Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 25 Φεβρουαρίου 2018
Survival of patients with hepatobiliary tract and duodenal cancer sites in Germany and the United States in the early 21st century
Abstract
Hepatobiliary tract cancers (HBTC) are a heterogeneous group of cancers with high mortality. Because most of these cancers, with the exception of hepatocellular carcinoma (HCC) are rare, few data are available concerning the population level survival expectations of patients with HBTC. Here, we describe survival of patients with HBTC in Germany with comparison to survival in the United States (US). Therefore, data were extracted from 12 databases in Germany and the Surveillance, Epidemiology and End Results (SEER13) database in the US. Period analysis and modeled period analysis were used to calculate 5-year relative survival estimates for patients with HBTC diagnosed from 1997-2013. HCC was the most common HBTC in each database, accounting for over 1/3 of HBTC in Germany and about half of cases in the US. Overall age adjusted 5-year relative survival for HBTC in 2006-13 was 19.1% in Germany and 20.6% in the US. Five year relative survival increased by 3.8 percent units in Germany and 4.5 percent units in the US between 2002-05 and 2010-13. Five year relative survival for individual types of HBTC ranged from 9.8% in Germany and 2.9% in the US for not otherwise specified biliary tract cancers to 44.4% and 50.1%, respectively, in Germany and the US for duodenal cancers. In conclusion, survival for HBTC remains poor in both Germany and the US, although a small increase in survival in the past decade was observed. Further work to find better treatment options for HBTC is needed to improve survival. This article is protected by copyright. All rights reserved.
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Cervicovaginal microbiota composition correlates with the acquisition of high-risk human papillomavirus types
Abstract
High-risk (hr) human papillomavirus (HPV) infection is closely associated with the clinical conditions of both squamous intraepithelial lesions (SILs) and cervical carcinoma. However, it remains unclear what factors determine the type of hrHPV infection. Here, we have comprehensively investigated the bacterial composition of the cervicovaginal microbiota of 280 women infected with one type of hrHPV (HPV 16, 52, or 58) by the pyrosequencing of barcoded 16S rRNA genes. Differential microbiota composition was observed among various SIL groups and within the subgroups of each group. This result showed that it is not the microbiota diversity or the common microbiota, but rather agents that are specific to each SIL that might have a positive influence on the acquisition of hrHPV types, independent of abundance. Specifically, a composition of Oribacterium, Lachnobacterium and Thermus in the cervicovaginal microbiota is more likely to be associated with HPV 16, while a composition of Motilibacter in the cervicovaginal microbiota is more likely to be associated with HPV 52, and a composition of Litorilinea and Paludibaculum with a concomitant paucity of L. iners in the cervicovaginal microbiota is more likely to be associated with HPV 58. Furthermore, functional predictions regarding infectious diseases and cancer-related genes disclosed significant differences (P < 0.01) among the different (sub)groups. Our study provides an elucidation of the relationship between the composition of the cervicovaginal microbiota and the type of hrHPV acquired. This article is protected by copyright. All rights reserved.
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Prospective study of blood metabolites associated with colorectal cancer risk
Abstract
Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In the current study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios (ORs) per standard deviation (SD) increase of transformed metabolites: 0.31 to 1.98; p values: 0.002 to 1.25 × 10−10]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids, and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. This article is protected by copyright. All rights reserved.
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Cervicovaginal microbiota composition correlates with the acquisition of high-risk human papillomavirus types
Abstract
High-risk (hr) human papillomavirus (HPV) infection is closely associated with the clinical conditions of both squamous intraepithelial lesions (SILs) and cervical carcinoma. However, it remains unclear what factors determine the type of hrHPV infection. Here, we have comprehensively investigated the bacterial composition of the cervicovaginal microbiota of 280 women infected with one type of hrHPV (HPV 16, 52, or 58) by the pyrosequencing of barcoded 16S rRNA genes. Differential microbiota composition was observed among various SIL groups and within the subgroups of each group. This result showed that it is not the microbiota diversity or the common microbiota, but rather agents that are specific to each SIL that might have a positive influence on the acquisition of hrHPV types, independent of abundance. Specifically, a composition of Oribacterium, Lachnobacterium and Thermus in the cervicovaginal microbiota is more likely to be associated with HPV 16, while a composition of Motilibacter in the cervicovaginal microbiota is more likely to be associated with HPV 52, and a composition of Litorilinea and Paludibaculum with a concomitant paucity of L. iners in the cervicovaginal microbiota is more likely to be associated with HPV 58. Furthermore, functional predictions regarding infectious diseases and cancer-related genes disclosed significant differences (P < 0.01) among the different (sub)groups. Our study provides an elucidation of the relationship between the composition of the cervicovaginal microbiota and the type of hrHPV acquired. This article is protected by copyright. All rights reserved.
http://ift.tt/2sUCDQ2
Survival of patients with hepatobiliary tract and duodenal cancer sites in Germany and the United States in the early 21st century
Abstract
Hepatobiliary tract cancers (HBTC) are a heterogeneous group of cancers with high mortality. Because most of these cancers, with the exception of hepatocellular carcinoma (HCC) are rare, few data are available concerning the population level survival expectations of patients with HBTC. Here, we describe survival of patients with HBTC in Germany with comparison to survival in the United States (US). Therefore, data were extracted from 12 databases in Germany and the Surveillance, Epidemiology and End Results (SEER13) database in the US. Period analysis and modeled period analysis were used to calculate 5-year relative survival estimates for patients with HBTC diagnosed from 1997-2013. HCC was the most common HBTC in each database, accounting for over 1/3 of HBTC in Germany and about half of cases in the US. Overall age adjusted 5-year relative survival for HBTC in 2006-13 was 19.1% in Germany and 20.6% in the US. Five year relative survival increased by 3.8 percent units in Germany and 4.5 percent units in the US between 2002-05 and 2010-13. Five year relative survival for individual types of HBTC ranged from 9.8% in Germany and 2.9% in the US for not otherwise specified biliary tract cancers to 44.4% and 50.1%, respectively, in Germany and the US for duodenal cancers. In conclusion, survival for HBTC remains poor in both Germany and the US, although a small increase in survival in the past decade was observed. Further work to find better treatment options for HBTC is needed to improve survival. This article is protected by copyright. All rights reserved.
http://ift.tt/2F5jBv9
Prospective study of blood metabolites associated with colorectal cancer risk
Abstract
Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In the current study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios (ORs) per standard deviation (SD) increase of transformed metabolites: 0.31 to 1.98; p values: 0.002 to 1.25 × 10−10]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids, and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. This article is protected by copyright. All rights reserved.
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Regional Cerebral Oxygen Saturation Changes After Decompressive Craniectomy for Malignant Cerebral Venous Thrombosis: A Prospective Cohort Study
Background: Decompressive craniectomy (DC) is a life-saving intervention for malignant cerebral venous thrombosis (CVT). Earlier studies have shown increase in cerebral oxygenation after DC in traumatic brain injury but similar studies are lacking in CVT. We hypothesized that regional cerebral (tissue) oxygen saturation (rSO2) on the side of CVT is lower than the contralateral side and improves after DC. Materials and Methods: In this prospective cohort study, rSO2 was monitored using near-infrared spectroscopy technique, before and after DC on both cerebral hemispheres. Data regarding factors likely to affect rSO2 such as systolic blood pressure, partial pressure of oxygen and carbon dioxide in blood (PaO2 and PaCO2), and hemoglobin were simultaneously collected. The primary outcome measure was pre-post change in rSO2 on the ipsilateral cerebral hemisphere. The secondary outcomes were in-hospital mortality and duration of postoperative hospital stay. Results: Seventeen patients underwent DC during the 6-month study period. Their mean age was 39.2±12.4 years. The pre-post DC change in rSO2 on the hemisphere with CVT was significant (mean difference=3.6%; 95% confidence interval, 1.5-5.7; P=0.002). One patient died in the hospital. There was no difference in the duration of postoperative hospital stay (10 d [range, 6 to 21 d] vs. 14 d [range, 1 to 30 d], P=0.92) between patients with preoperative ipsilateral rSO2 60%. There was no correlation between PaO2, PaCO2, systolic blood pressure, and hemoglobin with rSO2. Conclusions: Patients with malignant CVT had a lower rSO2 on ipsilateral side of the lesion, which improved significantly after DC. Preoperative rSO2 was not correlated with the duration of hospital stay. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Kamath Sriganesh, DM, Department of Neuroanaesthesia and Neurocritical Care, 3rd Floor, Neurosciences Faculty Block, NIMHANS, Hosur Road, Bengaluru 560029, India (e-mail: drsri23@gmail.com). Received November 7, 2017 Accepted January 25, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved
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Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo
Ovarian cancer is the most leading cause of death and the third most common gynecologic malignancy in women. Traditional chemotherapy has inevitable drawbacks of nonspecific tumor targeting, high toxicity, and...
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Role of p62 in the regulation of cell death induction
Abstract
p62 is a multifunctional adaptor protein implicated in various cellular processes. It has been found to regulate selective autophagy, cell survival, cell death, oxidative stress, DNA repair and inflammation, and to play a role in a number of diseases, such as tumourigenesis, Paget's disease of bone, neurodegenerative disease, diabetes, and obesity. Cell death induction is an important cellular process. The dysregulation of cell death induction is involved in the pathogenesis of various diseases, such as cancer, neurodegeneration diseases, and diabetes. In this review, we discuss the functional role of p62 in inducing cell death in response to multiple stimuli, and we summarize the potential signaling pathways that contribute to this regulation. Given the important role of p62 in regulating cell death, p62 is considered to be a reasonable target for managing cell death dysregulation-related pathogenic conditions. A better understanding of the role of p62 and its related mechanisms in regulating cell death is necessary for the more precise utilization of p62 as a target for treating relevant diseases.
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Exploratory analysis of the association of depth of response and survival in patients with metastatic non-small-cell lung cancer treated with a targeted therapy or immunotherapy
Ann Oncol 2017; 28: 2707–2714 (doi: 10.1093/annonc/mdx414)
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The patient's perspective on breast radiotherapy: Initial fears and expectations versus reality
BACKGROUND
Although the efficacy and toxicity of breast radiotherapy (RT) has been studied extensively, to the authors' knowledge little is known regarding the patient's perspective on the modern breast RT experience. To better inform future patients and providers, the authors explored patient perceptions of their RT experience.
METHODS
Consecutive patients who were free of disease recurrence and who had been treated between 2012 and 2016 were surveyed regarding their original fears, how short-term and long-term toxicities compared with initial expectations, and how pretreatment beliefs concerning RT compared with the actual experience.
RESULTS
A total of 502 patients were surveyed, with a response rate of 65% (327 patients). The median patient age and posttreatment follow-up was 59 years and 31 months, respectively. Approximately 83% of patients (269 patients) underwent breast conservation therapy. Although approximately 68% of patients (221 patients) endorsed that they initially had little to no knowledge regarding RT, approximately 47% (152 patients) reported that they had heard frightening stories. Approximately 2% of patients (6 patients) agreed that the negative stories they previously heard about RT were actually true. Approximately 92% of patients treated with breast conservation (247 patients) and 81% of patients who underwent mastectomy (47 patients) agreed with the statement "If future patients knew the real truth about RT, they would be less scared about treatment." Approximately 83% (272 patients) and 84% (274 patients), respectively, of all patients reported the overall severity of short-term and long-term side effects to be better than or as expected.
CONCLUSIONS
Breast RT is associated with misconceptions and fears. Patients' experiences with modern breast RT appear to be superior to expectations, and the majority of patients in the current study agreed that their initial negative impressions were unfounded. Cancer 2017. © 2017 American Cancer Society.
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The patient's perspective on breast radiotherapy: Initial fears and expectations versus reality
BACKGROUND
Although the efficacy and toxicity of breast radiotherapy (RT) has been studied extensively, to the authors' knowledge little is known regarding the patient's perspective on the modern breast RT experience. To better inform future patients and providers, the authors explored patient perceptions of their RT experience.
METHODS
Consecutive patients who were free of disease recurrence and who had been treated between 2012 and 2016 were surveyed regarding their original fears, how short-term and long-term toxicities compared with initial expectations, and how pretreatment beliefs concerning RT compared with the actual experience.
RESULTS
A total of 502 patients were surveyed, with a response rate of 65% (327 patients). The median patient age and posttreatment follow-up was 59 years and 31 months, respectively. Approximately 83% of patients (269 patients) underwent breast conservation therapy. Although approximately 68% of patients (221 patients) endorsed that they initially had little to no knowledge regarding RT, approximately 47% (152 patients) reported that they had heard frightening stories. Approximately 2% of patients (6 patients) agreed that the negative stories they previously heard about RT were actually true. Approximately 92% of patients treated with breast conservation (247 patients) and 81% of patients who underwent mastectomy (47 patients) agreed with the statement "If future patients knew the real truth about RT, they would be less scared about treatment." Approximately 83% (272 patients) and 84% (274 patients), respectively, of all patients reported the overall severity of short-term and long-term side effects to be better than or as expected.
CONCLUSIONS
Breast RT is associated with misconceptions and fears. Patients' experiences with modern breast RT appear to be superior to expectations, and the majority of patients in the current study agreed that their initial negative impressions were unfounded. Cancer 2017. © 2017 American Cancer Society.
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Survival of breast cancer patients in rural Ethiopia
Abstract
Purpose
To describe the histopathological characteristics and survival of female breast cancer (BC) patients in a rural setting with limited access to adjuvant treatment.
Methods
A prospective study of 107 histologically confirmed BC patients treated with surgery from 2010 to 2016 from rural parts of western Ethiopia. Referral pathology was performed, and active follow-up was conducted. Adjusted cox regression analysis (hazard ratio [HR]) was performed.
Results
The median age at diagnosis was 45 (16–83) years; 57% of the patients presented with cT3/4 tumors, 71% with clinically positive lymph nodes, 21% with HER2-overexpression (Dako3+) and 68% with grade 3 tumors. Estrogen and/or progesterone receptor expressions were present in 66% and triple-negative disease in 25%. The estimated 1- and 2-year overall survival probability rates were 78 and 53%, respectively. The 2-year survival for patients with clinically positive lymph nodes was 44% compared to 73% for patients with lymph node-negative disease (HR 2.44; 95% confidence interval [95% CI] 1.19–5.02). The corresponding 2-year survival for patients with cT4 tumors was 25% versus 68% for patients with cT1–2 tumors (cT1–3 vs. cT4 HR 3.86; 95% CI 1.82–13.63). The 2-year survival for patients with hormone receptor-negative disease was 40% compared to 59% for patients with hormone receptor-positive disease (HR 1.92; 95% CI 1.06–3.47).
Conclusion
The majority of breast cancer patients treated with surgery in rural parts of western Ethiopia are diagnosed at advanced stage and have hormone receptor-positive disease. Nearly half of the patients die within 2 years. These findings underscore the need for provision of adjuvant hormonal therapy and for the establishment of pathology service including hormone receptor testing.
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Glioblastoma-activated pericytes support tumor growth via immunosuppression
Abstract
Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.
Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Pericytes support glioblastoma growth in vitro and in vivo.
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Validating the pivotal role of the immune system in low-dose radiation-induced tumor inhibition in Lewis lung cancer-bearing mice
Abstract
Although low-dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR-induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high-dose radiation (HDR) of 1 Gy. Additionally, the LDR-induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR-activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR-induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.
We demonstrate that immune enhancement plays a key role in low-dose radiation (LDR)-induced tumor inhibition. Our findings emphasize the importance of immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.
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Establishment and validation of a two-step screening scheme for improved performance of serological screening of nasopharyngeal carcinoma
Abstract
Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein–Barr virus (EBV), is one of the most prevalent cancers in southeast China. Most NPC patients are diagnosed at late stage due to inconspicuous symptoms at the early stage, and the prognosis of these patients is poor. The early diagnosis rate of NPC could be significantly increased by serological screening, but the positive predictive value (PPV) is relatively low. A simple two-step serological screening scheme was established to improve the PPV of the screening strategy and was validated by a prospective cohort. Serum antibodies specific for EBNA1, Zta, Thymidine Kinase (TK), EAD, EAR, and VCA were detected by enzyme-linked immunosorbent assay. The combination of EBNA1/IgA and VCA/IgA was used in the first step of screening, and anti-early antigens (EAs) were used in the second step of screening. EAD/IgA was the most prominent marker in the second step of screening, and other anti-EAs were complementary to EAD/IgA. As validated by a prospective cohort including 4200 participants, using the combination of EAD/IgA and TK/IgA in the second step decreased the number of high-risk participants from 128 to 27, and increased the PPV from 4.69% to 18.52%, with only one very early-stage case missed. The two-step screening scheme provides a standardized approach for NPC screening with an improved PPV and may be used in future field studies. With this two-step serological screening method, more people benefit from the screening program without increasing the need for fiberoptic endoscopy.
A simple two-step screening scheme was established to improve the PPV of the screening, with the combination of EBNA1/IgA and VCA/IgA in the first step of screening and anti-EAs in the second step. The PPV could be increased from 4.69% in the first step of screening to 18.52% after the second step of screening. With this two-step serological screening, more people could be benefited from the screening program.
http://ift.tt/2CjUNyO
Glioblastoma-activated pericytes support tumor growth via immunosuppression
Abstract
Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.
Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Pericytes support glioblastoma growth in vitro and in vivo.
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Validating the pivotal role of the immune system in low-dose radiation-induced tumor inhibition in Lewis lung cancer-bearing mice
Abstract
Although low-dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR-induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high-dose radiation (HDR) of 1 Gy. Additionally, the LDR-induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR-activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR-induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.
We demonstrate that immune enhancement plays a key role in low-dose radiation (LDR)-induced tumor inhibition. Our findings emphasize the importance of immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.
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Establishment and validation of a two-step screening scheme for improved performance of serological screening of nasopharyngeal carcinoma
Abstract
Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein–Barr virus (EBV), is one of the most prevalent cancers in southeast China. Most NPC patients are diagnosed at late stage due to inconspicuous symptoms at the early stage, and the prognosis of these patients is poor. The early diagnosis rate of NPC could be significantly increased by serological screening, but the positive predictive value (PPV) is relatively low. A simple two-step serological screening scheme was established to improve the PPV of the screening strategy and was validated by a prospective cohort. Serum antibodies specific for EBNA1, Zta, Thymidine Kinase (TK), EAD, EAR, and VCA were detected by enzyme-linked immunosorbent assay. The combination of EBNA1/IgA and VCA/IgA was used in the first step of screening, and anti-early antigens (EAs) were used in the second step of screening. EAD/IgA was the most prominent marker in the second step of screening, and other anti-EAs were complementary to EAD/IgA. As validated by a prospective cohort including 4200 participants, using the combination of EAD/IgA and TK/IgA in the second step decreased the number of high-risk participants from 128 to 27, and increased the PPV from 4.69% to 18.52%, with only one very early-stage case missed. The two-step screening scheme provides a standardized approach for NPC screening with an improved PPV and may be used in future field studies. With this two-step serological screening method, more people benefit from the screening program without increasing the need for fiberoptic endoscopy.
A simple two-step screening scheme was established to improve the PPV of the screening, with the combination of EBNA1/IgA and VCA/IgA in the first step of screening and anti-EAs in the second step. The PPV could be increased from 4.69% in the first step of screening to 18.52% after the second step of screening. With this two-step serological screening, more people could be benefited from the screening program.
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Spinal Cord Stimulation 50 Years Later: Clinical Outcomes of Spinal Cord Stimulation Based on Randomized Clinical Trials—A Systematic Review
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Neuraxial Anesthesia During Cesarean Delivery for Placenta Previa With Suspected Morbidly Adherent Placenta: A Retrospective Analysis
BACKGROUND: General anesthesia (GA) is often selected for cesarean deliveries (CD) with placenta previa and suspected morbidly adherent placenta (MAP) due to increased risk of hemorrhage and hysterectomy. We reviewed maternal outcomes and risk factors for conversion to GA in a cohort of patients undergoing CD and hysterectomy under neuraxial anesthesia (NA). METHODS: We performed a single-center, retrospective cohort study of parturients undergoing nonemergent CD for placenta previa with suspected MAP from 1997 to 2015. Patients were classified according to whether they received GA, NA, or intraoperative conversion from NA to GA. The primary outcome measure was postoperative acuity, defined as the need for intensive care unit admission, arterial embolization, reoperation, or ongoing transfusion with ≥3 units packed red blood cells. We additionally identified variables positively associated with intraoperative conversion from NA to GA during hysterectomy. Confounding was controlled with logistic regression models. RESULTS: Of 129 patients undergoing nonemergent CD for placenta previa with suspected MAP, 122 (95%) received NA as the primary anesthetic. NA was selected in the majority of patients with a body mass index ≥40 kg/m2 (9 of 10, 90%), a history of ≥3 prior CDs (18 of 20, 90%), suspected placenta increta or percreta (29 of 35, 83%), and Mallampati classification ≥3 (19 of 21, 90%). Of 72 patients with NA at the time of delivery who required hysterectomy, 15 (21%) required conversion to GA intraoperatively. Converted patients had a higher rate of major packed red blood cell transfusion (60% vs 25%; P = .01), with similar rates of massive transfusion (9% vs 7%; P = 1.0). Converted patients also had a higher incidence of postoperative acuity (47% vs 4%; P
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Point-of-Care Fibrinogen Testing in Pregnancy
Agreement between estimated fibrinogen concentration via thromboelastography and traditional assays is not established in the parturient. We therefore recruited 56 parturients and performed Clauss and functional fibrinogen level (FLEV) tests. Mean difference of measurements was 36.8 mg/dL (95% CI, 21.8–51.9) with a standard deviation of 52.8 mg/dL. Calculated limits of agreement were 140.2 mg/dL (95% CI, 166.3–114.6) and −66.6 mg/dL (95% CI, −40.8 to −92.5), within the maximum allowable difference of 165 mg/dL. We therefore conclude that while most measurements fell within the limits of agreement, more work is needed to clearly define the role of this test in the obstetric population. Accepted for publication December 29, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Summary Statement: In this study, the relationship between formal laboratory Clauss and thromboelastography-derived fibrinogen counts is examined. Reprints will not be available from the authors. Address correspondence to Daniel Katz, MD, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Pl, Box 1010 KCC 8th Floor, New York, NY 10029. Address e-mail to Daniel.Katz@mountsinai.org. © 2018 International Anesthesia Research Society
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Analgesic Effects of Oxycodone Relative to Those of Sufentanil, in the Presence of Midazolam, During Endoscopic Injection Sclerotherapy for Patients With Cirrhosis and Esophageal Varices
BACKGROUND: We evaluated the efficacy and gastroenterologist/patient satisfaction of midazolam combined with oxycodone, relative to that of midazolam combined with sufentanil, for anesthesia during endoscopic injection sclerotherapy (EIS) in patients with cirrhosis and esophageal varices. METHODS: Patients with cirrhosis (20–69 years of age), body mass index, 18–25 kg/m2, American Society of Anesthesiology patient classification physical status I–II who underwent elective EIS were randomly assigned to 1 of 2 groups. In this prospective, double-blinded, randomized controlled trial, 1 group received midazolam and oxycodone (n = 64), and the other group received midazolam and sufentanil (n = 63). Primary and secondary outcome measures were compared between groups. The primary outcome measure was the incidence of hypoxia. Secondary outcome measures included perioperative limb movement, need for rescue analgesics, need for additional sedative propofol, specified adverse reactions (postoperative myoclonus, nausea, vomiting, dizziness, and drowsiness), gastroenterologist satisfaction, and patient satisfaction with postoperative analgesia. RESULTS: Patients in the midazolam–oxycodone group had 32% fewer episodes of hypoxia than did those in the midazolam–sufentanil group (95% confidence interval [CI], –45% to –18%; P
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Does A Low 6-Minute Walk Distance Predict Elevated Postoperative Troponin?
Our study of 100 major vascular and renal transplant patients evaluated the 6-minute walk test (6MWT) as an indicator of perioperative myocardial injury, using troponin as a marker. Using logistic regression and the area under the receiving operator characteristic curve, we compared the 6MWT to the Revised Cardiac Risk Index and metabolic equivalents. Only the 6MWT was associated with elevated postoperative troponins (95% CI, 0.98–0.99). However, the 6MWT area under the receiving operator characteristic curve (0.71 [95% CI, 0.57–0.85]) was not different from the Revised Cardiac Risk Index (P = .23) or metabolic equivalents (P = .14). The 6MWT may have a role in cardiac risk stratification in the perioperative setting. Accepted for publication January 16, 2018. Funding: None. The authors declare no conflicts of interest. Institutional review board contact information: 310-825-5344; webIRBHelp@research.ucla.edu. Reprints will not be available from the authors. Address correspondence to Dana L. Russell, MPH, Department of Anesthesiology, David Geffen School of Medicine, University of California Los Angeles, 757 Westwood Pl, Los Angeles, CA 90095. Address e-mail to danarussell@mednet.ucla.edu. © 2018 International Anesthesia Research Society
http://ift.tt/2sSpwPD
http://ift.tt/2sSpwPD
The Migration of Caudally Threaded Thoracic Epidural Catheters in Neonates and Infants
BACKGROUND: The migration of pediatric thoracic epidural catheters via a thoracic insertion site has been described. We assessed the migration of caudally threaded thoracic epidural catheters in neonates and infants at our institution. METHODS: The anesthesia records and diagnostic imaging studies of neonates and infants who had caudal epidural catheters placed during a 26-month period at our hospital were analyzed. Imaging studies were reviewed for changes in epidural catheter tip position. RESULTS: Eighty-five patients 1–325 days of age (median, 51 days; interquartile range, 39–78 days) and weights of 2.5–9.5 kg (median, 5 kg; interquartile range, 4.3–5.8 kg) met the study criteria. Fifty-four (64%) of the patients (95% CI, 52%–73%) experienced catheter migration of 1 or more vertebral levels (range, 3 levels caudad [outward] to 3 levels cephalad [inward]), and 23 (27%) of the patients (95% CI, 18%–38%) experienced catheter migration to the T4 level or higher. Migration of 2 or more vertebral levels occurred only in children who weighed
http://ift.tt/2Co6BzY
http://ift.tt/2Co6BzY
Correlation Coefficients: Appropriate Use and Interpretation
Correlation in the broadest sense is a measure of an association between variables. In correlated data, the change in the magnitude of 1 variable is associated with a change in the magnitude of another variable, either in the same (positive correlation) or in the opposite (negative correlation) direction. Most often, the term correlation is used in the context of a linear relationship between 2 continuous variables and expressed as Pearson product-moment correlation. The Pearson correlation coefficient is typically used for jointly normally distributed data (data that follow a bivariate normal distribution). For nonnormally distributed continuous data, for ordinal data, or for data with relevant outliers, a Spearman rank correlation can be used as a measure of a monotonic association. Both correlation coefficients are scaled such that they range from –1 to +1, where 0 indicates that there is no linear or monotonic association, and the relationship gets stronger and ultimately approaches a straight line (Pearson correlation) or a constantly increasing or decreasing curve (Spearman correlation) as the coefficient approaches an absolute value of 1. Hypothesis tests and confidence intervals can be used to address the statistical significance of the results and to estimate the strength of the relationship in the population from which the data were sampled. The aim of this tutorial is to guide researchers and clinicians in the appropriate use and interpretation of correlation coefficients. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication January 11, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Patrick Schober, MD, PhD, MMedStat, Department of Anesthesiology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, the Netherlands. Address e-mail to p.schober@vumc.nl. © 2018 International Anesthesia Research Society
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http://ift.tt/2F6NefQ
Treatment Patterns and Clinical Outcomes in Neonates Diagnosed With Respiratory Distress Syndrome in a Low-Income Country: A Report From Bangladesh
Respiratory distress syndrome remains a leading cause of neonatal mortality worldwide. This retrospective study describes practice patterns for respiratory distress syndrome in a resource-limited setting and seeks to identify both risk factors for mortality and beneficial treatment modalities. Health, demographic, and treatment data were collected. Potential associations were analyzed using univariable and multivariable logistic regression. Of 104 children included for analysis, 38 died. Although most children were initially treated with noninvasive respiratory support, 59 progressed to invasive ventilation. Requirement for invasive ventilation was associated with death. A clear trend toward improved survival in mechanically ventilated patients was seen with surfactant administration. Accepted for publication January 11, 2018. Funding: This study was supported in part by the National Institutes of Heath (NIH) Building Interdisciplinary Research Careers in Women's Health (BIRCWH) NIH K12HD043441 scholar funds to G.L. The project described was supported by NIH through grant number UL1TR001857. Support for data collection on-site in Bangladesh ($650 total) was provided via the crowd-funding website https://experiment.com/. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Richard M. Hubbard, MD, 710 Beaver St, Sewickley, PA 15143. Address e-mail to rhubbardmd@gmail.com. © 2018 International Anesthesia Research Society
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http://ift.tt/2sTGMUy
Research Needs Assessment for Children With Obstructive Sleep Apnea Undergoing Diagnostic or Surgical Procedures
Recent concerns have been raised about the quality and safety of adenotonsillectomy, a common surgery performed to treat obstructive sleep apnea (OSA) in children. OSA is a risk factor for opioid-related perioperative respiratory complications including those associated with anoxic brain injury or death. Our objective was to identify controversial issues related to the care of children with OSA. A standardized Delphi consensus technique involving an interdisciplinary group of 24 pediatric OSA experts identified 3 key issues: "postoperative disposition, preoperative screening, and pain management." These topics are prime candidates for future systematic reviews and will guide Society of Anesthesia and Sleep Medicine–related research endeavors. Accepted for publication December 19, 2017. Funding: This study was supported solely by institutional and/or departmental sources. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Kimmo T. Murto, MD, FRCPC, Department of Anesthesiology and Pain Medicine, Children's Hospital of Eastern Ontario-Ottawa Children's Treatment Center, University of Ottawa, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. Address e-mail to kmurto@cheo.on.ca. © 2018 International Anesthesia Research Society
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http://ift.tt/2F4c13V
Development and Initial Evaluation of a Novel, Ultraportable, Virtual Reality Bronchoscopy Simulator: The Computer Airway Simulation System
BACKGROUND: Virtual reality (VR) simulation is an effective and safe method of teaching bronchoscopic skills. Few VR bronchoscopy simulators exist; all are expensive. The present study aimed to describe the design, development, and evaluation of a new, affordable, VR bronchoscopy simulator. METHODS: Anesthesiologists and engineers collaborated to design and develop the Computer Airway Simulation System (CASS), an iPad-based, high-fidelity, VR bronchoscopy simulator. We describe hardware and software development, as well as the technical and teaching features of the CASS. Twenty-two senior anesthesiologists evaluated various aspects of the simulator (using a 5-point Likert scale) to assess its face validity. RESULTS: Anesthesiologists performed a simulated bronchoscopy (mouth to carina) with a median (range) procedural time of 66 seconds (30–96). The simulator's ease of use was rated 4.3 ± 0.8 and the bronchoscope proxy's handling 4.0 ± 0.7. Criticisms included that excessive system reactivity created handling difficulties. Anatomical accuracy, 3-dimensional bronchial segmentation, and mucosal texture were judged to be very realistic. The simulator's usefulness for teaching and its educational value were highly rated (4.9 ± 0.3 and 4.8 ± 0.4, respectively). CONCLUSIONS: We describe the design, development, and initial evaluation of the CASS—a new, ultraportable, affordable, VR bronchoscopy simulator. The simulator's face validity was supported by excellent assessments from senior anesthesiologists with regard to anatomical realism, quality of graphics, and handling performance, even though some future refinements are required. All the practitioners agreed on the significant educational potential of the CASS. Accepted for publication December 29, 2017. Funding: Cardiocentro Ticino's Department of Cardiac Anesthesia and Intensive Care in Lugano, Switzerland, employs Gabriele Casso and Tiziano Cassina. This institution received financial support for the CASS research and development project from the Foundation for Cardiological Research and Education and the FLAVA Foundation (Fondation Latine des Voies Aériennes), both charitable (not-for-profit) organizations. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Gabriele Casso, MD, Department of Cardiac Anesthesia and Intensive Care, Cardiocentro Ticino, Lugano, Switzerland. Address e-mail to gabriele.casso@cardiocentro.org. © 2018 International Anesthesia Research Society
http://ift.tt/2sTGOf8
http://ift.tt/2sTGOf8
Laparoscopic repair of vesicovaginal fistulae with a transperitoneal approach at Universitas Gadjah Mada Urological Institute: a case report
A vesicovaginal fistula is an abnormal fistulous tract extending between the bladder and the vagina that allows the continuous involuntary discharge of urine into the vaginal vault. In addition, the sequelae f...
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[Autoimmune hypophysitis associated with new anti-cancer immunotherapies].
[Autoimmune hypophysitis associated with new anti-cancer immunotherapies].
Bull Cancer. 2018 Feb 20;:
Authors: Jannin A, Merlen E, Do Cao C, Penel N
Abstract
Recently developed immunotherapeutic agents, like anti-cytotoxic T lymphocyte antigen 4 antibody (CTLA4), anti-programmed cell death 1 (PD1) or anti-programmed cell death-ligand 1 (PDL1), have demonstrated substantial potential for the treatment of a variety of malignancies. Autoimmune side effects from these agents are diverse and can include multiple endocrinopathies like immunotherapy induced hypophysitis (IH). These toxicities appear to be more frequent in patients receiving anti-CTLA4 antibody compared to PD1/PDL1 agents. The diagnosis of IH is generally based on the presence of new hypopituitarism without an alternative etiology and radiographic pituitary enlargement or not while on treatment with Immunotherapy. Patients with IH frequently present non-specifics symptoms like headache, fatigue or weakness. ACTH and TSH deficiencies are more frequent. TSH and gonadotrophin deficiencies may be reversible but ACTH deficiency appears permanent. Glucocorticoid and thyroid hormone replacement should be instituted early after the diagnosis of IH, androgen replacement can be deferred initially and discussed by the patient. High-dose glucocorticoid does not improve the outcome of IH and should be reserved for patients with persistent severe headache, severe hyponatremia or visual defects. Patient education, early identification by measuring TSH, free thyroxine, morning ACTH and cortisol levels before each treatment cycle and proper treatment are the core of IH management.
PMID: 29475597 [PubMed - as supplied by publisher]
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[Radiation therapy in inflammatory breast cancer].
[Radiation therapy in inflammatory breast cancer].
Bull Cancer. 2018 Feb 20;:
Authors: Jardel P, Alami Z, Vignot S, Creisson A, Danhier S, Geffrelot J, Levy C, Kammerer E, Lebrun JF, Thariat J
Abstract
BACKGROUND: Inflammatory breast cancer accounts for 1-5% of all breast cancers. It is associated with a poor prognosis, because of an increased risk to develop metastases in comparison with all breast malignancies. The treatment is multimodal. We have evaluated the role of radiotherapy: indications, techniques and impact for local control and overall survival.
METHOD: The series of the literature with more than 40 patients irradiated for inflammatory breast cancer published since 1995 were analyzed.
RESULTS: Chemotherapy was always delivered first. Adjuvant radiotherapy was associated with local control and overall survival at 10 years of 63-92% and 51-64 respectively. Without surgery, local control was 65% and overal survival 38% at 10years. Results of concomitant radiochemotherapy were reported: the studies were heterogenous. Modalities of radiotherapy were detailed with respect to dose and fractionation, target-volumes and technical considerations (including bolus).
CONCLUSION: The multimodal strategy comprises systematically radiotherapy with an evaluation of tumor response to maximise resecability.
PMID: 29475596 [PubMed - as supplied by publisher]
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[Onco-Hematology Division (ONCOH) ANSM: A willingness to be in tune with the needs of patients and to facilitate clinical research in a secure environment].
[Onco-Hematology Division (ONCOH) ANSM: A willingness to be in tune with the needs of patients and to facilitate clinical research in a secure environment].
Bull Cancer. 2018 Feb 20;:
Authors: Albin N
PMID: 29475595 [PubMed - as supplied by publisher]
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LncRNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer
Summary
This study aimed to investigate the effect of long non-coding RNA (lncRNA) RP11-552M11.4 on cells proliferation, apoptosis, migration and invasion as well as its targeting genes in epithelial ovarian cancer (EOC) cells. LncRNA RP11-552M11.4 expression was detected in 67 tumor tissues and paired adjacent tissues obtained from EOC patients. lncRNA RP11-552M11.4 mimic/inhibitor plasmids were transferred into ovarian cancer cells (SKOV3, A-2780) and normal ovarian epithelial cells (IOSE80 cells). In addition, rescue experiment was performed by transferring BRCA2 inhibitor&lncRNA RP11-552M11.4 inhibitor plasmids into SKOV3 and A-2780 cells. qPCR, western blot, CKK-8, AV/PI, wound-healing and matrigel invasion assays were performed to detect RNA expression, protein expression, cells proliferation, apoptosis, migration and invasion respectively. LncRNA RP11-552M11.4 expression was elevated in tumor tissues compared with paired adjacent tissues and correlated with higher pathological grade, FIGO stage and worse overall survival in EOC patients. LncRNA RP11-552M11.4 promoted SKOV3 cells proliferation, migration and invasion while inhibited the apoptosis. Rescue experiment and luciferase reporter assay revealed that lncRNA RP11-552M11.4 regulated SKOV3 cells functions via binding BRCA2. Further experiments in A-2780 cells also validated that lncRNA RP11-552M11.4 induced A-2780 cells proliferation while repressed apoptosis by targeting BRCA2. In addition, upregulation of lncRNA RP11-552M11.4 increased IOSE80 cells proliferation, migration and invasion while decreased apoptosis. In conclusion, lncRNA RP11-552M11.4 correlates with worse prognosis, and promotes cells proliferation, migration, invasion and inhibits cells apoptosis by downregulating BRCA2 in EOC.
This article is protected by copyright. All rights reserved.
http://ift.tt/2CJ31Mn
Bortezomib plus dexamethasone versus thalidomide plus dexamethasone for relapsed or refractory multiple myeloma
Abstract
A randomized phase II selection design study (JCOG0904) was conducted to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex: BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal-naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥ 20 and < 80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) with ≥ 1 prior therapies were randomized to receive BD (Bor 1.3 mg/m2) or TD (Thal 200 mg/day). In both arms, 8 cycles of induction (3-week cycle) were followed by maintenance phase (5-week cycle) until disease progression, unacceptable toxicity or patient refusal. The primary endpoint was 1-year progression-free survival (PFS). Forty-four patients were randomized and assigned to receive BD and TD (n = 22, each). At a median follow-up of 34.3 months, the 1-year PFS in the BD and TD arms were 45.5% (95% confidence interval (CI) 24.4%-64.3%) and 31.8% (95%CI 14.2%-51.1%), respectively, while the overall response rates were 77.3% and 40.9% respectively. The 3-year overall survival (OS) was 70.0% (95%CI 44.9%-85.4%) in the BD, and 48.8% (95%CI 25.1%-69.0%) in the TD arm. Among grade 3/4 adverse events, thrombocytopenia (54.5% vs 0%) and sensory peripheral neuropathy (22.7% vs 9.1%) were more frequent in BD when compared with the TD arm. BD had better outcomes than TD with regard to the 1-year PFS and 3-year OS. Thus, BD was prioritized over TD for further investigations in Bor and Thal-naïve RRMM patients. (UMIN000003135).
This article is protected by copyright. All rights reserved.
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The roles of protein kinase R in cancer: Potential as a therapeutic target
Summary
Double-stranded (ds) RNA-dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune anti-viral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of the antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. PKR was initially thought to be a tumor suppressor due to its ability to suppress cell growth and interact with major tumor suppressor genes. However, in several types of malignant diseases such as colon and breast cancers, its role remains controversial. In hepatocellular carcinoma, hepatitis C virus is the main cause of liver cancer, and PKR inhibits HCV replication, indicating its role as a tumor suppressor. However, PKR is overexpressed in cirrhotic patients, and acts as a tumor promoter through enhancement of cancer cell growth by mediating MAPK or signal transducer and activator of transcription pathways. Moreover, PKR is reportedly required for the activation of inflammasomes and influences metabolic disorders. In this review, we introduce the multifaceted roles of PKR such as antiviral function, tumor cell growth, regulation of inflammatory immune responses, and maintaining metabolic homeostasis; and discuss future perspectives on PKR biology including its potential as a therapeutic target for liver cancer.
This article is protected by copyright. All rights reserved.
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Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis
Abstract
The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were performed to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan.
Ovid MEDLINE and Ichushi-Web were searched from inception through May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis.
The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% CI: 0.18 – 1.96%; I2 = 99%) for conventional cytology and 0.04% (95% CI: 0.00 – 0.35%; I2 = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on 4 direct and 9 comparative studies, showed no significant difference (summary odds ratio = 3.5×10-2 favoring LBC [95% CI: 6.9×10-4 – 1.7]; I2 = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests.
In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population.
This article is protected by copyright. All rights reserved.
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LncRNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer
Summary
This study aimed to investigate the effect of long non-coding RNA (lncRNA) RP11-552M11.4 on cells proliferation, apoptosis, migration and invasion as well as its targeting genes in epithelial ovarian cancer (EOC) cells. LncRNA RP11-552M11.4 expression was detected in 67 tumor tissues and paired adjacent tissues obtained from EOC patients. lncRNA RP11-552M11.4 mimic/inhibitor plasmids were transferred into ovarian cancer cells (SKOV3, A-2780) and normal ovarian epithelial cells (IOSE80 cells). In addition, rescue experiment was performed by transferring BRCA2 inhibitor&lncRNA RP11-552M11.4 inhibitor plasmids into SKOV3 and A-2780 cells. qPCR, western blot, CKK-8, AV/PI, wound-healing and matrigel invasion assays were performed to detect RNA expression, protein expression, cells proliferation, apoptosis, migration and invasion respectively. LncRNA RP11-552M11.4 expression was elevated in tumor tissues compared with paired adjacent tissues and correlated with higher pathological grade, FIGO stage and worse overall survival in EOC patients. LncRNA RP11-552M11.4 promoted SKOV3 cells proliferation, migration and invasion while inhibited the apoptosis. Rescue experiment and luciferase reporter assay revealed that lncRNA RP11-552M11.4 regulated SKOV3 cells functions via binding BRCA2. Further experiments in A-2780 cells also validated that lncRNA RP11-552M11.4 induced A-2780 cells proliferation while repressed apoptosis by targeting BRCA2. In addition, upregulation of lncRNA RP11-552M11.4 increased IOSE80 cells proliferation, migration and invasion while decreased apoptosis. In conclusion, lncRNA RP11-552M11.4 correlates with worse prognosis, and promotes cells proliferation, migration, invasion and inhibits cells apoptosis by downregulating BRCA2 in EOC.
This article is protected by copyright. All rights reserved.
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Bortezomib plus dexamethasone versus thalidomide plus dexamethasone for relapsed or refractory multiple myeloma
Abstract
A randomized phase II selection design study (JCOG0904) was conducted to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex: BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal-naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥ 20 and < 80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) with ≥ 1 prior therapies were randomized to receive BD (Bor 1.3 mg/m2) or TD (Thal 200 mg/day). In both arms, 8 cycles of induction (3-week cycle) were followed by maintenance phase (5-week cycle) until disease progression, unacceptable toxicity or patient refusal. The primary endpoint was 1-year progression-free survival (PFS). Forty-four patients were randomized and assigned to receive BD and TD (n = 22, each). At a median follow-up of 34.3 months, the 1-year PFS in the BD and TD arms were 45.5% (95% confidence interval (CI) 24.4%-64.3%) and 31.8% (95%CI 14.2%-51.1%), respectively, while the overall response rates were 77.3% and 40.9% respectively. The 3-year overall survival (OS) was 70.0% (95%CI 44.9%-85.4%) in the BD, and 48.8% (95%CI 25.1%-69.0%) in the TD arm. Among grade 3/4 adverse events, thrombocytopenia (54.5% vs 0%) and sensory peripheral neuropathy (22.7% vs 9.1%) were more frequent in BD when compared with the TD arm. BD had better outcomes than TD with regard to the 1-year PFS and 3-year OS. Thus, BD was prioritized over TD for further investigations in Bor and Thal-naïve RRMM patients. (UMIN000003135).
This article is protected by copyright. All rights reserved.
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The roles of protein kinase R in cancer: Potential as a therapeutic target
Summary
Double-stranded (ds) RNA-dependent protein kinase (PKR) is a ubiquitously expressed serine/threonine protein kinase. It was initially identified as an innate immune anti-viral protein induced by interferon (IFN) and activated by dsRNA. PKR is recognized as a key executor of the antiviral host defense. Moreover, it contributes to inflammation and immune regulation through several signaling pathways. In addition to IFN and dsRNA, PKR is activated by multiple stimuli and regulates various signaling pathways including the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. PKR was initially thought to be a tumor suppressor due to its ability to suppress cell growth and interact with major tumor suppressor genes. However, in several types of malignant diseases such as colon and breast cancers, its role remains controversial. In hepatocellular carcinoma, hepatitis C virus is the main cause of liver cancer, and PKR inhibits HCV replication, indicating its role as a tumor suppressor. However, PKR is overexpressed in cirrhotic patients, and acts as a tumor promoter through enhancement of cancer cell growth by mediating MAPK or signal transducer and activator of transcription pathways. Moreover, PKR is reportedly required for the activation of inflammasomes and influences metabolic disorders. In this review, we introduce the multifaceted roles of PKR such as antiviral function, tumor cell growth, regulation of inflammatory immune responses, and maintaining metabolic homeostasis; and discuss future perspectives on PKR biology including its potential as a therapeutic target for liver cancer.
This article is protected by copyright. All rights reserved.
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Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis
Abstract
The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were performed to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan.
Ovid MEDLINE and Ichushi-Web were searched from inception through May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis.
The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% CI: 0.18 – 1.96%; I2 = 99%) for conventional cytology and 0.04% (95% CI: 0.00 – 0.35%; I2 = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on 4 direct and 9 comparative studies, showed no significant difference (summary odds ratio = 3.5×10-2 favoring LBC [95% CI: 6.9×10-4 – 1.7]; I2 = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests.
In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population.
This article is protected by copyright. All rights reserved.
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