Strain-dependent damage in mouse lung after carbon ion irradiation.

Purpose: To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung.

Methods And Materials: Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with ¹³⁷Cs γ-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining.

Combination effects of distinct cores in 11q13 amplification region on cervical lymph node metastasis of oral squamous cell carcinoma.

Lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC) is known to associate with a significant decrease of 5-year survival. Genetic factors related to the difference of the LNM status in the OSCC have been not fully elucidated. Array-based comparative genomic hybridization (CGH) with individual gene-level resolution and real-time quantitative polymerase chain reaction (QPCR) were conducted using primary tumor materials resected from 54 OSCC patients with (n=22) or without (n=32) cervical LNM.

Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung.

There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice.

Villin1, a diagnostic marker for endometrial adenocarcinoma with high grade nuclear atypia.

Villin1 (VIL1) has a role in regulating actin dynamics, cell morphology, anti-apoptotic mechanisms, and epithelial-to-mesenchymal transition. Previously we reported VIL1 as a novel diagnostic marker for cervical adenocarcinoma (AC) with poor radioresponse. This study further investigated the diagnostic role of VIL1 in gynecological tumors especially endometrial AC.

X-ray irradiation and Rho-kinase inhibitor additively induce invasiveness of the cells of the pancreatic cancer line, MIAPaCa-2, which exhibits mesenchymal and amoeboid motility.

Tumor cells can migrate and invade tissue by two modes of motility: mesenchymal and amoeboid. X-ray or γ-ray irradiation increases the invasiveness of tumor cells with mesenchymal motility through the induction of matrix metalloproteinases (MMP), and this increase is suppressed by MMP inhibitors (MMPI). However, the effects of X-ray or γ-ray irradiation on the invasiveness of tumor cells with amoeboid motility remain unclear.

Genetic variants of NPAT-ATM and AURKA are associated with an early adverse reaction in the gastrointestinal tract of patients with cervical cancer treated with pelvic radiation therapy.

Purpose: This study sought to associate polymorphisms in genes related to cell cycle regulation or genome maintenance with radiotherapy (RT)-induced an early adverse reaction (EAR) in patients with cervical cancer.

Methods And Materials: This study enrolled 243 cervical cancer patients who were treated with pelvic RT. An early gastrointestinal reaction was graded using the National Cancer Institute Common Toxicity Criteria, version 2.

Combining carbon ion radiotherapy and local injection of α-galactosylceramide-pulsed dendritic cells inhibits lung metastases in an in vivo murine model.

Purpose: Our previous report indicated that carbon ion beam irradiation upregulated membrane-associated immunogenic molecules, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of local combination therapy of carbon ion radiotherapy and immunotherapy was examined by use of an in vivo murine model.

Methods And Materials: Tumors of mouse squamous cell carcinoma (NR-S1) cells inoculated in the legs of C3H/HeSlc mice were locally irradiated with a single 6-Gy dose of carbon ions (290 MeV/nucleon, 6-cm spread-out Bragg peak).

Vascular homeostasis regulators, Edn1 and Agpt2, are upregulated as a protective effect of heat-treated zinc yeast in irradiated murine bone marrow.

Purpose: To elucidate the mechanism underlying the in vivo radioprotection activity by Zn-containing, heat-treated Saccharomyces cerevisiae yeast (Zn-yeast).

Materials And Methods: Zn-yeast suspension was administered into C3H/He mice immediately after whole body irradiation (WBI) at 7.5 Gy.

Subtypes of cervical adenosquamous carcinomas classified by EpCAM expression related to radiosensitivity.

Adenosquamous carcinoma (ASC) is a relatively uncommon histological subtype of cervical cancer (CC). A point of controversy is the relative prognosis of ASC compared to squamous cell carcinoma (SCC). We hypothesized that ASC could be classified into two intrinsic molecular subtypes with different outcomes.

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.

Background: The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.

Methods: Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180).

Change in fibroblast growth factor 2 expression as an early phase radiotherapy-responsive marker in sequential biopsy samples from patients with cervical cancer during fractionated radiotherapy.

Background: The authors previously demonstrated that fibroblast growth factor 2 (FGF2) expression levels in tumor cells (FGF2-T) may be an indicator of the efficacy of radiotherapy in patients with cervical cancer (CC). In the current study, this finding was extended in newly enrolled patients and was investigated further in stromal FGF2 (FGF2-S) expression.

Methods: Sixty-nine patients with CC were recruited as a validation set for the immunohistochemical detection of FGF2-T from biopsy samples that were taken before (pretreatment) or 1 week after the initiation of radiotherapy (midtreatment).

Villin1, a novel diagnostic marker for cervical adenocarcinoma.

The number of new cervical adenocarcinoma (AD) cases has risen slowly, however, its histological similarity to other tumor types and the difficulty of identifying the site of the original tumor makes the diagnosis of cervical AD particularly challenging. We investigated a novel molecular biomarker for cervical AD through the integration of multiple methods of genomic analysis. Tumor samples in discovery set were obtained from 87 patients who underwent radiotherapy, including 31 cervical AD.

Application of carbon-ion beams or gamma-rays on primary tumors does not change the expression profiles of metastatic tumors in an in vivo murine model.

Purpose: To clarify how carbon-ion radiotherapy (C-ion) on primary tumors affects the characteristics of subsequently arising metastatic tumor cells.

Methods And Materials: Mouse squamous cell carcinomas, NR-S1, in synergic C3H/HeMsNrs mice were irradiated with a single dose of 5-50 Gy of C-ion (290 MeV per nucleon, 6-cm spread-out Bragg peak) or gamma-rays ((137)Cs source) as a reference beam. The volume of the primary tumors and the number of metastatic nodules in lung were studied, and histologic analysis and microarray analysis of laser-microdissected tumor cells were also performed.

The proangiogenic factor ephrin-A1 is up-regulated in radioresistant murine tumor by irradiation.

While the pre-treatment status of cancer is generally correlated with outcome, little is known about microenvironmental change caused by anti-cancer treatment and how it may affect outcome. For example, treatment may lead to induction of gene expression that promotes resistance to therapy. In the present study, we attempted to find a gene that was both induced by irradiation and associated with radioresistance in tumors.

In-gel multiple displacement amplification of long DNA fragments diluted to the single molecule level.

The isolation and multiple genotyping of long individual DNA fragments are needed to obtain haplotype information for diploid organisms. Limiting dilution of sample DNA followed by multiple displacement amplification is a useful technique but is restricted to short (<5 kb) DNA fragments. In the current study, a novel modification was applied to overcome these problems.

Expression profiles are different in carbon ion-irradiated normal human fibroblasts and their bystander cells.

Evidence has accumulated that ionizing radiation induces biological effects in non-irradiated bystander cells having received signals from directly irradiated cells; however, energetic heavy ion-induced bystander response is incompletely characterized. Here we performed microarray analysis of irradiated and bystander fibroblasts in confluent cultures. To see the effects in bystander cells, each of 1, 5 and 25 sites was targeted with 10 particles of carbon ions (18.

CD44 and Bak expression in IL-6 or TNF-alpha gene knockout mice after whole lung irradiation.

To understand the molecular mechanisms that underlie radiation pneumonitis, we examined whether knockout of the TNF or the IL-6 gene could give mice an inherent resistance to radiation in the acute phase of alveolar damage after thoracic irradiation. The temporal expression of inflammation (CD44) and apoptosis (Bak) markers in lung after thoracic irradiation was measured to determine the degree of alveolar damage. At 4 weeks post-irradiation (10 Gy), small inflammatory foci were observed in all mice, but there were no obvious histological differences between control (C57BL/6JSlc), TNF-alpha knockout (TNF KO), and IL-6 knockout (IL-6 KO) mice.

Visible Genotype Sensor Array.

A visible sensor array system for simultaneous multiple SNP genotyping has been developed using a new plastic base with specific surface chemistry. Discrimination of SNP alleles is carried out by an allele-specific extension reaction using immobilized oligonucleotide primers. The 3'-ends of oligonucleotide primers are modified with a locked nucleic acid to enhance their efficiency in allelic discrimination.

Gene expression analysis in human malignant melanoma cell lines exposed to carbon beams.

Purpose: To elucidate the molecular changes in response to carbon beams (C-ions) in melanoma.

Materials And Methods: We examined expression profiles of 6 melanoma cell lines exposed to C-ions or X-rays with 2 Gy using single-color microarrays.

Results: Twenty-two genes, including nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA), responded to C-ions in all six cell lines, based on analysis of variance (ANOVA) filtering (p < 0.

Influence of multiple genetic polymorphisms on genitourinary morbidity after carbon ion radiotherapy for prostate cancer.

Purpose: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients.

Methods And Materials: A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows: Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients.

p73 protein expression correlates with radiation-induced apoptosis in the lack of p53 response to radiation therapy for cervical cancer.

Purpose: p73 belongs to the p53 tumor suppressor family of genes and can inhibit cell growth in a p53-like manner by inducing apoptosis or cell cycle arrest. Here, we investigated whether p73 could compensate for impaired p53 function in apoptosis induced by radiation therapy (RT) for cervical cancer.

Methods And Materials: Sixty-eight patients with squamous cell carcinoma of the cervix who received definitive RT combined with (n=37) or without (n=31) cisplatin were investigated.

Prediction of lymphatic metastasis based on gene expression profile analysis after brachytherapy for early-stage oral tongue carcinoma.

Background And Purpose: The management of lymphatic metastasis of early-stage oral tongue carcinoma patients is crucial for its prognosis. The purpose of this study was to evaluate the predictive ability of lymphatic metastasis after brachytherapy (BRT) for early-stage tongue carcinoma based on gene expression profiling.

Patients And Methods: Pre-therapeutic biopsies from 39 patients with T1 or T2 tongue cancer were analyzed for gene expression signatures using Codelink Uniset Human 20K Bioarray.

Upregulation of stress-response genes with cell cycle arrest induced by carbon ion irradiation in multiple murine tumors models.

Objective: To elucidate the in vivo biological effects induced by carbon-ion irradiation using comprehensive expression analysis.

Results: In all tumors, the level of expression of several tens of genes, including Ccl3, Ccng1, Cd80, Cdkn1a, Cxcl2, IL7r, Lrdd, Mgmt, Mmp8 and Polk, was significantly altered 6 h and day 1 following C-ion irradiation. At day 3, several hundred genes, many of which are also classified as stress-response or cell-communication genes, including Tnfrsf5, Ikbke and Icam1, were upregulated following C-ion irradiation.

Chemoradiation-induced expression of fibroblast growth factor-2 and laminin in patients with cervical cancer.

Objective: To investigate the protein expression change of FGF2 in cervical cancers during chemoradiotherapy, as indicated in our previous study using microarray analysis. In addition, we sought to examine the predictive value of such changes in expression for disease failure after chemoradiotherapy.

Patients And Methods: Biopsy specimens were obtained from 35 patients with cervical cancers before (pretreatment) and 1 week after initiation (midtreatment) of chemoradiotherapy (CRT) (9 Gy and 40 mg/m(2) of cisplatin).