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Fulltext Annexin II Light Chain p11 Interacts With ENaC to Increase Functional Activity at the Membrane

Cheung TT, Ismail NAS, Moir R, Arora N, McDonald FJ, Condliffe SB

Front Physiol, 2019;10:7.
PMID: 30800070 DOI: 10.3389/fphys.2019.00007

The epithelial Na+ channel (ENaC) provides for Na+ absorption in various types of epithelia including the kidney, lung, and colon where ENaC is localized to the apical membrane to enable Na+ entry into the cell. The degree of Na+ entry via ENaC largely depends on the number of active channels localized to the cell membrane, and is tightly controlled by interactions with ubiquitin ligases, kinases, and G-proteins. While regulation of ENaC endocytosis has been well-studied, relatively little is understood of the proteins that govern ENaC exocytosis. We hypothesized that the annexin II light chain, p11, could participate in the transport of ENaC along the exocytic pathway. Our results demonstrate that all three ENaC channel subunits interacted with p11 in an in vitro binding assay. Furthermore, p11 was able to immunoprecipitate ENaC in epithelial cells. Quantitative mass spectrometry of affinity-purified ENaC-p11 complexes recovered several other trafficking proteins including HSP-90 and annexin A6. We also report that p11 exhibits a robust protein expression in cortical collecting duct epithelial cells. However, the expression of p11 in these cells was not influenced by either short-term or long-term exposure to aldosterone. To determine whether the p11 interaction affected ENaC function, we measured amiloride sensitive Na+ currents in Xenopus oocytes or mammalian epithelia co-expressing ENaC and p11 or a siRNA to p11. Results from these experiments showed that p11 significantly augmented ENaC current, whereas knockdown of p11 decreased current. Further, knockdown of p11 reduced ENaC cell surface population suggesting p11 promotes membrane insertion of ENaC. Overall, our findings reveal a novel protein interaction that controls the number of ENaC channels inserted at the membrane via the exocytic pathway.
Fulltext Efficacy of radiofrequency ablation compared with transarterial chemoembolization for the treatment of recurrent hepatocellular carcinoma: a comparative survival analysis

Koh PS, Chan AC, Cheung TT, Chok KS, Dai WC, Poon RT, et al.

HPB (Oxford), 2016 Jan;18(1):72-8.
PMID: 26776854 DOI: 10.1016/j.hpb.2015.07.005

This study aims to assess if radiofrequency ablation (RFA) has any oncological superiority over transarterial chemoembolization (TACE) on post-hepatectomy recurrence.
Efficacy of radiofrequency ablation compared with transarterial chemoembolization for the treatment of recurrent hepatocellular carcinoma: a comparative survival analysis

Koh PS, Chan AC, Cheung TT, Chok KS, Dai WC, Poon RT, et al.

HPB (Oxford), 2015 Oct 16.
PMID: 26473770 DOI: 10.1111/hpb.12495

BACKGROUND: This study aims to assess if radiofrequency ablation (RFA) has any oncological superiority over transarterial chemoembolization(TACE) on post-hepatectomy recurrence.
METHODS: From 2002 to 2011, 60.15% of 823 patients developed recurrence after hepatectomy for HCC. One hundred and two patients with recurrence underwent RFA (n = 42) or TACE (n = 60) for tumour size ≤5 cm and number of lesions ≤ 3 when tumours were not resectable or transplantable. Those with renal impairment, portal vein thrombosis and poor liver reserve were excluded. The primary outcome was overall survival, which was determined using log-rank test and Kaplan-Meier plots performed. Categorical data were analysed using the chi-square test and continuous variable were analysed using the Mann-Whitney U-test.
RESULTS: Demographics and primary tumour characteristics were similar in both groups (P > 0.05). Overall survival (OS) after an initial hepatectomy and salvage treatment for recurrence was similar (P > 0.05) in both groups with a 5-year OS after salvage treatment for RFA and TACE at 24.1% and 25.7%, respectively. For patients with the second recurrence after salvage treatment, an interchangeable treatment strategy of RFA and TACE conferred a better survival outcome than a stand-alone treatment with RFA or TACE (P < 0.05).
CONCLUSIONS: RFA and TACE may be equally effective for intrahepatic recurrence after hepatectomy when the tumour size is ≤ 5 cm and ≤ 3 lesions when re-resection or salvage transplantation is not considered feasible.
Fulltext The Asia Pacific Consensus Statement on Laparoscopic Liver Resection for Hepatocellular Carcinoma: A Report from the 7th Asia-Pacific Primary Liver Cancer Expert Meeting Held in Hong Kong

Cheung TT, Han HS, She WH, Chen KH, Chow PKH, Yoong BK, et al.

Liver Cancer, 2018 Mar;7(1):28-39.
PMID: 29662831 DOI: 10.1159/000481834

Background: Laparoscopic liver resection has been gaining momentum, and it has become an accepted practice after the two international consensus conferences where experts worked up guidelines to standardize this approach and improve its safety. However, most laparoscopic hepatectomies were performed in patients with liver metastases. The concurrent presence of liver cirrhosis with hepatocellular carcinoma (HCC) poses a great challenge to clinicians trying to establish a routine use of laparoscopic liver resection for HCC.
Summary: The first Asia Pacific consensus meeting on laparoscopic liver resection for HCC was held in July 2016 in Hong Kong. A group of expert liver surgeons with experience in both open and laparoscopic hepatectomy for HCC convened to formulate recommendations on the role and perspective of laparoscopic liver resection for primary liver cancer. The recommendations consolidate the most recent evidence pertaining to laparoscopic hepatectomy together with the latest thinking of practicing clinicians involved in laparoscopic hepatectomy, and give detailed guidance on how to deploy the treatment effectively for patients in need.
Key Message: The panel of experts gathered evidence and produced recommendations providing guidance on the safe practice of laparoscopic hepatectomy for patients with HCC and cirrhosis. The inherent advantage of the laparoscopic approach may result in less blood loss if the procedure is performed in experienced centers. The laparoscopic approach to minor hepatectomy, particularly left lateral sectionectomy, is a preferred practice for HCC at experienced centers. Laparoscopic major liver resection for HCC remains a technically challenging operation, and it should be carried out in centers of excellence. There is emerging evidence that laparoscopic liver resection produces a better oncological outcome for HCC when compared with radiofrequency ablation, particularly when the lesions are peripherally located. Augmented features in laparoscopic liver resection, including indocyanine green fluorescence, 3D laparoscopy, and robot, will become important tools of surgical treatment in the near future. A combination of all of these features will enhance the experience of the surgeons, which may translate into better surgical outcomes. This is the first consensus workforce on laparoscopic liver resection for HCC, which is a unique condition that occurs in the Asia Pacific region.