Antitumor Activity of Lurbinectedin, a Selective Inhibitor of Oncogene Transcription, in Patients with Relapsed Ewing Sarcoma: Results of a Basket Phase II Study

Ewing Sarcoma; LurbinectedinSarcoma de Ewing; LurbinectedinaSarcoma d'Ewing; LurbinectedinaPurpose: Lurbinectedin suppresses the oncogenic transcription factor EWS-FLI1 through relocalization to the nucleolus, and delays tumor growth in mice bearing Ewing sarcoma xenografts. On the basis of this rationale, lurbinectedin was evaluated in patients with relapsed Ewing sarcoma. Patients and Methods: This open-label, single-arm, Basket phase II trial included a cohort of 28 treated adult patients with confirmed Ewing sarcoma, measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1, Eastern Cooperative Oncology Group performance status ≤2, adequate organ function, no central nervous system metastasis, and pretreated with ≤2 chemotherapy lines for metastatic/recurrent disease. Patients received lurbinectedin 3.2 mg/m2 as a 1-hour infusion every 3 weeks. Primary endpoint was overall response rate (ORR) as per RECIST v.1.1. Secondary endpoints included time-to-event parameters and safety profile. Results: ORR was 14.3% [95% confidence interval (CI), 4.0%–32.7%], with median duration of response of 4.2 months (95% CI, 2.9–5.5 months). Median progression-free survival was 2.7 months (95% CI, 1.4–4.3 months), clinical benefit rate was 39.3%, and disease control rate was 57.1%. With 39% censoring, median overall survival was 12.0 months (95% CI, 8.5–18.5 months). Most common grade 3/4 adverse events were neutropenia (57%), anemia, thrombocytopenia, and treatment-related febrile neutropenia (14% each). No deaths or discontinuations were due to toxicity. Conclusions: Lurbinectedin was active in the treatment of relapsed Ewing sarcoma and had a manageable safety profile. Lurbinectedin could represent a valuable addition to therapies for Ewing sarcoma, and is currently being evaluated in combination with irinotecan in advanced Ewing sarcoma in a phase Ib/II trial

A Randomized Study on Postrelapse Disease-Free Survival with Adjuvant Mistletoe versus Oral Etoposide in Osteosarcoma Patients

Background. Osteosarcoma is a highly malignant bone tumour. After the second relapse, the 12-month postrelapse disease-free survival (PRDFS) rate decreases below 20%. Oral Etoposide is often used in clinical practice after surgery as an “adjuvant” outside any protocol and with only limited evidence of improved survival. Viscum album fermentatum Pini (Viscum) is an extract of mistletoe plants grown on pine trees for subcutaneous (sc) injection with immunomodulatory activity. Methods. Encouraged by preliminary findings, we conducted a study where osteosarcoma patients free from disease after second metastatic relapse were randomly assigned to Viscum sc or Oral Etoposide. Our goal was to compare 12-month PRDFS rates with an equivalent historical control group. Results. Twenty patients have been enrolled, with a median age of 34 years (range 11–65) and a median follow-up time of 38.5 months (3–73). The median PRDSF is currently 4 months (1–47) in the Etoposide and 39 months (2–73) in the Viscum group. Patients getting Viscum reported a higher quality of life due to lower toxicity. Conclusion. Viscum shows promise as adjuvant treatment in prolonging PRDFS after second relapse in osteosarcoma patients. A larger study is required to conclusively determine efficacy and immunomodulatory mechanisms of Viscum therapy in osteosarcoma patients

Pregnant teenagers treated at the obstetric center of a university hospital

According to the definition of the World Health Organization, adolescence is the phase of life between 10 and 19 years of age, a period marked by physiological and biopsychosocial changes, in which pregnancy is considered a risk factor for both mother and fetus from the biomedical point of view. Several factors have been associated with teenage pregnancy with negative maternal and neonatal impacts, such as: social vulnerability, low levels of education, income, and sexual education. This is a descriptive cross-sectional study with a quantitative approach, which aimed to identify obstetric factors and neonatal outcomes of greater frequency among pregnant adolescents treated at the obstetric center of a university hospital. Data collection was performed through a logbook of daily procedures at the obstetric center, so that all parturients under 19 years of age treated in 2018 were included in the study. The variables studied were age, parity, type of delivery, gestational age, diagnosis of syphilis and HIV, number of prenatal consultations, and insertion of an intrauterine device (IUD). As for the newborn, the following were analyzed: weight and hospital destination after birth. The data were processed using the SOFA.5.2 software (Statistics Open for All) and the significance level established was 95%, with a value of (P ≤ 0.05). Three thousand four hundred and thirty pregnant women were evaluated. There was a birth rate of 19.3% among adolescents, with a correlation between the low weight of the newborn with the longest hospital stay and the number of prenatal visits, and also the identification of low insertion of contraceptive methods immediately after delivery. Adolescent pregnancy was correlated with low-birth-weight newborns and a longer stay in neonatal units, consequences often associated with the insufficient number of prenatal consultations. Public health policies for the inclusion of qualified nursing professionals in the management of insertion of the intrauterine device for the prevention of subsequent pregnancies deserve special attention

Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma

Abstract Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and >IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HRA). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti–IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HRA, and IGFIR) act complementarily for an IGF-II–mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth. [Cancer Res 2009;69(6):2443–52

TLR-4 and VEGF polymorphisms in chronic periaortitis

Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP

Carpal tunnel syndrome in cardiac amyloidosis: implications for early diagnosis and prognostic role across the spectrum of aetiologies

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Identification of biomarkers in patients with rheumatoid arthritis responsive to DMARDs but with progressive bone erosion

IntroductionRheumatoid arthritis (RA) is an inflammatory autoimmune disease that may cause joint destruction and disability. The pharmacological treatment of RA aims at obtaining disease remission by effectively ceasing joint inflammation and arresting progressive bone erosions. Some patients present bone lesions accrual even after controlling joint inflammation with current therapies. Our study aimed to analyze lymphocyte subsets and levels of circulating cytokines in patients with RA with progressive bone erosions.MethodsWe enrolled 20 patients with a diagnosis of RA and 12 healthy donors (HD). Patients with RA were divided into patients with bone erosions (RA-BE+) and without bone erosions (RA-BE-). Lymphocyte subsets in peripheral blood were evaluated by flow cytometry. Circulating cytokines levels were evaluated by protein array.ResultsThe distribution of lymphocyte subsets was not able to separate HD from AR patients and RA-BE+ and RA-BE- in cluster analysis. We observed a significant expansion of CXCR5- PD1+ T peripheral helper cells (Tph cells) and a reduction in both total memory B cells and switched memory B cells in RA patients compared to HD. We observed an expansion in the frequency of total B cells in RA-BE+ patients compared to RA-BE- patients. Unsupervised hierarchical clustering analysis of 39 cytokines resulted in a fairly good separation of HD from RA patients but not of RA-BE+ patients from RA-BE- patients. RA-BE+ patients showed significantly higher levels of IL-11 and IL-17A than RA-BE- patients.ConclusionWe show that patients with progressive erosive disease are characterized by abnormalities in B cells and in cytokines with a proven role in bone reabsorption. Understanding the role played by B cells and the cytokine IL-11 and IL-17A in progressive erosive disease can help identify novel biomarkers of erosive disease and design treatment approaches aimed at halting joint damage in RA

Correction to: ABCA6 affects the malignancy of Ewing sarcoma cells via cholesterol-guided inhibition of the IGF1R/AKT/MDM2 axis

In this article an incorrect affiliation had inadvertently been added. The original article has been updated