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- Rider, Jennifer R., et al.
(författare)
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iNOS expression and lethal prostate cancer in patients with localized disease
- 2017
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; :22S
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Tidskriftsartikel (refereegranskat)abstract
- Inducible nitric oxide synthase (iNOS) has demonstrated both tumor-promoting and tumor-inhibiting effects in prostate cancer. However, the relationship between iNOS protein expression and long-term prostate cancer outcomes is unclear. We evaluated iNOS expression in tumor epithelia and stroma in 300 men with localized tumors diagnosed incidentally by transurethral resection of the prostate (TURP) in Sweden. In this extreme case-control design, cases (N=132) died of prostate cancer and controls (N=168) survived at least 8 years following diagnosis without death from prostate cancer or a competing cause. Immunohistochemistry was undertaken with a polyclonal rabbit anti-human NOS2 antibody (Abcam) and the Ventana (Roche) semi-automated staining system. Two observers individually scored the staining according to intensity and number of positive cells from 0-3. The median value across cores in each patient were then categorized as <1, >1-<2, and >2, separately for epithelial and stromal compartments. Odds ratios for lethal prostate cancer were estimated with logistic regression controlling for the matching factors (age, calendar year of diagnosis), as well as tumor stage, Gleason score, and percent tumor. iNOS was expressed by stromal-associated M1 macrophages and fibroblasts, as well as tumor cells. Gleason score was positively associated with both stromal and epithelial iNOS staining. In the stroma, there was no statistically significant association between iNOS expression and lethal prostate cancer after adjustment for clinical covariates. However, the odds of lethal prostate cancer increased with tumor expression of iNOS in the fully adjusted model. Compared to patients with the lowest category of iNOS expression, the odds ratios for lethal prostate cancer were 2.96 (95% CI: 1.26-6.96) for patients in the second category and 3.80 (95% CI: 1.45-9.97) for patients in the top category. These results suggest that iNOS may help to identify patients with aggressive prostate cancer at the time of diagnosis, or may be a therapeutic target. Given previously reported in vitro data suggesting that iNOS promotes proliferation of androgen-independent prostate tumors, future analyses will investigate association between iNOS expression and time to castration-resistant prostate cancer in this patient population.
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- Wang, Chengshi, et al.
(författare)
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Cardiovascular mortality among cancer survivors who developed breast cancer as a second primary malignancy
- 2020
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 80:16
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with breast cancer are at increased risk of cardiovascular diseases and cardiovascular mortality, potentially due to treatment-related cardiotoxicity, early menopause, and psychological distress. Cancer survivors who developed breast cancer as a second malignancy (BCa-2) are common and may experience cancer treatment and distress for a second time. It is however unknown whether BCa-2 patients have increased risk of cardiovascular mortality compared to patients with breast cancer as the first malignancy (BCa-1) and the cancer-free female population.Methods: Using the Surveillance, Epidemiology, and End Results database, we conducted a cohort study including 1,024,047 patients with BCa-1 and 41,744 with BCa-2 diagnosed at age of 30 years and older during 1975-2016, and the corresponding female population of 994,415,911 person-years in the U.S.. Compared with patients with BCa-1 and the general population, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among patients with BCa-2 by using multivariable Poisson regression.Results: During the median follow-up of 5.9 years (interquartile range, 2.4-11.3 years), 3,550 and 71,298 cardiovascular deaths were observed in BCa-2 and BCa-1 patients. Overall, BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the general population (IRR 1.07, 95% CI 1.03-1.10) and BCa-1 patients (IRR 1.13, 95% CI 1.10-1.17) with the adjustment of demographic factors. When comparing BCa-2 with BCa-1, the association was further independent of tumor characteristics and treatment modes (IRR 1.15, 95% CI 1.11-1.19). The elevated risk of cardiovascular mortality was mostly pronounced at age of follow-up between 30 and 79 years (IRR 1.31, 95% CI 1.23-1.40 compared with the general population; IRR 1.34, 95% CI 1.25-1.43 compared with BCa-1), whereas the risk was mildly increased, if any, at age of 80+ years compared with BCa-1 (IRR 1.07, 95% CI 1.02-1.11). The increased risk at age of 30-79 years in BCa-2 was particularly greater within the first month after cancer diagnosis compared with the general population (IRR 3.20, 95% CI 2.34-4.38). In contrast, cardiovascular mortality rate in BCa-2 was comparable to that in BCa-1 within the first month (IRR 0.87, 95% CI 0.63-1.21).Conclusions: Our findings suggest that patients with BCa-2, particularly in patients younger than 80 years, are at increased risk of cardiovascular mortality, compared with the general population and patients with BCa-1.
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- Bekele, Maheteme, et al.
(författare)
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Tumor and immune cell profiling in breast cancer using highly multiplexed imaging mass cytometry single-cell technology demonstrates tumor heterogeneity and immune phenotypic abnormality in Ethiopian women
- 2020
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 80:21 Suppl.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Tumor heterogeneity represents a complex challenge to cancer treatment, disease recurrence, and patient survival. Imaging mass cytometry (IMC) is an emerging proteomic tool for cancer profiling in tumor tissue samples. IMC enables digital image analysis by multiplexed immunostaining of cells and proteins within tissue and preserves spatial relations within tumor environment. We have applied IMC based approach to study the heterogeneity of invasive breast carcinoma protein expression pattern in formalin fixed paraffin embedded tissues.Methods: A total of 10 region of interest (ROI) derived from 5 patients with primary invasive breast carcinoma representing three molecular subclasses (HR+/HER2-,HER2+/HR- and TNBC) were stained with a 30-marker IMC metal labeled antibody panel (α-SMA, EGFR, p53, CD33, CD16, CD163, CD11b, PDL1, CD31, CD45, D44,Vimentin, FoxP3, CD4, ECadherin, CD68, CD20, CD8a, Cytokeratin7, PD1, GranzymeB, Ki67, ColTypeI, CD3, CD45RO, HLADR, DARC & CD11c). Tissue imaging was done by quantifying the abundance of bound antibody with a Hyperion IMC. MCD Viewer was used for visualization purpose and to export raw 16-bit tiff images for segmentation on CellProfiler. Segmentation masks were combined with the individual tiff files to extract single-cell information from each individual image. HistoCAT was applied to perform unbiased clustering of cell populations using the PhenoGraph algorithm and clustered cell populations was overlaid on t-SNE plot. The relative marker expression was used to generate heat-maps and each cluster was manually assigned a phenotype based on its expression profile.Results: The t-SNE generated from each ROI revealed different distinct cell populations and we report the presence of diverse tumor and immune cell populations in our samples. The (min, max) number of PhenoGraph clustered tumor cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. Similarly, the (min, max) number of PhenoGraph clustered immune cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. We also document the presence of inter and intra-tumor heterogeniety in expression of PD1 and PDL1 in all the tumor subtypes studied. Additionally, we report a phenotypic abnormality in the immune cell populations identified with dual or triple markers expression of the canonical CD antigens of T-Cells, B-Cells and macrophages.Conclusion: The current study demonstrates high-dimensional visualization with the simultaneous analysis of epithelial, immune, and stromal components using IMC can be used to explore cell populations in tumor tissue to quantify tumor heterogeneity or identification of novel clustering patterns that has potential for translational research and clinical practice. Significance: This study presents the potential of Imaging Mass Cytometry and single cell analysis algorithms in multiplex high throughput tumor tissue studies.
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- Akre [Fall], Katja, 1971-, et al.
(författare)
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Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement
- 2000
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Ingår i: Cancer Research. - Birmingham, USA : American Asoociation for Cancer Research. - 0008-5472 .- 1538-7445. ; 60, s. 6376-
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Tidskriftsartikel (refereegranskat)abstract
- Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationwide case-control study nested in a cohort of 39,154 patients who underwent hip replacement surgery between 1965 and 1983. Such patients frequently receive prophylactic antibiotic treatment. During follow-up through 1989, we identified 189 incident cases of gastric cancer. For each case, three controls were selected from the cohort. Exposure data were abstracted from hospital records. Blood samples from a separate cohort undergoing hip replacement surgery were analyzed for anti-H. pylori IgG before and after surgery. Both long-term antibiotic treatment before surgery [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7] and prophylactic antibiotic treatment (OR, 0.7; 95% CI, 0.5-1.1) conferred a reduction in gastric cancer risk. The reduction appeared stronger after 5 years (OR, 0.6; 95% CI, 0.3-1.2) than during shorter follow-up after hip replacement (OR, 0.8; 95% CI, 0.4-1.7). There was an apparent decrease in risk with increasing body weight-adjusted doses of antibiotics (P = 0.13). However, the rate of H. pylori antibody disappearance was not strikingly higher in the cohort of patients undergoing hip replacement than in a control cohort. Our findings provide indirect support for the hypothesis that treatment with antibiotics at a relatively advanced age reduces the risk of gastric cancer.
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