Nodular lymphocyte predominant Hodgkin lymphoma behaves as a distinct clinical entity with good outcome: evidence from 14-year followup in the West of Scotland Cancer Network

Clinically and biologically, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has much more in common with germinal-center derived B-cell non-Hodgkin lymphoma (NHL) than with classical Hodgkin lymphoma (cHL). Management of NLPHL remains controversial. In a 14-year multicenter series, 69 cases were analyzed, and the median follow-up was 53 months (range 11–165.) B-symptoms were present in only 4.3% of patients, and 81.1% of patients had stage I/II disease. Treatment was with radiotherapy (53.6%), chemotherapy (21.7%), combined modality (17.4%), and observation (7.2%). In all, 10.1% of patients relapsed and 2.9% of patients developed high-grade transformation to DLBCL. All relapses and transformations were salvageable. No patient died of their disease. The 5-year relapse-free survival was 92%, transformation-free survival 98.4%, and overall survival 100%. We conclude that NLPHL behaves as a distinct clinical entity, often presenting at an early stage without risk factors. It has an excellent outcome. It may be possible, in early-stage disease, to reduce the intensity of therapy in NLPHL, to single-modality radiotherapy, without affecting OS

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients' overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis

Scientific possibilities of a solar electric powered rendezvous with comet Encke

The minimum scientific spacecraft instrumentation is considered that is likely to result in as complete an understanding of the composition, structure, and activity of a cometary nucleus as is possible without landing on it. The payload will also give useful results on secondary goals of a better understanding of physical processes in the inner and outer coma. Studies of composition, by means of an actual landing on the surface, details of the internal structure of the nucleus, and sample return were considered beyond the scope of this mission

Scientific questions for the exploration of the terrestrial planets and Jupiter - Advanced planetary missions technology program Progress report

Scientific questions and experimental design for planetary exploration of Jupiter, Mars, Mercury, and Venu

A fully 3-dimensional thermal model of a comet nucleus

A 3-D numerical model of comet nuclei is presented. An implicit numerical scheme was developed for the thermal evolution of a spherical nucleus composed of a mixture of ice and dust. The model was tested against analytical solutions, simplified numerical solutions, and 1-D thermal evolution codes. The 3-D code was applied to comet 67P/Churyumov-Gerasimenko; surface temperature maps and the internal thermal structure was obtained as function of depth, longitude and hour angle. The effect of the spin axis tilt on the surface temperature distribution was studied in detail. It was found that for small tilt angles, relatively low temperatures may prevail on near-pole areas, despite lateral heat conduction. A high-resolution run for a comet model of 67P/Churyumov-Gerasimenko with low tilt angle, allowing for crystallization of amorphous ice, showed that the amorphous/crystalline ice boundary varies significantly with depth as a function of cometary latitude.Comment: 19 pages, 10 figure

The role of Aurora-A inhibitors in cancer therapy.

Recently, new chemotherapy agents which target the non-structural components of mitosis have been developed. An important protein involved in several mitotic phases is the Aurora-A protein. By means of the phosphorylation of different substrates, Aurora-A regulates the correct development of the various phases of mitosis. The kinase activity of this protein makes Aurora-A an excellent candidate as an oncogene. The first data of Aurora-A involvement in cancer regarded the identification of Aurora-A overexpression in primary breast and colon tumour samples. With regard to the predictive role of Aurora-A, it has been shown that its overexpression disrupts the spindle checkpoint activated by paclitaxel (Taxol) or nocodazole treatment, thus inducing the cells to become resistant to these drugs. The development therefore of small molecules with an Aurora-A inhibition function may make it possible to reduce or block the oncogenic activity of Aurora-A and in addition may improve the survival of oncological patients showing resistance to paclitaxel or nocodazole treatment. Three novel Aurora kinase inhibitors have recently been described--Hesperadin, ZM447439 and VX-680. All these three drugs have been designed to target the ATP-binding site of Aurora kinase, so they inhibit all three Aurora kinase family members showing a similar phenotype when tested in cell-based assays. Among these three different molecules, VX-680 has shown promising results in in vitro and in vivo studies. In conclusion, it is clear that we are entering a new era in anti-mitotic therapy with the identification and now clinical translation of new targets in mitosis beyond tubulin but many questions remain with regard to Aurora function

Anti-endothelin drugs in solid tumors

Importance of the field: The endothelin (ET) axis, which includes the biological functions of ETs and their receptors, has played a physiological role in normal tissue, acting as a modulator of vasomotor tone, tissue differentiation and development, cell proliferation and hormone production. Interestingly, it also functions in the growth and progression of various tumors. Several researchers have identified the blockade of the ET-1 receptor as a promising therapeutic approach. Areas covered in this review: The clinical investigation of an orally bioavailable ET antagonist, atrasentan, in prostate cancer, is encouraging. In this neoplasia, it has shown antitumor activity, bone metastasis control and amelioration of cancer-related pain but improvement in time to progression and overall survival has still not been demonstrated. The clinical trials of other ET antagonists are reported. Literature research was performed by Pubmed and Pharmaprojects. What the reader will gain: A comprehensive view about the use of atrasentan in the treatment of castration-resistant prostate cancer (CRPC) is provided together with the scientific rationale based on the function of ET and its receptor in various cancer development mechanisms. Take home message: Atrasentan seems to be active in CRPC, although strong scientific evidence is still to be found. Interesting clinical findings regard zibotentan

Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway

The angiopoietin-like 4 (ANGPTL4) protein belongs to a superfamily of secreted proteins structurally related to factors modulating angiogenesis known as angiopoietins. At first, ANGPTL4 has been identified as an adipokine exclusively involved in lipid metabolism, because of its prevalent expression in liver and adipose tissue. This protein regulates lipid metabolism by inhibiting lipoprotein lipase (LPL) activity and stimulating lipolysis of white adipose tissue (WAT), resulting in increased levels of plasma triglycerides (TG) and fatty acids. Subsequently, ANGPTL4 has been shown to be involved in several nonmetabolic and metabolic conditions, both physiological and pathological, including angiogenesis and vascular permeability, cell differentiation, tumorigenesis, glucose homoeostasis, lipid metabolism, energy homeostasis, wound healing, inflammation, and redox regulation. The transcriptional regulation of ANGPTL4 can be modulated by several transcription factors, including PPAR\uce\ub1, PPAR\uce\ub2/\uce\ub4, PPAR\uce\ub3, and HIF-1\uce\ub1, and nutritional and hormonal conditions. Several studies showed that high levels of ANGPTL4 are associated with poor prognosis in patients with various solid tumors, suggesting an important role in cancer onset and progression, metastasis, and anoikis resistance. Here, we have discussed the potential role of ANGPTL4 in mediating the cross talk between metabolic syndromes, such as diabetes and obesity, and cancer through regulation of its expression by PPARs