The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models

Colorectal cancer is the second most common cause of cancer-related death in the United States. Recent studies showed that interleukin-8 (IL-8) and its receptors (CXCR1 and CXCR2) are significantly upregulated in both the tumor and its microenvironment, and act as key regulators of proliferation, angiogenesis, and metastasis. Our previous study showed that IL-8 overexpression in colorectal cancer cells triggers the upregulation of the CXCR2-mediated proliferative pathway. The aim of this study was to investigate whether the CXCR2 antagonist, SCH-527123, inhibits colorectal cancer proliferation and if it can sensitize colorectal cancer cells to oxaliplatin both in vitro and in vivo. SCH-527123 showed concentration-dependent antiproliferative effects in HCT116, Caco2, and their respective IL-8-overexpressing variants colorectal cancer cell lines. Moreover, SCH-527123 was able to suppress CXCR2-mediated signal transduction as shown through decreased phosphorylation of the NF-κB/mitogen-activated protein kinase (MAPK)/AKT pathway. These findings corresponded with decreased cell migration and invasion, while increased apoptosis in colorectal cancer cell lines. In vivo results verified that SCH-527123 treatment decreased tumor growth and microvessel density when compared with vehicle-treated tumors. Importantly, these preclinical studies showed that the combination of SCH-527123 and oxaliplatin resulted in a greater decrease in cell proliferation, tumor growth, apoptosis, and angiogenesis that was superior to single-agent treatment. Taken together, these findings suggest that targeting CXCR2 may block tumor proliferation, migration, invasion, and angiogenesis. In addition, CXCR2 blockade may further sensitize colorectal cancer to oxaliplatin treatment.

L'Archiviste : revue historique et documentaire publiée d'après des documents tirés des collections publiques et privées de la France et de l'étranger / sous la direction de L. Séché

1892/12 (T1,N1)-1893/06 (T1,N9).

L'Archiviste : revue historique et documentaire publiée d'après des documents tirés des collections publiques et privées de la France et de l'étranger / sous la direction de L. Séché

1893/07 (T2,N10)-1893/10 (T2,N13).

Escuelas Pías (Escolapios) -Sch. P-.

José de Calasanz, tras su formación en Roma, funda en 1617 las Escuelas Pías. Se fundan como misión educativa cristiana destinada a jóvenes y niños, compartida desde, y en una comunidad de vida religiosa y realizada sobre todo por sacerdotes. Es la primera orden religiosa dedicada específicamente a la educación cristiana popular a través de la escuela. Algunos de los rasgos del sistema educativo de los escolapios son considerar como primeros destinatarios los niños desfavorecidos; crear para los alumnos ambientes educativos propios y acogedores; estar abiertos a nuevos métodos pedagógicos y en consonancia con las nuevas tecnologías; potenciar la acción social y el voluntariado y dar importancia a la educación no formal. Hoy en día es un sistema educativo presente en treinta y cuatro países en los que trabajan tanto religiosos como laicos. Adjunta una ficha con los datos y direcciones de la congregación.

Análise da atividade antimicrobiana dos extratos de Cordia verbenacea DC, Mikania laevigata Sch. Bip. ex Baker e Psidium Cattleianum frente a microrganismos endodônticos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Produção de biomassa e teor de cumarina em folhas de guaco (Mikania laevigata Sch. Bip. ex Baker) em diferentes idades da planta

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Produção de biomassa e teor de cumarina em folhas de guaco (Mikania laevigata Sch. Bip. ex Baker) em diferentes idades da planta

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS

To determine the efficacy and toxicity of SCH 39304 in the treatment and suppression of cryptococcal meningitis, we conducted a prospective, noncomparative study in three groups of patients: patients with acute cryptococcal meningitis, patients with acute cryptococcal meningitis in whom other therapies have failed (salvage), and patients who required maintenance therapy. As primary therapy, the patients received up to 14 days or 1 g of amphotericin B followed by SCH 39304 200 mg once daily for 12 weeks. As maintenance therapy, the patients received SCH 39304 600 mg once weekly for 12 months. Of five salvage patients, none completed the study. Two patients died, two patients clinically deteriorated, and one patient was noncompliant. Two of three patients with acute cryptococcal meningitis completed the 12-week primary therapy, and one patient was discontinued from therapy because of a skin rash (95% confidence interval, 14-100%). All four patients who were receiving weekly maintenance therapy followed up to 27 weeks were clinically stable with no change in their serum cryptococcal antigen titer from baseline when the study was prematurely terminated. Elevation of liver function test results developed in three patients and skin rash developed in one patient. The unique pharmacologic and pharmacokinetic properties of SCH 39304 (low incidence of toxicity, long serum half-life, and good penetration into the cerebrospinal fluid) lend promise to pursue other triazole antifungals at higher doses as primary therapy and less frequent dosing for maintenance therapy.

Portraitbüste des Herrn Sch. [Illustration]

Arnold Monat

Aus der Sammlung "Briefe" : An Herrn Sch. Dubnow in Petersburg

Esther Mieses

Szenenbilder aus den Aufführungen des Hebräischen Theaters "Ohel" in Tel-Aviv [Illustration] : Aus dem Drama "Jakob und Rachel" [und] aus: J. L. Perez: Sch'mah Jisrael

Scan von Monochrom-Mikroform