In this research we aimed to investigate the anti-proliferative properties of three South African plants: Kedrostis foetidissima, Euphorbia mauritanica and Elytropappus rhinocerotis against breast cancer cells. This was done on the basis of their documented ethno-medicinal use against cancer and other ailments. The plant extracts were screened for cytotoxicity and pro-apoptotic activity against two breast cancer cell lines MCF-7 and YMB-1. With an IC50 ~ 100 μg/ml, K. foetidissima was the only extract that exhibited significant cytotoxicity on both cell lines, whilst E. mauritanica was cytotoxic to MCF-7 cells only. The cytotoxicity assay was followed by the Annexin-V detection assay to evaluate the occurrence of apoptosis. The results observed suggested that K. foetidissima was inducing significant apoptosis on both YMB-1 and MCF-7 cells, whilst E. mauritanica was inducing significant apoptosis on MCF-7 cells. Since both K. foetidissima and E. mauritanica crude extracts induced apoptosis to MCF-7 cells, they were selected for gene expression studies on MCF-7 using real-time PCR. This was done with the aim of investigating if these extracts were having an effect on the tumour suppressors p53 and RBBP6, which were shown in previous studies to be deregulated in up to 50% of cancers. From the real-time PCR data we observed no changes in the expression levels of these genes following treatment with the herbal extracts. This may suggest that these plants have an effect on other components of the apoptotic pathway other than the tumour suppressors p53 and RBBP6. The antiproliferative activity observed whilst treating these particular cell lines with K. foetidissima and E. mauritanica suggests that these South African herbal plants present themselves as potential future cancer therapeutic agents; however, further studies on these herbal plants need to be performed to validate these results. KEYWORDS: Apoptosis Breast cancer Euphorbia mauritanica Kedrostis foetidissima p53

With the rising rates of heart disease incidents in the United States and the increase in lung cancer deaths as well, many individuals suffer and get their treatments compromised due to these diseases. Especially considering that many lung cancer and heart disease patients are over 70 years of age, treatment options and success rates drop significantly. Due to this, a great concern is raised for patients with co-existing heart disease and lung cancer. This was a case-control study that assessed lung cancer treatment options and success rates for patients with co-existing heart disease. We used research papers that discussed lung cancer treatment success in patients with heart disease to gather data on the subject. Furthermore, we used the 2020 NHIS to gather demographic data on the interviewed adults who answered the questions regarding lung cancer and heart disease. At the start, we hypothesized that there wasn’t going to be a high success rate for lung cancer treatment in patients with heart disease due to the invasive nature of the treatment available. We found that most patients with pre-existing heart disease that sought lung cancer treatment had their condition worsened due to severe invasive treatments such as chemotherapy and radiotherapy. In most surgical lung cancer treatment options, patients with pre-existing heart disease were more likely to die after the operation than patients without pre-existing heart disease. Currently and in future times, it’s more likely to find individuals with both diseases due to the rising culture which endorses poor habits in eating, alcohol consumption, smoking, and the utilization of drugs. Understanding the difficulty and dangers that are found in current treatment options for heart disease patients suffering from lung cancer will allow for innovation and improvement in treating such patients.

Cancer is a leading cause of death in the United States and the world. Based on the literature, the side effects of prolonged use of cancer treatment pose a threat to the patient's treatment compliance and efficacy. This study aims to determine the extent to which calorie restriction and fasting can improve the efficacy of cancer treatments, tolerability of cancer treatments, and compliance with cancer treatments through a systematic review. The search for studies involved the use of key terms and extenders based on population, intervention, comparator, outcomes, and study designs (PICOS) framework including participants receiving cancer treatment, dietary interventions, and cancer treatment outcomes. All search results were uploaded to Covidence® software and two independent blinded reviewers screened the studies, and three independent reviewers extracted the data. Studies were first screened based on the title and abstract, and then they were screened based on the full text. If the synthesized data had similar characteristics and there were enough studies available, then the meta-analysis would be performed. While Riedinger et al., Voss et al., and de Groot et al. did not find any significant difference in treatment efficacy between fasting and control groups, the earlier study done by de Groot et al. showed that the effects of fasting can show significant improvement in decreasing the amount of DNA damage in noncancerous cells. Regarding the effects of fasting and calorie restriction on patient tolerability when receiving chemotherapy or radiotherapy, all studies covering the effect demonstrate a trend suggesting that there is no significant difference between the dietary intervention groups and control groups. Overall, there is not enough information from these studies to conclude the effect of fasting on treatment compliance.

Gliomas are aggressive glial cell tumors that are nearly impossible to treat successfully, yielding strikingly low survival rates for patients. Glioblastomas, the most severe type of gliomas, have even poorer prognoses. In the past decade, new literature has shown that H19, a long non-coding RNA (lncRNA), is not only highly expressed in human gliomas, but that it plays several important roles in glioma progression and can even impede certain treatment measures. H19 directly and indirectly promotes several features of glioma cells including their survival, growth, migration, invasion, metastasis – essentially every stage of glioma development – and even stemness. Simply knocking down H19, in vitro, hampered every single one of these features to some degree. High H19 levels have also been linked to a lack of response to temozolomide and radiation treatments, two of the main therapeutic methods currently used to target gliomas. In vivo observations also followed this pattern of high H19 levels correlating with glioma tumorigenicity. So far, due to the accumulation of such findings, H19 has already become valued as both a prognostic and theragnostic marker. However, having seen how damaging H19 knockdown is to gliomas, there is no reason the role of H19 should be limited to that of an indicator; rather, the proto-oncogenic lncRNA should be viewed as a potential therapeutic target. Moreover, given that high H19 expression is an attribute unique to the human embryo stage, any instances of upregulation are typically oncogenic in nature, making H19 an ideal target for cancer therapy. Thus, targeting H19 in glioma patients should be integrated into existing treatment plans as this will obstruct glioma tumorigenesis, improve responsiveness to other therapies, and is not likely to impede normal biological functions.

No description available.

Biological screening of extracts of various bryophytes showed that the species Dicranum fulvum gave extracts with activity in both <u>in vitro</u> and <u>in vivo</u> bioassays. This plant was thus selected for extraction and fractionation, monitored by i<u>in vitro</u> bioassays. Isolation was guided by a combination of bioassay and chemical methods, and led to the isolation of three compounds, betulin, 9,l9- cyclolanostâ 23â eneâ 3,25â diol, and B-sitosterol. Purification was achieved by open column, flash column, gel filtration, thin layer chromatography, the chromatotron and crystallization. The isolated compounds were identified by comparisons of spectroscopic data with those of authentic samples and the matching of experimental and literature melting points and optical rotations. / Master of Science

Systemic chemotherapy is a major therapeutic approach for nearly all types and stages of cancer. Success of this treatment depends not only on the efficacy of the therapeutics but also on the transport of the drug to all tumor cells in sufficient concentrations. Intratumoral drug transport is limited by characteristics of the tumor microenvironment such as elevated interstitial pressure and sparse, irregular vascularization. Moreover, poor tumor selectivity, leads to systemic toxicity. Bacteria possess a host of characteristics that address the aforementioned challenges in conventional drug delivery approaches including tumor selectivity, preferential tumor colonization, effective tumor penetration, which can be augmented via genetic engineering. However, in clinical trials conducted to date, bacteria have rarely been able to inhibit tumor growth solely by their presence in the tumor. The overall goal of this doctoral dissertation is to develop a novel tumor treatment system based on Salmonella Typhimurium VNP20009 (genetically modified for preferential tumor colonization and attenuation) coupled with biodegradable copolymer, poly(lactic-co-glycolic acid) nanoparticles, hereafter referred to as NanoBEADS (Nanoscale Bacteria Enabled Autonomous Drug Delivery System). To this end, a NanoBEADS fabrication procedure that is robust and repeatable was established and a microfluidic chemotaxis-based sorting platform for the separation NanoBEADS from unattached nanoparticles was developed. The transport efficacy of NanoBEADS compared to the commonly used passively-diffusing nanoparticle was investigated in vitro and in vivo and the intratumoral penetration of the therapeutic vectors was quantified using a custom image processing algorithm. The mechanism of intratumoral penetration was elucidated through 2D and 3D invasion assays. Lastly, we developed a biophysical model of intratumoral transport of NanoBEADS based on the intratumoral penetration experimental results towards the theoretical evaluation of the drug transport profile following the administration of NanoBEADS. / PHD / Currently, the transport of chemotherapeutic drugs into tumors is limited by numerous characteristics of the tumor microenvironment. This problem is exacerbated by poor tumor selectivity, leading to severe side effects to patients. Bacteria possess a host of characteristics that address the aforementioned shortcomings in conventional drug delivery approaches including preferential tumor colonization and anti-tumor effects, which may be mediated naturally or enhanced via genetic engineering. The overall goal of this doctoral dissertation is to develop a novel tumor treatment system based on genetically modified bacteria for safety and efficiency, Salmonella Typhimurium VNP20009 coupled with a polymeric nanoparticles, hereafter referred to as NanoBEADS (Nanoscale Bacteria Enabled Autonomous Drug Delivery Systems). To this end, a NanoBEADS fabrication procedure that is robust and repeatable was established and a microfluidic chemotaxis-based sorting platform for the separation NanoBEADS from unattached nanoparticles was developed. The transport efficiency of NanoBEADS compared to the commonly used nanoparticle was investigated in vitro and in vivo and the intratumoral penetration of the therapeutic vectors was quantified using a custom image processing algorithm. The mechanism of intratumoral penetration was elucidated through 2D and 3D invasion assays. Lastly, we developed a biophysical model of intratumoral transport of NanoBEADS based on the intratumoral penetration experimental results towards the theoretical evaluation of the drug transport profile following the administration of NanoBEADS.

Yes / Boron neutron capture therapy (BNCT) has a long history of unfulfilled promises for the treatment of aggressive cancers. In the last two decades, chemists, physicists, and clinical scientists have been coordinating their efforts to overcome practical and scientific challenges needed to unlock its full therapeutic potential. From a chemistry point of view, the two current small-molecule drugs used in the clinic were developed in the 1950s, however, they both lack some of the essential requirements for making BNCT a successful therapeutic modality. Novel strategies are currently used to design new drugs, more selective towards cancer cells and tumours, as well as able to deliver high boron contents to the target. In this context, macromolecules, including polymers, are promising tools to make BNCT an effective, accepted, and front-line therapy against cancer. In this review, we will provide a brief overview of BNCT, and its potential and challenges, and we will discuss the most promising strategies that have been developed so far.

Modifications of the potent anticancer agent taxol were carried out in order to gain an understanding of the chemical reactivity of the drug and the factors which contribute to its biological activity. The C-2' and/or the C-7 hydroxyl groups of taxol were substituted with acetyl, ßalanyl, silyl, succinyl, trichloroethyloxycarbonyl or carbonate linked dibenzylidene protected glucosyl groups. The C-7 position was selectively epimerized under free radical conditions and a 2'-epiacetyltaxol was produced via base catalysed epimerization. The C-2' amide became nucleophilic in the presence of base and could attack a C-2; acyl substituent. The C-13 ester side chain was selectively reduced by borohydride. The 7 position of taxol was selectively oxidized by Jones reagent and longer reaction times also oxidized the 2' position. The D rings of the 7 oxotaxols were readily opened via beta elimination; hydrogenation of the double bond in the enone of the D seco products produced a product in which the C ring was opened. The D ring was also susceptible to electrophilic attack. Reaction of taxol with triethyloxonium tetrafluoroborate or acetyl chloride/HC1 produced D seco taxols. C-7 deoxygenation was not achieved due to steric hindrance at C-7 and the instability of taxol under free radical conditions. Biological testing of modified taxols showed that substitution of the C-2' hydroxyl removed biological activity but that C-2' acyl groups were readily removed vivo. The water soluble 2'-βalanyItaxol possessed in vivo activity equal to that of taxol. Substitution of the C-7 hydroxyl did not inhibit the ability of a taxol derivative to polymerize tubulin but did decrease in vivo activity; epimerization of C-7 decreased in vivo activity slightly. A 2'-oxotaxol was found to be less active than, but still comparable to, its nonoxidized analogue. All taxol derivatives having a 7-oxo group and/or not possessing a D ring lost almost all biological activity. / Ph. D.

Cheung, Wing Ki. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 100-112). / Abstracts in English and Chinese. / Acknowledgments / Abbreviations / Abstract 一 English --- p.i / - Chinese --- p.iii / Chapter Chapter 1 --- General Introduction / Chapter 1.1. --- Colon Cancer / Chapter 1.1.1. --- Colon cancer statistic in Hong Kong --- p.1 / Chapter 1.1.2. --- Development of Colon cancer --- p.1 / Chapter 1.1.3. --- Treatment --- p.2 / Chapter 1.2. --- Chemistry of ascorbates / Chapter 1.2.1. --- Sodium-L-ascorbate --- p.3 / Chapter 1.2.2. --- "Sodium 5,6-benazylidene-L-ascorbate" --- p.4 / Chapter 1.3. --- "Reactive oxygen species and reactive nitrogen species, and their biological consequences" --- p.5 / Chapter 1.4. --- Cell cycle --- p.7 / Chapter 1.5. --- Autophagy --- p.8 / Chapter 1.6. --- Human colon cancer HT29 cells for anti-tumor study --- p.9 / Chapter 1.7 --- Aim of study --- p.10 / Chapter Chapter 2 --- Comparative studies of cytotoxicity of SAA and SBA in short term treatment / Chapter 2.1. --- Introduction --- p.11 / Chapter 2.2. --- Materials and Methods --- p.14 / Chapter 2.3. --- Results --- p.17 / Chapter 2.4. --- Discussion --- p.26 / Chapter Chapter 3 --- Comparative studies of SAA and SBA in oxidative stress induction and their corresponding ROS inhibitors / Chapter 3.1. --- Introduction --- p.28 / Chapter 3.2. --- Materials and Methods --- p.31 / Chapter 3.3. --- Results --- p.35 / Chapter 3.4. --- Discussion --- p.42 / Chapter Chapter 4 --- "Effects of SAA and SBA treatments on cell cycle regulatory proteins and the induction of transient cell cycle arrests in Gl, S and G2 phases Cell Cycle" / Chapter 4.1. --- Introduction --- p.45 / Chapter 4.2. --- Materials and Methods --- p.49 / Chapter 4.3. --- Results --- p.53 / Chapter 4.4. --- Discussion --- p.69 / Chapter Chapter 5 --- Autophagy induction during SBA treatment and autophagy inhibition during SAA treatment / Chapter 5.1. --- Introduction --- p.72 / Chapter 5.2. --- Materials and Methods --- p.74 / Chapter 5.3. --- Results --- p.77 / Chapter 5.4. --- Discussion --- p.91 / Chapter Chapter 6 --- General Discussion --- p.93 / References --- p.100