We assessed the efficacy of simultaneous agonism at the glucagon-like peptide-1 receptor (GLP-1R) and the melanocortin-4 receptor (MC4R) for the treatment of obesity and diabetes in rodents. Diet-induced obese (DIO) mice were chronically treated with either the long-acting GLP-1R agonist liraglutide, the MC4R agonist RM-493 or a combination of RM-493 and liraglutide. Co-treatment of DIO mice with RM-493 and liraglutide improves body weight loss and enhances glycemic control and cholesterol metabolism beyond what can be achieved with either mono-therapy. The superior metabolic efficacy of this combination therapy is attributed to the anorectic and glycemic actions of both drugs, along with the ability of RM-493 to increase energy expenditure. Interestingly, compared to mice treated with liraglutide alone, hypothalamic Glp-1r expression was higher in mice treated with the combination therapy after both acute and chronic treatment. Further, RM-493 enhanced hypothalamic Mc4r expression. Hence, co-dosing with MC4R and GLP-1R agonists increases expression of each receptor, indicative of minimized receptor desensitization. Together, these findings suggest potential opportunities for employing combination treatments that comprise parallel MC4R and GLP-1R agonism for the treatment of obesity and diabetes.
Background
Adenoid cystic carcinoma of the head and neck (ACC) is a rare but highly malignant tumor. Cancer testis antigens (CTA) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy.
Methods
Eighty-four cases of ACC were identified, the CTAs pan-MAGE (M3H67) and NY-ESO-1 (E978) were detected immunohistochemically and correlated with clinical data.
Results
Expression of NY-ESO-1 was found in 48/84 (57.1%) and of pan-MAGE in 28/84 (31.2%). Median OS in NY-ESO-1 positive vs. negative patients was 130.8 and 282.0 months (p=0.223), respectively. OS in pan-MAGE positive vs. negative patients was 105.3 and 190.5 months, respectively (p=0.096). Patients expressing both, NY-ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared to 282.0 months in negative patients (p=0.047).
Conclusions
A significant fraction of ACC patients show expression of the cancer testis antigens NY-ESO-1 and/or Pan-MAGE with promising immunotherapeutic implications.
Background:
Synchronous unilateral tumors in the parotid glands account for less than 5–10% of all salivary gland neoplasms. Mostly these are cystadenolymphomas, but tumors of different histological types can be found as well. In these cases it is often pleomorphic adenoma in combination with cystadenolymphoma. Ultrasound is the first choice imaging modality.
Case report:
We present two patients with two simultaneous tumors in a unilateral parotid gland. In each case, B-mode ultrasound showed two hypoechoic masses, one of which was predominantly cystic. The subsequent use of Virtual Touch Imaging Quantification (VTIQ) showed tumors of elastic tissue. After a parotidectomy, both cases were diagnosed with pleomorphic adenoma combined with cystadenolymphoma.
Conclusion:
The combination of B-mode ultrasound and VTIQ is an important diagnostic modality and may improve diagnostic accuracy to differentiate between benign and malignant lesions. Every clinician should be aware of the co-existence of different histological types of tumors in unilateral salivary glands.
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