Wilson's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Wilson's Disease, including details on treatment, causes, symptoms, medication.

The dual EGFR/HER-2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38.

Labonte MJ, Manegold PC, Wilson PM, Fazzone W, Louie SG, Lenz HJ, Ladner RD

The Departments of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089.

Members of the human epidermal receptor (HER) family are frequently associated with aggressive disease and poor prognosis in multiple malignancies. Lapatinib is a dual tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR) and HER-2. This study evaluated the therapeutic potential of lapatinib, alone and in combination with SN-38, the active metabolite of irinotecan (CPT-11), in colon and gastric cancer cell lines. Concentration-dependent antiproliferative effects of both lapatinib and SN-38 were observed in all colon and gastric cancer cell lines tested but varied significantly between individual cell lines (lapatinib range, 0.08 - 11.7 muM; SN-38 range, 3.6 - 256 nM). Lapatinib potently inhibited the growth of a HER-2 overexpressing gastric cancer cell line and demonstrated moderate activity in gastric and colon cancer cells with detectable HER-2 expression. The combination of lapatinib and SN-38 interacted synergistically to inhibit cell proliferation in all colon and gastric cancer cell lines tested. Co-treatment with lapatinib and SN-38 also resulted in enhanced cell cycle arrest and the induction of apoptosis with subsequent cellular pharmacokinetic analysis demonstrating that lapatinib promoted the increased intracellular accumulation and retention of SN-38 when compared to SN-38 treatment alone. Finally, the combination of lapatinib and CPT-11 demonstrated synergistic anti-tumor efficacy in the LoVo colon cancer mouse xenograft model with no apparent increase in toxicity compared to CPT-11 monotherapy. These results provide compelling preclinical rationale indicating lapatinib to be a potentially efficacious chemotherapeutic combination partner for irinotecan in the treatment of gastrointestinal carcinomas. (c) 2009 UICC.

Published 18 June 2009 in Int J Cancer.
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Articles on Wilson's Disease published 18 June 2009:

Screening: why, when, and how.   Kidney Int.

Screening refers to the early detection of individuals with unrecognized disease or with early stages of disease among a population. Early detection allows early medical intervention, which may ultimately slow progression of the disease and reduce both morbidity and mortality. As such, screening is an important tool in improving public health. In 1968, Wilson and Jungner proposed 10 criteria to consider prior to starting screening for a disease. This review discusses these criteria when applied ... [Abstract] [Full-text]

Articles on Wilson's Disease published 17 June 2009:

Autophagy: from basic science to clinical application.   Mucosal Immunol, 2(4): 315-30.

Autophagy is a cellular pathway involved in protein and organelle degradation, which is likely to represent an innate adaptation to starvation. In times of nutrient deficiency, the cell can self-digest and recycle some nonessential components through nonselective autophagy, thus sustaining minimal growth requirements until a food source becomes available. Over recent years, autophagy has been implicated in an increasing number of clinical scenarios, notably infectious diseases, cancer, ... [Abstract] [Full-text]

Articles on Wilson's Disease published 16 June 2009:

Special stain and X-ray probe microanalysis of livers with Wilson disease.   Hepatol Res, 39(6): 563-8.

Aim: Primary copper toxicosis due to Wilson disease is clinically complex, often leading to delayed diagnosis. Because the metabolic disorder is frequently complicated by iron overload due to hypoceruloplasminemia, either a special stain or microanalysis has been recommended for liver biopsy specimens. Methods: Liver biopsy was performed in three patients in whom Wilson disease was highly suspected. Light microscopic study included rubeanic acid stain for copper and Berlin blue stain for iron. ... [Abstract] [Full-text]

The mRNA-destabilizing protein tristetraprolin is suppressed in many cancers, altering tumorigenic phenotypes and patient prognosis.   Cancer Res, 69(12): 5168-76.

AU-rich element-binding proteins (ARE-BP) regulate the stability and/or translational efficiency of mRNAs containing cognate binding sites. Many targeted transcripts encode factors that control processes such as cell division, apoptosis, and angiogenesis, suggesting that dysregulated ARE-BP expression could dramatically influence oncogenic phenotypes. Using several approaches, we evaluated the expression of four well-characterized ARE-BPs across a variety of human neoplastic syndromes. AUF1, ... [Abstract] [Full-text]

Donepezil delays progression to AD in MCI subjects with depressive symptoms.   Neurology, 72(24): 2115-21.

OBJECTIVE: To determine whether the presence of depression predicts higher rate of progression to Alzheimer disease (AD) in patients with amnestic mild cognitive impairment (aMCI) and whether donepezil treatment beneficially affect this relationship. METHODS: The study sample was composed of 756 participants with aMCI from the 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study drug trial of donepezil and vitamin E. Beck Depression Inventory (BDI) was used to assess ... [Abstract] [Full-text]

Primary cutaneous T-cell lymphoma localized to the lower leg: a distinct, locally aggressive cutaneous T-cell lymphoma.   Arch Dermatol, 145(6): 677-82.

BACKGROUND: Distinct categories of skin lymphoma with preferential site localization and unique clinical behavior, including leg-type primary cutaneous diffuse large B-cell lymphoma, have recently been described. Although these entities are rare, they exhibit reproducible clinicopathologic features, and their recognition may allow more appropriate treatment protocols. OBSERVATIONS: We describe the distinctive clinicopathologic features that were observed in 3 patients with an unusual variant of ... [Abstract] [Full-text]

Detecting sarcasm from paralinguistic cues: Anatomic and cognitive correlates in neurodegenerative disease.   Neuroimage.

While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic ... [Abstract] [Full-text]

Articles on Wilson's Disease published 15 June 2009:

Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis.   Clin Exp Allergy, 39(6): 820-8.

BACKGROUND: Leukotrienes (LTs) and prostanoids are potent pro-inflammatory and vasoactive lipid mediators implicated in airway disease, but their cellular sources in the nasal airway in naturally occurring allergic rhinitis (AR) are unclear. OBJECTIVE: To quantify cellular expression of enzymes of the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways by immunohistochemistry in nasal biopsies from patients with symptomatic perennial AR (PAR, n = 13) and seasonal AR (SAR, n = 14) and from ... [Abstract] [Full-text]

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