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Results for “Radiation-Sensitizing Agents”

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At least 19 recordsLinked to original sources
PubMed1976

[Five-years synchronized radiotherapy in treatment of carcinoma of the head and neck: clinical results, 1970--1974 (author's transl)].

Increased tumor radiosensitivity can be achieved by the technique of synchronisation, although as yet this relationship has only been partial. Our clinical experiences from 1970-1974 with this technique lead to the following considerations: 1. Synchronized radiotherapy (Telecobalt) is administered twice weekly, independent of adjunctive medications (such as fluoro-uracil, vincristin or bleomycin). 2. Synchronized radiotherapy does not change previous indications for operative intervention. 3. The described technique permits successful treatment of advanced tumors as well as postoperative tumor recurrences of recurrences in previously-irradiated tisssues. 4. The radiosensitivity of poorly oxygenated tumor tissues may be increased. 5. Radiation dosage must not be reduced. 6. Distant tumor metastases can also be treated with additional chemotherapy (as synchronized chemotherapy).

Antineoplastic Agents↗
PubMed1979

The biologic basis for combined modality treatment of cancer.

Strategies related to cancer should be aimed at optimization of local and regional treatment. Delineation of subsets of patients with high risk for recurrence would have a significant impact, upon which such adjunctive systems of therapeutic management should be evaluated. In disseminated disease, or where the probability of dissemination is high, evaluation of any realistic potential combination of treatment for tumor control should be pursued. It is necessary to delineate optimal palliative therapy where tumor control is not possible, but also to test new drugs, immunotherapeutic tools and combination regimens in all such situations where the disseminated compartment of the disease is of high probability. Only under such circumstances will the most practical and important optimization of treatment programs be achieved. The development of the above basic attributes for each tumor type needs to be studied so that protocols can be developed with a clear understanding of the nature of the disease, condition to be studied, and the general therapeutic strategies to be followed.

Antineoplastic Agents↗
PubMed1978

Toxicity, radiation sensitivity modification, and metabolic effects of dehydroascorbate and ascorbate in mammalian cells.

Dehydroascorbate, an electron affinic metabolite of vitamin C, sensitized Ehrlich ascites tumor cells, in vivo, to radiation and was selectively toxic to V79 Chinese hamster lung cells under hypoxic conditions (without radiation). The radiosensitization may involve both the electron affinic nature of dehydroascorbate as well as its ability to oxidize the intracellular NAD(P)H and non-protein sulfhydryl. Dehydroascorbate's oxidation of NAD(P)H required higher concentrations than other sulfhydryl oxidants such as N-ethylmaleimide and diamide. The oxidation of NAD(P)H by dehydroascorbate could be reversed by glucose. Hypoxic cell radiosensitization of V79 cells in tissue culture by dehydroascorbate could not be easily demonstrated because of the rapid breakdown and appreciable cytotoxicity of the drug at high concentration. The cytotoxicity was found to occur with both high and low densities of V79 cells. With low cell densities small amounts of oxygen did not reduce the cytotoxicity of dehydroascorbate, but virtually eliminated the cytotoxicity of nitroaromatic electron affinic compounds (metronidazole and Ro-07-0582). The cytotoxicity to dense cell suspensions was found to depend upon the type of buffer included in the reaction medium. The maximum cytotoxicity was obtained in buffer free saline. The reduced form of dehydroascorbate, vitamin C, was found to be toxic only under aerobic conditions. The aerobic cytotoxicity could be prevented by the addition of catalase to the growth medium or by an increase in cell density, suggesting it was caused entirely by the production of H2O2 from the oxidation of vitamin C.

Aerobiosis↗
PubMed1976

Hypoxic cell sensitisers in radiotherapy.

Solid tumours contain poorly oxygenated cells, and these are disproportionately resistant to therapeutic radiation. Several methods of overcoming this problem have been used clinically, including the administration of hyperbaric oxygen during irradiation, radiotherapy with heavy nuclear particles such as neutrons from cyclotrons, optimum size and spacing of multiple doses of conventional radiation, and, most recently, chemical radiosensitisers. These radiosensitisers mimic the sensitising effect of oxygen and are active only against hypoxic cells. They do not, therefore, increase radiation response in well-oxygenated normal tissues. They are not rapidly metabollised and so can penetrate further than oxygen from the vascular capillaries and effectively reach the hypoxic cells in the tumour. Some of these drugs are of considerable clinical promise. The results of in vitro and in vivo studies with radiosensitisers are summarised and preliminary clinical work is described.

Animals↗
PubMed2026

CRISPR Screen Identifies HDAC3 as a Novel Radiosensitizing Target in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is an aggressive malignancy, with most patients presenting with prognostically poor extensive-stage disease. Limited progress in standard care stresses the urgent need for novel therapies. Radiotherapy offers some survival benefit for selected patients with SCLC but could be enhanced with radiosensitizers. In this study, we identify HDAC3 as a novel radiosensitizing target in SCLC using a CRISPR knockout screen and demonstrate its efficacy and mechanism. SBC5 cells were transduced with a custom EpiDrug single-guide RNA library and treated with ionizing radiation (IR) to identify radiosensitizing genes. HDAC3 emerged as a candidate and was validated through genetic knockdown and pharmacologic inhibition (RGFP966) in multiple SCLC cell lines. Both approaches enhanced radiosensitivity, as shown by cell viability (dose modification factor10 = 1.14-1.69) and clonogenic assays (dose modification factor10 = 1.16-1.41). We assessed changes in chromatin accessibility by assay for transposase-accessible chromatin using sequencing and IR-induced DNA damage and repair using γH2AX foci detection, double-strand break (DSB) repair assays, and immunoblotting of repair proteins. HDAC3-deficient cells exhibited increased chromatin accessibility, greater IR-induced DSBs, and impaired repair capacity, resulting in persistent DNA damage. This repair defect sensitized cells to PARP inhibitors, for which combining RGFP966 with olaparib or talazoparib produced additive to synergistic effects. In SCLC xenograft models, HDAC3 knockdown or RGFP966, combined with IR, achieved significant tumor growth inhibition. Collectively, we identified HDAC3 as a novel radiosensitizing target in SCLC. Its functional loss increased the generation and persistence of IR-induced DNA DSBs, effectively sensitizing SCLC cell lines and xenografts to IR, providing a potential radiosensitization strategy to treat SCLC.

Humans↗
PubMed1979

Radiation sensitivity change of hemopoietic cells induced by hydroxyurea.

Hemopoietic tissues of mice contain cells capable of proliferation and differentiation to form endogenous spleen colonies (Endo-CFU-S) in irradiated animals. Hydroxyurea (HU) given before irradiation of C57BL mice for endogenous CFU assay increased the number of surviving CFU-S twofold. Either HU or HSATT given after the initial stimulus abolished this rise. In vivo and in vitro 'suicide' assays of spleen cells indicated that cells were stimulated by the HU or the initial stimulus to enter into DNA synthesis shortly after stimulation. The resting CFU cell population appeared to be positioned close to DNA-S phase and responded to the stimulus by entry into S phase. Whole body irradiation at intervals after HU revealed a changing radiation sensitivity of the endogenous CFU-S consistent with drug-induced progression with decreased radiation sensitivity of the S phase cohort of cells.

Animals↗
PubMed1976

Large-dose bleomycin therapy and pulmonary toxicity. A possible role of prior radiotherapy.

Bleomycin sulfate pulmonary toxicity was encountered in nine of 101 patients receiving high-dose therapy for widespread testicular cancer. The pulmonary presentation was separable into two categories: (1) an early or minimal from with dyspnea on exertion, minimal roentgenographic findings, and normal arterial partial pressure of oxygen at rest and (2) a severe form, with prominent roentgenographic findings and hypoxemia at rest. All five patients with the severe form died, while the remaining four patients with the minimal presentation recovered. Prior thoracic radiotherapy appeared to predispose to bleomycin pulmonary toxicity, as this complication developed in five of 12 patients receiving prior chest radiotherapy vs four of 89 not receiving radiotherapy (p less than .001). The fatality rate of 5% with high-dose bleomycin therapy is acceptable in view of the 75% response rate and substantially improved survival achieved with bleomycin combination chemotherapy in metastatic testicular cancer.

Adolescent↗
PubMed1978

Radiotherapy and hyperbaric oxygen. Report of a Medical Research Council Working Party.

The M.R.C. Working Party has coordinated randomised clinical trials to assess hyperbaric oxygen as a sensitiser in radiotherapy. 1669 patients were registered in these studies between 1963 and 1976. Hyperbaric oxygen significantly improved both survival and local tumour control after radiotherapy for head-and-neck tumours and for advanced carcinoma of the cervix. In carcinoma of the bronchus there seemed to be some improvement in survival but this was not statistically singificant. In carcinoma of the bladder hyperbaric oxygen has shown no benefit. Centres already equipped with hyperbaric chambers should continue to use them for those types of tumour shown to benefit. Since hyperbaric oxygen treatment makes great demands on medical and other staff, extension of its use must await comparison with other methods for improving radiotherapy which are now being evaluated.

Atmosphere Exposure Chambers↗