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Breast cancer patients are commonly treated with sequential administrations of epirubicin–cyclophosphamide (EC) and paclitaxel (TAX). The chronic effect of this treatment induces skeletal muscle alterations, but the specific effect of each chemotherapy agent is unknown. This study aimed to investigate the effect of EC or TAX administration on skeletal muscle homeostasis in breast cancer patients. Twenty early breast cancer patients undergoing EC followed by TAX chemotherapies were included. Two groups of 10 women were established and performed vastus lateralisskeletal muscle biopsies either before the first administration (pre) of EC (50 ± 14 years) or TAX (50 ± 16 years) and 4 days later (post). Mitochondrial respiratory capacity recording, reactive oxygen species production, western blotting and histological analyses were performed. Decrease in muscle fibres cross‐sectional area was only observed post‐EC (−25%; P< 0.001), associated with a reduction in mitochondrial respiratory capacity for the complex I (CI)‐linked substrate state (−32%; P= 0.001), oxidative phosphorylation (OXPHOS) by CI (−35%; P= 0.002), CI&CII (−26%; P= 0.022) and CII (−24%; P= 0.027). If H2O2production was unchanged post‐EC, an increase was observed post‐TAX for OXPHOS by CII (+25%; P= 0.022). We found a decrease in makers of mitochondrial content, as shown post‐EC by a decrease in the protein levels of citrate synthase (−53%; P< 0.001) and VDAC (−39%; P< 0.001). Despite no changes in markers of mitochondrial fission, a decrease in the expression of a marker of mitochondrial inner‐membrane fusion was found post‐EC (OPA1; −60%; P< 0.001). We explored markers of mitophagy and found reductions post‐EC in the protein levels of PINK1 (−63%; P< 0.001) and Parkin (−56%; P= 0.005), without changes post‐TAX. An increasing trend in Bax protein level was found post‐EC (+96%; P= 0.068) and post‐TAX (+77%; P= 0.073), while the Bcl‐2 level was decreased only post‐EC (−52%; P= 0.007). If an increasing trend in TUNEL‐positive signal was observed post‐EC (+68%; P= 0.082), upregulation was highlighted post‐TAX (+86%; P< 0.001), suggesting activation of the apoptosis process. We demonstrated that a single administration of EC induced, in only 4 days, skeletal muscle atrophy and mitochondrial alterations in breast cancer patients. These alterations were characterized by reductions in mitochondrial function and content as well as impairment of mitochondrial dynamics and an increase in apoptosis. TAX administration did not worsen these alterations as this group had already received EC during the preceding weeks. However, it resulted in an increased apoptosis, likely in response to the increased H2O2production.

Chemotherapy is extensively used to treat breast cancer and is associated with skeletal muscle deconditioning, which is known to reduce patients' quality of life, treatment efficiency, and overall survival. To date, skeletal muscle mitochondrial alterations represent a major aspect explored in breast cancer patients; nevertheless, the cellular mechanisms remain relatively unknown. This study was dedicated to investigating overall skeletal muscle mitochondrial homeostasis in early breast cancer patients undergoing chemotherapy, including mitochondrial quantity, function, and dynamics. Women undergoing (neo)adjuvant anthracycline‐cyclophosphamide and taxane‐based chemotherapy participated in this study (56 ± 12 years). Two muscle biopsies were collected from the vastus lateralis muscle before the first and after the last chemotherapy administration. Mitochondrial respiratory capacity, reactive oxygen species production, and western blotting analyses were performed. Among the 11 patients, we found a decrease in key markers of mitochondrial quantity, reaching −52.0% for citrate synthase protein levels (P= 0.02) and −38.2% for VDAC protein levels (P= 0.04). This mitochondrial content loss is likely explained by reduced mitochondrial biogenesis, as evidenced by a decrease in PGC‐1α1 protein levels (−29.5%; P= 0.04). Mitochondrial dynamics were altered, as documented by a decrease in MFN2 protein expression (−33.4%; P= 0.01), a key marker of mitochondrial outer membrane fusion. Mitochondrial fission is a prerequisite for mitophagy activation, and no variation was found in either key markers of mitochondrial fission (Fis1 and DRP1) or mitophagy (Parkin, PINK1, and Mul1). Two contradictory hypotheses arise from these results: defective mitophagy, which probably increases the number of damaged and fragmented mitochondria, or a relative increase in mitophagy through elevated mitophagic potential (Parkin/VDAC ratio; +176.4%; P< 0.02). Despite no change in mitochondrial respiratory capacity and COX IV protein levels, we found an elevation in H2O2production (P< 0.05 for all substrate additions) without change in antioxidant enzymes. We investigated the apoptosis pathway and found an increase in the protein expression of the apoptosis initiation marker Bax (+72.0%; P= 0.04), without variation in the anti‐apoptotic protein Bcl‐2. This study demonstrated major mitochondrial alterations subsequent to chemotherapy in early breast cancer patients: (i) a striking reduction in mitochondrial biogenesis, (ii) altered mitochondrial dynamics and potential mitophagy defects, (iii) exacerbated H2O2production, and (iv) increased initiation of apoptosis. All of these alterations likely explain, at least in part, the high prevalence of skeletal muscle and cardiorespiratory deconditioning classically observed in breast cancer patients.

Genomic profiling is a major component for first-line treatment decisions in patients with NSCLC and the timeliness of biomarker testing is essential to improve time to treatment initiation (TTI) or avoid inappropriate treatment.

Combined treatment with anti-PD-1 and anti-CTLA-4 antibodies has shown superiority over chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC), but data for older patients (aged ≥70 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 or those with an ECOG performance status of 2 are scarce. We aimed to test the superiority of the PD-1 antibody nivolumab and the CTLA-4 antibody ipilimumab over platinum-based doublet chemotherapy as first-line treatment in patients with NSCLC aged 70 years or older or with an ECOG performance status of 2.

Grâce à un accès de plus en plus facile aujourd’hui à Internet, le patient porteur d’un cancer bronchique et ses proches peuvent y chercher des informations et s’y exprimer.

High grade gliomas (HGG) are usually associated with a very dismal prognosis, which was moderately improving in the last decade with the introduction of the alkylating agent temozolomide in their treatment. The methylation status of MGMT (O6 methylguanine DNA-methyltransferase) promoter is one of the strongest predictive and prognostic factors for the patient chemoresponse. For instance, the molecular method of assessment for MGMT promoter status is not standardized. In this background, we developed a fluorescent capillary gel electrophoresis-based methylation specific-PCR. This technique allowed a semi-quantitative estimate of the relative ratio between methylated and unmethylated alleles. The efficacy and accuracy of the technique was assessed in a retrospective cohort of 178 newly diagnosed adult HGGs, who were homogeneously treated. First, we analyzed the impact on survival of different cut-off points in the MGMT promoter methylation and, to go further, we correlated these different rates to other well-known prognostic molecular factors involved in adult HGGs. This strategy allowed to validate our technique as a very sensitive technique (detection of a low methylation percentage, < 5%), which was feasible in fresh-frozen as well as in FFPE samples and had the propensity to detect intra-tumor heterogeneity. This technique identified a new sub-group of anaplastic oligodendrogliomas or oligoastrocytomas defined by a minor methylation and a worse outcome and, therefore, will help to substratify accurately into more homogeneous subgroups of methylated tumors.

Background: Glioblastoma invariably recurs after primary Stupp tumor therapy and portends a poor prognosis. Cryoablation is a well-established treatment strategy for extra-cranial tumors. The safety and efficacy of interventional MR-guided cryoablation (iMRgC) has not been explored in recurrent glioblastoma.

Pulmonary hypertension at the end stage of chronic liver disease is not an uncommon situation. This association termed portopulmonary hypertension raises the question of the feasibility of performing orthotopic liver transplantation (OLT). In the case reported herein, there was a favorable outcome after OLT, even though the mean pulmonary artery pressure (MPAP) before transplantation was increased to 45 mm Hg. Before OLT, the cardiac index (CI) was considerably elevated (7.69 L/min/m2), giving evidence of a marked hyperdynamic circulatory state. The CI decreased significantly after OLT (3.38 L/min/m2), and this produced a significant decrease in the MPAP. Our observation suggests that portopulmonary hypertension due to a marked increase in the CI can be managed successfully by OLT.