1,484 research outputs found
The 2018 World Health Organization classification of cutaneous, mucosal, and uveal melanoma detailed analysis of 9 distinct subtypes defined by their evolutionary pathway
Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours
O-59 Single centre experience of 500 patients with intra-operative RT-PCR breast sentinel node analysis
Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside
Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress. © 1999 Cancer Research Campaig
Deep Neural Networks for Energy and Position Reconstruction in EXO-200
We apply deep neural networks (DNN) to data from the EXO-200 experiment. In
the studied cases, the DNN is able to reconstruct the relevant parameters -
total energy and position - directly from raw digitized waveforms, with minimal
exceptions. For the first time, the developed algorithms are evaluated on real
detector calibration data. The accuracy of reconstruction either reaches or
exceeds what was achieved by the conventional approaches developed by EXO-200
over the course of the experiment. Most existing DNN approaches to event
reconstruction and classification in particle physics are trained on Monte
Carlo simulated events. Such algorithms are inherently limited by the accuracy
of the simulation. We describe a unique approach that, in an experiment such as
EXO-200, allows to successfully perform certain reconstruction and analysis
tasks by training the network on waveforms from experimental data, either
reducing or eliminating the reliance on the Monte Carlo.Comment: Accepted version. 33 pages, 28 figure
Search for nucleon decays with EXO-200
A search for instability of nucleons bound in Xe nuclei is reported
with 223 kgyr exposure of Xe in the EXO-200 experiment. Lifetime
limits of 3.3 and 1.9 yrs are established for
nucleon decay to Sb and Te, respectively. These are the most
stringent to date, exceeding the prior decay limits by a factor of 9 and 7,
respectively
Phase I trial combining gemcitabine and treosulfan in advanced cutaneous and uveal melanoma patients
Gemcitabine and treosulfan are DNA-damaging agents. Preclinical studies suggest that synergism exists when melanoma cells are exposed to both drugs concurrently. We conducted a phase I trial in advanced melanoma patients to determine the optimal dose of gemcitabine to be combined with treosulfan. Cohorts of three patients received increasing doses of gemcitabine, commencing at 0.5 g m−2, followed by a fixed dose of 5.0 g m−2 treosulfan on day one of a 21-day cycle. Patients alternately received a first cycle of single-agent gemcitabine or treosulfan before subsequent cycles of both drugs. Peripheral blood lymphocytes were collected in cycles 1 and 2 at various time points until 48 h post-treatment. The single-cell gel electrophoresis (Comet) assay was used to measure chemotherapy-induced DNA damage. A total of 27 patients were enrolled, no objective responses were observed, but two uveal melanoma patients had minor responses. Dose-limiting myelosuppression was reached at 3.0 g m−2 gemcitabine. DNA single-strand breaks were detected 4 h post-gemcitabine, repaired by 24 h. DNA interstrand crosslinks were detected 4 h post-treosulfan, fully removed by 48 h. Following combination chemotherapy, treosulfan-induced DNA crosslinks persisted, still being detectable 48 h post-treatment, supporting the hypothesis that gemcitabine potentiates treosulfan-induced cytotoxicity. The recommended regimen for further study is 2.5 g m−2 gemcitabine combined with 5.0 g m−2 treosulfan
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