Showing papers in "Critical Reviews in Oncology Hematology in 1995"

Apoptosis and cancer: the failure of controls on cell death and cell survival☆

Abstract: 6. Tipping the balance in favour of cell death 147 6.1. Improvement of existing chemotherapy regimens to favour apoptotic cell death 147 6.2. Use of antisense oligonucleotides as a molecular switch 148 6.3. Liposomes and retroviruses as vectors for the delivery of apoptosis-inducers into cells .... 148 6.4. Delivery of apoptosis-inducing signals by antibody 149

Advances in glyoxalase research. Glyoxalase expression in malignancy, anti-proliferative effects of methylglyoxal, glyoxalase I inhibitor diesters and S-D-lactoylglutathione, and methylglyoxal-modified protein binding and endocytosis by the advanced glycation endproduct receptor

Abstract: 5. Introduction: the glyoxalase system 1.1. The glyoxalase system in oncology and haematology 1.1.1. The interest for oncologists and haematologists 1.1.2. The glyoxalase system: a definition 1.2. Glyoxalase I 1.2.1. Distribution and molecular characteristics 1.2.2. Physiological substrates, kinetics and mechanism 1.2.3. The active site and catalytic mechanism 1.2.4. Genetics, polymorphism and gene cloning 1.25. Non-giyoxalase I-dependent metabolism of methylglyoxal by aldehyde reductases to lactaldehyde and hydroxyacetone 1.3. Glyoxalase II 1.3.1. Distribution and molecular characteristics 1.3.2. Substrate specificity, kinetics and mechanism 1.3.3. Genetics and polymorphism 1.3.4. D-Lactate metabolism and excretion

The hepatocyte nuclear factor-3/forkhead transcription regulatory family in development, inflammation, and neoplasia

Abstract: HNF-3/FKH genes are a large family of transcriptional activators. They are expressed in specific developmental and tissue patterns. Indeed, several of them are known to be essential for normal development (e.g. Dfkh and slp-1,2). Mutation within one of these genes produces mutant fruitfly embryos that are unable to survive. This family shares conserved DNA binding and transcriptional activation domains. The DNA binding domain has been crystallized, and its structure determined. Although it has resemblance to helices of homeodomains and H5 histones, it represents a new DNA binding motif, which has been called the ‘winged helix,’, because it contains additional interactive peptide regions called termed wings. Subtle amino acid variations in a region adjacent to the DNA recognition helix influence the recognition specificity of each HNF-3/FKH protein and therefore confer selectivity in promoter regulation. Members of this family are important in regulating the inflammatory response of the liver (the three HNF-3 genes). In addition, several members may be important in blood cell development (H3 and 5-3). Finally, two of these genes have been found to produce neoplasia (qin and FKHR). As investigation progresses, the mechanism by which these genes regulate development, inflammation and neoplasia will become more clear.

The acute phase response and the hematopoietic system: the role of cytokines☆

Abstract: 1. The acute phase response 2 2. Role of inflammation-associated cytokines in regulation of acute phase protein synthesis ........ 3 3. Changes in the hematopoietic system during the acute phase response 4 4. Regulation of normal hematopoiesis 4 Thrombocytosis 6 5.1. The role of IL-6 in megakaryocytopoiesis 6 5.2. Effect of IL-I on platelet production 7 5.3. Effect of IL-11 on platelet production 7 5.4. Effects of TNF and TGF/I on platelet production 7 Anemia of chronic inflammation 8 6. I. Erythropoietin production 8 6.2. Suppression of erythropoiesis 8 6.3. Response to erythropoietin 9 6.4. Iron and related molecules 10 Granulocytosis IO 7.1. Granulopoiesis 11. 7.2. Induction of hematopoietic growth factors 11 Effect on hematopoietic stem cells 12 9. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Acknowledgments 14 Reviewer 14 Note added in proof 14 References 14 Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 l Corresponding author.

Bleeding and thrombosis in myeloproliferative disorders: mechanisms and treatment

Abstract: 2. Thrombohemor rhag ic diathesis of myeloprol i fera t ive disorders: main clinical features . . . . . . . . 204 2. I. Hemorrhag ic diathesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 2.2. Thrombot i c diathesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 2.2. I. Ar ter ia l th romboses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 2.2.2. Venous thromboses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 2.2.3. Pregnancy compl ica t ions in ET pat ients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 2.3. Prevalence of th rombot ic and hemorrhagic compl ica t ions . . . . . . . . . . . . . . . . . . . . . . . . . . 205 2.3.1. Incidence of hemorrhages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 2.3.2. Mor ta l i ty f rom th rombohemor rhag ic accidents . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 2.4. Clinical var iables inf luencing the th rombohemor rhag ic diathesis . . . . . . . . . . . . . . . . . . . . . 209 2.4. I. Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 2.4.2. History of pr ior th rombos is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 2.4.3. Effect of the hematocr i t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 2.4.4. Effect of white cell count . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 2.4,5. Effect of platelet count . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210

Familial polyposis: recent advances☆

Abstract: Familial adenomatous polyposis (FAP) is a dominantly inherited disease characterized by the development of numerous adenomatous polyps and a high risk of colorectal cancer. Affected individuals have multiple adenomas at various intermediate stages between benign and malignant, so FAP is a supportive model for the adenoma-carcinoma sequence of colorectal carcinogenesis. The APC (adenomatous polyposis coli) gene, which is a tumor suppressor gene, was discovered in 1991, and mutation of this gene was found to be the cause of FAP. To date, more than 150 germ-line mutations have been determined in FAP patients, and more than 300 somatic mutations of the APC gene have been detected in colorectal adenomas and carcinomas from both FAP and non-FAP patients - almost all of these resulting in truncated APC protein. The nature of germline and somatic mutations is described in detail herein, including the finding of several codons in which no germ-line, but only somatic mutation, frequently occurs. Existence of somatic APC mutations in adenomas from both FAP and non-FAP patients suggests that inactivation of the APC gene by two mutations is generally involved in the development of adenoma. Further development of adenoma to advanced carcinoma is associated with loss of heterozygosity (LOH) of the APC gene and additional inactivation of multiple tumor suppressor genes (possibly through mutation and LOH) that include the p53 gene, DCC gene and tumor suppresor genes on chromosomes 1p, 8p and 22q in both FAP and non-FAP patients. Recent findings on the correlation of these genetic changes with the adenomacarcinoma sequence are also described. In vitro models for carcinogenesis, and experiments of suppression of tumorigenicity in advanced colon carcinoma cells by introduction of a normal single chromosome or a normal suppressor gene are also referred to. Furthermore, evidence of inactivation of the APC gene in extracolonic tumors, in FAP patients, including desmoid and adrenocortical tumors, is demonstrated. This confirms the pleiotropic effect of the mutant APC gene on both colonic and extracolonic manifestations in FAP patients, and that the normal APC gene acts as a growth control gene throughout the body

The present state of the art in chemotherapy for soft tissue sarcomas in adults: the EORTC point of view.

Abstract: 2. Single agent chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 2. I. Anthracycl ines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 2.2. Dacarbaz ine and related drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 2.3. Oxazophosphor ines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 2.4. New d rug test ing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

Mechanisms of action of endocrine treatment in breast cancer.

Abstract: Endocrine treatment plays an important role in the therapy of breast cancer. While the basic mechanisms are understood, additional mechanisms may be of importance to their action and they may also contribute to the mechanism(s) of acquired resistance. Currently, several novel drugs are entering into clinical trials. Observations of the absence or presence of cross resistance to novel 'pure' steroidal antiestrogens and the non-steroidal tamoxifen may add important information to our understanding of the mechanisms of action of both classes of drugs. Similarly, exploration of different aromatase inhibitors in sequence or concert, as well as the combining of different endocrine treatment options may be warranted. Additionally, alterations in different biochemical parameters such as growth factors should not only be carefully explored in relation to treatment options but should also be followed during the course of treatment to asess alterations over time and in relation to the development of drug resistance.

Angiogenesis and cancer metastases: therapeutic approaches

Abstract: 4. Drug discovery 4.1. Antiangiogenic agents 4.1. I. Angiostatic steroids/heparin. 4.1.2. Tetracyclines 4.1.3. Fumagillin derivative (TNP-470). 4.1.4. Retinoids/carotenoids 4.1.5. Genistein 4.1.6. Linomide 4.1.7. Other small molecules. 4.1.8. Platelet factor 4 and other peptides. 4.1.9. Interferon alpha-2a 4.1.10. Anticancer agents. 4.2. Antimetastatic agents 4.2. I. Anticoagulants, cyclooxygenase and lipoxygenase inhibitors. 4.2.2. CAI ...... 4.2.3. Inhibitors of urokinase and extracellular matrix proteinases. 4.2.4. Anticancer agents II II 12 I2 I5 I9 21 21 22 22 23 23 23 23 26 27 28

Biologic and clinical advances in familial Mediterranean fever.

Abstract: Familial Mediterranean fever (FMF) is an inherited disease manifested by acute but reversible attacks of sterile inflammation affecting serosal and synovial spaces. The encoding gene for the disease is located on the short arm of chromosome 16. Patients from certain ethnic groups tend to develop amyloidosis, clinically manifested by nephropathy. Both clinical syndromes can be prevented by prophylactic treatment with colchicine. The cause of the inflammatory attacks in FMF appears to be an inherited deficiency of a C5a/IL-8 inactivating protease in the serosal tissues.

Human megakaryocyte biology and pathophysiology

Abstract: 2. Megakaryocyte biology 136 2.1. Megakaryocyte proliferative (progenitor cell) compartment 136 2.2. Megakaryocyte maturative compartment 138 2.3. Regulation of megakaryocyte progenitor cell proliferation 139 2.4. Regulation of megakaryocyte maturation 140 2.5. Effect of in vivo treatment with recombinant cytokines on platelet cell count either in animal modelsorin clinical trials 142 2.6. Megakaryocyte molecular regulation 143

The role of chemotherapy in osteogenic sarcoma.

Abstract: 3.7. Non-randomizedstudies. 3.1.1. Intravenous chemotherapy. 3.1.2. Intra-arterial chemotherapy. Randomized studies 3.2.1. Chemotherapy versus control. 3.2.2. Studies evaluating the role of HDMTX. 3.2.3. Miscellaneous studies. Dose intensity of chemotherapy Effect of chemotherapy on pattern of metastases. Chemotherapy for tumors in axial sites. 3.5.1. Skull (including jaw). 3.5.2. Pelvis and spine. Chemotherapy for unusual variants of osteosarcoma. 3.6.1. Telangiectatic OS. Toxicity of chemotherapy.

Hematopoietic stem cells and microenvironment : the proliferation and differentiation of stromal cells

Abstract: 5. R e g u l a t i o n a n d s u p p o r t o f hematopoietic stern/progenitor cells by cell adhesion or cell s u r f a c e molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257 5. I . C D 3 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 5.2. H o m i n g r e c e p t o r . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 5.3. V C A M I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 5.4. c K i t ligand (stem cell factor) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

Exposure to and activation of dietary heterocyclic amines in humans

Abstract: * Corresponding author. drates, proteins and fats, and also on the relationship between energy intake and cancer susceptibility. However, recently research in this area has expanded, and the role played in human tumorigenesis by a number of dietary micro-components, including dietary mutagens, has come under greater scrutiny. A large number of mutagens occur naturally in our diet [3]. These substances are either intrinsically present in food(s) and drink(s), e.g., alkaloids or nitrosamines in plants and hydrazines in mushrooms, or are present as contaminants, e.g., fungal mycotoxins and pesticide re-

Detection and treatment of early cancers of the oral cavity

Abstract: 2. Diagnosis 2.1. History 2.1.1. Age and gender 2.1.2. Habits 2.1.2.1. Betel chewing. 2.1.2.2. Cigarette smoking. 2.1.2.3. Cigar smoking. 2.1.2.4. Pipe smoking 2.1.2.5. Bidi smoking. 2.1.2.6. Smokeless tobacco. 2.1.2.7. Alcohol 2.1.2.8. Mouthwashes 2.1.3. General health 2.1.4. Oral health 2.1.5. Infactions 2.1.5.1. Syphilis 2.1.5.2. candida albicans. 2.1.5.3. Viruses 2.1.6. Actinic radiation 2.1.7. Racial and geographic factors 2.1.8. Immune defects 2.1.9. Genetic factors 2.2. Physical examination 2.2.1. Main premalignant oral lesions. 2.2.1.1. Erythroplasia (etythroplakia). 2.2.1.2. White lesions 2.2.2. oral carcinoma 2.2.2.1. Second primary tumours 2.2.3. Metaatases.. 2.3. Investigations 2.3.1. Biopsy 2.3.1.1. Exfoliativecytotogy 2.3.1.2. Lymph node biopsy. 2.3.2. Photography 2.3.3. Radiography. 2.3.4. Other imaging investigations.