Medial sural artery perforator free flap versus radial forearm free flap in oral cavity reconstruction and donor site morbidity.

OBJECTIVE: Radial Forearm Free flap (RFFF) is widely used in head and neck reconstruction, yet its donor site defect remains a significant drawback. The Medial Sural Artery Perforator Free Flap (MSAPFF) is considered an alternative flap to RFFF. This study aims to comprehensively analyze their characteristics, outcomes, and their impact on patient quality of life. METHODS: All patients who underwent oral cavity reconstruction using RFFF and MSAPFF between February 2017 and April 2023 were included in this study. Flap characteristics, outcomes and post-operative complications were recorded and compared. Subjective donor site morbidity, aesthetic and functional results, and quality of life were also analyzed. RESULTS: The study included 76 patients: 37 underwent reconstruction with RFFF, and 39 with MSAPFF. There was no significance difference between the RFFF and MSAPFF regarding the success rate (97.2% vs 97.4%), flap size (4.8 × 8.8 cm2 vs 5 × 9.8 cm2), hospital of stay (15.5 days vs 13.5 days) and recipient site complications (P > 0.05). However, MSAPFF showed larger flap thickness (P = 0.001), smaller arterial caliber (P = 0.008), shorter pedicle length (P = 0.001), and longer harvesting time (P < 0.001). No significant difference was observed between the pre-and postoperative ranges of wrist and ankle movements or in recipient site complications. MSAPFF showed a significant difference in donor site morbidity (P < 0.05). CONCLUSION: The MSAPFF is an excellent alternative to the RFFF for repairing oral cavity defects, with additional advantage of a well-hidden scar on the posterior calf, a larger flap thickness, accepted pedicle length and arterial caliber. However, one should consider the harvesting time and surgical skills required in comparison to the RFFF. CLINICAL RELEVANCE: The study highlights the importance of the MSAPFF as an alternative option for RFFF with less donor site morbidity and high success rate in oral cavity reconstruction and improved patient Quality of life after ablative surgery.

Modified submandibular mandibulotomy approach versus lip-splitting approach in tongue cancer surgery: a retrospective paired-cohort study.

OBJECTIVES: The surgical approach for resection and reconstruction of tongue cancer (TSCC) with or without the lip-splitting incision is controversial. This study introduced a modified approach without lip-splitting and the clinical results were assessed. METHODS: Sixty-eight TSCC patients underwent surgery using the modified submandibular mandibulotomy (MSMM) approach without lip-splitting, and another matched 68 patients using lip-splitting mandibulotomy (LSM) approach were enrolled in this study. The clinical results including intraoperative relevance and surgical morbidities, survival status, facial appearance and scar scores, function of lower lip, and quality of life (QOL) were evaluated. RESULTS: The primary tumors were en bloc resected through the MSMM approach with excellent tumor exposure and R0 resection margins as LSM approach. The survival status and complications were similar in both groups. The function of lower lip was better in patients of MSMM group at 1 month after surgery. The MSMM approach was associated with significantly better facial appearance and recreation compared to LSM approach by scar scores and QOL assessment. CONCLUSION: The MSMM approach without lip-splitting achieves similar tumor control, better aesthetic results, and QOL compared to LSM approach. It is a safe and effective surgical approach for patients with TSCC. CLINICAL RELEVANCE: The MSMM approach without lip-splitting is oncological safety in tongue cancer surgery and is scrutinized as one part of the treatment concept for better aesthetic results.

Perioperative risk factors impact on intensive care unit length of stay (ICU length of stay) in oral squamous cell carcinoma.

BACKGROUND: The trend in postoperative care for free flap patients is to deescalate from routine ICU admission into a specialty recovery unit. This study aims to investigate the predictive parameters in a routine perioperative clinical assessment that are expected to be directly correlated with prolonged ICU length of stay in at-risk patients who received oral reconstructive surgery for squamous cell carcinoma (OSCC). METHODS: All patients who underwent ablative surgery for OSCC with free flap reconstruction and were managed in the ICU were included in this study. The primary outcome was ICU-length of stay. Perioperative, operative and postoperative parameters were analyzed using single test ( t-test, ANOVA analysis, correlation coefficients, effect size) and multivariate regression test. The P-value was set as < 0.005 to be considered statically significant. RESULTS: The study included 136 homogeneous patients, with a mean ICU length of stay of 4.5 (± 4.43 day). Patients with pre-operative positive renal dysfunction (P = 0.004), peripheral vascular disease (P < 0.001), postoperative complications (P = 0.028) or positive heart failure class III (P < 0.001 ) were recognized as at-risk patients for a significantly longer ICU length of stay. CONCLUSION: Patients with perioperative severe renal dysfunction, peripheral vascular disease, postoperative complication or high NYHA class are prone to have a significantly longer ICU length of stay. Several factors were considered as confounders contributing to increased ICU management time in combination with other variables. Additionally, in highly risk patient, the presence of the highly trained medical support, including the appropriate nursing care, is more critical than those patients without these risk factors.

Mesenchymal stem cell-derived CCN2 promotes the proliferation, migration and invasion of human tongue squamous cell carcinoma cells.

Recent studies have demonstrated that mesenchymal stem cells (MSC) exhibit a tropism to tumors and form the tumor stroma. In addition, we found that MSC can secrete different types of factors. However, the involvement of MSC-derived factors in human tongue squamous cell carcinoma (TSCC) growth has not been clearly addressed. The CCN family includes multifunctional signaling molecules that affect the initiation and development events of various tumors. In our study, we report that CCN2/connective tissue growth factor (CTGF) was the most highly induced among the CCN family members in MSC that were co-cultured with TSCC cells. To evaluate the relationship between CCN2 and TSCC growth, we downregulated MSC-derived CCN2 expression with shRNA targeting CCN2 and found that MSC-secreted CCN2 promotes TSCC cell proliferation, migration and invasion. We also confirmed that MSC-derived CCN2 partially accelerated tumor growth in vitro. Taken together, these results suggest that MSC-derived CCN2 contributes to the promotion of proliferation, migration and invasion of TSCC cells and may be a possible therapy target in the future.

Overexpression of HMGA2 promotes tongue cancer metastasis through EMT pathway.

BACKGROUND: Metastasis to long distance organs is the main reason leading to morality of tongue squamous cell carcinoma (TSCC); however, the molecular mechanisms are still unknown. High mobility group AT-hook 2 (HMGA2) is highly expressed in multiple metastatic carcinomas, in which it contributes to cancer progression, metastasis and poor prognosis by upregulating Snail expression and inducing epithelial mesenchymal transition (EMT). This study focuses on investigating the role and mechanism of regulation of HMGA2 in the metastasis of TSCC. METHODS: HMGA2 mRNA and protein expression were examined in TSCC specimens by quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry (IHC). Western blotting, IHC and immunofluorescence were also used to measure the expression and localization of EMT marker E-Cadherin and Vimentin both in TSCC cells and tissues. Knockdown assay was performed in vitro in TSCC cell lines using small interfering RNAs and the functional assay was carried out to determine the role of HMGA2 in TSCC cell migration and invasion. RESULTS: TSCC mRNA and protein expression were significantly up-regulated in tumor tissues when compared to adjacent non-tumor tissues, and the overexpression of HMGA2 was closely correlated with lymph nodes metastasis. Clinicopathological analysis indicated that HMGA2 expression was associated with clinical stage (P = 0.001), lymph node metastasis (P = 0.000), histological differentiation (P = 0.002) and survival (P = 0.000). Silencing the HMGA2 expression in Cal27 and UM1 resulted in the inhibition of cell migration and invasion, meanwhile down-regulation of HMGA2 impaired the phenotype of EMT in TSCC cell lines and tissues. The Multivariate survival analysis indicates that HMGA2 can be an independent prognosis biomarker in TSCC. CONCLUSION: Our findings demonstrate that HMGA2 promotes TSCC invasion and metastasis; additionally, HMGA2 is an independent prognostic factor which implied that HMGA2 can be a biomarker both for prognosis and therapeutic target of TSCC.

FGF1-FGFR1 axis promotes tongue squamous cell carcinoma (TSCC) metastasis through epithelial-mesenchymal transition (EMT).

Increasing evidences suggest a close association between tumor metastasis and the inflammatory factors secreted by tumor microenvironment. It has been reported that epithelial mesenchymal-transition (EMT) plays a significant role during multiple types of tumor metastasis and progression induced by inflammatory factor from tumor microenvironment. Previous researches implied that fibroblast growth factor 1 (FGF1) can promote tumor progression and cause poor prognosis in several types of malignant tumors via interacting with its receptor fibroblast growth factor receptor 1 (FGFR1). However, the effects of FGF1-FGFR1 on tongue squamous cell carcinoma (TSCC) are not yet completely understood. In the present study, we evaluated the effects and function of FGF1-FGFR1 axis on TSCC metastasis. In addition, we investigated whether the EMT pathway is involved in these effects, thus modulating the TSCC progression. The expression of FGFR1 was measured both in tongue cancer cell lines and tissues by qRT-PCR and western blot. We found that FGFR1 was up-regulated in TSCC tissues compared to non-neoplastic tongue tissues. Additionally, overexpression of FGFR1 is positively associated with poor differentiation and metastasis potential. Furthermore, the function of FGF1-FGFR1 was examined in TSCC cell line. The results implied that FGF1 can obviously promote Cal27 cells migration and invasion abilities through FGFR1, while the motile and invasive capabilities can be severely attenuated when knockdown the expression of FGFR1 by specific siRNAs. Further investigation results show that FGF1-FGFR1 axis promotes TSCC metastasis by modulating EMT pathway. However, this effect can be inhibited by blocking the FGF1-FGFR1 axis using FGFR1 specific siRNAs. In conclusion, our findings of the present study provide the evidences that FGF1-FGFR1 axis promotes the TSCC metastasis through the EMT pathway.

Minimally invasive selective neck dissection: a prospective study of endoscopically assisted dissection via a small submandibular approach in cT(1-2_N(0) oral squamous cell carcinoma.

BACKGROUND: Selective neck dissection (SND) in clinical N0 (cN0) cases of oral squamous cell carcinoma (SCC) has been performed by surgeons using a retroauricular or modified facelift approach with robotic or endoscopic assistance. However, these procedures provide cosmetic satisfaction at the cost of possible maximal invasiveness. In this prospective study, we introduced and evaluated the feasibility as well as surgical invasiveness and cosmetic outcome of endoscopically-assisted SND via a small submandibular approach. METHODS: Forty-four patients with cT1-2N0 oral SCC (OSCC) were randomly divided into two groups of endoscopically-assisted SND and conventional SND. Perioperative and postoperative outcomes of patients were evaluated, including the length of the incision, operating time for neck dissection, estimated blood loss during the operation, amount and duration of drainage, total hospitalization period, total number of lymph nodes retrieved, satisfaction scores based on the cosmetic results, perioperative local complications, shoulder syndrome, and follow-up information. RESULTS: The mean operation time in the endoscopically-assisted group (126.04 ± 12.67 min) was longer than that in the conventional group (75.67 ± 16.67 min). However, the mean length of the incision was 4.33 ± 0.76 cm in the endoscopically-assisted SND group, and the amount and duration of drainage, total hospital stay, postoperative shoulder pain score, and cosmetic outcomes were superior in the endoscopically-assisted SND group. Additionally, the retrieved lymph nodes and complications were comparable. CONCLUSIONS: Endoscopically-assisted SND via a small submandibular approach had a longer operation time than the conventional approach. However, endoscopically-assisted SND was feasible and reliable while providing minimal invasiveness and satisfactory appearance.

Neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective cohort study.

BACKGROUND: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. MATERIALS AND METHODS: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. RESULTS: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. CONCLUSIONS: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

Reverse facial artery flap to reconstruct the medium-sized defects in the middle facial region following cancer ablation.

This retrospective clinical study assessed the reliability of the reverse facial artery flap to reconstruct the medium-sized defects in the middle facial region following cancer ablation.Fifteen medium-sized defects were repaired with reversed facial artery flap following cancer surgery. The ages of the patients ranged from 2 to 69 years; 9 were male and 6 were female. The primary lesions included palate (5 cases), maxillary gingival (6 cases), cheek or buccal mucosa (3 case), and upper lip (1 case). The size of the skin paddle varied from 4.0 cm × 6.0 cm to 5.0 cm × 10.0 cm. Direct closure was achieved at all donor sites. Fourteen of the 15 flaps survived. No donor-site problems occurred. Two patients appeared to have temporary injury of facial nerve after operation. The follow-up period ranged from 8 to 36 months; 1 patient died as a result of local recurrence and 1 patient developed cervical recurrence.Consequently, it has been demonstrated that the reversed facial artery flap had reliable blood supply and can reliably and conveniently be used for reconstruction of the medium-sized defects, especially in the middle third of oral and maxillofacial region.

Modified submandibular mandibulotomy approach without lip-splitting in tongue cancer.

Lip-splitting approach for oncologic resection and defect reconstruction of tongue squamous cell carcinoma (TSCC) needs modification to avoid unfavorable esthetic results. Forty-three patients with TSCC underwent surgery using the modified submandibular mandibulotomy(MSMM) approach without lip-splitting and another matched 43 patients using lip-splitting mandibulotomy (LSM) approach were reviewed retrospectively. Clinical outcomes evaluation consisted of tumor exposure, resection margin, surgical morbidity, locoregional recurrence, survival status, scar scores and quality of life (QOL). All the tumors were en bolc removed by MSMM approach and LSM approach through combined intraoral routes with excellent tumor exposure and R0 resection margins. Tumor recurrence rates and swallowing, chewing, speech were similar in both groups. The MSMM approach was associated with significantly better facial appearance and recreation than LSM approach. The MSMM approach without lip-splitting is safe and effective, achieves better QOL compared to LSM approach in patients with TSCC.

Is the retromandibular approach a suitable approach to anatomical reduction of unilateral subcondylar fracture? A non-randomized clinical trial.

The aim of this study was to evaluate the efficacy of the retromandibular approach (RMA) to produce three-dimensional (3-D) reduction of the unilateral subcondylar fracture and Temporomandibular Joint (TMJ) functional implication. METHODS:  A prospective cohort study was designed. Twenty-nine patients with unilateral subcondylar fracture underwent consecutively Open Reduction, and Internal Fixation. The cohorts were divided into two groups; RMA group (n = 16, 55.17%) and submandibular approach SMA group (n = 13, 44.82%). The primary outcome was the anatomical 3-D reduction of the condyle. The secondary outcome was to compare the condyle position and inclination finding with TMJ outcomes. Helkimo Index score was used to evaluate the TMJ outcome at six months postoperatively. RESULT:  There was a significant difference between the mediolateral condylar inclination, condylar medial and vertical positions when RMA compared with SMA groups (P < 0.05). The medial joint space was correlated with the medial condylar position in both groups (P < 0.05). The Helkimo Ai and Di was associated with mediolateral condylar inclination in SMG; however, Helkimo Ai was found to be correlated with the RMA group. CONCLUSION:  The current study demonstrates that the RMA could re-establish the anatomical position of the unilateral subcondylar fracture in patients undergoing ORIF. The clinical outcome of the TMJ with RMA was better than SMA.

Comparison of 3 techniques of surgical treatment of carotid body tumors.

OBJECTIVE: Carotid body tumors (CBTs) are benign but challenging. This study compared outcomes of 3 techniques of the surgical treatment of CBTs. STUDY DESIGN: This retrospective observational study was conducted from April 2013 to March 2019. The 38 patients enrolled in the study had primary tumors, including 1 with bilateral tumors and another with adrenal gland pheochromocytoma. We collected data on age, sex, size of tumor, Shamblin classification, treatment, blood loss, operative time, hospital stay, complications, and recurrence. Statistical analyses were performed using IBM SPSS Statistics version 20 software. RESULTS: Twenty-four patients were male, and 12 were female, and they ranged in age from 11 to 71 years. Cases were assigned to Shamblin groups I (n = 6), II (n = 19), and III (n = 14). Tumor size ranged from 2.0 × 2.0 cm to 5.0 × 6.0 cm. Eleven CBTs underwent blunt dissection (BD), 20 underwent BD plus resection of external carotid artery division plus vessels of encapsulation with allograft dermal matrix (BD + RECA + VE), and 8 tumors underwent surgical resection of tumors plus common carotid artery-internal carotid artery artificial vascular reconstruction (SR +C-IAVR). No perioperative death or stroke occurred. There was a significant difference between Shamblin groups I, II, and III in terms of the size of the tumor, type of treatment used, blood loss, operative time, hospital stay, and complications. Six patients had mandibular branch facial nerve transient paresis; 7 patients had hypoglossal nerve dysfunction; 3 patients had Horner syndrome; and dysphasia occurred in 2 patients. The patients were seen in follow-up for 16 to 45 months, and 1 recurrence was observed. CONCLUSIONS: Three surgical techniques-BD, BD + RECA + VE, and SR + C-IAVR-are safe and feasible for the treatment of CBTs according to Shamblin classifications.

Survivin shRNA induces caspase-3-dependent apoptosis and enhances cisplatin sensitivity in squamous cell carcinoma of the tongue.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family; it is overexpressed in most cancer tissues and induces resistance to chemotherapy. In this study, we investigated whether a short hairpin RNA (shRNA) targeting survivin can induce apoptosis and enhance chemosensitivity to cisplatin in squamous cell carcinoma of the tongue. Results showed that chemosensitivity to cisplatin was surviving dependent in three cell lines (Tca8113, Bca885, and MCF7); higher survivin mRNA expression levels were associated with lower sensitivity to cisplatin. A plasmid-containing survivin shRNA was constructed and transfected into cell line Tca8113. Survivin shRNA inhibited expression of survivin mRNA and protein (63% and 65% inhibition, respectively), significantly inhibited cell proliferation, and enhanced chemosensitivity to cisplatin (p < 0.05). Apoptosis and caspase-3 activity were induced when cells were treated with survivin shRNA and/or cisplatin. Survivin shRNA induced caspase-3-dependent apoptosis and enhanced chemosensitivity to cisplatin in these tongue squamous cell carcinoma cell lines.

Quality of life of patients with tongue cancer 1 year after surgery.

PURPOSE: To study the changes and factors affecting the quality of life (QOL) of patients with tongue cancer 1 year after primary surgery. PATIENTS AND METHODS: A total of 289 consecutive patients with tongue cancer who had undergone primary surgery from 2003 to 2008 at our hospital were recruited. Patient QOL was evaluated using the University of Washington Quality of Life Questionnaire, version 4. Statistical analysis was conducted using a paired-samples t test and multiple stepwise linear regression with Statistical Package for Social Sciences, version 11.5 (SPSS, Chicago, IL). RESULTS: At 1 year after surgery, the appearance, activity, speech, swallowing, shoulder function, salivary, and taste domain scores were significantly lower than the preoperative scores (P < .05). However, the pain, anxiety, and mood scores were significantly better 1 year after surgery (P < .05). The overall QOL had increased greatly 1 year after surgery but did not reach the pretreatment level. Multiple stepwise linear regression analysis showed that the main factors affecting QOL were radiotherapy, advanced clinical stage (P < .05), socioeconomic status, and patient age. Radiotherapy, advanced clinical stage (P < .05), socioeconomic status, and age (P < .05) were independently associated with QOL. CONCLUSIONS: The patients with tongue cancer who have been diagnosed and treated early might have a better QOL. A greater socioeconomic status can also improve the QOL of patients with tongue cancer after primary surgery.

Correction: Antegrade versus retrograde facial nerve dissection in benign parotid surgery: Is there a difference in postoperative outcomes? A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0206028.].

Posterior Tibial Artery Flap with an Adipofascial Extension: Clinical Application in Head and Neck Reconstruction with Detailed Insight into Septocutaneous Perforators and Donor-Site Morbidity.

BACKGROUND: The general aim of this study is to describe a new modification to the posterior tibial artery flap and its clinical application in head and neck reconstruction and to investigate the distribution of septocutaneous perforators of the posterior tibial artery. The specific aim of this study is to evaluate the effectiveness of this new modification to the posterior tibial artery flap and describe the flap survival rate and donor-site morbidity. METHODS: From November of 2017 to August of 2018, 85 consecutive patients underwent posterior tibial artery flap reconstruction of the head and neck region after tumor extirpation. All posterior tibial artery flaps were harvested with a long adipofascial extension, and donor-site defects were closed with a triangular full-thickness skin graft harvested adjacent to the flap. Special consideration was given to the harvesting technique, distribution of the posterior tibial artery septocutaneous perforators, flap outcomes, and associated donor-site morbidity. RESULTS: Flap survival was 100 percent. The number of septocutaneous perforators varied from one to five per leg, with a mean of 2.61 ± 1.15, and the septocutaneous perforators were mostly clustered in the middle and distal thirds of the medial surface of the leg. The prevalence of the presence of one, two, three, four, and five septocutaneous perforators per leg was 7, 33, 27, 19, and 14 percent, respectively. Total and partial skin graft loss at the donor site was reported in two and six patients, respectively, who were managed conservatively. There was no statistically significant difference when comparing the preoperative and postoperative range of ankle movements (p > 0.05). CONCLUSION: This new modification to the posterior tibial artery flap allows for the incorporation of more septocutaneous perforators into the flap, omits the need for a second donor site to close the donor-site defect, and provides sufficient tissue to fill the dead space after tumor resection and neck dissection. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival.

BACKGROUND: The mitotic Aurora-A kinase exerts crucial functions in maintaining mitotic fidelity. As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated. RESULTS: Here, we found that Aurora-A overexpression was closely correlated with clinic stage and lymph node metastasis in tongue carcinoma. Aurora-A inhibitory VX-680 suppressed proliferation, induced apoptosis and markedly reduced migration in cancer cells. We further showed that insulin-like growth factor-1, a PI3K physiological activator, reversed VX-680-decreased cell survival and motility. Conversely, wortmannin, a PI3K inhibitor, combined with VX-680 showed a synergistic effect on inducing apoptosis and suppressing migration. In addition, Aurora-A inhibition suppressed Akt activation, and VX-680-induced apoptosis was attenuated by Myr-Akt overexpression, revealing a cross-talk between Aurora-A and PI3K pathway interacting at Akt activation. Significantly, we showed that suppression of Aurora-A decreased phosphorylated Akt and was associated with increased IkappaBalpha expression. By contrast, Aurora-A overexpression upregulated Akt activity and downregulated IkappaBalpha, these changes were accompanied by nuclear translocation of nuclear factor-kappaB and increased expression of its target gene Bcl-xL. Lastly, Aurora-A overexpression induced IkappaBalpha reduction was abrogated by suppression of Akt either chemically or genetically. CONCLUSION: Taken together, our data established that Aurora-A, via activating Akt, stimulated nuclear factor-kappaB signaling pathway to promote cancer cell survival, and promised a novel combined chemotherapy targeting both Aurora-A and PI3K in cancer treatment.

Antitumor effects of targeting hTERT lentivirus-mediated RNA interference against KB cell lines.

Squamous cell carcinomas are the leading frequent malignant tumors in the oral and maxillofacial region. Currently available treatment options are of limited efficacy, and there is an urgent need for development of alternative therapies. RNA interference (RNAi) is a sequence-specific RNA degradation process. In this study, we screened and identified an in vitro-transcribed 21-bp shRNA targeting human telomerase reverse transcriptase (hTERT) from three candidates and generated a lentivirus vector. Subsequent experiments indicated that this lentiviral transgenic system could effectively transfer into target KB cells, above 80% gene transfer efficiency at MOI of 2.5, and significantly and specifically inhibited hTERT expression both in mRNA (73.42%) and protein (74.67-82.91%) levels. To further evaluate the role of hTERT-targeted RNAi, we found that hTERT inhibition consequently induced suppression of cyclin D1 (54.67%), upregulation of caspase-3 (100.10%), and caspase-9 (42.67%) of KB cells. Therefore, the apoptosis rates of KB cells were increased by 206.33%. In conclusion, these data indicated the potential of lentivirus vectors in cancer gene therapy, especially after development of more efficient vector production methods, and higher virus titers demonstrated that targeting hTERT RNAi may result in telomere uncapping, which triggers cell cycle arrest and apoptosis signal and leads to tumor suppression.

EMMPRIN expression in tongue squamous cell carcinoma.

BACKGROUND: Extracellular matrix metalloproteinase inducer (EMMPRIN) is identified as a tumor-cell membrane protein that stimulates matrix metalloproteinases (MMPs) production. Several studies have shown that higher EMMPRIN expression is associated with shorter survival time and correlated significantly with more advanced clinico-parameters of cancer. The aim of this study was to investigate the relationship between clinico-pathologic characteristics and EMMPRIN, and prognostic significance of EMMPRIN expression in human tongue squamous cell carcinoma. METHODS: Extracellular MMP inducer expression was examined immunohistochemically on paraffin-embedded tissue specimens from 68 patients with tongue squamous cell carcinoma and who underwent radical surgeries from 1996 to 2006. The 68 patients were followed up from 1 to 119 months, with an average of 27.5 months. Nonparametric tests were performed for the comparison of EMMPRIN expression between two independent groups. Survival analysis was performed to find the prognostic significance of EMMPRIN expression. RESULTS: We found that EMMPRIN expression in tongue squamous cell carcinoma is significantly higher than that in non-cancerous epithelium adjacent to carcinoma of tongue. In addition, EMMPRIN expression is significantly associated with tumor diameter and clinical stage in the samples, but did not correlate with gender, age, tumor metastasis, and pathological grade. Finally, survival analysis indicates that EMMPRIN overexpression correlates significantly with poor overall survival in the patient cohort. CONCLUSION: These results suggest that EMMPRIN might represent an attractive target for immunotherapeutic approaches in a subgroup of patients with tongue squamous cell carcinoma.

Risk factors for postoperative hemorrhage in patients with oral squamous cell carcinoma: A retrospective study.

BACKGROUND: Postoperative hemorrhage is one of the life-threatening complications of oral cancer surgery. The purpose of this study was to identify the risk factors in a large cohort. PATIENTS AND METHODS: Patients with oral squamous cell carcinoma who had received surgery were enrolled. The variables between patients with and without postoperative hemorrhage were compared using univariate and multivariate models. RESULTS: Of the 1513 patients (or 1581 cases) enrolled in the study, 34 patients suffered from postoperative hemorrhage. In the univariate analysis, cigarette, and alcohol consumption, floor of mouth tumors, T4 classified tumors, flap reconstruction, surgical site infection, and flap necrosis were risk factors for postoperative hemorrhage. In the multivariate model, flap necrosis and surgical site infection were independent risk factors for postoperative hemorrhage. CONCLUSIONS: The patients with surgical site infection or flap necrosis should be closely monitored in order to avoid postoperative hemorrhage.