Depressive symptoms during the first month of chemotherapy and survival in patients with hematological malignancies: A prospective cohort study.

OBJECTIVE: The objective of the study is to investigate depressive symptoms before and after the initiation of chemotherapy and their impact on overall survival (OS) among patients with hematological malignancies. METHODS: We performed a prospective analysis of consecutive patients with newly diagnosed malignant lymphoma or multiple myeloma enrolled between September 2010 and March 2016. We evaluated depression symptoms at two time points: before starting chemotherapy (T1) and 1 month later (T2), using PHQ-9 and known prognostic factors. We allocated participants with depressive symptoms at T1 and/or T2 to a depression group that was subdivided as follows: new depressive symptoms at T2, ("new-onset"), remission of depressive symptoms at T2 ("remission"), and persistent depressive symptoms from T1 to T2 ("persistent"). The main outcome, OS, was evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards modeling. RESULTS: Of the 294 eligible participants, we analyzed 255 patients, including 83 with depression. There were 19 participants in the new-onset, 38 in the remission, and 26 in the persistent depression group. The OS of participants with depression was significantly shorter than that of those without depression (adjusted hazard ratio [AjHR] 2.43; 95% confidence interval [CI] 1.43-4.12; P < .001). Using the never-depressive symptoms group as a reference group, AjHRs were as follows: new-onset, 1.91 (95% CI, 0.77-4.75; 0.166); remission, 2.98 (95% CI, 1.55-5.74; 0.001), and persistent, 2.17 (95%CI, 1.01-4.68; 0.047). CONCLUSIONS: Among patients with mature lymphoid malignancy, the group with depression at baseline had a poorer survival, both in the group that remained depressive and the group that recovered from depressive symptoms.

What is the appropriate communication style for family members confronting difficult surrogate decision-making in palliative care?: A randomized video vignette study in medical staff with working experiences of clinical oncology.

BACKGROUND: The family members of terminally ill patients are often requested to make difficult surrogate decisions during palliative care. This study sought to clarify the appropriate communication style for physicians as perceived by family members confronting difficult surrogate decision-making. METHODS: This experimental psychological study used scripted videos. In the videos, the physician described treatment options including continuous deep sedation to the family members of patients with cancer and terminal delirium using an autonomous or paternalistic style. Medical professionals with clinical experience in oncology were randomly assigned to either group viewing the videos. The primary outcomes were physician compassion, decisional conflict and emotion scores. We also evaluated the communication style preference. RESULTS: In total, 251 participants completed this study. Although participants in both groups reported high physician compassion, participants in the autonomous style group reported lower compassion scores (reflecting higher physician compassion) (mean 15.0 vs. 17.3, P = 0.050), lower decisional conflicts scores (51.1 vs. 56.8, P = 0.002) and comparable emotions compared with those in the paternalistic style group. Seventy-six percent of participants preferred the autonomous style. CONCLUSIONS: Regarding difficult surrogate decision-making, the autonomous style might be more appropriate than the paternalistic style. However, various factors, such as family members' communication style preferences, family members' values, physician-family relationships and ethnic cultures, should be considered.

Cognitive dysfunction among newly diagnosed older patients with hematological malignancy: frequency, clinical indicators and predictors.

BACKGROUND: Medical staff often overlook or underestimate the presence or severity of cognitive dysfunction. The purpose of this study was to clarify the frequency, clinical indicators and predictors of cognitive dysfunction among newly diagnosed older patients with hematologic malignancy receiving first-line chemotherapy. METHODS: Patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were consecutively recruited. Cognitive dysfunction was evaluated using the Mini-Mental State Examination (MMSE) twice: before starting chemotherapy (T1) and 1 month later (T2). Participants also underwent a comprehensive geriatric assessment at T1. Potential clinical indicators that were associated with cognitive dysfunction were explored via cross-sectional analysis at T1. Predictors of cognitive dysfunction at T2 were also investigated among patients without cognitive dysfunction at T1. RESULTS: A total of 145 participants participated in the study; cognitive dysfunction at T1 was present in 20%. Multivariate analysis demonstrated that lower educational attainment and poorer instrumental activities of daily living were significant clinical indicators of cognitive dysfunction. Among 99 patients who did not have cognitive dysfunction at T1 and underwent cognitive assessment at T2, 7% developed dysfunction. Subjective perception of difficulty remembering at T1 was the only factor which significantly predicted new-onset cognitive dysfunction at T2. CONCLUSIONS: The prevalence rate of cognitive dysfunction was non-negligible among older patients with hematologic malignancy before and immediately after initial chemotherapy. Attention to the clinical indicators and predictors found in this study may provide facilitate the identification of cognitive dysfunction in patients with cancer.

Galectin-1 enhances the generation of neural crest cells.

Neural crest (NC) cells are multipotent cells that emerge from the dorsal region of the neural tube. After delaminating from the neural tube, NC cells migrate throughout the developing embryo and differentiate into various cells: neurons and glial cells of the peripheral nervous system, melanocytes of skin, and skeletal elements of the face and head. We previously analyzed the gene expression profile of a NC subpopulation isolated from Sox10-IRES-Venus mice and found that the carbohydrate-binding protein, Galectin-1 (Gal-1) was strongly expressed in generating NC cells. In the present study, we identified GAL-1 as a factor that promotes NC cell generation. Gal-1 was significantly expressed in NC cells generated in explanted neural tubes. The presence of GAL-1 enhanced the generation of NC-like cells from mouse embryonic stem (ES) cells. In the differentiation of ES cells into NC-like cells, GAL-1 enhanced neurogenesis in the early stages and facilitated NC-like cell generation in the later stages. GAL-1 also enhanced the generation of NC cells from explanted neural tubes. These results suggest that GAL-1 plays a facilitative role in NC cell generation.

Overexpression of KIF11 in Gastric Cancer with Intestinal Mucin Phenotype.

OBJECTIVE: Gastric cancer (GC) is one of the most common human cancers. A useful method of gastric cancer stem cell (CSC) characterization is spheroid colony formation. Previously, we reported that KIF11 expression is >2-fold in spheroid-body-forming GC cells compared with parental cells. Here, we analyzed the expression and distribution of KIF11 in human GC by immunohistochemistry. METHODS: Expression of KIF11 in 165 GC cases was determined using immunohistochemistry. For mucin phenotypic expression analysis of GC, immunostaining of MUC5AC, MUC6, MUC2 and CD10 was evaluated. RNA interference was used to inhibit KIF11 expression in GC cell lines. RESULTS: In total, 119 of 165 GC cases (72%) were positive for KIF11. Expression of KIF11 was not associated with any clinicopathologic characteristics; however, it was observed frequently in GC exhibiting an intestinal phenotype. Both the number and size of spheres formed by MKN-74 cells were significantly reduced following transfection of KIF11-targeting siRNA compared with negative-control siRNA. Furthermore, levels of phosphorylated Erk1/2 were lower in KIF11 siRNA-transfected cells than with negative-control siRNA-transfected cells. CONCLUSION: These results indicate that KIF11 is involved in intestinal mucin phenotype GC.

Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells.

Neural crest cells (NC cells) are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs) into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+) cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells.

Multipotency of melanoblasts isolated from murine skin depends on the Notch signal.

BACKGROUND: Melanoblasts (MBs), derived from neural crest cells, only differentiate into melanocytes (Ms) in vivo. We previously showed that MBs isolated from mouse skin were multipotent, generating neurons (Ns) and glial cells (Gs) together with Ms. Using Sox10-IRES-Venus mice and mouse embryonic stem cells, we investigated how MBs expressed their multipotency. RESULTS: MBs generated colonies containing Ns, Gs, and Ms in the presence of ST2 stromal cells, but they generated only M colonies when incubated with keratinocytes or ST2 culture supernatant, thus showing that MBs required contact with ST2 stromal cells for expression of their multipotency. Notch signaling was shown to be one of the important cues for the maintenance and differentiation of MBs through cell-cell contact. When Notch signaling was inhibited, MBs mainly generated colonies that contained just one type of cells, Ns, Gs, or Ms; the number of colonies containing two or three types of cells markedly decreased even on ST2 stromal cells, showing restriction of their differentiation potency. Whereas when Notch signaling was activated, the number of colonies containing two or three types of cells increased, indicating that their multipotency had been maintained. CONCLUSIONS: Our results demonstrate that Notch signaling played novel roles in MB multipotency.