bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decision support system for treatment selection: Application of a statistical expert advisor to the problem of prostate cancer treatment selection
Authors: Whittington Richard , Altschuler Martin D. 
Published: February 2007

AbstractFor clinical cases with difficult combinations of patient parameter values, treatment selection may be complex or controversial and require considerable time. Treatment selection may be affected by a clinician's experience with a disease and expertise with a treatment, existing protocols, capabilities of local medical facilities, and patient preference. We discuss the concepts and clinical applications of an interactive statistical package (isp) software shell which can create systems that reproduce the judgment of one or more expert clinicians in the management of a patient. An isp system can 1) be taught, verified, updated, and tailored to local facilities quickly and easily by an individual clinician, 2) compute and rank treatment selection probabilities for a presented case in accord with the treatment preferences of its human teacher and explain to a clinician the logical and statistical basis of each step of the decision process, 3) identify sensitive variables of a case for additional verification and to allow questions of the type “what would be the treatment preferences if the value of this variable were changed?”, 4) accumulate statistics for unusual cases (rare combinations of patient parameter values), and 5) continue to learn and achieve further (statistical) insight by recognizing variable combinations (joint variables) whose values are more sensitive to the selection of a particular treatment. An isp system can be used for 1) second opinions, by estimating the treatment preferences of one or more clinical experts for a particular case, 2) allowing patient involvement in the treatment decision in cases for which several treatment options may provide the same outcome, 3) quality assurance, by helping a clinician to identify and review critical patient parameter values and pivotal questions, and to check a treatment decision with his own isp system and those of colleagues, 4) avoiding unnecessary diagnostic tests, by identifying parameters that do not affect the treatment selection for a case, 5) documenting the decision factors of a case, 6) finding the reasons for differences among experts in treatment selection for different types of cases, and 7) teaching residents. The concepts and clinical application of an isp system are discussed. © 1993 Wiley‐Liss, Inc.
Reduction in tumor blood flow in skin flap tumor after hydralazine is not due to a vascular steal phenomenon
Authors: Dewhirst Mark W. , Madwed David , Meyer Robert E. , Ong Edgardo T. , Klitzman Bruce , Rosner Gary L. , Dodge Richard 
Published: February 2007

AbstractThe purpose of this study was to evaluate whether a “vascular steal” mechanism (preferential arteriolar vasodilation in normal vs. tumor tissue concomitant with a reduction in blood pressure) is responsible for tumor blood flow reduction after hydralazine administration. Fischer‐344 rats, fitted with dorsal flap window chambers that allowed visualization of tumor and normal healing subcutaneous tissue vasculature, were the experimental subjects. Intravital microscopy of tumor and normal microvasculature was used to measure microvessel diameters and red cell velocities before and after hydralazine (0.4 mg/kg, i.v.) administration. Hydralazine caused an average drop in mean arterial pressure of 32 mmHg and a concomitant 70% drop in capillary and venous blood flow in central tumor regions in both 9‐ and 14‐day‐old tumors. Intermittent blood flow frequency increased in capillaries and veins from 3% prior to drug to 46% after drug administration. In contrast, capillary and venous flow increased in adjacent normal tissues by 30%. Normal and tumor arterioles showed no significant change in diameter after hydralazine administration. Since the reductions in tumor blood flow were not accompanied by preferential arteriolar dilation in normal arterioles, the hypothesis that a vascular steal phenomenon was responsible for the observed reduction in tumor blood flow in this model system was disproved. A more likely explanation is that the reduction in tumor vessel diameter and concomitant flow reduction are a passive effect related to the relative difference between intravascular pressure and interstitial fluid pressure and/or tissue pressures, the latter of which are known to be increased in tumors. The results suggest that reduction in tumor blood flow might be expected following blood pressure reduction, even when the tumor resides in normal tissue beds that are not actively vasodilated by an antihypertensive agent. © 1994 Wiley‐Liss, Inc.
Oxygen tension measurements in human tumors: The institut gustave‐roussy experience
Authors: Lartigau Lric , Randrianarivelo Harizo , Martin Laurent , Stern Sabine , Thomas Carole D. , Guichard Marcelle , Weeger Pascal , le Ridant Anne‐Marie , Luboinski Bernard , Nguyen Tiem , Ortoli Jean‐Christophe , Grange Florent , Avril Marie‐Françoise , Lusinchi Antoine , Wibault Pierre , Haie‐Meder Christine , Gerbaulet Alain , Eschwege François 
Published: February 2007

AbstractTumor hypoxia contributes to the response to radiotherapy and to chemotherapy. The oxygenation status of normal tissues and tumors was evaluated using the KIMOC‐6650 histograph in 35 patients with head and neck tumors, 13 patients with metastatic malignant melanoma (MMM), and 6 patients with uterine cervical carcinoma. Patient compliance was good. The pO2 values measured in tumors were in general lower than those measured in normal tissues of the same patient. The pO2 in the tumors varied along the track and from one track to another. Important pO2 variability was also detected from one tumor to another. Patients with head and neck tumors had a median pO2 of 6.76 kPa (52 mmHg) in normal tissues (subcutaneous) and 1.33 kPa (10 mmHg) in tumors with 25% of the values below 0.26 kPa (2 mmHg). Patients with MMM had a median pO2 of 3.64 kPa (28 mmHg) in normal tissues (subcutaneous tissues and muscles) and pO2 was 0.91 kPa (7 mmHg) in tumors with 18% of the values below 0.26 kPa. Patients with uterine cervical carcinoma had a median pO2 of 6.37 kPa (49 mmHg) in normal tissues (vagina) and 2.73 kPa (21 mmHg) in tumors with 16% of the values below 0.26 kPa. The data for N2 and N3 head and neck nodes showed significantly more values below 0.26 kPa (2 mmHg) as nodal size increased (P < 0.001 by chi‐square test). The best parameters to describe tissue oxygenation are discussed. © 1994 Wiley‐Liss, Inc.
Pilot study evaluating nicotinamide in metastatic brain tumors treated with radiation
Authors: Pisch Julianna , Sood Brij M. , Alfieri Alan , Berson Anthony M. , Chadha Manjeet , Vikram Bhadrasain 
Published: February 2007

AbstractNicotinamide (NAM) has been shown to be an effective radiosensitizer in animal studies, but to date no clinical studies have substantiated this effect. Twenty‐nine patients with brain metastases were randomized to receive NAM and external radiation therapy (RT) (n = 14) or irradiation alone (n = 15). NAM was started on day 1 at 3 g/day and continued until radiation was completed. The RT dose to the whole brain was 30 Gy in 10 fractions in 12–14 days. To evaluate response, a computed tomographic (CT) scan of the head was repeated 1 month post‐treatment. Toxicity was graded from the skin, liver, and gastrointestinal tract. There were no toxicities observed at 39.0 g total dose of NAM. Median survival for the 29 patients, calculated by the Kaplan‐Meier method, was 3.5 months for the NAM + RT group (14 patients) and 3.9 months for the RT alone group (15 patients). Eighteen patients were evaluable for 1 month tumor response by CT scan. Response rates were compared with Fisher's exact two‐tailed test. There was no difference in complete response (CR) (P = 0.62) or CR + partial response (PR) (P = 1.000) between the two groups. Adjuvant NAM, given in doses of 3.0 g/day (39.0 g total dose) in the treatment of brain metastases, has shown no benefit in survival or response in this preliminary Study. © 1994 Wiley‐Liss, Inc.
Protein expression patterns of radiation‐transformed human epidermal keratinocytes: A two‐dimensional gel electrophoretic approach
Authors: Prasad Sarada , Dritschilo Anatoly , Rhim Johng , Worland Peter , Thraves Peter 
Published: February 2007

AbstractWe have previously reported the radiation‐induced malignant transformation of immortalized human epidermal keratinocytes. Two sets of tumorigenic transformants (treated with either 2 Gy or 4 Gy twice) and their respective clonal derivatives were characterized [Thraves et al.: Proc Natl Acad Sci USA 87:1174–1177, 1990]. We have tested the hypothesis that the multiple changes which take place during cellular transformation are reflected at the level of protein expression. Toward this end, we have compared protein expression in the non‐tumorigenic, parental keratinocytes and their radiationtransformed derivatives during the various stages of progression to tumorigenicity. We employed two‐dimensional gel electrophoresis (2D‐PAGE) coupled with silver staining and computer‐assisted data analyses. Eighteen differentially expressed proteins were identified in the various transformed cultures. Changes in 8 of these proteins exhibited a similar pattern in both the 2 and 4 Gy transformants, while the expression of the other 10 varied. Two of the eight proteins that showed identical changes in both sets of transformed keratinocytes have been identified as tropomyosin and proliferating cell nuclear antigen (PCNA) by their characteristic 2D‐map locations and reactivity with specific antisera. The identification of these differentially expressed polypeptides in the tumorigenic keratinocytes constitutes a preliminary step in the study of the complex process of radiation‐induced transformation and its regulation by specific gene products. © 1994 Wiley‐Liss, Inc.
Combining D,L‐α‐difluoromethylornithine with [3H] thymidine increases killing of rat gliosarcoma cells in vitro
Authors: Boggs Sallie S. , Grudziak Aleksandra G. , Deutsch Melvin , Redgate Edward S. 
Published: February 2007

AbstractThe present studies were done to test the hypothesis that the cytostasis caused by D,L‐α‐difluoromethylornithine (DFMO) would enhance cellular retention of [3H] thymidine and thereby increase the effective internal radiation dose and cell killing. To test this hypothesis, 9L rat brain tumor cells were cultured in the presence of 10 μCi of [3H] thymidine for 4 days (about 5 divisions) with or without 1 mM DMFO. After 4 days the [3H] thymidine was removed from the cultures and both groups of cells were treated with 1 mM DFMO for the remainder of the experiment. After 24 days the untreated control group had 2.5 × 1014 colony‐forming cells (CFC) and the group with [3H] thymidine or DFMO alone had 2 × 109 and 2 × 106 CFC, respectively. The group with sequential treatments (4 days [3H] thymidine followed by DFMO) had only 6 × 103 CFC, but the group with simultaneous treatments (DFMO added on day 0 with the [3H] thymidine) had too few CFC remaining by day 8 to measure accurately. In the group given [3H] thymidine and DFMO sequentially, retention of [3H] thymidine was enhanced, but in the group given DFMO simultaneously there was almost total retention as well as increased initial uptake of [3H] thymidine. These studies suggest that combining DFMO with short‐range radioemitters may be a useful approach to brain tumor therapy. © 1994 Wiley‐Liss, Inc.
Fraction size dependent sparing effects of clinically relevant fractionated radiotherapy protocols on human glioma multicellular spheroids
Authors: Li Derui , Class Reiner , Emrich Jacqueline , Miyamoto Curtis , Brady Luther W. 
Published: February 2007

AbstractClinically relevant X‐ray irradiation protocols were chosen to evaluate the radiation response of human glioma cell lines, A1207 and U‐373 MG, grown as multicellular spheroids. The protocols included single‐dose fraction (SF), conventional fractionation (CF; 2 Gy per fraction, 24 hr interval), hyperfractionation (HF; 1.0 Gy per fraction, 12 hr interval), and accelerated hyperfractionation (AHF; 1.5 Gy per fraction, 6 hr interval). Spheroids from both cell lines are clearly more refractory to the cytotoxic effects of multifractionated irradiation than the single‐dose irradiation. Dose‐sparing effects of CF or HF were comparable in the two cell ilnes. More detailed studies of A1207 spheroids showing sparing effects are fraction size dependent. The smaller the dose size per fraction, the larger the sparing effect. In order to achieve the same biological effect using multifractionated irradiation, compared to single dose, a higher dose is needed to compensate for sublethal damage repair which occurred in the fraction intervals. The relative doses required for achieving isoeffect as SF were 145%, 160%, and 169% for CF, AHF, and HF, respectively, when a total dose of 10 Gy was administered. The isoeffective doses for AHF and HF compared to CF were 113% and 126%, respectively. There was also an increase in sparing effect with increasing total dose administered as multifraction. Our results suggest that in the design of multifractionated radiotherapy regimens, fraction size dependent sparing effects related to dose per fraction and total dose on human gliomas should be taken into consideration to optimize therapeutic outcome. © 1994 Wiley‐Liss, Inc.
Graphic analysis of isobiological effectiveness for twice‐a‐day radiotherapy regimens and its application
Authors: Huang David T. , Schmidt‐Ullrich Rupert , Lin Peck‐Sun 
Published: February 2007

AbstractThe effectiveness of twice‐a‐day (BID) hyperfractionated radiotherapy (RT) schedules has been demonstrated for carcinomas of the head and neck, the lung, and advanced stage breast cancers. Fractionation choices include identical or different doses of the two daily treatments referred to as equally split or unequally split BID doses, respectively. The choices of equally split, unequally split, or a mixture of both are based on the consideration of maximal tumor control or minimal late tissue effect. The comparison of biological effectiveness of different regimens is commonly done by computing the individual biological effective doses (BED) to tumor and late tissue. For this purpose, a different theoretical approach which adopts the concept of isobiological effectiveness may be more general and analytic than point dose computation. Taking advantage of the quadratic nature, a graphic analysis of isobiological effectiveness (GAIBE) was developed to analyze how to optimize the regimens for tumor killing effect and late tissue sparing effect. In this analysis, a Cartesian plot of two dose axes representing the two daily doses is used. The loci of isobiological effective dose (isoBED) regimens are circular on this plot. Thus, the effects of many regimens on tumor and late reacting tissue may be observed simultaneously by comparing the isoBED loci. Graphically, with GAIBE analysis and, mathematically, for a given isoBED to tumor, we have demonstrated that equally split hyperfractionation schedules will deliver the lowest biological effectiveness to late reacting tissues among all isoBED regimens to tumor. Situations when unequally split regimens are beneficial are also discussed. Another variable of clinical importance is the repopulation phenomenon which may counteract the biological effectiveness with increasing length of treatment course. The additive nature of BED from daily treatments allows GAIBE analysis to compensate for the repopulation phenomenon and aid the determination of the course length. Our analysis can also be used for the design of concomitant boost BID regimens. A subroutine in BASIC language has been developed and is available upon request. As a corollary of GAIBE analysis, for a chosen total dose, once‐daily treatment (QD) will result in the most tumor killing and the BID half‐dose exposures will have the least tumor killing. Other combinations of BID exposures with the sum of doses equal to QD exposure will have varying degrees of tumor killing which fall in between these two extremes. This concept from GAIBE analysis may be applied to determine α/β values for tumor cell lines using equally split exposures. © 1994 Wiley‐Liss, Inc.
Complications following radiosurgery: A review
Authors: Marks Lawrence B. 
Published: February 2007

AbstractThe complication rates following radiosurgery (RS) for a variety of intracranial lesions are reviewed. While complications are generally uncommon, increased rates are seen with larger doses and treatment volumes. The deep portions of the brain (e.g., brain stem) and the optic structures are particularly sensitive. The risks of RS need to be considered as RS gains popularity and is used to treat a wider variety of intracranial lesions. © 1994 Wiley‐Liss, Inc.
Increased formation of diacylglycerol in tumor cells that are resistant to ionizing radiations
Authors: Pacini Stefania , Santucci Maria A. , Milano Franco , Casamassima Franco , Greenberger Joel S. , Pierce Jacalyn H. , Ruggiero Marco 
Published: February 2007

AbstractIn order to study the biochemical mechanisms underlying resistance to ionizing radiations we developed tumorigenic 32D hematopoietic cell lines that were resistant to gamma irradiation at clinical low dose rate. In these autonomously growing cultures, we studied alterations of mitogenic signaling. The cultures did not secrete autocrine growth factors and their conditioned medium could not sustain survival or growth of normal factor‐dependent cells. The pattern of protein tyrosine phosphorylation did not change after stimulation with the growth factor interleukin‐3. Transformed cultures showed an increased level of the intracellular second messenger diacylglycerol without a corresponding increase of inositol phosphates. These data suggest that aberrant diacylglycerol accumulation and protein kinase C activation might be involved in the development of resistance to the killing effects of ionizing radiations in spontaneous transformants. © Wiley‐Liss, Inc.
Proliferative activity measured by flow cytometry and Ki‐67 of nodal negative breast cancer as a prognostic parameter for local recurrences and distant metastases ‐first results
Authors: Fietkau R. , Tulusan A. H. , Dressel V. , Günther P. , Wolter Ch. , Lang N. , Meyer M. , Sauer R. 
Published: February 2007

AbstractThe prognostic value of proliferative activity [percentage of S‐phase cells = S‐phase fraction (SPF) and Ki‐67] was determined in nodal negative breast carcinomas and correlated with no evidence of disease (NED) survival and analysis of recurrence. Overall 193 breast carcinomas were investigated. SPF of 183 breast carcinomas was determined by one‐dimensional flow cytometry. Histochemically the percentage of Ki‐67‐positive cells was measured in 188 patients. Slowly proliferating tumors determined by SPF (SPF < median) had a better 5‐year NED survival (91%), a lower rate of distant metastases (1%), and a lower rate of loco‐regional recurrences (4.5%) compared to fast proliferating tumors (SPF > median; NED survival 63%; distant metastases 15.7%; loco‐regional recurrences 21%). Slowly proliferating tumors determined by Ki‐67 (Ki‐67 < 20%) had a better 5‐year NED survival (77%) and a lower rate of distant metastases (6.1%) compared to fast proliferating tumors (percentage of Ki‐67‐positive cells > 20%; NED survival 63%; distant metastases 17.9%). However, there was no significant difference in loco‐regional control. Stepwise multivariate analysis showed that SPF (P= 0.002) was the only independent prognostic factor for NED survival: SPF in interaction with grading (P= 0.001) and family history (P= 0.044) for distant metastases; and SPF (P= 0.0039), method of surgical treatment (P =0.071), and grading (P =0.0956) for loco‐regional recurrences. In conclusion, proliferative activity is a relevant prognostic parameter for nodal negative breast Cancer. © Wiley‐Liss, Inc.
Total lymphoid irradiation prior to bone marrow transplantation for severe aplastic anemia:Analysis of 20 cases
Authors: Zapatero Almudena , Cerro Elia Del , Pinar Beatriz , Cerezo Laura , Domínguez Pedro , Torrubia Armando Pérez 
Published: February 2007

AbstractTwenty patients with severe aplastic anemia were treated with allogeneic bone marrow transplantation (BMT) between June 1986 and August 1992. The conditioning regimen included high‐dose cyclophosphamide, 50 mg/kg over 4 consecutive days, followed by 7 Gy total lymphoid irradiation (TLI) in 2 fractions the day before BMT. A combination of methotrexate and cyclosporine was used for prophylaxis of graft vs. host disease (GVHD). All recipients were previously transfused. Fourteen of the 20 transplanted patients are alive with a median follow‐up of 42 months. Actuarial survival was 70 ± 15% for the entire group and 83 ± 20% for the 6 patients ≤18 years. There was not any case of graft rejection following BMT. The incidence of moderate and severe acute GVHD was 29% and of chronic GVHD was 14%. Our findings indicate that the combination of cyclophosphamide and 7 Gy TLI prior to BMT provides excellent transfusion free survival and is extremely effective in decreasing rejection rates in previously transfused patients with severe aplastic anemia. © Wiley‐Liss, Inc.
Value of surgery and radiotherapy in the treatment of brain metastases
Authors: Nieder C. , Niewald M. , Schnabel K. , Berberich W. 
Published: February 2007

AbstractIn this study the results of surgery and radiotherapy (RT) in 26 patients, compared with those of 42 patients who had only RT are analyzed. The most frequent sites of primary tumors were the lung and breast. In the first years 20 × 2 Gy was given; later on 10 × 3 Gy was administered. Sixteen non‐operated patients received 20 × 2 Gy followed by a local boost of 10–20 Gy. Because a matched cohort pair method was chosen for this analysis, all prognostic factors were equally distributed between the operation (OP) + whole‐brain irradiation (WBI) and the WBI only group. The local remission rate after OP + WBI was 81% vs. 38.5% after WBI only and 69% after WBI + boost. Median survival after surgery (17 months) was significantly longer, but the dose of RT had no influence on survival (7 vs. 8 months). The distribution of prognostic factors was significantly different between the WBI + boost group and the other groups, and therefore a prospective randomized trial will become necessary to verify the superiority of surgical treatment compared to “high‐dose” RT. When compared to “standard” RT equivalent to the 10 × 3 Gy schedule, surgery + RT is significantly superior. © Wiley‐Liss, Inc.