies , Combined Modality Therapy
7.
J Med Ultrason (2001) ; 51(2): 227-233, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38700561

ABSTRACT

Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Humans , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Endosonography/methods , Constriction, Pathologic/diagnostic imaging , Gallbladder Neoplasms/diagnostic imaging , Gallbladder Neoplasms/pathology , Gallbladder/diagnostic imaging , Gallbladder/pathology , Biliary Tract Diseases/diagnostic imaging , Biliary Tract Neoplasms/diagnostic imaging , Biliary Tract Neoplasms/pathology
8.
Eur J Radiol ; 176: 111505, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38796886

ABSTRACT

PURPOSE: To identify high-risk computed tomography (CT) features for predicting gallbladder (GB) cancer in patients presenting with localized GB wall thickening. METHODS: This retrospective analysis included 120 patients (mean age: 63.9 ± 10.0 years; 51 men) exhibiting localized GB wall thickening on CT scans obtained between January 2008 and May 2017. Two radiologists independently evaluated CT imaging features for predicting GB cancer. The diagnostic performance of significant imaging features and their combinations was evaluated. High-risk CT features ranked by accuracy were delineated for predicting GB cancer. RESULTS: This study included 55 patients with GB cancer and 65 with benign GB conditions. The top-four most accurate CT imaging features for predicting GB cancer were identified: heterogeneously enhancing single layer or strongly enhancing thick inner layer; GB wall thickness > 6.5 mm; hyperenhancement on arterial phase; and absence of intramural small cystic lesions (accuracies of 90.0 %, 88.3 %, 85.0 %, and 85.0 %, respectively). The combination of any three high-risk features exhibited the highest accuracy (94.2 %). The presence of any high-risk feature yielded a sensitivity of 100 %, whereas that of all high-risk features indicated a specificity of 100 %. CONCLUSION: CT imaging features, whether alone or in combination, could effectively and accurately predict GB cancer among patients with localized GB wall thickening. This finding holds significance in guiding decisions regarding further diagnostic tests and treatment planning.


Subject(s)
Gallbladder Neoplasms , Sensitivity and Specificity , Tomography, X-Ray Computed , Humans , Gallbladder Neoplasms/diagnostic imaging , Male , Female , Middle Aged , Tomography, X-Ray Computed/methods , Retrospective Studies , Aged , Gallbladder/diagnostic imaging , Gallbladder/pathology , Reproducibility of Results , Diagnosis, Differential , Aged, 80 and over , Adult
9.
Hepatology ; 79(6): 1324-1336, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38758104

ABSTRACT

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.


Subject(s)
Biliary Tract Neoplasms , Coffee , Tea , Humans , Male , Female , Middle Aged , Biliary Tract Neoplasms/epidemiology , Biliary Tract Neoplasms/etiology , Aged , Incidence , Gallbladder Neoplasms/epidemiology , Gallbladder Neoplasms/etiology , Gallbladder Neoplasms/prevention & control , Risk Factors , Adult , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/etiology
10.
Vet Clin Pathol ; 53(2): 234-241, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38806404

ABSTRACT

A 12-year-old spayed female Dalmatian presented with acute vomiting and anorexia. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and multiple diffuse splenic hypoechogenic nodules. Cholecystectomy was performed to remove the obstruction, followed by liver biopsy and splenectomy. Histopathological and immunohistology evaluation of the spleen, liver, and gallbladder revealed splenic marginal zone lymphoma (MZL) with gallbladder and hepatic infiltration of neoplastic CD20/CD79α-positive cells. Moreover, we observed clonal rearrangements of the immunoglobulin heavy-chain (IgH) gene in all three tissues. The dog was in good condition without chemotherapy. However, there was progressive elevation of liver enzymes, which could be attributed to neoplastic hepatic infiltration. Chlorambucil and prednisolone were administered until day 108, when the liver enzyme levels normalized. On day 156, the dog developed diffuse large B-cell lymphoma (DLBCL) of the peripheral lymph nodes. Sequence analysis of the clonally rearranged IgH gene revealed that all neoplastic cells in the spleen, gallbladder, and liver at initial presentation, as well as lymph nodes on day 156, possessed the same sequence identity of the amplified IgH fragments. This demonstrated that all neoplastic cells were derived from the same B-lymphocyte clone. The DLBCL was considered to have transformed from the splenic MZL, with gallbladder involvement. In cases of splenic MZL, it is important to consider gallbladder involvement and transformation to DLBCL. Moreover, gallbladder lymphoma should be included in the differential diagnosis of dogs with gallbladder abnormalities. Further studies are warranted to investigate the prognosis of splenic MZL.


Subject(s)
Dog Diseases , Lymphoma, B-Cell, Marginal Zone , Lymphoma, Large B-Cell, Diffuse , Splenic Neoplasms , Animals , Dogs , Female , Dog Diseases/pathology , Dog Diseases/diagnosis , Splenic Neoplasms/veterinary , Splenic Neoplasms/pathology , Lymphoma, B-Cell, Marginal Zone/veterinary , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, Large B-Cell, Diffuse/veterinary , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Gallbladder Neoplasms/veterinary , Gallbladder Neoplasms/pathology , Gallbladder/pathology
11.
Cancer Lett ; 592: 216923, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38697462

ABSTRACT

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.


Subject(s)
Cell Movement , Gallbladder Neoplasms , Liver Neoplasms , Ribonucleoproteins , Ubiquitination , Animals , Humans , Mice , Cell Line, Tumor , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Liver Neoplasms/secondary , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Mitophagy , Neoplasm Invasiveness , Ribonucleoproteins/metabolism , Ribonucleoproteins/genetics , Tyrosine Transaminase
13.
BMC Cancer ; 24(1): 597, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755562

ABSTRACT

BACKGROUND: With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations. METHODS AND RESULTS: We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT. CONCLUSIONS: About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.


Subject(s)
Biliary Tract Neoplasms , Humans , Middle Aged , Female , Male , Aged , Adult , Scotland/epidemiology , Aged, 80 and over , Biliary Tract Neoplasms/therapy , Biliary Tract Neoplasms/epidemiology , Cholangiocarcinoma/therapy , Cholangiocarcinoma/pathology , Gallbladder Neoplasms/therapy , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/epidemiology , Chemotherapy, Adjuvant
14.
J Biochem Mol Toxicol ; 38(6): e23733, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38770938

ABSTRACT

The aim of this investigation was to evaluate the differential expression of the sterol O-acyltransferase 1 (SOAT1) protein in gallbladder cancer tissues and cells, investigate the impact of Avastin on the proliferation, migration, invasion capabilities of gallbladder cancer cells, and its potential to induce cell apoptosis. Immunohistochemical analysis of samples from 145 gallbladder cancer patients was conducted, along with analysis of SOAT1 protein, mRNA expression levels, and cholesterol content in gallbladder cancer cell lines SGC-996, NOZ, and gallbladder cancer (GBC)-SD using Western blot and q-PCR techniques. Furthermore, the effects of Avastin on the proliferation, migration, and invasion capabilities of these gallbladder cancer cell lines were studied, and its ability to induce cell apoptosis was evaluated using flow cytometry, Western blot, and immunohistochemical methods. Additionally, gene expression and pathway analysis were performed, and the synergistic therapeutic effects of Avastin combined with gemcitabine were tested in a gallbladder cancer xenograft model. The study found that SOAT1 expression was significantly upregulated in GBC tissues and positively correlated with lymph node metastasis and TNM staging. In vitro experiments demonstrated that Avastin significantly inhibited the proliferation, migration, and invasion capabilities of SGC-996 and GBC-SD cell lines and induced apoptosis. RNA sequencing analysis revealed multiple differentially expressed genes in cells treated with Avastin, primarily enriched in biological pathways such as signaling transduction, malignant tumors, and the immune system. In vivo, experiments confirmed that Avastin could effectively suppress tumor growth in a gallbladder cancer xenograft model and enhanced the treatment efficacy when used in combination with gemcitabine. Overall, these findings provide new insights and strategies for targeted therapy in gallbladder cancer.


Subject(s)
Gallbladder Neoplasms , Sterol O-Acyltransferase , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/drug therapy , Gallbladder Neoplasms/metabolism , Gallbladder Neoplasms/genetics , Humans , Female , Male , Cell Line, Tumor , Animals , Middle Aged , Sterol O-Acyltransferase/metabolism , Sterol O-Acyltransferase/genetics , Mice , Gemcitabine , Cell Proliferation/drug effects , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Mice, Nude , Apoptosis/drug effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Cell Movement/drug effects , Xenograft Model Antitumor Assays , Aged , Gene Expression Regulation, Neoplastic/drug effects , Mice, Inbred BALB C , Neoplasm Proteins/metabolism , Neoplasm Proteins/genetics
16.
Medicine (Baltimore) ; 103(18): e37880, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701302

ABSTRACT

INTRODUCTION: Incidental gallbladder carcinoma refers to a discovery of gallbladder cancer during or after cholecystectomy. Late port-site metastasis (PSM) following Laparoscopic cholecystectomy (LC) is rare with an incidence rate of 10.3%. PATIENT CONCERNS: We report a case of a 58-year-old man who presented with a painful abdominal wall mass for 6 weeks. He had a history of LC for symptomatic cholelithiasis, 8 years prior. DIAGNOSIS: Histopathological examination revealed a positive result for metastatic adenocarcinoma from the abdominal wall mass. Moreover, Positron emission tomography (PET) showed a small focus of intense fluorodeoxyglucose (FDG) uptake in the gallbladder bed, which was highly suspicious for malignancy. INTERVENTION: Decision was to proceed with surgery owing to uptake in the gallbladder bed with single-site metastasis to the previous port site. In addition, in the board meeting, an agreement was reached for performing distal pancreatectomy with splenectomy owing to uncertainty of malignancy based on what was discovered during the full metastatic workup. Diagnostic laparoscopy followed by midline laparotomy performed. Radical completion cholecystectomy with lymphadenectomy was done. Followed by complete resection of the anterior abdominal wall. Distal pancreatectomy and splenectomy were then performed. OUTCOME: Pathological diagnosis showed metastatic/invasive, moderately differentiated adenocarcinoma with positive margins on the posterior surface of excised port-site mass. The positive margins necessitated further chemoradiotherapy, followed by adjuvant chemotherapy until lung metastasis was identified. After this, the patient was scheduled for palliative chemotherapy. CONCLUSION: Presence of PSM is often associated with peritoneal metastasis. For this reason, it is advised to evaluate the patient for possible metastasis.


Subject(s)
Adenocarcinoma , Cholecystectomy, Laparoscopic , Gallbladder Neoplasms , Humans , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/secondary , Gallbladder Neoplasms/surgery , Cholecystectomy, Laparoscopic/adverse effects , Male , Middle Aged , Adenocarcinoma/secondary , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Neoplasm Seeding , Abdominal Wall/pathology , Incidental Findings
17.
Front Cell Infect Microbiol ; 14: 1374238, 2024.
Article in English | MEDLINE | ID: mdl-38774627

ABSTRACT

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system with the worst prognosis. Even after radical surgery, the majority of patients with GBC have difficulty achieving a clinical cure. The risk of tumor recurrence remains more than 65%, and the overall 5-year survival rate is less than 5%. The gut microbiota refers to a variety of microorganisms living in the human intestine, including bacteria, viruses and fungi, which profoundly affect the host state of general health, disease and even cancer. Over the past few decades, substantial evidence has supported that gut microbiota plays a critical role in promoting the progression of GBC. In this review, we summarize the functions, molecular mechanisms and recent advances of the intestinal microbiota in GBC. We focus on the driving role of bacteria in pivotal pathways, such as virulence factors, metabolites derived from intestinal bacteria, chronic inflammatory responses and ecological niche remodeling. Additionally, we emphasize the high level of correlation between viruses and fungi, especially EBV and Candida spp., with GBC. In general, this review not only provides a solid theoretical basis for the close relationship between gut microbiota and GBC but also highlights more potential research directions for further research in the future.


Subject(s)
Bacteria , Gallbladder Neoplasms , Gastrointestinal Microbiome , Humans , Gallbladder Neoplasms/microbiology , Bacteria/classification , Bacteria/isolation & purification , Animals , Dysbiosis/microbiology , Virulence Factors , Fungi/pathogenicity , Fungi/classification
18.
Clin Nucl Med ; 49(7): 688-689, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38598517

ABSTRACT

ABSTRACT: A 64-year-old woman presented with chest pain while eating and was referred to our hospital. Physical examination revealed abdominal distension, tenderness, and lower-extremity edema. Imaging revealed a large gallbladder tumor infiltrating the liver, with ascites and pleural effusion. A biopsy confirmed a poorly differentiated adenocarcinoma with SMARCA4 deficiency (cT3N2M1, cStage IV). Chemotherapy was ineffective and led to tumor progression. The patient died 9 months later. Recently, attention has been paid to SMARCA4 deficiency, which is a genetic mutation found in tumors. Here, we report on poorly differentiated adenocarcinomas of the gallbladder based on imaging findings, including FDG PET.


Subject(s)
Adenocarcinoma , DNA Helicases , Gallbladder Neoplasms , Nuclear Proteins , Transcription Factors , Humans , Female , Middle Aged , Gallbladder Neoplasms/diagnostic imaging , Gallbladder Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Transcription Factors/genetics , DNA Helicases/genetics , Nuclear Proteins/genetics
19.
J Cell Mol Med ; 28(9): e18328, 2024 May.
Article in English | MEDLINE | ID: mdl-38683130

ABSTRACT

Gallbladder cancer is a rare but fatal malignancy. However, the mechanisms underlying gallbladder carcinogenesis and its progression are poorly understood. The function of m6A modification and its regulators was still unclear for gallbladder cancer. The current study seeks to investigate the function of YTH m6A RNA-binding protein 1 (YTHDF1) in gallbladder cancer. Transcriptomic analysis and immunochemical staining of YTHDF1 in gallbladder cancer tissues revealed its upregulation compared to paracancerous tissues. Moreover, YTHDF1 promotes the proliferation assays, Transwell migration assays, and Transwell invasion assays of gallbladder cancer cells in vitro. And it also increased tumour growth in xenograft mouse model and metastases in tail vein injection model in vivo. In vitro, UHRF1 knockdown partly reversed the effects of YTHDF1 overexpression. Mechanistically, dual-luciferase assays proved that YTHDF1 promotes UHRF1 expression via direct binding to the mRNA 3'-UTR in a m6A-dependent manner. Overexpression of YTHDF1 enhanced UHRF1 mRNA stability, as demonstrated by mRNA stability assays, and Co-IP studies confirmed a direct interaction between YTHDF1 and PABPC1. Collectively, these findings provide new insights into the progression of gallbladder cancer as well as a novel post-transcriptional mechanism of YTHDF1 via stabilizing target mRNA.


Subject(s)
Adenosine , Gallbladder Neoplasms , Gene Expression Regulation, Neoplastic , RNA-Binding Proteins , Ubiquitin-Protein Ligases , Animals , Female , Humans , Male , Mice , Adenosine/analogs & derivatives , CCAAT-Enhancer-Binding Proteins/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/metabolism , Mice, Nude , RNA Stability/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics
20.
Acta Radiol ; 65(5): 422-431, 2024 May.
Article in English | MEDLINE | ID: mdl-38584372

ABSTRACT

BACKGROUND: Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. PURPOSE: To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. MATERIAL AND METHODS: All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. RESULTS: In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). CONCLUSION: It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.


Subject(s)
Contrast Media , Gallbladder Neoplasms , Gallbladder , Tomography, X-Ray Computed , Humans , Male , Female , Gallbladder Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Middle Aged , Aged , Diagnosis, Differential , Adult , Gallbladder/diagnostic imaging , Retrospective Studies , Aged, 80 and over , Nomograms , Radiographic Image Enhancement/methods , Reproducibility of Results , Sensitivity and Specificity , Radiomics
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