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The objective of this study is to analyze the expression of E6 Humanpapilloma virus (HPV), p53, and p16INK4A in cervical adenocarcinoma grade well differentiated (WD), moderately differentiated (MD), and poorly differentiated (PD). A cross sectional study conducted at Department of Anatomic Pathology, Dr. Soetomo General Academic Hospital Surabaya Indonesia using formalin fix paraffin embedded (FFPE) from cervical normal and cervical adenocarcioma grade WD, MD, and PD. The expression of E6 HPV, p53, and p16INK4A was performed by immunohistochemistry (IHC) staining. Data were analyzed with Kruskal-Wallis and continued with Mann-Withney test. The expression of E6 HPV in the cervical adenocarcinoma showed 35.9% specimens represented negative and 64.1% specimens represented positive. There was no significant difference in the expression of E6 HPV and p53 in cervical adenocarcinoma between grade WD, MD, and PD. The p16INK4A was overexpressed, shown as diffuse appearance in 89.7% of the specimens. There was a significant difference in the expression of p16INK4A between grade WD and MD with PD. In conclusion, some of cervical adecarcinoma were not caused by infection of HPV type 16 or 18 and the expression of p16INK4A might take a role in the developing of malignancy that caused by infection of HPV. more...

Introduction: Cervical adenocarcinoma is the second most common type of cervical cancer. The marker to predict the risk of this cancer is still need to be improved. This study aimed to evaluate the correlation between expression of E6 HPV with p53 and p16INK4A in cervical adenocarcinoma and cervical normal. Methods: This study was a cross sectional study conducted at the Department of Anatomic Pathology, Dr. Soetomo General Academic Hospital Surabaya Indonesia using 49 paraffin blocks during period January-December 2017. The E6 HPV, p53, and p16INK4A expression were detected by immunohistochemistry staining. Results: There were significant differences between the expression of E6 HPV and p16INK4A in cervical adenocarcinoma and cervical normal, but the expression of p53 was no significant difference with p=0.060 (P>0.05). There was a positive correlation between the expression of E6 HPV with p53 and p16INK4A (p<0.05) in cervical adenocarcinoma and cervical normal, and in cervical adenocarcinoma group, there was a significant correlation between the expression of E6 HPV with p53 (p=0.004) and p16INK4A (p=0.028), but no correlation was found between p53 with p16INK4A expression (p=0,092). Conclusion: It suggests that p16INK4A might serve as marker for predicting the risk of developing cervical cancer from the epithelium of cervical normal. [ABSTRACT FROM AUTHOR] more...

Abstract Background Genetic engineering of T-cells to express specific T cell receptors (TCR) has emerged as a novel strategy to treat various malignancies. More widespread utilization of these types of therapies has been somewhat constrained by the lack of closed culture processes capable of expanding sufficient numbers of T-cells for clinical application. Here, we evaluate a process for robust clinical grade manufacturing of TCR gene engineered T-cells. Methods TCRs that target human papillomavirus E6 and E7 were independently tested. A 21 day process was divided into a transduction phase (7 days) and a rapid expansion phase (14 days). This process was evaluated using two healthy donor samples and four samples obtained from patients with epithelial cancers. Results The process resulted in ~ 2000-fold increase in viable nucleated cells and high transduction efficiencies (64–92%). At the end of culture, functional assays demonstrated that these cells were potent and specific in their ability to kill tumor cells bearing target and secrete large quantities of interferon and tumor necrosis factor. Both phases of culture were contained within closed or semi-closed modules, which include automated density gradient separation and cell culture bags for the first phase and closed GREX culture devices and wash/concentrate systems for the second phase. Conclusion Large-scale manufacturing using modular systems and semi-automated devices resulted in highly functional clinical-grade TCR transduced T-cells. This process is now in use in actively accruing clinical trials and the NIH Clinical Center and can be utilized at other cell therapy manufacturing sites that wish to scale-up and optimize their processing using closed systems. more...

The objective of this study is to analyze the expression of E6 Humanpapilloma virus (HPV), p53, and p16INK4A in cervical adenocarcinoma grade well differentiated (WD), moderately differentiated (MD), and poorly differentiated (PD). A cross sectional study conducted at Department of Anatomic Pathology, Dr. Soetomo General Academic Hospital Surabaya Indonesia using formalin fix paraffin embedded (FFPE) from cervical normal and cervical adenocarcioma grade WD, MD, and PD. The expression of E6 HPV, p53, and p16INK4A was performed by immunohistochemistry (IHC) staining. Data were analyzed with Kruskal-Wallis and continued with Mann-Withney test. The expression of E6 HPV in the cervical adenocarcinoma showed 35.9% specimens represented negative and 64.1% specimens represented positive. There was no significant difference in the expression of E6 HPV and p53 in cervical adenocarcinoma between grade WD, MD, and PD. The p16INK4A was overexpressed, shown as diffuse appearance in 89.7% of the specimens. There was a significant difference in the expression of p16INK4A between grade WD and MD with PD. In conclusion, some of cervical adecarcinoma were not caused by infection of HPV type 16 or 18 and the expression of p16INK4A might take a role in the developing of malignancy that caused by infection of HPV. [ABSTRACT FROM AUTHOR] more...

Background: Genetic engineering of T-cells to express specific T cell receptors (TCR) has emerged as a novel strategy to treat various malignancies. More widespread utilization of these types of therapies has been somewhat constrained by the lack of closed culture processes capable of expanding sufficient numbers of T-cells for clinical application. Here, we evaluate a process for robust clinical grade manufacturing of TCR gene engineered T-cells.Methods: TCRs that target human papillomavirus E6 and E7 were independently tested. A 21 day process was divided into a transduction phase (7 days) and a rapid expansion phase (14 days). This process was evaluated using two healthy donor samples and four samples obtained from patients with epithelial cancers.Results: The process resulted in ~ 2000-fold increase in viable nucleated cells and high transduction efficiencies (64-92%). At the end of culture, functional assays demonstrated that these cells were potent and specific in their ability to kill tumor cells bearing target and secrete large quantities of interferon and tumor necrosis factor. Both phases of culture were contained within closed or semi-closed modules, which include automated density gradient separation and cell culture bags for the first phase and closed GREX culture devices and wash/concentrate systems for the second phase.Conclusion: Large-scale manufacturing using modular systems and semi-automated devices resulted in highly functional clinical-grade TCR transduced T-cells. This process is now in use in actively accruing clinical trials and the NIH Clinical Center and can be utilized at other cell therapy manufacturing sites that wish to scale-up and optimize their processing using closed systems. [ABSTRACT FROM AUTHOR] more...

Lung cancer is the most common cause of cancer deaths worldwide. Although tobacco smoking is considered to be the main risk factor and the most well-established risk factor for lung cancer, a number of patients who do not smoke have developed this disease. This number varies between 15 % to over one-half of lung cancer cases, and the deaths from lung cancer in non-smokers are increasing every year. There are many other agents that are thought to be etiological, including diesel exhaust exposure, metals, radiation, radon, hormonal factors, cooking oil, air pollution and infectious diseases, such as human papillomavirus (HPV). Studies in various parts of the world have detected HPV DNA at different rates in lung tumors. However, the role of HPV in lung cancer is still unclear. Thus, in this review, we investigated some molecular mechanisms of HPV protein activity in host cells, the entry of HPV into lung tissue and the possible route used by the virus to reach the lung cells. [ABSTRACT FROM AUTHOR] more...