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A randomized phase 2 study comparing different dose-approaches of induction treatment (first cycle) of regorafenib in metastatic colorectal cancer (mCRC) patients

ABSTRACT: Primary objectives: To evaluate the safety and tolerability of different dose-escalation approaches of regorafenib in mCRC patients. Primary endpoints: Percentage of patients with G3/G4 treatment-related AEs in each arm according to CTCAE v4.03 criteria.

DISEASE(S): Metastatic Colorectal Cancer,Cancer Colorectal Metastásico

PROVIDER: 2535505 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Study Comparing Different Dose Approaches of Induction Treatment of Regorafenib in MCRC

Project description:The purpose of this study is to assess the safety and tolerability of different dose-escalation approaches of regorafenib in mCRC patients.

| 2220026 | ecrin-mdr-crc

Study investigating efficacy of a medicine lanreotide on decrease of chemotherapy induced diarrhoea (CID) in patiens with cancer of colon and rectum.

Project description:Primary objectives: Definition of efficacy of lanreotid in the therapy of CID which is defined as a rate of regression of CID to grade G1 from the entry value (grade G3 or G4) according to CTCAE v.4.03 Primary endpoints: Paremeter of efficacy is the rate of regression of CID to grade G1 from the entry value (grade G3 or G4) during 7 days from the first administration of the investigational medicinal product.

| 2533818 | ecrin-mdr-crc

Primary cilia control translation and the cell cycle in medulloblastoma

Project description:The primary cilium, a signaling organelle projecting from the surface of a cell, controls cellular physiology and behavior. The presence or absence of primary cilia is a distinctive feature of a given tumor type; however, whether and how the primary cilium contributes to tumorigenesis is unknown for most tumors. Medulloblastoma (MB) is a common pediatric brain cancer comprising four groups: SHH, WNT, group 3 (G3), and group 4 (G4). From 111 cases of MB, we show that primary cilia are abundant in SHH and WNT MBs but rare in G3 and G4 MBs. Using WNT and G3 MB mouse models, we show that primary cilia promote WNT MB by facilitating translation of mRNA encoding β-catenin, a major oncoprotein driving WNT MB, whereas cilium loss promotes G3 MB by disrupting cell cycle control and destabilizing the genome. Our findings reveal tumor type–specific ciliary functions and underlying molecular mechanisms. Moreover, we expand the function of primary cilia to translation control and reveal a molecular mechanism by which cilia regulate cell cycle progression, providing new frameworks for studying cilia function in normal and pathologic conditions.

2022-07-04 | GSE207008 | GEO

Project description:WES of wild type and Terc-/- in G3 tail, G3 testis, G3 TTF, G3 ASC, G3 ESC, G4 early ESC, G4 late ESC.

| PRJNA764419 | ENA

Genome unstable murine prostate cancers acquire genomic aberrations and bone metastatic features of the human disease

Project description:Gene copy numbers of prostate tumors of G3 and G4 generations of LSL-mTert PB-Pten/p53 mouse model Prostate tumors were developed in G3 and G4 generations of LSL-mTert PB-Pten/p53 mice. These tumors were profiled with affy and aCGH. We used affy gene expression to correlate with the copy number alterations in the mouse prostate tumors.

2012-01-21 | E-GEOD-35247 | biostudies-arrayexpress

RNA-Seq of wild type and Terc-/- in G3 tail, G3 liver, G3 testis, G3 TTF, G3 ASC, G4 early ESC, G4 late ESC

Project description:RNA-Seq of wild type and Terc-/- in G3 tail, G3 liver, G3 testis, G3 TTF, G3 ASC, G4 early ESC, G4 late ESC

| PRJNA764681 | ENA

Genome unstable murine prostate cancers acquire genomic aberrations and bone metastatic features of the human disease

Project description:Gene copy numbers of prostate tumors of G3 and G4 generations of LSL-mTert PB-Pten/p53 mouse model

2012-01-21 | GSE35247 | GEO

TULIPs decorate the three-dimensional genome of PFA ependymoma

Project description:Hi-C and RNA-seq for a large cohort of pediatric brain tumors including ependymoma (PFA, PFB, Ste, spinal), medulloblastoma (G3, G4, SHH), high grade glioma (H3K27 and H3-WT), pilocytic astrocytoma, and more.

2024-07-05 | GSE186599 | GEO

Single cell transcriptional and chromatin accessibility profiling identify the cellular heterogeneity of human medulloblastoma

Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of chromosome occupation and single cell gene expression or single nuclei chromatin accessibility in medulloblastoma tissues or cells. To further define the cellular identity at the single cell level, we characterized 26 MB tissues including 18 newly diagnosed MB tumor tissues by single cell scRNA-seq and scATAC-seq (the assay for transposase-accessible chromatin-sequencing) together with 8 previously reported MB single cell transcriptomics. The newly diagnosed MB tumors included four SHH-MBs (45,731 cells), nine G3-MBs (82,834 cells), thirteen G4 MBs (77,521 cells) with a median of 7,926 cells for scRNA-seq and 9,342 cells for scATAC-seq per MB tumor, respectively. To decipher how dynamic accessibility at the cis-regulatory elements (CREs) relates to the gene regulatory program in TCP-like cells from G3- and G4- MBs, we performed single nuclei ATAC-seq (snATAC-seq) to determine the single-cell chromatin accessibility landscape using high-quality nuclei from a set of fresh G3 and G4 MB tumors that matched with scRNA-seq. Finally, we show that gene expression with chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. Our studies identified a human-specific intermediate progenitor population important for cerebellar neural lineage development and the growth and metastasis of aggressive MBs, highlighting potential therapeutic targets.

2022-10-08 | GSE198565 | GEO

Expression data between WT and G3/4 Terc KO mouse ESCs during differentiation

Project description:Mammalian telomeres are formed by tandem repeats of the TTAGGG sequence, and shorten with each round of cell division in the absence of telomerase. Telomere shortening and dysfunction has been implicated in the pathology of several age-related diseases and premature ageing syndromes. Telomerase is important for telomere length maintenance. Telomerase RNA component, also known as TERC, is a component of telomerase. Terc knockout leads to telomerase deficiency and telomere shortening. Heterozygous telomerase-deficient (Terc+/-) mice were housed and bred for homozygous generation. ESC lines were generated with high efficiency from wild-type (WT, Terc+/+), heterozygous (Het, Terc+/-) and early- to late-generation (G1, G3 and G4) Terc-/- mouse blastocysts. Telomeres were shorter in Terc+/- ES cells than in WT ES cells, and further shortened from G1 to G4 Terc-/- ES cells. We took advantage of ES cell lines with various telomere lengths to investigate roles of telomere length on differentiation capacity of ES cells. We found that telomere length, but not telomerase activity, is required for differentiation of ES cells into epidermis. We performed microarray analysis to investigate differential gene expression profile at genome-wide levels between WT and G3/G4 Terc-/- (KO) mouse ES cells and during differentiation in vitro of WT and G4 Terc-/- mouse ES cells.

2016-01-29 | GSE77362 | GEO

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