Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies.

Related Articles

Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies.

Oral Maxillofac Surg. 2016 Feb 13;

Authors: Grimm M, Hoefert S, Krimmel M, Biegner T, Feyen O, Teriete P, Reinert S

Abstract
INTRODUCTION: One of the common malignant tumors of the head and neck worldwide with generally unfavorable prognosis is squamous cell carcinoma (OSCC) of the oral cavity. Early detection of primary, secondary, or recurrent OSCC by liquid biopsy tools is much needed.
CASE PRESENTATION: Twelve blood biomarkers were used for monitoring a case of OSCC suffering from precancerous oral lichen ruber planus mucosae (OLP). After curative R0 tumor resection of primary OSCC (buccal mucosa), elevated epitope detection in monocytes (EDIM)-Apo10, EDIM-transketolase-like-1 (TKTL1), squamous cell carcinoma antigen (SCC-Ag), total serum lactate dehydrogenase (LDH), and its anaerobic isoforms (LDH-4, LDH-5) decreased to normal levels. Three and six months after surgery, transformation of suspicious mucosal lesions has been accompanied with an increase of EDIM scores, total serum LDH values, and a metabolic shift from aerobic (decrease of LDH-1, LDH-2) to anaerobic (increase of LDH-4, LDH-5) conditions. Two months later, secondary OSCC was histopathologically analyzed after tissue biopsy. Cytokeratin fraction 21-1 (CYFRA 21-1), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were not affected during the clinical course of carcinogenesis.
CONCLUSIONS: A combination strategy using a standardized panel of established (metabolic) blood biomarkers (TKTL1, LDH, LDH isoenzymes) is worth and can be recommended among others (apoptosis resistance-related Apo10, SCC-Ag) for early detection and diagnosis of primary, secondary, and recurrent OSCC. A tandem strategy utilizing (metabolic pronounced) routine liquid biopsies with imaging techniques may enhance diagnosis of OSCC in the future. Although we demonstrated the diagnostic utility of separated liquid biopsies in our previous study cohorts, further investigations in a larger patient cohort are necessary to recommend this combination strategy (EDIM blood test, LDH value, metabolic shift of LDH isoenzymes, and others, e.g., SCC-Ag or immunophenotyping) as a diagnostic tool for the addition to the OSCC staging system and as a routine procedure in the aftercare.

PMID: 26875085 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiUGbQ
via IFTTT

The increasing incidence of paranasal organizing hematoma: a 20-year experience of 23 cases at a single center.

Related Articles

The increasing incidence of paranasal organizing hematoma: a 20-year experience of 23 cases at a single center.

Rhinology. 2016 Feb 14;

Authors: Kim JS, Oh JS, Kwon SH

Abstract
BACKGROUND AND OBJECTIVES: Sinonasal organized hematoma is a rare, benign disease that can be locally aggressive and may be mistaken for malignancy. Because of its rarity, the clinical characteristics are not well known. The aim of this study is to investigate the distinguishing features of organized hematoma with an emphasis on incidence change.
MATERIALS AND METHODS: In this retrospective study, we reviewed the records of 23 patients with organized hematoma con rmed histopathologically among 5,378 patients who underwent endoscopic sinus surgery performed by a single surgeon from January 1995 to December 2014 at a tertiary care center. Clinical symptoms, endoscopic photography, computed tomography, and operative ndings were reviewed. We also reviewed the relevant literature. Age, sex, site, origin subsite and histopathology were investigated. A statistical review was performed using R 3.1.2 to examine incidence change.
RESULTS: The most common complaint was frequent epistaxis and nasal obstruction (52.1%). Of the 23 patients, eight were women and 15 were men with an age range of 18 to 75 years. (mean 38.9 years). Nine of these hematomas occurred on the right side and 14 on the left side. The predominant occurrence site was the antrum (65%), followed by the septum (17.3%), inferior turbinate (8%), and ethmoid sinus (8%). The incidence steadily increased over 20 years.
CONCLUSION: Investigation of the clinical characteristics and incidence change of organized hematoma can provide useful information. Through analysis of the 23 cases in our study, the age distribution was found to be bimodal and the incidence of organizing hematoma was observed to steadily increase. Clinicians should be aware of these characteristics to avoid misdiagnoses of malignant tumors.

PMID: 26874999 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Tl4cYl
via IFTTT

Cholesteatoma growth patterns: are there audiometric differences between posterior epitympanic and posterior mesotympanic cholesteatoma?

Related Articles

Cholesteatoma growth patterns: are there audiometric differences between posterior epitympanic and posterior mesotympanic cholesteatoma?

Eur Arch Otorhinolaryngol. 2016 Feb 13;

Authors: Rosito LP, Teixeira AR, Netto LS, Selaimen FA, da Costa SS

Abstract
The objective of this is to verify whether the hearing impairment caused by posterior epitympanic differed from that caused by posterior mesotympanic cholesteatomas by a cross-sectional study. We evaluated 264 ears of patients with cholesteatoma, who had not been subjected to ear surgery. Otoendoscopy and pure-tone audiometry were performed. Analyzed route involved in cholesteatoma formation: posterior epitympanic or posterior mesotympanic, air-bone gaps at 512-4000 Hz and pure-tone averages. The mean age of the patients enrolled in this study was 33.8 years, and 51.8 % of them was male. Posterior epitympanic cholesteatoma was found in 50.4 % of the study population. When the air-bone gaps were compared, the mesotympanic group had greater thresholds at 500, 2000 Hz, and a greater pure-tone average (P = 0.003, P = 0.03, and P = 0.02, respectively). Posterior mesotympanic cholesteatoma showed greater air-bone gaps thresholds at the speech frequencies than posterior epitympanic cholesteatoma did. Moreover, the two growth patterns were very similar with regard to all other audiometric parameters analyzed in this study.

PMID: 26874734 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Tl4cHV
via IFTTT

Predictors of post-treatment smoking and drinking behavior of head and neck cancer survivors: results of a population-based survey.

Related Articles

Predictors of post-treatment smoking and drinking behavior of head and neck cancer survivors: results of a population-based survey.

Eur Arch Otorhinolaryngol. 2016 Feb 13;

Authors: Schiller U, Inhestern J, Burger U, Singer S, Guntinas-Lichius O

Abstract
Predictors for smoking and alcohol drinking behavior were investigated in head and neck cancer survivors (HNCS) with survivorship of ≥6 months. 165 HNCS registered in a regional cancer registry and treated 2005-2014 were included. Patients completed a survey including the Fagerström Test for nicotine dependence and the Alcohol Use Disorders Identification Test. Smoking and drinking cessation rates were 51 and 13 %, respectively. Multinomial logistic regression analyses showed that male patients [odds ratio (OR) 35.4; confidence interval (CI) 7.5-168.1; p < 0.0001], single persons (OR 9.9; CI 2.5-40.0; p = 0.001), and younger patients (OR 1.1; CI 1.0-1.1; p = 0.002) had significantly higher probability to be current smokers. Male gender (OR 48.7; CI 5.0-470.7; p < 0.0001) and younger age (OR 1.1; CI 1.0-1.3; p = 0.003) were predictors of risky alcohol consumption. Male, young, and single smoking and/or drinking HNCS should be stimulated to take part in smoking and/or alcohol drinking cessation programs.

PMID: 26874733 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/214nP8y
via IFTTT

Effectiveness of superselective intra-arterial chemoradiotherapy targeting retropharyngeal lymph node metastasis.

Related Articles

Effectiveness of superselective intra-arterial chemoradiotherapy targeting retropharyngeal lymph node metastasis.

Eur Arch Otorhinolaryngol. 2016 Feb 13;

Authors: Suzuki T, Sakashita T, Homma A, Hatakeyama H, Kano S, Mizumachi T, Yoshida D, Fujima N, Onimaru R, Tsuchiya K, Yasuda K, Shirato H, Suzuki F, Fukuda S

Abstract
We sought to evaluate the efficacy and feasibility of superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (hereafter RADPLAT) for head and neck squamous cell cancer (hereafter HNSCC) patients with retropharyngeal lymph node (hereafter RPLN) metastasis. A retrospective case series review was conducted at University medical center in Japan. Ten HNSCC patients with RPLN metastasis treated by RADPLAT were analyzed. The ascending pharyngeal artery was targeted for the treatment of RPLN metastasis in 9 patients. The median total dose of cisplatin was 26.6 mg/m(2) (mean 31.5 mg/m(2), range 11.7-87.9 mg/m(2)). In the remaining patient, the RPLN was supplied by the ascending palatine artery. As grade 3 and 4 adverse effects, leukopenia was observed in three, mucositis in four and nausea in one patient. No neurological complications were observed in any patients. Metastatic RPLNs were evaluated as a complete response in all patients. There was no recurrence of RPLN metastasis in any patients. Four patients remain alive without any evidence of disease and six patients died of disease. The 5-year overall survival rate was 50 %. We have shown that superselective intra-arterial cisplatin infusion for RPLNs was a feasible and effective approach for HNSCC patients with RPLN metastasis.

PMID: 26874732 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/214nRwU
via IFTTT

Nodal yield of neck dissections and influence on outcome in laryngectomized patients.

Related Articles

Nodal yield of neck dissections and influence on outcome in laryngectomized patients.

Eur Arch Otorhinolaryngol. 2016 Feb 13;

Authors: Böttcher A, Dommerich S, Sander S, Olze H, Stromberger C, Coordes A, Jowett N, Knopke S

Abstract
The appropriate extent of neck dissection (ND) in head and neck squamous cell carcinoma (SCC) continues to be investigated. This study aimed to determine whether the extent of ND as measured by nodal yield (NY) is a prognostic factor in patients undergoing primary total laryngectomy (TL) for advanced laryngeal SCC. A retrospective review at a tertiary referral centre identified 54 patients who underwent TL with elective (n = 39, cN0) or therapeutic (n = 15, cN+) ND with curative intent between 2002 and 2014. Survival analysis was obtained via regression analysis, calculated for overall (OS) and disease-free survival (DFS). Stage-independent 5-year OS was 32.1 %. Mean NY was 18.67 (standard deviation 9.898; range 0-45). The rate of cervical lymph node metastasis on pathology (pN+) was 27.8 %. Uni- and multivariate regression analysis detected no association between NY and OS or DFS (P ≥ 0.05). Advantages in OS and DFS were seen among patients without cervical lymph node metastasis (pN0) in comparison to those with pN+ necks (OS: hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.046-0.693; P = 0.013, and DFS: HR 0.190; 95 % CI 0.061-0.590; P = 0.004). ND resulted in pathologic upstaging of the neck in seven patients and downgrading in eight; increasing NY was not associated with an increased probability of a change in nodal stage. No significant association was found between NY and OS or DFS in patients undergoing TL with ND as primary therapy for advanced laryngeal SCC.

PMID: 26874731 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiUGbH
via IFTTT

Skp2 Regulates the Expression of MMP-2 and MMP-9, and Enhances the Invasion Potential of Oral Squamous Cell Carcinoma.

Related Articles

Skp2 Regulates the Expression of MMP-2 and MMP-9, and Enhances the Invasion Potential of Oral Squamous Cell Carcinoma.

Pathol Oncol Res. 2016 Feb 13;

Authors: Yamada SI, Yanamoto S, Naruse T, Matsushita Y, Takahashi H, Umeda M, Nemoto TK, Kurita H

Abstract
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck regions and accounts for more than 90 % of cancers in the oral cavity. S-phase kinase-associated protein-2 (Skp2) is a member of the F-box protein family and the substrate recognition subunit of the Skp1-Cullin-F box protein E3 ubiquitin ligase complex. Skp2 is oncogenic and overexpressed in human cancers. The aims of the present study were to determine the clinicopathological significance of Skp2 in OSCC and clarify its function in OSCC cell lines in vitro. Multiple methods including immunohistochemical staining, RT-PCR, western blotting, migration and invasion assays, and siRNA transfection were employed in order to investigate the clinicopathological significance and molecular function of Skp2 in OSCC. The overexpression of Skp2 was more frequent in OSCC than in the normal oral epithelium. It was also more frequently detected in cancers with higher grades according to the T classification, N classification, and pattern of invasion. The high-Skp2 expression group had a significantly poorer prognosis, at 30.1 %, than that of the low-expression group, at 63.0 %. The downregulation of Skp2 decreased migration and invasion potentials in HSC3 cells. Moreover, the suppression of Skp2 reduced the enzyme activities of MMP-2 and MMP-9 via Sp1. Skp2 may be a prognostic factor in OSCC patients, and may also play crucial roles in the migration and invasion potentials of OSCC cells.

PMID: 26874697 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiUFVd
via IFTTT

Eosinophil chemotaxis assay in nasal polyps by using a novel optical device EZ-TAXIScan: Role of CC-chemokine receptor 3.

Related Articles

Eosinophil chemotaxis assay in nasal polyps by using a novel optical device EZ-TAXIScan: Role of CC-chemokine receptor 3.

Allergol Int. 2016 Feb 10;

Authors: Saito H, Honda K, Asaka C, Ueki S, Ishikawa K

Abstract
BACKGROUND: The chemokine receptor, CC-chemokine receptor 3 (CCR3), and its major ligands, eotaxin, RANTES, and MCP-4, are involved in eosinophil chemotaxis. It is thought that CCR3 plays an important role in the recruitment and activation of eosinophils in nasal polyposis. We examined nasal polyp extract-induced eosinophil chemotaxis and the effect of a CCR3 antagonist using EZ-TAXIScan, a novel real-time chemotaxis assay device.
METHODS: Nasal polyps were obtained from chronic rhinosinusitis (CRS) patients during surgery. The polyps were homogenized and eotaxin levels in the extracts were measured. Eosinophils were purified from human peripheral blood by the CD16 negative selection method. Nasal polyp extract-induced eosinophil chemotaxis, with or without CCR3 antagonist, was assessed by EZ-TAXIScan.
RESULTS: There was a significant positive correlation between the eosinophil counts in nasal polyp and eotaxin levels in the nasal polyp extracts. Using EZ-TAXIScan, eosinophil chemotactic responses were observed following stimulation with nasal polyp extracts. There was a significant positive correlation between the chemotactic index toward the nasal polyp extracts and their eotaxin levels. Nasal polyp extract-induced chemotaxis was completely inhibited by CCR3 antagonist but not by chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist which inhibited PGD2-induced eosinophil chemotaxis.
CONCLUSIONS: The CCR3 pathway may play an important role in the pathogenesis of eosinophil recruitment in nasal polyps through selective eosinophil chemotaxis.

PMID: 26874579 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1LpuHEr
via IFTTT

Assessment of voice, speech, and related quality of life in advanced head and neck cancer patients 10-years+ after chemoradiotherapy.

Related Articles

Assessment of voice, speech, and related quality of life in advanced head and neck cancer patients 10-years+ after chemoradiotherapy.

Oral Oncol. 2016 Feb 10;

Authors: Kraaijenga SA, Oskam IM, van Son RJ, Hamming-Vrieze O, Hilgers FJ, van den Brekel MW, van der Molen L

Abstract
OBJECTIVES: Assessment of long-term objective and subjective voice, speech, articulation, and quality of life in patients with head and neck cancer (HNC) treated with concurrent chemoradiotherapy (CRT) for advanced, stage IV disease.
MATERIALS AND METHODS: Twenty-two disease-free survivors, treated with cisplatin-based CRT for inoperable HNC (1999-2004), were evaluated at 10-years post-treatment. A standard Dutch text was recorded. Perceptual analysis of voice, speech, and articulation was conducted by two expert listeners (SLPs). Also an experimental expert system based on automatic speech recognition was used. Patients' perception of voice and speech and related quality of life was assessed with the Voice Handicap Index (VHI) and Speech Handicap Index (SHI) questionnaires.
RESULTS: At a median follow-up of 11-years, perceptual evaluation showed abnormal scores in up to 64% of cases, depending on the outcome parameter analyzed. Automatic assessment of voice and speech parameters correlated moderate to strong with perceptual outcome scores. Patient-reported problems with voice (VHI>15) and speech (SHI>6) in daily life were present in 68% and 77% of patients, respectively. Patients treated with IMRT showed significantly less impairment compared to those treated with conventional radiotherapy.
CONCLUSION: More than 10-years after organ-preservation treatment, voice and speech problems are common in this patient cohort, as assessed with perceptual evaluation, automatic speech recognition, and with validated structured questionnaires. There were fewer complaints in patients treated with IMRT than with conventional radiotherapy.

PMID: 26874554 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Tl4crm
via IFTTT

Patient derived xenografts as tools in pharmaceutical development.

Related Articles

Patient derived xenografts as tools in pharmaceutical development.

Clin Pharmacol Ther. 2016 Feb 13;

Authors: Izumchenko E, Meir J, Bedi A, Wysocki PT, Hoque M, Sidransky D

Abstract
Successful drug development in Oncology is grossly suboptimal, manifested by the very low percentage of new agents being developed that ultimately succeed in clinical approval. This poor success is in part due to the inability of standard cell-line xenograft models to accurately predict clinical success and to tailor chemotherapy specifically to a group of patients more likely to benefit from the therapy. Patient-derived xenografts (PDXs) maintain the histopathological architecture and molecular features of human tumors, and offer potential solution to maximize drug development success and ultimately generate better outcomes for patients. Although imperfect in mimicking all aspects of human cancer, PDXs are a more predictable platform for preclinical evaluation of treatment effect and in selected cases can guide therapeutic decision making in the clinic. This manuscript summarizes the current status of PDX models, challenges associated with modeling human cancer and various approaches that have been applied to overcome these challenges and improve the clinical relevance of PDX cancer models. This article is protected by copyright. All rights reserved.

PMID: 26874468 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1RFCynV
via IFTTT

Serum sTREM-1 level is quite higher in Crimean Congo Hemorrhagic Fever, a viral infection

Abstract

Background

Members of triggering receptor expressed on myeloid cells (TREM) family are known as immunmodulators in several infectious or noninfectious inflammatory disorders. The information about their role in viral infections is very limited. To enlighten if there's a relation between soluble TREM-1(sTREM-1) and a viral infection, Crimean Congo Haemorrhagic Fever (CCHF).

Methods

We investigated the levels of sTREM-1 in the sera of 39 CCHF patients both at admission and at recovery and compared with 40 healthy controls by using microELISA technique. Statistical analysis was made by using Statistical Package for Social Sciences (SPSS) for Windows 20 programme. Value of p < 0.05 was accepted as significant for statistical analyses.

Results

Median sTREM-1 level was higher in CCHF group when compared to the control group (1961 pg/mL vs 151.1 pg/mL, respectively; p < 0.001). In CCHF patients, sTREM-1 levels were significantly decreased at recovery compared to initial level measured at hospital admission (1961 pg/mL vs 948 pg/mL, respectively; p = 0.019). ▵sTREM-1 is correlated with ▵CRP, ▵WBC and ▵Plt. We found that serum levels of sTREM-1 higher than 405.9 pgm/L existed as a cut off point for differentiating CCHF patients and control group with a sensitivity of 94.9% and specifity of 87.5%.

Conclusions

It is proved that sTREM-1 is increased and correlates with the clinical and laboratory findings in CCHF, a viral infection characterised by activation of inflammation. This finding may lead new studies to enlighten the pathogenesis of infections developing by activation of inflammatory cascades and high level cytokine releases, especially. This article is protected by copyright. All rights reserved

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1XsSRVu
via IFTTT

Ganglioglioma arising from olfactory sheath: A rare site of an uncommon tumor.

Related Articles

Ganglioglioma arising from olfactory sheath: A rare site of an uncommon tumor.

J Clin Neurosci. 2016 Feb 10;

Authors: Singla N, Gupta K, Kapoor A

Abstract
Gangliogliomas are rare slow growing tumors with a mixed population of dysplastic ganglion cells and glial components, reported at variable sites within the central nervous system, including the frontal, parietal and occipital lobes, the striatum, cerebellum, pituitary and pineal glands as well as the spinal cord. Rarely gangliogliomas have been reported arising within the cranial nerves, including the optic and trigeminal nerve. We present the first patient, to our knowledge, where such a tumor originated from the olfactory sheath. Migration defects leading to entrapment of sensory neurons during development is believed to be responsible for the pathogenesis of these lesions. The extent of surgical extirpation and histopathological anaplasia are important prognosticators. While gangliogliomas are rare tumors, it is crucial to consider them in the differential diagnosis of non-enhancing, poorly localized lesions along the cranial nerves.

PMID: 26874814 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1QgK7SJ
via IFTTT

Is high cancer rate in human due to a weakness in biology resulting from the rapid increase in lifetime expectancy?

Related Articles

Is high cancer rate in human due to a weakness in biology resulting from the rapid increase in lifetime expectancy?

Bull Cancer. 2016 Feb 10;

Authors: Denis F, Letellier C

PMID: 26874976 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U34DG0
via IFTTT

[Systemic therapies administration for adult patients in neuro-oncology: The standards of the Association of the neuro-oncologists of French expression (ANOCEF)].

Related Articles

[Systemic therapies administration for adult patients in neuro-oncology: The standards of the Association of the neuro-oncologists of French expression (ANOCEF)].

Bull Cancer. 2016 Feb 10;

Authors: Simon N, Vasseur M, Chauffert B, Taillandier L, Le Rhun E

PMID: 26874975 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U34Bhr
via IFTTT

Correlation between overall survival and other endpoints in metastatic breast cancer with second- or third-line chemotherapy: Literature-based analysis of 24 randomized trials.

Related Articles

Correlation between overall survival and other endpoints in metastatic breast cancer with second- or third-line chemotherapy: Literature-based analysis of 24 randomized trials.

Bull Cancer. 2016 Feb 10;

Authors: Liu L, Chen F, Zhao J, Yu H

Abstract
BACKGROUND AND OBJECTIVE: Correlations between overall survival (OS) and other endpoints have been evaluated in patients with metastatic breast cancer (MBC) who received first-line chemotherapy. However, no corresponding analysis has been accomplished for patients who have undergone second- or third-line chemotherapy.
METHODS: We evaluated the potential of progression-free survival (PFS)/time to progression (TTP) and objective response rate (ORR) as surrogates of OS when OS data were not available. Correlations were evaluated by Spearman's rank correlation coefficient (rs) and weighted linear regression model. Subgroup analyses were performed for previous chemotherapy, regimen, study endpoint, study period and HER2 status.
RESULTS: Twenty-four randomized trials involving 8617 patients were included for analysis. The correlation between PFS/TTP and OS was 0.7824 (95% CI: 0.6034-0.8702), whereas ORR did not strongly correlate with OS (rs=0.5398, 95%CI: 0.2942-0.7233). Further, the association between hazard ratios (HRs) of PFS/TTP and OS of the 22 randomized studies showed a moderate correlation (rs=0.5725, 95%CI: 0.1735-0.8277); the slope of the regression model (β) was 0.5366 (95%CI: 0.3479-0.7253). In particular, the PFS/OS correlation for HER2-positive MBC patients was stronger (rs=0.9515, 95%CI: 0.7009-1.0000; β=0.8728, 95%CI: 0.0795-1.6661).
CONCLUSIONS: These results suggest that PFS/TTP is a useful early endpoint for patients with MBC who have undergone second- or third-line chemotherapy, especially for those who are HER2-positive.

PMID: 26874974 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1U34DpG
via IFTTT

Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report.

Related Articles

Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report.

Int J Surg Case Rep. 2016 Feb 6;21:6-11

Authors: Acar Ö, Mut T, Sağlıcan Y, Sag AA, Falay O, Selcukbiricik F, Tabak L, Esen T

Abstract
INTRODUCTION: Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far.
CASE PRESENTATION: A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor.
DISCUSSION: Late recurrence of RCC has been reported to occur in 10-20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition.
CONCLUSION: To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnostic.

PMID: 26874583 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Tl4bUn
via IFTTT

Primary signet ring cell carcinoma of the cervix: A case report and review of the literature.

Related Articles

Primary signet ring cell carcinoma of the cervix: A case report and review of the literature.

Int J Surg Case Rep. 2016 Feb 6;21:1-5

Authors: Sal V, Kahramanoglu I, Turan H, Tokgozoglu N, Bese T, Aydin O, Demirkiran F, Arvas M

Abstract
INTRODUCTION: Primary signet cell carcinoma of the cervix has been reported only in 18 cases to date.
PRESENTATION OF CASE: A 48-year-old woman was seen at our Gynecologic Oncology Unit, because she complained postcoital bleeding during the last three months. She had 1-2 cm cervical mass, originating from the endocervical canal. A biopsy revealed a signet ring cell-type adenocarcinoma. Suspected primary sites were excluded after gastroscopy, colonoscopy and mammography. The patient underwent a laparoscopic type-3 radical hysterectomy with bilateral salpingo-oophorectomy, pelvic lymph node dissection and paraaortic lymph node dissection with a presumed diagnosis of primary signet ring cell carcinoma of the cervix. Microscopically, the tumour consisted of 70% signet ring cell type and 30% endocervical adenocarcinoma. She did not receive any adjuvant treatment. Follow-up at 18 months after surgery showed no evidence of recurrence.
DISCUSSION: Nineteenth case of a primary signet ring cell carcinoma of the cervix was presented. Immunohistochemical studies and HPV DNA positivity may help in diagnosis.
CONCLUSION: It is crucial to differentiate primary tumour from metastatic signet cell carcinoma, while treatment and prognosis differ significantly.

PMID: 26874582 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1ogcmEv
via IFTTT

Liposarcoma of Hypopharynx and Esophagus: a Unique Entity?

Related Articles

Liposarcoma of Hypopharynx and Esophagus: a Unique Entity?

J Gastrointest Cancer. 2016 Feb 13;

Authors: Riva G, Sensini M, Corvino A, Garzaro M, Pecorari G

Abstract
PURPOSE: Liposarcoma is the most common soft tissue sarcoma in adults. It represents approximately 20 % of all mesenchymal malignancies. It most frequently involves retroperitoneum, trunk, and extremities. Hypopharyngeal and esophageal localization of liposarcoma is extremely rare.
METHODS: We performed a systematic review of literature and reported 26 and 33 cases of hypopharyngeal and esophageal liposarcoma. We analyzed natural history, imaging features, histology, treatment, and prognosis, with a specific focus to similarities and differences between tumors of hypopharynx and esophagus.
RESULTS: Hypopharyngeal and esophageal liposarcomas have more similarities than differences. Incidence has a peak at 6th and 7th decades. The diagnostic procedures are barium swallow, endoscopic examination, and CT/MR imaging. Well-differentiated liposarcoma represents the most frequent histological subtype. Surgical excision is the main treatment. Endoscopic resection can be useful for pedunculated tumors of hypopharynx and cervical esophagus. Differences between hypopharyngeal and esophageal liposarcoma are represented by local recurrence rate (greater for hypopharyngeal tumors), number of giant tumors, and time to recurrence (greater for esophageal tumors). Finally, liposarcomas of distal esophagus need more extended approaches.
CONCLUSIONS: Liposarcomas of hypopharynx and cervical esophagus could be considered a unique pathological entity, with similar features and treatment options. Survival rate is dependent on histological type and location. Local recurrence is common, especially for hypopharyngeal liposarcoma, while the risk of lymph node or distant metastasis is very low. Patients should undergo regular examinations to rule out local recurrence, also for a long time, especially for esophageal tumors.

PMID: 26875081 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Wn05sS
via IFTTT

Macromol. Rapid Commun. 4/2016

Front Cover: Electron-donating alkylthio and alkoxy side chains often show unique properties that can tune the electronic character of conjugated polymer donor materials in organic solar cell applications. In this review, such rational electron-donating side chain engineering in improving the photovoltaic properties of the resulting polymer donors is surveyed and discussed. Further details can be found in the article by C. Cui,* and W.-Y. Wong* on page 287.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1VglVy1
via IFTTT

Contents: Macromol. Rapid Commun. 4/2016

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1RFAk80
via IFTTT

Macromol. Rapid Commun. 4/2016

Back Cover: Potential uses in full-color displays and back-lighting units for liquid crystal displays are described. We fabricated white-light-emitting, electrospun PEO sheets containing a hyperbranched conjugated polymer (HBP), which has the unique property of exhibiting a variety of fluorescence colors, leading to easy manipulation of the emission colors of the PEO sheets by simple variation of the HBP concentrations in the PEO. Further details can be found in the article by J. Kim, and T. S. Lee* on page 303.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1VglSSS
via IFTTT

Masthead: Macromol. Rapid Commun. 4/2016

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1RFAk7M
via IFTTT

Eosinophilic pustular folliculitis: A published work-based comprehensive analysis of therapeutic responsiveness

Abstract

Eosinophilic pustular folliculitis (EPF) is a non-infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression-associated EPF, which is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non-HIV and infancy-associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non-HIV and infancy-associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei-to (a Chinese–Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin-resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Wn0cVd
via IFTTT

Traumatic neuroma on the digital tip: Immunohistochemical analysis of inflammatory signaling pathways

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Wn0cER
via IFTTT

Pustular prurigo pigmentosa treated with doxycycline

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Wn0cEF
via IFTTT

Successful treatment of primary cutaneous Nocardia brasiliensis infection with oral potassium iodide

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiV89U
via IFTTT

Eosinophilic pustular folliculitis: Trends in therapeutic options

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Wn0eMU
via IFTTT

Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized, double-blind, phase 3 study

Abstract

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double-blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open-label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end-points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) and Physician's Global Assessment of "clear" or "almost clear" (PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria (ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty-seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiV9ea
via IFTTT

Association of anti-RNA polymerase III antibody and silicone breast implants in patients with systemic sclerosis

Abstract

Systemic sclerosis (SSc) is believed to be caused by a complex interplay between genetic factors and environmental influences. Although silicone has been considered to be a candidate of environmental agents, clinical data presented so far fail to show a significant association between silicone breast implant (SBI) and the development of SSc. Because we recently experienced two consecutive SSc patients with anti-RNA polymerase III (RNAP III) antibody who underwent SBI, we here investigated the association of SBI history with the development of SSc positive for anti-RNAP III antibody. Among 262 Japanese SSc patients, of note, the frequency of SBI history was significantly higher in the anti-RNAP III antibody group (16.0% [4/25]) than in the anti-topoisomerase I antibody group (0% [0/87], P < 0.005) and in the anticentromere antibody group (1.2% [2/150], P < 0.005). These results suggest that SBI could influence the development of SSc in a certain subset of patients with anti-RNAP III antibody.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Wn0eMN
via IFTTT

Extensive tumoral melanosis associated with ipilimumab-treated melanoma

Abstract

Tumoral melanosis describes a pigmented lesion clinically similar to melanoma but that histologically reveals dense aggregates of melanin-laden, benign macrophages without malignant cells. In the few reported cases, tumoral melanosis has arisen in the skin or lymph node of a patient with a regressed melanoma or an epithelioid tumor. As a marker of regressed primary melanoma, its discovery may prompt investigation and surveillance for undiagnosed local or metastatic disease. Here, we present a unique case of extensive tumoral melanosis arising during ipilimumab treatment of in-transit metastases from a previously excised melanoma.

This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/20yJa7V
via IFTTT

Eric Cline, 1177 B.C. The year civilization collapsed

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiV8Xv
via IFTTT

Seafaring, trade, and knowledge transfer: maritime politics and commerce in early middle period to early modern China

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiV75S
via IFTTT

Perspectives for a comparative cultural history of the Ostend company interactions in Bengal and China

Taking the source material of the Ostend Company's 18th century maritime trading activities into China and Bengal as a vantage point, this article explores its potential for a comparative history on cultural interaction in the Indian Ocean world. It compares how agents from this Company engaged in cultural interaction as a prerequisite for further economic interaction. Beyond a colonial or econocentric approach, it takes an anthropological perspective considering cultural interaction as a performative learning process, revealing how these agents participated in and made sense of foreign customs and policies. By comparing the diaries of a 1723 merchant-diplomat in Bengal and a 1726 merchant in Canton, it shows similarities and differences in their learning process in both maritime trading environments. This provides a summary of several key themes for a comparative history of cultural interaction, such as performative courtly rituals, the role of informants and information on learning how to interact, and the personal reflections of European merchants. The article also demonstrates the potential for a collaborative approach, via the inclusion of a comparison with older Chinese sources, in establishing a longue durée perspective on specific cultural phenomena as aspects of the learning process, such as the differing significance of clothing, or the ritual use of tea or tobacco in the receiving of guests. Its focus on interaction also reveals the mediating role of Persian or Armenian merchants. Finally, the article also points at the role of unexpected occurrences such as shipwrecks or robbery, as hazardous aspects of maritime trading environments, and the human response to these on both direct and institutional levels. Against an overtly structural approach, this reveals how human-environment interaction also contained an element of unpredictability.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1oiV5v1
via IFTTT

Dietary practices at the castle of Middelburg, Belgium: organic residue analysis of 16th- to 17th-century ceramics

Between 2002 and 2004, excavations on the castle of Middelburg (Belgium) revealed ample pottery assemblages dating to the 16th and 17th centuries. Gas chromatography mass spectrometry (GC–MS) analysis of preserved surface residues on these ceramics allowed the identification of biomarkers for animal and vegetal foods, and thermal processing. This paper furthermore reinforces the methodology for examining food residues by GC–MS, particularly in pottery in which highly varied meals were prepared. For example, this study forms the first instance in which dairy signals have been identified in mid-chain ketones. Moreover, insights are gained in the multiple uses of vessel types and questions arise on the dietary and medicinal practices of the inhabitants of this particular castle site.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Wn0bRb
via IFTTT

Het relaas van een boekhandel in Nairobi

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1PMjP5k
via IFTTT

When cultural modifications are taken into account: Ibsen's a doll's house on Iranian screen

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1RFzMic
via IFTTT

Oscar Wilde as a temporal designer: a case study of the picture of Dorian Gray

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1RFzKXD
via IFTTT

Towards deciphering proteomes via the proteoform, protein speciation, moonlighting and protein code concepts

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): P.R. Jungblut, B. Thiede, H. Schlüter




from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOKcU
via IFTTT

Editorial Board

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134





from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOL0h
via IFTTT

Special Issue Content Lists

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134





from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/214kS7N
via IFTTT

Protein species as diagnostic markers

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): Pascal Steffen, Marcel Kwiatkowski, Wesley D. Robertson, Arash Zarrine-Afsar, Diana Deterra, Verena Richter, Hartmut Schlüter
Many diseases are associated with protein species perturbations. A prominent example of an established diagnostic marker is the glycated protein species of hemoglobin, termed HbA1c. HbA1c concentration is increased in the blood of diabetes mellitus patients due to their poor control of blood glucose levels resulting in an increased non-enzymatic glycosylation of hemoglobin producing HbA1c. This important diagnostic marker is routinely measured in the blood of diabetes patients. As in the case of HbA1c, protein species can mirror pathophysiological events. Shifts in the levels of protein species can be associated with or even be responsible for disease making them well suited as diagnostic markers. However, only a few protein species are currently used as diagnostic markers in routine clinical chemistry laboratories, despite being widely established in clinical proteomics research. This review provides an overview of the biochemical characteristics associated with protein species as well as examples of pathophysiological mechanisms, which cause modifications in the protein species composition, thereby emphasizing the importance of screening for protein markers at the species level. Further, we highlight techniques, which are currently utilized for investigating protein species markers in clinical research.Biological significanceThe success rate of FDA approved diagnostic protein markers until today is very low compared to the number of published candidate disease markers. It is hypothesized that one important reason is the gene-centric view which is still followed in clinical proteomics: In many investigations proteins are still digested in small peptides thus making it nearly impossible to discriminate between healthy proteins and pathologic proteins causing diseases. Thus this review is focusing on the biochemistry and patho-biochemistry of proteins, is highlighting the need for screening for disease markers on the protein species level and is giving an overview about available techniques.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/214kRRf
via IFTTT

Biological significance of co- and post-translational modifications of the yeast 26S proteasome

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): Hisashi Hirano, Yayoi Kimura, Ayuko Kimura
In yeast (Saccharomyces cerevisiae), co- and post-translational modifications of the 26S proteasome, a large protein complex, were comprehensively detected by proteomic techniques, and their functions were investigated. The presence, number, site, and state of co- and post-translational modifications of the 26S proteasome differ considerably among yeast, human, and mouse. The roles of phosphorylation, N^α-acetylation, N^α-myristoylation, N^α-methylation, and N-terminal truncation in the yeast 26S proteasome were investigated. Although there is only one modification site for either N^α-acetylation, N^α-myristoylation, or N^α-methylation, these modifications play an important role in the functions of the yeast proteasome. In contrast, there are many phosphorylation sites in the yeast 26S proteasome. However, the phosphorylation patterns might be a few, suggesting that tiny modifications exert considerable effects on the function of the proteasome.Biological significanceProtein co- and post-translational modifications produce different protein species which often have different functions. The yeast 26S proteasome, a large protein complex, consisting of many subunits has a number of co- and post-translational modification sites. This review describes the effects of the modifications on the function of the protein complex.This article is part of a Special Issue entitled: Protein species. Guest Editors: Peter Jungblut, Hartmut Schlüter and Bernd Thiede.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOIlg
via IFTTT

Hexose-derived glycation sites in processed bovine milk

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): Sanja Milkovska-Stamenova, Ralf Hoffmann
Milk products are consumed by many people on a daily basis, which demands sophisticated technical processes to guarantee the microbiological safety and to retain the nutritional value. The heating during pasteurization and ultra high temperature (UHT) treatment triggers diverse chemical reactions, such as the reaction of sugars and amino groups of proteins typically termed protein glycation. The glycation by lactose as dominant sugar in milk has been recently investigated, whereas the contribution of hexoses remains open. We identified first hexose-derived glycation sites in raw milk, colostrum, three brands of pasteurized milk, three brands of UHT milk, five brands of infant formula, and one brand of lactose-free pasteurized and UHT milk using tandem mass spectrometry and electron transfer dissociation. In total, we could identify 124 hexosylated tryptic peptides in a bottom-up proteomics approach after enriching glycated peptides by boronate affinity chromatography, which corresponded to 86 glycation sites in 17 bovine milk proteins. In quantitative terms glycation increased from raw milk to pasteurized milk to UHT milk and infant formula. Lactose-free milk contained significantly higher hexosylation degrees than the corresponding regular milk product. Interestingly, the glycation degrees varied considerably among different brands with lactose-free UHT milk and infant formula showing the highest levels.Biological significanceThe established proteomics strategy enables the identification and relative quantification of different protein glycation types in diverse milk products ranging from raw milk to milk powders. This will allow detailed in vitro studies to judge positive or negative aspects when consuming differently processed milk products including lactose-free milk that is obligatory for people with lactose intolerance but is increasingly consumed by the general population assuming health benefits. The established analytics will also permit studying the influence of each technical processing step on the glycation degrees and thus offers the possibility to reduce glycation early during production, as obvious from the variation among different brands. Special attention should be given to the high hexose- and lactose-derived glycation levels found in infant formula, although it is still controversially discussed if protein glycation has a negative biological impact.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOIl3
via IFTTT

Protein species-specific characterization of conformational change induced by multisite phosphorylation

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): Jingxi Pan, Suping Zhang, Christoph H. Borchers
Phosphorylation is a central mechanism for regulating the structure and function of proteins in the cell, but accurate characterization of a specific protein phospho-species is challenging due to the difficulty of separating it from other species, as well as the limitations of the traditional structural methods. By using selective top-down ETD, we were able to identify six specific phospho-species of calmodulin (CaM). Phosphorylation of CaM at four sites by CK2 was found to follow a sequential order, with Ser81 as the first, Thr79 as the second, and Ser101 or Thr117 as the third. By combining top-down ETD with hydrogen/deuterium exchange, the impact of phosphorylation on CaM's structure was elucidated in a species-specific manner. A negligible structural effect was observed for mono-phosphorylation at Ser81, or di-phosphorylation at Ser81-Thr79, or tri-phosphorylation at Ser81-Thr79-Ser101 or Ser81-Thr79-Thr117. However, it was found that a significant phosphorylation-induced conformational change in CaM was caused by simultaneous phosphorylation at Ser101 and Thr117. The dramatically increased deuterium incorporation for residues between 102 and 119 strongly suggests that the structure of this region has been greatly changed.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOJWf
via IFTTT

A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): Catherine Aude-Garcia, Bastien Dalzon, Jean-Luc Ravanat, Véronique Collin-Faure, Hélène Diemer, Jean Marc Strub, Sarah Cianferani, Alain Van Dorsselaer, Marie Carrière, Thierry Rabilloud
The cellular responses of the J774 macrophage cell line to zinc oxide and zirconium oxide nanoparticles have been studied by a comparative quantitative, protein level based proteomic approach. The most prominent results have been validated by targeted approaches. These approaches have been carried out under culture conditions that stimulate mildly the aryl hydrocarbon receptor, thereby mimicking conditions that can be encountered in vivo in complex environments. The comparative approach with two nanoparticles allows to separate the common responses, which can be attributed to the phagocytosis event per se, from the response specific to each type of nanoparticles.The zinc-specific responses are the most prominent ones and include mitochondrial proteins too, but also signaling molecules such as MyD88, proteins associated with methylglyoxal detoxification (glyoxalase 2, aldose reductase) and deoxyribonucleotide hydrolases. The in cellulo inhibition of GAPDH by zinc was also documented, representing a possible source of methylglyoxal in the cells, leading to an increase in methylglyoxal-modified DNA bases. These observations may be mechanistically associated with the genotoxic effect of zinc and its selective effects on cancer cells.Biological significanceThe responses of the murine J774 macrophage cell lines to two types of metallic oxide nanoparticles (zinc oxide and zirconium dioxide) were studied by a comparative 2D gel based approach. This allows sorting of shared responses from nanoparticle-specific responses.Zinc oxide nanoparticles induced specifically a strong decrease in the mitochondrial function, in phagocytosis and also an increase in the methylglyoxal-associated DNA damage, which may explain the well known genotoxicity of zinc.In conclusion, this study allows highlighting of pathways that may play an important role in the toxicity of the zinc oxide nanoparticles.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOI4J
via IFTTT

Differentiation of protein species of alpha-2u-globulin according to database entries: A half-theoretical approach

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): Sevil Aksu, Fatmagül Tanrikulu
The alpha-2u-globulin protein, the main subject of this study, is the most abundant protein in adult male rat urine. In this investigation there are 19 spots identified as alpha-2u-globulin by 2-DE and MALDI-TOF/TOF-MS. All of them are in the low molecular weight region, at approximately 15–25kDa. Searches within both, SwissProt and NCBI databases gave different from each other, but on the majority the same database entry as the highest ranked result for all spots. For this half-theoretical approach all entries from the NCBI database for the protein alpha-2u-globulin were considered in more detail. The sequences and the masses of the theoretically resulting tryptic peptides were compared with the PMF spectra of the spots identified as alpha-2u-globulin. This study presents a trial to distinguish between different protein species of that protein, only on the amino acid level. Other modifications like phosphorylation, glycosylation or any other group modification could not be considered here. Different protein species can be predicted for groups of closer positioned spots. Statements about which spot contains which peptide variant can be done, too. But it was found that several spots contain more than one protein species.Biological significanceIn this investigation a half-theoretically approach was shown to differentiate between protein species of different spots identified as the same protein. Different positions of spots in 2-DE gels mean different contents of protein species. Here, peptide masses from sequences of protein database entries were searched in the PMF spectra of alpha-2u-globulin. Different peptide variants could be assigned to different spots. It was also found that several spots contain more than one peptide variant and therefore more than one protein species. In addition, the insufficiency of the database has been demonstrated.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOJFS
via IFTTT

Homogenization of tissues via picosecond-infrared laser (PIRL) ablation: Giving a closer view on the in-vivo composition of protein species as compared to mechanical homogenization

Publication date: 16 February 2016
Source:Journal of Proteomics, Volume 134
Author(s): M. Kwiatkowski, M. Wurlitzer, A. Krutilin, P. Kiani, R. Nimer, M. Omidi, A. Mannaa, T. Bussmann, K. Bartkowiak, S. Kruber, S. Uschold, P. Steffen, J. Lübberstedt, N. Küpker, H. Petersen, R. Knecht, N.O. Hansen, A. Zarrine-Afsar, W.D. Robertson, R.J.D. Miller, H. Schlüter
Posttranslational modifications and proteolytic processing regulate almost all physiological processes. Dysregulation can potentially result in pathologic protein species causing diseases. Thus, tissue species proteomes of diseased individuals provide diagnostic information. Since the composition of tissue proteomes can rapidly change during tissue homogenization by the action of enzymes released from their compartments, disease specific protein species patterns can vanish. Recently, we described a novel, ultrafast and soft method for cold vaporization of tissue via desorption by impulsive vibrational excitation (DIVE) using a picosecond-infrared-laser (PIRL). Given that DIVE extraction may provide improved access to the original composition of protein species in tissues, we compared the proteome composition of tissue protein homogenates after DIVE homogenization with conventional homogenizations. A higher number of intact protein species was observed in DIVE homogenates. Due to the ultrafast transfer of proteins from tissues via gas phase into frozen condensates of the aerosols, intact protein species were exposed to a lesser extent to enzymatic degradation reactions compared with conventional protein extraction. In addition, total yield of the number of proteins is higher in DIVE homogenates, because they are very homogenous and contain almost no insoluble particles, allowing direct analysis with subsequent analytical methods without the necessity of centrifugation.Biological significanceEnzymatic protein modifications during tissue homogenization are responsible for changes of the in-vivo protein species composition. Cold vaporization of tissues by PIRL-DIVE is comparable with taking a snapshot at the time of the laser irradiation of the dynamic changes that occur continuously under in-vivo conditions. At that time point all biomolecules are transferred into an aerosol, which is immediately frozen.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOI4D
via IFTTT

Cancers, Vol. 8, Pages 22: Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors

The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. Aberrant activation of the Shh pathway has been shown in a variety of human cancers, including, basal cell carcinoma, malignant gliomas, medulloblastoma, leukemias, and cancers of the breast, lung, pancreas, and prostate. Tumorigenesis, tumor progression and therapeutic response have all been shown to be impacted by the Shh signaling pathway. Downstream effectors of the Shh pathway include smoothened (SMO) and glioma-associated oncogene homolog (GLI) family of zinc finger transcription factors. Both are regarded as important targets for cancer therapeutics. While most efforts have been devoted towards pharmacologically targeting SMO, developing GLI-targeted approach has its merit because of the fact that GLI proteins can be activated by both Shh ligand-dependent and -independent mechanisms. To date, two SMO inhibitors (LDE225/Sonidegib and GDC-0449/Vismodegib) have received FDA approval for treating basal cell carcinoma while many clinical trials are being conducted to evaluate the efficacy of this exciting class of targeted therapy in a variety of cancers. In this review, we provide an overview of the biology of the Shh pathway and then detail the current landscape of the Shh-SMO-GLI pathway inhibitors including those in preclinical studies and clinical trials.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1ObnK9G
via IFTTT

The coordinated regulation of phospholipase D by ADP-ribosylation factors and their exchange factors.

Ha, V.L.; (2004) The coordinated regulation of phospholipase D by ADP-ribosylation factors and their exchange factors. Doctoral thesis, University of London. Green open access

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SrOI4x
via IFTTT

Radial glia and neurogenesis in the embryonic zebrafish hindbrain.

Guy, A.T.; (2004) Radial glia and neurogenesis in the embryonic zebrafish hindbrain. Doctoral thesis, University of London. Green open access

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/214kTsm
via IFTTT