Targeting cancer cell death using aptamer tagged nano-formulated survivin antagonists

 My findings established survivin antagonist SR9 as an efficient anti-cancer therapeutic and highly promising cancer cell and cancer stem cell targeted locked nucleic acid conjugated nanocarriers as a ray of hope for therapy against colon cancer.

Fabrication of high specificity hollow mesoporous silica nanoparticles assisted by Eudragit for targeted drug delivery.

Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for effective drug delivery due to their large surface area, high volume for drug loading and excellent biocompatibility. However, the non-ionic surfactant templated HMSNs often have a broad size distribution and a defective mesoporous structure because of the difficulties involved in controlling the formation and organization of micelles for the growth of silica framework. In this paper, a novel "Eudragit assisted" strategy has been developed to fabricate HMSNs by utilising the Eudragit nanoparticles as cores and to assist in the self-assembly of micelle organisation. Highly dispersed mesoporous silica spheres with intact hollow interiors and through pores on the shell were fabricated. The HMSNs have a high surface area (670m(2)/g), small diameter (120nm) and uniform pore size (2.5nm) that facilitated the effective encapsulation of 5-fluorouracil within HMSNs, achieving a high loading capacity of 194.5mg(5-FU)/g(HMSNs). The HMSNs were non-cytotoxic to colorectal cancer cells SW480 and can be bioconjugated with Epidermal Growth Factor (EGF) for efficient and specific cell internalization. The high specificity and excellent targeting performance of EGF grafted HMSNs have demonstrated that they can become potential intracellular drug delivery vehicles for colorectal cancers via EGF-EGFR interaction.

IPA: Integrated predictive gene signature from gene expression based breast cancer patient samples

Background: Novel predictive markers are needed to accurately diagnose the breast cancer patients so they do not need to undergo any unnecessary aggressive therapies. Various gene expression studies based predictive gene signatureshave generated in the recent past to predict the binary estrogen-receptor subclass or to predict the therapy response subclass. However, the existing algorithms comes with many limitations, including low predictive performances over multiple cohorts of patients and non-significant or limited biological roles associated with thepredictive gene signatures. Therefore, the aim of this study is to develop novel predictive markers with improved performances.Methods: We propose a novel prediction algorithm called IPA to construct a predictive gene signature for performing multiple prediction tasks of predicting estrogen-receptor based binary subclass and predicting chemotherapy response (neoadjuvantly) based binary subclass. The constructed gene signature with considering multiple classification techniques was used to evaluate the algorithm performance on multiple cohorts of breast cancer patients.Results: The evaluation on multiple validation cohorts demonstrated that proposed algorithm achieved stable and high performance to perform prediction tasks, with consideration given to any classification techniques. We show that the predictive gene signature of our proposed algorithm reflects the mechanisms underlying the estrogen-receptors or response to therapy with significant greater biological interpretations, compared with the other existing algorithm.

Community attitudes towards the early detection of cancer in Victoria, Australia

Objectives: To describe people's attitudes towards early detection of cancer.

Methods: We conducted a telephone survey of Victorian adults aged 18+ years, during April-May 2005, using a market research company.

Results: 1,502 (41%) people participated; 80% of respondents believed that detecting cancer early meant that treatment saved lives most of the time or always; 88% believed finding cancer early enabled more effective treatment most of the time or always; and 70% indicated they would want to be tested for a cancer even if no treatment were available.  Two-thirds or more of adults considered survival would be very much improved by early detection for breast, melanoma and prostate cancers; 49% for bowel cancer, and 30% for lung cancer.

Conclusions and Implications : Community support for the early detection of cancer was evident even in the absence of effective treatment.  There was a lower perceived survival benefit for the early diagnosis of bowel cancer or melanoma.  An education campaign is required that focuses on the gains associated with early detection and benefits of screening for bowel cancer.

Families as carers-information needs in a cultural context

While the important role of family as a carer has been increasingly recognised in healthcare service provision, particularly for patients with acute or chronic illnesses, the carer’s information needs have not been well understood and adequately supported by current health information systems. In order to effectively provide continuous and home-based care for the patient, a family relative as the primary carer needs sufficient access to medical knowledge and patient’s health information. There are two challenges. First, being a family relative, the primary carer is often a non-medical practitioner. Second, in Australia, many primary carers are family relatives of patients from a non-English speaking background. They are often seen as interpreters in clinical consultation sessions. Their roles and responsibilities as an interpreter and a carer are often mixed and blurry.
Therefore, their information needs are often seen as secondary to the patient or neglected. The primary carer’s information needs are currently not yet well understood.

This paper reports finding from a case study which examines an on-line diary of a husband-carer who provided support and care for his wife, who at the time of care was a lung cancer patient. The case study examines an ongoing learning process that the husband went through, identifies information needs by the carer and cultural factors which played an important role in the husband’s interpretation of information, decision making and provision of care. The finding extends a current model of the user’s information needs in the literature and suggests implications for further research into developing health information systems to meet information needs by the family carer.

The decision-making journey of a family carer : information and social needs in a cultural context

While the important role of family as carer has been increasingly recognised in healthcare service provision, particularly for patients with acute or chronic illnesses, the carer's information and social needs have not been well understood and adequately supported. In order to provide continuous and home-based care for the patient, and to make informed decisions about the care, a family carer needs sufficient access to medical information in general, the patient's health information specifically, and supportive care services. Two key challenges are the carer's lack of medical knowledge and the many carers with non-English speaking and different cultural backgrounds. The informational and social needs of family carers are not yet well understood. This paper analyses the web-log of a husband-carer who provided support for his wife, who at the time of care was a lung cancer patient. It examines the decision-making journey of the carer and identifies the key issues faced in terms of informational and social practices surrounding care provision.

Non-invasive collection and examination of human corneal epithelial cells

Purpose. To report the development of a new apparatus for non-invasive collection of human corneal epithelial cells.

Methods. Previous methods of non-invasive, irrigative corneal cell collection resulted in low cell yields limiting potential analysis. A new ocular surface cell collection apparatus (OSCCA) was designed to collect more epithelial cells from direct irrigation of the corneal surface to allow for clinical comparisons. Forty-five samples were obtained (unilateral or bilateral over seven visits) from five human participants. Cell yield, size, phenotype, and corneal staining (prior and post eye wash) were examined.

Results. On average 364 ± 230 epithelial cells were collected from the cornea per eye. Epithelial cell sizes ranged from 8.21 to 51.69 μm in diameter, and 67.30 to 2098.85 μm2 area. The proportion of corneal specific cells collected per sample was 75 ± 14% as determined by positive K3 expression with AE5. On average, 77 ± 0.2% of epithelial cells harvested were nucleated, the remainder were non-nucleated ghost cells. Corneal staining was reduced in the OSCCA-washed vs. contralateral non-washed eyes (p = 0.02).

Conclusions. The OSCCA allows collection of human corneal epithelial cells with significantly higher yields, and greater specificity than previously reported. Reduced corneal staining observed post eye-wash demonstrated the safety of the technique, and its ability to remove cells directly from the corneal surface. The OSCCA could provide an objective non-invasive method of investigating pathological changes, effects of topical therapeutics, and impact of contact lenses and care-solutions of the cells of the ocular surface.

An epidemiological analysis of the 'autism as mercury poisoning' hypothesis

Where direct experimental research into a causal hypothesis of a disease is impossible due to ethical and practical considerations, epidemiological inference is the accepted route to establishing cause. Therefore, to examine the autism as mercury poisoning hypothesis, this paper reviews the existing scientific literature within the context of established epidemiological criteria and finds that the evidence for a causal relationship is compelling. Exposure to mercury (via vaccines and maternal dental amalgam) in utero and during infant years is confirmed; mercury poisoning is known to cause symptoms consistent with autism; animal modeling supports the link and, critically, mercury levels are higher in both the urine and blood of autistic children than in non-autistic peers. Analogous to epidemiological evidence of the smoking–lung cancer relationship, a mercury–autism relationship is confirmed. The precautionary principle demands that health professionals not take an action if there is suspicion that the action may cause severe or lifelong health effects: it does not require certainty. Therefore, given the severity, devastating lifelong impact and extremely high prevalence of autism, it would be negligent to continue to expose pregnant and nursing mothers and infant children to any amount of avoidable mercury.

Microfluidic platforms for biomarker analysis

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.