Websites on Bladder Cancer: an Appropriate Source of Patient Information?

Abstract

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term "bladder cancer." After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy.

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The Effect of Educational Intervention Based on Health Belief Model and Social Support on Promoting Skin Cancer Preventive Behaviors in a Sample of Iranian Farmers

Abstract

Skin cancer is one of the most common cancers in Iran. Farmers are exposed to the sun's ultraviolet radiation due to their job and are susceptible to skin cancer. The aim of this study is to survey the effect of educational intervention based on health belief model and social support on promoting skin cancer preventive behaviors in farmers of Fasa City, Fars province, Iran. In this quasi-experimental study, 200 farmers (100 in experimental group and 100 in control group) in Fasa City, Fars, Iran, were selected in 2017. The educational intervention for the experimental group consisted of eight training sessions (introduction to skin cancer, risk factors, complications, benefits and barriers to proper use of sunscreen, UV sunglasses and physical protection, self-efficacy in applying preventive behaviors, role of social support). A questionnaire consisting of demographic information, knowledge, HBM constructs (perceived susceptibility, severity, benefits, barriers, self-efficacy and cues to action), and social support was used to measure skin cancer preventive behaviors before, 3 months after the intervention, and 6 months later. Data were analyzed using SPSS-22 via chi-squared, independent samples t test, Mann-Whitney, and repeated measures ANOVA at a significance level of 0.5. The mean age of the farmers was 42.21 ± 10.52 years in the experimental group and 44.28 ± 10.16 years in the control group. Three months after the intervention and 6 months after the intervention, the experimental group showed a significant increase in the knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, cues to action, social support, and skin cancer preventive behaviors compared to the control group. This study showed the effectiveness of the intervention based on the HBM constructs and social support in adoption of skin cancer preventive behaviors in 3 and 6 months post intervention in farmers. Hence, these models can act as a framework for designing and implementing educational interventions for the prevention of skin cancer.

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CD146 positive human dental pulp stem cells promote regeneration of dentin/pulp-like structures

Abstract

CD146 and STRO-1 are endothelial biomarkers that are co-expressed on the cellular membranes of blood vessels within human dental pulp tissue. This study characterized the percentage of dentin-like structures produced by CD146-positive (CD146⁺) human dental pulp stem cells (DPSCs), compared with their CD146-negative (CD146⁻) counterparts. DPSC populations were enriched using magnetic-activated cell sorting (MACS), yielding CD146⁺ and CD146⁻ cells, as well as mixtures composed of 25% CD146⁺ cells and 75% CD146⁻ cells (CD146^+/−). Cell growth assays indicated that CD146⁺ cells exhibit an approximate 3–4 h difference in doubling time, compared with CD146⁻ cells. Cell cycle distributions were determined by flow cytometry analysis. The low percentage of CD146⁺ cells' DNA content in G₀/G₁ phase were compared with CD146⁻ and non-separated cells. In contrast to CD146⁻ and non-separated cells, prompt mineralization was observed in CD146⁺ cells. Subsequently, qRT-PCR revealed high mRNA expression of CD146 and Alkaline phosphatase in mineralization-induced CD146⁺ cells. CD146⁺ cells were also observed high adipogenic ability by Oil red O staining. Histological examinations revealed an increased area of dentin/pulp-like structures in transplanted CD146⁺ cells, compared with CD146⁻ and CD146^+/− cells. Immunohistochemical studies detected dentin matrix protein-1 (DMP1) and dentin sialophosphoprotein (DSPP), as well as human mitochondria, in transplanted DPSCs. Co-expression of CD146 and GFP indicated that CD146 was expressed in transplanted CD146⁺ cells. CD146⁺ cells may promote mineralization and generate dentin/pulp-like structures, suggesting a role in self-renewal of stem cells and dental pulp regenerative therapy.

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Websites on Bladder Cancer: an Appropriate Source of Patient Information?

Abstract

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term "bladder cancer." After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy.

http://ift.tt/2mbY6hR

The Effect of Educational Intervention Based on Health Belief Model and Social Support on Promoting Skin Cancer Preventive Behaviors in a Sample of Iranian Farmers

Abstract

Skin cancer is one of the most common cancers in Iran. Farmers are exposed to the sun's ultraviolet radiation due to their job and are susceptible to skin cancer. The aim of this study is to survey the effect of educational intervention based on health belief model and social support on promoting skin cancer preventive behaviors in farmers of Fasa City, Fars province, Iran. In this quasi-experimental study, 200 farmers (100 in experimental group and 100 in control group) in Fasa City, Fars, Iran, were selected in 2017. The educational intervention for the experimental group consisted of eight training sessions (introduction to skin cancer, risk factors, complications, benefits and barriers to proper use of sunscreen, UV sunglasses and physical protection, self-efficacy in applying preventive behaviors, role of social support). A questionnaire consisting of demographic information, knowledge, HBM constructs (perceived susceptibility, severity, benefits, barriers, self-efficacy and cues to action), and social support was used to measure skin cancer preventive behaviors before, 3 months after the intervention, and 6 months later. Data were analyzed using SPSS-22 via chi-squared, independent samples t test, Mann-Whitney, and repeated measures ANOVA at a significance level of 0.5. The mean age of the farmers was 42.21 ± 10.52 years in the experimental group and 44.28 ± 10.16 years in the control group. Three months after the intervention and 6 months after the intervention, the experimental group showed a significant increase in the knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, cues to action, social support, and skin cancer preventive behaviors compared to the control group. This study showed the effectiveness of the intervention based on the HBM constructs and social support in adoption of skin cancer preventive behaviors in 3 and 6 months post intervention in farmers. Hence, these models can act as a framework for designing and implementing educational interventions for the prevention of skin cancer.

http://ift.tt/2qDGD6p

CD146 positive human dental pulp stem cells promote regeneration of dentin/pulp-like structures

Abstract

CD146 and STRO-1 are endothelial biomarkers that are co-expressed on the cellular membranes of blood vessels within human dental pulp tissue. This study characterized the percentage of dentin-like structures produced by CD146-positive (CD146⁺) human dental pulp stem cells (DPSCs), compared with their CD146-negative (CD146⁻) counterparts. DPSC populations were enriched using magnetic-activated cell sorting (MACS), yielding CD146⁺ and CD146⁻ cells, as well as mixtures composed of 25% CD146⁺ cells and 75% CD146⁻ cells (CD146^+/−). Cell growth assays indicated that CD146⁺ cells exhibit an approximate 3–4 h difference in doubling time, compared with CD146⁻ cells. Cell cycle distributions were determined by flow cytometry analysis. The low percentage of CD146⁺ cells' DNA content in G₀/G₁ phase were compared with CD146⁻ and non-separated cells. In contrast to CD146⁻ and non-separated cells, prompt mineralization was observed in CD146⁺ cells. Subsequently, qRT-PCR revealed high mRNA expression of CD146 and Alkaline phosphatase in mineralization-induced CD146⁺ cells. CD146⁺ cells were also observed high adipogenic ability by Oil red O staining. Histological examinations revealed an increased area of dentin/pulp-like structures in transplanted CD146⁺ cells, compared with CD146⁻ and CD146^+/− cells. Immunohistochemical studies detected dentin matrix protein-1 (DMP1) and dentin sialophosphoprotein (DSPP), as well as human mitochondria, in transplanted DPSCs. Co-expression of CD146 and GFP indicated that CD146 was expressed in transplanted CD146⁺ cells. CD146⁺ cells may promote mineralization and generate dentin/pulp-like structures, suggesting a role in self-renewal of stem cells and dental pulp regenerative therapy.

http://ift.tt/2FdM9jD

A Case Report of Abdominal Desmoplastic Small Round Cell Tumor in a Young Tunisian Woman

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A Case Report of Abdominal Desmoplastic Small Round Cell Tumor in a Young Tunisian Woman

http://ift.tt/2m7S7K5

Websites on Bladder Cancer: an Appropriate Source of Patient Information?

Abstract

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term "bladder cancer." After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy.

http://ift.tt/2mbY6hR

The Effect of Educational Intervention Based on Health Belief Model and Social Support on Promoting Skin Cancer Preventive Behaviors in a Sample of Iranian Farmers

Abstract

Skin cancer is one of the most common cancers in Iran. Farmers are exposed to the sun's ultraviolet radiation due to their job and are susceptible to skin cancer. The aim of this study is to survey the effect of educational intervention based on health belief model and social support on promoting skin cancer preventive behaviors in farmers of Fasa City, Fars province, Iran. In this quasi-experimental study, 200 farmers (100 in experimental group and 100 in control group) in Fasa City, Fars, Iran, were selected in 2017. The educational intervention for the experimental group consisted of eight training sessions (introduction to skin cancer, risk factors, complications, benefits and barriers to proper use of sunscreen, UV sunglasses and physical protection, self-efficacy in applying preventive behaviors, role of social support). A questionnaire consisting of demographic information, knowledge, HBM constructs (perceived susceptibility, severity, benefits, barriers, self-efficacy and cues to action), and social support was used to measure skin cancer preventive behaviors before, 3 months after the intervention, and 6 months later. Data were analyzed using SPSS-22 via chi-squared, independent samples t test, Mann-Whitney, and repeated measures ANOVA at a significance level of 0.5. The mean age of the farmers was 42.21 ± 10.52 years in the experimental group and 44.28 ± 10.16 years in the control group. Three months after the intervention and 6 months after the intervention, the experimental group showed a significant increase in the knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, cues to action, social support, and skin cancer preventive behaviors compared to the control group. This study showed the effectiveness of the intervention based on the HBM constructs and social support in adoption of skin cancer preventive behaviors in 3 and 6 months post intervention in farmers. Hence, these models can act as a framework for designing and implementing educational interventions for the prevention of skin cancer.

http://ift.tt/2qDGD6p

Websites on Bladder Cancer: an Appropriate Source of Patient Information?

Abstract

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term "bladder cancer." After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients' health literacy.

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via IFTTT

The Effect of Educational Intervention Based on Health Belief Model and Social Support on Promoting Skin Cancer Preventive Behaviors in a Sample of Iranian Farmers

Abstract

Skin cancer is one of the most common cancers in Iran. Farmers are exposed to the sun's ultraviolet radiation due to their job and are susceptible to skin cancer. The aim of this study is to survey the effect of educational intervention based on health belief model and social support on promoting skin cancer preventive behaviors in farmers of Fasa City, Fars province, Iran. In this quasi-experimental study, 200 farmers (100 in experimental group and 100 in control group) in Fasa City, Fars, Iran, were selected in 2017. The educational intervention for the experimental group consisted of eight training sessions (introduction to skin cancer, risk factors, complications, benefits and barriers to proper use of sunscreen, UV sunglasses and physical protection, self-efficacy in applying preventive behaviors, role of social support). A questionnaire consisting of demographic information, knowledge, HBM constructs (perceived susceptibility, severity, benefits, barriers, self-efficacy and cues to action), and social support was used to measure skin cancer preventive behaviors before, 3 months after the intervention, and 6 months later. Data were analyzed using SPSS-22 via chi-squared, independent samples t test, Mann-Whitney, and repeated measures ANOVA at a significance level of 0.5. The mean age of the farmers was 42.21 ± 10.52 years in the experimental group and 44.28 ± 10.16 years in the control group. Three months after the intervention and 6 months after the intervention, the experimental group showed a significant increase in the knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, cues to action, social support, and skin cancer preventive behaviors compared to the control group. This study showed the effectiveness of the intervention based on the HBM constructs and social support in adoption of skin cancer preventive behaviors in 3 and 6 months post intervention in farmers. Hence, these models can act as a framework for designing and implementing educational interventions for the prevention of skin cancer.

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Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up

Abstract

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

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via IFTTT

Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up

Abstract

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

from Cancer via ola Kala on Inoreader http://ift.tt/2ADN7C9
via IFTTT

Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up

Abstract

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

http://ift.tt/2ADN7C9

APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution

Abstract

The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants. We hypothesize similar functions of APOBEC will also hold true in cancer.

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PD-1 blockade with nivolumab in endemic Kaposi sarcoma

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Outcome in colorectal cancer – tumour, stroma and so much more

colorectal cancerprognosisinflammationtumour microenvironment

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APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution

Abstract

The APOBEC mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporting the role of APOBEC mutagenesis in creating HIV genome heterogeneity, drug resistance, and immune escape variants. We hypothesize similar functions of APOBEC will also hold true in cancer.

http://ift.tt/2CMTc4n

PD-1 blockade with nivolumab in endemic Kaposi sarcoma

http://ift.tt/2ma2z3Q

Outcome in colorectal cancer – tumour, stroma and so much more

colorectal cancerprognosisinflammationtumour microenvironment

http://ift.tt/2CRwTKG

The T-cell Receptor {beta}-Chain Is an Immunotherapy Target for Lymphomas [Lymphoma]

Targeting the TRBC gene expressed by T-cell malignancies mitigates severe immunosuppression.

http://ift.tt/2COwQ2d

Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression [Research Briefs]

Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote the persistence of a fraction of the original cell population, facilitating the eventual outgrowth of inhibitor-resistant tumor clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1, to targeted therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in diverse cellular and in vivo cancer models. We propose that targeted therapy induces a state of transcriptional dependency in a subpopulation of cells poised to become drug tolerant, which THZ1 can exploit by blocking dynamic transcriptional responses, promoting remodeling of enhancers and key signaling outputs required for tumor cell survival in the setting of targeted therapy. These findings suggest that the addition of THZ1 to targeted therapies is a promising broad-based strategy to hinder the emergence of drug-resistant cancer cell populations.

Significance: CDK7/12 inhibition prevents active enhancer formation at genes, promoting resistance emergence in response to targeted therapy, and impedes the engagement of transcriptional programs required for tumor cell survival. CDK7/12 inhibition in combination with targeted cancer therapies may serve as a therapeutic paradigm for enhancing the effectiveness of targeted therapies. Cancer Discov; 8(1); 59–73. ©2017 AACR.

See related commentary by Carugo and Draetta, p. 17.

This article is highlighted in the In This Issue feature, p. 1

http://ift.tt/2m3ow4m

First-Line Osimertinib Beneficial in Advanced NSCLC [News in Brief]

Osimertinib is more effective as first-line therapy than other EGFR inhibitors for patients with advanced EGFR-mutated non–small cell lung cancer—notably Asians, who have a higher incidence of the disease compared with Western populations. The conclusion is based on data from a subgroup analysis of the phase III FLAURA trial.

http://ift.tt/2COmgIO

The DNA Transposase PGBD5 Sensitizes Tumors to Inhibition of DNA Repair [Pediatric Cancers]

PGBD5 expression in pediatric solid tumors confers sensitivity to inhibitors of DNA damage signaling.

http://ift.tt/2m7VuAr

Dasatinib Approved for Pediatric CML [News in Brief]

The FDA approved dasatinib to treat pediatric chronic myeloid leukemia. This drug is the second tyrosine kinase inhibitor, alongside imatinib, approved for this indication and represents an important new option for first- and second-line treatment.

http://ift.tt/2CNQpId

PMN-MDSC Infiltration Blocks the Antitumor Effects of CSF1R Inhibition [Immunology]

CSF1R inhibition both reduces protumorigenic TAMs and recruits protumorigenic PMN-MDSCs.

http://ift.tt/2m3oolo

Blocking IDO1 Helps Shrink Bladder, Cervical Tumors [News in Brief]

Findings from a phase I/IIa study indicate that combining the investigational indoleamine 2,3-dioxygenase 1 inhibitor BMS-986205 with nivolumab is safe and boosts response rates among patients with bladder and cervical cancers.

http://ift.tt/2CR5PeD

PD-1 Functions as a Tumor Suppressor in T-cell Lymphoma [Lymphoma]

Oncogenic T-cell signaling upregulates PD-1, which increases PTEN expression to suppress oncogenesis.

http://ift.tt/2m7Vrof

People [News in Brief]

Josep Tabernero, MD, PhD, and Alexis A. Thompson, MD, MPH, are featured.

http://ift.tt/2CPc9mP

BLU-285 Targets KIT/PDGFRA Conformation and Activating Loop Mutations [Targeted Therapy]

The small-molecule inhibitor BLU-285 inhibits clinically relevant KIT and PDGFRA mutations.

http://ift.tt/2m7Vkcj

Basket Study Yields Approval for Rare Cancer [News in Brief]

The FDA, in a regulatory first, approved a targeted therapy based on a basket study. The move, which expanded the indications for the BRAF inhibitor vemurafenib to include Erdheim–Chester disease, points to a new approval pathway for drugs that treat rare cancers.

http://ift.tt/2CPf6DR

In This Issue [In This Issue]

http://ift.tt/2m7VccP

JCAR015 in ALL: A Root-Cause Investigation [News in Brief]

After conducting an internal probe of the five deaths that halted JCAR015's development for acute lymphoblastic leukemia, Juno Therapeutics has concluded that multiple factors were at play. A surge in inflammatory cytokine levels from rapid, early T-cell proliferation may have provoked the blood–brain barrier disruption seen in these patients, inducing fatal cerebral edema.

http://ift.tt/2CMoEQj

NFS1 Expression Protects Lung Tumor Cells from Ferroptosis [Lung Cancer]

NFS1 activity is essential for maintenance of iron–sulfur cluster biosynthesis in response to oxidative stress.

http://ift.tt/2m7UZGz

Poziotinib Shows Promise for Rare Lung Cancer [News in Brief]

Poziotinib, an EGFR inhibitor that was previously shelved as ineffective against non–small cell lung cancer, is showing promising activity in a subset of patients with EGFR exon 20 insertions. According to preliminary data from a phase II trial, the drug led to a 73% overall response rate in patients with this disease subtype, which is typically highly resistant to standard therapy.

http://ift.tt/2CR3qQY

Osteoblasts Promote Release of Tumor-Promoting SiglecFhi Neutrophils [Lung Cancer]

Lung tumors activate OCN⁺ osteoblasts in distant bone stroma to supply tumor-infiltrating neutrophils.

http://ift.tt/2m4W2Y7

FDA Approves Second CAR T-cell Therapy [News in Brief]

The FDA approved the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel, making it the second such treatment for blood cancers in the United States. The therapy is indicated for adults with certain non-Hodgkin lymphomas who have tried at least two other treatments.

http://ift.tt/2CMWQLz

Pancreatitis-Induced p62 Accumulation Promotes Pancreatic Cancer [Pancreatic Cancer]

Defective autophagy and stress in acinar cells drives the progression of PanIN1 lesions to PDAC.

http://ift.tt/2m5cmIg

Rare Tumors in Kids May Respond to Tazemetostat [News in Brief]

In a phase I trial of the EZH2 inhibitor tazemetostat, children with INI1-deficient tumors—including relapsed or refractory malignant rhabdoid tumors, atypical teratoid rhabdoid tumors, epithelioid sarcomas, and poorly differentiated chordomas—responded well to treatment, with some experiencing durable responses.

http://ift.tt/2CRE060

NTZ Increases {beta}-catenin Citrullination to Suppress WNT Signaling [Signaling]

The antiparasitic drug NTZ inhibits WNT signaling and APC-mutant colorectal cancer cell growth.

http://ift.tt/2m5cis0

The T-cell Receptor {beta}-Chain Is an Immunotherapy Target for Lymphomas [Lymphoma]

Targeting the TRBC gene expressed by T-cell malignancies mitigates severe immunosuppression.

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Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression [Research Briefs]

Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote the persistence of a fraction of the original cell population, facilitating the eventual outgrowth of inhibitor-resistant tumor clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1, to targeted therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in diverse cellular and in vivo cancer models. We propose that targeted therapy induces a state of transcriptional dependency in a subpopulation of cells poised to become drug tolerant, which THZ1 can exploit by blocking dynamic transcriptional responses, promoting remodeling of enhancers and key signaling outputs required for tumor cell survival in the setting of targeted therapy. These findings suggest that the addition of THZ1 to targeted therapies is a promising broad-based strategy to hinder the emergence of drug-resistant cancer cell populations.

Significance: CDK7/12 inhibition prevents active enhancer formation at genes, promoting resistance emergence in response to targeted therapy, and impedes the engagement of transcriptional programs required for tumor cell survival. CDK7/12 inhibition in combination with targeted cancer therapies may serve as a therapeutic paradigm for enhancing the effectiveness of targeted therapies. Cancer Discov; 8(1); 59–73. ©2017 AACR.

See related commentary by Carugo and Draetta, p. 17.

This article is highlighted in the In This Issue feature, p. 1

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First-Line Osimertinib Beneficial in Advanced NSCLC [News in Brief]

Osimertinib is more effective as first-line therapy than other EGFR inhibitors for patients with advanced EGFR-mutated non–small cell lung cancer—notably Asians, who have a higher incidence of the disease compared with Western populations. The conclusion is based on data from a subgroup analysis of the phase III FLAURA trial.

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The DNA Transposase PGBD5 Sensitizes Tumors to Inhibition of DNA Repair [Pediatric Cancers]

PGBD5 expression in pediatric solid tumors confers sensitivity to inhibitors of DNA damage signaling.

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Dasatinib Approved for Pediatric CML [News in Brief]

The FDA approved dasatinib to treat pediatric chronic myeloid leukemia. This drug is the second tyrosine kinase inhibitor, alongside imatinib, approved for this indication and represents an important new option for first- and second-line treatment.

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PMN-MDSC Infiltration Blocks the Antitumor Effects of CSF1R Inhibition [Immunology]

CSF1R inhibition both reduces protumorigenic TAMs and recruits protumorigenic PMN-MDSCs.

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Blocking IDO1 Helps Shrink Bladder, Cervical Tumors [News in Brief]

Findings from a phase I/IIa study indicate that combining the investigational indoleamine 2,3-dioxygenase 1 inhibitor BMS-986205 with nivolumab is safe and boosts response rates among patients with bladder and cervical cancers.

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PD-1 Functions as a Tumor Suppressor in T-cell Lymphoma [Lymphoma]

Oncogenic T-cell signaling upregulates PD-1, which increases PTEN expression to suppress oncogenesis.

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People [News in Brief]

Josep Tabernero, MD, PhD, and Alexis A. Thompson, MD, MPH, are featured.

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BLU-285 Targets KIT/PDGFRA Conformation and Activating Loop Mutations [Targeted Therapy]

The small-molecule inhibitor BLU-285 inhibits clinically relevant KIT and PDGFRA mutations.

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Basket Study Yields Approval for Rare Cancer [News in Brief]

The FDA, in a regulatory first, approved a targeted therapy based on a basket study. The move, which expanded the indications for the BRAF inhibitor vemurafenib to include Erdheim–Chester disease, points to a new approval pathway for drugs that treat rare cancers.

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In This Issue [In This Issue]

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JCAR015 in ALL: A Root-Cause Investigation [News in Brief]

After conducting an internal probe of the five deaths that halted JCAR015's development for acute lymphoblastic leukemia, Juno Therapeutics has concluded that multiple factors were at play. A surge in inflammatory cytokine levels from rapid, early T-cell proliferation may have provoked the blood–brain barrier disruption seen in these patients, inducing fatal cerebral edema.

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NFS1 Expression Protects Lung Tumor Cells from Ferroptosis [Lung Cancer]

NFS1 activity is essential for maintenance of iron–sulfur cluster biosynthesis in response to oxidative stress.

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Poziotinib Shows Promise for Rare Lung Cancer [News in Brief]

Poziotinib, an EGFR inhibitor that was previously shelved as ineffective against non–small cell lung cancer, is showing promising activity in a subset of patients with EGFR exon 20 insertions. According to preliminary data from a phase II trial, the drug led to a 73% overall response rate in patients with this disease subtype, which is typically highly resistant to standard therapy.

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Osteoblasts Promote Release of Tumor-Promoting SiglecFhi Neutrophils [Lung Cancer]

Lung tumors activate OCN⁺ osteoblasts in distant bone stroma to supply tumor-infiltrating neutrophils.

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FDA Approves Second CAR T-cell Therapy [News in Brief]

The FDA approved the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel, making it the second such treatment for blood cancers in the United States. The therapy is indicated for adults with certain non-Hodgkin lymphomas who have tried at least two other treatments.

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Pancreatitis-Induced p62 Accumulation Promotes Pancreatic Cancer [Pancreatic Cancer]

Defective autophagy and stress in acinar cells drives the progression of PanIN1 lesions to PDAC.

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Rare Tumors in Kids May Respond to Tazemetostat [News in Brief]

In a phase I trial of the EZH2 inhibitor tazemetostat, children with INI1-deficient tumors—including relapsed or refractory malignant rhabdoid tumors, atypical teratoid rhabdoid tumors, epithelioid sarcomas, and poorly differentiated chordomas—responded well to treatment, with some experiencing durable responses.

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NTZ Increases {beta}-catenin Citrullination to Suppress WNT Signaling [Signaling]

The antiparasitic drug NTZ inhibits WNT signaling and APC-mutant colorectal cancer cell growth.

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Health care disparities among octogenarians and nonagenarians with stage III lung cancer

BACKGROUND

To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB).

METHODS

In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used.

RESULTS

A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72).

CONCLUSIONS

In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018. © 2018 American Cancer Society.

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Health care disparities among octogenarians and nonagenarians with stage III lung cancer

BACKGROUND

To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB).

METHODS

In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used.

RESULTS

A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72).

CONCLUSIONS

In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018. © 2018 American Cancer Society.

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Rabdocoestin B exhibits antitumor activity by inducing G2/M phase arrest and apoptosis in esophageal squamous cell carcinoma

Abstract

Purpose

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is generally resistant to chemotherapy. In the present study, the cytotoxic activity of Rabdocoestin B (Rabd-B) against ESCC and the underlying mechanisms were investigated.

Methods

The inhibitory effect of Rabd-B on KYSE30 and KYSE450 was evaluated by Cell Counting Kit-8 (CCK8) and colony formation assays in vitro. The cell cycle distribution and apoptosis of cells treated with Rabd-B were determined by flow cytometry. The mechanisms underlying the effects of Rabd-B were systematically examined by Western blot. The in vivo anti-tumor ability of Rabd-B was measured in mouse xenograft models and cisplatin (DDP) was used as positive control.

Results

Rabd-B efficiently induced G2/M phase arrest in ESCC cells by upregulating the Chk1/Chk2-Cdc25C axis to inhibit the G2→M transition facilitated by Cdc2/Cyclin B1. Furthermore, Rabd-B suppressed ATM/ATR phosphorylation, thereby inhibiting BRCA1-mediated DNA repair, which resulted in mitotic catastrophe and induced cell apoptosis. Rabd-B also decreased the activity of the Akt and NF-κB survival signaling pathways and ultimately initiated the caspase-9-dependent intrinsic apoptotic pathway in ESCC cells. The apoptosis induced by Rabd-B could be partially reversed by a caspase-9-specific inhibitor (Z-LEHD-FMK) and a pan-caspase inhibitor (Z-VAD-FMK). Moreover, Rabd-B effectively suppressed tumor growth in mouse xenografts which was comparable to that of DDP without significant injuries to the mice.

Conclusion

Taken together, these findings indicate that Rabd-B is a promising precursor compound that may be useful as a treatment for ESCC and thus warrants further investigation.

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Rabdocoestin B exhibits antitumor activity by inducing G2/M phase arrest and apoptosis in esophageal squamous cell carcinoma

Abstract

Purpose

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is generally resistant to chemotherapy. In the present study, the cytotoxic activity of Rabdocoestin B (Rabd-B) against ESCC and the underlying mechanisms were investigated.

Methods

The inhibitory effect of Rabd-B on KYSE30 and KYSE450 was evaluated by Cell Counting Kit-8 (CCK8) and colony formation assays in vitro. The cell cycle distribution and apoptosis of cells treated with Rabd-B were determined by flow cytometry. The mechanisms underlying the effects of Rabd-B were systematically examined by Western blot. The in vivo anti-tumor ability of Rabd-B was measured in mouse xenograft models and cisplatin (DDP) was used as positive control.

Results

Rabd-B efficiently induced G2/M phase arrest in ESCC cells by upregulating the Chk1/Chk2-Cdc25C axis to inhibit the G2→M transition facilitated by Cdc2/Cyclin B1. Furthermore, Rabd-B suppressed ATM/ATR phosphorylation, thereby inhibiting BRCA1-mediated DNA repair, which resulted in mitotic catastrophe and induced cell apoptosis. Rabd-B also decreased the activity of the Akt and NF-κB survival signaling pathways and ultimately initiated the caspase-9-dependent intrinsic apoptotic pathway in ESCC cells. The apoptosis induced by Rabd-B could be partially reversed by a caspase-9-specific inhibitor (Z-LEHD-FMK) and a pan-caspase inhibitor (Z-VAD-FMK). Moreover, Rabd-B effectively suppressed tumor growth in mouse xenografts which was comparable to that of DDP without significant injuries to the mice.

Conclusion

Taken together, these findings indicate that Rabd-B is a promising precursor compound that may be useful as a treatment for ESCC and thus warrants further investigation.

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Viruses, bacteria, and parasites – oh my! a resurgence of interest in microbial-based therapy for cancer

Abstract

As infections and cancer are two of the most common maladies affecting human beings, a concerted effort is needed to better understand their potential interactions and to further explore their use in microbial-based cancer treatments. Studies focusing on the interaction between pathogens and cancer began over 4000 years ago, but therapeutic application of pathogens has often been bypassed as other cancer therapies have gained wider interest. To many, the field of microbial-based cancer treatment may feel antiquated and already sufficiently explored. However, closer examination reveals that our current knowledge is but a series of dim reflections amongst many yet-unexplored shadows. Particularly, with our increased understanding of pathogen entry, replication, and senescence, coupled with our quickly increasing knowledge regarding cancer initiation, growth, and metastasis, and capped by our realization of the complexity and plasticity of the immune response, we are just now beginning to realize the vastness of the undiscovered area encompassing this field. At the same time, we are now uniquely poised with gained knowledge and discovered tools to join together across disciplines, uncover new positive and negative interactions between pathogens and cancer, and make important progress toward saving cancer patient lives.

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Viruses, bacteria, and parasites – oh my! a resurgence of interest in microbial-based therapy for cancer

Abstract

As infections and cancer are two of the most common maladies affecting human beings, a concerted effort is needed to better understand their potential interactions and to further explore their use in microbial-based cancer treatments. Studies focusing on the interaction between pathogens and cancer began over 4000 years ago, but therapeutic application of pathogens has often been bypassed as other cancer therapies have gained wider interest. To many, the field of microbial-based cancer treatment may feel antiquated and already sufficiently explored. However, closer examination reveals that our current knowledge is but a series of dim reflections amongst many yet-unexplored shadows. Particularly, with our increased understanding of pathogen entry, replication, and senescence, coupled with our quickly increasing knowledge regarding cancer initiation, growth, and metastasis, and capped by our realization of the complexity and plasticity of the immune response, we are just now beginning to realize the vastness of the undiscovered area encompassing this field. At the same time, we are now uniquely poised with gained knowledge and discovered tools to join together across disciplines, uncover new positive and negative interactions between pathogens and cancer, and make important progress toward saving cancer patient lives.

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Heparin-Bridging Therapy and Risk of Bleeding After Endoscopic Submucosal Dissection for Gastric Neoplasms: a Meta-Analysis

Abstract

Purpose

Peri-procedural heparin is recommended as bridging therapy for patients with high thromboembolic risk who need to withhold anticoagulant for endoscopic submucosal dissection (ESD) for gastric neoplasms. However, little is known about the bleeding risk from heparin-bridging therapy itself.

Methods

MEDLINE and EMBASE databases were searched through August 2017 for studies that compared the risk of post-ESD bleeding in patients who received heparin-bridging therapy in lieu of anticoagulant for gastric neoplasms and those who discontinued anticoagulant without receiving heparin. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity was quantified using the Q statistic and I².

Results

A total of four studies consisting of 350 patients were identified. A significantly increased risk of post-ESD bleeding among the bridged patients compared with the non-bridged patients was observed with the pooled RR of 2.99 (95% CI, 1.51 to 5.92). The statistical heterogeneity was insignificant with I² of 0%.

Conclusions

A significantly increased risk of post-ESD bleeding among patients who received heparin-bridging therapy in lieu of anticoagulant compared to patients who did not receive it was demonstrated in this study.

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Heparin-Bridging Therapy and Risk of Bleeding After Endoscopic Submucosal Dissection for Gastric Neoplasms: a Meta-Analysis

Abstract

Purpose

Peri-procedural heparin is recommended as bridging therapy for patients with high thromboembolic risk who need to withhold anticoagulant for endoscopic submucosal dissection (ESD) for gastric neoplasms. However, little is known about the bleeding risk from heparin-bridging therapy itself.

Methods

MEDLINE and EMBASE databases were searched through August 2017 for studies that compared the risk of post-ESD bleeding in patients who received heparin-bridging therapy in lieu of anticoagulant for gastric neoplasms and those who discontinued anticoagulant without receiving heparin. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity was quantified using the Q statistic and I².

Results

A total of four studies consisting of 350 patients were identified. A significantly increased risk of post-ESD bleeding among the bridged patients compared with the non-bridged patients was observed with the pooled RR of 2.99 (95% CI, 1.51 to 5.92). The statistical heterogeneity was insignificant with I² of 0%.

Conclusions

A significantly increased risk of post-ESD bleeding among patients who received heparin-bridging therapy in lieu of anticoagulant compared to patients who did not receive it was demonstrated in this study.

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