Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities.

PURPOSE: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. METHODS AND MATERIALS: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2[4h]) and 24 hours (SF2[24h]) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. RESULTS: The SF2(4h) was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio(30min) (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio(4h)/γH2AX-ratio(30min)) showed a significant direct association with high toxicity grade (P=.01). CONCLUSIONS: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with efficient DSB repair ability, predicts for increased radiation tolerance.

The angiogenetic effect of intramuscular administration of b-FGF and a-FGF on cardiac muscle: the influence of exercise on muscle angiogenesis.

Although angiogenetic therapy using recombinant growth factors holds much hope for the treatment of ischaemic diseases, there are still many unanswered questions, including the method of administration, the correct dose of these factors, and the duration of the therapeutic approach. Exercise has also been suggested to induce neovascularizaiton in muscles. We evaluated the angiogenetic effects of the intramuscular administration of basic-fibroblast growth factor (b-FGF) and acidic-fibroblast growth factor (a-FGF) in rat heart, compared with rats who exercised daily. In conclusion, both the intramuscular administration of b-FGF and exercise increased significantly angiogenesis in the heart in contrast to the intramuscular administration of a-FGF, which was ineffective.

NSC 290205-based therapy in murine pancreatic adenocarcinoma PAN02 in combination with adriamycin (ADR).

BACKGROUND: NSC 290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. In this study, the antitumor activity of A in combination with ADR (AHOP) was investigated in comparison with the standard CHOP regimen. MATERIALS AND METHODS: PAN02 adenocarcinoma was used in this study. C57Bl mice were used for chemotherapy evaluation. The activity was assessed from the inhibition of tumor growth and the oncostatic parameter T/C%. RESULTS: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both the CHOP and AHOP regimens showed significant and comparable antitumor effects. AHOP caused the maximum effect, inhibiting tumor growth by 56.8%. CHOP was less effective, producing 47.7% tumor inhibition. CONCLUSION: It is very likely that the D-lactamic steroid (androstan) alkylator forA, containing the amide group -NH-CO-, combined with ADR which intercalates between DNA base-pairs, is the explanation for the higher activity of AHOP as compared to CHOP.

The angiogenetic effect of intramuscular administration of VEGF on muscle. The influence of exercise on angiogenesis.

UNLABELLED: Although angiogenetic therapy using recombinant growth factors holds much hope for the treatment of ischemic diseases, there are still unanswered questions including the method, doses or duration of therapeutic approach. We evaluated the angiogenetic effects of vascular endothelial growth factor (VEGF) on rat heart and gastrocnemius muscles when this was administered intramuscularly and compared them to those obtained from rats, which exercised daily. CONCLUSION: Both daily swimming exercise and intramuscular administration of VEGF increased angiogenesis in rat heart, even though exercise alone was the only one that increased angiogenesis quite significantly. The combined protocol (administration of growth factor and exercise) led to an increase of angiogenesis in cardiac muscles. In contrast, there was no effect on the lateral gastrocnemius muscle either by VEGF or exercise, whereas these together induced angiogenesis locally at the site of injection.