Search

Objectives: Thrombi in cerebral large vessel occlusion associated with active cancer are often fibrin and platelet-rich white thrombi. However, evaluating the thrombus composition in a short time before thrombectomy is often ineffective. We sought to determine factors related to white thrombi in acute ischemic stroke due to large vessel occlusion in cancer patients., Methods: Consecutive cancer patients undergoing thrombectomy for acute ischemic stroke due to large vessel occlusion between January 2018 and May 2022 were retrospectively reviewed. The patients were classified into white thrombus and red thrombus groups on the basis of the pathological findings of retrieved thrombi. Patient characteristics and laboratory findings were compared between the two groups., Results: There were 12 patients in the white thrombus group and 11 patients in the red thrombus group. Active cancer was significantly more in the white thrombus group than in the red thrombus group (91.7% vs. 36.3%, p = 0.0094). Internal carotid artery occlusion was significantly less in the white thrombus group than in the red thrombus group (0% vs. 36.4%, p = 0.037). Among laboratory findings, D-dimer levels were an independent factor associated with white thrombi (odds ratio 8.97 [95% confidence interval 1.71-368.99], p < 0.0001). The cutoff value of D-dimer levels for predicting white thrombi was 3.5 μg/mL (83.3% sensitivity and 100% specificity)., Conclusions: In acute ischemic stroke in cancer patients, active cancer, no internal carotid artery occlusion, and higher D-dimer levels (≥3.5 μg/mL) may be associated with occlusion with fibrin and platelet-rich white thrombi.

Strategies to develop cancer therapies using inhibitors that target matrix metalloproteinases (MMPs), particularly membrane type-1 MMP (MT1-MMP), have failed. This is predominantly attributed to the specificity of MMP inhibitors and numerous functions of MMPs; therefore, targeting substrates with such broad specificity can lead to off-target effects. Thus, new drug development for cancer therapeutics should focus on the ability of MT1-MMP to break down substrates, such as functional cell membrane proteins, to regulate the functions of these proteins that promote tumor malignancy. In this review, we discuss the mechanism by which proteolysis of cell surface proteins by MT1-MMP promotes progression of malignant tumor cells. In addition, we discuss the two protein fragments generated by limited cleavage of erythropoietin-producing hepatoma receptor tyrosine kinase A2 (EphA2-NF, -CF), which represent a promising basis for developing new cancer therapies and diagnostic techniques., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: It is well known that specific occupations can cause harm in developing malignant neoplasms. Chemical exposure is particularly high in the manufacturing industry and workers in this sector may face a higher occupational risk for cancer. We aimed to estimate inequalities in the risk of cancers related to occupational chemical exposure in various manufacturing categories., Methods: Using nationwide clinical inpatient data (1984-2017) in Japan, we undertook a multicenter, case-control study with regard to risks of developing cancers among various manufacturing industry categories. Using the food manufacturing industry as the reference group, odds ratios and 95% confidence intervals for each industry were estimated by conditional logistic regression, adjusted for sex, age, admission period, and the admitting hospital. Medical record summaries accounting for 89% of industrial categories with high odds ratios were collected to confirm diagnoses made on the basis of histology. We estimated industrial hazards based on the Pollutant Release and Transfer Register., Results: A reduced risk for some of common cancers was observed among lumber and wood products industries. Leather tanning, leather products and fur tended to show a higher risk: 2.36 (95% CI 1.15-4.83) for pancreatic cancer, 2.85 (95% CI 1.26-6.47) for liver cancer and 2.00 (95% CI 1.01-3.99) for lung cancer. For the electronics category, observations of high risk ranged from 2.09 (95%CI 1.18-3.70) for ureter cancer, to 2.49 (95% CI 1.79-3.55) for kidney cancer., Conclusions: This study revealed industry risk inequalities in manufacturing categories were present with regard to the risk of common cancers in Japan.

Objectives: Little is known about the risk of developing various cancers according to occupation and occupational physical activity., Methods: Using nationwide clinical inpatient data (1984-2017) in Japan, we undertook a multicentered, matched case-control study with regard to the risk of developing various cancers according to occupation and using patients admitted with fractures as controls. Using standardized national occupation and industrial classifications, we first identified the longest-held job for each patient. Using sales workers as the reference group, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression, adjusted for age, admission period, and the admitting hospital, with smoking, alcohol consumption, and lifestyle diseases as covariates. The risk of high and low occupational physical activity was also estimated., Results: Across all occupations, a reduced risk for all common cancers among males was observed among those occupations associated with high physical activities, such as agriculture. People in these occupations tended to show a lower risk for most cancers, including, for example, prostate cancer (OR 0.58, 95% CI 0.45-0.75) and lung cancer (OR 0.63, 95% CI 0.51-0.76). For females, the breast cancer risk was low in women engaged in agriculture (OR 0.58, 95% CI 0.45-0.75) and in those occupations with high levels of occupational physical activity (OR 0.58, 95% CI 0.52-0.66)., Conclusions: This study revealed differences in cancer risk among diverse occupations in Japan. Specifically, those occupations associated with high levels of physical activity may be associated with a decreased risk of cancer., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Little is known about socioeconomic inequalities in male cancer incidence in nonwestern settings. Using the nationwide clinical and occupational inpatient data (1984-2016) in Japan, we performed a multicentered, matched case-control study with 214 123 male cancer cases and 1 026 247 inpatient controls. Based on the standardized national classifications, we grouped patients' longest-held occupational class (blue-collar, service, professional, manager), cross-classified by industrial cluster (blue-collar, service, white-collar). Using blue-collar workers in blue-collar industries as the referent group, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression with multiple imputation, matched for age, admission date, and admitting hospital. Smoking and alcohol consumption were additionally adjusted. Across all industries, a reduced risk with higher occupational class (professionals and managers) was observed for stomach and lung cancer. Even after controlling for smoking and alcohol consumption, the reduced odds persisted: OR of managers in white-collar industries was 0.80 (95% CI 0.72-0.90) for stomach cancer, and OR of managers in white-collar industries was 0.66 (95% CI 0.55-0.79) for lung cancer. In white-collar industries, higher occupational class men tended to have lower a reduced risk for most common types of cancer, with the exception of professionals who showed an excess risk for prostate cancer. We documented socioeconomic inequalities in male cancer incidence in Japan, which could not be explained by smoking and alcohol consumption., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The immunostaining based Laser-capture microdissection (LCM) method called immune-LCM allows us to quantify the mRNA. Immune-LCM has recently been introduced to enhance identification of cells carrying a particular protein from frozen tissue samples. We have recently performed the immune-LCM of formaldehyde-fixated, paraffin-embedded tissues immunostained with a monoclonal antibody Factor VIII. This method could be useful for quantitative gene expression analysis in blood vessels from tumors of patients that have been treated with antiangiogenic drugs, allowing for validation of the effect of drug on the expected targets. Such capability might be exceedingly useful for the evaluation of the bioactivity of new drugs. This method is also useful to compare gene expression patterns in tumor cells versus endothelial cells during tumor progression or tumor angiogenesis.

Laser capture microdissection (LCM) allows microscopic procurement of specific cell types from tissue sections that can then be used for gene expression analysis. In conventional LCM, frozen tissues stained with hematoxylin are normally used to the molecular analysis. Recent studies suggested that it is possible to carry out gene expression analysis of formaldehyde-fixated paraffin embedded (FFPE) tissues that were stained with hematoxylin. However, it is still unclear if quantitative gene expression analyses can be performed from LCM cells from FFPE tissues that were subjected to immunostaining to enhance identification of target cells. In this proof-of-principle study, we analyzed by reverse transcription-PCR (RT-PCR) and real time PCR the expression of genes in factor VIII immunostained human endothelial cells that were dissected from FFPE tissues by LCM. We observed that immunostaining should be performed at 4 degrees C to preserve the mRNA from the cells. The expression of Bcl-2 in the endothelial cells was evaluated by RT-PCR and by real time PCR. Glyceraldehyde-3-phosphate dehydrogenase and 18S were used as house keeping genes for RT-PCR and real time PCR, respectively. This report unveils a method for quantitative gene expression analysis in cells that were identified by immunostaining and retrieved by LCM from FFPE tissues. This method is ideally suited for the analysis of relatively rare cell types within a tissue, and should improve on our ability to perform differential diagnosis of pathologies as compared to conventional LCM.

Purpose: The presence of immunological dysfunction has not been well demonstrated in cancer patients. Recent studies have revealed that the immune response can be classified into types 1 and 2, and in the present work the immunological function of patients was studied from the perspective of these two types of response., Methods: Types 1 and 2 immune response were evaluated by monitoring the production of various cytokines by peripheral blood mononuclear cells from 38 patients with advanced cancer of various organs and 20 healthy subjects. The usual immunological parameters, differential cell leukocyte counts, the level of T cell subsets (CD4 and CD8) and natural killer activity were also examined., Results: The production of interleukin-2 (IL-2), interferon gamma, IL-10, IL-12 and tumor necrosis factor alpha was found to be significantly lower in the patients (75 +/- 57, 171 +/- 205, 40 +/- 34, 8 +/- 8, 1450 +/- 1010 pg/ml) than in healthy subjects (143 +/- 99, 422 +/- 296, 64 +/- 34, 16 +/- 10, 2550 +/- 950 pg/ml); however, the mean level of IL-4 in the patients seemed to be higher. The correlations between different cytokine levels suggested that they were produced differently. Lymphocyte counts were significantly lower in patients, but there was no difference in the other usual immunological parameters., Conclusions: Patients with advanced cancer are deficient in monocytes and the type 1 immune response. The measurement of various cytokines reported in this study provides a more sensitive and valuable tool for evaluating the function of cell-mediated immunity in cancer patients than do the usual tests.

Background: A reported imbalance of Th1 and Th2 may be responsible for the occurrence and progress of certain diseases. Patients with advanced cancer may have impaired cell-mediated immunity caused by a switch from Th1 to Th2. We investigated the balance of Th1 and Th2 in cancer patients using two approaches., Methods: Flow cytometry was used to define Th1 and Th2 using intracellular cytokines, thereby determining the frequency of these helper T cells in CD4+ peripheral blood mononuclear cells (PBMC). The amount of cytokines secreted by stimulated PBMC in bulk culture was determined., Results: Production of TNF-alpha and IFN-gamma in the culture was significantly lower in 9 patients (1188 +/- 634 pg/ml and 46 +/- 84 pg/ml) than in 10 healthy subjects (2491 +/- 1037 pg/ml and 295 +/- 219 pg/ml) (p < 0.002 and p < 0.003), while the production of IL-4 was slightly higher in cancer patients than in the healthy subjects. The percentage of IFN-gamma-IL-4+ cells in CD4+ cells was significantly higher in the patients than in healthy subjects (4.3 +/- 2.0% and 2.4 +/- 0.7%); there was no difference in IFN-gamma+IL-4- cells between the two groups. The ratio of IFN-gamma+IL-4- and IFN-gamma-IL-4+ cells per individual was significantly lower in the patients., Conclusion: These results indicated that an imbalance of Th1 and Th2 was found not only in the frequency of the subsets in PBMC, but also in the capacity for cytokine-production.