Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms ...remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTS
). These NTS
neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTS
→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.
(1) Background: We compared the outcomes of patients with nasopharyngeal carcinoma treated with IMPT and VMAT. (2) Methods: We performed a retrospective propensity score matching analysis (1:1) of ...patients treated with IMPT (years: 2016–2018) and VMAT (2014–2018). Survival was estimated using the Kaplan–Meier method. Multivariate Cox proportional hazards regression analysis was used to identify the independent predictors of survival. Binary toxicity endpoint analyses were performed using a Cox model and logistic regression. (3) Results: Eighty patients who received IMPT and VMAT were included. The median follow-up time was 24.1 months in the IMPT group. Progression-free survival (PFS) and overall survival (OS) were not statistically different between the two groups but potentially better in IMPT group. In multivariate analysis, advanced N-stage and body weight loss (BWL; >7%) during radiotherapy were associated with decreased PFS. The IMPT group had significantly less requirement for nasogastric (NG) tube placement and BWL during treatment. The mean oral cavity dose was the only predictive factor in stepwise regression analysis, and IMPT required a significantly lower mean dose. However, IMPT increased the grade 3 radiation dermatitis. (4) Conclusions: IMPT is associated with reduced rates of NG tube insertion and BWL through reducing oral mean dose, potentially producing better oncologic outcomes.
Background: Nasopharyngeal carcinoma (NPC) involves host genetics, environmental and viral factors. In clinical observations, patients of young and old ages were found to have higher recurrence and ...metastatic rates. Methods: Cytokine array was employed to screen druggable target(s). The candidate target(s) were confirmed through patient-derived xenografts (PDXs) and a new EBV-positive cell line, NPC-B13. Results: Overexpression of epithelial growth factor (EGF) and EGF receptor (EGFR) was detected in young patients than in older patients. The growth of NPC PDX tumors and cell lines was inhibited by EGFR inhibitors (EGFRi) cetuximab and afatinib when used separately or in combination with the cell cycle blocker palbociclib. Western blot analysis of these drug-treated PDXs demonstrated that the blockade of the EGF signaling pathway was associated with a decrease in the p-EGFR level and reduction in PDX tumor size. RNA sequencing results of PDX tumors elucidated that cell cycle-related pathways were suppressed in response to drug treatments. High EGFR expression (IHC score ≥ grade 3) was correlated with poor survival in metastatic patients (p = 0.008). Conclusions: Our results provide encouraging preliminary data related to the combination treatment of EGFRi and palbociclib in patients with NPC.
Reconstruction of defects measuring approximately two‐thirds of the lower lip width is traditionally reconstructed utilizing loco‐regional flap utilizing lip and cheek tissues. This often results in ...microstomia and unsatisfactory aesthetic outcome. This may hinder the psychosocial aspect of a recovering cancer survivor. Here we describe a single‐stage reconstruction in a 79‐year‐old male patient who received lower lip resection for squamous cell carcinoma. The reconstruction was accomplished using a facial artery musculomucosal flap together with a free radial forearm flap for vermilion and soft tissue defect reconstruction after lip tumor resection with uneventful postoperative course. The patient remains disease‐free after 2‐year follow‐up and does not require revision surgeries for functional or aesthetic reason. This approach may be considered a good option for reconstruction of missing lip and soft tissue simultaneously when the facial vessels are well‐preserved during neck dissection. Aesthetically pleasing and functionally satisfactory outcomes may be produced.
The effect of aeration on the performance of docosahexaenoic acid (DHA) production by Schizochytrium sp. was investigated in a 1,500-L bioreactor using fed-batch fermentation. Six parameters, ...including specific growth rate, specific glucose consumption rate, specific lipid accumulation rate, cell yield coefficient, lipid yield coefficient, and DHA yield coefficient, were used to understand the relationship between aeration and the fermentation characteristics. Based on the information obtained from the parameters, a stepwise aeration control strategy was proposed. The aeration rate was controlled at 0.4 volume of air per volume of liquid per minute (vvm) for the first 24 h, then shifted to 0.6 vvm until 96 h, and then switched back to 0.4 vvm until the end of the fermentation. High cell density (71 g/L), high lipid content (35.75 g/L), and high DHA percentage (48.95%) were achieved by using this strategy, and DHA productivity reached 119 mg/L h, which was 11.21% over the best results obtained by constant aeration rate.
Purpose of Review
Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we ...assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients.
Recent Findings
In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy.
Summary
Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.
Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads ...to local recurrence, becoming a substantial factor in treatment failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs to inhibit protein translation. Although several studies have indicated that the dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family's role in radioresistance remains limited. This study determined the role of miR-630 in regulating radiosensitivity in HNC. We discovered that miR-630 functions as an oncomiR, marked by its overexpression in HNC patients, correlating with a poorer prognosis. We further delineated the malignant function of miR-630 in HNC cells. While it had a minimal impact on cell growth, the miR-630 contributed to radioresistance in HNC cells. This result was supported by decreased cellular apoptosis and caspase enzyme activities. Moreover, miR-630 overexpression mitigated irradiation-induced DNA damage, evidenced by the reduced levels of the γ-H2AX histone protein, a marker for double-strand DNA breaks. Mechanistically, the overexpression of miR-630 decreased the cellular ROS levels and initiated Nrf2 transcriptional activity, resulting in the upregulation of the antioxidant enzyme GPX2. Thus, this study elucidates that miR-630 augments radioresistance by inducing an anti-apoptotic effect via the Nrf2-GPX2 molecular axis in HNC. The modulation of miR-630 may serve as a novel radiosensitizing target for HNC.
Background
DNA copy number variations (CNVs) are a hallmark of cancer, and the current study aimed to demonstrate the profile of the CNVs for oral cavity squamous cell carcinoma (OSCC) and elucidate ...the clinicopathological associations and molecular mechanisms of a potential marker derived from CNVs, mixed‐lineage leukemia translocated to chromosome 3 protein (MLLT3), in OSCC carcinogenesis.
Materials and Methods
CNVs in 37 OSCC tissue specimens were analyzed using a high‐resolution microarray, the OncoScan array. Gene expression was analyzed by real‐time polymerase chain reaction in 127 OSCC and normal tissue samples. Cell function assays included cell cycle, migration, invasion and chromatin immunoprecipitation assays.
Results
We found a novel copy number amplified region, chromosome 9p, encompassing MLLT3 via the comparison of our data set with six other OSCC genome‐wide CNV data sets. MLLT3 overexpression was associated with poorer overall survival in patients with OSCC (p = .048). MLLT3 knockdown reduced cell migration and invasion. The reduced invasion ability in MLLT3‐knockdown cells was rescued with double knockdown of MLLT3 and CBP/p300‐interacting transactivator with ED rich carboxy‐terminal domain 4 (CITED4; 21.0% vs. 61.5%). Knockdown of MLLT3 impaired disruptor of telomeric silencing‐1‐like (Dot1L)‐associated hypermethylation in the promoter of the tumor suppressor, CITED4 (p < .001), and hence dysregulated HIF‐1α‐mediated genes (TWIST, MMP1, MMP2, VIM, and CDH1) in OSCC cells.
Conclusion
We identified unique CNVs in tumors of Taiwanese patients with OSCC. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L‐mediated transcriptional repression of CITED4, leading to dysregulation of HIF‐1α‐mediated genes.
Implications for Practice
This article reports unique copy number variations in oral cavity squamous cell carcinoma (OSCC) tumors of Taiwanese patients. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L‐mediated transcriptional repression of CITED4, leading to dysregulation of HIF‐1α‐mediated genes.
DNA copy number variations are a hallmark of cancer. This article reports a potential biomarker derived from copy number variations, MLLT3, in oral cavity squamous cell carcinoma carcinogenesis.
Background
Little is known about the appropriate treatment and long‐term survival of patients with multiple concomitant oral cavity cancers (MOC). The aim of this study was to clarify the ...clinicopathological features of MOC, to compare the prognosis of MOC patients with that of patients with single oral cavity cancers (SOC), and to describe reconstructive options based on the concept of economy in autologous tissue transfer.
Methods
Data from 603 patients diagnosed with at least one squamous cell carcinoma of the oral cavity who underwent surgery for primary oral cavity cancers between 2006 and 2014 were reviewed retrospectively to identify MOC patients.
Results
Among 603 cases of surgically resected primary oral cancers, 20 cases (3.3%) with MOC were identified. Patients with MOC did not differ from patients with SOC in age, and their index lesions did not differ in pT value, pN value, pathological stage, extracapsule spread, or perineural or bone invasion. The 5‐year overall and disease‐free survival rates for MOC and SOC cases were 72.6% versus 68.7%, and 65.3% versus 64.8%, respectively (P = 0.785 and 0.770, respectively). The anterolateral thigh flap was widely applied. According to its origin of blood supply, the reconstructive options of MOC patients with separated defects were classified and proposed.
Conclusions
MOC and SOC were similar in clinicopathological characteristics. The prognosis of patients with MOC was similar to that of patients with SOC. Resections were performed with curative intent. A multidisciplinary team management approach is essential for customized treatment in MOC patients.
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