TY  - JOUR
A1  - Kroeber, Jana
A1  - Wenger, Barbara
A1  - Schwegler, Manuela
A1  - Daniel, Christoph
A1  - Schmidt, Manfred
A1  - Djuzenova, Cholpon S
A1  - Polat, Bülent
A1  - Flentje, Michael
A1  - Fietkau, Rainer
A1  - Distel, Luitpold V.
T1  - Distinct increased outliers among 136 rectal cancer patients assessed by \(\gamma\)H2AX
JF  - Radiation Oncology
N2  - Background: 
In recent years attention has focused on \(\gamma\)H2AX as a very sensitive double strand break indicator. It has been suggested that \(\gamma\)H2AX might be able to predict individual radiosensitivity. Our aim was to study the induction and repair of DNA double strand breaks labelled by \(\gamma\)H2AX in a large cohort. 

Methods: 
In a prospective study lymphocytes of 136 rectal cancer (RC) patients and 59 healthy individuals were ex vivo irradiated (IR) and initial DNA damage was compared to remaining DNA damage after 2 Gy and 24 hours repair time and preexisting DNA damage in unirradiated lymphocytes. Lymphocytes were immunostained with anti-\(\gamma\)H2AX antibodies and microscopic images with an extended depth of field were acquired. \(\gamma\)H2AX foci counting was performed using a semi-automatic image analysis software. 

Results: 
Distinct increased values of preexisting and remaining \(\gamma\)H2AX foci in the group of RC patients were found compared to the healthy individuals. Additionally there are clear differences within the groups and there are outliers in about 12% of the RC patients after ex vivo IR. 

Conclusions: 
The \(\gamma\)H2AX assay has the capability to identify a group of outliers which are most probably patients with increased radiosensitivity having the highest risk of suffering radiotherapy-related late sequelae.
KW  - histone H2AX
KW  - blood lymphocytes
KW  - in vivo
KW  - foci
KW  - individual radiosensitivity
KW  - rectal cancer
KW  - radiotherapy
KW  - DNA double strand breaks
KW  - phosphorylation
KW  - neck cancer
KW  - oral mucositis
KW  - DNA damage
KW  - radiosensitivity
KW  - repair
KW  - \(\gamma\)h2ax
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144085
VL  - 10
IS  - 36
ER  - 
TY  - JOUR
A1  - Cardani, Diego
A1  - Sardi, Claudia
A1  - La Ferla, Barbara
A1  - D'Orazio, Guiseppe
A1  - Sommariva, Michele
A1  - Marcucci, Fabrizio
A1  - Olivero, Daniela
A1  - Tagliabue, Elda
A1  - Koepsell, Hermann
A1  - Nicotra, Francesco
A1  - Balsari, Andrea
A1  - Rumio, Christiano
T1  - Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis
JF  - Molecular Cancer
N2  - Background: Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis. 
Methods: Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1. Intestinal mucosal epithelium integrity was assessed by histological analysis, cellular proliferation assays, real-time PCR gene expression assays and Western blot assays. Student's t-test (paired two-tailed) and X-2 analyses were used for comparisons between groups. Differences were considered significant at p < 0.05. 
Results: BLF501 administration in mice treated with DXR and/or 5-FU decreased the injuries to the mucosa in terms of epithelial integrity and cellular proliferative ability. Co-treatment with BLF501 led to a normal expression and distribution of both zonula occludens-1 (ZO-1) and beta-catenin, which were underexpressed after treatment with either chemotherapeutic agent alone. BLF501 administration also restored normal expression of caspase-3 and ezrin/radixin/moesin (ERM), which were overexpressed after treatment with DXR and 5-FU. In SGLT1-/- mice, BLF501 had no detectable effects. BLF501 administration in wild-type mice with growing A431 tumors did not modify antitumor activity of DXR. 
Conclusions: BLF501-induced protection of the intestinal mucosa is a promising novel therapeutic approach to reducing the severity of chemotherapy-induced mucositis.
KW  - apoptosis
KW  - prevention
KW  - doxorubicin
KW  - cancer
KW  - gastrointestinal mucositis
KW  - SGLT-1
KW  - synthetic D-glucose analogy
KW  - chemotherapy
KW  - inflammation
KW  - clinical practice guidelines
KW  - intestinal mucositis
KW  - epithelial cells
KW  - oral mucositis
KW  - gene-expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117352
SN  - 1476-4598
VL  - 13
IS  - 23
ER  -