HER2 inhibition increases non-muscle myosin IIA to promote tumorigenesis in HER2+ breast cancers.

HER2 is over-expressed in around 15% to 20% of breast cancers. HER3 plays a critical role in HER2 mediated tumorigenesis. Increased HER3 transcription and protein levels occur upon inhibition of HER2. We aimed to identify proteins that bound to HER3 upon inhibition of the HER family with the pan-HER inhibitor neratinib in HER2+ breast cancer cells. Immunoprecipitation of HER3 followed by mass spectrometry experiments found non-muscle myosin IIA (NMIIA) increased upon neratinib treatment relative to vehicle DMSO treatment. MYH9 is the gene that encodes for the heavy chain of NMIIA. Breast cancer patients with high MYH9 were significantly associated with a shorter disease specific survival compared to patients with low MYH9 expression from the METABRIC cohort of patients. In addition, high MYH9 expression was associated with HER2+ tumors from this cohort. Immunoblots of whole cell lysates of BT474 and MDA-MB-453 HER2+ breast cancer cells demonstrated elevated HER3 and NMIIA protein levels upon neratinib treatment for 24 hours. To examine the role of NMIIA in HER2+ breast cancer, we modulated NMIIA levels in BT474 and MDA-MB-453 cells using doxycycline inducible shRNA targeting MYH9. MYH9 knockdown reduces HER3 protein levels and concomitant reduction in downstream P-Akt. In addition, loss of MYH9 suppresses cell growth, proliferation, migration, and invasion. Our data reveals that NMIIA regulates HER3 and loss of NMIIA reduces HER2+ breast cancer growth.

Practice of ear candling during lockdown due to COVID-19 in the Kingdom of Saudi Arabia.

Objectives: Cerumen production is a protective process for the ear canal. Cerumen impaction causes unpleasant symptoms. There are various cerumen removal practices. These include irrigation, application of softeners/solvents, mechanical removal, and micro-suction. However, during the lockdown period of the COVID-19 pandemic, some patients opted for some procedures, such as ear candling, which are not evidence-based. This study aimed to explore the awareness of ear candling among otolaryngology doctors and record cases with complications of such practice in the Kingdom of Saudi Arabia (KSA). Methods: This was a cross-sectional study. A questionnaire was developed after an extensive literature search, and distributed to otolaryngology residents, fellows, and consultants of different hospitals across the country. A total of 80 respondents agreed to participate in the study. Results: A total of 16 doctors reported seeing cases of ear candling, of which 13 patients had different complications, of which ear pain was the most commonly reported. The majority of participants (42.5%) thought the lack of medical access during lockdown enhanced the practice of alternative medicine for ear-related complaints in society compared to 35% of participants who had a neutral response regarding this idea and 22.5% who disagreed. Conclusions: Although the practice of ear candling is not widely spread in KSA, different types of ear complications were recorded by the otolaryngologist. We would like to encourage the doctors to report such complications, especially after the lockdown period.