Head and Neck Diseases by Alexandros G.Sfakianakis: 06/04/17

Κυριακή 4 Ιουνίου 2017

Heme oxygenase-1 directly binds STAT3 to control the generation of pathogenic Th17 cells during neutrophilic airway inflammation

Abstract

Background

Specific JAK/STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO-1, a stress-inducible protein, inhibits Th17 cell differentiation and alleviates neutrophilic airway inflammation, but the responsible molecular basis remains unclear.

Methods

We employed Th17-skewing differentiation and NEA mouse models to study the role of HO-1 regulating IL-6-STAT3-RORγt/SOCS3 signaling pathway to control Th17 cell-mediated neutrophilic airway inflammation. The levels of cytokines and expressions of relative signaling molecular were measured by ELISA, western blot and qPCR, respectively. Frequency of CD4⁺IL-17A⁺, CD4⁺IL-6R⁺ and CD4⁺IL-23R⁺ cells was analyzed by FCM. The interaction between HO-1 and signaling pathway-related proteins was determined by Co-Immunoprecipitation and western blot.

Results

Here, we show that hemin-induced HO-1 over-expression is required to mediate this process. Specifically, HO-1 decreased STAT3 phosphorylation but not IL-6R/IL-23R expression or JAK1/JAK2 activation in CD4⁺ T cells. The effect was accompanied by co-inhibition of SOCS3, a negative feedback factor of STAT3 activation. HO-1 bound to three domains on STAT3, (DNA-binding, linker and transactivation domains) to directly regulate STAT3 activation. Conversely, either forced expression of a constitutively active STAT3 mutant or application of small interfering RNA (siRNA) for HO-1 reversed these effects.

Conclusions

Our data suggest that HO-1 exerts its inhibitory effect on Th17 cell differentiation by directly associating and blocking STAT3 phosphorylation. We speculate that hemin may be a potential therapeutic candidate for the treatment of other types of immune and pulmonary inflammatory-related diseases.

http://ift.tt/2sGhPXC

Heme oxygenase-1 directly binds STAT3 to control the generation of pathogenic Th17 cells during neutrophilic airway inflammation

Abstract

Background

Methods

Results

Conclusions

http://ift.tt/2sGhPXC

Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer’s disease

Publication date: Available online 3 June 2017
Source:Progress in Neurobiology
Author(s): Hassan Bukhari, Annika Glotzbach, Katharina Kolbe, Gregor Leonhardt, Christina Loosse, Thorsten Müller
Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus. As a consequence nuclear −potentially toxic- structures emerge, which were recently found to a high extent in human AD tissue and thus, may contribute to neurodegeneration. Relevant for the signaling machinery are modifications at the very C-terminal end of the precursor protein, the APP intracellular domain (AICD). In this review we update the knowledge on mechanisms on AICD referring to our 2008 article: The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics—Relevance for Alzheimer's disease [1]. We summarize how AICD is generated and degraded, we describe its intramolecular motifs, translational modifications, and how those as well as APP dimerization influence AICD generation and function. Moreover, we resume the AICD interactome and elucidate AICDs involvement in nuclear signaling, transcriptional regulation, cell death, DNA repair and cell cycle re-entry and we give insights in its physiological function. Results are summarized in the comprehensive poster "The world of AICD".

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Ethmoid malformation associated with pediatric nasal polyposis and allergic fungal sinusitis

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Abstract

A 17-year-old female with allergic fungal sinusitis and nasal polyposis presented with epistaxis in the emergency room. On examination, right-sided proptosis and irregular nasal obstruction were observed in the right nasal cavity. CT imaging revealed massive right-sided polyposis and significant ipsilateral malformation with boney architecture preservation of the ethmoidal labyrinth and lamina papyracea. The patient was treated surgically with symptomatic improvement. These findings indicate a unique malformation of the ethmoid while the patient was in development. To the authors' knowledge, this anatomical malformation has not been previously described in the literature. Physicians should implement diagnostic procedures early if nasal polyposis and allergic fungal sinusitis is suspected in pediatric patients, especially with periocular involvement, to mitigate the risk of boney malformations of the sinuses.

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Atypical presentation of sigmoid carcinoma

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Abstract

Colorectal carcinoma is common worldwide and its metastasis represents the main cause of mortality related to the disease. Inguinal metastization of this tumor has been considered almost impossible, owing to colon anatomy and its cranial lymphatic drainage. We report the case of a 63-year-old man submitted to laparoscopical sigmoid colectomy, due a sigmoid adenocarcinoma. During follow-up, a right inguinal lymphadenopathy with 25 mm was detected. Fine needle aspiration biopsy revealed that it was a colon adenocarcinoma metastasis, and thus the patient underwent an inguinal lymphadenectomy. The histological study confirmed metastatic adenocarcinoma of the colon and the patient was submitted to 5-fluouracil and oxaliplatin chemotherapy. This case coursed with metastasis to the right inguinal region; although, the pathophysiological mechanism involved is difficult to understand. There are no solid data for the management of these patients. Inguinal lymphadenectomy and chemotherapy, proved to be effective.

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Primary extrahepatic bile duct neuroendocrine tumor with obstructive jaundice masquerading as a Klatskin tumor

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Abstract

Neuroendocrine tumors (NETs) of the extrahepatic bile duct are extremely rare and reported infrequently in the literature. These tumors are difficult to diagnose preoperatively, and the prognosis is variable, often determined by extent of disease, tumor grade and resectability. This case report presents a 45-year-old male with history of biliary obstruction relieved by endobiliary stents with common hepatic duct stricture just above the cystic duct, thought to be a Klatskin's cholangiocarcinoma. Final pathological examination was consistent with primary extrahepatic NET.

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Laparoscopic harvest of the gastro-omental free flap for reconstruction after total pharyngolaryngectomy: Operative technique

Abstract

Circumferential defects following salvage pharyngolaryngectomy present significant challenges in reconstructive surgery. The gastro-omental free flap has been shown to reduce the incidence of major fistula and catastrophic complications. The current technique for harvest of the flap requires laparotomy, which is potentially associated with significant post-operative complications. Laparoscopic harvest of the gastro-omental free flap can negate some of the risks associated with open surgery. We describe here the operative technique for laparoscopic gastro-omental free flap harvest for use in reconstruction following total pharyngolaryngectomy. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

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Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy

Abstract

Background

We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma.

Methods

Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases.

Results

We reviewed 135 records (120 men and 15 women; age range, 36–84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, >3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS.

Conclusion

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Multiple single nucleotide polymorphism analysis and association of specific genotypes in FHIT, SAMD4A, and ANKRD17 in Indian patients with oral cancer

Abstract

Background

Oral cancer has a high incidence primarily because of tobacco chewing habits. However, a small proportion of habitués develop oral cancer, implying a role for genomic variants in its susceptibility.

Methods

Thirteen single nucleotide polymorphisms (SNPs) in an Indian cohort comprising patients with oral cancer (n = 500) and healthy controls (n = 500) were genotyped using allelic discrimination real-time polymerase chain reaction (PCR).

Results

Prevalence of SNPs rs11130760, rs1957358, rs2306058, rs4883543, rs12637722, rs1457115, rs2353292, rs709821, rs2194861, rs4789378, rs3827538, rs2667552, and rs2886093 was determined in the Indian cohort. A significant association of rs11130760 GG (odds ratio [OR] 1.41; 95% confidence interval [CI] 1.08-1.84) and rs1957358 TT (OR 1.44; 95% CI 1.10-1.90) indicated increased risk; whereas rs1957358 TC (OR 0.67; 95% CI 0.53-0.87) and rs2306058 CT (OR 0.72; 95% CI 0.56-0.93) reflected decreased risk. The SNP rs11130760 wild-type (WT) allele G indicated an increased risk for oral cancer (OR 1.38; 95% CI 1.09-1.73), whereas SNP allele T indicated a decreased risk (OR 0.73; 95% CI 0.58-0.92) for oral cancer.

Conclusion

Our study identified SNPs with susceptibility to oral cancer in high-risk populations.

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Functional outcomes of fasciocutaneous free flap and pectoralis major flap for salvage total laryngectomy

Abstract

Background

Pectoralis major muscle flaps (PMMFs) and fasciocutaneous free flaps (FFFs) are commonly used for reconstruction of the surgical defect after salvage total laryngectomy. This study compared swallowing function in patients who underwent reconstruction with either PMMF or FFF.

Methods

This study was based on a retrospective cohort of patients treated at the CHU de Québec between January 2000 and March 2015. Demographics, chemoradiation data, surgical protocol, pathologic results, complications, evolution, esophageal dilation, diet intake, and feeding tube dependence were documented.

Results

A total of 126 patients were analyzed (93 PMMFs and 33 FFFs). Of the patients who received PMMFs, 38.7% had a limited oral intake compared to 15.2% of patients who received FFFs (odds ratio [OR] 3.54; 95% confidence interval [CI] 1.25-9.99; P = .02). The need for esophageal dilation tended to be greater for PMMF patients (25% vs 9%; OR 3.38; 95% CI 0.94-12.13; P = .06). Complication rates were similar.

Conclusion

The FFF reconstruction led to better results in terms of swallowing function than PMMF reconstruction.

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AHNS Series – Do you know your guidelines? Lip cancer

Abstract

Background

Lip cancer is one of the most curable primary head and neck malignancies, as the prominent location typically lends to an early diagnosis. The incidence of lip cancer varies by sex, ethnicity, and region, but is estimated to be up to 2.5/100 000 in the United States (squamous cell carcinoma [SCC]).

Methods

This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of lip cancer.

Results

Resection of lip cancer with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy.

Conclusion

Lip cancer remains highly curable when diagnosed at an early stage. A multidisciplinary approach is crucial to treating patients with advanced-stage lip cancer.

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Morphologic and topographic radiologic features of human papillomavirus–related and unrelated oropharyngeal carcinoma

Abstract

Background

The purpose of this study was to compare the clinicoradiologic characteristics of human papillomavirus (HPV)-related (HPV-positive) and HPV-unrelated (HPV-negative) oropharyngeal carcinoma (OPC).

Methods

Primary tumor and lymph node features of HPV-positive and HPV-negative OPCs from 2008 to 2013 were compared on pretreatment CT/MRI. Intrarater/interrater concordance was assessed. Multivariable analyses identified factors associated with HPV-positivity to be used in nomogram construction.

Results

Compared to HPV-negative (n = 194), HPV-positive (n = 488) tumors were more exophytic (73% vs 63%; p = .02) with well-defined border (58% vs 47%; p = .033) and smaller axial dimensions; lymph node involvement predominated (89% vs 69%; p < .001) with cystic appearance (45% vs 32%; p = .009) but similar topography. Intrarater/interrater concordance varied (fair to excellent). Nomograms combining clinical (age, sex, smoking pack-years, subsite, T/N classification) and/or radiologic (nonnecrotic tumor and cystic lymph node) features were used to weigh the likelihood of HPV-driven tumors (area under the curve [AUC] = 0.84).

Conclusion

HPV-positive OPC has different radiologic tumor (exophytic/well-defined border/smaller axial dimension) and lymph node (cystic) features but similar lymph node topography.

http://ift.tt/2qWpzn6

Laparoscopic harvest of the gastro-omental free flap for reconstruction after total pharyngolaryngectomy: Operative technique

Abstract

http://ift.tt/2rrQ47p

Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy

Abstract

Background

We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma.

Methods

Results

Conclusion

http://ift.tt/2qWPMC4

Multiple single nucleotide polymorphism analysis and association of specific genotypes in FHIT, SAMD4A, and ANKRD17 in Indian patients with oral cancer

Abstract

Background

Oral cancer has a high incidence primarily because of tobacco chewing habits. However, a small proportion of habitués develop oral cancer, implying a role for genomic variants in its susceptibility.

Methods

Results

Conclusion

Our study identified SNPs with susceptibility to oral cancer in high-risk populations.

http://ift.tt/2rrQ33l

Functional outcomes of fasciocutaneous free flap and pectoralis major flap for salvage total laryngectomy

Abstract

Background

Methods

Results

Conclusion

The FFF reconstruction led to better results in terms of swallowing function than PMMF reconstruction.

http://ift.tt/2qW7KVk

AHNS Series – Do you know your guidelines? Lip cancer

Abstract

Background

Methods

This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of lip cancer.

Results

Resection of lip cancer with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy.

Conclusion

Lip cancer remains highly curable when diagnosed at an early stage. A multidisciplinary approach is crucial to treating patients with advanced-stage lip cancer.

http://ift.tt/2rrVm2P

Morphologic and topographic radiologic features of human papillomavirus–related and unrelated oropharyngeal carcinoma

Abstract

Background

The purpose of this study was to compare the clinicoradiologic characteristics of human papillomavirus (HPV)-related (HPV-positive) and HPV-unrelated (HPV-negative) oropharyngeal carcinoma (OPC).

Methods

Results

Conclusion

HPV-positive OPC has different radiologic tumor (exophytic/well-defined border/smaller axial dimension) and lymph node (cystic) features but similar lymph node topography.

http://ift.tt/2qWpzn6

Issue Information

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Issue Information

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Plant genetics: Branching out for crop improvement

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Pain and Opioids in Cancer Care: Benefits, Risks, and Alternatives.

Pain and Opioids in Cancer Care: Benefits, Risks, and Alternatives.

Am Soc Clin Oncol Educ Book. 2017;37:705-713

Authors: Bennett M, Paice JA, Wallace M

Abstract
Pain remains common in the setting of malignancy, occurring as a consequence of cancer and its treatment. Several high-quality studies confirm that more than 50% of all patients with cancer experience moderate to severe pain. The prevalence of pain in cancer survivors is estimated to be 40%, while close to two-thirds of those with advanced disease live with pain. Progress has occurred in the management of cancer pain, yet undertreatment persists. Additionally, new challenges are threatening these advances. These challenges are numerous and include educational deficits, time restraints, and limited access to all types of care. New challenges to access are occurring as a result of interventions designed to combat the prescription drug abuse epidemic, with fewer clinicians willing to prescribe opioids, pharmacies reluctant to stock the medications, and payers placing strict limits on reimbursement. A related challenge is our evolving understanding of the risks of long-term adverse effects associated with opioids. And reflective of the opioid abuse epidemic affecting the general population, the potential for misuse or abuse exists in those with cancer. Guidelines have been developed to support oncologists when prescribing the long-term use of opioids for cancer survivors. The challenges surrounding the use of opioids, and the need for safe and effective alternative analgesics, are leading to intense interest in the potential benefits of cannabis for cancer-related pain. Oncologists are faced with questions regarding the types of cannabis available, differences between routes of administration, data concerning safety and efficacy, and legal and regulatory dynamics.

PMID: 28561731 [PubMed - in process]

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Pharmacokinetic/Pharmacodynamic Modeling for Drug Development in Oncology.

Pharmacokinetic/Pharmacodynamic Modeling for Drug Development in Oncology.

Am Soc Clin Oncol Educ Book. 2017;37:210-215

Authors: Garralda E, Dienstmann R, Tabernero J

Abstract
High drug attrition rates remain a critical issue in oncology drug development. A series of steps during drug development must be addressed to better understand the pharmacokinetic (PK) and pharmacodynamic (PD) properties of novel agents and, thus, increase their probability of success. As available data continues to expand in both volume and complexity, comprehensive integration of PK and PD information into a robust mathematical model represents a very useful tool throughout all stages of drug development. During the discovery phase, PK/PD models can be used to identify and select the best drug candidates, which helps characterize the mechanism of action and disease behavior of a given drug, to predict clinical response in humans, and to facilitate a better understanding about the potential clinical relevance of preclinical efficacy data. During early drug development, PK/PD modeling can optimize the design of clinical trials, guide the dose and regimen that should be tested further, help evaluate proof of mechanism in humans, anticipate the effect in certain subpopulations, and better predict drug-drug interactions; all of these effects could lead to a more efficient drug development process. Because of certain peculiarities of immunotherapies, such as PK and PD characteristics, PK/PD modeling could be particularly relevant and thus have an important impact on decision making during the development of these agents.

PMID: 28561730 [PubMed - in process]

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European/U.S. Comparison and Contrasts in Ovarian Cancer Screening and Prevention in a High-Risk Population.

European/U.S. Comparison and Contrasts in Ovarian Cancer Screening and Prevention in a High-Risk Population.

Am Soc Clin Oncol Educ Book. 2017;37:124-127

Authors: Mourits MJ, de Bock GH

Abstract
The history of screening and prevention of ovarian cancer among high-risk women in the United States and Europe is one of mutual inspiration, with researchers learning from each others' findings and insights and collaborating with investigators from both sides of the Atlantic ocean. Examples of simultaneous and joint development of knowledge and scientific points of view include the paradigm shift from ovarian to fallopian tube high-grade serous cancer and the cessation of simultaneous adoption of ovarian cancer screening by clinicians in both the United States and Europe. Examples of joint efforts with fruitful results include international collaboration in large population-based, genome-wide association studies and in epidemiologic database studies. Research in the field of hereditary ovarian cancer is a great example of mutual inspiration and joint efforts for the purpose of improving knowledge and health care for women with hereditary ovarian cancer.

PMID: 28561729 [PubMed - in process]

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Adoptive T-Cell Therapy for Solid Tumors.

Adoptive T-Cell Therapy for Solid Tumors.

Am Soc Clin Oncol Educ Book. 2017;37:193-204

Authors: Yeku O, Li X, Brentjens RJ

Abstract
Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of immunotherapy wherein autologous T cells are genetically modified to express chimeric receptors encoding an antigen-specific single-chain variable fragment and various costimulatory molecules. Upon administration, these modified T cells traffic to, and recognize, cancer cells in an HLA-independent manner. CAR T-cell therapy has shown remarkable success in the treatment of CD-19-expressing B-cell acute lymphocytic leukemia. However, clinical gains to the same magnitude have not been reported in solid tumors. Several known obstacles to CAR T-cell therapy for solid tumors include target antigen identification, effective trafficking to the tumor, robust activation, proliferation, and in vivo cytotoxicity. Beyond these T-cell intrinsic properties, a complex and dynamic immunosuppressive tumor microenvironment in solid tumors hinders T-cell efficacy. Notable advancements in CAR design to include multiple costimulatory molecules, ligands, and soluble cytokines have shown promise in preclinical models, and some of these are currently in early-phase clinical trials. In this review, we discuss selected solid tumor malignancies and relevant preclinical data and highlight clinical trial results that are available. Furthermore, we outline some obstacles to CAR T-cell therapy for each tumor and propose strategies to overcome some of these limitations.

PMID: 28561728 [PubMed - in process]

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Social Media for Networking, Professional Development, and Patient Engagement.

Social Media for Networking, Professional Development, and Patient Engagement.

Am Soc Clin Oncol Educ Book. 2017;37:782-787

Authors: Markham MJ, Gentile D, Graham DL

Abstract
Social media has become an established method of communication, and many physicians are finding these interactive tools and platforms to be useful for both personal and professional use. Risks of social media, or barriers to its use, include perceived lack of time, privacy concerns, and the risk of damage to one's reputation by unprofessional behavior. Of the social media platforms, Twitter has become favored by physicians and other health care professionals. Although one of the most obvious uses of social media is for rapid dissemination and receipt of information, oncologists are finding that social media is important for networking through blogs, Facebook, and Twitter. These platforms also have potential for providing opportunities for professional development, such as finding collaborators through networking, participation in Twitter journal clubs, and participating in online case-based tumor boards. Social media can also be used for patient engagement, such as through participation in tweet chats. There is emerging data that patient engagement through these platforms may lead to improvement in some health-related outcomes; however, data are sparse for oncology-specific outcomes. Efforts are underway to determine how to assess how social media engagement impacts health outcomes in oncology patients.

PMID: 28561727 [PubMed - in process]

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Caring for the Older Population With Advanced Lung Cancer.

Caring for the Older Population With Advanced Lung Cancer.

Am Soc Clin Oncol Educ Book. 2017;37:587-596

Authors: Presley CJ, Reynolds CH, Langer CJ

Abstract
The management of advanced lung cancer is changing rapidly, with new drug approvals occurring almost monthly. The average age of a newly diagnosed patient with advanced lung cancer remains around age 70. Caring for the older adult with advanced cancer differs from the care of younger adults. Chronologic age often does not accurately reflect the physiologic and functional status of older adults. Selecting treatment based on age alone results in undertreatment and overtreatment of many older adults. Addressing issues such as multiple chronic conditions, polypharmacy, geriatric syndromes, and heterogeneity in functional status among an expanding menu of treatment options for advanced disease is increasingly difficult, particularly among older adults historically underrepresented in clinical trials. In this article, we highlight key issues in caring for the older adult with advanced non-small cell lung cancer and the continued need for data supporting current and emerging treatment options. Key issues include the unique challenges of managing advanced lung cancer and a summary of the current treatment evidence as they apply to the elderly lung cancer population including supportive care strategies, risk stratification, and patient-reported outcomes.

PMID: 28561726 [PubMed - in process]

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Challenges in Opening and Enrolling Patients in Clinical Trials.

Challenges in Opening and Enrolling Patients in Clinical Trials.

Am Soc Clin Oncol Educ Book. 2017;37:139-143

Authors: Vose JM, Chuk MK, Giles F

Abstract
Clinical trials are key elements of the processes that account for many of the recent advances in cancer care, including decreased mortality rates and increased survivorship; better supportive care; and improved understanding of cancer risk, prevention, and screening. This research also has led to the validation of numerous exciting new types of cancer treatments, such as molecularly targeted therapies and immunotherapies. Clinical trials, however, are becoming more and more challenging to conduct. Research programs must comply with legal and regulatory requirements that can be inefficient and costly to implement and often are variably interpreted by institutions and sponsors and sponsors' representatives, including contract research organizations. Some of these requirements are essential to protect the safety of trial participants, to promote the scientific integrity of research, or to ensure that trial conduct is efficient and adequately resourced. Such requirements are important to preserve. However, some requirements do not fulfill any of these goals and, in fact, hinder research and slow patient access to safe and effective treatments. This article discusses some of the identified issues that are slowing the process of cancer clinical trials, such as conservatively interpreted guidelines by pharmaceutical companies and contract research organizations; overprotective language for contracts; and patient protections by health systems and universities. The article also discusses possible solutions to these problems that are slowing down the cancer therapies that patients need.

PMID: 28561725 [PubMed - in process]

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Strategies to Maximize Patient Participation in Clinical Trials.

Strategies to Maximize Patient Participation in Clinical Trials.

Am Soc Clin Oncol Educ Book. 2017;37:216-221

Authors: Rubin EH, Scroggins MJ, Goldberg KB, Beaver JA

Abstract
Despite considerable interest and success in oncology drug development, the minority of patients with cancer diagnoses enroll in clinical trials. Multiple obstacles account for this low enrollment rate. An improvement in patient participation in clinical trials could increase patient access to novel and potentially promising agents, provide faster trial results, and, with implementation of rational eligibility criteria, allow for a better understanding of the drug's safety and efficacy in a heterogeneous population. We present barriers and potential solutions to maximize patient participation, including a review of the ASCO and Friends of Cancer Research (FoCR) Modernizing Eligibility Criteria Project, U.S. Food and Drug Administration (FDA) regulatory considerations, an industry perspective, and a patient perspective.

PMID: 28561724 [PubMed - in process]

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Wedge Resection Versus Anatomic Resection: Extent of Surgical Resection for Stage I and II Lung Cancer.

Wedge Resection Versus Anatomic Resection: Extent of Surgical Resection for Stage I and II Lung Cancer.

Am Soc Clin Oncol Educ Book. 2017;37:426-433

Authors: Asamura H, Aokage K, Yotsukura M

Abstract
Currently, surgery for lung cancer with curative intent consists of resection (removal) of the proper extent of lung parenchyma that bears the cancer lesion along with locoregional lymph nodes to assess possible cancer metastasis. Lobectomy, at least, is preferred with regard to the extent of parenchymal resection. The history of lung cancer surgery, which started around 1933 as pneumonectomy (resection of the entire lung on either side), can be characterized as an attempt to minimize the extent of parenchymal resection. In the early 1960s, pneumonectomy was replaced by lobectomy, which has long been respected as the standard surgical mode. However, the transition from lobectomy to a lesser resection, such as segmentectomy or wedge resection, was not recommended because of the results of a randomized trial performed by the North American Lung Cancer Study Group in the 1980s. As of now, the extent of parenchymal resection remains lobectomy, and lesser resection is indicated only for patients who have a compromised pulmonary reserve. Very recently, because of the advent of CT screening programs and improvements in imaging technology, fainter and smaller lung cancers are being discovered. For these smaller and earlier lung cancers, there is some uncertainty about whether lobectomy still should be indicated, as it is for larger tumors with a diameter of 3 cm or more. Therefore, several randomized trials are ongoing to compare lobectomy with lesser resections; endpoints are overall survival and postoperative pulmonary function. Until the results of these trials are available, lung cancer should still be removed by lobectomy rather than by limited resection, such as segmentectomy or wedge resection.

PMID: 28561723 [PubMed - in process]

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Therapeutic Bone-Modifying Agents in the Nonmetastatic Breast Cancer Setting: The Controversy and a Value Assessment.

Therapeutic Bone-Modifying Agents in the Nonmetastatic Breast Cancer Setting: The Controversy and a Value Assessment.

Am Soc Clin Oncol Educ Book. 2017;37:116-122

Authors: Gnant M, Van Poznak C, Schnipper L

Abstract
Clinical trials and meta-analyses investigating bisphosphonates as an adjuvant breast cancer therapy have shown a consistent trend, with postmenopausal women and women receiving ovarian suppression with gonadotropin-releasing hormone therapy gaining improved breast cancer outcomes with the use of adjuvant bisphosphonate therapy. The interpretation of these data is controversial, because the primary endpoints of the majority of adjuvant bisphosphonate studies have been negative. Pros and cons as well as the value of adjuvant bisphosphonate therapy are discussed here.

PMID: 28561722 [PubMed - in process]

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Managing Resistance to EFGR- and ALK-Targeted Therapies.

Managing Resistance to EFGR- and ALK-Targeted Therapies.

Am Soc Clin Oncol Educ Book. 2017;37:607-618

Authors: Lovly CM, Iyengar P, Gainor JF

Abstract
Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.

PMID: 28561721 [PubMed - in process]

http://ift.tt/2qJ5Ozj

mHealth: Mobile Technologies to Virtually Bring the Patient Into an Oncology Practice.

mHealth: Mobile Technologies to Virtually Bring the Patient Into an Oncology Practice.

Am Soc Clin Oncol Educ Book. 2017;37:144-154

Authors: Pennell NA, Dicker AP, Tran C, Jim HSL, Schwartz DL, Stepanski EJ

Abstract
Accompanied by the change in the traditional medical landscape, advances in wireless technology have led to the development of telehealth or mobile health (mHealth), which offers an unparalleled opportunity for health care providers to continually deliver high-quality care. This revolutionary shift makes the patient the consumer of health care and empowers patients to be the driving force of management of their own health through mobile devices and wearable technology. This article presents an overview of technology as it pertains to clinical practice considerations. Telemedicine is changing the way clinical care is delivered without regard for proximity to the patient, whereas nonclinical telehealth applications affect distance education for consumers or clinicians, meetings, research, continuing medical education, and health care management. Technology has the potential to reduce administrative burdens and improve both efficiency and quality of care delivery in the clinic. Finally, the potential for telehealth approaches as cost-effective ways to improve adherence to treatment is explored. As telehealth advances, health care providers must understand the fundamental framework for applying telehealth strategies to incorporate into successful clinical practice.

PMID: 28561720 [PubMed - in process]

http://ift.tt/2rsFZrj

Chronic Myeloid Leukemia: What Every Practitioner Needs to Know in 2017.

Chronic Myeloid Leukemia: What Every Practitioner Needs to Know in 2017.

Am Soc Clin Oncol Educ Book. 2017;37:468-479

Authors: Khoury HJ, Williams LA, Atallah E, Hehlmann R

Abstract
The prognosis of chronic phase chronic myeloid leukemia (CML) has improved so that life expectancy for patients responding to tyrosine kinase inhibitors (TKIs) is now equivalent to age-matched controls. Attention should be paid to comorbidities that impact survival. The success of TKI therapy can be easily and reliably assessed at well-accepted time points using quantitative polymerase chain reaction (PCR) standardized to the international scale. Patient-reported outcome (PRO) tools are readily available for use in the clinic and provide complementary information on the tolerance of TKIs. Effectively managing adverse events of TKIs can improve compliance and quality of life. Discontinuation of TKIs is the next frontier in CML. In select patients with sustained deep molecular remission, a discontinuation of TKI is associated with a durable treatment-free remission in approximately 50%. Patient engagement in their discontinuation can be achieved through a provider multi-team coaching, is complementary to the available guidelines, and may provide an additional safety net so that these discontinuations remain safe when applied in general practices.

PMID: 28561719 [PubMed - in process]

http://ift.tt/2rV3OZO

Systemic Therapy for Metastatic Colorectal Cancer: From Current Standards to Future Molecular Targeted Approaches.

Systemic Therapy for Metastatic Colorectal Cancer: From Current Standards to Future Molecular Targeted Approaches.

Am Soc Clin Oncol Educ Book. 2017;37:246-256

Authors: Atreya CE, Yaeger R, Chu E

Abstract
Over the past 20 years, substantial advances have been made in the treatment of patients with metastatic colorectal cancer (mCRC). In particular, there is now a wide range of options for the front-line treatment of mCRC. Sophisticated molecular technologies have been developed to identify novel prognostic and predictive biomarkers for CRC. DNA sequencing technology has made remarkable advances in recent years, primarily as a result of the development of next-generation sequencing and whole exome sequencing, which are powerful new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of personalized medicine. In addition to tumor tissue, recent efforts have focused on analyzing circulating tumor DNA in peripheral blood. Herein, we review the evolution of standard chemotherapy and targeted therapy strategies for the treatment of mCRC in the front-line setting, the molecular technologies that are presently being used to facilitate our ability to practice individualized medicine, and the practical aspects of applying molecular biomarkers to everyday clinical practice.

PMID: 28561718 [PubMed - in process]

http://ift.tt/2rXy1qV

Addressing the Survivorship Care Needs of Patients Receiving Extended Cancer Treatment.

Addressing the Survivorship Care Needs of Patients Receiving Extended Cancer Treatment.

Am Soc Clin Oncol Educ Book. 2017;37:674-683

Authors: Jacobsen PB, Nipp RD, Ganz PA

Abstract
Cancer survivorship care and research has typically focused on the health care needs of people with cancer following the acute phase of treatment. Work in this area, however, has faced challenges in identifying when treatment is complete for many forms of cancer. Acknowledging this challenge, the scope of survivorship research is often expanded to include patients also receiving maintenance or prophylactic therapy. Inherent in this expanded definition is the recognition that for many individuals, cancer is a chronic disease requiring extended treatment over many years. Three distinct patient populations can be identified for which extended treatment poses important survivorship care needs that, to date, have not been adequately addressed. The first group includes patients receiving extended endocrine therapy, such as women with breast cancer receiving tamoxifen and/or aromatase inhibitors as well as men with prostate cancer receiving androgen deprivation therapy. The second group includes patients receiving extended targeted therapy to control disease, as exemplified by patients with chronic myelogenous leukemia receiving treatment with tyrosine kinase inhibitors. A key issue in both of these patient groups is the need to identify and address factors that contribute to difficulties in maintaining high levels of adherence to the prescribed therapy over extended periods of time. The third group includes patients receiving novel therapies for advanced or metastatic cancer that can extend life for prolonged periods. A key issue for this group is the need to understand and address their unique supportive care needs.

PMID: 28561717 [PubMed - in process]

http://ift.tt/2rVx0jg

Breast Cancer After Childhood, Adolescent, and Young Adult Cancer: It's Not Just About Chest Radiation.

Breast Cancer After Childhood, Adolescent, and Young Adult Cancer: It's Not Just About Chest Radiation.

Am Soc Clin Oncol Educ Book. 2017;37:736-745

Authors: Hodgson D, van Leeuwen F, Ng A, Morton L, Henderson TO

Abstract
Women who have been treated for a childhood, adolescent, or young adult cancer are at an increased risk for developing breast cancer at a young age, and breast cancer accounts for the most common subsequent malignant neoplasm among female childhood and adolescent cancer survivors. Risk of breast cancer in these survivors appears to be a multifaceted relationship between constitutional factors, exposures to radiation therapy (RT) and chemotherapy, and genetic predisposition. Given the significant morbidities and mortality associated with a breast cancer diagnosis, it is imperative that health care providers understand the risks, biology and genetics, recommended surveillance guidelines for early detection, and potential prevention strategies for women who have survived pediatric and young adult cancer.

PMID: 28561716 [PubMed - in process]

http://ift.tt/2suE9nO

Endometrial Cancer: Is This a New Disease?

Endometrial Cancer: Is This a New Disease?

Am Soc Clin Oncol Educ Book. 2017;37:435-442

Authors: Moore K, Brewer MA

Abstract
The incidence of endometrial cancer is increasing, and the age of onset is younger than in prior years. Although endometrial cancer still occurs more commonly in older women, for whom the mortality rate is increasing, it also is being diagnosed in younger and younger women. The underlying cause of the increase in incidence is the epidemic of obesity and the resulting hyperinsulinemia. Conservative treatment may be indicated for younger women who wish to retain their fertility. Lifestyle modifications such as diet and exercise can modulate the risk of developing endometrial cancer as well as prevent recurrence and other comorbidities associated with obesity.

PMID: 28561715 [PubMed - in process]

http://ift.tt/2rVoVLF

Personalizing Adjuvant Therapy for Stage II/III Colorectal Cancer.

Personalizing Adjuvant Therapy for Stage II/III Colorectal Cancer.

Am Soc Clin Oncol Educ Book. 2017;37:232-245

Authors: McCleary NJ, Benson AB, Dienstmann R

Abstract
This review focuses on three areas of interest with respect to the treatment of stage II and III colon and rectal cancer, including (1) tailoring adjuvant therapy for the geriatric population, (2) the controversy as to the optimal adjuvant therapy strategy for patients with locoregional rectal cancer and for patients with colorectal resectable metastatic disease, and (3) discussion of the microenvironment, molecular profiling, and the future of adjuvant therapy. It has become evident that age is the strongest predictive factor for receipt of adjuvant chemotherapy, duration of treatment, and risk of treatment-related toxicity. Although incorporating adjuvant chemotherapy for patients who have received neoadjuvant chemoradiation and surgery would appear to be a reasonable strategy to improve survivorship as an extrapolation from stage III colon cancer adjuvant trials, attempts at defining the optimal rectal cancer population that would benefit from adjuvant therapy remain elusive. Similarly, the role of adjuvant chemotherapy for patients after resection of metastatic colorectal cancer has not been clearly defined because of very limited data to provide guidance. An understanding of the biologic hallmarks and drivers of metastatic spread as well as the micrometastatic environment is expected to translate into therapeutic strategies tailored to select patients. The identification of actionable targets in mesenchymal tumors is of major interest.

PMID: 28561714 [PubMed - in process]

http://ift.tt/2qEk3Gz

Collaborating With Advanced Practice Providers: Impact and Opportunity.

Collaborating With Advanced Practice Providers: Impact and Opportunity.

Am Soc Clin Oncol Educ Book. 2017;37:e1-e7

Authors: Hylton HM, Smith GL

Abstract
Although significant progress has been made in cancer care, access to coordinated, high-quality care across the cancer care continuum remains a challenge for many patients. With significant workforce shortages in oncology anticipated, physician assistants (PAs) and nurse practitioners (NPs)-known collectively as advanced practice providers (APPs)-are considered to be a part of the solution to bridging the gap between the supply of and demand for oncology services. APPs are integral to the provision of team-based care in oncology, and optimizing the roles of all members of the patient's care team is vital to ensuring the teams are cost-effective and that each team member is performing at the functional level intended. Studies have shown significant patient, physician, and APP satisfaction with collaborative care models, and APPs are well positioned to enhance value for patients in the oncology setting. Understanding the full scope of APP impact can be challenging as it extends well beyond direct patient care. As rapid progress in cancer care continues, innovative approaches to care delivery will be necessary to ensure patients' access. Effective oncologist-APP partnerships will be key to providing optimal, value-centered care to patients.

PMID: 28561713 [PubMed - in process]

http://ift.tt/2rUTOj9

Novel Targeted Agents and Immunotherapy in Breast Cancer.

Novel Targeted Agents and Immunotherapy in Breast Cancer.

Am Soc Clin Oncol Educ Book. 2017;37:65-75

Authors: Mayer IA, Dent R, Tan T, Savas P, Loi S

Abstract
The treatment of breast cancer is generally determined according to breast cancer subtype: hormone receptor-positive (luminal), triple-negative (basal-like), and HER2-overexpressing breast cancer. Recent years have seen the development of exciting novel and potent therapeutics based on molecular pathways, immune modulation, and antibody conjugates. In this article, we cover new and emerging therapeutic areas and ongoing clinical trials that may result in further improvements in breast cancer outcomes.

PMID: 28561712 [PubMed - in process]

http://ift.tt/2suifkH

The motor repertoire in 3- to 5-month old infants with Down syndrome

Publication date: August 2017
Source:Research in Developmental Disabilities, Volume 67
Author(s): Dafne Herrero, Christa Einspieler, Carolina Y. Panvequio Aizawa, Akmer Mutlu, Hong Yang, Alice Nogolová, Jasmin Pansy, Karin Nielsen-Saines, Peter B. Marschik
BackgroundEven though Down syndrome is the most common chromosomal cause of intellectual disability, studies on early development are scarce.AimTo describe movements and postures in 3- to 5-month-old infants with Down syndrome and assess the relation between pre- and perinatal risk factors and the eventual motor performance.Methods and proceduresExploratory study; 47 infants with Down syndrome (26 males, 27 infants born preterm, 22 infants with congenital heart disease) were videoed at 10–19 weeks post-term (median=14 weeks). We assessed their Motor Optimality Score (MOS) based on postures and movements (including fidgety movements) and compared it to that of 47 infants later diagnosed with cerebral palsy and 47 infants with a normal neurological outcome, matched for gestational and recording ages.Outcomes and resultsThe MOS (median=13, range 10–28) was significantly lower than in infants with a normal neurological outcome (median=26), but higher than in infants later diagnosed with cerebral palsy (median=6). Fourteen infants with Down syndrome showed normal fidgety movements, 13 no fidgety movements, and 20 exaggerated, too fast or too slow fidgety movements. A lack of movements to the midline and several atypical postures were observed. Neither preterm birth nor congenital heart disease was related to aberrant fidgety movements or reduced MOS.Conclusions and implicationsThe heterogeneity in fidgety movements and MOS add to an understanding of the large variability of the early phenotype of Down syndrome. Studies on the predictive values of the early spontaneous motor repertoire, especially for the cognitive outcome, are warranted.What this paper addsThe significance of this exploratory study lies in its minute description of the motor repertoire of infants with Down syndrome aged 3–5 months. Thirty percent of infants with Down syndrome showed age-specific normal fidgety movements. The rate of abnormal fidgety movements (large amplitude, high/slow speed) or a lack of fidgety movements was exceedingly high. The motor optimality score of infants with Down syndrome was lower than in infants with normal neurological outcome but higher than in infants who were later diagnosed with cerebral palsy. Neither preterm birth nor congenital heart disease were related to the motor performance at 3–5 months.

http://ift.tt/2qR09fE

Efficacy of low-level laser therapy in carpal tunnel syndrome management: a systematic review and meta-analysis

Abstract

We performed this meta-analysis to investigate the efficacy of low-level laser therapy (LLLT), a physiotherapy modality with anti-inflammatory and analgesic effects, in the management of mild-to-moderate carpal tunnel syndrome (CTS). We searched PubMed, Web of Knowledge, Scopus, Cochrane Central, and Virtual Health Library for randomized controlled trials (RCTs) that compared the effects of LLLT with or without splinting versus placebo on functional and electromyographic outcomes in CTS. All outcomes were pooled as mean differences (MD) under the inverse variance or random effects model, using the statistical add-in (MetaXL, version 5.0). Eight RCTs (473 patients/631 wrists) were eligible for the final analysis. The overall effect estimates did not favor LLLT therapy group over placebo in all primary outcomes: visual analogue scale (MD −1.11, 95% CI [−2.58, 0.35]), symptom severity scale score (MD −1.41, 95% CI [−5.12, 2.29]), and functional status scale score (MD −1.33, 95% CI [−3.27, 0.61]). However, LLLT was superior to placebo in terms of grip strength (MD 2.19, 95% CI [1.63, 2.76]) and inferior to placebo in terms of sensory nerve action potential (MD −2.74, 95% CI [−3.66, −1.82]). Laser therapy is superior to placebo in terms of improving the grip strength; however, no significant difference was found between both groups in terms of functional status improvement, pain reduction, or motor electrodiagnostic evaluations. Further high-quality trials with longer follow-up periods are required to establish the efficacy of LLLT for CTS treatment.

http://ift.tt/2rrpQlG

Implications of the lysophosphatidic acid signaling axis in liver cancer

Publication date: Available online 4 June 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Chiara Lopane, Pasquale Agosti, Isabella Gigante, Carlo Sabba, Antonio Mazzocca
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in western countries. The major risk factors for HCC are hepatitis C or B viruses, alcohol and metabolic disorders. The increasing risk of HCC in patients with metabolic disorders (i.e. obesity, diabetes and non-alcoholic steatohepatitis/NASH) regardless of the presence of liver cirrhosis is becoming relevant. Nevertheless, molecular mechanisms linking these risk factors to liver oncogenesis are unclear. This review focuses on the pathogenic role of the lysophosphatidic acid (LPA) pathway in HCC, highlighting the implications of this bioactive phospholipid in liver cancer biology and metabolism and as potential therapeutic target.

http://ift.tt/2rUsamk

Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis

Background: Amniotic membrane is tissue obtained from human placenta rich in cytokines, growth factors, and stem cells that possess the ability to inhibit infection, improve healing, and stimulate regeneration. Methods: A meta-analysis was performed examining randomized controlled trials comparing amniotic tissue products with standard of care in nonhealing diabetic foot ulcers including PubMed, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. Results: A search of 3 databases identified 596 potentially relevant articles. Application of selection criteria led to the selection of 5 randomized controlled trials. The 5 selected randomized controlled trials represented a total of 311 patients. The pooled relative risk of healing with amniotic products compared with control was 2.7496 (2.05725–3.66524, P

http://ift.tt/2pE55iw

Plastic and Reconstructive Surgery in Global Health: Let’s Reconstruct Global Surgery

Summary: Since the inception of the Lancet Commission in 2013 and consequent prioritization of Global Surgery at the World Health Assembly, international surgical outreach efforts have increased and become more synergistic. Plastic surgeons have been involved in international outreach for decades, and there is now a demand to collaborate and address local need in an innovative way. The aim of this article was to summarize new developments in plastic and reconstructive surgery in global health, to unify our approach to international outreach. Specifically, 5 topics are explored: current models in international outreach, benefits and concerns, the value of research, the value of international surgical outreach education, and the value of technology. A "Let's Reconstruct Global Surgery" network has been formed using Facebook as a platform to unite plastic and reconstructive surgeons worldwide who are interested in international outreach. The article concludes with actionable recommendations from each topic.

http://ift.tt/2q9axgL

Rebamipide reduces amyloid-β 1–42 (Aβ42) production and ameliorates Aβ43-lowered cell viability in cultured SH-SY5Y human neuroblastoma cells

Publication date: Available online 3 June 2017
Source:Neuroscience Research
Author(s): Kenta Fukui, Kazuma Yachi, Hidemi Yoshida, Kunikazu Tanji, Tomoh Matsumiya, Ryo Hayakari, Kazushi Tsuruga, Hiroshi Tanaka, Tadaatsu Imaizumi
Amyloid-beta (Aβ) peptides, Aβ 1–42 (Aβ42) and Aβ43, in particular, have been implicated in the pathophysiology of neurodegenerative disease such as Alzheimer's disease (AD). Rebamipide (REB), a gastrointestinal protective drug, can cross the blood-brain barrier after oral administration; however, the effects of REB on neuronal cells have not yet been reported. In this study, we investigated the effects of REB on Aβ43-induced cytotoxicity (monomers, 10μM) in cultured SH-SY5Y human neuroblastoma cells. Addition of REB (10–1000nM) into the media partially ameliorated the reduced cell viability observed after Aβ43 treatment, which was determined by the MTT assay. REB reduced the levels of intracellular Aβ oligomers (100–150kDa) that were formed from the exogenous addition of Aβ43 monomers. In addition, REB (30nM) reduced endogenous Aβ42 secretion, which was analyzed by the enzyme-linked immunosorbent assay. Furthermore, REB enhanced the expression of tumor necrosis factor-α-converting enzyme/a disintegrin and metalloproteinase-17, neprilysin, matrix-metalloproteinase-14 (MMP-14)/membrane type-1 MMP, cyclooxygenase-2, and sirtuin 1, even in cells challenged with Aβ43. These results suggest that REB improves the cell viability by inducing genes that regulate Aβ levels and also genes that are cytoprotective. The secondary use of REB may have potential in the prevention of Aβ-mediated diseases, particularly AD.

http://ift.tt/2qVRbbP

Biomolecular MRI Reporters: evolution of new mechanisms

Publication date: Available online 3 June 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Arnab Mukherjee, Hunter C. Davis, Pradeep Ramesh, George J. Lu, Mikhail G. Shapiro
Magnetic resonance imaging (MRI) is a powerful technique for observing the function of specific cells and molecules inside living organisms. However, compared to optical microscopy, in which fluorescent protein reporters are available to visualize hundreds of cellular functions ranging from gene expression and chemical signaling to biomechanics, to date relatively few such reporters are available for MRI. Efforts to develop MRI-detectable biomolecules have mainly focused on proteins containing or transporting paramagnetic metals for T1 and T2 relaxation enhancement or large numbers of exchangeable protons for chemical exchange saturation transfer. While these pioneering developments established several key uses of biomolecular MRI, such as imaging of gene expression and functional biosensing, they also revealed that low molecular sensitivity poses a major challenge for broader adoption in biology and medicine. Recently, new classes of biomolecular reporters have been developed based on alternative contrast mechanisms, including enhancement of spin diffusivity, interactions with hyperpolarized nuclei, and modulation of blood flow. These novel reporters promise to improve sensitivity and enable new forms of multiplexed and functional imaging.

Graphical abstract

http://ift.tt/2rHsy73

No FAD, No CRY: Redox and Circadian Rhythms

Publication date: Available online 4 June 2017
Source:Trends in Biochemical Sciences
Author(s): David Pritchett, Akhilesh B. Reddy
There is growing evidence of reciprocal interactions between the endogenous circadian clock and subcellular redox pathways. Recently, researchers at the University of California unearthed another possible link between redox metabolism and the mammalian circadian clock: the redox cofactor FAD stabilises the clock protein cryptochrome (CRY), modifying rhythmic clock gene expression.

http://ift.tt/2s7NsNj

Programmable cells of monocytic origin as a source of osteochondroprogenitors: Effect of growth factors on osteogenic differentiation

We have demonstrated previously that peripheral blood monocytes can be converted in vitro to a multipotent stem cell−like cell termed programmable cell of monocytic origin (PCMO) and subsequently into cells with chondrocyte-like phenotype. Here, we investigated whether PCMO could also be differentiated into osteoblast-like cells using growth factors with known osteoinductive potency. Following stimulation with BMP-2, BMP-7, IGF-1 or TGF-β1 for 7 and 14 days, PCMOs were analysed for mRNA expression of collagen types I and V, alkaline phosphatase, osteocalcin, runt-related transcription factor-2 (Runx2) and Osterix (Osx) by quantitative RT-PCR (qPCR) and the levels of collagen I in culture supernatants by ELISA.

http://ift.tt/2qQsUJo

The impact of glucocorticosteroids administered for systemic diseases on the osseointegration and survival of dental implants placed without bone grafting—a retrospective study in 31 patients

To evaluate the impact of glucocorticosteroids, administered for the treatment of systemic diseases, on the osseointegration and survival of dental implants placed without bone grafting.

http://ift.tt/2rzPzXe

The impact of surgical intervention and antibiotics on MRONJ stage II and III – retrospective study

Metastatic bone disease and osteoporosis are the main indications for bisphosphonates and anti-resorptive agent therapy. Inhibition of bone turnover and angiogenesis are mainly responsible for the development of Medication Related Osteonecrosis of Jaws (MRONJ) as therapeutic side-effect. Yet, the role of infection for the development and recurrence of MRONJ is not fully elucidated. The aim of this retrospective study is to explore if a difference in antibiotic regimes has an impact on the surgical intervention needed to achieve a painless stable stage of the disease.

http://ift.tt/2qQCBqV

Genotoxicity of metal based engineered nanoparticles in aquatic organisms: a review

Publication date: Available online 4 June 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): N. Mahaye, M. Thwala, D.A. Cowan, N. Musee
Engineered nanoparticles (ENPs) are an emerging class of environmental contaminants, but are generally found in very low concentrations and are therefore likely to exert sub-lethal effects on aquatic organisms. In this review, we: (i) highlight key mechanisms of metal-based ENP-induced genotoxicity, (ii) identify key nanoparticle and environmental factors which influence the observed genotoxic effects, and (iii) highlight the challenges involved in interpreting reported data and provide recommendations on how these challenges might be addressed. We review the application of eight different genotoxicity assays, where the Comet Assay is generally preferred due to its capacity to detect low levels of DNA damage. Most ENPs have been shown to cause genotoxic responses; e.g., DNA or/and chromosomal fragmentation, or DNA strand breakage, but at unrealistic high concentrations. The genotoxicity of the ENPs was dependent on the inherent physico-chemical properties (e.g. size, coating, surface chemistry, e.tc.), and the presence of co-pollutants. To enhance the value of published genotoxicity data, the role of environmental processes; e.g., dissolution, aggregation and agglomeration, and adsorption of ENPs when released in aquatic systems, should be included, and assay protocols must be standardized. Such data could be used to model ENP genotoxicity processes in open environmental systems.

http://ift.tt/2sEVKZA

AGC kinases, mechanisms of regulation ‎and innovative drug development

Publication date: Available online 4 June 2017
Source:Seminars in Cancer Biology
Author(s): Alejandro E. Leroux, Jörg Schulze, Ricardo M. Biondi
The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signaling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation. In the present review, we update the knowledge of the mechanisms of regulation of different AGC kinases. The conformation of the catalytic domain of many AGC kinases is regulated allosterically through the modulation of the conformation of a regulatory site on the small lobe of the kinase domain, the PIF-pocket. The PIF-pocket acts like an ON-OFF switch in AGC kinases with different modes of regulation, i.e. PDK1, PKB/Akt, LATS and Aurora kinases. In this review, we make emphasis on how the knowledge of the molecular mechanisms of regulation can guide the discovery and development of small allosteric modulators. Molecular probes stabilizing the PIF-pocket in the active conformation are activators, while compounds stabilizing the disrupted site are allosteric inhibitors. One challenge for the rational development of allosteric modulators is the lack of complete structural information of the inhibited forms of full-length AGC kinases. On the other hand, we suggest that the available information derived from molecular biology and biochemical studies can already guide screening strategies for the identification of innovative mode of action molecular probes and the development of selective allosteric drugs for the treatment of human diseases.

http://ift.tt/2rzlYgU

Current state of knowledge on the traditional uses, phytochemistry, and pharmacology of the genus Hymenaea

Publication date: 12 July 2017
Source:Journal of Ethnopharmacology, Volume 206
Author(s): Pone Kamdem Boniface, Sabrina Baptista Ferreira, Carlos Roland Kaiser
Ethnopharmacological relevancePlants of the genus Hymenaea (Fabaceae) are used in South American and Asian traditional medicines to treat a multitude of disorders, like cough, diarrhea, dysentery, intestinal colic, pulmonary weakness, asthma, anemia, sore throat, and for the treatment of kidney problems, viral related disorders, chronic cystitis, bronchitis, and bladder infections. Some Hymenaea species are also used as vermifuge, and for the treatment of arthritis, and inflammation conditions. This review deals with updated information on the traditional uses, phytochemistry and pharmacology of ethnomedicinally important Hymenaea species in order to provide an input for the future research prospects.MethodsLiterature available in various recognized databases including Google Scholar, PubMed, SciFinder, Scopus, Springer, Wiley, ACS, Scielo and Web of Science, as well as from theses, dissertations, books, reports, and other relevant websites (www.theplantlist.org), are surveyed, analysed, and included in this review. Herein, the literature related to chemical constituents and pharmacological activities were searched in November 2016.ResultsThe literature provided information on ethnopharmacological uses of the South American and African species of the genus Hymenaea (e.g., H. courbaril, H. stigonocarpa, H. onblogifolia, H. martiana, H. parvifolia (South America) and H. verrucosa (African species)) for the treatment of multi-factorial diseases. From these plant species, more than 130 compounds, including fatty acids, flavonoids, terpenoids and steroids, phthalides, phenolic acids, procyanidins and coumarins were identified. Experimental evidences confirmed that the Hymenaea spp. could be used in treating inflammatory disorders, asthma, diarrhea, and some microbial infections. However, reports on the toxicity of Hymenaea species remain scarce.ConclusionPlants of this genus have offered bioactive samples, both from crude extracts and pure compounds, thus substantiating their effectiveness in traditional medicine. However, intensive investigations of all the species of Hymenaea spp. relating to phytochemical and pharmacological properties, especially their mechanism of action, safety and efficacy could be the future introspection.

Graphical abstract

http://ift.tt/2rzuigi

Safety assessment of cultivated fruiting body of Ophiocordyceps sinensis evaluated through subacute toxicity in rats

Publication date: Available online 3 June 2017
Source:Journal of Ethnopharmacology
Author(s): Shin Yee Fung, Sook Shien Lee, Nget Hong Tan, Jayalakshmi Pailoor
Ethnopharmacological relevanceOphiocordyceps sinensis (Berk.) G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora is one of the most renowned traditional Chinese medicine used as tonic, renal, respiratory and reproductive health, promote longevity and overall improvement in quality of life. Natural production of O. sinensis is limited due to its extreme specificity in host range and confined geographic distribution. Therefore, cultivation of the fungus was developed to meet high demand for commercialization as nutraceutical. O. sinensis fruiting body has recently been successfully cultivated in large scale using rice based solid medium, providing wider source options for consumers and scientific researchers.Aims of the studyThe present study aims to establish safety profile for the consumption of cultivated fruiting body of O. sinensis (FBOS) by 28-days sub-acute toxicity study in Sprague Dawley rats.Materials and methodsRats were orally administered with cultivated FBOS at three graded doses (250, 500 and 1000mg/kg), once daily for 28 consecutive days. Control group received distilled water. General observations (gross behavioral changes and toxic symptoms) and body weight of each animal were monitored daily. Haematological, serum biochemical and histopathological analysis were carried out at the end of the experiment (Day 29).ResultsNo behavioral changes, toxic symptoms or death was observed in rats throughout the dosing period. Cultivated FBOS treatment up to 1000mg/kg did not cause any adverse effect on the growth of the animals. Results from haematology and serum biochemistry revealed no toxic effect following cultivated FBOS treatment at three graded doses for 28 days. In addition, no treatment related histopathological changes were noted in heart, spleen, kidney, lung and liver of the animals.ConclusionThe present study revealed that oral administration of cultivated FBOS for 28 days, at dosage up to 1000mg/kg did not pose toxicological concern in rats. Therefore, the no-observed-adverse-effect level (NOAEL) dose of cultivated FBOS in 28-days subacute toxicity study is higher than 1000mg/kg.

Graphical abstract

http://ift.tt/2rzujRo

Functional characterization of Aedes aegypti alkaline phosphatase ALP1 involved in the toxicity of Cry toxins from Bacillus thuringiensis subsp. israelensis and jegathesan

Publication date: Available online 3 June 2017
Source:Peptides
Author(s): Jianwu Chen, Karly Aimanova, Sarjeet S. Gill
Presently three major groups of proteins from Aedes aegypti, cadherin, alkaline phosphatases (ALP) and aminopeptidases N (APN), have been identified as Cry11Aa toxin receptors. To further characterize their role on toxicity, transgenic mosquitoes with silenced Aedes cadherin expression were previously generated and the role of cadherin in mediating the toxicity of four different mosquitocidal toxins (Cry11Aa, Cry11Ba, Cry4Aa and Cry4Ba) was demonstrated. Here, we investigated the role of another reported Cry11Aa receptor, ALP1. As with Aedes cadherin, this protein is localized in the apical cell membrane of distal and proximal gastric caecae and the posterior midgut. We also successfully generated transgenic mosquitoes that knockdowned ALP1 transcript levels using an inducible Aedes heat shock promoter, Hsp70A driving dsALP1RNA. Four different mosquitocidal toxins were used for larval bioassays against this transgenic mosquito. Bioassay results show thatCry11Aa toxicity to these transgenic larvae following a heat shock decreased (4.4 fold) and Cry11Ba toxicity is slightly attenuated. But Cry4Aa and Cry4Ba toxicity to ALP1 silenced larvae is unchanged. Without heat shock, toxicity of all four toxins does not change, suggesting this heat shock promoter is heat-inducible. Notably, transgenic mosquitoes with ALP1 knockdown are about 3.7 times less resistant to Cry11Aa toxin than those with Aedes cadherin knockdown. These results demonstrate that the ALP1 is an important secondary receptor for Cry11Aa and Cry11Ba, but it might not be involved in Cry4Aa and Cry4Ba toxicity.

http://ift.tt/2qVjKWT

Effect of physicochemical properties of peptides from soy protein on their antimicrobial activity

Publication date: Available online 3 June 2017
Source:Peptides
Author(s): Ning Xiang, Yuan Lyu, Xiao Zhu, Arun K. Bhunia, Ganesan Narsimhan
Antimicrobial peptides (AMPs) kill microbial cells through insertion and damage/permeabilization of the cytoplasmic cell membranes and has applications in food safety and antibiotic replacement. Soy protein is an attractive, abundant natural source for commercial production of AMPs. In this research, explicit solvent molecular dynamics (MD) simulation was employed to investigate the effects of (i) number of total and net charges, (ii) hydrophobicity (iii) hydrophobic moment and (iv) helicity of peptides from soy protein on their ability to bind to lipid bilayer and their transmembrane aggregates to form pores. Interaction of possible AMP segments from soy protein with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPC/POPG) bilayers, a mimic of bacterial cell membrane, was investigated. Pore formation was insensitive to helicity and occurred for hydrophobicity threshold in the range of −0.3 to 0kcal/mol, hydrophobic moment threshold of 0.3kcal/mol, net charge threshold of 2. Though low hydrophobicity and high number of charges help in the formation of water channel for transmembrane aggregates, insertion of peptides with these properties requires overcome of energy barrier, as shown by potential mean force calculations, thereby resulting in low antimicrobial activity. Experimental evaluation of antimicrobial activity of these peptides against Gram positive L. monocytogenes and Gram negative E. coli as obtained by spot-on-lawn assay was consistent with simulation results. These results should help in the development of guidelines for selection of peptides with antimicrobial activity based on their physicochemical properties.

http://ift.tt/2rqNkqX

Burrowing as a Novel Voluntary Strength Training Method for Mice: A Comparison Of Various Voluntary Strength or Resistance Exercise Methods

Publication date: Available online 3 June 2017
Source:Journal of Neuroscience Methods
Author(s): P. Roemers, P.N. Mazzola, P.P. De Deyn, W.J. Bossers, M.J.G van Heuvelen, E.A. van der Zee
BackgroundVoluntary strength training methods for rodents are necessary to investigate the effects of strength training on cognition and the brain. However, few voluntary methods are available.New methodThe current study tested functional and muscular effects of two novel voluntary strength training methods, burrowing (digging a substrate out of a tube) and unloaded tower climbing, in male C57Bl6 mice. To compare these two novel methods with existing exercise methods, resistance running and (non-resistance) running were included. Motor coordination, grip strength and muscle fatigue were measured at baseline, halfway through and near the end of a fourteen week exercise intervention. Endurance was measured by an incremental treadmill test after twelve weeks.ResultsBoth burrowing and resistance running improved forelimb grip strength as compared to controls. Running and resistance running increased endurance in the treadmill test and improved motor skills as measured by the balance beam test. Post-mortem tissue analyses revealed that running and resistance running induced Soleus muscle hypertrophy and reduced epididymal fat mass. Tower climbing elicited no functional or muscular changes.Comparison with existing methodsAs a voluntary strength exercise method, burrowing avoids the confounding effects of stress and positive reinforcers elicited in forced strength exercise methods. Compared to voluntary resistance running, burrowing likely reduces the contribution of aerobic exercise components.ConclusionsBurrowing qualifies as a suitable voluntary strength training method in mice. Furthermore, resistance running shares features of strength training and endurance (aerobic) exercise and should be considered a multi-modal aerobic-strength exercise method in mice.

http://ift.tt/2rzODSL

Comparison of estimates of neuronal number obtained using the isotropic fractionator method and unbiased stereology in day old chicks (Gallus domesticus)

Publication date: Available online 3 June 2017
Source:Journal of Neuroscience Methods
Author(s): Ayanda Ngwenya, Janae Nahirney, Ben Brinkman, Lauren Williams, Andrew N. Iwaniuk
BackgroundThe relative size and neuronal density of brain regions are important metrics in both comparative and experimental studies in neuroscience. Consequently, it is imperative to have accurate, reliable and reproducible methods of quantifying cell number.New methodThe isotropic fractionator (IF) method estimates the number of neurons and non-neurons in the central nervous system by homogenizing tissue into discrete nuclei and determining the proportion of neurons from non-neurons using immunohistochemistry (Herculano- Herculano-Houzel and Lent, 2005).Comparison with existing methodOne of the advantages of IF is that it is considerably faster than stereology. However, as the method is relatively new, concerns about its accuracy remain, particularly whether homogenization results in underestimation of cell number. In this study, we compared estimates of neuronal number in the telencephalon and 'rest of brain' (i.e. the diencephalon and brainstem excluding the optic lobes) of day old chicks using the IF method and stereology.ResultsIn the telencephalon, there was a significant difference in estimates of neuronal number between the 2 methods, but not estimates of neuronal density (neurons/mg of tissue). Whereas in the 'rest of brain', there was a significant difference in estimates of neuronal density, but not neuronal number. In all cases, stereological estimates were lower than those obtained using the IF method.ConclusionDespite the statistically significant differences, there was considerable overlap (all estimates were within 16% of one another) between estimates obtained using the two methods suggesting that the two methods provide comparable estimates of neuronal number in birds.

http://ift.tt/2qQwdQF

A novel operant task to assess social reward and motivation in rodents

Publication date: Available online 3 June 2017
Source:Journal of Neuroscience Methods
Author(s): Johnathan M. Borland, Kyle J. Frantz, Lauren M. Aiani, Kymberly N. Grantham, Zhimin Song, H. Elliott Albers
BackgroundSocial reward plays a critical role in the development of beneficial social relationships, and disorders of the mechanisms controlling social reward are involved in the etiology of many psychiatric diseases.New methodWe present a novel operant social preference task to quantify social reward in rodents using an apparatus with three chambers separated by one-way vertical-swing doors. The experimental animal is placed in the larger chamber while the two smaller chambers either remain empty or contain a stimulus animal or other potential reward stimulus. Adding weights to the door can alter effort required for rewards.ResultsHamsters (Mesocricetus auratus) entered the chamber containing a stimulus hamster significantly more frequently than an empty chamber. When the reinforcing effects of social interactions were compared to food reward under progressive cost requirements, the reinforcing effects of social interaction and sunflower seeds were similar. Progressively increasing the door weight decreased number of entries, but increased time spent attempting to open the doors.Comparison with existing methodsThe quantification of the rewarding properties of social interactions has almost exclusively used the conditioned place preference (CPP) paradigm. Although robust and reliable, CPP includes a memory component, because it relies on the association of place with the social interaction while the operant task presented here does not.ConclusionsThis task allows for detailed and direct assessment of social and non-social rewards that may serve as effective behavioral reinforcers in this operant conditioning model, and it can be used to investigate the neural mechanisms regulating motivation.

http://ift.tt/2rzGaPx

Miglustat therapy in a case of early-infantile Niemann-Pick type C

Publication date: Available online 3 June 2017
Source:Brain and Development
Author(s): Miho Usui, Akihiko Miyauchi, Yuko Nakano, Sachie Nakamura, Eriko Jimbo, Shinji Itamura, Kaori Adachi, Eiji Nanba, Aya Narita, Takanori Yamagata, Hitoshi Osaka
Niemann-Pick disease type C (NPC) is a rare, progressive autosomal recessive disease. It is caused by mutations in either the NPC1 or NPC2 genes, resulting in defective regulation of intracellular lipid trafficking. Miglustat, which reversibly inhibits glucosylceramide synthase, reportedly has beneficial effects on the progressive neurological symptoms of NPC and was approved in Japan in 2012. Some reports suggested that miglustat therapy delayed the onset or progression of NPC when treatment was initiated before the onset of neurological manifestation or at an early stage. We report here a patient with the early-infantile form of NPC who started on miglustat at 4months of ages. To our knowledge, this patient is the youngest reported patient with NPC in which miglustat therapy was initiated. Our patient, who had hypotonia and developmental delay before treatment, remained stable and showed no new neurological symptoms. In addition, pulmonary involvement was improved during miglustat therapy. Our case and previous reports underscore the importance of early initiation of miglustat therapy for NPC.

http://ift.tt/2rqa9uF

Comment on relative brain size in early primates and the use of encephalization quotients in primate evolution

Publication date: Available online 3 June 2017
Source:Journal of Human Evolution
Author(s): Christopher C. Gilbert, William L. Jungers

http://ift.tt/2rGvDnG

Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis

Publication date: August 2017
Source:Oral Oncology, Volume 71
Author(s): Héliton S. Antunes, Daniel Herchenhorn, Isabele A. Small, Carlos M.M. Araújo, Celia Maria Pais Viégas, Gabriela de Assis Ramos, Fernando L. Dias, Carlos G. Ferreira
BackgroundThe impact of low-level laser therapy (LLLT) to prevent oral mucositis in patients treated with exclusive chemoradiation therapy remains unknown. This study evaluated the overall, disease-free and progression-free survival of these patients. Methods: Overall, disease-free and progression-free survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx cancer, who participated on a phase III study, was evaluated from 2007 to 2015. The patients were subjected to conventional radiotherapy plus cisplatin every 3weeks. LLLT was applied with an InGaAlP diode (660nm–100mW–1J–4J/cm²).ResultsWith a median follow-up of 41.3months (range 0.7–101.9), patients receiving LLLT had a statistically significant better complete response to treatment than those in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT also displayed increase in progression-free survival than those in the placebo group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07–3.5) and had a tendency for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92–2.91).ConclusionThis is the first study to suggest that LLLT may improve survival of head and neck cancer patients treated with chemoradiotherapy. Further studies, with a larger sample, are necessary to confirm our findings.

http://ift.tt/2stgVhN

Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma

Publication date: August 2017
Source:Oral Oncology, Volume 71
Author(s): Marc L. Ooft, Jolique A. van Ipenburg, Weibel W. Braunius, Charlotte I. Zuur, Senada Koljenović, Stefan M. Willems
ObjectivesTumor infiltrating lymphocytes (TILs) correlate with both better and worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up till now there is limited prognostic data on the role of TILs in NPC, so we assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and negative NPC.MethodsTissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and PDL1 expression in the tumor's micro-environment. Correlations between clinicopathological characteristics was assessed using the Pearson X² test, Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression between EBV positive and negative NPCs were evaluated using the Mann-Whitney U test. Two-tailed P values below 0.05 were considered statistically significant.ResultsEBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than EBV negative NPC. In the whole NPC group, increased CD8 count is associated with better overall survival (OS) (HR 0.219 (95%CI 0.075–0.640)), but also in cases with PDL1 co-expression (HR 0.073 (95%CI 0.010–0.556)). In EBV positive NPC co-expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI 0.195–0.850)) and OS (HR 0.170 (95%CI 0.037–0.787)).ConclusionsAlthough TILs are significantly different between EBV positive and negative NPCs, it is especially composition of the infiltrate which determines prognosis. Effects of PD1 and CD8 need more study, because these findings show much potential in using immunotherapeutic modalities in NPC treatment.

http://ift.tt/2rTIK69

A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)☆

Publication date: August 2017
Source:Oral Oncology, Volume 71
Author(s): Katarzyna J. Jerzak, Keemo Delos Santos, Ronak Saluja, Kelly Lien, Justin Lee, Kelvin K.W. Chan
ObjectivesThe current standard therapy for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is platinum-based chemotherapy plus concurrent radiotherapy (CRT), but several systemic therapies have been evaluated. We performed a Bayesian network meta-analysis (NMA) with random effects to enable direct and indirect comparisons of all existing treatment modalities for LASCCHN simultaneously.Material and methodsA systematic review was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and the Cochrane Central of Registered Trials using Cochrane methodology to identify randomized controlled trials (RCTs) up to June 2016. Only abstracts that involved the same definitive radiotherapy in the arms for the RCT were included.ResultsSixty-five RCTs involving 13,574 patients and 16 different treatment strategies were identified. Chemotherapy plus concurrent radiation (CRT) was superior to RT with a HR of 0.74 (95%CR 0.69–0.79) for OS in the NMA. Only 3 trials compared RT alone to concurrent therapy with an EGFR antibody (ERT), demonstrating a superior OS (HR 0.75, 95% CR 0.60–0.94), but this difference was not statistically significant when interpreted in a NMA (HR 0.84, 95%CR 0.65–1.08). ERT was not superior to CRT (HR 1.19, 95%CR 0.93–1.54), and the addition of neo-adjuvant taxane-based chemotherapy to CRT was not beneficial (HR 0.86, 95% CR 0.70–1.07).ConclusionThe addition of either adjuvant or neoadjuvant chemotherapy to the CRT backbone does not confer an OS benefit in the treatment of LASCCHN. Similarly, ERT does not confer an OS benefit for patients who are eligible for CRT.

http://ift.tt/2qQ3GKZ

ITV, mid-ventilation, gating or couch tracking – A comparison of respiratory motion-management techniques based on 4D dose calculations

Publication date: Available online 3 June 2017
Source:Radiotherapy and Oncology
Author(s): Stefanie Ehrbar, Alexander Jöhl, Adrianna Tartas, Luisa Sabrina Stark, Oliver Riesterer, Stephan Klöck, Matthias Guckenberger, Stephanie Tanadini-Lang
PurposeRespiratory motion-management techniques (MMT) aim to ensure tumor dose coverage while sparing lung tissue. Dynamic treatment-couch tracking of the moving tumor is a promising new MMT and was compared to the internal-target-volume (ITV) concept, the mid-ventilation (MidV) principle and the gating approach in a planning study based on 4D dose calculations.MethodsFor twenty patients with lung lesions, planning target volumes (PTV) were adapted to the MMT and stereotactic body radiotherapy treatments were prepared with the 65%-isodose enclosing the PTV. For tracking, three concepts for target volume definition were considered: Including the gross tumor volume of one phase (single-phase tracking), including deformations between phases (multi-phase tracking) and additionally including tracking latencies of a couch tracking system (reliable couch tracking). The accumulated tumor and lung doses were estimated with 4D dose calculations based on 4D-CT datasets and deformable image registration.ResultsSingle-phase tracking showed the lowest ipsilateral lung Dmean (median: 3.3Gy), followed by multi-phase tracking, gating, reliable couch tracking, MidV and ITV concepts (3.6, 3.8, 4.1, 4.3 and 4.8Gy). The 4D dose calculations showed the MidV and single-phase tracking overestimated the target mean dose (−2.3% and −1.3%), while it was slightly underestimated by the other MMT (<+1%).ConclusionThe ITV concept ensures tumor coverage, but exposes the lung tissue to a higher dose. The MidV, gating and tracking concepts were shown to reduce the lung dose. Neglecting non-translational changes of the tumor in the target volume definition for tracking results in a slightly reduced target coverage. The slightly inferior dose coverage for MidV should be considered when applying this technique clinically.

http://ift.tt/2rEtsAY

Reproducibility discrepancies following reanalysis of raw data for a previously published study on diisononyl phthalate (DINP) in rats

Publication date: August 2017
Source:Data in Brief, Volume 13
Author(s): Min Chen, Rebecca Alyea, Peter Morfeld, Rainer Otter, Jessica Kemmerling, Christine Palermo
A 2011 publication by Boberg et al. entitled "Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats" [1] reported statistically significant changes in sperm parameters, testicular histopathology, anogenital distance and retained nipples in developing males. Using the statistical methods as reported by Boberg et al. (2011) [1], we reanalyzed the publically available raw data ([dataset] US EPA (United States Environmental Protection Agency), 2016) [2]. The output of our reanalysis and the discordances with the data as published in Boberg et al. (2011) [1] are highlighted herein. Further discussion of the basis for the replication discordances and the insufficiency of the Boberg et al. (2011) [1] response to address them can be found in a companion letter of correspondence (doi: 10.1016/j.reprotox.2017.03.013.; (Morfeld et al., 2011) [3]).

http://ift.tt/2sElSnw

Ultra high-field (7T) multi-resolution fMRI data for orientation decoding in visual cortex

Publication date: August 2017
Source:Data in Brief, Volume 13
Author(s): Ayan Sengupta, Renat Yakupov, Oliver Speck, Stefan Pollmann, Michael Hanke
Multivariate pattern classification methods have been successfully applied to decode orientation of visual grating stimuli from BOLD fMRI activity recorded in human visual cortex (Kamitani and Tong, 2005; Haynes and Rees, 2005) [12,10]. Though there has been extensive research investigating the true spatial scale of the orientation specific signals (Op de Beeck, 2010; Swisher et al., 2010; Alink et al., 2013; Freeman et al., 2011, 2013) [2,15,1,4,5], it remained inconclusive what spatial acquisition resolution is required, or is optimal, for decoding analyses. The research article entitled "The effect of acquisition resolution on orientation decoding from V1 BOLD fMRI at 7T" Sengupta et al. (2017) [14] studied the effect of spatial acquisition resolution and also analyzed the strength and spatial scale of orientation discriminating signals. In this article, for the first time, we present empirical ultra high-field fMRI data, obtained as a part of the aforementioned study, which were recorded at four spatial resolutions (0.8mm, 1.4mm, 2mm, and 3mm isotropic voxel size) for orientation decoding in visual cortex. The dataset is compliant with the BIDS (Brain Imaging Data Structure) format, and freely available from the OpenfMRI portal (dataset accession number: http://ift.tt/2sEwp1P ds000113c).

http://ift.tt/2rGqAnj

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Κυριακή 4 Ιουνίου 2017

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