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Lin, S. H.

Publications and source records attributed to Lin, S. H..

2 recordsLinked to original sources

Cell lines of the same anatomic site and histologic type show large variability in intrinsic radiosensitivity and relative biological effectiveness to protons and carbon ions

PurposeTo show that radiation response across cancer cell lines of the same anatomic site and histologic type varies remarkably for protons and carbon (C) ions. Materials and MethodsWe measured and obtained from the literature clonogenic survival of human cancer cell lines of the lung (n=18), brain (n=10) and pancreas (n=10) exposed to photons, protons, and C-ions to assess their variability in response. We also treated cancer cell lines with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability in response. We quantified the variability in response by calculating the relative range (range/mean) and the coefficient of variation (COV) of the dose at 10% survival fraction (D10%) and relative biological effectiveness (RBE10%). ResultsThe relative range of D10% for lung cancer cell lines varied from 55-92% for photons, protons, and C-ions, with the relative range in RBE varying from 16-45% for protons and C-ions. For brain and pancreatic cancer cell lines, the relative range of D10% varied from 95-112%, and 39-75%, respectively, with the relative range in RBE varying from 27-33% and 25-50%, respectively. However, the COVs in D10% were approximately equal across radiation qualities, varying from 0.24{+/-}0.07-0.35{+/-}0.10, 0.35{+/-}0.09-0.69{+/-}0.62 and 0.13{+/-}0.03- 0.21{+/-}0.04 for lung, brain and pancreatic cancer cell lines, respectively. Greater relative ranges in D10% were observed in the cell lines with inhibited DNA repair, varying from 108%-157% for photons, protons, and C-ions, with relative ranges in RBE varying from 29-67%. The COVs in the D10% were also greater for the cell lines treated with inhibitors of DNA repair, varying from 0.34{+/-}0.09-0.41{+/-}0.06. ConclusionCell lines of the same anatomic site and histologic type have a remarkable variability in response, not only to photons but also to protons and C-ions. We attributed this variability to differences in DNA repair capacity. CategoryBiological Physics and Response Prediction

biophysics

Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons.

GABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuronal markers such as Pvalb. Here, we show that Lhx6 is necessary for the survival of hypothalamic neurons. Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.

neuroscience