Microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper transcription factor involved in the lineage-specific regulation of melanocytes, osteoclasts and mast cells. MITF is also involved in the progression of melanomas and other carcinomas, including the liver, pancreas and lung. However, the role of MITF in clear cell renal cell carcinoma (ccRCC) is largely unknown. This study investigates the functional role of MITF in cancer and the molecular mechanism underlying disease progression in ccRCC. MITF knockdown inhibited cell proliferation and shifted the cell cycle in ccRCC cells. In addition, MITF knockdown reduced wound healing, cell migration and invasion compared with the controls. Conversely, MITF overexpression in SN12C and SNU482 cells increased cell migration and invasion. Overexpression of MITF activated the RhoA/YAP signaling pathway, which regulates cell proliferation and invasion, and increased YAP signaling promoted cell cycle-related protein expression. Additionally, tumor formation was impaired by MITF knockdown and enhanced by MITF overexpression in vivo. In summary, MITF expression was associated with aggressive tumor behavior, and increased the migratory and invasive capabilities of ccRCC cells. These effects were reversed by MITF suppression. These results suggest that MITF is a potential therapeutic target for the treatment of ccRCC.

Background: We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer. Methods: This was a multicenter, randomized, open-label, phase II trial in five centers. Patients randomly received rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily)/apixaban (10 mg twice daily for the first 7 days, then 5 mg twice daily) or dalteparin (200 IU/kg once daily for the first month, then 150 IU/kg once daily). Randomization was stratified by the Eastern Cooperative Oncology Group Performance Status, primary cancer type, active chemotherapy, and participating centers. The primary endpoint was the rates of clinically relevant bleeding (CRB) in the full analysis set (FAS). Results: A total of 90 patients were randomly assigned to the DOAC (n = 44) and dalteparin groups (n = 46) in FAS. CRB and major bleeding (MB) rates were 34.1% and 13.0% (p = 0.018) and 18.2% and 4.3% (p = 0.047) for the DOAC and dalteparin groups, respectively. Time to CRB and MB was higher in the DOAC group than in the dalteparin group (hazard ratio [HR] 2.83; p = 0.031 and HR 4.32; p = 0.064). Cancer involvement at the GI mucosa was also a significant risk factor for CRB. Recurrent CA-VTE occurred in 2.3% and 2.2% of patients given DOAC and dalteparin, respectively (p = 1.000). Conclusion: DOAC therapy further increased the risk of bleeding compared with dalteparin in patients with active advanced upper GI tract, hepatobiliary, or pancreatic cancer, suggesting that extra caution should be taken when selecting anticoagulants for CA-VTE.

In this study, we aimed to develop and validate an instrument that could be used by patients with cancer to evaluate their quality of palliative care. Development of the questionnaire followed the four-phase process: item generation and reduction, construction, pilot testing, and field testing. Based on the literature, we constructed a list of items for the quality of palliative care from 104 quality care issues divided into 14 subscales. We constructed scales of 43 items that only the cancer patients were asked to answer. Using relevance and feasibility criteria and pilot testing, we developed a 44-item questionnaire. To assess the sensitivity and validity of the questionnaire, we recruited 220 patients over 18 years of age from three Korean hospitals. Factor analysis of the data and fit statistics process resulted in the 4-factor, 32-item Quality Care Questionnaire-Palliative Care (QCQ-PC), which covers appropriate communication with health care professionals (ten items), discussing value of life and goals of care (nine items), support and counseling for needs of holistic care (seven items), and accessibility and sustainability of care (six items). All subscales and total scores showed a high internal consistency (Cronbach alpha range, 0.89 to 0.97). Multi-trait scaling analysis showed good convergent (0.568–0.995) and discriminant (0.472–0.869) validity. The correlation between the total and subscale scores of QCQ-PC and those of EORTC QLQ-C15-PAL, MQOL, SAT-SF, and DCS was obtained. This study demonstrates that the QCQ-PC can be adopted to assess the quality of care in patients with cancer.

Lee MW, et al. J Korean Med Sci. 2022 Mar;37(11):e87. https://doi.org/10.3346/jkms.2022.37.e87

Background: Evans blue dye (EBD) is the most common indicator to analyze the extent of blood-brain barrier (BBB) breakdown in several neurological disease models. However, the high-dose of EBD (51.9 mg/kg) is usually required for visualization of blue color by the human eye that brings potential safety issues.

Individuals diagnosed with advanced cancer often experience stress and depression, factors linked to worse survival. Curability belief—defined as the hope and expectation of cure through treatment, based on affective forecasting—may differ from the patient’s actual life expectancy (i.e., likelihood estimation) and has shown variable associations with cancer survival. In this study, multivariate Cox regression analyses were used to examine the effect of curability belief and depression on 1-year survival after adjustment for physical factors. Additionally, regularized partial correlations among physical and psychological factors were assessed using mixed graphical models to elucidate their roles in mediating the relationship between curability belief and 1-year survival. This multi-center cohort study, conducted across 13 tertiary hospitals (including four ranked among the ‘World’s Best Specialized Hospitals 2025’ in oncology), involved 382 adults with stage IV advanced cancer and an oncologist-estimated survival of more than 6 months. Baseline data included demographics, primary tumor site, number of metastatic sites, symptom burdens (EORTC QLQ-C15-PAL), performance status (ECOG-PS), depression levels (PHQ-9), anti-cancer treatment type, patient’s life expectancy estimation, and curability belief. Follow-up data included 1-year survival and end-of-life care (place of death) for deceased patients. Multivariate Cox proportional hazards models were used to assess adjusted hazard ratios (aHRs) for curability belief, depression, and their interaction on 1-year survival, adjusting for significant demographic and clinical factors from univariate Cox regressions. The Kaplan–Meier method was used to plot survival probability by curability belief and depression interaction. Mixed graphical models estimated regularized partial correlations among 1-year survival, curability belief, patient’s life expectancy, depression, primary tumor site, anti-cancer treatment type, performance status, and symptom burden. In terms of healthcare utilization, patients with curability belief were more likely to receive standard or advanced anti-cancer therapy, while those without curability belief tended to suspend or discontinue therapy (P < 0.001). Among patients who did not survive the 1-year follow-up (N = 161), end-of-life care settings differed significantly between those with curability belief (predominantly nursing homes and home settings) and those without (primarily hospice and tertiary/secondary hospitals; P = 0.036). In multivariate Cox regression, curability belief (P = 0.003), depression (PHQ-9 score ≥ 10; P = 0.003), and their interaction (P = 0.040) were significantly associated with 1-year survival, after adjusting for sex, residential area, primary tumor site, performance status, anti-cancer treatment type, and symptom burdens (fatigue and appetite loss). The relationship between curability belief and 1-year survival was significant only in patients without depression [PHQ-9 score < 10; aHR (95% CI) = 2.20 (1.31–3.70); P = 0.003]. In the mixed graphical model, node predictability values for curability belief, depression, and 1-year survival were 0.68, 0.50, and 0.70, respectively, with curability belief showing partial correlations with depression (r = 0.30) and patients’ life expectancy (r = 0.20); depression correlated with fatigue (r = 0.53), anorexia (r = 0.16), life expectancy (r = 0.24), performance status (r = 0.23), and curability belief; and 1-year survival correlated with suspended/stopped anti-cancer treatment (r = 0.45), primary tumor site (r = 0.24), and performance status (r = 0.15). Partial correlations of performance status with depression and discontinued treatment mediated the association between curability belief and 1-year survival. Curability belief among stage IV advanced cancer patients with an oncologist-estimated survival of over 6 months was associated with depression levels and patients’ perceived life expectancy estimations. Performance status, depression, and anti-cancer treatment status mediate the relationship between curability belief and improved 1-year survival in patients without depression. Further research using longitudinal modeling of depression, performance status, and healthcare utilization, with curability belief and primary tumor site as covariates, is warranted. Trial registration: Clinical Trial Number (ClinicalTrials.gov): NCT03222258; Study Registration Dates (First submitted: 2017-06-05; First submitted following the QC criteria: 2017-07-16; First posted: 2017-07-19).