Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we report evidence of the damage effects of sonodynamic therapy (SDT) on a novel intracellular target, cytoskeletal F-actin, that has great importance for cancer treatment. Ehrlich ascites carcinoma (EAC) cells suspended in PBS were exposed to ultrasound at 1.34 MHz for up to 60s in the presence and absence of protoporphyrin IX (PPIX). To evaluate the polymeric state and distribution of actin filaments (AF) we employed FITC-Phalloidin staining. The percentage of cells with intact AF was decreased with 10-80 microM PPIX after ultrasonic exposure, while only few cells with disturbed F-actin were observed with 80 microM PPIX alone. The fluorescence intensity of FITC-Phalloidin labeled cells was detected by flow cytometry. The morphological changes of EAC cells were observed by scanning electron microscope (SEM). The nuclei were stained with Hoechst 33258 to determine apoptosis. Cytoskeletal F-actin and cell morphological changes were dependent on the time after SDT. Some cells suffered deformations of plasma membrane as blebs that reacted positively to FITC-Phalloidin at 2h after SDT treatment. Many of the cells showed the typically apoptotic chromatin fragmentation. The alterations were more significant 4h later. Our results showed that cytoskeletal F-actin might represent an important target for the SDT treatment and the observed effect on F-actin and the subsequent bleb formation mainly due to apoptosis formation due to the treatment.
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PMID:Damage effects of protoporphyrin IX - sonodynamic therapy on the cytoskeletal F-actin of Ehrlich ascites carcinoma cells. 1861 92

Intravenous administration of bacteria leads to their accumulation in tumors and to sporadic tumor regression. We therefore explored the hypothesis that Salmonella typhimurium engineered to express the proapoptotic cytokine Fas ligand (FasL) would exhibit enhanced antitumor activity. Immunocompetent mice carrying tumors derived from syngeneic murine D2F2 breast carcinoma or CT-26 colon carcinoma cells were treated intravenously with FasL-expressing S. typhimurium or with phosphate-buffered saline (PBS; control). Treatment with FasL-expressing S. typhimurium inhibited growth of primary tumors by an average of 59% for D2F2 tumors and 82% for CT-26 tumors (eg, at 25 days after initial treatment, mean volume of PBS-treated CT-26 colon carcinomas = 1385 mm(3) and of S. typhimurium FasL-treated CT-26 tumors = 243 mm(3), difference = 1142 mm(3), 95% confidence interval = 800 mm(3) to 1484 mm(3), P < .001). Pulmonary D2F2 metastases (as measured by lung weight) were reduced by 34% in S. typhimurium FasL-treated mice compared with PBS-treated mice. FasL-expressing S. typhimurium had similar effects on growth of murine B16 melanoma tumors in wild-type mice but not in lpr/lpr mice, which lack Fas, or in mice with disrupted host inflammatory responses. Antitumor activity was achieved without overt toxicity. These preclinical results raise the possibility that using attenuated S. typhimurium to deliver FasL to tumors may be an effective and well-tolerated therapeutic strategy for some cancers.
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PMID:Inhibition of tumor growth using salmonella expressing Fas ligand. 1866 57

Hematoporphyrin derivative (HPD), a sensitizer used in photodynamic therapy (PDT) of malignancies, is progressively destroyed during the treatment. Prior studies suggested that upon PDT the photobleaching of HPD in tumor tissues is largely mediated by self-sensitized singlet oxygen. However, little is known about the role of other reactive oxygen species (ROS). The main aim of this work was to clarify the significance of H2O2, superoxide (O2.(-)) and hydroxyl (OH.) radicals in bleaching of HPD in tumor cells subjected to PDT. Experiments were performed on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in PBS and then irradiated with red light at 630 nm in the same buffer. Studies showed that photosensitization of EAC cells by HPD led to the formation of significant amounts of H2O2, O2.(-) and OH., and that these ROS could be involved in the photobleaching of HPD during PDT. In fact, we found that addition of catalase (CAT, a scavenger H2O2), Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Tiron (scavengers of O2.(-)), Na-benzoate, mannitol and deferoxamine (scavengers of OH.) caused a substantial decrease in the rate of HPD photobleaching in EAC cells. In these cells, the inhibitory effects of Na-benzoate, mannitol and deferoxamine on the photodegradation of HPD correlated well with suppression of the OH. generation, a highly active oxidizer. In EAC cells, the glutathione redox cycle and CAT (scavengers of H2O2) as well as Cu/Zn-SOD was found to suppress the photoinduced degradation of HPD. It was also established that HPD can directly scavenge H2O2 and oxygen free radicals; in a phosphate buffer its second-order rate constants were measured as 5.51+/-0.32 x 10(3)M(-1)s(-1) (for the reaction with O2.(-)), 5.08+/-0.31 x 10(4)M(-1)s(-1) (for H2O2), and 3.44+/-0.08 x 10(10)M(-1)s(-1) (for OH.). Thus, our data suggest that OH. could be one of the main oxidants mediating the photobleaching behavior of HPD in malignancies. Studies showed that photoexcited moieties of HPD can oxidize cell proteins with the formation of protein peroxides (PPO), which currently are regarded as a new form of ROS. Model experiments suggest that PPO could also participate in bleaching of HPD in tumors treated with PDT. It was found that HPD may destroy in tumor cells after cessation of photoirradiation and that this event is largely mediated by the presence of H2O2, a precursor of OH(.).
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PMID:Active oxygen intermediates in the degradation of hematoporphyrin derivative in tumor cells subjected to photodynamic therapy. 1876 Jun 22

In this study we investigated cytotoxic, mutagenic and genotoxic effects of different concentrations of wastewater from the phosphoric gypsum depot near the factory for fertilizing agents 'INA Petrokemija' (Kutina, Croatia). The Ames test was performed on Salmonella typhimurium TA98 and TA100 strains, in the presence of S9 mix, glutathione and buffer, respectively. Cytotoxicity was studied on human laryngeal carcinoma cells (HEp2) and human cervical cells (HeLa). The level of lipid peroxidation in these two cell lines was evaluated in parallel. To establish the levels of primary DNA damage, the alkaline comet assay was performed on treated human peripheral blood leukocytes. No mutagenic effects of phosphoric gypsum on Salmonella typhimurium strains in the presence of S9 mix, GSH or PBS were observed. However, strong cytotoxic effect was observed on both human cell lines when they were treated with different concentrations of wastewater. Lipid peroxidation was induced and increased by prolonged time of incubation, highlighting that the damage was not repaired, but increased with the time of incubation. The results of the alkaline comet assay indicate significant DNA damaging potential of wastewater for human leukocytes. Since phosphoric gypsum transport water in its present composition and acidity is highly toxic and acts as prooxidant, causing free radicals formation and DNA damage, urgent neutralization/purification of the wastewater to a level acceptable for disposal into the environment is mandatory.
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PMID:The assessment of genotoxic effects of wastewater from a fertilizer factory. 1878 84

As an effort to prepare new efficient gene delivery vectors, we have recently developed and reported an amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) D(2)-PLLA-D(2) with two-generation PLL dendrons and a PLLA block. In this work, we continued to explore the roles of dendritic PLL generation in DNA binding and intracellular delivery of gene, and a new series of amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine)s D(n)-PLLA-D(n) (n = 3-5) were synthesized and were structurally characterized. Furthermore, plasmid DNA binding affinity for these cationic amphiphiles was examined by agarose gel electrophoresis and fluorescence titration assay in pure water and PBS buffer solution containing 150 mM NaCl (pH = 7.4), respectively. By dynamic light scattering (DLS) and transmission electronic microscopy (TEM), the interaction and complexation in between were investigated, concerning the DNA/vector polyplex particle morphologies and zeta potentials. Utilizing a human hepatocellular carcinoma cell-line SMMC-7721, cell toxicity, and gene transfection in vitro were explored. To further improve transgene efficiency for these synthetic cationic amphiphiles as gene delivery vectors, new structural DE(n)-PLLA-DE(n) (n = 2-3) were prepared through an amino termini modification of the D(n)-PLLA-D(n) (n = 2-3) with less toxic 4,7,10,13-tetraazatridecanoic acids, and gene transfection with these DE(n)-PLLA-DE(n) (n = 2-3) was examined with an alternative human gastric carcinoma cell-line HGC-27. As a result, the high plasmid DNA binding affinity, low cytotoxicity, and much enhanced transgene efficacy suggest a new possible clue to design effective synthetic gene delivery vectors with amphiphilic skeleton and less toxic polyamine building blocks.
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PMID:Dendritic poly(L-lysine)-b-Poly(L-lactide)-b-dendritic poly(L-lysine) amphiphilic gene delivery vectors: roles of PLL dendritic generation and enhanced transgene efficacies via termini modification. 1958 45

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic disease of unknown etiology characterized by vague bladder pain and nonspecific urinary symptoms, such as urgency and frequency. Although it was initially considered to be a rare condition, its prevalence has significantly increased, possibly because of different definitions used and greater physician awareness. Because of the multiple diagnostic criteria used, there is significant variation in its prevalence. In addition, there is often a delay in the diagnosis of PBS/IC. It affects predominantly women of middle age, and it significantly decreases quality of life. Diagnosis of PBS/IC is mainly a diagnosis of exclusion; there are no characteristic symptoms or pathognomonic findings. Therefore, it is important to rule out diseases that have a similar clinical picture (i.e., urinary infections, bladder carcinoma) but definite therapies and worse prognosis if left untreated. PBS/IC management suffers from lack of evidence; many therapies are empiric or based on small studies and case series. Treatment includes supportive therapies (psychosocial, behavioral, physical), oral treatments, and intravesical treatments, whereas other more invasive treatments such as electric neuromodulation and reconstructive surgery are reserved for refractory cases. Physicians should always keep in mind the diagnosis of PBS/IC in patients presenting with chronic urinary symptoms after excluding other more common diseases.
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PMID:Interstitial cystitis: an unsolved enigma. 1980 25

G22, an anti-idiotype single chain antibody screened from human nasopharyngeal carcinoma phage anti-idiotype antibody library, has been already identified by He et al. G22 DNA vaccine was produced by cloning G22 gene and inserting the cloned gene into pcDNA3.1. To investigate the immunogenicity of pcDNA3.1-G22, C57BL/6 mice were immunized with the vaccine, pcDNA3.1 and PBS individually and the antibody response, T cell phenocyte at the 15th, 22th, 29th, 36th day after the last immunity were detected. In the tumor protection experiment, the immunized mice were then challenged with CMT-93-G22 cells or CMT-93-mock cells. The tumor size and the survival time of the animals were compared between these groups. The results showed that DNA vaccine pcDNA3.1-G22 could raise G22-specific humoral and cellular immune responses. Furthermore, pcDNA3.1-G22 could prolong the survival time and lessen the tumor size of the CMT-93-G22-bearing mice but had no protection effect on the mice attacked by CMT-93-mock cells. These results were expected to lay foundation for further studies on the clinical application of pcDNA3.1-G22 DNA vaccine.
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PMID:Immunogenicity and efficacy of a DNA vaccine encoding a human anti-idiotype single chain antibody against nasopharyngeal carcinoma. 2011 60

Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment.
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PMID:Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice. 2020 45

Vasculature is essential for the sustained growth of solid tumors and metastases. Tumor cells surviving vascular-disruptive therapeutic intervention (especially those present at the tumor rim) can contribute to tumor regrowth. The aim was to strengthen, by carrier-mediated delivery of a chemotherapeutic, the curative effects of a bifunctional anti-vascular oligopeptide capable of inducing vascular shutdown and tumor shrinkage. For the in vitro experiments and animal therapy, ACDCRGDCFC-GG-(D)(KLAKLAK)(2) peptide (900 microM in D-PBSA, i.e. Dulbecco's PBS without Ca(2+) and Mg(2+)) and size-calibrated, passively or actively targeted liposomes based on distearoylphosphatidylcholine, cholesterol, and N-carbamoyl-methoxypolyethyleneglycol coupled to distearoylphosphatidylethanolamine (PEG-DSPE) and containing gradient-entrapped doxorubicin were used. The KB (human nasopharyngeal carcinoma) cell line overexpressing folate receptors was used in the fluorescence studies of liposomal uptake. The B16-F10 melanoma cell line was used for confirming, by flow cytometry and confocal microscopy, doxorubicin intracellular transfer as well as to induce experimental tumors in C57BL/6 mice. Animal therapy was achieved with injections of vascular-disrupting peptide, doxorubicin-loaded liposomes, or alternating combined therapy. The results (tumor growth inhibition and survival) were compared using the Mann-Whitney U test and the log-rank test. Necrosis in H&E-stained tumor sections was assessed microscopically by pathologists. Treatment of C57BL/6 mice bearing B16-F10 experimental tumors with a combination of vascular-disruptive peptide and doxorubicin-carrying pegylated liposomes (either passively targeted liposomes (PTL) or folate receptor targeted) gave better therapeutic effects when tumor development was re-challenged with a second cycle of combined therapy. Marked inhibition of tumor growth and a statistically significant extension of the lifespan of the treated mice were observed when the re-challenge involved the use of folate receptor-targeted liposomes (FTL). Anticancer therapy involving vascular-disruptive peptide and doxorubicin delivered via pegylated folate receptor-targeted liposomes is more effective than either monotherapy, especially when tumor growth is re-challenged with the therapeutic combination.
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PMID:Experimental anticancer therapy with vascular-disruptive peptide and liposome-entrapped chemotherapeutic agent. 2038 51

Ascorbate and menadione (Apatone) in a ratio of 100:1 kills tumor cells by autoschizis. In this study, vitamin-induced changes in nucleolar structure were evaluated as markers of autoschizis. Human bladder carcinoma (T24) cells were overlain with vitamins or with culture medium. Supernatants were removed at 1-hr intervals from 1 to 4 hr, and the cells were washed with PBS and prepared for assay. Apatone produced marked alterations in nucleolar structure including redistribution of nucleolar components, formation of ring-shaped nucleoli, condensation and increase of the proportion of perinucleolar chromatin, and the enlargement of nucleolar fibrillar centers. Immunogold labeling of the nucleolar rRNA revealed a granular localization in treated and sham-treated cells, and immunogold labeling of the rDNA revealed a shift from the fibrillar centers to the condensed perinucleolar chromatin. Fibrillarin staining shifted from the fibrillar centers and adjacent regions to a more homogeneous staining of the entire nucleolus and was consistent with the percentage of autoschizic cells detected by flow cytometry. Because autoschizis entails sequential reactivation of DNase I and DNase II, and because the fibrillarin redistribution following DNase I and Apatone treatment is identical, it appears that the nucleolar and fibrillarin changes are markers of autoschizis.
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PMID:Nucleolar changes and fibrillarin redistribution following apatone treatment of human bladder carcinoma cells. 2038 87


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