Medical countermeasures for the hematopoietic-subsyndrome of acute radiation syndrome in space.

More than 50 years after the Apollo missions ended, the National Aeronautical and Space Administration (NASA) and other international space agencies are preparing a return to the moon as a step towards deep space exploration. At doses ranging from a fraction of a Gray (Gy) to a few Gy, crew will be at risk for developing bone marrow failure associated with the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) requiring pharmacological intervention to reduce risk to life and mission completion. Four medical countermeasures (MCM) in the colony stimulating factor class of drugs are now approved for treatment of myelosuppression associated with ARS.

Secondary Malignancies in the Era of High-Precision Radiation Therapy.

Although modern radiation therapy delivers a localized distribution of ionizing energy that can be used to cure primary cancers for many patients, the inevitable radiation exposure to non-targeted normal tissue leads to a risk of a radiation-related new cancer. Modern therapies often produce a complex spectrum of secondary particles, both charged and uncharged, that must be considered both in their physical radiation transport throughout the patient and their potential to induce biological damage, which depends on the microscopic energy deposition from the cascade of primary, secondary, and downstream particles. This work summarizes the experimental data for relative biological effectiveness for particles associated with modern radiotherapy in light of their capacity to induce secondary malignancies in patients.

The Role of the Apoptotic Machinery in Ionizing Radiation-Induced Carcinogenesis.

Ionizing radiation is an established cause of cancer based on epidemiologic and experimental evidence. According to epidemiological data, virtually all tissues in the human body are sensitive to the carcinogenic action of radiation. Apoptosis represents a major barrier to cancer because apoptotic cell death eliminates dangerous cells that may initiate tumor development.

Bioengineering radioresistance by overproduction of RPA, a mammalian-type single-stranded DNA-binding protein, in a halophilic archaeon.

Halobacterium sp. NRC-1 is a wild-type extremophilic microbe that is naturally tolerant to high levels of ionizing radiation. Mutants of strain NRC-1 with even higher levels of resistance to ionizing radiation, named RAD, were previously isolated after selecting survival to extremely high doses of ionizing radiation.

The effect of docetaxel (taxotere) on human gastric cancer cells exhibiting low-dose radiation hypersensitivity.

Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells in the G(2)/M phase of the cell cycle.

The synergistic effect of dimethylamino benzoylphenylurea (NSC #639829) and X-irradiation on human lung carcinoma cell lines.

Purpose: The present study was designed to investigate the ability of N-[4-(5-bromo-2-pyrimidyloxy)-3-methylphenyl]-(dimemethylamino)-benzoylphenylurea (dimemethylamino benzoylphenylurea; BPU) to sensitize cells to radiation and to examine the relationship between phenotype versus survival, DNA damage, apoptosis, or cell cycle progression in non-small cell lung cancer (NSCLC) cell lines.

Methods: Asynchronous cultures of three NSCLC (phenotype) lines, A549 (adenocarcinoma), NCI-H226 (squamous) and NCI-H596 (adenosquamous) were used. Cells were treated for 24 h with BPU at various concentrations (0-10 microM) to obtain drug doses for inhibiting cell survival by approximately 50% (IC50).

Cytotoxicity of docetaxel (Taxotere) used as a single agent and in combination with radiation in human gastric, cervical and pancreatic cancer cells.

Background: Docetaxel (Taxotere) has gained increasing attention in clinical applications. We investigated the cytotoxic and radiosensitizing potential of docetaxel at nanomolar concentrations in six cell lines derived from tumors that rarely respond to radiation or chemotherapy, with special consideration of mechanisms of resistance, including the p53 mutational status.

Methods: Cells derived from carcinomas of the human stomach (p53 mutant Hs746T, p53 wild type AGS), cervix (p53 wild type CaSki, p53 mutant HeLa) or pancreas (p53 mutant BxPC3 and Capan-1) were treated for 24 h with docetaxel at various concentrations (0.

Coordinate late expression of trefoil peptide genes (pS2/TFF1 and ITF/TFF3) in human breast, colon, and gastric tumor cells exposed to X-rays.

The trefoil factors (TFFs) are pleiotropic factors involved in organization and homeostasis of the gastrointestinal tract, estrogen responsiveness, inflammatory disorders, and carcinogenesis. In an earlier study using cDNA array technologies to identify new genes expressed in irradiated cell survivors, we isolated a cDNA clone corresponding to the reported human TFF1 gene (E. K.