The response of Escherichia coli to the alkylating agents chloroacetaldehyde and styrene oxide.

DNA damage is ubiquitous and can arise from endogenous or exogenous sources. DNA-damaging alkylating agents are present in environmental toxicants as well as in cancer chemotherapy drugs and are a constant threat, which can lead to mutations or cell death. All organisms have multiple DNA repair and DNA damage tolerance pathways to resist the potentially negative effects of exposure to alkylating agents.

Continuous-wave Thulium Laser for Heating Cultured Cells to Investigate Cellular Thermal Effects.

An original method to heat cultured cells using a 1.94 µm continuous-wave thulium laser for biological assessment is introduced here. Thulium laser radiation is strongly absorbed by water, and the cells at the bottom of the culture dish are heated through thermal diffusion.

Clinical results and toxicity for short-course preoperative radiotherapy and total mesorectal excision in rectal cancer patients.

Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009.

The role of perfusion effects in monitoring of chemoradiotherapy of rectal carcinoma using diffusion-weighted imaging.

Purpose: The aim of this study was to characterize and understand the therapy-induced changes in diffusion parameters in rectal carcinoma under chemoradiotherapy (CRT). The current literature shows conflicting results in this regard. We applied the intravoxel incoherent motion model, which allows for the differentiation between diffusion (D) and perfusion (f) effects, to further elucidate potential underlying causes for these divergent reports.

Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer - a retrospective single center analysis.

Background: We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT).

Methods: The medical records of 49 patients with histologically proven primary nasopharygeal carcinoma treated with IMRT and concurrent platin-based CHT (predominantly cisplatin weekly) were retrospectively reviewed. The majority of patients showed advanced clinical stages (stage III/IV:72%) with undifferentiated histology (82%).

Local setup errors in image-guided radiotherapy for head and neck cancer patients immobilized with a custom-made device.

Purpose: To evaluate the local positioning uncertainties during fractionated radiotherapy of head-and-neck cancer patients immobilized using a custom-made fixation device and discuss the effect of possible patient correction strategies for these uncertainties.

Methods And Materials: A total of 45 head-and-neck patients underwent regular control computed tomography scanning using an in-room computed tomography scanner. The local and global positioning variations of all patients were evaluated by applying a rigid registration algorithm.

Brain alpha-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: a comparative investigation.

Alpha-synuclein is a major component of Lewy bodies and glial cytoplasmic inclusions, pathological hallmarks of idiopathic Parkinson's disease and multiple system atrophy, and it is assumed to be aetiologically involved in these conditions. However, the quantitative status of brain alpha-synuclein in different Parkinsonian disorders is still unresolved and it is uncertain whether alpha-synuclein accumulation is restricted to regions of pathology. We compared membrane-associated, sodium dodecyl sulfate-soluble alpha-synuclein, both the full-length 17 kDa and high molecular weight species, by western blotting in autopsied brain of patients with Parkinson's disease (brainstem-predominant Lewy body disease: n = 9), multiple system atrophy (n = 11), progressive supranuclear palsy (n = 16), and of normal controls (n = 13).

Intraoperative electron radiotherapy for the management of aggressive fibromatosis.

Purpose: We analyzed our experience with intraoperative electron radiotherapy (IOERT) followed by moderate doses of external beam radiotherapy (EBRT) after organ-sparing surgery in patients with primary or recurrent aggressive fibromatosis.

Methods And Materials: Indication for IOERT and postoperative EBRT as an individual treatment approach to avoid mutilating surgical procedures was seen when complete surgical removal seemed to be unlikely or impossible. A total of 31 lesions in 30 patients were treated by surgery and IOERT with a median dose of 12 Gy.

Quantitative assessment of image-guided radiotherapy for paraspinal tumors.

Purpose: To evaluate stereotactic positioning uncertainties of patients with paraspinal tumors treated with fractionated intensity-modulated radiotherapy; and to determine whether target-point correction via rigid registration is sufficient for daily patient positioning.

Patients And Methods: Forty-five patients with tumors at the cervical, thoracic, and lumbar spine received regular control computed-tomography (CT) scans using an in-room CT scanner. All patients were immobilized with the combination of Scotch cast torso and head masks.

Neoadjuvant chemoradiation in patients with pancreatic adenocarcinoma.

In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. Surgical therapy currently offers the only potential monomodal cure for pancreatic adenocarcinoma.

Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC).

Background: The clinical results after stereotactic single-dose radiotherapy of nonsmall-cell lung cancer (NSCLC) stages I and II were evaluated.

Methods: Forty-two patients with biopsy-proven NSCLC received stereotactic radiotherapy. Patients were treated in a stereotactic body frame and breathing motion was reduced by abdominal compression.

Randomized phase II--study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer--PARC: study protocol [ISRCTN56652283].

Background: Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies.

L-DOPA biotransformation: correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients.

The objectives of this study were to determine (1) the effects of dose and drug absorption on pathways of biotransformation of L-DOPA in Parkinsonian patients treated with Sinemet, and (2) the extent to which genetically-determined variations in the activities of erythrocyte catechol O-methyltransferase and/or platelet phenol sulfotransferase might be reflected in individual differences in L-DOPA metabolism. In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites. Levels of activity for erythrocyte COMT were also reflected in individual variation in the metabolism of L-DOPA.

3-D-conformal radiation therapy for pediatric giant cell tumors of the skull base.

Background: Giant cell tumors (GCT) of the base of skull are rare neoplasms. This report reviews the treatment of four pediatric patients presenting with aggressive giant cell tumor, using fractionated and combined, conformal proton and photon radiation therapy at Massachusetts General Hospital and Harvard Cyclotron Laboratory.

Patients And Methods: Three female patients and one adolescent male, ages 10-15 years, had undergone prior, extensive surgical resection(s) and were treated for either primary (two patients) or recurrent (two patients) disease.

Conformal proton radiation therapy for pediatric low-grade astrocytomas.

Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC).

Patients And Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.

Neuropathology of two members of a German-American kindred (Family C) with late onset parkinsonism.

We present genealogical and longitudinal clinical observations and autopsy findings of a previously reported kindred, Family C (German-American), with late-onset autosomal dominant parkinsonism with evidence for linkage on chromosome 2p13. The clinical phenotype includes the cardinal features of idiopathic Parkinson's disease. In addition, postural tremor and dementia are detected in some individuals.

Tumor angiogenesis of low-grade astrocytomas measured by dynamic susceptibility contrast-enhanced MRI (DSC-MRI) is predictive of local tumor control after radiation therapy.

Purpose: To assess regional cerebral blood volume (rCBV) as a surrogate marker of angiogenesis in patients with low-grade fibrillary astrocytoma before radiation therapy and to correlate measured values with clinical outcome after fractionated stereotactic radiotherapy (FSRT).

Methods: Twenty-five patients with histologically proven fibrillary astrocytomas were examined using dynamic susceptibility contrast-enhanced MRI before radiotherapy. Radiotherapy was delivered to mean and median total doses of 60.

Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature.

There is no clear consensus regarding the frequency (and hence, the risk), of dyskinesias or motor fluctuations during chronic levodopa therapy for Parkinson's disease (PD). Multiple clinical series have tabulated these frequencies since the advent of levodopa over 30 years ago. We were interested in determining: (1) the aggregate frequency figures in the existing literature; and (2) how clinical series from the early levodopa era, which included patients with longer durations of parkinsonism, compare to more recent (modern era) series.

Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p.

The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-synuclein as a component of Lewy bodies has heralded a new era in the study of Parkinson's disease. We have identified a large family with Lewy body parkinsonism linked to a novel locus on chromosome 4p15 that does not have a mutation in the alpha-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight alpha-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology.

Motor unit changes in sporadic idiopathic Parkinson's disease.

We studied motor unit changes in 20 patients with Parkinson's disease (PD) and 20 age-matched control subjects to look for evidence of motorneuron degeneration in sporadic idiopathic PD. Patients and control subjects were screened by clinical criteria and nerve conduction studies to exclude those with peripheral neuropathic processes. Changes in motor unit morphology were investigated with subjective and computerized quantitative electromyography (QEMG) of the anterior tibialis (AT) and first dorsal interosseous.

Electrophysiological observations in hereditary parkinsonism-dementia with Lewy body pathology.

We studied the only two living affected individuals who are part of a previously reported kindred that expresses a hereditary parkinsonism-dementia syndrome with Lewy body pathology. The electrophysiological characteristics of the hyperkinetic movement disorders in these patients were examined to provide physiological insights into the clinical phenotype of this syndrome. Evaluation of both patients showed 7-9 Hz electromyographic discharges in upper extremity muscles during postural activation, and one patient showed a 4-5 Hz discharge pattern correlating to a rest tremor.

A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor.

We investigated a large family with levodopa-responsive, Lewy body parkinsonism in which the disease segregates as an apparent autosomal dominant trait. After performing a genome screen, we identified a chromosome 4p haplotype that segregates with the disease. However, this haplotype also occurs in individuals in the pedigree who do not have clinical Lewy body parkinsonism but rather suffer from postural tremor, consistent with essential tremor.