Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [F]Fluoromisonidazole ([F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements.

Purpose: The purpose of this study is to use dynamic [F]fluoromisonidazole ([F]FMISO) positron emission tomography (PET) to compare estimates of tumor hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood ratios (TBR), and independent oxygen (pO) measurements.

Procedures: BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO measurements. Data from 120-min dynamic [F]FMISO scans were fit to two-compartment irreversible three rate constant (K , k , k ) and Patlak models (K ).

Role of chitinase 3-like-1 and semaphorin 7a in pulmonary melanoma metastasis.

The prototypic chitinase-like protein Chi3l1 is induced in cancers and portends a poor prognosis, but whether it contributes to cancer progression is unknown. To address this gap in knowledge, we investigated the production of Chi3l1 in melanoma lung metastases. We found that Chi3l1 was induced during pulmonary melanoma metastasis and that this induction was regulated by the semaphorin Sema7a, interacting in stimulatory or inhibitory ways with its β1 integrin or Plexin C1 receptors, respectively.

Fenbendazole as a potential anticancer drug.

Background/aims: To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes.

Materials And Methods: We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens.

Results: Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia.

Community-university partnerships in community-based research.

Problem: Community-engaged research (CEnR) is a complex, collaborative process that presents many challenges and requires investment of time and commitment by both community and university research partners.

Purpose: This paper describes the experience of a group of university and community members developing a set of guidelines for the ethical conduct of CEnR projects.

Key Points: The paper outlines the process of guideline development and lessons learned from this collaborative effort, which was based upon approaches and methods of community-based participatory research (CBPR).

Targeting cancer with a lupus autoantibody.

Systemic lupus erythematosus (SLE) is distinct among autoimmune diseases because of its association with circulating autoantibodies reactive against host DNA. The precise role that anti-DNA antibodies play in SLE pathophysiology remains to be elucidated, and potential applications of lupus autoantibodies in cancer therapy have not previously been explored. We report the unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA repair-deficient malignancies.

Tumor-associated mutations in O⁶ -methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality.

MGMT is the primary vehicle for cellular removal of alkyl lesions from the O-6 position of guanine and the O-4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well-characterized, but somatic variants found in tumors were, prior to this work, uncharacterized.

Preliminary studies with a new hypoxia-selective cytotoxin, KS119W, in vitro and in vivo.

Agents with selective toxicity to hypoxic cells have shown promise as adjuncts to radiotherapy. Our previous studies showed that the bioreductive alkylating agent KS119 had an extremely large differential toxicity to severely hypoxic and aerobic cells in cell culture, and was effective in killing the hypoxic cells of EMT6 mouse mammary tumors in vivo. However, the limited solubility of that compound precluded its development as an anticancer drug.

Preclinical studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as a potential adjunct to radiation therapy.

Objective: Abdominal and pelvic radiotherapy is limited by the radiosensitivity of the small and large intestine. PHY906 (KD018), a state-of-the-art, well defined adaptation of a traditional Chinese medicine, decreased intestinal injury from chemotherapy in preclinical studies and is in clinical trials with chemotherapy. This project assessed whether PHY906 would also reduce intestinal injury from abdominal irradiation in mice.

Use of fenbendazole-containing therapeutic diets for mice in experimental cancer therapy studies.

Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility-wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice.

Broadcasting in the airways: the fifth anniversary of the Radiation Research Podcast (1).

The Radiation Research Podcast was funded just over five years ago by a few Radiation Research Society members. To date, the volunteers running the podcast have produced and published online, open access, over 70 audio interviews. The program includes monthly interviews with authors of articles, award winners, and other recordings at conferences, such as round table discussions.

A prospective, multicenter study of complementary/alternative medicine (CAM) utilization during definitive radiation for breast cancer.

Purpose: Although complementary and alternative medicine (CAM) utilization in breast cancer patients is reported to be high, there are few data on CAM practices in breast patients specifically during radiation. This prospective, multi-institutional study was conducted to define CAM utilization in breast cancer during definitive radiation.

Materials/methods: A validated CAM instrument with a self-skin assessment was administered to 360 Stage 0-III breast cancer patients from 5 centers during the last week of radiation.

Preclinical evaluation of Laromustine for use in combination with radiation therapy in the treatment of solid tumors.

Purpose: These studies explored questions related to the potential use of Laromustine in the treatment of solid tumors and in combination with radiotherapy.

Materials And Methods: The studies used mouse EMT6 cells (both parental and transfected with genes for O(6)-alkylguanine-DNA transferase [AGT]), repair-deficient human Fanconi Anemia C and Chinese hamster VC8 (BRCA2(-/-)) cells and corresponding control cells, and EMT6 tumors in mice assayed using cell survival and tumor growth assays.

Results: Hypoxia during Laromustine treatment did not protect EMT6 cells or human fibroblasts from this agent.

Subclinical vitamin A deficiency does not increase development of tumors in irradiated or unirradiated lungs.

Cancer patients often have subclinical vitamin A deficiencies and low vitamin A lung levels. Previous studies showed that subclinical vitamin A deficiency increased the severity of pneumonitis induced by whole-lung irradiation in rats. Many studies have shown that lung irradiation increases the number of lung tumors developing from intravenously injected tumor cells in mice.

The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers.

Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the (131)Cs, (125)I and (103)Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int.

Spontaneous coagulopathy in inbred WAG/RijYcb rats.

Here we describe a series of cases of spontaneous coagulopathy in a colony of inbred WAG/RijYcb (WAG/RijY) rats. This strain previously had been bred at our institution without symptomatology for several decades. The index case was a 10-wk-old male rat that developed a large hematoma at a subcutaneous injection site.

Aplidin as a potential adjunct to radiation therapy: in vitro studies.

Purpose: Aplidin (plitidespin) is a novel cyclic depsipeptide, currently in Phase II clinical trials for solid and hematologic malignancies. We examined the effects of oxygen on the cytotoxicity of Aplidin and the interactions between Aplidin and radiation. These factors will be important if Aplidin is used clinically in combination with radiotherapy.

American Society for Radiation Oncology (ASTRO) survey of radiation biology educators in U.S. and Canadian radiation oncology residency programs.

Purpose: To obtain, in a survey-based study, detailed information on the faculty currently responsible for teaching radiation biology courses to radiation oncology residents in the United States and Canada.

Methods And Materials: In March-December 2007 a survey questionnaire was sent to faculty having primary responsibility for teaching radiation biology to residents in 93 radiation oncology residency programs in the United States and Canada.

Results: The responses to this survey document the aging of the faculty who have primary responsibility for teaching radiation biology to radiation oncology residents.

Hypoxia and radiation therapy: past history, ongoing research, and future promise.

Tumor hypoxia influences the outcome of treatment with radiotherapy, chemotherapy and even surgery, not only for the treatment of large bulky tumors with extensive necrosis, but also in the treatment of very small primary tumors and recurrences, micrometastases, and surgical margins with microscopic tumor involvement. Because hypoxic tumor cells are resistant to radiation and to many anticancer drugs, many approaches to circumventing the therapeutic resistance induced by hypoxia have been examined in laboratory studies and clinical trials. In this review, these approaches and the results of past laboratory and clinical studies are described and the limitations of the past agents and their testing are discussed.

The FDP Faculty Burden Survey.

To better understand the administrative burdens placed on faculty who perform research, the Faculty Standing Committee of the Federal Demonstration Partnership (FDP) invited 23,325 full-time faculty members who were Principal Investigators (PI) or Co-Principal Investigators (Co-PI) on active federally funded research grants to participate in a web-based survey that contained questions on the nature, size, and impact of the administrative tasks associated with their research projects. The responses of the 6,081 faculty respondents show that the administrative burden on faculty is very significant: 42% of the time spent by an average PI on a federally funded research project was reported to be expended on administrative tasks related to that project rather than on research. This administrative burden does not stem from one or a few exceptionally onerous tasks, but instead reflects the cumulative effect of the many administrative burdens imposed by different funding agencies, different offices within agencies, auditing and accrediting agencies, and academic institutions.

Mapping DNA adducts of mitomycin C and decarbamoyl mitomycin C in cell lines using liquid chromatography/ electrospray tandem mass spectrometry.

The antitumor antibiotic and cancer chemotherapeutic agent mitomycin C (MC) alkylates and crosslinks DNA, forming six major MC-deoxyguanosine adducts of known structures in vitro and in vivo. Two of these adducts are derived from 2,7-diaminomitosene (2,7-DAM), a nontoxic reductive metabolite of MC formed in cells in situ. Several methods have been used for the analysis of MC-DNA adducts in the past; however, a need exists for a safer, more comprehensive and direct assay of the six-adduct complex.

The interactions of polarographic measurements of oxygen tension and histological grade in human glioma.

Purpose: The purpose of this study is to investigate the implications of hypoxia and histological grade for survival in patients with gliomas.

Materials And Methods: Tissue oxygen tension was measured intraoperatively using an Eppendorf pO2 Histograph. Survival was calculated from the date of the Eppendorf study to the date of last follow-up.

Development of a statewide hospital plan for radiologic emergencies.

Although general guidelines have been developed for triage of victims in the field and for hospitals to plan for a radiologic event, specific information for clinicians and administrators is not available for guidance in efficient management of radiation victims during their early encounter in the hospital. A consensus document was developed by staff members of four Connecticut hospitals, two institutions of higher learning, and the State of Connecticut Department of Environmental Protection and Office of Emergency Preparedness, with assistance of the American Society for Therapeutic Radiology and Oncology. The objective was to write a practical manual for clinicians (including radiation oncologists, emergency room physicians, and nursing staff), hospital administrators, radiation safety officers, and other individuals knowledgeable in radiation monitoring that would be useful for evaluation and management of radiation injury.

Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors.

Carboplatin, a member of the platinum family of alkylating agents, is often used in combination with radiotherapy. Some studies, including a recent publication from our laboratory, have suggested that the cytotoxic effects of platinum compounds may be altered by changes in the post-treatment oxygenation. The study reported here assessed whether post-treatment changes in tumor oxygenation caused by oxygen breathing alone or in combination with efaproxiral (RSR13) altered the effects of carboplatin.