Cancers, Vol. 12, Pages 469: Personalized Assessment of Normal Tissue Radiosensitivity via Transcriptome Response to Photon, Proton and Carbon Irradiation in Patient-Derived Human Intestinal Organoids

Cancers, Vol. 12, Pages 469: Personalized Assessment of Normal Tissue Radiosensitivity via Transcriptome Response to Photon, Proton and Carbon Irradiation in Patient-Derived Human Intestinal Organoids Cancers doi: 10.3390/cancers12020469 Authors: Ali Nowrouzi Mathieu G. Sertorio Mahdi Akbarpour Maximillian Knoll Damir Krunic Matthew Kuhar Christian Schwager Stephan Brons Jürgen Debus Susanne I. Wells James M. Wells Amir Abdollahi Radiation-induced normal tissue toxicity often limits the curative treatment of cancer. Moreover, normal tissue relative biological effectiveness data for high-linear energy transfer particles are urgently needed. We propose a strategy based on transcriptome analysis of patient-derived human intestinal organoids (HIO) to determine molecular surrogates for radioresponse of gastrointestinal (GI) organs at risk in a personalized manner. HIO were generated from induced pluripotent stem cells (iPSC), which were derived from skin biopsies of three patients, including two patients with FANCA deficiency as a paradigm for enhanced radiosensitivity. For the two Fanconi anemia (FA) patients (HIO-104 and 106, previously published as FA-A#1 IND-iPS1 and FA-A#2 IND-iPS3), FANCA expression was reconstituted as a prerequisite for generation of HIO via lentiviral expression of a doxycycline inducible construct. For radiosensitivity analysis, FANCA deficient and FANCA rescued as well as wtHIO were sham treated or irradiated with 4Gy ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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Every cancer carries genomic mutations. Although almost all these mutations arise after fertilization, a minimal count of cancer predisposition mutations are already present at the time of genesis of germ cells. Of the cancer predisposition genes identified to date, BRCA1 and BRCA2 have been determined to be associated with hereditary breast and ovarian cancer syndrome. Such cancer predisposition genes have recently been attracting attention owing to the emergence of molecular genetics, thus, affecting the strategy of cancer prevention, diagnostics, and therapeutics. In this review, we summarize the molecular significance ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
We examined the subcellular localization of FANCD2 in primary OSE cells from consenting patients with ovarian cancer or a normal ovary. Ovarian tissue microarray was stained with anti-FANCD2 antibody by immunohistochemistry and the correlation of FANCD2 localization with patient outcomes was assessed. FANCD2 binding partners were identified by immunoprecipitation of cytoplasmic FANCD2. RESULTS: Nuclear and cytoplasmic localization of FANCD2 was observed in OSEs from both normal and ovarian cancer patients. Patients with cytoplasmic localization of FANCD2 (cFANCD2) experienced significantly longer median survival time (...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
We report that monoubiquitination does not promote any specific exogenous protein:protein interactions, but instead stabilizes FANCI:FANCD2 heterodimers on dsDNA. This clamping requires monoubiquitination of only the FANCD2 subunit. We further show that purified monoubiquitinated FANCI:FANCD2 forms filament-like arrays on long dsDNA using electron microscopy. Our results reveal how monoubiquitinated FANCI:FANCD2, defective in many cancer types and all cases of FA, is activated upon DNA binding.
Source: eLife - Category: Biomedical Science Tags: Chromosomes and Gene Expression Source Type: research
Discussion Neuropenia is defined as a neutrophil count
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Mu-Yan Cai, Connor E. Dunn, Wenxu Chen, Bose S. Kochupurakkal, Huy Nguyen, Lisa A. Moreau, Geoffrey I. Shapiro, Kalindi Parmar, David Kozono, Alan D. D’AndreaSummaryCells deficient in ataxia telangiectasia mutated (ATM) are hypersensitive to ionizing radiation and other anti-cancer agents that induce double-strand DNA breaks. ATM inhibitors may therefore sensitize cancer cells to these agents. Some cancers may also have underlying genetic defects predisposing them to an ATM inhibitor monotherapy response. We have conducted a genome-w...
Source: Cell Reports - Category: Cytology Source Type: research
AbstractDespite the acceptance of NextGen sequencing as a diagnostic modality suitable for probands and carriers of Mendelian diseases, its efficiency in identifying causal mutations is limited by both technical aspects of variant call algorithms and by imperfect, consensus-based criteria for assessing the pathogenicity of the findings. Here we describe the medical history of the family with a child born with Fanconi anemia. In this case, typical diagnostic routines were complicated by unusual combination of mutations.PALB2 variant NM_024675.3:c.172_175delTTGT (p.Gln60Argfs) in maternal sample, previously classified as a d...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Our data present a complete preclinical analysis and promising therapeutic line of the first FDA/EMA approved anticancer drugs exerting cancer specific toxicity for HNSCC in FA patients. PMID: 32005748 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Authors: Nagano S, Tsukamoto M, Yokoyama T Abstract Fanconi anemia (FA) is a type of bone marrow failure syndrome based on an autosomal recessive inherited trait with increased predisposition for other cancers. It is extremely rare and is characterized by short stature, polydactyly, and pancytopenia. At present, the only effective treatment for FA is allogeneic hematopoietic stem cell transplantation (SCT). Chemotherapy is necessary prior to allogeneic SCT. Dental treatment is usually performed before chemotherapy to reduce potential infections. We experienced the anesthetic management of a 4-year-old boy diagnosed...
Source: Anesthesia Progress - Category: Anesthesiology Tags: Anesth Prog Source Type: research
A Brief Review on a New DNA Repairing Pathway in Resistant Chemotherapy &Current Medicine. Mini Rev Med Chem. 2020 Jan 02;: Authors: Ghosal K, Agatemor C Abstract Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, failing the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. T...
Source: Mini Reviews in Medicinal Chemistry - Category: Chemistry Authors: Tags: Mini Rev Med Chem Source Type: research
vageau Alexander Thompson High expression of the HOXA cluster correlates with poor clinical outcome in acute myeloid leukemias, particularly those harboring rearrangements of the mixed-lineage-leukemia gene (MLLr). Whilst decreased HOXA expression acts as a readout for candidate experimental therapies, the necessity of the HOXA cluster for leukemia maintenance has not been fully explored. Primary leukemias were generated in hematopoietic stem/progenitor cells from Cre responsive transgenic mice for conditional deletion of the Hoxa locus. Hoxa deletion resulted in reduced proliferation and colony formation in which su...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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