JNK pathway plays a critical role for expansion of human colorectal cancer in the context of BRG1 suppression

Tumor stem cells (TSCs), capable of self-renewal and continuous production of progeny cells, could be potential therapeutic targets. We have recently reported that chromatin remodeling regulator Brg1 is required for maintenance of murine intestinal TSCs and stemness feature of human colorectal cancer (CRC) cells by inhibiting apoptosis. However, it is still unclear how BRG1 suppression changes the underlying intracellular mechanisms of human CRC cells. We found that Brg1 suppression resulted in upregulation of the JNK signaling pathway in human CRC cells and murine intestinal TSCs. Simultaneous suppression of BRG1 and the JNK pathway, either by pharmacological inhibition or silencing of c-JUN, resulted in even stronger inhibition of the expansion of human CRC cells compared to Brg1 suppression alone. Consistently, high c-JUN expression correlated with worse prognosis for survival in human CRC patients with low BRG1 expression. Therefore, the JNK pathway plays a critical role for expansion and stemness of human CRC cells in the context of BRG1 suppression, and thus a combined blockade of BRG1 and the JNK pathway could be a novel therapeutic approach against human CRC

Pancreatic RECK inactivation promotes cancer formation, epithelial-mesenchymal transition, and metastasis

膵癌悪性化の分子機構解明 --RECK発現の低下が膵癌の浸潤・転移を引き起こす--. 京都大学プレスリリース. 2023-09-19.RECK is downregulated in various human cancers; however, how RECK inactivation affects carcinogenesis remains unclear. We addressed this issue in a pancreatic ductal adenocarcinoma (PDAC) mouse model and found that pancreatic Reck deletion dramatically augmented the spontaneous development of PDAC with a mesenchymal phenotype, which was accompanied by increased liver metastases and decreased survival. Lineage tracing revealed that pancreatic Reck deletion induced epithelial-mesenchymal transition (EMT) in PDAC cells, giving rise to inflammatory cancer-associated fibroblast–like cells in mice. Splenic transplantation of Reck-null PDAC cells resulted in numerous liver metastases with a mesenchymal phenotype, whereas reexpression of RECK markedly reduced metastases and changed the PDAC tumor phenotype into an epithelial one. Consistently, low RECK expression correlated with low E-cadherin expression, poor differentiation, metastasis, and poor prognosis in human PDAC. RECK reexpression in the PDAC cells was found to downregulate MMP2 and MMP3, with a concomitant increase in E-cadherin and decrease in EMT-promoting transcription factors. An MMP inhibitor recapitulated the effects of RECK on the expression of E-cadherin and EMT-promoting transcription factors and invasive activity. These results establish the authenticity of RECK as a pancreatic tumor suppressor, provide insights into its underlying mechanisms, and support the idea that RECK could be an important therapeutic effector against human PDAC

Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms

The relationship between trait emotional intelligence and interaction with ostracized others' retaliation.

BACKGROUND: Regulation of emotions in others is distinct from other activities related to trait emotional intelligence in that only such behavior can directly change other people's psychological states. Although emotional intelligence has generally been associated with prosociality, emotionally intelligent people may manipulate others' behaviors to suit their own interests using high-level capabilities to read and manage the emotions of others. This study investigated how trait emotional intelligence was related to interacting with ostracized others who attempt retaliation. METHOD: We experimentally manipulated whether two people were simultaneously ostracized or not by using an online ball-tossing game called Cyberball. Eighty university students participated in Cyberball for manipulating ostracism and a "recommendation game," a variation of the ultimatum game for assessing how to interact with others who attempt retaliation, with four participants. After the recommendation game, participants rated their intention to retaliate during the game. RESULTS: People with higher interpersonal emotional intelligence were more likely to recommend that the ostracized other should inhibit retaliation and maximize additional rewards when they have a weaker intention to retaliate. However, they were more likely to recommend that the ostracized other should retaliate against the ostracizers when they have a stronger intention to retaliate. CONCLUSION: This is the first laboratory study that empirically reveals that people with high interpersonal emotional intelligence influence others' emotions based on their own goals contrary to the general view. Trait emotional intelligence itself is neither positive nor negative, but it can facilitate interpersonal behaviors for achieving goals. Our study offers valuable contributions for the refinement of the trait emotional intelligence concept in the respect of its social function

Means and standard deviations of emotions felt during Cyberball.

<p>Means and standard deviations of emotions felt during Cyberball.</p

Interactive effect of interpersonal emotional intelligence and intention to retaliate.

<p>The graph illustrates the result of simple slopes for the association between interpersonal emotional intelligence and participants' recommendation to the ostracized person depending on intention to retaliate.</p

Synthesis and optical reactivity of 6,13-α-diketoprecursors of 2,3,9,10-tetraalkylpentacenes in solution, films and crystals

Tetraalkylpentacenes having alkyl chains at 2,3,9,10-positions (Et-PEN, Pr-PEN and Hex-PEN) were prepared from their precursors Et-PDK, Pr-PDK and Hex-PDK, respectively. Photoreactions proceeded both in solutions, thin-films, and crystals, thus the properties of Et-PDK in films can be studied despite the instability of the pentacenes in solution. Et-PEN showed significantly different aggregation-nature compared with the parent pentacene. The hole mobilities of Et-PEN and Pr-PEN in films were 3.4 [times] 10-6 and 8.1 [times] 10-7 cm2 V-1 s-1, respectively, determined by space-charge-limited current measurement, comparable with the order 10-6 cm2 V-1 s-1 of the electron mobility of Alq3

ニュウボウ オンゾン ジュツゴ ノ ニュウガン カンジャ ニ オケル ホウシャセン チリョウ シュウリョウ マエ ノ フクスウ ノ ショウジョウ タイケン ト ソノ タイショ

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