Targeting the ubiquitin proteasome system in haematological malignancies

The ubiquitin proteasome system (UPS) plays a central role in cellular protein homeostasis through the targeted destruction of damaged/misfolded proteins and regulatory proteins that control critical cellular functions. The UPS comprises a sequential series of enzymatic activities to covalently attach ubiquitin to proteins to target them for degradation through the proteasome. Aberrancies within this system have been associated with transformation and tumourigenesis and thus, the UPS represents an attractive target for the development of anti-cancer therapies. The use of the first-in-class proteasome inhibitor, bortezomib, in the treatment of Plasma Cell Myeloma and Mantle Cell Lymphoma has validated the UPS as a therapeutic target. Following on its success, efforts are focused on the development of second-generation proteasome inhibitors and small molecule inhibitors of other components of the UPS. This review will provide an overview of the UPS and discuss current and novel therapies targeting the UPS.

Towards optimal clinical and epidemiological registration of haematological malignancies: Guidelines for recording progressions, transformations and multiple diagnoses

Haematological malignancies (HM) represent over 6% of the total cancer incidence in Europe and affect all ages, ranging between 45% of all cancers in children and 7% in the elderly. Thirty per cent of childhood cancer deaths are due to HM, 8% in the elderly. Their registration presents specific challenges, mainly because HM may transform or progress in the course of the disease into other types of HM. In the context of cancer registration decisions have to be made about classifying subsequent notifications on the same patient as the same tumour (progression), a transformation or a new tumour registration. Allocation of incidence date and method of diagnosis must also be standardised. We developed European Network of Cancer Registries (ENCR) recommendations providing specific advice for cancer registries to use haematology and molecular laboratories as data sources, conserve the original date of incidence in case of change of diagnosis, make provision for recording both the original as well as transformed tumour and to apply precise rules for recording and counting multiple diagnoses. A reference table advising on codes which reflect a potential transformation or a new tumour is included. This work will help to improve comparability of data produced by population-based cancer registries, which are indispensable for aetiological research, health care planning and clinical research, an increasing important area with the application of targeted therapies.

Subcutaneous inflammation mimicking metastatic malignancy induced by injection of mistletoe extract

We describe the histological features of subcutaneous inflammation induced by mistletoe, a popular Christmas decoration, when used as an anticancer complementary therapy. We also outline the use of extract of mistletoe in this context.

The impact of next generation sequencing technologies on haematological research - A review

Next-generation sequencing (NGS) technologies have begun to revolutionize the field of haematological malignancies through the assessment of a patient's genetic makeup with a minimal cost. Significant discoveries have already provided a unique insight into disease initiation, risk stratification and therapeutic intervention. Sequencing analysis will likely form part of the routine diagnostic testing in the future. However, a number of important issues need to be addressed for that to become a reality with regard to result interpretation, laboratory workflow, data storage and ethical issues. In this review we summarize the contribution that NGS has already made to the field of haematological malignancies. Finally, we discuss the challenges that NGS technologies will bring in relation to data storage, ethical and legal issues and laboratory validation. Despite these challenges, we predict that high-throughput DNA sequencing will redefine haematological malignancies based on individualized genomic analysis.

Leukaemogenesis, gene interplay, and the role of the haemopoietic environment

Malignant initiation, leukaemic transformation, and disease progression in haematological malignancies involves a series of mutational events in genes involved in normal housekeeping functions of the cell. These acquired genetic changes can lead to either increased proliferation or a decreased rate of apoptosis, thus allowing expansion of the malignant clone. Although leukaemia can arise as a de novo disease, it has become increasingly clear that therapies, including the use of irradiation and/or chemotherapy, can give rise to malignancy. Therapy-associated myelodysplasia (t-MDS) and therapy-associated acute myeloid leukaemia (t-AML) account for 10-20% of new cases of these diseases. Although these secondary malignancies have been recognised as a clinical entity for nearly 30 years, molecular studies are now pinpointing various regions of the genome that are susceptible to DNA damage by these chemotherapeutic/radiotherapeutic strategies. The detection of new malignancies (both solid tumours and haematological tumours) following allogeneic bone marrow transplantation (BMT) is also providing us with some clues to the nature of leukaemogenesis, particularly with the observation that leukaemia can occur in donor cells postallogeneic BMT.

Haematological responses of green mussel Perna viridis (Linnaeus) to heavy metals copper and mercury

Department of Marine Biology, Microbiology and Biochemistry, Cochin University of Science and Technology

Photodiagnosis of Oral Malignancy using Laser-Induced Fluorescence and Diffuse Reflectance Spectroscopy

Biophotonics Laboratory,Centre for Earth Science Studies

Haematological Studies on the Freshwater Mussel - Lamellidens Marginalis ( Lamark, 1819 )

School of Environmental Studies, Cochin University of Science and Technology

Haematological responses of Penaeus monodon to environmental alterations and pathogenic invasion

This thesis Entitled Haematological responses of penaeus monodon to environmental alterations and pathogenic invasion. Thesis concluded from the present study that stress is accompanied by alterations in haemolymph metabolic variables and immune responses that influences the susceptibility of P. monodon to infection. Acute salinity variations were proved to be a stress condition that enhances the susceptibility of P. monodon to V. harveyi and WSSV infection. Ambient Cu at 0.1 mg 1" and ambient Zn at 1.0 mg 1" proved immunostimulatory in increasing the immunocompetence of P. monodon to WSSV infection and higher concentrations of Cu and Zn proved immunosuppressive. Haemolymph total protein, total carbohydrates and total lipids showed the highest relation with immune responses. THC, PO, ACP and ALP that greatly correlated with the survival rate proposed as reliable biomarkers of health in P. monodon. The study highlights the need for proper management practices and regular health monitoring to be adopted to avoid mass mortality in shrimp culture ponds.

Haematological and Toxicological studies on brackish water fish Etroplus maculatus (Bloch)”

Fishes are one of the most important members of the aquatic food chain, and through them some toxicants may reach human beings as well. The selection of organisms for toxicity test is mainly based on certain criteria like its ecological status, position within the food chain, suitability for laboratory studies, genetically stable, uniform populations and adequate background data on the organism (Buikema et al., 1982). The species selected for the present study Etroplus maculatus satisfy most of the above protocols. Rechten (1980) opined it as a laboratory favorite of fish researchers. However, there are difficulties in the rise of fishes for pollution assessment impact. Most important of these is our limited understanding of the mechanism of toxicity. The interpretation of the significance or specificity of a measured biological response could there for become difficult. Not withstanding these limitations, attempts have been made to the normal haematology and to analyze the impact of heavy metal at realistic levels to the experimental media, on the haematology, and enzymatic activity and histology of Etroplus maculatus

Haematological characteristics of Brazilian Teleosts: III. Parameters of the hybrid tambacu (Piaractus mesopotamicus Holmberg x Colossoma macropomum Cuvier) (Osteichthyes, Characidae)

Fifty six specimens of the hybrid tambacu (Piaractus mesopotamicus Holmberg, 1887 male x Colossoma macropomum Cuvier, 1818 female) were collected from fishfarm of Guariba, São Paulo, to evaluate their haematology. Fishes presented 400.0 to 3,100.0 g total weight and 20.0 to 52.0 cm total length. Haemoglobin, haematocrit, mean corpuscular haemoglobin content (MCHC) and percentage of defense blood cells including leucocytes and thrombocytes, were studied. Statistical analysis showed positive correlation (P<0.01) between haematocrit, MCHC and haemoglobin rate. Nevertheless, thrombocytes and lymphocytes showed negative correlation (P<0.01).

Infection of commercial laying hens with Salmonella Gallinarum: clinical, anatomopathological and haematological studies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Haematological and biochemical reference intervals for farmed channel catfish

The reference intervals for biochemical variables and red blood cell indices of healthy intensively bred channel catfish Ictalurus punctatus were determined. The blood variables were determined using standardized clinical methods. The reference intervals (25th and 75th percentiles) were established using a non-parametric method. Reference intervals for plasma glucose, serum total protein, sodium, potassium, calcium, magnesium, chloride concentration, primary and secondary red blood cell indices were established. The haematological and biochemical reference intervals established may allow important clinical decisions about channel catfish. (c) 2007 the Authors Journal compilation (C) 2007 the Fisheries Society of the British Isles.

Alternative treatment for Anacanthorus penilabiatus (Monogenea : Dactylogyridae) infection in cultivated pacu, Piaractus mesopotamicus (Osteichthyes : Characidae) in Brazil and its haematological effects

The present work, studied the effect of 0, 1,000, 1,500 and 2,000 mg of garlic powder/kg dry ration for Piaractus mesopotamicus (Osteichthyes Characidae), weighting 73.6+/-39.4 9 and measuring 15.0+/-2.7 cm, fed for a period of 15, 30 and 45 days. Fifteen days after treatment with 1,000 and 2,000 Prig of garlic/kg dry ration, significant reduction of Anacanthorus penilabiatus (Monogenea: Dactylogyridae) in the gills was related. Nevertheless, the addition of garlic to the ration caused significant increase in the erythrocyte number and in the thrombocyte percentage in the circulating blood. However, a decrease in the lymphocyte percentage was also observed. After 45 days, fish fed with garlic showed significant increase in the erythrocyte number, leucocyte, haemoglobin rate, hematocrit and thrombocyte.

Haematological and gill responses in parasitized tilapia from valley of Tijucas River, SC, Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)