Antithrombotic therapy and survival in patients with malignant disease

A broad range of studies suggest a two-way relationship between cancer and venous thromboembolism (VTE). Patients with cancer have consistently been shown to be at elevated risk for VTE; this risk is partly driven by an intrinsic hypercoagulable state elicited by the tumour itself. Conversely, thromboembolic events in patients without obvious risk factors are often the first clinical manifestation of an undiagnosed malignancy. The relationship between VTE and cancer is further supported by a number of trials and meta-analyses which, when taken together, strongly suggest that antithrombotic therapy can extend survival in patients with cancer by a mechanism that extends beyond its effect in preventing VTE. Moreover, accumulating evidence from in vitro and in vivo studies has shown that tumour growth, invasion, and metastasis are governed, in part, by elements of the coagulation system. On 22 May 2009, a group of health-care providers based in the United Kingdom met in London, England, to examine recent advances in cancer-associated thrombosis and its implications for UK clinical practice. As part of the discussion, attendees evaluated evidence for and against an effect of antithrombotic therapy on survival in cancer. This paper includes a summary of the data presented at the meeting and explores potential mechanisms by which antithrombotic agents might exert antitumour effects. The summary is followed by a consensus statement developed by the group

Quinine doped hybrid sol-gel coatings for wave guiding and optical applications

Pure and quinine doped silica coatings have been prepared over sodalime glasses. The coatings were consolidated at low temperature (range 60-180 A degrees C) preserving optical activity of quinine molecule. We designed a device to test the guiding properties of the coatings. We confirmed with this device that light injected in pure silica coatings is guided over distances of meters while quinine presence induces isotropic photoluminescence. With the combined use of both type of coatings, it is possible to design light guiding devices and illuminate regions in glass elements without electronic circuits

Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

Ethical issues in autologous stem cell transplantation (ASCT) in advanced breast cancer: A systematic literature review

BACKGROUND: An effectiveness assessment on ASCT in locally advanced and metastatic breast cancer identified serious ethical issues associated with this intervention. Our objective was to systematically review these aspects by means of a literature analysis. METHODS: We chose the reflexive Socratic approach as the review method using Hofmann's question list, conducted a comprehensive literature search in biomedical, psychological and ethics bibliographic databases and screened the resulting hits in a 2-step selection process. Relevant arguments were assembled from the included articles, and were assessed and assigned to the question list. Hofmann's questions were addressed by synthesizing these arguments. RESULTS: Of the identified 879 documents 102 included arguments related to one or more questions from Hofmann's question list. The most important ethical issues were the implementation of ASCT in clinical practice on the basis of phase-II trials in the 1990s and the publication of falsified data in the first randomized controlled trials (Bezwoda fraud), which caused significant negative effects on recruiting patients for further clinical trials and the doctor-patient relationship. Recent meta-analyses report a marginal effect in prolonging disease-free survival, accompanied by severe harms, including death. ASCT in breast cancer remains a stigmatized technology. Reported health-related-quality-of-life data are often at high risk of bias in favor of the survivors. Furthermore little attention has been paid to those patients who were dying. CONCLUSIONS: The questions were addressed in different degrees of completeness. All arguments were assignable to the questions. The central ethical dimensions of ASCT could be discussed by reviewing the published literature

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field