Clinical significance of OCT4 and SOX2 protein expression in cervical cancer

Abstracts

Background

Cancer stem cell markers have become a major research focus because of their relationship with radiation or chemotherapy resistance in cancer therapy. Cancer stem cell markers including OCT4 and SOX2 have been found in various solid tumors. Here, we investigate the expression and clinical significance of OCT4 and SOX2 in cervical cancer.

Methods

To define the clinical significance of OCT4 and SOX2 expression, we performed immunohistochemistry for OCT4 and SOX2 on 305 normal cervical epithelium samples, 289 cervical intraepithelial neoplasia samples, and 161 cervical cancer cases and compared the data with clinicopathologic factors, including survival rates of patients with cervical cancer.

Results

OCT4 and SOX2 expression was higher in cervical cancer than normal cervix (both p < 0.001). OCT4 overexpression was associated with lymphovascular space invasion (p = 0.045), whereas loss of SOX2 expression was correlated with large tumor size (p = 0.015). Notably, OCT4 and SOX2 were significantly co-expressed in premalignant cervical lesions, but not in malignant cervical tumor. OCT4 overexpression showed worse 5-year disease-free and overall survival rates (p = 0.012 and p = 0.021, respectively) when compared to the low-expression group, while SOX2 expression showed favorable overall survival (p = 0.025). Cox regression analysis showed that OCT4 was an independent risk factor (hazard ratio = 11.23, 95 % CI, 1.31 – 95.6; p = 0.027) for overall survival while SOX2 overexpression showed low hazard ratio for death (hazard ratio = 0.220, 95 % CI, 0.06–0.72; p = 0.013).

Conclusions

These results suggest that OCT4 overexpression and loss of SOX2 expression are strongly associated with poor prognosis in patients with cervical cancer.

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Low-power photodynamic therapy induces survival signaling in perihilar cholangiocarcinoma cells

Abstract

Background

Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways).

Methods

To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm2). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo.

Results

PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic.

Conclusions

PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.

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Low-power photodynamic therapy induces survival signaling in perihilar cholangiocarcinoma cells

Abstract

Background

Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways).

Methods

To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm2). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo.

Results

PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic.

Conclusions

PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.

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Can Serum glucose level in early admission, predict outcome in patints with severe head trauma ?

Can Serum glucose level in early admission, predict outcome in patints with severe head trauma ?

World Neurosurg. 2015 Dec 15;

Authors: Salehpour F, Bazzazi AM, Aghazadeh J, Abbasivash R, Forouhideh Y, Mirzaei F, Naseri Alavi SA

Abstract
BACKGROUND: Traumatic brain Injury is a major general health concern. This study aims to evaluate possible relationship between serum level of glucose during admission and outcome of patients with severe traumatic brain injury.
METHODS: In this prospective study, 80 patients with severe traumatic brain injury were recruited from emergency department of Urmia Imam Khomeini hospital. Serum level of glucose was measured at the time of admission and its correlation was investigated with Glasgow Coma Scale (GCS) score (admission, 24h, 48h, 1week, and discharge) and Glasgow Outcome Score (GOS). The value of admission serum glucose was compared between expired and discharged patients, as well.
RESULTS: Eighty patients with severe head trauma, 71 males (88%) and 9 females (11.2%) with a mean age of 31.71±15.66 were enrolled into the study. The inhospital mortality rate was 25% (n=20). There was no significant correlation between serum glucose level and GCS score (at different intervals) or GOS. The mean serum level of glucose was comparable between expired and discharged cases (186.10±51.36 vs. 187.98±76.03 mg/dl, respectively; p=0.91).
CONCLUSION: Apparently, admission serum glucose is not a significant indicator of outcome in patients with severe head trauma.

PMID: 26704213 [PubMed – as supplied by publisher]

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Subacute Posttraumatic Ascending Myelopathy after an Incomplete Spinal Cord injury from Gunshot Wound to the Spine – Case Report and Review of the Literature.

Subacute Posttraumatic Ascending Myelopathy after an Incomplete Spinal Cord injury from Gunshot Wound to the Spine – Case Report and Review of the Literature.

World Neurosurg. 2015 Dec 15;

Authors: Miller BA, Roy AK, Boucher A, Pradilla G, Ahmad FU

PMID: 26704212 [PubMed – as supplied by publisher]

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Perspective of Value-Based Management of Spinal Disorders in Brazil.

Perspective of Value-Based Management of Spinal Disorders in Brazil.

World Neurosurg. 2015 Dec 15;

Authors: Teles AR, Righesso O, Gullo MC, Ghogawala Z, Falavigna A

PMID: 26704211 [PubMed – as supplied by publisher]

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Simulation in Neurosurgery – a brief review and commentary.

Simulation in Neurosurgery – a brief review and commentary.

World Neurosurg. 2015 Dec 15;

Authors: Cobb MI, Taekman JM, Zomorodi AR, Gonzalez LF, Turner DA

Abstract
Neurosurgery is one of the most technically demanding and liable of all medical professionals. More than 75% of neurosurgical errors deemed as preventable and technical in nature. Yet in a specialty that requires such high level of technical expertise, with large consequences for error, there are even fewer opportunities for residents in training to practice on the most complicated cases. Although there is no replacement for actual experiences in the operating room, inter-personal mentorship, coaching, and training, there is room to supplement residency education through simulation. Here we review the evidence to support surgical simulation, describe the strengths and weaknesses of existing technologies in direct neurosurgery specific and indirect simulation applications, and advocate for the development of more neurosurgery specific applications using emerging kinetic technologies.

PMID: 26704209 [PubMed – as supplied by publisher]

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Outcome of microscopic Transsphenoidal Surgery in Cushing’s disease: a case series of 96 patients.

Outcome of microscopic Transsphenoidal Surgery in Cushing's disease: a case series of 96 patients.

World Neurosurg. 2015 Dec 15;

Authors: Shirvani M, Motiei-Langroudi R, Sadeghian H

PMID: 26704208 [PubMed – as supplied by publisher]

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Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigro-Striatal Disconnection.

Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigro-Striatal Disconnection.

World Neurosurg. 2015 Dec 15;

Authors: Rowe J, Khan A, Romanowski C, Isaac C, Khan S, Mair R, Aziz T, Yianni J

PMID: 26704205 [PubMed – as supplied by publisher]

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A dissecting aneurysm of the distal medial lenticulostriate artery: Case report.

A dissecting aneurysm of the distal medial lenticulostriate artery: Case report.

World Neurosurg. 2015 Dec 15;

Authors: Saito A, Kon H, Nakamura T, Sasaki T

Abstract
BACKGROUND: Medial lenticulostriate artery (MLSA) aneurysms are rare; to our knowledge only 2 cases without an association with Moyamoya disease have been documented. We treated a ruptured dissecting aneurysm of the distal MLSA surgically using a tube retractor.
CASE DESCRIPTION: A 66-year-old woman suffered sudden-onset consciousness disturbance. Computed tomography showed diffuse subarachnoid hemorrhage and a dense intraventricular hematoma associated with acute hydrocephalus. She underwent emergent ventricular drainage. Angiography revealed a 3-mm distal MLSA aneurysm. On repeat angiographs the aneurysm had not disappeared. As the stenotic, narrow structure of the proximal portion of the MLSA disallowed the endovascular approach we performed direct surgery via the transventricular approach using a tube retractor. The aneurysm on the intraventricular surface of the anterior horn of the lateral ventricle adjacent to the caudate nucleus was exposed. We resected the aneurysm under transcranial motor-evoked potential monitoring because neck clipping would have endangered the patency of the MLSA. Her postoperative course was uneventful. The pathological diagnosis was ruptured dissecting aneurysm.
CONCLUSIONS: There is no definitive strategy to treat distal MLSA aneurysms. Our experience illustrates that natural healing of the vessel wall cannot be expected in all cases. Therefore, less invasive direct surgical- as well as endovascular treatment should not be ruled out in patients with ruptured distal MLSA aneurysms.

PMID: 26704207 [PubMed – as supplied by publisher]

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Preoperative embolization of spinal tumors: A systematic review and meta-analysis.

Preoperative embolization of spinal tumors: A systematic review and meta-analysis.

World Neurosurg. 2015 Dec 15;

Authors: Griessenauer CJ, Salem M, Hendrix P, Foreman PM, Ogilvy CS, Thomas AJ

Abstract
BACKGROUND: Spinal tumors are referred for preoperative embolization to minimize intraoperative blood loss and facilitate surgical resection.
OBJECTIVE: To perform a systematic review and meta-analysis and provide comprehensive data on embolization technique, efficacy, and complications.
METHODS: A systematic review of PubMed articles was performed with the following inclusion criteria: original studies, studies of ≥ 10 patients (except Onyx due to scarcity of available data), embolization through vascular access, and reporting of the embolic agent used. Additionally the manuscript needed to contain at least one of the following variables: demographics, tumor type, location, vascularity, degree of devascularization, complications, time to operation, type of operation, estimated blood loss (EBL), and use of blood transfusion.
RESULTS: Thirty-seven studies with a total of 1,305 patients met inclusion criteria. Renal cell carcinoma was the most commonly embolized tumor comprising 47.4% (95% CI 39.4 – 55.4) of all tumor embolizations. The rate of complete devascularization for all tumor types was 68.3% (95% CI 60.0 – 76.6). There was a significant decrease in operative EBL in more recently published studies as compared to earlier studies, however, the rate of complete embolization remained stable. Polyvinyl alcohol (PVA) and Onyx(®) were associated with similar EBL and rates of complete embolization. The overall complication rate was 3.1% (95% CI 1.2 – 4.9).
CONCLUSIONS: The rapid evolution of neurointervention and spinal tumor embolization has made scientific inquiry and definitive conclusion on the safety and efficacy of the practice difficult. The data supporting the procedure is fragmented and largely based on a multitude of retrospective studies utilizing varying techniques. Review of the available literature support embolization of spinal tumors as a safe and efficacious treatment adjunct prior to surgery.

PMID: 26704206 [PubMed – as supplied by publisher]

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Naringin, a natural dietary compound, prevents intestinal tumorigenesis in Apc Min/+ mouse model

Conclusion Naringin prevented intestinal tumorigenesis likely through a collection of activities including anti-proliferation, induction of apoptosis, modulation of GSK-3β and APC/β-catenin pathways and anti-inflammation. Naringin is a potential chemopreventive agent for reducing the risk of colonic cancers. (Source: Journal of Cancer Research and Clinical Oncology)

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Long-term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression

Publication date: Available online 24 December 2015 Source:Cancer Cell Author(s): Tikvah K. Hayes, Nicole F. Neel, Chaoxin Hu, Prson Gautam, Melissa Chenard, Brian Long, Meraj Aziz, Michelle Kassner, Kirsten L. Bryant, Mariaelena Pierobon, Raoud Marayati, Swapnil Kher, Samuel D. George, Mai Xu, Andrea Wang-Gillam, Ahmed A. Samatar, Anirban Maitra, Krister Wennerberg, Emanuel F. Petricoin, Hongwei H. Yin, Barry Nelkin, Adrienne D. Cox, Jen Jen Yeh, Channing J. Der Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent pho…

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Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

J Craniofac Surg. 2015 Dec 16;

Authors: Mhlaba JM, Chen ML, Bandla HP, Baroody FM, Reid RR

Abstract
Three-dimensional computed tomography has been used in both preoperative planning of mandibular distraction osteogenesis and in the evaluation of postoperative resolution of tongue-based airway obstruction. The authors present a case report using software to predict postdistraction airway volume during virtual surgical planning (VSP) of mandibular distraction osteogenesis in a 7 year old. The predicted increase in airway volume derived from VSP was 33.57% (1716 mm preoperatively to 2292 mm postvirtual distraction). Based on the three-dimensional computed tomography, the actual airway volume increased to 2211 mm postoperatively, a 28.85% increase.The implications of this advancing technology are far-reaching. An illustrative case is presented herein to demonstrate the efficacy of the airway prediction and its limitations. The authors believe that, with continued investigation, this novel approach may be a standard feature of all VSP sessions for the treatment of tongue-based airway obstruction.

PMID: 26703061 [PubMed – as supplied by publisher]

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CML: Mit Dosiseskalation zu höheren Ansprechraten

Individualisierte Imatinib-Therapie
Zwei Drittel aller Patienten mit chronischer myeloischer Leukämie sind bei einer Imatinib-Therapie in der Standarddosis von 400 mg pro Tag unterdosiert – das legt eine aktuelle Studie nahe. Die Betroffenen würden von einer individualisierten Dosisadaptation deutlich profitieren.

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MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.

MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.

Exp Mol Pathol. 2015 Dec 15;

Authors: Jing P, Sa N, Liu X, Liu X, Xu W

Abstract
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides that negatively regulate gene expression at the post-transcriptional level. Downexpression of miR-140-5p was reported in some human cancers, and combined with a reduction of cell migration and invasion, suggesting that miR-140-5p functions as a tumor suppressor. However, little is known about the expression and function of miR-140-5p in hypopharyngeal squamous cell carcinoma(HSCC). In this research, we found that miR-140-5p was significantly downregulated in HSCC tissues and correlated to tumor classification and lymph node metastasis. Restoration of miR-140-5p suppressed the migration and invasion of FaDu cells, and decreased the protein expression levels of ADAM10. Furthermore, the luciferase reporter assay revealed that miR-140-5p was directly bound to ADAM10 mRNA and knockdown of ADAM10 could inhibit FaDu cells migration and invasion and reduced the protein expression levels of and Notch1 intracellular domain (NICD1). Of note, knockdown of Notch1 could inhibit the migration and invasion of FaDu cells and rescued the effect of miR-140-5p inhibitor in FaDu cells. Taken together, our study demonstrate that miR-140-5p suppresses tumor migration and invasion by inhibiting ADAM10-mediated Notch1 signaling pathway and suggest that miR-140-5p could have potential therapeutic applications in HSCC.

PMID: 26704053 [PubMed – as supplied by publisher]

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Factors Associated With Patient-perceived Hoarseness in Spasmodic Dysphonia Patients.

Factors Associated With Patient-perceived Hoarseness in Spasmodic Dysphonia Patients.

J Voice. 2015 Dec 15;

Authors: Hu A, Hillel A, Meyer T

Abstract
OBJECTIVES/HYPOTHESIS: The American Academy of Otolaryngology-Head and Neck Surgery Clinical Practice Guidelines on Hoarseness distinguishes between hoarseness, which is a symptom perceived by the patient, and dysphonia, which is a diagnosis made by the clinician. Our objective was to determine factors that are associated with patient-perceived hoarseness in spasmodic dysphonia (SD) patients.
STUDY DESIGN: Retrospective study.
METHODS: Adductor SD patients who presented for botulinum toxin injections from September 2011 to June 2012 were recruited. The main outcome variable, Voice Handicap Index-10 (VHI-10), was used to quantify patient-perceived hoarseness. Clinical data, Hospital Anxiety and Depression Scale (HADS), and VHI-10 were collected. Clinician-perceived dysphonia was measured by a speech-language pathologist with Consensus Auditory Perceptual Evaluation of Voice (CAPE-V). Statistical analysis included univariate analyses and multiple linear regression.
RESULTS: One hundred thirty-nine SD patients had VHI-10 score of 26.0 ± 7.2 (mean ± standard deviation), disease duration of 10.5 + 7.0 years, CAPE-V overall score of 43.2 ± 21.8, HADS anxiety score of 6.7 ± 3.8, and HADS depression score of 3.6 ± 2.8. In univariate analyses, there were positive correlations (P < 0.05) between VHI-10 and female gender, CAPE-V overall, older age, HADS anxiety, and depression. There was no correlation with professional voice use and disease duration. In multiple linear regression (R(2) = 0.178, P < 0.001), age, HADS anxiety, female gender, and CAPE-V were significant.
CONCLUSIONS: Older age, higher anxiety levels, female gender, and clinician-perceived dysphonia are associated with higher levels of patient-perceived hoarseness in SD patients. Hoarseness is a very personal symptom. Multiple factors determine its self-perception.

PMID: 26704415 [PubMed – as supplied by publisher]

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Evaluating Preoperative Models: A Methodological Contribution.

Evaluating Preoperative Models: A Methodological Contribution.

World Neurosurg. 2015 Dec 15;

Authors: Fasel JH, Uldin T, Vaucher P, Beinemann J, Stimec B, Schaller K

PMID: 26704215 [PubMed – as supplied by publisher]

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Can Serum glucose level in early admission, predict outcome in patints with severe head trauma ?

Can Serum glucose level in early admission, predict outcome in patints with severe head trauma ?

World Neurosurg. 2015 Dec 15;

Authors: Salehpour F, Bazzazi AM, Aghazadeh J, Abbasivash R, Forouhideh Y, Mirzaei F, Naseri Alavi SA

Abstract
BACKGROUND: Traumatic brain Injury is a major general health concern. This study aims to evaluate possible relationship between serum level of glucose during admission and outcome of patients with severe traumatic brain injury.
METHODS: In this prospective study, 80 patients with severe traumatic brain injury were recruited from emergency department of Urmia Imam Khomeini hospital. Serum level of glucose was measured at the time of admission and its correlation was investigated with Glasgow Coma Scale (GCS) score (admission, 24h, 48h, 1week, and discharge) and Glasgow Outcome Score (GOS). The value of admission serum glucose was compared between expired and discharged patients, as well.
RESULTS: Eighty patients with severe head trauma, 71 males (88%) and 9 females (11.2%) with a mean age of 31.71±15.66 were enrolled into the study. The inhospital mortality rate was 25% (n=20). There was no significant correlation between serum glucose level and GCS score (at different intervals) or GOS. The mean serum level of glucose was comparable between expired and discharged cases (186.10±51.36 vs. 187.98±76.03 mg/dl, respectively; p=0.91).
CONCLUSION: Apparently, admission serum glucose is not a significant indicator of outcome in patients with severe head trauma.

PMID: 26704213 [PubMed – as supplied by publisher]

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Subacute Posttraumatic Ascending Myelopathy after an Incomplete Spinal Cord injury from Gunshot Wound to the Spine – Case Report and Review of the Literature.

Subacute Posttraumatic Ascending Myelopathy after an Incomplete Spinal Cord injury from Gunshot Wound to the Spine – Case Report and Review of the Literature.

World Neurosurg. 2015 Dec 15;

Authors: Miller BA, Roy AK, Boucher A, Pradilla G, Ahmad FU

PMID: 26704212 [PubMed – as supplied by publisher]

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Perspective of Value-Based Management of Spinal Disorders in Brazil.

Perspective of Value-Based Management of Spinal Disorders in Brazil.

World Neurosurg. 2015 Dec 15;

Authors: Teles AR, Righesso O, Gullo MC, Ghogawala Z, Falavigna A

PMID: 26704211 [PubMed – as supplied by publisher]

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Simulation in Neurosurgery – a brief review and commentary.

Simulation in Neurosurgery – a brief review and commentary.

World Neurosurg. 2015 Dec 15;

Authors: Cobb MI, Taekman JM, Zomorodi AR, Gonzalez LF, Turner DA

Abstract
Neurosurgery is one of the most technically demanding and liable of all medical professionals. More than 75% of neurosurgical errors deemed as preventable and technical in nature. Yet in a specialty that requires such high level of technical expertise, with large consequences for error, there are even fewer opportunities for residents in training to practice on the most complicated cases. Although there is no replacement for actual experiences in the operating room, inter-personal mentorship, coaching, and training, there is room to supplement residency education through simulation. Here we review the evidence to support surgical simulation, describe the strengths and weaknesses of existing technologies in direct neurosurgery specific and indirect simulation applications, and advocate for the development of more neurosurgery specific applications using emerging kinetic technologies.

PMID: 26704209 [PubMed – as supplied by publisher]

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Outcome of microscopic Transsphenoidal Surgery in Cushing’s disease: a case series of 96 patients.

Outcome of microscopic Transsphenoidal Surgery in Cushing's disease: a case series of 96 patients.

World Neurosurg. 2015 Dec 15;

Authors: Shirvani M, Motiei-Langroudi R, Sadeghian H

PMID: 26704208 [PubMed – as supplied by publisher]

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Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigro-Striatal Disconnection.

Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigro-Striatal Disconnection.

World Neurosurg. 2015 Dec 15;

Authors: Rowe J, Khan A, Romanowski C, Isaac C, Khan S, Mair R, Aziz T, Yianni J

PMID: 26704205 [PubMed – as supplied by publisher]

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A dissecting aneurysm of the distal medial lenticulostriate artery: Case report.

A dissecting aneurysm of the distal medial lenticulostriate artery: Case report.

World Neurosurg. 2015 Dec 15;

Authors: Saito A, Kon H, Nakamura T, Sasaki T

Abstract
BACKGROUND: Medial lenticulostriate artery (MLSA) aneurysms are rare; to our knowledge only 2 cases without an association with Moyamoya disease have been documented. We treated a ruptured dissecting aneurysm of the distal MLSA surgically using a tube retractor.
CASE DESCRIPTION: A 66-year-old woman suffered sudden-onset consciousness disturbance. Computed tomography showed diffuse subarachnoid hemorrhage and a dense intraventricular hematoma associated with acute hydrocephalus. She underwent emergent ventricular drainage. Angiography revealed a 3-mm distal MLSA aneurysm. On repeat angiographs the aneurysm had not disappeared. As the stenotic, narrow structure of the proximal portion of the MLSA disallowed the endovascular approach we performed direct surgery via the transventricular approach using a tube retractor. The aneurysm on the intraventricular surface of the anterior horn of the lateral ventricle adjacent to the caudate nucleus was exposed. We resected the aneurysm under transcranial motor-evoked potential monitoring because neck clipping would have endangered the patency of the MLSA. Her postoperative course was uneventful. The pathological diagnosis was ruptured dissecting aneurysm.
CONCLUSIONS: There is no definitive strategy to treat distal MLSA aneurysms. Our experience illustrates that natural healing of the vessel wall cannot be expected in all cases. Therefore, less invasive direct surgical- as well as endovascular treatment should not be ruled out in patients with ruptured distal MLSA aneurysms.

PMID: 26704207 [PubMed – as supplied by publisher]

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Preoperative embolization of spinal tumors: A systematic review and meta-analysis.

Preoperative embolization of spinal tumors: A systematic review and meta-analysis.

World Neurosurg. 2015 Dec 15;

Authors: Griessenauer CJ, Salem M, Hendrix P, Foreman PM, Ogilvy CS, Thomas AJ

Abstract
BACKGROUND: Spinal tumors are referred for preoperative embolization to minimize intraoperative blood loss and facilitate surgical resection.
OBJECTIVE: To perform a systematic review and meta-analysis and provide comprehensive data on embolization technique, efficacy, and complications.
METHODS: A systematic review of PubMed articles was performed with the following inclusion criteria: original studies, studies of ≥ 10 patients (except Onyx due to scarcity of available data), embolization through vascular access, and reporting of the embolic agent used. Additionally the manuscript needed to contain at least one of the following variables: demographics, tumor type, location, vascularity, degree of devascularization, complications, time to operation, type of operation, estimated blood loss (EBL), and use of blood transfusion.
RESULTS: Thirty-seven studies with a total of 1,305 patients met inclusion criteria. Renal cell carcinoma was the most commonly embolized tumor comprising 47.4% (95% CI 39.4 – 55.4) of all tumor embolizations. The rate of complete devascularization for all tumor types was 68.3% (95% CI 60.0 – 76.6). There was a significant decrease in operative EBL in more recently published studies as compared to earlier studies, however, the rate of complete embolization remained stable. Polyvinyl alcohol (PVA) and Onyx(®) were associated with similar EBL and rates of complete embolization. The overall complication rate was 3.1% (95% CI 1.2 – 4.9).
CONCLUSIONS: The rapid evolution of neurointervention and spinal tumor embolization has made scientific inquiry and definitive conclusion on the safety and efficacy of the practice difficult. The data supporting the procedure is fragmented and largely based on a multitude of retrospective studies utilizing varying techniques. Review of the available literature support embolization of spinal tumors as a safe and efficacious treatment adjunct prior to surgery.

PMID: 26704206 [PubMed – as supplied by publisher]

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Naringin, a natural dietary compound, prevents intestinal tumorigenesis in Apc Min/+ mouse model

Conclusion Naringin prevented intestinal tumorigenesis likely through a collection of activities including anti-proliferation, induction of apoptosis, modulation of GSK-3β and APC/β-catenin pathways and anti-inflammation. Naringin is a potential chemopreventive agent for reducing the risk of colonic cancers. (Source: Journal of Cancer Research and Clinical Oncology)

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Long-term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression

Publication date: Available online 24 December 2015 Source:Cancer Cell Author(s): Tikvah K. Hayes, Nicole F. Neel, Chaoxin Hu, Prson Gautam, Melissa Chenard, Brian Long, Meraj Aziz, Michelle Kassner, Kirsten L. Bryant, Mariaelena Pierobon, Raoud Marayati, Swapnil Kher, Samuel D. George, Mai Xu, Andrea Wang-Gillam, Ahmed A. Samatar, Anirban Maitra, Krister Wennerberg, Emanuel F. Petricoin, Hongwei H. Yin, Barry Nelkin, Adrienne D. Cox, Jen Jen Yeh, Channing J. Der Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent pho…

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Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

J Craniofac Surg. 2015 Dec 16;

Authors: Mhlaba JM, Chen ML, Bandla HP, Baroody FM, Reid RR

Abstract
Three-dimensional computed tomography has been used in both preoperative planning of mandibular distraction osteogenesis and in the evaluation of postoperative resolution of tongue-based airway obstruction. The authors present a case report using software to predict postdistraction airway volume during virtual surgical planning (VSP) of mandibular distraction osteogenesis in a 7 year old. The predicted increase in airway volume derived from VSP was 33.57% (1716 mm preoperatively to 2292 mm postvirtual distraction). Based on the three-dimensional computed tomography, the actual airway volume increased to 2211 mm postoperatively, a 28.85% increase.The implications of this advancing technology are far-reaching. An illustrative case is presented herein to demonstrate the efficacy of the airway prediction and its limitations. The authors believe that, with continued investigation, this novel approach may be a standard feature of all VSP sessions for the treatment of tongue-based airway obstruction.

PMID: 26703061 [PubMed – as supplied by publisher]

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CML: Mit Dosiseskalation zu höheren Ansprechraten

Individualisierte Imatinib-Therapie
Zwei Drittel aller Patienten mit chronischer myeloischer Leukämie sind bei einer Imatinib-Therapie in der Standarddosis von 400 mg pro Tag unterdosiert – das legt eine aktuelle Studie nahe. Die Betroffenen würden von einer individualisierten Dosisadaptation deutlich profitieren.

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MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.

MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.

Exp Mol Pathol. 2015 Dec 15;

Authors: Jing P, Sa N, Liu X, Liu X, Xu W

Abstract
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides that negatively regulate gene expression at the post-transcriptional level. Downexpression of miR-140-5p was reported in some human cancers, and combined with a reduction of cell migration and invasion, suggesting that miR-140-5p functions as a tumor suppressor. However, little is known about the expression and function of miR-140-5p in hypopharyngeal squamous cell carcinoma(HSCC). In this research, we found that miR-140-5p was significantly downregulated in HSCC tissues and correlated to tumor classification and lymph node metastasis. Restoration of miR-140-5p suppressed the migration and invasion of FaDu cells, and decreased the protein expression levels of ADAM10. Furthermore, the luciferase reporter assay revealed that miR-140-5p was directly bound to ADAM10 mRNA and knockdown of ADAM10 could inhibit FaDu cells migration and invasion and reduced the protein expression levels of and Notch1 intracellular domain (NICD1). Of note, knockdown of Notch1 could inhibit the migration and invasion of FaDu cells and rescued the effect of miR-140-5p inhibitor in FaDu cells. Taken together, our study demonstrate that miR-140-5p suppresses tumor migration and invasion by inhibiting ADAM10-mediated Notch1 signaling pathway and suggest that miR-140-5p could have potential therapeutic applications in HSCC.

PMID: 26704053 [PubMed – as supplied by publisher]

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Factors Associated With Patient-perceived Hoarseness in Spasmodic Dysphonia Patients.

Factors Associated With Patient-perceived Hoarseness in Spasmodic Dysphonia Patients.

J Voice. 2015 Dec 15;

Authors: Hu A, Hillel A, Meyer T

Abstract
OBJECTIVES/HYPOTHESIS: The American Academy of Otolaryngology-Head and Neck Surgery Clinical Practice Guidelines on Hoarseness distinguishes between hoarseness, which is a symptom perceived by the patient, and dysphonia, which is a diagnosis made by the clinician. Our objective was to determine factors that are associated with patient-perceived hoarseness in spasmodic dysphonia (SD) patients.
STUDY DESIGN: Retrospective study.
METHODS: Adductor SD patients who presented for botulinum toxin injections from September 2011 to June 2012 were recruited. The main outcome variable, Voice Handicap Index-10 (VHI-10), was used to quantify patient-perceived hoarseness. Clinical data, Hospital Anxiety and Depression Scale (HADS), and VHI-10 were collected. Clinician-perceived dysphonia was measured by a speech-language pathologist with Consensus Auditory Perceptual Evaluation of Voice (CAPE-V). Statistical analysis included univariate analyses and multiple linear regression.
RESULTS: One hundred thirty-nine SD patients had VHI-10 score of 26.0 ± 7.2 (mean ± standard deviation), disease duration of 10.5 + 7.0 years, CAPE-V overall score of 43.2 ± 21.8, HADS anxiety score of 6.7 ± 3.8, and HADS depression score of 3.6 ± 2.8. In univariate analyses, there were positive correlations (P < 0.05) between VHI-10 and female gender, CAPE-V overall, older age, HADS anxiety, and depression. There was no correlation with professional voice use and disease duration. In multiple linear regression (R(2) = 0.178, P < 0.001), age, HADS anxiety, female gender, and CAPE-V were significant.
CONCLUSIONS: Older age, higher anxiety levels, female gender, and clinician-perceived dysphonia are associated with higher levels of patient-perceived hoarseness in SD patients. Hoarseness is a very personal symptom. Multiple factors determine its self-perception.

PMID: 26704415 [PubMed – as supplied by publisher]

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“My Mind Is Doing It All”: No “Brake” to Stop Speech Generation in Jargon Aphasia.

"My Mind Is Doing It All": No "Brake" to Stop Speech Generation in Jargon Aphasia.

Cogn Behav Neurol. 2015 Dec;28(4):229-41

Authors: Robinson GA, Butterworth B, Cipolotti L

Abstract
OBJECTIVE: To study whether pressure of speech in jargon aphasia arises out of disturbances to core language or executive processes, or at the intersection of conceptual preparation.
BACKGROUND: Conceptual preparation mechanisms for speech have not been well studied. Several mechanisms have been proposed for jargon aphasia, a fluent, well-articulated, logorrheic propositional speech that is almost incomprehensible.
METHODS: We studied the vast quantity of jargon speech produced by patient J.A., who had suffered an infarct after the clipping of a middle cerebral artery aneurysm. We gave J.A. baseline cognitive tests and experimental word- and sentence-generation tasks that we had designed for patients with dynamic aphasia, a severely reduced but otherwise fairly normal propositional speech thought to result from deficits in conceptual preparation.
RESULTS: J.A. had cognitive dysfunction, including executive difficulties, and a language profile characterized by poor repetition and naming in the context of relatively intact single-word comprehension. J.A.'s spontaneous speech was fluent but jargon. He had no difficulty generating sentences; in contrast to dynamic aphasia, his sentences were largely meaningless and not significantly affected by stimulus constraint level.
CONCLUSIONS: This patient with jargon aphasia highlights that voluminous speech output can arise from disturbances of both language and executive functions. Our previous studies have identified three conceptual preparation mechanisms for speech: generation of novel thoughts, their sequencing, and selection. This study raises the possibility that a "brake" to stop message generation may be a fourth conceptual preparation mechanism behind the pressure of speech characteristic of jargon aphasia.

PMID: 26705270 [PubMed – in process]

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In vivo monitoring of the anti-angiogenic therapeutic effect of the pan-deacetylase inhibitor panobinostat by small animal PET in a mouse model of gastrointestinal cancers.

In vivo monitoring of the anti-angiogenic therapeutic effect of the pan-deacetylase inhibitor panobinostat by small animal PET in a mouse model of gastrointestinal cancers.

Nucl Med Biol. 2016 Jan;43(1):27-34

Authors: Maschauer S, Gahr S, Gandesiri M, Tripal P, Schneider-Stock R, Kuwert T, Ocker M, Prante O

Abstract
INTRODUCTION: Deacetylase inhibitors have recently been established as a novel therapeutic approach to solid and hematologic cancers and have also been demonstrated to possess anti-angiogenic properties. Although these compounds show a good efficacy in vitro and in vivo, no data on monitoring and predicting treatment response are currently available. We therefore investigated the effect of the pan-deacetylase inhibitor panobinostat (LBH589) on gastrointestinal cancer models and the suitability of 2-[(18)F]FGlc-RGD as a specific agent for imaging integrin αvβ3 expression during tumor angiogenesis using small animal positron emission tomography (PET).
METHODS: The effect of panobinostat on cell viability in vitro was assessed with a label-free impedance based real-time analysis. Nude mice bearing HT29 and HepG2 tumors were treated with daily i.p. injections of 10mg/kg panobinostat for 4weeks. During this time, tumor size was determined with a calliper and mice were repeatedly subjected to PET imaging. Tumor tissues were analyzed immunohistochemically with a focus on proliferation and endothelial cell markers (Ki-67, Meca-32) and by Western blot applying specific markers of apoptosis.
RESULTS: In vitro, panobinostat inhibited the proliferation of HepG2 and HT29 cells. Contrary to the situation in HepG2 tumors in vivo, where panobinostat treatment is known to reduce proliferation and vascularization resulting in a decreased tumor growth, HT29 tumors did not show any effect on these parameters. We demonstrated by Western blotting, that panobinostat induced apoptosis in HT29 tumors in vivo. Longitudinal PET imaging studies in HepG2 tumor-bearing mice using 2-[(18)F]FGlc-RGD demonstrated that the standard uptake value (SUVmax) in HepG2 tumors was significantly decreased by 39% at day 7 after treatment. The comparative PET study using HT29 tumor-bearing animals did not reveal any response of the tumors to panobinostat treatment.
CONCLUSIONS: Small-animal PET imaging using 2-[(18)F]FGlc-RGD was successfully applied to the non-invasive monitoring of the HepG2-tumor response to panobinostat in nude mice early after begin of treatment. Thus, PET imaging of angiogenesis using 2-[(18)F]FGlc-RGD could be a valuable tool to monitor panobinostat therapy in further preclinical studies.
ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: When successfully translated to the clinical surrounding, PET imaging of angiogenesis could therefore facilitate therapy planning and monitoring of therapy success with panobinostat in hepatocellular carcinoma.

PMID: 26702784 [PubMed – in process]

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Hypothesis: Metalloproteinase Inhibitors Decrease Risks of Cardiovascular Disease.

Hypothesis: Metalloproteinase Inhibitors Decrease Risks of Cardiovascular Disease.

J Cardiovasc Pharmacol Ther. 2015 Dec 24;

Authors: Lizotte-Waniewski M, Brew K, Hennekens CH

Abstract
The hypothesis that matrix metalloproteinase (MMP) inhibitors reduce risks of cardiovascular disease in humans is plausible, unproven, and difficult to test, due, in part, to differences in specificity and route of administration. Endogenous tissue inhibitors of metalloproteinases (TIMPs) are tight-binding, protein inhibitors that function in vivo and can be engineered to enhance specificity for desired targets. Nonetheless, TIMPs have been difficult to test, in part, because their secondary functions, including cell growth promotion and angiogenesis, raise concerns about side effects and they cannot be delivered orally. In contrast, doxycycline and other chemically modified tetracyclines are broad-spectrum, reversible MMP inhibitors with lower affinity but can be taken orally and have US Food and Drug Administration approval. The completed phase 2 randomized trials in humans of MMP inhibitors have methodologic limitations but generally show no significant benefits with adverse effects. At present, the principal research challenge is to achieve a better understanding of the complexities of biological functions of MMPs and subsequently to conduct large-scale phase 3 trials.

PMID: 26703451 [PubMed – as supplied by publisher]

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Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines.

Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines.

Rheumatology (Oxford). 2015 Dec 24;

Authors: Tsou PS, Rabquer BJ, Ohara RA, Stinson WA, Campbell PL, Amin MA, Balogh B, Zakhem G, Renauer PA, Lozier A, Arasu E, Haines GK, Kahaleh B, Schiopu E, Khanna D, Koch AE

Abstract
OBJECTIVES: Angiogenesis plays a critical role in SSc (scleroderma). The aim of this study was to examine the expression of growth-regulated protein-γ (Gro-γ/CXCL3), granulocyte chemotactic protein 2 (GCP-2/CXCL6) and their receptor CXCR2 in endothelial cells (ECs) isolated from SSc skin and determine whether these cells mount an angiogenic response towards pro-angiogenic chemokines. The downstream signalling pathways as well as the pro-angiogenic transcription factor inhibitor of DNA-binding protein 1 (Id-1) were also examined.
METHODS: Skin biopsies were obtained from patients with dcSSc. ECs were isolated via magnetic positive selection. Angiogenesis was measured by EC chemotaxis assay.
RESULTS: Gro-γ/CXCL3 and GCP-2/CXCL6 were minimally expressed in both skin types but elevated in SSc serum. Pro-angiogenic chemokine mRNA was greater in SSc ECs than in normal ECs. SSc ECs did not migrate to vascular endothelial growth factor (VEGF), Gro-γ/CXCL3, GCP-2/CXCL6 or CXCL16. The signalling pathways stimulated by these chemokines were also dysregulated. Id-1 mRNA in SSc ECs was lower compared with normal ECs, and overexpression of Id-1 in SSc ECs increased their ability to migrate towards VEGF and CXCL16.
CONCLUSION: Our results show that SSc ECs are unable to respond to pro-angiogenic chemokines despite their increased expression in serum and ECs. This might be due to the differences in the signalling pathways activated by these chemokines in normal vs SSc ECs. In addition, the lower expression of Id-1 also decreases the angiogenic response. The inability of pro-angiogenic chemokines to promote EC migration provides an additional mechanism for the impaired angiogenesis that characterizes SSc.

PMID: 26705326 [PubMed – as supplied by publisher]

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The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6 J mice.

The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6 J mice.

J Ethnopharmacol. 2015 Dec 15;

Authors: Woo S, Yoon M, Kim J, Hong Y, Kim MY, Shin SS, Yoon M

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from Melissa officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy.
MATERIALS AND METHODS: ALS-L1023 was prepared by a two-step organic solvent fractionation from Melissa officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches.
RESULTS: ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice.
CONCLUSIONS: These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.

PMID: 26702505 [PubMed – as supplied by publisher]

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Long-term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression

Publication date: Available online 24 December 2015 Source:Cancer Cell Author(s): Tikvah K. Hayes, Nicole F. Neel, Chaoxin Hu, Prson Gautam, Melissa Chenard, Brian Long, Meraj Aziz, Michelle Kassner, Kirsten L. Bryant, Mariaelena Pierobon, Raoud Marayati, Swapnil Kher, Samuel D. George, Mai Xu, Andrea Wang-Gillam, Ahmed A. Samatar, Anirban Maitra, Krister Wennerberg, Emanuel F. Petricoin, Hongwei H. Yin, Barry Nelkin, Adrienne D. Cox, Jen Jen Yeh, Channing J. Der Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent pho…

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Long-term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression

Publication date: Available online 24 December 2015 Source:Cancer Cell Author(s): Tikvah K. Hayes, Nicole F. Neel, Chaoxin Hu, Prson Gautam, Melissa Chenard, Brian Long, Meraj Aziz, Michelle Kassner, Kirsten L. Bryant, Mariaelena Pierobon, Raoud Marayati, Swapnil Kher, Samuel D. George, Mai Xu, Andrea Wang-Gillam, Ahmed A. Samatar, Anirban Maitra, Krister Wennerberg, Emanuel F. Petricoin, Hongwei H. Yin, Barry Nelkin, Adrienne D. Cox, Jen Jen Yeh, Channing J. Der Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent pho…

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Tunnels and grooves for supraclavicular nerves within the clavicle: review of the literature and clinical impact.

Tunnels and grooves for supraclavicular nerves within the clavicle: review of the literature and clinical impact.

Surg Radiol Anat. 2015 Dec 24;

Authors: Natsis K, Totlis T, Chorti A, Karanassos M, Didagelos M, Lazaridis N

Abstract
Perforation of the clavicle by supraclavicular nerves is a common anatomical variation. This variation has been reported in several studies based on post-mortem, surgical and radiologic findings, with an overall frequency between 1 and 6.6 %. The penetrating branch passes either through a bony tunnel or a groove on the superior surface of the bone. Entrapment neuropathy of the perforating branch is a documented clinical entity reported in the literature. The intraosseous course of the supraclavicular nerves makes them vulnerable to injury in case of clavicular fractures or during surgical manipulations of these fractures. Furthermore, this variation should be taken into account during the interpretation of chest and shoulder radiographs. The purpose of the current study is to perform an extended review of the relevant literature, highlighting the clinical impact of this variation, as well as to incorporate our own findings into them.

PMID: 26702936 [PubMed - as supplied by publisher]

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CML: Mit Dosiseskalation zu höheren Ansprechraten

Individualisierte Imatinib-Therapie
Zwei Drittel aller Patienten mit chronischer myeloischer Leukämie sind bei einer Imatinib-Therapie in der Standarddosis von 400 mg pro Tag unterdosiert – das legt eine aktuelle Studie nahe. Die Betroffenen würden von einer individualisierten Dosisadaptation deutlich profitieren.

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CML: Mit Dosiseskalation zu höheren Ansprechraten

Individualisierte Imatinib-Therapie
Zwei Drittel aller Patienten mit chronischer myeloischer Leukämie sind bei einer Imatinib-Therapie in der Standarddosis von 400 mg pro Tag unterdosiert – das legt eine aktuelle Studie nahe. Die Betroffenen würden von einer individualisierten Dosisadaptation deutlich profitieren.

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Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health.

Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health.

Chem Cent J. 2015;9:68

Authors: Lv X, Zhao S, Ning Z, Zeng H, Shu Y, Tao O, Xiao C, Lu C, Liu Y

Abstract
Citrus fruits, which are cultivated worldwide, have been recognized as some of the most high-consumption fruits in terms of energy, nutrients and health supplements. What is more, a number of these fruits have been used as traditional medicinal herbs to cure diseases in several Asian countries. Numerous studies have focused on Citrus secondary metabolites as well as bioactivities and have been intended to develop new chemotherapeutic or complementary medicine in recent decades. Citrus-derived secondary metabolites, including flavonoids, alkaloids, limonoids, coumarins, carotenoids, phenolic acids and essential oils, are of vital importance to human health due to their active properties. These characteristics include anti-oxidative, anti-inflammatory, anti-cancer, as well as cardiovascular protective effects, neuroprotective effects, etc. This review summarizes the global distribution and taxonomy, numerous secondary metabolites and bioactivities of Citrus fruits to provide a reference for further study. Flavonoids as characteristic bioactive metabolites in Citrus fruits are mainly introduced.

PMID: 26705419 [PubMed]

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Neuroanatomical Markers of Neurological Soft Signs in Recent-Onset Schizophrenia and Asperger-Syndrome

Abstract

Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin. Previous MRI studies in schizophrenia have shown that NSS are associated with abnormal cortical, thalamic and cerebellar structure and function. So far, however, no neuroimaging studies investigated brain correlates of NSS in individuals with Asperger-Syndrome (AS) and the question whether the two disorders exhibit common or disease-specific cortical correlates of NSS remains unresolved. High-resolution MRI data at 3 T were obtained from 48 demographically matched individuals (16 schizophrenia patients, 16 subjects with AS and 16 healthy individuals). The surface-based analysis via Freesurfer enabled calculation of cortical thickness, area and folding (local gyrification index, LGI). NSS were examined on the Heidelberg Scale and related to cortical measures. In schizophrenia, higher NSS were associated with reduced cortical thickness and LGI in fronto-temporo-parietal brain areas. In AS, higher NSS were associated with increased frontotemporal cortical thickness. This study lends further support to the hypothesis that disorder-specific mechanisms contribute to NSS expression in schizophrenia and AS. Pointing towards dissociable neural patterns may help deconstruct the complex processes underlying NSS in these neurodevelopmental disorders.

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Traumatic arteriovenous fistula of the superficial temporal artery.

Traumatic arteriovenous fistula of the superficial temporal artery.

J Surg Case Rep. 2015;2015(12)

Authors: Asai K, Tani S, Imai Y, Mineharu Y, Sakai N

Abstract
Traumatic arteriovenous fistula (AVF) of the superficial temporal artery (STA) is rare. We report a case of surgically treated, histopathologically confirmed traumatic AVF of the STA. A 24-year-old male was admitted to our hospital after a traffic accident. Computed tomography scan on admission showed an acute epidural hematoma on the right surface of frontal lobe, which was emergently treated by surgical evacuation. One month later, he was aware of pulsatile tinnitus around the left ear. Digital subtraction angiogram showed an AVF, mainly fed by the left STA. After total removal of the fistula, his tinnitus immediately disappeared. Histopathological examination demonstrated that the artery was connected to the vein through the thin-walled vessels lacking internal elastic lamina and muscularized media, suggesting that the connecting vessels were newly formed.

PMID: 26703929 [PubMed]

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Microvascular Decompression Surgery for Hemifacial Spasm.

Microvascular Decompression Surgery for Hemifacial Spasm.

J Craniofac Surg. 2015 Dec 16;

Authors: Qi H, Zhang W, Zhang X, Zhao C

Abstract
OBJECTIVE: This study aims to investigate the operative efficacy, surgical complication rate, and surgical strategy of microvascular decompression (MVD) for hemifacial spasm (HFS).
METHODS: Clinical data of 46 patients with HFS who underwent MVD were retrospectively analyzed.
RESULTS: During surgery, it was found that the facial nerve root exit zone was compressed by the following arterial vessels: anterior inferior cerebellar artery in 24 patients (52.17%); posterior inferior cerebellar artery in 14 patients (30.43%); vertebral artery and a small artery in 7 patients (15.22%); and vertebral artery in 1 patient (2.18%). Symptoms of 38 patients were immediately remitted completely after surgery and symptoms of 8 patients were significantly reduced. Main complications included dizziness and tinnitus in 9 patients, hearing loss in 5 patients, cerebrospinal fluid leakage in 1 patient, and infection in 2 patients. No patient died during surgery.
CONCLUSIONS: MVD is the preferred choice for treating idiopathic hemifacial spasm, and hearing impairment is the main complication. Skilled microsurgical techniques, as well as identifying and completely decompressing offending vessels, are the key to ensuring a successful microvascular decompression.

PMID: 26703065 [PubMed - as supplied by publisher]

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Features and prognostic utility of biopsy in oral squamous cell carcinoma.

Features and prognostic utility of biopsy in oral squamous cell carcinoma.

Head Neck. 2015 Dec 24;

Authors: Dhanda J, Uppal N, Chowlia H, Opie N, Al-Qamachi L, Shelat D, Aslam A, Yuffa A, Martin T, Risk J, Triantafyllou A, Shaw R, Parmar S, Mehanna H

Abstract
BACKGROUND: Traditional approaches in oral squamous cell carcinoma (OSCC) management utilize biopsy tissue for diagnostic purposes only. Adverse prognostic features, such as the tumor depth, are usually determined from final resection specimens, but are seldom studied in biopsy tissue.
METHODS: A preliminary study of 139 consecutive biopsies compared biopsy size with T classification, tumor site, and operator grade, and biopsy tumor depth with the true tumor depth.
RESULTS: This study demonstrated that biopsy size is independent of T classification (p = .44), subsite (p = .86), and operator grade (p = .10). The biopsy tumor depth significantly underrepresented true tumor depth (2.5 mm, 95% confidence interval [CI] = 2.4-2.9 vs 8.2 mm, 95% CI = 6.5-9.9; p < .001), confirming the limited prognostic utility of biopsies in OSCC.
CONCLUSION: A future clinical trial will compare the routine biopsy technique with standardized deeper biopsy techniques using punch biopsy to sample invasive fronts and investigate opportunities for up-front staging using a combination of histological features and epithelial and stromal molecular biomarkers in OSCC. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.

PMID: 26705271 [PubMed - as supplied by publisher]

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Role of perioperative antibiotic treatment in parotid gland surgery.

Role of perioperative antibiotic treatment in parotid gland surgery.

Head Neck. 2015 Dec 24;

Authors: Shkedy Y, Alkan U, Roman BR, Hilly O, Feinmesser R, Bachar G, Mizrachi A

Abstract
BACKGROUND: The value of routine prophylactic antibiotic treatment in parotid gland surgery remains undetermined.
METHODS: A retrospective analysis was conducted of all patients who underwent parotidectomy at a university-affiliated tertiary care center between 1992 and 2009. Patients with insufficient data, specifically regarding postoperative complications and antibiotic administration were excluded from the study cohort.
RESULTS: A total of 593 patients underwent parotidectomy during the study period. After exclusion, 464 patients were eligible for the study. Perioperative antibiotic treatment was given to 206 patients (45%). There was no difference in wound infection rates between patients who received perioperative antibiotic therapy and those who did not (p = .168). Multivariate analysis showed that female sex, neck dissection, and drain output >50 cc/24 hours were predictive of postoperative wound infection.
CONCLUSION: Routine prophylactic antibiotic treatment has no role in parotid gland surgery. Perioperative antibiotic treatment is recommended for patients undergoing extensive parotid gland surgery with neck dissection. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.

PMID: 26702565 [PubMed - as supplied by publisher]

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Long-term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression

Publication date: Available online 24 December 2015 Source:Cancer Cell Author(s): Tikvah K. Hayes, Nicole F. Neel, Chaoxin Hu, Prson Gautam, Melissa Chenard, Brian Long, Meraj Aziz, Michelle Kassner, Kirsten L. Bryant, Mariaelena Pierobon, Raoud Marayati, Swapnil Kher, Samuel D. George, Mai Xu, Andrea Wang-Gillam, Ahmed A. Samatar, Anirban Maitra, Krister Wennerberg, Emanuel F. Petricoin, Hongwei H. Yin, Barry Nelkin, Adrienne D. Cox, Jen Jen Yeh, Channing J. Der Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent pho…

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Long-term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression

Publication date: Available online 24 December 2015 Source:Cancer Cell Author(s): Tikvah K. Hayes, Nicole F. Neel, Chaoxin Hu, Prson Gautam, Melissa Chenard, Brian Long, Meraj Aziz, Michelle Kassner, Kirsten L. Bryant, Mariaelena Pierobon, Raoud Marayati, Swapnil Kher, Samuel D. George, Mai Xu, Andrea Wang-Gillam, Ahmed A. Samatar, Anirban Maitra, Krister Wennerberg, Emanuel F. Petricoin, Hongwei H. Yin, Barry Nelkin, Adrienne D. Cox, Jen Jen Yeh, Channing J. Der Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent pho…

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