Cancer initiation and progression: an unsimplifiable complexity

BACKGROUND: Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated. CONCLUSION: There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours

Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics

We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to the common ‘spaghetti-like’ structures but to dense matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance, these morphological indicators may have prognostic value.Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) of South Africa.http://www.cardiab.com/hb201

Sorafenib for the treatment of solid malignancies: what about the cancer microenvironment?

Ciprian Tomuleasa, Andrei Cucuianu, Mihaela Aldea, Ioana Berindan-NeagoeResearch Center of Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, RomaniaWe have read with great interest the study of Kim et al, recently published in the International Journal of Nanomedicine.1 The physicians from South Korea describe the anti-tumor efficacy of sorafenib in cholangiocarcinoma, a malignancy with a dismal prognosis and refractory to most chemotherapy options. Surgery is the only curative option, but is limited to only a small number of cases due to the late diagnosis.2 This emphasizes the need to develop new approaches for such cases and the first potential new option is the tyrosine kinase inhibitor sorafenib, already proven to improve the therapeutic ratio of hepatocellular carcinoma, as according to Llovet et al.3 But unlike hepatocellular carcinoma, cholangiocarcinomas are epithelial cancers with a highly developed desmoplastic stroma due to the interaction between the cancer cell and the cancer associated fibroblasts (CAFs), as well as the macrophages, and the natural killer (NK) cells.4 This tumor microenvironment makes it difficult for a chemotherapy drug to reach the cancer cell and be efficient, which partially explains the reason why Kim et al1 developed a sorafenib-coated stent, that can be placed inside the biliary tree and deliver the drug continuously.View original paper by Kim and colleagues

Bicytopenia as a paraneoplastic syndrome for pseudomyxoma peritonei. Hematologic manifestations of a subtle disease

Ciprian Tomuleasa,1,2 Bobe Petrushev,2 Madalina Vedean,2 Alexandru Irimie,2,3 Florin Zaharie,2 Ana-Maria Rosu,1 Delia Dima,1 Andrei Cucuianu1,2 1Department of Hematology, Ion Chiricuta Oncology Institute, 2Iuliu Hatieganu University of Medicine and Pharmacy, 3Department of Surgery, Ion Chiricuta Oncology Institute, Cluj Napoca, RomaniaWe have read with great interest the paper of de Oliveira et al, in which the authors report the case of a 76-year-old woman who presented with increased abdominal girth and dyspnea for 2 weeks.1 After extensive investigations, the patient was diagnosed with an abdominal pseudomyxoma peritonei and underwent right oophorectomy, omentectomy, and pseudomyxoma debulking. View original paper by de Oliveira and colleagues&nbsp

High-dose cytotoxic therapy with autologous bone marrow or peripheral blood progenitor cell transplantation in malignant lymphomas.

The present paper is an attempt to assess the efficiency of high-dose cytotoxic therapy followed by autologous bone marrow or peripheral progenitor cell rescue with hematopoietic growth factor support given in a group of 27 patients (16 men, 11 women) at the Department of Hematology of the Mont Godinne University Clinics, mainly in the same interval 1990-1994. The reasons for introducing such a therapy in these patients (6 with Hodgkin's disease, 14 with intermediate or high grade, aggressive non Hodgkin lymphomas and 7 with low grade follicular non Hodgkin lymphomas) were relapse of disease after conventional therapy (11 cases), resistance to initial therapy (5 patients) or because of histologically proven transformation to a more aggressive form (one case); in 10 patients with extended, poor prognosis forms, the procedure was used as part of the first line therapy. The conditioning high dose chemotherapy was given according to various regimens, most of them containing Cyclophosphamide, BCNU and Etoposide, with or without total body irradiation. In 14 patients, bone marrow (BM) graft was used, while peripheral blood progenitor cells (PBPC) were infused in the remaining 13 patients. The number of infused granulocyte-macrophage colony forming units (CFU-GM) ranged between 7,650 and 3,900,000/kg, with a mean value of 461,000/kg. The median time intervals required to reach an absolute neutrophil count > 500/microliter, a platelet count > 50,000/microliter and a hematocrit > 30% were 13 days, 20 days and 23 days respectively. Growth factors (GM-CSF and G-CSF) and PBPC use shortened the time for neutrophil recovery as well as neutropenia-related complications. No procedure-related death was observed and complete remission was achieved in 22 cases (81.4%); after a mean follow-up of 32.6 months, 14 patients (55.5%) are alive and free of disease, while in 7 patients (31% of the complete responders) relapse occurred at an average time interval of 8.2 months since the procedure