Background: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched ­CD19+IgD−CD27+ on-class-switched ­CD19+IgD+CD27+ memory B cell subsets and ­CD19 + CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. Methods: This cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. Results: The frequency of ­­CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both ­CD19+IgD−CD27+ class-switched and ­­CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of ­CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. Conclusion This study is the first to demonstrate a dysregulated proportion of ­CD19+IgD+CD27+ non-class-switched memory B cells and ­CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

Background: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched ­CD19+IgD−CD27+ on-class-switched ­CD19+IgD+CD27+ memory B cell subsets and ­CD19 + CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. Methods: This cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. Results: The frequency of ­­CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both ­CD19+IgD−CD27+ class-switched and ­­CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of ­CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. Conclusion This study is the first to demonstrate a dysregulated proportion of ­CD19+IgD+CD27+ non-class-switched memory B cells and ­CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

Background: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched ­CD19+IgD−CD27+ on-class-switched ­CD19+IgD+CD27+ memory B cell subsets and ­CD19 + CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. Methods: This cross-sectional case–control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. Results: The frequency of ­­CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both ­CD19+IgD−CD27+ class-switched and ­­CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of ­CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. Conclusion This study is the first to demonstrate a dysregulated proportion of ­CD19+IgD+CD27+ non-class-switched memory B cells and ­CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

There is no doubt that the incidence of cancer sufferers is rising in the world, and it is estimated that in the next several decades, the number of people suffering from malignancies or the cancer rate will double. Diagnostic and therapeutic targeting of noncoding RNAs (ncRNAs), especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), represent an excellent approach for cancer diagnosis and treatment, as well as many other diseases. One of the latest miRNAs is miR-4492, upregulating some genes in tumor tissues including ROMO1, HLA-G, NKIRAS2, FOXK1, and UBE2C.It represents an attractant example of a miRNA acting at multiple levels to affect the same malignancy hallmark. Based on the studies, miR-4492 plays a key role in several cancers such as, breast cancer, bladder cancer, osteosarcoma, glioblastoma multiforme, hepatocellular carcinoma, colorectal cancer, and ovarian cancer. Putting it all together, identifying the precise mechanisms of miR-4492 in the pathogenesis of cancer, could pave the way to find better diagnostic and therapeutic strategies for cancer sufferers. For this reason, it might be a novel potential diagnostic biomarker and therapeutic target for neoplasms.

OBJECTIVE: Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life. To assess the role of parabens in this phenomenon, the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province, Iran. METHODS: Adjacent normal-malignant breast tissue samples were obtained from 53 subjects. The parabens including methyl-paraben (MePB), ethyl-paraben (EtPB), propyl-paraben (PrPB), and butylparaben (BuPB) were extracted from the sample supernatant and then subjected to gas chromatography analysis. RESULTS: Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer. We observed a significant association for dose-response pattern of MePB [OR = 98.34 (11.43-185.2), P = 0.027] for both ER+ and PR+ women and MePB [OR = 164.3 (CI: 112.3-216.3), P < 0.001] for HER2+ women than women with negative receptors. The risk of 95-fold increase in MePB dose and 164-fold increase in ΣPBs dose were significant for women with hereditary breast cancer in first-degree relatives. CONCLUSION These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.

OBJECTIVES: Colorectal cancer (CRC) patients are considered to have been cured when the mortality rate of individuals with the disease returns to the same level as expected in the general population. This study aimed to assess the impact of various risk factors on the cure fraction of CRC patients using a real dataset of Iranian CRC patients with a non-mixture non-parametric cure model. METHODS: This study was conducted on the medical records of 512 patients who were definitively diagnosed with CRC at Taleghani Hospital, Tehran, Iran from 2001 to 2007. A non-mixture non-parametric cure rate model was applied to the data after using stepwise selection to identify the risk factors of CRC. RESULTS: For non-cured cases, the mean survival time was 1,243.83 days (95% confidence interval [CI], 1,174.65 to 1,313.00) and the median survival time was 1,493.00 days (95% CI, 1,398.67 to 1,587.33). The 1- and 3-year survival rates were 92.9% (95% CI, 91.0 to 95.0) and 73.4% (95% CI, 68.0 to 79.0), respectively. Pathologic stage T1 of the primary tumor (estimate=0.58; p=0.013), a poorly differentiated tumor (estimate=1.17; p<0.001), a body mass index (BMI) between 18.6 and 24.9 kg/m2 (estimate=−0.60; p=0.04), and a BMI between 25.0 and 29.9 kg/m2 (estimate=−1.43; p<0.001) had significant impacts on the cure fraction of CRC in the multivariate analysis. The proportion of cured patients was 64.1% (95% CI, 56.7 to 72.4). CONCLUSIONS: This study found that the pathologic stage of the primary tumor, tumor grade, and BMI were potential risk factors that had an impact on the cure fraction. A non-mixture non-parametric cure rate model provides a flexible framework for accurately determining the impact of risk factors on the long-term survival of patients with CRC.
Body Mass Index ; Colorectal Neoplasms* ; Dataset ; Humans ; Iran* ; Medical Records ; Mortality ; Multivariate Analysis ; Risk Factors ; Survival Analysis ; Survival Rate

OBJECTIVES: Colorectal cancer (CRC) patients are considered to have been cured when the mortality rate of individuals with the disease returns to the same level as expected in the general population. This study aimed to assess the impact of various risk factors on the cure fraction of CRC patients using a real dataset of Iranian CRC patients with a non-mixture non-parametric cure model.METHODS: This study was conducted on the medical records of 512 patients who were definitively diagnosed with CRC at Taleghani Hospital, Tehran, Iran from 2001 to 2007. A non-mixture non-parametric cure rate model was applied to the data after using stepwise selection to identify the risk factors of CRC.RESULTS: For non-cured cases, the mean survival time was 1,243.83 days (95% confidence interval [CI], 1,174.65 to 1,313.00) and the median survival time was 1,493.00 days (95% CI, 1,398.67 to 1,587.33). The 1- and 3-year survival rates were 92.9% (95% CI, 91.0 to 95.0) and 73.4% (95% CI, 68.0 to 79.0), respectively. Pathologic stage T1 of the primary tumor (estimate=0.58; p=0.013), a poorly differentiated tumor (estimate=1.17; p<0.001), a body mass index (BMI) between 18.6 and 24.9 kg/m2 (estimate=−0.60; p=0.04), and a BMI between 25.0 and 29.9 kg/m2 (estimate=−1.43; p<0.001) had significant impacts on the cure fraction of CRC in the multivariate analysis. The proportion of cured patients was 64.1% (95% CI, 56.7 to 72.4).CONCLUSIONS: This study found that the pathologic stage of the primary tumor, tumor grade, and BMI were potential risk factors that had an impact on the cure fraction. A non-mixture non-parametric cure rate model provides a flexible framework for accurately determining the impact of risk factors on the long-term survival of patients with CRC.
Body Mass Index ; Colorectal Neoplasms ; Dataset ; Humans ; Iran ; Medical Records ; Mortality ; Multivariate Analysis ; Risk Factors ; Survival Analysis ; Survival Rate