The epidermal growth factor receptor directed antibody, cetuximab, is an effective clinical therapy for patients with colorectal, head and neck and non-small cell lung cancer patients particularly for those with KRAS and BRAF wild type cancers. Treatment in all patients is limited eventually by the development of acquired resistance but little is known about the underlying mechanism. Here we show, that activation of ERBB2 signaling, either through ERBB2 amplification or through heregulin upregulation, leads to persistent ERK 1/2 signaling and consequently cetuximab resistance. Inhibition of ERBB2 or disruption of ERBB2/ERBB3 heterodimerization restores cetuximab sensitivity in vitro and in vivo. A subset of colorectal cancer patients that exhibit either de novo or acquired resistance to cetuximab based therapy possess ERBB2 amplification or high levels of circulating heregulin. Collectively, these findings identify two distinct resistance mechanisms, both of which promote aberrant ERBB2 signaling, that mediate cetuximab resistance. Moreover, these results suggest that ERBB2 inhibitors, in combination with cetuximanb, represent a rational therapeutic strategy that should be assessed in cetuximab-resistant cancers.

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The objective of this study was to investigate if antibody to cyclic citrullinated peptide (anti-CCP) is detected in sera of patients with chronic hepatitis B virus (HBV) infection. Serum anti-CCP and IgA, IgG, and IgM rheumatoid factor (RF) isotypes were measured by enzyme-linked immunosorbent assay on 176 non-arthritic patients with HBV infection. IgA RF, IgG RF, and IgM RF were detectable in 29.5, 21, and 18.8% of the tested sera, respectively, with a total seropositivity rate of 42.7%. Marginally elevated anti-CCP was detected in one patient (0.6%). By regression analysis, there was no statistically significant association between the serum levels of anti-CCP and serum IgA, IgG, or IgM RF (R (2) = 0.033, with respective p values of 0.224, 0.297, and 0.334). In conclusion, anti-CCP was rarely detected in non-arthritic patients with HBV infection in contrast to RF. Thus, testing for anti-CCP may be a useful tool for the diagnosis of rheumatoid arthritis in this population.

The Allplex Respiratory Panel 1/2/3 (All16) is a multiplex PCR assay for detecting 16 respiratory viruses with influenza A virus (FluA) subtyping, and the first clinical assay based on multiple detection temperatures. We compared the results between All16 and Anyplex II RV16 (Any16) in 426 clinical samples. Samples showing discrepancies between the two tests were further tested using monoplex PCR. FluA subtyping based on the hemagglutinin type results of All16, which yielded H1, H3, and non-H1/H3, was compared with the results of the BioFire FilmArray respiratory panel. The positive and negative percent agreements and kappa value for each virus between All16 and Any16 ranged from 54.5-100.0%, 84.7-100.0%, and 0.57-1.00, respectively. FluA subtype results from All16 for 26 samples were consistent with those from FilmArray. Good agreement was observed between the two methods, except when analyzing human enterovirus (kappa value 0.70), and the All16 showed reliable FluA subtyping results. For parainfluenza virus 3, the All16 was more sensitive than Any16. When testing 28 samples simultaneously, the mean test time and hands-on time were 4.3 and 0.5 hours, respectively in All16. In conclusion, All16 showed reliable performance, but further studies are needed regarding human enterovirus analysis.

1Background : Immature platelet fraction (IPF) is the percentage of reticulated platelet (RP) of total platelet count. We measured an IPF reference range using XE-2100 blood cell counter with upgraded software (Sysmex, Japan) and evaluated the clinical utility of this parameter for the laboratory diagnosis of thrombocytopenia due to an increase in peripheral platelet destruction.Methods : Peripheral blood samples collected into K2EDTA (Beckton Dickinson, USA) were analyzed at Chonbuk National University Hospital. One hundred forty-two samples from apparently healthy adults (all routine full blood count parameters including platelets within the healthy reference range) were used to establish a normal reference range for IPF. The patients were classified into 3 groups including hypoplastic (consisted of 22 patients undergoing chemotherapy with falling platelet counts and 14 with aplastic anemia), cirrhotic (40 with cirrhosis of liver), and idiopathic thrombocytopenic purpura (ITP) (14 with ITP) groups.Results : An IPF reference range in healthy individuals was established as 0.4-5.4%, with a mean of 1.7%. A significant increase in IPF values was found in the ITP patient group. The cut-off value of IPF was 6.1% and its sensitivity and specificity were 92.9%, and 82.9% respectively. Reproducibility was good.Conclusions : A rapid, inexpensive automated method for measuring IPF is feasible and should become a standard parameter in evaluating thrombocytopenic patients. (Korean J Lab Med 2007;27:1-6)