Parasitaemia and haematological changes in malaria-infected refugees in South Africa

Background. Haematological changes associated with malaria are well recognised, but may vary with level of malaria endemicity and patient background, haemoglobinopathy, nutritional status, demographic factors and malaria immunity. Although malaria in South Africa (SA) has been reduced dramatically in endemic areas, little is known about the haematological changes associated with malaria infection among refugee populations who live in SA cities.Objective. To describe haematological alterations among malaria-infected refugees living in Durban, SA.Methods. A cross-sectional study was conducted from September 2012 to July 2013 inclusive at a refugee centre in central Durban. Blood samples from 102 adult black African refugees were examined for infection with malaria parasites, and haematological profiles were compared with standard normal values.Results. Malaria infection was detected in 16 (15.7%) of the 102 participants. The mean haemoglobin (Hb) value was reduced (mean 9.2 g/dL) in the participants with malaria, who also had an extremely low mean packed cell volume (PCV) of 28.3%. The mean Hb value in the non-malaria-infected participants was normal (12.6 g/dL), and the mean PCV was slightly low (38.0%).Conclusions. Anaemia was more common among participants with malaria infection than among those who were uninfected. Other haematological changes were common in both infected and uninfected participants, suggesting that infections other than malaria, or other underlying factors that cause haematological alterations, may be present. This research needs to be expanded to include a large sample and other areas and infections

Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer

Assessing Measurable Residual Disease in Chronic Myeloid Leukemia. BCR-ABL1 IS in the Avant-Garde of Molecular Hematology

Chronic myelogenous leukemia (CML) is a malignancy of the myeloid cell lineage characterized by a recurrent chromosomal abnormality: the Philadelphia chromosome, which results from the reciprocal translocation of the chromosomes 9 and 22. The Philadelphia chromosome contains a fusion gene called BCR-ABL1. The BCR-ABL1 codes for an aberrantly functioning tyrosine kinase that drives the malignant proliferation of the founding clone. The advent of tyrosine kinase inhibitors (TKI) represents a landmark in the treatment of CML, that has led to tremendous improvement in the remission and survival rates. Since the introduction of imatinib, the first TKI, several other TKI have been approved that further broadened the arsenal against CML. Patients treated with TKIs require sensitive monitoring of BCR-ABL1 transcripts with quantitative real-time polymerase chain reaction (qRT-PCT), which has become an essential part of managing patients with CML. In this review, we discuss the importance of the BCR-ABL1 assay, and we highlight the growing importance of BCR-ABL1 dynamics. We also introduce a mathematical correction for the BCR-ABL1 assay that could help homogenizing the use of the ABL1 as a control gene. Finally, we discuss the growing body of evidence concerning treatment-free remission. Along with the continuous improvement in the therapeutic arsenal against CML, the molecular monitoring of CML represents the avant-garde in the struggle to make CML a curable disease

Assessment of temozolomide action encapsulated in chitosan and polymer nanostructures on glioblastoma cell lines

Purpose: Glioblastoma multiforme (GBM) remains one of the most devastating diseases known to mankind and affects more than 17,000 patients in the United States alone every year. This malignancy infiltrates the brain early in its course and makes complete neurosurgical resection almost impossible. Recent years have brought significant advances in tumor biology. Many cancers, including gliomas, appear to be supported by cells with stem-like properties. Nanoparticles are excellent candidates to serve as delivery vectors of drugs or biologically active molecules because of their unique chemical and physical properties that result in specific transportation and deposition of such agents in specific organs and tissues.In the current study we have investigated the in vitro action of nanostructural systems (temozolomide encapsulated in chitosan and polymer nanostructures) on high-grade glioma-derived cancer stem cells (CSCs), with the intention of developing a new therapy to treat specific brain tumors with increased efficacy and minimal toxicity. In vitro cytotoxicity and apoptosis measurements indicated that the drug/vector combination facilitated the ability of the alkylating drug TMZ to alter the resistance of these cancer stem cells, suggesting a new chemotherapy strategy even for patients diagnosed with inoperable or recurrent malignant gliomas.Methods: At the National Institute for R & D of Isotopic and Molecular Technologies form Cluj Napoca were synthesized three types of nanostructures chitosan-TMZ, TMZ-chitosan-PEG (poly-ethylene glycol), TMZ-chitosan-PPG (polypropylene glycol). Three type of cell lines (Glioma-derived stem, HFL and HUVEC) were treated with the 3 types of nanostructures and the survival rate of the cells was compare to standard therapy (TMZ).Results: The results showed a reduction in the rate of survival of the tumor cells. Cell proliferation assays clearly demonstrate the differences between conventional chemotherapy (TMZ) and temozolomide encapsulated in chitosan and polymer nanostructures. Conclusion: Nanostructures like chitosan, PEG, PPG are useful as vectors for drugs transport.Despite combined therapy (surgery, radiotherapy, chemotherapy), currently median patient survival is reduced. The key to improving life expectancy could be an effective therapy targeted, customized for each case. An increasingly important role will be new methods of treatment such as immunotherapy, gene therapy or nanotherapy

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

Nanopharmacology in translational hematology and oncology

Ciprian Tomuleasa,1,2,* Cornelia Braicu,1,* Alexandra Irimie,3 Lucian Craciun,1 Ioana Berindan-Neagoe1,4,51Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 2Department of Hematology, Ion Chiricuta Cancer Center, 3Department of Prosthetic Dentistry and Dental Materials, 4Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, 5Department of Functional Genomics and Experimental Pathology, the Oncological Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania*These authors contributed equally to this workAbstract: Nanoparticles have displayed considerable promise for safely delivering therapeutic agents with miscellaneous therapeutic properties. Current progress in nanotechnology has put forward, in the last few years, several therapeutic strategies that could be integrated into clinical use by using constructs for molecular diagnosis, disease detection, cytostatic drug delivery, and nanoscale immunotherapy. In the hope of bringing the concept of nanopharmacology toward a viable and feasible clinical reality in a cancer center, the present report attempts to present the grounds for the use of cell-free nanoscale structures for molecular therapy in experimental hematology and oncology.Keywords: hematological malignancies, nanoparticles, translational medicin

Castleman’s disease in the HIV-endemic setting

Esam-Rajab Mahroug,1 Candice Sher-Locketz,1 Minodora-Silvia Desmirean,2,3 Emmanuel-Akinola Abayomi,1,4 Ciprian Tomuleasa,3,5,6 Ravnit Grewal1,7 1Division of Haematology, Department of Pathology, University of Stellenbosch, Tygerberg Academic Hospital, Cape Town, South Africa; 2Department of Pathology, Military Hospital of Cluj Napoca, Cluj Napoca, Romania; 3Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania; 4Department of Hematology, Nigeria Institute for Medical Research, Lagos, Nigeria; 5Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania; 6Department of Hematology, Ion Chiricuta Clinical Research Center, Cluj Napoca, Romania; 7Department of Pathology, South African Bioinformatics Institute, University of The Western Cape, Bellville, South Africa Introduction: Castleman’s disease (CD), first described by Benjamin Castleman in 1954, is a giant or angiofollicular lymph node hyperplasia, described as a rare monotypic polyclonal B-cell lymphoproliferative disorder with an incompletely understood pathogenesis and variable clinical behavior. This study aimed to determine the incidence of CD diagnosis over an 11-year period. Additionally, the study aimed to describe the demographic, laboratory, and pathological features of CD. Methods: This is a retrospective study where the demographic and laboratory data were retrieved from the Tygerberg Academic Hospital (TAH) patient electronic records and Tygerberg Lymphoma Study Group (TLSG) and statistical analysis performed on the patients diagnosed with CD. Results: Fifty-four patients were diagnosed with CD during this period. The median age at presentation was 39 years (range: 9–58). HIV serology was available in 53 patients, of which 51 were HIV-positive and two were HIV-negative. The history of initiation of antiretroviral therapy at diagnosis was available in 43 patients (38 on treatment, four were not on treatment, and one defaulted treatment). The median CD4 count was 232.50 cells/μL (range: 2–883). The HIV viral load was performed in 43 patients at diagnosis, which was <49 HIV-1 RNA copies/μL in more than half of the patients (58%). Diagnosis was made on lymph node biopsies in 53 patients, with one case diagnosed on a spleen biopsy. Kaposi sarcoma was found on the same tissue biopsy in 13 cases. A bone marrow biopsy was performed in 31 patients. The predominant features noted were a disorganized hypercellular marrow with plasmocytosis. Conclusion: CD is a rare polyclonal B-cell lymphoproliferative disorder. However, we demonstrated a significant increase in the incidence of HIV-associated multicentric CD over the last decade in our area in South Africa. Keywords: Castleman’s disease, HIV-endemic setting, HHV-8 status, CD4 count, clinicopathological correlatio