Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Background Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. Methods In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). Results In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). Conclusion In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression

Exploration of patterns in different contexts

International audienceAs part of a research project focusing on investigative approaches to mathematics, a teacher in a Sámi school created an interdisciplinary teaching unit about patterns: skiing- mathematics- Sámi language. The 1–2 grade students painted their own patterns and they created patterns using their skis and poles in the snow. The analysis shows that the students developed their rules for what constitutes a pattern when the context changed from classroom work to skis on snow. One more aspect of pattern is focused: Sámi languages do not use any overarching term for pattern. At least three words are needed to cover the meaning of pattern in the mathematics curriculum

Exploration of patterns in different contexts

International audienceAs part of a research project focusing on investigative approaches to mathematics, a teacher in a Sámi school created an interdisciplinary teaching unit about patterns: skiing- mathematics- Sámi language. The 1–2 grade students painted their own patterns and they created patterns using their skis and poles in the snow. The analysis shows that the students developed their rules for what constitutes a pattern when the context changed from classroom work to skis on snow. One more aspect of pattern is focused: Sámi languages do not use any overarching term for pattern. At least three words are needed to cover the meaning of pattern in the mathematics curriculum

TINF2 is a major susceptibility gene in Danish patients with multiple primary melanoma

Summary: TINF2 encodes the TINF2 protein, which is a subunit in the shelterin complex critical for telomere regulation. Three recent studies have associated six truncating germline variants in TINF2 that have previously been associated with a cancer predisposition syndrome (CPS) caused by elongation of the telomeres. This has added TINF2 to the long telomere syndrome genes, together with other telomere maintenance genes such as ACD, POT1, TERF2IP, and TERT.We report a clinical study of 102 Danish patients with multiple primary melanoma (MPM) in which a germline truncating variant in TINF2 (p.(Arg265Ter)) was identified in four unrelated participants. The telomere lengths of three variant carriers were >90% percentile. In a routine diagnostic setting, the variant was identified in two more families, including an additional MPM patient and monozygotic twins with thyroid cancer and other cancer types. A total of 10 individuals from six independent families were confirmed carriers, all with cancer history, predominantly melanoma. Our findings suggest a major role of TINF2 in Danish patients with MPM.In addition to melanoma, other cancers in the six families include thyroid, renal, breast, and sarcoma, supporting a CPS in which melanoma, thyroid cancer, and sarcoma predominate. Further studies are needed to establish the full spectrum of associated cancer types and characterize lifetime cancer risk in carriers