WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

Purpose Standardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. Methods The International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [ 18 F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations. Results New guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin’s and Hodgkin’s lymphoma. Standardized definitions of end points are provided. Conclusion We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma. J Clin Oncol 25:579-586. © 2007 by American Society of Clinical Oncology

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Revised response criteria for malignant lymphoma

Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Human antibodies derived from immunized xenomice

/pdf/secretory-products-of-macrophages-5cf7rlxshh.pdf

Secretory products of macrophages.

The complementary DNAs and genes encoding the four major human myeloid growth factors--granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and interleukin-3--have all been molecularly cloned. These DNA clones have proved valuable for studying the molecular biology of these important regulatory molecules as well as for the large-scale production of the recombinant growth factor proteins. These advances have led to a much better understanding of the role of the myeloid growth factors in regulating hematopoiesis in vivo that should soon find practical application in clinical medicine.

https://science.sciencemag.org/content/sci/236/4806/1229.full.pdf

The human hematopoietic colony-stimulating factors

Progress in understanding the biology of multiple myeloma (MM), a plasma cell malignancy, has been slow. The discovery of microRNAs (miRNAs), a class of small noncoding RNAs targeting multiple mRNAs, has revealed a new level of gene expression regulation. To determine whether miRNAs play a role in the malignant transformation of plasma cells (PCs), we have used both miRNA microarrays and quantitative real time PCR to profile miRNA expression in MM-derived cell lines (n = 49) and CD138+ bone marrow PCs from subjects with MM (n = 16), monoclonal gammopathy of undetermined significance (MGUS) (n = 6), and normal donors (n = 6). We identified overexpression of miR-21, miR-106b approximately 25 cluster, miR-181a and b in MM and MGUS samples with respect to healthy PCs. Selective up-regulation of miR-32 and miR-17 approximately 92 cluster was identified in MM subjects and cell lines but not in MGUS subjects or healthy PCs. Furthermore, two miRNAs, miR-19a and 19b, that are part of the miR-17 approximately 92 cluster, were shown to down regulate expression of SOCS-1, a gene frequently silenced in MM that plays a critical role as inhibitor of IL-6 growth signaling. We also identified p300-CBP-associated factor, a gene involved in p53 regulation, as a bona fide target of the miR106b approximately 25 cluster, miR-181a and b, and miR-32. Xenograft studies using human MM cell lines treated with miR-19a and b, and miR-181a and b antagonists resulted in significant suppression of tumor growth in nude mice. In summary, we have described a MM miRNA signature, which includes miRNAs that modulate the expression of proteins critical to myeloma pathogenesis.

https://www.pnas.org/content/pnas/105/35/12885.full.pdf

MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis

Tumor necrosis factor (TNF) is synthesized by macrophages exposed to endotoxin. It produces haemorrhagic necrosis of a variety of tumours in mice and is cytostatic or cytocidal against various transformed cell lines in vitro, but viability of normal human or rodent cells is unaffected. The role of TNF is unlikely to be restricted to the rejection of tumours. Colony-stimulating factors (CSFs) are required for survival, proliferation and differentiation of haematopoietic progenitor cells. The haematopoietic growth factor known as granulocyte-monocyte colony-stimulating factor (GM-CSF) has the ability to stimulate proliferation and differentiation of normal granulocyte-monocyte and eosinophil stem cells and enhance the proliferation of pluripotent, megakaryocyte and erythroid stem cells. In addition, GM-CSF stimulates a variety of functional activities in mature granulocytes and macrophages, for example inhibition of migration, phagocytosis of microbes, oxidative metabolism, and antibody-dependent cytotoxic killing of tumour cells. We show here that TNF markedly stimulates production of GM-CSF messenger RNA and protein in normal human lung fibroblasts and vascular endothelial cells, and in cells of several malignant tissues.

Recombinant human TNF induces production of granulocyte–monocyte colony-stimulating factor

Initially considered an epiphenomenon, micro ribonucleic acids (also called miRNAs) and other small noncoding RNA molecules are now considered major players in cell biology. MiRNAs regulate gene expression through effects on translation, transcription and chromatin modification. Multiple miRNAs are dysregulated in human cancer and affect the proliferation and apoptosis, metastatic behaviour, invasiveness and phenotype of cancer cells. Virtually every cell type and cancer have a particular expression pattern of miRNA expression. This miRNA profile permits to classify cancer and often gives prognostic information. Profiling based on miRNAs may be more specific and robust than profiling based on mRNAs. MiRNAs can be studied in virtually all tissues including plasma. More work is necessary, but miRNAs have already improved our understanding of the pathogenesis of cancer and appear promising for diagnostic purposes as biomarkers and for the development of new genetic treatments.



Key Concepts: 



MicroRNAs regulate gene expression.




MicroRNAs are important in the pathogenesis and progression of human cancer.




MicroRNAs can function as tumour suppressors and as tumour promoters (oncomirs).




MicroRNAs can serve as biomarkers for cancer and may become useful for the treatment of cancer.






Keywords:

microRNAs;
noncoding RNAs;
gene profiling;
cancer;
leukaemia;
malignancy

Reinhold Munker

Papers

MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis

Recombinant human TNF induces production of granulocyte–monocyte colony-stimulating factor

MicroRNAs in Cancer

Recombinant human TNF alpha stimulates production of granulocyte colony- stimulating factor

Update on desmoid tumors