CAXII Is a Sero-Diagnostic Marker for Lung Cancer

To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using pulmonary adenocarcinoma (AD)-derived A549 cells as antigens by employing the random immunization method. Hybridoma supernatants were immunohistochemically screened for antibodies with AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice through limiting dilutions. From the obtained monoclonal antibodies, we selected an antibody designated as KU-Lu-5 which showed intense membrane staining of A549 cells. Based on immunoprecipitation and MADLI TOF/TOF-MS analysis, this antibody was recognized as carbonic anhydrase XII (CAXII). To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed dot blot analysis with a training set consisting of sera from 70 lung cancer patients and 30 healthy controls. The CAXII expression levels were significantly higher in lung cancer patients than in healthy controls in the training set (P<0.0001), and the area under the curve of ROC was 0.794, with 70.0% specificity and 82.9% sensitivity. In lung cancers, expression levels of CAXII were significantly higher in patients with squamous cell carcinoma (SCC) than with AD (P = 0.035). Furthermore, CAXII was significantly higher in well- and moderately differentiated SCCs than in poorly differentiated ones (P = 0.027). To further confirm the utility of serum CAXII levels as a sero-diagnostic marker, an additional set consisting of sera from 26 lung cancer patients and 30 healthy controls was also investigated by dot blot analysis as a validation study. Serum CAXII levels were also significantly higher in lung cancer patients than in healthy controls in the validation set (P = 0.030). Thus, the serum CAXII levels should be applicable markers discriminating lung cancer patients from healthy controls. To our knowledge, this is the first report providing evidence that CAXII may be a novel sero-diagnostic marker for lung cancer

The Japanese Clinical Practice Guideline for acute kidney injury 2016

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search

Clinical characteristics of psoriasis patients.

<p>Clinical characteristics of psoriasis patients.</p

Detection of Autoantibodies by 2D-immunoblotting.

<p>(<b>A</b>) The 2-DE protein pattern after CBB staining. Immunoblot analysis with mixed sera from patients with psoriasis vulgaris (<b>B</b>) and psoriatic arthritis (<b>C</b>) as primary antibodies, respectively. Several proteins were positively detected as autoantigens in each disease.</p

Serum moesin (A and B), K17 (C and D), and STIP1 (E, F and G) levels in patients with psoriasis vulgaris, psoriatic arthritis, and healthy controls.

<p>(A) Serum moesin levels were significantly higher in psoriasis vulgaris and psoriatic arthritis patients compared to healthy controls (*: <i>P</i><0.05 and §: <i>P</i><0.001, respectively). (B) Receiver-operating characteristic curve (ROC) analysis of moesin as a serum marker for psoriasis vulgaris or psoriatic arthritis. The corresponding area under the curve (AUC) was 0.747 for psoriasis vulgaris. With a 76.9% specificity, the sensitivity of moesin for psoriasis vulgaris was 71.0% at a cut-off value corresponding to 146.6. (C) Serum K17 levels were significantly higher in psoriatic arthritis than in healthy controls and psoriasis vulgaris (*: <i>P</i><0.05, $: <i>P</i><0.01). (D) ROC analysis of K17 as a serum marker for psoriatic arthritis. AUC was 0.72 for psoriatic arthritis. With a 80.6% specificity, the sensitivity of K17 for psoriatic arthritis was 66.7% at a cut-off value corresponding to 439.5. (E) Serum STIP1 levels were significantly higher in psoriasis vulgaris and psoriatic arthritis compared to healthy controls (<i>P</i><0.005 each). Serum STIP1 levels were also significantly higher in psoriatic arthritis compared to healthy controls or psoriasis vulgaris (*: <i>P</i><0.05, **: <i>P</i><0.005, #: <i>P</i><0.005). (F) ROC analysis of STIP1 as a serum marker for psoriatic vulgaris. AUC was 0.79 for psoriatic vulgaris. With a 69.2% pecificity, the sensitivity of Stip-1 for psoriatic arthritis was 80.7% at a cut-off value corresponding to 105.8. (G) ROC of STIP1 as a serum marker for psoriatic arthritis. AUC was 0.70 for psoriatic arthritis. With a 42.9% specificity, the sensitivity of STIP1 for psoriatic arthritis was 66.7% at a cut-off value corresponding to 195.4.</p

Autoantigens identified using sera from psoriatic arthritis patients<b>.</b>

<p>Autoantigens identified using sera from psoriatic arthritis patients<b>.</b></p

Clinicopathological characteristics of the patients.

a<p>Adenocarcinoma.</p>b<p>Squamous cell carcinoma.</p>c<p>Small cell lung carcinoma.</p>d<p>Large cell neuroendocrine carcinoma.</p

Expression of CAXII antibody in lung cancer cell lines and tissues.

<p>(A) Immunoblot analysis of CAXII in lung cancer cell lines. CAXII was detected as an approximately 40-kDa protein with A549 cells. (B) Immunostaining of CAXII in A549 cells (a), adenocarcinoma (b), and squamous cell carcinoma (c) of the lung, and each showed membranous staining of CAXII.</p