Research progress of biomineralization for the diagnosis and treatment of malignant tumors.

Malignant tumors have long been a prominent subject of research in order to foster innovation and advancement in diagnostic and therapeutic modalities. However, the current clinical treatment of malignant tumors faces significant limitations. In light of recent advancements, the World Health Organization (WHO) officially designated malignant tumors as a chronic disease in 2006. Accordingly, maintaining the tumor in a stable state and minimizing its detrimental impact on the body emerges as a potentially advantageous approach to oncological treatment. One emerging strategy that has garnered substantial attention from the academic community is the construction of a biomineralized layer surrounding solid tumors for tumor blockade therapy. This innovative approach is regarded as safe, effective, and long-lasting. This review aims to provide a comprehensive summary of the advancements made in the utilization of biomineralization for the diagnosis and treatment of malignant tumors.

Oral Microbiota from Periodontitis Promote Oral Squamous Cell Carcinoma Development via γδ T Cell Activation.

Oral squamous cell carcinoma (OSCC) is a fatal disease, and periodontitis is associated with OSCC development. However, the pathogenesis in the context of OSCC with periodontitis has not been fully understood. Here, we demonstrated that periodontitis promoted OSCC development, accompanied by alterations in the oral bacterial community and the tumor immune microenvironment. The oral microbiota from periodontitis maintained the dominant position throughout the whole process of OSCC with periodontitis, of which Porphyromonas was the most abundant genus. The oral microbiota from periodontitis could activate interleukin-17-positive (IL-17+) γδ T cells directly. The activated γδ T cells were necessary for the IL-17/signal transducer and activator of transcription 3 (STAT3) pathway and promoted M2-tumor-associated macrophage (TAM) infiltration in OSCC proliferation. Our data provide insight into the carcinogenesis of OSCC with periodontitis by outlining the tumor-associated immune response shaped by the oral microbiota from periodontitis. Thus, oral commensal bacteria and IL-17+ γδ T cells might be potential targets for monitoring and treating OSCC. IMPORTANCE The work reveals the role of the oral microbiota from periodontitis in carcinogenesis. Furthermore, our study provides insight into the pathogenesis of OSCC with periodontitis by outlining the tumor-associated immune response shaped by the oral microbiota from periodontitis, which might identify new research and intervention targets for OSCC with periodontitis.

An implant-supported overdenture for a mandibular defect after tumor resection guided by 3-dimensional finite element analysis: A clinical report.

This clinical report describes the rehabilitation of a mandibular defect after tumor resection with an implant-supported overdenture and the attachment selection as guided by 3-dimensional finite element analysis. Autologous bone grafting was declined by the patient who demanded the restoration of lateral appearance and mastication function. Three implants were placed based on the condition of the bone, and a satisfactory definitive prosthesis was provided that corresponded with the results of the finite element analysis.

Case of primary extracranial meningioma of the maxillary sinus presenting as buccal swelling associated with headache: A case report.

BACKGROUND: Meningiomas are benign tumors that originate from the meningothelial arachnoid cells, but they rarely develop extracranially. There is no specific surgical guideline for resecting them in the maxillary sinus, and little is known about their biological behavior and operative management. CASE SUMMARY: We present a 54-year-old female patient referred to our department with a primary extracranial meningioma that presented as buccal swelling associated with headache. On clinical examination the mass was non-tender, fixed, sessile and non-pulsatile situating in the right maxillary sinus. Computed tomography scan showed a well-defined mass of 7 cm × 6 cm × 6 cm compressing the surrounding structures. Magnetic resonance imaging revealed a well circumscribed heterogenous lesion with necrotic center and relatively hypointense on T2-weighted imaging. Imaging studies revealed no evidence of intracranial extension and metastatic nests. Biopsy showed grade I primary extracranial with low mitotic activity. Total maxillectomy with excision of tumor and adjacent paranasal structures following reconstruction of the orbit and maxilla with tissue patch was done by the maxillofacial surgeon. The biopsy reported fibrous meningioma based on the hematoxylin and eosin section. On immunohistochemistry the tumor cells were positive for vimentin, focally positive for epithelial membrane antigen and CD99 and negative for signal transducer and activator of transcription 6. The mass was removed surgically with reconstruction, and the pathological studies confirmed the diagnosis to be an extracranial meningioma. The present study briefly reviews the current knowledge concerning the diagnosis and treatment of extracranial meningiomas in the head and neck area and offers suggestions for managing extracranial meningiomas in the paranasal sinuses. CONCLUSION: To conclude, extracranial meningiomas in the paranasal sinuses may be successfully managed by surgical treatment without evident post-surgery complications.

Reconstruction of an Extensive Maxillofacial Avulsion Injury Caused by Bear Attack With a Double-Island Anterolateral Thigh Free Flap.

ABSTRACT: Bear attack, a relatively rare cause of maxillofacial trauma, could lead to severe facial deformity as well as functional impairment. A 45-year-old male ranger was attacked by a bear and suffered an extensive maxillofacial avulsion injury, resulting in massive soft tissue loss (17.5 × 10 cm 2 ) on his left temporal-facial region with an intraoral defect (3 × 2 cm 2 ), surrounded by pus and necrotic tissue. Computed tomography revealed a comminuted fracture of the mandible, as well as bone defects in the left zygomatic bone, zygomatic arch, and part of the lateral orbital wall. in contrast with tumor resection, this large defect wound resulting from trauma was an infected wound with extensive loss of soft tissue and bone, which presented many operational challenges. The initial goal was to control local infection and then repair the maxillofacial and intraoral defects simultaneously. The left oral mucosal lining and maxillofacial skin after infection control were repaired by transposition of a double-island anterolateral thigh flap, and the fractured mandible was fixed, achieving primary closure for the reconstruction of large soft and hard tissue injuries in the oral and maxillofacial region. Five months postoperatively, the flap had healed and the patient was satisfied with the profile. This patient demonstrated how a rare severe injury caused by a bear attack was treated by preliminary closure of an extremely large post-traumatic oral and maxillofacial defect. The authors recommend the 1 pedi- cled double-island free anterolateral thigh flap as a worthwhile choice for the reconstruction of complicated oral and maxillofacial tissue defects combined with an intraoral defect. To our knowledge, this is the largest clinical application reported to date of an anterolateral thigh flap (approximately 200 cm 2 ) for a post-traumatic oral and maxillofacial defect.

Synchronous Reconstruction of the Jaw Using a "One and a Half"-Barrel Fibular Bone Graft for Ossifying Fibroma Patients.

BACKGROUND: Ossifying fibroma is one of the common benign tumors that affect the appearance and functions of the jaw. Ossifying fibroma may exhibit a wide range of biological behaviors, leading to deformities involving the jaw and other secondary facial deformities. Hence, to improve the function of the jaw and the patient's general facial appearance (bearing in mind each patient's facial shape and, or appearance), the authors thus, however, used a ''one and a half"-barrel fibular bone graft to achieve the ideal height and radian of the bone graft. CASE PRESENTATION: Between July 2017 and January 2021, the authors retrospectively collected and analyzed clinical and surgical data from 39 patients who had undergone operations in our hospital. Twenty patients were operated on using our new surgical method, whereas 19 patients received conventional or debulking operation. Clinical factors associated with the operation were assessed, including classification of the jaw defects, perioperative complications, and postoperative outcomes. RESULTS: All the flaps ultimately survived. According to the postoperative satisfaction survey, patients who underwent reconstruction were satisfied with their postoperative facial appearance, with an average of 8.5 out of 10. Based on the preoperative clinical data, 26 patients had suitable bone grafts for dentures to improve their oral function. CONCLUSIONS: A ''one and a half''-barrel fibular bone graft effectively improves the facial appearance of patients and as well as provides an appropriate height and radian for the bone graft.

Sentinel lymph node biopsy versus elective neck dissection in squamous cell carcinoma of the oral cavity with a clinically N0 neck: Systematic review and meta-analysis of prospective studies.

Sentinel lymph node biopsy (SLNB) is an emerging strategy for managing early-stage oral squamous cell carcinoma (SCC) with a clinically N0 (cN0) neck. However, the role of SLNB in this scenario is debatable. Herein, relevant literature was systematically reviewed, and a meta-analysis was performed to evaluate the potential dividends of SLNB compared to elective neck dissection (END) for these patients. The meta-analysis, including six prospective studies, showed comparable results of the two management strategies in terms of regional recurrence (risk ratio [RR] = 0.99; 95% confidence interval [CI], 0.58-1.70), 5-year disease-free survival (RR = 0.99; 95% CI, 0.87-1.11), and 5-year overall survival (RR = 1.01; 95% CI, 0.90-1.13). Fewer adverse events occurred in the SLNB arm than in the END arm (RR = 0.12; 95% CI, 0.02-0.70). Overall, SLNB results in as favorable an oncologic prognosis for patients with cN0 oral SCC as END, while significantly lessening side effects and unnecessary surgeries.

Advances of adipose-derived mesenchymal stem cells-based biomaterial scaffolds for oral and maxillofacial tissue engineering.

The management of oral and maxillofacial tissue defects caused by tumors, trauma, and congenital or acquired deformities has been a major challenge for surgeons over the last few decades. Autologous tissue transplantation, the gold standard of tissue reconstruction, is a valid method for repairing the oral and maxillofacial functions and aesthetics. However, several limitations hinder its clinical applications including complications of donor sites, limited tissue volume, and uncertain long-term outcomes. Adipose-derived mesenchymal stem cells (ADMSCs) widely exist in adipose tissue and can be easily obtained through liposuction. Like the bone marrow-derived mesenchymal stem cells (BMSCs), ADMSCs also have the multi-pluripotent potencies to differentiate into osteoblasts, chondrocytes, neurons, and myocytes. Therefore, the multilineage capacity of ADMSCs makes them valuable for cell-based medical therapies. In recent years, researchers have developed many candidates of ADMSCs-based biomaterial scaffolds to cater for the needs of oral and maxillofacial tissue engineering due to their superior performance. This review presents the advances and applications of ADMSCs-based biomaterial scaffolds, and explores their tissue engineering prospects in oral and maxillofacial reconstructions.

Nanotechnology-based drug delivery systems for enhanced diagnosis and therapy of oral cancer.

Oral cancer is a common malignant life-threatening tumor. Despite some advances in traditional therapy, mortality and mobidity rates are high due to delayed diagnosis and ineffective treatment. Additionally, some patients inevitably suffer from various fatal adverse effects during the course of therapy. Therefore, it is imperative to develop novel methods to eradicate oral cancer cells with minimal adverse effects on normal cells. Nanotechnology is a promising and novel vehicle for the diagnosis and treatment of oral cancer with encouraging recent achievements. In this review, we present state-of-the-art nanotechnology-based drug delivery systems employed in the domain of oral cancer, especially for its enhanced diagnosis and therapy. We describe in detail the types of nanotechnology used in the management of oral cancer and summarize administration routes of nanodrugs. Finally, the potential and prospects of nanotechnology-based drug delivery systems as promising modalities of diagnosis and therapy of oral cancer are highlighted.

Effects of inducing apoptosis and inhibiting proliferation of siRNA on polyadenylate-binding protein-interacting protein 1 in tongue cell carcinoma.

BACKGROUND: It has been reported that the polyadenylate-binding protein-interacting protein 1 (PAIP1) pathway is closely connected with the progression of some malignant tumors. Here we examined the potential functional mechanism of PAIP1 in tongue squamous cell carcinoma (TSCC). METHODS: PAIP1 was knocked down in TSCC cell lines and proliferation and apoptosis in vitro analyzed. The molecular features of TSCC were determined using quantitative proteome and succinylome analyses. The results were confirmed in the mouse model. RESULTS: PAIP1 promoted cell proliferation and inhibited apoptosis. Its knockdown decreased Ki67 and Pcna expressions and increased Bax/Bcl2 index and Caspase-3 expression. Bioinformatics analysis for proteomics revealed that PAIP1 knockdown correlated with the changes in differential protein expression. CONCLUSIONS: Upregulation of PAIP1 induces cell proliferation and inhibits apoptosis in TSCC; PAIP1 might be a diagnostic biomarker and a significant drug target.

The stress hormone norepinephrine promotes tumor progression through ß2-adrenoreceptors in oral cancer.

OBJECTIVE: Chronic stress hormone norepinephrine (NE) has been previously reported to play a role in the development of cancer, but the correlation between NE and oral squamous cell carcinoma (OSCC) progression is not well understood. METHOD: To address this, the expression of adrenergic receptors (ARs) in human OSCC cell lines and clinic OSCC samples was detected, and the role of NEin vivo and in vitro was further investigated. RESULTS: It was found that ß2-AR was the main AR of NE in OSCC. Stimulation of OSCC cells with NE significantly increased the OSCC proliferation and invasion, which was, however, blocked by ß2-AR inhibitor. NE could induce the phosphorylation of extracellular regulated protein kinases (ERK) and cAMP-response element binding protein (CREB). Inhibition of ERK and CREB pathway abrogated NE-induced OSCC invasion and proliferation. NE could enhance cancer stem cells (CSCs)-like phenotype and up-regulate the expression of stemness marker. In tumor-bearing nude mice, it was found that consecutive administration of NE significantly promoted the tumor growth, while daily injection of ß2-AR inhibitor blocked this phenomenon. CONCLUSIONS: Those findings indicated a critical role of the chronic stress hormone NE in OSCC progression. Inhibition of ß2-AR may serve as a potential therapeutic strategy for protecting OSCC patients from chronic stress related deleterious effect.

A novel CPC composite cement reinforced by dopamine coated SCPP fibers with improved physicochemical and biological properties.

Traditional CPC cements have attracted wide attentions in repairing bone defects for injectability, easy plasticity and good osseointegration. However, its further application was limited by poor mechanical properties, long setting time and unsatisfactory biocompatibility. To solve these problems, polydopamine (DOPA) coated strontium-doped calcium polyphosphate (SCPP) fibers were added into CPC cements for the first time. A doping amount at fiber weight fraction of 0%, 1%, 2% and 5% was designed to develop a multifunctional composite fitting for bone tissues' regeneration and reconstruction and the optimum amount was selected through subsequent physicochemical and biological characterizations. The results implied DOPA coating successfully formed stable connections between SCPP fibers and CPC matrix, which simultaneously reinforced biomechanical strength and tenacity (5% SCPP/D/CPC samples exhibited more prominent mechanical property than others). In addition, 5% D/SCPP fibers doped composite cements were characterized as markedly-improved cytocompatibility: Sr2+ introduction induced cytoactive and significantly accelerated proliferation, attachment and spreading of osteoblasts. Besides, it also stimulated the secretion of OT, Col-I and ALP from seeded MG63, which was a critical character for further inducing osteogenic process, mineralization and bone tissues formation. The promoted cytocompatibility and improved osteogenesis-related growth factors' secretion could be attributed to constant and controllable release of Sr2+ and this deduction was approved by ICP analysis. In addition, Sr doping made this novel cement had a potential efficacy to inhibit aseptic loosening. In a word, present studies all demonstrated 5% SCPP/D/CPC composites could be a potential candidate material employed in bone regeneration and reconstruction for excellent mechanical property and cytocompatibility.

Double-Layer Microsphere Incorporated with Strontium Doped Calcium Polyphosphate Scaffold for Bone Regeneration.

To design and prepare a novel controlled release system for sustained release of two drugs. In this study, a double-layer microsphere was incorporated with strontium-doped calcium polyphosphate (SCPP) scaffold to facilitate bone regeneration and achieve skull repair. The double-layer microsphere combining tetracycline loaded sodium alginate and matrix metalloproteinase-2 (MMP-2) loaded chitosan was manufactured by electrospinning, which were further adhered to SCPP scaffold. The characteristics of microstructure were observed through scanning electron microscope. Loading efficiencies and the optimal ratio of microsphere of the obtained controlled release system were investigated. In addition, the cytotoxicity and the effects on osteoblast proliferation and expressions of osteogenesis-related factors were examined in vitro. Thereafter, the compound material with the controlled release system was implanted in the skull defect of rabbit to evaluate its properties of promoting bone regeneration. The results indicated that this novel controlled release system with SCPP scaffold and the double-layer microspheres loaded with tetracycline and MMP-2 could be a promising material for bones repair.

Enhanced Osteoconductivity and Osseointegration in Calcium Polyphosphate Bioceramic Scaffold via Lithium Doping for Bone Regeneration.

Calcium polyphosphate (CPP) is a novel bioceramic bone substitute, which is favored because its composition is highly similar to natural bone. According to previous studies, doping ions into CPP is an effective and convenient method for overcoming the shortcomings, such as poor osteoconductivity of CPP. Lithium (Li) is a fairly new additive to bone substitutes that brought attention due to its role in osteogenesis. The present study was conducted to assess whether doping Li into CPP could influence the microstructure, degradation, and osteoinductivity of CPP. The results found that both CPP and Li-doped CPP (LiCPP) had a single beta-CPP phase, indicating that Li did not affect the crystallized phase. SEM images revealed that both scaffolds were porous, while the surface of LiCPP was rougher and more uneven compared to CPP. Also, a better degradation property of LiCPP was observed via weight loss and ion release tests. In vitro study found that LiCPP extracts had advantages of promoting osteoblasts' proliferation and differentiation over CPP extracts. In vivo study on rabbit's cranial defects was also conducted. Microcomputed tomography and histological staining showed that LiCPP had better osteoconductivity than CPP. This study proved that doping Li into CPP is a feasible modification method, and LiCPP might be a suitable bioceramic for bone tissue engineering.

Elective Neck Dissection Versus Observation in Squamous Cell Carcinoma of Oral Cavity With Clinically N0 Neck: A Systematic Review and Meta-Analysis of Prospective Studies.

PURPOSE: To assess the possible benefits of elective neck dissection (END) in patients with squamous cell carcinoma (SCC) of the oral cavity and clinically N0 neck. MATERIALS AND METHODS: Medline, Embase, the China National Knowledge Infrastructure, and the Wan Fang Database were systematically searched. A meta-analysis was performed to evaluate the possible benefits of END to such patients. RESULTS: Six prospective studies involving 865 patients fulfilled the inclusion criteria. Meta-analysis of all included studies showed that END substantially lowered the risk of regional recurrences (risk ratio [RR] = 0.27; 95% confidence interval [CI], 0.21-0.36) in the fixed-effect model compared with observation only. Three of the 6 included studies showed that the specific death rate related to regional recurrences was lower in the END group than in the observation group in the fixed-effect model (RR = 0.35; 95% CI, 0.19-0.65). The mean metastasis rate of occult cervical lymph node was 30.27% (standard deviation, 9.42%). When the fixed-effect model was applied, 4 of the 6 included studies showed less recurrence in the END group compared with the observation group (RR = 0.53; 95% CI, 0.44-0.64). CONCLUSIONS: END substantially decreases recurrences and deaths related to regional recurrences in early-stage SCC of the oral cavity with clinically N0 neck, especially SCC of the oral tongue and floor of the mouth, which is necessary for such patients.

Introducing copper and collagen (via poly(DOPA)) coating to activate inert ceramic scaffolds for excellent angiogenic and osteogenic capacity.

Traditional calcium polyphosphate (CPP) scaffolds have attracted wide attention for repairing bone defects owing to their low cytotoxicity and controllable degradation. However, because of poor mechanical strength, significant brittleness and suboptimal osteoinductivity and osteoconductivity, their further clinical applications are restricted. To overcome these limitations, collagen (Col) coated Cu(ii) ion-doped calcium polyphosphate (CCPP) scaffolds were employed and dopamine (DOPA) was used as a linkage (CCPP/D/Col) to ensure their stable and tight structure. Controllable Cu(ii) ion continuously released from scaffolds together with collagen coating could simultaneously enhance the cytocompatibility, compressive strength and ductility, bone-related gene expression and new bone regeneration. In comparison with the initial CPP specimens, these multifunctional CCPP/D/Col composite scaffolds' crystal grains of CCPP were arranged regularly and well-ordered, and the size and rugosity were more suitable for cell spreading and attachment. Murine bone marrow stem cells (BMSCs) seeded on CCPP/D/Col scaffolds possessed better proliferation and migration, rapid attachment and enhanced expression of osteogenic-related genes, which indicated better bone regeneration. The potential mechanism of this process was further elucidated. Both copper doping and collagen coating could effectively stabilize hypoxia-inducible factor-1α (HIF-1α) that thus stimulates the expression of vascular endothelial growth factor (VEGF). In addition, they could also promote the osteogenic differentiation of cells through stimulating bone-related gene expression. The concept of introducing active ions and biological macromolecules to modify inert ceramics may offer a new strategy to construct a multifunctional composite scaffold for bone tissue regeneration.

Synergistic effect of wire bending and salivary pH on surface properties and mechanical properties of orthodontic stainless steel archwires.

BACKGROUND: The aim of this study was to investigate the corrosive behaviour of stainless steel archwires in a more clinically relevant way by bending and exposing to various pH. METHODS: One hundred and twenty pieces of rectangular stainless steel wires (0.43 × 0.64 mm) were randomly assigned into four groups. In each group, there were 15 pieces of bent wires and 15 straight ones. Prior to measurements of the wires, as individual experimental groups (group 1, 2, and 3), the wires were exposed to artificial saliva for 4 weeks at pH 5.6, 6.6, and 7.6, respectively. A control group of wires (group 4) remained in air for the same period of time before sent for measurements. Surface roughness (Ra-value) was measured by a profilometer. Young's modulus and maximum force were determined by a four-point flexural test apparatus. Scanning electron microscopy was used to observe the surface morphology of straight wire. Differences between groups were examined using a two-way analysis of variance (ANOVA). RESULTS: Mean surface roughness values, flexural Young's moduli, and maximum force values of bent wires are significantly different from those of the straight wires, which was the main effect of wire bending, ignoring the influence of pH. A significant effect was found between Ra-values regarding the main effect of pH, ignoring the influence of shape. There was a significant interaction effect of bending and pH on flexural Young's moduli of stainless steel archwires, while pH did not show much impact on the maximum force values of those stainless steel wires. Bigger surface irregularities were seen on SEM images of straight wires immersed in artificial saliva at pH 5.6 compared to artificial saliva at other pH values. Surface depth (Rz) was more sensitive than Ra in revealing surface roughness, both measured from 3D reconstructed SEM images. Ra showed a comparable result of surface roughness to Ra-value measured by the profilometer. CONCLUSIONS: Bending has a significant influence on surface roughness and mechanical properties of rectangular SS archwires. pH plays a synergistic effect on the change of mechanical properties of stainless steel (SS) wires along with wire bending.

Chronic stress promotes oral cancer growth and angiogenesis with increased circulating catecholamine and glucocorticoid levels in a mouse model.

OBJECTIVES: Chronic stress was previously reported to play a role in the development of oral cancer, yet the correlation between stressors and oral cancer progression is not well understood. MATERIALS AND METHODS: We implanted human oral cancer cell line CAL 27 in nude mice to investigate the effects of chronic stress on tumor growth, and designed a physical restraint system to create an experimentally stressed animal model, in which periodic immobilization induced characteristic chronic stress. Tumor burdened animal were randomly assigned into four groups: (a) control group, (b) daily stress for 2h with light, (c) daily stress for 2h in dark, and (d) daily stress for 6h with light. Animals were sacrificed after three weeks. Various analyses were performed on parameters including body weight, tumor weight, in situ expression of MMP-2 and VEGF, and the plasma concentrations of epinephrine, norepinephrine and glucocorticoid. RESULTS AND CONCLUSION: Our data showed that chronic stress resulted in greater tumor size, more expression of MMP-2 and VEGF, higher level of plasma catecholamines, and more invasive growth of oral carcinoma cells in a mice model. We have successfully set up an animal model, which studied the effect of chronic stress on oral carcinoma growth rate and progression. These data further suggested that catecholamine and glucocorticoid might stimulate tumor progression under chronic stress.

Association of increased circulating catecholamine and glucocorticoid levels with risk of psychological problems in oral neoplasm patients.

BACKGROUND: Noradrenergic pathways and glucocorticoid-mediated signal pathways have been implicated in the growth and progression of oral cancer. Patients with oral neoplasms can have high psychological distress levels, but the effects of stress-related hormones on oral neoplasm growth are unknown. METHODS: We have investigated the relationships between pre-surgical measurements of psychological problems with Symptom Checklist-90-revised Inventory (SCL90-R), tumor histology, circulating blood catecholamine and glucocorticoid levels among 75 oral neoplasm patients, including 40 oral cancer patients and 35 benign oral tumor patients. RESULTS: The results showed that most dimension scores of SCL90-R did not show a significant difference between the two groups except depression (p = 0.0201) and obsessive-compulsion (p = 0.0093), with the scores for these symptoms being higher among oral cancer group versus the benign oral tumor group. The differences of total score, average score and other monomial factor scores were not statistically significant. The mean concentrations of catecholamine and glucocorticoid in peripheral blood of the oral cancer group were higher than those in benign oral tumor group (p<0.01). We also examined whether associations observed between biobehavioral measures and circulating blood catecholamine and glucocorticoid levels extended to other compartments in the oral cancer group. CONCLUSIONS: These findings suggest that stress hormones may affect oral cancer behavior by influencing the tumor micro-environment though the circulating blood.