Successful role of adjuvant radiotherapy in a rare case of tracheal inflammatory myofibroblastic tumor: a case report

BACKGROUND:: Inflammatory myofibroblastic tumor (IMT) is a rare benign cancer that can express a more aggressive phenotype related to the genetic mutation of the anaplastic lymphoma kinase receptor (ALK). Involvement of trachea is extremely rare and due to the clinical and radiologic nonspecificity, the definitive diagnosis is based on the histologic evaluation of tissue specimens. Total surgical excision is curative and chemotherapy or radiotherapy has been employed in the treatment of unresectable tumors or as adjuvant therapies. CASE PRESENTATION:: The case described here is being reported because of the rare tracheal location and the atypical treatment approach used for an ALK-positive IMT. A 7-week pregnant woman voluntary interrupted pregnancy and underwent total surgical excision that resulted to have close margins. Although ALK-positive expression indicated the use of ALK inhibitors, she refused any type of adjuvant therapy that could affect ovarian function. Thus, 3D conformational external beam radiotherapy was performed with a daily dose of 180 cGy, 5 times per week, up to 45 Gy at the level of trachea. A total of 62 months of follow-up showed and no signs of disease recurrence or late radiation therapy-related toxicity. CONCLUSIONS: This report describes an extremely rare case of a tracheal IMT, underlying the key role of radiotherapy as adjuvant treatment able to definitively cure IMT, limiting systemic chemotherapy-related toxicity

Educational Technology Primer: A Guide for Pre-Service Teachers

The Educational Technology Primer grew out of the realization that today’s teacher education students have different needs than their predecessors. Current students arrive on campus less intimidated by technology and more experienced with the use of technology in instruction. However, many introductory educational technology texts still highlight the acquisition of basic technology operations; knowledge and skills that made sense when students entering an introductory educational technology course lacked technology experiences, but not today

RELATIONSHIP BETWEEN POLYMORPHISMS OF TAS2R38 BITTER TASTE RECEPTOR AND CHRONIC UPPER AIRWAY INFECTIONS

1Department of Neuroscience, ENT Section, “Federico II” University of Naples, Italy 2Department of Translational Medical Sciences, European Laboratory for Food Induced Diseases, Napoli, Italy The presence of taste receptors in extra-oral tissues may suggest additional roles apart from taste perception. Recently, an increasing number of reports demonstrated that the bitter taste G-protein coupled receptors family T2R, expressed in ciliated epithelial cells of the respiratory tract, are able to detect bacterial products and to stimulate innate immune defense against pathogens. Most microbial agents, secretes chemical signals known as quorum-sensing molecules that regulate the expression of genes involved in biofilm formation, virulence and other vital processes for microorganisms. Among the quorum-sensing molecules, the AHLs produced by P. aeruginosa, activate the receptor for bitter T2R38 expressed in ciliated epithelial cells of the respiratory tract, whereas mutants of P. aeruginosa lacking the AHL are not able to activate it. The activation of the receptor results in an increase of the Ca2+ flow and the ciliary beat frequency, as well as stimulating the production of NO which acts as a bactericide against the pathogen. The Caucasian population express three common polymorphisms (Pro49Ala, Ala262Val, Val296Ile) for TAS2R38 that lead to two major haplotypes PAV and AVI. The expression of either haplotype gives respectively 2 forms of receptors ̶ functional or non-functional ̶ i.e. unable to respond to specific agonists such phenylthiocarbamide and propylthiouracil (PROP). The two haplotypes PAV and AVI segregate into two major phenotypic classes: the "functional", sensitive to bitter, are homo- or heterozygous for the allele PAV, the "non-functional", are homozygous for the allele AVI. The genetic variations of the receptor TAS2R38 that affect sensitivity to bitter taste can help determine individual differences in susceptibility to bacterial infections of the respiratory tract allowing to plan a “target therapy”. Cellular cultures from homozygous PAV/PAV individuals showed a more effective NO production, mucociliary clearance and bactericide effect than cultures from AVI/PAV or AVI/AVI individuals. As a consequence it is reasonable to assume that patients with genotype AVI/PAV or AVI/AVI are at greater risk of contracting infections from gram-negative, compared with homozygous PAV. Some authors have studied the correlation between genotype and microbiological results TAS2R38 tissue of respiratory mucosa. The result of this analysis proved to be very interesting, because it showed a significant difference in the frequency of non-functional (AVI) than functional (PAV) among patients whose cultures were positive for Gram-negative bacteria, including P. aeruginosa. The aim of the study was to characterize phenotypically the sensitivity to PROP and the receptor polymorphisms of TAS2R38, in patients with chronic or recurrent infections of the upper respiratory tract to identify high risk patients. The identification of high-risk individuals would allow to draw up protocols for specific follow-up and appropriate “target therapy”

Head and Neck squamocellular carcinomas: E-cadherin and Keratin 5 as biomolecular markers

E- Cadherin is a transmembranar protein that plays an important role in the cellular adhesion and insure the connection of the tissue cells; it is present in the epithelial cells and its aberrant expression is correlated with different kinds of head and neck squamocellular carcinoma. Keratin 5 (K5) is present in the basal layer of a stratified squamous keratinized and non keratinized epithe-lium. The purpose of the present study was to identify the expression particularities of E-cadherin and Keratin 5 in rapport with the localization and the differentiation of various head and neck squamocellular carcinomas (larynx, pharynx, hard palate, tongue, submandibular, lip, gingival sulcus, nasal pyramid, maxillary, zygomatic). Immunoreactions for E-cadherin in the tumoral cells were examined according to the this score: 0 (0% positive cells), 1 (30%). The presence of maximum score (value 3) of E-cadherin was found in well-differentiated squamocellular carcinomas of laryngeal, tongue, lip, nasal pyramid, zygomatic area origin. A lower value of the score was present in the less differentiated histopathological type. The role of E-cadherin in the squamocellular carcinomas is far from being clarified. It seems that the trials to estimate a prognosis in this clinical entity should include a combination between the molecular markers, the histopathological data and clinical parameters. K5 expression was observed in all squamocellular carcinomas included in the present study with scores between 1 and 3. For well and moderately differentiated histopathological types, a maximum score of 3 was recorded for all of the cases, not including the laryngeal area, which presented a score of 2. The following scores were identified in the regions of the poorly differentiated carcinomas: Jaw, 3; gingival sulcus, 2; and tongue and submandibular area, 1. The present study confirms the role of K5 in the definition of the differentiation of squamocellular carcinoma of head and neck revealing a differential expression depending on the anatomic site of the primary tumor. These observations may aid with an improved stratification of head and neck squamocellular carcinoma, thus improving the diagnosis and treatment strategies for this type of cancer

Aggressiveness pattern and second primary tumor risk associated with basaloid squamous cell carcinoma of the larynx

Basaloid squamous cell carcinoma (BSCC) is a rare, aggressive and distinct variant of squamous cell carcinoma (SCC) of the upper respiratory and digestive tract. We have evaluated disease specific survival (DSS) and overall survival (OS) through Kaplan-Meier method and mortality risk through univariate statistical analysis of Cox in 42 cases of BSCC and other 42 of laryngeal SCC (LSCC) matched for both age and sex. We demonstrated that laryngeal BSCC is a more aggressive tumor than LSCC as is associated to higher nodal recurrence of pathology (5 vs 2 patients, median survival, OR 2.7), a reduced survival (median survival 34 vs 40 months, OR 3.2 for mortality); in addition, basaloid patients have a higher risk to be affected by second primary tumors (13 vs 3 patients, OR 5.8) and a higher probability to die for this second tumor (Hazard Risk, HR 4.4). The analysis of survival shows an increased mortality risk concurrent with the parameters assessed by univariate analyses that assume a predictive and statistical significance in second tumor and grading in basaloid LSSC.Basaloid squamous cell carcinoma (BSCC) is a rare, aggressive and distinct variant of squamous cell carcinoma (SCC) of the upper respiratory and digestive tract. We have evaluated disease specific survival (DSS) and overall survival (OS) through Kaplan-Meier method and mortality risk through univariate statistical analysis of Cox in 42 cases of BSCC and other 42 of laryngeal SCC (LSCC) matched for both age and sex. We demonstrated that laryngeal BSCC is a more aggressive tumor than LSCC as is associated to higher nodal recurrence of pathology (5 vs 2 patients, median survival, OR 2.7), a reduced survival (median survival 34 vs 40 months, OR 3.2 for mortality); in addition, basaloid patients have a higher risk to be affected by second primary tumors (13 vs 3 patients, OR 5.8) and a higher probability to die for this second tumor (Hazard Risk, HR 4.4). The analysis of survival shows an increased mortality risk concurrent with the parameters assessed by univariate analyses that assume a predictive and statistical significance in second tumor and grading in basaloid LSSC

TERT Promoter Mutations are Associated with Visceral Spreading in Melanoma of the Trunk

Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TERT promoter mutations have been recently associated with a poor prognosis in stage I-II melanomas. Usually, it is not recommended to perform a mutational test on primary melanoma, as the results do not always reflect the mutational status of metastases. In particular, trunk melanomas have been reported to have an unfavourable prognosis. A series of 105 advanced melanoma patients were analysed by TERT promoter Sanger sequencing. Univariate/multivariate binary logistic regression models were performed using progression to a visceral site as the dependent variable and patient/tumour characteristics as covariates. Performance of the model was assessed in an external independent primary melanoma patients' dataset. Male gender (odds ratio (OR), 344; 95% CI, 1.12⁻10.6; p = 0.031), AJCC (American Joint Committee on Cancer) classification (OR, 022; 95% CI, 0.07⁻0.67; p = 0.008), SLNB (Sentinel Lymph Node Biopsy) status (OR, 3.05; 95% CI, 1.06⁻8.78; p = 0.039) and TERT-mutated trunk lesions (OR, 3.78; 95% CI, 1.35⁻10.6; p = 0.011) were significantly associated with the risk of developing a visceral spreading as first site of progression using multivariate logistic regression analysis. These results were confirmed in the external validation control group. Therefore, in trunk primary melanomas, due to their high risk of progression to visceral sites, we encourage somatic TERT mutation analysis at diagnosis to identify those patients who would potentially benefit from a more intensive follow-up protocol and a prompt initiation of therapy

Molecular Characterization of Cancer Associated Fibroblasts in Prostate Cancer

Background: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor–stroma interactions may yield novel therapeutic targets for prostate cancer. Methods: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity®: IPA® software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF). Results: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-β as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs. Conclusions: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells