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The Lancet. Oncology May 2024
Topics: Humans; Pyridines; Mitotane; Adrenal Cortex Neoplasms; Anilides; Adrenocortical Carcinoma; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents, Hormonal; Treatment Outcome
PubMed: 38608692
DOI: 10.1016/S1470-2045(24)00151-7 -
BMC Cancer Apr 2024Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two...
PURPOSE
Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function.
METHODS
We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro.
RESULTS
In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration.
CONCLUSIONS
In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.
Topics: Humans; Acetyltransferases; Adenocarcinoma; Adenocarcinoma of Lung; Adrenal Cortex Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Chromosomal Proteins, Non-Histone; Colonic Neoplasms; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Thymus Neoplasms
PubMed: 38605349
DOI: 10.1186/s12885-024-12213-w -
Dermatitis : Contact, Atopic,... Apr 2024
PubMed: 38593446
DOI: 10.1089/derm.2023.0325 -
Scientific Reports Apr 2024The crosstalk between the chromaffin and adrenocortical cells is essential for the endocrine activity of the adrenal glands. This interaction is also likely important...
The crosstalk between the chromaffin and adrenocortical cells is essential for the endocrine activity of the adrenal glands. This interaction is also likely important for tumorigenesis and progression of adrenocortical cancer and pheochromocytoma. We developed a unique in vitro 3D model of the whole adrenal gland called Adrenoid consisting in adrenocortical carcinoma H295R and pheochromocytoma MTT cell lines. Adrenoids showed a round compact morphology with a growth rate significantly higher compared to MTT-spheroids. Confocal analysis of differential fluorescence staining of H295R and MTT cells demonstrated that H295R organized into small clusters inside Adrenoids dispersed in a core of MTT cells. Transmission electron microscopy confirmed the strict cell-cell interaction occurring between H295R and MTT cells in Adrenoids, which displayed ultrastructural features of more functional cells compared to the single cell type monolayer cultures. Adrenoid maintenance of the dual endocrine activity was demonstrated by the expression not only of cortical and chromaffin markers (steroidogenic factor 1, and chromogranin) but also by protein detection of the main enzymes involved in steroidogenesis (steroidogenic acute regulatory protein, and CYP11B1) and in catecholamine production (tyrosine hydroxylase and phenylethanolamine N-methyltransferase). Mass spectrometry detection of steroid hormones and liquid chromatography measurement of catecholamines confirmed Adrenoid functional activity. In conclusion, Adrenoids represent an innovative in vitro 3D-model that mimics the spatial and functional complexity of the adrenal gland, thus being a useful tool to investigate the crosstalk between the two endocrine components in the pathophysiology of this endocrine organ.
Topics: Humans; Pheochromocytoma; Adrenal Glands; Catecholamines; Chromogranins; Adrenal Gland Neoplasms
PubMed: 38580769
DOI: 10.1038/s41598-024-58664-w -
Diagnostic and Interventional Imaging Apr 2024The purpose of this study was to evaluate the capabilities of multiparametric magnetic resonance imaging (MRI) in differentiating between lipid-poor adrenal adenoma...
PURPOSE
The purpose of this study was to evaluate the capabilities of multiparametric magnetic resonance imaging (MRI) in differentiating between lipid-poor adrenal adenoma (LPAA) and adrenocortical carcinoma (ACC).
MATERIALS AND METHODS
Patients of two centers who underwent surgical resection of LPAA or ACC after multiparametric MRI were retrospectively included. A training cohort was used to build a diagnostic algorithm obtained through recursive partitioning based on multiparametric MRI variables, including apparent diffusion coefficient and chemical shift signal ratio (i.e., tumor signal intensity index). The diagnostic performances of the multiparametric MRI-based algorithm were evaluated using a validation cohort, alone first and then in association with adrenal tumor size using a cut-off of 4 cm. Performances of the diagnostic algorithm for the diagnosis of ACC vs. LPAA were calculated using pathology as the reference standard.
RESULTS
Fifty-four patients (27 with LPAA and 27 with ACC; 37 women; mean age, 48.5 ± 13.3 [standard deviation (SD)] years) were used as the training cohort and 61 patients (24 with LPAA and 37 with ACC; 47 women; mean age, 49 ± 11.7 [SD] years) were used as the validation cohort. In the validation cohort, the diagnostic algorithm yielded best accuracy for the diagnosis of ACC vs. LPAA (75%; 46/61; 95% CI: 55-88) when used without lesion size. Best sensitivity was obtained with the association of the diagnostic algorithm with tumor size (96%; 23/24; 95% CI: 80-99). Best specificity was obtained with the diagnostic algorithm used alone (76%; 28/37; 95% CI: 60-87).
CONCLUSION
A multiparametric MRI-based diagnostic algorithm that includes apparent diffusion coefficient and tumor signal intensity index helps discriminate between ACC and LPAA with high degrees of specificity and accuracy. The association of the multiparametric MRI-based diagnostic algorithm with adrenal lesion size helps maximize the sensitivity of multiparametric MRI for the diagnosis of ACC.
PubMed: 38575426
DOI: 10.1016/j.diii.2024.03.005 -
Cureus Mar 2024Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Its diagnosis requires clinical suspicion and confirmation through laboratory and imaging...
Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Its diagnosis requires clinical suspicion and confirmation through laboratory and imaging studies, including computed tomography (CT), magnetic resonance imaging (MRI), and abdominal ultrasound, as well as histological confirmation. Positron emission tomography (PET) is useful for distinguishing between benign and malignant lesions and for evaluating tumor recurrences or metastases. A case is described in which the uptake of fluorodeoxyglucose (18F-FDG) in a remnant adrenal gland could be misinterpreted as tumoral pathology. The article presents the case of a patient with ACC who, after treatment, showed increased FDG uptake in the remnant adrenal gland, which disappeared after discontinuation of treatment with mitotane. Possible explanations for this increase in FDG uptake are discussed, including the action of mitotane. In summary, it is highlighted that FDG uptake in remnant adrenal glands in patients treated with mitotane does not always indicate tumor recurrence or adrenal hypertrophy.
PubMed: 38571874
DOI: 10.7759/cureus.55486 -
Heliyon Apr 2024The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the...
BACKGROUND
The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients.
METHODS
The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The "-Tile" program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively.
RESULTS
A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using -tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (>8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, < 0.001). Subgroup analyses revealed no statistical significance and a consistent proportionate effect of tumor size on CSS and OS across all eight pre-specified subgroups. Interestingly, an additional subgroup analysis showed that ACC patients could not benefit from chemotherapy in terms of CSS and OS.
CONCLUSION
The study suggests that tumor size is a crucial prognostic factor in ACC patients and a cutoff value 8.5 cm might indicate a poor outcome. Given the limitations of the available data, it is challenging to conclusively determine the benefit of chemotherapy in adult ACC patients across different tumor size ranges.
PubMed: 38571632
DOI: 10.1016/j.heliyon.2024.e28160 -
European Journal of Cancer (Oxford,... May 2024
Topics: Humans; Adrenocortical Carcinoma; Doxorubicin; Etoposide; Adrenal Cortex Neoplasms
PubMed: 38554541
DOI: 10.1016/j.ejca.2024.114035 -
European Journal of Endocrinology Mar 2024Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still...
OBJECTIVE
Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.
METHODS
A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.
RESULTS
We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.
CONCLUSIONS
The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.
Topics: Humans; Child; Mitotane; Adrenocortical Carcinoma; Antineoplastic Agents, Hormonal; Adrenal Cortex Neoplasms; Drug-Related Side Effects and Adverse Reactions
PubMed: 38552173
DOI: 10.1093/ejendo/lvae038