Minimally invasive treatment of colorectal liver metastases.

Minimally invasive approaches are increasingly used in the treatment of colorectal liver metastases (CRLMs) and for increasingly complex cases. Herein, we review the spectrum of modalities used in the minimally invasive treatment of CRLM, focusing on one of the newest approaches, robotic liver resection, and on local regional therapies, both operative and percutaneous. Oncologic outcomes after minimally invasive therapies are also evaluated. Although there are no randomized trials comparing minimally invasive liver resection to open resection, an increasing quantity of nonrandomized data suggest favorable outcomes with a minimally invasive approach. The future of minimally invasive treatment of CRLM will likely include specifying training and credentialing criteria as well as an enlarging role for the combined surgical treatment of CRLM and extrahepatic colorectal metastases.

Anion, cation, and zwitterion selectivity of phospholemman channel molecules.

Phospholemman (PLM), a 72-amino acid membrane protein with a single transmembrane domain, forms taurine-selective ion channels in lipid bilayers. Because taurine forms zwitterions, a taurine-selective channel might have binding sites for both anions and cations. Here we show that PLM channels indeed allow fluxes of both cations and anions, making instantaneous and voltage-dependent transitions among conformations with drastically different ion selectivity characteristics. This surprising and novel ion channel behavior offers a molecular explanation for selective taurine flux across cell membranes and may explain why molecules in the phospholemman family can induce cation- or anion-selective conductances when expressed in Xenopus oocytes.

Unitary anion currents through phospholemman channel molecules.

Phospholemman (PLM) is a 72-amino-acid peptide with a single transmembrane domain, the expression of which induces chloride currents in Xenopus oocytes. It has remained unknown whether PLM is an ion channel or acts as a channel regulator. Here we show, by measuring unitary anion currents across planar phospholipid bilayers to which immunoaffinity-purified recombinant PLM was added, that it does indeed form ion channels. Excised patches of oocytes expressing PLM had similar currents. Of the ions tested, the sulphonic amino acid taurine was the most permeant, and expression of PLM increased fluxes of radiolabelled taurine in oocytes. Phospholemman is the smallest protein in cell membranes known to form an ion channel and the taurine selectivity suggests that it is involved in cell volume regulation.

Mat-8, a novel phospholemman-like protein expressed in human breast tumors, induces a chloride conductance in Xenopus oocytes.

We recently identified a novel 8-kDa transmembrane protein, Mat-8, that is expressed in a subset of murine breast tumors. We have now cloned a cDNA encoding the human version of Mat-8 and show that it is expressed both in primary human breast tumors and in human breast tumor cell lines. The extracellular and transmembrane domains of Mat-8 are homologous to those of phospholemman (PLM), the major plasmalemmal substrate for cAMP-dependent protein kinase and protein kinase C in several different tissues. PLM, which induces chloride currents when expressed in Xenopus oocytes, contains consensus phosphorylation sites for both cAMP-dependent protein kinase A and protein kinase C in its cytoplasmic domain. In contrast, the cytoplasmic domain of Mat-8 contains no such consensus phosphorylation sites and is, in fact, unrelated to the cytoplasmic domain of PLM. RNA blot analysis reveals that Mat-8 and PLM exhibit distinct tissue-specific patterns of expression. We show that expression of Mat-8 in Xenopus oocytes induces hyperpolarization-activated chloride currents similar to those induced by PLM expression. These findings suggest that Mat-8 and PLM, the products of distinct genes, are related proteins that serve as Cl- channels or Cl- channel regulators but have different roles in cell and organ physiology.

Hyperpolarization-activated chloride currents in Xenopus oocytes.

During hyperpolarizing pulses, defolliculated Xenopus oocytes have time- and voltage-dependent inward chloride currents. The currents vary greatly in amplitude from batch to batch; activate slowly and, in general, do not decay; have a selectivity sequence of I- > NO3- > Br- > Cl- > propionate > acetate; are insensitive to Ca2+ and pH; are blocked by Ba2+ and some chloride channel blockers; and have a gating valence of approximately 1.3 charges. In contrast to hyperpolarization-activated chloride currents induced after expression of phospholemman (Palmer, C. J., B. T. Scott, and L. R. Jones. 1991. Journal of Biological Chemistry. 266:11126; Moorman, J. R., C. J. Palmer, J. E. John, J. E. Durieux, and L. R. Jones. 1992. 267:14551), these endogenous currents are smaller; have a different pharmacologic profile; have a lower threshold for activation and lower voltage-sensitivity of activation; have different activation kinetics; and are insensitive to pH. Nonetheless, the endogenous and expressed current share striking similarities. Recordings of macroscopic oocyte currents may be inadequate to determine whether phospholemman is itself an ion channel and not a channel-modulating molecule.