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Targeting of Vacuolar Membrane Localized Members of the TPK Channel Family

Molecular Plant 2008年第6期1卷 938-949页

作者： Marcel Dunkel Andreas Latz Karin Schumacher Thomas Muller dirk Becker Rainer Hedrich Molecular Plant Physiology and Biophysics Julius-von-Sachs-lnstitute University of W0rzburg Julius-von-Sachs-Platz 2 97082 Worzburg Germany Heidelberger Institut fur Pflanzenwissenschaften (HIP) University of Heidelberg Im Neuenheimer Feld 230 69120 Heidelberg Germany (K.S.) Present address: Physiological Ecology of Plants University ot T(3bingen Aut der Morgenstelle 1 72016 Tubingen Germany

Four members of the tandem-pore potassium channel family of Arabidopsis thaliana （TPK1, 2, 3, and 5） reside in the vacuolar membrane, whereas TPK4 is a plasma membrane K^＋-channel. By constructing chimeras between TPK1 and TPK4, we attempted to identify channel domains involved in the trafficking process and found that the TPK1 cytoplasmic C-terminal domain （CT） is critical for the ERas well as Golgi-sorting steps. Following site-directed mutagenesis, we identified a diacidic motif （DLE） required for ER-export of TPK1. However, this diacidic motif in the C-terminus is not conserved among other members of the TPK family, and TPK3 sorting is independent of its CT. Moreover, the 14-3-3 binding site of TPK1, essential for channel activation, is not involved in channel sorting.

关键词： Vacuolar Membrane TPK Channel Family Arabidopsis thaliana

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Pancreatic cancer–Palliative therapy: chemotherapy

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The Chinese-German Journal of Clinical Oncology 2007年第2期6卷 142-148页

作者： Anne Katrin Berger dirk Jger Medizinische Onkologie Nationales Centrum für Tumorerkrankungen Universittsklinik Heidelberg Im Neuenheimer Feld 350 69120 Heidelberg Germany

Single-agent Gemcitabine has been the standard treatment for advanced pancreatic adenocarcinoma in the past years. Due to the aggressive and often chemotherapy-refractory character of this malignancy, systemic treatment options still remain limited. Many combination therapies have been evaluated in clinical trials to improve survival over Gemcitabine alone, until recently without satisfying results. Based on the positive results of a recent randomized trial, the combination of Gemcitabine and Capecitabine might become a new standard as first-line treatment for advanced pancreatic cancer. The clinical advantage of Erlotinib as a novel targeted agent in combination with Gemcitabine seems to be only marginal. Due to the small number of studies, there is still no standard of care in second-line therapy, but Oxaliplatin seems to be an active treatment option in Gemcitabine refractory disease. This article will review the development of cytotoxic antitumoral treatment for advanced pancreatic adenocarcinoma (locally advanced, irresectable and/or metastatic disease) including monotherapies and newer approaches with combination therapies.

关键词：胰腺癌姑息疗法化疗腺癌吉西他宾

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