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Clinical and Translational Medicine Jun 2024Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
BACKGROUND
Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
METHODS
Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations.
RESULTS
There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues.
CONCLUSIONS
We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications.
HIGHLIGHTS
Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.
Topics: Humans; Parathyroid Neoplasms; Adenoma; Inflammation; Histone-Lysine N-Methyltransferase; Myeloid-Lymphoid Leukemia Protein; Proto-Oncogene Mas; Cell Proliferation
PubMed: 38888967
DOI: 10.1002/ctm2.1734 -
Frontiers in Oncology 2024Atypical Parathyroid Adenoma (APA) is a type of tumor that lies somewhere between parathyroid adenoma and parathyroid carcinoma. It often affects adults over the age of...
Atypical Parathyroid Adenoma (APA) is a type of tumor that lies somewhere between parathyroid adenoma and parathyroid carcinoma. It often affects adults over the age of 60, and the clinical symptoms are consistent with those of hyperparathyroidism. This condition has a low occurrence, and its ultrasonographic signs are strikingly similar to thyroid malignant tumors, making it easily misdiagnosed. As a result, a case of APA ultrasonography misdiagnosis admitted to our hospital was recorded in order to serve as a reference point for APA diagnosis.
PubMed: 38884084
DOI: 10.3389/fonc.2024.1375373 -
Clinical Case Reports Jun 2024Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment...
KEY CLINICAL MESSAGE
Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1-associated NEN.
ABSTRACT
Multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor gene. Patients with MEN1-associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45-year-old man who developed MEN1-associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67-positive cells (2%) in MEN1-associated NEN. Further evaluation unveiled MEN1-associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc-HYNIC-TOC scintigraphy showed that focally increased radioactivity in the mid-upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6-month follow-up. Thus, acute chest pain can be the first manifestation of MEN1-associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1-associated NEN.
PubMed: 38883224
DOI: 10.1002/ccr3.9031 -
Cureus May 2024Oncocytes are frequently encountered in routine thyroidectomies. The distinction between oncocytic hyperplastic nodules and oncocytic adenomas (OAs) may be challenging....
Oncocytes are frequently encountered in routine thyroidectomies. The distinction between oncocytic hyperplastic nodules and oncocytic adenomas (OAs) may be challenging. Although both entities are benign, a precise diagnosis is essential. We present two cases of solitary oncocytic lesions carrying pathogenic mutations in the p53 and NRAS genes, respectively, leading to a histological diagnosis of oncocytic hyperplastic nodules. Additionally, similar oncocytic nodules from two cases of autoimmune thyroiditis did not show any significant findings on molecular analysis (next-generation sequencing, NGS). Hence, this brief investigative series study is of particular diagnostic interest because it prompts pathologists to use the term adenoma when a solitary oncocytic nodule is encountered, regardless of the established criteria for the diagnosis of adenoma. This viewpoint leads to the possible need for the reevaluation of the histological criteria of adenomas when it comes to oncocytic lesions in order to gain a common diagnostic approach and nomenclature among pathologists and overcome any controversies in such cases.
PubMed: 38882980
DOI: 10.7759/cureus.60361 -
F1000Research 2023Apocrine carcinoma is an extremely rare malignant cutaneous neoplasm that usually arises in areas with a high density of apocrine glands. Diagnosis can be challenging as...
Apocrine carcinoma is an extremely rare malignant cutaneous neoplasm that usually arises in areas with a high density of apocrine glands. Diagnosis can be challenging as tumours share histological and immunophenotypic characteristics with them. At first evaluation, the disease is often assumed to be benign. There have been approximately 100 reports of apocrine neoplasms in the literature. A 48-year-old male presented with a right axillary mass which increased in size over a period of 2 years. The patient was reported to have had ayurvedic therapy, but his swelling remained unchanged. Axillary lymph nodes were palpable. USG axilla suggested a well-defined fungating solid isoechoic lesion. USG neck did not reveal any abnormality. The mass was surgically excised as a whole by removing the overlying skin with margins and lymph node excision. The patient was diagnosed with primary apocrine carcinoma after surgical excision. The differentials include adenocarcinoma of breast and prostate and apocrine adenoma. There are no established standards for the care of this form of carcinoma due to its rarity and the absence of clinical studies. A literature evaluation and further reporting will aid in developing diagnostic standards and the most efficient treatment options.
Topics: Humans; Male; Middle Aged; Apocrine Glands; Sweat Gland Neoplasms; Skin Neoplasms; Diagnosis, Differential; Carcinoma
PubMed: 38882714
DOI: 10.12688/f1000research.135154.3 -
Ear, Nose, & Throat Journal Jun 2024Canalicular adenoma (CA) is a rare benign tumor of the salivary glands, predominantly affecting elderly females, with a strong predilection for the upper lip. While CA...
Canalicular adenoma (CA) is a rare benign tumor of the salivary glands, predominantly affecting elderly females, with a strong predilection for the upper lip. While CA commonly arises in the minor salivary glands, its occurrence in the parotid gland is exceptionally rare. In this report, we present a unique case of CA in the parotid gland, adding to the scant literature with only 8 documented instances. The patient, a 57-year-old Asian male, presented with a painless swelling in the left parotid gland that had been persisting for 8 years. Clinical examination and imaging studies identified a lobulated mass, prompting surgical intervention. The patient underwent a superficial parotidectomy, and pathological examination of the excised tissue confirmed the diagnosis of CA, with no signs of malignancy. This case illustrates the diagnostic and management challenges associated with CA, particularly given its rare presentation in the parotid gland. Accurate diagnosis is reliant on surgical biopsy, and careful surgical planning is imperative, especially considering the proximity of the facial nerve. Our case underscores the need for heightened awareness of CA's unique presentations, particularly within the Asian population. Given the potential for recurrence, long-term follow-up is essential. Further research is needed to elucidate the biological behavior of CA and to refine management strategies for optimal patient outcomes.
PubMed: 38881446
DOI: 10.1177/01455613241262652 -
Zhongguo Fei Ai Za Zhi = Chinese... May 2024Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Lung Neoplasms; Molecular Targeted Therapy; Pleural Neoplasms; Animals; Endoplasmic Reticulum Chaperone BiP
PubMed: 38880927
DOI: 10.3779/j.issn.1009-3419.2024.102.18 -
Clinical Proteomics Jun 2024Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis,...
BACKGROUND
Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival.
METHODS
Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays.
RESULTS
High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas.
CONCLUSIONS
GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.
PubMed: 38879494
DOI: 10.1186/s12014-024-09492-7 -
The American Journal of Clinical... Jun 2024A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated...
Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: A secondary analysis of the seAFOod polyp prevention trial.
BACKGROUND
A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for pro-inflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs.
OBJECTIVE
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2 x 2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 months (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by PCR blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention versus placebo. Presence of at least one Indel I allele and an interaction term (I allele x active intervention) were co-variates.
RESULTS
In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR] 0.92, 95% confidence interval 0.74, 1.16), mirroring original seAFOod trial analysis. However, presence of at least one I allele identified EPA users with a significant reduction in colorectal polyp number (IRR 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR.
CONCLUSIONS
The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted.
TRIAL REGISTRATION
The seAFOod polyp prevention trial and STOP-ADENOMA study are registered with https://www.isrctn.com as ISRCTN05926847.
PubMed: 38879016
DOI: 10.1016/j.ajcnut.2024.06.004 -
Ear, Nose, & Throat Journal Jun 2024Pleomorphic adenoma (PA) represents the most frequently occurring benign tumor within both major and minor salivary glands. However, in rare instances, nasal PA is an...
Pleomorphic adenoma (PA) represents the most frequently occurring benign tumor within both major and minor salivary glands. However, in rare instances, nasal PA is an epithelial-derived borderline tumor, often originating from the nasal septum. Diagnosis usually relies on histopathological analysis. Under general anesthesia, these rare nasal tumors can be completely resected via endoscopic surgery. This article reports a case of PA originating from the nasal septum in a 49-year-old patient presenting with nasal congestion, along with a brief review of the current literature. The diagnostic nasal endoscopic examination showed a pink neoplastic mass in the left nasal cavity. Subsequent radiologic examination demonstrated a soft tissue mass in the anterior part of the nasal septum. After complete resection under nasal endoscopy, histopathological examination confirmed it as PA. Fortunately, no related complications occurred perioperatively and postoperatively. After surgery, performing a thorough examination with nasal endoscopy and scheduling regular follow-ups are crucial steps to prevent local recurrence.
PubMed: 38877652
DOI: 10.1177/01455613241261457