Occupational Histories of Cancer Patients in a Canadian Cancer Treatment Centre and the Generated Hypothesis Regarding Breast Cancer and Farming

Occupational exposures increase cancer risks. The Windsor Regional Cancer Centre in Windsor, Ontario, was the first Canadian cancer treatment center to collect the work histories of its patients, which were recorded using a computer-based questionnaire. Breast cancer cases represented the largest respondent group. The lifetime occupational histories of 299 women with newly diagnosed breast cancers were compared with those of 237 women with other cancers. Odds ratios (ORs) were calculated using logistic regression, adjusting for age, social class, and education. The OR for women £ 55 years of age with breast cancer who had ever farmed, compared with women of the same age with other cancers, was 9.05 (95% CI 1.06, 77.43). Patients’ occupational histories can help to inform understanding of cancer etiology and prevention. This effort points to a need for investigation of the possible association between breast cancer and agricultural hazards such as pesticides

Cancer and Construction: What Occupational Histories in a Canadian Community Reveal

From 2000 to 2002, male patients at a Canadian cancer treatment center with new-incident head-and-neck or esophageal cancers were invited to participate in a population-based study. The study population included 87 cases and 172 controls. A lifetime-history questionnaire was administered. Odds ratios (ORs) were calculated for occupational groups with a minimum of five cases, adjusted for duration of employment, age, smoking, alcohol, education, and income. A significantly increased risk was shown for construction workers (OR = 2.20; 95% CI 1.25–3.91). This investigation of a set of rare cancers over a limited time period demonstrates the feasibility of this research approach. The increased risk among construction workers supports the need for more comprehensive study of exposures in this occupational group

Breast Tumor Cells with PI3K Mutation or HER2 Amplification Are Selectively Addicted to Akt Signaling

Dysregulated PI3K/Akt signaling occurs commonly in breast cancers and is due to HER2 amplification, PI3K mutation or PTEN inactivation. The objective of this study was to determine the role of Akt activation in breast cancer as a function of mechanism of activation and whether inhibition of Akt signaling is a feasible approach to therapy.A selective allosteric inhibitor of Akt kinase was used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate PI3K/Akt signaling: HER2 amplification or PI3K or PTEN mutations in order to determine the biochemical and biologic consequences of inhibition of this pathway. A variety of molecular techniques and tissue culture and in vivo xenograft models revealed that tumors with mutational activation of Akt signaling were selectively dependent on the pathway. In sensitive cells, pathway inhibition resulted in D-cyclin loss, G1 arrest and induction of apoptosis, whereas cells without pathway activation were unaffected. Most importantly, the drug effectively inhibited Akt kinase and its downstream effectors in vivo and caused complete suppression of the growth of breast cancer xenografts with PI3K mutation or HER2 amplification, including models of the latter selected for resistance to Herceptin. Furthermore, chronic administration of the drug was well-tolerated, causing only transient hyperglycemia without gross toxicity to the host despite the pleiotropic normal functions of Akt.These data demonstrate that breast cancers with PI3K mutation or HER2 amplification are selectively dependent on Akt signaling, and that effective inhibition of Akt in tumors is feasible and effective in vivo. These findings suggest that direct inhibition of Akt may represent a therapeutic strategy for breast and other cancers that are addicted to the pathway including tumors with resistant to Herceptin

A systematic review of optical coherence tomography findings in adults with mild traumatic brain injury

Mild traumatic brain injury (mTBI) is common with many patients suffering disabling long-term sequelae, with visual symptoms frequently reported. There are no objective biomarkers of mTBI that are routinely used in clinical practice. Optical coherence tomography (OCT) has been used in mTBI research, as it enables visualisation of the neuroretina, allowing measurement of the retinal nerve fibre layer and ganglion cell layer. This systematic review aims to appraise the available literature and assess whether there are significant changes within the retinal nerve fibre layer and ganglion cell layer in subjects after mTBI. A systematic review was carried out in accordance with PRISMA guidelines and registered with PROSPERO (Number: CRD42022360498). Four databases were searched for relevant literature published from inception until 1 September 2022. Abstracts and full texts were screened by three independent reviewers. Initial screening of databases yielded 341 publications, of these, three fulfilled all the criteria for inclusion. All three studies showed thinning of the retinal nerve fibre layer, whereas there were no significant changes in the ganglion cell layer. This systematic review demonstrated that thinning of the retinal nerve fibre layer (but not of the ganglion cell layer) is associated with mTBI. It provides preliminary evidence for the use of the retinal nerve fibre layer as a potential biomarker of damage to the visual system in mTBI. Further prospective longitudinal studies ensuring uniform diagnosis and accurate phenotyping of mTBI are needed to understand the effects on the visual system and potential of OCT as a prognostic biomarker