Detection and adequacy evaluation of erythrocyte glutathione transferase on levels of circulating toxins in hemodialysis patients.

Detection and adequacy evaluation of erythrocyte glutathione transferase on levels of circulating toxins in hemodialysis patients.

Artif Cells Nanomed Biotechnol. 2016 Apr 28;:1-4

Authors: Yin R, Qiu H, Zuo H, Cui M, Zhai N, Zheng H, Zhang D, Huo P, Hong M

Abstract
To explore detection and adequacy evaluation of erythrocyte glutathione S transferase (GST) on levels of circulating toxins in hemodialysis patients in Qinhuangdao region in China, this study divided 84 cases of long-term, end-stage hemodialysis patients into 2 groups: one group of 33 cases of adequate hemodialysis (spKt/V ≥ 1.3) and another group of 51 cases of inadequate hemodialysis (spKt/V < 1.3), according to the urea index value of the unit chamber model (spKt/V). Another 50 cases of subjects found healthy by a physical examination were taken as the control group, and the differences in the related clinical and biochemical indexes of the 3 groups were compared and analyzed. The levels of GST, creatinine, high sensitivity C-reactive protein (hs-CRP), transferrin saturation (TSAT), parathyroid hormone (PTH), interleukin-2,6,8 (IL-2,6,8) and tumor necrosis factor-a (TNF-a) in the hemodialysis group were significantly higher than those in the control group (P < 0.05), and GST, IL-2, 6, 8, and TNF-a levels in the inadequate hemodialysis group were significantly higher than in the adequate hemodialysis group (P < 0.05). Pearson's relevant analysis showed that the levels of GST and spKt/V, IL-2, IL-6, IL-8, and TNF-a have a positive correlation (P < 0.05), and they have no correlation with levels of creatinine, hs-CRP, TSAT, and PHT (P > 0.05). There were 23 patients with levels of spKt/V ≥ 1.3 after adjusting the dialysis solution for 51 cases of inadequate hemodialysis patients, and the GST level after the adjustment was significantly lower than that before the adjustment, but still higher than that in the adequate dialysis group. This concludes that the maintenance of hemodialysis in patients has certain relevance on spKt/V and associated inflammatory factors. Through the study, it can be determined that GST can effectively respond to adequate hemodialysis, which has a guiding significance on adjusting the blood dialysis solution in clinical practice.

PMID: 27121915 [PubMed - as supplied by publisher]

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The role of professional learning communities for beginning teachers' learning outcomes and intention to leave the job

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A novel approach to an efficient LED on SOI

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Novelty low-cost integrated photonic biosensor using broadband source and on-chip spectral filter

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Design of an electronically tunable laser diode integrated on the SOI platform

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On-chip axicon for light sheet microscopy

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Si and SiN biophotonic Technology Platform, Applied to Biosensing, Spectroscopy, and Lens-Free Imaging

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Low optical loss ohmic contacts on heavily doped n-type InGaAs for InP membrabes devices

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Trametinib in metastatic melanoma.

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Trametinib in metastatic melanoma.

Expert Rev Anticancer Ther. 2015;15(7):749-60

Authors: Chopra N, Nathan PD

Abstract
The treatment of metastatic melanoma is rapidly changing. In 2002, the BRAF mutation was described in over 50% of melanomas and led to the first BRAF inhibitor, vemurafenib, being approved for clinical use in 2011. Clinical responses are often rapid but duration of response is limited due to the development of resistance. MEK is the next downstream target from BRAF in the MAP kinase pathway. Trametinib was the first MEK inhibitor to be approved for clinical use in 2013. Preclinical studies demonstrated a delay in resistance and a reduction in cutaneous toxicity by combined BRAF and MEK inhibition. Here, we review the rationale for clinical development of trametinib and give an update on recent clinical trials of trametinib alone and in combination with braf inhibition in melanoma.

PMID: 26107021 [PubMed - indexed for MEDLINE]

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Invadopodia: a new therapeutic target to block cancer metastasis.

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Invadopodia: a new therapeutic target to block cancer metastasis.

Expert Rev Anticancer Ther. 2015;15(7):733-5

Authors: Stoletov K, Lewis JD

Abstract
Cancer cells become dangerous when they acquire the ability to invade through physical barriers in the body and disseminate to distant sites. Recent evidence has demonstrated that cancer cells utilize specialized structures called invadopodia, unique protrusions that concentrate proteases such as matrix metalloproteinases (MMPs), to escape blood vessels during the process of extravasation. Perhaps most exciting is the fact that inhibition of invadopodia through genetic or pharmacological means reduces the ability of cancer cells to extravasate and effectively blocks metastasis. This opens the door for the development of novel therapies targeting invadopodia and cancer metastasis.

PMID: 26098830 [PubMed - indexed for MEDLINE]

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Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma.

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Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma.

Expert Rev Anticancer Ther. 2015;15(7):737-48

Authors: Richardson PG, Laubach JP, Lonial S, Moreau P, Yoon SS, Hungria VT, Dimopoulos MA, Beksac M, Alsina M, San-Miguel JF

Abstract
Outcomes for patients with multiple myeloma (MM) have improved significantly over the past decade. Despite these advances, MM remains incurable and an unmet medical need remains for patients who are relapsed and/or refractory. Panobinostat is a potent, oral pan-deacetylase inhibitor that elicits anti-myeloma activity through epigenetic modulation of gene expression and disruption of protein metabolism. Preclinical data demonstrated that panobinostat has synergistic effects on myeloma cells when combined with bortezomib and dexamethasone. In a Phase III clinical trial evaluating bortezomib and dexamethasone in combination with panobinostat or placebo in patients with relapsed or relapsed and refractory MM (PANORAMA 1), panobinostat led to a significant increase in median progression-free survival. Panobinostat is currently under regulatory review with a recent accelerated approval granted for the treatment of relapsed disease, in which both bortezomib and immunomodulatory drugs have failed. Here, we summarize the preclinical, pharmacokinetic and clinical data for panobinostat in MM.

PMID: 26051506 [PubMed - indexed for MEDLINE]

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Maintenance therapy in non-small cell lung cancer.

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Maintenance therapy in non-small cell lung cancer.

Expert Rev Anticancer Ther. 2015;15(7):839-46

Authors: Genestreti G, Di Battista M, Cavallo G, Bartolotti M, Brandes AA

Abstract
Several randomized trials have investigated the role of maintenance treatment for patients with advanced non-small cell lung cancer (NSCLC) not progressed after completion of first-line chemotherapy, with good performance score (PS) and no persistent chemotherapy-induced toxicity. Two separate strategies have been developed: the immediate use of non-cross-resistant drug (switch maintenance or early second-line therapy) or the continuation of platinum partner alone (continuation maintenance) or in combination with other drug (combination maintenance). Here we discuss how the benefits demonstrated in these studies may change clinical practice (in terms of potential toxicity and costs) and reflect on factors that may identify subgroups of patients who might benefit from maintenance therapy in general, and which maintenance therapy specifically.

PMID: 26027675 [PubMed - indexed for MEDLINE]

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Use of angiotensin-converting enzyme inhibitors in the prophylaxis of anthracycline or trastuzumab-related cardiac dysfunction: preclinical and clinical considerations.

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Use of angiotensin-converting enzyme inhibitors in the prophylaxis of anthracycline or trastuzumab-related cardiac dysfunction: preclinical and clinical considerations.

Expert Rev Anticancer Ther. 2015;15(7):829-37

Authors: Abdel-Rahman O, Alorabi M

Abstract
Cardiac toxicity is one of the most important long-term toxicities experienced by cancer survivors so that survival rate due to anticancer therapy may be negatively affected due to cardiac complications. Thus, the search for novel methods to lower the incidence of treatment-related cardiotoxicity is a priority for all cancer-related disciplines. In this review, we provide an overview of the available preclinical and clinical data evaluating the role of angiotensin-converting enzyme inhibitors in the prophylaxis of cardiac dysfunction secondary to anthracyclines and trastuzumab use. The available clinical data suggest some degree of protective utility for the use of some angiotensin-converting enzyme inhibitors against anthracycline-related cardiotoxicity while the data are scarce with regard to a similar role for patients receiving trastuzumab.

PMID: 26013380 [PubMed - indexed for MEDLINE]

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Novel approaches to pediatric leukemia treatment.

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Novel approaches to pediatric leukemia treatment.

Expert Rev Anticancer Ther. 2015;15(7):811-28

Authors: Thomas X

Abstract
Despite remarkable improvements in the treatment of pediatric acute leukemia (AL) over the last decades, relapse still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. This review summarizes recent data from the literature regarding advances in drug discovery based on biological evidence and the novel targeted drug therapies for childhood AL. Significant challenges still remain for novel drug development in childhood AL. However, first results combined with a large number of new agents currently being investigated are very encouraging. Furthermore, therapeutic advances will depend upon combination strategies using the specific action of each agent and their complementary effects on leukemia cells.

PMID: 26004287 [PubMed - indexed for MEDLINE]

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Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with everolimus, temsirolimus or ridaforolimus: a comparative systematic review and meta-analysis.

Related Articles

Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with everolimus, temsirolimus or ridaforolimus: a comparative systematic review and meta-analysis.

Expert Rev Anticancer Ther. 2015;15(7):847-58

Authors: Abdel-Rahman O, Fouad M

Abstract
BACKGROUND: The authors performed a systematic review and meta-analysis of diarrhea and stomatitis associated with the use of everolimus, temsirolimus or ridaforolimus in patients with solid tumors.
PATIENTS AND METHODS: Eligible studies included randomized trials of patients with solid tumors on everolimus, temsirolimus or ridaforolimus, describing the events of diarrhea and stomatitis.
RESULTS: After exclusion of ineligible studies, a total of 18 clinical trials including 8143 patients were considered eligible for the meta-analysis. The relative risk ratios of all-grade diarrhea and stomatitis were 1.94 (95% CI: 1.6-2.36; p < 0.00001) and 3.54 (95% CI: 2.59-4.84; p < 0.00001), respectively, while the relative risk ratios of high-grade diarrhea and stomatitis were 3.49 (95% CI: 2.39-5.09; p < 0.00001) and 6.98 (95% CI: 4.76-10.26; p < 0.00001), respectively. On subgroup analysis, there was no statistically significant difference between everolimus and temsirolimus in the risk of relevant adverse events.
CONCLUSIONS: This meta-analysis demonstrated that regimens containing everolimus, temsirolimus or ridaforolimus for the treatment of solid tumors are associated with a significantly increased risk of all-grade and high-grade diarrhea and stomatitis. Close clinical monitoring is required when administering these drugs.

PMID: 25994247 [PubMed - indexed for MEDLINE]

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Challenges in the diagnosis and management of cervical neuroendocrine carcinoma.

Related Articles

Challenges in the diagnosis and management of cervical neuroendocrine carcinoma.

Expert Rev Anticancer Ther. 2015;15(7):805-10

Authors: Burzawa J, Gonzales N, Frumovitz M

Abstract
Neuroendocrine carcinoma represents about 1% all cervical cancers accounting for 100-200 diagnoses annually in the USA. Although it is uncommon, it is an aggressive histologic subtype of this otherwise favorable disease. To date, there are no prospective studies or randomized trials specific to this disease to guide standard of care management. Published literature consists of small case series mostly describing single-institution experiences. The Society of Gynecologic Oncology and Gynecologic Cancer InterGroup have issued consensus guidelines about the treatment of this disease based on the existing retrospective literature and expert opinion. Ongoing research is focused on further clarifying the best treatment regimen and defining molecular alterations of these tumors that can be exploited by novel treatment mechanisms. The objective of this manuscript is to describe this entity, review the literature, summarize current treatment recommendations, and propose possible research efforts for women with neuroendocrine cervical cancer.

PMID: 25980782 [PubMed - indexed for MEDLINE]

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When crizotinib-induced bradycardia becomes symptomatic: role of concomitant drugs.

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When crizotinib-induced bradycardia becomes symptomatic: role of concomitant drugs.

Expert Rev Anticancer Ther. 2015;15(7):761-3

Authors: Gallucci G, Tartarone A, Lombardi L, Aieta M

Abstract
Crizotinib is an orally active multi-target tyrosine kinase inhibitor which is the standard of care in patients with anaplastic lymphoma kinase translocated non-small-cell lung cancer. Common adverse events in clinical trials with crizotinib included visual disorders, nausea-vomiting, diarrhea and elevated transaminases. Less common toxicities are emerging, such as bradycardia and QT interval prolongation. We report on a case of a presyncopal episode which occurred under crizotinib and metoclopramide treatment.

PMID: 25961872 [PubMed - indexed for MEDLINE]

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Radiotherapy treatment for nonmelanoma skin cancer.

Related Articles

Radiotherapy treatment for nonmelanoma skin cancer.

Expert Rev Anticancer Ther. 2015;15(7):765-76

Authors: Rong Y, Zuo L, Shang L, Bazan JG

Abstract
Non-melanoma skin cancer is the most common malignancy in the USA, with an estimated 3.5 million cases per year. Treatment options include surgical excision, radiation therapy (RT), photodynamic therapy and topical agents. Although surgical excision remains the mainstay of therapy, RT offers an effective alternative. RT can be used as an adjunct to surgery in high-risk situations, or in cases where surgical excision would lead to impaired cosmesis and/or functional outcomes. Radiation treatment modalities for non-melanoma skin cancers are diverse. Studies in the literature have examined the clinical effects of a wide variety of modalities, areas of the body and dosages. The most common modalities include superficial or orthovoltage RT, electron beam therapy and high dose-rate brachytherapy. This article aims to review the diverse radiotherapy treatment modalities for non-melanoma skin cancers, focusing on tumor control and toxicity.

PMID: 25955383 [PubMed - indexed for MEDLINE]

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Prognostic indicators of lenalidomide for multiple myeloma: consensus and controversy.

Related Articles

Prognostic indicators of lenalidomide for multiple myeloma: consensus and controversy.

Expert Rev Anticancer Ther. 2015;15(7):787-804

Authors: Kuroda J, Kobayashi T, Taniwaki M

Abstract
The long-term outcome of multiple myeloma (MM) has been greatly improved through new agents, one being lenalidomide (LEN). Based upon the findings of in vitro experiments, its mode of action against MM occurs through a combination of direct tumoricidal effects on myeloma cells, modulatory effects on tumor immunity and tumor microenvironment-regulatory effects. However, it has not been clearly defined whether the clinical response and long-term outcome of MM with LEN treatment truly reflect the mechanisms of action of LEN proposed by in vitro studies. To ascertain what is known and what remains to be elucidated with LEN, we review the current literature on the mode of action of LEN in association with myeloma pathophysiology, and discuss the prognostic indicators in the treatment of MM with LEN.

PMID: 25947283 [PubMed - indexed for MEDLINE]

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Surgical treatment of unruptured dissecting intracranial aneurysms of vertebral - posterior inferior cerebellar artery region and review of the literature.

Surgical treatment of unruptured dissecting intracranial aneurysms of vertebral - posterior inferior cerebellar artery region and review of the literature.

J Neurosurg Sci. 2016 Apr 28;

Authors: Balik V, Yamada Y, Talari S, Yamashiro K, Rile W, Suyama D, Kawase T, Takagi K, Takizawa K, Kato Y

Abstract
AIM: A lack of published surgical experience and higher symptomatic recurrence than previously recognized prompted the authors to present their experience with the surgical treatment of unruptured intracranial dissecting aneurysms (UIDAs).
METHODS: Hospital records, neuroimaging studies, operative reports, and follow-up records were retrospectively reviewed. Four patients with vertebral - posterior inferior cerebellar artery (VA-PICA) UIDAs surgically treated between September 2014 and September 2015 were included in the study along with a review of the literature.
RESULTS: There were 3 men and 1 woman in the studied group, their age ranging from 42 to 66 years. Three presented with chronic headache, and in one the dissecting aneurysm was detected incidentally. All patients underwent surgical exploration of the lesion with proximal clipping of the parent artery through a far-lateral suboccipital craniotomy with or without partial condylar resection. In two patients (Cases 1 and 4) an occipital artery (OA)-PICA bypass was performed. Case 1 had a nasal cerebrospinal fluid (CSF) leak and loss of sweet taste postoperatively. The CSF leak was successfully treated conservatively and loss of sweet taste gradually improved. All patients reached a modified Rankin scale of 0-1 at discharge. The follow-up period ranged from 1 to 28 weeks with a mean of 17 weeks. No hemorrhagic or ischemic complications were observed during the follow-up period.
CONCLUSION: The surgical treatment of VA-PICA UIDAs has acceptable risk regarding perioperative mortality and morbidity. The incidence of aneurysmal recurrence or the need for retreatment seems to be less than that associated with anticoagulation/antiplatelet therapy or endovascular treatment.

PMID: 27124175 [PubMed - as supplied by publisher]

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Reconstruction of the Base of Skull Defect-Lessons Learned over 25 Combined Years.

Reconstruction of the Base of Skull Defect-Lessons Learned over 25 Combined Years.

J Neurol Surg B Skull Base. 2016 Apr;77(2):161-8

Authors: Rowe D, Emmett J

Abstract
With an increased understanding of the pathological processes involved in perinerual spread, surgery has come to play a greater role in its management. As skull base techniques have been refined, the reconstructive surgeon has been presented with increasingly complex and voluminous defects requiring repair. To enable such surgery to have acceptable outcomes, attention to form and function is paramount. This article describes the methods of repair, which have evolved over the last 25 years of practice, and that we find to be both reliable and durable. Our accumulated experience is presented as a treatment algorithm, which will aid the skull base reconstructive surgeon to achieve success for the wide variety of defects encountered with these patients.

PMID: 27123392 [PubMed]

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Development and validation of a smartphone-based digits-in-noise hearing test in South African English.

Development and validation of a smartphone-based digits-in-noise hearing test in South African English.

Int J Audiol. 2016 Apr 28;:1-7

Authors: Potgieter JM, Swanepoel W, Myburgh HC, Hopper TC, Smits C

Abstract
OBJECTIVE: The objective of this study was to develop and validate a smartphone-based digits-in-noise hearing test for South African English.
DESIGN: Single digits (0-9) were recorded and spoken by a first language English female speaker. Level corrections were applied to create a set of homogeneous digits with steep speech recognition functions. A smartphone application was created to utilize 120 digit-triplets in noise as test material. An adaptive test procedure determined the speech reception threshold (SRT). Experiments were performed to determine headphones effects on the SRT and to establish normative data.
STUDY SAMPLE: Participants consisted of 40 normal-hearing subjects with thresholds ≤15 dB across the frequency spectrum (250-8000 Hz) and 186 subjects with normal-hearing in both ears, or normal-hearing in the better ear.
RESULTS: The results show steep speech recognition functions with a slope of 20%/dB for digit-triplets presented in noise using the smartphone application. The results of five headphone types indicate that the smartphone-based hearing test is reliable and can be conducted using standard Android smartphone headphones or clinical headphones.
CONCLUSION: A digits-in-noise hearing test was developed and validated for South Africa. The mean SRT and speech recognition functions correspond to previous developed telephone-based digits-in-noise tests.

PMID: 27121117 [PubMed - as supplied by publisher]

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The New Interventional Radiology Pathways

Publication date: Available online 28 April 2016
Source:Academic Radiology
Author(s): Michael Recht, J. Mark McKinney, Anthony M. Alleman, Lisa H. Lowe, James B. Spies
The new interventional radiology (IR) pathways have generated much discussion with articles and editorials pointing out perceived advantages and disadvantages compared to the current pathways. To briefly review, under the new system, there are three pathways to enter IR: the integrated (INT) IR residency, the independent (IND) IR residency, and the early specialization in interventional radiology (ESIR) program. The pathways have been designed to provide maximum flexibility to programs for implementation and to radiology residents for planning their subspecialty training. As a result, there are many potential permutations for these training programs, and understanding the variety of options can be a challenge at first. We offer three potential solutions, based on the different circumstances or requirements a department might face. The first two solutions involve integrated programs created through newly funded and converted diagnostic radiology slots, respectively. The third involves establishing ESIR and IND programs only. Hopefully, the examples provided will be useful for those currently planning for the future of their IR training programs.



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Diastereoselective Three-Component Cascade Reaction to Construct Oxindole-Fused Spirotetrahydro­furochroman Scaffolds for Drug Discovery

Abstract

A one-pot synthesis of new oxindole-fused polycyclic scaffolds is reported. The process involves a three-component [3+2] cycloaddition followed by cyclization through an intramolecular Michael addition. The reaction gives easy access to oxindole-fused spirotetrahydrofurochromans in moderate to good yields with high regio- and diastereoselectivity. These compounds could be useful for for drug discovery. Further modification was achieved by reduction of the nitro group, and intramolecular amide formation to give the corresponding lactams. The resulting heterocyclic products show good inhibitory activity against the enzyme PTP1B in vitro.

A one-pot three-component cascade reaction involving a [3+2] cycloaddition followed by a cyclization through intramolecular Michael addition was used to generate two families of oxindole-fused spirotetrahydrofurochroman polyheterocycles with high regio- and diastereoselectivity. The resulting polycyclic products were found to inhibit the enzyme PTP1B in vitro.

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Baylis–Hillman Acetates in Synthesis: Copper(I)/tert-Butyl Hydroperoxide Promoted One-Pot Oxidative Intramolecular Cyclization Protocol for the Preparation of Pyrrole-Fused Compounds and the Formal Synthesis of (±)-Crispine A

Abstract

A convenient one-pot protocol for the synthesis of benzo-fused and indole-fused indolizines from Baylis–Hillman acetates was developed. This strategy involves CuBr/tert-butyl hydroperoxide promoted oxidation, intramolecular cyclization, and aromatization as key steps. The efficacy of this methodology was demonstrated by the formal synthesis of (±)-crispine A, a biologically active molecule.

A one-pot, four-step strategy involving alkylation, oxidation, intramolecular cyclization, and aromatization is developed for the synthesis of pyrrole-fused tri- and tetracyclic compounds by using Baylis–Hillman acetates as the starting materials. A formal synthesis of biologically active (±)-crispine A is also achieved. EWG = electron-withdrawing group.

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Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma.

Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma.

Expert Opin Pharmacother. 2016 Apr 28;

Authors: Konstas AG, Holló G

Abstract
INTRODUCTION: Medical therapy of glaucoma aims to maintain the patient's visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence. Areas covered. The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®). Expert opinion. The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.

PMID: 27123557 [PubMed - as supplied by publisher]

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A dual-site two-photon fluorescent probe for visualizing lysosomes and tracking lysosomal hydrogen sulfide with two different sets of fluorescence signals in the living cells and mouse liver tissues

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC02368A, Communication

Yong Liu, Fangfang Meng, Longwei He, Keyin Liu, Weiying Lin
Herein, we have developed a novel dual-site two-photon fluorescent probe TP-PMVC as the first paradigm of the probes which can concurrently report lysosomes and lysosomal H2S with two different sets...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Effect of MP4 Therapy Videos on Adherence to Voice Therapy Home Practice in Children With Dysphonia

Publication date: Available online 28 April 2016
Source:Journal of Voice
Author(s): Maia N. Braden, Eva van Leer
Objectives/HypothesisVoice disorders in children are often treated with behavioral voice therapy, which requires home practice of exercises. Previous studies with adults demonstrated increased practice frequency when patients were given videos of a clinician and patient performing therapy tasks. The purpose of this study was to determine whether videos of practice exercises would increase adherence to therapy in children.Study DesignThe study used a randomized double crossover research design.MethodsTwenty-eight patients, aged 6–18, referred for voice therapy were included in the study. Two conditions were alternated on a weekly basis: standard-of-care therapy and standard-of-care therapy with video models added. Participants recorded practice frequency and participated in semi-structured interviews, which were analyzed for themes.ResultsParticipants practiced an average of 1.79 times per day without videos and 1.72 with videos (P = 0.743), indicating no significant difference between conditions. There was also no age group effect (P = 0.314). Qualitative analysis of interview responses established the following themes: (1) I knew how to do my exercises, (2) I didn't like seeing/hearing myself, (3) Videos helped me remember to practice, (4) I didn't like the video player itself, (5) The videos didn't make a difference with practice, and (6) Practicing was no fun.ConclusionsVideo models of therapy tasks do not appear to influence adherence to home practice frequency in children with voice disorders, in contrast to findings in adults. Videos were found useful by several participants as reminders to practice.



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Characterization of Flow-resistant Tubes Used for Semi-occluded Vocal Tract Voice Training and Therapy

Publication date: Available online 28 April 2016
Source:Journal of Voice
Author(s): Simeon L. Smith, Ingo R. Titze
ObjectivesThis study aimed to characterize the pressure-flow relationship of tubes used for semi-occluded vocal tract voice training/therapy, as well as to answer these major questions: (1) What is the relative importance of tube length to tube diameter? (2) What is the range of oral pressures achieved with tubes at phonation flow rates? (3) Does mouth configuration behind the tubes matter?MethodsPlastic tubes of various diameters and lengths were mounted in line with an upstream pipe, and the pressure drop across each tube was measured at stepwise increments in flow rate. Basic flow theory and modified flow theory equations were used to describe the pressure-flow relationship of the tubes based on diameter and length. Additionally, the upstream pipe diameter was varied to explore how mouth shape affects tube resistance.ResultsThe modified equation provided an excellent prediction of the pressure-flow relationship across all tube sizes (6% error compared with the experimental data). Variation in upstream pipe diameter yielded up to 10% deviation in pressure for tube sizes typically used in voice training/therapy.ConclusionsUsing the presented equations, we can characterize resistance for any tube based on diameter, length, and flow rate. With regard to the original questions, we found that (1) For commonly used tubes, diameter is the critical variable for governing flow resistance; (2) For phonation flow rates, a range of tube dimensions produced pressures between 0 and 7.0 kPa; and (3) The mouth pressure behind the lips will vary slightly with different mouth shapes, but this effect can be considered relatively insignificant.



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Novel reduced graphene oxide-glycol chitosan nanohybrid for the assembly of amperometric enzyme biosensor for phenols

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C5AN02640G, Paper

Abderrahmane Boujakhrout, Sandra Jimenez, Paloma Martinez-Ruiz, Alfredo Sanchez, Paula Diez, Jose M Pingarron, Reynaldo Villalonga
A novel water-soluble graphene derivative was prepared from graphene oxide through a two-step modification approach. Graphene oxide was first provided with reactive epoxy groups by covalent modification with (3-glycidyloxypropyl)trimethoxysilane and...
The content of this RSS Feed (c) The Royal Society of Chemistry

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IJMS, Vol. 17, Pages 651: Data Interoperability of Whole Exome Sequencing (WES) Based Mutational Burden Estimates from Different Laboratories

Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. Several independent studies suggest that higher non-synonymous mutational burden assessed by whole exome sequencing (WES) in tumors is associated with improved objective response, durable clinical benefit, and progression-free survival in immune checkpoint inhibitors treatment. Next-generation sequencing (NGS) is a promising technology being used in the clinic to direct patient treatment. Cancer genome WES poses a unique challenge due to tumor heterogeneity and sequencing artifacts introduced by formalin-fixed, paraffin-embedded (FFPE) tissue. In order to evaluate the data interoperability of WES data from different sources to survey tumor mutational landscape, we compared WES data of several tumor/normal matched samples from five commercial vendors. A large data discrepancy was observed from vendors' self-reported data. Independent data analysis from vendors' raw NGS data shows that whole exome sequencing data from qualified vendors can be combined and analyzed uniformly to derive comparable quantitative estimates of tumor mutational burden.

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IJMS, Vol. 17, Pages 645: Over-Expression of GmGIa-Regulated Soybean miR172a Confers Early Flowering in Transgenic Arabidopsis thaliana

Flowering is a pivotal event in the life cycle of plants. miR172 has been widely confirmed to play critical roles in flowering time control by regulating its target gene expression in Arabidopsis. However, the role of its counterpart in soybean remains largely unclear. In the present study, we found that the gma-miR172a was regulated by a GIGANTEA ortholog, GmGIa, in soybean through miRNA metabolism. The expression analysis revealed that gma-miR172a has a pattern of diurnal rhythm expression and its abundance increased rapidly as plants grew until the initiation of flowering phase in soybean. One target gene of gma-miR172a, Glyma03g33470, was predicted and verified using a modified RLM 5′-RACE (RNA ligase-mediated rapid amplification of 5′ cDNA ends) assay. Overexpression of gma-miR172a exhibited an early flowering phenotype and the expression of FT, AP1 and LFY were simultaneously increased in gma-miR172a-transgenic Arabidopsis plants, suggesting that the early flowering phenotype was associated with up-regulation of these genes. The overexpression of the gma-miR172a-resistant version of Glyma03g33470 weakened early flowering phenotype in the toe1 mutant of Arabidopsis. Taken together, our results suggested that gma-miR172a played an important role in GmGIa-mediated flowering by repressing Glyma03g33470, which in turn increased the expression of FT, AP1 and LFY to promote flowering in soybean.

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IJMS, Vol. 17, Pages 647: Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI.

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Guillain-Barré syndrome occurring synchronously with systemic lupus erythematosus as initial manifestation treated successfully with low-dose cyclophosphamide.

Guillain-Barré syndrome occurring synchronously with systemic lupus erythematosus as initial manifestation treated successfully with low-dose cyclophosphamide.

J Community Hosp Intern Med Perspect. 2016;6(2):30689

Authors: Ali N, Rampure R, Malik F, Jafri SI, Amberker D

Abstract
Systemic lupus erythematous (SLE) is frequently encountered in clinical practice; a widespread immunological response can involve any organ system, sometimes leading to rare and diagnostically challenging presentations. We describe a 38-year-old female who presented with symmetric numbness and tingling of the hands and feet, and cervical pain. Imaging studies were not diagnostic of any serious underlying pathology. The patient developed ascending paresis involving lower extremities and cranial muscles (dysphagia and facial weakness). Guillain-Barré syndrome (GBS) was diagnosed on the basis of electromyography and lumbar puncture showing albuminocytologic dissociation. Intravenous immunoglobulins (IVIG) were administered for 5 days. Supported by anti-dsDNA antibody, oral ulcers, proteinuria of 0.7 g in 24 h, and neurological manifestation, she was diagnosed with lupus. After completion of IVIG, she received pulse-dose corticosteroids and one dose of low-dose cyclophosphamide. Her neurological symptoms improved and she had complete neurological recovery several months after her initial presentation. Literature search provides evidence of co-occurrence of lupus and GBS occurring mostly later in the course of the disease. However, GBS as initial manifestation of SLE is exceedingly rare and less understood. The association of GBS with lupus is important to recognize for rapid initiation of appropriate therapy and for consideration of immunosuppressive therapy which may affect the outcome.

PMID: 27124163 [PubMed - as supplied by publisher]

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Polymorphous low-grade adenocarcinoma of the epiglottis: A case report.

Polymorphous low-grade adenocarcinoma of the epiglottis: A case report.

Mol Clin Oncol. 2016 May;4(5):779-782

Authors: Larbcharoensub N, Sanpaphant S, Witoonpanich P, Tuntiyatorn L, Tungkeeratichai J, Cheewaruangroj W

Abstract
Polymorphous low-grade adenocarcinoma is an uncommon malignant tumor derived from the terminal duct cells of the salivary glands. The present study described a rare case of polymorphous low-grade adenocarcinoma, T2N0M0 stage 2, in a 65-year-old man, who presented with a sore throat and painful dysphagia. Computed tomography revealed an infiltrative heterogenous enhancing mass involving the left aryepiglottic fold. He underwent a tumor removal with frozen section for evaluating the surgical margin. Subsequent supraglottic laryngectomy was performed. Polymorphous low-grade adenocarcinoma was diagnosed histologically, characterized by cytologic uniformly, morphologic diversity and an infiltrative growth pattern. Epiglottic cartilaginous invasion by the tumor is demonstrated. Clinical, radiological, endoscopic and pathological features with briefly reviewed relevant literatures are discussed. This is the first reported description in the literature, to the best of our knowledge, of an epiglottic polymorphous low-grade adenocarcinoma receiving successful supraglottic laryngectomy with 7 year disease free survival.

PMID: 27123278 [PubMed - as supplied by publisher]

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Esophageal cancer diagnosed by high-resolution manometry of the esophagus: A case report.

Esophageal cancer diagnosed by high-resolution manometry of the esophagus: A case report.

Oncol Lett. 2016 May;11(5):3131-3134

Authors: Liu R, Chu H, Xu F, Chen S

Abstract
A 48-year-old female who presented with a history of dysphagia for 5 months and regurgitation for 1 week was referred to the Sir Run Run Shaw Hospital (Hangzhou, China) for further evaluation, since the gastroscopy and endoscopic ultrasound performed in local hospitals did not reveal the presence of cancer. High-resolution manometry (HRM) of the esophagus was performed to determine the patient's condition, and revealed an abnormal high-pressure zone that was located 33 cm from the incisor and did not relax upon swallowing. Synchronous waves were observed, and the pressure of the esophageal lumen was found to increase with secondary synchronous peristaltic waves. The lower esophageal sphincter was 39 cm from the incisor and relaxed upon swallowing. The abnormal high-pressure zone could have been caused by an obstruction, and therefore an upper gastrointestinal series (barium swallow) test and gastroscopy were recommended to further pinpoint the cause. Following the two examinations, mid-esophageal cancer was considered as a possible diagnosis. A biopsy was performed and the final diagnosis was that of basaloid squamous cell carcinoma. The findings of the present study suggest that, for patients with evident symptoms of esophageal motor dysfunction without significant gastroscopy findings, HRM is recommended.

PMID: 27123076 [PubMed - as supplied by publisher]

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Synchronous metastatic skull base chordoma to the breast: case report and literature review.

Synchronous metastatic skull base chordoma to the breast: case report and literature review.

Curr Oncol. 2016 Apr;23(2):e154-7

Authors: Shakir SI, Pelmus M, Florea A, Boileau JF, Guiot MC, Di Maio S, Muanza TM

Abstract
CLINICAL SCENARIO: During routine staging work-up for a left breast mass, a 68-year-old woman complained of dysphagia and dysphonia. During further investigations, a left-sided lesion at the foramen magnum was observed on brain imaging. Both lesions were biopsied and showed a classical chordoma.
MANAGEMENT: The skull-base lesion and the breast lesion were surgically resected, and adjuvant radiotherapy was given.
SUMMARY: Chordoma is a rare primary central nervous system tumour that seldom metastasizes. The lung is the most common site of metastasis. Synchronous breast metastasis from a skull-base chordoma is very rare, and a safe management option includes a maximum resection followed by adjuvant radiotherapy.

PMID: 27122985 [PubMed]

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An Interdisciplinary Approach To Dysphagia.

An Interdisciplinary Approach To Dysphagia.

Provider. 2016 Mar;42(3):37-8, 40-2

Authors: Kinder R

PMID: 27120877 [PubMed - in process]

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Randomized Controlled Trial of Laparoscopic and Open Nissen Fundoplication in Children.

Related Articles

Randomized Controlled Trial of Laparoscopic and Open Nissen Fundoplication in Children.

Ann Surg. 2015 Jun;261(6):1061-7

Authors: Fyhn TJ, Knatten CK, Edwin B, Schistad O, Aabakken L, Kjosbakken H, Pripp AH, Emblem R, Bjørnland K

Abstract
OBJECTIVE: The aim was to compare recurrence of gastroesophageal reflux disease (GERD) in children randomized to laparoscopic (LF) or open Nissen fundoplication (OF).
BACKGROUND: LF is considered superior to OF by most pediatric surgeons even though this has not been shown in any randomized controlled trial in children.
METHODS: Patients referred for fundoplication between 2003 and 2009 were eligible for inclusion in this 2-center, unstratified, randomized, parallel-group study conducted in Norway. The main outcome measure was recurrence of GERD, which was defined as GERD combined with a reflux index greater than 4 on pH monitoring and/or gastroesophageal reflux and/or herniated wrap on upper gastrointestinal (UGI) contrast study. Only experienced laparoscopic surgeons performed the LF. Postoperative follow-up included 24-hour pH monitoring, UGI contrast study, and a clinical examination at 6 months and phone interviews after 1, 2, and 4 years.
RESULTS: Eighty-seven children were included and randomized to either LF (n = 44) or OF (n = 43). Median age was 4.7 years (0.2-15.4) in the LF group and 3.7 years (0.2-14.2) in the OF group. Twenty-three patients in both groups were neurologically impaired. Median follow-up time was 4.0 years (0.3-8.9). Significantly more patients undergoing LF (37%) experienced recurrence of GERD compared to those undergoing OF (7%); risk ratio for recurrence in the LF group was 5.2 (95% confidence interval: 1.6-16.6) (P = 0.001).
CONCLUSIONS: Children operated with LF have a higher recurrence rate of GERD than those operated with OF.

PMID: 26291953 [PubMed - indexed for MEDLINE]

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The assessment of children with suspected laryngopharyngeal reflux: An Otorhinolaringological perspective.

Related Articles

The assessment of children with suspected laryngopharyngeal reflux: An Otorhinolaringological perspective.

Int J Pediatr Otorhinolaryngol. 2015 Oct;79(10):1613-9

Authors: Galluzzi F, Schindler A, Gaini RM, Garavello W

Abstract
The assessment of pediatric laryngopharyngeal reflux (LPR) is controversial. Otorhinolaryngologists may play a role in the evaluation of children with suspected LPR detecting typical airway endoscopic findings and/or associated diseases and may help in the selection of children to be subjected to further instrumental tests. In this perspective the present review aims at examining the available evidence in the literature regarding the assessment of LPR in children. After careful literature search there are no current validated symptoms assessment questionnaires for LPR evaluation in children; flexible fiberoptic nasopharyngolaryngoscopy remains controversial as a diagnostic tool in suspect LPR cases; even though the multichannel intraluminal impedance with pH monitoring has been proposed as the instrumental gold standard, further evidence need to be found for validation in children with typical features of LPR.

PMID: 26279249 [PubMed - indexed for MEDLINE]

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The surgical management of achalasia in the morbid obese patient.

Related Articles

The surgical management of achalasia in the morbid obese patient.

J Gastrointest Surg. 2015 Jun;19(6):1139-43

Authors: Fisichella PM, Orthopoulos G, Holmstrom A, Patti MG

Abstract
INTRODUCTION: Morbid obesity and achalasia may coexist in the same patient. The surgical management of the morbidly obese patient with achalasia is complex, and the most effective treatment still remains controversial. The goal of our report is to provide our evidence-based approach for the surgical management of the patient with achalasia and morbid obesity.
RESULTS: Three main surgical approaches have been used for the concomitant treatment of morbid obesity and achalasia: 1) a laparoscopic Heller myotomy and a laparoscopic Roux-en-Y gastric bypass (LRYGB); 2) a laparoscopic Heller myotomy with bilio-pancreatic diversion; and 3) a laparoscopic Heller myotomy with a sleeve gastrectomy. Our approach of choice is the first one discussed, that is the laparoscopic Heller myotomy with a LRYGB, as this approach can provide excellent relief of symptoms and control of reflux while at the same time treating obesity and its comorbidities.
CONCLUSIONS: Achalasia and obesity can coexist, albeit infrequently. A laparoscopic Heller myotomy with a LRYGB allows the simultaneous treatment of both diseases. When a morbidly obese patient with achalasia chooses to have a myotomy alone and not a LRYGB, a thorough discussion of the risks and benefits should occur and the autonomy of the patient's decision-making should be respected.

PMID: 25759076 [PubMed - indexed for MEDLINE]

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Sub-5V germanium waveguide avalanche photodiode based 25 Gb/s 1310 nm optical receiver

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Demonstration of a 4 x 4-port univeral coupler

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Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden.

Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden.

Acta Oncol. 2016 May;55(5):554-560

Authors: Borg S, Nahi H, Hansson M, Lee D, Elvidge J, Persson U

Abstract
BACKGROUND: Multiple myeloma (MM) patients who have progressed following treatment with both bortezomib and lenalidomide have a poor prognosis. In this late stage, other effective alternatives are limited, and patients in Sweden are often left with best supportive care. Pomalidomide is a new anti-angiogenic and immunomodulatory drug for the treatment of MM. Our objective was to evaluate the cost effectiveness of pomalidomide as an add-on to best supportive care in patients with relapsed and refractory MM in Sweden.
MATERIAL AND METHODS: We developed a health-economic discrete event simulation model of a patient's course through stable disease and progressive disease, until death. It estimates life expectancy, quality-adjusted life years (QALYs) and costs from a societal perspective. Effectiveness data and utilities were taken from the MM-003 trial comparing pomalidomide plus low-dose dexamethasone with high-dose dexamethasone (HIDEX). Cost data were taken from official Swedish price lists, government sources and literature.
RESULTS: The model estimates that, if a patient is treated with HIDEX, life expectancy is 1.12 years and the total cost is SEK 179 976 (€19 100), mainly indirect costs. With pomalidomide plus low-dose dexamethasone, life expectancy is 2.33 years, with a total cost of SEK 767 064 (€81 500), mainly in drug and indirect costs. Compared to HIDEX, pomalidomide treatment gives a QALY gain of 0.7351 and an incremental cost of SEK 587 088 (€62 400) consisting of increased drug costs (59%), incremental indirect costs (33%) and other healthcare costs (8%). The incremental cost-effectiveness ratio is SEK 798 613 (€84 900) per QALY gained.
CONCLUSION: In a model of late-stage MM patients with a poor prognosis in the Swedish setting, pomalidomide is associated with a relatively high incremental cost per QALY gained. This model was accepted by the national Swedish reimbursement authority TLV, and pomalidomide was granted reimbursement in Sweden.

PMID: 27123742 [PubMed - as supplied by publisher]

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Pattern of employment and associated factors in long-term lymphoma survivors 10 years after high-dose chemotherapy with autologous stem cell transplantation.

Pattern of employment and associated factors in long-term lymphoma survivors 10 years after high-dose chemotherapy with autologous stem cell transplantation.

Acta Oncol. 2016 May;55(5):547-553

Authors: Kiserud CE, Fagerli UM, Smeland KB, Fluge Ø, Bersvendsen H, Kvaløy S, Holte H, Dahl AA

Abstract
Background This study examined employment patterns and associated factors in lymphoma survivors treated with high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) from diagnosis to a follow-up survey at a mean of 10 years after HDT-ASCT. Patients and methods All lymphoma survivors aged ≥18 years at HDT-ASCT in Norway from 1987 to 2008, and alive at the end of 2011 were eligible for this cross-sectional study performed in 2012/2013. Participants completed a mailed questionnaire. Job status was dichotomized as either employed (paid work) or not-employed (disability and retirement pension, on economic support, home-makers, or students). Results The response rate was 78%, and the sample (N = 312) contained 60% men. Mean age at HDT-ASCT was 44.3 and at survey 54.0 years. At diagnosis 85% of survivors were employed, 77% before and 77% after HDT-ASCT, and 58% at follow-up. Forty seven percent of the survivors were employed at all time points. The not-employed group at survey was significantly older and included significantly more females than the employed group. No significant between-group differences were observed for lymphoma-related variables. Fatigue, mental distress and type D personality were significantly higher among those not-employed, while quality of life was significantly lower compared to the employed group. Older age at survey, being female, work ability and presence of type D personality remained significantly related to being not-employed at survey in the multivariable analysis. Conclusions Our findings show that not-employed long-term survivors after HDT-ASCT for lymphoma have more comorbidity, cognitive problems and higher levels of anxiety/depression than employed survivors. These factors should be checked and eventually treated in order to improve work ability.

PMID: 27123741 [PubMed - as supplied by publisher]

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Effect of coenzyme A on outer hair cells in cisplatin ototoxicity: functional and ultrastructural study.

Effect of coenzyme A on outer hair cells in cisplatin ototoxicity: functional and ultrastructural study.

Histol Histopathol. 2016 Apr 28;:11775

Authors: Fernández-Cervilla F, Martínez-Martínez M, Fernández-Segura E, Cañizares-García FJ, Crespo-Ferrer PV

Abstract
The aim of this study was to use functional and morphological analyses to evaluate the protective effect of coenzyme A (CoA) in cisplatin-induced toxicity in outer hair cells (OHC). Three groups of 8 guinea pigs were used: control (group I), cisplatin-treated (group II) and cisplatin + CoA-treated (group III). In groups II and III, a single ototoxic dose of cisplatin (10 mg/kg) was injected intraperitoneally. Group III was co-treated with CoA (900 μg/kg per day for 7 consecutive days). Electrocochleography (ECoG) recordings were made before and after the 7-day treatment period in all groups. After ECoG on day 7, all animals were anesthetized and the cochleae were removed and fixed for ultrastructural analysis. Cell damage in OHC was observed with transmission electron microscopy. Cisplatin induced a significant increase in auditory thresholds (p<0.001) compared to group I (control). In contrast, group III (cisplatin + CoA) had significantly reduced thresholds (p<0.001) compared to the group treated with cisplatin alone (group II).We found no significant differences between the control group and animals co-treated with cisplatin and CoA. The electron microscopy findings in OHC were consistent with these results. Ultrastructural analysis of OHC in group II showed morphological indications of necrosis, i.e. cytoplasmic swelling and vacuolation, and mitochondrial swelling. In group III the cell morphology of OHC was preserved, with ultrastructural characteristics similar to the control group. In conclusion, co-treatment with cisplatin with CoA inhibited antineoplastic-induced cytotoxicity in OHC in a guinea pig model.

PMID: 27121633 [PubMed - as supplied by publisher]

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Determination of energy absorption and exposure buildup factors by using G-P fitting approximation for radioprotective agents

10.1080/09553002.2016.1175681<br/>Esra Kavaz

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5´-AMP-activated Protein Kinase (AMPK) Regulates Papillary (TPC-1 and BCPAP) Thyroid Cancer Cell Survival, Migration, Invasion and Epithelial-to-Mesenchymal Transition.

5´-AMP-activated Protein Kinase (AMPK) Regulates Papillary (TPC-1 and BCPAP) Thyroid Cancer Cell Survival, Migration, Invasion and Epithelial-to-Mesenchymal Transition.

Thyroid. 2016 Apr 27;

Authors: Cazarin JM, Coelho RG, Hecht F, Andrade BM, Carvalho DP

Abstract
BACKGROUND: Differentiated thyroid carcinomas (DTC) are associated with a good prognosis and a high survival rate. However, tumor recurrence occurs in approximately 20% to 30% of DTC patients, reinforcing the importance of identifying new molecular targets for cancer management. We have shown that the 5´-AMP-activated protein kinase (AMPK) is over-activated in papillary thyroid cancer (PTC). In this study, we aimed to investigate the effects of AICAR, an AMPK activator, on various aspects of thyroid cancer cell behavior, including cell survival, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT), in the human thyroid cancer cell lines BCPAP and TPC-1.
METHODS: BCPAP and TPC-1 cells were cultivated in DMEM, and the non-tumor-derived cell line Nthy-ORI was grown in RPMI. Cells were treated or not with AICAR for different periods of time. We analyzed the cell growth rate, cell cycle phase, apoptosis, cell migration and invasion using Transwell inserts, and EMT was quantified by the expression of mesenchymal and epithelial markers.
RESULTS: AMPK is activated in thyroid cancer cell lines and AICAR treatment further increased AMPK phosphorylation. After 48 h of AICAR treatment, the percentage of cells in the G2/M phase decreased and a G0/G1-phase arrest was induced in all of the cells. AMPK activation effectively induced apoptosis in the BCPAP and TPC-1 cancer cell lines, while no apoptosis induction was observed in Nthy-ORI. AICAR also reduced the migration of Nthy-ORI and BCPAP cells by 30% and approximately 60% in TPC-1 cells. AICAR had no effect on cell invasion in Nthy-ORI and TPC-1 cells, but a significant reduction of cell invasion was observed in BCPAP cells. AICAR induced a significant reduction of N-cadherin and no changes in the expression of vimentin or TCF/Zeb1 protein in BCPAP cells. No differences in the expression of EMT markers were found in the AICAR-treated NTHY-ORI cells. A remarkable reduction of vimentin, TCF/Zeb1 and N-cadherin protein expression was detected in the TPC-1 cells.
CONCLUSIONS: Increased activation of AMPK in PTC cell lines leads to a strong anti-tumor response, as measured by the inhibition of cell proliferation, cell migration and induction of cell death. We also demonstrate that AMPK activation reverses EMT in TPC-1 cells.

PMID: 27121619 [PubMed - as supplied by publisher]

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Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion-Preliminary Observations.

Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion-Preliminary Observations.

J Thyroid Res. 2016;2016:2454989

Authors: Sarosiek K, Gandhi AV, Saxena S, Kang CY, Chipitsyna GI, Yeo CJ, Arafat HA

Abstract
According to the epidemiological studies, about 4.4% of American general elderly population has a pronounced hypothyroidism and relies on thyroid hormone supplements daily. The prevalence of hypothyroidism in our patients with pancreatic cancer was much higher, 14.1%. A retrospective analysis was performed on patients who underwent pancreaticoduodenectomy (Whipple procedure) or distal pancreatectomy and splenectomy (DPS) at Thomas Jefferson University Hospital, Philadelphia, from 2005 to 2012. The diagnosis of hypothyroidism was correlated with clinicopathologic parameters including tumor stage, grade, and survival. To further understand how thyroid hormone affects pancreatic cancer behavior, functional studies including wound-induced cell migration, proliferation, and invasion were performed on pancreatic cancer cell lines, MiaPaCa-2 and AsPC-1. We found that hypothyroid patients taking exogenous thyroid hormone were more than three times likely to have perineural invasion, and about twice as likely to have higher T stage, nodal spread, and overall poorer prognostic stage (P < 0.05). Pancreatic cancer cell line studies demonstrated that exogenous thyroid hormone treatment increased cell proliferation, migration, and invasion (P < 0.05). We conclude that exogenous thyroid hormone may contribute to the progression of pancreatic cancer.

PMID: 27123358 [PubMed]

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A case of juvenile polyposis of the stomach with multiple early gastric cancers.

A case of juvenile polyposis of the stomach with multiple early gastric cancers.

Mol Clin Oncol. 2016 May;4(5):851-854

Authors: Saito R, Fukuda T, Fujikuni N, Abe T, Amano H, Nakahara M, Yonehara S, Noriyuki T

Abstract
The present study described the case of a 24-year-old man who was diagnosed with multiple gastric hyperplastic polyps in 2004. Repeated Helicobacter pylori tests were negative, and colonoscopy revealed no specific findings. The patient started taking a proton-pump inhibitor and iron supplements as a result of anemia caused from the occasional bleeding from the polyps. The number and size of the polyps had increased over time. Endoscopic mucosal resection was occasionally performed when bleeding occurred from large polyps. Finally, histological examination revealed that the surface of the polyp had been replaced with well-differentiated adenocarcinoma in 2014. Laparoscopy-assisted total gastrectomy with Roux-en-Y esophagojejunostomy was performed in 2014. The final diagnosis was juvenile polyposis of the stomach with multiple early gastric cancers. Juvenile polyposis of the stomach is a rare disease, and its malignant potential has been reported previously. The present case highlighted the importance of not delaying surgical intervention in cases of juvenile polyposis of the stomach, since it is associated with a high occurrence of gastric cancer.

PMID: 27123294 [PubMed - as supplied by publisher]

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