Sarah A Krueger

Beaumont Health System · Department of Radiation Oncology

Purpose: Radiation cystitis (RC), a severe inflammatory bladder condition, develops as a side effect of pelvic radiation therapy in cancer patients. There are currently no effective therapies to treat RC, in part from the lack of preclinical model systems. In this study, we developed a mouse model for RC and used a Small Animal Radiation Research P...

Purpose: To assess the efficacy of 3-week schedules of low-dose pulsed radiation treatment (PRT) and standard radiation therapy (SRT), with concurrent cisplatin (CDDP) in a head and neck squamous cell carcinoma xenograft model. Methods and materials: Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO female mice. A total of 30...

Purpose: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Methods and materials: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off sch...

To evaluate the efficacy of low-dose pulsed radiation therapy (PRT) in 2 head and neck squamous cell carcinoma (HNSCC) xenografts and to investigate the mechanism of action of PRT compared with standard radiation therapy (SRT). Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO femal...

This study primarily sought to determine if the Small Animal Radiation Research Platform (SARRP) can create a rat radiation cystitis (RC) model via targeted bladder irradiation (phase I). The response to treatment of early phase RC in rats via transurethral catheter instillation of liposomal tacrolimus (lipo-tacrolimus) was examined in phase II. In...

To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with...

To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. Orthotopic U87MG hGBM tumors were established in Nu-Foxn1(nu) mice and imaged weekly using a small-animal micropositron emission tomography (PET)/comp...

Purpose: To determine if ultra-fractionation using repeated pulses of radiation (10 × 0.2 Gray [Gy]) would be more cytotoxic than continuously-delivered radiation to the same total dose (2 Gy) in four glioma cell lines. Materials and methods: Human T98G, U373, U87MG and U138MG cells were conventionally X-irradiated with 0.1-8 Gy and clonogenic s...

To compare dose-escalated pulsed low-dose radiation therapy (PLRT) and standard radiation therapy (SRT). Intracranial U87MG GBM tumors were established in nude mice. Animals received whole brain irradiation with daily 2-Gy fractions given continuously (SRT) or in ten 0.2-Gy pulses separated by 3-min intervals (PLRT). Tumor response was evaluated us...

The androgen regulated transmembrane serine protease (TMPRSS2) and ETS transcription factor (ERG) gene fusion is a strong prognostic factor for disease recurrence following prostatectomy. Expression of TMPRSS2/ETS-related gene (ERG) fusion gene transcripts is linked with tumor proliferation, invasion, and an aggressive phenotype. The aim of this st...

Measurement of DNA content was one of the first applications to be developed in the use of flow cytometry and is still used routinely in many experimental and, to a lesser extent, clinical studies. The goal of this technique is to produce a high quality DNA profiles for accurate analysis of DNA content and cell cycle distribution. In this chapter,...

Survival 0.0 0.2 0.4 0.6 0.8 1.0 1.2 T98Gg U373 U87-MG U138-MG Clonogenic Survival-Clonogenic cell survival and MTT assays were performed in T98G, U87MG, U138 and U373 GBM cell lines after X-irradiation with 2 Gy or 10 x 0.2 Gy, with a 3-minute or 10 minute pulse interval.-Cell cycle progression into mitosis and early G2-phase checkpoint arrest wer...

An association between low-dose hyper-radiosensitivity (HRS) and the "early" G2/M checkpoint has been established. An improved molecular understanding of the temporal dynamics of this relationship is needed before clinical translation can be considered. This study was conducted to characterize the dose response of the early G2/M checkpoint and then...

This chapter discusses the biology of low-dose hyper-radiosensitivity (HRS) with reference to radiation-induced DNA damage and cellular repair processes. Particular attention is paid to the significance of G2-phase cell cycle check-points in overcoming low-dose hyper-radiosensitivity and the impact of HRS on low-dose rate radiobiology. The history...

The molecular basis of low-dose hyper-radiosensitivity (HRS) is only partially understood. The aim of this study was to define the roles of ataxia telangiectasia mutated (ATM) activity and the downstream ATM-dependent G(2)-phase cell cycle checkpoint in overcoming HRS and triggering radiation resistance. Survival was measured using a high-resolutio...

Little is known about the mode of cell killing associated with low-dose hyper-radiosensitivity, the radiation response that describes the enhanced sensitivity of cells to small doses of ionizing radiation. Using a technique that measures the activation of caspase 3, we have established a relationship between apoptosis detected 24 h after low-dose r...

In recent years, enhanced sensitivity in the radiation survival response of mammalian cells has been identified at doses below 0.5 Gray (Gy). Termed low-dose hyper-radiosensitivity (HRS), the response is typified by enhanced sensitivity of cells in the 0.1 and 0.2 Gy range, followed by increasing resistance to killing per unit dose up to 1.0 Gy whe...