CD146 is a potential immunotarget for neuroblastoma

Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to arise from neural crest-derived immature cells. The prognosis of patients with high-risk or recurrent/refractory neuroblastoma remains quite poor despite intensive multimodality therapy; therefore, novel therapeutic interventions are required. We examined the expression of a cell adhesion molecule CD146 (melanoma cell adhesion molecule [MCAM]) by neuroblastoma cell lines and in clinical samples and investigated the anti-tumor effects of CD146-targeting treatment for neuroblastoma cells both in vitro and in vivo. CD146 is expressed by 4 cell lines and by most of primary tumors at any stage. Short hairpin RNA-mediated knockdown of CD146, or treatment with an anti-CD146 polyclonal antibody, effectively inhibited growth of neuroblastoma cells both in vitro and in vivo, principally due to increased apoptosis via the focal adhesion kinase and/or nuclear factor-kappa B signaling pathway. Furthermore, the anti-CD146 polyclonal antibody markedly inhibited tumor growth in immunodeficient mice inoculated with primary neuroblastoma cells. In conclusion, CD146 represents a promising therapeutic target for neuroblastoma

Pathological complete response following neoadjuvant chemotherapy for locally advanced intrahepatic cholangiocarcinoma

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cases when found are often advanced with vascular invasion, and radical resection is often difficult. Despite curative resection, the postoperative recurrence rate of patients with histological lymph node metastasis is high, and their prognosis is poor. Therefore, there is an urgent need to establish multidisciplinary treatment that combines chemotherapy and surgical resection. The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced ICC is unclear. In this report, a case of locally advanced ICC in which pathological complete response (pCR) was achieved after NAC is described. Case presentation A 79-year-old woman was admitted to a local hospital with appetite loss. Computed tomography showed a 100 × 90 mm low-contrast tumor in the left hepatic lobe and segment 1 with invasion to the inferior vena cava (IVC), and several lymph nodes along the left gastric artery and lesser curvature were enlarged. Therefore, she was treated with a combined chemotherapy regimen of gemcitabine and cisplatin. After four courses, the tumor size decreased to 30 × 60 mm without invasion to the IVC. Left hepatectomy extending to segment 1 with bile duct resection combined with middle hepatic vein resection (H1234-B-MHV), dissection of regional lymph nodes and pyloroplasty were performed. After radical resection, pCR was achieved. She is alive with no evidence of disease, 2 years after surgery. Conclusions In this case, a patient with locally advanced ICC achieved pCR to NAC. NAC may be effective for ICC. Patients who achieve pCR may have a better prognosis

Combined Pre-Supernova Alert System with Kamland and Super-Kamiokande

International audiencePreceding a core-collapse supernova, various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande via inverse beta decay interactions. Once these pre-supernova neutrinos are observed, an early warning of the upcoming core-collapse supernova can be provided. In light of this, KamLAND and Super-Kamiokande have been monitoring pre-supernova neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and Super-Kamiokande on pre-supernova neutrino detection. A pre-supernova alert system combining the KamLAND detector and the Super-Kamiokande detector is developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-supernova neutrino signal from a 15 M$_{\odot}$ star within 510 pc of the Earth, at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hours in advance

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes