Sex hormone-binding globulin (SHBG) is a potential early diagnostic biomarker for gastric cancer

Abstract

The use of blood plasma biomarkers in gastric cancer (GC) management is limited due to a lack of reliable biomarkers. An LC-MS/MS assay and a bioinformatic analysis were performed to identify blood plasma biomarkers in a GC discovery cohort. The data obtained were verified and validated by western blotting and an ELISA in an independent study cohort. A label-free quantification analysis of the MS data using PEAKS7 software found that four plasma proteins of apolipoprotein C-1, gelsolin, sex hormone-binding globulin (SHBG), and complement component C4-A were significantly overexpressed in GC patients. A western blot assay of these plasma proteins showed that only SHBG was consistently overexpressed in the patient group. ELISA measurement of SHBG blood plasma levels confirmed that the patient group had significantly higher SHBG levels than the control group. SHBG levels in the patient group remained significantly higher after being stratified by gender, age, and disease stage. These findings show that LC-MS/MS is powerful and highly sensitive for plasma biomarker discovery, and SHBG could be a potential plasma biomarker for GC management.

Discovery of plasma biomarker with powerfully and high sensitively LC-MS/MS analysis, SHBG could be a potential plasma biomarker for GC management.

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

SNP association study in PMS2-associated Lynch syndrome

Abstract

Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2–3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5–4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients.

http://ift.tt/2zbzuOz

Baerveldt Scleral Patch Graft Abscess Secondary to Coagulase-Negative Staphylococcus

We report the case of a 69-year-old female who underwent a Baerveldt implant placement for severe-stage primary open-angle glaucoma and developed a bacterial infection of the conjunctiva and abscess of the scleral patch graft with subsequent tube exposure. The infection was identified 3 weeks postoperatively and a topical antibiotic was immediately initiated. A concurrent systemic staphylococcal infection was discovered by an outside physician and oral cephalexin was initiated. Despite antibiotic treatment, the conjunctival erosion progressed, and tube revision was required. Culture of the abscess revealed coagulase-negative Staphylococcus. As alluded to above, the patient also had multiple abscesses on the skin that cultured positive for Staphylococcus aureus. To our knowledge, this is the first case in the literature of coagulase-negative Staphylococcus causing an early postoperative abscess of the scleral patch graft following glaucoma drainage device placement.
Case Rep Ophthalmol 2017;8:521–526

http://ift.tt/2hGpqWu

Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma

Dysregulation of miRNAs is associated with cancer development by coordinately suppressing abundant target genes. Emerging evidence indicates that miR-31 plays a dual role in tumorigenicity. However, whether mi...

from Cancer via ola Kala on Inoreader http://ift.tt/2ANk93c
via IFTTT

TGF-β2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion

Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focuse...

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

Adherence to Mediterranean diet and subjective cognitive function in men

Abstract

Benefits of a Mediterranean diet for cognition have been suggested, but epidemiologic studies have been relatively small and of limited duration. To prospectively assess the association between long-term adherence to a Mediterranean dietary pattern and self-reported subjective cognitive function (SCF). Prospective observational study. The Health Professionals' Follow-up Study, a prospective cohort of 51,529 men, 40–75 years of age when enrolled in 1986, of whom 27,842 were included in the primary analysis. Mediterranean diet (MD) score, computed from the mean of five food frequency questionnaires, assessed every 4 years from 1986 to 2002. Self-reported SCF assessed by a 6-item questionnaire in 2008 and 2012, and validated by association with genetic variants in apolipoprotein-4. Using the average of 2008 and 2012 SCF scores, 38.0% of men were considered to have moderate memory scores and 7.3% were considered to have poor scores. In a multivariate model, compared with men having a MD score in the lowest quintile, those in the highest quintile had a 36% lower odds of a poor SCF score (odds ratio 0.64, 95% CI 0.55–0.75; P, trend < 0.001) and a 24% lower odds of a moderate SCF score (OR 0.76, 95% CI 0.70–0.83; P, trend < 0.001). Both remote and more recent diet contributed to this relation. Associations were only slightly weaker using baseline dietary data and a lag of 22 years. Long-term adherence to the Mediterranean diet pattern was strongly related to lower subjective cognitive function. These findings provide further evidence that a healthy dietary pattern may prevent or delay cognitive decline.

from Cancer via ola Kala on Inoreader http://ift.tt/2z8Li4b
via IFTTT

Physical activity across adulthood and subjective cognitive function in older men

Abstract

Low subjective cognitive function (SCF), which is associated with APOE4 genotype, adversely impacts quality of life and has predicted clinical dementia. We examined whether physical activity during early adulthood or mid-to-late life is associated with late-life SCF. We followed 28,481 US male health professionals aged 40–75 years who reported their physical activity in 1986 and biennially thereafter. SCF was reported in 2008 and 2012. The SCF score was averaged for the 2008 and 2012 assessments and categorized as "good", "moderate", and "poor". Men in the highest versus lowest quintile of mid-to-late life physical activity in 1986 had 38% lower odds of poor versus good SCF score (multivariable-adjusted odds ratio (OR) 0.62; 95% CI 0.53, 0.72; P for trend < 0.0001). Being physically active in early adulthood was also associated with a 23% lower odds of poor SCF, independent of later activity, and being active both in early and mid-to-late adulthood was associated with a 48% lower odds of poor SCF score compared with those who were always sedentary (OR 0.52; 95% CI 0.38, 0.71). Our results suggest that being physically active during early adulthood and mid-to-late life independently contribute to prevention of poor subjective cognitive function in late-life.

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

Adherence to Mediterranean diet and subjective cognitive function in men

Abstract

Benefits of a Mediterranean diet for cognition have been suggested, but epidemiologic studies have been relatively small and of limited duration. To prospectively assess the association between long-term adherence to a Mediterranean dietary pattern and self-reported subjective cognitive function (SCF). Prospective observational study. The Health Professionals' Follow-up Study, a prospective cohort of 51,529 men, 40–75 years of age when enrolled in 1986, of whom 27,842 were included in the primary analysis. Mediterranean diet (MD) score, computed from the mean of five food frequency questionnaires, assessed every 4 years from 1986 to 2002. Self-reported SCF assessed by a 6-item questionnaire in 2008 and 2012, and validated by association with genetic variants in apolipoprotein-4. Using the average of 2008 and 2012 SCF scores, 38.0% of men were considered to have moderate memory scores and 7.3% were considered to have poor scores. In a multivariate model, compared with men having a MD score in the lowest quintile, those in the highest quintile had a 36% lower odds of a poor SCF score (odds ratio 0.64, 95% CI 0.55–0.75; P, trend < 0.001) and a 24% lower odds of a moderate SCF score (OR 0.76, 95% CI 0.70–0.83; P, trend < 0.001). Both remote and more recent diet contributed to this relation. Associations were only slightly weaker using baseline dietary data and a lag of 22 years. Long-term adherence to the Mediterranean diet pattern was strongly related to lower subjective cognitive function. These findings provide further evidence that a healthy dietary pattern may prevent or delay cognitive decline.

http://ift.tt/2z8Li4b

Physical activity across adulthood and subjective cognitive function in older men

Abstract

Low subjective cognitive function (SCF), which is associated with APOE4 genotype, adversely impacts quality of life and has predicted clinical dementia. We examined whether physical activity during early adulthood or mid-to-late life is associated with late-life SCF. We followed 28,481 US male health professionals aged 40–75 years who reported their physical activity in 1986 and biennially thereafter. SCF was reported in 2008 and 2012. The SCF score was averaged for the 2008 and 2012 assessments and categorized as "good", "moderate", and "poor". Men in the highest versus lowest quintile of mid-to-late life physical activity in 1986 had 38% lower odds of poor versus good SCF score (multivariable-adjusted odds ratio (OR) 0.62; 95% CI 0.53, 0.72; P for trend < 0.0001). Being physically active in early adulthood was also associated with a 23% lower odds of poor SCF, independent of later activity, and being active both in early and mid-to-late adulthood was associated with a 48% lower odds of poor SCF score compared with those who were always sedentary (OR 0.52; 95% CI 0.38, 0.71). Our results suggest that being physically active during early adulthood and mid-to-late life independently contribute to prevention of poor subjective cognitive function in late-life.

http://ift.tt/2mxJsUu

Initial psycho-oncological counselling in neuro-oncology: analysis of topics and needs of brain tumour patients

Abstract

Diagnosis of a brain tumour is associated with a tremendous disruption of emotional, physical and social well-being. Due to the complexity of the disease and the affection of the central organ, the brain, brain tumour patients differ from other cancer patients. The purpose of this study was to evaluate the concerns and burdens presented by brain tumour patients during their initial psycho-oncological consultation. We performed a retrospective analysis of 53 patients with the diagnosis of either benign or malignant brain tumour, seeking counsel by a neurosurgeon specialised in psycho-oncology. We performed a thematic analysis of the interviews at first consultation identifying themes and patterns and created thematic categories. The main concerns of the patients presented during the first consultations were psychological problems, reported by 40 patients (75.5%). Death and dying was mentioned by more than half of the patients (n = 30, 56.6%). In addition, 62.3% of the patients (n = 33) asked for information regarding the medical treatment and diagnosis. With our study, we created greater awareness of the psychological needs of brain tumour patients in order to define treatment strategies for this important aspect of disease. We showed that there is a need for patients to talk about death even during the initial consultation. Psycho-oncologist in a neuro-oncological setting should be prepared for topics like that and should have a neurosurgical background or collaborate with members of the surgical team in order to provide the patients with medical details and to better understand the impact of the disease.

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

18F-FDG PET/CT in primary brain lymphoma

Abstract

The actual role of 18F-FDG PET/CT in evaluating primary brain lymphoma is still an open issue. Brain lymphoma usually show elevated 18F-FDG uptake, often higher than other brain tumors or inflammatory processes, but the metabolic behavior of this lymphoma is not still understood. Our aim was to investigate the particular metabolic behavior of this lymphoma. Forty six patients (21 female, 25 male) with histologically-confirmed brain lymphoma who underwent 18F-FDG PET/CT from vertex to the mid-thigh for initial staging were retrospectively evaluated. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax), lesion-to-liver SUVmax ratio, lesion-to-blood pool SUVmax ratio and the tumor to normal brain uptake ratio (T/N ratio) and compared with epidemiological (age, sex, HIV infection) and morphological (tumor size, MRI appearance) characteristics. Thirty-eight patients (83%) had positive 18F-FDG PET/CT (average SUVmax was 15.6 ± 9.2; lesion-to-liver SUVmax ratio 5.8 ± 2.8; lesion-to-blood pool SUVmax ratio 7.1 ± 3.8, T/N ratio 3.1 ± 1.7) at the corresponding brain lesion; the remaining 8 (17%) were not 18F-FDG avid. 18F-FDG avidity was significantly associated with morphological appearance and tumor size and not correlated with other features. 18F-FDG PET/CT detected extracranial disease in two cases (4%) with negative bone marrow biopsies and CT. In conclusion, brain lymphomas are 18F-FDG avid in 83% of cases showing high 18F-FDG uptake and 18F-FDG avidity is correlated with tumor size and morphological appearance of the lesion. PET/CT helped to recognize extracranial disease in two patients.

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

Initial psycho-oncological counselling in neuro-oncology: analysis of topics and needs of brain tumour patients

Abstract

Diagnosis of a brain tumour is associated with a tremendous disruption of emotional, physical and social well-being. Due to the complexity of the disease and the affection of the central organ, the brain, brain tumour patients differ from other cancer patients. The purpose of this study was to evaluate the concerns and burdens presented by brain tumour patients during their initial psycho-oncological consultation. We performed a retrospective analysis of 53 patients with the diagnosis of either benign or malignant brain tumour, seeking counsel by a neurosurgeon specialised in psycho-oncology. We performed a thematic analysis of the interviews at first consultation identifying themes and patterns and created thematic categories. The main concerns of the patients presented during the first consultations were psychological problems, reported by 40 patients (75.5%). Death and dying was mentioned by more than half of the patients (n = 30, 56.6%). In addition, 62.3% of the patients (n = 33) asked for information regarding the medical treatment and diagnosis. With our study, we created greater awareness of the psychological needs of brain tumour patients in order to define treatment strategies for this important aspect of disease. We showed that there is a need for patients to talk about death even during the initial consultation. Psycho-oncologist in a neuro-oncological setting should be prepared for topics like that and should have a neurosurgical background or collaborate with members of the surgical team in order to provide the patients with medical details and to better understand the impact of the disease.

http://ift.tt/2hGAvXx

18F-FDG PET/CT in primary brain lymphoma

Abstract

The actual role of 18F-FDG PET/CT in evaluating primary brain lymphoma is still an open issue. Brain lymphoma usually show elevated 18F-FDG uptake, often higher than other brain tumors or inflammatory processes, but the metabolic behavior of this lymphoma is not still understood. Our aim was to investigate the particular metabolic behavior of this lymphoma. Forty six patients (21 female, 25 male) with histologically-confirmed brain lymphoma who underwent 18F-FDG PET/CT from vertex to the mid-thigh for initial staging were retrospectively evaluated. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax), lesion-to-liver SUVmax ratio, lesion-to-blood pool SUVmax ratio and the tumor to normal brain uptake ratio (T/N ratio) and compared with epidemiological (age, sex, HIV infection) and morphological (tumor size, MRI appearance) characteristics. Thirty-eight patients (83%) had positive 18F-FDG PET/CT (average SUVmax was 15.6 ± 9.2; lesion-to-liver SUVmax ratio 5.8 ± 2.8; lesion-to-blood pool SUVmax ratio 7.1 ± 3.8, T/N ratio 3.1 ± 1.7) at the corresponding brain lesion; the remaining 8 (17%) were not 18F-FDG avid. 18F-FDG avidity was significantly associated with morphological appearance and tumor size and not correlated with other features. 18F-FDG PET/CT detected extracranial disease in two cases (4%) with negative bone marrow biopsies and CT. In conclusion, brain lymphomas are 18F-FDG avid in 83% of cases showing high 18F-FDG uptake and 18F-FDG avidity is correlated with tumor size and morphological appearance of the lesion. PET/CT helped to recognize extracranial disease in two patients.

http://ift.tt/2jzFJEV

U-CH17P, -M, and -S, a new cell culture system for tumour diversity and progression in chordoma

Abstract

Chordoma is a rare bone tumour with a known intrinsic heterogeneity. Here, we address this tumour heterogeneity in a new cell culture model for tumour diversity and progression in chordoma. The three cell lines U-CH17P, U-CH17M, and U-CH17S were established from a primary sacral chordoma and its derived metastases, a soft tissue and a skin metastasis, respectively. The lesions had divergent differentiation patterns which are conserved in the derived cell lines making them a suitable in vitro model for the analysis of tumorigenesis in chordoma. A common feature of the three cell lines is the expression of typical chordoma markers, such as Brachyury, vimentin, cytokeratins, EMA, and S100 protein. A comparison of the genomic aberrations by array comparative genomic hybridization of the cell lines and the corresponding parental tumour tissues revealed that the precursor cells of U-CH17P, U-CH17M, and U-CH17S were already present in the primary tumour. Therefore, we show that clonal diversity of this chordoma exists in the primary tumour and that not all of these subclones tend to metastasize. All cell lines had a CDKN2A loss. A comparison of the gene expression profiles of the cell lines revealed significant differences in the expression of several genes like MAGEC2 and SEMA6A known to be associated with the tendency to metastasize or proliferation and migration. Since the underlying mechanisms of tumour progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology. This article is protected by copyright. All rights reserved.

http://ift.tt/2hFZj1A

U-CH17P, -M, and -S, a new cell culture system for tumour diversity and progression in chordoma

Abstract

Chordoma is a rare bone tumour with a known intrinsic heterogeneity. Here, we address this tumour heterogeneity in a new cell culture model for tumour diversity and progression in chordoma. The three cell lines U-CH17P, U-CH17M, and U-CH17S were established from a primary sacral chordoma and its derived metastases, a soft tissue and a skin metastasis, respectively. The lesions had divergent differentiation patterns which are conserved in the derived cell lines making them a suitable in vitro model for the analysis of tumorigenesis in chordoma. A common feature of the three cell lines is the expression of typical chordoma markers, such as Brachyury, vimentin, cytokeratins, EMA, and S100 protein. A comparison of the genomic aberrations by array comparative genomic hybridization of the cell lines and the corresponding parental tumour tissues revealed that the precursor cells of U-CH17P, U-CH17M, and U-CH17S were already present in the primary tumour. Therefore, we show that clonal diversity of this chordoma exists in the primary tumour and that not all of these subclones tend to metastasize. All cell lines had a CDKN2A loss. A comparison of the gene expression profiles of the cell lines revealed significant differences in the expression of several genes like MAGEC2 and SEMA6A known to be associated with the tendency to metastasize or proliferation and migration. Since the underlying mechanisms of tumour progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2hFZj1A
via IFTTT

A ROLE FOR CXCR4 IN PERITONEAL AND HEMATOGENOUS OVARIAN CANCER DISSEMINATION

Epithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time, most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a patient-derived tissue macroarray and mRNA expression analysis we observed high CXCR4 levels in high-grade serous epithelial ovarian carcinomas, the most metastatic tumor, compared with those in endometrioid carcinomas. CXCR4 inhibition by treatment with the CXCR4 antagonist AMD3100 or by expression of shRNA anti-CXCR4 similarly inhibited angiogenesis in several models of ovarian carcinomas orthotopically grown in nude mice, but the effect on tumor growth was correlated with the levels of CXCR4 expression. Moreover, CXCR4 inhibition completely blocked dissemination and metastasis. This effect was associated with reduced levels of active Src, active ERKs, the inhibition of EMT transition and block of hematogenous ovarian cancer dissemination decreasing circulating human tumoral cells (CTCs). In tumors, CXCR4-expressing cells also had more mesenchymal characteristics. In conclusion, our results indicate that CXCR4 expression confers a proinvasive phenotype to ovarian carcinoma cells. Thus anti-CXCR4 therapy is a possible agent for a complementary treatment of advanced disseminated epithelial high-grade serous ovarian cancer patients.

from Cancer via ola Kala on Inoreader http://ift.tt/2ySdpk1
via IFTTT

A ROLE FOR CXCR4 IN PERITONEAL AND HEMATOGENOUS OVARIAN CANCER DISSEMINATION

Epithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time, most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a patient-derived tissue macroarray and mRNA expression analysis we observed high CXCR4 levels in high-grade serous epithelial ovarian carcinomas, the most metastatic tumor, compared with those in endometrioid carcinomas. CXCR4 inhibition by treatment with the CXCR4 antagonist AMD3100 or by expression of shRNA anti-CXCR4 similarly inhibited angiogenesis in several models of ovarian carcinomas orthotopically grown in nude mice, but the effect on tumor growth was correlated with the levels of CXCR4 expression. Moreover, CXCR4 inhibition completely blocked dissemination and metastasis. This effect was associated with reduced levels of active Src, active ERKs, the inhibition of EMT transition and block of hematogenous ovarian cancer dissemination decreasing circulating human tumoral cells (CTCs). In tumors, CXCR4-expressing cells also had more mesenchymal characteristics. In conclusion, our results indicate that CXCR4 expression confers a proinvasive phenotype to ovarian carcinoma cells. Thus anti-CXCR4 therapy is a possible agent for a complementary treatment of advanced disseminated epithelial high-grade serous ovarian cancer patients.

http://ift.tt/2ySdpk1

Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax [Review]

Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL2 biology and facilitated the clinical development of venetoclax.

Significance: Basic research into the pathways governing programmed cell death have paved the way for the discovery of apoptosis-inducing agents such as venetoclax, a BCL2-selective inhibitor that was recently approved by the FDA and the European Medicines Agency. Preclinical studies aimed at identifying BCL2-dependent tumor types have translated well into the clinic thus far and will likely continue to inform the clinical development of venetoclax and other BCL2 family inhibitors. Cancer Discov; 7(12); 1–18. ©2017 AACR.

from Cancer via ola Kala on Inoreader http://ift.tt/2j2BXjI
via IFTTT

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity, Published online: 16 November 2017; doi:10.1038/bjc.2017.412

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

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in <i>ALK</i>-positive NSCLC, Published online: 16 November 2017; doi:10.1038/bjc.2017.395

from Cancer via ola Kala on Inoreader http://ift.tt/2zJJ7Dj
via IFTTT

Reply to ‘Comment on ‘Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study’’

Reply to 'Comment on 'Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study''

Reply to 'Comment on 'Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study'', Published online: 16 November 2017; doi:10.1038/bjc.2017.406

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

Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation

Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation

<i>Treponema denticola</i> chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation, Published online: 16 November 2017; doi:10.1038/bjc.2017.409

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

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity, Published online: 16 November 2017; doi:10.1038/bjc.2017.412

http://ift.tt/2hxeqqt

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in <i>ALK</i>-positive NSCLC, Published online: 16 November 2017; doi:10.1038/bjc.2017.395

http://ift.tt/2zJJ7Dj

Reply to ‘Comment on ‘Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study’’

Reply to 'Comment on 'Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study''

Reply to 'Comment on 'Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study'', Published online: 16 November 2017; doi:10.1038/bjc.2017.406

http://ift.tt/2hwYODl

Comment on ‘Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study’

Comment on 'Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study'

Comment on 'Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study', Published online: 16 November 2017; doi:10.1038/bjc.2017.342

http://ift.tt/2zMBqMA

Disappearing Lump—an Unusual Presentation of Large Metastatic Small Bowel Malignant Melanoma

from Cancer via ola Kala on Inoreader http://ift.tt/2ipeo4T
via IFTTT

Disappearing Lump—an Unusual Presentation of Large Metastatic Small Bowel Malignant Melanoma

http://ift.tt/2ipeo4T

The NOTCH4-HEY1 pathway induces epithelial mesenchymal transition in head and neck squamous cell carcinoma

Background: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood. Methods: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell cycle assays. We also compared the relationships among NOTCH4, HEY1 and epithelial mesenchymal transition (EMT) related genes using the TCGA data set and in vitro assays. Results: HEY1 is specifically up-regulated in HNSCC compared with normal tissues in the TCGA data set. NOTCH4 is more significantly related to HEY1 activation in HNSCC in comparison to other NOTCH receptors. NOTCH4 promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell cycle dysregulation. Furthermore, NOTCH4 and HEY1 up-regulation resulted in decreased E-cadherin expression and increased Vimentin, Fibronectin, TWIST1, and SOX2 expression. NOTCH4 and HEY1 expression were associated with an EMT phenotypes as well as increased invasion and cell migration. Conclusion: In HNSCC the NOTCH4-HEY1 pathway is specifically up-regulated, induces proliferation and cisplatin resistance, and promotes EMT.

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

Development of a function-blocking antibody against fibulin-3 as targeted reagent for glioblastoma

Purpose: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. Experimental Design: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3. mAb428.2 was tested in cultures to measure its inhibitory effect on fibulin-3 signaling. Nude mice carrying subcutaneous and intracranial GBM xenografts were treated with the maximum achievable dose of mAb428.2 to measure target engagement and anti-tumor efficacy. Results: We identified a critical 23-amino acid sequence of fibulin-3 that activates its signaling mechanisms. mAb428.2 binds to that epitope with nanomolar affinity and blocks the ability of fibulin-3 to activate ADAM17, Notch, and NF-kB signaling in GBM cells. mAb428.2 treatment of subcutaneous GBM xenografts inhibited fibulin-3, increased tumor cell apoptosis, and enhanced the infiltration of inflammatory macrophages. The antibody reduced tumor growth and extended survival of mice carrying GBMs as well as other fibulin-3-expressing tumors. Locally-infused mAb428.2 showed efficacy against intracranial GBMs, increasing tumor apoptosis and reducing tumor invasion and vascularization, which are enhanced by fibulin-3. Conclusions: To our knowledge this is the first rationally-developed, function-blocking antibody against an ECM target in GBM. Our results offer a proof of principle for using "anti-ECM" strategies towards more efficient targeted therapies for malignant glioma.

from Cancer via ola Kala on Inoreader http://ift.tt/2zL3H66
via IFTTT

The NOTCH4-HEY1 pathway induces epithelial mesenchymal transition in head and neck squamous cell carcinoma

Background: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood. Methods: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell cycle assays. We also compared the relationships among NOTCH4, HEY1 and epithelial mesenchymal transition (EMT) related genes using the TCGA data set and in vitro assays. Results: HEY1 is specifically up-regulated in HNSCC compared with normal tissues in the TCGA data set. NOTCH4 is more significantly related to HEY1 activation in HNSCC in comparison to other NOTCH receptors. NOTCH4 promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell cycle dysregulation. Furthermore, NOTCH4 and HEY1 up-regulation resulted in decreased E-cadherin expression and increased Vimentin, Fibronectin, TWIST1, and SOX2 expression. NOTCH4 and HEY1 expression were associated with an EMT phenotypes as well as increased invasion and cell migration. Conclusion: In HNSCC the NOTCH4-HEY1 pathway is specifically up-regulated, induces proliferation and cisplatin resistance, and promotes EMT.

http://ift.tt/2hEjwoy

Development of a function-blocking antibody against fibulin-3 as targeted reagent for glioblastoma

Purpose: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. Experimental Design: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3. mAb428.2 was tested in cultures to measure its inhibitory effect on fibulin-3 signaling. Nude mice carrying subcutaneous and intracranial GBM xenografts were treated with the maximum achievable dose of mAb428.2 to measure target engagement and anti-tumor efficacy. Results: We identified a critical 23-amino acid sequence of fibulin-3 that activates its signaling mechanisms. mAb428.2 binds to that epitope with nanomolar affinity and blocks the ability of fibulin-3 to activate ADAM17, Notch, and NF-kB signaling in GBM cells. mAb428.2 treatment of subcutaneous GBM xenografts inhibited fibulin-3, increased tumor cell apoptosis, and enhanced the infiltration of inflammatory macrophages. The antibody reduced tumor growth and extended survival of mice carrying GBMs as well as other fibulin-3-expressing tumors. Locally-infused mAb428.2 showed efficacy against intracranial GBMs, increasing tumor apoptosis and reducing tumor invasion and vascularization, which are enhanced by fibulin-3. Conclusions: To our knowledge this is the first rationally-developed, function-blocking antibody against an ECM target in GBM. Our results offer a proof of principle for using "anti-ECM" strategies towards more efficient targeted therapies for malignant glioma.

http://ift.tt/2zL3H66

ATP-binding cassette transporters limit the brain penetration of Wee1 inhibitors

Summary

Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters. Methods We have here conducted a comprehensive set of in vitro and in vivo experiments to determine to what extent two dominant efflux transporters in the BBB, P-gp (ABCB1) and BCRP (ABCG2), exhibit affinity towards AZD1775 and PD0166285 and restrict their brain penetration. Results Using these studies, we demonstrate that AZD1775 is efficiently transported by both P-gp and BCRP, whereas PD0166285 is only a substrate of P-gp. Nonetheless, the brain penetration of both compounds was severely restricted in vivo, as indicated by a 5-fold (PD0166285) and 25-fold (AZD1775) lower brain-plasma ratio in wild type mice compared to Abcb1a/b;Abcg2^−/− mice. Conclusion The brain penetration of these Wee1 inhibitors is severely limited by ABC transporters, which may compromise their clinical efficacy against intracranial neoplasms such as DIPG and GBM.

http://ift.tt/2APqFWW

Issue Information - TOC

http://ift.tt/2AUM7dZ

Issue Information - Ed Board

http://ift.tt/2yP9kgk

Issue Information - TOC

from Cancer via ola Kala on Inoreader http://ift.tt/2AUM7dZ
via IFTTT

Issue Information - Ed Board

from Cancer via ola Kala on Inoreader http://ift.tt/2yP9kgk
via IFTTT

Issue Information - TOC

http://ift.tt/2AUM7dZ

Issue Information - Ed Board

http://ift.tt/2yP9kgk

Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation

http://ift.tt/2jxuEEm

Reply to ‘Comment on ‘Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study’’

http://ift.tt/2hFwPVI

Comment on ‘Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study’

http://ift.tt/2jxuE7k

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity

http://ift.tt/2hFrePi

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

http://ift.tt/2jyKWNh

Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation

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

Reply to ‘Comment on ‘Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study’’

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

Comment on ‘Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study’

from Cancer via ola Kala on Inoreader http://ift.tt/2jxuE7k
via IFTTT

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity

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

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

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

Impact of WHO 2016 update of brain tumor classification, molecular markers and clinical outcomes in pleomorphic xanthoastrocytoma

Abstract

We present outcomes of pleomorphic xanthoastrocytoma (PXA) and correlate the impact of clinical, pathologic and molecular markers. Between 2006 and 2016, 37 patients with histologically verified PXA form the study cohort. All underwent maximal safe resection; those who had good resection and young age were observed. Adjuvant radiotherapy was given in patients with some atypical features such as high MIB-1 index (> 5%), residual disease or at recurrence. Patients with anaplastic PXA were administered adjuvant radiotherapy and systemic therapy. Median age at diagnosis was 20 years (range 4–45). At median follow-up of 33 months, 3-year and 5-year overall survival (OS) was 80.2 and 74% respectively. Patients who underwent GTR (23 cases, 62%) had significantly better 3-year PFS of 85.6% compared to 32.3% (p = 0.001) achieved with STR (13 cases, 35%). PFS was significantly superior in PXA grade II as compared to anaplastic PXA group (3-year estimates 80.2 vs. 32%; p = 0.007). 13 out of 27 patients where BRAFV600E testing was successful showed a mutation (48%). 3-year PFS and OS survival in BRAFV600E mutated patients was 51.9 and 76.9% compared to 73 and 75% in BRAFV600E non-mutated patients, respectively. No patient had IDH1 mutation. This data may provide valuable insights and act as a benchmark for future studies.

from Cancer via ola Kala on Inoreader http://ift.tt/2ASOmP4
via IFTTT

Metastasis in the mandibular condyle: a case report

Most bone metastases are observed in the trunk of the body. Metastasis in the mandibular condyle is rare. In many case reports, temporary common temporomandibular joint disorder-like symptoms can be a sign of ...

http://ift.tt/2mwHTGt

Impact of WHO 2016 update of brain tumor classification, molecular markers and clinical outcomes in pleomorphic xanthoastrocytoma

Abstract

We present outcomes of pleomorphic xanthoastrocytoma (PXA) and correlate the impact of clinical, pathologic and molecular markers. Between 2006 and 2016, 37 patients with histologically verified PXA form the study cohort. All underwent maximal safe resection; those who had good resection and young age were observed. Adjuvant radiotherapy was given in patients with some atypical features such as high MIB-1 index (> 5%), residual disease or at recurrence. Patients with anaplastic PXA were administered adjuvant radiotherapy and systemic therapy. Median age at diagnosis was 20 years (range 4–45). At median follow-up of 33 months, 3-year and 5-year overall survival (OS) was 80.2 and 74% respectively. Patients who underwent GTR (23 cases, 62%) had significantly better 3-year PFS of 85.6% compared to 32.3% (p = 0.001) achieved with STR (13 cases, 35%). PFS was significantly superior in PXA grade II as compared to anaplastic PXA group (3-year estimates 80.2 vs. 32%; p = 0.007). 13 out of 27 patients where BRAFV600E testing was successful showed a mutation (48%). 3-year PFS and OS survival in BRAFV600E mutated patients was 51.9 and 76.9% compared to 73 and 75% in BRAFV600E non-mutated patients, respectively. No patient had IDH1 mutation. This data may provide valuable insights and act as a benchmark for future studies.

http://ift.tt/2ASOmP4

Impact of WHO 2016 update of brain tumor classification, molecular markers and clinical outcomes in pleomorphic xanthoastrocytoma

Abstract

We present outcomes of pleomorphic xanthoastrocytoma (PXA) and correlate the impact of clinical, pathologic and molecular markers. Between 2006 and 2016, 37 patients with histologically verified PXA form the study cohort. All underwent maximal safe resection; those who had good resection and young age were observed. Adjuvant radiotherapy was given in patients with some atypical features such as high MIB-1 index (> 5%), residual disease or at recurrence. Patients with anaplastic PXA were administered adjuvant radiotherapy and systemic therapy. Median age at diagnosis was 20 years (range 4–45). At median follow-up of 33 months, 3-year and 5-year overall survival (OS) was 80.2 and 74% respectively. Patients who underwent GTR (23 cases, 62%) had significantly better 3-year PFS of 85.6% compared to 32.3% (p = 0.001) achieved with STR (13 cases, 35%). PFS was significantly superior in PXA grade II as compared to anaplastic PXA group (3-year estimates 80.2 vs. 32%; p = 0.007). 13 out of 27 patients where BRAFV600E testing was successful showed a mutation (48%). 3-year PFS and OS survival in BRAFV600E mutated patients was 51.9 and 76.9% compared to 73 and 75% in BRAFV600E non-mutated patients, respectively. No patient had IDH1 mutation. This data may provide valuable insights and act as a benchmark for future studies.

from Cancer via ola Kala on Inoreader http://ift.tt/2ASOmP4
via IFTTT

Medulloblastoma in adults

Abstract

Purpose

Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution.

Methods

Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients' demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated.

Results

In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2 Gy) and a boost to the posterior fossa (median dose 19.8 Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5‑ and 10-year OS was 89 and 80%, respectively. Estimated 5‑ and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS.

Conclusions

The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible.

http://ift.tt/2AMxE2X

Radiotherapy for extramedullary leukaemic manifestation (Chloroma)

Abstract

Purpose

Extramedullary leukaemic disease (EMD, synonym chloroma) is a rare solid manifestation of myeloid leukaemia for which the value of radiotherapy (RT) as a treatment strategy remains controversial. The aim of this study is to analyse the effectiveness of various RT doses for EMD in the modern treatment era.

Materials and methods

Between January 2000 and June 2016, 20 patients with total of 45 lesions underwent RT for EMD at our institution.

Results

With a median radiation dose of 26 Gy (range 4–42 Gy), local remission could be achieved in 91% of patients (complete remission rate: 71%). The median duration of local control (DOLC) was 17 months (95% confidence interval [CI] 0.5–33) and the median overall survival (OS) after chloroma onset was 24 months (95% CI 11–38). No noticeable difference between high- and low-dose regimens has been observed (74% versus 68%; P = 0.5). In the multivariate analysis, only Eastern Cooperative Oncology Group (ECOG) score and bone marrow state during RT have proven to be determinant for durable local control and OS.

Conclusions

Low-dose RT (≤26 Gy) achieves good local control compared to high-dose regimes. Bone marrow state during RT and ECOG score during RT may play a crucial role, influencing both DOLC and OS.

http://ift.tt/2imW78i

Executive summary of the 12th HHT international scientific conference

Abstract

Hereditary hemorrhagic telangiectasia is an autosomal dominant trait affecting approximately 1 in 5000 people. A pathogenic DNA sequence variant in the ENG, ACVRL1 or SMAD4 genes, can be found in the majority of patients. The 12th International Scientific HHT Conference was held on June 8–11, 2017 in Dubrovnik, Croatia to present and discuss the latest scientific achievements, and was attended by over 200 scientific and clinical researchers. In total 174 abstracts were accepted of which 58 were selected for oral presentations. This article covers the basic science and clinical talks, and discussions from three theme-based workshops. We focus on significant emergent themes and unanswered questions. Understanding these topics and answering these questions will help to define the future of HHT research and therapeutics, and ultimately bring us closer to a cure.

http://ift.tt/2zIDIwO

Executive summary of the 12th HHT international scientific conference

Abstract

Hereditary hemorrhagic telangiectasia is an autosomal dominant trait affecting approximately 1 in 5000 people. A pathogenic DNA sequence variant in the ENG, ACVRL1 or SMAD4 genes, can be found in the majority of patients. The 12th International Scientific HHT Conference was held on June 8–11, 2017 in Dubrovnik, Croatia to present and discuss the latest scientific achievements, and was attended by over 200 scientific and clinical researchers. In total 174 abstracts were accepted of which 58 were selected for oral presentations. This article covers the basic science and clinical talks, and discussions from three theme-based workshops. We focus on significant emergent themes and unanswered questions. Understanding these topics and answering these questions will help to define the future of HHT research and therapeutics, and ultimately bring us closer to a cure.

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

Medulloblastoma in adults

Abstract

Purpose

Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution.

Methods

Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients' demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated.

Results

In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2 Gy) and a boost to the posterior fossa (median dose 19.8 Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5‑ and 10-year OS was 89 and 80%, respectively. Estimated 5‑ and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS.

Conclusions

The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible.

http://ift.tt/2AMxE2X

Radiotherapy for extramedullary leukaemic manifestation (Chloroma)

Abstract

Purpose

Extramedullary leukaemic disease (EMD, synonym chloroma) is a rare solid manifestation of myeloid leukaemia for which the value of radiotherapy (RT) as a treatment strategy remains controversial. The aim of this study is to analyse the effectiveness of various RT doses for EMD in the modern treatment era.

Materials and methods

Between January 2000 and June 2016, 20 patients with total of 45 lesions underwent RT for EMD at our institution.

Results

With a median radiation dose of 26 Gy (range 4–42 Gy), local remission could be achieved in 91% of patients (complete remission rate: 71%). The median duration of local control (DOLC) was 17 months (95% confidence interval [CI] 0.5–33) and the median overall survival (OS) after chloroma onset was 24 months (95% CI 11–38). No noticeable difference between high- and low-dose regimens has been observed (74% versus 68%; P = 0.5). In the multivariate analysis, only Eastern Cooperative Oncology Group (ECOG) score and bone marrow state during RT have proven to be determinant for durable local control and OS.

Conclusions

Low-dose RT (≤26 Gy) achieves good local control compared to high-dose regimes. Bone marrow state during RT and ECOG score during RT may play a crucial role, influencing both DOLC and OS.

http://ift.tt/2imW78i

Hematological adverse effects in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors: a systematic review and meta-analysis

Abstract

Background

The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic breast cancer. CDK 4/6 inhibitors induce cell cycle arrest via liberating the tumor suppressor retinoblastoma protein from CDK4/6 inhibitory effect. Preliminary studies suggested an increase in the hematological toxicities which might affect the quality of life in such palliative setting.

Methods

We searched PubMed, ASCO, ESMO and San Antonio meeting databases for randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors with safety data provided on the incidence of hematological adverse effects.

Results

Our search identified 1012 citations that were screened for relevance. Thirty-six studies were found to be potentially eligible. After excluding the ineligible studies, six studies were deemed to be eligible for meta-analysis. The risk ratio (RR) was 11.31 [95% confidence interval (CI) 8.06–15.87; p < 0.0001] for all-grade leucopenia, 14.86 (95% CI 11.37–19.41; p < 0.0001) for all-grade neutropenia, 9.04 (95% CI 3.78–21.63; p < 0.0001) for all-grade thrombocytopenia and 3.57 (95% CI 2.65–4.81; p < 0.0001) for all-grade anemia. The RR for grade 3/4 leucopenia was 33.86 (95% CI 14.59–78.57; p < 0.0001), for grade 3/4 neutropenia was 44.00 (95% CI 24.72–78.33; p < 0.0001), for grade 3/4 thrombocytopenia was 5.70 (95% CI 2.03–16.01; p = 0.001) and for grade 3/4 anemia was 2.80 (95% CI 1.45–5.41; p = 0.002). There was no significant increase in the RR of febrile neutropenia with RR of 3.29 (95% CI 0.93–11.57; p = 0.06).

Conclusion

Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.

http://ift.tt/2zHkxn1

Risk factors associated with the progression and metastases of hindgut neuroendocrine tumors: a retrospective study

Abstract

Background

The worldwide incidence of neuroendocrine tumors (NETs) has increased remarkably, with the hindgut being the second most common site for such tumors. However, the mechanisms underlying progression and metastasis of hindgut NETs are unclear. A retrospective study was conducted to elucidate these mechanisms.

Methods

Clinicopathological data of cases of hindgut NET between April 1996 and September 2015 were analyzed, retrospectively. Patients with neuroendocrine carcinoma were excluded. Formalin-fixed paraffin-embedded tissues of hindgut NET cases were subjected to detailed morphometric and immunohistochemical analyses. Statistical analyses were performed using the non-parametric Mann-Whitney U test, Spearman's correlation coefficient, and chi-squared test. Multivariate logistic regression analysis was conducted as appropriate for the data set.

Results

Fifty-six hindgut NET cases were considered. Microvessel density and lymphatic microvessel density were identified as significant risk factors for venous and lymphatic invasion. There was a positive correlation between microvessel density and the maximum tumor diameter. Multivariate logistic regression analysis revealed that the maximum tumor diameter alone was an independent predictor of lymph node metastasis, whereas lymphovascular invasion and MVD was not the predictor of lymph node metastasis. There were no significant correlations between the Ki-67 labeling index and any of the parameters evaluated including age, sex, the maximum tumor diameter, venous invasion, lymphatic invasion, microvessel density, lymphatic microvessel density, and lymph node metastasis.

Conclusions

Angiogenic mechanisms may play important roles in the progression of hindgut NET. Otherwise, the maximum tumor diameter alone was an independent predictor of lymph node metastasis in hindgut NETs. Moreover, our study raises the question of whether the presence of lymphovascular invasion, in endoscopically obtained hindgut NET tissues, is an absolute indication for additional surgery or not.

http://ift.tt/2hD13J0

Editorial Board

Publication date: December 2017
Source:Cancer Genetics, Volumes 218–219





http://ift.tt/2AML8Ml

Table of Contents

Publication date: December 2017
Source:Cancer Genetics, Volumes 218–219





http://ift.tt/2imY04P

Cover

Publication date: December 2017
Source:Cancer Genetics, Volumes 218–219





http://ift.tt/2ALiiMa

Decoding colorectal cancer epigenomics

Publication date: Available online 15 November 2017
Source:Cancer Genetics
Author(s): Khalid El Bairi, Kanwal Tariq, Imane Himri, Abdeslam Jaafari, Wiam Smaili, Abdul Hafeez Kandhro, Adel Gouri, Bouchra Ghazi
Colorectal cancer (CRC) is very heterogeneous and presents different types of epigenetic alterations including DNA methylation, histone modifications and microRNAs. These changes are considered as characteristics of various observed clinical phenotypes. Undoubtedly, the discovery of epigenetic pathways with novel epigenetic-related mechanisms constitutes a promising advance in cancer biomarker discovery. In this review, we provide an evidence-based discussing of the current understanding of CRC epigenomics and its role in initiation, epithelial-to-mesenchymal transition and metastasis. We also discuss the recent findings regarding the potential clinical perspectives of these alterations as potent biomarkers for CRC diagnosis, prognosis, and therapy in the era of liquid biopsy.

Graphical abstract

http://ift.tt/2imfeQ3

Gradually Worsening Pruritic Plaques

A woman in her 20s taking valproic acid and phenytoin for epilepsy presented to the clinic with a 2-month history of gradually worsening pruritic plaques that initially involved the scalp, face, and neck, and later affected the anterior and posterior chest wall, abdomen, upper arms and thighs. What is your diagnosis?

from Cancer via ola Kala on Inoreader http://ift.tt/2AVtUx1
via IFTTT

Critical Lessons From High-Value Oncology Practices

This qualitative analysis of interview results assesses the attributes of "positive deviant" oncology practices that deliver high-quality cancer care at low total cost for testing and adoption by other practices.

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

Incorrect Percentages in the Abstract

In the article titled "Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer: Secondary Analysis of the TRIO-013/LOGiC Randomized Clinical Trial," the percentages corresponding with disease control rate in the Results section of the Abstract were reversed. The sentence should read "…and disease control rate (72% vs 83%; P = .02)…". This article was corrected online.

from Cancer via ola Kala on Inoreader http://ift.tt/2hEMm8y
via IFTTT

Immune Checkpoint Inhibition and Targeted Therapy in Stage IV Melanoma

This study uses data from the National Cancer Database to examine the population-level efficacy of novel therapies for advanced-stage melanoma.

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

Rethinking Extended Adjuvant Antiestrogen Therapy for Breast Cancer

This Viewpoint discusses the potential for reducing recurrence and mortality in patients with high-risk estrogen receptor–positive breast cancer by using an affordable intermittent salvage therapy.

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

Ipilimumab in Women With Human Papillomavirus–Related Cervical Carcinoma

This phase1/2 trial evaluates the safety and antitumor activity of ipilimumab in women with recurrent cervical cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2jyu09P
via IFTTT

Biospecimen donation among black and white breast cancer survivors: opportunities to promote precision medicine

Abstract

Purpose

Advances in precision medicine (PM) have potential to reduce and/or eliminate breast cancer disparities in both treatment and survivorship. However, compared to white Americans, black Americans are often underrepresented in genetic research. This report assessed factors that influence receipt of buccal cells via saliva kits.

Methods

This prospective study recruited women with confirmed hormonal-positive (HR+) breast cancer (BC). A standardized telephone survey collected sociodemographic, socio-cultural (e.g., religiosity), and healthcare process factors. Clinical information was abstracted from medical records. After the baseline survey, return postage-paid envelopes and mouthwash collection kits were mailed. Univariate and adjusted logistic regression models estimated the probability of biospecimen donation.

Results

Seventy percent of the sample provided buccal cells which were of good quality. No differences were noted by race or other demographic factors. In the multivariable logistic model, time spent with providers (OR 1.61 per 1-point increase; 95% CI 1.242, 2.088) and religiosity (OR 0.957 per 1-point increase; 95% CI 0.931, 0.984) remained associated with biospecimen provision. Women with lower-stage cancer (vs. higher stage III+) were more likely to donate biospecimens (p < 0.05).

Conclusions

Cancer care experiences predicted specimen donation. Understanding the contextual reasons for lower receipt among women with higher religiosity scores and higher stage warrants further examination.

Implications for cancer survivors

PM is relevant to cancer survivors because of its potential to inform targeted therapies, understand disease resistance, and aide in prediction of toxicity and/or recurrence. Future efforts to launch precision medicine trials with BC survivors may benefit from engaging medical oncologists and/or leveraging patient-provider encounters for trial participation.

http://ift.tt/2yNZQ55

Biospecimen donation among black and white breast cancer survivors: opportunities to promote precision medicine

Abstract

Purpose

Advances in precision medicine (PM) have potential to reduce and/or eliminate breast cancer disparities in both treatment and survivorship. However, compared to white Americans, black Americans are often underrepresented in genetic research. This report assessed factors that influence receipt of buccal cells via saliva kits.

Methods

This prospective study recruited women with confirmed hormonal-positive (HR+) breast cancer (BC). A standardized telephone survey collected sociodemographic, socio-cultural (e.g., religiosity), and healthcare process factors. Clinical information was abstracted from medical records. After the baseline survey, return postage-paid envelopes and mouthwash collection kits were mailed. Univariate and adjusted logistic regression models estimated the probability of biospecimen donation.

Results

Seventy percent of the sample provided buccal cells which were of good quality. No differences were noted by race or other demographic factors. In the multivariable logistic model, time spent with providers (OR 1.61 per 1-point increase; 95% CI 1.242, 2.088) and religiosity (OR 0.957 per 1-point increase; 95% CI 0.931, 0.984) remained associated with biospecimen provision. Women with lower-stage cancer (vs. higher stage III+) were more likely to donate biospecimens (p < 0.05).

Conclusions

Cancer care experiences predicted specimen donation. Understanding the contextual reasons for lower receipt among women with higher religiosity scores and higher stage warrants further examination.

Implications for cancer survivors

PM is relevant to cancer survivors because of its potential to inform targeted therapies, understand disease resistance, and aide in prediction of toxicity and/or recurrence. Future efforts to launch precision medicine trials with BC survivors may benefit from engaging medical oncologists and/or leveraging patient-provider encounters for trial participation.

from Cancer via ola Kala on Inoreader http://ift.tt/2yNZQ55
via IFTTT

Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma

Abstract

Background

Dysregulation of miRNAs is associated with cancer development by coordinately suppressing abundant target genes. Emerging evidence indicates that miR-31 plays a dual role in tumorigenicity. However, whether miR-31 plays as an oncogene in esophageal squamous cell carcinoma (ESCC) and the potential target molecules are still unclear. MiR-31 role in ESCC was investigated and an association of the target molecules with EMT was identified in the progression of ESCC.

Methods

Western blot assays and qRT-PCR was performed to detect the protein and mRNA levels. We investigated the role of miR-31 in the regulation of LATS2 expression in ESCC cell lines via functional assays both in vivo and in vitro. The luciferase reporter assays was conducted to confirm LATS2 is a potential target of miR-31. Immunohistochemistry was used to measure LATS2 and TAZ expression in normal and ESCC tissue.

Results

LATS2 is a component of the Hippo tumor-suppressive signaling pathway. Frequent loss of heterozygosity of LATS2 has been reported in esophageal cancer. We analyzed the reciprocal expression regulation of miR-31 and LATS2 and demonstrated that LATS2 expression was elevated by down-regulation of miR-31 at the post-transcriptional level in ESCC. Moreover, miR-31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3′-UTR, a key molecule in the Hippo pathway. Then, LATS2 consequently promoted the translocation of TAZ, which was examined using immunohistochemistry. Silencing of miR-31 significantly inhibited the cell proliferation, induced apoptosis and decreased the ability of migration/invasion in vitro. LATS2 impedes ESCC cell proliferation and invasion by suppressing miR-31, as well as mice xenograft model in vivo. Meanwhile, the nuclear localization of LATS2 constrained the phosphorylation of TAZ. Then, the expression level of TAZ was notably heightened with a high risk of recurrence compared to that observed in the low-risk patients, as well as, the higher expression associated with a poor survival.

Conclusions

Our study demonstrated that overexpression of miR-31 undertook an oncogenic role in ESCC by repressing expression of LATS2 via the Hippo Pathway and activating epithelial-mesenchymal transition. LATS2 and TAZ could be potential novel molecular markers for predicting the risk of recurrence and prognosis of ESCC.

from Cancer via ola Kala on Inoreader http://ift.tt/2mwS7Xv
via IFTTT

TGF-β2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion

Abstract

Background

Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood.

Methods

U251, T98 and U87 GBM cell lines as well as GBM cells from a primary human specimen were used in vitro and in vivo to evaluate the effect of TGF-β2 on autophagy. Western blot, qPCR, immunofluorescence and transmission-electron microscope were used to detect target molecular expression. Lentivirus and siRNA vehicle were introduced to establish cell lines, as well as mitotracker and seahorse experiment to study the metabolic process in glioma. Preclinical therapeutic efficacy was evaluated in orthotopic xenograft mouse models.

Results

Here we demonstrated that TGF-β2 activated autophagy in human glioma cell lines and knockdown of Smad2 or inhibition of c-Jun NH2-terminal kinase, attenuated TGF-β2-induced autophagy. TGF-β2-induced autophagy is important for glioma invasion due to the alteration of epithelial-mesenchymal transition and metabolism conversion, particularly influencing mitochondria trafficking and membrane potential (△Ψm). Autopaghy also initiated a feedback on TGF-β2 in glioma by keeping its autocrine loop and affecting Smad2/3/7 expression. A xenograft model provided additional confirmation on combination of TGF-β inhibitor (Galunisertib) and autophagy inhibitor (CQ) to better "turn off" tumor growth.

Conclusion

Our findings elucidated a potential mechanism of autophagy-associated glioma invasion that TGF-β2 could initiate autophagy via Smad and non-Smad pathway to promote glioma cells' invasion.

from Cancer via ola Kala on Inoreader http://ift.tt/2z7e8lo
via IFTTT

LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition

Abstract

Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling. Attenuate binding between EZH2 and APC promoter was observed upon lncAPC knockdown. What is more, lncAPC-EZH2-APC axis can be targeted to eliminate liver TICs. Altogether, LncAPC promotes liver TIC self-renewal through EZH2-dependent APC transcriptional inhibition. This article is protected by copyright. All rights reserved

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

MiR-5100 increases the cisplatin resistance of the lung cancer stem cells by inhibiting the Rab6

Abstract

Cisplatin-based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR-5100 is overexpressed in lung cancer, but it is unknown whether and how miR-5100 regulates cisplatin resistance. Here, we demonstrated that miR-5100 was significantly up-regulated in CD44 + CD133+ lung cancer stem cells (LCSCs) compared with non-CSCs. Additionally, over-expression of miR-5100 increased CSC properties, cell growth and tumor sphere formation in lung cancer cell line A549 or H1299, and that miR-5100 inhibitor significantly increased sensitivity of LCSCs to cisplatin in vitro. Surprisingly, the combination with miR-5100 inhibitor significantly decreased the IC50 of LCSCs to cisplatin. Furthermore, miR-5100 increased CSC properties and cisplatin resistance by inhibiting Rab6, a direct target gene of miR-5100. We demonstrated that miR-5100 overexpression increases the cisplatin resistance of the LCSCs through the mitochondrial apoptosis pathway. In conclusion, our results suggest that miR-5100 increases the cisplatin resistance of the LCSCs by inhibiting the Rab6. This study provides novel insight into the regulation of LCSCs by miRNA. This article is protected by copyright. All rights reserved

from Cancer via ola Kala on Inoreader http://ift.tt/2z7xGq2
via IFTTT

Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma

Abstract

Background

Dysregulation of miRNAs is associated with cancer development by coordinately suppressing abundant target genes. Emerging evidence indicates that miR-31 plays a dual role in tumorigenicity. However, whether miR-31 plays as an oncogene in esophageal squamous cell carcinoma (ESCC) and the potential target molecules are still unclear. MiR-31 role in ESCC was investigated and an association of the target molecules with EMT was identified in the progression of ESCC.

Methods

Western blot assays and qRT-PCR was performed to detect the protein and mRNA levels. We investigated the role of miR-31 in the regulation of LATS2 expression in ESCC cell lines via functional assays both in vivo and in vitro. The luciferase reporter assays was conducted to confirm LATS2 is a potential target of miR-31. Immunohistochemistry was used to measure LATS2 and TAZ expression in normal and ESCC tissue.

Results

LATS2 is a component of the Hippo tumor-suppressive signaling pathway. Frequent loss of heterozygosity of LATS2 has been reported in esophageal cancer. We analyzed the reciprocal expression regulation of miR-31 and LATS2 and demonstrated that LATS2 expression was elevated by down-regulation of miR-31 at the post-transcriptional level in ESCC. Moreover, miR-31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3′-UTR, a key molecule in the Hippo pathway. Then, LATS2 consequently promoted the translocation of TAZ, which was examined using immunohistochemistry. Silencing of miR-31 significantly inhibited the cell proliferation, induced apoptosis and decreased the ability of migration/invasion in vitro. LATS2 impedes ESCC cell proliferation and invasion by suppressing miR-31, as well as mice xenograft model in vivo. Meanwhile, the nuclear localization of LATS2 constrained the phosphorylation of TAZ. Then, the expression level of TAZ was notably heightened with a high risk of recurrence compared to that observed in the low-risk patients, as well as, the higher expression associated with a poor survival.

Conclusions

Our study demonstrated that overexpression of miR-31 undertook an oncogenic role in ESCC by repressing expression of LATS2 via the Hippo Pathway and activating epithelial-mesenchymal transition. LATS2 and TAZ could be potential novel molecular markers for predicting the risk of recurrence and prognosis of ESCC.

http://ift.tt/2mwS7Xv

TGF-β2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion

Abstract

Background

Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood.

Methods

U251, T98 and U87 GBM cell lines as well as GBM cells from a primary human specimen were used in vitro and in vivo to evaluate the effect of TGF-β2 on autophagy. Western blot, qPCR, immunofluorescence and transmission-electron microscope were used to detect target molecular expression. Lentivirus and siRNA vehicle were introduced to establish cell lines, as well as mitotracker and seahorse experiment to study the metabolic process in glioma. Preclinical therapeutic efficacy was evaluated in orthotopic xenograft mouse models.

Results

Here we demonstrated that TGF-β2 activated autophagy in human glioma cell lines and knockdown of Smad2 or inhibition of c-Jun NH2-terminal kinase, attenuated TGF-β2-induced autophagy. TGF-β2-induced autophagy is important for glioma invasion due to the alteration of epithelial-mesenchymal transition and metabolism conversion, particularly influencing mitochondria trafficking and membrane potential (△Ψm). Autopaghy also initiated a feedback on TGF-β2 in glioma by keeping its autocrine loop and affecting Smad2/3/7 expression. A xenograft model provided additional confirmation on combination of TGF-β inhibitor (Galunisertib) and autophagy inhibitor (CQ) to better "turn off" tumor growth.

Conclusion

Our findings elucidated a potential mechanism of autophagy-associated glioma invasion that TGF-β2 could initiate autophagy via Smad and non-Smad pathway to promote glioma cells' invasion.

http://ift.tt/2z7e8lo

LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition

Abstract

Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling. Attenuate binding between EZH2 and APC promoter was observed upon lncAPC knockdown. What is more, lncAPC-EZH2-APC axis can be targeted to eliminate liver TICs. Altogether, LncAPC promotes liver TIC self-renewal through EZH2-dependent APC transcriptional inhibition. This article is protected by copyright. All rights reserved

http://ift.tt/2mxOIYd

MiR-5100 increases the cisplatin resistance of the lung cancer stem cells by inhibiting the Rab6

Abstract

Cisplatin-based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR-5100 is overexpressed in lung cancer, but it is unknown whether and how miR-5100 regulates cisplatin resistance. Here, we demonstrated that miR-5100 was significantly up-regulated in CD44 + CD133+ lung cancer stem cells (LCSCs) compared with non-CSCs. Additionally, over-expression of miR-5100 increased CSC properties, cell growth and tumor sphere formation in lung cancer cell line A549 or H1299, and that miR-5100 inhibitor significantly increased sensitivity of LCSCs to cisplatin in vitro. Surprisingly, the combination with miR-5100 inhibitor significantly decreased the IC50 of LCSCs to cisplatin. Furthermore, miR-5100 increased CSC properties and cisplatin resistance by inhibiting Rab6, a direct target gene of miR-5100. We demonstrated that miR-5100 overexpression increases the cisplatin resistance of the LCSCs through the mitochondrial apoptosis pathway. In conclusion, our results suggest that miR-5100 increases the cisplatin resistance of the LCSCs by inhibiting the Rab6. This study provides novel insight into the regulation of LCSCs by miRNA. This article is protected by copyright. All rights reserved

http://ift.tt/2z7xGq2

Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions

Abstract

Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.

from Cancer via ola Kala on Inoreader http://ift.tt/2jxn90g
via IFTTT

Source estimation of epileptic activity using eLORETA kurtosis analysis

Exact low-resolution brain electromagnetic tomography (eLORETA) is a technique for three-dimensional representation of the distribution of sources of electrical activity in the brain. Kurtosis analysis allows for identification of spiky activity in the brain. To evaluate the reliability of eLORETA kurtosis analysis, the results of the analysis were compared with those of equivalent current dipole (ECD) and synthetic aperture magnetometry (SAM) kurtosis analysis of magnetoencephalography (MEG) data in a patient with epilepsy with elementary visual seizures in a 6-year follow-up.

The results of electroencephalography (EEG) eLORETA kurtosis analysis indicative of a right superior temporal spike source partially overlapped with MEG ECD/SAM kurtosis results in all recordings, with a total overlapping at the end of the follow-up period. Overall findings suggest that eLORETA kurtosis analysis of EEG data may aid in the localisation of spike activity sources in patients with epilepsy.

http://ift.tt/2z7XH8B

Endovascular rescue treatment through stent positioning after surgical clipping of intracranial aneurysms complicated by parent artery obstruction

During aneurysm clipping, ischemic complications may occur and require a rescue treatment, usually surgical. We present two such cases that required urgent rescue treatment, performed through an endovascular route. Our first case presented with a non-ruptured right posterior inferior cerebellar artery (PICA) aneurysm. After permanent clip positioning, occlusion of the PICA occurred. An unsuccessful attempt of clip repositioning was performed. We therefore positioned a stent obtaining complete flow restoration. Our second case was that of a ruptured giant left middle cerebral artery aneurysm with focal critical stenosis of the parent vessel, likely due to an underlying dissection. Initially, the aneurysm was secured through coiling. However, after permanent clip positioning, parent artery occlusion occurred. DSA showed occlusion of the parent artery downstream to the clip and persistence of the preaneurismatic stenosis. We achieved full recanalization through stent positioning. In both cases, there were no ischemic or hemorrhagic complications.

http://ift.tt/2mwNtc1

Rare cause of adrenal insufficiency

A 72-year-old man presented with weight loss, night sweats and haemoptysis and was hypotensive. CT imaging showed rapidly enlarging bilateral adrenal masses, and he was found to have primary adrenal insufficiency. An adrenal gland biopsy revealed the rare diagnosis of primary adrenal lymphoma. This unique case highlights possible rare causes of adrenal masses and adrenal insufficiency, their investigation and management principles.

http://ift.tt/2z7TAt4

Primary intraventricular haemorrhage due to rupture of giant varix of the basal vein of Rosenthal in a patient with long-standing direct CCF: angiographic features and treatment considerations

Direct carotid cavernous fistulae (CCF) are often detected early and treated promptly resulting in a paucity of literature regarding its long-term evolution. We present a case of high flow post-traumatic direct CCF that was neglected for over 6 years and presented with a rare manifestation of primary intraventricular haemorrhage. Occlusions of the primary venous outlets likely resulted in engorgement of the deep venous system. The segmental anatomy of the shunting basal vein is critical to the clinical presentation and may range from basal ganglia or brainstem oedema/infarctions to uniquely, as in our case, isolated intraventricular haemorrhage secondary to variceal rupture. Treatment in such chronic cases requires a consideration of cerebral hyperperfusion syndrome necessitating deconstructive techniques with subsequent anticoagulation to avoid accelerated thrombosis of the venous varices.

http://ift.tt/2mvA9o9

Keratoderma blennorrhagica

Description

A 26-year-old woman, previously healthy, that a month ago started complaining of pain in the soles of both feet, which followed, additionally, to the right knee, the left knee, left elbow and right shoulder. She reported morning stiffness exceeding 1 hour that decreased with physical activity, worsened with rest, but improved with administration of non-steroidal anti-inflammatory drugs (NSAIDs). Three weeks later, skin lesions appeared on the soles of the feet.

Seven to 8 weeks before, the patient would have had two successive episodes of a urinary tract infection, treated, respectively, with fosfomycin and ciprofloxacin. The patient did not present gastrointestinal symptoms, previous weight loss or sweating.

On physical exam , it was verified pain at knee mobilisation, more intense in the left, where it presented articular effusion.

The cutaneous lesions were about 0.5 cm in diameter, were maculopapular, on a background of diffuse erythema and of desquamation on large blades (

http://ift.tt/2z6ylYD

Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions

Abstract

Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.

http://ift.tt/2jxn90g

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas associated with an invasive component: a case report with review of the literature

Abstract

Background

Intraductal tubulopapillary neoplasm (ITPN) depicts a distinct entity in the subgroup of premalignant epithelial tumors of the pancreas. Although the histomorphological and immunophenotypical characterization of ITPN has been described by several authors in terms of report of case series in the past, the rarity of that tumor subtype and similarity to other entities still makes identification of ITPN a challenge for radiologists and pathologists. To date, little is known about tubulopapillary carcinoma that can evolve from ITPN.

Case presentation

In the present work, we analyze one case of ITPN associated with an invasive component and discuss the results involving the current literature. Collected patient data included medical history, clinical symptoms, laboratory tests, radiological imaging, reports of interventions and operation, and histopathological and immunohistochemical examinations. The patient initially presented with acute pancreatitis. A solid tumor obstructing the main pancreatic duct and sticking out of the papilla of Vater was detected and caught via endoscopic intervention. Histopathological examination of the specimen revealed mainly tubular growth pattern with back to back tubular glands. Immunohistochemically, the tumor was strongly positive for keratin 7 (CK7) and pankeratin AE1/AE3, and alpha 1 antichymotrypsin; negative for synaptophysin and chromogranin A, CDx2, CK20, S100, carcinoembryonic antigen (CEA), MUC 2, MUC5AC, and somatostatin; and in part positive for CA19-9. Extended pancreatoduodenectomy was performed, the final diagnosis was tubulopapillary carcinoma grown in an ITPN.

Conclusion

The identification of an ITPN of the pancreas can be a challenging task. Endoscopic retrograde cholangiopancreaticography is an excellent tool to directly see and indirectly visualize the intraductal solid tumor and to take a biopsy for histopathological evaluation at the same time. Together with a thorough immunohistochemical workup, differential diagnoses can be ruled out quickly. To date, reports of ITPN are rare and little is known about the potential for malignant transformation and the prognosis of tubulopapillary carcinoma grown from an ITPN. Radical surgical resection following oncologic criteria is recommended; however, more data will be needed to assess an adequate treatment and follow-up standard.

http://ift.tt/2A4298l

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas associated with an invasive component: a case report with review of the literature

Abstract

Background

Intraductal tubulopapillary neoplasm (ITPN) depicts a distinct entity in the subgroup of premalignant epithelial tumors of the pancreas. Although the histomorphological and immunophenotypical characterization of ITPN has been described by several authors in terms of report of case series in the past, the rarity of that tumor subtype and similarity to other entities still makes identification of ITPN a challenge for radiologists and pathologists. To date, little is known about tubulopapillary carcinoma that can evolve from ITPN.

Case presentation

In the present work, we analyze one case of ITPN associated with an invasive component and discuss the results involving the current literature. Collected patient data included medical history, clinical symptoms, laboratory tests, radiological imaging, reports of interventions and operation, and histopathological and immunohistochemical examinations. The patient initially presented with acute pancreatitis. A solid tumor obstructing the main pancreatic duct and sticking out of the papilla of Vater was detected and caught via endoscopic intervention. Histopathological examination of the specimen revealed mainly tubular growth pattern with back to back tubular glands. Immunohistochemically, the tumor was strongly positive for keratin 7 (CK7) and pankeratin AE1/AE3, and alpha 1 antichymotrypsin; negative for synaptophysin and chromogranin A, CDx2, CK20, S100, carcinoembryonic antigen (CEA), MUC 2, MUC5AC, and somatostatin; and in part positive for CA19-9. Extended pancreatoduodenectomy was performed, the final diagnosis was tubulopapillary carcinoma grown in an ITPN.

Conclusion

The identification of an ITPN of the pancreas can be a challenging task. Endoscopic retrograde cholangiopancreaticography is an excellent tool to directly see and indirectly visualize the intraductal solid tumor and to take a biopsy for histopathological evaluation at the same time. Together with a thorough immunohistochemical workup, differential diagnoses can be ruled out quickly. To date, reports of ITPN are rare and little is known about the potential for malignant transformation and the prognosis of tubulopapillary carcinoma grown from an ITPN. Radical surgical resection following oncologic criteria is recommended; however, more data will be needed to assess an adequate treatment and follow-up standard.

from Cancer via ola Kala on Inoreader http://ift.tt/2A4298l
via IFTTT

“Mind the gaps”: Cognition and cancer

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

Renal failure during chemotherapy: renal biopsy for assessing subacute nephrotoxicity of pemetrexed

Abstract

Background

Pemetrexed, a multitargeted antifolate cytotoxic agent, is currently used primarily in combination with cisplatin for metastatic non-small cell lung cancer and for malignant mesothelioma. Acute renal toxicity of pemetrexed has been recently described with polychemotherapy, in which the individual responsibility of each drug is difficult to establish. Only one recent report documents renal involvement in long-term exposed patients.

Case presentation

We report on a case of rapidly progressive nephropathy leading to the cessation of platinum salts and the secondary interruption of pemetrexed and bevacizumab. Acute tubular necrosis shown on the renal biopsy could potentially be due to pemetrexed. Persistent severe renal failure after the resumption of all drugs led to new treatment lines with gemcitabine (while the glomerular filtration rate was below 30 ml/min/1.73m²), then followed by Taxol.

Conclusions

The optimal strategy with regard to renal complications in cancer patients is not clear. Acute or chronic loss in renal function generally leads to a new treatment line, possibly impairing the overall success of the treatment. The use of chemotherapy in patients with a glomerular filtration rate below 30 ml/min/1.73m² is usually associated with an increased risk of side effects when not contraindicated by renal elimination of the drug.

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

“Mind the gaps”: Cognition and cancer

http://ift.tt/2zIgNla

Renal failure during chemotherapy: renal biopsy for assessing subacute nephrotoxicity of pemetrexed

Abstract

Background

Pemetrexed, a multitargeted antifolate cytotoxic agent, is currently used primarily in combination with cisplatin for metastatic non-small cell lung cancer and for malignant mesothelioma. Acute renal toxicity of pemetrexed has been recently described with polychemotherapy, in which the individual responsibility of each drug is difficult to establish. Only one recent report documents renal involvement in long-term exposed patients.

Case presentation

We report on a case of rapidly progressive nephropathy leading to the cessation of platinum salts and the secondary interruption of pemetrexed and bevacizumab. Acute tubular necrosis shown on the renal biopsy could potentially be due to pemetrexed. Persistent severe renal failure after the resumption of all drugs led to new treatment lines with gemcitabine (while the glomerular filtration rate was below 30 ml/min/1.73m²), then followed by Taxol.

Conclusions

The optimal strategy with regard to renal complications in cancer patients is not clear. Acute or chronic loss in renal function generally leads to a new treatment line, possibly impairing the overall success of the treatment. The use of chemotherapy in patients with a glomerular filtration rate below 30 ml/min/1.73m² is usually associated with an increased risk of side effects when not contraindicated by renal elimination of the drug.

http://ift.tt/2hylKSY

Autoimmune diseases and breast cancer risk by tumor hormone-receptor status among elderly women

Abstract

The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ-specific autoimmune diseases and risk of breast cancer by tumor estrogen receptor (ER)- and progesterone receptor (PR)- status. Here we evaluate associations between selected systemic and organ-specific autoimmune diseases and breast cancer risk overall and by tumor ER- and PR-status. We used linked Surveillance, Epidemiology and End Results (SEER)-Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992-2011) (N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer-free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR=0.84; 99.9% CI 0.79-0.89), systemic lupus erythematosus (OR=0.82; 99.9% CI 0.70-0.97), and pernicious anemia (OR=0.90; 99.9% CI 0.83-0.97), and increased risk among those with psoriasis (OR=1.16; 99.9% CI 1.06-1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER-positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER-status were statistically significant (p-heterogeneity=.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment. This article is protected by copyright. All rights reserved.

http://ift.tt/2A3n4sc

Autoimmune diseases and breast cancer risk by tumor hormone-receptor status among elderly women

Abstract

The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ-specific autoimmune diseases and risk of breast cancer by tumor estrogen receptor (ER)- and progesterone receptor (PR)- status. Here we evaluate associations between selected systemic and organ-specific autoimmune diseases and breast cancer risk overall and by tumor ER- and PR-status. We used linked Surveillance, Epidemiology and End Results (SEER)-Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992-2011) (N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer-free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR=0.84; 99.9% CI 0.79-0.89), systemic lupus erythematosus (OR=0.82; 99.9% CI 0.70-0.97), and pernicious anemia (OR=0.90; 99.9% CI 0.83-0.97), and increased risk among those with psoriasis (OR=1.16; 99.9% CI 1.06-1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER-positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER-status were statistically significant (p-heterogeneity=.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2A3n4sc
via IFTTT

Prognostic relevance of programmed cell death ligand 1 expression in glioblastoma

Abstract

The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation assay and fluorescence in situ hybridization (FISH) for the assessment of 1p/19q deletion were performed. Expression of PD-L1 in tumour cells and TIIs was found in 37 (32.2%) and 6 (5.2%) patients, respectively. Kaplan–Meier analysis indicated that PD-L1 expression in tumour cells was significantly associated with poor overall survival (OS) (P = 0.017), though multivariate Cox analysis did not confirm this association (hazard ratio 1.204; P = 0.615). PD-L1 expression in TIIs did not correlate with the patient prognosis (P = 0.545). In addition, MGMT methylation and IDH-1 (R132H) expression were associated with a better prognosis (P < 0.001 and P = 0.024, respectively). The expression of PD-L1 was associated with CD3-positive T-cell infiltration (P < 0.001), and IDH-1 wild type status (P = 0.008). A deeper insight into PD-L1 expression could help to ensure the success of future immunotherapy in GBM. Our study suggested that PD-L1 target therapy might be beneficial for PD-L1-expressing GBM patients with a poor prognosis.

from Cancer via ola Kala on Inoreader http://ift.tt/2inx7hh
via IFTTT