0000000000124313
AUTHOR
Bruno Chauffert
Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation
The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)–β receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-β–dependent manner in mice and rats. Tumor cells are necessary a…
A New Major Triterpene Saponin from the Roots of Cucurbita foetidissima
Foetidissimoside B (1), a novel triterpene saponin, was isolated from the roots of Cucurbita foetidissima. Based on spectroscopic data, especially direct and long-range heteronuclear 2D NMR analysis and on chemical transformations, the structure of 1 was elucidated as 3-O-beta-D-glucuronopyranosyl-echinocystic acid 28-O-beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranosyl(1-->3)-[beta- D-xylopyranosyl (1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside . Compound 1 did not show any ability to potentiate in vitro cisplatin cytotoxicity in a human colon cancer cell line.
Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial
SummaryBackground A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC). Aim To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life. Methods Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300–500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients. Results Twenty-one patients were enrolled, inclu…
Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level
International audience; TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti-cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells. TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL-induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells. This sensitization, which ma…
Novel Acylated Triterpene Glycosides from Muraltia heisteria
Four new acylated triterpene glycosides (1-4) have been isolated as two inseparable mixtures of the trans- and cis-3,4,5-trimethoxycinnamoyl derivatives (1,2 and 3,4) from the roots of Muraltia heisteria. The structures of these compounds were elucidated by various 1D and 2D NMR techniques, including (1)H and (13)C, COSY, NOESY, HSQC, TOCSY, and HMBC experiments and FABMS. Compounds 3 and 4 were shown to be cytotoxic in a human colon cancer cell line but did not show any ability to potentiate in vitro cisplatin cytotoxicity.
Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma
// Aurelie Bertaut 1 , Caroline Truntzer 2 , Rachid Madkouri 3 , Coureche Guillaume Kaderbhai 4 , Valentin Derangere 5 , Julie Vincent 4 , Bruno Chauffert 6 , Marie Helene Aubriot-Lorton 7 , Wahlid Farah 3 , Klaus Luc Mourier 3 , Romain Boidot 5,8 and Francois Ghiringhelli 4,5,8,9 1 Biostatistics unit Georges Francois Leclerc Cancer Center, Dijon, France 2 CLIPP, Research Center, University of Burgundy, Dijon, France 3 Department of Neurosurgery, CHU, Dijon, France 4 Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon, France 5 Platform of Transfer in Cancer Biology Genetic and histology, Georges Francois Leclerc Cancer Center, Dijon, France 6 Department of Medical…
Tumor cells can escape DNA-damaging cisplatin through DNA endoreduplication and reversible polyploidy
Cancer chemotherapy can induce tumor regression followed, in many cases, by relapse in the long-term. Thus this study was performed to assess the determinants of such phenomenon using an in vivo cancer model and in vitro approaches. When animals bearing an established tumor are treated by cisplatin, the tumor initially undergoes a dramatic shrinkage and is characterized by giant tumor cells that do not proliferate but maintain DNA synthesis. After several weeks of latency, the tumor resumes its progression and consists of small proliferating cells. Similarly, when tumor cells are exposed in vitro to pharmacological concentrations of cisplatin, mitotic activity stops initially but cells main…
cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-ones: Synthesis and cytotoxicity in human cancer cell lines in vitro
A novel family of cisplatin-type complexes tethered to dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene chain and their nonplatinated counterparts were prepared. Their potential cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116, SW480 and HT-29 and compared to the reference molecules cisplatin and oxaliplatin. Platinated compounds were poorly active whilst nonplatinated dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic properties than cisplatin and oxaliplatin whatever the length of the polymethylene chain; molecules containing the tri- and hexamethylene chain length were the most cytotoxic.
Triterpene Saponins from the Roots of Achyranthes bidentata
Three saponins, oleanolic acid-28- O -s-D-glucopyranoside (1), chikusetsusaponin V (2), and 3- O -s-D-glucopyranosyl-oleanolic acid-28- O -s-D-glucopyranoside (3) were isolated from the roots of Achyranthes bidentata Blume (Amaranthaceae). No activity was shown in the granulocyte phagocytosis test nor in the test of the potentiation of the cytotoxicity of cisplatin in human colon cancer cells. This is the first report of compounds 1, 2 and 3 isolated from Achyranthes species. Furthermore, the NMR data of 2 completed the partially published data.
Using A Heating Cable Within The Abdomen To Make Hyperthermic Intraperitoneal Chemotherapy Easier: Feasibility And Safety Study In The Swine
International audience; BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex, expensive and time-consuming procedure. Despite its good results in the treatment of peritoneal carcinomatosis, these factors have precluded the wider use of this procedure around the world. We hypothesized that HIPEC could be performed by heating the liquid within the abdomen and thus avoiding the need for an external heating circuit and a pump. The aim of this study was to assess the feasibility and safety of an internal heating device for hyperthermic intraperitoneal chemotherapy in an experimental model. METHODS: Four large-white pigs underwent one-hour open intraperitoneal hyperthermia w…
Randomised controlled trial of lipiodol transarterial chemoembolisation with or without amiodarone for unresectable hepatocellular carcinoma.
Abstract Background There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma. Aim The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group. Methods Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions. Results Thirteen patients were randomised in the amiodarone group, and 14 we…
TH-302 + Gemcitabine (G + T) vs Gemcitabine (G) in Patients with Previously Untreated advanced Pancreatic Cancer (PAC)
ABSTRACT Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G…
Cancer du pancréas localement évolué non resécable : chimioradiothérapie d’induction suivie de chimiothérapie par gemcitabine contre chimiothérapie exclusive par gemcitabine : résultats définitifs de l’étude de phase III 2000–2001de la FFCD et de la SFRO
Resume Objectif de l’etude Etudier l’apport de la chimioradiotherapie concomitante suivie de chimiotherapie dans le cancer pancreatique localement evolue, par rapport a la chimiotherapie seule. Patients et methodes Cent dix-neuf patients atteints d’un cancer pancreatique localement evolue, avec indice de performance de 0 a 2 selon l’Organisation mondiale de la sante, ont ete randomises entre une chimioradiotherapie concomitante d’induction (60 Gy, 2 Gy/fraction ; perfusion concomitante de 5-fluoro-uracile de 300 mg/m2 par jour, de j1 a j5 pendant six semaines ; cisplatine, 20 mg/m2 par jour, de j1 a j5 pendant la premiere et la cinquieme semaines) et une chimiotherapie d’induction par gemci…
Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19).
Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289…
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…
New Diosgenin Glycosides from Costus afer
Two new steroidal saponins, aferosides B (1) and C (2), together with the known saponins, dioscin (3) and paryphyllin C (4), were isolated from the roots of Costus afer. The known flavonoid glycoside, kaempferol 3-O-α-l-rhamnopyranoside (5), was obtained from the aerial parts. The structures of the new compounds were elucidated principally by 2D NMR spectral methods. A structural revision of the sugar sequence was made for the previously reported saponin aferoside A (6) on the basis of detailed spectroscopic analysis. Saponins 1−4 and 6 did not show any ability to potentiate in vitro cisplatin cytotoxicity in a human colon cancer cell line.
Bidentatoside I, a New Triterpene Saponin from Achyranthes bidentata
Bidentatoside I (1) is a new triterpene saponin bearing an unusual dioxopropionic acid unit, isolated from the roots of Achyranthes bidentata. Structural elucidation was performed mainly by chemical and homo- and heteronuclear 2D NMR techniques. This compound did not show any potentiation of the in vitro cytotoxicity of cisplatin in the HT 29 human colon cancer cell line.
Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.
IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations…
The role of reactive oxygen species and subsequent DNA-damage response in the emergence of resistance towards resveratrol in colon cancer models
AbstractIn spite of the novel strategies to treat colon cancer, mortality rates associated with this disease remain consistently high. Tumour recurrence has been linked to the induction of resistance towards chemotherapy that involves cellular events that enable cancer cells to escape cell death. Treatment of colon cancer mainly implicates direct or indirect DNA-damaging agents and increased repair or tolerances towards subsequent lesions contribute to generate resistant populations. Resveratrol (RSV), a potent chemosensitising polyphenol, might share common properties with chemotherapeutic drugs through its indirect DNA-damaging effects reported in vitro. In this study, we investigated how…
Saponins-mediated potentiation of cisplatin accumulation and cytotoxicity in human colon cancer cells.
The triterpene saponins jenisseensosides A, B, C, D were found to increase the accumulation and cytotoxicity of the anticancer agent cisplatin in human colon tumor cells. These compounds are glycosides of quillaic acid whose fucose residue was acylated by a trans- or cis-p methoxycinnamic acid. In contrarst, other saponins derivatives without this acyl moiety were not found to potentiate the accumulation and cytotoxicity of cisplatin. These results suggested the importance of the acyl moiety for activity.