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1.
Oncol Res ; 32(6): 1079-1091, 2024.
Article in English | MEDLINE | ID: mdl-38827318

ABSTRACT

Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNAS-expressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/ß-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/ß-catenin signaling pathway.


Subject(s)
Chromogranins , Epithelial-Mesenchymal Transition , GTP-Binding Protein alpha Subunits, Gs , Growth Hormone-Secreting Pituitary Adenoma , Mutation , Neoplasm Invasiveness , RNA, Long Noncoding , GTP-Binding Protein alpha Subunits, Gs/genetics , GTP-Binding Protein alpha Subunits, Gs/metabolism , Animals , Humans , Growth Hormone-Secreting Pituitary Adenoma/genetics , Growth Hormone-Secreting Pituitary Adenoma/pathology , Growth Hormone-Secreting Pituitary Adenoma/metabolism , Mice , Chromogranins/genetics , Chromogranins/metabolism , Epithelial-Mesenchymal Transition/genetics , RNA, Long Noncoding/genetics , Female , Male , Cell Line, Tumor , Adenoma/genetics , Adenoma/pathology , Adenoma/metabolism , Middle Aged , Adult , Cell Proliferation/genetics , Xenograft Model Antitumor Assays , Wnt Signaling Pathway/genetics , Gene Expression Regulation, Neoplastic
3.
Cesk Patol ; 60(1): 68-70, 2024.
Article in English | MEDLINE | ID: mdl-38697830

ABSTRACT

The diagnosis of pathological conditions of the parathyroid glands is the answer to clinically more frequently detected hypercalcemic conditions, including MEN syndromes. In routine biopsy practice, enlarged bodies are also a differential diagnosis for the diagnosis of thyroid nodules. In the chapter of parathyroid tumors, the 5th edition of the WHO classification brings changes influenced similarly to other endocrine organs by the increase in genetic information. At the terminological level, the concept of hyperplasia has been narrowed down to secondary hyperplasia, most of the previously primary hyperplasias are referred to as multiglandular parathyroid disease due to evidence of multiglandular clonal proliferations. The term atypical parathyroid tumor replacing atypical adenoma is newly introduced - the uncertain biological behaviour is emphasized. The basic examination includes parafibromin immunohis- tochemistry, the deficiency of parafibromin being an indicator of an inactivating CDC73 mutation and an increased risk of familial forms, or MEN. Methodologically, refinements are introduced in the quantification of mitotic activity per 10 mm2. Oncocytic subtypes have an arbitrarily declared threshold of more than 75% oncocytes. The definition of lipoadenoma (multiplication of both components, more than 50% of adipose tissue in the tumor) is similarly specified. The diagnosis of cancer remains histopathological with unequivocal evidence of invasion, or microscopically verified metastasis.


Subject(s)
Parathyroid Neoplasms , World Health Organization , Humans , Parathyroid Neoplasms/pathology , Parathyroid Neoplasms/genetics , Parathyroid Neoplasms/diagnosis , Parathyroid Neoplasms/classification , Adenoma/pathology , Adenoma/genetics , Adenoma/classification , Adenoma/diagnosis
4.
Sci Rep ; 14(1): 10105, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38698020

ABSTRACT

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan-Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC.


Subject(s)
Adenoma , Colorectal Neoplasms , Computational Biology , Gene Expression Regulation, Neoplastic , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Adenoma/genetics , Adenoma/immunology , Adenoma/pathology , Republic of Korea , Computational Biology/methods , Male , Female , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Prognosis , Middle Aged , Aged , Biomarkers, Tumor/genetics , Kaplan-Meier Estimate , Gene Expression Profiling
5.
BMC Med Genomics ; 17(1): 124, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711024

ABSTRACT

BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. CASE PRESENTATION: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of ß-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. CONCLUSION: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.


Subject(s)
Glycogen Storage Disease Type I , Liver Neoplasms , Liver Transplantation , Humans , Glycogen Storage Disease Type I/genetics , Glycogen Storage Disease Type I/complications , Glycogen Storage Disease Type I/pathology , Female , Adolescent , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/complications , Adenoma/genetics , Adenoma/complications , Adenoma/pathology , Adenoma, Liver Cell/genetics , Adenoma, Liver Cell/complications , Adenoma, Liver Cell/pathology , Inflammation/genetics , Inflammation/pathology , Inflammation/complications
6.
Tumour Biol ; 46(1): 1-11, 2024.
Article in English | MEDLINE | ID: mdl-38728194

ABSTRACT

BACKGROUND: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the "mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)", and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. OBJECTIVE: The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. METHODS: The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. RESULTS: MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017). CONCLUSIONS: Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.


Subject(s)
Adenoma , Colorectal Neoplasms , Formins , MAP Kinase Kinase 1 , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Formins/genetics , Formins/metabolism , Adenoma/pathology , Adenoma/genetics , Adenoma/metabolism , Female , Male , Middle Aged , Aged , MAP Kinase Kinase 1/genetics , MAP Kinase Kinase 1/metabolism , Adult , Immunohistochemistry , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Carcinoma/pathology , Carcinoma/genetics , Carcinoma/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics
7.
Pathol Res Pract ; 258: 155332, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38696856

ABSTRACT

Necroptosis can either be the cause of tumorigenesis or it can impede its process. Recently, it has been proved that long non-coding RNAs (lncRNAs) have different crucial roles at cellular level, especially on cell death. Regarding the important role of necroptosis and lncRNAs in the pathogenesis of different cancers, especially pituitary adenomas (PAs), we assessed expression levels of two necroptosis related genes, namely TRADD and BIRC2, in addition to three related lncRNAs, namely FLVCR1-DT, MAGI2-AS3, and NEAT1 in PAs compared with adjacent normal tissues (ANTs). TRADD had no significant difference between two groups; however, BIRC2, FLVCR1-DT, MAGI2-AS3, and NEAT1 were upregulated in PAs compared to ANTs (Expression ratios [95% CI] = 2.3 [1.47-3.6], 2.13 [1.02-4.44], 3.01 [1.76-5.16] and 2.47 [1.37-4.45], respectively). When taking into account different types of PAs, significant upregulation of BIRC2, MAGI2-AS3 and NEAT1 was recorded in non-functioning PAs compared with corresponding ANTs (Expression ratios [95% CI] =1.9 [1.04-3.43], 2.69 [1.26-5.72] and 2.22 [0.98-5.01], respectively). Additionally, higher levels of BIRC2 were associated with higher flow of CSF (P value=0.048). Moreover, higher Knosp classified tumors had lower levels of BIRC2 (P value=0.001). Finally, lower levels of MAGI2-AS3 were associated with larger tumor size (P value=0.006). NEAT1 expression was correlated with FLVCR1-DT and TRADD. TRADD expression was correlated with FLVCR1-DT. Additional correlation was observed between expression of BIRC2 and MAGI2-AS3. In sum, this study provides evidence that dysregulated levels of studied genes could contribute to the pathogenesis of pituitary tumors.


Subject(s)
Necroptosis , Pituitary Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Pituitary Neoplasms/metabolism , Male , Middle Aged , Female , Adult , Necroptosis/genetics , Aged , Gene Expression Regulation, Neoplastic/genetics , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/metabolism , Adenoma/genetics , Adenoma/pathology , Adenoma/metabolism
8.
CNS Neurosci Ther ; 30(5): e14749, 2024 05.
Article in English | MEDLINE | ID: mdl-38739004

ABSTRACT

AIMS: A bone-invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF-α promotes bone invasion by facilitating the differentiation of osteoclasts, however, before bone-invasive pituitary adenoma invades bone tissue, it needs to penetrate the dura mater, and this mechanism is not yet clear. METHODS: We performed transcriptome microarrays on specimens of bone-invasive pituitary adenomas (BIPAs) and noninvasive pituitary adenomas (NIPAs) and conducted differential expressed gene analysis and enrichment analysis. We altered the expression of TNF-α through plasmids, then validated the effects of TNF-α on GH3 cells and verified the efficacy of the TNF-α inhibitor SPD304. Finally, the effects of TNF-α were validated in in vivo experiments. RESULTS: Pathway act work showed that the MAPK pathway was significantly implicated in the pathway network. The expression of TNF-α, MMP9, and p-p38 is higher in BIPAs than in NIPAs. Overexpression of TNF-α elevated the expression of MAPK pathway proteins and MMP9 in GH3 cells, as well as promoted proliferation, migration, and invasion of GH3 cells. Flow cytometry indicated that TNF-α overexpression increased the G2 phase ratio in GH3 cells and inhibited apoptosis. The expression of MMP9 was reduced after blocking the P38 MAPK pathway; overexpression of MMP9 promoted invasion of GH3 cells. In vivo experiments confirm that the TNF-α overexpression group has larger tumor volumes. SPD304 was able to suppress the effects caused by TNF-α overexpression. CONCLUSION: Bone-invasive pituitary adenoma secretes higher levels of TNF-α, which then acts on itself in an autocrine manner, activating the MAPK pathway and promoting the expression of MMP9, thereby accelerating the membrane invasion process. SPD304 significantly inhibits the effect of TNF-α and may be applied in the clinical treatment of bone-invasive pituitary adenoma.


Subject(s)
Adenoma , MAP Kinase Signaling System , Matrix Metalloproteinase 9 , Neoplasm Invasiveness , Pituitary Neoplasms , Tumor Necrosis Factor-alpha , Tumor Necrosis Factor-alpha/metabolism , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Humans , Adenoma/pathology , Adenoma/metabolism , Animals , Matrix Metalloproteinase 9/metabolism , MAP Kinase Signaling System/physiology , MAP Kinase Signaling System/drug effects , Male , Cell Line, Tumor , Female , Mice , Mice, Nude , Autocrine Communication/physiology , Autocrine Communication/drug effects , Middle Aged , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Adult , Rats , Cell Movement/drug effects , Cell Movement/physiology , Signal Transduction/physiology , Signal Transduction/drug effects
9.
J Nippon Med Sch ; 91(2): 227-232, 2024.
Article in English | MEDLINE | ID: mdl-38777783

ABSTRACT

BACKGROUND: Detective flow imaging (DFI) is a new imaging technology that displays low-velocity blood flow, which is difficult to visualize on conventional color Doppler ultrasonography (CDU). In this study, we compared the usefulness of DFI with that of CDU and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for detecting parathyroid adenoma (PA) in patients with primary hyperparathyroidism (PHPT). METHODS: From March 2021 to March 2023, 87 PHPT patients underwent surgery, and 66 had a single PA. We performed preoperative conventional ultrasonography with CDU, MIBI scintigraphy, and DFI for 42 patients (5 males and 37 females; mean age: 61.6 ± 15.4 years). RESULTS: MIBI scintigraphy detected PA in 85.7% (36/42) patients, and both CDU and DFI detected PA in all patients. The rates of vascularity in PA detected by CDU and DFI were 71.4% (30/42) and 85.7% (36/42), respectively. Vascularity was detected by DFI in 6 patients who were negative for vascularity on MIBI scintigraphy. Furthermore, DFI detected blood supply in 6 of the 12 patients with undetectable blood supply on CDU. Fisher's exact test revealed that high or low blood flow, as determined by DFI, was significantly associated with detection of feeding vessels in PA by CDU (P < 0.001). CONCLUSIONS: DFI was useful for preoperative detection of PA blood flow.


Subject(s)
Adenoma , Hyperparathyroidism, Primary , Parathyroid Neoplasms , Ultrasonography, Doppler, Color , Humans , Female , Male , Middle Aged , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/surgery , Parathyroid Neoplasms/complications , Hyperparathyroidism, Primary/diagnostic imaging , Hyperparathyroidism, Primary/surgery , Aged , Ultrasonography, Doppler, Color/methods , Adenoma/diagnostic imaging , Radionuclide Imaging/methods , Technetium Tc 99m Sestamibi , Adult , Blood Flow Velocity
10.
Acta Neurochir (Wien) ; 166(1): 225, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772927

ABSTRACT

PURPOSE: To identify differences in the presentation and surgical outcomes between very large (30-39 mm) and giant (≥ 40 mm) (LARGE group) pituitary adenomas (PAs) compared to the smaller group (< 30 mm) (non-LARGE group). METHODS: Eighty patients with very large (n = 44) or giant (n = 36) PAs and 226 patients in the non-LARGE group who underwent tumor resection by pituitary surgery between 2008 and 2023 were studied. Hormonal, radiological, ophthalmological, and pathological data, and surgical outcomes were evaluated. RESULTS: Preoperatively, patients of the LARGE group presented more frequently with visual impairment (82.5% vs. 22.1%, P < 0.001) and with pituitary apoplexy (15.0% vs. 2.7%, P < 0.001) than the non-LARGE group. Moreover, the LARGE group were more commonly associated with preoperative panhypopituitarism (28.8% vs. 6.2%, P < 0.001). This group presented cavernous sinus invasion more frequently (71.3% vs. 23.9%, P < 0.001). The non-LARGE group achieved surgical cure more often than the LARGE group (79.7% vs. 50.0%, P < 0.001), and the rate of major complications was higher in the latest (8.8% vs. 1.3%, P < 0.004). CONCLUSIONS: PAs ≥ 30 mm are most frequently accompanied by hormonal dysfunction, cavernous sinus invasion, and visual impairment. All this implies lower resection rates and higher postoperative complications than the smaller adenomas, posing a real surgical challenge.


Subject(s)
Adenoma , Pituitary Neoplasms , Humans , Pituitary Neoplasms/surgery , Pituitary Neoplasms/pathology , Pituitary Neoplasms/diagnostic imaging , Adenoma/surgery , Adenoma/pathology , Adenoma/diagnostic imaging , Male , Female , Middle Aged , Adult , Treatment Outcome , Aged , Cohort Studies , Vision Disorders/etiology , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Hypopituitarism/etiology , Retrospective Studies , Tumor Burden
11.
BMJ Case Rep ; 17(5)2024 May 22.
Article in English | MEDLINE | ID: mdl-38782444

ABSTRACT

Glycogen storage disease type 1A (GSD1A), also known as Von Gierke's disease, is a rare autosomal recessive disorder affecting glycogen metabolism in the liver. It most commonly presents in infancy with hypoglycaemia and failure to thrive, but cases have been reported as undiagnosed until adulthood. A woman in her early 20s with diabetes mellitus presented with right upper quadrant pain and was found to have several haemorrhagic hepatic adenomas. This patient had insulin-dependent diabetes since a pancreatectomy at age 9 months due to continued episodes of hypoglycaemia and suspected insulinoma. During the hospital stay, the hepatic adenomas were embolised, but significant lactic acidosis and hypoglycaemia continued. Further workup revealed a chronic lactic acid level, during several hospital stays, of above 5 mmol/L. After cytology of hepatic tissue ruled out hepatocellular carcinoma, the patient was discharged and recommended to follow-up for genetic testing, which confirmed the diagnosis of GSD1A.


Subject(s)
Congenital Hyperinsulinism , Glycogen Storage Disease Type I , Liver Neoplasms , Humans , Female , Liver Neoplasms/genetics , Liver Neoplasms/diagnosis , Congenital Hyperinsulinism/genetics , Congenital Hyperinsulinism/diagnosis , Glycogen Storage Disease Type I/complications , Glycogen Storage Disease Type I/genetics , Glycogen Storage Disease Type I/diagnosis , Adult , Adenoma, Liver Cell/genetics , Adenoma, Liver Cell/diagnosis , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/genetics , Young Adult , Adenoma/genetics , Adenoma/diagnosis , Adenoma/complications , Adenoma/surgery , Diagnosis, Differential
13.
Khirurgiia (Mosk) ; (5): 138-145, 2024.
Article in Russian | MEDLINE | ID: mdl-38785250

ABSTRACT

All adenomas of the major duodenal papilla (MDP) require resection regardless of morphological structure due to high risk of malignancy. Currently, intraluminal endoscopic interventions are preferable for these adenomas. MDP neoplasms with intraductal spread (type III and IV) are of particular difficulty for endoscopic techniques. Intraductal radiofrequency ablation provides new opportunities for minimally invasive treatment of patients with MDP adenomas and intraductal component. A 72-year-old patient after previous endoscopic papillectomy for MDP adenoma admitted to the Vishnevsky National Research Medical Center of Surgery due to residual adenomatous growths within the papillectomy zone extending to the common bile duct throughout 13 mm. The patient underwent intraductal RFA under endosonography and cholangioscopy. Despite difficult localization of residual growths extending to the common bile duct, endosonography-guided intraductal RFA provided total destruction of residual tumor that was confirmed by cholangioscopy. Length of treatment was 4 months, relapse-free period - 10 months. Minimally invasive endoscopic technology for residual MDP adenoma provided good clinical results.


Subject(s)
Ampulla of Vater , Radiofrequency Ablation , Humans , Aged , Ampulla of Vater/surgery , Radiofrequency Ablation/methods , Endosonography/methods , Adenoma/surgery , Adenoma/diagnostic imaging , Adenoma/pathology , Male , Treatment Outcome , Common Bile Duct Neoplasms/surgery
14.
PLoS One ; 19(5): e0304374, 2024.
Article in English | MEDLINE | ID: mdl-38787836

ABSTRACT

Colonoscopy-based screening provides protection against colorectal cancer (CRC), but the optimal starting age and time intervals of screening colonoscopies are unknown. We aimed to determine an optimal screening schedule for the US population and its dependencies on the objective of screening (life years gained or incidence, mortality, or cost reduction) and the setting in which screening is performed. We used our established open-source microsimulation model CMOST to calculate optimized colonoscopy schedules with one, two, three or four screening colonoscopies between 20 and 90 years of age. A single screening colonoscopy was most effective in reducing life years lost from CRC when performed at 55 years of age. Two, three and four screening colonoscopy schedules saved a maximum number of life years when performed between 49-64 years; 44-69 years; and 40-72 years; respectively. However, for maximum incidence and mortality reduction, screening colonoscopies needed to be scheduled 4-8 years later in life. The optimum was also influenced by adenoma detection efficiency with lower values for these parameters favoring a later starting age of screening. Low adherence to screening consistently favored a later start and an earlier end of screening. In a personalized approach, optimal screening would start earlier for high-risk patients and later for low-risk individuals. In conclusion, our microsimulation-based approach supports colonoscopy screening schedule between 45 and 75 years of age but the precise timing depends on the objective of screening, as well as assumptions regarding individual CRC risk, efficiency of adenoma detection during colonoscopy and adherence to screening.


Subject(s)
Adenoma , Colonoscopy , Colorectal Neoplasms , Early Detection of Cancer , Humans , Middle Aged , Adenoma/diagnosis , Aged , Early Detection of Cancer/methods , Adult , Colorectal Neoplasms/diagnosis , Male , Female , Aged, 80 and over , Patient Compliance , Time Factors , Computer Simulation , Mass Screening/methods , Young Adult
15.
Clin Ter ; 175(3): 98-116, 2024.
Article in English | MEDLINE | ID: mdl-38767067

ABSTRACT

Background: The human microbiome, consisting of diverse bacte-rial, fungal, protozoan and viral species, exerts a profound influence on various physiological processes and disease susceptibility. However, the complexity of microbiome data has presented significant challenges in the analysis and interpretation of these intricate datasets, leading to the development of specialized software that employs machine learning algorithms for these aims. Methods: In this paper, we analyze raw data taken from 16S rRNA gene sequencing from three studies, including stool samples from healthy control, patients with adenoma, and patients with colorectal cancer. Firstly, we use network-based methods to reduce dimensions of the dataset and consider only the most important features. In addition, we employ supervised machine learning algorithms to make prediction. Results: Results show that graph-based techniques reduces dimen-sion from 255 up to 78 features with modularity score 0.73 based on different centrality measures. On the other hand, projection methods (non-negative matrix factorization and principal component analysis) reduce dimensions to 7 features. Furthermore, we apply supervised machine learning algorithms on the most important features obtained from centrality measures and on the ones obtained from projection methods, founding that the evaluation metrics have approximately the same scores when applying the algorithms on the entire dataset, on 78 feature and on 7 features. Conclusions: This study demonstrates the efficacy of graph-based and projection methods in the interpretation for 16S rRNA gene sequencing data. Supervised machine learning on refined features from both approaches yields comparable predictive performance, emphasizing specific microbial features-bacteroides, prevotella, fusobacterium, lysinibacillus, blautia, sphingomonas, and faecalibacterium-as key in predicting patient conditions from raw data.


Subject(s)
Microbiota , RNA, Ribosomal, 16S , Supervised Machine Learning , Unsupervised Machine Learning , Humans , Microbiota/genetics , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/analysis , Colorectal Neoplasms/microbiology , Gastrointestinal Microbiome/genetics , Algorithms , Feces/microbiology , Adenoma/microbiology
16.
CNS Neurosci Ther ; 30(5): e14729, 2024 05.
Article in English | MEDLINE | ID: mdl-38738958

ABSTRACT

BACKGROUND: Pituitary adenoma is one of the most common brain tumors. Most pituitary adenomas are benign and can be cured by surgery and/or medication. However, some pituitary adenomas show aggressive growth with a fast growth rate and are resistant to conventional treatments such as surgery, drug therapy, and radiation therapy. These tumors, referred to as refractory pituitary adenomas, often relapse or regrow in the early postoperative period. The tumor microenvironment (TME) has recently been identified as an important factor affecting the biological manifestations of tumors and acts as the main battlefield between the tumor and the host immune system. MAIN BODY: In this review, we focus on describing TME in pituitary adenomas and refractory pituitary adenomas. Research on the immune microenvironment of pituitary adenomas is currently focused on immune cells such as macrophages and lymphocytes, and extensive research and experimental verifications are still required regarding other components of the TME. In particular, studies are needed to determine the role of the TME in the specific biological behaviors of refractory pituitary adenomas, such as high invasion, fast recurrence rate, and high tolerance to traditional treatments and to identify the mechanisms involved. CONCLUSION: Overall, we summarize the similarities and differences between the TME of pituitary adenomas and refractory pituitary adenomas as well as the changes in the biological behavior of pituitary adenomas that may be caused by the microenvironment. These changes greatly affect the outcome of patients.


Subject(s)
Adenoma , Pituitary Neoplasms , Tumor Microenvironment , Pituitary Neoplasms/therapy , Pituitary Neoplasms/pathology , Humans , Tumor Microenvironment/physiology , Tumor Microenvironment/immunology , Adenoma/therapy , Adenoma/pathology , Animals , Treatment Outcome
17.
Sci Rep ; 14(1): 11633, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38773186

ABSTRACT

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan-Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.


Subject(s)
Adenoma , Colonoscopy , Colorectal Neoplasms , Life Style , Nomograms , Humans , Colorectal Neoplasms/diagnosis , Male , Female , Middle Aged , Adenoma/diagnosis , Retrospective Studies , Aged , Risk Factors , Adult , Proportional Hazards Models , ROC Curve
18.
BMC Cancer ; 24(1): 611, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773399

ABSTRACT

RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.


Subject(s)
Adenoma , Colorectal Neoplasms , MicroRNAs , Pyruvic Acid , RNA, Long Noncoding , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Adenoma/genetics , Adenoma/metabolism , Adenoma/pathology , Pyruvic Acid/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Gene Expression Regulation, Neoplastic , Metabolic Reprogramming
19.
Cancer Med ; 13(10): e7290, 2024 May.
Article in English | MEDLINE | ID: mdl-38770646

ABSTRACT

BACKGROUND: This study aimed to establish the standardized procedure of trans-areola single site endoscopic parathyroidectomy (TASSEP), and to compare the performance of TASSEP with that of conventional open parathyroidectomy (COP). METHODS: This study enrolled 40 patients with primary hyperparathyroidism (PHPT) who underwent TASSEP, and included 40 of 176 PHPT patients who underwent COP based on propensity score matching. The retrospective analysis was conducted based on prospectively collected data. Perioperative outcomes, including surgical profile, surgical burden and cosmetic results and follow-up were reported. The learning curve was described using a cumulative sum (CUSUM) analysis. RESULTS: 40 TASSEPs were completed successfully without conversions or severe complications. There was no statistically significant difference in operation time between TASSEP and COP groups (80.83 ± 11.95 vs. 76.95 ± 7.30 min, p = 0.084). Experience of 17 cases was necessitated to reach the learning curve of TASSEP. Postoperative pain score and traumatic index (C-reactive protein and erythrocyte sedimentation rate) in TASSEP were apparently lower than those in COP group (p < 0.05). During the proliferation and stabilization phases, TASSEP was associated with significantly better incision recovery and cosmetic scores. Postoperative serum calcium and PTH levels throughout the follow-up period indicated satisfactory surgical qualities in both groups. CONCLUSION: Based on precise preoperative localization and intraoperative planning facilitated by three-dimensional (3D) virtual modeling, TASSEP can be feasibly performed on selected patients with satisfactory success rates and low complication rates, providing preferable cosmetic results and alleviating the surgical burden to a certain extent.


Subject(s)
Parathyroid Neoplasms , Parathyroidectomy , Humans , Parathyroidectomy/methods , Male , Female , Middle Aged , Parathyroid Neoplasms/surgery , Parathyroid Neoplasms/pathology , Retrospective Studies , Adenoma/surgery , Adenoma/pathology , Endoscopy/methods , Treatment Outcome , Adult , Hyperparathyroidism, Primary/surgery , Aged , Propensity Score , Operative Time
20.
Sci Rep ; 14(1): 10750, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38729988

ABSTRACT

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.


Subject(s)
Adenoma , Artificial Intelligence , Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/classification , Adenoma/diagnosis , Adenoma/classification , Colonoscopy/methods , Early Detection of Cancer/methods , Colonic Polyps/diagnosis , Colonic Polyps/classification , Colonic Polyps/pathology , Algorithms
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