Avelumab: A Review in Metastatic Merkel Cell Carcinoma

Abstract

Avelumab (Bavencio^®) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200. In Part A of the study, confirmed objective responses were observed in approximately one-third of patients with chemotherapy-refractory metastatic MCC treated with avelumab. The responses were observed early and appeared to be durable, with an estimated 74% of responses having a duration ≥ 12 months. Furthermore, interim results from a separate cohort of patients (Part B) indicate an objective response rate for avelumab of > 60% in patients who were chemotherapy-naïve in the metastatic disease setting. Avelumab is associated with a risk of immune-related adverse events but, overall, has an acceptable and manageable safety and tolerability profile. In conclusion, currently available data suggest that avelumab presents a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis.

https://ift.tt/2kiRVam

Case 16-2018: A 45-Year-Old Man with Fever, Thrombocytopenia, and Elevated Aminotransferase Levels

Presentation of Case. Dr. Alyssa Sclafani (Medicine): A 45-year-old man presented to the emergency department of this hospital during the summer with fever, thrombocytopenia, and elevated aminotransferase levels. Three weeks before presentation, fever occurred (with temperatures as high as 40.0°C),…

https://ift.tt/2GJonvp

Odd‐skipped related 1 inhibits lung cancer proliferation and invasion by reducing Wnt signaling through the suppression of SOX9 and β‐catenin

Cancer Science, EarlyView.


https://ift.tt/2IILaZM

Stromal immunoglobulin κC expression is associated with initiation of breast cancer in TA2 mice and human breast cancer

Cancer Science, EarlyView.


https://ift.tt/2IHypTx

Efficacy and safety of 3‐month dosing regimen of degarelix in Japanese subjects with prostate cancer: A phase III study

Cancer Science, EarlyView.


https://ift.tt/2xeabe2

Management of Non-Diffuse Large B Cell Lymphoma Post-Transplant Lymphoproliferative Disorder

Opinion statement

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common neoplasms seen after solid organ and hematopoietic stem cell transplantation, and is associated with significant morbidity and mortality. The pathogenesis is related to post-transplant immunosuppression and EBV infection. Prevention of PTLD depends upon judicious use of immunosuppression and serial EBV monitoring. Preemptive therapy consists of reduction of immunosuppression, antiviral medications, and single-agent rituximab. There are no randomized phase III trials on PTLD treatment, so current management guidelines are largely based on recent phase II trials, single-institution retrospective studies, and expert opinion. Management of PTLD is dependent upon its subtypes. Early-type and polymorphic PTLD generally respond to reduction of immunosuppression and rituximab monotherapy, whereas monomorphic PTLD often requires additional concurrent or sequential use of chemotherapy. For rare subtypes of PTLD, standard-of-care guidelines for de novo lymphomas are recommended. Surgical resection or radiotherapy may be used as adjunctive therapy depending on the extent of disease. Non-chemotherapy options such as adoptive T cell therapy have shown promising efficacy and must be explored further. Despite progress in the last decade, overall survival rates continue to be low in published series. This review highlights the need for prospective randomized trials incorporating novel agents to improve outcomes in PTLD.

https://ift.tt/2s4oMno

Follicular Lymphoma: Past, Present, and Future

Opinion statement

Even in the modern era, follicular lymphoma (FL) remains largely an incurable but treatable disease with both standard and novel treatment modalities. Despite the abundance of efficacious treatment modalities currently available, there is no universally agreed upon standard approach to treatment for patients with FL, particularly in the relapsed/refractory (R/R) setting. There is an increasing need for better tools to risk-stratify patients and to identify those likely to experience relapse early. Additionally, the use of gene expression profiling and next-generation sequencing techniques in recent years has led to a wealth of knowledge regarding the molecular drivers of lymphomagenesis; however, much of this knowledge is not currently applicable on a day to day basis in the clinic setting. Further studies are needed to determine a validated, clinically relevant predictive model that incorporates patient factors and molecular factors that will guide clinicians on the most effective treatment strategy. With many questions left unanswered, it is our opinion that the treatment of FL and sequencing of therapy in the R/R setting should be a personalized approach that balances patient-specific factors such as preferences and comorbidities with treatment-related factors such as known response rates and toxicity profiles.

https://ift.tt/2ILBcah

Quality Assurance and Improvement in Head and Neck Cancer Surgery: From Clinical Trials to National Healthcare Initiatives

Opinion statement

It is without question in the best interest of our patients, if we can identify ways to improve the quality of care we deliver to them. Great progress has been made within the last 25 years in terms of development and implementation of quality-assurance (QA) platforms and quality improvement programs for surgery in general, and within this context for head and neck surgery. As of now, we have successfully identified process indicators that impact outcome of our patients and the quality of care we deliver as surgeons. We have developed risk calculators to determine the risk for complications of individual surgical patients. We have created perioperative guidelines for complex head and neck procedures. We have in Europe and North America created audit registries that can gather and analyze data from institutions across the world to better understand which processes need change to obtain good outcomes and improve quality of care. QA platforms can be tested within the clearly defined environment of prospective clinical trials. If positive, such programs could be rolled out within national healthcare systems, if feasible. Testing quality programs in clinical trials could be a versatile tool to help head neck cancer patients benefit directly from such initiatives on a global level.

https://ift.tt/2s4oyN4

Exosomal miR‐423‐5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer

Molecular Carcinogenesis, EarlyView.


https://ift.tt/2LoZAjP

Atorvastatin and Caffeine in Combination Regulates Apoptosis, Migration, Invasion and Tumorspheres of Prostate Cancer Cells

Abstract

Atorvastatin is the most prescribed cholesterol-lowering statin, while caffeine enhances chemo-sensitivity and induces apoptosis of tumor cells through its DNA repair-inhibiting effect. The present study investigated the effects and mechanisms of atorvastatin and caffeine in combination on human prostate cancer cells cultured in vitro. Cell growth were determined by the trypan blue exclusion assay. The cell apoptosis and colony formation were determined by morphological assessment. The ability of cell migration and invasion were performed using a scratch wound-healing and Transwell assay. Tumorspheres were formed in suspension under the condition of non-adherence and serum-free medium. Finally, the western blot assay was used to determine the levels of proteins. The combination synergistically suppressed proliferation and induced apoptotic death. Meanwhile, the migration, invasion, and the formation of tumorspheres were significantly inhibited by the combination. We found that atorvastatin and caffeine in combination downregulated phospho-Akt, phospho-Erk1/2, anti-apoptotic Bcl-2 and Survivin protein levels. Results of the present study indicate treatment with the combination of caffeine and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.

https://ift.tt/2IZW5BL

Risk factors for pneumonitis in patients treated with anti‐programmed death‐1 therapy: A case‐control study

Cancer Medicine, EarlyView.


https://ift.tt/2x7VOIj

From the Desk of the Editor

https://ift.tt/2IFkSMm

Comprehensive profiling of DNA repair defects in breast cancer identifies a novel class of endocrine therapy resistance drivers

Purpose: This study was undertaken to conduct a comprehensive investigation of the role of DNA damage repair (DDR) defects in poor outcome ER+ disease. Experimental Design: Expression and mutational status of DDR genes in ER+ breast tumors were correlated with proliferative response in neoadjuvant aromatase inhibitor therapy trials (discovery data set), with outcomes in METABRIC, TCGA and Loi data sets (validation data sets), and in patient derived xenografts. A causal relationship between candidate DDR genes and endocrine treatment response, and the underlying mechanism, was then tested in ER+ breast cancer cell lines. Results: Correlations between loss of expression of three genes: CETN2 (p<0.001) and ERCC1 (p=0.01) from the nucleotide excision repair (NER) and NEIL2 (p=0.04) from the base excision repair (BER) pathways were associated with endocrine treatment resistance in discovery data sets, and subsequently validated in independent patient cohorts. Complementary mutation analysis supported associations between mutations in NER and BER pathways and reduced endocrine treatment response. A causal role for CETN2, NEIL2 and ERCC1 loss in intrinsic endocrine resistance was experimentally validated in ER+ breast cancer cell lines, and in ER+ patient-derived xenograft models. Loss of CETN2, NEIL2 or ERCC1 induced endocrine treatment response by dysregulating G1/S transition, and therefore, increased sensitivity to CDK4/6 inhibitors. A combined DDR signature score was developed that predicted poor outcome in multiple patient cohorts. Conclusions:This report identifies DDR defects as a new class of endocrine treatment resistance drivers and indicates new avenues for predicting efficacy of CDK4/6 inhibition in the adjuvant treatment setting.

https://ift.tt/2kmk3JH

Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor-Positive Advanced Breast Cancer

Purpose: This single-arm, open label Phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer. Experimental Design: Patients received 6 mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for PIK3CA mutations. Adverse events (AEs) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1. Results: Median treatment duration was 4.6 (range: 0.9-40.5) months. All patients experienced ≥1 AE, 30 (50.0%) had grade ≥3 AEs, and 19 (31.7%) experienced 35 serious AEs. Forty-seven of sixty patients had evaluable tissue for central PIK3CA mutation testing (20 had mutations, 27 had no mutation detected [MND]). In patients with baseline measurable disease, clinical activity was observed in tumors with PIK3CA mutations (best confirmed response rate: 38.5% [5/13; 95% CI 13.9-68.4]; clinical benefit rate [CBR]: 38.5% [5/13; 95% CI 13.9-68.4]), PIK3CA-MND (best confirmed response rate: 14.3% [3/21; 95% CI 3.0-36.3]; CBR: 23.8% [5/21; 95% CI 8.2-47.2]), and unknown PIK3CA mutation status (best confirmed response rate: 20.0% [2/10; 95% CI 2.5-55.6]; CBR: 30.0% [3/10; 95% CI 6.7-65.2]). Conclusions: Taselisib plus fulvestrant had clinical activity irrespective of PIK3CA mutation status, with numerically higher objective response rate and CBR in patients with PIK3CA-mutated (versus -MND) locally advanced or metastatic HER2-negative, HR-positive breast cancer. No new safety signals were reported. A confirmatory Phase III trial is ongoing.

https://ift.tt/2xa3I40

Manipulating macrophage polarization and function using classical HDAC inhibitors: implications for autoimmunity and inflammation

Publication date: Available online 23 May 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Asadollah Mohammadi, Atefeh Sharifi, Reza Pourpaknia, Saeed Mohammadian, Amirhossein Sahebkar
Macrophages are important player in defense against invading pathogens and their dysfunction is linked to most of inflammatory and autoimmune diseases. Inflammation is a normal and physiological response of the immune system against harmful stimuli such as infection and injury. However, when allowed to continue unchecked, under certain conditions it turns into autoimmune or inflammatory diseases, neurodegeneration, and carcinogenesis. Currently, several safe and effective anti-inflammatory drugs are available with many more drugs in the development pipeline, among which are histone deacetylase inhibitors. In this review we discuss how post-translational modifications of histones influence the innate and adaptive immunity through macrophage survival, proliferation, polarization and functional responses. We also discuss how emerging classes of pharmacological agents which developed for use as anti-cancer agents, have been applied as anti-inflammatory drugs to treat macrophage-mediated inflammatory and autoimmune diseases.



https://ift.tt/2kjFKdb

BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC

Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK. Bromodomain-containing protein-4 (BRD4) has been shown to regulate the transcription of various RTK in the context of resistance to PI3K and HER2 inhibition in breast cancer models. We hypothesized that, in HNSCC, targeting BRD4 could overcome cetuximab resistance by depleting alternative RTK expression. We generated independent models of cetuximab resistance in HNSCC cell lines and interrogated their RTK and BRD4 expression profiles. Cetuximab-resistant clones displayed increased expression and activation of several RTK, such as MET and AXL, as well as an increased percentage of BRD4-expressing cells. Both genetic and pharmacologic inhibition of BRD4 abrogated cell viability in models of acquired and intrinsic cetuximab resistance and was associated with a robust decrease in alternative RTK expression by cetuximab. Combined treatment with cetuximab and bromodomain inhibitor JQ1 significantly delayed acquired resistance and RTK upregulation in PDX models of HNSCC. These findings indicate that the combination of cetuximab and bromodomain inhibition may be a promising therapeutic strategy for HNSCC patients.

https://ift.tt/2xazON6

Metabolic and physiologic imaging biomarkers of the tumor microenvironment predict treatment outcome with radiation or a hypoxia-activated prodrug in mice.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here we define two imaging biomarkers that predict differences in tumor response to therapy: 1) partial oxygen pressure (pO2), measured by EPR imaging; and 2) [1-13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa-2, and Su.86.86) were grown in mice. The median pO2 of the mature Hs766t, MiaPaCa-2, and Su.86.86 tumors was 9.1±1.7, 11.1±2.2, and 17.6±2.6 mmHg, and the rate of pyruvate-to-lactate conversion was 2.72±0.48, 2.28±0.26, and 1.98±0.51 min-1, respectively (n=6, each). These results are in agreement with steady state data of matabolites quantified by mass spectroscopy and histological analysis indicating glycolytic and hypoxia profile in Hs766t, MiaPaca-2, and Su.86.86 tumors. Fractionated radiation therapy (5 Gy x 5) resulted in a tumor growth delay of 16.7±1.6 and 18.0±2.7 days in MiaPaca-2 and Su.86.86 tumors, respectively, compared to 6.3±2.7 days in hypoxic Hs766t tumors. Treatment with gemcitabine, a first-line chemotherapeutic agent, or the hypoxia-activated prodrug TH-302 was more effective against Hs766t tumors (20.0±3.5 and 25.0±7.7 days increase in survival time, respectively) than MiaPaCa-2 (2.7±0.4 and 6.7±0.7 days) and Su.86.86 (4.7±0.6 and 0.7±0.6 days) tumors. Collectively, these results demonstrate the ability of molecular imaging biomarkers to predict the response of PDAC to treatment with radiation therapy and TH-302.

https://ift.tt/2kj2Gcw

Atorvastatin and Caffeine in Combination Regulates Apoptosis, Migration, Invasion and Tumorspheres of Prostate Cancer Cells

Abstract

Atorvastatin is the most prescribed cholesterol-lowering statin, while caffeine enhances chemo-sensitivity and induces apoptosis of tumor cells through its DNA repair-inhibiting effect. The present study investigated the effects and mechanisms of atorvastatin and caffeine in combination on human prostate cancer cells cultured in vitro. Cell growth were determined by the trypan blue exclusion assay. The cell apoptosis and colony formation were determined by morphological assessment. The ability of cell migration and invasion were performed using a scratch wound-healing and Transwell assay. Tumorspheres were formed in suspension under the condition of non-adherence and serum-free medium. Finally, the western blot assay was used to determine the levels of proteins. The combination synergistically suppressed proliferation and induced apoptotic death. Meanwhile, the migration, invasion, and the formation of tumorspheres were significantly inhibited by the combination. We found that atorvastatin and caffeine in combination downregulated phospho-Akt, phospho-Erk1/2, anti-apoptotic Bcl-2 and Survivin protein levels. Results of the present study indicate treatment with the combination of caffeine and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.

https://ift.tt/2IZW5BL

Pediatric superior vena cava syndrome: An evidence‐based systematic review of the literature

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2IG8ZFF

Localized vaginal/uterine rhabdomyosarcoma—results of a pooled analysis from four international cooperative groups

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2kjwbuX

Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2s9H9qt

Diastolic dysfunction is associated with exercise impairment in patients with sickle cell anemia

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2GJezkI

New approach to accurate interpretation of sickle cell disease newborn screening by applying multiple of median cutoffs and ratios

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2kmfGhL

Pegylated asparaginase as cause of fatal hyperammonemia in patients with latent urea cycle disorder

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2s8d6iP

Synoptic operative reports for quality improvement in pediatric cancer care

Pediatric Blood &Cancer, EarlyView.


https://ift.tt/2IFdzEq

Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer, Published online: 24 May 2018; doi:10.1038/s41416-018-0108-8

Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

https://ift.tt/2x7e9oU

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams), Published online: 24 May 2018; doi:10.1038/s41416-018-0107-9

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

https://ift.tt/2x2lUMO

Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials

Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials

Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials, Published online: 24 May 2018; doi:10.1038/s41416-018-0102-1

Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials

https://ift.tt/2J5lcDl

The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma

The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma

The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma, Published online: 24 May 2018; doi:10.1038/s41416-018-0104-z

The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma

https://ift.tt/2s7q9RI

The sVEGFR1-i13 splice variant regulates a β1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma

The sVEGFR1-i13 splice variant regulates a β1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma

The sVEGFR1-i13 splice variant regulates a β1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma, Published online: 24 May 2018; doi:10.1038/s41416-018-0128-4

The sVEGFR1-i13 splice variant regulates a β1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma

https://ift.tt/2klltnP

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

Cancer Science, EarlyView.


https://ift.tt/2x6WVYT

Senescent cells re‐engineered to express soluble programmed death receptor‐1 for inhibiting programmed death receptor‐1/programmed death ligand‐1 as a vaccination approach against breast cancer

Cancer Science, EarlyView.


https://ift.tt/2IJB4fe

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

Cancer Science, EarlyView.


https://ift.tt/2xgXwYb

Endoplasmic reticulum stress‐mediated autophagy protects against β,β‐dimethylacrylshikonin‐induced apoptosis in lung adenocarcinoma cells

Cancer Science, EarlyView.


https://ift.tt/2LnfScK

Prognostic value of nutritional risk screening 2002 scale in nasopharyngeal carcinoma: A large‐scale cohort study

Cancer Science, EarlyView.


https://ift.tt/2xgXvU7

PRMT9 promotes hepatocellular carcinoma invasion and metastasis via activating PI3K/Akt/GSK‐3β/Snail signaling

Cancer Science, Volume 109, Issue 5, Page 1414-1427, May 2018.


https://ift.tt/2IGzz1G

Issue Information

Cancer Science, Volume 109, Issue 5, Page 1277-1279, May 2018.


https://ift.tt/2IJT70Q

LKB1 obliterates Snail stability and inhibits pancreatic cancer metastasis in response to metformin treatment

Cancer Science, Volume 109, Issue 5, Page 1382-1392, May 2018.


https://ift.tt/2LqBUvt

Current state of therapeutic development for rare cancers in Japan, and proposals for improvement

Cancer Science, Volume 109, Issue 5, Page 1731-1737, May 2018.


https://ift.tt/2IJWwgi

Podoplanin: An emerging cancer biomarker and therapeutic target

Cancer Science, Volume 109, Issue 5, Page 1292-1299, May 2018.


https://ift.tt/2LpAdhQ

In this Issue

Cancer Science, Volume 109, Issue 5, Page 1280-1281, May 2018.


https://ift.tt/2II6P4o

Merkel cell carcinoma: Clinical outcome and prognostic factors in 351 patients

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2LruAPV

MRI‐based EMVI positivity predicts systemic recurrence in rectal cancer patients with a good tumor response to chemoradiotherapy followed by surgery

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2x7UZ2m

Comparison of sentinel lymph node biopsy guided by blue dye with or without indocyanine green in early breast cancer

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2Lol14s

Predictors of new‐onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population‐based analysis

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2x7UOnI

MET in gastric cancer with liver metastasis: The relationship between MET amplification and Met overexpression in primary stomach tumors and liver metastasis

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2IICh6E

Calculation of breast volumes from mammogram: Comparison of four separate equations relative to mastectomy specimen volumes

Journal of Surgical Oncology, EarlyView.


https://ift.tt/2IGFVK5

Effectiveness of nonpharmacological interventions to reduce procedural anxiety in children and adolescents undergoing treatment for cancer: A systematic review and meta‐analysis

Psycho-Oncology, EarlyView.


https://ift.tt/2LmxjtU

Incongruence between women's survey‐ and interview‐determined decision control preferences: A mixed methods study of decision‐making in metastatic breast cancer

Psycho-Oncology, EarlyView.


https://ift.tt/2xdCl90

Maternal perceptions of BRCA genetic counseling communication processes about disclosing cancer risk information to children and adult relatives

Psycho-Oncology, EarlyView.


https://ift.tt/2IFZaaL

Chemotherapy‐associated cognitive impairments in Korean cancer patients: Risk factors and functional outcome

Psycho-Oncology, EarlyView.


https://ift.tt/2IIcebA

Risk for use of antidepressants, anxiolytics, and hypnotics in partners of glioma patients—A nationwide study covering 19 years of prescriptions

Psycho-Oncology, EarlyView.


https://ift.tt/2IJfLe9

Loss of cyclin‐dependent kinase‐like 2 predicts poor prognosis in gastric cancer, and its overexpression suppresses cells growth and invasion

Cancer Medicine, EarlyView.


https://ift.tt/2x9sKQK

Genetically determined height was associated with lung cancer risk in East Asian population

Cancer Medicine, EarlyView.


https://ift.tt/2J21j04

Rolapitant for the prevention of nausea in patients receiving highly or moderately emetogenic chemotherapy

Cancer Medicine, EarlyView.


https://ift.tt/2x90hdX

Gemcitabine and cisplatin regimen facilitates prognosis of advanced nasopharyngeal carcinoma

Cancer Medicine, EarlyView.


https://ift.tt/2kkq2OX

Upregulation of miR‐374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer

Cancer Medicine, EarlyView.


https://ift.tt/2s7a1zH

The effects of aberrant expression of LncRNA DGCR5/miR‐873‐5p/TUSC3 in lung cancer cell progression

Cancer Medicine, EarlyView.


https://ift.tt/2kjwXYP

A distinctively expressed long noncoding RNA, RP11‐466I1.1, may serve as a prognostic biomarker in hepatocellular carcinoma

Cancer Medicine, EarlyView.


https://ift.tt/2xdgZZM

Long noncoding RNA UFC1 is activated by E2F1 and exerts oncogenic properties by functioning as a ceRNA of FOXP3

Cancer Medicine, EarlyView.


https://ift.tt/2J5stD9

Prognostic significance of combined pretreatment lymphocyte counts and body mass index in patients with head and neck cancer treated with radiation therapy

Cancer Medicine, EarlyView.


https://ift.tt/2s9pmzo

Differences in cancer survival among white and black cancer patients by presence of diabetes mellitus: Estimations based on SEER‐Medicare‐linked data resource

Cancer Medicine, EarlyView.


https://ift.tt/2kmU6ts

Glioblastoma recurrence correlates with NLGN3 levels

Cancer Medicine, EarlyView.


https://ift.tt/2x5MHrN

LGR5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial–mesenchymal transition through the Notch1 signaling pathway

Cancer Medicine, EarlyView.


https://ift.tt/2J0tZGJ

Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics

Cancer, EarlyView.


https://ift.tt/2IZKR05

Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics

Cancer, EarlyView.


https://ift.tt/2x9T9Oo

The pendulum swings back: Screening for prostate cancer in 2018

Cancer, EarlyView.


https://ift.tt/2klqA7g

PSA screening, prostate biopsy, and treatment of prostate cancer in the years surrounding the USPSTF recommendation against prostate cancer screening

Cancer, EarlyView.


https://ift.tt/2x6UTYR

Moving toward a more rational, evidence‐based approach to PSA screening, diagnosis, and treatment of prostate cancer

Cancer, EarlyView.


https://ift.tt/2klquMW

Liquid biopsies offer promise and challenges

Cancer, Volume 124, Issue 11, Page 2269-2270, June 1, 2018.


https://ift.tt/2s4a3YM

Issue Information

Cancer, Volume 124, Issue 11, Page 2259-2268, June 1, 2018.


https://ift.tt/2IZCGAX

More evidence that gum disease increases cancer risk

Cancer, Volume 124, Issue 11, Page 2270-2271, June 1, 2018.


https://ift.tt/2x69Nye

The sVEGFR1-i13 splice variant regulates a β1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma

https://ift.tt/2LnZo48

Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials

https://ift.tt/2x7dZOk

The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma

https://ift.tt/2LrEZLI

Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer

https://ift.tt/2IIBte6

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

https://ift.tt/2IGbzf7

Ketamine and electroconvulsive therapy: so happy together?

Purpose of review Anesthetics, such as thiopental, methohexital, propofol and ketamine have been used to induce unconsciousness for electroconvulsive therapy (ECT), each with its advantages and disadvantages. Only until recently was it discovered that ketamine may have inherent antidepressant effects. We reviewed the side effect profile of ketamine and examined the literature for whether or not ketamine augments the antidepressant effects of ECT. Recent findings Systematic reviews and meta-analyses of randomized controlled trials of the potential benefits of adding ketamine to ECT treatment have generated varied conclusions. Currently there is a lack of clear evidence that ketamine with ECT is more efficacious than ECT alone. Summary Large, multicenter randomized controlled trials are needed to further investigate the potential advantages of adding ketamine to ECT for patients with severe or refractory depression. The addition of ketamine to ECT treatment may have some early beneficial effect in patients with acute depressive disorders. Most likely, ECT itself is responsible for lasting remission from severe depression. Ketamine's side effect profile may be undesirable in certain patient populations, and so the risks and benefits of the addition of this drug to ECT treatment must be weighed. Correspondence to Kathryn Cobb, MD, N2198 UNC Hospitals, CB# 7010, Chapel Hill, NC 27599-7010, USA. Tel: +1 919 966 5136; e-mail: kathryn_cobb@med.unc.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2kl4nGA

Treatment of ventriculoperitoneal shunt infection and ventriculitis caused by Acinetobacter baumannii: a case report

Acinetobacter baumannii (A. baumannii) infections are a recognized problem in healthcare, causing ventriculoperitoneal shunt infection and ventriculitis. Such infections are serious intracranial infection that ca...

https://ift.tt/2x6ejNv

Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches

Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial...

https://ift.tt/2IF0xqk

Perioperative Hyperchloremia and its Association With Postoperative Acute Kidney Injury After Craniotomy for Primary Brain Tumor Resection: A Retrospective, Observational Study

Background: Hyperchloremia is known to influence postoperative outcomes and may result in postoperative acute kidney injury (AKI). This study sought to investigate whether hyperchloremia was associated with postoperative AKI in patients who underwent surgery for primary brain tumor resection. Materials and Methods: This is a retrospective, observational study of patients who underwent craniotomy for primary brain tumor resection at a single tertiary care hospital between January 2005 and October 2017. Maximum levels of serum chloride (mmol/L) measured on postoperative days (PODs) 0 to 3 and increase in serum chloride (mmol/L), (maximum serum chloride−baseline serum chloride before surgery) were measured. We examined whether perioperative hyperchloremia was associated with postoperative AKI during PODs 0 to 3. Univariate and multivariate logistic regression analyses were used in this study. Results: A total of 726 patients were included in the analysis; of these, 39 (5.4%) were diagnosed with postoperative AKI during PODs 0 to 3. The risk of postoperative AKI was associated with maximum chloride levels (odds ratio, 1.10; 95% confidence interval, 1.02-1.19; P=0.015) and with an increase in serum chloride levels during PODs 0 to 3 (odds ratio, 1.11; 95% confidence interval, 1.04-1.19; P=0.004). Conclusions: Our study shows that perioperative hyperchloremia during PODs 0 to 3 was associated with an increased risk of postoperative AKI during this period after craniotomy for primary brain tumor resection. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Sang-Hwan Do, MD, PhD, Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 166, Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, South Korea (e-mail: shdo@snu.ac.kr). Received January 31, 2018 Accepted April 19, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

https://ift.tt/2s0BeEY

Understanding metabolic changes in aging bone marrow

Abstract

Background

Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone marrow related to aging have not been studied.

Methods

In this study, we characterized the metabolome and transcriptome of aging murine bone marrow and compared it with bone marrow from young healthy mice and chemotherapy treated mice; chemotherapy treatment is known to induce age-related changes in hematopoiesis.

Results

The metabolome of the aging bone marrow exhibited a signature of suppressed fatty-acid oxidation: accumulation of free fatty acids, reduced acyl-carnitines and low β-hydroxy butyric acid. The aged bone marrow also exhibited a significant reduction in amino acid and nucleic acid pool. The transcriptome of the aging bone marrow revealed a signature of oxidative stress, known to be associated with mitochondrial dysfunction. Lastly, the metabolic and transcriptomic profiles of the bone marrow of chemotherapy treated mice did not show broad age-related changes but rather mostly resembled young healthy mice, suggestive of a lack of 'metabolic aging' with chemotherapy exposure.

Conclusion

Our results revealed broad changes in lipids, amino acids, and nucleotides in aging marrow tissue. Together, these data provide a rich resource for the study of metabolic changes associated with aging in bone marrow.

https://ift.tt/2IZO2VI

The impact of MRI steady-state sequences as an additional assessment modality in vestibular schwannoma patients after LINAC stereotactic radiotherapy or radiosurgery

Abstract

Purpose

Data concerning the clinical usefulness of steady-state sequences (SSS) for vestibular schwannomas (VS) after linear accelerator (LINAC) stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) are scarce. The aim of the study was to investigate whether SSS provide an additional useful follow-up (FU) tool to the established thin-layered T1 sequences with contrast enhancement.

Methods

Pre- and post-treatment SSS were identified in 45 consecutive VS patients (2012–2016) with a standardized FU protocol including SSS at 2–3 months and 6 months/yearly in our prospective database and were retrospectively re-evaluated. The SSS were used throughout for the segmentation of the cochlea and partly of the trigeminal nerve in the treatment planning. Data analysis included signal conversion in SSS and possible correlation with neuro-otological outcome and volumetric assessment after a certain time interval.

Results

The series included 42 SRS and 3 SRT patients (31 female/14 male; mean age 59.3 years, range: 25–81 years). An SSS signal conversion was observed in 20 tumors (44.4%) within a mean time of 11 months (range: 7–15 months). Mean FU time was 26 months (median of 4 FU visits) and demonstrated tumor volume shrinkage in 29 cases (64.4%) correlating with FU time (p = 0.07). The incidence rate of combined shrinkage and signal conversion (48.3%) compared to those without signal conversion (51.7%) did not differ significantly (p = 0.49). In case of an early signal conversion at the first FU, a weak statistical significance (p = 0.05) for a higher shrinkage rate of VS with signal conversion was found. Side effects in cases with signal conversion (9/20, 45%) were more frequently than without signal conversion (6/25, 24%) without reaching statistical significance (p = 0.13).

Conclusion

Our data confirmed the usefulness of SSS for anatomical segmentation of VS in LINAC-SRS/SRT treatment planning and add data supporting their potential as an adjunctive FU option in VS patients.

https://ift.tt/2s4Kt6Q

Characterization of tumor-derived mesenchymal stem cells potentially differentiating into cancer-associated fibroblasts in lung cancer

Abstract

Purpose

The goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence.

Methods

MSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0. Isolated cells were characterized for the presence of molecular markers (identified by routine diagnostic characterization in differentiated tumoral cells), stemness properties, and CAF-related markers expression. Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion.

Results

C- and T-MSCs did not present EGFR mutations unlike tumor tissue and showed a stem-like immunophenotype, characterized by the ability to differentiate towards osteo-, chondro- and adipogenic lineages. The expression of markers referred to CAFs (α-SMA, HI-1α, MMP11, VEGF, CXCL12, TGF-β1, TGF-βRII, IL6, TNFα) was significantly higher in T-MSCs than in C-MSCs. The co-cultures with A549 cells led to the over-expression of selected oncogenes and to the increase of IL6 secretion in T-MSCs but not in C-MSCs.

Conclusions

MSCs isolated from tumor tissue displayed distinct properties compared to MSCs isolated from healthy tissue, suggesting T-MSCs differentiation towards a CAF-related phenotype under the influence of the tumoral microenvironment.

https://ift.tt/2IIi9Ob

Characterization of tumor-derived mesenchymal stem cells potentially differentiating into cancer-associated fibroblasts in lung cancer

Abstract

Purpose

The goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence.

Methods

MSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0. Isolated cells were characterized for the presence of molecular markers (identified by routine diagnostic characterization in differentiated tumoral cells), stemness properties, and CAF-related markers expression. Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion.

Results

C- and T-MSCs did not present EGFR mutations unlike tumor tissue and showed a stem-like immunophenotype, characterized by the ability to differentiate towards osteo-, chondro- and adipogenic lineages. The expression of markers referred to CAFs (α-SMA, HI-1α, MMP11, VEGF, CXCL12, TGF-β1, TGF-βRII, IL6, TNFα) was significantly higher in T-MSCs than in C-MSCs. The co-cultures with A549 cells led to the over-expression of selected oncogenes and to the increase of IL6 secretion in T-MSCs but not in C-MSCs.

Conclusions

MSCs isolated from tumor tissue displayed distinct properties compared to MSCs isolated from healthy tissue, suggesting T-MSCs differentiation towards a CAF-related phenotype under the influence of the tumoral microenvironment.

https://ift.tt/2IIi9Ob

Some Children with Wilms Tumor Can Receive Less Therapy, Study Suggests

Results from an NCI-sponsored clinical trial may point to an important change in how some children with advanced Wilms tumor, a form of kidney cancer, are treated.

https://ift.tt/2Lnf4EU

Tumour-infiltrating lymphocytes, programmed death ligand 1 and cyclooxygenase-2 expression in skin melanoma of elderly patients: clinicopathological correlations

Age is an important prognostic factor in melanoma; notably, elderly patients tend to present with advanced stage skin melanoma (SM) and worse outcome. Moreover, SM is an immunogenic cancer, and its interaction with the aging immune system could have an effect on biologic behaviour of this disease. Tumour-infiltrating lymphocytes (TILs) could represent the host response in SM; it has been shown that higher grade of TILs is associated with better survival. Moreover, programmed death ligand 1 (PD-L1) and cyclooxygenase-2 (COX-2) are potential markers of host immune response and inflammation. We retrospectively reviewed 113 consecutive cases of early-stage SM that occurred in patients aged greater than or equal to 65 years at the time of diagnosis, followed between January 2010 and March 2014 at the University and General Hospital of Udine, Italy. The aim of this study was to evaluate TILs grade, PD-L1 expression on TILs and tumour expression of PD-L1 and COX-2 and their prognostic value in elderly patients with early SM. A better disease-free survival as well as melanoma-specific survival (MSS) was significantly associated with TILs [hazard ratios (HR): 0.41, 95% confidence interval (CI): 0.20–0.84, P=0.02 and HR: 0.37, 95% CI: 0.17–0.82, P=0.01, respectively]. PD-L1 positivity on TILs was associated with a better MSS (HR: 0.41, 95% CI: 0.17–0.97, P=0.04). Moreover, among patients with TILs, those showing COX-2 positivity on tumour cells and no PD-L1 expression on TILs had a worse disease-free survival and MSS (HR: 5.18, 95% CI: 1.33–20.23, P=0.018; HR: 6.21, 95% CI: 1.20–32.24, P=0.03; respectively). Immune and inflammatory markers deserve further investigation in aging patients with melanoma. Correspondence to Alessandro Marco Minisini, MD, PhD, Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Piazzale S. Maria della Misericordia, 33100 Udine, Italy Tel/fax: +39 043 255 2751; e-mail: alessandro.minisini@asuiud.sanita.fvg.it Received October 2, 2017 Accepted April 13, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2x6iKrq

Ultrasound-guided single injection versus continuous sciatic nerve blockade on pain management and mobilisation after total knee arthroplasty (CoSinUS trial): A randomised, triple-blinded controlled trial

BACKGROUND Combining continuous femoral nerve blockade with single injection sciatic nerve blockade is standard peripheral nerve block practice for total knee arthroplasty (TKA) during the first 24 postoperative hours. OBJECTIVES To assess the analgesic benefits and mobilisation capability of continuous sciatic blockade in conjunction with continuous femoral nerve blockade for 72 h after arthroplasty. DESIGN Randomised, triple-blinded controlled trial. SETTING Single-Centre, German University Hospital. PATIENTS In total, 50 patients receiving continuous femoral nerve blockade (5 ml h−1 ropivacaine 0.2%) for TKA under general anaesthesia. INTERVENTIONS Patients were randomised to receive a sciatic nerve catheter with an initial dose of 10 ml ropivacaine 0.2% followed by either continuous double-blinded application of 5 ml h−1 ropivacaine 0.2% (CO) or 5 ml h−1 saline infusion (SIN). MAIN OUTCOME Measures primary endpoint: cumulative morphine consumption until 48 h postoperatively. Further endpoints included morphine consumption, pain scores, mobilisation, dynamometry until postoperative day 3. RESULTS Median [25th to 75th percentiles] cumulative morphine consumption at postoperative day 2 differed significantly between groups (CO 15 mg [11 to 25] versus SIN, 43 mg [27 to 67.5, P 

https://ift.tt/2GJPbvd

Physical decline and its implications in the management of oesophageal and gastric cancer: a systematic review

Abstract

Purpose

The management of oesophageal and gastric cancer can cause significant physical decline, impacting on completion rates and outcomes. This systematic review aimed to (i) determine the impact of chemotherapy, chemoradiotherapy and surgery on physical function; (ii) identify associations between physical function and post-operative outcomes; and (iii) examine the effects of rehabilitation on physical function.

Methods

We included randomised controlled trials (RCT), non-RCTs of interventions and cohort studies that measured physical function by objective means in patients with oesophageal or gastric cancer. EMBASE, PubMed, CINAHL, Cochrane Library, SCOPUS, PEDro and the WHO Trial Registry were searched up to June 2016. Risk of bias assessment was performed using a suite of validated tools.

Results

Twenty-five studies involving 1897 participants were included. A meta-analysis was not indicated due to the heterogeneity of the literature. Significant reductions in physical function occur in patients undergoing neoadjuvant treatment and in the first 3 months post-resection. Lower pre-operative exercise capacity is associated with an increased risk of post-operative pulmonary complications (PPCs). Evidence to support exercise prehabilitation and rehabilitation in these treatment pathways is currently lacking.

Conclusions

Chemotherapy, chemoradiation and surgery lead to reduced physical function in patients with oesophageal and gastric cancer. High quality evidence is lacking to prove the benefit of interventions that improve physical function through the treatment pathway and in recovery, and well-designed studies are required. This review was limited due to the heterogeneity of the literature, high risk of bias in some articles and the lack of high quality research encompassing sufficient time points in the patient journey.

Implications for Cancer Survivors

Curative treatment for oesophago-gastric cancer can negatively impact on physical function. Rehabilitation programmes have considerable potential to enhance physical function across the oesophago-gastric cancer journey.

https://ift.tt/2GIEqcA

Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches

Abstract

Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Therefore it is an appropriate target for diagnostic and therapy of prostate cancer and its metastases. This article discusses several articles on radionuclide treatments in prostate cancer and the results on PSMA therapy with either beta or alpha emitters as a salvage therapy.

https://ift.tt/2x8bD1I

Involvement of the CB 2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212–2 in renal cell carcinoma

Abstract

Background

The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB₁ and CB₂), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB₁ and CB₂ receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB₁ and CB₂ receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212–2 (WIN-55)] in RCC cell lines.

Methods

Human RCC cell lines were used for this study. The CB₁ and CB₂ gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB₁ and CB₂ receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB₁ and CB₂ receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells.

Results

The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB₂ receptor as compared to CB₁ in RCC cells. Immunocytochemical staining also confirmed the expression of the CB₁ and CB₂ proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB₂ agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis.

Conclusions

This study elucidated the involvement of CB₂ in the in vitro inhibition of RCC cells, and future applications of CB₂ agonists in the prevention and management of RCC are discussed.

https://ift.tt/2LnqxEc

The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer

Abstract

Background

CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels.

Methods

The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFRβ was established in MDA-MB-231 cells to detect CDCP1 upon WHF treatment. Immunohistochemical staining was used to detect the expression of CDCP1 and PDGFRβ in TNBC clinical samples.

Results

We discovered that PDGF-BB-mediated activation of PDGFRβ increases CDCP1 protein expression through the downstream activation of ERK1/2. Inhibition of ERK1/2 activity reduced per se CDCP1 expression, evidence strengthening its role in CDCP1 expression regulation. Knock-down of PDGFRβ in TNBC cells impaired CDCP1 increase induced by WHF treatment, highlighting the role if this receptor as a central player of the WHF-mediated CDCP1 induction. A significant association between CDCP1 and PDGFRβ immunohistochemical staining was observed in TNBC specimens, independently of CDCP1 gene gain, thus corroborating the relevance of the PDGF-BB/PDGFRβ axis in the modulation of CDCP1 expression.

Conclusion

We have identified PDGF-BB/PDGFRβ–mediated pathway as a novel player in the regulation of CDCP1 in TNCBs through ERK1/2 activation. Our results provide the basis for the potential use of PDGFRβ and ERK1/2 inhibitors in targeting the aggressive features of CDCP1-positive TNBCs.

https://ift.tt/2LqivKP

Conversation with Elizabeth Jaffee: An Immuno-Oncology Update

Decades of basic research in immunotherapy has resulted in dramatically improved cancer treatments for patients with tumors with high mutational burdens. The next challenge is to understand how to attack cancers with fewer mutations.

https://ift.tt/2IIOOTF

Spanish National Oncological Research Center (CNIO): a bibliometric portrait

Abstract

Introduction

Madrid's CNIO (Spanish National Oncological Research Center) ranks among the three first institutions in the world, specifically dedicated to cancer research. CNIO research mainly focuses on three aspects: use of stem cells to fix problematic cancer damage, searches for genes that cause cancer disease, and use of drug design to manage oncological disorders.

Objectives

The main goal of this study is to determine the effectiveness of the 'translation' of basic discoveries generated at this cancer research center, into new interventions aimed at preventing and treating various types of cancer, with bibliometric criteria.

Methods

A corpus of published articles and citations received by CNIO between 1998 and 2016 has been retrieved from the Web of Science (WoS) database. Bibliometric indicators considered here are: citation practices, use of journals on the basis of their impact factors, scientific literature citing CNIO publications, and international connectedness of CNIO researchers.

Results

A total of 3510 articles were published by CNIO between 1998 and 2016, 23% of which in journals with impact factors between 10 and 15 and above 15. Along the same period, the institution received 135,769 citations published in more than 5800 journals, where the most important citing journals were the Plos One with 3.6% of all the citing articles, Oncotarget with 1.8%, and Scientific Reports with 1.2%. The highest number of citations was 18,005 in 2007; in terms of average citation rate, the first ranked CNIO research program was in the area of experimental therapeutics (77.79%), followed by molecular oncology (68.1%). This position was provided by the active growth in citation to the articles whose themes are related to the problems of the consequences of the design of preclinical drug candidates and the study of oncological disorders.

Conclusions

From this study on a number of bibliometric characteristics of the Spanish National Oncological Research Center (CNIO), we conclude that the publication activity (since 2006 its scientific production has increased in about 83%), the number of high-quality journals used per year, the high influence, and impact of the journals and organizations citing the institution, consolidate its image as a top-notch oncological research center.

https://ift.tt/2kkfpvA

Management of patients with implanted cardiac devices during radiotherapy: results of a Spanish survey in radiation oncology departments

Abstract

Background

There is an increasing number of patients with cardiac implantable electronic devices (CIED), either pacemakers or defibrillators, who are receiving a course of radiotherapy. Several guidelines have been published by national societies, but no Spanish national guidelines for management of these patients have been published. More importantly, national clinical practice regarding these patients is not standardised.

Materials and methods

Members of the Spanish Breast Cancer Radiation Oncology Group (GEORM in Spanish) were surveyed through an online questionnaire on behalf of the Spanish radiation oncology departments.

Results

Only 39.3% of the Spanish radiation oncology departments have policies aimed at CIED carrier patients. Regardless of that, 96.4% of those who responded to the survey refer these patients to their Cardiology department before the start of the course of radiotherapy, and 17.8% of respondents said to manipulate the CIED without any cardiology department direction. A wide range of responses was obtained related to concepts such as "distance from the irradiation field to the CIED" or "safe accumulated doses".

Conclusions

Our results demonstrate the need for national guidelines for CIED patients and the need to promote educational activities addressed to standardise clinical management of these patients in the radiation oncology departments.

https://ift.tt/2s53YLW

Spanish National Oncological Research Center (CNIO): a bibliometric portrait

Abstract

Introduction

Madrid's CNIO (Spanish National Oncological Research Center) ranks among the three first institutions in the world, specifically dedicated to cancer research. CNIO research mainly focuses on three aspects: use of stem cells to fix problematic cancer damage, searches for genes that cause cancer disease, and use of drug design to manage oncological disorders.

Objectives

The main goal of this study is to determine the effectiveness of the 'translation' of basic discoveries generated at this cancer research center, into new interventions aimed at preventing and treating various types of cancer, with bibliometric criteria.

Methods

A corpus of published articles and citations received by CNIO between 1998 and 2016 has been retrieved from the Web of Science (WoS) database. Bibliometric indicators considered here are: citation practices, use of journals on the basis of their impact factors, scientific literature citing CNIO publications, and international connectedness of CNIO researchers.

Results

A total of 3510 articles were published by CNIO between 1998 and 2016, 23% of which in journals with impact factors between 10 and 15 and above 15. Along the same period, the institution received 135,769 citations published in more than 5800 journals, where the most important citing journals were the Plos One with 3.6% of all the citing articles, Oncotarget with 1.8%, and Scientific Reports with 1.2%. The highest number of citations was 18,005 in 2007; in terms of average citation rate, the first ranked CNIO research program was in the area of experimental therapeutics (77.79%), followed by molecular oncology (68.1%). This position was provided by the active growth in citation to the articles whose themes are related to the problems of the consequences of the design of preclinical drug candidates and the study of oncological disorders.

Conclusions

From this study on a number of bibliometric characteristics of the Spanish National Oncological Research Center (CNIO), we conclude that the publication activity (since 2006 its scientific production has increased in about 83%), the number of high-quality journals used per year, the high influence, and impact of the journals and organizations citing the institution, consolidate its image as a top-notch oncological research center.

https://ift.tt/2kkfpvA

Management of patients with implanted cardiac devices during radiotherapy: results of a Spanish survey in radiation oncology departments

Abstract

Background

There is an increasing number of patients with cardiac implantable electronic devices (CIED), either pacemakers or defibrillators, who are receiving a course of radiotherapy. Several guidelines have been published by national societies, but no Spanish national guidelines for management of these patients have been published. More importantly, national clinical practice regarding these patients is not standardised.

Materials and methods

Members of the Spanish Breast Cancer Radiation Oncology Group (GEORM in Spanish) were surveyed through an online questionnaire on behalf of the Spanish radiation oncology departments.

Results

Only 39.3% of the Spanish radiation oncology departments have policies aimed at CIED carrier patients. Regardless of that, 96.4% of those who responded to the survey refer these patients to their Cardiology department before the start of the course of radiotherapy, and 17.8% of respondents said to manipulate the CIED without any cardiology department direction. A wide range of responses was obtained related to concepts such as "distance from the irradiation field to the CIED" or "safe accumulated doses".

Conclusions

Our results demonstrate the need for national guidelines for CIED patients and the need to promote educational activities addressed to standardise clinical management of these patients in the radiation oncology departments.

https://ift.tt/2s53YLW

Pulse actinomycin D as first-line treatment of low-risk post-molar non-choriocarcinoma gestational trophoblastic neoplasia

Abstract

Background

Little data exists predicting the resistance to actinomycin D (Act-D) single-agent for gestational trophoblastic neoplasia (GTN). The objective was to determine the overall success of pulse Act-D and the factors predictive of resistance to pulse Act-D in the treatment of low-risk, non-choriocarcinoma post-molar GTN.

Methods

From January 2013 to October 2016, according to the FIGO criteria for the diagnosis of post-molar disease and the FIGO risk-factor scoring system for GTN, a total of 135 patients with post-molar non-choriocarcinoma GTN who were chemotherapy-naive with a FIGO score < 7 were treated with single-agent pulse Act-D as a first-line regimen, in Peking Union Medical College Hospital. The pulse Act-D regimen is defined as 1.25 mg/m² (max 2 mg) IV push every other week. All patients were followed until May 2017. Epidemiological and clinical data were compared between patients with remission and resistance to Act-D to determine predictive factors by univariate and multivariate analysis.

Results

Ninety-six of 135 patients (71.1%) achieved complete remission after first-line chemotherapy of pulse Act-D. In multivariate analysis, existing invasive uterine lesions observed by pre-chemotherapy transvaginal ultrasound (odds ratio [OR] 7.5, 95% confidence intervals [CI] 2.7–20.8), FIGO score ≥ 5 (OR 15.2, 95% CI 1.5–156.1) and pre-chemotherapy levels of β-hCG ≥ 4000 IU/L (OR 3.1, 95% CI 1.2–8.3) were independent high-risk factors predicting resistance to pulse Act-D as single-agent chemotherapy. During follow-up, no relapse, treatment-associated serious adverse events, or death occurred.

Conclusions

As first-line chemotherapy, pulse Act-D was effective and tolerable for patients with low-risk post-molar non-choriocarcinoma. Existing invasive uterine lesions observed by pre-chemotherapy transvaginal ultrasound, a FIGO score ≥ 5, and pre-chemotherapy levels of β-hCG ≥ 4000 IU/L were independent factors for resistance to pulse Act-D.

https://ift.tt/2s5M6jT

Carbonic anhydrase related protein expression in astrocytomas and oligodendroglial tumors

Abstract

Background

Carbonic anhydrase related proteins (CARPs) VIII, X and XI functionally differ from the other carbonic anhydrase (CA) enzymes. Structurally, they lack the zinc binding residues, which are important for enzyme activity of classical CAs.

The distribution pattern of the CARPs in fetal brain implies their role in brain development. In the adult brain, CARPs are mainly expressed in the neuron bodies but only weaker reactivity has been found in the astrocytes and oligodendrocytes. Altered expression patterns of CARPs VIII and XI have been linked to cancers outside the central nervous system.

There are no reports on CARPs in human astrocytomas or oligodendroglial tumors. We wanted to assess the expression of CARPs VIII and XI in these tumors and study their association to different clinicopathological features and tumor-associated CAs II, IX and XII.

Methods

The tumor material for this study was obtained from surgical patients treated at the Tampere University Hospital in 1983–2009. CARP VIII staining was analyzed in 391 grade I-IV gliomas and CARP XI in 405 gliomas.

Results

CARP VIII immunopositivity was observed in 13% of the astrocytomas and in 9% of the oligodendrogliomas. Positive CARP XI immunostaining was observed in 7% of the astrocytic and in 1% of the oligodendroglial tumor specimens. In our study, the most benign tumors, pilocytic astrocytomas, did not express CARPs at all. In WHO grade II-IV astrocytomas, CARPs were associated with molecular events related to more benign behavior, which was the case with CARP VIII in oligodendrogliomas and oligoastrocytomas as well.

Conclusions

The study observations suggest that the CARPs play a role in tumorigenesis of diffusively infiltrating gliomas. Furthermore, the molecular mechanisms beneath the cancer promoting qualities of CARPs have not yet been discovered. Thus, more studies concerning role of CARPs in oncogenesis are needed.

https://ift.tt/2J1jx1t

ASH 2017: highlights in chronic myeloid leukemia

Summary

Despite remarkable achievements in the management of chronic myeloid leukemia (CML), there remain a number of challenges in the field. At the American Society of Hematology (ASH) Meeting 2017 several presentations addressed current problems around the topics CML stem cells, progression of CML into blast crisis (BC), and personalized treatment.

https://ift.tt/2GK2P1o

Current and future developments of immunotherapy in lung cancer

Summary

Lung cancer is the leading cause of cancer-associated death worldwide. Traditionally, lung cancer is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). While the prognosis of metastatic SCLC has remained dismal, the outcome of advanced NSCLC has improved over the last decades mainly by the improved molecular characterization of the disease and the introduction of targeted therapies in well-defined subpopulations. However, even in localized or locally advanced lung cancer many patients eventually have a relapse and will die of their disease. Therefore, novel treatment approaches are urgently needed. Lung cancer is generally characterized by high frequencies of genetic and epigenetic alterations resulting in tumor-associated antigens which are potential targets of cytotoxic T cells. Immune checkpoint inhibitors (ICIs) have shown to re-activate and improve this specific T cell response. Several clinical trials have demonstrated meaningful response rates, sustained clinical benefit with encouraging survival rates and good tolerability in advanced NSCLC and have established ICIs as a new standard of care in different indications. This article summarizes the current evidence for ICIs in early and advanced NSCLC as well as in SCLC. Furthermore, current data and ongoing clinical trials on combination therapies are discussed as well as challenges of immunotherapy in lung cancer patients.

https://ift.tt/2kksaXe

Spontaneous acalculous gallbladder perforation post-cardiac transplantation

Spontaneous acalculous gallbladder perforation is a rare radiological and clinical phenomenon with life-threatening consequences. In the setting of recent cardiac transplantation, the condition is increasingly uncommon and difficult to diagnose preoperatively. We describe a case of spontaneous acalculous gallbladder perforation in an intensive care unit (ICU) patient, most likely due to a combination of cardiac transplantation and immunosuppression. There are no such documented cases in the literature with an established preoperative diagnosis, to the best of our knowledge. Abdominal CT and targeted ultrasound proved complimentary in establishing the diagnosis, facilitating successful and timely treatment with urgent cholecystectomy.

https://ift.tt/2IDtAdL

Stuck guidewire due to soft tissue imposition: a rare complication of central line catheter placement

Central venous catheter (CVC) placement is a commonly done procedure but is associated with a few complications, and guidewire-related complications are one of them. In our case after induction of general anaesthesia, we planned to insert a CVC in the right internal jugular vein under ultrasound guidance. After the insertion of the introducer needle, when we tried to insert the guidewire, it got stuck and was neither moving forward nor in a backward direction. Too much force was not applied to remove the guidewire as it might have caused shearing of the guidewire and further complicated the picture. This problem was solved by simultaneous withdrawal of guidewire along with the needle, and on examination we found soft tissue debris lodged within the lumen which was preventing the guidewire movement in both directions. So, it is suggested that guidewire should be removed along with needle as a single unit if it is required.

https://ift.tt/2s4SVCs

Neuromyelitis optica spectrum disorder presenting as rhomboencephalitis

Rhomboencephalitis, at least in its acute phase, is often a severely disabling syndrome, and can be life threatening. A range of underlying conditions can lead to this clinical syndrome. Rapid diagnosis to initiate treatment early is key to a beneficial outcome. We report the case of a 22 year old Afro-Caribbean woman, who presented with a two -week history of walking difficulties, upper limb incoordination and slurred speech. Her brainstem function deteriorated at pace, and she developed hypersomnia. A broad diagnostic approach led to prophylactic treatment for the most common infectious causes. This did not improve her symptoms. Non-infectious inflammatory causes were therefore considered and plasma exchange treatment was initiated leading to marked improvement within days. Screening for autoimmune conditions confirmed aquaporin-4 positive neuromyelitis optica spectrum disorder (NMOSD) as the underlying cause. Immunotherapy with rituximab was started. So far, no relapse has been observed. While the definition of NMOSD continues to be refined, aquaporin-4 testing should be considered early in patients presenting with rhomboencephalitis who do not respond to antibiotic and antiviral treatment. Vigilance and early intervention are key to limit morbidity and mortality from NMOSD.

https://ift.tt/2IFQJfN

Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention

Abstract

Purpose

To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy.

Methods

Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses.

Results

The median follow-up was 35 months (range 3–143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16–357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T‑category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (<grade 3).

Conclusion

Re-RT with 45 Gy (1.8 Gy per fraction) for partial breast or mastectomy scar after the second surgery resulted in high local control rates and tolerable skin toxicity.

https://ift.tt/2KNY8Gi

Incidence and survival of primary central nervous system lymphoma (PCNSL): results from the Girona cancer registry (1994–2013)

https://ift.tt/2GKeEET

Incidence and survival of primary central nervous system lymphoma (PCNSL): results from the Girona cancer registry (1994–2013)

https://ift.tt/2GKeEET

Downregulation of STARD8 in gastric cancer and its involvement in gastric cancer progression

https://ift.tt/2rWJ2rb

Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†

https://ift.tt/2KIWzta

Transition

https://ift.tt/2GIXEif

Editorial

https://ift.tt/2x7p9Tg

Breast cancer metastasis through the lympho-vascular system

Abstract

Breast cancer metastasizes through the lymphovascular system to the regional lymph nodes in the axilla and to both visceral and non-visceral sites. Renewed interest in the route by which tumor cells gain access to blood and lymphatic capillaries are the subject of research at mechanical, anatomic, pathologic, genetic, epidemiologic and molecular levels. Two papers presented at the 7th International Symposium on Cancer Metastasis in San Francisco showed tumor cells entering the systemic circulation through the sentinel lymph node. This information challenges the current paradigm where clinicians believe that access is gained through intra- and peri-tumoral blood vessels and that metastasis to axillary lymph nodes is an interesting epi-phenomenon. The sentinel lymph node era has changed the modern surgical approach to the axilla and the basis of this change is summarized in this paper. A new approach to the management of axillary metastases after systemic therapy relies on determining whether there is a complete pathologic response; if no tumor is found in the previously biopsied node, a complete axillary lymph node dissection may be avoided. African American women seem to inherit a trait from West African ancestors and tend to develop more lethal types of breast cancer. These tumors may have a molecular machinery that enhances their ability to metastasize to visceral sites and future research may unearth the mechanisms for this phenomenon.

https://ift.tt/2s4HmLr

Right Versus Left Colon Cancer: Resectable and Metastatic Disease

Opinion statement

Colorectal cancer does not represent a single anatomic entity and side of origin has a key impact on prognosis and response to different systemic therapies. Compared to tumours arising in left colon, right colorectal cancers rely on the activation of different molecular pathways (e.g. BRAF mutation and MSI status). From a clinical point of view, this results in a different response to anti-EGFR agents. Current guidelines suggest the use of cetuximab or panitumumab in RAS wild-type disease and left colon cancer especially for cytoreduction/conversion purposes, since the expected benefit in right colon cancer is absent or clinically modest. The prognostic role of microbiota in colorectal cancer disease deserves more clarification before being considered in common clinical practice. Screening policies could also be affected by these new acquisitions. At the moment, sidedness should be considered as a strong prognostic variable and a surrogate predictor of different activity of anti-EGFR agents in the metastatic setting. Its role in early stages of resected disease is still uncertain.

https://ift.tt/2s3Rowv

Management of Myelofibrosis-Related Cytopenias

Abstract

Purpose of Review

Cytopenias, particularly anemia, are frequently encountered in patients with myelofibrosis. Management of cytopenias in myelofibrosis can be very challenging because current therapeutic interventions are only of modest efficacy and ruxolitinib, the only approved drug for myelofibrosis, is myelosuppressive. Yet, dose optimization of ruxolitinib is important for its survival benefit in patients with advanced disease. We sought to summarize the data on treatments for cytopenias available at present and review promising agents in development and emerging strategies.

Recent Findings

The activin receptor ligand traps hold considerable promise for the treatment of anemia and could represent an attractive combination strategy with ruxolitinib. Low-dose thalidomide, which could offset both anemia and thrombocytopenia caused by ruxolitinib, represents another potential partner for ruxolitinib. The anti-fibrotic agent PRM-151 produced sustained improvements in cytopenias in some patients, and further data on this drug are eagerly awaited. Finally, several preclinical leads with translational potential are worthy of clinical investigation as strategies to halt/reverse bone marrow fibrosis and thereby improve cytopenias.

Summary

Cytopenias remain a significant hurdle in myelofibrosis management, but several novel investigational agents hold considerable promise for the future.

https://ift.tt/2KLNP5B