A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo.

PURPOSE: The melanoma cellular adhesion molecule, also known as MUC18, is highly expressed on several tumors, including bone sarcomas. The level of MUC18 expression has been found to correlate directly with tumor progression and metastatic potential. These observations have established MUC18 as a candidate mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might be a potential target for immunotherapy against several MUC18-expressing tumors, including human bone sarcomas. EXPERIMENTAL DESIGN: To investigate whether blockade of MUC18 might be a potential target for immunotherapy against osteosarcoma, we have recently developed a fully human anti-MUC18 antibody, ABX-MA1. We studied the effect of ABX-MA1 on growth, adhesion, invasion, and metastasis of human osteosaroma cells both in vitro and in vivo. RESULTS: MUC18 was widely expressed on both osteosarcoma and Ewing's sarcoma cells. ABX-MA1 had no effect on the proliferation of osteosarcoma cells in vitro, nor did it significantly inhibit the growth of KRIB human osteosarcoma cells when they were orthotopically implanted into the tibias of nude mice. However, after 6 weeks, significantly fewer ABX-MA1-treated mice developed spontaneous pulmonary metastases than did IgG-treated control mice. Additionally, ABX-MA1 decreased the invasion of osteosarcoma cells through Matrigel-coated filters and disrupted homotypic adhesion between osteosarcoma cells and their heterotypic interaction with human vascular endothelial cells. CONCLUSIONS: Our findings demonstrate that MUC18 plays a central role in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by ABX-MA1 may be a novel immunotherapeutic approach in the management of this tumor.     

Large Scale Manufacturing of B43(Anti-CD19)-Genistein for Clinical Trials in Leukemia and Lymphoma

We have conjugated the murine monoclonal anti-CD 19 antibody B43 to the tyrosine kinase inhibitor genistein to construct an effective immunoconjugate against CD 19 antigen positive hematologic malignancies. The scaled-up production and purification of B43 antibody, genistein, and B43-Genistein immunoconjugate permitted the manufacturing of a highly purified clinical-grade B43-Genistein preparation. In clonogenic assays, B43-Genistein elicited selective and potent cytotoxicity against CD 19 antigen positive human leukemia cells. To our knowledge, this work represents the first effort of producing a clinical-grade genistein immunoconjugate for treatment of B-lineage leukemia and lymphoma.     

Thrombopoietin receptor agonist switch in children with persistent and chronic severe immune thrombocytopenia: A retrospective analysis in a large tertiary center

We retrospectively analyzed sequential therapy with romiplostim and eltrombopag in 23 children with immune thrombocytopenia: switching from romiplostim to eltrombopag (10 patients) or vice versa (13 patients). The median age of patients at enrollment in the study was 5.6 years (2‐15 years). Switching from romiplostim to eltrombopag was effective in eight (80%) patients, whereas switching from eltrombopag to romiplostim was effective in eight (62%) patients. The response rate was similar in patients failing the first thrombopoietin receptor agonist and those who had previous response. To date, all responders continue to maintain platelets over 50 × 10⁹/L at 13‐39 months after switching.     

Use of Street Methadone in Italian Heroin Addicts Presenting for Opioid Agonist Treatment

ABSTRACT

It is commonly assumed that people who are addicted to certain substances would abuse any substance. This position has never been supported by validly collected and analyzed research data. In this study, the authors examine the use of street methadone by heroin addicts seeking their first agonist opioid treatment in a clinical setting. Fifty-four heroin addicts who resorted to street methadone use were compared by socio-demographic, current clinical, and disease-related variables to 251 peers who do not use street methadone. Heroin addicts who resort to street methadone use are more likely to be females and to have a higher degree of education, are less likely to engage in polyabuse (use of more than three substances), are less severely ill, have been addicted for a shorter period of time, and have been seeking treatment sooner in the course of their disease. Also, they suffer from a wider range of psychopathological distress symptoms. In Italy, resorting to street methadone does not seem to be a surrogate form of heroin addiction, but rather represents means of harm reduction, with treatment seeking occurring shortly after its initiation. This should be accounted for when deciding on take-home policies and issues of potential methadone diversion.     

Tc-99m diethylenetriamine pentaacetic acid (DTPA): Is it reliable for assessment of methotrexate-induced cumulative effect on renal filtration in rheumatoid arthritis patients?

Methotrexate[MTX] is commonly employed as the initial DMARD used for treatment of Rheumatoid arthritis[RA]. We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. Fifty two RA adult females with normal base-line serum creatinine and GFR at the initial diagnosis of the disease were included. Group-1[G1] included 30 patients[mean age 40.4 ± 4.4 years] on MTX and NSAIDS, while 22 RA patients[mean age 38.5 ± 8.2 years] who received NSAIDs only served as the control group[G2]. Renal function was assessed by GFR-measurement using Technetium diethylenetriamine-pentaacetic acid[Tc-99 m-DTPA] at the point of the study time corresponding to disease duration. 21/30[70%] in G1 showed reduced GFR compared to 6/22[27.3%] in G2[P0.007] with 3.3 ± 0.5% annual reduction of GFR. Reduced GFR in G1 showed significant negative correlation with age[r = ?0.396, P = 0.005], MTX-cumulative dose[r = ?0.263, P = 0.049], MTX-intake duration[r = ?0.293, P = 0.031] and NSAID-intake duration[r = ?0.344, P = 0.014]. Low dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction over time that could be monitored by Tc-99 m DTPA.     

Intrauterine Interventions for the Treatment of Twin Anemia-Polycythemia Sequence: A Systematic Review

BackgroundTwin anemia-polycythemia sequence (TAPS) is a complication of monochorionic, multiple gestation pregnancies in which blood shunting through placental anastomoses results in chronic anemia in one fetus and chronic polycythemia in another. The outcomes of different treatment modalities for TAPS are not well known.ObjectiveTo determine the outcomes of the intrauterine interventions used to treat TAPS.Study DesignA systematic literature search of MEDLINE, EMBASE, and CENTRAL was performed in June 2016. Primary outcomes were mortality, morbidity, and adverse perinatal outcomes. Data were summarized in the form of weighted means, and statistical difference was determined.ResultsTwenty-one articles were identified for inclusion in this review and were composed of 105 cases of TAPS. In the cases presented in the literature, there was no statistically significant difference in mortality, morbidity, or emergent Caesarean section rates between expectant management, intrauterine transfusion (IUT), and laser ablation therapy. Laser ablation therapy and IUT were found to have a significantly lower rate of adverse perinatal outcomes when compared to expectantly managed cases.ConclusionsThe literature looking into the treatment of TAPS is very limited, with no randomized controlled trials and only one includable comparative study. Based on the data in the case report and case study literature, there is no mortality difference between any of the treatment modalities. Expectant management may be associated with an increase in adverse perinatal outcomes when compared to laser therapy and IUT. More comparative studies are needed to assist clinicians in adopting an evidence-based approach to the treatment of TAPS.