Oct4, c-Myc and CD44 can be used to predict local recurrence and the outcome of treatment in oral cancer patients. In addition, these molecules may find use as molecular targets for effective therapy.
To study multistep tumorigenesis process, there is a need of in-vitro 3D model simulating in-vivo tissue. Present study aimed to reconstitute in-vitro tissue models comprising various stages of neoplastic progression of tongue tumorigenesis and to evaluate the utility of these models to investigate the role of stromal fibroblasts in maintenance of desmosomal anchoring junctions using transmission electron microscopy. We reconstituted in-vitro models representing normal, dysplastic, and malignant tissues by seeding primary keratinocytes on either fibroblast embedded in collagen matrix or plain collagen matrix in growth factor-free medium. The findings of histomorphometry, immunohistochemistry, and electron microscopy analyses of the three types of 3D cultures showed that the stratified growth, cell proliferation, and differentiation were comparable between co-cultures and their respective native tissues; however, they largely differed in cultures grown without fibroblasts. The immunostaining intensity of proteins, viz., desmoplakin, desmoglein, and plakoglobin, was reduced as the disease stage increased in all co-cultures as observed in respective native tissues. Desmosome-like structures were identified using immunogold labeling in these cultures. Moreover, electron microscopic observations revealed that the desmosome number and their length were significantly reduced and intercellular spaces were increased in cultures grown without fibroblasts when compared with their co-culture counterparts. Our results showed that the major steps of tongue tumorigenesis can be reproduced in-vitro. Stromal fibroblasts play a role in regulation of epithelial thickness, cell proliferation, differentiation, and maintenance of desmosomalanchoring junctions in in-vitro grown tissues. The reconstituted co-culture models could help to answer various biological questions especially related to tongue tumorigenesis.
The purpose of this work is to report the results of commissioning and to establish a quality assurance (QA) program for commercial 3D treatment planning system (TPS) based on IAEA Technical Report Series 430. Eclipse v 7.3.10, (Varian Medical Systems, Palo Alto, CA, U.S.A.) TPS was commissioned for a Clinac 6EX (Varian Medical Systems, Palo Alto, CA, USA) linear accelerator. CT images of a phantom with various known in-homogeneities were acquired. The images were transferred to TPS and tested for various parameters related to patient data acquisition, anatomical modeling, plan evaluation and dose calculation. Dosimetric parameters including open, asymmetric and wedged shaped fields, oblique incidence, buildup region behavior and SSD dependence were evaluated. Representative clinical cases were tested for MU calculation and point doses. The maximum variation between the measured and the known CT numbers was 20 +/- 11.7 HU (1 SD). The results of all non-dosimetric tests were found within tolerance, however expansion at the sharp corners was found distorted. The accuracy of the DVH calculations depends on the grid size. TPS calculations of all the dosimetric parameters were in good agreement with the measured values, however for asymmetric open and wedged fields, few points were found out of tolerance. Smaller grid size calculation showed better agreement of dose calculation in the build-up region. Independent tests for MU calculation showed a variation within +/-2% (relative to planning system), meanwhile variation of 3.0% was observed when the central axis was blocked. The test results were in agreement with the tolerance specified by IAEA TRS 430. A subset of the commissioning tests has been identified as a baseline data for an ongoing QA program.
Innate lymphoid cells (ILCs) encompass a diverse array of lymphocyte subsets with unique phenotype that initiate inflammation and provide host defenses in specific microenvironments. In this report we identify a rare human CD4+CD3− innate-like lymphoid population with high TNF expression that is enriched in blood from patients with rheumatoid arthritis. These CD4+CD3− cells belong to the T cell lineage but the lack of antigen receptor at the cell surface renders them nonresponsive to TCR-directed stimuli. By developing a culture system that sustains survival, we show that CD4+CD3− innate-like T cells display IL-7-dependent induction of surface lymphotoxin-αβ (LTαβ) demonstrating their potential to modify tissue microenvironments. Furthermore, expression of CCR6 on CD4+CD3− population defines a CD127high subset that is highly responsive to IL-7. This CD4+CD3− population is enriched in the peripheral blood from rheumatoid arthritis patients suggesting a link to their involvement in chronic inflammatory disease.
Peripheral doses (PD) from uniform dynamic multileaf collimation (DMLC) fields were measured for 6 MV x-rays on a Varian linear accelerator using a 0.6 cc ionization chamber inserted at 5 cm depth into a 35 x 35 x 105 cm3 plastic water phantom. PD measurements were also carried out under identical conditions for seven patients treated for head and neck and cervical cancer employing sliding window intensity-modulated radiotherapy (IMRT). The measured PD from these patient-specific intensity-modulated beams (IMBs) were compared with the corresponding data from uniform DMLC fields having similar jaws setting. The measured PD per monitor unit (PD/MU) decreases almost exponentially with out-of-field distance for all uniform DMLC and static fields. For the same strip field width of 1.2 cm, uniform DMLC fields with a larger size of 14 x 22 cm2 deliver an average of 3.51 (SD = 0.51) times higher PD/MU at all out-of-field distances compared to 6 x 6 cm2. Similar to uniform DMLC fields, PD/MU measured from different patient-specific IMBs was found to decrease almost exponentially with out-of-field distance and increase with increase in field dimension. PD per MU from uniform DMLC fields and patient-specific IMBs having similar jaws setting shows good agreement (+/-7%) except at the most proximal distance, where a variation of more than 10% (maximum 15%) was observed. Our study shows that PD data generated from uniform DMLC fields can be used as baseline data to estimate out-of-field critical organ or whole-body dose in patients treated employing sliding window IMRT if an appropriate correction factor for field dimension is applied. The whole-body dose information can be used to estimate the possible increase in risk of fatal secondary malignancy in patients treated employing sliding window IMRT.
Use of an onlay pectoralis major myofascial flap did not decrease the pharyngocutaneous fistula rate, although fistula duration was shortened. A well-designed randomised-controlled trial is needed to establish parameters for its routine use in clinical practice.
Concurrent chemoradiation is currently the accepted 'standard of care' for locally advanced laryngeal and hypopharyngeal cancers. However, there is a subset of patients not suitable for chemoradiation, in whom primary surgery is the best option. Speech preservation is of prime importance in these patients. Near-total laryngectomy is a voice-preserving procedure which can be considered as an alternative to total laryngectomy for selected patients with lateralised, locally advanced cancers of the larynx and hypopharynx. Although these patients are left with a permanent tracheostomy, lung-powered speech is maintained by way of a dynamic shunt created from the uninvolved tissues of the larynx. Since its first description in the early 1980s, the procedure has been shown by various authors to be oncologically sound, with high success rates. Unfortunately, the procedure has not gained wide acceptance due to perceived fears of surgical complexity. In this review, we discuss the various issues related to the procedure and we review the relevant literature.
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