tetracycline and Lymphoma

Modelling human disease in the mouse has become an essential activity in biomedical research in order to unravel molecular mechanisms underlying pathological conditions as well as to determine in vivo the consequences of aberrant gene function. The mouse is by far the most accessible mammalian system physiologically similar to humans. Furthermore, the development of novel techniques for manipulating the murine genome, which allow the in vivo modification of virtually any genomic region in a time and/or tissue specific manner, renders the mouse an ideal model system to study human pathological conditions. Modelling human diseases in mice has reached an even greater relevance in the field of haematological malignancies, due to the already advanced characterization of the molecular basis of many haematological disorders. In this review, we describe the most important technological developments that made it possible to reproduce in the mouse the genetic lesions that characterize human haematological malignancies, thus often generating faithful mouse models of the human condition. We provide specific examples of the advantages and limitations of the various genetic approaches utilized to model leukaemia and lymphoma in the mouse. Finally, we discuss the power of mouse modelling in developing and testing novel therapeutic modalities in pre-clinical studies.

Topics: Animals; Disease Models, Animal; Fusion Proteins, bcr-abl; Hematologic Neoplasms; Humans; Leukemia; Leukemia, Promyelocytic, Acute; Lymphoma; Mice; Mice, Transgenic; Models, Biological; Tetracycline

This paper describes for the first time the isolation of Streptococcus lutetiensis in a cat with intestinal lymphoma. The Streptococcus bovis group has undergone significant taxonomic changes over the past two decades and, in 2002, Poyart et al. described two distinct novel species within the genus Streptococcus: Streptococcus lutetiensis and Streptococcus pasteurianus. The bovis group streptococci include commensal species and subspecies or opportunistic pathogens of humans and animals. The cat was referred to the Veterinary Teaching Hospital, University of Bologna for chronic diarrhoea associated with fresh blood. A diagnosis of intestinal lymphoma was advanced. S. lutetiensis was accidentally isolated from the faeces of the cat and identified through MALDI-TOF and 16s rRNA sequencing. The Kirby-Bauer test revealed that the isolate was resistant to enrofloxacin, erythromycin, clindamycin, marbofloxacin and tetracycline. The detection of S. lutetiensis in cat faeces might suggest that it could be a normal inhabitant of cat intestinal tract or that it could be involved in the manifestation of intestinal diseases. Since bacteria belonging to the S. bovis group are considered emerging pathogens, additional research is required to evaluate the role of S. lutetiensis in cats and its role in the transmission of antimicrobial resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study the isolation of Streptococcus lutetiensis from a cat with intestinal lymphoma was described for the first time. An antimicrobial susceptibility test performed by means of the disc diffusion method revealed that the isolate was resistant to enrofloxacin, erythromycin, clindamycin, marbofloxacin and tetracycline. Nowadays the ecological or pathogenetic role of S. lutetiensis in the gut of animals remains unclear but, even if its role as commensal bacterium was confirmed, the presence of multi-resistant S. lutetiensis in cat gut could favour the transmission of antimicrobial resistance to other bacteria.

Topics: Animals; Anti-Bacterial Agents; Cat Diseases; Cats; Clindamycin; Diarrhea; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Erythromycin; Feces; Female; Fluoroquinolones; Intestinal Neoplasms; Intestines; Lymphoma; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptococcal Infections; Streptococcus; Tetracycline

RNA interference (RNAi) is a conserved posttranscriptional gene silencing mechanism that has recently emerged as a breakthrough genetic tool in functional genomics and drug target discovery. An increasing number of studies applying RNAi in high-throughput screens have begun to unravel complex signaling networks underlying diverse cellular processes. This chapter describes an approach to construct a conditional small-hairpin (sh)RNA library and its application in human lymphoma cell lines. A library cloning procedure outlines the incorporation of shRNA sequences and random 60-mer "bar code" oligonucleotides, enabling rapid identification of the hairpin by microarrays. Lymphoma cell lines are optimized for efficient retroviral transduction and tetracycline inducibility. The shRNA library is suitable for identifying molecular targets in cancer, but also versatile for various screening strategies.

Topics: Cell Line, Tumor; Cloning, Molecular; Fluorescent Dyes; Gene Library; Genetic Techniques; HEK293 Cells; Humans; Lymphoma; Nucleic Acid Hybridization; Oligodeoxyribonucleotides; Oligonucleotide Array Sequence Analysis; Phenotype; Retroviridae; RNA Interference; RNA Probes; RNA, Small Interfering; Tetracycline; Transduction, Genetic

Cellular senescence acts as a potent barrier to tumorigenesis and contributes to the anti-tumor activity of certain chemotherapeutic agents. Senescent cells undergo a stable cell cycle arrest controlled by RB and p53 and, in addition, display a senescence-associated secretory phenotype (SASP) involving the production of factors that reinforce the senescence arrest, alter the microenvironment, and trigger immune surveillance of the senescent cells. Through a proteomics analysis of senescent chromatin, we identified the nuclear factor-κB (NF-κB) subunit p65 as a major transcription factor that accumulates on chromatin of senescent cells. We found that NF-κB acts as a master regulator of the SASP, influencing the expression of more genes than RB and p53 combined. In cultured fibroblasts, NF-κB suppression causes escape from immune recognition by natural killer (NK) cells and cooperates with p53 inactivation to bypass senescence. In a mouse lymphoma model, NF-κB inhibition bypasses treatment-induced senescence, producing drug resistance, early relapse, and reduced survival. Our results demonstrate that NF-κB controls both cell-autonomous and non-cell-autonomous aspects of the senescence program and identify a tumor-suppressive function of NF-κB that contributes to the outcome of cancer therapy.

Topics: Animals; Cell Line; Cell Line, Tumor; Cell Survival; Cellular Senescence; Drug Resistance; Gene Expression Regulation, Neoplastic; Humans; Lymphoma; Mice; Phenotype; Protein Synthesis Inhibitors; RNA, Small Interfering; Tetracycline; Transcription Factor RelA; Tumor Suppressor Protein p53

Patients with ARF and haematological malignancy (excluding myeloma), presenting to a single unit over 10 years were analyzed to see if patients likely to benefit from intensive renal supportive therapy could be identified. 31 episodes of ARF were identified in 29 patients (mean age 51 +/- 2.9 yr): 19 were associated with acute leukaemia (13 AML, 6 ALL); 10 with lymphoma. Acute tubular necrosis (ATN) was identified as the cause of ARF in 26 cases, with sepsis (96%) and exposure to nephrotoxic drugs (88%), especially aminoglycosides, being the commonest precipitating factors. Toxic levels of the latter were commonly documented. Patient survival was 45%. Requirement for mechanical ventilation resulted in a universally fatal outcome; age greater than 55 yr and the presence of CNS symptoms or signs were also significantly associated with a poor outcome. Non-ATN causes (urate nephropathy or obstruction) carried a better prognosis. However, only 4 patients (14%) lived for more than 6 months following ARF. Thus, although a subgroup of patients more likely to benefit from treatment can be identified, the overall prognosis is poor and limited by that of the underlying disease. The potential benefit of avoiding nephrotoxic drugs, especially aminoglycosides, in these patients is highlighted by this study.

Topics: Acute Kidney Injury; Adolescent; Adult; Age Factors; Aged; Aminoglycosides; Cyclosporins; Female; Humans; Kidney Tubular Necrosis, Acute; Leukemia, Myeloid; Lymphoma; Male; Middle Aged; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Risk Factors; Tetracycline

Topics: Diagnosis, Differential; Heavy Chain Disease; Humans; Immunoglobulin alpha-Chains; Immunoglobulin Heavy Chains; Intestinal Neoplasms; Intestine, Small; Lymphoma; Male; Middle Aged; Radiography; Tetracycline

Malabsorption studies were performed on five Iranian patients with primary small intestinal lymphoma. The effect of oral tetracycline (1.0 g daily) was also studied in three of the above subjects. The results of breath tests (utilizing glycine-1-14C-cholic acid) were abnormal in all five subjects before the antibiotic treatment. Oral tetracycline had a striking effect towards normalizing the results of breath tests. Schilling tests (with intrinsic factor) improve in two patients and steatorrhea improved in all and there was significant weight gain. The antibiotic had no apparent effect on D-xylose or folate absorption tests. It is concluded that bacterial overgrowth in the small intestinal lumen is an important contributory factor to the malabsorption syndrome of this disease.

Topics: Adult; Bacterial Infections; Female; Humans; Intestinal Neoplasms; Intestine, Small; Iran; Lymphoma; Malabsorption Syndromes; Male; Tetracycline

Topics: Administration, Oral; Adult; Aged; Biopsy; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Female; Fluorescence; Humans; Injections, Intravenous; Laryngeal Neoplasms; Leukoplakia; Lymphoma; Male; Methods; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Pharyngeal Neoplasms; Tetracycline; Time Factors

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteroides; Bacteroides Infections; Breast Neoplasms; Child; Colonic Neoplasms; Female; Genital Neoplasms, Female; Hospitals, Special; Humans; Leukemia; Lymphoma; Male; Middle Aged; Neoplasms; Pressure Ulcer; Sepsis; Surgical Wound Infection; Tetracycline; Time Factors

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Bacteroides; Brucella; Chloramphenicol; Complement System Proteins; Endotoxins; Erythromycin; Hodgkin Disease; Humans; Leukemia; Leukopenia; Lymphadenitis; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Neoplasms; Penicillins; Primary Myelofibrosis; Properdin; Research; Sarcoma; Streptomycin; Tetracycline

Topics: Absorption; Anilides; Antineoplastic Agents; Biomedical Research; Blood; Dogs; Kidney Diseases; Kidney Neoplasms; Kidney Tubules; Lymphoma; Lymphoma, Non-Hodgkin; Metabolic Diseases; Metabolism; Tetracycline; Toxicology; Urine

Topics: Achlorhydria; Ascites; Bile; Biomedical Research; Body Fluids; Duodenal Ulcer; Fluorescence; Gastric Lavage; Hernia, Diaphragmatic; Humans; Leiomyosarcoma; Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms; Pancreatic Juice; Pleural Effusion; Polyps; Secretin; Stomach; Stomach Neoplasms; Stomach Ulcer; Tetracycline

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood Chemical Analysis; Hematocrit; L-Lactate Dehydrogenase; Leukocyte Count; Lymphoma; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Metabolism; Mice; Muscles; Neoplasms, Experimental; Penicillins; Research; Streptomycin; Tetracycline