0000000000451080
AUTHOR
Sylvain Ladoire
Les cancers du rein non à cellules claires : caractéristiques clinico-biologiques et prise en charge thérapeutique hors chirurgie
Resume Les cancers du rein non a cellules claires representent pres de 25 % de l’ensemble des cancers du rein, et constituent un groupe de tumeurs tres heterogenes a la fois en termes de varietes histologiques, mais egalement d’anomalies biologiques oncogeniques. La presentation clinique ainsi que le pronostic des patients sont egalement tres variables. Compte tenu de la rarete de chaque entite tumorale, il n’existe que tres peu d’essais cliniques ayant porte sur une variete bien definie de cancer non a cellules claires. Ceci rend difficile l’interpretation de ces etudes, et donc l’emission de recommandations claires de prise en charge medicale pour la maladie avancee. Dans cet article, les…
Population Pharmacokinetics of Palbociclib in aReal-World Situation
Palbociclib is an oral cyclin-dependent kinase inhibitor that is used in combination with aromatase inhibitors in the treatment of postmenopausal women with metastatic breast cancer. Its metabolism profile is associated with an important interpatient variability. We performed a population pharmacokinetics study of palbociclib in women routinely followed in a cancer center. One hundred and fifty-one samples were analyzed. The sampling times after administration ranged from 0.9 to 75 h and the samples were taken between 1 and 21 days after the beginning of the palbociclib cycle. Palbociclib was determined using a validated mass spectrometry method. The best model that described the concentrat…
Bevacizumab efficacy in metastatic colorectal cancer is dependent on primary tumor resection.
Purpose Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis. Methods We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the infl…
Effect of obesity on disease-free and overall survival in node-positive breast cancer patients in a large French population: A pooled analysis of two randomised trials
Abstract Background To examine the association between baseline body mass index (BMI), and disease-free survival (DFS) and overall survival (OS) in a large French early-stage breast cancer population included in the UNICANCER Programme d’Action Concerte Sein-01 (PACS01) and PACS04 phase III randomised trials. Methods After a median follow-up of 5.9 years, this report analyses 4996 patients with node-positive breast cancer, and randomly assigned to adjuvant anthracycline-based chemotherapy combined or not with taxanes. Univariate analyses were used to study the effects of well known prognostic factors and BMI on DFS and OS. BMI was obtained at baseline, before chemotherapy initiation, and ob…
Radical cystectomy or bladder preservation with radiochemotherapy in elderly patients with muscle-invasive bladder cancer: Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators.
IF 3.156; International audience; Background: Radical cystectomy (RC) and radiochemotherapy (RCT) are curative options for muscle-invasive bladder cancer (MIBC). Optimal treatment strategy remains unclear in elderly patients.Material and methods: Patients aged 80 years old and above with T2-T4aN0-2M0-Mx MIBC were identified in the Retrospective International Study of Cancers of the Urothelial Tract (RISC) database. Patients treated with RC were compared with those treated with RCT. The impact of surgery on overall survival (OS) was assessed using a Cox proportional hazard model. Progression included locoregional and metastatic relapse and was considered a time-dependent variable.Results: Be…
Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression
International audience; Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-β expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-β-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to thei…
Pharmacokinetic/Pharmacodynamic Model of Neutropenia in Real-Life Palbociclib-Treated Patients
Palbociclib is an oral CDK4/6 inhibitor indicated in HR+/HER2- advanced or metastatic breast cancer in combination with hormonotherapy. Its main toxicity is neutropenia. The aim of our study was to describe the kinetics of circulating neutrophils from real-life palbociclib-treated patients. A population pharmacokinetic (popPK) model was first constructed to describe palbociclib pharmacokinetic (PK). Individual PK parameters obtained were then used in the pharmacokinetic/pharmacodynamic (PK/PD) model to depict the relation between palbociclib concentrations and absolute neutrophil counts (ANC). The models were built with a population of 143 patients. Palbociclib samples were routinely collec…
Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients
International audience; Tumor-infiltrating T and B lymphocytes could have the potential to affect cancer prognosis. The objective of this study was to investigate the prognostic significance of tumor infiltration by CD8 and CD4 T cells, and B lymphocytes in patients with localized gastric cancer. In a retrospective cohort of 82 patients with localized gastric cancer and treated by surgery we quantitatively assessed by immunohistochemistry on surgical specimen, immune infiltrates of IL-17(+), CD8(+), Foxp3(+), Tbet(+) T cells and CD20(+) B cells both in the tumor core and at the invasive margin via immunohistochemical analyses of surgical specimens. We observed that CD8(+) and IL17(+) T-cell…
The Khorana Score in Predicting Venous Thromboembolism for Patients With Metastatic Urothelial Carcinoma and Variant Histology Treated With Chemotherapy
Background: The Khorana score is a predictive risk model for venous thromboembolism (VTE) in patients with cancer planning to receive chemotherapy. Urothelial carcinoma and variant histologies (UC/VH) were underrepresented in the model. We sought to evaluate whether the Khorana score predicts for VTE in a retrospective multinational data set of patients with metastatic UC/VH. Methods: Patients diagnosed with metastatic UC/VH who received chemotherapy were eligible. Those with incomplete or miscoded data were excluded. Khorana scores were calculated based on the pretreatment data and categorized into high (≥3) or intermediate (1-2) VTE risk. Other patient-, tumor-, and therapy-related factor…
Semi-ResMass Study: Residual masses after salvage chemotherapy in men with pure seminoma—A multicenter retrospective analysis.
420 Background: Only scarce data exist on the management of residual masses in men who have received two lines of chemotherapy for advanced seminoma. Due to the lack of data, the role of PET scanning, surgery and other additional treatments is controversial in these men. Methods: Data from men with pure seminoma and residual masses after salvage chemotherapy were retrospectively collected from 10 high-volume centers in 3 European countries. We analyzed the clinical management of residual masses (imaging, surgery, pathological data, and additional treatment modalities) and long-term outcomes. Residual mass was defined as a lesion of ≥1 cm after two lines of platin-based chemotherapy. Result…
Etude LYMPHOREC. Réponse immunitaire intra-tumorale à la radiothérapie préopératoire pour des cancers du rectum de stades II-III: nouveau paramètre pronostic de la survie des patients
National audience
Venous thromboembolism in metastatic urothelial carcinoma or variant histologies: incidence, associative factors, and effect on survival.
Venous thromboembolism (VTE) is common in cancer patients. However, little is known about VTE risk in metastatic urothelial carcinoma or variant histologies (UC/VH). We sought to characterize the incidence, associative factors, including whether various chemotherapy regimens portend different risk, and impact of VTE on survival in metastatic UC/VH patients. Patients diagnosed with metastatic UC/VH from 2000 to 2013 were included in this multicenter retrospective, international study from 29 academic institutions. Cumulative and 6-month VTE incidence rates were determined. The association of first-line chemotherapy (divided into six groups) and other baseline characteristics on VTE were anal…
Human FOXP3 and cancer.
FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but FOXP3 can also be transiently expressed in T-cell antigen receptor-activated human nonregulatory T cells. Recent data indicate that FOXP3 is also expressed by some nonlymphoid cells, in which it can repress various oncogenes that are restored following FOXP3 deletion or mutation. This review summarizes major advances in (1) the understanding of Foxp3 functions in human regulatory T cells, (2) the prognostic significance of Foxp3-expressing T cells in human malignancies and (3) the signifi…
SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth.
Abstract Activation of the transcription factor PPARγ by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARγ are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARγ. SOCS3 promoter binding and gene transactivation by PPARγ was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARγ by DHA. Furthermore, naïve CD4…
Tendances de prescription de l’hormonothérapie et survie chez les femmes atteintes d’un cancer du sein non métastatique à récepteurs hormonaux positifs traitées par hormonothérapie - Étude sur base de données populationnelle
Introduction La plupart des donnees sur l’efficacite de l’hormonotherapie proviennent d’essais cliniques randomises. Peu ou moins de donnees existent sur l’efficacite de l’hormonotherapie en vie reelle et sa prescription au cours du temps. Cette etude avait pour objectif d’identifier les facteurs pronostiques de la survie chez les femmes atteintes d’un cancer du sein non metastatique a recepteurs hormonaux positifs (RH +). Methodes Une etude observationnelle retrospective a ete realisee a partir du Registre des cancers du sein et autres cancers gynecologiques de Cote d’Or en France. Toutes les femmes ayant recu un diagnostic de cancer du sein RH + invasif primaire non metastatique entre 199…
Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?
Recent clinical trials revealed the impressive efficacy of immunological checkpoint blockade in different types of metastatic cancers. Such data underscore that immunotherapy is one of the most promising strategies for cancer treatment. In addition, preclinical studies provide evidence that some cytotoxic drugs have the ability to stimulate the immune system, resulting in anti-tumor immune responses that contribute to clinical efficacy of these agents. These observations raise the hypothesis that the next step for cancer treatment is the combination of cytotoxic agents and immunotherapies. The present review aims to summarize the immune-mediated effects of chemotherapeutic agents and their …
Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.
Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma (TN-IDC) and hormone receptor-positive invasive lobular carcinoma (HR + ILC). All primary TN-ILCs registered in our database between 2000 and 2018 (n = 38) were compared to tumors from control groups, matched by stage and Elston/Ellis grade, with regard to clinical, pathologic, and immunohistochemical characteristics. A comparative molecular analy…
Analyse des infiltrats immunitaires CD3 et CD8 chez 1280 malades atteints de cancers coliques de stade III : approche par intelligence artificielle entièrement automatisée
L’etude retrospective de tumeurs par immunohistochimie constitue un enjeu majeur dans l’amelioration de la prise en charge atteints de pathologies cancereuses. Cependant l’analyse est chronophage pour le pathologiste et reste le plus souvent semi-quantitative pouvant entrainer une perte d’information. L’intelligence artificielle, qui consiste en une approche d’analyse automatisee a haut debit, pourrait permettre de s’affranchir dans ce contexte du pathologiste en apportant de plus une information quantitative. Nous avons ainsi etudie deux parametres immunitaires, CD3 et CD8 sur 1280 lames de malades de la cohorte PETACC8 [1] , une etude europeenne de patients atteints de cancers coliques de…
Bleomycin Exerts Ambivalent Antitumor Immune Effect by Triggering Both Immunogenic Cell Death and Proliferation of Regulatory T Cells
International audience; Bleomycin (BLM) is an anticancer drug currently used for the treatment of testis cancer and Hodgkin lymphoma. This drug triggers cancer cell death via its capacity to generate radical oxygen species (ROS). However, the putative contribution of anticancer immune responses to the efficacy of BLM has not been evaluated. We make here the observation that BLM induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surface exposure of chaperones, including calreticulin and ERp57, and liberation of HMBG1 and ATP. BLM induces anti-tumor immunity which relies on calreticulin, CD8(+) T cells and inte…
Human ectonucleotidase-expressing CD25 high Th17 cells accumulate in breast cancer tumors and exert immunosuppressive functions
IF 7.644; International audience; Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25(high) Th17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4(+) and CD8(+) T cell activation. These cells expressed both Ror gamma t and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-beta and IL-6. Finally, immunohistochemical …
Accumulation of MDSC and Th17 Cells in Patients with Metastatic Colorectal Cancer Predicts the Efficacy of a FOLFOX-Bevacizumab Drug Treatment Regimen
Abstract Host immunity controls the development of colorectal cancer, and chemotherapy used to treat colorectal cancer is likely to recruit the host immune system at some level. Athough preclinical studies have argued that colorectal cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin, exert such effects, their combination as employed in the oncology clinic has not been evaluated. Here, we report the results of prospective immunomonitoring of 25 metastatic colorectal cancer (mCRC) patients treated with a first-line combination regimen of 5-FU, oxaliplatin, and bevacizumab (FOLFOX–bevacizumab), as compared with 20 healthy volunteers. Before this therapy was initiated, T regulatory ce…
La réponse immunitaire anti-tumorale dans le cancer du sein : état des lieux et perspectives thérapeutiques
The role of the immune response in breast cancer is now well recognized and increasingly taken in account. The goal of this article is, in the first part, to underline its prognostic impact and to precise the immunosurvelliance, immunoselection and the immunosubversion concepts involved in the control and evasion of breast carcinoma. In the second part, therapeutic strategies for the restauration of anti-tumor immunity are developed. Vaccination strategies and checkpoints inhibitors blockade strategies are discussed as well as the immunogenic death linked to the conventional treatments of breast cancer.
Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
IF 5.008; International audience; Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred and twenty eight patients diagnosed with advanced colorectal cancer with a KRAS and NRAS unmutated tumor. These patients were treated with cetuximab or panitumumab alone or with chemotherapy as second or third-line. Univariate and multivariate Cox model analysis were performed to estimate the effect of a previous bevacizumab regimen on progression free survival a…
Stratégies en cas de positivité du ganglion sentinelle dans les cancers du sein
Resume Les strategies de prise en charge en cas de ganglion(s) sentinelle(s) micro ou macrometastatique(s) dans les cancers du sein ont ete profondement modifiees depuis une dizaine d’annees et la publication de cinq essais randomises : ACOSOG Z0011, IBCSG 23-01, et AATRM comparant curage axillaire versus abstention ; et AMAROS et OTOASOR comparant curage axillaire versus radiotherapie axillaire. Malgre les limites methodologiques de certains de ces essais, notamment de l’ACOSOG Z0011, les recommandations internationales (ASCO, NCCN) et le consensus d’experts de St Gallen ne preconisent pas la realisation d’un curage axillaire complementaire en cas d’envahissement macro ou micrometastatique…
Liver X Receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization
Increasing evidence indicates that Liver X Receptors (LXRs) have some anticancer properties. We recently demonstrated that LXR ligands induce colon cancer cell pyroptosis through an LXRβ-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXRβ. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXRβ with the truncated form of RXRα (t-RXRα) was responsible for the sequestration of LXRβ in the cytoplasm in colon cancer cells. Moreover t-RXRα was not expressed in normal colon epithelial cells. These cells presented a predominantl…
Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents.
Abstract Purpose. A better identification of patients who are more likely to benefit from vascular endothelial growth factor–targeted therapy is warranted in metastatic renal cell carcinoma (mRCC). As adipose tissue releases angiogenic factors, we determined whether parameters such as visceral fat area (VFA) were associated with outcome in these patients. Experimental Design. In 113 patients with mRCC who received antiangiogenic agents (bevacizumab, sunitinib, or sorafenib) (n = 64) or cytokines (n = 49) as first-line treatment, we used computed tomography to measure VFA and subcutaneous fat area (SFA). We evaluated associations linking body mass index (BMI), SFA, and VFA to time to progres…
Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study
IF 7.719; International audience; Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impa…
Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer
Background: Trimodality bladder preservation therapy (BPT) in muscle invasive bladder cancer (MIBC) includes a maximal transurethral resection followed by concurrent chemoradiotherapy as an alternative to radical cystectomy (RC) in appropriately selected patients, or as a treatment option in non-cystectomy candidates. Several chemotherapy regimens can be used in BPT, but little is known about current practice patterns. Objective: To describe utilization patterns of BPT and associated survival outcomes in MIBC. Methods: Data were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3,024 consecutive patients from 29 international acade…
Impact of the Prone Position in an Animal Model of Unilateral Bacterial Pneumonia Undergoing Mechanical Ventilation
Abstract Background: The prone position (PP) has proven beneficial in patients with severe lung injury subjected to mechanical ventilation (MV), especially in those with lobar involvement. We assessed the impact of PP on unilateral pneumonia in rabbits subjected to MV. Methods: After endobronchial challenge with Enterobacter aerogenes, adult rabbits were subjected to either “adverse” (peak inspiratory pressure = 30 cm H2O, zero end-expiratory pressure; n = 10) or “protective” (tidal volume = 8 ml/kg, 5 cm H2O positive end-expiratory pressure; n = 10) MV and then randomly kept supine or turned to the PP. Pneumonia was assessed 8 h later. Data are presented as median (interquartile range). Re…
5-Fluorouracil Selectively Kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor Immunity
AbstractMyeloid-derived suppressor cells (MDSC) accumulate in the spleen and tumor bed during tumor growth. They contribute to the immune tolerance of cancer notably by inhibiting the function of CD8(+) T cells. Thus, their elimination may hamper tumor growth by enhancing antitumor T-cell functions. We have previously reported that some anticancer agents relied on T cell–dependent anticancer responses to achieve maximal efficacy. However, the effect of anticancer agents on MDSC has remained largely unexplored. In this study, we observed that gemcitabine and 5-fluorouracil (5FU) were selectively cytotoxic on MDSC. In vivo, the treatment of tumor-bearing mice with 5FU led to a major decrease …
Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort
Summary Purpose In the ACOSOG Z0011 trial, patients with primary breast cancer and 1–2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The ai…
Venous Thromboembolism Risk in Patients With Locoregional Urothelial Tract Tumors
Data de publicació electrónica: 24-08-2017 BACKGROUND: Venous thromboembolism (VTE) is common in cancer patients, but there is limited data on patients with urothelial tract tumors (UTT). We previously identified several associative factors for increased VTE rates in patients with metastatic UTT. In this study, we assessed the frequency, associative factors, and impact on survival of VTE in patients with locoregional UTT. METHODS: Patients with locoregional bladder, upper urinary tract, or urethral cancer were included in this multi-center study from 29 academic institutions. Patients with N1, or M1 disease at diagnosis were excluded. Patients with incomplete clinical staging or miscoded/mi…
Evaluation of tumor immune contexture among intrinsic molecular subtypes helps to predict outcome in early breast cancer
BackgroundThe prognosis of early breast cancer is linked to clinic-pathological stage and the molecular characteristics of intrinsic tumor cells. In some patients, the amount and quality of tumor-infiltrating immune cells appear to affect long term outcome. We aimed to propose a new tool to estimate immune infiltrate, and link these factors to patient prognosis according to breast cancer molecular subtypes.MethodsWe performed in silico analyses in more than 2800 early breast cancer transcriptomes with corresponding clinical annotations. We first developed a new gene expression deconvolution algorithm that accurately estimates the quantity of immune cell populations (tumor immune contexture,…
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
International audience; The immune system is routinely confronted with cell death resulting from the physiological turnover of renewable tissues, as well as from pathological insults of several types. We hypothesize the existence of a mechanism that allows the immune system to discriminate between physiological and pathological instances of cell death, but the factors that determine whether cellular demise is perceived as a neutral, tolerogenic or immunogenic event remain unclear 1. Infectious insults are accompanied by so-called microbe-associated molecular patterns (MAMPs), i.e., viral or bacterial products that activate immune cells through a panel of pattern-recognition receptors (PRRs)…
Metronomic oral cyclophosphamide prednisolone chemotherapy is an effective treatment for metastatic hormone-refractory prostate cancer after docetaxel failure.
There is currently no standard of treatment for patients with hormone refractory prostate cancer (HRPC) after failure of docetaxel-based chemotherapy. The purpose of this study was to assess the anticancer activity and tolerance of metronomic cyclophosphamide prednisolone combination in this setting.From 2005 to 2010, patients with HRPC who failed at least docetaxel-based chemotherapy were proposed metronomic cyclophosphamide-prednisolone regimen, and were prospectively registered. Twenty-three patients received 50 mg cyclophosphamide and 10 mg prednisolone per os daily until disease progression. Treatment tolerance and efficacy on PSA decrease and pain were studied.Metronomic cyclophospham…
Seroprevalence of SARs-CoV-2 among the staff and patients of a French cancer centre after first lockdown: the canSEROcov study
Abstract Background In view of the potential gravity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection for patients with cancer, epidemiological data are vital to assess virus circulation among patients and staff of cancer centres. We performed a prospective study to investigate seroprevalence of SARS-CoV-2 antibodies among staff and patients with cancer at a large cancer centre, at the end of the period of first national lockdown in France and to determine factors associated with the risk of SARS-CoV-2 infection. Methods After the first lockdown, all medical and non-medical staff, as well as all patients attending the medical oncology department were invited to unde…
Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.
How dying tumor cells get noticed Besides killing tumor cells directly, some chemotherapies, such as anthracyclines, also activate the immune system to kill tumors. Vacchelli et al. discovered that in mice, anthracycline-induced antitumor immunity requires immune cells to express the protein formyl peptide receptor 1 (FPR1). Dendritic cells (DCs) near tumors expressed especially high amounts of FPR1. DCs normally capture fragments of dying tumor cells and use them to activate nearby T cells to kill tumors, but DCs lacking FPR1 failed to do this effectively. Individuals with breast or colon cancer expressing a variant of FPR1 and treated with anthracyclines showed poor metastasis-free and ov…
Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer
International audience; Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease, resulting in increased local drug concentrations. Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy. The patient was treated with a combination of gemcitabine and oxaliplatin using HAI. The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI. The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed…
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to…
Transcatheter embolization of a renal artery pseudoaneurysm after open partial nephrectomy.
Twelve days after an open partial nephrectomy, a 31-year-old man was re-admitted urgently for acute lumbar pain. An emergent helical computed tomography scan with intravenous contrast revealed a 3-cm renal artery pseudoaneurysm at the site of the partial nephrectomy, which was responsible for a large perirenal hematoma. Transarterial hyperselective embolization successfully occluded the pseudoaneurysm with less than 1 mL of N-butyl-2-cyanoacrylate, an embolizing agent less costly than coils. The kidney parenchyma was fully preserved.
Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model
BackgroundThe lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP.MethodsFirst, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolera…
Autophagy
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide…