A.M. Chen

Astrocytes Attenuate Mitochondrial Dysfunctions in Human Dopaminergic Neurons Derived from iPSC

Summary Astrocytes, the most populous glial cell type in the brain, are critical for regulating the brain microenvironment. In various neurodegenerative diseases, astrocytes determine the progression and outcome of the neuropathological process. We have recently revealed the direct involvement of mitochondrial function in human pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neuronal differentiation. Using the astroglial-neuronal co-culture system, we show here that astrocytes effectively rescue defects in neurogenesis of DA neurons with mitochondrial respiratory chain disruption. Co-culture of astrocytes with defective DA neurons completely restored mitochondrial functions and dynamics insulted by mitochondrial toxins. These results suggest the significance of astroglia in maintaining mitochondrial development and bioenergetics during differentiation of hiPSC-derived DA neurons. Our study also provides an active astroglial-neuronal interaction model for future investigation of mitochondrial involvement in neurogenesis and neurodegenerative diseases.

Brachial plexopathy after stereotactic body radiation therapy for apical lung cancer: Dosimetric analysis and preliminary clinical outcomes

Purpose The treatment of apical lung tumors with stereotactic body radiation therapy (SBRT) is challenging due to the proximity of the brachial plexus and the concern for nerve damage. Methods and materials Between June 2009 and February 2017, a total of 75 consecutive patients underwent SBRT for T1-T3N0 non-small cell lung cancer involving the upper lobe of the lung. All patients were treated with 4-dimensional computed tomography (CT)-based image guided SBRT to a dose of 40 to 60 Gy in 3 to 5 fractions. For dosimetric analysis, only apical tumors as defined by the location of the tumor epicenter superior to the aortic arch were included. The anatomical brachial plexus was delineated using the Radiation Therapy Oncology Group atlas. Results Thirty-one patients with 31 apical lung tumors satisfied the anatomical criteria for inclusion. The median age was 73 years (range, 58-89). The median planning target volume was 26.5 cc (range, 8.2-81.4 cc). The median brachial plexus, brachial plexus maximum dose (Dmax), Dmax per fraction, V22 (cc, 3-4 fractions), V30 (cc, 5 fractions), and biologically effective dose 3 Gy were 15.8 Gy (range, 1.7-66.5 Gy), 3.4 Gy (range, 0.6-14.7 Gy), 0.0 cc (range, 0-0.9 cc), 0.06 cc (range, 0-2.5 cc), and 31.5 Gy (range, 3.3-133.1 Gy), respectively. At a median follow-up of 17 months, the observed incidence of brachial plexopathy was 0%. Conclusions There is significant variation in dose to the brachial plexus for patients treated with SBRT for apical lung tumors. Although the incidence of neuropathic symptoms in this series was zero, further attention should be focused on the clinical implications of these findings.

Re-Irradiation Therapy for Locally Recurrent Head and Neck Cancer: A National Survey of Practice Patterns

ABSTRACT Using a customized survey consisting of two de-identified clinical scenarios with a total of 86 questions, we showed that substantial variability exists regarding recommendations for therapy of recurrent head and neck cancer. For inoperable gross recurrence arising in a previously irradiated field, recommendations were re-irradiation with curative intent (73%), re-irradiation with palliative intent (4%), chemotherapy alone (5%), and referral to tertiary center (18%). After salvage surgery, only 33% recommended adjuvant re-irradiation, with the remainder preferring observation (46%), chemotherapy alone (10%), and referral to tertiary center (11%). Significant differences were observed with respect to dose, fractionation, technique, and systemic therapy recommendations.