Use of steroids to suppress vascular response to radiation

A quantitative measure of the vascular permeability surface area product (PS) for albumin has been made using a double isotope technique. PS was significantly elevated in irradiated rat lung, heart, skin, and muscle, between 19 and 26 days following 18 or 25 Gray thorax irradiation. Administration of dexamethasone from 2 days before irradiation through the day of measurement suppressed the expected increase in PS in lung, heart, and muscle, but not in skin. Shorter periods of steroid administration were not as effective in suppressing this response to radiation exposure. Increased vascular permeability following radiation may be an essential element in the development of radiation fibrosis. We hypothesize that the ability to suppress this response could result in a long term reduction in the incidence of fibrosis.     

Classification of cancer chemotherapeutic drugs according to their ability to potentiate contact sensitivity to dinitrofluorobenzene

The anticancer chemotherapeutic drugs cyclophosphamide (CY), melphalan (L-phenylalanine mustard; L-PAM), 5-fluorouracil (5-FU), methotrexate (MTX), and daunorubicin (DAU) were tested for ability to potentiate contact sensitization (CS) to dinitrofluorobenzene (DNFB) in mice and to inhibit induction of unresponsiveness to such sensitization by preceding exposure to dinitrobenzenesulfonate (DNBS). Administration of CY and L-PAM but not of 5-FU, MTX, and DAU, after DNBS treatment (and before DNFB sensitization) reduced the degree of unresponsiveness effected by DNBS. It is suggested that the test system of CS might be utilized for screening the ability of cancer chemotherapeutic agents to act as nonspecific immuno-modulators.     

Approaches to predicting the reaction of human tumors to radiotherapy

Immunofluorescent method using anti-thymidine antibodies was employed to assess proliferative activity of 217 human tumors including oropharyngeal, esophageal, gastric, rectal and lung cancer. The activity was evaluated before and, in 38 neoplasms, in the course of radiotherapy. It was shown that changes in the proliferative activity of oropharyngeal and gastric malignancies observed early in the course of radiation treatment may serve for predicting response.     

Autophagy contributes to resistance of tumor cells to ionizing radiation

Background and purpose

Autophagy signaling is a novel important target to improve anticancer therapy. To study the role of autophagy on resistance of tumor cells to ionizing radiation (IR), breast cancer cell lines differing in their intrinsic radiosensitivity were used.

Materials and methods

Breast cancer cell lines MDA-MB-231 and HBL-100 were examined with respect to clonogenic cell survival and induction of autophagy after radiation exposure and pharmacological interference of the autophagic process. As marker for autophagy the appearance of LC3-I and LC3-II proteins was analyzed by SDS-PAGE and Western blotting. Formation of autophagic vacuoles was monitored by immunofluorescence staining of LC3.

Results

LC3-I and LC3-II formation differs markedly in radioresistant MDA-MB-231 versus radiosensitive HBL-100 cells. Western blot analyses of LC3-II/LC3-I ratio indicated marked induction of autophagy by IR in radioresistant MDA-MB-231 cells, but not in radiosensitive HBL-100 cells. Indirect immunofluorescence analysis of LC3-II positive vacuoles confirmed this differential effect. Pre-treatment with 3-methyladenine (3-MA) antagonized IR-induced autophagy. Likewise, pretreatment of radioresistant MDA-231 cells with autophagy inhibitors 3-MA or chloroquine (CQ) significantly reduced clonogenic survival of irradiated cells.

Conclusion

Our data clearly indicate that radioresistant breast tumor cells show a strong post-irradiation induction of autophagy, which thus serves as a protective and pro-survival mechanism in radioresistance.     

立体定向放射治疗技术在前列腺增生症治疗中的应用探索

目的：观察立体定向放射治疗（X刀）前列腺增生症（BPH）的有效性及安全性。方法：应用X刀治疗12例重度BPH，靶区为整个前列腺，采用90％的等剂量曲线包绕靶区，（1．5—2）Gy／f，共（5—8）f，隔日一次，每周3次。治疗前、后比较国际前列腺症状评分、生活质量指数、前列腺体积、膀胱残余尿量、最大尿流速。结果：临床治愈8例，显效4例，各项指标变化显著（P〈0．01）。结论：立体定向放射治疗BPH安全、有效。     

Relation of environmental exposure to erionite fibres to risk of respiratory cancer

During the period 1979-1983, IARC, in collaboration with the Department of Chest Diseases of Hacettepe University in Ankara and the MRC Pneumoconiosis Unit in Penarth, conducted an epidemiological and environmental survey in 4 villages in central Turkey affected by a high incidence of mesothelial tumours. Recent data point to erionite, a zeolite fibre, as the most plausible etiological agent. From animal experiments, erionite appears to be the most powerful carcinogenic fibre so far known. During the study period, 17 pleural mesotheliomas and 7 lung cancer cases have been reported among the villagers. These cancer cases are analysed in relation to exposure to fibres. We assume exposure to occur from birth onwards and therefore consider duration of exposure equal to age. On this basis, the incidence of mesothelial and lung tumours is analysed in relation to age and cumulative exposure to fibres computed using the airborne fibre levels measured during the survey.     

Development of techniques to monitor for exposure to vinyl chloride: monoclonal antibodies to ethenoadenosine and ethenocytidine

Monoclonal antibodies which specifically recognize etheno-adenosineand ethenocytidine, two of the adducts resulting from exposureto vinyl chloride, have been developed. The sensitivity andspecificity of these antibodies have been determined by enzyme-linkedimmunosorbent assay (ELISA). The antibody to ethenoadenosine(1G4) reacts with both the ribose (50% inhibition at 600 fmol)and deoxyribose (50% inhibition at 980 fmol) form of the adduct.The antibody to ethenocytidine (6F5) also reacts with both theribose (50% inhibition at 800 fmol) and deoxyribose (50% inhibitionat 1000 fmol) form of the adduct. Neither antibody cross-reactswith non-modified DNA or the normal nucleotides. A more sensitivefluorescence ELISA was developed for antibody 1G4 with 50% inhibitionat 212 fmol of ethenoadenosine and for antibody 6F5 with 50%inhibition at 192 fmol ethenocytidine. These antibodies havebeen used to determine the level of etheno derivatives in DNAmodified in vitro with chloroacet-aldehyde and in the DNA andRNA of cells treated in culture.     

Overcoming cultural barriers to giving bad news: Feasibility of training to promote truth-telling to cancer patients

Background. In many countries, physicians are reluctant to disclose unfavorable medical information to patients with advanced cancer and instead give the bad news to the family. Methods. The authors modified standard communication workshops to help Italian senior oncologists overcome cultural, social, and attitudinal barriers to disclosure of diagnosis and prognosis. Results. Fifty-seven physicians participated; 88% believed the workshops would improve their medical practice. Many pursued further training and organized communication skills programs of their own. Conclusions. Communication skills workshops can be modified to meet educational and social norms and help clinicians acquire the interpersonal skills needed for honest communication with patients.     

The potential of carp to bioactivate benzo[a]pyrene to metabolites that bind to DNA

We have investigated the formation of DNA adducts in starved, fed and 5,6-benzoflavone-pretreated carp following i.p. administration of benzo(a)pyrene. 32P-postlabeling analysis of the liver DNAs showed the presence of one predominant (greater than 92%) adduct in all three groups. Cochromatography experiments revealed that the main adduct was identical to authentic BPDEI-dG (10 beta-(deoxyguanosin-N2-yl)-7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene). The formation of the adduct was evident as early as 1.5 h post-treatment and the levels increased steadily up to 7 days, reaching about 125, 110 and 102 attomole/microgram DNA in starved, fed and benzoflavone-pretreated carp, respectively. During this period, the benzo[a]pyrene-induced benzo[a]-pyrene monooxygenase activity increased from the uninduced, natural level of about 3 pmol/mg per min to levels of 35, 62 and 79 pmol/mg per min in starving, fed and 5,6-benzoflavone pretreated fish, respectively. A slow but steady formation of the diolepoxide-dG adduct was also observed in the liver DNA of carp following p.o. treatment. These results indicate that carp can biotransform polycyclic aromatic hydrocarbons such as benzo[a]pyrene to 'reactive' metabolites that bind to DNA.