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The sphingolipid sphingosine-1-phosphate (S1P) promotes tumor development through a variety of mechanisms including promoting proliferation, survival, and migration of cancer cells. Moreover, S1P emerged as an important regulator of tumor microenvironmental cell function by modulating, among other mechanisms, tumor angiogenesis. Therefore, S1P was proposed as a target for anti-tumor therapy. The clinical success of current cancer immunotherapy suggests that future anti-tumor therapy needs to consider its impact on the tumor-associated immune system. Hereby, S1P may have divergent effects. On the one hand, S1P gradients control leukocyte trafficking throughout the body, which is clinically exploited to suppress auto-immune reactions. On the other hand, S1P promotes pro-tumor activation of a diverse range of immune cells. In this review, we summarize the current literature describing the role of S1P in tumor-associated immunity, and we discuss strategies for how to target S1P for anti-tumor therapy without causing immune paralysis.
MicroRNAs have been projected as promising tools for diagnostic and prognostic purposes in cancer. More recently, they have been highlighted as RNA therapeutic targets for cancer therapy. Though miRs perform a generic function of post-transcriptional gene regulation, their utility in RNA therapeutics mostly relies on their biochemical nature and their assembly with other macromolecules. Release of extracellular miRs is broadly categorized into two different compositions, namely exosomal (extracellular vesicles) and non-exosomal. This nature of miRs not only affects the uptake into target cells but also poses a challenge and opportunity for RNA therapeutics in cancer. By virtue of their ability to act as mediators of intercellular communication in the tumor microenvironment, extracellular miRs perform both, depending upon the target cell and target landscape, pro- and anti-tumor functions. Tumor-derived miRs mostly perform pro-tumor functions, whereas host cell- or stroma-derived miRs are involved in anti-tumor activities. This review deals with the recent understanding of exosomal and non-exosomal miRs in the tumor microenvironment, as a tool for pro- and anti-tumor activity and prospective exploit options for cancer therapy.
Objective: Our aim was to explore whether general practitioners (GPs) communicate with cancer patients on complementary and integrative medicine (CIM) in a patient-centred and case-specific manner.
Methods: We designed two cases of standardised breast cancer patients and allocated 29 GPs to hold a consultation either with Case 1 or Case 2. Case 1 presented with fears of possible physical side effects of hormone treatment. Case 2 feared a loss in social functioning because of nausea and emesis as possible side effects of chemotherapy. Consultations were audiotaped and analysed using the Roter Interaction Analysis System (RIAS). We analysed whether recommended CIM treatments and GPs' focus on psychosocial or medical and therapy-related content differed according to whether they were counselling Case 1 or Case 2.
Results: In consultations with Case 1, GPs rather focused on medical and therapy-related content and most often recommended mistletoe, diets and sports. In contrast, GPs focused on psychosocial content and they most often recommended methods of self-care when counselling Case 2.
Conclusion: The GPs in our sample reacted case-specifically to the patients' interest in CIM. Such responsive and patient-centred communication is a valuable resource but is often time-consuming. Adequate training and reimbursement should therefore be considered for GPs.
Whereas the clinical approach in pediatric cancer patients with febrile neutropenia is well established, data on non-neutropenic infectious episodes are limited. We therefore prospectively collected over a period of 4 years of data on all infectious complications in children treated for acute lymphoblastic or myeloid leukemia (ALL or AML) and non-Hodgkin lymphoma (NHL) at two major pediatric cancer centers. Infections were categorized as fever of unknown origin (FUO), and microbiologically or clinically documented infections. A total of 210 patients (median age 6 years; 142 ALL, 23 AML, 38 NHL, 7 leukemia relapse) experienced a total of 776 infectious episodes (571 during neutropenia, 205 without neutropenia). The distribution of FUO, microbiologically and clinically documented infections, did not significantly differ between neutropenic and non-neutropenic episodes. In contrast to neutropenic patients, corticosteroids did not have an impact on the infectious risk in non-neutropenic children. All but one bloodstream infection in non-neutropenic patients were due to Gram-positive pathogens. Three patients died in the context of non-neutropenic infectious episodes (mortality 1.4%). Our results well help to inform clinical practice guidelines in pediatric non-neutropenic cancer patients presenting with fever, in their attempt to safely restrict broad-spectrum antibiotics and improve the quality of life by decreasing hospitalization.