Context Lung cancer is one of the most common cancers affecting both men and women and is associated with high symptom burden and psychological distress. Lung cancer patients’ family caregivers also show high rates of distress. However, few interventions have been tested to alleviate significant problems of this population. Objectives This study examined the preliminary efficacy of telephone-based symptom management (TSM) for symptomatic lung cancer patients and their family caregivers. Methods Symptomatic lung cancer patients and caregivers (N=106 dyads) were randomly assigned to 4 sessions of TSM consisting of cognitive-behavioral and emotion-focused therapy or an education/support condition. Patients completed measures of physical and psychological symptoms, self-efficacy for managing symptoms, and perceived social constraints from the caregiver; caregivers completed measures of psychological symptoms, self-efficacy for helping the patient manage symptoms and managing their own emotions, perceived social constraints from the patient, and caregiving burden. Results No significant group differences were found for all patient outcomes and caregiver self-efficacy for helping the patient manage symptoms and caregiving burden at 2 and 6-weeks post-intervention. Small effects in favor of TSM were found regarding caregiver self-efficacy for managing their own emotions and perceived social constraints from the patient. Study outcomes did not significantly change over time in either group. Conclusion Findings suggest that our brief telephone-based psychosocial intervention is not efficacious for symptomatic lung cancer patients and their family caregivers. Next steps include examining specific intervention components in relation to study outcomes, mechanisms of change, and differing intervention doses and modalities.
Tissue transglutaminase (TG2) is a multifunctional protein that binds to fibronectin and exerts protein transamidating activity in the presence of Ca(2+). We previously reported that TG2 is upregulated in ovarian tumors and enhances intraperitoneal (i.p.) metastasis. TG2 is secreted abundantly in ovarian cancer (OC) ascites as an active enzyme, yet its function in the extracellular compartment remains unknown. To study the distinct functions of secreted TG2, we used recombinant His6-tagged TG2 and catalytically inactive enzyme in vitro and in vivo. By using i.p. and orthotopic ovarian xenografts, we show that extracellular transglutaminase promoted OC peritoneal metastasis. The main pathway activated by extracellular TG2 was noncanonical nuclear factor-kappa B (NF-κB) signaling, and the enzymatic function of the protein was required to induce phosphorylation of IκB kinase α and processing of the precursor protein p100 into the active p52 subunit. A specific target of TG2-activated p52/RelB complex is the hyaluronan receptor, CD44. Noncanonical NF-κB activation by extracellular TG2 induced CD44 up-regulation and epithelial-to-mesenchymal transition, contributing to increased cancer cell invasiveness and OC peritoneal dissemination. Taken together, our data support that noncanonical NF-κB activation is the pathway through which extracellular TG2 promotes OC metastasis.
Thymic malignancies are sensitive to a broad spectrum of systemic agents. Thymic carcinoma has a distinct clinical presentation and worse therapeutic outcomes than thymoma. Despite reproducible high response rates in thymoma, durable complete remissions are rare. Thus, novel new therapeutic targets need to be identified and appropriate agents developed to have further impact on this disease.
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