Ction, PKA (protein kinase A) pathway activation [1,3,4], and the stimulation of

Ction, PKA (protein kinase A) pathway activation [1,3,4], and the stimulation of PKC (protein kinase C) [3,5], PI3K (phosphatidylinositol 3-kinase [6], MAPKs (mitogen-activated protein kinases) [7?] and NF-kB [9]. The effects of VIP and PACAP are mainly mediated through VPAC1 and VPAC2 receptors [1,4], and they are involved in many physiological and pathophysiological processes, such as growth, cancer, immune responses, circadian rhythms, the control of neuronal andendocrine cells, and functions of the digestive, respiratory, reproductive and cardiovascular systems 11967625 [10]. In normal human tissues, VPAC1 receptors are preferentially expressed in most epithelial tissues, while VPAC2 receptors are mainly expressed in smooth muscle tissue [11]. However, VIPRs are highly overexpressed in human tumors and their metastases. Similar to their expression pattern in normal tissues, VPAC1 receptors are overexpressed in frequently occurring malignant epithelial neoplasms, such as cancers of the colon, rectum, lung, breast, and prostate. In contrast to the ubiquitous expression of VPAC1 receptors in most human tumors, VPAC2 receptors predominate in a small subset of tumors, including leiomyomas and gastrointestinal stromal tumors [11,12]. The difference in the cell surface profile between cancer cells and their normal counterparts can be utilized as a molecular signature for targeted imaging. Furthermore, the overexpressed VPAC1 receptors play a major role in the progression of a number of malignancies, including cancers of the lung, brain, gut, and prostate in addition to neuroblastomas [13,14], and they mediate tumor angiogenesis through theScreening of a VPAC1-Binding Peptidetransactivation of epidermal growth factor receptor (EGFR) and the expression of vascular endothelial growth factor (VEGF) [15,16]. Thus, these data indicate that the VPAC1 receptor is a potential target for tumor diagnosis and MedChemExpress 1485-00-3 therapy. The finding that most tumors predominantly express VPAC1 receptors at high levels has led to the development of in vivo imaging Methyl linolenate site methods for the localization of certain types of tumors by targeting the VPAC1 receptor with 1655472 radioactively labeled substances. Colorectal cancers (CRCs) are optimal tumors for targeting because of the relatively lower expression level of VPAC1 receptors in normal intestinal tract tissues compared with all other human tissues [11]. Thus, a higher tumor-to-background ratio can be obtained in CRCtargeted imaging and therapy. Therefore, the VPAC1 receptor is a potentially valuable target for the diagnosis and treatment of CRC, and the development of a specific molecular probe targeting the VPAC1 receptor would allow for early CRC detection and increased therapeutic efficacy. Currently, the conventional noninvasive imaging diagnostic methods for the detection of new CRC lesions or changes in the size of a known lesion caused by cancer growth are computed tomography (CT) and magnetic resonance imaging (MRI) [17]. Even endoscopic techniques, which are the most sensitive conventional diagnostic methods, are limited in their sensitivity because the detection of CRC is limited to lesions the examiner can visualize [18]. Despite the widespread use of these conventional imaging modalities, their accuracy and sensitivity for the detection of CRC as well as recurrence and metastasis are relatively low. In view of this, the development of new methods that can sensitively detect CRC at earlier stages could have an important clinical imp.Ction, PKA (protein kinase A) pathway activation [1,3,4], and the stimulation of PKC (protein kinase C) [3,5], PI3K (phosphatidylinositol 3-kinase [6], MAPKs (mitogen-activated protein kinases) [7?] and NF-kB [9]. The effects of VIP and PACAP are mainly mediated through VPAC1 and VPAC2 receptors [1,4], and they are involved in many physiological and pathophysiological processes, such as growth, cancer, immune responses, circadian rhythms, the control of neuronal andendocrine cells, and functions of the digestive, respiratory, reproductive and cardiovascular systems 11967625 [10]. In normal human tissues, VPAC1 receptors are preferentially expressed in most epithelial tissues, while VPAC2 receptors are mainly expressed in smooth muscle tissue [11]. However, VIPRs are highly overexpressed in human tumors and their metastases. Similar to their expression pattern in normal tissues, VPAC1 receptors are overexpressed in frequently occurring malignant epithelial neoplasms, such as cancers of the colon, rectum, lung, breast, and prostate. In contrast to the ubiquitous expression of VPAC1 receptors in most human tumors, VPAC2 receptors predominate in a small subset of tumors, including leiomyomas and gastrointestinal stromal tumors [11,12]. The difference in the cell surface profile between cancer cells and their normal counterparts can be utilized as a molecular signature for targeted imaging. Furthermore, the overexpressed VPAC1 receptors play a major role in the progression of a number of malignancies, including cancers of the lung, brain, gut, and prostate in addition to neuroblastomas [13,14], and they mediate tumor angiogenesis through theScreening of a VPAC1-Binding Peptidetransactivation of epidermal growth factor receptor (EGFR) and the expression of vascular endothelial growth factor (VEGF) [15,16]. Thus, these data indicate that the VPAC1 receptor is a potential target for tumor diagnosis and therapy. The finding that most tumors predominantly express VPAC1 receptors at high levels has led to the development of in vivo imaging methods for the localization of certain types of tumors by targeting the VPAC1 receptor with 1655472 radioactively labeled substances. Colorectal cancers (CRCs) are optimal tumors for targeting because of the relatively lower expression level of VPAC1 receptors in normal intestinal tract tissues compared with all other human tissues [11]. Thus, a higher tumor-to-background ratio can be obtained in CRCtargeted imaging and therapy. Therefore, the VPAC1 receptor is a potentially valuable target for the diagnosis and treatment of CRC, and the development of a specific molecular probe targeting the VPAC1 receptor would allow for early CRC detection and increased therapeutic efficacy. Currently, the conventional noninvasive imaging diagnostic methods for the detection of new CRC lesions or changes in the size of a known lesion caused by cancer growth are computed tomography (CT) and magnetic resonance imaging (MRI) [17]. Even endoscopic techniques, which are the most sensitive conventional diagnostic methods, are limited in their sensitivity because the detection of CRC is limited to lesions the examiner can visualize [18]. Despite the widespread use of these conventional imaging modalities, their accuracy and sensitivity for the detection of CRC as well as recurrence and metastasis are relatively low. In view of this, the development of new methods that can sensitively detect CRC at earlier stages could have an important clinical imp.