tetracycline and Lung-Neoplasms

Afatinib has shown long progression free survival and improvement in quality of life in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Although afatinib causes acneiform rash, it can be manageable. Tetracyclines are usually used to treat it; nonetheless, there is no trial that evaluates their prophylactic efficacy on afatinib induced-skin toxicities (AIST).. This open-label, randomized, controlled trial assessed the preventive effect of tetracycline for reducing afatinib-skin toxicities in NSCLC patients receiving afatinib 40 mg/day. Patients were randomly assigned to receive pre-emptive treatment with tetracycline 250 mg every 12h for 4 weeks or not. Reactive treatment in both groups included general dermatological recommendations such as use of skin moisturizers, sunscreen and topical steroids, according to toxicity severity. All patients were blindly monitored for skin toxicities by an expert dermatologist at the start of treatment with afatinib (day 0), weeks 2 and 4 of treatment. The protocol is registered on clinicaltrials.gov (NCT01880515).. We included 90 patients, no differences were found in clinical and dermatological baseline characteristics. Rash incidence of any grade, and grade ≥2 was less frequent in the pre-emptive arm vs. the control arm (44.5 vs. 75.6%, RR 0.4 [95% CI 0.17-0.99], p=0.046 and 15.6 vs. 35.6%, RR 0.35 [95% CI, 0.12-0.91], p=0.030, respectively). No difference was found in paronychia, xerosis, mucositis, folliculitis, and skin fissure. No adverse event was associated with tetracycline. Neither rash nor pre-emptive tetracycline impacted on response rate, progression-free or overall survivals.. Pre-emptive tetracycline was well tolerated and reduced the rash incidence and severity associated with afatinib in more than 60%.

Topics: Adult; Afatinib; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Pre-Exposure Prophylaxis; Quinazolines; Risk Factors; Skin Diseases; Tetracycline

We reviewed 36 cases of symptomatic malignant pericardial effusion managed with pericardiocentesis at our institution from 1982 to 1989. There were 13 men and 23 women, aged 49 +/- 12 years (range, 33-76 years). The commonest underlying tumours were lung cancer (12 cases, 33%) and breast cancer (11 cases, 30%). Pericardiocentesis was successful as the initial management in 34 of 36 patients (94%); one patient died as a result of the procedure and another required subxiphoid incision and tube drainage of the effusion. When intrapericardial sclerotherapy was performed, only three of 28 patients required repeat pericardiocentesis, and when sclerotherapy was not performed initially, four of seven patients had recurrent symptomatic effusions. Median survival following pericardiocentesis in breast cancer patients was 10 months (range, 0-36 months) and in all other malignancies was four months (range, 0-12 months). We conclude that pericardiocentesis with intrapericardial sclerotherapy provides good local control for symptomatic malignant pericardial effusion in the majority of patients. In spite of this, the median survival of such patients is poor, especially in patients with malignancies other than breast cancer, with few patients surviving more than a few months.

Topics: Adult; Aged; Breast Neoplasms; Drainage; Echocardiography; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Palliative Care; Pericardial Effusion; Pericardium; Prognosis; Punctures; Sclerotherapy; Survival Rate; Tetracycline

Topics: Carcinoma, Squamous Cell; Humans; Lung Neoplasms; Methotrexate; Tetracycline; Time Factors

Burkholderia cenocepacia is a Gram-negative, opportunistic pathogen that is a cause of morbidity and mortality in patients with cystic fibrosis (CF). Research efforts over the past few decades contributed to our understanding of these infections by identifying virulence factors. However, little is known about how this pathogen adapts to the harsh environment found inside the CF airways, which is characterized by a unique mucus containing high concentrations of inflammatory markers. The current study developed a novel model to further investigate this phenomenon.. Monolayers of human A549 lung carcinoma cells (HLCCs) were exposed to a mixture of artificial CF sputum medium (ASMDM) in tissue culture growth medium, and subsequently infected with B. cenocepacia K56-2 for 24 h. The data showed that this model supported B. cenocepacia growth. In addition, consistent with similar studies using current models such as CF airway tissue samples, HLCC viability was reduced by more than 70 % when grown in 60 % ASMDM and infected with B. cenocepacia compared to mock-infected controls and medium alone. Furthermore, the amount of B. cenocepacia cells associated with the HLCC monolayer was more than 10 times greater in 60 % ASMDM when compared to medium controls.. These findings suggest that HLCC monolayers in 60 % ASMDM serve as a valid alternative to study B. cenocepacia infections in patients with CF, and possibly other chronic diseases of the airways. Furthermore, the results obtained in this study suggest an important role for CF sputum in B. cenocepacia pathogenesis.

Topics: A549 Cells; Burkholderia cenocepacia; Burkholderia Infections; Chronic Disease; Culture Media, Conditioned; Cystic Fibrosis; Humans; Kartagener Syndrome; Lung Neoplasms; Microbial Viability; Sputum; Tetracycline; Virulence Factors

To date a variety of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) mouse models have been developed that mimic human lung cancer. Chemically induced or spontaneous lung cancer in susceptible inbred strains has been widely used, but the more recent genetically engineered somatic mouse models recapitulate much better the genotype-phenotype correlations found in human lung cancer. Additionally, improved orthotopic transplantation of primary human cancer tissue fragments or cells into lungs of immune-compromised mice can be valuable tools for preclinical research such as antitumor drug tests. Here we give a short overview of most somatic mouse models for lung cancer that are currently in use. We accompany each different model with a description of its practical use and application for all major lung tumor types, as well as the intratracheal injection or direct injection of fresh or freeze-thawed tumor cells or tumor cell lines into lung parenchyma of recipient mice. All here presented somatic mouse models are based on the ability to (in) activate specific alleles at a time, and in a tissue-specific cell type, of choice. This spatial-temporal controlled induction of genetic lesions allows the selective introduction of main genetic lesions in an adult mouse lung as found in human lung cancer. The resulting conditional somatic mouse models can be used as versatile powerful tools in basic lung cancer research and preclinical translational studies alike. These distinctively advanced lung cancer models permit us to investigate initiation (cell of origin) and progression of lung cancer, along with response and resistance to drug therapy. Cre/lox or FLP/frt recombinase-mediated methods are now well-used techniques to develop tissue-restricted lung cancer in mice with tumor-suppressor gene and/or oncogene (in)activation. Intranasal or intratracheal administration of engineered adenovirus-Cre or lentivirus-Cre has been optimized for introducing Cre recombinase activity into pulmonary tissues, and we discuss here the different techniques underlying these applications. Concomitant with Cre/Flp recombinase-based models are the tetracycline (Tet)-inducible bitransgenic systems in which presence or absence of doxycycline can turn the expression of a specific oncogene on or off. The use of several Tet-inducible lung cancer models for NSCLC is presented here in which the reversal of oncogene expression led to complete tumor regression and provided us wi

Topics: Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Cryopreservation; Disease Models, Animal; DNA Nucleotidyltransferases; Doxycycline; Drinking Water; Female; Humans; Integrases; Lung; Lung Neoplasms; Male; Mice; Mice, Transgenic; Tamoxifen; Tetracycline

The aim of this study was to investigate the expression of bone morphogenetic protein 7 (BMP7), in human pulmonary cancer tissues/cells and to evaluate the cellular impact of bone morphogenetic proteins on pulmonary cancer cells. BMP7 expression was determined in human lung cancer cell lines. The invasiveness and growth of cells transfected with BMP7, in vitro, were evaluated using the in vitro invasion assay and in vitro tumour models. Cellular migration was analysed using wounding assays. BMP7-positive tumours correlated with the absence of bone metastasis (P=0.040). In this analysis, we identified that 4 of 4 small cell lung cancer (SCLC) tissue specimens had no BMP7 expression, which illustrated that BMP7 may have no role in SCLC. BMP7 expression was not correlated with the overall survival time in lung cancer patients. Downregulation of BMP7 expression significantly inhibited the invasiveness of SPC-A1 cells (P<0.001) and forced-expression of BMP7 dramatically increased the motility of A549 cells. Overexpression of BMP7 in A549 cells and its knockdown in SPC-A1 cells did not significantly alter proliferation compared with the control cells (P>0.5 respectively). In conclusion, we have demonstrated that BMP7 has an important role in controlling lung cancer cell motility and invasiveness, without affecting the growth process, cell proliferation and cell apoptosis. A higher BMP7 expression may be an indicator for bone metastasis. The therapeutic role of BMP7 warrants further investigation.

Topics: Bone Morphogenetic Protein 7; Cell Line, Tumor; Cell Proliferation; Cohort Studies; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Neoplasm Invasiveness; Prognosis; RNA, Small Interfering; Staining and Labeling; Tetracycline; Time Factors; Tumor Stem Cell Assay; Wound Healing

Topics: Animals; Biomedical Research; Bleomycin; Breast Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Mesothelioma; Pleural Effusion, Malignant; Pleurodesis; Povidone-Iodine; Rabbits; Talc; Tetracycline

Activating mutations of the oncogene K-ras are found in one third of all human cancers. Much of our knowledge on K-ras signal transduction and its influence on tumor initiation and progression come from in vitro studies with cell lines. However, mouse models of human cancer allow a much more faithful recapitulation of the human disease, and the in vivo perspective is crucial for our understanding of neoplasia. In recent years, several new murine models for K-ras-induced tumorigenesis have been described. They allow new insights into the specific role that oncogenic K-ras proteins play in different solid tumors, and they permit the molecular dissection of the pathways that are initiated by somatic mutations in subsets of cells. Key advances have been made by the use of tissue-specific and inducible control of expression, which is achieved by the Cre/loxP technology or the tetracycline system. From these sophisticated models, a common picture emerges: the effects of K-ras on tumor initiation depend strongly on the cellular context, and different tissues vary in their susceptibility to K-ras transformation.

Topics: Animals; Crosses, Genetic; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Gene Transfer Techniques; Genes, ras; Genes, Tumor Suppressor; Intestinal Mucosa; Intestinal Neoplasms; Lung Neoplasms; Mice; Mice, Transgenic; Mutation; Neoplasms; Neoplastic Stem Cells; Organ Specificity; Pancreatic Neoplasms; Protein Synthesis Inhibitors; ras Proteins; Tetracycline; Transgenes

Gene therapy is a new therapeutic approach for the treatment of human cancers. Gene expression systems that can be regulated by drugs have been developed to improve the safety and efficacy of therapeutic transgene delivery. One of the most promising systems is the tetracycline (Tet)-responsive system in the Tet-On configuration. A major problem of the Tet-On system if used in viral vectors is the high basal activity of the Tet response element (TRE) promoter leading to leaky expression of transgenes under uninduced conditions. We therefore evaluated novel TRE promoters for controlling gene expression in an adenovirus vector (AdV) Tet-On system and further investigated them for expression of the pro-apoptotic CD95/Fas ligand (FasL) in human epithelial carcinoma cell line (HeLa) and lung cancer cells. Plasmid-based reporter gene assays showed that modifications within the tetO (7) and minimal immediate early cytomegalovirus promoter (CMV)(min) sequence of the TRE promoter reduced its leakiness and led to a markedly improved regulatability by doxycycline. Among several TRE promoters tested, a new construct (TRE-Tight1) containing modifications of both the tetO (7) sequence and the CMV(min) showed 11-fold reduced leakiness and 1.5-fold increased absolute transgene expression levels after induction, as compared to the original TRE. Under induced conditions, a TRE-Tight1 promoter-dependent AdV expressing the pro-apoptotic CD95L/FasL induced apoptosis and cell lysis in HeLa cells as efficiently as an AdV containing the original TRE promoter. In contrast to the latter, however, the vector with the modified TRE promoter left cells totally unaffected in the absence of the inducer. Stringently regulated induction of apoptosis and cell death by TRE-Tight1-AdV was also demonstrated in three human lung cancer cell lines. These data show that the novel TRE-Tight1 promoter has a high potential for closely controlled and efficient expression of cytotoxic genes in AdV-based anti-cancer approaches.

Topics: Adenoviridae; Apoptosis; Doxycycline; Fas Ligand Protein; Gene Expression Regulation; Genetic Therapy; Genetic Vectors; HeLa Cells; Humans; Lung Neoplasms; Membrane Glycoproteins; Promoter Regions, Genetic; Tetracycline; Toxicity Tests; Tumor Cells, Cultured; Tumor Necrosis Factors

In some cell types either DNA damage or p53 expression leads to minimal cell death, while combining the two leads to a strong apoptotic response. To further understand features of p53 that contribute to this increased cell death we used clones of H1299 cells that express wild-type or several mutant forms of p53 under a tetracycline-regulated promoter. In these cells the induction of wild-type p53 leads to significant apoptosis only when combined with exposure to a number of chemotherapeutic agents. A common target of p53, p21, is itself not sufficient to cause apoptosis in the presence of these chemotherapeutic compounds. Many agents also effectively increase cell death when a transcriptionally-defective p53, p53([gln22ser23]), is induced, although a dramatic exception is treatment with 5-FU, which strongly cooperates with wild-type but not p53([gln22ser23]). Our results with 5-FU thus show that genetically separable functions of p53 are involved in its ability to respond to DNA-damaging agents to induce apoptosis. Notably as well, deleting the C-terminal 30 amino acids of p53 does not affect this cooperative effect with DNA-damaging agents. By contrast, a p53 mutant lacking the PXXP-domain between residues 60-90, while at least partially transcriptionally-competent, cannot be rendered apoptotic by any compounds that we tested. Thus the PXXP domain provides an essential component of the ability of p53 to respond to DNA-damaging agents to cause cell death.

Topics: Antineoplastic Agents; Apoptosis; Camptothecin; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Clone Cells; Colchicine; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Daunorubicin; DNA Damage; DNA, Neoplasm; Etoposide; Fluorouracil; Gene Expression Regulation, Neoplastic; Genes, p53; Humans; Lung Neoplasms; Models, Biological; Proline; Promoter Regions, Genetic; Protein Structure, Tertiary; Recombinant Fusion Proteins; Structure-Activity Relationship; Tetracycline; Transcription, Genetic; Tumor Cells, Cultured; Tumor Suppressor Protein p53

We investigated the clinical characteristics separating pneumonia as a complication in elderly lung cancer patients into obstructive and non-obstructive pneumonia. Two hundred and five patients with pneumonia as a complication in elderly lung cancer patients were classified into two groups; 64 patients with obstructive pneumonia and 141 patients with non-obstructive pneumonia. Most of the patients in both groups were male. Concerning histological findings, while most of the patients with obstructive pneumonia had squamous cell carcinoma, those with non-obstructive pneumonia had the same proportion of squamous cell carcinoma as all elderly patients with lung cancer. Most of the patients with obstructive pneumonia were in good general condition including their nutritional condition, but the patients with non-obstructive pneumonia were in significantly poor condition. A low percent of microorganisms were isolated from the sputum obtained from the patients with non-obstructive pneumonia, but a high percentage were obtained from those with non-obstructive pneumonia. Frequent involvement of gram-negative bacilli such as Pseudomonas aeruginosa and Klebsiella pneumoniae or Staphylococcus aureus containing MRSA was also found in these patients. Regarding treatment, although carbapenem was used either alone or in combination therapy as the regimen of treatment for pneumonia as a complication in elderly lung cancer patients with both the obstructive and non-obstructive pneumonia patients, the efficacy rate was poor in 50% with obstructive pneumonia and in 26% with non-obstructive pneumonia. The mortality rate was 11% in the patients with obstructive pneumonia, while it was 61% in the patients with non-obstructive pneumonia. The prognosis was significantly poorer in the patients with non-obstructive pneumonia. We concluded that although the prognosis was not so poor for patients with obstructive pneumonia if the appropriate treatment was given, in the patients with non-obstructive pneumonia, the treatment for underlying diseases and the improvement of their general condition, including the determination of causative microorganisms, was important.

Topics: Aged; Carbapenems; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Penicillins; Pneumonia, Bacterial; Prognosis; Tetracycline

Iron regulatory protein 1 (IRP1), a major posttranscriptional regulator of cellular iron and energy metabolism, is controlled by an iron-sulfur cluster switch. Cysteine-437 is critical for coordinating the cluster, and its replacement yields mutants that do not respond to iron perturbations and constitutively bind to cognate mRNA iron-responsive elements (IREs). The expression of IRP1(C437S) in cells has been associated with aberrations in iron homeostasis and toxicity. We have established clones of human lung (H1299) and breast (MCF7) cancer cells that express high levels of IRP1(C437S) in a tetracycline-inducible manner. As expected, IRP1(C437S) stabilizes transferrin receptor mRNA and inhibits translation of ferritin mRNA in both cell types by binding to their respective IREs. However, H1299 transfectants grown at high densities are able to overcome the IRP1(C437S)-mediated inhibition in ferritin synthesis. The mechanism involves neither alteration in ferritin mRNA levels nor utilization of alternative transcription start sites to eliminate the IRE or relocate it in less inhibitory downstream positions. The derepression of ferritin mRNA translation occurs under conditions where global protein synthesis appears to be impaired, as judged by a significant enrichment in the expression of the underphosphorylated form of the translational regulator 4E-BP1. Collectively, these data document an example where ferritin mRNA translation evades control of the IRE-IRP system. The physiological implications of this response are reflected in protection against iron-mediated toxicity, oxidative stress, and apoptosis.

Topics: Adaptor Proteins, Signal Transducing; Breast Neoplasms; Carrier Proteins; Cell Cycle Proteins; Cell Division; Cells, Cultured; Cysteine; Female; Ferritins; Gene Expression Regulation; Humans; Iron; Iron Regulatory Protein 1; Iron-Regulatory Proteins; Iron-Sulfur Proteins; Lung Neoplasms; Phosphoproteins; Promoter Regions, Genetic; Protein Biosynthesis; Response Elements; RNA-Binding Proteins; RNA, Messenger; Tetracycline; Tumor Cells, Cultured

To evaluate the efficacy of small-bore (12 French vanSonnenberg) catheters compared with standard large-bore chest tubes in the drainage and sclerotherapy of malignant pleural effusions.. Retrospective review.. An academic tertiary care hospital.. Adult patients with documented neoplasms and malignant pleural effusions, treated between 1986 and 1995.. All patients included in the study underwent drainage of malignant pleural effusions either by large-bore chest tube or by ultrasound-guided small-bore catheter. After drainage, pleurodesis was performed.. Outcome as defined by recurrence of effusion was determined by blinded examination of all postpleurodesis chest radiographs. We identified 58 cases of malignant pleural effusion in which small-bore catheters were used and 44 in which large-bore chest tubes were used. The majority of patients had breast (n = 56, 55%) or lung cancer (n = 29, 28%). The median age was 65 years. Fifty-nine patients were actively being treated with chemotherapy at the time of pleurodesis. The following sclerosing agents were used: talc, 27 (26%); tetracycline, 72 (70%); bleomycin, 2 (2%); and interferon, 1 (1%). Actuarial probabilities of recurrence at 6 weeks and 4 months were 45% and 53% for the small tubes vs 45% and 51% for the large tubes. Univariate and multivariate analyses failed to demonstrate that tube size had any influence on the rate of recurrence.. We were unable to detect any major differences in outcomes with the use of either size of chest tube. Our study suggests that small-bore catheters may be effective in the treatment of malignant pleural effusions and deserve further evaluation in prospectively designed trials.

Topics: Adult; Aged; Aged, 80 and over; Bleomycin; Breast Neoplasms; Chest Tubes; Drainage; Female; Humans; Interferon Type I; Lung Neoplasms; Male; Middle Aged; Pleural Effusion, Malignant; Pleurodesis; Probability; Recurrence; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Survival Rate; Talc; Tetracycline

To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4b(G12D) under the control of doxycycline in type II pneumocytes. Focal proliferative lesions of alveolar type II pneumocytes were observed as early as seven days after induction with doxycycline; after two months of induction, the lungs contained adenomas and adenocarcinomas, with focal invasion of the pleura at later stages. Removal of doxycycline caused a rapid fall in levels of mutant K-Ras RNA and concomitant apoptotic regression of both the early proliferative lesions and the tumors. Tumor burden was dramatically decreased by three days after withdrawal, and tumors were undetectable after one month. When similar experiments were performed with animals deficient in either the p53 gene or the Ink4A/Arf locus, tumors arose more quickly (within one month of exposure to doxycycline) and displayed more obvious histological features of malignancy; nevertheless, these tumors also regressed rapidly when the inducer was removed, implying that continued production of mutant K-Ras is necessary to maintain the viability of tumor cells in the absence as well as the presence of tumor suppressor genes. We also show that the appearance and regression of these pulmonary tumors can be readily monitored in anesthetized transgenic animals by magnetic resonance imaging.

Topics: Adenocarcinoma; Adenoma; Animals; Apoptosis; Bromodeoxyuridine; Cyclin-Dependent Kinase Inhibitor p16; DNA Primers; Gene Expression Regulation, Neoplastic; Genes, ras; Genes, Tumor Suppressor; Genotype; In Situ Nick-End Labeling; Lung Neoplasms; Mice; Mice, Knockout; Mice, Transgenic; Models, Genetic; Neoplasm Recurrence, Local; Reverse Transcriptase Polymerase Chain Reaction; Tetracycline; Transgenes; Tumor Suppressor Protein p53

Sialomucin complex (SMC), a rat homologue of the human mucin MUC4, is a large membrane-bound mucin complex, originally isolated from highly metastatic ascites 13762 mammary adenocarcinoma cells. When overexpressed, SMC exerts potent anti-adhesive effects, which sterically disrupt molecular interactions for cell-cell and cell-ECM adhesions. SMC similarly suppresses anti-tumor immunity by inhibition of interactions between cytotoxic lymphocytes and target tumor cells. Previously, recombinant cDNAs for SMC were transfected and inducibly expressed in A375 human melanoma cells using a tetracycline-responsive expression system. In the current studies, we investigated the role of MUC4/SMC in tumor metastasis by regulating SMC expression of tumor transplants in vivo. Intravenous injection of SMC-overexpressing cells resulted in substantially greater lung metastasis than injection of SMC-repressed cells. Injection of SMC-overexpressing cells followed by in vivo downregulation of SMC did not lower the frequency of lung metastasis. Growth of the micrometastatic lesions was the same for all 3 cases in short-term (3-week) assays. Further, subcutaneous injection of A375 cells followed by in vivo induction of SMC overexpression within the solid tumor resulted in spontaneous distant metastasis. These studies suggest that SMC potentiates metastasis by contributing to the establishment of metastatic foci. These studies directly demonstrate for the first time that tumor metastasis can be modulated by the regulation of MUC4/SMC expression.

Topics: Animals; Cell Adhesion; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Nude; Mucin-4; Mucins; Neoplasm Transplantation; Protein Synthesis Inhibitors; Rats; Tetracycline; Transfection; Tumor Cells, Cultured

p53 is mutated in approximately 50% of human cancers, whereas mutations of the related p73 gene are rare. p73 can activate p53-responsive promoters and induce apoptosis when overexpressed in certain p53-deficient tumor cells. We show that p73 isoforms, p73alpha and p73beta, can each induce permanent growth arrest with markers of replicative senescence when overexpressed in a tetracycline-regulatable manner in human cancer cells lacking functional p53. Human homologue of mouse double minute 2 gene product (hMDM2), but not an NH(2)-terminal deletion mutant, coimmunoprecipitated with p73alpha or p73beta, and inhibited p73 transcriptional activity as with p53. In contrast to p53, ectopically expressed hemagglutinin (HA)-tagged p73 proteins were not stabilized by treatment with several DNA damaging agents. Furthermore, unlike normal p53, which increases in response to DNA damage due to enhanced protein stability in MCF7 cells, endogenous p73 protein levels were not increased in these cells under the same conditions. Thus, although p73 has an ability, comparable to that of p53, to suppress tumor cell growth in p53-deficient cells, p73 induction is regulated differently from p53. These findings suggest that the selective pressures for p53 rather than p73 inactivation in tumors may reflect their differential responses to stresses such as DNA damage, rather than their capacities to induce permanent growth arrest or apoptosis programs.

Topics: Animals; Breast Neoplasms; Cell Cycle; Cell Line; DNA Damage; DNA-Binding Proteins; Female; Genes, Tumor Suppressor; Humans; Lung Neoplasms; Mice; Neoplasm Proteins; Nuclear Proteins; Protein Isoforms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Recombinant Proteins; Tetracycline; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Tumor Protein p73; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Urinary Bladder Neoplasms

Biloma is an extraductular collection of bile within a defined capsular space. Prior reports have documented an association between biloma and abdominal trauma, and between biloma and iatrogenic injury resulting from abdominal surgery, percutaneous catheter drainage, or transhepatic cholangiogram. To our knowledge, bilomas have not previously been associated with lung cancer. We report a case of spontaneous biloma that developed as a complication of small cell lung cancer.

Topics: Aged; Bile; Carcinoma, Small Cell; Hepatomegaly; Humans; Lung Neoplasms; Male; Neoplasm Staging; Organotechnetium Compounds; Peritoneal Cavity; Pyrrolidines; Radionuclide Imaging; Radiopharmaceuticals; Tetracycline; Tomography, X-Ray Computed; Ultrasonography

To establish a tetracycline-regulated expression model and to determine and verify whether a specific point mutant type p53 minigene, containing an Arg-->Leu substitution at amino acid 172, possesses a suppressing effect on human lung cancer.. The tumor suppressing effects of inducing apoptosis and inhibition of the formation of G418 resistant colonies of the specific point mutated p53 minigene in a structural expression vector on a human cancer cell line PG with preexisting dominant negative p53 were preliminarily verified. Then the specific p53 minigene was sub-cloned into a tetracycline-transactivative controlled expression vector pBPSTR1 by gene recombination methods. Through LipofectaMINE, the vector was transfected into PG cells under the presence of tetracycline (1.0 mg/ml), and the transfectants were screened in the selecting medium containing 1.5 micrograms/ml puromycin, the p53 minigene expression and tumor suppressing effects were studied dynamically in presence/absence (1.0/0 mg/ml) of tetracycline.. The specific mutant p53 minigenes had a stronger tumor suppressing effect than wild type p53 minigene on colony formation and transient expression could induce PG cell apoptosis (P < 0.05). The tetracycline transactivative p53 minigene-regulated transgene model was successfully established. When tetracycline was absent, a large amount of apoptosis cells in transgenic passage colonies could be detected. Therefore the tumor suppressing effects were further verified.. The specific point mutant p53 minigene may be a good candidate for cancer gene therapy. The tetracycline transactivative response promoter was found to be a good regulator of down stream gene expression, this may be useful in future gene therapy.

Topics: Animals; Apoptosis; Carcinoma, Giant Cell; Gene Expression Regulation, Neoplastic; Genes, p53; Genetic Therapy; Humans; Lung Neoplasms; Mice; Mice, Nude; Point Mutation; Tetracycline; Transcriptional Activation; Tumor Cells, Cultured

The management of malignant pericardial effusion remains controversial. We present our experience with 93 patients referred for drainage and sclerosing procedures between 1979 and 1994.. With continuous electrocardiographic monitoring, a Kifa catheter was inserted percutaneously into the pericardial sac and allowed to drain. A 100 mg dose of lidocaine hydrochloride was instilled intrapericardially, followed by 500 to 1000 mg tetracycline or doxycycline hydrochloride in 20 to 50 ml normal saline solution. The catheter was clamped for 1 to 2 hours and then reopened, and the procedure was repeated daily until the net drainage was less than 25 ml in 24 hours.. Subjects included 53 women and 40 men (median age 58 years). Eight patients could not undergo sclerosis because of technical failure. Eighty-five patients underwent sclerosis and required a median dose of 1500 mg of the sclerosing agent (range 500 to 700 mg), given in a median of three injections (range one to eight). Complications included pain (17 patients), atrial arrhythmias (eight patients), fever with temperature greater than 38.5 degrees C (seven patients), and infection (one patient). Two patients had cardiac arrest before sclerosis could be attempted. Sixty-eight patients (73%) had the effusion controlled for longer than 30 days, for an overall control rate of 81%. Seven other patients had control of the effusion but died of progressive malignant disease in less than 30 days. The overall median survival was 98 days (range 1 to 1724 days). Comparison of these results with outcomes reported for patients with malignant pericardial effusion who underwent surgical drainage indicates that drainage and sclerosis provide similar survivals but sclerosis carries lower morbidity, mortality, and recurrence rates.. Percutaneous drainage and sclerosis constitutes a safe and effective treatment for malignant pericardial effusion. Surgical management should be reserved for the small percentage of cases that cannot be controlled by this method.

Topics: Adult; Aged; Anesthetics, Local; Anti-Bacterial Agents; Arrhythmias, Cardiac; Bacterial Infections; Breast Neoplasms; Cardiac Tamponade; Catheterization; Doxycycline; Drainage; Electrocardiography, Ambulatory; Female; Fever; Follow-Up Studies; Heart Arrest; Humans; Lidocaine; Lung Neoplasms; Male; Middle Aged; Pain; Pericardial Effusion; Pericardium; Sclerosing Solutions; Survival Rate; Tetracycline; Treatment Outcome

Topics: Adult; Carcinoma, Non-Small-Cell Lung; Drainage; Electrocardiography; Humans; Lung Neoplasms; Male; Middle Aged; Pericardial Effusion; Pericardium; Tetracycline

Pleurodesis for effective control of malignant pleural effusion can be induced with various methods and agents. In 18 patients with histologically or cytologically proven malignant pleural effusion, 500 mg doxycycline hydrochloride diluted in 30 ml of saline was instilled into the emptied pleural space. Tube drainage was performed using suction or gravity. More than one doxycycline instillation was required in 13 cases. Serial chest radiography showed the response to be complete in 11 of the 18 patients and partial in four, while three did not respond. There was no difference between the results obtained with the two drainage systems. In all of the complete responders who died there was no sign of reaccumulated pleural effusion at terminal admission, despite clinical evidence of systemic tumor progression. Three patients--all with breast carcinoma--are alive after 5-27 months, two as complete responders and one as partial responder. The most common side effect was pleuritic pain, defined as significant if narcotic analgesics were required. A moderate febrile reaction appeared in four patients during the first 24 hours post-instillation. The study showed doxycycline to be an effective sclerosing agent for inducing pleurodesis, with acceptable adverse effects.

Topics: Aged; Aged, 80 and over; Animals; Breast Neoplasms; Doxycycline; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pleural Effusion; Rabbits; Tetracycline

A 36-year-old man presented with malaise, myalgia, fever, and weight loss. Liver function tests were moderately abnormal and chest x-ray film revealed an irregular mass in the right lower lobe. Bronchoscopy with cytology was not helpful. Serology revealed markedly elevated titers to Q fever. The mass was presumed to represent the presence of a Q fever pseudotumor. The patient responded to therapy with resolution of symptoms and chest x-ray film and decrease in titers to Q fever.

Topics: Adult; Fibroma; Humans; Lung Neoplasms; Male; Q Fever; Radiography; Tetracycline

Topics: Breast Neoplasms; Cardiac Tamponade; Drainage; Emergencies; Female; Heart Neoplasms; Humans; Lung Neoplasms; Pericardial Effusion; Pericardium; Tetracycline

A 57-year-old woman with bilateral pneumothoraces secondary to pulmonary metastases from leiomyosarcoma of the uterus was treated successfully by intrapleural instillation of tetracycline.

Topics: Female; Humans; Leiomyosarcoma; Lung Neoplasms; Middle Aged; Pleura; Pneumothorax; Tetracycline

Analysis of clinical features of infectious complications of lung cancer was carried out to obtain the informations necessary for the efficient management. Infectious complications developed in 114 patients out of 188 patient of primary lung cancer who were admitted to the institute during the period of two years from 1982 to 1983. From the results of the analysis it was revealed that anticancer chemotherapy was extensively restricted by coexistent infectious complications. Therefore, complete and partial responses in the patients associated with infections was significantly (p less than 0.05) lower than that in the patients without infection. Survival rate at the point of one year after the admission was also lower with significance (p less than 0.05) in the patients with infections than that in the patients without infections. Main and direct cause of the infection was bronchial obstruction. Therefore, the incidence of the infectious complication was the highest in the patients with squamous cell carcinoma. Of defence mechanism against infection, cellular immunity seemed to play the more important role as compared with that of humoral immunity. And it was shown that decrease in number of lymphocytes was most closely related to the development of serious or terminal infections. Causative organisms in most of the pulmonary infections were opportunistic Gram-negative bacilli. Recently, the incidence of the infections due to E. colioand K. pneumoniae decreased and that due to Enterobacteriaceae except for these two species increased. Therapeutic efficacy rate of antimicrobial agents including cephems of the 3rd generation remained as low as 50% or so. However, the cure rate of the triple regimen consisted of beta-lactam, aminoglycoside and tetracycline was revealed to be satisfactorily high.

Topics: Anti-Bacterial Agents; Bacterial Infections; gamma-Globulins; Humans; Lactams; Leukocyte Count; Lung Neoplasms; Prognosis; Respiratory Tract Infections; Serum Albumin; Tetracycline

Topics: Breast Neoplasms; Humans; Injections; Lung Neoplasms; Pleura; Pleural Effusion; Tetracycline

A 44-year-old woman was seen with the clinical and histologic picture of lymphangiomyomatosis syndrome. She also had dermatologic and neurologic stigmata of tuberous sclerosis. After the development of a recurring chylothorax, she had a downhill course unresponsive to dietary, bronchodilator, corticosteroid and progesterone therapy. In an open lung specimen, the search for steroid receptor for estrogen was positive. The discovery in this case of an estrogen receptor represents important evidence for establishing an association between tuberous sclerosis and lymphangiomyomatosis. Tamoxifen therapy and tetracycline pleurodesis were successful in stopping the progressive course and controlling the chylothorax.

Topics: Adhesiveness; Adult; Chylothorax; Female; Humans; Lung Neoplasms; Lymphangiomyoma; Lymphoproliferative Disorders; Neoplasms, Hormone-Dependent; Pleura; Receptors, Estrogen; Tamoxifen; Tetracycline; Tuberous Sclerosis

The treatment of 15 patients with neoplastic pleurisy and 25 with spontaneous pneumothorax occurring for the second time is described. All were given endopleural tetracycline therapy for symphyseal purposes. In the neoplastic pleurisy cases, the treatment reduced the number of thoracenteses required. In only 1 case did spontaneous pneumothorax recur a short time after treatment.

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Central Nervous System Diseases; Female; Humans; Injections; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pleura; Pleurisy; Pneumothorax; Rectal Neoplasms; Skin Neoplasms; Tetracycline

Thirty-three unselected patients with cardiac tamponade secondary to malignant pericardial effusion were treated by intrapericardial instillation of tetracycline hydrochloride. Complete control of the initial signs and symptoms of tamponade was obtained in 30 patients without concomitant chemotherapy or radiotherapy. The procedure did not result in clinically significant complications. Failure of the technique was related to premature removal of the catheter by the patient (one patient) or the inability to totally remove hemorrhagic, clot-filled pericardial fluid (two patients). Survival ranged between 28-704 days and extended survival was related to the performance status and/or chemoradiosensitivity of the primary cancer. No patient successfully treated subsequently developed recurrent cardiac tamponade or alternatively, constrictive pericarditis. Tetracycline pericardial instillation remains a safe, simple, and efficacious treatment of tamponade secondary to malignant disease.

Topics: Adult; Aged; Carcinoma, Bronchogenic; Cardiac Tamponade; Electrocardiography; Female; Heart Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Pericardial Effusion; Radiography; Sclerosing Solutions; Tetracycline

Topics: Aged; Breast Neoplasms; Cardiac Tamponade; Catheterization; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pericardial Effusion; Pericardium; Tetracycline

Salmonella empyema in an immunologically compromised patient with malignant pleural effusion is described. Antimicrobial treatment was ineffective when given parenterally. Intrapleural administration of antibiotics resulted in a rapid rise of the antibacterial activity of the pleural fluid, leading to rapid clinical improvement and eradication of the infections.

Topics: Adenocarcinoma; Empyema; Humans; Lung Neoplasms; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasm Metastasis; Pleural Effusion; Salmonella; Salmonella Infections; Tetracycline; Thyroid Neoplasms

Tumor-seeking radiopharmaceuticals have been employed in the diagnosis of primary neoplasms, in the detection of distant disease, particularly in the localization of tumor foci to facilitate biopsies and the planning of radiation portals, and in assessing the response to tumor therapy. At the present, there is no ideal tumor-scanning agent. However, several approaches appear to be useful and offer promise for further study. The greatest experience has been with Gallium-67, which has major utility in the staging of Hodgkin's disease, in the diagnosis of bronchogenic carcinoma, in the detection of certain metastatic brain tumors, in the identification of recurrent disease, and in the noninvasive diagnosis of leukemic complications. A number of radiolabeled antibiotic and chemotherapeutic agents have shown promise, including tetracycline and bleomycin. A major drawback, however, of these agents which is shared with Gallium-67 is that they appear to be sequestered by inflammatory as well as neoplastic tissue. A most intriguing approach is the use of radiolabeled antibodies to tumor-associated antigens. Animal and clinical experiments have employed antifibrin, antifibrinogen, anticarcinoembryonic antigen, and antiferritin. Theoretically, agents such as these should allow for greater tumor specificity.

Topics: Antibodies, Neoplasm; Bleomycin; Brain Neoplasms; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Gallium Radioisotopes; Hodgkin Disease; Humans; Indium; Leukemia; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Radiography; Radioisotopes; Radionuclide Imaging; Technetium; Tetracycline

Topics: Breast Neoplasms; Drainage; Female; Humans; Lung Neoplasms; Pleural Effusion; Sodium Hydroxide; Tetracycline

The "tetracycline fluorescence test" is considered, as a consequence of the experiments made by various AA., specific for the diagnosis of tumourous cases. With a purpose to confirm its validity, in the broncopleuropulmonary cases, A. examines 30 spittings and 10 pleural fluids of suspicious cases, comparing the results got by means of this test with those of the routine cytohystological examinations. The results confirm 96% positivity with said test against the 60% postivity of the routine cytohystological ones.

Topics: Bronchial Neoplasms; Fluorescence; Lung Neoplasms; Pleural Effusion; Pleural Neoplasms; Sputum; Tetracycline

Topics: Adenocarcinoma; Animals; Carcinoma, Bronchogenic; Carcinoma, Hepatocellular; Gallium; Glioblastoma; Hodgkin Disease; Humans; L-Lactate Dehydrogenase; Liver Neoplasms; Lung Neoplasms; Mediastinal Neoplasms; Methane; Mice; Muscular Diseases; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Nitrosourea Compounds; Osteosarcoma; Rabbits; Radioisotopes; Radionuclide Imaging; Rats; Sarcoma; Sarcoma, Experimental; Technetium; Tetracycline; Transplantation, Homologous

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: Carcinoma, Bronchogenic; Carcinoma, Small Cell; Cyclophosphamide; Humans; Lung Neoplasms; Neoplasm Metastasis; Tetracycline; Time Factors

Topics: Adolescent; Adult; Animals; Antigens, Neoplasm; Blood Proteins; Bone Neoplasms; Child; Child, Preschool; Epitopes; Female; Femoral Neoplasms; Fluoresceins; Humans; Immune Sera; Immunity, Active; Immunity, Maternally-Acquired; Immunization, Passive; Immunodiffusion; Immunoelectrophoresis; Immunotherapy; Infant; Leukocyte Count; Lung Neoplasms; Lymphocyte Activation; Lymphocytes; Male; Neoplasm Metastasis; Neoplasm Transplantation; Osteosarcoma; Rabbits; Skin Tests; Tetracycline; Tibia

Topics: Adult; Aged; Breast Neoplasms; Evaluation Studies as Topic; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Methods; Middle Aged; Neoplasm Metastasis; Pleural Effusion; Radiography, Thoracic; Tetracycline

Topics: Alpha-Globulins; Diagnosis, Differential; Female; Fluorescence; Humans; Lung Neoplasms; Male; Methods; Pleural Effusion; Pneumonia; Sputum; Tetracycline

Topics: Adult; Bone Neoplasms; Cervical Vertebrae; Cobalt Isotopes; Cyclophosphamide; Humans; Lung Neoplasms; Male; Metacarpus; Neoplasm Metastasis; Nose Neoplasms; Petrous Bone; Radiography; Sarcoma, Ewing; Skull Neoplasms; Tetracycline; Thoracic Vertebrae

Topics: Adult; Aged; Diagnosis, Differential; Female; Fluorescence; Humans; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Stomach Diseases; Stomach Neoplasms; Tetracycline

Topics: Adult; Aged; Chronic Disease; Drug Resistance, Microbial; Female; Follow-Up Studies; Humans; Infant; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Pneumococcal Infections; Prospective Studies; Serotyping; Streptococcus pneumoniae; Tetracycline

Topics: Adult; Aged; Female; Fluoroscopy; Humans; Lung Neoplasms; Male; Methods; Middle Aged; Tetracycline

Topics: Adult; Aged; Carcinoma, Bronchogenic; Female; Fluorescence; Humans; Lung Neoplasms; Male; Middle Aged; Tetracycline

Topics: Aspergillosis; Bronchiectasis; Bronchitis; Bronchopneumonia; Cysts; Humans; Lung Abscess; Lung Diseases; Lung Neoplasms; Methacycline; Tetracycline

Topics: Fluorescence; Humans; Lung Neoplasms; Tetracycline

Topics: Bronchial Neoplasms; Carcinoma, Bronchogenic; Cytodiagnosis; Humans; Lung Diseases; Lung Neoplasms; Microscopy, Fluorescence; Pleural Effusion; Tetracycline

Topics: Anti-Bacterial Agents; Fluorescence; Humans; Lung Neoplasms; Neoplasms; Tetracycline

Topics: Bronchial Neoplasms; Carcinoma, Bronchogenic; Cyclophosphamide; Geriatrics; Leukopenia; Lung Neoplasms; Nitrogen Mustard Compounds; Prednisolone; Tetracycline; Toxicology; Urethane

Topics: Adenocarcinoma; Animals; Calcium; Calcium, Dietary; Cortisone; Cricetinae; Fluorescence; Humans; Lung Neoplasms; Neoplasm Transplantation; Research; Tetracycline

Topics: Anti-Bacterial Agents; Biomedical Research; Bronchi; Bronchial Neoplasms; Bronchitis; Chloramphenicol; Drug Resistance; Drug Resistance, Microbial; Haemophilus influenzae; Humans; Lung Diseases; Lung Neoplasms; Neisseria; Pneumococcal Infections; Respiratory Tract Infections; Sputum; Streptomycin; Sulfonamides; Tetracycline