Next-generation tissue engineering exploits the body’s own regenerative capacity by providing an optimal niche via a scaffold for the migration and subsequent proliferation of endogenous cells to the site of injury, enhancing regeneration and healing and bypassing laborious in vitro cell-culturing procedures. Such systems are also required to have a sufficient angiogenic capacity for the subsequent patency of implanted scaffolds. The exploitation of redox properties of nanodimensional ceria (nCeO2) in in situ tissue engineering to promote cell adhesion and angiogenesis is poorly investigated. As a novel strategy, electrospun polycaprolactone based tissue-engineering scaffolds loaded with nCeO2 were developed and evaluated for morphological and physicomechanical features. In addition, in vitro and in vivo studies were performed to show the ability of nCeO2-containing scaffolds to enhance cell adhesion and angiogenesis. These studies confirmed that nCeO2-containing scaffolds supported cell adhesion and angiogenesis better than bare scaffolds. Gene-expression studies had shown that angiogenesis-related factors such as HIF1α and VEGF were up-regulated. Overall results show that incorporation of nCeO2 plays a key role in scaffolds for the enhancement of angiogenesis, cell adhesion, and cell proliferation and can produce a successful outcome in in situ tissue engineering.
Thyroid swellings are a significant clinical problem in the general population but majority of them are nonneoplastic and do not require surgery. The initial screening procedures include ultrasonography, fine needle aspiration cytology (FNAC) and radionucleotide scan. An initial screening test which will diagnose thyroid lesions accurately will help to avoid surgery in nonneoplastic conditions. The aim of the present study is to correlate the cytology findings with final histopathology. Two hundred and forty-eight cases of thyroid nodules which underwent FNAC followed by surgery were included in this study. The cytology diagnoses were classified into nondiagnostic/unsatisfactory, benign, atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, suspicious for malignancy and malignant. The fine needle aspiration diagnosis was compared with the histopathology diagnosis. In majority of cases the FNA diagnosis was in concordance with final histopathology. A high incidence of follicular variant of papillary carcinoma thyroid was detected in this study. The awareness of this entity and the search for fine nuclear details of papillary carcinoma can lead to proper identification of this category of tumors and thus help to avoid false negative and equivocal results. Fine needle aspiration cytology is a simple, cost effective, rapid to perform procedure with high degree of accuracy and is recommended as the first line investigation for the diagnosis of thyroid lesions.
Marginal Mandibular Nerve (MMN) is a branch of the facial nerve. Muscles supplied by this nerve are responsible for facial symmetry, facial expressions and phonation. Aim was to study the branching pattern and variations in the position of marginal mandibular nerve. 202 patients who underwent neck dissection from June 2005 to October 2006 at Regional Cancer Centre, Trivandrum, India were included in the study. During the course of neck dissection, the marginal mandibular nerve was first identified around the point where the facial artery crossed the lower border of the mandible. Once the nerve was identified, it was traced both backwards and forward till the whole nerve was exposed. Position of the nerve and its relation to lower border of mandible at the point where the facial artery crossed the lower border of the mandible was noted and number and position of each branches were recorded. In 161of the 202 patients (79.7%) the MMN had a single division. Two branches were noted in 26 patients (12.9%). Three branches for MMN are not uncommon, it was noted in 14 patients (6.9%) and in one patient there were four branches. Every effort should be made to preserve all the branches of MMN to ensure cosmesis and decrease morbidity. The mean distance from the lower border of the mandible to the point where the marginal mandibular nerve crossed the facial artery for all the branches taken together was 1.73 mm below the mandible. In 49 patients there was communication between MMN and the cervical branch of facial nerve. The point where the facial artery crosses the lower border of the mandible is a reliable landmark to locate the MMN. Variation in the branching pattern of marginal mandibular nerve is very common.
Recent advancements in cancer research have shown that cancer stem cell (CSC) niche is a crucial factor modulating tumor progression and treatment outcomes. It sustains CSCs by orchestrated regulation of several cytokines, growth factors, and signaling pathways. Although the features defining adult stem cell niches are well-explored, the CSC niche is poorly characterized. Since membrane trafficking proteins have been shown to be essential for the localization of critical proteins supporting CSCs, we investigated the role of TUBB4B, a probable membrane trafficking protein that was found to be overexpressed in the membranes of stem cell enriched cultures, in sustaining CSCs in oral cancer. Here, we show that the knockdown of TUBB4B downregulates the expression of pluripotency markers, depletes ALDH1A1+ population, decreases in vitro sphere formation, and diminishes the tumor initiation potential in vivo. As TUBB4B is not known to have any role in transcriptional regulation nor cell signaling, we suspected that its membrane trafficking function plays a role in constituting a CSC niche. The pattern of its expression in tissue sections, forming a gradient in and around the CSCs, reinforced the notion. Later, we explored its possible cooperation with a signaling protein, Ephrin-B1, the abrogation of which reduces the self-renewal of oral cancer stem cells. Expression and survival analyses based on the TCGA dataset of head and neck squamous cell carcinoma (HNSCC) samples indicated that the functional cooperation of TUBB4 and EFNB1 results in a poor prognosis. We also show that TUBB4B and Ephrin-B1 cohabit in the CSC niche. Moreover, depletion of TUBB4B downregulates the membrane expression of Ephrin-B1 and reduces the CSC population. Our results imply that the dynamics of TUBB4B is decisive for the surface localization of proteins, like Ephrin-B1, that sustain CSCs by their concerted signaling.
The primary intention of the study was to find out whether Adult Comorbidity Evaluation Index (ACE-27) was better than the American Society of Anaesthesiologists’ (ASA) risk classification system in predicting postoperative morbidity in head and neck oncosurgery. Another goal was to identify other risk factors for complications which are not included in these indexes. Univariate and multivariate analyses were performed on 250 patients to determine the impact of seven variables on morbidity-ACE-27 grade, ASA class, age, sex, duration of anaesthesia, chemotherapy and radiotherapy. In univariate analysis ACE-27 index, ASA score, duration of anaesthesia, radiotherapy and chemotherapy were significant. As both comorbidity scales were significant in univariate analysis they were analyzed together and separately in multivariate analysis to illustrate their individual strength. In the first multivariate analysis (excluding ACE-27 grade) ASA class, duration of anaesthesia, radiotherapy and chemotherapy were significant. The positive predictive value (PPV) of this model to predict morbidity was 60.86% and negative predictive value (NPV) was 77.9%. The sensitivity was 75% and specificity 62.2%. In the second multivariate analysis (excluding ASA class) ACE-27 grade, duration of anaesthesia and radiotherapy were significant. The PPV of this model to predict morbidity was 62.1% and NPV was 76.5%. The sensitivity was 61.6% and specificity 70.9%. In the third multivariate analysis which included both ACE-27 grade and ASA class only ASA class, duration of anaesthesia, radiotherapy and chemotherapy remained significant. In conclusion, ACE-27 grade and ASA class were reliable predictors of major complications but ASA class had more impact on complications than ACE-27 grade.
Transforming growth factor beta (TGF-β) signaling is a pleiotropic cytokine signaling pathway, which controls cellular activities ranging from embryogenesis to apoptosis. Although many molecular alterations in this pathway have been described in cancers, the central point of concern, that is how these alterations influence the treatment outcome, has been addressed to a lesser extent. In this study, we have characterized the alterations of TGF-β-SMAD signaling in 97 oral squamous cell carcinoma (OSCC) samples and assessed the association between these alterations and the outcome of the treatment. Genomic level alteration analysis using reverse transcriptase polymerase chain reaction-single-strand conformation polymorphism/sequencing revealed that there were 25% samples harboring genomic level alterations in this pathway. Altogether, 21% samples showed TGFBR2 mutations, whereas three cases were found to harbor novel SMAD3 mutations. Notably, 14 out of 24 TGFBR2 mutations are of one type (c.*6C>A), which supplemented complementarity for hsa-miR-3189-5p. These samples showed significantly low TGFBR2 transcript levels (P = 0.026). In addition, transcript level studies using quantitative real-time PCR revealed a strong association between low TGFBR2 transcript levels and poor disease-free survival (P = 0.028) as well as poor overall survival (P = 0.013). In brief, our results showed that oral cancers with TGFBR2 downregulation comprise a different group with more aggressive nature. These results suggest that in OSCCs, TGFBR2 transcript levels may be developed as a promising prognostic biomarker. Furthermore, for the first time, this study reports SMAD3 mutations in oral carcinoma.
The study's results emphasize the need for the clinician to do an accurate reevaluation and follow-up of patients with incidental occult metastasis for detection of primary thyroid tumor. A thorough sampling and screening of lymph nodes in neck dissection specimens by the pathologist is also essential. Incidentally discovered thyroid tissue in cervical lymph nodes need not always be benign inclusions. Aggressive therapy, however, may not be needed in all cases.
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