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S Malone

Publications and source records attributed to S Malone.

At least 19 recordsLinked to original sources
PubMed2004

Application of metabolite profiling to the identification of traits in a population of tomato introgression lines.

Naturally occurring variation in wild species can be used to increase the genetic diversity of cultivated crops and improve agronomic value. Populations of introgression lines carrying wild species alleles afford an opportunity to identify traits associated with the introgressed regions, and facilitate characterization of the biochemistry and genetics underlying these phenotypes. Understanding plant metabolic pathways and the interactions between genes, phenotype, and environment is fundamental to functional genomics. Successful analysis of the complex network of plant metabolism requires analytical methods able to record information on as many metabolites as possible. Metabolite profiling is used to provide a snapshot of the metabolome in samples which differ in a known factor such as genetic background. Differences between the metabolite profiles can identify those metabolites/metabolic pathways affected by the introgression and allow genetic maps for metabolic alterations to be established. A Time-of-Flight Mass Spectrometry method is presented, with associated data reduction, used for profiling aqueous metabolites fom tomato. Analysis of ripe fruits of two tomato species, Lycopersicon esculentum and L. pennellii, showed differences in the amounts of many metabolites, including organic acids and sugars. Six introgression lines, L. pennellii introgressions within L. esculentum, were also examined and showed that Principal Component Analysis can reveal subtle differences in metabolism of the introgressed lines when compared to their parents.

Fruit↗
PubMed2004

New eudesmane derivatives from Melampodium camphoratum from the Suriname rainforest.

Bioassay-guided fractionation of an EtOAc extract of the leaves of Melampodium camphoratum using an assay for inhibitors of the degradation of hemin resulted in the isolation of six new eudesmane sesquiterpenes (1-6) and the known 6-epi-beta-verbesinol coumarate (7). The structures of compounds 1-6 were established as 6alpha-(4'-O-methyl-7'E-coumaryloxy)eudesm-4(14)-ene (1), 6alpha-({4'-O-stearyl}-7'E-coumaryloxy)eudesm-4(14)-ene (2), 6alpha-({4'-O-palmityl}-7'E-coumaryloxy)eudesm-4(14)-ene (3), 6alpha-({4'-O-[9' 'Z-hexadecenoyl]}-7'E-coumaryloxy)eudesm-4(14)-ene (4), 6alpha-(7'Z-coumaryloxy)eudesm-4(14)-ene (5), and 6alpha-({4'-acetoxy}-7'Z-coumaryloxy)eudesm-4(14)-ene (6). Compounds 1-4 showed weak activity in the hemin degradation assay, while compounds 5-7 were inactive.

Animals↗
PubMed2003

[Radiation sensitivity testing and late neurological complications following radiosurgery for AVM: the use of SF2 from fibroblasts as a predictive factor].

PURPOSE: To identify SF2 as a prognostic factor of late complications from radiosurgery in patients treated for AVM. PATIENTS AND METHODS: Five patients with AVM treated in three canadian institutions and who suffered clinically significant neurological sequelaes secondary to radiosurgery were identified. Their fibroblasts were cultured and their radiation sensitivity tested to determine the SF2 for each patient. RESULTS: Patients who developed a neurological complication from radionecrosis, secondary to radiosurgery had an SF2 different than the two control patients with AVM and no complications and also from a group of five cancer patients without late radiation complications (P = 0.005). CONCLUSION: Radiosurgery is an elective procedure. The identification of a subgroup of patients who are radiosensitive and at a higher risk of radiation induced complications can allow the treatment team to reduce the risk of such complications. SF2 as a new predictive factor should be incorporated in predictive models of risk from treatment of AVM by radiosurgery. This work needs to be confirmed in a larger cohort of patients.

Cell Survival↗
PubMed2002

Bioactive saponins from Acacia tenuifolia from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Acacia tenuifolia using the engineered yeast strains 1138, 1140, 1353, and Sc7 as the bioassay tool resulted in the isolation of the three new saponins 3, 5, and 6 and the three known saponins 1, 2, and 4. The structures of the new compounds were established on the basis of HRMS, 1D and 2D NMR spectral data on the intact saponins, and GC-MS analyses of the sugars. Compounds 1,2 and 5,6 showed cytotoxicity against mammalian cell lines.

Acacia↗
PubMed2001

Treatment planning aids in prostate cancer: friend or foe?

BACKGROUND: Rectal barium is commonly used as a treatment planning aid for prostate cancer to delineate the anterior rectal wall. Previous research at the Ottawa Regional Cancer Centre demonstrated that retrograde urethrography results in a systematic shift of the prostate. We postulated that rectal barium could also cause prostate motion. PURPOSE: The study was designed to evaluate the effects of rectal barium on prostate position. METHODS AND MATERIALS: Thirty patients with cT1-T3 prostate cancer were evaluated. Three fiducial markers were placed in the prostate. During simulation, baseline posterior-anterior and lateral films were taken. Repeat films were taken after rectal barium opacification. The prostate position (identified by the fiducials) relative to bony landmarks was compared before and after rectal barium. Films were analyzed using PIPsPro software. RESULTS: The rectal barium procedure resulted in a significant displacement of the prostate in the anterior and superior direction. The mean displacement of the prostate measured on the lateral films was 3.8 mm (SD: 4.4 mm) in the superior direction and 3.0 mm (SD: 3.1) in the anterior direction. CONCLUSIONS: Rectal barium opacification results in a systematic shift of the prostate. This error could result in a geographic miss of the target; therefore, alternate methods of normal tissue definition should be used.

Aged↗
PubMed2001

Origins and consequences of age at first drink. I. Associations with substance-use disorders, disinhibitory behavior and psychopathology, and P3 amplitude.

BACKGROUND: Although an early age at first drink has been repeatedly associated with substantially elevated rates of alcoholism, the mechanisms underlying this association remain unclear. We investigated whether the association of age at first drink (AFD) with alcoholism was more consistent with the hypothesis that the former causes the latter or the hypothesis that both are manifestations of some common vulnerability. METHODS: We investigated whether substance use and mental health disorders, education, IQ, and personality were associated with AFD in a sample of 2670 adults; whether P3 amplitude was associated with AFD in a sample of 1127 17 year olds; and whether indicators of disinhibitory psychopathology assessed at age 11 predicted AFD by age 14 in a sample of 1343 adolescents. RESULTS: In adults, AFD was associated not only with alcohol dependence, but also with a broad array of indicators of disinhibitory behavior and psychopathology including nicotine dependence, illicit drug abuse and dependence, conduct disorder, antisocial personality disorder, underachievement in school, and the personality trait of constraint. In 17 year olds, AFD was also associated with reduced P3 amplitude, a well-documented psychophysiological marker of alcoholism risk. Finally, in the early-adolescence sample, measures of behavioral disinhibition, including oppositionality, hyperactivity/impulsivity, and inattentiveness assessed at age 11 predicted drinking onset by age 14. CONCLUSIONS: Our findings indicated that AFD is not specifically associated with alcoholism but rather is correlated with a broad range of indicators of disinhibited behavior and psychopathology. Moreover, individuals who first drink at a relatively early age manifest elevated rates of disinhibitory behavior and psychopathology before they first try alcohol. Taken together, these findings suggest that the association of AFD with alcoholism reflects, at least in part, a common underlying vulnerability to disinhibitory behavior. Whether an early AFD directly influences risk of adult alcoholism remains unclear.

Adolescent↗
PubMed2000

Severe normal tissue complication correlates with increased in vitro fibroblast radiosensitivity in radical prostate radiotherapy: a case report.

The radiation responses of fibroblasts taken from four patients undergoing radiotherapy for prostate cancer were evaluated in vitro. One patient exhibited a severe normal tissue late reaction after radiotherapy, and the fibroblasts from this patient also showed increased radiosensitivity. The other three patients exhibited a normal clinical response, and their fibroblast response in vitro was also considered normal when compared with previously published data from our laboratory. When cells were allowed to repair potentially lethal damage (PLDR), the differences between cell lines were reduced; therefore, a deficiency in PLDR did not cause the differences in radiosensitivity. Fractionated radiation resulted in elevated survival due to repair of sublethal damage (SLDR), and the differences in radiosensitivity were increased. In addition, the survival curves displayed an upward bending nature, indicative of an adaptive response. Thus, adaptive response and ability to modify it may play an important role in fractionated radiotherapy. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 336-342 (2000).

Aged↗
PubMed2000

A prospective comparison of three systems of patient immobilization for prostate radiotherapy.

PURPOSE: The study compared the setup reliability of 3 patient immobilization systems, a rubber leg cushion, the alpha cradle, and the thermoplastic Hipfix device, in 77 patients with cT1-T3, N0, M0 prostate cancer receiving conformal radiotherapy. METHODS AND MATERIALS: Port films were analyzed and compared to simulation films to estimate the setup errors in the three coordinate axes (anterior-posterior, cranial-caudal, medial-lateral). A total vector error was calculated from these shifts. RESULTS: The Hipfix was found significantly superior to the other two devices in reducing mean setup errors in all axes (p < 0.005). The average field-positioning error with the Hipfix ranged from 1.9 mm to 2.6 mm for all axes, whereas the deviation for the other two systems ranged from 2.7 to 3. 4 mm. Errors greater than 10 mm were virtually eliminated with the Hipfix system. There was a reduction in the mean total vector error in the alpha cradle and Hipfix patient cohorts over time, reflecting improved efficacy as a result of experience. CONCLUSION: There was a significant difference in the performance of each immobilization device. The Hipfix was consistently more reliable in reducing setup errors than the other devices.

Analysis of Variance↗
PubMed2000

Postradiotherapy prostate biopsies: what do they really mean? Results for 498 patients.

PURPOSE: Postradiotherapy (RT) prostate biopsies are prone to problems in interpretation. False negatives due to sampling error, false positives due to delayed tumor regression, and indeterminate biopsies showing radiation effect in residual tumor of uncertain viability are common occurrences. METHODS AND MATERIALS: A cohort of 498 men treated with conventional RT from 06/87-10/96 were followed prospectively with systematic transrectal ultrasound (TRUS)-guided post-RT prostate biopsies, starting 12-18 months after RT. If there was residual tumor but further decline in serum prostate-specific antigen (PSA), biopsies were repeated every 6-12 months. Patients with negative biopsies were rebiopsied at 36 months. Residual tumor was evaluated for RT effect and proliferation markers. The 498 men had 978 biopsies. Median time of the first biopsy (n = 498) was 13 months, biopsy #2 (n = 342) 28 months, biopsy #3 (n = 110) 36 months, biopsy #4 (n = 28) 44 months, and biopsy #5 (n = 4) 55 months. Median follow-up is 54 months (range 13-131). One hundred seventy-five patients (34%) had prior hormonal therapy for a median of 5 months (range 1-60). RESULTS: Clinical stage distribution was T1b: 46; T1c: 50; T2a: 115; T2b/c: 170; T3: 108; T4: 11; Tx: 1. Distribution by Gleason score was: 28% Gleason score 2-4; 42%: 5-6; 18%: 7; and 12%: 8-10. Seventy-one men have died, 26 of prostate cancer and 45 of other causes. Actuarial failure-free survival by T stage at 5 years is T1b: 78%; T1c: 76%; T2a: 60%; T2b/c: 55%; T3: 30%; and T4: 0%. Actuarial freedom from local failure at 5 years is T1b: 83%; T1c: 88%; T2a: 72%; T2b/c: 66%; T3: 58%; and T4: 0%. The proportion of indeterminate biopsies decreases with time, being 33% for biopsy 1, 24% for biopsy 2, 18% for biopsy 3, and 7% for biopsy 4. Thirty percent of indeterminate biopsies resolved to NED status, regardless of the degree of RT effect, 18% progressed to local failure, and 34% remained as biopsy failures with indeterminate status within the time frame of this report. Positive staining for proliferation markers was associated with both subsequent local failure and also any type of failure. In multivariate analysis, only PSA nadir (p = 0.0002) and biopsy status at 24-36 months (p = 0. 0005) were independent predictors of outcome. CONCLUSIONS: Post-RT prostate biopsies are not a gold standard of treatment efficacy, but are an independent predictor of outcome. Positive immunohistochemical staining for markers of cellular proliferation is associated with subsequent local failure. Indeterminate biopsies, even when showing marked RT effect, cannot be considered negative.

Adult↗
PubMed2000

Respiratory-induced prostate motion: quantification and characterization.

PURPOSE: The precise localization of the prostate is critical for dose-escalated conformal radiotherapy. This study identifies and characterizes a potential cause of inaccurate prostatic localization-respiratory-induced movement. METHODS AND MATERIALS: Prostate movement during respiration was measured fluoroscopically using implanted gold fiducial markers. Twenty sequential patients with CT(1)-T(3) N(0) M(0) prostate carcinoma were evaluated prone, immobilized in customized thermoplastic shells. A second 20 patients were evaluated both prone (with and without their thermoplastic shells) and supine (without their shells). RESULTS: When the patients were immobilized prone in thermoplastic shells, the prostate moved synchronously with respiration. In the study the prostate was displaced a mean distance of 3.3 +/- 1.8 (SD) mm (range, 1-10.2 mm), with 23% (9/40) of the displacements being 4 mm or greater. The respiratory-associated prostate movement decreased significantly when the thermoplastic shells were removed. CONCLUSION: Significant prostate movement can be induced by respiration when patients are immobilized in thermoplastic shells. This movement presumably is related to transmitted intraabdominal pressure within the confined space of the shells. Careful attention to the details of immobilization and to the possibility of respiratory-induced prostate movements is important when employing small field margins in prostatic radiotherapy.

Algorithms↗
PubMed2000

Enhanced in vitro radiosensitivity of skin fibroblasts in two patients developing brain necrosis following AVM radiosurgery: a new risk factor with potential for a predictive assay.

PURPOSE: Radiosurgery is an effective treatment for arteriovenous malformations (AVM) with a low risk of developing brain necrosis. Models have been developed to predict the risk of complications. We postulated that genetic differences in radiosensitivity may also be a risk factor. METHODS AND MATERIALS: Fibroblast cultures were established from skin biopsies in two AVM patients developing radiation necrosis. The results of clonogenic survival assays were compared to a parallel study with two groups of cancer patients treated with radiation: 1) patients without late side effects; 2) patients experiencing severe late sequelae. RESULTS: The survival fraction at 2 Gy (SF2) of the 2 AVM patients was 0.17 (0.14-0.19) and 0.18 (0.14-0.22). The SF2's of the cancer patients ranged between 0.25-0.38 (mean = 0.31) for the control group, and between 0. 10-0.20 (mean = 0.17) for the hypersensitive group. The SF2's of the AVM patients who developed brain necrosis were comparable to that of the hypersensitive group (p = 0.85) but significantly lower than the control group (p = 0.05). CONCLUSION: The two patients who developed radiation necrosis demonstrate increased fibroblast radiosensitivity. The SF2 of skin fibroblasts may potentially be used as a predictive assay to detect patients at risk for brain necrosis.

Adult↗
PubMed2000

Correlation between normal tissue complications and in vitro radiosensitivity of skin fibroblasts derived from radiotherapy patients treated for variety of tumors.

PURPOSE: To assess the relationship between fibroblast intrinsic radiosensitivity in vitro and late reactions of normal tissues in patients treated by definitive radiotherapy for variety of tumors. PATIENTS AND METHODS: Ten patients were selected for this study. They were treated by radical radiotherapy for variety of tumors, including non-Hodgkin's lymphoma, prostate, glottic larynx, anal canal, cervix, bladder, thyroid gland, and tonsil pillar. Five patients did not develop any significant late reactions (normally sensitive group, NS). The other five developed late complications in different normal tissues and organs that proved to be fatal in one patient (clinically hyper-sensitive group, HS). Fibroblast cultures were established from punch skin biopsy and radiosensitivity in vitro was measured. The survival fraction at 2 Gy (SF2) was calculated and compared between the two groups. RESULTS: SF2 ranged between 0.10 and 0.38 with a mean of 0.24. The mean SF2 for each of the NS and the HS groups were 0.31 and 0.17, respectively. The non-parametric rank test of Mann-Whitney shows that the difference between the two groups is statistically significant (p = 0.01). CONCLUSION: This study indicates that the in vitro radiosensitivity of skin fibroblasts is correlated with late complications in different organs and normal tissues following radiotherapy for variety of tumors. It also lends support to the existence of a common genetic component determining the radiosensitivity of cells targeted by the late effects of ionizing radiation.

Adult↗
PubMed2000

Effects of urethrography on prostate position: considerations for radiotherapy treatment planning of prostate carcinoma.

PURPOSE: Retrograde urethrography is commonly used to define the prostate apex at simulation. This study evaluated the hypothesis that urethrography causes prostate displacement, resulting in an error in treatment planning. METHODS AND MATERIALS: Forty-five patients with carcinoma of the prostate were evaluated. Gold seeds were placed in the apex, posterior wall, and base of the gland. In the first 20 patients, the position of the seed-defined apex was compared at simulation (with urethrogram) and on day 1 of treatment (without urethrogram). In the second cohort of 25 patients, the effects of urethrography on prostate position were evaluated directly at simulation by comparing the position of apex pre- and post-urethrography. An analysis was performed to estimate the possible impact of urethrogram-induced prostate motion on target coverage. RESULTS: The mean superior displacement in the first and second cohort was 5.2 mm and 6.8 mm, respectively (combined mean shift 6.1 mm). With a 10-mm field margin below the tip of the urethrogram cone, 56% of patients in this study would have inadequate planning target volume (PTV) coverage. CONCLUSION: Retrograde urethrography causes a significant superior shift of the prostate. Strict reliance on urethrography in determining the inferior field margin could result in inadequate treatment.

Adenocarcinoma↗
PubMed2000

Bioactive saponins from Swartzia schomburgkii from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Swartzia schomburgkii using the engineered yeast strains 1138, 1140, and 1353 as the bioassay tool resulted in the isolation of five active (2, 4-7) and three inactive (1, 3, 8) saponins. Saponins 4 and 6 are previously unreported. The structures of all of the saponins were established based on 1D and 2D NMR spectral analysis, on acid and alkaline hydrolysis followed by TLC and GC-MS, and by comparison with literature data for known compounds. Three of the isolated compounds (4-6) showed weak cytotoxicity against the M-109 cell line.

Antifungal Agents↗
PubMed1999

Intermittent androgen suppression in the management of prostate cancer.

OBJECTIVES: Intermittent androgen suppression (IAS) has been suggested as a means of attenuating the androgen deprivation syndrome in men with incurable prostate cancer. Laboratory data suggest that intermittent therapy may prolong the duration of androgen dependence. METHODS: Since October 1993, 54 patients have entered a Phase II protocol consisting of 8 months of total androgen blockade (TAB) using leuprolide (Lupron) depot and nilutamide (Anandron) followed by an off-treatment interval of variable length. Eleven patients had biopsy-proven local failure after radiotherapy, 4 had biochemical failure, 24 had distant metastases (fewer than six axial sites on bone scan), 11 had combined local and distant failure, and 4 were treated as primary management for nodal disease. Mean prostate-specific antigen (PSA) at entry was 37 ng/mL (range 3.8 to 196). After 8 months of TAB, hormonal therapy was discontinued for those patients whose PSA was less than 4.0 ng/mL and stable or decreasing and was resumed (cycle 2) when PSA increased to greater than 10 ng/mL. RESULTS: As of April 1 998, mean follow-up was 33 months (range 14 to 53). Patients have completed at least one, and up to five treatment cycles. The mean time to nadir PSA in cycle 1 was 20 weeks, and the mean time off was 35 weeks (31 weeks for those with metastatic disease versus 39 for local or biochemical failure). In cycle 2, the mean time to PSA nadir was 17 weeks, and the mean time off was 30 weeks (28 weeks for metastatic disease and 38 weeks for local or biochemical failure). In cycle 3, the time to PSA nadir was 19 weeks. Full testosterone data are available for 40 patients in cycle 1. Normal levels were achieved during the off-treatment interval in 73% by a mean of 18 weeks (median 9). Testosterone normalization in cycle 2 was achieved in 71% at a mean time of 17 weeks (median 14). CONCLUSIONS: TAB can be used intermittently, and appears to be more appropriate for patients with local or biochemical failure. Testosterone recovery is not universal in the off-treatment intervals. IAS needs to be investigated in a randomized trial to determine the effect on overall survival and quality of life.

Adenocarcinoma↗
PubMed1999

Synthesis and biological evaluation of analogues of cryptolepine, an alkaloid isolated from the Suriname rainforest.

Bioassay-guided fractionation of an extract of a mixture of Microphilis guyanensis and Genipa americanacollected in the rainforest of Suriname yielded the known alkaloid cryptolepine (2) as the major active compound in a yeast bioassay for potential DNA-damaging agents; the same compound was later reisolated from M. guyanensis. The structure of cryptolepine was identified unambiguously by spectral data and by its total synthesis. Several cryptolepine derivatives (3-29, 32-41) were synthesized based on modifications of the C-2, N-5, N-10, and C-11 positions. Two cryptolepine dimers (30, 31) were also prepared. The structure modifications did not result in compounds with a higher potency than the parent compound cryptolepine in the yeast assay system, although some derivatives did show significant activity. Selected compounds (6, 7, 17, 22, 23, 26, and 27) were also tested for cytotoxicity in mammalian cell culture, and two compounds showed significant cytotoxic activity.

Alkaloids↗