On the significance of the different geometrical and dosimetric parameters in microbeam and minibeam radiation therapy a retrospective evaluation.

Introduction: Spatially Fractionated Radiation Therapy (SFRT) is an unconventional therapeutic approach with the potential to disrupt the classical paradigms of conventional radiation therapy. The high spatial dose modulation in SFRT is believed to activate distinct radiobiological mechanisms which lead to remarkable increases in normal tissue tolerance. To make optimal use of SFRT and its benefits, a deeper understanding of the biological response and its relationship with the complex dosimetric and geometric components of SFRT is essential.

The FLASH effect-an evaluation of preclinical studies of ultra-high dose rate radiotherapy.

FLASH radiotherapy (FLASH-RT) is a novel radiotherapy approach based on the use of ultra-high dose radiation to treat malignant cells. Although tumours can be reduced or eradicated using radiotherapy, toxicities induced by radiation can compromise healthy tissues. The FLASH effect is the observation that treatment delivered at an ultra-high dose rate is able to reduce adverse toxicities present at conventional dose rates.

The immune system prevents recurrence of transplanted but not autochthonous antigenic tumors after oncogene inactivation therapy.

Targeted oncogene inactivation by small molecule inhibitors can be very effective but tumor recurrence is a frequent problem in the clinic. Therapy by inactivation of the cancer-driving oncogene in transplanted tumors was shown to be augmented in the presence of T cells. However, these experiments did not take into account the long-term, usually tolerogenic, interaction of de novo malignancies with the immune system.

The tumour suppressor, miR-137, inhibits malignant melanoma migration by targetting the TBX3 transcription factor.

The transcription factor, TBX3, is a key driver of malignant melanoma and any drug that impacts its expression is likely to have an impact on the treatment of this highly aggressive and treatment resistant cancer. Replacement of miRNAs that target oncogenes has gained much attention as a therapy because it is anticipated to be effective with little side-effects since miRNAs are naturally occurring and often target large set of genes in the same oncogenic pathway. Here we show that miR-137 levels correlate inversely with TBX3 mRNA levels in a panel of melanoma cell lines and in a cohort of patients with primary melanoma.

New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis.

Molecular signatures specific to particular tumor types are required to design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used for drug development share such signatures. We developed similarity core analysis (SCA), a universal and unsupervised computational framework for extracting core molecular features common to tumors and cell lines.

Food-Nonfood Discrimination in Ancestral Vertebrates: Gamete Cannibalism and the Origin of the Adaptive Immune System.

Adaptive immunity is a complex system that appeared twice in vertebrates (in gnathostomes and in jawless fish) although it is not required for invertebrate defence. The adaptive immune system is tightly associated with self-non-self discrimination, and it is now clear that this interplay is not limited to the prevention of autoreactivity. Micro-organisms are usually considered for their pathogenicity or symbiotic ability, but, for most small metazoans, they mainly constitute food.

Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression.

Deregulation of signaling pathways that control differentiation, expansion and migration of neural crest-derived melanoblasts during normal development contributes also to melanoma progression and metastasis. Although several epithelial-to-mesenchymal (EMT) transcription factors, such as zinc finger E-box binding protein 1 (ZEB1) and ZEB2, have been implicated in neural crest cell biology, little is known about their role in melanocyte homeostasis and melanoma. Here we show that mice lacking Zeb2 in the melanocyte lineage exhibit a melanoblast migration defect and, unexpectedly, a severe melanocyte differentiation defect.