A selection of abstracts presented at the 43rd annual conference of the anatomical society of Southern Africa (ASSA), 9–13 May 2015, Khaya iBHUBESI Conference Venue, Parys, Free State, South Africa

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Microbioma and probiotics: from gut to Mars

Bruno Acatauassú Paes Barreto
Braz J Otorhinolaryngol 2018;84:1-2

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IV Brazilian Consensus on Rhinitis – an update on allergic rhinitis

Eulalia Sakano, Emanuel S.C. Sarinho, Alvaro A. Cruz, Antonio C. Pastorino, Edwin Tamashiro, Fábio Kuschnir, Fábio F.M. Castro, Fabrizio R. Romano, Gustavo F. Wandalsen, Herberto J. Chong‐Neto, João F. de Mello Jr., Luciana R. Silva, Maria Cândida Rizzo, Mônica A.M. Miyake, Nelson A. Rosário Filho, Norma de Paula M. Rubini, Olavo Mion, Paulo A. Camargos, Renato Roithmann, Ricardo N. Godinho, Shirley Shizue N. Pignatari, Tania Sih, Wilma T. Anselmo‐Lima, Dirceu Solé
Braz J Otorhinolaryngol 2018;84:3-14

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Cochlear implantation in autistic children with profound sensorineural hearing loss

Magdalena Lachowska, Agnieszka Pastuszka, Zuzanna Łukaszewicz‐Moszyńska, Lidia Mikołajewska, Kazimierz Niemczyk
Braz J Otorhinolaryngol 2018;84:15-9

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Bayesian analysis of high‐resolution ultrasonography and guided fine needle aspiration cytology in diagnosis of palpable thyroid nodules

Niranjan Sahu, Rabindra Nath Padhy
Braz J Otorhinolaryngol 2018;84:20-7

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Intratympanic steroid injection and hyperbaric oxygen therapy for the treatment of refractory sudden hearing loss

Filiz Gülüstan, Zahide Mine Yazıcı, Wesam M.E. Alakhras, Omer Erdur, Harun Acipayam, Levent Kufeciler, Fatma Tulin Kayhan
Braz J Otorhinolaryngol 2018;84:28-33

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The seroprevalence of hepatitis B, hepatitis C, and human immunodeficiency virus in patients undergoing septoplasty

Ozlem Onerci Celebi, Ela Araz Server, Bahtiyar Hamit, Özgür Yiğit
Braz J Otorhinolaryngol 2018;84:34-9

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Correlation between acoustic rhinometry, computed rhinomanometry and cone‐beam computed tomography in mouth breathers with transverse maxillary deficiency

Raquel Harumi Uejima Satto Sakai, Fernando Augusto Lima Marson, Emerson Taro Inoue Sakuma, José Dirceu Ribeiro, Eulália Sakano
Braz J Otorhinolaryngol 2018;84:40-50

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Evaluation of peripheral auditory pathways and brainstem in obstructive sleep apnea

Erika Matsumura, Carla Gentile Matas, Fernanda Cristina Leite Magliaro, Raquel Meirelles Pedreño, Geraldo Lorenzi‐Filho, Seisse Gabriela Gandolfi Sanches, Renata Mota Mamede Carvallo
Braz J Otorhinolaryngol 2018;84:51-7

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Temporal bone paragangliomas: 15 years experience

Mehmet Düzlü, Hakan Tutar, Recep Karamert, Furkan Karaloğlu, Muammer Melih Şahin, Mehmet Göcek, Mehmet Birol Uğur, Nebil Göksu
Braz J Otorhinolaryngol 2018;84:58-65

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Effect of hearing aids use on speech stimulus decoding through speech‐evoked ABR

Renata Aparecida Leite, Fernanda Cristina Leite Magliaro, Jeziela Cristina Raimundo, Mara Gândara, Sergio Garbi, Ricardo Ferreira Bento, Carla Gentile Matas
Braz J Otorhinolaryngol 2018;84:66-73

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Prognostic role of margin status in open and CO2 laser cordectomy for T1a–T1b glottic cancer

Vincenzo Landolfo, Carmine Fernando Gervasio, Giuseppe Riva, Massimiliano Garzaro, Rita Audisio, Giancarlo Pecorari, Roberto Albera
Braz J Otorhinolaryngol 2018;84:74-81

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Preclinical evaluation of Luffa operculata Cogn. and its main active principle in the treatment of bacterial rhinosinusitis

Leonardo Silva, Henrique Olival Costa, Flávia Coelho de Souza, Elaine Monteiro Cardoso Lopes, Suely Mitoi Ykko Ueda
Braz J Otorhinolaryngol 2018;84:82-8

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Volumetric evaluation of pharyngeal segments in obstructive sleep apnea patients

Marcos Marques Rodrigues, Valfrido Antonio Pereira Filho, Mário Francisco Real Gabrielli, Talles Fernando Medeiros de Oliveira, Júlio Américo Pereira Batatinha, Luis Augusto Passeri
Braz J Otorhinolaryngol 2018;84:89-94

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Simultaneous idiopathic bilateral sudden hearing loss – characteristics and response to treatment

Ferit Akil, Umur Yollu, Mehmet Yilmaz, H. Murat Yener, Marlen Mamanov, Ender Inci
Braz J Otorhinolaryngol 2018;84:95-101

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Osteonecrosis of the jaws: a review and update in etiology and treatment

Guilherme H. Ribeiro, Emanuely S. Chrun, Kamile L. Dutra, Filipe I. Daniel, Liliane J. Grando
Braz J Otorhinolaryngol 2018;84:102-8

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Effectiveness of Otolith Repositioning Maneuvers and Vestibular Rehabilitation exercises in elderly people with Benign Paroxysmal Positional Vertigo: a systematic review

Karyna Figueiredo Ribeiro, Bruna Steffeni Oliveira, Raysa V. Freitas, Lidiane M. Ferreira, Nandini Deshpande, Ricardo O. Guerra
Braz J Otorhinolaryngol 2018;84:109-18

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Aggressive osteoblastoma of the temporal bone: an unusual cause of facial palsy

Rashmi Dixit, Swati Gupta, Veena Chowdhury, Nita Khurana
Braz J Otorhinolaryngol 2018;84:119-21

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Middle turbinate angiofibroma: an unusual location for juvenile angiofibroma

Yuksel Toplu, Sermin Can, Mukadder Sanlı, Nurhan Sahin, Ahmet Kizilay
Braz J Otorhinolaryngol 2018;84:122-5

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Iatrogenic nasal vestibular stenosis after maxillofacial reconstructive surgery

Byung‐Woo Yoon, Dong‐Won Kim, Soo‐Jong Choi, Kyu‐Sup Cho
Braz J Otorhinolaryngol 2018;84:126-30

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Effects of exposure to 2100MHz GSM‐like radiofrequency electromagnetic field on auditory system of rats

Seyed Mohammad Javad Mortazavi, Seyed Ali Reza Mortazavi, Maryam Paknahad
Braz J Otorhinolaryngol 2018;84:131

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Influenza Virus: Dealing with a Drifting and Shifting Pathogen

Viral Immunology , Vol. 0, No. 0.


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Immunization with a Mixture of Nucleoprotein from Human Metapneumovirus and AbISCO-100 Adjuvant Reduces Viral Infection in Mice Model

Viral Immunology , Vol. 0, No. 0.


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Association between preoperative thyrotrophin and clinicopathological and aggressive features of papillary thyroid cancer

Abstract

Purpose

We aimed to investigate the relation between preoperative serum thyrotrophin (TSH) and clinicopathological features in patients with papillary thyroid carcinoma (PTC) and microcarcinoma (PTMC).

Methods

Patients who underwent thyroidectomy and diagnosed to have benign nodular disease or PTC/PTMC in our clinic were evaluated retrospectively. Patients with a previous history of thyroid surgery, patients using antithyroid medications or thyroid hormone and patients with tumors known to be unresponsive to TSH were excluded.

Results

Data of 1632 patients were analyzed. Histopathological diagnosis was benign in 969 (59.4%) and malignant in 663 (40.6%) patients. Preoperative median serum TSH was significantly higher in malignant compared to benign group (1.41 IU/dL vs. 0.98 IU/dL, p < 0.001). Malignancy risk increased gradually as going from hyperthyroidism to euthyroidism and hypothyroidism (20, 40.6, and 59.1%, respectively, p < 0.05). Serum TSH was lowest in benign nodular disease, higher in PTMC and highest in PTC (p < 0.001). This was also true when patients with positive antithyroid peroxidase/antithyroglobulin and with lymphocytic thyroiditis were excluded from the analysis (p < 0.001). Serum TSH was higher in patients with bilateral tumor, capsular invasion and lymph node metastasis (LNM) compared to patients with unilateral tumor, without capsule invasion and without LNM, respectively (p = 0.036, p = 0.002, and p = 0.001, respectively). Patients with aggressive variant PTC had higher serum TSH than nonaggressive ones (p < 0.05).

Conclusion

Preoperative serum TSH is associated with PTMC, PTC and LNM. Serum TSH seems to be related with thyroid cancer regardless of autoimmunity. With the present study, for the first time, we showed an association between serum TSH and aggressive variants of PTC.

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A phase II study of tipifarnib and gemcitabine in metastatic breast cancer

Summary

Background Tipifarnib is an orally active, competitive inhibitor of farnesyltransferase which has shown encouraging signs of activity either alone or when combined with other agents. Clinical studies of tipifarnib in combination with anti-estrogen therapy have yielded disappointing results. In contrast, tipifarnib appears to be synergistic in combination with anthracycline based chemotherapy. Here we report the results of the first prospective phase II trial evaluating the efficacy of the novel combination of tipifarnib and gemcitabine in the treatment of metastatic breast cancer. Patients and Methods 30 postmenopausal women with metastatic breast cancer were treated on a 21-day cycle with tipifarnib 300 mg PO twice daily from days 1 through 14. Gemcitabine was administered intravenously at a dose of 1000 mg/m² on days 1 and 8. Patients were treated until disease progression or unacceptable toxicity. Results There was one complete response and four partial responses yielding an objective response rate of 16.7%. Median progression-free survival and overall survival was 2.5 months (95% confidence interval: 1.6–5.7 months) and 13.1 months (95% confidence interval: 9.1–20.6 months), respectively. 40% of patients experienced grade 4 neutropenia in this study. Conclusion The combination of tipifarnib and gemcitabine is not well tolerated with high rates of myelosuppression and is not more effective than gemcitabine monotherapy in the treatment of metastatic breast cancer.

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Association between preoperative thyrotrophin and clinicopathological and aggressive features of papillary thyroid cancer

Abstract

Purpose

We aimed to investigate the relation between preoperative serum thyrotrophin (TSH) and clinicopathological features in patients with papillary thyroid carcinoma (PTC) and microcarcinoma (PTMC).

Methods

Patients who underwent thyroidectomy and diagnosed to have benign nodular disease or PTC/PTMC in our clinic were evaluated retrospectively. Patients with a previous history of thyroid surgery, patients using antithyroid medications or thyroid hormone and patients with tumors known to be unresponsive to TSH were excluded.

Results

Data of 1632 patients were analyzed. Histopathological diagnosis was benign in 969 (59.4%) and malignant in 663 (40.6%) patients. Preoperative median serum TSH was significantly higher in malignant compared to benign group (1.41 IU/dL vs. 0.98 IU/dL, p < 0.001). Malignancy risk increased gradually as going from hyperthyroidism to euthyroidism and hypothyroidism (20, 40.6, and 59.1%, respectively, p < 0.05). Serum TSH was lowest in benign nodular disease, higher in PTMC and highest in PTC (p < 0.001). This was also true when patients with positive antithyroid peroxidase/antithyroglobulin and with lymphocytic thyroiditis were excluded from the analysis (p < 0.001). Serum TSH was higher in patients with bilateral tumor, capsular invasion and lymph node metastasis (LNM) compared to patients with unilateral tumor, without capsule invasion and without LNM, respectively (p = 0.036, p = 0.002, and p = 0.001, respectively). Patients with aggressive variant PTC had higher serum TSH than nonaggressive ones (p < 0.05).

Conclusion

Preoperative serum TSH is associated with PTMC, PTC and LNM. Serum TSH seems to be related with thyroid cancer regardless of autoimmunity. With the present study, for the first time, we showed an association between serum TSH and aggressive variants of PTC.

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Effectiveness of laser adjunctive therapy for surgical treatment of gingival recession with flap graft techniques: a systematic review and meta-analysis

Abstract

Various flap graft techniques in the treatment of gingival recession have already been reported in the literatures for root coverage. Laser therapy has effects of ablative, hemostatic, and decontamination. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of flap surgery combined with laser with surgery alone for treating gingival recession. The studies were searched from PubMed, Embase, Web of science, and the Cochrane Central Register of Controlled Trials by two reviewers up to August 2017. The quality of RCTs was assessed by Cochrane Handbook. Data were extracted from studies and analyzed by Review Manager 5.3. 95% confidence interval (CI) and risk ratio (RR) were calculated for dichotomous data. Seven RCTs with 173 patients and 296 teeth were included in the meta-analysis. We found no statistically significant differences between two groups in GRD (gingival recession depth) (P = 0.21), GRW (gingival recession width) (P = 0.92), RES (root esthetic score) (P = 0.21), and CRC (complete root coverage) (P = 0.09). Statistically significant differences were found between two groups in the WKT (width of keratinized tissue) (P < 0.0001) and 1-year follow-up of PD (probing depth) (P = 0.03) and CAL (clinical attachment level) (P < 0.00001). The meta-analysis found that surgery with laser therapy provided clinical advantages in terms of WKT and 1-year follow-up of PD and CAL. However, flap graft associated with laser did not offer additional benefit to root coverage and esthetics in treating gingival recession. More long-term studies are required to assess these parameters.

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Possible effect of SNAIL family transcriptional repressor 1 polymorphisms in non-syndromic cleft lip with or without cleft palate

Abstract

Objective

Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state.

Materials and methods

Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P. A total of 632 families from Italy and Asia participated to the study.

Results

Evidence of allelic association was found with polymorphisms of SNAI1; in particular, the rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds ratio = 0.69 (95% C.I. 0.54–0.89)]. However, the adjusted significance value corrected for all the performed tests was P = 0.051.

Conclusions

The findings emerging by the present study suggest for the first time an involvement of SNAI1 in the nsCL/P onset.

Clinical relevance

Interestingly, SNAI1 is known to promote epithelial to mesenchymal transition by repressing E-cadherin expression, but it needs an intact PRC2 to act this function. Alterations of this process could contribute to the complex etiology of nsCL/P.

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Epidermotropic Presentation by Splenic B-cell Lymphoma: The Importance of Clinical-Pathologic Correlation

Abstract

There are exceedingly rare reports of patients with epidermotropic B-cell lymphomas. A subset presented with intermittent, variably pruritic papular eruptions and involvement of their spleens, peripheral blood, and bone marrow at the time of diagnosis. Furthermore, some experienced an indolent course despite dissemination of their lymphomas. We report a 66-year-old woman with a 12-year history of intermittent eruptions of nonpruritic salmon-colored papules on her torso and proximal extremities that occurred in winter and resolved with outdoor activity in spring. Skin biopsy revealed an epidermotropic B-cell lymphoma with a non-specific B-cell phenotype and heavy chain class switching with IgG expression. On workup, our patient exhibited mild splenomegaly and low-level involvement of her peripheral blood and bone marrow by a kappa-restricted B-cell population. A splenic B-cell lymphoma was diagnosed. Considering her longstanding history and absences of cytopenias, our patient has been followed without splenectomy or systemic therapy. Furthermore, the papules have responded dramatically to narrowband UVB. Our case and a review of similar rare reports aim to raise awareness among dermatopathologists and dermatologists of a clinically distinct and indolent subset of epidermotropic splenic lymphomas with characteristic clinical and histologic findings.

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A quantitative comparison between SOX10 and MART-1 immunostaining to detect melanocytic hyperplasia in chronically sun-damaged skin

Abstract

Histologic differentiation of melanoma in situ (MIS) from solar keratosis on chronically sun-damaged skin is challenging. The first-line immunostain is usually MART-1/Melan-A, which can exaggerate the epidermal melanocytes, causing a diagnostic pitfall for MIS. By comparing MART-1 and SOX10 immunostaining, we scored the percentage of epidermal melanocytes per 2-mm diameter fields in pigmented actinic keratosis (n=16), lichenoid keratosis (n=7), junctional melanocytic nevus (n=6), keratosis with atypical melanocytic proliferation (AMP, n=17) and MIS (n=10). These cases represented an older population (68 years median age) and the head and neck (50%) was the most common anatomic site. MART-1 score was significantly higher than SOX10 (P value < 0.05) in solar keratoses, but showed no difference in detecting melanocytic proliferations, demonstrating their equal detection rate of melanocytes. The sensitivity of both MART-1 and SOX10 was 100% while their specificities were 17% and 96%, respectively. These results show SOX10 is more specific than MART-1 in distinguishing epidermal melanocytes on sun-damaged skin by avoiding over diagnosis of melanoma.

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Periodontal Treatment in Cancer Patients: an Interdisciplinary Approach

Abstract

Purpose of Review

Dental care is an essential component in the comprehensive treatment for a cancer patient. As such, a review of the literature was completed to determine the relationships between periodontal and dental care in the cancer patient and provide strategic suggestions.

Recent Findings

Periodontal treatment must be personalized depending on the patient's current oral health status, systemic status, and progress in treatment. Oral mucositis, periodontal status, and osteonecrosis of the jaw (ONJ) remain periodontal concerns in providing dental care to the cancer patient. Risk factors for development of ONJ include root amputation (OR = 6.64), extraction of a single tooth (OR = 3.7), severe tooth mobility (OR = 3.60), and unclosed wound (OR = 2.51).

Summary

Preventive maintenance, oral hygiene instruction, use of fluoride and chlorhexidine are all important therapeutic strategies. If extractions are required in patients who have received bone-modifying drug infusions, flap management and primary wound closure are needed to reduce the risk of complications.

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Possible effect of SNAIL family transcriptional repressor 1 polymorphisms in non-syndromic cleft lip with or without cleft palate

Abstract

Objective

Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state.

Materials and methods

Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P. A total of 632 families from Italy and Asia participated to the study.

Results

Evidence of allelic association was found with polymorphisms of SNAI1; in particular, the rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds ratio = 0.69 (95% C.I. 0.54–0.89)]. However, the adjusted significance value corrected for all the performed tests was P = 0.051.

Conclusions

The findings emerging by the present study suggest for the first time an involvement of SNAI1 in the nsCL/P onset.

Clinical relevance

Interestingly, SNAI1 is known to promote epithelial to mesenchymal transition by repressing E-cadherin expression, but it needs an intact PRC2 to act this function. Alterations of this process could contribute to the complex etiology of nsCL/P.

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Wide expression and significance of alternative immune checkpoint molecules, B7x and HHLA2, in PD-L1 negative human lung cancers

Purpose: Immunotherapy targeting the PD-1/PD-L1 pathway has changed the treatment landscape of non-small-cell lung carcinoma (NSCLC). We demonstrated that HHLA2, a newly identified immune inhibitory molecule, was widely expressed in NSCLC. We now compared the expression and function of PD-L1 with alternative immune checkpoints, B7x and HHLA2. Experimental Design: Expression was examined in tissue microarrays consisting of 392 resected NSCLC tumors. Effects of PD-L1, B7x and HHLA2 on human T cell proliferation and cytokine production were investigated. Results: PD-L1 expression was identified in 25% and 31% of tumors in the discovery and validation cohorts, and was associated with higher stage and lymph node involvement. The multivariate analysis showed that stage, TIL status and lymph node involvement were independently associated with PD-L1 expression. B7x was expressed in 69% and 68%, while HHLA2 was positive in 61% and 64% of tumors in the two sets. The co-expression of PD-L1 with B7x or HHLA2 was infrequent, 6% and 3%. The majority (78%) of PD-L1 negative cases expressed B7x, HHLA2 or both. The triple positive group had more TIL infiltration than the triple negative group. B7x-Ig and HHLA2-Ig inhibited TCR-mediated proliferation of CD4 and CD8 T cells more robustly than PD-L1-Ig. All three significantly suppressed cytokine productions by T cells. Conclusion: The majority of PD-L1 negative lung cancers express alternative immune checkpoints. The roles of the B7x and HHLA2 pathway in mediating immune evasion in PD-L1 negative tumors deserves to be explored to provide the rationale for an effective immunotherapy strategy in these tumors.

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The strategy of PIKing a target: What is AKTually most effective?

Breast and gynecological cancers harboring PIK3CA mutations showed no significant responses to AZD5363, a pan-AKT catalytic inhibitor, in contrast with previous in vitro data showing activity of the drug in this subset of cancers. These results raise the question on how to select the most accurate predictive biomarkers of response.

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Immune biomarkers predictive for disease-free survival with adjuvant sunitinib in high-risk locoregional renal cell carcinoma: from randomized phase III S-TRAC study

Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma in the S-TRAC trial (ClinicalTrials.gov number, NCT00375674). A prospectively-designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of PD-L1, CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, Receiver Operating Characteristics curves were generated. Results: Baseline characteristics were similar in patients with (n=191) and without (n=419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8+ T-cell density ≥ versus < median (median [95% CI], not reached [6.83-not reached] vs. 3.47 years [1.73-not reached]; hazard ratio 0.40 [95% CI, 0.20-0.81]; P=0.009) treated with sunitinib (n=101), but not with placebo (n=90). The sensitivity and specificity for CD8+ T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1+ versus PD-L1- tumors (hazard ratio 1.75; P=0.103). Among all patients with PD-L1+ tumors, DFS was numerically longer with sunitinib versus placebo (hazard ratio 0.58; P=0.175). Conclusions: Greater CD8+ T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk non-metastatic renal cell carcinoma should also be further explored.

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Small Cell Neuroendocrine Tumors: Cell State Trumps the Oncogenic Driver.

Small cell neuroendocrine cancers often originate in the lung, but can also arise in the bladder or prostate. Phenotypically, small cell carcinoma of the bladder (SCCB) shares many similarities with small cell lung cancer (SCLC). It is unknown whether SCCB and SCLC share common genetic driver mutations.

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Circulating tumor cells with stem-like phenotypes for diagnosis, prognosis and therapeutic response evaluation in hepatocellular carcinoma

Purpose: In present study, we assessed the clinical value of circulating tumor cells (CTCs) with stem-like phenotypes for diagnosis, prognosis and surveillance in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by an optimized QPCR-based detection platform. Experimental Design:Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter-patient study with independent validation (total n=1006), including healthy individuals, patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL) and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of CTC panel in treatment response surveillance and its prognostic significance were further investigated. Results: The AUC of CTC panel was 0.88 in training set [sensitivity=72·5%, specificity=95.0%, positive predictive value (PPV) =92.4, negative predictive value (NPV)=77.8] and 0.93 in validation set (sensitivity=82·1%; specificity=94.2%, PPV=89.9, NPV=89.3). This panel performed equally well in detecting early-stage and α-fetoprotein (AFP)-negative HCC, as well as differentiating HCC from CHB, LC and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of CTC panel in predicting tumor recurrence was further confirmed (training: HR=2.692, 95% CI, 1.617-4.483, P<0.001; validation: HR=3.127, 95% CI, 1.360-7.190, P=0.007). Conclusions: Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies.

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RNF6 promotes colorectal cancer by activating the Wnt/{beta}-catenin pathway via ubiquitination of TLE3

Gene amplification is a hallmark of cancer and is frequently observed in colorectal cancer (CRC). Previous whole-genome sequencing of CRC clinical specimens identified amplification of Ring finger protein 6 (RNF6), a RING-domain E3 ubiquitin ligase. In this study, we show that RNF6 is upregulated in 73.5% (147/200) of CRC patients, and was positively associated with RNF6 gene amplification. Further, RNF6 expression and its gene amplification were independent prognostic factors for poor outcome of CRC patients. RNF6 promoted cell growth, cell cycle progression, and epithelial-to-mesenchymal transition in CRC cells; RNF6 also promoted colorectal tumor growth and lung metastasis in mouse models. Mechanistic investigations revealed that RNF6 bound and ubiquitylated transducin-like enhancer of split 3 (TLE3), a transcriptional repressor of the β-catenin/TCF4 complex. RNF6-mediated degradation of TLE3 significantly suppressed the association of TLE3 with TCF4/LEF, which in turn led to recruitment of β-catenin to TCF4/LEF, triggering Wnt/β-catenin activation. Restoration of TLE3 expression abolished the oncogenic effects of RNF6. Taken together, these results demonstrate that RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis.

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MicroRNA-508 defines the stem-like/mesenchymal subtype in colorectal cancer

Colorectal cancer (CRC) includes an invasive stem-like/mesenchymal subtype but its genetic drivers, functional and clinical relevance are uncharacterized. Here we report the definition of an altered microRNA (miR) signature defining this subtype which includes a major genomic loss of miR-508. Mechanistic investigations showed that this microRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, BMI1 and BMI1. Loss of miR-508 in CRC was associated with upregulation of the novel hypoxia-induced long non-coding RNA AK000053. Ectopic expression of miR-508 in CRC cells blunted epithelial-mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro and in vivo. In clinical CRC specimens, expression of miRNA-508 negatively correlated with stemness and EMT-associated gene expression and inversely correlated with patient survival. Overall, our results showed that miRNA-508 is a key functional determinant of the stem-like/mesenchymal CRC subtype and a candidate therapeutic target for its treatment.

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Metformin-induced reduction of CD39 and CD73 blocks myeloid-derived suppressor cell activity in patients with ovarian cancer

Metformin is a broadlyprescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer (OC) by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α (AMPKα) and subsequently suppressed hypoxia-inducible factor-α (HIF-1α), which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with OC, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+MDSC and a concomitant increase in the antitumor activities of circulating CD8+T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in OC patients.

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Forkhead box F2 suppresses gastric cancer through a novel FOXF2-IRF2BPL-{beta}-catenin signaling axis

DNA methylation has been identified as a hallmark of gastric cancer (GC). Identifying genes that are repressed by DNA promoter methylation is essential in providing insights into the molecular pathogenesis of GC. Using genome-wide methylation studies we identified that transcription factor forkhead box F2 (FOXF2) was preferentially methylated in GC. We then investigated the functional significance and clinical implication of FOXF2 in GC. FOXF2 was silenced in GC cell lines and cancer tissues by promoter methylation, which was negatively associated with mRNA expression. Ectopic expression of FOXF2 inhibited proliferation, colony formation, G1-S cell cycle transition, induced apoptosis of GC cell lines and suppressed growth of xenograft tumors in nude mice; knockdown of FOXF2 elicited opposing effects. FOXF2 inhibited Wnt signaling by inducing β-catenin protein ubiquitination and degradation independently of GSK-3β. FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2 binding protein like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation. Multivariate Cox regression analysis identified FOXF2 hypermethylation as an independent prognostic factor of poor survival in early stage GC patients. In conclusion, FOXF2 is a critical tumor suppressor in gastric carcinogenesis whose methylation status serves as an independent prognostic factor for GC patients.

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An Efficient ELLAM Implementation for Modeling Solute Transport in Fractured Porous Media

Abstract

The goal of this study is to introduce an adaptation of the Eulerian-Lagrangian localized adjoint method (ELLAM) for the simulation of mass transport in fractured porous media, and to evaluate the performance of ELLAM in such a case. The fractures are represented explicitly using the discrete fracture model. The velocity field was calculated using the mixed hybrid finite element method. A sound ELLAM implementation is developed to address numerical artifacts (spurious oscillations and numerical dispersion) arising from the presence of fractures. The efficiency of the developed ELLAM implementation was further improved by taking advantage of the parallel computing on shared memory architecture for the tasks related to particles tracking and linear system resolving. The performance of ELLAM was tested by comparing its results with the Eulerian discontinuous Galerkin method based on several benchmark problems dealing with different fracture configurations. The results highlight the robustness and accuracy of ELLAM, as it allows the use of large time steps, and overcomes the Courant-Friedrichs-Lewy (CFL) restriction. The outcome also shows that ELLAM is more efficient when fracture density is increased.

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Dr. David Singh, D.Sc., PhD, DMD, Introduces You to Non-surgical Upper Airway Remodeling for OSA

Dr. Dave Singh

I will be presenting "Non-surgical Upper Airway Remodeling for OSA" at the Sleep and Wellness Conference 2018, hosted by the American Sleep and Breathing Academy (ASBA).  In that presentation, I will be covering the concept that while continuous positive airway pressure (CPAP) and surgical, bimaxillary advancement procedures are thought to represent curative options for OSA, mandibular advancement devices (MADs) are favored by dental professionals for the management of OSA, in conjunction with their medical sleep specialist colleagues.  But, the approach currently taken by most MADs is generally geared towards symptomatic relief with little attention being paid to the underlying etiology of the condition. While MADs are undoubtedly successful in the short- to mid-term in the clinical management of OSA, unwanted long-term side effects of MADs, such as disruption of the occlusion and temporo-mandibular joint pain, have been reported.

In contrast, I will present my studies showing that biomimetic oral appliance therapy can reduce the AHI to <5 in some adults diagnosed with mild to moderate OSA (AHI < 29), and sometimes virtually eliminate it completely.  In addition to exploring the efficacy of this exciting, new approach, I intend to conclude my presentation at the ASBA's Sleep and Wellness conference in Las Vegas with the notion that pediatric epigenetics embraces a firm promise in the prevention of sleep disordered breathing in young children.  I encourage you to register, bring your staff and finally, reach out to your colleagues.

Register at sleep-conference.com 

 

Dr. G. Dave Singh DDSc PhD DMD is a US citizen who was born, educated and trained in England, UK. He holds three doctorates, including a Degree in Dental Surgery; a Ph.D. in Craniofacial Development, and a D.D.Sc in Orthodontics. He was invited to relocate to the Center for Craniofacial Disorders, USA on the basis of being an "outstanding professor", where he led a NIH-funded program of craniofacial research. Currently, he is a member of: the American Sleep and Breathing Association; the World Sleep Federation; an Academic Fellow of the World Federation of Orthodontists, and Fellow of the International Association for Orthodontics, where he was awarded prizes in 2005, 2013 and 2014. Dr Singh holds several patents in the USA, Canada and Europe as well as international patents. He has published numerous articles and books in the peer-reviewed medical, dental and orthodontic literature, and has lectured in Australia, Asia, Europe, Africa and North America.

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Authors' Response to Critical Commentaries: Reliability and Validity of the DC/TMD Axis I.

Related Articles

Authors' Response to Critical Commentaries: Reliability and Validity of the DC/TMD Axis I.

J Oral Facial Pain Headache. 2018 Winter;32(1):27-28

Authors: Steenks MH, Türp JC, de Wijer A

Abstract
No abstract available.

PMID: 29370325 [PubMed - in process]

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Critical Commentary 3: Reliability and Validity of the DC/TMD Axis I.

Related Articles

Critical Commentary 3: Reliability and Validity of the DC/TMD Axis I.

J Oral Facial Pain Headache. 2018 Winter;32(1):25-26

Authors: Svensson P, Bendixen K

Abstract
No abstract available.

PMID: 29370324 [PubMed - in process]

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Critical Commentary 2: Reliability and Validity of the DC/TMD Axis I.

Related Articles

Critical Commentary 2: Reliability and Validity of the DC/TMD Axis I.

J Oral Facial Pain Headache. 2018 Winter;32(1):22-24

Authors: Schiffman E, Ohrbach R

Abstract
No abstract available.

PMID: 29370323 [PubMed - in process]

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Critical Commentary 1: Reliability and Validity of the DC/TMD Axis I.

Related Articles

Critical Commentary 1: Reliability and Validity of the DC/TMD Axis I.

J Oral Facial Pain Headache. 2018 Winter;32(1):19-21

Authors: Okeson JP

Abstract
No abstract available.

PMID: 29370322 [PubMed - in process]

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Reliability and Validity of the Diagnostic Criteria for Temporomandibular Disorders Axis I in Clinical and Research Settings: A Critical Appraisal.

Related Articles

Reliability and Validity of the Diagnostic Criteria for Temporomandibular Disorders Axis I in Clinical and Research Settings: A Critical Appraisal.

J Oral Facial Pain Headache. 2018 Winter;32(1):7-18

Authors: Steenks MH, Türp JC, de Wijer A

Abstract
The recently published Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I, which is recommended for use in clinical and research settings, has provided an update of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The authors of the DC/TMD based their publication on the results of a Validation Project (2001-2008) and consecutive workgroup sessions held between 2008 and 2013. The DC/TMD represents a major change in both content and procedures; nonetheless, earlier concerns and new insights have only partly been followed up when drafting the new recommendations. Moreover, the emphasis on immediate implementation in clinical and research settings is not in line with the provided external evidence on which the DC/TMD is based. This Focus Article describes these concerns with regard to several aspects of the DC/TMD: the additional classification categories; the high dependency on pressure-pain results from use of the recommended palpation technique; the TMD pain screening instrument; the test population characteristics; the utility of additional subgroups; the use of a reference standard; the dichotomy between pain and dysfunction; and the DC/TMD algorithms. Thus, although the DC/TMD represents an improvement over the RDC/TMD, its immediate implementation in research and clinical care does not yet appear to be adequately substantiated.

PMID: 29370321 [PubMed - in process]

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Tranexamic acid as a local hemostasis method after dental extraction in patients on warfarin: a randomized controlled clinical study

Abstract

Objectives

The present work is a controlled, blinded, and randomized clinical trial comparing hemostatic measures for the control of post-tooth extraction hemorrhage in patients on anticoagulation therapy with warfarin.

Materials and methods

The sample consisted of 37 patients (37.8% male and 62.2% female) with a mean age of 45.5 years. After randomization, 20 patients were allocated to the control group (conventional hemostasis measures) and 17 to the study group (addition of local tranexamic acid). All variables that could influence the outcome were similar between the groups and no significant difference was seen (p > 0.05).

Results

In the assessment of immediate hemostasis, for the control group, the time to achieve cessation of bleeding was 9.1 (± 3.6) minutes. For the study group this was much lower, and this difference (6.018 / confidence interval of 95%, 4.677 to 7.359) was statistically significant (p < 0.001). In evaluating the control of intermediate hemorrhage, the use of tranexamic acid was more significantly associated with the absence of bleeding, especially in the first 24 h.

Conclusions and clinical relevance

Thus, this measure of local hemostasis in topical form with gauze compression and irrigation was shown to be more effective in reducing the time to attain immediate hemostasis, and in preventing intermediate hemorrhage.

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Tranexamic acid as a local hemostasis method after dental extraction in patients on warfarin: a randomized controlled clinical study

Abstract

Objectives

The present work is a controlled, blinded, and randomized clinical trial comparing hemostatic measures for the control of post-tooth extraction hemorrhage in patients on anticoagulation therapy with warfarin.

Materials and methods

The sample consisted of 37 patients (37.8% male and 62.2% female) with a mean age of 45.5 years. After randomization, 20 patients were allocated to the control group (conventional hemostasis measures) and 17 to the study group (addition of local tranexamic acid). All variables that could influence the outcome were similar between the groups and no significant difference was seen (p > 0.05).

Results

In the assessment of immediate hemostasis, for the control group, the time to achieve cessation of bleeding was 9.1 (± 3.6) minutes. For the study group this was much lower, and this difference (6.018 / confidence interval of 95%, 4.677 to 7.359) was statistically significant (p < 0.001). In evaluating the control of intermediate hemorrhage, the use of tranexamic acid was more significantly associated with the absence of bleeding, especially in the first 24 h.

Conclusions and clinical relevance

Thus, this measure of local hemostasis in topical form with gauze compression and irrigation was shown to be more effective in reducing the time to attain immediate hemostasis, and in preventing intermediate hemorrhage.

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Whole blood viscosity and cerebral blood flow velocities in obese hypertensive or obese normotensive adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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The utility of body mass index as an indicator for lipid abnormalities in non-fasted children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Hypercalcemia, hyperkalemia and supraventricular tachycardia in a patient with subcutaneous fat necrosis

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Brain gray matter volume differences in obese youth with type 2 diabetes: a pilot study

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Cancers, Vol. 10, Pages 33: The Ever-Evolving Concept of the Cancer Stem Cell in Pancreatic Cancer

Cancers, Vol. 10, Pages 33: The Ever-Evolving Concept of the Cancer Stem Cell in Pancreatic Cancer

Cancers doi: 10.3390/cancers10020033

Authors: Sandra Valle Laura Martin-Hijano Sonia Alcalá Marta Alonso-Nocelo Bruno Sainz Jr.

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is the 4th most frequent cause of cancer-related death worldwide, primarily due to the inherent chemoresistant nature and metastatic capacity of this tumor. The latter is believed to be mainly due to the existence of a subpopulation of highly plastic "stem"-like cells within the tumor, known as cancer stem cells (CSCs), which have been shown to have unique metabolic, autophagic, invasive, and chemoresistance properties that allow them to continuously self-renew and escape chemo-therapeutic elimination. As such, current treatments for the majority of PDAC patients are not effective and do not significantly impact overall patient survival (&lt;7 months) as they do not affect the pancreatic CSC (PaCSC) population. In this context, it is important to highlight the need to better understand the characteristics of the PaCSC population in order to develop new therapies to target these cells. In this review, we will provide the latest updates and knowledge on the inherent characteristics of PaCSCs, particularly their unique biological properties including chemoresistance, epithelial to mesenchymal transition, plasticity, metabolism and autophagy.

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Computed tomography and magnetic resonance imaging evaluation of pelvic lymph node metastasis in bladder cancer

Accurate evaluation of lymph node metastasis in bladder cancer (BCa) is important for disease staging, treatment selection, and prognosis prediction. In this study, we aimed to evaluate the diagnostic accuracy...

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Nodes and paranodes; alternative treatments in MS

People with multiple sclerosis (MS) use complementary and alternative treatments (CAM), but what does the evidence say? Patient's Choice, Professor Bruce Taylor (University of Tasmania) discusses the modern evidence for CAM use. Read the paper here: http://ift.tt/2DSezBC. What roles do nodes and paranodes play in complex neuropathies? Dr Simon Rinaldi (University of Oxford) summarises the involvement of these specialised domains as this month's Editor's Choice. Read the full paper here: http://ift.tt/2FjF4gr.

Read the JNNP's January 2018 issue here: http://ift.tt/2DSmbV3.

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Commentary on: “Comparison of the Effect of Dexamethasone and Tranexamic Acid, Separately or in Combination on Post-rhinoplasty and Edema and Ecchymosis”

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InnerScope Launches PSAP Web Store

​InnerScope Hearing Technologies (http://www.innd.com/) now offers purchase options and hearing resources to personal sound amplifier products (PSAPs) consumers on its direct-to-consumer e-commerce site, Hearingbenefit.com. They can sign up to receive an e-book produced by InnerScope called The Senior Medical Controversy on Hearingbenefit.com to learn about the consequences of untreated hearing loss, including cognitive issues such as Alzheimer's and dementia. InnerScope has also created a separate landing page (http://www.howtohearbetter.com/) to assist consumers through the evaluation and decision phase of choosing a device. Matthew Moore, CEO of InnerScope, said once people click onto their e-commerce store, it is easy for them to navigate and make a decision to purchase. "We have taken the stress off the buying process, by offering easy payments with zero down and zero interest. We know that for years the tens of millions of hearing impaired people have been an underserved market… We offer these people through our Hearingbenefit.com website easy and simple access to hearing products that can help improve their hearing immediately without hurting their pocketbook, and even a money back guarantee," Moore said.

Published: 1/26/2018 7:36:00 AM

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Commentary on: “Comparison of the Effect of Dexamethasone and Tranexamic Acid, Separately or in Combination on Post-rhinoplasty and Edema and Ecchymosis”

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A Narrative Evaluation of Mandarin-Speaking Children With Language Impairment

Purpose

We aimed to study narrative skills in Mandarin-speaking children with language impairment (LI) to compare with children with LI speaking Indo-European languages.

Method

Eighteen Mandarin-speaking children with LI (mean age 6;2 [years;months]) and 18 typically developing (TD) age controls told 3 stories elicited using the Mandarin Expressive Narrative Test (de Villiers & Liu, 2014). We compared macrostructure-evaluating descriptions of characters, settings, initiating events, internal responses,plans, actions, and consequences. We also studied general microstructure, including productivity, lexical diversity, syntactic complexity, and grammaticality. In addition, we compared the use of 6 fine-grained microstructure elements that evaluate particular Mandarin linguistic features.

Results

Children with LI exhibited weaknesses in 5 macrostructure elements, lexical diversity, syntactic complexity, and 3 Mandarin-specific, fine-grained microstructure elements. Children with LI and TD controls demonstrated comparable performance on 2 macrostructure elements, productivity, grammaticality, and the remaining 3 fine-grained microstructure features.

Conclusions

Similarities and differences are noted in narrative profiles of children with LI who speak Mandarin versus those who speak Indo-European languages. The results are consistent with the view that profiles of linguistic deficits are shaped by the ambient language. Clinical implications are discussed.

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Well-Being and Resilience in Children With Speech and Language Disorders

Purpose

Children with speech and language disorders are at risk in relation to psychological and social well-being. The aim of this study was to understand the experiences of these children from their own perspectives focusing on risks to their well-being and protective indicators that may promote resilience.

Method

Eleven 9- to 12-year-old children (4 boys and 7 girls) were recruited using purposeful sampling. One participant presented with a speech sound disorder, 1 presented with both a speech and language disorder, and 9 with language disorders. All were receiving additional educational supports. Narrative inquiry, a qualitative design, was employed. Data were generated in home and school settings using multiple semi-structured interviews with each child over a 6-month period. A total of 59 interviews were conducted. The data were analyzed to identify themes in relation to potential risk factors to well-being and protective strategies.

Results

Potential risk factors in relation to well-being were communication impairment and disability, difficulties with relationships, and concern about academic achievement. Potential protective strategies were hope, agency, and positive relationships.

Conclusion

This study highlights the importance of listening to children's narratives so that those at risk in relation to well-being can be identified. Conceptualization of well-being and resilience within an ecological framework may enable identification of protective strategies at both individual and environmental levels that can be strengthened to mitigate negative experiences.

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Future Surgeon Workforce: Sufficient to Treat Cancer Patients?

Will our surgical workforce in 2035 be sufficient to care for the anticipated number of patients with cancer? Dr Lowenfels comments on a recent study published in Surgery.
Medscape General Surgery

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Pressure pain thresholds over the cranio-cervical region in headache: a systematic review and meta-analysis

Sensitivity of tissues can be measured by algometry. Decreased pressure pain thresholds over the cranio-cervical area are supposed to reflect signs of sensitization of the trigemino-cervical nucleus caudalis. ...

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A novel glycocluster molecule prevents timothy induced allergic airway inflammation in mice

Abstract

Background

Allergen specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th) 2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytocine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipid A (MPLA) in a grass allergen induced chronic allergic inflammation model in mice.

Methods

Female BALB/c mice were intranasally sensitized with 50 μl of timothy grass pollen extract (TE) twice a week for a period of 15 weeks. Therapeutic intranasal treatments were then performed once a week after the tenth intranasal TE instillation using TADM (10 or 25μg/50 μl), CpG-ODN (20μg/50 μl) or MPLA (2μg/50μl). Groups of 9-10 animals per treatment were sacrificed 24 h after the last timothy dosage. Blood, bronchoalveolar lavage (BAL) fluids and lung biopsies were taken for subsequent analysis.

Results

When mice were repeatedly exposed to TE for 15 weeks, the number of eosinophils and lymphocytes increased in the BAL fluids. The eosinophil and lymphocyte counts decreased dose-dependently, and were practically abolished in the mice treated with TADM. Treatments with MPLA or CpG significantly increased the numbers of neutrophils, while CpG nonsignificantly decreased eosinophilia compared to timothy exposure.

Conclusions

A novel synthetic glycocluster molecule inhibited the development of grass induced eosinophilic pulmonary inflammation in mice when administrated in the airways. This compound could be a candidate to be used either as an adjuvant in SIT or as a topical anti-inflammatory treatment.

This article is protected by copyright. All rights reserved.

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Sequential decitabine and carboplatin treatment increases the DNA repair protein XPC, increases apoptosis and decreases proliferation in melanoma

Abstract

Background

Melanoma has two key features, an over-representation of UV-induced mutations and resistance to DNA damaging chemotherapy agents. Both of these features may result from dysfunction of the nucleotide excision repair pathway, in particular the DNA damage detection branch, global genome repair (GGR). The key GGR component XPC does not respond to DNA damage in melanoma, the cause of this lack of response has not been investigated. In this study, we investigated the role of methylation in reduced XPC in melanoma.

Methods

To reduce methylation and induce DNA-damage, melanoma cell lines were treated with decitabine and carboplatin, individually and sequentially. Global DNA methylation levels, XPC mRNA and protein expression and methylation of the XPC promoter were examined. Apoptosis, cell proliferation and senescence were also quantified. XPC siRNA was used to determine that the responses seen were reliant on XPC induction.

Results

Treatment with high-dose decitabine resulted in global demethylation, including the the shores of the XPC CpG island and significantly increased XPC mRNA expression. Lower, clinically relevant dose of decitabine also resulted in global demethylation including the CpG island shores and induced XPC in 50% of cell lines. Decitabine followed by DNA-damaging carboplatin treatment led to significantly higher XPC expression in 75% of melanoma cell lines tested. Combined sequential treatment also resulted in a greater apoptotic response in 75% of cell lines compared to carboplatin alone, and significantly slowed cell proliferation, with some melanoma cell lines going into senescence. Inhibiting the increased XPC using siRNA had a small but significant negative effect, indicating that XPC plays a partial role in the response to sequential decitabine and carboplatin.

Conclusions

Demethylation using decitabine increased XPC and apoptosis after sequential carboplatin. These results confirm that sequential decitabine and carboplatin requires further investigation as a combination treatment for melanoma.

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Is ERAS effective and safe in laparoscopic gastrectomy for gastric carcinoma? A meta-analysis

Abstract

Background

It is still unclear whether enhanced recovery after surgery is effective and safe in laparoscopic gastrectomy for gastric carcinoma.

Methods

Cochrane library databases, Medline, Embase, and Pubmed were searched from January 1, 1986, to December 31, 2016. Randomized controlled trials (RCTs) comparing fast-track recovery with conventional recovery strategies in laparoscopic radical gastrectomy for gastric carcinoma were included. The main outcomes measured were postoperative hospital stay, time to first flatus, hospital charge, and overall complication rate.

Results

Six RCTs with 400 patients were included in this study. Fast-track surgery has shorter postoperative hospital stays (weighted mean difference (WMD) − 2.65; 95% CI, − 4.01 to − 1.29, z = 3.82, P < 0.01) and less hospitalization expenditure (WMD − 523.43; 95% CI, − 799.79 to − 247.06, z = 3.71, P < 0.01) than conventional recovery strategies. There was no significant difference with respect to duration to first flatus (WMD − 17.72; 95% CI, − 39.46–4.02, z = 1.60, P = 0.11) and complication rate (OR 1.57; 95% CI, 0.82–2.98, z = 1.37, P = 0.17).

Conclusions

Enhanced recovery after surgery is effective and safe and is thus recommended in laparoscopic radical gastrectomy for gastric carcinoma.

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Renal sympathetic nerve activity after catheter-based renal denervation

Abstract

Background

Catheter-based renal sympathetic denervation (RDN) has been considered a potential treatment for therapy resistant hypertension (RHT). However, in a randomized placebo-controlled trial, RDN did not lead to a substantial blood pressure (BP) reduction. We hypothesized that variation in the reported RDN efficacy might be explained by incomplete nerve disruption as assessed by renal ¹²³I–meta-iodobenzylguanidine (¹²³I–mIBG) scintigraphy.

Methods

In 21 RHT patients (median age 60 years), we performed ¹²³I–mIBG scintigraphy before and 6 weeks after RDN. Additionally, we assessed changes in BP (24 h day, night, and average), plasma- and urinary-catecholamines and plasma renin activity (PRA) before and after RDN. Planar scintigraphy was performed at 15 min and 4 h after ¹²³I–mIBG administration. The ratio of the mean renal (specific) counts vs. muscle (non-specific) counts represented ¹²³I–mIBG uptake. Renal ¹²³I–mIBG washout was calculated between 15 min and 4 h.

Results

After RDN office-based systolic BP decreased from 172 to 153 mmHg (p = 0.036), while diastolic office BP (p = 0.531), mean 24 h systolic and diastolic BP (p = 0.602, p = 0.369, respectively), PRA (p = 0.409) and plasma catecholamines (p = 0.324) did not significantly change post-RDN. Following RDN, ¹²³I–mIBG renal uptake at 15 min was 3.47 (IQR 2.26–5.53) compared to 3.08 (IQR 2.79–4.95) before RDN (p = 0.289). Renal ¹²³I–mIBG washout did not change post-RDN (p = 0.230). In addition, there was no significant correlation between the number of denervations and the renal ¹²³I–mIBG parameters.

Conclusions

No changes were observed in renal ¹²³I–mIBG uptake or washout at 6 weeks post-RDN. These observations support incomplete renal denervation as a possible explanation for the lack of RDN efficacy.

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Factors Affecting the Result of Intralesional Corticosteroid Injection in Patients With Oral Lichen Planus.

Related Articles

Factors Affecting the Result of Intralesional Corticosteroid Injection in Patients With Oral Lichen Planus.

Clin Exp Otorhinolaryngol. 2018 Jan 26;:

Authors: Lee YC, Lee JS, Jung AR, Park JM, Eun YG

Abstract
Objectives: To examine the factors which affect the improvement or the recurrence of disease after intralesional steroid injection in patients with oral lichen planus (OLP).
Methods: Sixty-two patients diagnosed as OLP were treated with intralesion corticosteroid injection. To evaluate the objective severity of OLP, total severity score of OLP was assessed. To examine the factors affecting the therapeutic effect of intralesional steroid injection, factors were compared between the symptom-improved group and symptom-not-improved group. To assess the symptom of patients, patients filled in 10-cm visual analogue scale, along with an Oral Health Impact Profile-14.
Results: Symptoms improved in 50 patients (80.6%, symptom-improved group), but not in 12 patients (symptom-not-improved group). In a comparison between both group, OLP with lip involvement was the only variable which showed significant difference (P=0.008). Twenty-nine of 50 patients had recurrence of OLP (58%, recurrence group) and 21 of 50 patients did not have recurrence (42%, no-recurrence group). Statistically significant differences were not found between both groups.
Conclusion: This study suggested that patients suffering from OLP with lesion on the lip might not be effective in treating with intralesional corticosteroid injection.

PMID: 29366304 [PubMed - as supplied by publisher]

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A comparison of symptoms and quality of life before and after nasal septoplasty and radiofrequency therapy of the inferior turbinate

Abstract

Background

The primary goal of this study is to compare pre- and postoperative symptoms and health related quality of life (HQOL) in 57 patients who underwent septoplasty (group-1), 56 patients who underwent septoplasty combined with radiofrequency therapy of inferior turbinates (RFIT) (group-2) and 58 patients who underwent RFIT alone (group-3). The secondary goal is to investigate if the change in symptoms and HQOL differed between these three patient groups after surgery.

Methods

All patients reported symptoms on a visual analogue scale (VAS) and HQOL on Sino-Nasal-Outcome-Test-20 (SNOT-20) and Short-Form-Health-Survey-36 (SF-36) before and 6 months after surgery. The pre- and postoperative scores and improvement were compared within and between the three patient groups.

Results

Preoperatively the three patient groups had a fairly similar symptom burden and HQOL, except for group-1 which reported more symptoms of oral breathing than group-3 (p < 0.01) and group-3 which reported more problems in the ear/facial--subset of SNOT-20 and in the general-mental-health-domain of SF-36 than group-1 (p < 0.01).

Postoperatively all patient groups reported improved symptom scores of nasal obstruction, nasal discharge, snoring, oral breathing and reduced general health (p < 0.01), and better HQOL (p < 0.05). Patients in group-2 had less symptoms of nasal obstruction than group-3 (p < 0.05). Postoperative symptom score for nasal obstruction was 29.1 (SD67.6) in group-1, 27.5 (SD22.5) in group-2 and 37.2 (SD24.8) in group-3. Revision cases reported more nasal obstruction postoperatively; 41.3 (SD27) than non revision cases; 28.6 (SD24) (p < 0.01).

The HQOL after surgery was about the same in all three patient groups, but we found that patients with comorbidities as sleep apnea and asthma reported worse HQOL than other patients (p < 0.01).

Conclusion

Surgical treatment of nasal obstruction led to less symptoms and better HQOL for all three patient groups. Comparing the postoperative scores between the patient groups we find that all groups reached the same level of HQOL. Regarding symptoms, the patients who underwent septoplasty combined with RFIT reported postoperatively less nasal obstruction than patients who underwent RFIT alone which may indicate that a combined procedure of septoplasty and RFIT is better than RFIT alone to treat nasal obstruction. Furthermore, revision cases, patients with sleep apnea and asthma patients seem to have poorer outcome after surgery than other patients. Both disease specific and general QOL instruments add valuable information for identifying factors influencing outcome.

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Study Identifies Potential Cause of Hearing Loss from Cisplatin

A new study has found the commonly used chemotherapy drug cisplatin is retained in the inner ear of mice and humans for long periods. The finding may explain why many patients treated with the drug develop hearing loss and could point toward potential ways to prevent it.

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Forestier syndrome and obstructive sleep apnea: Surgical treatment.

Related Articles

Forestier syndrome and obstructive sleep apnea: Surgical treatment.

Eur Ann Otorhinolaryngol Head Neck Dis. 2018 Jan 20;:

Authors: Ribeiro DK, Pinto JA, Freitas GS

Abstract
INTRODUCTION: We report a case of obstructive sleep apnea that occurred as a result of Forestier disease and describe the surgical treatment that was performed.
SUMMARY: The patient is a 56-year-old man who presented dysphagia for solids and liquids, snoring (score 10) and excessive daytime sleepiness for 5 years. On fiber optic laryngoscopy examination, there was interarytenoid edema and protrusion of the posterior wall of the larynx. The cervical X-Ray showed protrusion of intervertebral disc between C3-C5 (skeletal hyperostosis) and the polysomnography revealed apnea-hypopnea index (AHI) of 56 events/h. Surgery was performed by the otorhinolaryngology and orthopedic teams. The patient evolved with complete symptom resolution and an AHI of 3,9 events/h on the control polysomnography.
DISCUSSIONS: This is the first reported case of Forestier Syndrome (FS) associated with Obstructive Sleep Apnea (OSA) that was proposed surgical treatment and the patient evolved with complete symptom improvement.

PMID: 29366867 [PubMed - as supplied by publisher]

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Development and validation of a standardized double-blind, placebo-controlled food challenge matrix for raw hazelnuts

Double-blind, placebo-controlled food challenge (DBPCFC) is considered the gold standard for food allergy diagnosis. However, this test is rarely performed routinely in clinical practice because of various pra...

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[Europe and Japan alliance for clinical research in oncology].

Related Articles

[Europe and Japan alliance for clinical research in oncology].

Bull Cancer. 2018 Jan 20;:

Authors: Evrard S

PMID: 29366499 [PubMed - as supplied by publisher]

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Forestier syndrome and obstructive sleep apnea: Surgical treatment.

Related Articles

Forestier syndrome and obstructive sleep apnea: Surgical treatment.

Eur Ann Otorhinolaryngol Head Neck Dis. 2018 Jan 20;:

Authors: Ribeiro DK, Pinto JA, Freitas GS

Abstract
INTRODUCTION: We report a case of obstructive sleep apnea that occurred as a result of Forestier disease and describe the surgical treatment that was performed.
SUMMARY: The patient is a 56-year-old man who presented dysphagia for solids and liquids, snoring (score 10) and excessive daytime sleepiness for 5 years. On fiber optic laryngoscopy examination, there was interarytenoid edema and protrusion of the posterior wall of the larynx. The cervical X-Ray showed protrusion of intervertebral disc between C3-C5 (skeletal hyperostosis) and the polysomnography revealed apnea-hypopnea index (AHI) of 56 events/h. Surgery was performed by the otorhinolaryngology and orthopedic teams. The patient evolved with complete symptom resolution and an AHI of 3,9 events/h on the control polysomnography.
DISCUSSIONS: This is the first reported case of Forestier Syndrome (FS) associated with Obstructive Sleep Apnea (OSA) that was proposed surgical treatment and the patient evolved with complete symptom improvement.

PMID: 29366867 [PubMed - as supplied by publisher]

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PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway.

Related Articles

PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway.

Cancer Biol Ther. 2018 Jan 25;:1-8

Authors: Ibrahim S, Li G, Hu F, Hou Z, Chen Q, Li G, Luo X, Hu J, Feng Y

Abstract
Phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) is overexpressed in different types of human cancer. We previously reported the important role of PIK3R3 in colorectal cancer (CRC). However, the prognosis effect of PIK3R3 in CRC is still remaining unclear. In this study, we explored online clinical databases to analyze the prognosis differences between higher and lower expression of PIK3R3 in CRC patients. Interestingly, we found that better disease-free survival (DFS) were occurred in patients with higher expression of PIK3R3, but there is no significant difference in overall survival (OS). For further, we showed that PIK3R3 could enhance 5-FU induced apoptosis by regulating the expression of thymmidine phosphorylase (TP). In conclusion, PIK3R3 could be considered as a predictor of 5-FU sensitivity for personalized treatment, and a therapeutic target for colorectal cancer.

PMID: 29370570 [PubMed - as supplied by publisher]

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Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

Related Articles

Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

Cancer Biol Ther. 2018 Jan 25;:1-9

Authors: Liu J, Qu X, Shao L, Hu Y, Yu X, Lan P, Guo Q, Han Q, Zhang J, Zhang C

Abstract
Melanoma is the deadliest form of commonly encountered skin cancer, and has fast propagating and highly invasive characteristics. Pim-3, a highly expressed oncogene in melanoma, is a highly conserved serine/threonine kinase with various biological activities, such as proliferation-accelerating and anti-apoptosis effects on cancer progression. However, whether Pim-3 regulates melanoma metastasis has not been determined. Here, we constructed a Pim-3-silencing short hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma cell line to investigate the effects of Pim-3 on migration and invasion in melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3 inhibited metastasis by regulating the expression of genes related to epithelial-mesenchymal transition (EMT). Further study revealed that by promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related changes and induced melanoma migration and invasion. Our study suggests that Pim-3 is a potential effective target for melanoma therapy.

PMID: 29370558 [PubMed - as supplied by publisher]

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BTB/POZ domain-containing protein 7 is inversely associated with fibronectin expression in salivary adenoid cystic carcinoma.

Related Articles

BTB/POZ domain-containing protein 7 is inversely associated with fibronectin expression in salivary adenoid cystic carcinoma.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Dec 28;:

Authors: Liu Y, Song J, Zhang J, Yang L, Liu Z, Wang X

Abstract
OBJECTIVE: This study aimed to investigate the relationship between BTB/POZ domain-containing protein 7 (BTBD7) and fibronectin (FN) expression in salivary adenoid cystic carcinoma (SACC) and the function of BTBD7 in proliferation, migration, and invasion of SACC cells.
STUDY DESIGN: The BTBD7 and FN expression in SACC and nontumor salivary tissues as well as SACC cells were characterized by immunohistochemistry and immunofluorescence. The effect of BTBD7 silencing on the proliferation, migration, and invasion of SACC-LM cells were determined by wound healing and transwell invasion assays.
RESULTS: The percentages of SACC with positive BTBD7 expression were significantly higher than those of SACC with FN expression. BTBD7 silencing significantly increased the relative levels of FN expression and inhibited the proliferation, migration, and invasion of SACC-LM cells.
CONCLUSIONS: The study data indicated that BTBD7 was inversely associated with FN expression in SACC. BTBD7 may inhibit FN expression, but it promotes the proliferation, migration, and invasion of SACC-LM cells. Hence, BTBD7 may be associated with metastasis and a new therapeutic target for intervention of SACC.

PMID: 29366608 [PubMed - as supplied by publisher]

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Surgical treatment of enterovirus D68 brainstem encephalitis-induced dysphagia.

Related Articles

Surgical treatment of enterovirus D68 brainstem encephalitis-induced dysphagia.

Auris Nasus Larynx. 2018 Jan 20;:

Authors: Togashi T, Baba H, Kitazawa M, Takahashi N, Samejima Y, Yumoto E, Horii A

Abstract
Cluster of acute flaccid paralysis and cranial nerve dysfunction was associated with a 2014 outbreak of enterovirus D68 (EV-D68) respiratory illness in US. We describe a 33 year-old male patient of refractory dysphagia due to EV-D68-induced brainstem encephalitis successfully treated by surgery. Following acute upper respiratory tract infection, he developed dysphagia and bilateral facial paralysis. A coughing reflex was readily produced when the laryngopharyngeal fiberscope touched the epiglottis, however, water infusion induced only very weak and slow swallowing reflex, suggesting that only motor component was impaired but sensory function was preserved during swallowing. Despite eight months-conservative rehabilitations, Food Intake Level Scale (FILS) remained level 4. Therefore, corrective surgeries including cricopharyngeal myotomy, laryngeal suspension, and pharyngeal flap were performed. Thirty-six days after surgery, FILS rapidly and dramatically improved to level 8. This is the first report describing a successful surgical intervention for EV-D68-induced refractory dysphagia. Surgical treatment was suitable for EV-D68-induced dysphagia, perhaps because sensory function was preserved and only motor disturbance was present during the pharyngeal stage of swallowing.

PMID: 29366609 [PubMed - as supplied by publisher]

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Presbiphonya.

Related Articles

Presbiphonya.

Acta Biomed. 2017 Apr 28;88(1):6-10

Authors: Bruzzi C, Salsi D, Minghetti D, Negri M, Casolino D, Sessa M

Abstract
AIM: This article attempts to describe the aging process of the vocal folds and the main features of the aged voice.
BACKGROUND: In the world ageing population era, aging diseases and aging disorders are crucial. Voice disorders (presbyphonia) are common in the elderly and have a significant impact on communication and quality of life. Some of these disorders depend on the vocal folds, which consist of an extracellular matrix (ECM), fibrous proteins, interstitial proteins, and glycosaminoglycans. The density and spatial arrangement of these elements are important, as changes in their deposition can alter the biomechanical properties and vibratory function of the vocal folds.
DISCUSSION: The aging voice process is analyzed in detail from mechanical factors like pulmonary bellows alteration, to hormonal factors and life style.
CONCLUSIONS: The elderly people undergoe mechanical, anatomical and functional changes: alterations of the pulmonary bellows, systemic changes like hormonal disregulation, and laryngeal changes, that resulting in hoarseness, which is difficult to treat.

PMID: 28467327 [PubMed - indexed for MEDLINE]

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Minimally Invasive Surgical Approach to Filum Lipoma.

Related Articles

Minimally Invasive Surgical Approach to Filum Lipoma.

Neurol Med Chir (Tokyo). 2018 Jan 23;:

Authors: Hayashi T, Kimiwada T, Kohama M, Shirane R, Tominaga T

Abstract
Filum terminale lipoma (FTL) causes various spinal symptoms known as tethered cord syndrome. The treatment for FTL is surgical untethering by sectioning the FTL, which can prevent symptom progression and often results in improvement of symptoms. This report describes a minimally invasive surgical strategy that we have introduced for FTL sectioning. The pediatric patients with FTL since 2007 were treated using this minimally invasive surgical strategy, which we refer to as an interlaminar approach (ILA). In summary, the surgical technique involves: minimal skin incision to expose the unilateral ligamentum flavum in the lower lumbar region; ligamentum flavum incision to expose the dural sac, and dural incision followed by identification and sectioning of the filum. Postoperatively, no bed rest was required. Prior to introducing ILA, we had used standard one level laminectomy/laminotomy (LL) with more than 1 week of postsurgical bed rest until 2007, providing an adequate control group for the benefit of the ILA. A total of 49 consecutive patients were treated using ILA. While 37 patients were treated using LL. Surgical complications that need surgery were seen only in one patient, who developed cerebrospinal fluid (CSF) leak in LL patients. No retethering or additional neurological symptoms were seen during follow-up. All patients complained of minimal postsurgical back pain, but no patients required postoperative bed rest in ILA patients, while LL patients need postsurgical bed rest because of back pain. The ILA strategy provides the advantage of a minimal tissue injury, associated with minimal postoperative pain, blood loss, and bed rest.

PMID: 29367470 [PubMed - as supplied by publisher]

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Functional Outcomes after Behavioral Treatment of Paradoxical Vocal Fold Motion in Adults

Objective: Paradoxical vocal fold motion (PVFM) is responsive to behavioral therapy, often resulting in a remission of symptoms, but little is known about whether treatment is beneficial with regard to PVFM-associated psychological symptoms or functional limitations. The goal of the study was to identify patient perceptions of the impact of treatment for PVFM and characteristics associated with treatment outcomes. Methods: A survey was conducted of all adults who had received at least 1 session of treatment for PVFM in our outpatient clinic over a 2-year period. Results: The 39 participants ranged in age from 18 to 82 and had received a median of 3 treatment sessions. At a median follow-up of 10 months following treatment, respondents reported improvements in a wide range of areas, including sports and leisure, daily activities, and social participation. The majority reported improvements in feelings of anxiety, helplessness, and control. Poorer outcomes were associated with more severe voice symptoms, fewer treatment sessions, and needing oral steroids for asthma control. Conclusion: There was a reduction in a wide range of activity limitations after treatment. Feelings of control were strongly associated with positive outcomes. The therapy appeared to be equally effective for adults with exercise-induced and environmental variants of PVFM.
Folia Phoniatr Logop 2017;69:154–168

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Being Mindful of Mindfulness Interventions in Cancer: a systematic review of intervention reporting and study methodology

Abstract

While mindfulness–based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) have demonstrated efficacy in clinical populations, the potential therapeutic benefit of mindfulness in the context of cancer is less clear. The aim of this review was to critically appraise mindfulness intervention reporting and study methodology.

Methods

Studies using randomized control trial design and/or a control arm were included. PubMed, Medline, PsycINFO, CINAHL and Embase databases between January 1999 and April 2017 were searched. Studies were assessed on (1) reported theoretical framework, (2) intervention description, and (3) justification of modifications to standardised MBSR/MBCT. The overall quality of study design and research methodology were also assessed.

Results

Of 30 studies identified, none adhered to MBSR. Modified versions of MBSR were reported in 19 studies. Five studies reported variants of MBCT, one used a combination of MBSR/MBCT, and five inadequately documented the intervention/ theoretical framework. Overall, component and timeline modifications were poorly documented and justified. Mean intervention contact time was less than standardized MBSR/MBCT protocols. Target outcomes were poorly justified and 12 studies failed to identify a primary aim, reporting multiple outcomes. Only nine of 15 studies recruiting clinical populations included clinical cutoffs and an active therapeutic control was included in four studies.

Conclusions

Mindfulness is increasingly considered a standard therapy in psycho-oncology. While many studies proclaim benefits, there is considerable variability, modification to standardized protocols, and claims of benefit often reflect decreases in sub-clinical supportive care symptomology rather than therapeutic relief of clinically significant psychological disorders.

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The argument for POEM in treatment of achalasia.

Related Articles

The argument for POEM in treatment of achalasia.

Minerva Chir. 2018 Jan 23;:

Authors: Bowers SP, Woodward T

Abstract
Although there has been debate regarding the optimal procedure to palliate dysphagia in patients with achalasia, emerging reports of longer term follow-up of patients after peroral endoscopic myotomy (POEM) suggest that the POEM procedure is efficacious in relief of dysphagia, and that there is infrequent need for subsequent procedures for treatment of failure or reflux. The number of centers in the United States of America performing POEM for esophageal achalasia continues to increase. This report assess the current knowledge of technical issues of POEM, outcomes after POEM and the status of POEM centers in the U.S.A., and presents the argument for surgeons to participate in the practice of POEM.

PMID: 29366317 [PubMed - as supplied by publisher]

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PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway.

PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway.

Cancer Biol Ther. 2018 Jan 25;:1-8

Authors: Ibrahim S, Li G, Hu F, Hou Z, Chen Q, Li G, Luo X, Hu J, Feng Y

Abstract
Phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) is overexpressed in different types of human cancer. We previously reported the important role of PIK3R3 in colorectal cancer (CRC). However, the prognosis effect of PIK3R3 in CRC is still remaining unclear. In this study, we explored online clinical databases to analyze the prognosis differences between higher and lower expression of PIK3R3 in CRC patients. Interestingly, we found that better disease-free survival (DFS) were occurred in patients with higher expression of PIK3R3, but there is no significant difference in overall survival (OS). For further, we showed that PIK3R3 could enhance 5-FU induced apoptosis by regulating the expression of thymmidine phosphorylase (TP). In conclusion, PIK3R3 could be considered as a predictor of 5-FU sensitivity for personalized treatment, and a therapeutic target for colorectal cancer.

PMID: 29370570 [PubMed - as supplied by publisher]

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Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

Cancer Biol Ther. 2018 Jan 25;:1-9

Authors: Liu J, Qu X, Shao L, Hu Y, Yu X, Lan P, Guo Q, Han Q, Zhang J, Zhang C

Abstract
Melanoma is the deadliest form of commonly encountered skin cancer, and has fast propagating and highly invasive characteristics. Pim-3, a highly expressed oncogene in melanoma, is a highly conserved serine/threonine kinase with various biological activities, such as proliferation-accelerating and anti-apoptosis effects on cancer progression. However, whether Pim-3 regulates melanoma metastasis has not been determined. Here, we constructed a Pim-3-silencing short hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma cell line to investigate the effects of Pim-3 on migration and invasion in melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3 inhibited metastasis by regulating the expression of genes related to epithelial-mesenchymal transition (EMT). Further study revealed that by promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related changes and induced melanoma migration and invasion. Our study suggests that Pim-3 is a potential effective target for melanoma therapy.

PMID: 29370558 [PubMed - as supplied by publisher]

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The biological treatment planning evolution of clinical fractionated radiotherapy using high LET

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Age-dependent differences in DNA damage after in vitro CT exposure

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Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation

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PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway

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EUS dating with laser ablation against the caudate lobe or left liver tumors: a win-win proposition?

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A systematic review and meta-analysis of psychological functioning in chronic tinnitus.

Related Articles

A systematic review and meta-analysis of psychological functioning in chronic tinnitus.

Clin Psychol Rev. 2017 Dec 30;:

Authors: Trevis KJ, McLachlan NM, Wilson SJ

Abstract
Chronic tinnitus, the phenomenon of a chronic ringing in the ears or head, has a significant negative impact on an individual's health and wellbeing. Despite this, there is no cure or consensus regarding factors maintaining ongoing awareness of the sensation in this population, or the severity of its impact. We aimed to comprehensively and systematically review behavioural studies investigating the psychological functioning of adults with chronic tinnitus. We identified 64 papers meeting our search criteria for inclusion, which are reviewed with regard to psychological factors involved with the presence of chronic tinnitus, and those relating to its severity. The majority of studies assessed the presence and impact of chronic tinnitus with regard to emotional wellbeing (n=59), with a more recent interest in cognitive functioning (n=16). A subset of 36 studies was included in meta-analyses investigating the relationships between emotional wellbeing and the presence and impact of chronic tinnitus using random-effects models. Our findings indicate the presence of chronic tinnitus may be associated with reduced cognitive functioning, particularly attention, and with reduced emotional wellbeing, particularly anxiety and depression. We also found consistent evidence indicating severity of chronic tinnitus is associated with a broad range of psychological features, primarily symptoms of depression and anxiety. We recommend investigating the complexity of the relationships between emotional wellbeing, cognitive functioning, and chronic tinnitus using a range of methodologies to further elucidate the role of psychological functioning in chronic tinnitus.

PMID: 29366511 [PubMed - as supplied by publisher]

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