The aluminium content of breast tissue taken from women with breast cancer

The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content in defatted tissue and oil from such tissues and thereby contribute towards our knowledge on aluminium and any role in breast cancer.

Genetic, structural, and molecular insights into the function of ras of complex proteins domains

Ras of complex proteins (ROC) domains were identified in 2003 as GTP binding modules in large multidomain proteins from Dictyostelium discoideum. Research into the function of these domains exploded with their identification in a number of proteins linked to human disease, including leucine-rich repeat kinase 2 (LRRK2) and death-associated protein kinase 1 (DAPK1) in Parkinson’s disease and cancer, respectively. This surge in research has resulted in a growing body of data revealing the role that ROC domains play in regulating protein function and signaling pathways. In this review, recent advances in the structural informa- tion available for proteins containing ROC domains, along with insights into enzymatic function and the integration of ROC domains as molecular switches in a cellular and organismal context, are explored.

Computational analysis of the LRRK2 interactome

LRRK2 was identified in 2004 as the causative protein product of the Parkinson’s disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson’s disease, alongside one associated with cancer. It is now well established that coding changes in LRRK2 are one of the most common causes of Parkinson’s. Genome-wide association studies (GWAs) have, more recently, reported single nucleotide polymorphisms (SNPs) around the LRRK2 locus to be associated with risk of developing sporadic Parkinson’s disease and inflammatory bowel disorder. The functional research that has followed these genetic breakthroughs has generated an extensive literature regarding LRRK2 pathophysiology; however, there is still no consensus as to the biological function of LRRK2. To provide insight into the aspects of cell biology that are consistently related to LRRK2 activity, we analysed the plethora of candidate LRRK2 interactors available through the BioGRID and IntAct data repositories. We then performed GO terms enrichment for the LRRK2 interactome. We found that, in two different enrichment portals, the LRRK2 interactome was associated with terms referring to transport, cellular organization, vesicles and the cytoskeleton. We also verified that 21 of the LRRK2 interactors are genetically linked to risk for Parkin- son’s disease or inflammatory bowel disorder. The implications of these findings are discussed, with particular regard to potential novel areas of investigation.

Cancer patients taking herbal medicines: a review of clinical purposes, associated factors, and perceptions of benefit or harm

Ethnopharmacological relevance: Cancer patients in all cultures are high consumers of herbal medicines (HMs) usually as part of a regime consisting of several complementary and alternative medicine (CAM) modalities, but the type of patient, the reasons for choosing such HM-CAM regimes, and the benefits they perceive from taking them are poorly understood. There are also concerns that local information may be ignored due to language issues. This study investigates aspects of HM-CAM use in cancer patients using two different abstracting sources: Medline, which contains only peer-reviewed studies from SCI journals, and in order to explore whether further data may be available regionally, the Thai national databases of HM and CAM were searched as an example. Materials and methods: the international and Thai language databases were searched separately to identify relevant studies, using key words chosen to include HM use in all traditions. Analysis of these was undertaken to identify socio-demographic and clinical factors, as well as sources of information, which may inform the decision to use HMs. Results: Medline yielded 5,638 records, with 49 papers fitting the criteria for review. The Thai databases yielded 155, with none relevant for review. Factors associated with HM-CAM usage were: a younger age, higher education or economic status, multiple chemotherapy treatment, late stage of disease. The most common purposes for using HM-CAM cited by patients were to improve physical symptoms, support emotional health, stimulate the immune system, improve quality of life, and relieve side-effects of conventional treatment. Conclusions: Several indicators were identified for cancer patients who are most likely to take HM-CAM. However, interpreting the clinical reasons why patients decide to use HM-CAM is hampered by a lack of standard terminology and thematic coding, because patients' own descriptions are too variable and overlapping for meaningful comparison. Nevertheless, fears that the results of local studies published regionally are being missed, at least in the case of Thailand, appeared to be unfounded.