ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells.

Background: Current strategies in circulating tumor cell (CTC) isolation in pancreatic cancer heavily rely on the EpCAM and cytokeratin cell status. EpCAM is generally not considered a good marker given its transitory change during Epithelial to Mesenchymal Transition (EMT) or reverse EMT. There is a need to identify other surface markers to capture the complete repertoire of PDAC CTCs. The primary objective of the study is to characterize alternate surface biomarkers to EpCAM on CTCs that express low or negligible levels of surface EpCAM in pancreatic cancer patients. Methods: Flow cytometry and surface mass spectrometry were used to identify proteins expressed on the surface of PDAC CTCs in culture. CTCs were grown under conditions of attachment and in co-culture with naïve neutrophils. Putative biomarkers were then validated in GEMMs and patient samples. Results: Surface proteomic profiling of CTCs identified several novel protein biomarkers. ALCAM was identified as a novel robust marker in GEMM models and in patient samples. Conclusions: We identified several novel surface biomarkers on CTCs expressed under differing conditions of culture. ALCAM was validated and identified as a novel alternate surface marker on EpCAMlow CTCs.

Identification of novel early pancreatic cancer biomarkers KIF5B and SFRP2 from "first contact" interactions in the tumor microenvironment.

BACKGROUND: Pancreatic cancer is one of the most difficult cancers to detect early and most patients die from complications arising due to distant organ metastases. The lack of bona fide early biomarkers is one of the primary reasons for late diagnosis of pancreatic cancer. It is a multifactorial disease and warrants a novel approach to identify early biomarkers. METHODS: In order to characterize the proteome, Extracellular vesicles (EVs) isolated from different in vitro conditions mimicking tumor-microenvironment interactions between pancreatic cancer epithelial and stromal cells were analyzed using high throughput mass spectrometry. The biological activity of the secreted EVome was analyzed by investigating changes in distant organ metastases and associated early changes in the microbiome. Candidate biomarkers (KIF5B, SFRP2, LOXL2, and MMP3) were selected and validated on a mouse-human hybrid Tissue Microarray (TMA) that was specifically generated for this study. Additionally, a human TMA was used to analyze the expression of KIF5B and SFRP2 in progressive stages of pancreatic cancer. RESULTS: The EVome of co-cultured epithelial and stromal cells is different from individual cells with distinct protein compositions. EVs secreted from stromal and cancer cells cultures could not induce significant changes in Pre-Metastatic Niche (PMN) modulation, which was assessed by changes in the distant organ metastases. However, they did induce significant changes in the early microbiome, as indicated by differences in α and ß-diversities. KIF5B and SFRP2 show promise for early detection and investigation in progressive pancreatic cancer. These markers are expressed in all stages of pancreatic cancer such as low grade PanINs, advanced cancer, and in liver and soft tissue metastases. CONCLUSIONS: Proteomic characterization of EVs derived from mimicking conditions of epithelial and stromal cells in the tumor-microenvironment resulted in the identification of several proteins, some for the first time in EVs. These secreted EVs cannot induce changes in distant organ metastases in in vivo models of EV education, but modulate changes in the early murine microbiome. Among all the proteins that were analyzed (MMP3, KIF5B, SFRP2, and LOXL2), KIF5B and SFRP2 show promise as bona fide early pancreatic cancer biomarkers expressed in progressive stages of pancreatic cancer.

Modulation of Early Neutrophil Granulation: The Circulating Tumor Cell-Extravesicular Connection in Pancreatic Ductal Adenocarcinoma.

Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tumor cells, CTCs) either alone or as tumor microemboli (clusters); the latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell-cell junction proteins and/or cytokine receptor pairs with other cells such as neutrophils, platelets, fibroblasts, etc. In the present study, we provide evidence for an extravesicular (EV) mode of communication between pancreatic cancer CTCs and neutrophils. Our results suggest that the EV proteome of CTCs contain signaling proteins that can modulate degranulation and granule mobilization in neutrophils and, also, contain tissue plasminogen activator and other proteins that can regulate cluster formation. By exposing naïve neutrophils to EVs isolated from CTCs, we further show how these changes are modulated in a dynamic fashion indicating evidence for a deeper EV based remodulatory effect on companion cells in clusters.

Willingness and appropriateness of peers participating in emerging adults' substance misuse treatment.

This study investigates the feasibility of adapting empirically-supported family treatments for emerging adult peer dyads. Data were collected (n=84) from emerging adults and their peers. Peers completed measures of substance use, willingness to participate in their friends' treatments, and an adapted version of the Significant Other Behavior Questionnaire (SBQ), which measures concerned significant others' (CSO) responses to another's use such a punishing, supporting, or withdrawing from the user. Peers were more likely to support sobriety or enable use, versus punishing use or withdrawing from their friends. Overall, peers were quite willing to assist in treatment, but heavily using peers were less enthusiastic. For some emerging adults, their current peers may represent untapped resources to integrate into treatment, and providing peer-enhanced treatments may expand the reach of services to non-treatment seeking populations.

Caring for a parent with lung cancer: caregivers' perspectives on the role of communication.

We investigated communication and care in the context of lung cancer through qualitative interviews with 35 adult children. Participants described two core influences on communication: situational and relational influences. Participants also suggested that the ways in which support was communicated impacted how they managed challenges and how they were able to cope with the loss of their parent. This research adds to the literature on caregiving and communicating social support by exploring the experiences of families coping with lung cancer. We suggest theoretical and practical implications for the ways family members might communicate about illness.

Sources of uncertainty in type 2 diabetes: explication and implications for health communication theory and clinical practice.

According to the American Diabetes Association, nearly 24 million Americans live with type 2 diabetes, and clinical data project that this figure will increase 165% from 2000 to 2050. Thus, there is a pressing need to understand not only the physiological and medical needs, but also the psychological demands associated with the illness. Even though uncertainty has been explicated in various other illness contexts and potentially shapes the experience of type 2 diabetes, very little attention has been paid to the nature of uncertainty in this context. The present study examines the nature of uncertainty through qualitative interviews with 49 individuals diagnosed with type 2 diabetes. Using grounded theory methods, various themes emerged relative to the sources of uncertainty. These themes are discussed in light of their potential extension of health communication theory and application to intervention and educational programs for individuals living with type 2 diabetes.