These are some interesting and perhaps relevant publications related to topics discussed earlier, as well as serving as references for the material presented.


Radiat Res 2001 Feb;155(2):360-8 
<b>Effects of radiation on tumor intravascular oxygenation, vascular configuration, development of hypoxia, and clonogenic survival.</b> 
Lord E, Paoni S. Department of Radiation Oncology, University of Rochester School of Medicine, New York, USA. 
The underlying physiological mechanisms leading to tumor reoxygenation after irradiation have elicited considerable interest, but they remain somewhat unclear. The current study was undertaken to determine the effects of a single dose of 10 Gy gamma radiation on both tumor pathophysiology and radiobiologically hypoxic fraction. .... At 24 h postirradiation, ... results demonstrate that tumor hypoxia develops at an increased distance from perfused blood vessels after irradiation,...By 72 h postirradiation, all physiological parameters had returned to the levels in volume-matched, nonirradiated controls. ... Although such direct measurements have previously proven valuable in predicting tumor response to therapy or oxygen manipulation, a combination of parameters is required to adequately describe the mechanisms underlying these changes after irradiation. 
&&url PMID: 11175672

<b>Hyperbaric oxygen corrects sacral plexopathy due to osteoradionecrosis appearing 15 years after pelvic irradiation.</b>
Videtic GM, Venkatesan VM Department of Radiation Oncology, London Regional Cancer Centre, Ontario,Canada. [Record supplied by publisher]
In 1982, a 55-year-old woman was treated by total cystectomy and adjuvant radiotherapy/chemotherapy for a leiomyosarcoma of the bladder. Fifteen years later she presented with symptoms and signs of sacral plexopathy. Investigations revealed osteoradionecrosis of the sacrum. Hyperbaric oxygen therapy (HBO2) was instituted and progressive resolution of the neurological complaints followed. HBO2 should be considered when managing late-onset sequelae in previously irradiated patients. 
&&url PMID: 10465478
Int J Radiat Oncol Biol Phys 1996 Apr 1;35(1):103-11


Toxicology 2000 Nov 30;155(1-3):73-82 
<b>Oxidative damage to mitochondria in normal and cancer tissues, and its modulation.</b> 
Kamat JP, Devasagayam TP. Cell Biology Division, Bhabha Atomic Research Centre, Mumbai, India. 
Cellular damage induced by reactive oxygen species (ROS) in normal tissues has been implicated in the etiology of several human ailments. Among the subcellular organelles, damage to mitochondria is considered crucial and can lead to cytotoxicity and cell death.... Our study shows that ROS can induce significant oxidative damage in mitochondria from both normal and tumor tissues and this can be inhibited by natural antioxidants like tocotrienols, nicotinamide and caffeine. Damage, on the other hand, can be enhanced by deuteration of the buffer and oxygenation. Our results hence demonstrated that mitochondria were sensitive to damage by ROS and its modulation may have potential uses in prevention of the disease in normal tissues; if damage can be selectively induced in tumor, it can lead to its regression. 
&&url PMID: 11154799 



Radiother Oncol 2000 Mar;54(3):261-71 
<b>Variation in sensitizing effect of caffeine in human tumour cell lines after gamma-irradiation.</b> 
Valenzuela MT, Mateos S, Ruiz de Almodovar JM, McMillan TJ. Laboratoio de Investigaciones Medicas y Biologia Tumoral, Departamento de Radiologia y Medicina Fisica, Facultad de Medicina, Universidad de Granada, 18071, Granada, Spain. 
... The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. 
&&url PMID: 10738085 


<b>Radiation-recall enteritis after actinomycin-D and adriamycin therapy.</b> 
Stein RS. 
A 22-year-old man developed four episodes of bowel obstruction after radiation therapy for a testicular tumor metastatic to retroperitoneal nodes. Each episode followed a course of chemotherapy with actinomycin-D or adriamycin. On one occasion bowel resection was required and revealed vascular changes compatible with radiation injury. The case appears to be an example of radiation recall injury involving the small bowel. The decision to use actinomycin-D or adriamycin must be weighed against the risk of tissue injury when a predisposition to radiation damage is present. 
&&url PMID: 684478 


Br J Radiol 2000 Oct;73(874):1100-4 
<b>Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures.</b> 
Baddeley H, Brodrick PM, Taylor NJ, Abdelatti MO, Jordan LC, Vasudevan AS, Phillips H, Saunders MI, Hoskin PJ. Paul Strickland Scanner Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK. 

The gas mixture carbogen may be breathed by patients to enhance the oxygenation level and therefore the radiosensitivity of tumours. However, owing to the high CO2 content, its inhalation is associated with patient intolerance. Our aim was to determine a suitable carbon dioxide and oxygen gas mixture with similar enhancement of arterial oxygenation to 5% carbogen and with improved patient tolerance. ... The results suggest that 2% CO2 in O2 enhances arterial oxygen levels to a similar extent as 3.5% and 5% CO2 and that it is well tolerated. 
&&url PMID: 11271904


Gan To Kagaku Ryoho 2000 Oct;27(12):1816-8 
<b>[Chemoradiotherapy with low-dose cisplatin and 5-FU for advanced esophageal cancer].</b> [Article in Japanese] 
Tajima M, Ichikawa W, Takagi Y, Uetake Y, Kojima K, Osanai T, Takenaka S, Nihei Z, Sugihara K. Dept. of Surgery II, Tokyo Medical and Dental University. 
We evaluated the efficacy of chemoradiotherapy (CRT) for advanced esophageal cancer, from the view point of response. The relationship between chemo-radiosensitivity and dihydropyridine dehydrogenase (DPD), thymidylate synthase (TS), and p53 was investigated immunohistochemically. ... 
&&url PMID: 11086419 


Radiother Oncol 2000 Oct;57(1):91-6 
<b>Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors.</b> 
Huang EY, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY, Wu JM. Department of Radiation Oncology, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan. 

To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer. ... Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P<0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P<0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis. ... In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis. Publication Types: Clinical trial 
&&url PMID: 11033193  


Int J Radiat Oncol Biol Phys 2000 Sep 1;48(2):339-45 
<b>Blood hemoglobin level may affect radiosensitivity-preliminary results on acutely reacting normal tissues.</b> 
Henke M, Bechtold C, Momm F, Dorr W, Guttenberger R. Abteilung Strahlentherapie, Radiologische Universitatsklinik, Freiburg, Germany. henke@uni-freiburg.de 
...A decreased blood hemoglobin concentration may-perhaps by an impaired tissue oxygenation-reduce the radiosensitivity of normal tissue such as skin and mucosa. However, the data is preliminary and needs further confirmation. 
&&url PMID: 10974446 


Cancer 1996 Jun 1;77(11):2407-12
<b>Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience.</b>
Ashamalla HL, Thom SR, Goldwein JW Department of Radiation Oncology, New York Methodist Hospital, Brooklyn 11215, USA. [Record supplied by publisher]
... <b>The role of hyperbaric oxygen (HBO) therapy in the treatment of radiation-related sequelae in adults is well known</b>... Except for two patients who had initial anxiety, nausea, and vomiting, the HBO treatments were well tolerated. In all but one patient, the outcome was excellent. In the six patients who had prophylactic HBO, all continued to demonstrate complete healing of their orthodontal scars at last follow-up. In the four patients who received HBO as a therapeutic modality, all 4 had documented disappearance of signs and symptoms of radionecrosis and two patients demonstrated new bone growth on follow-up computed tomography scan. One patient with vasculitis and seventh cranial nerve palsy had transient improvement of hearing; however, subsequent audiograms returned to baseline. .... <b>The use of hyperbaric oxygen for children with radiation-induced bone and soft tissue complications is safe and results in few significant adverse effects. It is a potentially valuable tool both in the prevention and treatment of radiation-related complications.</b> 
&&url PMID: 8635114


Clin Oncol (R Coll Radiol) 1999;11(3):198-9
<b>Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas.</b> 
Mohanti BK, Rath GK, Anantha N, Kannan V, Das BS, Chandramouli BA, Banerjee AK, Das S, Jena A, Ravichandran R, Sahi UP, Kumar R, Kapoor N, Kalia VK, Dwarakanath BS, Jain V. Kidwai Memorial Institute of Oncology, Bangalore, India. 
PURPOSE: <b>Evaluation of tolerance, toxicity, and feasibility of combining large fraction (5 Gy) radiotherapy with 2-deoxy-D-glucose (2DG), an inhibitor of glucose transport and glycolysis, which has been shown to differentially inhibit repair of radiation damage in cancer cells.</b> METHODS AND MATERIALS: Twenty patients with supratentorial glioma (Grade 3/4), following surgery were treated with four weekly fractions of oral 2DG (200 mg/kg body weight) followed by whole brain irradiation (5 Gy). Two weeks later, supplement focal radiation to the tumor (14 Gy/7 fractions) was given. Routine clinical evaluation, x-ray computerized tomography (CT), and magnetic resonance (MR) imaging were carried out to study the acute and late radiation effects. RESULTS: All the 20 patients completed the treatment without any interruption. The vital parameters were within normal limits during the treatment. None reported headache during the treatment. Mild to moderate nausea and vomiting were observed during the days of combined therapy (2DG + RT) in 10 patients. No significant deterioration of the neurological status was observed during the treatment period. Seven patients were alive at 63, 43, 36, 28, 27, 19, and 18 months of follow-up. In these patients, the clinical and MR imaging studies did not reveal any late radiation effects. CONCLUSIONS: <b>Feasibility of administering the treatment (2DG + 5 Gy) is demonstrated by the excellent tolerance observed in all 20 patients. Further, the clinical and MR studies also show the absence of any brain parenchymal damage.</b> Publication Types: Clinical trial Clinical trial, phase i 
&&url PMID: 8641905 


Radiother Oncol 1999 Dec;53(3):233-45 
<b>Acute and late toxicity, tumour control and intrinsic radiosensitivity of primary fibroblasts in vitro of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.</b> 
Rudat V, Dietz A, Nollert J, Conradt C, Weber KJ, Flentje M, Wannenmacher M. Department of Radiation Oncology, University of Heidelberg, Germany. 

The existence of hereditary factors influencing the cellular response to ionising radiation has led to the hypothesis that the inter-patient variability of clinical radiation reactions may, at least in part, be attributable to an individual, or intrinsic, radiosensitivity. Considerable effort has been spent in the development of test systems that would determine individual radiosensitivity before or early during radiotherapy to possibly predict treatment outcome, but the results are still conflicting. The present explorative study was therefore aimed at the detection of associations between acute and late radiation effects, tumour control and in vitro radiosensitivity of primary normal tissue fibroblasts. ...
 In our study of patients with advanced cancer of the head and neck, neither the normal fibroblast SF2 nor the severity of acute radiation effects were able to predict late radiation effects or locoregional tumour control. 
&&url PMID: 10660204  


Clin Cancer Res 2000 Aug;6(8):3159-65 
<b>Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy.</b> 
Kamijo T, Yokose T, Hasebe T, Yonou H, Sasaki S, Hayashi R, Ebihara S, Miyahara H, Hosoi H, Ochiai A. Pathology, Division, National Cancer Center Research Institute East, Chiba, Japan. 

Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and ... epidermal growth factor receptor overexpression) and microvessel density ... in biopsy specimens from 31 LSCC patients given radiotherapy ... ...These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment. 
&&url PMID: 10955798

Radiother Oncol 1998 Feb;46(2):185-91 
<b>In vitro radiation-induced apoptosis and early response to low-dose radiotherapy in non-Hodgkin's lymphomas.</b> 
Dubray B, Breton C, Delic J, Klijanienko J, Maciorowski Z, Vielh P, Fourquet A, Dumont J, Magdelenat H, Cosset JM. Departement d'Oncologie Radiotherapie, Institut Curie, Paris, France. 
PURPOSE: Prospective investigation of spontaneous and in vitro radiation-induced apoptosis to predict early response to palliative radiotherapy in patients with non-Hodgkin's lymphomas. ... Spontaneous and in vitro radiation-induced apoptosis can be easily and quickly assessed on cells obtained by fine-needle sampling of non-Hodgkin's lymphoma lesions. The present results suggest that in vitro radiation-induced apoptosis could be used as a predictive assay of early response to low-dose in vivo irradiation in patients with non-Hodgkin's lymphomas. 
&&url PMID: 9510046 


Radiother Oncol 1998 Mar;46(3):239-48 Comment in: Radiother Oncol. 1998 Mar;46(3):225-7 
<b>Age has no impact on acute and late toxicity of curative thoracic radiotherapy.</b> 
Pignon T, Gregor A, Schaake Koning C, Roussel A, Van Glabbeke M, Scalliet P. Department of Radiotherapy-Oncology, Hopital de la Timone, Marseille, France. 

Radiotherapy is a treatment method frequently employed in the management of thoracic tumours. Although the highest incidence of these tumours is found in elderly people, tolerance to radiotherapy is not well documented in older age groups. Many physicians are tempted to alter the radiotherapy planning in a population with a supposed lower life expectancy in order to prevent acute reactions whereas late reactions are often ignored. The current study aimed to determine the influence of age on the frequency and severity of acute and late side effects and also whether the prognosis of tumours sufficiently differed between ages to justify different attitudes towards their management. 
... The absence of toxicity observed in the current study regardless of age reinforces the conviction that age per se is not a sufficient reason to exclude patients in good general condition with thoracic tumour from curative radiotherapy when medically indicated. 
&&url PMID: 9572616 


Zhongguo Zhong Xi Yi Jie He Za Zhi 1997 Aug;17(8):465-6 
<b>[Clinical study of combined Chinese herbal medicine with move stripe field radiation in treating primary hepatocellular carcinoma].</b> [Article in Chinese] 
Han JQ, Chen SD, Zhai LM. Shandong Institute of Tumor Prevention and Treatment, Jinan. 

To find a more effective treatment of primary hepatocellular carcinoma by using combined therapy of Chinese herbal medicine with radiotherapy. ... Prospective study was conducted with double-blind method on prognosis of patients treated with combined therapy of Xuefu Zhuyu decoction and move stripe field radiation on entire liver. A control group was established and treated with placebo and radiotherapy. ... The 1-, 3- and 5-year survival rates of the test group were higher than those of the control group by 20.0%, 23.4% and 16.6% respectively. The remote metastatic rate of the two groups were not different significantly. ... Xuefu Zhuyu decoction showed coordinative effect with radiotherapy on antitumor, it could enhance the radiosensitivity of liver cancer cells, increase the radiation tolerance of normal hepatocytes and reduce the side effect of radiotherapy. 
&&url PMID: 10322831


<b>[The morphological characteristics of sarcoma M1 cells before and after irradiation].</b> [Article in Russian] 
Abrosimov AI, Skoropad VI. 
Morphology of the death of rat sarcoma M1, cells before and in varying time after irradiation at doses of 10 and 20 Gy with and without metronidazole (as a radiosensitizer) was investigated at the light optic and electron microscopic levels. Two types of death: necrosis and apoptosis with the prevalence of the former were revealed. Irradiation and the use of metronidazole did not influence the type of death of sarcoma M1 cells. 
&&url PMID: 1943570 


Int J Radiat Oncol Biol Phys 1989 Jan;16(1):139-42 
<b>Tumor bed effect-induced reduction of tumor radiocurability through the increase in hypoxic cell fraction.</b> 
Milas L, Hunter N, Peters LJ. University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030. 
... TBE causes the reduction in tumor radiocurability through the increase in hypoxic fraction of tumor cells. 
&&url PMID: 2912935  


Radiobiologiia 1986 Mar-Apr;26(2):227-31 
<b>[Radiosensitizing effect of interferon synthesis inducers].</b> [Article in Russian] 
Leonidze DL, Afanas'ev GG, Poverennyi AM, Pelevina II. 
The preinjection of inductors of leukocytic interferon synthesis of rapid (poly I.poly C, dextransulfate) and slow (tyloron) types to mice bearing inoculated solid sarcoma 37 considerably increases the efficiency of X-irradiation of tumors: the coefficient of tumor growth inhibition (kappa *) exceeds 1.0, and the number of animals with the completely regressed tumors increases. The effectiveness of the procedure depends on the time of the injection of the preparations and modes of irradiation. 
&&url PMID: 2422676


Clin Exp Metastasis 1985 Jan-Mar;3(1):21-7 
<b>Increase in radiosensitivity of lung micrometastases by hyperbaric oxygen.</b> 
Milas L, Hunter NM, Ito H, Brock WA, Peters LJ. 
Four-day-old artificial pulmonary micrometastases of two murine fibrosarcomas, designated FSA and NFSA, showed increased sensitivity to ionizing radiation by a factor of 1.13 when animals were exposed to hyperbaric oxygen breathing before and during irradiation, implying the presence of hypoxia in the micrometastases. At the time of irradiation the diameter of FSA and NFSA metastases was smaller than 200 and 100 microns, respectively, which, on the basis of oxygen diffusion, could not be responsible for hypoxia. It is assumed that hypoxia of micrometastases is passive, reflecting the radiobiological hypoxia of lung tissue that could exist under normal breathing conditions. 
&&url PMID: 4042454 

 
Int J Radiat Oncol Biol Phys 1984 Sep;10(9):1623-6 
<b>Enhanced tumor responses through therapies combining CCNU, MISO and radiation.</b> 
Siemann DW, Hill SA. 
Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)...  [In Mice]  
&&url PMID: 6480451 


Int J Radiat Oncol Biol Phys 1984 Sep;10(9):1545-9 
<b>Tumor sensitization and protection: influence of stromal injury on estimates of dose modification.</b> 
Williams MV, Rojas A, Denekamp J. 
Tumor regrowth delay is an assay which reflects tumor cell kill but can be modified by growth rate changes resulting from damage to the stroma (tumor bed effects). If the stromal damage is modified by radiosensitizers and radioprotectors to a different degree from the tumor cells, the overall measurement of dose modifying factors may be influenced by the choice of a regrowth size for the growth delay analysis...[In mice]  It appears that stromal damage may be the cause of the radioprotection observed in the carcinoma, whereas direct tumor cell radioprotection is indicated in the fibrosarcoma. Both direct tumor cell killing and cell death secondary to stromal damage will play an important role in determining the local control of irradiated tumors. 
&&url PMID: 6090359 


Int J Radiat Oncol Biol Phys 1984 Aug;10(8):1203-5 
<b>Hypoxic cell sensitizers and heavy charged particle beams may play complementary roles in killing hypoxic tumor cells.</b> 
Curtis SB, Tenforde TS, Afzal SM. 
[In Mice]  . 
&&url PMID: 6432747  

Br J Cancer 1980 Dec;42(6):861-70 
<b>In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: methotrexate, 5-fluorouracil and adriamycin.</b> 
Tannock IF. 
I have studied the effects on growth of two tumours in mice and on host toxicity, of combining Misonidazole (MISO) or Metronidazole (METRO) with ... METRO and MISO increase the anti-tumour effects of some anti-cancer drugs, but may also increase host toxicity. Nitroimidazoles should be used with caution in combination with chemotherapy. 
&&url PMID: 7459220 


Br J Cancer 1980 Jan;41(1):1-9 
<b>Is tumour radiosensitization by misonidazole a general phenomenon?</b> 
Denekamp J, Hirst DG, Stewart FA, Terry NH. 
&&url PMID: 7362769 


Vopr Onkol 1977;23(8):17-27 
<b>[Hyperbaric oxygenation in the preoperative radiotherapy of soft tissue sarcomas].</b> [Article in Russian] 
Sergeev SI, Dar'ialova SL, Lavnikova GA. 
Based on the study of clinical and morphological criteria for estimation of the efficacy of distance gammatherapy under hyperbaric oxygenation in the combined treatment of patients with soft tissue sarcomas, it was concluded that hyperbaric oxygenation employed in radiotherapy contributed to the increased rate of neoplasms damage. The latter resulted in a decreased percentage of the recurrence. The attenuation of local radiation and less number of postoperative complications indicate that healthy tissues surrounding the tumor are preserved. No rise in the percentage of distant metastases was noted in irradiation under hyperbaric oxygenation. Publication Types: Clinical trial 
&&url PMID: 333747
Vopr Onkol 1975;21(5):63-73 


<b>[Universal approaches to the control of tissue radiosensitivity during radiation therapy of malignant tumors].</b>[Article in Russian] 
Iarmonenko SP. 
Approaches to the problem of the control over tissue radiosusceptibility, united by the common purpose--a need for selective increase of the intact tissues tolerance to overcome tumor hypoxia, are discussed. Such universal approaches include an application of radiation characterized by high linear wastes of radiation energy, methods of increased oxygenation of tumors, the use of electron sink compounds, and irradiation under conditions of hypoxia--hypoxiradiotherapy. .... 
&&url PMID: 1210147