Παρασκευή 6 Οκτωβρίου 2017

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: An analysis of patients treated on the RICOVER-60 trial

Abstract
Background
The prognosis of elderly patients with aggressive B-NHL after first lymphoma-related treatment failure (TF-L) is not well described.
Methods
We analysed patient characteristics including presence of MYC rearrangements and MYC-expression (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 to 80 years who had been treated on the RICOVER-60 trial.
Results
TF-L occurred in 301 of 1222 (24.6%) patients; 297 patients could be analyzed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared to CHOP (23.0% vs. 36.4% at 2 years, p = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% vs. 0% at 2 years, p < 0.001) or negative MYC-IHC (41.0% vs. 16.8% at 2 years, p = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (p < 0.001). The benefit of R was significant after first-line CHOP (2-year-OS 49.6% vs. 19.1%, p < 0.001) as well as after R-CHOP (2-year-OS 33.1% and 22.5%, p = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen.
Conclusion
MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy, however survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

http://ift.tt/2hUemEK

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: An analysis of patients treated on the RICOVER-60 trial

Abstract
Background
The prognosis of elderly patients with aggressive B-NHL after first lymphoma-related treatment failure (TF-L) is not well described.
Methods
We analysed patient characteristics including presence of MYC rearrangements and MYC-expression (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 to 80 years who had been treated on the RICOVER-60 trial.
Results
TF-L occurred in 301 of 1222 (24.6%) patients; 297 patients could be analyzed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared to CHOP (23.0% vs. 36.4% at 2 years, p = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% vs. 0% at 2 years, p < 0.001) or negative MYC-IHC (41.0% vs. 16.8% at 2 years, p = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (p < 0.001). The benefit of R was significant after first-line CHOP (2-year-OS 49.6% vs. 19.1%, p < 0.001) as well as after R-CHOP (2-year-OS 33.1% and 22.5%, p = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen.
Conclusion
MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy, however survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

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

The long- and short-term variability of breathing induced tumor motion in lung and liver over the course of a radiotherapy treatment

To evaluate the short and long-term variability of breathing induced tumor motion.

http://ift.tt/2y2brhs

The expression profile and clinicopathological significance of Notch1 in patients with colorectal cancer: a meta-analysis

Future Oncology, Ahead of Print.


http://ift.tt/2y6GP00

Cancer-directed therapy and potential impact on survivals in nonresected hepatocellular carcinoma: SEER-Medicare population study

Future Oncology, Ahead of Print.


http://ift.tt/2fYntnk

Central nervous system complications after allogeneic hematopoietic stem cell transplantation

Future Oncology, Ahead of Print.


http://ift.tt/2y7bzy4

Latest advances in adult gastrointestinal stromal tumors

Future Oncology, Ahead of Print.


http://ift.tt/2fXyHsb

Comprehensive characterization of differentially expressed genes in thyroid cancer

Future Oncology, Ahead of Print.


http://ift.tt/2y6GKJK

Sanger Institute series: uncovering the genetics of cancer: an interview with David Adams

Future Oncology, Ahead of Print.


http://ift.tt/2fYnoA2

PD-L1 in immune-escape of breast and prostate cancers: from biology to therapy

Future Oncology, Ahead of Print.


http://ift.tt/2y6GH0w

Prognostic impact of germline mutations in inherited cancer syndromes

Future Oncology, Ahead of Print.


http://ift.tt/2fZa9PI

The current status of adjuvant treatment for high-risk renal cell carcinoma

Future Oncology, Ahead of Print.


http://ift.tt/2y7budK

Subsequent malignant neoplasms in the survivor of childhood cancer: where we have been and where we are going?

Future Oncology, Ahead of Print.


http://ift.tt/2fZa9zc

Why should we perform a D2 lymphadenectomy in gastric cancer?

Future Oncology, Ahead of Print.


http://ift.tt/2y6GBGc

Advances in systemic therapy for malignant mesothelioma: future perspectives

Future Oncology, Ahead of Print.


http://ift.tt/2fXi3ZE

S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway

Future Oncology, Ahead of Print.


http://ift.tt/2y7bnPm

The expression profile and clinicopathological significance of Notch1 in patients with colorectal cancer: a meta-analysis

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2y6GP00
via IFTTT

Cancer-directed therapy and potential impact on survivals in nonresected hepatocellular carcinoma: SEER-Medicare population study

Future Oncology, Ahead of Print.


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

Central nervous system complications after allogeneic hematopoietic stem cell transplantation

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2y7bzy4
via IFTTT

Latest advances in adult gastrointestinal stromal tumors

Future Oncology, Ahead of Print.


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

Comprehensive characterization of differentially expressed genes in thyroid cancer

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2y6GKJK
via IFTTT

Sanger Institute series: uncovering the genetics of cancer: an interview with David Adams

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2fYnoA2
via IFTTT

PD-L1 in immune-escape of breast and prostate cancers: from biology to therapy

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2y6GH0w
via IFTTT

Prognostic impact of germline mutations in inherited cancer syndromes

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2fZa9PI
via IFTTT

The current status of adjuvant treatment for high-risk renal cell carcinoma

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2y7budK
via IFTTT

Subsequent malignant neoplasms in the survivor of childhood cancer: where we have been and where we are going?

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2fZa9zc
via IFTTT

Why should we perform a D2 lymphadenectomy in gastric cancer?

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2y6GBGc
via IFTTT

Advances in systemic therapy for malignant mesothelioma: future perspectives

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2fXi3ZE
via IFTTT

S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway

Future Oncology, Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2y7bnPm
via IFTTT

Self-rated health and associated factors in elderly patients with non-Hodgkin lymphoma

S18777821.gif

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Lívia Maria Santiago, Daniel Richard Mercante, Inês Echenique Mattos
BackgroundSelf-rated health is a useful indicator for understanding health issues in elderly populations and considered to be a predictor of adverse health outcomes in this group. This study aims to identify factors associated with self-rated health in elderly people with non-Hodgkin's lymphoma.MethodsCross-sectional study performed at a cancer referral hospital in Rio de Janeiro, Brazil, included 162 patients, aged 60 or more years. All patients received a Multidimensional Geriatric Assessment, including seven health dimensions, and socio-demographic, epidemiological and it were collected clinical data. Descriptive analyses were performed and prevalence ratios were calculated to assess associations between self-rated health and the independent variables. Multivariate analysis was performed using Poisson's regression, to a ≤0.05 level of statistical significance.ResultsThe study population mean age was 68.8 (SD=7.1) years; most were women, lived with a partner and had little education. Prevalence of fair/poor self-rated health was 33.6%. Being female, not living with a partner, functional dependence, depressive symptoms and nutritional risk/malnutrion showed associations with fair/poor self-rated health. In the multiple model, dependence in instrumental activities of daily living (PR 2.96; 95%CI 1.66-5.30) and presence of depressive symptoms (PR 1.78; 95%CI 1.15-2.75) remained associated with fair/poor health.ConclusionVariation in perceived health status supports the hypothesis that self-rated health is related to multiple issues, regardless of disease status. The risk profile for poor self-rated health identified may be a useful tool in care for older cancer patients, as it points to those at higher risk of adverse health outcomes.



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

Self-rated health and associated factors in elderly patients with non-Hodgkin lymphoma

S18777821.gif

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Lívia Maria Santiago, Daniel Richard Mercante, Inês Echenique Mattos
BackgroundSelf-rated health is a useful indicator for understanding health issues in elderly populations and considered to be a predictor of adverse health outcomes in this group. This study aims to identify factors associated with self-rated health in elderly people with non-Hodgkin's lymphoma.MethodsCross-sectional study performed at a cancer referral hospital in Rio de Janeiro, Brazil, included 162 patients, aged 60 or more years. All patients received a Multidimensional Geriatric Assessment, including seven health dimensions, and socio-demographic, epidemiological and it were collected clinical data. Descriptive analyses were performed and prevalence ratios were calculated to assess associations between self-rated health and the independent variables. Multivariate analysis was performed using Poisson's regression, to a ≤0.05 level of statistical significance.ResultsThe study population mean age was 68.8 (SD=7.1) years; most were women, lived with a partner and had little education. Prevalence of fair/poor self-rated health was 33.6%. Being female, not living with a partner, functional dependence, depressive symptoms and nutritional risk/malnutrion showed associations with fair/poor self-rated health. In the multiple model, dependence in instrumental activities of daily living (PR 2.96; 95%CI 1.66-5.30) and presence of depressive symptoms (PR 1.78; 95%CI 1.15-2.75) remained associated with fair/poor health.ConclusionVariation in perceived health status supports the hypothesis that self-rated health is related to multiple issues, regardless of disease status. The risk profile for poor self-rated health identified may be a useful tool in care for older cancer patients, as it points to those at higher risk of adverse health outcomes.



http://ift.tt/2fYWMif

Krüppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Abstract

Krüppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR, Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial-mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC. The relationship between KLF8 expression and various clinicopathological features or EMT markers was investigated. The results showed m-RNA and protein of KLF8 were overexpressed in NSCLC and the percent of KLF8 positive cells was positively correlated with TNM stage, lymph node metastasis and poor overall survive. Moreover, high expression of KLF8 correlated with E-cadherin low expression, and Vimentin overexpression. Additionally, COX multivariate regression analysis suggested that TNM stage, KLF8, E-cadherin and Vimentin were independent prognostic indicators for overall survival of patients with NSCLC. The data demonstrate that KLF8 is overexpressed in NSCLC. KLF8 overexpression promotes the malignancy of NSCLC, which mechanism may be involved in EMT. KLF8 maybe serve as a potential therapeutic target for NSCLC.



http://ift.tt/2yuR4fZ

Inhibition of p300/CBP Suppresses Castration-Resistant Prostate Cancer [Research Watch]

A virtual ligand screen led to generation of A-485, a potent selective p300/CBP catalytic inhibitor.



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

Chromosome 1q21.3 Amplification Is Linked to Breast Cancer Recurrence [Research Watch]

The 1q21.3 amplification can be detected in cfDNA from most patients with recurrent breast cancer.



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

PAK Signaling Promotes Acquired Resistance to BRAF and MEK Inhibitors [Research Watch]

PAK signaling drives resistance to BRAF inhibition and dual BRAF/MEK inhibition via distinct mechanisms.



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

METTL3 Increases m6A to Block Differentiation and Promote Leukemogenesis [Research Watch]

METTL3 is upregulated in acute myeloid leukemia compared with other tumors and normal HSPCs.



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

The Splicing Regulator PRMT5 Is Critical for Glioblastoma Proliferation [Research Watch]

PRMT5 regulates the splicing of detained introns in proliferation-associated genes in GBM.



from Cancer via ola Kala on Inoreader http://ift.tt/2hSSl9u
via IFTTT

Aggressive differentiated thyroid cancer

Publication date: Available online 6 October 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Noor Janjua, Volkert B. Wreesmann
Differentiated thyroid cancer is characteristically associated with an innocuous clinical course, but a minority may manifest surprisingly aggressive behaviour. The latter are not only directly responsible for the majority of thyroid cancer related deaths, but also contribute indirectly to increased DTC-related morbidity, because our inability to differentiate these tumours from innocuous DTC at an early stage contributes to a significant degree of overtreatment that is observed for DTC around the globe. In the present paper we describe how improved understanding of the clinicopathological thyroid tumour progression model and optimization of clinical staging systems continues to improve our ability to diagnose and treat aggressive DTC. Early recognition of aggressive DTC allows instillation of an aggressive management strategy which is based upon oncologic completeness, and minimization of treatment-related sequelae through continued development of reconstructive options and focussed delivery of adjuvant treatments.



http://ift.tt/2y799Qc

Stereotactic vacuum-assisted breast biopsy: comparison between 11- and 8-gauge needles

Publication date: Available online 6 October 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Irene Ruggirello, Jacopo Nori, Isacco Desideri, Calogero Saieva, Elisabetta Giannotti, Giulia Bicchierai, Diego De Benedetto, Giulio Francolini, Simonetta Bianchi, Vania Vezzosi, Luis Sanchez, Tommaso Susini, Lorenzo Orzalesi, Icro Meattini, Lorenzo Livi, Vittorio Miele
PurposeThe 11-gauge (11G) stereotactic vacuum-assisted breast biopsy (VABB) showed a better profile than 14G-VABB in terms of feasibility, safety, microcalcification sampling, and accuracy. Underestimation rates were significantly lower with 11G-VABB than with 14G-VABB. Thus, the introduction of an even larger needle at the VABB procedure could reduce this rate further. The purpose of this study was to compare the overall performance of stereotactic VABB with 8G and 11G needles.Materials and methodsFour hundred and three VABBs performed between July 2012 and February 2015 at the Breast Diagnostic Unit of Careggi Hospital in Florence were retrospectively analyzed; 197 were performed with 11G-VABB and 206 with 8G-VABB. Lesions were classified according to mammographical patterns in microcalcifications, architectural distortions, or opacities, and all biopsy targets were classified according to BIRADS classification as BIRADS III, IV or V. Data were collected on radiological classification of targets, imaging presentation, procedure time, number of specimens per procedure, and microcalcification retrieval on histological findings. Surgery was always performed when high-risk or malignant lesions (B3 or B5) were detected; the final diagnosis was made on surgical pathology.ResultsCompared to VABB with an 11G needle, 8G-VABB allows a reduction in the time needed to complete the procedure (20.6 versus 27.4, P < 0.00001) and the number of specimens collected per lesion (21.6 versus 12.2, P < 0.00001). Moreover, 8G-VABB resulted in the same diagnostic accuracy, and the underestimation rates were comparable between the two groups for both B3 and DCIS lesions.ConclusionsThe 8G needle should be considered as a valid alternative option in VABB for breast lesions.



http://ift.tt/2fZm9AN

Copper Chelation Inhibits BRAFV600E-driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors

MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacological reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended towards an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma.

from Cancer via ola Kala on Inoreader http://ift.tt/2y674nf
via IFTTT

Loss of FOXO1 cooperates with TMPRSS2-ERG overexpression to promote prostate tumorigenesis and cell invasion

E26 transformation-specific (ETS) transcription factor ERG is aberrantly overexpressed in approximately 50% of all human PCa due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of PCa-associated ERG alone fail to develop PCa, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human PCa. Here we demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of PCa-associated ERG independently of FOXO1 transcriptional activity. Knockdown of endogenous FOXO1 increased invasion of TMPRSS2-ERG fusion positive VCaP cells, an effect completely abolished by ERG knockdown. Patient specimen analysis demonstrated that FOXO1 and ERG protein expression inversely correlated in a subset of human PCa. Although human ERG transgene expression or homozygous deletion of Foxo1 alone in the mouse prostate failed to promote tumorigenesis, concomitant ERG transgene expression and Foxo1 deletion resulted in upregulation of ERG target genes, increased cell proliferation and formation of high-grade prostatic intraepithelial neoplasia (HGPIN). Overall, we provide biochemical and genetic evidence that aberrantly activated ERG cooperates with FOXO1 deficiency to promote prostate tumorigenesis and cell invasion. Our findings enhance understanding of PCa etiology and suggest that the FOXO1-ERG signaling axis can be a potential target for treatment of PCa.

from Cancer via ola Kala on Inoreader http://ift.tt/2z4X6Rh
via IFTTT

Chemotherapeutic dose scheduling based on tumor growth rates provide a case for low-dose metronomic high entropy therapies

We extended the classical tumor regression models such as Skipper's laws and the Norton-Simon hypothesis from instantaneous regression rates to the cumulative effect over repeated cycles of chemotherapy. To achieve this end, we used a stochastic Moran process model of tumor cell kinetics coupled with a prisoner's dilemma game-theoretic cell-cell interaction model to design chemotherapeutic strategies tailored to different tumor growth characteristics. Using the Shannon entropy as a novel tool to quantify the success of dosing strategies, we contrasted maximum tolerated dose (MTD) strategies as compared with low-dose, high-density metronomic strategies (LDM) for tumors with different growth rates. Our results show that LDM strategies outperformed MTD strategies in total tumor cell reduction (TCR). This advantage was magnified for fast growing tumors that thrive on long periods of unhindered growth without chemotherapy drugs present and was not evident after a single cycle of chemotherapy but grew after each subsequent cycle of repeated chemotherapy. The evolutionary growth/regression model introduced in this paper agrees well with murine models. Overall, this model supports the concept of designing different chemotherapeutic schedules for tumors with different growth rates and develops quantitative tools to optimize these schedules for maintaining low volume tumors.

from Cancer via ola Kala on Inoreader http://ift.tt/2y5ZMjk
via IFTTT

Astrocytes promote medulloblastoma progression through hedgehog secretion

Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. While astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secreted the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drove expression of Nestin in MB cells through a Smoothened-dependent, Gli1-independent mechanism. Ablation of TAA dramatically suppressed Nestin expression and blocked tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression.

from Cancer via ola Kala on Inoreader http://ift.tt/2z3H7CV
via IFTTT

Copper Chelation Inhibits BRAFV600E-driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors

MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacological reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended towards an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma.

http://ift.tt/2y674nf

Loss of FOXO1 cooperates with TMPRSS2-ERG overexpression to promote prostate tumorigenesis and cell invasion

E26 transformation-specific (ETS) transcription factor ERG is aberrantly overexpressed in approximately 50% of all human PCa due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of PCa-associated ERG alone fail to develop PCa, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human PCa. Here we demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of PCa-associated ERG independently of FOXO1 transcriptional activity. Knockdown of endogenous FOXO1 increased invasion of TMPRSS2-ERG fusion positive VCaP cells, an effect completely abolished by ERG knockdown. Patient specimen analysis demonstrated that FOXO1 and ERG protein expression inversely correlated in a subset of human PCa. Although human ERG transgene expression or homozygous deletion of Foxo1 alone in the mouse prostate failed to promote tumorigenesis, concomitant ERG transgene expression and Foxo1 deletion resulted in upregulation of ERG target genes, increased cell proliferation and formation of high-grade prostatic intraepithelial neoplasia (HGPIN). Overall, we provide biochemical and genetic evidence that aberrantly activated ERG cooperates with FOXO1 deficiency to promote prostate tumorigenesis and cell invasion. Our findings enhance understanding of PCa etiology and suggest that the FOXO1-ERG signaling axis can be a potential target for treatment of PCa.

http://ift.tt/2z4X6Rh

Chemotherapeutic dose scheduling based on tumor growth rates provide a case for low-dose metronomic high entropy therapies

We extended the classical tumor regression models such as Skipper's laws and the Norton-Simon hypothesis from instantaneous regression rates to the cumulative effect over repeated cycles of chemotherapy. To achieve this end, we used a stochastic Moran process model of tumor cell kinetics coupled with a prisoner's dilemma game-theoretic cell-cell interaction model to design chemotherapeutic strategies tailored to different tumor growth characteristics. Using the Shannon entropy as a novel tool to quantify the success of dosing strategies, we contrasted maximum tolerated dose (MTD) strategies as compared with low-dose, high-density metronomic strategies (LDM) for tumors with different growth rates. Our results show that LDM strategies outperformed MTD strategies in total tumor cell reduction (TCR). This advantage was magnified for fast growing tumors that thrive on long periods of unhindered growth without chemotherapy drugs present and was not evident after a single cycle of chemotherapy but grew after each subsequent cycle of repeated chemotherapy. The evolutionary growth/regression model introduced in this paper agrees well with murine models. Overall, this model supports the concept of designing different chemotherapeutic schedules for tumors with different growth rates and develops quantitative tools to optimize these schedules for maintaining low volume tumors.

http://ift.tt/2y5ZMjk

Astrocytes promote medulloblastoma progression through hedgehog secretion

Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. While astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secreted the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drove expression of Nestin in MB cells through a Smoothened-dependent, Gli1-independent mechanism. Ablation of TAA dramatically suppressed Nestin expression and blocked tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression.

http://ift.tt/2z3H7CV

A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non–small cell lung cancer

S09598049.gif

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Jean-Charles Soria, Alex A. Adjei, Rastilav Bahleda, Benjamin Besse, Charles Ferte, David Planchard, Jing Zhou, Joseph Ware, Kari Morrissey, Geetha Shankar, Wei Lin, Jennifer L. Schutzman, Grace K. Dy, Harry J.M. Groen
AimThe phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non–small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC.Patients and methodsA 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1–14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination.ResultsAll 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients.ConclusionCombining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed.



from Cancer via ola Kala on Inoreader http://ift.tt/2yvpH5l
via IFTTT

Diarrhoea during checkpoint blockade, not always colitis

alertIcon.gif

Publication date: Available online 6 October 2017
Source:European Journal of Cancer
Author(s): Josephine J. Koldenhof, Karijn P.M. Suijkerbuijk




from Cancer via ola Kala on Inoreader http://ift.tt/2xo8NRd
via IFTTT

Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer

S09598049.gif

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Vincenzo Dadduzio, Lisa Salvatore, Beatrice Borelli, Filippo Pietrantonio, Yan Ning, Satoshi Okazaki, Martin D. Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Toshiharu Yamaguchi, Fotios Loupakis, Heinz-Josef Lenz
BackgroundTrifluridine (FTD) is an active cytotoxic component of the metastatic colorectal cancer (mCRC) drug TAS-102, and thymidine phosphorylase inhibitor (TPI) inhibits the rapid degradation of FTD. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in FTD metabolism and TPI excretion could predict outcome in patients with mCRC treated with TAS-102.Patients and methodsWe investigated three different cohorts: a training cohort (n = 52) and a testing cohort (n = 129) both receiving TAS-102 and a control cohort (n = 52) receiving regorafenib. SNPs of TK1, ENT1, CNT1, MATE1, MATE2 and OCT2 were analysed by polymerase chain reaction-based direct DNA sequencing.ResultsIn the training cohort, patients with any ENT1 rs760370 G allele had a significantly longer progression-free survival (PFS; 3.5 versus 2.1 months, respectively, hazard ratio [HR] 0.44, P = 0.004) and overall survival (OS; 8.7 versus 5.3 months, respectively, HR 0.27, P = 0.003) than the A/A genotype. These findings were validated in the testing cohort (P = 0.021 and 0.009 for PFS and OS, respectively). In addition, the combination of ENT1 rs760370, MATE1 rs2289669 and OCT2 rs316019 SNPs significantly stratified patients with the risk of PFS and OS in both cohorts (P < 0.001 for PFS and OS in the training cohort; P = 0.053 and 0.025 for PFS and OS, respectively, in the testing cohort). No significant differences were observed in the control group.ConclusionsThe combination of ENT1, MATE1 and OCT2 SNPs may serve as a predictive and prognostic marker in mCRC patients treated with TAS-102.



from Cancer via ola Kala on Inoreader http://ift.tt/2yvpv67
via IFTTT

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology

S09598049.gif

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): R.E. Kibbelaar, B.E. Oortgiesen, A.M. van der Wal-Oost, K. Boslooper, J.W. Coebergh, N.J.G.M. Veeger, P. Joosten, H. Storm, E.N. van Roon, M. Hoogendoorn
Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials.



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

Krüppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Abstract

Krüppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR, Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial-mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC. The relationship between KLF8 expression and various clinicopathological features or EMT markers was investigated. The results showed m-RNA and protein of KLF8 were overexpressed in NSCLC and the percent of KLF8 positive cells was positively correlated with TNM stage, lymph node metastasis and poor overall survive. Moreover, high expression of KLF8 correlated with E-cadherin low expression, and Vimentin overexpression. Additionally, COX multivariate regression analysis suggested that TNM stage, KLF8, E-cadherin and Vimentin were independent prognostic indicators for overall survival of patients with NSCLC. The data demonstrate that KLF8 is overexpressed in NSCLC. KLF8 overexpression promotes the malignancy of NSCLC, which mechanism may be involved in EMT. KLF8 maybe serve as a potential therapeutic target for NSCLC.



http://ift.tt/2yuR4fZ

Correction to: Breast cancer metastases to the thyroid gland - An uncommon sentinel for diffuse metastatic disease: A case report and literature review



http://ift.tt/2xmjCb7

Cardiac cycle efficiency and dicrotic pressure variations: new parameters for fluid therapy: An observational study

imageBACKGROUND: During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank–Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered. OBJECTIVE: To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP − Pdic and MAP − Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere. DESIGN: Observational study. SETTING: Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals. PATIENTS: Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed. INTERVENTIONS: A fluid challenge consisting of 500 ml of crystalloid infused over 10 min. MAIN OUTCOME MEASURES AND ANALYSIS: The changes in CCE, arterial elastance, SAP − Pdic and MAP − Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables. RESULTS: At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, ΔCCE and ΔSAP − Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion. CONCLUSION: In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg−1, a dynamic model of fluid challenge assessment, including PPV, ΔCCE and ΔSAP − Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration. TRIAL REGISTRATION: ACTRN12616001479493.

http://ift.tt/2y1D9KW

Continuous non-invasive haemodynamic monitoring: a beneficial impact on patient outcome is needed to gain ‘confidence in the technology’

imageNo abstract available

http://ift.tt/2y02Onf

Reply to: comparing C-MAC videolaryngoscope with direct laryngoscopy for emergency intubation

No abstract available

http://ift.tt/2ywreYY

The impact of continuous non-invasive arterial blood pressure monitoring on blood pressure stability during general anaesthesia in orthopaedic patients: A randomised trial

imageBACKGROUND: In patients undergoing general anaesthesia, intraoperative hypotension occurs frequently and is associated with adverse outcomes such as postoperative acute kidney failure, myocardial infarction or stroke. A history of chronic hypertension renders patients more susceptible to a decrease in blood pressure (BP) after induction of general anaesthesia. As a patient's BP is generally monitored intermittently via an upper arm cuff, there may be a delay in the detection of hypotension by the anaesthetist. OBJECTIVE: The current study investigates whether the presence of continuous BP monitoring leads to improved BP stability. DESIGN: Randomised, controlled and single-centre study. PATIENTS: A total of 160 orthopaedic patients undergoing general anaesthesia with a history of chronic hypertension. INTERVENTION: The patients were randomised to either a study group (n = 77) that received continuous non-invasive BP monitoring in addition to oscillometric intermittent monitoring, or a control group (n = 83) whose BP was monitored intermittently only. The interval for oscillometric measurements in both groups was set to 3 min. After induction of general anaesthesia, oscillometric BP values of the two groups were compared for the first hour of the procedure. Anaesthetists were blinded to the purpose of the study. MAIN OUTCOME MEASURE: BP stability and hypotensive events. RESULTS: There was no difference in baseline BP between the groups. After adjustment for multiple testing, mean arterial BP in the study group was significantly higher than in the control group at 12 and 15 min. Mean ± SD for study and control group, respectively were: 12 min, 102 ± 24 vs. 90 ± 26 mmHg (P = 0.039) and 15 min, 102 ± 21 vs. 90 ± 23 mmHg (P = 0.023). Hypotensive readings below a mean pressure of 55 mmHg occurred more often in the control group (25 vs. 7, P = 0.047). CONCLUSION: Continuous monitoring contributes to BP stability in the studied population. TRIAL REGISTRATION: NCT02519101.

http://ift.tt/2yv6TDh

Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial

imageBACKGROUND: Postoperative cognitive decline (POCD), a very common complication after cardiac surgery, is characterised by impairment of both memory function and intellectual ability as well as being associated with increased use of healthcare resources. The investigators focused on the role of the inflammatory response to a surgical procedure as a potential factor involved in the pathogenesis of POCD. OBJECTIVE: The use of prophylactic dexamethasone to attenuate the inflammatory response was hypothesised to reduce the risk of POCD. DESIGN: Randomised controlled study. SETTING: Single university teaching hospital, from March 2015 to January 2016. PATIENTS: A total of 169 patients scheduled for elective cardiac surgery were enrolled, and 161 patients were included in the analyses. INTERVENTION: Patients were randomised to receive a single intravenous bolus of 0.1 mg kg−1 dexamethasone (n = 85) or placebo (n = 84) 10 h before the surgery. MAIN OUTCOME MEASURES: The primary outcome measure in both groups was the incidence of POCD on the 6th day after surgery. The investigators also evaluated the effect of dexamethasone on the incidence of systemic inflammatory response syndrome, postoperative C-reactive protein levels and postoperative serum S100β protein levels. RESULTS: Compared to the placebo group, the dexamethasone group showed statistically significant reductions in the incidence of POCD (relative risk, 0.43; 95% confidence interval, 0.21 to 0.89; P = 0.02), the incidence of systemic inflammatory response syndrome (30.0 versus 58.0%, P 

http://ift.tt/2yv6Pn1

Validation of radial artery-based uncalibrated pulse contour method (PulsioFlex) in critically ill patients: A observational study

imageBACKGROUND: Because of their simplicity, uncalibrated pulse contour (UPC) methods have been introduced into clinical practice in critical care but are often validated with a femoral arterial waveform. OBJECTIVE: We aimed to test the accuracy of cardiac index (CI) measurements and trending ability from a radial artery with one UPC. DESIGN: An observational study. SETTING: Tertiary care mixed-surgical ICU. Data were obtained from April 2015 to July 2016. PATIENTS: We studied 20 critically ill mechanically ventilated patients monitored by UPC (PulsioFlex; Pulsion Medical Systems SE, Feldkirchen, Germany). We used transpulmonary thermodilution (PiCCO2) as a reference. MAIN OUTCOME MEASURES: Bland–Altman-analyses with percentage errors were calculated to assess the accuracy of CI values from radial pulse contour analysis (CIRAD), autocalibration (CIAC) and femoral pulse contour analysis (CIFEM). All were compared with a reference (CITD) at 4-h intervals for 24 h. Trending ability was assessed by polar-plots and four-quadrant-plots. CI is given in l min−1 m−2. RESULTS: Bland–Altman-analyses: for CIRAD, the mean bias was −0.1 with limits of agreement (LOA) of −2.9 to 2.7 and a percentage error of 70%; for CIAC, the mean bias was 0 with LOA −2.8 to 2.7 and a percentage error of 70%; for CIFEM, the mean bias was 0 with LOA −1.2 to 1.2 and a percentage error of 30%, respectively. Polar plots for trending: for CIRAD, the angular bias was 12° with radial LOA of 39°, a polar concordance rate of 73% and a concordance rate of 67% in the four-quadrant-plot; for CIAC, the angular bias was 4° with radial LOA of 41°, polar concordance rate of 79% and a concordance rate of 74% in the four quadrant plot; for CIFEM, the angular bias was −2° with radial LOA of 50°, polar concordance rate of 74% and a concordance rate of 81%. CONCLUSION: In critically ill patients, the PulsioFlex system connected to a radial arterial catheter is inaccurate for CI measurements and does not track changes in CI adequately. We therefore recommend using validated thermodilution techniques for monitoring in the critical care setting.

http://ift.tt/2yvNlyH

Re-evaluation of peri-operative cardiac risk (the MET REPAIR study): Study protocol of a prospective, multicentre cohort study sponsored by the European Society of Anaesthesiology

No abstract available

http://ift.tt/2y1Giun

The relative effects of dexmedetomidine and propofol on cerebral blood flow velocity and regional brain oxygenation: A randomised noninferiority trial

imageBACKGROUND: Dexmedetomidine constricts cerebral blood vessels without a concomitant reduction in cerebral metabolic oxygen consumption. Its safety as a sedative in patients with neurological diseases thus remains uncertain. OBJECTIVE: Our primary objective was to test the hypothesis that dexmedetomidine is noninferior to propofol as regards cerebral blood flow (CBF) velocity and brain oxygenation. DESIGN: Unblinded randomised trial. SETTING: Cleveland Clinic Hospital, Cleveland, from November 2010 to July 2013. PATIENTS: Forty-four patients scheduled for insertion of a deep-brain stimulating electrodes. INTERVENTIONS: Patients were randomised to receive either dexmedetomidine or propofol sedation during deep-brain stimulating electrode insertion. MAIN OUTCOME MEASURES: Intraoperative CBF velocity was measured with transcranial Doppler, and brain oxygenation was assessed with near-infrared spectroscopy. Noninferiority of dexmedetomidine to propofol was defined as a less than 20% difference in means. RESULTS: Twenty-three patients were given dexmedetomidine and 21 propofol. Baseline characteristics and operative management were similar in each group. Dexmedetomidine was noninferior to propofol on both CBF and brain oxygenation, confirming our primary hypothesis. For cerebral flood flow, the estimated ratio of means (dexmedetomidine/propofol) was 0.94 [90% CI: 0.84 to 1.05], P = 0.011 for noninferiority. For brain oxygenation, the estimated ratio of means was 0.99 [90% CI: 0.96 to 1.02], P 

http://ift.tt/2xZP24i

Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study

imageBACKGROUND: Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics. OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes. DESIGN: Laboratory rat study. SETTING: Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016. PATIENTS: A total of 32 adult male Wistar rats. INTERVENTIONS: After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg−1 h−1) or sevoflurane (2 vol%) continuously for 12 h. MAIN OUTCOME MEASURES: Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined. RESULTS: Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P 

http://ift.tt/2y0DwFK

Evaluation of preoperative oral carbohydrate administration on insulin resistance in off-pump coronary artery bypass patients: A randomised trial

imageBACKGROUND: In fasting cardiac surgery patients, preoperative carbohydrate (CHO) drink intake attenuated insulin resistance and improved cardiac metabolism, although its beneficial effects were not evident after cardiac surgery possibly due to cardiopulmonary bypass-related extreme systemic inflammation. OBJECTIVE: We aimed to evaluate whether preoperative CHO intake affected insulin resistance and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation. DESIGN: A randomised controlled trial. SETTING: Primary care in a university hospital in Korea from January 2015 to July 2016. PATIENTS: Sixty patients who underwent elective multi-vessel off-pump coronary revascularisation were randomised into two groups. Three patients were excluded from analysis and 57 patients completed study. INTERVENTION: The CHO group received oral CHO (400 ml) the prior evening and 2 to 3 h before surgery, and the control group was fasted from food and water according to standard protocol. MAIN OUTCOME MEASURES: Insulin resistance was assessed twice, after anaesthetic induction and after surgery via short insulin tolerance test. FFA, C-reactive protein and creatine kinase-myocardial band concentrations were determined serially for 48 h after surgery. RESULTS: Insulin sensitivity was greater (P = 0.002) and plasma FFA concentrations were lower (P = 0.001) after anaesthetic induction in the CHO group compared with the Control group, although there were no intergroup differences after surgery. The postoperative peak creatine kinase-myocardial band concentration was significantly lower in the CHO group compared with the Control group [8.8 (5.4 to 18.2) vs. 6.4 (3.5 to 9.7) ng ml−1, P = 0.031]. CONCLUSION: A preoperative CHO supplement significantly reduced insulin resistance and FFA concentrations compared with fasting at the beginning of the surgery, but these benefits were lost after off-pump coronary revascularisation. Despite their transient nature, these beneficial effects resulted in less myocardial injury, mandating further studies focused on the impact of preoperative CHO on myocardial ischaemia and cardiac function after coronary revascularisation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT 02330263.

http://ift.tt/2y1165p

Comparing C-MAC videolaryngoscope with direct laryngoscopy for emergency intubation

No abstract available

http://ift.tt/2yuaQIc

Echocardiography and passive leg raising in the postoperative period: A prospective observational study

imageBACKGROUND: Signs of hypovolaemia are frequent in the postoperative period, but not all patients need or respond to fluid administration. An increase in cardiac output (CO) after passive leg raising (PLR) has been demonstrated to be useful as a volume response predictor in non-surgical, spontaneously breathing patients. OBJECTIVE: The objective of this study was to evaluate the accuracy of transthoracic echocardiography after PLR to predict fluid responsiveness in post-surgical patients. DESIGN: A prospective observational study. SETTING: A tertiary hospital between January and July 2015. PATIENTS: Fifty-one spontaneously breathing postoperative patients with suspected hypovolaemia (arterial hypotension, oliguria, tachycardia or delayed capillary refill) were considered for the study. INTERVENTION: Demographic and personal data were collected, as well as heart rate variations, mean arterial pressure during PLR and after administering 500 ml of Ringer's lactate solution. CO was measured by transthoracic echocardiography. MAIN OUTCOME MEASURES: The primary outcome was measurement of CO before and after PLR and Ringer's lactate administration. RESULTS: Forty-one patients were included in the study (six patients were excluded because of a poor echocardiographic window and four because of misalignment of the Doppler and outflow tract of the left ventricle). Twenty-two patients (54%) were considered responders to fluid therapy, with an increase of stroke volume greater than or equal to 15% after 500 ml lactated Ringer's infusion. The highest area under the curve was found for an increase in CO (0.91 ± 0.05; 95% confidence interval 0.78 to 0.97). An increase in CO greater than 11% after the PLR manoeuvre predicts a volume response with 68% sensitivity and 100% specificity. CONCLUSION: This is the first study showing that measurement of CO after PLR can predict volume response in spontaneously breathing postoperative patients.

http://ift.tt/2yuWyHg

Oh Excellent Air Bag - Under the influence of Nitrous Oxide, 1799–1920

No abstract available

http://ift.tt/2xZOXxw

The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy

Abstract

Background

The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy.

Methods

This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien–Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival.

Results

Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029).

Conclusion

In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.



http://ift.tt/2hRxAe7

Total Mesenteric Peritonectomy for Peritoneal Metastases (with video)

ABSTRACT

Background

Complete cytoreductive surgery (CRS), combining organ resection and peritonectomy, is the only potentially curative treatment for patients with peritoneal metastases (PM).1 ,2 Diffuse mesenteric PM usually represents a contraindication for CRS.3 This report presents a standardized total mesenteric peritonectomy, which provides a therapeutic option of complete CRS for patients with diffuse mesenteric PM.

Patient

A 73-year-old man had a diagnosis of PM caused by an urachal adenocarcinoma (signet cell type). Initial assessment found a 60-mm urachal tumor above the dome of the urinary bladder. Dedicated magnetic resonance imaging (MRI)4 and explorative laparoscopy confirmed the presence of diffuse mucinous PM suspected of pseudomyxoma peritonei arising from urachus. The patient was treated by a systemic induction chemotherapy including cisplatin, fluorouracil, and docetaxel, with an almost full regression of the PM shown on control MRI. The man then was treated with CRS and hyperthermic intraperitoneal chemotherapy.5

Technique

Exploration found persistent diffuse macro-nodular PM with a good response to chemotherapy, a 16/39 peritoneal cancer index,6 and no digestive tract or other organ involvement. The CRS procedure included complete urachus resection, together with appendicectomy, cholecystectomy, omentectomy, and a total parietal and mesenteric peritonectomy, with a completeness of cytoreduction score6 of 1, as illustrated in the video. At this writing, after 6 months of follow-up evaluation, the patient remains free of symptomatic peritoneal disease or local recurrence.

Conclusion

Total mesenteric peritonectomy can be safely performed with the reported technique irrespective of how widespread PM is along the mesentery as long as few small bowel serous membranes are involved.



http://ift.tt/2fQGVyR

The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy

Abstract

Background

The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy.

Methods

This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien–Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival.

Results

Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029).

Conclusion

In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.



from Cancer via ola Kala on Inoreader http://ift.tt/2hRxAe7
via IFTTT

Total Mesenteric Peritonectomy for Peritoneal Metastases (with video)

ABSTRACT

Background

Complete cytoreductive surgery (CRS), combining organ resection and peritonectomy, is the only potentially curative treatment for patients with peritoneal metastases (PM).1 ,2 Diffuse mesenteric PM usually represents a contraindication for CRS.3 This report presents a standardized total mesenteric peritonectomy, which provides a therapeutic option of complete CRS for patients with diffuse mesenteric PM.

Patient

A 73-year-old man had a diagnosis of PM caused by an urachal adenocarcinoma (signet cell type). Initial assessment found a 60-mm urachal tumor above the dome of the urinary bladder. Dedicated magnetic resonance imaging (MRI)4 and explorative laparoscopy confirmed the presence of diffuse mucinous PM suspected of pseudomyxoma peritonei arising from urachus. The patient was treated by a systemic induction chemotherapy including cisplatin, fluorouracil, and docetaxel, with an almost full regression of the PM shown on control MRI. The man then was treated with CRS and hyperthermic intraperitoneal chemotherapy.5

Technique

Exploration found persistent diffuse macro-nodular PM with a good response to chemotherapy, a 16/39 peritoneal cancer index,6 and no digestive tract or other organ involvement. The CRS procedure included complete urachus resection, together with appendicectomy, cholecystectomy, omentectomy, and a total parietal and mesenteric peritonectomy, with a completeness of cytoreduction score6 of 1, as illustrated in the video. At this writing, after 6 months of follow-up evaluation, the patient remains free of symptomatic peritoneal disease or local recurrence.

Conclusion

Total mesenteric peritonectomy can be safely performed with the reported technique irrespective of how widespread PM is along the mesentery as long as few small bowel serous membranes are involved.



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

Uncertainties remain in the status of internal mammary lymph nodes in breast cancers located in lower inner zone



http://ift.tt/2ghRR9i

Timeline metastatic progression: in the wake of the « seed and soil » theory

Abstract

Little is known about the natural history of cancer and its evolution to metastasis. Paget was the first to postulate the important role played by microenvironment in metastasis progression. Since, the concept of his "seed and soil" theory has been supported and confirmed. Understanding the chronology and natural course that underlie metastasis is mandatory to deepen this concept and to progress in the development of novel therapeutic strategies. A total of 413 patients who underwent treatment for brain metastasis (2013–2016) were included. The identification of previous and newly diagnosed metastasis was made during the clinical and imaging follow-up. We identified 910 metastases in our series. The 2-, 5-, and 10-year survival estimates were 80% (SD 2), 59.1% (3), and 36% (4), respectively. The median time for first metastasis, referred as metastasis-free survival (MFS) was 15.2 months (SD 1.47). MFS were determined for each metastasis location and were as follows: 7.2 months (SD 8.0) for bone, adrenal 8.4 months (SD 9.4) for adrenal, 13.2 months (SD 1.7) for brain, 14.6 months (SD 5.4) for liver, 25.7 months (SD 11.7) for pleura, 27.7 months (SD 15.9) for peritoneum, 29.8 months (SD 7.2) for spine, 30.2 months (SD 5.2) for lungs, and 54.2 months (SD 12.4) for skin (p < 0.009 log rank). We identified a metastatic timeline process for breast cancer (p < 0.0001 log rank (Mantel–Cox)) and furthermore according to breast subtype cancer (p < 0.0001). We suggest that in addition to Paget's theory, a timeline and a natural history of metastasis exist in patients with cancer. We suppose that some, but not all, primary cancers follow chronological and scheduled metastatic processes to invade organs.



http://ift.tt/2yuC6pU

Timeline metastatic progression: in the wake of the « seed and soil » theory

Abstract

Little is known about the natural history of cancer and its evolution to metastasis. Paget was the first to postulate the important role played by microenvironment in metastasis progression. Since, the concept of his "seed and soil" theory has been supported and confirmed. Understanding the chronology and natural course that underlie metastasis is mandatory to deepen this concept and to progress in the development of novel therapeutic strategies. A total of 413 patients who underwent treatment for brain metastasis (2013–2016) were included. The identification of previous and newly diagnosed metastasis was made during the clinical and imaging follow-up. We identified 910 metastases in our series. The 2-, 5-, and 10-year survival estimates were 80% (SD 2), 59.1% (3), and 36% (4), respectively. The median time for first metastasis, referred as metastasis-free survival (MFS) was 15.2 months (SD 1.47). MFS were determined for each metastasis location and were as follows: 7.2 months (SD 8.0) for bone, adrenal 8.4 months (SD 9.4) for adrenal, 13.2 months (SD 1.7) for brain, 14.6 months (SD 5.4) for liver, 25.7 months (SD 11.7) for pleura, 27.7 months (SD 15.9) for peritoneum, 29.8 months (SD 7.2) for spine, 30.2 months (SD 5.2) for lungs, and 54.2 months (SD 12.4) for skin (p < 0.009 log rank). We identified a metastatic timeline process for breast cancer (p < 0.0001 log rank (Mantel–Cox)) and furthermore according to breast subtype cancer (p < 0.0001). We suggest that in addition to Paget's theory, a timeline and a natural history of metastasis exist in patients with cancer. We suppose that some, but not all, primary cancers follow chronological and scheduled metastatic processes to invade organs.



from Cancer via ola Kala on Inoreader http://ift.tt/2yuC6pU
via IFTTT

Androgen Receptor in Estrogen Receptor Positive Breast Cancer: beyond expression

alertIcon.gif

Publication date: Available online 6 October 2017
Source:Cancer Treatment Reviews
Author(s): Debora Basile, Marika Cinausero, Donatella Iacono, Giacomo Pelizzari, Marta Bonotto, Maria Grazia Vitale, Lorenzo Gerratana, Fabio Puglisi
In recent years, new therapeutic approaches have reshaped the overall strategy of breast cancer (BC) treatment and have markedly improved patient survival. This is, in part, due to novel therapies for estrogen receptor (ER)-positive BC. Unfortunately, many patients present de novo resistance to these therapies or develop an acquired resistance over time. Therefore, research is now focused on discovering new molecular targets to overcome these resistances. Interestingly, preclinical and clinical studies have shown a critical role for the cross-talk between androgen receptor (AR) and ER in luminal-like BC. AR is expressed in > 60% of BC and in up to 90% of ERα-positive tumors. Multiple studies suggest that AR is associated with a favorable prognosis. However, AR overexpression and, in particular, the high AR:ER ratio, seem to be involved in resistance to hormonal treatment. In this setting, a group of BCs could benefit from AR-inhibitors; nevertheless, some ER-positive BC patients do not seem to benefit from this strategy. Therefore, it is crucial to identify biomarkers that would enable the selection of patients who might benefit from combination treatment with ER and AR inhibitors.



http://ift.tt/2y4jziS

Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-β-hydroxylase expression

Summary

Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance. In the clinical setting, ASPH expression was negatively correlated with recurrence-free survival of luminal B breast cancer patients that received adjuvant endocrine therapy, but not in patients that did not receive adjuvant endocrine therapy. Luminal B breast cancer is one of the intrinsic molecular subtypes identified by the Prediction Analysis of Microarray 50 (PAM50) multiple gene classifier, and because of its poor response to endocrine therapy, chemotherapy in addition to endocrine therapy is generally required after surgical resection. Our results suggest that the endocrine sensitivity of luminal B breast cancer can be assessed by examining ASPH expression, which promotes the consideration of a prospective study on the association between ASPH expression at the mRNA and protein levels in luminal B breast cancer and subsequent response to endocrine therapy.

This article is protected by copyright. All rights reserved.



http://ift.tt/2xYWxsf

Esophageal adenocarcinoma microenvironment: peritumoral adipose tissue effects associated with chemoresistance

Abstract

Peritumoral microenvironment affects cancer development and chemoresistance, and visceral adipose tissue may play a critical role. We aimed to identify depot-specific adipose characteristics associated with carcinogenesis and resistance to neoadjuvant therapy, in esophageal adenocarcinoma (EAC). We analysed: 1) the peritumoral adipose tissue of rats, following the induction of esophageal carcinogenesis; 2) the peritumoral and distal (omental) adipose tissue of patients affected by EAC; 3) adipose-derived stem cells (ADSCs) isolated from healthy patients and treated with conditioned medium (CM), collected from tumoral and adipose tissue of patients with EAC. In peritumoral adipose tissue of rats, CD34, CD31 and VEGF expression increased progressively during EAC development. In patients with EAC, the expression of CD34, CD45, CD90 and Nucleostemin (NSTM) was higher in peritumoral than distal adipose tissue and decreased in the presence of neoadjuvant therapy. Moreover, the expression of NSTM, OCT-4 and VEGF was higher in peritumoral (but not distal) adipose tissue of chemoresistant patients. In ADSCs, the treatment with peritumoral adipose tissue CM increased the adipogenic potential and the expression of CD34, CD90, NSTM and OCT-4. These effects were similar to those induced by cancer-derived CM, but were not observed in ADSCs treated with distal adipose tissue CM and were partially reduced by a leptin antagonist. Lastly, ADSCs treated with peritumoral CM of chemoresistant patients, displayed increased expression of NSTM, OCT-4, leptin, leptin receptor, α-SMA, CD34 and VEGF. These results suggest that the peritumoral adipose tissue may promote, via paracrine signalling, the expression of depot-specific factors associated with therapeutic resistance.

This article is protected by copyright. All rights reserved.



http://ift.tt/2y4QYdw

A double-edged sword: the world according to Capicua in cancer

Abstract

CIC/Capicua is a HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes such as PEA3 family genes. The RTK/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity, and CIC thus acts as an important downstream molecule of the pathway and as a tumor suppressor. CIC loss-of-function mutations are frequently observed in several human neoplasms such as oligodendroglioma, and lung and gastric carcinoma. CIC is also involved in chromosomal translocation-associated gene fusions in highly aggressive small round cell sarcoma that is biologically and clinically distinct from Ewing sarcoma. In these mutations, PEA3 family genes and other important target genes are upregulated, inducing malignant phenotypes. Downregulation of CIC abrogates the effect of MAPK inhibitors, suggesting its potential role as an important modifier of molecular target therapies for cancer. These data reveal the importance of CIC as a key molecule in signal transduction, carcinogenesis and developing novel therapies.

This article is protected by copyright. All rights reserved.



http://ift.tt/2y0TBLP

The expression level of CXCL7 in peripheral blood cells is a potential biomarker for the diagnosis of renal cell carcinoma

Summary

There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly up-regulated in the peripheral blood cells of RCC patients. Importantly, aberrant CXCL7 expression was confirmed even in peripheral blood cells obtained from early stage (pT1a) RCC patients, and the expression level of CXCL7 in peripheral blood cells was a potential independent biomarker for the diagnosis of RCC by Receiver Operating Characteristic curve analysis (sensitivity of 70.0% and specificity of 64.0%, AUC = 0.722, a multiple logistic regression analysis, OR, 1.07; 95% CI, 1.03–1.11; P = 0.0004). Moreover, CXCL7 expression in peripheral blood cells significantly decreased after resection of the primary tumor. CXCL7 is more highly expressed in peripheral blood mononuclear cells than in neutrophils from both healthy controls and RCC patients. Interestingly, CXCL7 expression in peripheral blood mononuclear cells from healthy volunteers was significantly elevated following co-culture with RCC cells compared to those co-cultured with normal cells as a control. These results suggest that aberrant CXCL7 expression in peripheral blood cells is induced by RCC cells and may serve as a novel biomarker in the diagnosis of RCC.

This article is protected by copyright. All rights reserved.



http://ift.tt/2y4WqNz

Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-β-hydroxylase expression

Summary

Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance. In the clinical setting, ASPH expression was negatively correlated with recurrence-free survival of luminal B breast cancer patients that received adjuvant endocrine therapy, but not in patients that did not receive adjuvant endocrine therapy. Luminal B breast cancer is one of the intrinsic molecular subtypes identified by the Prediction Analysis of Microarray 50 (PAM50) multiple gene classifier, and because of its poor response to endocrine therapy, chemotherapy in addition to endocrine therapy is generally required after surgical resection. Our results suggest that the endocrine sensitivity of luminal B breast cancer can be assessed by examining ASPH expression, which promotes the consideration of a prospective study on the association between ASPH expression at the mRNA and protein levels in luminal B breast cancer and subsequent response to endocrine therapy.

This article is protected by copyright. All rights reserved.



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

Esophageal adenocarcinoma microenvironment: peritumoral adipose tissue effects associated with chemoresistance

Abstract

Peritumoral microenvironment affects cancer development and chemoresistance, and visceral adipose tissue may play a critical role. We aimed to identify depot-specific adipose characteristics associated with carcinogenesis and resistance to neoadjuvant therapy, in esophageal adenocarcinoma (EAC). We analysed: 1) the peritumoral adipose tissue of rats, following the induction of esophageal carcinogenesis; 2) the peritumoral and distal (omental) adipose tissue of patients affected by EAC; 3) adipose-derived stem cells (ADSCs) isolated from healthy patients and treated with conditioned medium (CM), collected from tumoral and adipose tissue of patients with EAC. In peritumoral adipose tissue of rats, CD34, CD31 and VEGF expression increased progressively during EAC development. In patients with EAC, the expression of CD34, CD45, CD90 and Nucleostemin (NSTM) was higher in peritumoral than distal adipose tissue and decreased in the presence of neoadjuvant therapy. Moreover, the expression of NSTM, OCT-4 and VEGF was higher in peritumoral (but not distal) adipose tissue of chemoresistant patients. In ADSCs, the treatment with peritumoral adipose tissue CM increased the adipogenic potential and the expression of CD34, CD90, NSTM and OCT-4. These effects were similar to those induced by cancer-derived CM, but were not observed in ADSCs treated with distal adipose tissue CM and were partially reduced by a leptin antagonist. Lastly, ADSCs treated with peritumoral CM of chemoresistant patients, displayed increased expression of NSTM, OCT-4, leptin, leptin receptor, α-SMA, CD34 and VEGF. These results suggest that the peritumoral adipose tissue may promote, via paracrine signalling, the expression of depot-specific factors associated with therapeutic resistance.

This article is protected by copyright. All rights reserved.



from Cancer via ola Kala on Inoreader http://ift.tt/2y4QYdw
via IFTTT

A double-edged sword: the world according to Capicua in cancer

Abstract

CIC/Capicua is a HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes such as PEA3 family genes. The RTK/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity, and CIC thus acts as an important downstream molecule of the pathway and as a tumor suppressor. CIC loss-of-function mutations are frequently observed in several human neoplasms such as oligodendroglioma, and lung and gastric carcinoma. CIC is also involved in chromosomal translocation-associated gene fusions in highly aggressive small round cell sarcoma that is biologically and clinically distinct from Ewing sarcoma. In these mutations, PEA3 family genes and other important target genes are upregulated, inducing malignant phenotypes. Downregulation of CIC abrogates the effect of MAPK inhibitors, suggesting its potential role as an important modifier of molecular target therapies for cancer. These data reveal the importance of CIC as a key molecule in signal transduction, carcinogenesis and developing novel therapies.

This article is protected by copyright. All rights reserved.



from Cancer via ola Kala on Inoreader http://ift.tt/2y0TBLP
via IFTTT

The expression level of CXCL7 in peripheral blood cells is a potential biomarker for the diagnosis of renal cell carcinoma

Summary

There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly up-regulated in the peripheral blood cells of RCC patients. Importantly, aberrant CXCL7 expression was confirmed even in peripheral blood cells obtained from early stage (pT1a) RCC patients, and the expression level of CXCL7 in peripheral blood cells was a potential independent biomarker for the diagnosis of RCC by Receiver Operating Characteristic curve analysis (sensitivity of 70.0% and specificity of 64.0%, AUC = 0.722, a multiple logistic regression analysis, OR, 1.07; 95% CI, 1.03–1.11; P = 0.0004). Moreover, CXCL7 expression in peripheral blood cells significantly decreased after resection of the primary tumor. CXCL7 is more highly expressed in peripheral blood mononuclear cells than in neutrophils from both healthy controls and RCC patients. Interestingly, CXCL7 expression in peripheral blood mononuclear cells from healthy volunteers was significantly elevated following co-culture with RCC cells compared to those co-cultured with normal cells as a control. These results suggest that aberrant CXCL7 expression in peripheral blood cells is induced by RCC cells and may serve as a novel biomarker in the diagnosis of RCC.

This article is protected by copyright. All rights reserved.



from Cancer via ola Kala on Inoreader http://ift.tt/2y4WqNz
via IFTTT

Novel method for intraoperative assessment of cerebral autoregulation by paced breathing

Abstract
Background
Cerebral autoregulation (CA) is the mechanism that maintains constancy of cerebral blood flow (CBF) despite variations in blood pressure (BP). Patients with attenuated CA have been shown to have an increased incidence of peri-operative stroke. Studies of CA in anaesthetized subjects are rare, because a simple and non-invasive method to quantify the integrity of CA is not available. In this study, we set out to improve non-invasive quantification of CA during surgery. For this purpose, we introduce a novel method to amplify spontaneous BP fluctuations during surgery by imposing mechanical positive pressure ventilation at three different frequencies and quantify CA from the resulting BP oscillations.
Methods
Fourteen patients undergoing sevoflurane anaesthesia were included in the study. Continuous non-invasive BP and transcranial Doppler-derived CBF velocity (CBFV) were obtained before surgery during 3 min of paced breathing at 6, 10, and 15 bpm and during surgery from mechanical positive pressure ventilation at identical frequencies. Data were analysed using frequency domain analysis to obtain CBFV-to-BP phase lead as a continuous measure of CA efficacy. Group averages were calculated. Values are means (sd), and P<0.05 was used to indicate statistical significance.
Results
Preoperative vs intraoperative CBFV-to-BP phase lead was 43 (9) vs 45 (8)°, 25 (8) vs 24 (10)°, and 4 (6) vs −2 (12)° during 6, 10, and 15 bpm, respectively (all P=NS).
Conclusions
During surgery, cerebral autoregulation indices were similar to values determined before surgery. This indicates that CA can be quantified reliably and non-invasively using this novel method and confirms earlier evidence that CA is unaffected by sevoflurane anaesthesia.
Clinical trial registration
NCT03071432.

http://ift.tt/2y0kdwk

Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1

Abstract

The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.



http://ift.tt/2fV5K00

Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1

Abstract

The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.



from Cancer via ola Kala on Inoreader http://ift.tt/2fV5K00
via IFTTT

Extracranial metastases of high-grade glioma: the clinical characteristics and mechanism

Abstract

Background

This presentation of two cases and literature review discusses the epidemiology, clinical manifestations, pathogenesis, diagnosis, treatment, and prognosis of high-grade glioma with extracranial metastases.

Methods

A retrospective analysis of the clinical features of two cases of malignant glioma, including metastatic sites, pathological data, and treatment methods, and a literature review was performed.

Results

Two patients developed extracranial metastases within 1 year after surgery for primary glioma. One patient developed cervical lymph node and bone metastases while the other developed bone metastases, and both patients died within 2 months after the diagnosis of the extracranial metastasis.

Conclusion

Extracranial metastases may develop from malignant gliomas. According to the literature, the most common extracranial site is intraspinal (along the neural axis), followed by the vertebrae, lungs, liver, and lymph nodes. The complex metastatic mechanism remains unclear, and the prognosis is very poor, with a survival duration of less than 6 months.



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

Thyroid hemiagenesis and Hashimoto’s thyroditis—diagnostic and treatment pitfalls

Abstract

Background

Thyroid hemiagenesis (TH) is a rare congenital disease with absence of a thyroid lobe; most patients have no clinical symptoms. The etiology of TH remains unclear. In this paper, we describe a rare case of TH and congenital absence of the ipsilateral parathyroid gland, found during the operation, combined with the autoimmune disease Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis.

Case Presentation

A 31-year-old woman was admitted to our hospital because of a mass in the right neck. Surgical exploration validated the absence of the left lobe of the thyroid and parathyroid glands, and pathological examination of the excised nodules confirmed Hashimoto's thyroiditis.

Patients with TH might show accompanying absence of the ipsilateral parathyroid gland. The case described here, in which TH was combined with Hashimoto's thyroiditis, is rare in the medical literature. The operation should be ended at once if Hashimoto's thyroiditis is diagnosed during surgery.

Conclusions

Absence of thyroid lobe may accompany with a congenital absence of the ipsilateral parathyroid gland and Hashimoto's thyroiditis. Fine needle aspiration is essential to diagnosis and decision-making of the treatment.



from Cancer via ola Kala on Inoreader http://ift.tt/2xnCN4e
via IFTTT

Extracranial metastases of high-grade glioma: the clinical characteristics and mechanism

Abstract

Background

This presentation of two cases and literature review discusses the epidemiology, clinical manifestations, pathogenesis, diagnosis, treatment, and prognosis of high-grade glioma with extracranial metastases.

Methods

A retrospective analysis of the clinical features of two cases of malignant glioma, including metastatic sites, pathological data, and treatment methods, and a literature review was performed.

Results

Two patients developed extracranial metastases within 1 year after surgery for primary glioma. One patient developed cervical lymph node and bone metastases while the other developed bone metastases, and both patients died within 2 months after the diagnosis of the extracranial metastasis.

Conclusion

Extracranial metastases may develop from malignant gliomas. According to the literature, the most common extracranial site is intraspinal (along the neural axis), followed by the vertebrae, lungs, liver, and lymph nodes. The complex metastatic mechanism remains unclear, and the prognosis is very poor, with a survival duration of less than 6 months.



http://ift.tt/2fXtbGa

Thyroid hemiagenesis and Hashimoto’s thyroditis—diagnostic and treatment pitfalls

Abstract

Background

Thyroid hemiagenesis (TH) is a rare congenital disease with absence of a thyroid lobe; most patients have no clinical symptoms. The etiology of TH remains unclear. In this paper, we describe a rare case of TH and congenital absence of the ipsilateral parathyroid gland, found during the operation, combined with the autoimmune disease Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis.

Case Presentation

A 31-year-old woman was admitted to our hospital because of a mass in the right neck. Surgical exploration validated the absence of the left lobe of the thyroid and parathyroid glands, and pathological examination of the excised nodules confirmed Hashimoto's thyroiditis.

Patients with TH might show accompanying absence of the ipsilateral parathyroid gland. The case described here, in which TH was combined with Hashimoto's thyroiditis, is rare in the medical literature. The operation should be ended at once if Hashimoto's thyroiditis is diagnosed during surgery.

Conclusions

Absence of thyroid lobe may accompany with a congenital absence of the ipsilateral parathyroid gland and Hashimoto's thyroiditis. Fine needle aspiration is essential to diagnosis and decision-making of the treatment.



http://ift.tt/2xnCN4e

Chronic disease research in Europe and the need for integrated population cohorts



from Cancer via ola Kala on Inoreader http://ift.tt/2hTdCj3
via IFTTT

The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway

ABSTRACT

As one of the most frequently diagnosed cancers in women, the development and progression of epithelial ovarian carcinoma (EOC) remains an open area of research. The role of long non-coding RNAs (lncRNAs) in EOC is an emerging field of study. We found that LncRNA TDRG1 (human testis development–related gene 1) was highly expressed in EOC tissues than in normal ovarian tissues, and expression differed significantly with differentiation. LncRNA TDRG1 downregulation suppressed EOC cell proliferation, migration, and invasion, while its overexpression had the opposite effect. Bioinformatic predictions and dual-luciferase reporter assays showed that LncRNA TDRG1 has possible miRNA-93 (miR-93) binding sites. LncRNA TDRG1 downregulation upregulated miR-93 expression, while its overexpression reduced miR-93 expression. In addition, TDRG1 downregulation reduced the expression of Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6K), Bcl-xL, and matrix metalloproteinase 2 (MMP2) protein, which are regulated by miR-93, while its upregulation induced RhoC, P70S6K, Bcl-xL, and MMP2 protein expression. In vivo, LncRNA TDRG1 overexpression induced tumor development and RhoC expression. Taken together, our results demonstrated for the first time that LncRNA TDRG1 may be a new and important diagnostic and therapeutic target in EOC. This article is protected by copyright. All rights reserved



http://ift.tt/2z1YMLf

The role of the long non-coding RNA TDRG1 in epithelial ovarian carcinoma tumorigenesis and progression through miR-93/RhoC pathway

ABSTRACT

As one of the most frequently diagnosed cancers in women, the development and progression of epithelial ovarian carcinoma (EOC) remains an open area of research. The role of long non-coding RNAs (lncRNAs) in EOC is an emerging field of study. We found that LncRNA TDRG1 (human testis development–related gene 1) was highly expressed in EOC tissues than in normal ovarian tissues, and expression differed significantly with differentiation. LncRNA TDRG1 downregulation suppressed EOC cell proliferation, migration, and invasion, while its overexpression had the opposite effect. Bioinformatic predictions and dual-luciferase reporter assays showed that LncRNA TDRG1 has possible miRNA-93 (miR-93) binding sites. LncRNA TDRG1 downregulation upregulated miR-93 expression, while its overexpression reduced miR-93 expression. In addition, TDRG1 downregulation reduced the expression of Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6K), Bcl-xL, and matrix metalloproteinase 2 (MMP2) protein, which are regulated by miR-93, while its upregulation induced RhoC, P70S6K, Bcl-xL, and MMP2 protein expression. In vivo, LncRNA TDRG1 overexpression induced tumor development and RhoC expression. Taken together, our results demonstrated for the first time that LncRNA TDRG1 may be a new and important diagnostic and therapeutic target in EOC. This article is protected by copyright. All rights reserved



from Cancer via ola Kala on Inoreader http://ift.tt/2z1YMLf
via IFTTT

American Journal of Cancer Research; +19 new citations

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

American Journal of Cancer Research

These pubmed results were generated on 2017/10/06

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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

Corneal Collagen Cross-Linking Combined with an Artiflex Iris-Fixated Anterior Chamber Phakic Intraocular Lens Implantation in a Patient with Progressive Keratoconus

We present here the case of a 24-year-old male who experienced progressive keratoconus and vision loss which adversely affected his ability to carry out everyday tasks. This landed him in the Hashmanis Hospital for consultation. He had a preoperative best corrected visual acuity of 6/12. He underwent multiple Oculus Pentacam examinations, which showed progressive keratoconus. Corneal collagen cross-linking (CXL) was performed to stabilize his cornea and, subsequently, an Artiflex anterior chamber iris-fixated phakic intraocular lens (ACIF-PIOL) was implanted to alleviate his refractive errors. The patient achieved a postoperative uncorrected visual acuity of 6/12. This report shows that CXL combined with ACIF-PIOL can be safe and effective in those with progressive keratoconus.
Case Rep Ophthalmol 2017;8:482–488

http://ift.tt/2yMrFKw

TERT-CLPTM1 locus polymorphism (rs401681) is associated with the prognosis of hepatocellular carcinoma

88x31.png



http://ift.tt/2fRdSv1

ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy

88x31.png



http://ift.tt/2xkIbFn

Cancers, Vol. 9, Pages 135: Can Intensity-Modulated-Radiotherapy Reduce Toxicity in Head and Neck Squamous Cell Carcinoma?

Cancers, Vol. 9, Pages 135: Can Intensity-Modulated-Radiotherapy Reduce Toxicity in Head and Neck Squamous Cell Carcinoma?

Cancers doi: 10.3390/cancers9100135

Authors: Julie van der Veen Sandra Nuyts

Intensity modulated radiotherapy (IMRT) is a modern radiotherapy technique that was implemented in the mid-1990s. It allows closer shaping of dose, to target volumes, thereby sparing organs at risk (OARs). Before the IMRT-era, two-dimensional radiotherapy (2DRT) and later three-dimensional conformal radiotherapy (3DCRT) were the techniques of choice, but this robust way of irradiating caused more normal tissue to receive a higher dose. Radiation of cancers in the head and neck region is complex because of close proximity to critical normal tissue and the large target volumes that need to be treated at high doses. IMRT offers an elegant solution compared with 3DCRT and surgery because it allows organ preservation and improved function preservation. In this manuscript, we review the rationales for IMRT, with an emphasis on toxicity outcomes compared with 3DCRT. We performed a review of the literature and looked at the most important randomised controlled trials comparing IMRT with 3DCRT. We conclude that IMRT is safe in regard to disease outcome, and that it allows better sparing of normal tissue, thereby causing less toxicity, resulting in a smaller impact on quality of life compared with conventional radiotherapy in the treatment of head and neck cancer.



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

A revision of the Tokuhashi revised score improves the prognostic ability in patients with metastatic spinal cord compression

Abstract

Purpose

The Tokuhashi revised score from 2005 (TR2005) is the most recommended prognostic scoring system in patients with metastatic spinal cord compression (MSCC). However, recent studies have questioned its prognostic ability and the need for a new revision has been proposed. We aimed to assess whether a revision of the TR2005 can improve the prognostic ability of the scoring system.

Methods

In 2011 and 2012, a total of 1143 consecutive patients admitted with MSCC were prospectively included in a 2011 and a 2012 cohort. For the patients admitted in 2011 (n = 544), the components of the TR2005 including primary cancer diagnosis were analyzed regarding the prognostic ability. Based on these findings, a revision of the TR2005 score was defined as the Tokuhashi revised score 2017 (TR2017). The prognostic abilities of the TR2005 and the TR2017 were compared by Kaplan Meyer (KM) curves, and receiver-operating characteristics' (ROC) analysis was compared in a cohort of patients admitted in 2012 (n = 599).

Results

KM curves and ROC analysis showed that the TR2017 had better prognostic ability compared to the TR2005. The ROC areas were as follows: <6-months survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for ≥6-month survival, TR2017 = 0.71 and TR2005 = 0.65, and p = 0.003; for ≥12-month survival TR2017 = 0.72 and TR2005 = 0.67, and p = 0.0015.

Conclusions

The TR2017 can improve the prognostic ability of the TR2005 in patients with MSCC. This could affect the preoperative evaluation of patients suffering from MSCC.



from Cancer via ola Kala on Inoreader http://ift.tt/2fP8ybd
via IFTTT