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International Journal of Molecular... May 2024Elevated oxidative stress can play a pivotal role in autoimmune diseases by exacerbating inflammatory responses and tissue damage. In Sjögren's disease (SjD), the...
Elevated oxidative stress can play a pivotal role in autoimmune diseases by exacerbating inflammatory responses and tissue damage. In Sjögren's disease (SjD), the contribution of oxidative stress in the disease pathogenesis remains unclear. To address this question, we created mice with a tamoxifen-inducible conditional knockout (KO) of a critical antioxidant enzyme, superoxide dismutase 2 (, in the salivary glands (i-sg- KO mice). Following tamoxifen treatment, deletion occurred primarily in the ductal epithelium, and the salivary glands showed a significant downregulation of expression. At twelve weeks post-treatment, salivary glands from the i-sg- KO mice exhibited increased 3-Nitrotyrosine staining. Bulk RNA-seq revealed alterations in gene expression pathways related to ribosome biogenesis, mitochondrial function, and oxidative phosphorylation. Significant changes were noted in genes characteristic of salivary gland ionocytes. The i-sg- KO mice developed reversible glandular hypofunction. However, this functional loss was not accompanied by glandular lymphocytic foci or circulating anti-nuclear antibodies. These data demonstrate that although localized oxidative stress in salivary gland ductal cells was insufficient for SjD development, it induced glandular dysfunction. The i-sg- KO mouse resembles patients classified as non-Sjögren's sicca and will be a valuable model for deciphering oxidative-stress-mediated glandular dysfunction and recovery mechanisms.
Topics: Animals; Superoxide Dismutase; Salivary Glands; Sjogren's Syndrome; Mice; Mice, Knockout; Epithelial Cells; Oxidative Stress; Mitochondria; Disease Models, Animal
PubMed: 38892170
DOI: 10.3390/ijms25115983 -
International Journal of Molecular... May 2024Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA)...
Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [At]PSMA-5 was administered to both normal male ICR mice ( = 85) and cynomolgus monkeys ( = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( = 10 per group) and 14 days ( = 5 per group). Monkeys were observed 24 h post-administration of [At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of At using a cyclotron supports its applicability for clinical use.
Topics: Animals; Male; Prostatic Neoplasms; Mice; Tissue Distribution; Mice, Inbred ICR; Astatine; Alpha Particles; Humans; Macaca fascicularis; Glutamate Carboxypeptidase II; Radiopharmaceuticals
PubMed: 38891856
DOI: 10.3390/ijms25115667 -
Animals : An Open Access Journal From... Jun 2024Identifying the potential presence of stress at the pig farm is fundamental since it affects pig welfare. As a result, a reliable and straightforward tool to monitor... (Review)
Review
Identifying the potential presence of stress at the pig farm is fundamental since it affects pig welfare. As a result, a reliable and straightforward tool to monitor stress could record the welfare status of the animals. Although numerous methods to assess the welfare of pigs have been developed in the past, no gold standard has been established yet. Recently, the value of saliva as a tool to identify chronic stress in piglets was explored, as it can be collected fast and non-invasively. Since the protein composition, i.e., the proteome of porcine saliva, responds to stress, the affected proteins could be used as salivary stress biomarkers. The present review first defines stress and its relationship with welfare. Next, the porcine gland-specific salivary proteome is characterized. Finally, six potential salivary biomarkers for stress are proposed, i.e., odorant-binding protein, vomeromodulin-like protein, chitinase, lipocalin-1, long palate lung and nasal epithelium protein, and alpha-2-HS-glycoprotein.
PubMed: 38891749
DOI: 10.3390/ani14111703 -
BMC Cancer Jun 2024Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key...
BACKGROUND
Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key treatment for patients with NACC. This study reported the long-term efficacy and safety of particle beam radiation therapy (PBRT) for NACC.
METHODS AND MATERIALS
Twenty-six patients with nonmetastatic NACC who received definitive PBRT alone were included in this retrospective study. The majority of patients (92.3%) had locally advanced disease. Twenty-five (96.15%) patients received intensity-modulated proton radiotherapy (IMPT) followed by a carbon ion radiotherapy (CIRT) boost, and one patient received CIRT alone. Overall survival (OS), local control (LC), regional control (RC), and distant metastasis control (DMC) rates were calculated via the Kaplan-Meier method.
RESULTS
The median follow-up time was 46.95 months for the entire cohort. Seven patients experienced local recurrence, and one patient experience neck lymph node recurrence. The 3- and 4-year OS, LC, RC, and DMC rates were 100% and 91.7%, 92.3% and 84.6%, 95.8% and 87.8%, and 90.2% and 71.3%, respectively. A total of 91.3% of the patients achieved complete remission of gross tumors at 1 year after PBRT. Severe acute toxicity was observed in only two patients. A grade 4 decrease in visual acuity was observed in one patient with orbital apex invasion. No late grade 3 or 5 toxicity was observed.
CONCLUSION
Definitive PBRT provided a satisfactory 4-year OS for patients with locally advanced NACC. The toxicity was acceptable and mild. Further follow-up is necessary to confirm the efficacy and safety of definitive PBRT for patients with NACC.
Topics: Humans; Carcinoma, Adenoid Cystic; Male; Female; Middle Aged; Nasopharyngeal Neoplasms; Adult; Retrospective Studies; Treatment Outcome; Aged; Proton Therapy; Radiotherapy, Intensity-Modulated; Young Adult; Follow-Up Studies; Nasopharyngeal Carcinoma; Neoplasm Recurrence, Local; Heavy Ion Radiotherapy
PubMed: 38890585
DOI: 10.1186/s12885-024-12471-8 -
BMC Nephrology Jun 2024Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We...
BACKGROUND
Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions.
CASE PRESENTATION
A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared.
CONCLUSION
This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.
Topics: Humans; Female; Middle Aged; Sarcoidosis; Kidney Diseases; Parotid Gland; Uterine Diseases; Prednisolone; Parotid Diseases; Radionuclide Imaging; Tomography, X-Ray Computed
PubMed: 38890580
DOI: 10.1186/s12882-024-03635-6 -
Frontiers in Oncology 2024Hyalinizing clear cell carcinomas (HCCCs) are infrequent, malignant tumors characterized by their low-grade nature. They typically originate from minor salivary glands....
Hyalinizing clear cell carcinomas (HCCCs) are infrequent, malignant tumors characterized by their low-grade nature. They typically originate from minor salivary glands. However, these tumors can potentially emerge in any location with minor salivary glands, including the nasopharynx. This report presents two cases of HCCC in females aged 61 and 72 years, with both tumors approximately 4 cm in size. In the first case, a 72-year-old female presented with recurrent bilateral epistaxis. Imaging studies revealed a nasopharyngeal mass, surgically excised, and histopathological analysis confirmed HCCC. Postoperatively, the patient received combined chemotherapy and radiotherapy, achieving a recurrence-free status 2.5 years later. The second case involves a 61-year-old female with a two-year history of bloody nasal discharge. Imaging studies identified a nasopharyngeal lesion, surgically removed, and histopathological examination confirmed HCCC. This patient underwent radiotherapy followed by combination chemotherapy with paclitaxel and carboplatin, displaying no signs of recurrence upon reevaluation after 10 months. These cases highlight the successful management of HCCC through a comprehensive, multimodal approach, integrating surgical intervention and adjuvant therapy. The favorable outcomes emphasize the significance of a thorough treatment strategy for HCCC in the nasopharynx, providing valuable insights for clinicians. Further studies are essential to enhance our understanding of this rare entity and refine treatment protocols for optimized patient outcomes.
PubMed: 38884096
DOI: 10.3389/fonc.2024.1384913 -
Clinical Case Reports Jun 2024A plunging ranula may present initially as an extensive vallecular cyst and correct diagnosis may be reached with the use of ultrasound, fluid aspiration for amylase...
KEY CLINICAL MESSAGE
A plunging ranula may present initially as an extensive vallecular cyst and correct diagnosis may be reached with the use of ultrasound, fluid aspiration for amylase detection, and MRI imaging.
ABSTRACT
The ranula is a pseudocyst of the sublingual salivary gland and can be divided into two known subtypes. The simple ranula and plunging ranula. While the simple type can be found in the floor of the mouth, the plunging ranula usually pervades the mylohoid muscle and presents as a cervical swelling. The presented case should outline the difficulties in diagnostic and treatment of an uncommon expression of a mucocele above the mylohoid muscle without presenting either a cervical or an intraoral swelling, only extending towards the vallecula. We present a previously unreported clinical manifestation of a ranula of an 18-year old male, which extends posteriorly, remaining confined in the supramylohyoid muscle space. The cystic lesion protrudes in the oropharynx, and clinically appears as an extensive vallecular cyst. On magnetic resonance imaging the initial suspected diagnosis of a vallecular cyst was changed to the final diagnosis of a plunging ranula. The marsupialization of the cyst sac was performed. Outpatient follow-up revealed a persisting ostium, indicating a continuous extravasation of the sublingual gland. The present case report describes an unusual clinical presentation of a plunging ranula, remaining above the mylohyoid muscle and protruding into the oropharynx, misdirecting to the first suspected diagnosis of a vallecular cyst. The case highlights the useful contribution of the MRI imaging for differential diagnoses and the need for criteria to indicate further investigations.
PubMed: 38883226
DOI: 10.1002/ccr3.8964 -
Cureus May 2024Secretory carcinoma of the salivary gland (SCSG) is a rare head and neck tumor in adults and exceptional at the pediatric age. Its varied histological subtypes and...
Secretory carcinoma of the salivary gland (SCSG) is a rare head and neck tumor in adults and exceptional at the pediatric age. Its varied histological subtypes and distinct clinical presentation pose diagnostic and therapeutic challenges. Therefore, standardized guidelines are of utmost importance for the care of these patients, especially in children. Here we present an 11-year-old male presented with a left cheek mass initially diagnosed as lipoma. A wide resection was performed and SCSG was revealed in the histopathologic and immunohistochemistry analysis. The presentation of this case provides valuable information on the diagnostic and therapeutic complexities of SCSG. It emphasizes the need for standardized guidelines and further research to optimize pediatric patient outcomes. Overall, this case report is a crucial resource for clinicians and researchers, highlighting the importance of interdisciplinary collaboration and early intervention in managing SCSG.
PubMed: 38883019
DOI: 10.7759/cureus.60355 -
Heliyon Jun 2024Treatment resistance after chemo-/immunotherapy occurs in patients with head and neck squamous cell cancers (HNSCs), including salivary gland cancers (SGCs)....
Treatment resistance after chemo-/immunotherapy occurs in patients with head and neck squamous cell cancers (HNSCs), including salivary gland cancers (SGCs). Interleukin-10 (IL-10), a cytokine with pro- and anti-cancer effects, has an unclear impact on HNSC/SGC cells. We show that HNSC patients exhibiting high expression of IL-10 and its receptor IL-10Rα experience have prolonged overall survival. Immunoreactive IL-10 was low in ductal cells of human SGC biopsies. Human (A253) and murine WR21-SGC cells expressed IL-10Rβ, but only A253 cells expressed IL-10 and IL-10Rα. The addition of recombinant IL-10 impaired SGC cell proliferation and induced apoptosis . N-acetylcysteine restored IL-10-induced reactive oxygen species (ROS) production but did not prevent IL-10-mediated viability loss. Mechanistically, recIL-10 delayed cell cycle progression from G0/G1 to the S phase with downregulation and upregulation of NF-kB. IL-10 increased tumor necrosis factor-α (TNF-α) in A253 and WR21 and in WR21 cells. Neutralizing antibodies against TNF-α and NF-kB inhibition restored SGC proliferation after IL-10 treatment, emphasizing the critical role of TNF-α and NF-kB in IL-10-mediated anti-tumor effects. These findings underscore the potential of IL-10 to impede SGC cell growth through apoptosis induction, unraveling potential therapeutic targets for intervention in salivary gland carcinomas.
PubMed: 38882335
DOI: 10.1016/j.heliyon.2024.e31777 -
Molecular and Clinical Oncology Aug 2024Lymphoepithelial cysts (LECs) of the salivary glands are relatively rare, benign cystic lesions. Characteristic histopathological features of LEC include presence of...
Lymphoepithelial cysts (LECs) of the salivary glands are relatively rare, benign cystic lesions. Characteristic histopathological features of LEC include presence of well-circumscribed unilocular cysts surrounded by dense lymphoid tissue with lymphoid follicles. These cysts are lined by a combination of squamous, ciliated, columnar and mucous epithelia. Fine-needle aspiration (FNA) cytology is the standard preoperative diagnostic procedure for salivary gland lesions. Although the cytological diagnosis of cystic salivary gland lesions is difficult, the use of Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) in the cytodiagnosis of cystic salivary gland lesions has been reported. However, only a few studies have described the cytological features of LEC. To the best of our knowledge, the present study reviewed the cytological features of a case series of LEC and evaluated the application of MSRSGC for the first time. This retrospective study included 13 patients with LEC of the salivary glands who underwent pre-operative FNA followed by surgical resection of the cyst. All the lesions were present in the parotid gland. Cytological analysis revealed no epithelial cell component in eight patients (62.5%) along with a proteinaceous background containing lymphocytes and/or foamy cells. Non-keratinising squamous epithelium was observed in three patients. Amylase crystalloids were noted in two patients. None of the patients were cytodiagnosed with LEC. Eight, three, one and one patients were categorised as MSRSGC I, II, III, and IVa, respectively. The results of the present study demonstrated that cytodiagnosis of LEC was difficult due to the absence of epithelial component in 62.5% of the specimens. However, evaluation of its benignity was not difficult. Thus, it can be summarized that MSRSGC may be useful for cytological evaluation of LECs.
PubMed: 38882218
DOI: 10.3892/mco.2024.2750