Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.

The aim of our study was to investigate the role of the excised vaginal cuff length as a prognostic factor in terms of DFS and recurrence rate/site, in low-risk endometrial cancer (EC) patients. Moreover, we correlated the recurrence with the expression of L1CAM.

From March 2001 to November 2016, a retrospective data collection was conducted of women undergoing surgical treatment for low-risk EC according to ESMO-ESGO-ESTRO consensus guidelines. Patients were divided into three groups according to their vaginal cuff length V0 without vaginal cuff, V1 with a vaginal cuff shorter than 1.5 cm and V2 with a vaginal cuff longer than or equal to 1.5 cm.

344 patients were included in the study 100 in the V0 group, 179 in the V1 group and 65 in the V2 group. The total recurrence rate was 6.1% the number of patients with recurrence was 8 (8%), 10 (5.6%) and 3 (4.6%), in the V0, V1 and V2 group, respectively. No statistically significant difference was found in the recurrence rate among the three groups. Although the DFS was higher in the V2 group, the result was not significant. L1CAM was positive in 71.4% of recurrences and in 82% of the distant recurrences.

The rate of recurrence in patients with EC at low risk of recurrence does not decrease as the length of the vaginal cuff removed increases. Furthermore, the size of the removed vaginal cuff does not affect either the site of recurrence or the likelihood of survival.

The rate of recurrence in patients with EC at low risk of recurrence does not decrease as the length of the vaginal cuff removed increases. Furthermore, the size of the removed vaginal cuff does not affect either the site of recurrence or the likelihood of survival.Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30-39 chromosomes) and near-haploidy (24-29 chromosomes), with unique cytogenetic and mutational landscapes. Hypodiploid B-ALL with less then 40 chromosomes has an extremely poor outcome, with 5-year overall survival rates below 50% and 20% in childhood and adult B-ALL, respectively. Accordingly, this genetic feature represents an adverse prognostic factor in B-ALL and is associated with early relapse and therapy refractoriness. Notably, half of all patients with hypodiploid B-ALL with less then 40 chromosomes cases ultimately exhibit chromosome doubling of the hypodiploid clone, resulting in clones with 50-78 chromosomes. Doubled clones are often the major clones at diagnosis, leading to „masked hypodiploidy”, which is clinically challenging as patients can be erroneously classified as hyperdiploid B-ALL. Here, we summarize the main cytogenetic and molecular features of hypodiploid B-ALL subtypes, and provide a brief overview of the diagnostic methods, standard-of-care treatments and overall clinical outcome. Finally, we discuss molecular mechanisms that may underlie the origin and leukemogenic impact of hypodiploidy and may open new therapeutic avenues to improve survival rates in these patients.This article presents the protective measures put in place at the „Institut de Cancérologie des Hospices de Lyon” (IC-HCL) during the first wave of the COVID-19 pandemic in France (spring 2020) and how they impacted IC-HCL clinical activity. Spring 2020 activities were compared to winter 2019-2020. Results showed a decrease of activity of 9% for treatment dispensations, 17% for multidisciplinary team meetings, 20% for head and neck and thoracic surgeries, and 58% for new patient enrolment in clinical trials. Characteristics of patients treated for solid cancer and hospitalized for COVID-19 during spring 2020 were collected in a retrospective study. Mortality was attributed to COVID-19 for half of the cases, 82% being patients above 70 and 73% being stage IV. This is in concordance with current findings concluding that the risk of developing severe or critical symptoms of COVID-19 is correlated with factors co-occurring in cancer patients and not to the cancer condition per se. While a number of routines and treatment regimens were changed, there was no major decline in numbers of treatments conducted at the IC-HCL during the first wave of the COVID-19 pandemic that hit France between March and May 2020, except for clinical trials and some surgery activities.Multiple Myeloma (MM) is a genetically complex and heterogeneous hematological cancer that remains incurable despite the introduction of novel therapies in the clinic. Sadly, despite efforts spanning several decades, genomic analysis has failed to identify shared genetic aberrations that could be targeted in this disease. Seeking alternative strategies, various efforts have attempted to target and exploit non-oncogene addictions of MM cells, including, for example, proteasome inhibitors. The surprising finding that MM cells present rampant genomic instability has ignited concerted efforts to understand its origin and exploit it for therapeutic purposes. A credible hypothesis, supported by several lines of evidence, suggests that at the root of this phenotype there is intense replicative stress. Here, we review the current understanding of the role of replicative stress in eliciting genomic instability in MM and how MM cells rely on a single protein, Ataxia Telangiectasia-mutated and Rad3-related protein, ATR, to control and survive the ensuing, potentially fatal DNA damage. From this perspective, replicative stress per se represents not only an opportunity for MM cells to increase their evolutionary pool by increasing their genomic heterogeneity, but also a vulnerability that could be leveraged for therapeutic purposes to selectively target MM tumor cells.The oxygen-responsive hypoxia inducible factor (HIF)-1 promotes several steps of the metastatic cascade. A hypoxic gene signature is enriched in triple-negative breast cancers (TNBCs) and is correlated with poor patient survival. Inhibiting the HIF transcription factors with small molecules is challenging; therefore, we sought to identify genes downstream of HIF-1 that could be targeted to block invasion and metastasis. Creatine kinase brain isoform (CKB) was identified as a highly differentially expressed gene in a screen of HIF-1 wild type and knockout mammary tumor cells derived from a transgenic model of metastatic breast cancer. CKB is a cytosolic enzyme that reversibly catalyzes the phosphorylation of creatine, generating phosphocreatine (PCr) in the forward reaction, and regenerating ATP in the reverse reaction. Creatine kinase activity is inhibited by the creatine analog cyclocreatine (cCr). Loss- and gain-of-function genetic approaches were used in combination with cCr therapy to define the contribution of CKB expression or creatine kinase activity to cell proliferation, migration, invasion, and metastasis in ER-negative breast cancers. CKB was necessary for cell invasion in vitro and strongly promoted tumor growth and lung metastasis in vivo. Similarly, cyclocreatine therapy repressed cell migration, cell invasion, the formation of invadopodia and lung metastasis. Moreover, in common TNBC cell line models, the addition of cCr to conventional cytotoxic chemotherapy agents was either additive or synergistic to repress tumor cell growth.Proton MiniBeam Radiation Therapy (pMBRT) is a novel strategy that combines the benefits of minibeam radiation therapy with the more precise ballistics of protons to further optimize the dose distribution and reduce radiation side effects. The aim of this study is to investigate possible strategies to couple pMBRT with dipole magnetic fields to generate a converging minibeam pattern and increase the center-to-center distance between minibeams. Magnetic field optimization was performed so as to obtain the same transverse dose profile at the Bragg peak position as in a reference configuration with no magnetic field. Monte Carlo simulations reproducing realistic pencil beam scanning settings were used to compute the dose in a water phantom. We analyzed different minibeam generation techniques, such as the use of a static multislit collimator or a dynamic aperture, and different magnetic field positions, i.e., before or within the water phantom. The best results were obtained using a dynamic aperture coupled with a magnetic field within the water phantom. For a center-to-center distance increase from 4 mm to 6 mm, we obtained an increase of peak-to-valley dose ratio and decrease of valley dose above 50%. The results indicate that magnetic fields can be effectively used to improve the spatial modulation at shallow depth for enhanced healthy tissue sparing.Epithelial ovarian cancer (EOC) remains a highly-lethal gynecological malignancy, characterized by frequent recurrence, chemotherapy resistance and poor 5-year survival. Identifying novel predictive molecular markers remains an overdue challenge in the disease’s clinical management. Herein, in silico analysis of TCGA-OV highlighted the tRNA-derived internal fragment (i-tRF-GlyGCC) among the most abundant tRFs in ovarian tumors, while target prediction and gene ontology (GO) enrichment analysis predicted its implication in key biological processes. Thereafter, i-tRF-GlyGCC levels were quantified in a screening EOC (n = 98) and an institutionally-independent serous ovarian cancer (SOC) validation cohort (n = 100, OVCAD multicenter study). Disease progression and patient death were used as clinical endpoints for the survival analysis. Internal validation was performed by bootstrap analysis and the clinical net benefit was estimated by decision curve analysis. The analysis highlighted the significant association of i-tRF-GlyGCC with advanced FIGO stages, suboptimal debulking and most importantly, with early progression and poor overall survival of EOC patients. The OVCAD validation cohort corroborated the unfavorable predictive value of i-tRF-GlyGCC in EOC. Ultimately, evaluation of i-tRF-GlyGCC with the established/clinically used prognostic markers offered superior patient risk-stratification and enhanced clinical benefit in EOC prognosis. In conclusion, i-tRF-GlyGCC assessment could aid towards personalized prognosis and support precision medicine decisions in EOC.