A rare localization of cerebral venous sinus thrombosis. Case report.

G Chir. 2015 Mar-Apr;36(2):79-83

Authors: Carangelo B, Lavalle L, Tiezzi G, Branco D, Lippa L, Mileo E, Costantino G, Mariottini A, Muscas G, Maturo A

Abstract
In this work the Authors report their experience on the treatment of a case of cavernous venous sinus thrombosis. The diagnosis is clinical and neuroradiological, CT, MRN, cerebral angiography and orbital venography have aided in establishing the diagnosis during life. Very interesting is the therapeutic approach.

PMID: 26017108 [PubMed - indexed for MEDLINE]

A study of mucosal melanoma of the oral cavity in India: a rare tumor.

Ear Nose Throat J. 2014 Aug;93(8):E4-7

Authors: Chaturvedi P, Lerra S, Gupta P, Pai PS, Chaukar DA, Agarwal JP, D'Cruz AK

Abstract
Malignant melanomas involving the mucosa are rare and aggressive lesions. Their rarity has made the formulation of staging and treatment protocols very difficult, as most of the available information comes from case reports and small case series. We conducted a retrospective study to analyze the behavior of melanomas of the oral mucosa in patients who were treated at Tata Memorial Hospital in Mumbai, a tertiary care referral center for malignancies and one of the largest cancer centers on the Indian subcontinent. During the 22-year period from January 1986 through December 2007, we found only 13 such cases, which had occurred in 8 men and 5 women, aged 26 to 70 years (mean: 37.5). All patients had been offered surgery with curative intent. Mucosal melanomas have exhibited a greater tendency for distant recurrence than for local treatment failure, which is why adjuvant radiation therapy has not been shown to confer any consistent benefit. In our study, only 3 of the 13 patients (23.1%) remained alive 2 years after diagnosis, despite aggressive treatment. Tumor staging, optimal treatment, and prognostic factors for oral mucosal melanoma are far from clear, and further research is needed. Despite the small number of patients in this study, it still represents one of the largest series of oral mucosal melanoma patients in India.

PMID: 25181674 [PubMed - indexed for MEDLINE]

Cytotoxicity of Salvia miltiorrhiza Against Multidrug-Resistant Cancer Cells.

Am J Chin Med. 2016 May 24;:1-24

Authors: Wu CF, Bohnert S, Thines E, Efferth T

Abstract
Salvia miltiorrhiza Bunge (Lamiaceae) is a well-known Chinese herb that possesses numerous therapeutic activities, including anticancer effects. In this study, the cytotoxicity and the biological mechanisms of S. miltiorrhiza (SM) root extract on diverse resistant and sensitive cancer cell lines were investigated. CEM/ADR5000 cells were 1.68-fold resistant to CCRF-CEM cells, while HCT116 (p53[Formula: see text] and U87.MG[Formula: see text]EGFR cells were hypersensitive (collateral sensitive) compared to their parental cells. SM root extract stimulated ROS generation, cell cycle S phase arrest and apoptosis. The induction of the intrinsic apoptotic pathway was validated by increased cleavage of caspase 3, 7, 9 and poly ADP-ribose polymerase (PARP). MAP kinases including JNK, ERK1/2 and p38 were obviously phosphorylated and nuclear P65 was downregulated upon SM treatment. Transcriptome-wide COMPARE analysis revealed that the expression of encoding genes with diverse functions were associated with the cellular response to cryptotanshinone, one of the main constituents of SM root extract. In conclusion, SM root extract exerted profound cytotoxicity towards various sensitive and resistant cancer cells and induced the intrinsic apoptotic pathway.

PMID: 27222067 [PubMed - as supplied by publisher]

Systems Metabolic Engineering of Escherichia coli.

EcoSal Plus. 2016 May;7(1)

Authors: Choi KR, Shin JH, Cho JS, Yang D, Lee SY

Abstract
Systems metabolic engineering, which recently emerged as metabolic engineering integrated with systems biology, synthetic biology, and evolutionary engineering, allows engineering of microorganisms on a systemic level for the production of valuable chemicals far beyond its native capabilities. Here, we review the strategies for systems metabolic engineering and particularly its applications in Escherichia coli. First, we cover the various tools developed for genetic manipulation in E. coli to increase the production titers of desired chemicals. Next, we detail the strategies for systems metabolic engineering in E. coli, covering the engineering of the native metabolism, the expansion of metabolism with synthetic pathways, and the process engineering aspects undertaken to achieve higher production titers of desired chemicals. Finally, we examine a couple of notable products as case studies produced in E. coli strains developed by systems metabolic engineering. The large portfolio of chemical products successfully produced by engineered E. coli listed here demonstrates the sheer capacity of what can be envisioned and achieved with respect to microbial production of chemicals. Systems metabolic engineering is no longer in its infancy; it is now widely employed and is also positioned to further embrace next-generation interdisciplinary principles and innovation for its upgrade. Systems metabolic engineering will play increasingly important roles in developing industrial strains including E. coli that are capable of efficiently producing natural and nonnatural chemicals and materials from renewable nonfood biomass.

PMID: 27223822 [PubMed - as supplied by publisher]

Cox process representation and inference for stochastic reaction-diffusion processes.

Nat Commun. 2016;7:11729

Authors: Schnoerr D, Grima R, Sanguinetti G

Abstract
Complex behaviour in many systems arises from the stochastic interactions of spatially distributed particles or agents. Stochastic reaction-diffusion processes are widely used to model such behaviour in disciplines ranging from biology to the social sciences, yet they are notoriously difficult to simulate and calibrate to observational data. Here we use ideas from statistical physics and machine learning to provide a solution to the inverse problem of learning a stochastic reaction-diffusion process from data. Our solution relies on a non-trivial connection between stochastic reaction-diffusion processes and spatio-temporal Cox processes, a well-studied class of models from computational statistics. This connection leads to an efficient and flexible algorithm for parameter inference and model selection. Our approach shows excellent accuracy on numeric and real data examples from systems biology and epidemiology. Our work provides both insights into spatio-temporal stochastic systems, and a practical solution to a long-standing problem in computational modelling.

PMID: 27222432 [PubMed - in process]

Data Mining for Identification of Molecular Targets in Ovarian Cancer.

Asian Pac J Cancer Prev. 2016;17(4):1691-9

Authors: Villegas-Ruiz V, Juarez-Mendez S

Abstract
Ovarian cancer is possibly the sixth most common malignancy worldwide, in Mexico representing the fourth leading cause of gynecological cancer death more than 70% being diagnosed at an advanced stage and the survival being very poor. Ovarian tumors are classified according to histological characteristics, epithelial ovarian cancer as the most common (~80%). We here used high-density microarrays and a systems biology approach to identify tissue-associated deregulated genes. Non-malignant ovarian tumors showed a gene expression profile associated with immune mediated inflammatory responses (28 genes), whereas malignant tumors had a gene expression profile related to cell cycle regulation (1,329 genes) and ovarian cell lines to cell cycling and metabolism (1,664 genes).

PMID: 27221839 [PubMed - in process]

Genomic Landscape of Colorectal Mucosa and Adenomas.

Cancer Prev Res (Phila). 2016 May 24;

Authors: Borras E, San Lucas FA, Chang K, Zhou R, Masand G, Fowler J, Mork ME, You YN, Taggart MW, McAllister F, Jones DA, Davies GE, Edelmann W, Ehli EA, Lynch PM, Hawk ET, Capella G, Scheet P, Vilar E

Abstract
The molecular basis of the adenoma-to-carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances (AI) in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer driver genes (APC, KRAS, FBXW7, TCF7L2) and AIs in chromosomes 5, 7, and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. Cancer Prev Res; 9(6); 1-11. ©2016 AACR.

PMID: 27221540 [PubMed - as supplied by publisher]

[Deepening the idea of systems biology and promoting the development of pan-vascular medical science].

Zhonghua Xin Xue Guan Bing Za Zhi. 2016 May 24;44(5):373-4

Authors: Ge JB

PMID: 27220570 [PubMed - in process]

Drugs affecting glycosaminoglycan metabolism.

Drug Discov Today. 2016 May 20;

Authors: Ghiselli G, Maccarana M

Abstract
Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu through pharmacological interventions. In this review, we provide a classification of small molecules affecting GAG metabolism based on their mechanism of action. Furthermore, we present evidence to show that clinically approved drugs affect GAG metabolism and that this could contribute to their therapeutic benefit.

PMID: 27217160 [PubMed - as supplied by publisher]

Mood, stress and longevity: convergence on ANK3.

Mol Psychiatry. 2016 May 24;

Authors: Rangaraju S, Levey DF, Nho K, Jain N, Andrews KD, Le-Niculescu H, Salomon DR, Saykin AJ, Petrascheck M, Niculescu AB

Abstract
Antidepressants have been shown to improve longevity in C. elegans. It is plausible that orthologs of genes involved in mood regulation and stress response are involved in such an effect. We sought to understand the underlying biology. First, we analyzed the transcriptome from worms treated with the antidepressant mianserin, previously identified in a large-scale unbiased drug screen as promoting increased lifespan in worms. We identified the most robust treatment-related changes in gene expression, and identified the corresponding human orthologs. Our analysis uncovered a series of genes and biological pathways that may be at the interface between antidepressant effects and longevity, notably pathways involved in drug metabolism/degradation (nicotine and melatonin). Second, we examined which of these genes overlap with genes which may be involved in depressive symptoms in an aging non-psychiatric human population (n=3577), discovered using a genome-wide association study (GWAS) approach in a design with extremes of distribution of phenotype. Third, we used a convergent functional genomics (CFG) approach to prioritize these genes for relevance to mood disorders and stress. The top gene identified was ANK3. To validate our findings, we conducted genetic and gene-expression studies, in C. elegans and in humans. We studied C. elegans inactivating mutants for ANK3/unc-44, and show that they survive longer than wild-type, particularly in older worms, independently of mianserin treatment. We also show that some ANK3/unc-44 expression is necessary for the effects of mianserin on prolonging lifespan and survival in the face of oxidative stress, particularly in younger worms. Wild-type ANK3/unc-44 increases in expression with age in C. elegans, and is maintained at lower youthful levels by mianserin treatment. These lower levels may be optimal in terms of longevity, offering a favorable balance between sufficient oxidative stress resistance in younger worms and survival effects in older worms. Thus, ANK3/unc-44 may represent an example of antagonistic pleiotropy, in which low-expression level in young animals are beneficial, but the age-associated increase becomes detrimental. Inactivating mutations in ANK3/unc-44 reverse this effect and cause detrimental effects in young animals (sensitivity to oxidative stress) and beneficial effect in old animals (increased survival). In humans, we studied if the most significant single nucleotide polymorphism (SNP) for depressive symptoms in ANK3 from our GWAS has a relationship to lifespan, and show a trend towards longer lifespan in individuals with the risk allele for depressive symptoms in men (odds ratio (OR) 1.41, P=0.031) but not in women (OR 1.08, P=0.33). We also examined whether ANK3, by itself or in a panel with other top CFG-prioritized genes, acts as a blood gene-expression biomarker for biological age, in two independent cohorts, one of live psychiatric patients (n=737), and one of suicide completers from the coroner's office (n=45). We show significantly lower levels of ANK3 expression in chronologically younger individuals than in middle age individuals, with a diminution of that effect in suicide completers, who presumably have been exposed to more severe and acute negative mood and stress. Of note, ANK3 was previously reported to be overexpressed in fibroblasts from patients with Hutchinson-Gilford progeria syndrome, a form of accelerated aging. Taken together, these studies uncover ANK3 and other genes in our dataset as biological links between mood, stress and longevity/aging, that may be biomarkers as well as targets for preventive or therapeutic interventions. Drug repurposing bioinformatics analyses identified the relatively innocuous omega-3 fatty acid DHA (docosahexaenoic acid), piracetam, quercetin, vitamin D and resveratrol as potential longevity promoting compounds, along with a series of existing drugs, such as estrogen-like compounds, antidiabetics and sirolimus/rapamycin. Intriguingly, some of our top candidate genes for mood and stress-modulated longevity were changed in expression in opposite direction in previous studies in the Alzheimer disease. Additionally, a whole series of others were changed in expression in opposite direction in our previous studies on suicide, suggesting the possibility of a "life switch" actively controlled by mood and stress.Molecular Psychiatry advance online publication, 24 May 2016; doi:10.1038/mp.2016.65.

PMID: 27217151 [PubMed - as supplied by publisher]

Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease.

Int J Antimicrob Agents. 2016 Apr 22;

Authors: Sbaraglini ML, Bellera CL, Fraccaroli L, Larocca L, Carrillo C, Talevi A, Alba Soto CD

Abstract
Despite current efforts worldwide to develop new medications against Chagas disease, only two drugs are available, nifurtimox and benznidazole. Both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with Trypanosoma cruzi. Recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. These compounds showed inhibitory effects on cruzipain, the major cysteine protease of T. cruzi, of different parasite stages and in a murine model of acute Chagas disease. The aim of this work was to determine the efficacy of these novel cruzipain inhibitors when administered in a murine model of chronic Chagas disease. Benidipine and clofazimine were able to reduce the parasite burden in cardiac and skeletal muscles of chronically infected mice compared with untreated mice as well as diminish the inflammatory process in these tissues. Further studies should be performed to study the synergism with benznidazole and nifurtimox in view of combined therapies.

PMID: 27216381 [PubMed - as supplied by publisher]

The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis.

Elife. 2016;5

Authors: Patterson S, Wyllie S, Norval S, Stojanovski L, Simeons FR, Auer JL, Osuna-Cabello M, Read KD, Fairlamb AH

Abstract
There is an urgent requirement for safe, oral and cost-effective drugs for the treatment of visceral leishmaniasis (VL). We report that delamanid (OPC-67683), an approved drug for multi-drug resistant tuberculosis, is a potent inhibitor of Leishmania donovani both in vitro and in vivo. Twice-daily oral dosing of delamanid at 30 mg kg(-1) for 5 days resulted in sterile cures in a mouse model of VL. Treatment with lower doses revealed a U-shaped (hormetic) dose-response curve with greater parasite suppression at 1 mg kg(-1) than at 3 mg kg(-1) (5 or 10 day dosing). Dosing delamanid for 10 days confirmed the hormetic dose-response and improved the efficacy at all doses investigated. Mechanistic studies reveal that delamanid is rapidly metabolised by parasites via an enzyme, distinct from the nitroreductase that activates fexinidazole. Delamanid has the potential to be repurposed as a much-needed oral therapy for VL.

PMID: 27215734 [PubMed - in process]

Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.

Pharmacogenomics J. 2016 May 24;

Authors: Zur RM, Roy LM, Ito S, Beyene J, Carew C, Ungar WJ

Abstract
Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.

PMID: 27217052 [PubMed - as supplied by publisher]

Clinical-pharmacogenetic predictive models for MTX discontinuation due to adverse events in rheumatoid arthritis.

Pharmacogenomics J. 2016 May 24;

Authors: Jenko B, Lusa L, Tomsic M, Praprotnik S, Dolzan V

Abstract
We describe a novel approach to investigate and evaluate combined effect of a large number of clinical and pharmacogenetic factors on treatment outcome. We have used this approach to investigate predictors of methotrexate (MTX)-induced adverse events (AEs) leading to treatment discontinuation in rheumatoid arthritis (RA) patients. In total, 333 RA patients were genotyped for 34 polymorphisms in MTX transporters, folate and adenosine pathways. The effect of clinical and pharmacogenetic factors was assessed with penalized regression in the cause-specific Cox proportional hazards model. The predictive capacity was evaluated with the area under time-dependent receiver operating characteristic curve where cross-validation was applied. SLC19A1, ABCG2, ADORA3 and TYMS were associated with discontinuation because of AEs in clinical-pharmacogenetic model. Cross-validation showed that both clinical-pharmacogenetic model and nongenetic model had worthless predictive ability for MTX discontinuation because of AEs. These models could be further improved, either with additional polymorphisms or with epigenetic predictors.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.36.

PMID: 27217051 [PubMed - as supplied by publisher]

Malignant Pyoderma Associated with Granulomatosis with Polyangiitis (Wegener Granulomatosis) as a Unique Indication for Facial Vascularized Composite Allotransplantation: Part I.

Plast Reconstr Surg. 2016 Jun;137(6):1007e-1015e

Authors: Gastman B, Hashem AM, Djohan R, Bernard S, Hendrickson M, Schwarz G, Gharb BB, Rampazzo A, Fernandez A, Zins J, Hoffman GS, Doumit G, Siemionow M, Papay F

Abstract
BACKGROUND: Granulomatosis with polyangiitis (Wegener granulomatosis) is a rare disease that commonly starts in the craniofacial region and can lead to considerable facial disfigurement. Granulomas and vasculitis, however, can involve many other tissues (especially pulmonary and renal). Dermatologic and subcutaneous components can lead to malignant pyoderma.
METHODS: The authors describe a unique pathologic condition, where significant Le Fort type trauma was associated with subsequent development of granulomatosis with polyangiitis and malignant pyoderma. Successive operations to excise necrotic tissue and reconstruct the defects were followed by worsening inflammation and tissue erosions. Trauma and surgery in proximity to the eye and sinuses masked the initial clinical presentation and led to delay in diagnosis and disease progression. The resultant facial disfigurement and tissue loss were substantial.
RESULTS: Despite multiple confounding factors, accurate diagnosis was eventually established. This was based on persistence of sinus inflammations in the absence of infective agents, proven sterility of lung lesions, and antineutrophil cytoplasmic antibody positivity with proteinase 3 specificity. Skin lesion biopsy specimens were identified as pyoderma gangrenosum and later as malignant pyoderma. Institution of immunosuppressive therapy allowed successful control of the disease and wound healing. The resulting craniofacial destruction, however, necessitated facial vascularized composite allotransplantation.
CONCLUSION: Recognition of this rare pathologic association is essential, to prevent delays in diagnosis and treatment that can lead to major craniofacial tissue loss.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID: 27219252 [PubMed - as supplied by publisher]

[Peutz-Jeghers syndrome manifested as massive melæna at CHU-JRA Madagascar hospital: a case report].

Pan Afr Med J. 2016;23:78

Authors: Martinetti AF, Andriantsoa RM, Andriambelo RT, Nicole RR, Enintsoa RN

Abstract
Peutz-Jeghers syndrome (SPJ) is characterized by intestinal hamartomatous polyps in association with mucocutaneous lentiginosis. Patients are exposed to mechanical and bleeding complications. It is a cancer predisposition syndrome. Our study highlights the diagnostic criteria for Peutz-Jeghers syndrome (SPJ), the complications and the therapeutic progresses in patient care. We report the case of a 32-year-old male presenting with a massive melaena. It was hospitalized in the surgical intensive care unit with hypovolemic shock difficult to control. This required surgical intervention to stop bleeding. We found a hamartomatous polyps in the small intestine which caused bleeding. Peutz Jeghers Syndrome was diagnosed on the basis of labial lentigines during childhood. Clinical and paraclinical explorations did not reveal the presence of cancer. In Madagascar, this disease is still poorly understood. In the literature, the diagnosis of Peutz Jeghers syndrome is based on clinical findings or on the presence of complications such as haemorrhage, invagination or bowel obstruction. In our case, the disease was complicated by gastrointestinal bleeding with hypovolemic shock. Endoscopic polypectomy using double-balloon enteroscopy can reduce emergency small bowel surgery. Peutz-Jeghers syndrome is a rare disease. Despite this, it is important for clinicians to know it and to take it into consideration in case of gastrointestinal bleeding.

PMID: 27217901 [PubMed - in process]

Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine tumors of the thymus: 30-year experience with 16 patients at a single institute in the People's Republic of China.

Onco Targets Ther. 2016;9:2193-201

Authors: Chen YY, Li SQ, Liu HS, Qin YZ, Li L, Huang C, Bi YL, Meng YX, He J, Zhou XY, Ma DJ

Abstract
BACKGROUND AND PURPOSE: Thymic neuroendocrine carcinomas (TNECs) are extremely uncommon. Certain cases of TNECs can produce the adrenocorticotropic hormone (ACTH) and cause ectopic ACTH syndrome (EAS). The current literature on this topic consists mainly of case reports, and therapeutic guidelines are lacking. The aim of this study was to discuss the diagnosis, surgical management, and prognosis of EAS caused by TNECs to improve clinical experience with this rare disease.
METHODS: From June 1984 to June 2014, at the Peking Union Medical College Hospital, the surgical interventions and follow-up outcomes of 16 consecutive patients (eight men and eight women) with EAS caused by TNECs were retrospectively analyzed.
RESULTS: The median age was 32.5 years (range: 13-47 years), and the median disease duration was 8.5 months (range: 1-150 months). All patients presented with clinical and biochemical evidence indicating a diagnosis of Cushing's syndrome. Contrast-enhanced thoracic computed tomography scans were critical to locating the ACTH-producing tumor and evaluating the feasibility of resection. All patients underwent surgery. One patient died of septicemia in the intensive care unit 2 weeks after surgery. No other morbidity or mortality occurred during the perioperative period. The median overall survival (OS) was 41 months (95% CI: 30.3-51.7 months), and the progression-free survival was 28 months (95% CI: 21.6-34.3 months). Both overall survival (P=0.002) and progression-free survival (P=0.030) improved significantly after complete resection.
CONCLUSION: TNEC is an extremely aggressive disease that should be considered when treating patients with Cushing's syndrome due to ectopic ACTH secretion. In particular, all suspected patients should undergo contrast-enhanced thoracic computed tomography scans to facilitate early diagnosis. The current first-line treatment is surgical resection, and complete resection is a favorable prognostic factor. However, additional patients and a longer follow-up will be needed to determine the variables that are predictive of survival and to improve patient prognosis.

PMID: 27217765 [PubMed]

Clear Cell Mypepithelial Carcinoma of the Base Tongue Managed by the Mandible Preserving Pull-Through Oropharyngectomy Approach.

Indian J Surg Oncol. 2015 Sep;6(3):263-6

Authors: Krishnamurthy A

Abstract
Myoepithelial carcinoma (MC) is rare disease that comprises of only about 2 % of all salivary gland carcinomas and MC that focally or predominantly displays clear cell-type tumor cells are considered as CCMC. We recently got to treat a rare case of a base tongue clear cell myoepithelial carcinoma. (CCMC) Our patient, to the best of our knowledge is the second case of base tongue CCMC and the first with metastatic involvement of the cervical lymph nodes. We successfully managed the tumor using the "mandible preserving pull-through oropharyngectomy approach" Knowledge of the different surgical approaches and techniques is thus vital for better oncologic, functional and aesthetic outcomes following surgery for tumors especially in challenging sub sites like the oropharynx.

PMID: 27217675 [PubMed]

[A Case of Inflammatory Myofibroblastic Tumor of Urinary Bladder].

Hinyokika Kiyo. 2016 Apr;62(4):201-4

Authors: Tanaka K, Ikeda A, Miyakawa T, Komine M, Tsutsumi M, Ishikawa S, Kawai K, Nishiyama H

Abstract
A 61-year-old man presenting with voiding pain was diagnosed with a bladder tumor by ultrasound in another hospital, and was subsequently referred to our hospital. Cystoscopy showed a nodular tumor and surrounding edematous mucosa in the right wall of the bladder. Initially, we suspected bladder invasion of gastrointestinal malignancy, but abdominal computed tomography, magnetic resonance imaging, and a series of tumor marker tests revealed no abonormalities. We performed transurethral resection of the bladder tumor under the clinical diagnosis of a submucosal tumor originating from the bladder wall. Histopathological examination revealed spindle cell proliferation, which was positively stained with anti-anaplastic lymphoma kinase (ALK) antibody. Based on the findings, the diagnosis of an inflammatory myofibroblastic tumor (IMT) was made. Therefore, we performed partial cystectomy to reduce the risk of local recurrence. The pathological diagnosis was IMT, and the surgical margins were negative. Bladder IMT is a rare disease, and surgical resection is the only recommended treatment. In the literature, if completely resected, the prognosis of patients with bladder IMT is excellent. Also, in the present case, no recurrence has been detected for over 6 months.

PMID: 27217015 [PubMed - in process]

Evidence of pathogenicity of a mutation in 3' untranslated region causing mild haemophilia A.

Haemophilia. 2016 May 24;

Authors: Pezeshkpoor B, Berkemeier AC, Czogalla KJ, Oldenburg J, El-Maarri O

Abstract
INTRODUCTION: Despite the high mutation detection rate, in a small group of haemophilia A patients, using current screening methods, no causal mutation in F8 can be detected. In such cases, the causal mutation might be in the non-coding sequences of F8.
AIM: Rarely, mutations in non-coding sequences reveal a pivotal role. Here, we analysed a mild haemophilia A patient harbouring a mutation in the 3' untranslated region (UTR) of F8 and elucidated the molecular mechanism leading to haemophilia phenotype.
METHODS: To find the causal mutation, the complete F8 genomic region was analysed by next generation sequencing. The effect of the identified alteration on F8 expression was evaluated in silico and analysed for the splicing effect at mRNA level. Moreover, in vitro studies using a luciferase reporter system were performed to functionally analyse the mutation.
RESULTS: We identified an alteration in the 3' UTR (c.*56G>T) as the only change in F8 gene. Pedigree analysis showed a segregation pattern for three affected members for the presumptive mutation. Moreover, the variant was predicted in silico to create a new donor splice site, which was also detected at mRNA level, resulting in a 159 bp deletion in 3' UTR of F8. Finally, the variant showed reduced expression of the gene reporter firefly luciferase in cell line expression analysis.
CONCLUSION: Our results advocate the patient specific c.*56G>T base change in the 3' UTR to be a disease-associated mutation leading to alternative splicing explaining the mild haemophilia A phenotype.

PMID: 27216882 [PubMed - as supplied by publisher]