52 research outputs found
Patterns of chromosomal copy-number alterations in intrahepatic cholangiocarcinoma
International audienceBackground: Intrahepatic cholangiocarcinomas (ICC) are relatively rare malignant tumors associated with a poor prognosis. Recent studies using genome-wide sequencing technologies have mainly focused on identifying new driver mutations. There is nevertheless a need to investigate the spectrum of copy number aberrations in order to identify potential target genes in the altered chromosomal regions. The aim of this study was to characterize the patterns of chromosomal copy-number alterations (CNAs) in ICC. Methods: 53 patients having ICC with frozen material were selected. In 47 cases, DNA hybridization has been performed on a genomewide SNP array. A procedure with a segmentation step and a calling step classified genomic regions into copy-number aberration states. We identified the exclusively amplified and deleted recurrent genomic areas. These areas are those showing the highest estimated propensity level for copy loss (resp. copy gain) together with the lowest level for copy gain (resp. copy loss). We investigated ICC clustering. We analyzed the relationships between CNAs and clinico-pathological characteristics. Results: The overall genomic profile of ICC showed many alterations with higher rates for the deletions. Exclusively deleted genomic areas were 1p, 3p and 14q. The main exclusively amplified genomic areas were 1q, 7p, 7q and 8q. Based on the exclusively deleted/amplified genomic areas, a clustering analysis identified three tumors groups: the first group characterized by copy loss of 1p and copy gain of 7p, the second group characterized by 1p and 3p copy losses without 7p copy gain, the last group characterized mainly by very few CNAs. From univariate analyses, the number of tumors, the size of the largest tumor and the stage were significantly associated with shorter time recurrence. We found no relationship between the number of altered cytobands or tumor groups and time to recurrence. Conclusion: This study describes the spectrum of chromosomal aberrations across the whole genome. Some of the recurrent exclusive CNAs harbor candidate target genes. Despite the absence of correlation between CNAs and clinico-pathological characteristics, the co-occurence of 7p gain and 1p loss in a subgroup of patients may suggest a differential activation of EGFR and its downstream pathways, which may have a potential effect on targeted therapies
Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer
Background:
Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m2) and triplet hepatic artery infusion (HAI) within European trial OPTILIV.
Methods:
Irinotecan (180 mg/m2), 5-fluorouracil (2800 mg/m2) and oxaliplatin (85 mg/m2) were given as chronomodulated or conventional delivery. Patients were retrospectively categorised as early responders (complete or partial RECIST response after three courses) or non-early responders (late or no response). Prognostic factors were determined using multivariate logistic or Cox regression models.
Results:
Response was assessed in 57 of 64 registered patients (89%), who had previously received one to three prior systemic chemotherapy protocols. An early response occurred at 6 weeks in 16 patients (28%; 9 men, 7 women), aged 33–76 years, with a median of 12 liver metastases (LMs) (2–50), involving five segments (1–8). Ten patients had a late response, and 31 patients had no response. Grade 3–4 fatigue selectively occurred in the non-early responders (0% versus 26%; p = 0.024). Early tumour response was jointly predicted by chronomodulation—odds ratio (OR): 6.0 (1.2–29.8; p = 0.029)—and LM diameter ≤57 mm—OR: 5.3 (1.1–25.0; p = 0.033). Early tumour response predicted for both R0-R1 liver resection—OR: 11.8 (1.4–100.2; p = 0.024) and overall survival—hazard ratio: 0.39 (0.17–0.88; p = 0.023) in multivariate analyses.
Conclusions:
Early tumour response on triplet HAI and systemic cetuximab predicted for complete macroscopic liver resection and prolonged survival for LM-CRC patients within a multicenter conversion-to-resection medicosurgical strategy. Confirmation is warranted for early response on HAI to guide decision making
Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05
L’objectif de ce travail était la recherche de biomarqueurs moléculaires
prédictifs de la tolérance et de l’efficacité des chimio–
thérapies utilisées dans le colorectal (CCR) métastatique. Nous
avons effectué le génotypage de 20 polymorphismes présents au
sein de 9 gènes connus ou suspectés d’être impliqués dans la
voie du 5FU, de l’oxaliplatine, ou de l’irinotécan, à partir de l’ADN
extrait du sang de 346 patients traités dans le cadre d’un essai de
phase III. Cet essai comparait une chimiothérapie séquentielle par
5FU (schéma LV5FU2) suivie d’une association 5FU plus oxali–
platine (schéma FOLFOX) à une chimiothérapie combinée de type
FOLFOX d’emblée en première ligne de traitement. Nous avons
trouvé un risque de toxicité hématologique sévère sous FOLFOX
significativement augmenté chez les patients porteurs de l’allèle
ERCC2-K751QC. La présence de l’allèle TS-5’UTR3RG du
gène de la thymidylate synthase était associée à un taux de
réponse significativement plus élevé sous LV5FU2. Le taux de
réponse au FOLFOX en 2e ligne était significativement supérieur
chez les patients porteurs de l’allèle ERCC1-IVS3+74G, et chez
ceux ayant au moins un allèle de GSTT1 présent. L’analyse
prédictive a montré un effet dépendant du traitement de certains
polymorphismes. En effet, une survie sans progression significativement
allongée par l’ajout de l’oxaliplatine en 1re ligne a été
observée uniquement chez les patients ayant un génotype
TS-5’UTR2R/2R ou 2R/3R, suggérant l’absence de bénéfice
d’une bithérapie par FOLFOX d’emblée en première ligne chez les
patients TS-5’UTR3R/3R. Ces résultats montrent que l’étude des
polymorphismes constitutionnels permettent de prédire non
seulement la toxicité mais aussi l’efficacité des chimiothérapies
antitumorales du cancer colorectal, et ainsi (sous réserve d’une
validation sur une population indépendante) d’orienter la stratégie
thérapeutique à l’échelle de l’individu
Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer
Chemophoresis as a driving force for intracellular organization: Theory and application to plasmid partitioning
Conséquences de l'introduction de sépiolite sur l'utilisation digestive de l'aliment et les performances du porc en croissance
6 tablesNational audienc
Conséquences de l'introduction de sépiolite sur l'utilisation digestive de l'aliment et les performances du porc en croissance
6 tablesNational audienc
Association de parois végétales et de graisses dans le régime de lactation des truies. Effet sur l'utilisation digestive et la composition du lait et des porcelets
National audienc
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