Screening for breast cancer : medicalization, visualization and the embodied experience

Women’s perspectives on breast screening (mammography and breast awareness) were explored in interviews with midlife women sampled for diversity of background and health experience. Attending mammography screening was considered a social obligation despite women’s fears and experiences of discomfort. Women gave considerable legitimacy to mammography visualizations of the breast, and the expert interpretation of these. In comparison, women lacked confidence in breast awareness practices, directly comparing their sensory capabilities with those of the mammogram, although mammography screening did not substitute breast awareness in a straightforward way. The authors argue that reliance on visualizing technology may create a fragmented sense of the body, separating the at risk breast from embodied experience

Gemcitabine: Efficacy in the Treatment of Advanced Stage Nonsquamous Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death in many countries. Approximately half of the patients with non-small cell lung cancer have advanced disease and systemic chemotherapy, especially platinum-based doublets, is currently the standard treatment. Several trials have recently indicated the importance of histological subtype for treatment with molecular target chemotherapy and pemetrexed. Over the last decade, gemcitabine, a pyrimidine nucleoside antimetabolite, has been one of the most effective agents for patients with advanced non-small cell lung cancer. It is unknown whether histological type is a predictor of the outcome of treatment with this agent. This is a review of the past trials and reviews of first-line treatment for advanced NSCLC, focusing on efficacy and safety of treatment with gemcitabine according to histological subtype

Safety and Efficacy of Vinorelbine in the Treatment of Non-Small Cell Lung Cancer

Lung cancer remains the most frequently diagnosed cancer in the United States, excluding non-melanoma skin cancer. Non-small cell lung cancer (NSCLC) constitutes the majority (more than 80%) of lung cancer diagnoses. Systemic therapy, with either cytotoxic chemotherapy and/or targeted therapies, has been established to provide benefit to patients with NSCLC in both the adjuvant and advanced disease settings. Vinorelbine, a semi-synthetic vinca-alkaloid has been extensively tested alone and in combination with other cytotoxic or targeted agents in the treatment of NSCLC. Its safety has been well established with neutropenia, anemia, nausea, and vomiting being the most frequently encountered toxicities. The data defining the risks and benefits of vinorelbine in the treatment of NSCLC will be summarized

Cancer Incidence among Former Love Canal Residents

Ba c k g r o u n d: The Love Canal was a rectangular 16-acre, 10-ft-deep chemical waste landfill situated in a residential neighborhood in Niagara Falls, New York. This seriously contaminated site came to public attention in 1978. Only one prior study examined cancer incidence in former residents of the Love Canal neighborhood (LC). Objective: In this study we aimed to describe cancer incidence in former LC residents from 1979 to 1996 and to investigate whether it differs from that of New York State (NYS) and Niagara County (NC). Me t h o d s: From 1978 to 1982, we interviewed 6,181 former residents, and 5,052 were eligible to be included in this study. In 1996, we identified 304 cancer diagnoses in this cohort using the NYS Cancer Registry. We compared LC cancer incidence with that of NYS and NC using standardized incidence ratios (SIRs), and we compared risks within the LC group by potential exposure to the landfill using survival analysis. Res u l t s: SIRs were elevated for cancers of the bladder [SIR NYS = 1.44; 95 % confidence interval (CI), 0.91–2.16] and kidney (SIR NYS = 1.48; 95 % CI, 0.76–2.58). Although CIs included 1.00, other studies have linked these cancers to chemicals similar to those found at Love Canal. We also found higher rates of bladder cancer among residents exposed as children, based on two cases. Co n c l u s i o n s: In explaining these excess risks, the role of exposure to the landfill is unclear given such limitations as a relatively small and incomplete study cohort, imprecise exposure measurements, and the exclusion of cancers diagnosed before 1979. Given the relatively young age of the cohort, further surveillance is warranted. Key w o r d s: cancer, community health, exposure assessment, hazardous waste sites, Love Canal. Environ Health Perspect 117:1265–1271 (2009). doi:10.1289/ehp.0800153 available vi

The influence of antidiabetic medications on the development and progression of prostate cancer

AbstractBackgroundThe development of prostate tumors has been linked to co-morbid diabetes mellitus (DM) in several studies, potentially through the stimulation of insulin-like growth factor receptor (IGFR). This study evaluates the effect of anti-diabetic medication use on the development of high grade tumors and time to tumor progression compared to non-diabetics.MethodsThis retrospective, nested case control study identified patients with prostate cancer (PCa) from the Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at least one of the following antidiabetic medications; sulfonylureas, insulin, metformin or TZDs. Cases were further stratified on their insulin exposure resulting from therapy. Controls were those with PCa without DM or any anti-diabetic medications.ResultsThe use of metformin or TZDs trended toward decreased odds of high-grade tumors and decreased risk of progression, while sulfonylureas and high-dose insulin tended toward an increased odds of high-grade tumors and increase the risk of progression compared to non-diabetics.ConclusionsFuture studies should be conducted to further evaluate the effects of anti-diabetic medications on tumor grade and time to prostate cancer progression

The association of polymorphisms in hormone metabolism pathway genes, menopausal hormone therapy, and breast cancer risk: a nested case-control study in the California Teachers Study cohort

Abstract Introduction The female sex steroids estrogen and progesterone are important in breast cancer etiology. It therefore seems plausible that variation in genes involved in metabolism of these hormones may affect breast cancer risk, and that these associations may vary depending on menopausal status and use of hormone therapy. Methods We conducted a nested case-control study of breast cancer in the California Teachers Study cohort. We analyzed 317 tagging single nucleotide polymorphisms (SNPs) in 24 hormone pathway genes in 2746 non-Hispanic white women: 1351 cases and 1395 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by fitting conditional logistic regression models using all women or subgroups of women defined by menopausal status and hormone therapy use. P values were adjusted for multiple correlated tests (P ACT). Results The strongest associations were observed for SNPs in SLCO1B1, a solute carrier organic anion transporter gene, which transports estradiol-17β-glucuronide and estrone-3-sulfate from the blood into hepatocytes. Ten of 38 tagging SNPs of SLCO1B1 showed significant associations with postmenopausal breast cancer risk; 5 SNPs (rs11045777, rs11045773, rs16923519, rs4149057, rs11045884) remained statistically significant after adjusting for multiple testing within this gene (P ACT = 0.019-0.046). In postmenopausal women who were using combined estrogen-progestin therapy (EPT) at cohort enrollment, the OR of breast cancer was 2.31 (95% CI = 1.47-3.62) per minor allele of rs4149013 in SLCO1B1 (P = 0.0003; within-gene P ACT = 0.002; overall P ACT = 0.023). SNPs in other hormone pathway genes evaluated in this study were not associated with breast cancer risk in premenopausal or postmenopausal women. Conclusions We found evidence that genetic variation in SLCO1B1 is associated with breast cancer risk in postmenopausal women, particularly among those using EPT

Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer

Background: Crosstalk between neoplastic and stromal cells fosters prostate cancer (PCa) progression and dissemination. Insight in cell-to-cell communication networks provides new therapeutic avenues to mold processes that contribute to PCa tumor microenvironment (TME) alterations. Here we performed a detailed characterization of PCa tumor endothelial cells (TEC) to delineate intercellular crosstalk between TEC and the PCa TME. Methods: TEC isolated from 67 fresh radical prostatectomy (RP) specimens underwent multi-omic ex vivo characterization as well as orthogonal validation of both TEC functions and key markers by immunohistochemistry (IHC) and immunofluorescence (IF). To identify cell-cell interaction targets in TEC, we performed single-cell RNA sequencing (scRNA-seq) in four PCa patients who underwent a RP to catalogue cellular TME composition. Targets were cross-validated using IHC, publicly available datasets, cell culture expriments as well as a PCa xenograft mouse model. Results: Compared to adjacent normal endothelial cells (NEC) bulk RNA-seq analysis revealed upregulation of genes associated with tumor vasculature, collagen modification and extracellular matrix remodeling in TEC. PTGIR, PLAC9, CXCL12 and VDR were identified as TEC markers and confirmed by IF and IHC in an independent patient cohort. By scRNA-seq we identified 27 cell (sub)types, including endothelial cells (EC) with arterial, venous and immature signatures, as well as angiogenic tip EC. A focused molecular analysis revealed that arterial TEC displayed highest CXCL12 mRNA expression levels when compared to all other TME cell (sub)populations and showed a negative prognostic role. Receptor-ligand interaction analysis predicted interactions between arterial TEC derived CXCL12 and its cognate receptor CXCR4 on angiogenic tip EC. CXCL12 was in vitro and in vivo validated as actionable TEC target by highlighting the vessel number- and density- reducing activity of the CXCR4-inhibitor AMD3100 in murine PCa as well as by inhibition of TEC proliferation and migration in vitro. Conclusions: Overall, our comprehensive analysis identified novel PCa TEC targets and highlights CXCR4/CXCL12 interaction as a potential novel target to interfere with tumor angiogenesis in PCa

The Limits of Responsible Innovation: Exploring Care, Vulnerability and Precision Medicine

Drawing on insights from feminist and Science and Technology Studies writing on care and vulnerability, this paper will critically explore conceptualisations of responsibility, care and vulnerability in relation to contemporary approaches to Responsible Innovation (RI). Drawing on examples of some of the social and ethical challenges of precision medicine, we highlight the on-going, distributed and complex nature of innovation and responsibilities in relation to markets, patient and carer experience and data practices associated with these new technologies to highlight some of the limits of RI. We end by reflecting on the implications of our analysis for the social and ethical challenges of precision medicine and RI more generally

Chance mechanisms affecting the burden of metastases

BACKGROUND: The burden of cancer metastases within an individual is commonly used to clinically characterize a tumor's biological behavior. Assessments like these implicitly assume that spurious effects can be discounted. Here the influence of chance on the burden of metastasis is studied to determine whether or not this assumption is valid. METHODS: Monte Carlo simulations were performed to estimate tumor burdens sustained by individuals with cancer, based upon empirically derived and validated models for the number and size distributions of metastases. Factors related to the intrinsic metastatic potential of tumors and their host microenvironments were kept constant, to more clearly demonstrate the contribution from chance. RESULTS: Under otherwise identical conditions, both the simulated numbers and the sizes of metastases were highly variable. Comparable individuals could sustain anywhere from no metastases to scores of metastases, and the sizes of the metastases ranged from microscopic to macroscopic. Despite the marked variability in the number and sizes of the metastases, their respective growth times were rather more narrowly distributed. In such situations multiple occult metastases could develop into fully overt lesions within a comparatively short time period. CONCLUSION: Chance can have a major effect on the burden of metastases. Random variability can be so great as to make individual assessments of tumor biology unreliable, yet constrained enough to lead to the apparently simultaneous appearance of multiple overt metastases