We propose incorporation of metabolome data into the diagnostics algorithm in PPGLs to guide genetic testing and variant interpretation and to help identify rare cases with PV in FH and IDHx.

The data suggest that DT has acceptable overall accuracy and reliability as a screening tool for testing distress severity and specific problems causing distress in Chinese cancer patients. It is worth being used in oncology clinic, the rapid screening and interview could help caregivers to identify psychological and psychiatric problems of cancer patients and provide useful information for further treatment.

Cluster I pheochromocytomas and paragangliomas (PCPGs) tend to develop malignant transformation, tumor recurrence, and multiplicity. Transcriptomic profiling suggests that cluster I PCPGs and other related tumors exhibit distinctive changes in the tricarboxylic acid (TCA) cycle, the hypoxia signaling pathway, mitochondrial electron transport chain, and methylation status, suggesting that therapeutic regimen might be optimized by targeting these signature molecular pathways. In the present study, we investigated the molecular signatures in clinical specimens from cluster I PCPGs in comparison with cluster II PCPGs that are related to kinase signaling and often present as benign tumors. We found that cluster I PCPGs develop a dependency to mitochondrial complex I, evidenced by the upregulation of complex I components and enhanced NADH dehydrogenation. Alteration in mitochondrial function resulted in strengthened NAD metabolism, here considered as a key mechanism of chemoresistance, particularly, of succinate dehydrogenase subunit B ()-mutated cluster I PCPGs via the PARP1/BER DNA repair pathway. Combining a PARP inhibitor with temozolomide, a conventional chemotherapeutic agent, not only improved cytotoxicity but also reduced metastatic lesions, with prolonged overall survival of mice with knockdown PCPG allograft. In summary, our findings provide novel insights into an effective strategy for targeting cluster I PCPGs, especially those with mutations..

Background Both demoralization and depression are common forms of psychological distress in cancer patients. This study aimed to investigate the severity of demoralization in Chinese cancer patients and to explore the factors influencing depression and demoralization and their effects on quality of life to better understand the differences and the relationship between demoralization and depression. Methods Cross‐sectional study design, in‐patients sequentially recruited from a tertiary‐level cancer hospital in Beijing between January 2016 and April 2016 completed Mandarin version of Demoralization Scale (DS‐MV), Patient Health Questionnaire‐9 (PHQ‐9), Revised Life Orientation Test (CLOT‐R), Beck Hopelessness Scale (BHS), and the 12‐items Short Form Health Survey, version 2 (SF‐12 V2) and provided socio‐demographic and clinical information. Results 296/424 (70.0%) of patients completed questionnaires. The mean score of DS is 30.4 (SD = 13.0). There are 28% (83/296) patients who experienced a low level of depression but a high level of demoralization. Resignation medical coping method (b = 0.279, P < .001), hopelessness (b = 0.492, P < .001), positive life orientation (b = −0.170, P < .001), and education level (b = −0.132, P < .001) were found to be predictors of demoralization, while only resignation medical coping method (b = 0.373, P < .001) and hopelessness (b = 0.350, P < .001) were found to be predictors of depression. Depression is a mediator between demoralization and physical aspects of quality of life (γ = −0.1604, LLCI = −0.244, ULCI = −0.080). Conclusion Demoralization is a prevalent psychiatric problem in Chinese cancer patients, and a large proportion of patients had low depression but high demoralization. Therefore, screening for demoralization in Chinese oncology practice is essential. A positive life orientation was found to be protective against demoralization.

PURPOSE Effective interventions to improve prognosis in metastatic esophagogastric cancer (EGC) are urgently needed. We assessed the effect of the early integration of interdisciplinary supportive care for patients with metastatic EGC on overall survival (OS). PATIENTS AND METHODS An open-label, phase III, randomized, controlled trial was conducted at Peking University Cancer Hospital & Institute. Patients with previously untreated metastatic EGC were enrolled. Patients were randomly assigned (2:1) to either early interdisciplinary supportive care (ESC) integrated into standard oncologic care or standard care (SC). ESC was provided by a team of GI medical oncologists, oncology nurse specialists, dietitians, and psychologists; patients in the SC group received standard oncologic care alone. The primary end point was OS in the intention-to-treat population. RESULTS Between April 16, 2015, and December 29, 2017, 328 patients were enrolled: 214 in the ESC group and 114 in the SC group. At the data cutoff date of January 26, 2019, 15 (5%) patients were lost to follow-up. The median number of cycles of first-line chemotherapy was five (interquartile range [IQR], 4-7) in the ESC group and four (IQR, 2-6) in the SC group. The median OS was 14.8 months (95% CI, 13.3 to 16.3) in the ESC group and 11.9 months (95% CI, 9.6 to 13.6) in the SC group (hazard ratio, 0.68; 95% CI, 0.51 to 0.9; P = .021). CONCLUSION The early integration of interdisciplinary supportive care is an effective intervention with survival benefits for patients with metastatic EGC. Further optimization and standardization are warranted.

Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

BackgroundTo evaluate the relationship between quality of life (QOL) and physical as well as psychological variables in Chinese breast cancer patients.MethodsThis multicenter cross-sectional study enrolled 254 Chinese breast cancer patients in different stages and treatment phases. They answered standard instruments assessing QOL (EORTC), somatic symptom severity (PHQ-15), depression (PHQ-9), anxiety (GAD-7), health-related anxiety (WI-7), illness perception (BIPQ), and sense of coherence (SOC-9). Canonical correlation was applied to identify the strongest correlates between the physical, emotional and social QOL scales and the physical and psychological variables.ResultsIn our sample, a low global QOL was significantly associated with the following physical and psychological variables: symptom-related disability (Karnofsky Index) (r = .211, p < .01), somatic symptom severity (r = −.391, p < .001), depression (r = −.488, p < .001), anxiety (r = −.439, p < .001), health-related anxiety (r = −.398, p < .001), dysfunctional illness perception (r = −.411, p < .001), and sense of coherence (r = .371, p < .001). In the canonical correlation analysis, high somatic symptom severity, depression, anxiety, dysfunctional illness perception, and low sense of coherence showed the strongest correlations with low physical, emotional and social functioning. The first three significant canonical correlations between these two sets of variables were .78, .56, and .45.ConclusionsQOL in Chinese breast cancer patients is strongly associated with psychological factors. Our results suggest that Chinese physicians and nurses should incorporate these factors into their care for women with breast cancer to improve patients’ QOL.

Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi. Through an in-vitro and in-vivo approach utilizing cell lines for hepatocellular carcinoma (HCC), osteosarcoma (OS), and glioblastoma (GBM), we demonstrate that SAHA potently inhibits HIF-a nuclear translocation via direct acetylation of its associated chaperone, heat shock protein 90 (Hsp90). In the presence of SAHA we found elevated levels of acetyl-Hsp90, decreased interaction between acetyl-Hsp90 and HIF-a, decreased nuclear/cytoplasmic HIF-α expression, absent HIF-α association with its nuclear karyopharyin Importin, and markedly decreased HIF-a transcriptional activity. These changes were associated with downregulation of downstream hypoxia molecules such as endothelin 1, erythropoietin, glucose transporter 1, and vascular endothelial growth factor. Findings were replicated in an in-vivo Hep3B HRE-Luc expressing xenograft, and were associated with significant decreases in xenograft tumor size. Altogether, this study highlights a novel mechanism of action of an important class of chemotherapeutic.