Defibrotide for the management of sinusoidal obstruction syndrome in patients who undergo haemopoietic stem cell transplantation

Sinusoidal obstruction syndrome (VOD/SOS), previously known as veno-occlusive disease (VOD), is an established complication in patients undergoing haemopoietic stem cell transplantation (HSCT). VOD/SOS is associated with the intensity of conditioning regimens used in HSCT but has also been reported in patients receiving standard chemotherapy.[1–3] It has been reported that there is a higher incidence of VOD/SOS associated with allogeneic transplant compared to autologous transplant, even when the conditioning regimens are similar.

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Defibrotide for the management of sinusoidal obstruction syndrome in patients who undergo haemopoietic stem cell transplantation

Health-related quality of life assessment in contemporary phase iii trials in advanced colorectal cancer

Cancer poses an enormous burden on society, both in well- and less economically developed countries. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths from cancer occurred in 2012 worldwide. [1] Colorectal cancer (CRC) is one of the most prevalent types of cancer in the world, particularly in developed countries. According to GLOBOCAN, it is the third most common malignancy in men and second in women, estimated to cause 694,000 deaths in 2012 globally. [1] CRC incidence and mortality in the Western world has decreased over the past decade, probably as a consequence of wider use of screening, earlier detection of symptomatic disease and more effective therapy.

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Health-related quality of life assessment in contemporary phase iii trials in advanced colorectal cancer

Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: Findings from the MPN Landmark survey

BACKGROUND

This analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self-reported practices.

METHODS

The survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions.

RESULTS

Greater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%). Most physician respondents reported that their typical symptom assessments included asking patients about the most important symptoms or a full list of symptoms, whereas many patient respondents reported less specific assessments (eg, they were asked how they were feeling). Many patient respondents did not recognize common symptoms as MPN-related. For example, approximately one-half or more did not believe difficulty sleeping resulted from their MPN (MF, 49%; PV, 64%; ET, 76%). Physician respondents underestimated the proportion of patients who had symptomatic PV or ET at diagnosis compared with patient respondents. There was discordance regarding treatment goals: among patient respondents with MF or PV, “slow/delay progression of condition” was the most important treatment goal, whereas physician respondents reported “symptom improvement” and “prevention of vascular/thrombotic events,” respectively. Finally, more than one-third of patient respondents were not “very satisfied” with their physician’s overall management/communication.

CONCLUSIONS

The care and satisfaction of patients with MPN may be improved with increased patient education and improved patient-physician communication. Cancer 2016. © The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: Findings from the MPN Landmark survey

The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways

The formation of new lymphatic vessels provides an additional route for tumour cells to metastasize. Therefore, inhibiting lymphangiogenesis represents an interesting target in cancer therapy. First evidence s…

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The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways

COPD, emphysema and the onset of lung cancer. A systematic review

Publication date: 28 November 2016
Source:Cancer Letters, Volume 382, Issue 2
Author(s): Cecilia Mouronte-Roibás, Virginia Leiro-Fernández, Alberto Fernández-Villar, Maribel Botana-Rial, Cristina Ramos-Hernández, Alberto Ruano-Ravina
Chronic Obstructive Pulmonary Disease (COPD) and emphysema have been described as possible risk factors for lung cancer. We aim to assess the relationship between COPD, emphysema and the onset of lung cancer. We have developed a systematic review of the published literature in order to systematically analyze the scientific evidence available on this association, applying predefined inclusion and exclusion criteria. 11 Studies were included. Both COPD and emphysema seem to increase the risk of developing lung cancer, being this risk higher for smokers with heavier tobacco consumption. These results emphasize the need for physicians to perform spirometries in current and former smokers and lung image tests when needed in order to identify COPD and emphysema and thus select patients at higher risk of developing lung cancer.

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COPD, emphysema and the onset of lung cancer. A systematic review

The heparanase/heparan sulfate proteoglycan axis: A potential new therapeutic target in sarcomas

Publication date: 28 November 2016
Source:Cancer Letters, Volume 382, Issue 2
Author(s): Giuliana Cassinelli, Nadia Zaffaroni, Cinzia Lanzi
Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression. The clinical management of advanced diseases remains a challenge. In several sarcoma subtypes, high levels of heparanase expression have been correlated with poor prognosis associated factors. On the other hand, expression of cell surface-associated HSPGs (i.e. glypicans and syndecans) has been found altered in specific sarcoma subtypes. Recent studies provided the preclinical proof-of-principle of the role of the heparanase/HSPG axis as therapeutic target in various sarcoma subtypes. Although currently there are no clinical trials evaluating agents targeting heparanase and/or HSPGs in sarcomas, we here provide arguments for this strategy as potentially able to implement the therapeutic options for sarcoma patients.

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The heparanase/heparan sulfate proteoglycan axis: A potential new therapeutic target in sarcomas

The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways

Abstract

Background

The formation of new lymphatic vessels provides an additional route for tumour cells to metastasize. Therefore, inhibiting lymphangiogenesis represents an interesting target in cancer therapy. First evidence suggests that histone deacetylase inhibitors (HDACi) may mediate part of their antitumor effects by interfering with lymphangiogenesis. However, the underlying mechanisms of HDACi induced anti-lymphangiogenic properties are not fully investigated so far and in part remain unknown.

Methods

Human lymphatic endothelial cells (LEC) were cultured in vitro and treated with or without HDACi. Effects of HDACi on proliferation and cell cycle progress were analysed by BrdU assay and flow cytometry. Apoptosis was measured by quantifying mono- and oligonucleosomes in the cytoplasmic fraction of cell lysates. In vitro lymphangiogenesis was investigated using the Matrigel short term lymphangiogenesis assay. The effects of TSA on cell cycle regulatory proteins and apoptosis-related proteins were examined by western blotting, immunofluorescence staining and semi-quantitative RT-PCR. Protein- and mRNA half-life of p21 were analysed by western blotting and quantitative RT-PCR. The activity of the p21 promoter was determined using a dual luciferase assay and DNA-binding activity of Sp1/3 was investigated using EMSA. Furthermore, siRNA assays were performed to analyse the role of p21 and p53 on TSA-mediated anti-lymphangiogenic effects.

Results

We found that HDACi inhibited cell proliferation and that the pan-HDACi TSA induced G0/G1 arrest in LEC. Cell cycle arrest was accompanied by up-regulation of p21, p27 and p53. Additionally, we observed that p21 protein accumulated in cellular nuclei after treatment with TSA. Moreover, we found that p21 mRNA was significantly up-regulated by TSA, while the protein and mRNA half-life remained largely unaffected. The promoter activity of p21 was enhanced by TSA indicating a transcriptional mechanism. Subsequent EMSA analyses showed increased constitutive Sp1/3-dependent DNA binding in response to HDACi. We demonstrated that p53 was not required for TSA induced p21 expression and growth inhibition of LECs. Interestingly, siRNA-mediated p21 depletion almost completely reversed the anti-proliferative effects of TSA in LEC. In addition, TSA induced apoptosis by cytochrome c release contributed to activating caspases-9, −7 and −3 and downregulating the anti-apoptotic proteins cIAP-1 and −2.

Conclusions

In conclusion, we demonstrate that TSA – a pan-HDACi – has distinct anti-lymphangiogenic effects in primary human lymphatic endothelial cells by activating intrinsic apoptotic pathway and cell cycle arrest via p21-dependent pathways.

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via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways