Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: A cohort study from the European paediatric Soft tissue sarcoma Study Group

Background

Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.

Methods

This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.

Results

The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.

Conclusions

The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.

Plain Language Summary

• Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors.
• Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases.
• This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.

     

Topical Treatment of Oral Mucositis in Cancer Patients: A Systematic Review of Randomized Clinical Trials

Background and Purpose: Evidence-based protocols of topical therapy for oral mucositis (OM) induced by chemoradiotherapy (CRT) are continuously established and updated. Thus, the present systematic review aims to evaluate the scientific literature in terms of effectiveness of topical treatment of OM in cancer patients undergoing CRT.  Materials and Methods: This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist. Randomized clinical trials were identified through electronic database searches on CINAHL, Cochrane Library, LILACS, Livivo, PubMed, SCOPUS, and Web of Science. Grey literature was also assessed on Google Scholar, Open Grey, and ProQuest. The risk of bias in the included studies was assessed by the Cochrane Collaboration Risk of Bias Tool. Results: Twenty-three randomized clinical trials (n=1169 patients) met the inclusion criteria. Twenty-three different topical agents were examined and categorized into five groups: analgesics (30.4%), natural agents (21.7%), other topical agents (21.7%), antimicrobial agents (17.4%), and growth factors (8.8%). Of the included studies, 50% presented a resolution of OM within 14 days. Topical natural agents yielded good results with average resolution time of 3–7 days. The included studies generally demonstrated that patients treated with mouthwashes presented superior benefits compared to the control, depending on OM severity. Conclusion: Topical agents effectively reduced the severity of OM lesions and pain intensity in patients receiving chemoradiotherapy, although the effects varied by agent type. However, the heterogeneity in the results of these topical intervention studies underscores the need for standardized clinical trial methodologies. Clinical Relevance: Topical agents were effective in patients with severe OM lesions receiving chemoradiotherapy and are a good alternative of home care in relation to pain control, reduction of inflammation and consequent improvement in quality of life.     

Arginase and its mechanisms in Leishmania persistence

Leishmaniasis is a neglected infectious disease with clinical presentations ranging from asymptomatic or mild symptoms to chronic infection and eventual death. The mechanisms of disease susceptibility and pathology have been extensively studied, but there are no steadfast rules regarding leishmaniasis. A Th1 response is usually associated with infection control, while a predominant Th2 response is detrimental to the patient. In this scenario, the enzymes arginase and inducible nitric oxide synthase represent two possible pathways of immune response. While the former contributes to parasite replication, the latter is crucial for its control. In the present review, we collected study results that associate arginase expression in patients and in experimental models with disease susceptibility/chronicity and show some proposed mechanisms that explain the role of arginase in maintaining Leishmania infection, including polyamine and thiol synthesis, tissue-resident macrophage (TRM) proliferation and activation and T-cell suppression and exhaustion.     

Antimicrobial and antileukemic effects: in vitro activity of Calyptranthes grandifolia aqueous leaf extract

ABSTRACT

Natural products are still a promising source of bioactive molecules. Food and Drug Administration data showed that approximately 49% of the approved molecules originate naturally or chemically-resemble these substances, of which more than 70% are being used in anticancer therapy. It is noteworthy that at present there are no scientific studies to prove the effectiveness and safety of a number of plants used in folk medicine such as in the case of Calyptranthes grandifolia O. Berg (Myrtaceae) originally from South America. The aim of the present study was to determine the biological potential and toxicological effects of the aqueous leaf extract of C. grandifolia. The main detected phytoconstituents were condensed tannins and flavonoids and a high quantity of polyphenols. Regarding the antimicrobial potential, the extract exerted inhibitory activity against Pseudomonas aeruginosa. The results also revealed the extract induced DNA damage in a concentration-dependent manner in RAW 264.7 cells. In addition, C. grandifolia produced cytotoxicity in leukemia cell lines (HL60 and Kasumi-1) without affecting isolated human lymphocytes but significantly inhibited JAK3 and p38α enzyme activity. Taken together, these findings add important information on the biological and toxicological effects of C. grandifolia, indicating that aqueous extract may be a source of natural antimicrobial and antileukemic constituents.