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To be able to correlate for each subline the expression of these biochemical parameters with the growth response to PKI, we quantified the relevant immunoblot bands by densitometry.We also noted that androgenindependent tumors showed increased activation of ERK when compared with tumors grown in intact male mice. This observation was confirmed by serial analysis of androgendependent LAPC xenografts at various times postcastration during the evolution to androgen independence. This data are consistent with results of immunohistochemical analyses of human prostate cancer specimens using phosphospecific antibodies to ERK. Open symbols represent xenograft clones grown in intact mice; closed symbols represent xenograft clones growing in castrated animals.It may also offer some guidance for the design of such studies.PKI AND HUMAN PROSTATE CANCER XENOGRAFTS. Click on Request Permissions which will take you to the Copyright Clearance Centers Downloaded from cancerres.aacrjournals.org on April. American Association for Cancer Research. Here, we show its utility as a serum biomarker for a wide range of human cancers, and we offer evidence favoring the SDMA potential application of antiDKK antibodies for cancer treatment.Using an original ELISA system, high levels of DKK protein were found in serologic samples from patients with cancers of the pancreas, stomach, liver, bile duct, breast, and cervix, which also showed elevated expression levels of DKK.Additionally, antiDKK antibody inhibited the invasive activity and the growth of cancer cells in vitro and suppressed the growth of engrafted tumors in vivo.Tumor tissues treated with antiDKK displayed significant fibrotic changes and a decrease in viable cancer cells without apparent toxicity in mice.Our findings suggest DKK as a serum biomarker for screening against a variety of cancers, and antiDKK antibodies as potential theranostic tools for diagnosis and treatment of cancer.At present, two main approaches are available in clinical practice: therapeutic monoclonal antibodies. The results were promising when compared with responses of advanced cancers to conventionalcytotoxic agents, but the proportion of patients showing good response is still SDMA limited, and in some cases, the medication caused serious adverse effects including lifethreatening ones.Hence, the development of new therapeutic antibodies targeting transmembrane andor secreted prote ins, wh ich show a cancerspecific expression pattern and have an oncogenic function, is eagerly awaited.The evidence further prompted us to focus on DKK as a potential target for therapeutic antibodies as well as a serum biomarker for a wide range of human cancers.This mechanism of DKK action is important in limb and head development. Serum concentrations of DKK protein were reported to be increased in patients with multiple myeloma or osteosarcoma. In spite of recent accumulating reports that indicate the oncogenic potential of DKK activation and its usefulness as a cancer biomarker, there was no report indicating the direct antitumor effect of antiDKK antibodies.We here show evidence suggesting DKK as a diagnostic biomarker for a wide variety of cancers and results implicating the therapeutic potential of antiDKK antibody to neutralize the activity of DKK function for cancer cell invasion and growth.These serum samples from a total of cancer patients were selected for the study on the basis of the following criteria: their tumors were pathologically diagnosed as cancers.

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