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Supplementary Figure 4 from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Figure 3 from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Figure 6 from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Figure 1 A-C from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Tables 1-3 from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Figure 1 D-H from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Figure 5 from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Figure 2 from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Supplementary Materials, Figure Legends 1-6 from R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

Aerosol dosimetry estimates for mouse strains used as models for human disease are not available, primarily because of the lack of tracheobronchial airway morphometry data. By using micro‐CT scans of in‐situ prepared lung casts, tracheobronchial airway morphometry for four strains of mice were obtained: Balb/c, AJ, C57BL/6, and Apoe−/−. The automated tracheobronchial airway morphometry algorithms for airway length and diameter were successfully verified against previously published manual and automated tracheobronchial airway morphometry data derived from two identical in‐situ Balb/c mouse lung casts. There was also excellent agreement in tracheobronchial airway length and diameter between the automated and manual airway data for the AJ, C57BL/6, and Apoe−/− mice. Differences in branch angle measurements were partially due to the differences in definition between the automated algorithms and manual morphometry techniques. Unlike the manual airway morphometry techniques, the automated algorithms were able to provide a value for inclination to gravity for each airway. Inclusion of an inclination to gravity angle for each airway along with airway length, diameter, and branch angle make the current automated tracheobronchial airway data suitable for use in dosimetry programs that can provide dosimetry estimates for inhaled material. The significant differences in upper tracheobronchial airways between Balb/c mice and between C57BL/6 and Apoe−/− mice highlight the need for mouse strain‐specific aerosol dosimetry estimates.

INTRODUCTION Family caregivers of cancer patients often suffer from impaired quality of life (QOL) due to stress arising from the responsibility of caregiving. Most research on such QOL impairments was conducted in Western populations. Thus, this exploratory study sought to (a) examine the QOL levels of family caregivers of cancer patients in an Asian population in Singapore, in relation to caregivers from other countries within and outside of Asia; and (b) investigate the association between sociodemographic factors and QOL impairments in family caregivers in Singapore. METHODS A total of 258 family caregivers of cancer patients who were receiving outpatient treatment completed the Caregiver Quality of Life Index-Cancer (CQOLC) and a sociodemographic survey. We compared the published CQOLC total scores from Turkey, Iran, Taiwan, South Korea, the United Kingdom, the United States and Canada with the Singapore dataset and examined the demographic relationships. RESULTS Caregivers in Singapore and Asia had lower CQOLC total scores than their Western counterparts. Caregivers who were male, of Chinese ethnicity, had parental relationships with their care recipient, or cared for advanced-stage cancer patients were found to have impaired QOL. CONCLUSION The findings of this study highlight possible areas in which support can be provided for family caregivers of cancer patients, and underscore the need to reconcile cultural diversity, values, societal expectations and demographic characteristics in Singapore.

Family caregivers of cancer patients often experience an impaired quality of life (QOL) and emotional distress as a result of their caregiving duties, which may potentially influence the quality of care of their care recipients. The COPE (Caregivers of cancer Outpatients’ Psycho-Education support group therapy) intervention was developed as a response to the lack of work done among family caregivers of ambulatory cancer patients in Asia. This group intervention comprised four weekly sessions simultaneously targeting psychoeducation, skills training, and supportive therapy. The present study sought to evaluate the pilot COPE intervention using both quantitative and qualitative measures. The Hospital Anxiety and Depression Scale (HADS) was used to measure both depression and anxiety, while the Caregiver QOL – Cancer (CQOLC) measured caregiver QOL. These instruments were measured at baseline pre-intervention, and immediately post-intervention. A waitlist control group design was adopted. A subset of caregivers from the intervention group were invited for a semi-structured interview post-intervention. Quantitative analyses suggest that while QOL remained stable in control group participants, intervention group participants experienced QOL improvements – both in overall QOL and in the specific domain of burden. There were no significant differences in the trajectories of depression and anxiety in both groups. Qualitative analyses suggest that this might have been a result of the intervention not only equipping participants with the relevant coping skills, but also providing a platform for emotional expression and situational reappraisal. The COPE intervention has shown some efficacy in helping family caregivers of cancer patients, but more work is required before this can be implemented. Current Controlled Trials NCT02120183 . Registered 17 April 2014. Retrospectively registered.

Introduction: Research has shown that single-item tools, like the Distress Thermometer (DT), are comparable to longer ones, like the Hospital Anxiety and Depression Scale (HADS). In this study, we tested the validity of the DT in a population of Singapore cancer outpatients, and determined the cut-off scores on the DT for clinically relevant distress and an impaired quality of life (QOL). We also documented the prevalence of anxiety, depression, and QOL impairments in this population. Methods: One hundred and five patients (Mdn age = 51–60 years, 64% female, and 71% Chinese) diagnosed with various cancers participated in this study. They completed a standard socio-demographic form, the DT and the Problem List, the HADS, and the EuroQOL Quality of Life Scale (EQ-5D). Results: Almost a third of patients had clinically significant emotional distress, with 15%–16% having probable levels of anxiety and depression. Almost half (41%–55%) had an impaired QOL compared to Singapore population norms. Receiver operating characteristic curve analyses identified an area under the curve of 0.89 (SE = 0.36, 95% CI [0.82, 0.96], p

Introduction Despite the rising trend of cancer prevalence and increase in family caregiving, little attention has been paid to the efficacy of psychosocial interventions among Asian caregiver samples, particularly support groups, given the benefits that have been shown in studies on Western populations. This trial aims to evaluate the effectiveness of a pilot 4-week group psychotherapy for Singaporean family caregivers of patients receiving outpatient care. Methods and analysis Facilitated by a clinical psychologist, this intervention is primarily based on the brief integrative psychological therapy with a supportive-expressive intent. Participants will be recruited while they are accompanying their care recipients for outpatient consultations. Since this is a pilot study, a sample size of 120 participants is targeted on the basis of sample sizes of previous studies. The study adopts a quasi-experimental design, as participants are assigned the intervention or control arms based on their availability to attend the intervention. A mixed methods approach is used to evaluate the outcomes of the intervention. A self-administered battery of tests is completed at four time points: baseline, postintervention and follow-up at 1-month and 2-month postinterventions; semi-structured interviews are conducted at baseline and post-intervention. Primary outcomes are quality of life and anxious and depressive symptoms; secondary outcomes are stress and basic psychological needs. Analysis using analysis of covariance would be conducted to determine the effectiveness of the intervention. Ethics and dissemination This study protocol has ethics approval from the National Healthcare Group Domain Specific Review Board (NHG DSRB Ref: 2013/00662). Written informed consent is obtained from every participant. Results will be disseminated through journals and conferences, and will be particularly relevant for clinicians intending to implement similar support groups to address the psychosocial concerns of caregivers, as well as for researchers seeking to refine the structure and evaluate the effectiveness of such programmes. Trial registration number Current Controlled Trials NCT02120183 (https://clinicaltrials.gov/show/NCT02120183)

Accumulating evidence suggests important roles for the receptor tyrosine kinase Axl in cancer progression, invasion, metastasis, drug resistance, and patient mortality, highlighting Axl as an attractive target for therapeutic development. We have generated and characterized a potent and selective small-molecule inhibitor, R428, that blocks the catalytic and procancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. Pharmacologic investigations revealed favorable exposure after oral administration such that R428-treated tumors displayed a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, R428 inhibited angiogenesis in corneal micropocket and tumor models. R428 administration reduced metastatic burden and extended survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis. Additionally, R428 synergized with cisplatin to enhance suppression of liver micrometastasis. Our results show that Axl signaling regulates breast cancer metastasis at multiple levels in tumor cells and tumor stromal cells and that selective Axl blockade confers therapeutic value in prolonging survival of animals bearing metastatic tumors. Cancer Res; 70(4); 1544–54