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Supplementary Table S1, Supplementary legends for Figures S1-S3, Supplementary Methods and References

EGFRvIII promotes glutamate release by glioma cells in a kinase-independent manner.

EGFR interacts with the central portion of xCT and thereby promotes surface expression of xCT.

Sulfasalazine does not affect intracellular ROS levels in Becker or U87MG cells.

Objective: The present study aims to describe fall-related self-efficacy as perceived by patients with chemotherapy-induced peripheral neuropathy (CIPN). The characteristics of patients associated with low perceived self-efficacy of preventing falls were investigated. Methods: A cross-sectional study of four hospitals in Japan. In this study, 100 outpatients who were receiving chemotherapy for cancer and experiencing CIPN were recruited. Participants completed an anonymous, self-administered questionnaire. Self-efficacy was measured with the falling self-efficacy (FSE) scale, and the severity and impact of CIPN was assessed with the Comprehensive Assessment Scale for CIPN in Survivors of Cancer (CAS-CIPN). Data about the demographic information of the patients, cancer diagnosis and treatment, pain and fatigue symptoms, and history of previous falls were collected. Logistic regression analysis was used to assess relationships between variables. Results: A total of 81 (81.0%) participants with CIPN completed the questionnaire. They reported experiencing fear of falling during their daily activities, which include the act of standing up, walking, and using the stairs. Small events, such as unstable postures and uncomfortable situations, affected their confidence of preventing falls. Logistic regression revealed that low FSE scores were significantly associated with female sex (P = 0.022), low body mass index (BMI; P = 0.026), and the CAS-CIPN score (P < 0.001). Conclusions: Female patients with CIPN and low BMI might have an increased need for enhanced fall-related self-efficacy. A comprehensive assessment of CIPN in patients at risk of low FSE scores is likely to be beneficial.

Objective This study was performed to clarify the influence of financial conditions on stress in patients with advanced recurrent colorectal cancer undergoing outpatient chemotherapy. Methods A self-administered questionnaire survey was completed by patients with advanced and recurrent colorectal cancer receiving outpatient chemotherapy in five hospitals in the Kansai region. The questionnaire included basic information (age, sex, current employment availability, and subjective financial condition (3 choices)), and the 29-item stress scale from Japanese version of the Mastery of Stress Instrument (5-point scale with a total score of 29-140 points) . Results Responses were received from 76 outpatients (response rate: 95%). The patients’ mean age was 66.6 ± 8.5 years, and they comprised 50 men (65.8%) and 26 jobholders (34.2%). Three patients (3.9%) always had financial leeway (Yutori group), 37 (48.7%) had a satisfactory financial margin (sufficient group), and 36 (47.4%) had no financial margin (marginless group). The mean stress score was 70.0 ± 15.3 points. The stress score was significantly higher in the unemployed group than in the working group. With respect to the patients’ subjective financial condition, the stress score was significantly higher in the marginless group than in the sufficient group. The Yutory group did not differ significantly from any other groups. Discussion and Conclusion Patients with advanced recurrent colorectal cancer undergoing outpatient chemotherapy often follow a long-term treatment course. Therefore, financial problems while undergoing cancer treatment may be a heavy burden. Patients who are unemployed and have no income appear to experience stressful conditions during treatment, such as distress and confusion. These findings suggest the need to provide both mental support and employment support to patients undergoing treatment for cancer. This work was supported by KAKENHI Grant Number A16H055760.

Unfinished business often causes psychological issues after bereavement. Providing care for families of terminally ill patients with cancer to prevent unfinished business is important.To clarify the prevalence and types of unfinished business in families of end-of-life patients with cancer admitted to palliative care units (PCUs), explore depression and grief associated with unfinished business, and explore the factors affecting unfinished business.We conducted a cross-sectional, anonymous, self-report questionnaire survey with 967 bereaved families of patients with cancer admitted to PCUs. The questionnaire assessed the presence or the absence of unfinished business, content of unfinished business, depression, grief, process of preparedness, condition of the family and patient, and the degree of involvement of health care professionals.Questionnaires were sent to 967 families, and 73.0% responded. In total, 26.0% of families had some unfinished business, with improvement of the patient-family relationship being a common type of unfinished business. Families with unfinished business had significantly higher depression and grief scores after bereavement compared with those without. Factors that influenced the presence or the absence of unfinished business were preparedness for the patient's death (P = 0.001), discussion between the patient and family about the disease trajectory and way to spend daily life (P 0.001), good patient-family relationship (P = 0.011), and family and health care professionals considering together the appropriate timing to accomplish the family's wishes (P = 0.021).Many families have unfinished business. Health care professionals should coordinate the appropriate timing for what the family wishes to do, with consideration of family dynamics, including the family's preparedness, communication pattern, and relationships.

Extracellular free amino acids contribute to the interaction between a tumor and its microenvironment through effects on cellular metabolism and malignant behavior. System xc(–) is composed of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. Here, we show that the EGFR interacts with xCT and thereby promotes its cell surface expression and function in human glioma cells. EGFR-expressing glioma cells manifested both enhanced antioxidant capacity as a result of increased cystine uptake, as well as increased glutamate, which promotes matrix invasion. Imaging mass spectrometry also revealed that brain tumors formed in mice by human glioma cells stably overexpressing EGFR contained higher levels of reduced glutathione compared with those formed by parental cells. Targeted inhibition of xCT suppressed the EGFR-dependent enhancement of antioxidant capacity in glioma cells, as well as tumor growth and invasiveness. Our findings establish a new functional role for EGFR in promoting the malignant potential of glioma cells through interaction with xCT at the cell surface. Cancer Res; 76(10); 2954–63. ©2016 AACR.