Effective treatment of metastatic cancers usually requires the use of toxic chemotherapy. In most cases, multiple drugs are used, as resistance to single agents occurs almost universally. For this reason, elucidation of mechanisms that confer simultaneous resistance to different drugs with different targets and chemical structures - multidrug resistance - has been a major goal of cancer biologists during the past 35 years. Here, we review the most common of these mechanisms, one that relies on drug efflux from cancer cells mediated by ATP-binding cassette (ABC) transporters. We describe various approaches to combating multidrug-resistant cancer, including the development of drugs that engage, evade or exploit efflux by ABC transporters.

Targeting multidrug resistance in cancer

The retinoblastoma (RB) tumour suppressor gene is functionally inactivated in a broad range of paediatric and adult cancers, and a plethora of cellular functions and partners have been identified for the RB protein. Data from human tumours and studies from mouse models indicate that loss of RB function contributes to both cancer initiation and progression. However, we still do not know the identity of the cell types in which RB normally prevents cancer initiation in vivo, and the specific functions of RB that suppress distinct aspects of the tumorigenic process are poorly understood.

Cellular mechanisms of tumour suppression by the retinoblastoma gene

Mendelian Inheritance in Man

PURPOSE: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas. PATIENTS AND METHODS: Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors. RESULTS: The oligodendroglial phenotype was highly associated with loss of 1p (P = .0002), loss of 19q (P < .0001), and combined loss of 1p and 19q (P < .0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged over...

Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas

In this review we give an overview of the physiological functions of a group of ATP binding cassette (ABC) transporter proteins, which were discovered, and still referred to, as multidrug resistanc...

Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System

Pericardial infiltration during the blastic transformation phase of chronic granulocytic leukemia

[Cytochemical study of bone marrow in non-Hodgkin lymphoma with medullary involvement]

P096 After the 100th autologous peripheral haemopoietic stem cell transplantation in the 2nd Department of the Medicine, University of Debrecen, Hungary

The most frequent genetic change currently known in acute myeloid leukemia (AML) is the mutation of the nucleophosmin (NPM) gene. Aberrant cytoplasmic accumulation of NPM protein (NPMc+) is the result of this mutation, and it can be demonstrated by immunohistochemistry for the identification of a favorable subgroup within "AML with normal karyotype" according to the World Health Organization classification. NPM staining pattern was defined in 71 AML and 15 control cases by the use of bone marrow smears in order to overcome limitations observed due to immunohistochemistry. In 13/71 cases (18.3%), clear cytoplasmic staining of the leukemic blast cells was detectable that was comparable with the positivity of mitotic figures physiologically lacking nuclear membrane. The biological and genetic characteristics of the NPMc+ cases determined this way were identical with the previously published results including low CD34 and HLA-DR expression and lack of recurrent karyotype abnormalities. Bone marrow smears are well applicable and therefore a real alternative for the determination of NPM with the highest accuracy for optimal risk stratification in AML.

Identification of NPMc+ acute myeloid leukemia in bone marrow smears.

The authors report a case of a 20-year old woman, with all the characteristics of the Wiskott-Aldrich-syndrome. The main signs of the disease were recurrent infections, eczema, thrombocytopenia and mild mucosal bleeding. The size of platelets was reduced. Storage pool disease was based on the abnormal platelet aggregation and the lack of dense bodies shown by electronmicroscopic examination. The disturbances of the lymphocytes, neutrophils and monocytes, which resulted in immunodeficiency, could be proven by the immunological tests. This X-linked recessive disorder appeared with typical signs in a heterozygous carrier woman. According to our knowledge, no similar case has been reported before.

Attila Kiss

Papers

Pericardial infiltration during the blastic transformation phase of chronic granulocytic leukemia

[Cytochemical study of bone marrow in non-Hodgkin lymphoma with medullary involvement]

P096 After the 100th autologous peripheral haemopoietic stem cell transplantation in the 2nd Department of the Medicine, University of Debrecen, Hungary

Identification of NPMc+ acute myeloid leukemia in bone marrow smears.

[Wiskott-Aldrich syndrome in a hetrozygous woman].