bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation sensitization of chinese hamster V79 cells by paclitaxel
Authors: Cook John A. , Degraff William , Teague Diane , Liebmann James K.
Published: February 2007

Because paclitaxel has been reported to disrupt microtubules and block cells in G2/M of the cell cycle, the radiation response of Chinese hamster V79 cells exposed to various paclitaxel concentrations and durations of exposure was evaluated. Parallel to clonogenic cell survival studies, paclitaxel‐mediated perturbations on the cell cycle were also assessed by flow cytometry. While short‐term incubation (0–6 hr) with 0.1, 1, or 10 μM paclitaxel caused a gradual accumulation of cells into G2/M, no radiosensitization was observed. Incubation with 0.05—1 μM paclitaxel for 12 hr followed by X‐ray treatment resulted in radiosensitization (enhancement ratio at the 10% survival level = 1.7). Paclitaxel concentrations above 1 μM had similar effects on the cell cycle at lower concentrations, yet radiosensitization decreased such that at 10 μM no radiosensitization was observed. Likewise, no radiosensitization was observed for cells incubated for 24 hr with 0.1, 1 or 10 μM paclitaxel and irradiated. Cell cycle analysis indicated that cells receiving less than 0.25 μM paclitaxel for 12 hr were only transiently blocked in mitosis and then went on to complete mitosis; cells receiving greater than 0.25 μM paclitaxel for 12 hr or more became polyploid, i.e., cells moved into a semisynchronous tetraploid G1 state. (Cells irradiated at 24 hr had progressed to a tetraploid G2 state.) Taken as a whole, these results indicate that paclitaxel‐mediated radiosensitization and cell cycle perturbation are both time and concentration dependent. © 1993 Wiley‐Liss, Inc

This article is a US government work and, as such, is in the public domain in the United States of America.

.
Preliminary results of a prospective randomized controlled clinical trial with hydroxyurea and cisplatinum as radiosensitizers in advanced carcinoma of the cervix
Authors: Smit Ben , van der Merwe Andre
Published: February 2007

Sixty‐three patients with cervical carcinoma were randomized prospectively to receive radiation therapy alone, or hydroxyurea (HU) and cisplatinum as radiosensitizers. All patients were treated by a four field box technique, 2.5 Gy daily, 4 days per week, to a total dose of 50 Gy (TDF 90). A central boost by high dose rate intracavitary therapy (HDR‐ICT), 4.2 Gy daily × 4 was given on the same days (with a 6 hr gap between fractions) during the last 4 days of external beam therapy. This reduced the overall treatment time from 6 to 5 weeks. The Indwelling Intrauterine Tube technique was used. The summated dose at point A is 66.8 Gy (TDF 130). Twenty patients (group A) received radiation therapy (RT) only; 21 (group B) received cisplatinum 15 mg/m2 on alternate days, plus RT; 22 patients (Group C) received HU 80 mg kg/body weight on alternate days, plus RT. The median time of follow‐up is 14 months for group A and 19 months for the other two groups. The survival probability for patients with at least 20 months follow‐up (Kaplan‐Meier method) is 0.61, 0.88, and 0.84; disease‐free survival is 0.42, 0.63 and 0.62 for groups A, B, and C, respectively, which are not statistically significantly different. Early complications: Moderate to severe cystitis was seen in 15,4.76, and 9.09%; proctitis in 5,0, and 4.5%, and diarrhoea in 5, 14.29, and 13.64% for groups A, B, and C; for a total of 25, 19.05, and 27.28%, respectively. Late moderate to severe complications: Cystitis occurred in 0,9.5, and 4.55%, and proctitis in 10,4.76, and 9.09% in groups A, B, and C, respectively. One patient in group B (4.76%) and two patients in group C (9.09%) developed chronic diarrhoea giving a total late complication rate of 10, 19.04, and 22.7%, respectively. In addition, vaginal stenosis occurred in 15, 23.81, and 9.09% in groups A, B, and C, respectively. No rectovaginal fistulae developed in any of the three groups. All except 1 of the 63 patients completed their treatment. Three patients out of group A, 2 out of group B, and 1 out of group C were lost to follow‐up. One out of the 63 patients, 1.56% (group C) needed a colostomy for a grade III late proctitis. Drug related toxicity was not severe and proved that the regimens could be tolerated. Treatment had to be interrupted in group A, because of treatment related morbidity, for 2 days in one patient, 2 weeks in a second, and terminated in a third after 45 Gy teletherapy due to unrelated problems. There were no treatment interruptions in group B. In group C, 2 patients were rested for 7 days each as a result of a low white cell count (WCC). The incidence of metastatic disease was the lowest in group B; the complication rate the highest in group C. The results indicate that cooperative controlled studies based on these results should be considered. © 1993 Wiley‐Liss, Inc.
Expression of the transcriptional activator tax protein of human T‐cell leukemia virus type I increases the radiosensitivity of a mouse fibroblast cell line to ionizing radiation
Authors: Santucci Maria Alessandra , Holland Christie A. , Anklesaria Pervin , Das Indra , Fitzgerald T. J. , McKenna Michael G. , Sakakeeny Mary Ann , Greenberger Joel S.
Published: February 2007

Human T‐cell leukemia virus type I (HTLV‐1) is the etiologic agent for adult T‐cell leukemia (ATL). Among the X region products of HTLV‐1, the p42 kDa protein Tax was identified, as responsible for cell immortalization and transformation. However, the observations that only a low percentage of individuals infected with HTLV‐1 eventually progress to leukemia and that leukemic transformation of HTLV‐1‐infected cells is associated with aberrant karyotype suggest that additional genetic events are required for HTLV‐1‐induced malignant transformation. Results of our study demonstrate that expression of the Tax protein of HTLV‐1 increased the radiosensitivity of a mouse fibroblast cell line. These data are consistent with a previous report indicating a negative regulatory control by Tax on DNA repair. Unrepaired DNA damage and karyotypic instability could represent a common factor in both the initiation and progression of HTLV‐1‐related diseases. © 1993 Wiley‐Liss, Inc.
Frequencies of micronuclei in human lymphocytes: Comparison between healthy donors and cancer patients and their in vitro response to ionizing radiation
Authors: Lee Tung‐Kwang , Wiley Albert L. , Means Julie A. , Esinhart James D. , Blackburn Lisa D.
Published: February 2007

We obtained peripheral lymphocytes from both healthy donors (n = 7) and cancer patients (n = 14) for the cytokinesis‐blocked micronucleus (MN) assay. Lymphocytes were irradiated with 137Cs to 2 Gy. Cytochalasin B (6 μg/ml) was added to the incubation at 44 hr and the cells were harvested at 72 hr. We found that compared to healthy donors, lymphocytes of cancer patients revealed no significant difference in the MN baseline level (P = 0.86). Apparently DNA damage manifested as MN in the lymphocytes of cancer patients is not more severe than that of healthy donors. In addition, 2 Gy in vitro irradiation of lymphocytes caused no difference in the MN formation between cancer patients and healthy donors (P = 0.9). Radiation induced cell cycle delay as evaluated by the number of mononucleate, binucleate, and cells with >2 nuclei and by the mitotic indices showed similar results in both populations. However, the difference for MN frequency in lymphocytes before and after 2 Gy in vitro irradiation was highly significant for both cancer patients and healthy donors (P = 0.0001). These studies in general indicate that the MN frequency in cytochalasin B‐blocked human lymphocytes has the potential of serving as a quantitative biological dosimeter for the screening of radiation exposure to either healthy individuals or cancer patients. © 1993 Wiley‐Liss, Inc.
Morphometric studies in early stage breast ancer with an intraductal component using computerized image analysis
Authors: Mayr Nina A. , Robinson Robert A. , Wen B.‐Chen , Ross Cynthia S. , Hass A. Curtis , Stoffel Thomas J. , Fisher David J. , Vanmetre John E. , Hussey David H.
Published: February 2007

The hypothesis that hypoxia may be present in the intraductal component associated with infiltrating breast cancer was tested by studying the morphology of the intraductal component with respect to expansion of the tumor‐filled breast ducts and intraductal necrosis. Of 52 consecutive patients with T1–2N0–1M0 infiltrating ductal breast carcinoma, 10 had an extensive intraductal component (EIC), 27 had a limited intraductal component (LIC), and 15 had no intraductal component. The necrosis‐containing comedo‐ and cribriform‐predominant types of intraductal carcinoma were common (50%) in the EIC group, but infrequent (19%) in the LIC group. The frequency of intraductal necrosis increased with duct diameter. Seventy‐five percent of ducts with a radius exceeding the oxygen diffusion distance (>180 μm) contained necrosis compared with 33% of ducts below that size. The average duct diameter was significantly larger (404 μm; P = 0.0056) and intraductal necrosis was more common (61%) in the EIC group than in the LIC group (263 μm; 33%). All patients with local recurrence in the EIC group (20%) had the comedo‐predominant pattern, with a high percentage (79%) of necrotic ducts. The increasing frequency of intraductal necrosis with increasing duct size, particularly with radii of more than 180 μm, suggests that tumor cell hypoxia is present in the intraductal component. The larger duct size and higher frequency of necrosis in the EIC group suggest that hypoxia is more common in EIC than in LIC. © 1993 Wiley‐Liss, Inc.
Calculation of complication probability of pion treatment at paul scherrer institute using dose‐volume histograms
Authors: Nakagawa Keiichi , Akanuma Atsuo , Aoki Yukimasa , Karasawa Katsuyuki , Sasaki Yasuhito , Blattmann Hans , Coray Adorf
Published: February 2007

In conformation radiotherapy a target is irradiated uniformly, whereas surrounding organs receive non‐uniform radiation. Clinical data concerning complications with conventional radiation are not applicable there without appropriate compensation. A solution was proposed by Lyman [Int J Radiat Oncol Biol Phys 13:103–109, 1987 and 17:433–436, 1989; Radiat Res Suppl 8:13–19, 1985] using dose‐volume histograms. It reduces a given histogram to a single step which corresponds to the equivalent complication probability. It converts non‐uniform radiation into a unique dose to the whole organ which has the equivalent complication probability. This method was applied to actual patients treated by pion conformation technique at Paul Scherrer Institute (PSI). Of 90 pelvic tumors, 16 developed grade III‐TV bladder injury and 7 developed grade III‐IV rectal injury. The 90 cases were divided into roughly equal groups according to the equivalent doses to the entire bladder and rectum. Observed complication rates and the equivalent doses to the full organs in these groups could be represented by a sigmoid dose‐effect relation. When the relative biological effectiveness (RBE) is assumed to be 2.1 for bladder injury, the observed complication rates of the bladder fit best to the theoretical curve. When the RBE value is 2.3, the rates of rectal injury fit best. These values are close to the conversion factor of 2.0 used in clinical practice. This agreement suggests the feasibility of the method. © 1993 Wiley‐Liss, Inc.
Short‐term results of computerized tomographic‐based transperineal iodine‐125 prostate implantation
Authors: Wallner Kent , Roy Jitendra , Zelefsky Michael , Harrington Patrick , Fuks Zvi , Harrison Louis
Published: February 2007

There has recently been a resurgence of interest in iodine‐125 (I‐125) prostate implantation for early stage carcinoma due to the introduction of transrectal ultrasonography (TRUS) or computerized‐tomographic (CT)‐based transperineal techniques. The present study details initial tumor response and morbidity of CT‐based transperineal prostate implantation. Forty‐two patients with clinical stage T1 or T2 prostatic carcinoma had CT‐planned transperineal I‐125 implantation of the prostate and have been followed for 6–47 months (median: 19 months). Thirty‐eight patients had an elevated PSA before implantation (>4.0 ng/ml). A total of 35–73 mCi I‐125 was implanted (median: 48 mCi). At 1 year after implantation, 84% of 29 palpable tumors were no longer palpable. Of 38 patients with an elevated prostate specific antigen (PSA) prior to implantation, 98% returned to normal within 12 months of treatment. In 74% of patients, the PSA value fell to below 1.0 ng/ml within 12 months of implantation. Of 25 patients who were sexually potent prior to implantation, 80% remained potent at 3 years. Four patients developed radiation‐induced rectal ulcerations 9–19 months following implantation. Of those four patients, one has healed spontaneously, two are improving, and one was diagnosed only 1 month prior to this report. Initial tumor response to I‐125 implantation is comparable to that achieved with external beam irradiation, with acceptable morbidity and high preservation of sexual potency. With adjustments in technique, morbidity is expected to be lower in the future. © 1993 Wiley‐Liss, Inc.
Radiation response of NIH/3T3 mouse fibroblasts overexpressing human poly(adenosine diphosphate ribose) polymerase
Authors: Jorgensen Timothy J. , Notario Vicente , Thraves Peter J. , Dritschilo Anatoly
Published: February 2007

Poly(adenosine diphosphate ribose) [poly(ADP‐ribose)] polymerase is a mammalian enzyme which synthesizes long chains of ADP‐ribose attached to various nuclear proteins in response to DNA strand breaks. A role for this enzyme in cellular radioresistance has been postulated due to the radiosensitizing effect of chemical inhibitors of the enzyme on some cell lines. Inhibitor studies, however, lack specificity and direct evidence for involvement of the enzyme in radioresistance is still needed. In experiments described here, intracellular levels of the enzyme were modulated using vectors to express sense and antisense human cDNA transcripts of poly(ADP‐ribose) polymerase in stably transfected NIH/3T3 mouse fibroblasts. Although antisense constructs failed to lower enzyme levels, sense transcripts increased enzyme levels. None of the transfectants, however, showed any difference in either radiation sensitivity or DNA strand break repair rates. These results suggest that simple elevation of poly(ADP‐ribose) polymerase does not affect the intrinsic cellular radioresistance of these cells. © 1993 Wiley‐Liss, Inc.
Potentiation of antineoplastic drugs in vitro and in vivo by DNA intercalating bioreductive agents
Authors: Papadopoulou Maria V. , Miller Anna , Seskey Troy , Epperly Michael W. , Bloomer William D.
Published: February 2007

Three recently synthesized 2‐nitroimidazole‐linked acridine DNA intercalators (NLA‐1, NLA‐2, and NLA‐4) have been studied as potentiators of the cytotoxic effect of melphalan (L‐PAM), 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea (CCNU), cis‐diamminedichloroplatinum (II) (cis‐DDP), and doxorubicin in V79 cells. In vivo studies have also been performed with all three sensitizers and L‐PAM, while NLA‐1 alone was examined for potentiation of cis‐DDP, using C3H/HEJ mice, bearing a murine ovarian tumor. Significant chemosensitization was observed in vitro with L‐PAM, CCNU, and cis‐DDP after hypoxic preincubation treatment of the cells (37°C) at negligible concentrations of each sensitizer, while inhibition was observed with doxorubicin. Long hypoxic preexposure times at relatively low sensitizer doses were more effective than short hypoxic preexposure times at high sensitizer doses for potentiation. Glutathione depletion studies in vitro with diethyl maleate (DEM) showed that only less than half of the enhanced toxicity observed with NLA‐1 or NLA‐4 and L‐PAM is due to glutathione depletion by the sensitizer. The LD50/35 value in C3H/HEJ mice for NLA‐1, NLA‐2, and NLA‐4 was 45, 25, and 63 mg/kg, respectively. Significant antitumor effect was observed in vivo when 25 mg/kg of NLA‐1 was administered i.p. to tumor‐bearing mice 2 hr before L‐PAM administration (2.5 mg/ kg, i.p.). With this combination pattern of sensitizer:antineoplastic drug, 50% cures were observed in mice followed for >150 days; no long‐term survivors were observed with L‐PAM therapy alone. © 1993 Wiley‐Liss, Inc.
Low dose‐rate irradiation of human glioma cells and thermoradiosensitization by mild hyperthermia
Authors: Heller Dennis P. , Raaphorst G. Peter
Published: February 2007

Human brain tumors are clinically very resistant to radiation therapy. Recent clinical trials of combined simultaneous brachytherapy and mild hyperthermia have shown great promise. In this study two relatively radioresistant human glioma cell lines have been irradiated in plateau growth phase under low dose‐rate (LDR) conditions (<1 cGy/min) with and without concurrent mild (39–41°C) hyperthermia. The large degree of LDR sparing observed at 0.88 cGy/min (LDR1) was almost completely inhibited by concurrent heating at 41°C, resulting in a thermal enhancement ratio (TER) of 1.6 and 1.8 at the 1% survival level for U‐87MG and U‐373MG, respectively. At 0.41 cGy/min (LDR2) concurrent heating at 41°C resulted in greater thermoradiosensitization for U‐87MG (TER 2.1) and less thermoradiosensitization for U‐373MG (TER 1.5). For U‐87MG, thermoradiosensitization with LDR2 at 39 and 40°C was similar and suboptimal compared with concurrent 41°C hyperthermia. For U‐373MG, thermoradiosensitization was nearly absent at both 39 and 40°C. The direct cytotoxicity of 39, 40, and 41°C heating was similar in both cell lines. Survival after 48 hr of heating at 41°C was not less than 30% for either cell line. Hyperthermia delivered prior to LDR irradiation has shown varying degrees of sensitization both in vitro and in vivo. In this study, preheating with 8 hr at 41°C did not sensitize 9 Gy LDR2 at 37°C; however, 1 hr at 43°C did result in some thermoradiosensitization with a survival reduction factor (SRF) of 1.4. With 9 Gy LDR2 delivered at 41°C, preheating did result in additional thermoradiosensitization (SRF of 1.6, 3.5, respectively). The significant degree of thermoradiosensitization seen with concurrent LDR irradiation and 41°C hyperthermia with or without preheating supports the promising results seen in recent clinical trials. © 1993 Wiley‐Liss, Inc.
Radiobiology and radiation treatment of malignant melanoma: A review
Authors: Peschel Richard E.
Published: February 2007

The incidence of malignant melanoma (MM) has one of the fastest growth rates in the world and external beam radiation therapy (RT) is an important component in the total therapeutic management of MM. The radiobiology of MM provides a fascinating example of the complexities of radiation tumor biology. Both the multitarget model and the linear quadratic model predict that high dose per fraction (HDPF: 400 cGy or more) RT may be more efficacious than low dose per fraction (LDPF: 180–300 cGy) RT for some MM. However, other radiobiological factors such as repair of potentially lethal damage, reoxygenation, and repopulation appear to support the use of LDPF RT. Therefore, the MM radiobiological data predict a diverse response to a wide spectrum of HDPF and LDPF time‐dose prescriptions. The clinical data for MM are consistent with these radiobiological predictions. MM exhibits a high response rate to both HDPF and LDPF time‐dose prescriptions. RT is an effective therapy for MM in many clinical settings: 1) RT is the single most effective local therapy for metastatic disease with complete response rates of 23–72% and long‐term local tumor control rates of 48–82%; 2) heavy ion RT is the primary treatment for many ocular MM with 5‐year eye retention rates of 89% and 5‐year local tumor control rates of 96%; 3) RT is the treatment of choice for mucosal non‐cutaneous, non‐ocular MM with results that are equal or superior to radical surgery; and 4) recent reports suggest an important role for adjuvant RT in postoperative patients who are at high risk for local‐regional recurrence. The current roles for RT in MM should be reevaluated since it is likely that RT is being underutilized in the overall clinical management of MM. © 1994 Wiley‐Liss, Inc.
Tolerance of rhesus monkey liver to ionizing radiation
Authors: Stephens L. Clifton , Peters Lester J. , Ang K. Kian
Published: February 2007

This study was undertaken to determine if nonhuman primates are suitable models for the veno‐occlusive disease (VOD) that characterizes radiation hepatopathy in man. Adult rhesus monkeys had near total liver irradiation to 36 Gy in 8 fractions (Group 1, n = 5) or to 50 Gy in 20 fractions (Group II, n = 5). All had normal liver function and no lesions in liver biopsies 9 months after irradiation. A monkey from each group was given either doxorubicin, cyclophosphamide, cisplatin, or methotrexate over a 15‐week period. The one given 36 Gy in 8 fractions and doxorubicin died of congestive heart failure 1 month after the last course. The remainder of Group 1 animals had normal liver function and morphology 2 to 3 years after therapy. Group II animals given methotrexate or cisplatin had the liver retreated with 30 Gy in 30 fractions at 2 years after receiving 50 Gy in 20 fractions. Within 1 month, the animal given methotrexate developed massive hepatic necrosis. The other given a cumulative liver dose of 80 Gy remained clinically normal. This animal and the others in Group II underwent left hepatic lobectomy 2 years after the first radiation course. All had normal liver function and no VOD when they were sacrificed 1 year later. A monkey given methotrexate followed by liver irradiation (50 Gy in 20 fractions) developed hepatic necrosis 10 months later. Another given cyclophosphamide and 50 Gy in 20 fractions was normal for 2 years after treatment.

In summary, none of the monkeys developed classical VOD, and they apparently were resistant to induction of significant hepatic injury by radiation alone. Occult radiation injury was not exacerbated by either chemotherapy or partial hepatectomy.

Hepatic necrosis in this model was induced by methotrexate administration followed by liver irradiation. The reason for the difference in radiosensitivity of the monkey liver and human liver is unknown. © 1994 Wiley‐Liss, Inc.
Porfiromycin as an adjunct to radiation therapy in squamous cell carcinoma of the head and neck: Results of a phase I clinical trial
Authors: Haffty Bruce G. , Son Yung H. , Moini Marjaneh , Papac Rose , Fischer Diana , Rockwell Sara , Sartorelli Alan C. , Fischer James J.
Published: February 2007

Purpose: A phase I toxicity trial aimed at defining an appropriate dose of the bioreductive alkylating agent porfiromycin to be used in conjunction with radiation therapy in patients with squamous cell carcinoma of the head and neck. Methods and Materials: A total of 21 patients were entered into this phase I clinical trial. All patients had locally advanced squamous cell carcinoma of the head and neck and were treated with radiation therapy with or without surgical intervention. Porfiromycin was administered on days 5 and 47 of the course of radiation therapy. The initial dose of the drug was 50 mg/M2, but due to hematological toxicity the dose was lowered to 40 mg/M2. The final 12 of the 21 patients in this phase I clinical trial was treated at the dose of 40 mg/M2. Radiation therapy was directed at the primary site and regional lymph nodes as clinically indicated with conventional fractionations of 200 cGy/day to total doses in excess of 6,000 cGy. Results: Five patients were treated at the initial dose of 50 mg/M2, but due to excessive hematologic toxicity the dose was reduced to 45 mg/M2 for 4 patients and lowered again to 40 mg/M2 for the final 12 patients of the study. As expected, the major toxicity was hematological with thrombocytopenias and neutropenias. There were no clinically evident bleeding episodes secondary to thrombocytopenia and no neutropenic deaths during the course of the study. Of the 21 patients treated in the series, 10 remain alive no evidence of disease (NED) with a median follow‐up of 18.5 months. Four of the alive NED patients have been followed for over 2 years. Conclusions: The bioreductive alkylating agent porfiromycin may be safely administered at a dose of 40 mg/M2 to patients undergoing radiation therapy for squamous cell carcinoma of the head and neck. Based on the results of this phase I trial, we have now mounted a phase III clinical trial in patients with all stages of squamous cell carcinoma of the head and neck, comparing radiation therapy with porfiromycin to radiation therapy with mitomycin C. There is no radiation therapy without drug in this phase III clinical report. © 1994 Wiley‐Liss, Inc.
Role of transforming growth factor‐β and hepatocyte growth factor in late normal tissue effects of radiation
Authors: Anscher Mitchell S. , Jirtle Randy L.
Published: February 2007

Conventional radiation therapy practice (i.e., dose, field size, beam arrangement, fraction size, etc.) has been largely derived empirically from decades of clinical observation. Much emphasis has been placed upon maximizing the dose to the tumor while minimizing the risk of complications. In practice, however, it is often the normal tissues that limit the total dose of radiation that can be delivered to the tumor since excessive doses of radiation frequently result in severe fibrotic reactions developing in the exposed normal tissues. It is now becoming apparent that growth factors, in particular Transforming Growth Factor‐β (TGF‐β) and Hepatocyte Growth Factor (HGF), are important mediators in the repair of normal tissue injury under a variety of circumstances, including following radiotherapy or chemotherapy. Herein, we have discussed the evidence implicating HGF and TGF‐β in normal tissue repair and fibrosis formation, and describe their potential usefulness as predictors of late normal tissue damage. © 1994 Wiley‐Liss, Inc.
Tumor growth retardation and pathophysiological effects of adenosine 5′‐triphosphate therapy measured by thallium washout, 31P nuclear magnetic resonance, laser doppler flowmetry, and intradermal angiogenesis
Authors: Okunieff Paul , Froio John , Soni Rajesh , Kahn Julia , Gerweck Leo , Zlotecki Robert , Abraham Edward H.
Published: February 2007

Transplants of a spontaneous murine fibrosarcoma (FSaII) treated with intraperitoneal (i.p.) adenosine 5′‐triphosphate (ATP) were studied in vitro, and in vivo in both C3H and nu/nu mice. In vivo daily ATP treatments caused a small dose‐dependent reduction in the total neovascular lumen area and thallium washout. There was an associated reduction in tumor volume doubling time but a similar growth rate reduction was also seen in vitro where flow has no impact. Daily ATP treatments at the maximally tolerated dose (2 mmol/kg i.p.) did not significantly affect the pH nuclear magnetic resonance or the phosphocreatine/inorganic phosphate (PCr/Pi), βATP/Pi, or phosphomonoester (PME)/ βATP ratios. The acute systemic physiological effects of i.p. ATP were mild, consisting of a transient reduction in skin laser Doppler flow and mean arterial pressure. Systemic toxicities of ATP given as daily boluses at doses capable of producing significant growth retardation of FSaII tumors were transient. Our results are most consistent with the hypothesis that the growth retarding effects of ATP are primarily a result of a decreased proliferation rather than tumor cytotoxicity or systemic pathophysiology. The main toxicity of ATP at active dose levels is cardiovascular. ATP might be useful as a biological modifier of chemotherapy or radiation. © 1994 Wiley‐Liss, Inc

This article is a US Government work and, as such, is in the public domain in the United Stales of America.

.
Differential modulation of radiosensitivity following induction of cis‐platinum resistance in radiation‐sensitive and radiation‐resistant human tumor cells
Authors: Britten Richard A. , Warenius Hilmar M. , Carraway Alma V. , Murray David
Published: February 2007

The effect of the induction of cis‐platinum resistance on clinically relevant radiosensitivity, i.e., surviving fraction at 2 Gy (SF2), has been studied in 8 human tumor cell lines with SF2 values ranging from 0.32 to 0.70. The induction of cis‐platinum resistance was accompanied by alterations in radiosensitivity in all of the cell lines studied; however, there was no relationship between the degree of induced cis‐platinum resistance (which varied from 1.5‐ to 7‐fold) and the concomitant change in radiosensitivity. The extent (up to 1.55‐fold) and the direction of the modulation of radiosensitivity were inversely related (P < 0.01) to the inherent radiosensitivity of the parental line prior to the induction of cis‐platinum resistance. cis‐Platinum resistance was associated with the radio‐protection of initially radiosensitive cells and the radiosensitization of inherently radioresistant phenotypes. If this inverse relationship between the initial radiosensitivity of the parental line and the cis‐platinum‐mediated alteration in SF2 values occurs in the clinical setting it could have important ramifications for treatment outcome. Clearly if patients with tumors that are ordinarily radioresponsive were to receive neo‐adjuvant cis‐platinum‐based chemotherapy, there could be a significant reduction in radioresponsiveness. On the other hand, there may be some advantage in the use of cis‐platinum‐based chemotherapy followed by radiotherapy in typically radioresistant tumors. © Wiley‐Liss, Inc.
Brain tumor uptake of thallium‐201 from the cerebrospinal fluid compartment: A preliminary study of uptake and diffusion dynamics
Authors: Rubertone Joseph A. , Woo David V. , Emrich Jacqueline G. , Brady Luther W.
Published: February 2007

Thallium‐201 (201Tl) has become a potent diagnostic tool for imaging brain tumors. Since intrathecal injections of 201T1 result in high resolution images of normal brain, experiments were designed to study tumor uptake and diffusion of 201T1 subsequent to cerebrospinal fluid (CSF) injection. A1SA5 astrocytoma cells were injected into the rat caudoputamen. Two weeks post‐implantation, rats received lateral ventricle injections of 201T1. Deeply anesthetized rats were perfused with 4.0% buffered formalin. Brains were removed, sectioned, and processed for autoradiography. Autoradiographs (ARGs) were developed and mounted sections were stained with hematoxylin and eosin. ARGs reveal a high degree of tumor to background resolution. Small tumor processes and cellular metastasis parallel to fiber tracts are readily visualized. 201TI labeling in areas of no apparent histologic disease, immediately surrounding and caudal to tumors, is suggestive of uptake by cells undergoing transformation. These studies are the first to demonstrate tumor uptake subsequent to 201T1 CSF injection and provide insights into the movement of 201T1 through tumor and adjacent neuropil. © Wiley‐Liss, Inc.
The doubling time of human tumours during radiotherapy: An analysis based on comparison between clinical and in vitro tumour cell radioresponsiveness
Authors: Brodin O.
Published: February 2007

A correspondence between the effect of 2 Gy in vitro for human tumour cell lines and the clinical effect of radiotherapy of the corresponding tumours has earlier been described. In this analysis data on surviving fraction (SF) in vitro have been applied to clinical studies in a predictive model similar to the linear‐quadratic model for the calculation of isodoses. In addition, a proliferation factor describing exponential growth has been included. Different proliferation rates have been tested and the predicted probabilities for local control have been compared with the clinical local control rates of respective studies. The best correspondence between predicted and clinical results were found for a potential doubling time of 2–3 days during a whole treatment course, even for radiotherapy courses shorter than 3–4 weeks. The possible impact of hypoxia is discussed. © Wiley‐Liss, Inc.
DNA supercoiling and repair in peripheral lymphocytes as a measure of acute radiation response after radiotherapy
Authors: Rosemann Michael , Schulze Brigitte , Abel Helmut
Published: February 2007

DNA supercoiling density and incision kinetics during ultraviolet (UV) excision repair hav been measured in lymphocytes from 20 cancer patients and 17 healthy donors. Nucleoid sedimentation was used, which allows the sensitive detection of both DNA damage and alterations in chromatin structure. The release of DNA supercoiling after ethidium bromide intercalation and the kinetics of the incision step following UV irradiation were compared in lymphocytes derived from cancer patients and those from normal donors. The classification into lymphocytes with normal or reduced repair and normal or altered supercoiling, respectively, revealed that reduced repair as well as altered chromatin structure occurred more frequently in lymphocytes derived from patients (40% and 85%, respectively) than in those from healthy donors (35% and 23%, respectively). Even more striking was the simultaneous occurrence of both characteristics in tumor patients: in 34% of all cases reduced repair was associated with altered supercoiling density, whereas among healthy donors this association occurred in only 18% of all cases. Supercoiling density may be related to functional integrity of lymphocytes and repair capacity to recovery after radiation damage. Since both parameters are important for the radiation response of normal tissue, we consider these measurements a potential prognostic assay aimed at reducing acute reaction of the normal tissue. © Wiley‐Liss, Inc.
Radiation response and other characteristics of the 9l rat glioma grown as an epigastric tissue isolate
Authors: Evans Sydney M. , Koch Cameron J.
Published: February 2007

We studied the 9L tumor as a tissue isolated epigastric implant. Data supporting its applicability to this site, including tumor blood flow, glucose metabolism, plating efficiency, radiation response, and histophatologic appearance, are described. Implants were performed on 175‐250 g male Fischer rats by tying 2–3 mm3 pieces of tumor onto the proximal segment of the epigastric branch of the femoral artery. Characteristics of the model include recovered cell yields of 6.1 ± 4.2 × 107 cells/g; 19–23% plating efficiency; 5% relative surviving fraction at 19.3 and 27.6 Gy in air breathing and euthanized rats, respectively; mean glucose utilization rate of 229 ± 182 nmol/min/g; and tumor blood flow of 1.9–21.3 ml/min/100 g in 0.4–303 g tumors. These characteristics, for the first time, provide a common framework for simultaneous evaluation of tumor metabolism and radiation response. © Wiley‐Liss, Inc.
Chemoradiotherapy for anal carcinoma: What is the optimal radiation dose?
Authors: Fung Claire Y. , Willett Christopher G. , Efird Jimmy T. , Shellito Paul C. , Kaufman Donald S.
Published: February 2007

A dose‐response analysis was undertaken in a group of patients with clinically node‐negative carcinoma of the anal canal treated with a sphincter‐sparing approach. Twenty‐three patients underwent biopsy of the primary tumor, followed by concurrent radiation and chemotherapy. The chemotherapy regimen of 5‐fluorouracil and mitomycin C and radiation technique were uniform in all patients. The total radiation dose, given in daily fractions of 180–200 cGy, was escalated over the years as an institutional policy. The total radiation dose was ≤5,200 cGy (mean 4,550 cGy) in 11 cases treated before September 1989 and >5,200 cGy (mean 5,572 cGy) in 12 cases treated subsequently. The 3‐year actuarial local control rates were 53% vs. 100% for the low vs. high dose groups, respectively (P = 0.015). The 3‐year actuarial overall survival rates were 82% vs. 100% in the 2 groups, respectively. No increase in late toxicity in the high dose group has been observed compared to the low dose group. These results, albeit based on limited patient numbers, suggest that total radiation dose is an important determinant of long‐term tumor control in patients with localized anal canal carcinoma. A total radiation dose of approximately 5,500 cGy has led to excellent tumor control and sphincter function. © Wiley‐Liss, Inc.
Increased radioresistance at clinical doses: Investigations from the survival perspective
Authors: Skov Kirsten , Marples Brian
Published: February 2007

Standard models of radiation action do not accurately describe survival at low clinically relevant X‐ray doses. This was made evident by survival experiments using methods which assayed a precise number of cells. At extremely low doses of X‐rays (<<0.5 Gy) a hypersensitive response exists which results in an inflection in the survival curve describing the response of many cell lines. In the case of sparsely ionizing radiations, this sensitive response is typically followed by an increased resistant response with a further increment in dose, which varies with cell line. This phenomenon may be explained as resistance induced by small doses of radiation. The background of this clinically interesting effect is described, as are methods to measure survival up to doses of ∼4 Gy. Evidence for increased radioresistance is reviewed and then briefly compared with the adaptive response which has been well studied in lymphocytes at still lower doses using endpoints other than survival. Possible implications for clinical treatment are considered. In addition, we summarize our recent studies directed toward understanding the molecular basis of the increased radioresistance using modifiers of radiation response, repair‐deficient cell lines, and radiation of different linear energy transfer (LET). While DNA damage appears to be a possible trigger for the response, the natures of the exact lesion(s) and the molecular response(s) which result remain unknown. © Wiley‐Liss, Inc.
Radiation response of human cervical carcinoma cells transfected with sense and antisense p53 retroviral constructs
Authors: Stevens Craig W. , Velasco Juan A. , Dipaolo Joseph A. , Dritschilo Anatoly , Notario Vicente
Published: February 2007

Dominant transforming genes such as raf, myc, and ras, alone or in combinations, have been shown to modify the radiation response of various cell types. Recent studies have shown that the status of the expression of p53, the gene detected most frequently altered in human cancer, participates in the response of various cell types to DNA‐damaging agents, including ionizing radiation. We now report the radiation responses of three human cervical carcinoma cell lines expressing various endogenous levels of wild‐type or mutant p53. In order to modulate the levels of p53, cervical carcinoma cells were transfected with retroviral vectors in which a wild‐type full‐length human p53 cDNA was inserted in the sense or antisense orientation relative to the retroviral promoter sequences. Results showed that alterations in the endogenous levels of p53 did not result in consistent differences in the cellular responses to ionizing radiation. These data indicate that the level of wild‐type p53 is not a major participant in the mechanisms of response to ionizing radiation by these cervical carcinoma cells. © 1995 Wiley‐Liss, Inc.
Interleukin‐Iß plasma levels decrease following local radiation therapy for breast cancer
Authors: Fenig Eyal , Sulkes Aaron , Rescigno John , Shohat Batya
Published: February 2007

Exogenous interleukin‐1 (IL‐1) has been shown to confer radioprotection to normal tissues. However, there is little information on the effects of radiotherapy on endogenous cytokine production. The purpose of this study was to examine the influence of breast radiotherapy on plasma IL‐1 levels and lymphocyte subpopulations in patients with early‐stage breast cancer. IL‐1 and lymphocyte subsets were determined in 13 patients before and after radiation therapy utilizing specific immunologic assays. Local radiation to the breast caused significant reduction in plasma IL‐1 levels (mean 269 ± 177 vs. 3 ± 50 pg/ml, P < 0.01). This was accompanied by a marked decrease in the lymphocyte counts of all patients (1850 ± 560 vs. 1013 ± 344, P < 0.05). Local radiotherapy can have a significant effect on systemic cytokine levels that may potentially impact on the radiation response of normal tissues and tumors. To our knowledge this is the first report of the effect of local radiotherapy on plasma levels of IL‐1. It is hoped that this may provide further insights into the biological responses to radiation and their impact on clinical outcome. © 1995 Wiley‐Liss, Inc.
Effect of self‐adhesive, silicone‐coated polyamide net dressing on irradiated human skin
Authors: Adamietz Irenäus A. , Mose Stephan , Haberl Annette , Saran Frank H. , Thilmann Christoph , Böttcher Heinz D.
Published: February 2007

There is no established biological or pharmacological procedure to prevent acute skin reactions during irradiation. Mechanical protection of irradiated skin during treatment is therefore essential. Some silicone‐coated materials developed for skin transplants may be beneficial to irradiated patients in this respect. In a prospective study, the tolerance of silicone‐coated polyamide net was tested in 21 patients receiving radiotherapy (RT) due to malignant disease. In 7 patients the portal skin was intact and in 14 patients the portal included an epitheliolysis and a skin ulcer. The ability of silicone‐coated net strips to adhere to irradiated skin and the local skin irritation under the adherent net were evaluated. Patient tolerance of dressing strips was good. There were no reactions to the adherent dressing net by non‐irradiated skin. No additional skin irritation due to the tested material was observed in the irradiated region. The ulcers covered by silicone‐coated dressings reepithelialized quickly during RT. There was no injury to new epithelium during changes of dressing. Our results demonstrate that silicone‐coated polyamide net dressings could be used for skin protection during irradiation. © 1995 Wiley‐Liss, Inc.
Acute parotitis during mantle irradiation: Incidence, onset, duration, and treatment
Authors: Fein Douglas A. , Corn Benjamin W. , Hanlon Alexandra L. , Curran Walter J. , Coia Lawrence R.
Published: February 2007

Detailed information, including the incidence, onset, and duration of symptoms, as well as the management of irradiation‐related sialadenitis, is not well defined in the literature. Between June 1967 and October 1993 126 patients received mantle irradiation in the treatment of Hodgkin's disease at the Fox Chase Cancer Center. All patients were treated with continuous course, once daily external beam radiotherapy (RT) using megavoltage equipment. The mantle fields extended from the level of the external acoustic meatus to the level of the insertion of the diaphragm. Seven of 126 patients (5.5%) treated with mantle irradiation developed clinical signs of parotitis during their RT treatments. Each patient described a painful sensation over the parotid gland. Palpable swelling over the parotid gland was appreciated in three patients. No systemic symptoms developed in any patient. All patients developed symptoms within the first week of treatment. Six patients were treated with aspirin and in each case the symptoms resolved within 48 hr. One patient did not receive medication and his symptoms persisted for 5 days. © 1995 Wiley‐Liss, Inc.
Low‐dose‐rate dependence of the phenotypic and genotypic expressions of mutagenesis by 137Cs γ‐rays
Authors: Xing Y. , Lindquist K. , Liu J. , Crompton N. E. A. , Kitani H. , Patel T. C. , Martin S. G. , Elkind M. M.
Published: February 2007

To examine the dependence on exposure rate of killing and mutagenesis by γ‐rays, two lines of Chinese hamster cells were studied. V79 cells were used to induce 6‐thioguanine resistance (6‐TGr) due to a mutation of the constitutive gene hypoxanthine‐guanine phosphoribosyl transferase (hgprt). Mutation of the bacterial gene guanine phosphoribosyl transferase (gpt) was studied in a line of mutated CHO cells, hgprt—which carried a single copy of gpt—by scoring cells that became 6‐TGr. The purpose of the study was to determine if the induction of either the mutant phenotypes or genotypes depended on dose rate, i.e., presumably were influenced by repair. To simulate a cell‐renewal population of cells in vivo, low enough dose rates of γ‐rays were used which permitted essentially continuous growth for 50–100 doublings in cell number. Considerable repair of mutagenesis as well as lethality was evident. Compared to exposures at high‐dose‐rate, the decreased frequency of mutants at low‐dose‐rate appeared to be accompanied by a shift in genotype toward that of unexposed cells, i.e., in a shift toward a higher frequency of intragenic mutations than was observed with high‐dose‐rate exposures. © 1995 Wiley‐Liss, Inc.
Radiosensitization of mouse breast cancer cells in vitro by estramustine
Authors: Rockwell Sara
Published: February 2007

Estramustine, a conjugate of estradiol and nitrogen mustard, has been shown previously to depolymerize microtubules, inhibiting the formation of mitotic spindles and arresting cells in G2/M. Estramustine at concentrations of 10–30 μM inhibited the growth of EMT6 mouse breast carcinoma cells in a concentration‐dependent fashion. The viability (clonogenicity) of the cells also decreased as the drug concentration and exposure time increased. Pretreatment of EMT6 cells for 48 hr with 10 or 20 μM estramustine increased the radiosensitivity on EMT6 cells, producing enhancement ratios of 1.2 and 2.1, respectively. © 1995 Wiley‐Liss, Inc.
Alteration of Ki‐67, DNA content and cell cycle distribution during radiotherapy for cervix cancer
Authors: Bravo Isabel , Sansonetty Filipe , Craveiro Rogéria , José Bento M. , Figueiredo Graciette , Vieira Elio
Published: February 2007

In a prospective study involving 158 patients with carcinoma of the uterine cervix, DNA content, S‐phase fraction (SPF), and Ki‐67 proliferative index were evaluated in fresh tissue using flow cytometry and immunocytochemical analysis. Of all tumors, 57.1% were aneuploid. In this subgroup, 25% of tumors had a DNA index between 1.6 and 1.8. SPF values ranged from 0.5 to 57.2% and were significantly higher (P < 0.0001) in tumors with an abnormal DNA content (aneuploid). Ki‐67 labeling index ranged from 1.7 to 65.0%. No association was found between any of the above‐mentioned parameters and clinical stage or histological type of tumor. When analyzing overall survival, a statistically significant difference was found between stage IIB patients with aneuploid and diploid DNA content. In 39 carcinomas evaluated after 1 week of radiotherapy, irradiation induced a significant decrease in Ki‐67 index. In 7 aneuploid tumors where cell cycle analysis was feasible, a significant increase in G2 + M phase fraction was observed (P < 0.02). We suggest these parameters are therefore useful to monitor radiation‐induced alterations in cell cycle and proliferation. © 1995 Wiley‐Liss, Inc.
Acoustic pulse generated in a patient during treatment by pulsed proton radiation beam
Authors: Hayakawa Yoshinori , Tada Junichiro , Arai Norio , Hosono Katsuhisa , Sato Masaru , Wagai Toshio , Tsuji Hiroshi , Tsujii Hirohiko
Published: February 2007

Acoustic pulses were detected from a patient treated by a pulsed proton radiation beam. The dose rate of the proton beam was 0.3 cGy/pulse. The signals from 100 to 700 pulses were accumulated to improve the signal to noise ratio. After accumulation, the random noise level was negligibly small compared to the signal. These results suggest the feasibility of non‐invasive monitoring of proton dose distributions in patients by sensing acoustic pulses generated during irradiation by a pulsed proton radiation beam. © 1995 Wiley‐Liss, Inc.