Gender Differences In Susceptibility To Normative Social Influence On The Purchase Decisions Of Designer Label Apparel

This study examines susceptibility to normative social influence on purchase decisions of designer label apparel in Malaysia. The study focuses on the youth market with special consideration given to gender differences. Influences of family and peers were examined along with celebrity influences. A total of 319 youth participated in the study. Results indicate that gender differences do exist with males exhibiting a higher likelihood of being influenced by their reference groups. Celebrity influence was also found to be weaker than that exerted by direct reference groups

Characterisation of the expression of tumour antigens and biomarkers in myeloid leukaemia and ovarian cancer

A thesis submitted to the Faculty of Creative Arts, Technologies and Science, University of Bedfordshire in fulfilment of the requirements for the degree of Doctor of PhilosophyAcute myeloid leukaemia (AML) and ovarian cancer (OVC) are two difficult to treat cancers. AML is often treatable however minimal residual disease (MRD) endures such that many patients who achieve remission eventually relapse and succumb to the disease. OVC affects approximately 7000 women in the U.K. every year. It can occur at any age but is most common after menopause. Diagnosis at an early stage of disease greatly improves the chances of survival however, patients tend to be diagnosed in the later stages of disease when treatment is often less effective. Immunotherapy has the potential to reduce MRD and delay or prevent relapse. In order for immunotherapy to work, tumour antigens need to be identified and characterised so they can be effectively targeted. Personalised treatments require the identification of biomarkers, for disease detection and confirmation, as well as to provide an indication of best treatment and the prediction of survival. PASD1 has been found to be frequently expressed in haematological malignancies and I wanted to determine if there was a correlation between the presence of antigen-specific T cells in the periphery of patients with AML and PASD1 protein expression in the leukaemic cells. The expression of other leukaemia antigens were concurrently examined as comparators. I performed RT-PCR on nine antigens and immunocytochemistry on PASD1 in 18 samples from AML patients. I found a correlation between PASD1 expression in AML samples and the presence of PASD1-specific T cells as detected on the pMHC array. OVC lacks suitable targets for immunotherapy with few CTAs having been identified. I examined the expression of SSX2IP and the CTAs PASD1 and SSX2 in OVC. I compared the protein expression of these known tumour antigens to the “gold standard” biomarker for the diagnosis of OVC, CA125 and two other proteins known to be promising in the diagnosis of OVC, HE4 and WT1. I analysed commercially available paraffin-embedded OVC multiple tissue arrays (MTAs) containing 191 samples, predominantly stage I (n= 166), II (n= 15) and III (n= 6) OVC as well as healthy donor (n= 8) and normal adjacent tissues (n= 8). Scoring was performed in a single blinded fashion. I found SSX2A to be expressed at a score level of 3 with a frequency (37/191) that exceeded that of CA125 (14/191), HE4 (14/191), WT1 (1//191) or PASD1 (0/191). To confirm this expression I used two additional commercially-available antibodies that recognise the region common to SSX2A and B, and an antibody specific for SSX2A. Using SSX2 peptides, I blocked the immunolabelling of SSX2 in SSX2-positive cell lines showing that the immunolabelling of SSX2 and SSX2A was specific. I demonstrated that the expression of SSX2 and specifically SSX2A was reproducible and restricted to ovarian cancer with little or no expression in endometrial tissues, or diseased or inflamed endometrial tissue. In summary, these studies demonstrated that PASD1 expression in leukaemia cells correlated with the presence of PASD1-specific T cells in the periphery of presentation AML patients. I have shown that PASD1 specific-T cells are present in AML patients at diagnosis and that immunotherapy targeting PASD1 could be used to break tolerance and clear residual leukaemia cells during first remission. Analysis of the expression of three antigens in OVC, identified the specific expression of SSX2, in particular SSX2A in OVC but not healthy or diseased endometrial tissues. The expression of SSX2A was more frequent and more specific to OVC, than HE4 and WT1, and more frequent at higher intensity, especially in early stage OVC, than CA125. SSX2 and explicitly SSX2A requires further investigation to determine whether the high level of background at score 2 can be reduced with better blocking of non-specific sites. This may require the use of different SSX2 antibodies or an improved staining protocol

Identification and validation of targets for cancer immunotherapy: from the bench-to-bedside

Chapter 12 in Novel Gene Therapy Approache

PASD1: a promising target for the immunotherapy of haematological malignancies

In general, there is a lack of good immunotherapy targets within the spectrum of haematological malignancies. However haematopoietic stem cell transplants and continuing antigen discovery have allowed further insight into how further improvements in outcomes for patients might be achieved. Most patients with haematological malignancies can be treated with conventional therapies such as radio- and chemotherapy and will attain first remission. However the removal of residual diseased cells is essential to prevent relapse and its associated high mortality. PASD1 is one of the most tissue restricted cancer-testis (CT) antigens with expression limited to primary spermatagonia in healthy tissue. However, characterisation of PASD1 expression in cancers has been predominantly focussed on haematological malignancies where the inappropriate expression of PASD1 was first identified. PASD1 has one of the highest frequencies of expression of all CT antigens in acute myeloid leukaemia, with some suggestion of its role as a biomarker in diffuse large B-cell lymphoma. Here we describe the characterisation of the function and expression patterns of PASD1 in cell lines and primary tissues. Development of DNA vaccines targeting PASD1 epitopes demonstrate effective ex vivo T-cell responses in terms of IFNγ secretion and tumour cell killing. Of particular note these vaccines have led to the destruction of cells which process and present endogenous PASD1 indicating that effectively primed CTLs could kill PASD1-positive tumour cells

DEVELOPMENT AND CHARACTERIZATION OF TOPICAL NANOPARTICULATE ANTIPSORIATIC POLYHERBAL CREAM

Objective: The lack of possible cure and associated disadvantages of allopathic medicines in the topical treatment of psoriasis has led to extensive research for anti-psoriatic activities of plant-based drugs. The present study was aimed to develop topical cream formulation containing the Nanostructured Lipid Carriers of Azadirachta indica leaves extract (AE), Lawsonia inermis leaves extract (LE) and fruit extract of Mallotus philippensis (ME) and assessing the antipsoriatic activity of prepared cream formulation. Methods: The Drug loaded NLCs were prepared via hot homogenization technique and incorporated into the water in oil (w/o) cream base that was prepared by the emulsification method. Evaluation of cream formulation included advanced preclinical trials using Rat Ultraviolet Ray-B photodermatitis and Mousetail method, anti-lipid peroxidation assay, nitric oxide scavenging activity, cytotoxicity and DNA fragmentation on HaCat cell lines to ascertain antipsoriatic potential and in vitro drug diffusion. Results: In spite of the low amount of the drug loading in NLCs their potency was much higher as displayed in Advanced Preclinical studies and cell line studies for psoriasis indicating the suitability of NLCs loaded creams for skin applications due to their various desirable effects on the skin. Occlusive properties of the prepared NLC on the skin provide an increase in drug penetration particularly via skin moisturization. The in vitro drug diffusion studies suggest the prolonged and almost complete release of AE, LE and ME from NLC based cream up to 24 h that was found to be 81.24±0.51%, 74.31±0.25% and 70.43±0.78% respectively. The literature survey supports the novelty of such topical anti-psoriatic polyherbal nanoparticulate cream. Conclusion: It can be concluded that the AE, LE and ME loaded NLC based cream can be used for prolonged topical delivery of drugs for the management of Psoriasis

TOPICAL ANTI-PSORIATIC NANOPARTICULATE DRUG DELIVERY SYSTEM

Objective: Development of effective drug delivery in the treatment of psoriasis is the major challenge for its successful management. To develop and assess the potential of Nanostructured Lipid Carriers (NLCs) enriched with the powdered leaves extracts of Azadirachta indica (AE), Lawsonia inermis (LE) and fruit extract of Mallotus philippensis (ME) in the management of psoriasis. Methods: Drug loaded NLCs were prepared via hot homogenization technique by adopting 23 factorial design with factors X1 as the concentration of lipids, X2 concentration of surfactants and X3 being the number of homogenization cycle. The responses Y1 and Y2 were particle size and zeta potential. The optimized batch was obtained from Surface response plot and was evaluated for zeta potential, % entrapment efficiency, % drug loading, Scanning Electron Microscopy(SEM), % in vitro diffusion of drugs from the NLCs, anti-lipid peroxidation and nitric oxide scavenging activities, cytotoxicity on HaCat cell lines, Mouse Tail and Rat ultraviolet ray B photodermatitis models for Psoriasis. Results: The optimized batch of NLCs was found within the nanosized range with a relatively low polydispersity index and zeta potential of-20mV. The %EE for an optimized batch of NLCs was found to be 98.97±0.83%, 96.99±0.56% and 99.25±0.55% and the %DL of 21.84±0.15%, 8.55±045%, and 87.91±0.38% respectively for AE, LE and ME. The SEM images showed the spherical vesicular structures of drugs loaded NLCs. The in-vitro diffusion of drugs from the NLCs followed initial burst release thereafter sustained release for 24 h. The AE, LE and ME loaded NLCs proved to possess anti-lipid peroxidation and nitric oxide scavenging activities, cytotoxicity on HaCat cell lines, DNA fragmentation on HaCat cell lines which are biomarkers in the pathogenesis of psoriasis. The results of Mouse Tail and Rat ultraviolet ray B photodermatitis models for Psoriasis supported the anti-psoriatic potential of AE, LE and ME loaded NLCs. Conclusion: AE, LE and ME loaded NLCs can be used for prolonged topical delivery to the psoriatic skin for an effective treatment

Type 1 diabetes mellitus presenting with diabetic ketoacidosis (DKA) in a neonate

Neonatal diabetes mellitus (NDM) is a rare manifestation with an incidence of one affected individual among 400000 live births. NDM can be divided into Transient (TNDM) and Permanent (PNDM) types. A significant overlap occurs between both groups, to an extent that TNDM cannot be distinguished from PNDM based solely on clinical features. Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). DKA at diagnosis is more common in young children near the age of five years. Neonatal DKA is a rare occurrence causing it to be missed in the differential diagnosis of neonatal illness and results delay in appropriate management and increase in morbidity and mortality rate