tetracycline and Carcinoma

Topics: Actins; Ampicillin; Anti-Bacterial Agents; Antineoplastic Agents; Carcinoma; Humans; Tetracycline

Topics: Carcinoma; Cystoscopy; Fluorescence; History, 20th Century; Humans; Optical Imaging; Photosensitizing Agents; Tetracycline; Ultraviolet Rays; Urinary Bladder Neoplasms

While Newcastle disease virus (NDV) causes serious infections in birds, it is apparently nonpathogenic in mammalian species, including humans. Previous observations and small-scale clinical trials indicated that NDV exerts oncolytic effects. Isolates of NDV were found to have selective affinity to transformed cells. We previously showed that the attenuated NDV strain MTH-68/H causes apoptotic cell death in cultures of PC12 rat pheochromocytoma cells. The aim of the present study was to extend MTH-68/H cytotoxicity testing with human tumor cell lines and to analyze certain biochemical aspects of its oncolytic effect. MTH-68/H was found to be able to kill a wide range of transformed cells by apoptosis. While caspase-8 and caspase-9 are not involved in MTH-68/H-induced apoptosis, activation of caspase-3 and caspase-12 was detected in virus-infected PC12 cells. A human glioblastoma cell line with repressible expression of the p53 protein did not show any difference in MTH-68/H sensitivity in its p53-expressing and p53-depleted states, indicating that the apoptotic process induced by MTH-68/H does not depend on p53. Apoptosis was accompanied by virus replication in two tumor cell lines tested (PC12 cells and HeLa human cervical cells), and signs of endoplasmic reticulum stress (phosphorylation of protein kinase R-like endoplasmic reticulum kinase and eIF2alpha) were also detected in transformed cells. In contrast, proliferation of nontransformed mouse and rat fibroblast cell lines and human primary fibroblasts was not affected by MTH-68/H treatment. MTH-68/H thus selectively kills tumor cell cultures by inducing endoplasmic reticulum stress leading to p53-independent apoptotic cell death.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Carcinoma; Caspase 12; Caspase 3; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Viral; Endoplasmic Reticulum; Enzyme Activation; Female; Glioblastoma; HCT116 Cells; HeLa Cells; HT29 Cells; Humans; Newcastle disease virus; Oxidative Stress; Pancreatic Neoplasms; PC12 Cells; Rats; Tetracycline; Tumor Suppressor Protein p53; Virus Replication

The recent finding that the 1p36.3 locus gene encodes an array of different p73 isoforms with apparently distinct and sometimes opposing cellular functions, might explain the difficulty in establishing the protein's role as tumor suppressor. Therefore we need to investigate the roles of each of these splicing variants in cellular functions when expressed alone or in combination with other family members, as well as the genetic background on which the proteins are expressed. We investigated, in two p53 null cell lines, the human SCLC line H1299 and a subline derived from the human colon carcinoma cell line HCT116 (HCT116/379.2), the effects of DeltaNp73alpha overexpression on cell growth and the response to anticancer treatment. We generated three different clones overexpressing DeltaNp73alpha under a tetracycline inducible promoter. Immunofluorescent staining and luciferase reporter assays confirmed that clones HCT116/DeltaNA and H1299/DeltaN7 and H1299/DeltaN11 did express a functional, nuclear localized DeltaNp73alpha protein. The stable overexpression of DeltaNp73alpha protein did not confer any cell growth advantage. Doubling time of clones overexpressing DeltaNp73alpha were comparable to counterparts not expressing it. Clonogenic assays showed that the cytotoxic activity of different DNA damaging agents, such as cDDP, UV light and doxorubicin, were comparable in clones expressing DeltaNp73 or not. The overall data argue against an oncogenic role for this isoform. These findings are independent of the p53 status since they overlap with those previously obtained by our group in HCT116 cell lines, wild type for p53.

Topics: Alternative Splicing; Carcinoma; Cell Line, Tumor; Colonic Neoplasms; DNA-Binding Proteins; Humans; Nuclear Proteins; Promoter Regions, Genetic; Protein Isoforms; Sequence Deletion; Tetracycline; Transcriptional Activation; Tumor Protein p73; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

We have shown previously that wild type p53 can rapidly induce replicative senescence in EJ human bladder carcinoma cells lacking functional p53. A major effector of p53 functions is p21Waf1/Cip1/Sdi1, a potent cyclin-dependent kinase inhibitor. p21Waf1/Cip1/Sdi1 has been shown to be involved in both p53 dependent and independent control of cell proliferation, differentiation and death. To directly investigate the effects of p21Waf1/Cip1/Sdi1 in the p53 response observed in EJ tumor cells, we established p21Waf1/Cip1/Sdi1 inducible lines using the tetracycline-regulatable vector system. p21Waf1/Cip1/Sdi1 induction caused irreversible cell cycle arrest in both G1 and G2/M, and diminished Cdk2 kinase activity. In addition, p21Waf1/Cip1/Sdi1 induction led to morphological alterations characteristic of cells undergoing replicative senescence with morphological, biochemical and ultrastructural markers of the senescent phenotype. Furthermore, sustained p21Waf1/Cip1/Sdi1 induction sensitized EJ cells to apoptotic cell death induced by mitomycin C, a cross-linking DNA damaging agent. These findings support the function of p21Waf1/Cip1/Sdi1 as an inducer of replicative senescence and a major mediator of this phenomenon in response to p53. Moreover, our results imply that therapeutic intervention in human cancers might be aimed at sustained elevation of p21Waf1/Cip1/Sdi1 expression.

Topics: Apoptosis; beta-Galactosidase; Biomarkers; Carcinoma; CDC2-CDC28 Kinases; Cell Division; Cellular Senescence; Cross-Linking Reagents; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinases; Cyclins; G1 Phase; G2 Phase; Gene Expression Regulation, Neoplastic; Genetic Engineering; Humans; Mitomycin; Protein Serine-Threonine Kinases; Tetracycline; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms

By use of an assay system in vitro with cultured FM3A cells from a C3H mouse mammary carcinoma, tetracycline hydrochloride was found to have the ability to induce an 8-azaguanine-resistant mutation. It is suggested that an assay system using mammalian cells for the detection of mutagenicity of certain substances having antimicrobial action is more practical than a system using bacteria. As other effects of tetracycline hydrochloride on FM3A cells, the damage on chromosomes and the inhibition of syntheses of protein and nucleic acids were demonstrated.

Topics: Azaguanine; Breast Neoplasms; Carcinoma; Cell Line; Chromosome Aberrations; Mutagens; Mutation; Tetracycline

Topics: Adenocarcinoma; Adult; Aged; Ampicillin; Breast Neoplasms; Carcinoma; Cross Infection; Cysts; Disease Outbreaks; Erythromycin; Female; Foot; Gentamicins; Hallux Valgus; Herniorrhaphy; Humans; Kidney Diseases, Cystic; Leg; Male; Middle Aged; Ovarian Diseases; Penicillins; Peptic Ulcer; Quebec; Streptococcal Infections; Surgical Wound Infection; Tetracycline

Topics: Adult; Aminosalicylic Acids; Blister; Carcinoma; Chronic Disease; Cough; Diagnosis, Differential; Humans; Isoniazid; Lung; Lung Diseases; Lung Neoplasms; Male; Radiography; Smoking; Spirometry; Sputum; Streptomycin; Syncope; Tetracycline; Tomography

Topics: Amphotericin B; Animals; Carcinoma; Cell Line; Cell Survival; Culture Media; Depression, Chemical; Dose-Response Relationship, Drug; Drug Synergism; HeLa Cells; Humans; L Cells; Leucine; Mice; Mouth Neoplasms; Polymyxins; Protein Biosynthesis; Rifampin; RNA, Neoplasm; Tetracycline; Tritium; Uridine

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma; Drug Synergism; Female; Humans; Leukemia, Myeloid, Acute; Lung; Male; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Prednisone; Radiography; Remission, Spontaneous; Sarcoma; Tetracycline; Vincristine

Topics: Aged; Carcinoma; Diagnosis, Differential; Female; Granuloma Inguinale; Humans; Streptomycin; Tetracycline; Uterine Cervical Neoplasms

Topics: Adenocarcinoma; Carcinoma; Female; Fluorescence; Gastric Lavage; Gastritis; Humans; Male; Polyps; Stomach Neoplasms; Stomach Ulcer; Tetracycline

Topics: Animals; Antimalarials; Carcinoma; Cell Line; Coloring Agents; Coumarins; Culture Media; Culture Techniques; Fibroblasts; Haplorhini; Humans; Kidney; Laryngeal Neoplasms; Light; Methods; Penicillins; Phenothiazines; Photosensitivity Disorders; Porphyrins; Rabbits; Sulfanilamides; Tetracycline; Thiazoles; Tolbutamide

Topics: Carcinoma; Cystoscopy; Fluorometry; Humans; Papilloma; Tetracycline; Time Factors; Ultraviolet Rays; Urinary Bladder Neoplasms

Topics: Adenocarcinoma; Carcinoma; Colonic Neoplasms; Diagnosis, Differential; Diverticulitis, Colonic; Fluorescence; Humans; Microscopy, Fluorescence; Prognosis; Rectal Neoplasms; Sigmoid Neoplasms; Stomach Neoplasms; Tetracycline

Topics: Carcinoma; Cytodiagnosis; Fluorescence; Gastric Lavage; Humans; Injections, Intramuscular; Stomach Neoplasms; Tetracycline

Topics: Carcinoma; Carcinoma, Bronchogenic; Clinical Laboratory Techniques; Fluorescence; Humans; Lung Diseases; Microscopy; Microscopy, Fluorescence; Neoplasms; Sputum; Tetracycline; Ultraviolet Rays

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Squamous Cell; Cystoscopy; Fluorescence; Humans; Tetracycline; Ultraviolet Rays; Urinary Bladder Neoplasms

Topics: Acridines; Animals; Antineoplastic Agents; Carcinoma; Carcinoma, Ehrlich Tumor; Chemical Phenomena; Chemistry; Coloring Agents; Fluoresceins; Fluorescence; Merbromin; Mercury; Mice; Porphyrins; Protein Synthesis Inhibitors; Research; Tetracycline

Topics: Animals; Anti-Bacterial Agents; Carcinoma; Carcinoma, Ehrlich Tumor; Fluorescence; Fluorescent Dyes; Humans; Mice; Microscopy; Microscopy, Fluorescence; Neoplasms; Neoplasms, Experimental; Oxytetracycline; Rats; Research; Tetracycline

Topics: Carcinoma; Demeclocycline; Fluorescence; Fluorescent Dyes; Neoplasms; Protein Synthesis Inhibitors; Tetracycline

Exfoliative cytology is a useful tool in the differential diagnosis of gastric lesions. The simplified method developed by Klinger and Katz(4) using tetracycline fluorescence was subjected to a critical evaluation. Five cases of gastric carcinoma, two of esophageal carcinoma, 21 of benign peptic ulcer, one case of carcinoma eroding into the bile duct, one case of carcinoma of the pancreas penetrating into the stomach, five normal controls on no medication and two normal controls taking vitamin B(2) were studied. The most apparent drawback of this technique is the number of false negatives encountered in cases of gastric carcinoma (three negative results in five cases of carcinoma). One false-positive test was recorded among 21 patients with benign ulcer. Vitamin B(2) if taken a half hour prior to the test will also produce a false-positive test. It is concluded, therefore, that the tetracycline fluorescence test is inferior to accurate studies of exfoliative cytology.

Topics: Carcinoma; Cytodiagnosis; Diagnosis, Differential; Esophageal Neoplasms; Fluorescence; Humans; Stomach Neoplasms; Tetracycline

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Colloids; Diagnosis, Differential; Duodenal Ulcer; Fluorescence; Humans; Stomach Neoplasms; Stomach Ulcer; Tetracycline; Ultraviolet Rays