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https://www.selleckchem.com/products/acy-775.html Prior research suggests the afferent feedback from the Ia sensory fibers are likely attenuated during walking, while afferent feedback from the β polysynaptic sensory fibers are not. We suggest that the attenuated gamma oscillations seen during walking reflect the gating of the Ia afferents, while the similarity of theta-alpha oscillations across the experimental conditions is associated with the afferent information from the type II (Aα and β) polysynaptic sensory fibers.Background Brain metastases are frequent in HER2-positive breast cancer. ONT-380 (tucatinib) is a potent selective inhibitor of HER2 with intracranial activity in preclinical models. Patients and methods This was a phase I study of tucatinib with trastuzumab, without chemotherapy, in patients with progressive, measurable HER2-positive brain metastases. The study tested two schedules of tucatinib cohort A was twice-daily and cohort B was once-daily. The primary objective was determination of the maximum tolerated dose (MTD). Secondary endpoints included objective response (intracranial and extracranial) using modified RECIST and clinical benefit rate (CBR). Results Overall, 41 patients were enrolled (cohort A n=22, cohort B n=19). Patients had a median of 2 prior treatments for metastatic breast cancer and 83% had progressed after prior brain radiation. The MTD of tucatinib for cohort A was 300 mg twice-daily and for cohort B was 750 mg once-daily. The most common dose-limiting toxicities included thrombocytopenia and AST/ALT elevation. Grade 3/4 AST/ALT elevation occurred in 9/41 patients (22%). Intracranial responses were observed in two of 17 (12%) patients in Cohort A and one of 17 (6%) patient in Cohort B treated at the MTD. In cohort A, CBR at 16 weeks was 35% (n=6). In cohort B, CBR at 16 weeks was 53% (n=9). Of 15 patients overall who experienced clinical benefit, 12 (80%) had received prior neratinib and/or lapatinib. Median progression-free

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