No abstract

Cardiac hypertrophy is a chronic complex disease that occurs in response to hemodynamic load and is accompanied by oxidative stress and mitochondrial dysfunction. Mitochondrial ATP-sensitive K channels (mitoKATPs) have previously been shown to prevent oxidative cardiac damage under conditions of ischemia/reperfusion. However, the effect of these channels on cardiac hypertrophy has not been tested to date. In this study, we show that treatment of Swiss mice with isoproterenol (30 mg·kg·d) induces cardiac hypertrophy while significantly decreasing the levels of reduced protein thiols, glutathione, catalase, and superoxide dismutase activity, indicative of a condition of oxidative imbalance. Treatment with diazoxide (a mitoKATP opener, 5 mg·kg·d) normalized the levels of protein thiols and reduced glutathione, rescued superoxide dismutase activity, and significantly prevented cardiac hypertrophy. The protective effects of diazoxide were mitigated by the mitoKATP blockers 5-hydroxydecanoate (5 mg·kg·d) and glibenclamide (3 mg·kg·d), demonstrating that they were related to activation of the channel. Taken together, our results establish that mitoKATP activation promotes very robust prevention of cardiac hypertrophy and associated oxidative imbalance and suggest that these channels can be important drug targets for the pharmacological control of cardiac hypertrophy.

Introduction: Secretory carcinoma of the breast is a rare disease, accounting for approximately 0.15% of breast cancer cases. This entity was first described in a child in 1966. However, one of the largest case series with SEER data, encompassing a total of 190 patients, showed that the median age at diagnosis was 56 years, and it can affect both sexes, being much more common in women. In this same series, 58% and 40% of patients were positive for estrogen and progesterone hormone receptors, respectively. Most cases (86.86%) were well to moderately differentiated tumors without lymph node involvement. Older patients had a worse prognosis. In general, the secretory breast carcinoma has a more indolent course with excellent prognosis. The treatment is based mainly on surgery, followed by radiation therapy. The role of chemotherapy and hormone therapy in these cases is not yet well established in the literature. Parallel to basal-like breast cancer, the indolent clinical course as well as prolonged survival seems opposite to that of common triple-negative breast cancer. In most cases of secretory breast carcinoma, reaching a 92% positivity rate, there is a fusion of the ETV6-NTRK3 genes, activating aberrant cell proliferation pathways. Studies with NTRK inhibitors are being developed and will bring this therapeutic possibility soon. Due to the rarity of secretory carcinoma of the breast, notably in men, we report the case of a young man with this neoplasm. A.S.R., 20 years old, male, from Guaraciaba do Norte (CE), white, single, telecommunications technician, reported that he noticed a painless, small, stable nodule in his left breast in 2012. He did not seek medical help at the time. In June 2021, the patient suffered trauma to her left breast during a soccer match. After this event, she noticed a considerable growth of a nodule in the left breast, which became painful to palpation. He then sought medical attention in a health center and underwent an ultrasonography of the left breast in August 2021, which detected a hypoechoic nodular image, oval, with well-defined limits, and regular contours, measuring 16.1×9.6×13.7 cm, 1.8 mm away from the skin, without vascularization inside the nodule (CATEGORY: BIRADS 3); little amount of stromal and glandular tissue were observed. A core biopsy of the nodule, performed in August 26, 2022, showed atypical epithelial proliferation. Immunohistochemistry was compatible with hypersecretory atypical epithelial proliferation. After the diagnosis of secretory carcinoma of the breast, the patient was referred to the Haroldo Juaçaba Hospital, a reference hospital in oncologic treatment in the North/Northeast of Brazil, where he underwent a slide review and immunohistochemistry, which confirmed invasive carcinoma of the secretory type of breast. Staging CT scans and bone scintigraphy were performed in September 2021. Chest CT showed a nodule with irregular contours and contrast medium concentration in the left breast, in close contact with the retropectoral musculature, measuring 19×10×12 mm, in addition to adenomegaly in the right axillary region (levels I and II), measuring up to 38×27 mm. There were no other relevant findings, with no evidence of secondary disease in the abdomen and bones. Investigation of right axillary adenomegaly with core biopsy continued and was negative for neoplasia. Histological picture and immunohistochemical profile were compatible with mixed lymphoid hyperplasia, follicular, and interfollicular. In December 28, 2022, the patient underwent a left mastectomy with sentinel lymph node biopsy, which revealed a secretory invasive carcinoma, measuring 1.9×1.5 cm, grade I, lymphovascular invasion, and negative margins, no lymph nodes were involved, nipple with compromised dermis and intraductal extension. Pathological staging: pT1c pN0 (sn-). The patient is currently on adjuvant systemic treatment (chemotherapy) with good tolerance.