An Investigation of the Differential Expression of Her2/neu Gene Expression in Normal Oral Mucosa, Epithelial Dysplasia, and Oral Squamous Cell Carcinoma in Taiwan

BackgroundHer2/neu was thought to be a proto-oncogene with sequence homology to epidermal growth factor receptor (EGFR). Its overexpression was seen in many cancers and referred to regimens of anticancer therapy. The aim of this study was to investigate whether the abnormal expression existed in oral carcinogenesis.MethodsImmunohistochemistry (IHC) was used to detect Her2/neu expression in normal oral mucosa (NOM) (n = 20), oral precancerous lesions of epithelial dysplasia (ED) (n = 20), and oral squamous cell carcinoma (OSCC) (n = 30). The association of clinicopathologic covariates of areca use, tumor size, neck lymph node metastasis, differentiation and stages of cancer with the expression of Her2/neu was examined. The significance of Neu immunoreactivity in different groups or with different covariates was investigated using Fisher's exact test.ResultsHer2/neu immunoreactivity was very low with Her2/neu(+) in 10% (2/20) of NOM cases and in 25% (5/20) of ED cases, respectively. The Her2/neu expression was high in OSCC cases, with 40% (12/30) of Her2/neu(+) and 10% (3/30) of Her2/neu(++). Significant difference was observed between NOM/ED and OSCC cases (p < 0.05). All clinicopathologic covariates showed no significant relation to the expression of Her2/neu in OSCC cases.ConclusionThese findings suggested a dynamic change in Her2/neu expression during the development of OSCC. The overexpression of Her2/neu can be used as a marker in distinguishing NOM/ED from OSCC

Reconstruction for Mandibular Implant Failure

Mandibular defects may result from tumor ablations, trauma, or radiation necrosis. Significant segmental mandibular loss or hemimandibular loss may sometimes be replaced with mandibular implants by ENT surgeons/oral surgeons/head and neck surgeons. However, this may bring about mandibular implant failure in long-term follow-up. Mandibular implant failures usually manifest as: soft tissue atrophy, mandibular implant extrusion, infection, facial nerve involvement, facial asymmetry, derangement of occlusion and mastication, orocutaneous fistula, etc. Over 30 years, the authors have treated 102 patients with mandibular implant failure. Reconstruction may involve removal of the mandibular implant and immediate replacement of the mandibular defect with a piece of vascularized bone flap, not only to compensate for bone loss but also to replace neighboring soft tissue and possible skin defects. Frequently used flaps have been vascularized iliac bone (89/102) or vascularized fibula grafts (13/102). During follow-up, iliac bone flap reconstruction has yielded more favorable results due to its ample bone bulk and adequate soft tissue coverage. Fibula flaps with osteotomies have been associated with an increasing incidence of malunion/nonunion and subsequent easy deformation

The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

<p>Abstract</p> <p>Background</p> <p>MCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes.</p> <p>Results</p> <p>MCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation <it>in vivo</it>, the inhibitors of p53 (MDM2, Pirh2, and Cop1) are constantly stimulated by MCT-1 oncoprotein.</p> <p>Conclusions</p> <p>The oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development.</p

Impact of emotional and motivational regulation on putting performance: a frontal alpha asymmetry study

Background The efficacy of emotional and motivational regulation can determine athletic performance. Giving the short duration and fast changing nature of emotions experienced by athletes in competition, it is important to examine the temporal dynamics of emotional and motivational regulation. The aim of this study was to investigate emotional and motivational regulation as measured by frontal alpha asymmetry in skilled golfers during putting performance after a performance failure. Methods Twenty skilled university golfers were recruited and requested to perform 40 putts at an individualized difficulty level of 40–60% successful putting rate. Trials immediately after a failed putt were selected for analysis. Successful performances were those trials where a hole was and unsuccessful performances were those that failed. The frontal alpha asymmetry index of LnF4-LnF3 was derived for statistical analysis. Results (1) Successful performance was preceded by a larger frontal alpha asymmetry index at T2 than that of T1, and (2) a larger frontal alpha asymmetry index was observed for unsuccessful performance than for successful performance at T1. Discussion The results suggest that successful emotional and motivational regulation was characterized by a progressive increase of frontal alpha asymmetry, which led to subsequent putting success when facing an emotionally provocative putting failure. These findings shed light on the application of frontal alpha asymmetry for the understanding and enhancement of emotional and motivational regulation during sport performance

Impact of emotional and motivational regulation on putting performance: a frontal alpha asymmetry study

Chen T-T, Wang K-P, Cheng M-Y, Chang Y-T, Huang C-J, Hung T-M. Impact of emotional and motivational regulation on putting performance: a frontal alpha asymmetry study. PeerJ. 2019;7: e6777.**Background** The efficacy of emotional and motivational regulation can determine athletic performance. Giving the short duration and fast changing nature of emotions experienced by athletes in competition, it is important to examine the temporal dynamics of emotional and motivational regulation. The aim of this study was to investigate emotional and motivational regulation as measured by frontal alpha asymmetry in skilled golfers during putting performance after a performance failure. **Methods** Twenty skilled university golfers were recruited and requested to perform 40 putts at an individualized difficulty level of 40–60% successful putting rate. Trials immediately after a failed putt were selected for analysis. Successful performances were those trials where a hole was and unsuccessful performances were those that failed. The frontal alpha asymmetry index of LnF4-LnF3 was derived for statistical analysis. **Results** (1) Successful performance was preceded by a larger frontal alpha asymmetry index at T2 than that of T1, and (2) a larger frontal alpha asymmetry index was observed for unsuccessful performance than for successful performance at T1. **Discussion** The results suggest that successful emotional and motivational regulation was characterized by a progressive increase of frontal alpha asymmetry, which led to subsequent putting success when facing an emotionally provocative putting failure. These findings shed light on the application of frontal alpha asymmetry for the understanding and enhancement of emotional and motivational regulation during sport performance

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).</p> <p>Methods</p> <p>Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.</p> <p>Results</p> <p>HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.</p> <p>Conclusion</p> <p>Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.</p

Matrix Metalloproteinase-8 Mediates the Unfavorable Systemic Impact of Local Irradiation on Pharmacokinetics of Anti-Cancer Drug 5-Fluorouracil

Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for cancer treatment. However, the interactions between radiation and 5-FU remain unclear. Here, we evaluated the influence of local irradiation on the pharmacokinetics of 5-FU in rats. The single-fraction radiation was delivered to the whole pelvic fields of Sprague-Dawley rats after computerized tomography-based planning. 5-FU at 100 mg/kg was prescribed 24 hours after radiation. A high-performance liquid chromatography system was used to measure 5-FU in the blood. Matrix metalloproteinase-8 (MMP-8) inhibitor I was administered to examine whether or not RT modulation of 5-FU pharmacokinetic parameters could be blocked. Compared with sham-irradiated controls, whole pelvic irradiation reduced the area under the concentration versus time curve (AUC) of 5-FU in plasma and, in contrast, increased in bile with a radiation dose-dependent manner. Based on protein array analysis, the amount of plasma MMP-8 was increased by whole pelvic irradiation (2.8-fold by 0.5 Gy and 5.3-fold by 2 Gy) in comparison with controls. Pretreatment with MMP-8 inhibitor reversed the effect of irradiation on AUC of 5-FU in plasma. Our findings first indicate that local irradiation modulate the systemic pharmacokinetics of 5-FU through stimulating the release of MMP-8. The pharmacokinetics of 5-FU during concurrent chemoradiaiton therapy should be rechecked and the optimal 5-FU dose should be reevaluated, and adjusted if necessary, during CCRT

Rationalization and Design of the Complementarity Determining Region Sequences in an Antibody-Antigen Recognition Interface

Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities