The antibiotics have become so widely and successfully used in the practice of medicine that they are now considered to be essential. Among the antibiotics, the tetracycline group has achieved an enviable reputation for dependable medication, In spite of this, there remain several unanswered questions, One of these pertains to the interesting phenomenon for almost selective localization of tetracycline in certain tumor cells or masses, Although there have been numerous publications dealing with this phenomenon, as the following paragraphs will indicate, there is little agreement as to the factors involved. Indeed, there are some sharply conflicting opinions. The investigations described in this paper were undertaken to obtain information relative to the localization and retention of tetracycline in a transplantable mouse tumor.

No description available.

Development of liposome formulation of an amphiphilic anticancer peptide using the ANTS/DPX leakage assay. The effects of lipid composition on the liposomes' resistance to an amphiphilic cyclic peptide c[KS.S.S.KWL W] were studied by the ANTS/DPX leakage assay. One or more unsaturated acyl chains in the phospholipids, small phospholipid headgroup size, the presence of cholesterol, and the presence of PEG-lipid were demonstrated as critical parameters to stabilize the liposome membrane. A liposome formulation of the peptide comprising POPE/POPC/cholesterol/C16 mPEG 2000 ceramide (20.8:31.2:40:8, mol%) was thereby developed with a peptide-encapsulation efficiency of 47.8%. The liposomal cyclic peptide exhibited dose-dependent toxicity to MCF7 human breast cancer cells and stability under incubation. Design, construction and in vitro characterization of a hydrazone-based convertible liposomal system for anticancer drug delivery. A novel PEG-lipid, PEG2ooo-Hz-DHG, with an acid-labile hydrazone linker between the PEG2ooo head group and the lipidic DHG moiety was synthesized. PEG2000-Hz-DHG was relatively stable at normal physiological pH 7.4, but hydrolyzed more quickly at tumor interstitium pH 6.5-7.0 and endosomal/lysosomal pH 5.0. A novel pH-sensitive "Convertible Liposome System" (CLS) was constructed comprising PEG2ooo-Hz-DHG, positively charged lipid DOTAP, and the zwitterionic phospholipid POPC (8:15:77, mol%). CLS converted from neutrally charged "stealth" liposome to positively charged liposome at tumor interstitual pH owing to the hydrolysis ofPEG2ooo-Hz-DHG. The doxorubicin-encapsulated CLS that had been pre-incubated at pH 6.5 for 30 h exhibited more intensive binding and higher toxicity to Bl6-Fl0 murine melanoma and MDA-MB-435S human breast cancer cells than doxorubicin encapsulated in pH-insensitive stealth liposome.

Although the differential response of malignant cells to hyperthermia was observed at the end of the last century, few investigations into the phenomenon were made until fairly recently. At first the results obtained were inconsistent due mostly to the inefficient techniques in use at the time. The advent of cell and tissue culture, increased knowledge in tumor biology, advances in molecular biology, and the development of equipment which could raise and monitor the temperature of tumors during hyperthermic treatments, have made the study of the effects of supranormal temperature on malignant neoplasias substantially more reliable. The effectiveness of the combined treatment of hyperthermia and drugs has been established. A substantial amount of research to ascertain the most efficient uses of 2 combined treatments (or for finding or screening new drugs) remains to be done.

The availability of drug information that is useful to clinicians is an important need for those responsible for medication use in patients. Physicians, pharmacists, nurses, and patients routinely require access to relevant information related to rational drug therapy. The need for rapid access to relevant information has become increasingly important as the science, technology, and specialization within health care expand. Because of this expansion the literature has increased not only in size but also in complexity. The term drug information (e.g., used in drug information service, drug information center or drug information specialist) is defined as "knowledge of facts or circumstances acquired through reading, study or practical experience concerning the chemical substance intended for use in diagnosis, prevention, treatment or cure of disease or otherwise to enhance the physical or mental well-being of men or animals" (1). This definition may be expanded to include the ability to provide information to the user in a special manner known as a drug information service. Drug information service is defined as "the activities involved with accumulating, organizing, and retrieving drug information and may include provision of documents and bibliographic compilations or other medical library functions" (1).

Thesis (MSc.(Biochemistry)) -- University of Limpopo, 2021 / Drug discovery from medicinal plants continues to play an important role in the development of anticancer agents, this is because medicinal plants are reservoirs of bioactive compounds that exert a plethora of pharmacological effects on human beings. This study aimed to analyse the phytochemical constituents of the Momordica cardiospermoides crude acetone and methanol leaf extracts as well as investigate their potential anti-metastatic effects on the MDA-MB-231 breast cancer cell line. Momordica cardiospermoides leaves were extracted with absolute methanol or acetone to produce crude methanol and acetone extracts, respectively. The extracts were then screened and analysed for phytochemicals using thin layer chromatography, qualitative and quantitative phytochemical tests, and their antioxidant activity was determined using the quantitative 2,2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging activity assay. The fingerprint profiles of the M. cardiospermoides leaf extracts revealed that compounds of the acetone extracts were optimally separated in the nonpolar mobile phase (TAE), whereas those of the methanol extract separated best in the polar mobile phase (EMW), thereby suggesting that the crude acetone and methanol extracts had more non-polar and polar compounds present, respectively. Furthermore, the qualitative phytochemical analysis indicated the presence of various phytochemicals such as flavonoids, steroids, coumarins, and tannins in both plant extracts, however, saponins were found present in the methanol extract and not in the acetone extract. Moreover, quantification of major phytochemicals revealed that the acetone extract had the highest total phenolic content (23.0683 mg GAE/g), total tannin content (22.0442 mg GAE/g) and total flavonoid (32.6933 mg QE/g) content as compared to the methanol extract (14.2349 mg GAE/g, 11.3164 mg GAE/g and 7.692 mg QE/g respectively). The DPPH free radical scavenging activity assay revealed that the extracts exhibited an increase in percentage inhibition/ DPPH scavenging effect, with an increase in extract concentration. The results also revealed that the acetone extract possessed a higher radical scavenging activity as compared to the methanol extract. These results are in correlation with the quantitative analysis of the extracts, as all the major phytochemicals found in higher amounts in the acetone extract have antioxidant properties. The extracts were then assessed in vitro for their cytotoxic effects on MDA MB-231 breast cancer cells and HEK 293 cells using the cell count and viability assay and the results obtained revealed a concentration-dependent decrease in the viability of MDA-MB-231 cells at 24 hours of treatment with either the acetone or methanol extract. Comparatively, treatment of HEK 293 cells with the acetone extract resulted in a significant decrease in the percentage of viable cells, whereas treatment with the methanol extract had no significant effect on the viability of HEK 293 cells, as the percentage of viable cells was maintained at 85–98% at 24 hours of treatment. These results also revealed that the methanol extract is more selective to cancer cells in comparison to the acetone extract, suggesting that the methanol extract is a better antineoplastic candidate. The mode of cell death induced by the methanol or acetone extracts was assessed using the acridine orange and ethidium bromide dual staining assay and the annexin V and dead cell kit. The results from the acridine orange/ethidium bromide dual staining assay showed that both extracts induced nuclei and cellular morphological changes in a concentration-depended manner, at 24 hours of treatment. Moreover, the annexin V and dead assay kit results revealed that the acetone extract induced necrotic cell death, while the methanol extract induced apoptotic cell death. Since the acetone extract was shown to be non-selective towards normal cells and induced necrotic cell death, it was discontinued for further assays. The effect of the methanol extract on MDA-MB-231 cell migration and attachment was determined using the wound healing assay and the adhesion assay. The results revealed that treatment with 150 or 300 µg/ml significantly suppressed MDA-MB-231 cell migration, associated with serpin E1 downregulation and TIMP-1 upregulation, at 24 hours of treatment. Moreover, treatment with the methanol extract also significant inhibited MDA-MB-231 cell adhesion in a concentration-dependent manner, as evident by the decrease in the number of crystal violet stained cells. The effect of the methanol extract on the expression of matrix metalloproteinase-2 and -9 was assessed using western blotting, and the results revealed that the extract significantly downregulated the expression of both MMP-2 and -9, suggesting that the methanol extract has inhibitory effects on MDA-MB-231 cell invasion. The human angiogenesis antibody array kit was then used to determine the effect of the extract on the expression of angiogenesis-related proteins. Treatment with 150 or 300 µg/ml of the extract significantly upregulated the expression levels of tissue inhibitor of metalloproteinases (TIMP) -1 and thrombospondin-1 in a concentration-dependent manner. The results also revealed a significant downregulation in the expression of serpin E1, in a concentration-dependent manner, in comparison to the untreated control. However, the expression of uPA, VEGF, and IGFBP-1, 2 and -3 was upregulated following treatment with 150 and 300 µg/ml of the extract. In conclusion, the current study demonstrated the potential of M. cardiospermoides crude methanol extract as an effective anti-metastatic agent or a source of compounds with anti-metastatic properties / South African Medical Research Council (SAMRC) Research Capacity Development Initiative and National Research Foundation (NRF)

No / Anti-vascular effects of the novel Vinca alkaloid, vinflunine have been investigated in the MAC 15A transplantable murine colon adenocarcinoma model and compared with those induced by the most recently identified clinically useful third generation Vinca. Administration of the maximum tolerated dose of either vinflunine (50 mg kg-1) or vinorelbine (8 mg kg-1) resulted in significant tumour growth delay with subsequent histological analysis revealing substantial haemorrhagic necrosis. This suggested possible anti-vascular effects and these were confirmed by Hoechst 33342 perfusion studies. Vinflunine, currently undergoing Phase I trials in Europe, was found to be at least as effective as the clinically active vincristine and vinorelbine in this model and, remarkably, produced anti-vascular effects at doses much lower than the maximum tolerated dose. Although vinflunine caused apoptosis in HUVEC monolayer cultures this event did not occur within the first 8 hours of exposure whereas vascular shutdown in vivo was observed within the first 4 hours.

No / Aldehyde dehydrogenases (ALDHs) belong to a superfamily of 19 isozymes that are known to participate in many physiologically important biosynthetic processes including detoxification of specific endogenous and exogenous aldehyde substrates. The high expression levels of an emerging number of ALDHs in various cancer tissues suggest that these enzymes have pivotal roles in cancer cell survival and progression. Mapping out the heterogeneity of tumours and their cancer stem cell (CSC) component will be key to successful design of strategies involving therapeutics that are targeted against specific ALDH isozymes. This review summarises recent progress in ALDH-focused cancer research and discovery of small-molecule-based inhibitors.

No description available.

Cheung Sao Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves xxiv-xxxvii). / Abstracts in English and Chinese. / Examination Committee List --- p.i / Declaration --- p.ii / Acknowledgements --- p.iii / Abstract --- p.v / Abstract in Chinese --- p.viii / List of Figures and Tables --- p.x / List of Abbreviations --- p.xix / Table of Content --- p.xxiii / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Human Liver Cancer --- p.1 / Chapter 1.1.1 --- Incidence of Hepatocellular Carcinoma --- p.1 / Chapter 1.1.2 --- Causes and Symptoms of Hepatocellular Carcinoma --- p.4 / Chapter 1.1.3 --- Treatment Options for Hepatocellular Carcinoma --- p.4 / Chapter 1.1.4 --- Multi-drug Resistance --- p.5 / Chapter 1.1.4.1 --- Mechanisms of Multi-drug Resistance --- p.5 / Chapter 1.2 --- Traditional Chinese Medicine --- p.10 / Chapter 1.2.1 --- Sophora flavescens and Radix Sophorae --- p.10 / Chapter 1.2.2 --- Flavonoid and its Sub-classification --- p.13 / Chapter 1.2.3 --- Flavonoid and Human Health --- p.15 / Chapter 1.3 --- Cell Death --- p.17 / Chapter 1.3.1 --- Necrosis --- p.17 / Chapter 1.3.2 --- Apoptosis --- p.17 / Chapter 1.3.3 --- Signaling Pathways in Apoptosis --- p.18 / Chapter 1.3.3.1 --- Extrinsic (Death Receptor-mediated) Pathway --- p.20 / Chapter 1.3.3.2 --- Intrinsic (Mitochondrial) Pathway --- p.21 / Chapter 1.3.3.3 --- Cysteine Aspartatic Acid Proteases --- p.21 / Chapter 1.4 --- Research Objective (s) --- p.22 / Chapter Chapter 2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.1 --- Materials --- p.23 / Chapter 2.1.1 --- Cell Lines --- p.23 / Chapter 2.1.1.1 --- HepG2 --- p.24 / Chapter 2.1.1.2 --- RHepG2 --- p.24 / Chapter 2.1.1.3 --- WRL-68 --- p.25 / Chapter 2.1.2 --- Culture Media --- p.26 / Chapter 2.1.2.1 --- Rosewell Park Memorial Institute( RPMl) 1640 Medium --- p.26 / Chapter 2.1.2.2 --- Dulbecco's Modified Eagle's Medium (DMEM) --- p.26 / Chapter 2.1.3 --- Animals --- p.27 / Chapter 2.2 --- Traditional Chinese Medicines and Conventional Anti-cancer Drugs --- p.27 / Chapter 2.3 --- Antibodies --- p.29 / Chapter 2.4 --- Chemicals --- p.30 / Chapter 2.5 --- Reagents and Buffers --- p.34 / Chapter 2.5.1 --- Reagents for Silica Gel Column Chromatography --- p.34 / Chapter 2.5.2 --- Buffers for Common Use --- p.34 / Chapter 2.5.3 --- Reagents for Cell Viability Assay --- p.35 / Chapter 2.5.4 --- Reagents and Buffers for Typical Apoptosis Experiments --- p.35 / Chapter 2.5.4.1 --- Cell Cycle Analysis --- p.35 / Chapter 2.5.4.2 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.35 / Chapter 2.5.4.3 --- DNA Fragmentation Detection --- p.35 / Chapter 2.5.5 --- Reagents and Buffers for Western Blot Study --- p.36 / Chapter 2.5.5.1 --- Whole-cell Protein Extraction --- p.38 / Chapter 2.5.5.2 --- Mitochondrial and Cytosolic Fraction Protein Extraction --- p.38 / Chapter 2.5.6 --- Reagents and Buffers for Mitochondrial Transmembrane Potential Depolarization Measurement --- p.39 / Chapter 2.5.7 --- Reagents and Buffers for in vivo Animal Study --- p.39 / Chapter 2.5.8 --- Reagents and Buffers for Two-Dimensional Gel Electrophoresis --- p.40 / Chapter 2.5.8.1 --- Sample Preparation --- p.40 / Chapter 2.5.8.2 --- First Dimension Gel Electrophoresis - Isoelectric Focusing (IEF) --- p.40 / Chapter 2.5.8.3 --- Second Dimension Gel 日ectrophoresis - SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.40 / Chapter 2.5.8.4 --- Silver Staining --- p.41 / Chapter 2.5.9 --- Reagents for Mass Spectrometry Preparation --- p.42 / Chapter 2.5.9.1 --- Destaining --- p.42 / Chapter 2.5.9.2 --- Trypsin Digestion --- p.42 / Chapter 2.5.9.3 --- Desalting of Peptide Mixture --- p.43 / Chapter 2.5.10 --- Reagents and Buffers for Real-Time PCR --- p.43 / Chapter 2.6 --- Methods --- p.44 / Chapter 2.6.1 --- Isolation of Bioactive Constituents by Silica Gel Column Chromatography --- p.44 / Chapter 2.6.2 --- Cell Viability Assay --- p.45 / Chapter 2.6.3 --- Typical Apoptosis Experiments --- p.45 / Chapter 2.6.3.1 --- Cell Cycle Analysis --- p.46 / Chapter 2.6.3.2 --- Annexin V-FITC/ PI Staining Experiment --- p.47 / Chapter 2.6.3.3 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.48 / Chapter 2.6.3.4 --- DNA Fragmentation Reaction --- p.48 / Chapter 2.6.4 --- Western Blot Study --- p.49 / Chapter 2.6.4.1 --- Whole-cell Protein Extraction --- p.49 / Chapter 2.6.4.2 --- Mitochondrial and Cytosolic Fraction Protein Extraction --- p.50 / Chapter 2.6.5 --- Caspase Activity Determination --- p.54 / Chapter 2.6.6 --- Mitochondrial Transmembrane Potential Depolarization Measurement --- p.55 / Chapter 2.6.7 --- in vivo Animal Study --- p.56 / Chapter 2.6.8 --- Two-Dimensional Gel Electrophoresis --- p.58 / Chapter 2.6.8.1 --- Sample Preparation --- p.58 / Chapter 2.6.8.2 --- First Dimension Electrophoresis - Isoelectric Focusing (IEF) --- p.59 / Chapter 2.6.8.3 --- Second Dimension Electrophoresis - SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.60 / Chapter 2.6.8.4 --- Silver Staining --- p.61 / Chapter 2.6.9 --- Mass Spectrometry Preparation --- p.63 / Chapter 2.6.9.1 --- Destaining and Trypsin Digestion --- p.63 / Chapter 2.6.9.2 --- Peptide Extraction --- p.63 / Chapter 2.6.9.3 --- Desalting of Peptide Mixture --- p.64 / Chapter 2.6.10 --- Real-Time PCR --- p.65 / Chapter 2.6.11 --- Cellular Glutathione Level Detection --- p.69 / Chapter 2.7 --- Statistical Analysis --- p.70 / Chapter Chapter 3 --- RESULTS AND DISCUSSIONS - CYTOTOXICITY OF FLAVONOIDS ISOLATED FROM RADIX SOPHORAE --- p.72 / Chapter 3.1 --- Screening of Cytotoxic Flavonoids from Radix Sophorae --- p.72 / Chapter 3.2 --- Cytotoxicity of Leachianone A on Human Hepatoma Cell Lines --- p.74 / Chapter 3.3 --- Cytotoxicity of Leachianone A on Human Normal Liver Cell Line --- p.77 / Chapter 3.4 --- Cytotoxicity of Sophoraflavone J on Human Hepatoma Cell Line --- p.79 / Chapter 3.5 --- Cytotoxicity of Sophoraflavone J on Human Normal Liver Cell Line --- p.79 / Chapter 3.6 --- Cytotoxicities of Cisplatin and Taxol on Human Hepatoma as well as Normal Liver Cell Lines --- p.81 / Chapter 3.7 --- Conclusion --- p.86 / Chapter Chapter 4 --- "RESULTS AND DISCUSSIONS - MECHANISTIC STUDY OF LEACHIANONE A-INDUCED CELL DEATH IN HEPATOMA CELLS, HepG2 and RHepG2" --- p.88 / Chapter 4.1 --- Promotion of Cell Cycle Arrest --- p.88 / Chapter 4.2 --- Induction of Apoptosis as Evidenced by Phosphatidylserine Externalization and DNA Fragmentation --- p.93 / Chapter 4.2.1 --- Occurrence of Phosphatidylserine Externalization --- p.94 / Chapter 4.2.2 --- DNA Fragmentation Detection --- p.99 / Chapter 4.2.2.1 --- Terminal Deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick End Labeling (TUNEL) Assay --- p.99 / Chapter 4.2.2.2 --- DNA Laddering Pattern in Agarose Gel Electrophoresis --- p.103 / Chapter 4.3 --- Recruitment of Multiple Signaling Pathways in Leachianone A-induced Apoptosis --- p.105 / Chapter 4.3.1 --- "Activation of Caspases-3, -8, and -9" --- p.105 / Chapter 4.3.2 --- Altered Expressions of Bcl-2 Family Proteins --- p.112 / Chapter 4.3.3 --- Loss of Mitochondrial Membrane Potential --- p.115 / Chapter 4.4 --- in vivo Tumor Growth Inhibition in HepG2-bearing Nude Mice --- p.121 / Chapter 4.5 --- Conclusion --- p.127 / Chapter Chapter 5 --- RESULTS AND DISCUSSIONS - MECHANISTIC STUDY OF SOPHORAFLAVONE J-INDUCED CELL DEATH IN HEPATOMA CELLS HepG2 --- p.132 / Chapter 5.1 --- Execution of Cellular Apoptosis --- p.133 / Chapter 5.2 --- Involvement of Multiple Signaling Pathways in Sophoraflavone J-induced Apoptosis --- p.138 / Chapter 5.3 --- Differential Proteomes of Control and Sophoraflavone J-treated HepG2 Cells --- p.148 / Chapter 5.4 --- Conclusion --- p.167 / Chapter Chapter 6 --- OVERALL CONCLUSION AND FUTURE PERSPECTIVES --- p.169 / References --- p.xxiv