Host Genetic Associations with Salivary Microbiome in Oral Cancer.

Despite the growing recognition of a host genetic effect on shaping gut microbiota composition, the genetic determinants of oral microbiota remain largely unexplored, especially in the context of oral diseases. Here, we performed a microbiome genome-wide association study in 2 independent cohorts of patients with oral squamous cell carcinoma (OSCC, n = 144 and 67) and an additional group of noncancer individuals (n = 104). Besides oral bacterial dysbiosis and signatures observed in OSCC, associations of 3 loci with the abundance of genus-level taxa and 4 loci with ß diversity measures were detected (q < 0.05) at the discovery stage. The most significant hit (rs10906082 with the genus Lachnoanaerobaculum, P = 3.55 × 10-9 at discovery stage) was replicated in a second OSCC cohort. Moreover, the other 2 taxonomical associations, rs10973953 with the genus Kingella (P = 1.38 × 10-9) and rs4721629 with the genus Parvimonas (P = 3.53 × 10-8), were suggestive in the meta-analysis combining 2 OSCC cohorts. Further pathway analysis revealed that these loci were enriched for genes in regulation of oncogenic and angiogenic responses, implicating a genetic anchor to the oral microbiome in estimation of casual relationships with OSCC. Our findings delineate the role of host genotypes in influencing the structure of oral microbial communities.

[Ultrasound-guided percutaneous transluminal angioplasty in the treatment of arteriovenous fistula immaturation: day surgery mode and clinical efficacy].

Objective: To summarize the clinical effect of ultrasound-guided percutaneous transluminal angioplasty (PTA) in the treatment of arteriovenous fistula (AVF) immaturation under day surgery mode. Methods: The clinical data was retrospective analyzed of patients with AVF immaturation who were treated by ultrasound-guided PTA under day surgery mode from November 2016 to June 2019 in Renji Hospital. The basic information, lesion location, puncture approach, number and diameter of balloon used were counted. The primary and secondary patency rates were calculated at 6 and 12 months after operation. Results: In all of the 21 patients, 11 patients were male and 10 patients were female. The mean age was (52.6±12.9) years old. There were 20 of the 21 patients who were treated successfully. One patient had AVF reconstruction with vascular rupture, and the complication rate was 4.8% (1/21). The length of hospitalization was (1.05±0.71) days, and the cost was (11 487.7±4 401.4) yuan. The follow-up time was (19.7±8.3) months. The 6-month and 12-month primary patency rate were 70% and 55%, and the 6-month and 12-month secondary patency rate were both 90%. Conclusion: Ultrasound-guided PTA in the treatment of AVF immaturation under day surgery mode is safe and effective, which has a high technical success rate and good patency rate for AVF maturation.

Toll-like receptor signalling associated with immunomodulation of umbilical cord-derived mesenchymal stem cells in mice with systemic lupus erythematosus.

With potent immunomodulatory activities, mesenchymal stem cells (MSCs) have the potential to be a beneficial treatment option for diseases with aberrant immune responses such as systemic lupus erythematosus (SLE). However, the underlying mechanisms remain largely unknown. Here, we used NZBWF1 mice as a SLE animal model to examine immunomodulation of MSCs as well as to assess the role of Toll-like receptor signalling in this circumstance. We found that mice receiving MSCs had a significant decrease in severity of proteinuria at 20 and 22 weeks of age (p = 0.009 and p = 0.022, respectively). Serum anti-dsDNA levels were significantly lower compared with the control group (p = 0.016 and p = 0.036, respectively). C3 and C4 levels were significantly higher at 22 weeks of age (p = 0.046 and p = 0.016, respectively). Altered expression of inflammation-associated cytokine profiles in the serum was also noted in mice receiving MSCs. Down-regulation of myeloid differentiation factor 88 (MyD88)-nuclear factor-κB (NF-κB) signalling in the liver was demonstrated by quantitative polymerase chain reaction, ELISA and Western blotting. In addition to demonstrating the beneficial effects of MSC treatment in NZBWF1 mice, our study provided the first evidence for the association of MyD88-NF-κB signalling and MSC-mediated immunomodulation in this disease.

[Clinical effects of expanded super-thin perforator flaps in the shoulder, neck, and chest in reconstruction of extensive burn scars in the face].

Objective: To explore the clinical effects and key techniques of expanded super-thin perforator flaps in the shoulder, neck, and chest in reconstruction of extensive burn scars in the face. Methods: From January 2008 to November 2018, 22 patients with extensive burn scars in the face were admitted to the Department of Plastic Surgery of Dongguan Kanghua Hospital and the Department of Plastic Surgery of Dermatology Hospital of Southern Medical University, with 3 males and 19 females, aged from 4 to 48 years. There were 16 cases of type Ⅱ and 6 cases of type Ⅲ in facial scars. Before the first stage of expansion surgery, Doppler blood flow survey meter or multi-slice CT was used to locate the perforator vessels. One to four expanders with rated capacity ranged from 100 to 600 mL were placed in the patients. We gave 20% to 30% of the rated capacity of expander intro-operation and common injection with 10% to 15% of the rated capacity of expander per week post-operation until the volume reached 1.5 to 2.5 times of the rated capacity of expander during the past 3 to 4 months. At the second stage of surgery, the perforators were located again before surgery with the same method. The size of defects after the excision of facial scars ranged from 6 cm×4 cm to 18 cm×16 cm. With perforators used as nutrient vessels, narrow pedicle flaps or random flaps ranging from 6 cm×6 cm to 22 cm×18 cm were elevated as rotating or advancing to reconstruct the defects. The donor sites were sutured directly. Some of the flaps needed stage Ⅲ operation for cutting the pedicle. The survival of flaps, post-operation complications, and follow-up were assessed. Results: All flaps of 22 patients survived. All the donor sites were closed simultaneously. One patient underwent an additional surgery for 5 cm×4 cm necrosis on distal part of flap caused by subcutaneous hematoma. Two patients with epidermis blister on the flaps were healed by themselves after dressing change. Due to rapid expansion, blood capillary proliferation appeared on the central part of the flap in 3 cases, after slowing down the expansion speed properly, which had no impact on flap transfer. No ischemia or venous congestion phenomenon were observed in the other flaps. During follow-up of 5 to 48 months, the flaps of patients showed no significant bloated appearance, with good complexion and texture, and even could reproduce facial fine-grained expressions naturally. Conclusions: For the reconstruction of extensive burn scars in the face, expanded super-thin perforator flaps can not only acquire large and thin flaps with high matching degree surface skin defect, but also reproduce facial fine-grained expressions. It is a simple and safe method which conforms to the facial aesthetic standard.

[Advances in diagnosis and treatment of undifferentiated pancreatic carcinoma with osteoclast-like giant cells].

Undifferentiated pancreatic carcinoma with osteoclast-like giant cell(UOC) published to date, and most have been in Asia, is a rare occurrence making up 1% of all pancreatic malignancies.With the increasing number of reported cases of the disease, the degree of awareness of the disease also gradually deepened, but there are few summary articles for the clinical features, imaging features, pathological features, treatment programs, prognosis and other aspects of UOC.Hence, this article is going to introduce pathological features, clinical manifestations, diagnosis and treatment of adjuvant advances of UOC in detail.

Polymorphism in dural arteriovenous fistula: matrix metalloproteinase-2-1306 C/T as a potential risk factor for sinus thrombosis.

Essentials Sinus thrombosis may play a crucial role in development of dural arteriovenous fistula (DAVF). Little is known about the association between gene polymorphism and the development of DAVF. MMP-2-1306 C/T showed a higher prevalence rate in DAVF cases with sinus thrombosis. MMP-2-1306C/T polymorphism is likely a potential risk factor for sinus thrombosis in DAVF. SUMMARY: Background Dural arteriovenous fistula (DAVF) is a rare but important cerebrovascular disorder in adults. Little is known about the molecular genetic pathogenesis underlying DAVF development. Objectives To investigate the associations of gene polymorphisms and DAVF. Materials and Methods By the use of real-time PCR genotyping, seven single-nucleotide polymorphisms (SNPs) of angiogenesis-related genes were analyzed in 72 DAVF patients. Pertinent clinical and imaging data were subgrouped on the basis of location (cavernous sinus versus lateral sinus), lesions (single versus multiple), cerebral venous reflux (CVR) grading (Borden I versus Borden II/III), and sinus thrombosis (with versus without). Results We found that individuals carrying the polymorphic allele of matrix metalloproteinase (MMP)-2-1306 C/T (rs243865) had a significantly increased risk of sinus thrombosis in DAVF (odds ratio 6.2; 95% confidence interval 1.7-22.9). There was a weak difference in associations of tissue inhibitor of metalloproteinase (TIMP)-2 (rs2277698) gene polymorphism and DAVF patients subgrouped by CVR grading. Conclusions These preliminary results indicate that MMP-2-1306 C/T, but not MMP-9, TIMP-1, TIMP-2, and vascular endothelial growth factor A SNP variants, is a risk factor for the development of sinus thrombosis in DAVF patients.

Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer.

Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene- rs920778, rs1899663, rs4759314, and rs12427129-were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non-betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non-betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.

[Gradient treatment of acute superior mesenteric venous thrombosis: clinical analysis of 68 cases].

Objective: To investigate the effect of Gradient treatment for acute superior mesenteric venous thrombosis (ASMVT). Methods: Clinic data of 68 patients of ASMVT admitted in Department of General Surgery, Jinling Hospital, Medical School of Nanjing University from January 2009 to December 2014 were analyzed retrospectively. There were 50 male and 18 female patients with a mean age of (45±12) years. These patients were conducted by the stepwise treatment model (endovascular treatment-damage control surgery-surgical intensive care-intestinal rehabilitation treatment). Clinical outcomes and complications were compared during the follow-up period. Differences about bowel resection length of endovascular treatment and surgical procedures were evaluated with t test. Results: In the 68 cases, 24 cases were cured simply by endovascular treatment, 19 cases received surgical procedures alone (group surgery). Twenty-five patients received endovascular treatment combined with surgical procedures (group combined), including 6 cases temporary abdominal closure. The overall mortality rate was 2.9% (2/68) during hospitalization. The range of bowel resection of group combined significantly reduced compared with group surgery ((92±14) cm vs. (162±27) cm, t=-2.377, P=0.022). During 1-year follow-up period, 4 cases suffered from short bowel syndrome, whom underwent surgery alone. Conclusions: Early diagnosis and treatment is the key to treatment of ASMVT, the rapid improvement of intestinal ischemia is particularly important for prognosis. Combination therapy significantly save more residual small intestine and avoid short bowel syndrome. The selection of early gradient treatment can significantly reduce the mortality and improve the prognosis of ASMVT patients.

Nicotinamide Facilitates Mesenchymal Stem Cell Differentiation Into Insulin-Producing Cells and Homing to Pancreas in Diabetic Mice.

OBJECTIVE: This study aimed to investigate the effect of nicotinamide on differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) in vivo in mice and on homing of MSCs to the pancreas after being intravenously infused. METHODS: Streptozotocin (STZ)-induced diabetic Balb/c mice received syngeneic transplantation of carboxyfluorescein succinimidyl ester (CFSE)-labeled bone marrow MSCs into the liver or tail vein. Nicotinamide was intraperitoneally injected into mice at a dose of 500 mg/kg body weight per day after STZ administration. Mice who received saline solution injection instead of nicotinamide were involved as control. RESULTS: Mice that received nicotinamide injection showed lower blood glucose, higher serum insulin, and more improved glucose tolerance compared with the control group. Immunohistochemistry analysis showed that higher levels of insulin staining and higher percentages of CFSE+/insulin+ cells were observed in the liver and pancreas sections of mice who received nicotinamide injection compared with the control group. The percentage of CFSE+/insulin+ cells was positively correlated with serum insulin level. Real-time polymerase chain reaction results showed that the implanted MSCs in mice who received nicotinamide injection exhibited higher levels of ß-cell-related gene expression than the control group. More CFSE-labeled MSCs appeared in the pancreas of mice who received nicotinamide injection compared with the control group after being intravenously infused, whereas the amount of CFSE-labeled MSCs in the liver was not affected by nicotinamide injection. CONCLUSIONS: Nicotinamide facilitates MSCs differentiating into functional IPCs in vivo in diabetic mice and promotes intravenously infused MSCs to home to the pancreas.

Glucose-induced microRNA-17 promotes pancreatic beta cell proliferation through down-regulation of Menin.

OBJECTIVE: Menin, encoded by the Men1 gene, is responsible for ß-cell tumor formation in patients with multiple endocrine neoplasia type 1. Recently, Menin has been proven to negatively regulate ß-cell proliferation in several mouse models, including hyperglycemia. However, it is unclear how glucose regulates Menin expression in ß-cells. MATERIALS AND METHODS: In the present study, quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect the expression levels of MicroRNAs in Min-6 cells treated with high glucose, in which we found that miR-17 was significantly up-regulated. RESULTS: Further studies using bioinformatic prediction, luciferase and protein expression analysis suggested that miR-17 could inhibit protein levels of Menin through targeting its 3'-untranslated region. CONCLUSIONS: Our results indicate that miR-17 might serve as an important intracellular target of glucose to mediate the mitogenic effect that glucose exerts in pancreatic ß-cells.

Gene expression profiling analysis reveals weaning-induced cell cycle arrest and apoptosis in the small intestine of pigs.

In swine production, weaning is a critical event for porcine weaning-associated disease, such as postweaning stress syndrome, which involves intestinal dysfunction. However, little is known about the molecular mechanisms of intestinal dysfunction in pigs during weaning. To gain new insight into the interaction between weaning stress and intestinal function, 4 pigs at 25 d of age for each of the weaning and the suckling groups for a total of 40 pigs were used to analyze changes in the genomic expression in the intestines of weaned pigs by microarray analysis. Four hundred forty-five genes showed altered expression after weaning treatment (286 upregulated and 159 downregulated) at the cutoff criteria of the fold change ≥1.5 or <0.67 and P < 0.05. Most of these altered genes are cellular process related and regulators that may be involved in biological regulation, developmental processes, and metabolic processes. A keen interest was paid in deciphering expression changes in apoptosis or cell cycle control genes. The altered genomic expression of 8 selected genes related to the cell cycle process was confirmed by quantitative real-time PCR. Of the 8 genes tested, increased (P < 0.05) expression of genes involved in apoptosis (cytochrome c, somatic, and ataxia telangiectasia mutated), pro-inflammatory signals (tumor necrosis factor and NO synthases 2), and a transcription factor (nuclear factor of activated T cells, cytoplasmic, and calcineurin-dependent 2) were detected in weaned pigs compared with suckling pigs, but the expression of cell cycle control-related genes, such as E2F transcription factor 5-like, was lower (P < 0.05) in weaned pigs than suckling pigs. Weaned pigs also showed increased interleukin 8 expression and decreased SMAD family member 4 expression although no significant differences (P > 0.05) were observed when compared with the suckling pigs. These selected genes likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation. The results of this study provide a basis for understanding the molecular pathogenesis of weaning treatment.

Regulation of N-acetyl cysteine on gut redox status and major microbiota in weaned piglets.

This study was conducted to explore the regulation of N-acetyl cysteine (NAC) on gut redox status and proliferation of selected microbiota in weaned piglets. A total of 150 newborn piglets from 15 litters were randomly divided by litter to the control group (normally suckling), the weaning group (fed the basal diet), and the NAC group (basal + NAC diet) with 5 litters per group. Activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and inhibition capacity of hydroxyl radical (IHR), and contents of malondialdehyde (MDA), H2O2, and NO in the ileum, colon, and cecum were analyzed to profile oxidative stress states. The real-time absolute quantitative PCR reaction was employed to quantify the amounts of total bacteria, Lactobacillus, Bifidobacterium, and Escherichia coli. The N-acetyl cysteine, as a universal antioxidant, was used to improve the redox status. Results showed that weaning stress resulted in the occurrence of gut oxidative stress and changes of gut microbiota (P < 0.05). Compared with the weaned piglets, the activities of ileal, colonic, and cecal T-AOC; ileal and colonic GSH-Px; cecal SOD; and colonic and cecal IHR were enhanced (P < 0.05), and the concentrations of ileal and cecal H2O2, ileal and colonic NO, and colonic MDA were reduced (P < 0.05) in the NAC-treated piglets. An increase (P < 0.05) in gut Lactobacillus and Bifidobacterium, accompanied with a decrease (P < 0.05) in Escherichia coli counts, was also observed in the NAC group. Bivariate correlation indicated that Lactobacillus and Bifidobacterium were positively correlated (P < 0.05) with the activities of T-AOC, GSH-Px, and SOD and inversely related (P < 0.05) to increased levels of H2O2, NO, OH, and MDA, and Escherichia coli showed a strong positive association (P < 0.05) with increased levels of free radicals and MDA and a negative association (P < 0.05) with the activities of antioxidant enzymes in intestines of weaned piglets. We concluded that NAC constructively regulated on the changes of the gut redox status and microbiota in piglets in response to weaning stress. The observed correlations implied that the NAC effects on the gut microbiota were confirmed, partly through an effect on oxidative stress in piglets, providing evidence that gut microbiota may be potentially improved by the modulation of the redox status by an antioxidant, which has relevance for gut health and function.

Low/negative expression of DDX3 might predict poor prognosis in non-smoker patients with oral cancer.

OBJECTIVE: DDX3 has diverse biological functions in translation control, cell growth regulation, and tumor progression. Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide with a poor clinical prognosis. The impact of DDX3 expression in OSCC is seldom discussed. MATERIALS AND METHODS: Tumor tissues and adjacent normal tissues were obtained from 324 patients with OSCC. In this study, we used immunohistochemical staining methods to investigate the associations between DDX3 expression and the clinicopathological characteristics of OSCC. RESULTS: Low/negative DDX3 expression in tumor cells was significantly associated OSCC patient characteristics including male gender (P < 0.001), smoking (P < 0.001), alcohol consumption (P < 0.001), betel quid chewing (P = 0.002), poor relapse-free survival (P = 0.001), and poor overall survival (OS) (P = 0.001). Patients with low/negative DDX3 expression, and particularly non-smoker OSCC patients, had significantly worse OS as defined by the log-rank test (P = 0.020 for all cases; P = 0.008 for non-smoker patients). In non-smoker patients with OSCC, low/negative DDX3 expression in tumor cells was associated with poor prognosis (P = 0.024) and a 3.802-fold higher death risk, as determined by Cox regression. CONCLUSIONS: Low/negative DDX3 expression in tumor cells was significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in non-smoker patients with OSCC.

Sclerotherapy for the mucoceles of the anterior lingual salivary glands with pingyangmycin.

Recurrence is very common if the mucoceles of the anterior lingual salivary glands (ALSGs) are treated by surgery due to its anatomic characteristics. Therefore, more effective and less invasive treatment methods are urgently required to be applied instead of surgery. In this study, 40 patients with the mucocele of the ALSGs received the intralesional injections of pingyangmycin, and the median number of injections per patient was 2.075 (range, 1-3). All cases completely recovered with no recurrence after follow-up of more than 16 months. The complications included the local swelling, pain, and ulceration following injection, and all these symptoms resolved 7-10 days after the injection. Taken together, sclerotherapy with pingyangmycin is an effective and safe treatment method for the mucocele of the ALSGs and may be the primary treatment modality.

A PC-based laparoscopic surgery skills training and assessment system.

The purpose of this study is to build a cost-effective and easy-to-popularize laparoscopic training system based on improving traditional training box. The system has the capability of objective skills assessment and the function of automatic recording of training process and results, as well as 3-dimensional coordinate tracking of instruments. The results of pilot experiment in laparoscopic-assisted grip skill assessment had been shown the system can assess the different grip ability level between the senior surgeons and junior residents. Regarding to the evaluation of training effectiveness, five subjects without laparoscopic surgery experiences were asked to perform grip training for five days to observe their training curves. According to the experimental results, the total time taken for subject 1 to subject 5 are improved by 54.9%, 52.0%, 60.6%, 23.3%, and 63.5% separately.

Human lung cancer cell line SPC-A1 contains cells with characteristics of cancer stem cells.

Cancer stem cells (CSCs) play important roles in occurrence, development, recurrence and metastasis of cancer. Isolation and identification of CSCs have been performed from some cancer tissues or cells. In this paper, human lung adenocarcinoma stem cells were induced and isolated from SPC-A1 cells and their characteristics were determined. SPC-A1 cells were cultured in serum-free medium and epidermal growth factor and basic fibroblast growth factor were added into the medium to induce the formation of multicellular tumor spheroids. The results showed that floating multicellular tumor spheroids (named pulmospheres) were formed 5-10 d after the induction of SPC-A1 cells. Real-time PCR analysis showed that in the pulmospheres, the marker of bronchioalveolar stem cells, Clara cell secretary protein and the marker of AT2 cells, alveolar surfactant protein C were highly expressed. Furthermore, such embryonic stem cell markers as octamer-binding transcription factor 4 (OCT-4), Bmi-1, and thyroid transcription factor -1 (TTF-1) were also highly expressed. Some miRNAs as hsa-miR-126, hsa-miR-145, hsa-let-7g, hsa-let-7d, hsa-let-7c, hsa-let-7e and hsa-miR-98, which were lowly expressed in SPC-A1 cells, were not expressed in the pulmospheres. Cell cycle analysis showed that 94.29 % of the pulmosphere cells were in G1 stages. Further study showed that these cells possessed higher proliferation and invasion activity than SPC-A1 cells. Tumorigenicity activity experiments on BALB/c nude mice showed that 1 × 103 of the pulmosphere cells could form tumors with similar pathological features with lung adenocarcinoma. In conclusion, lung adenocarcinoma stem cells were enriched in the pulmosphere cells and were with high tumorigenicity.

Role of lipocalin 2 and its complex with matrix metalloproteinase-9 in oral cancer.

OBJECTIVES: Recent evidence demonstrated that lipocalin (LCN)2 is induced in many types of human cancer, while the detection of its complex with matrix metalloproteinase (MMP)-9 is correlated with the cancer disease status. We attempted to evaluate plasma expressions of LCN2, MMP-9, and their complex (LCN2/MMP-9) during the diagnostic work-up of patients with oral squamous cell carcinoma (OSCC) and investigated their correlations with disease progression. METHODS: In total, 195 patients with OSCC and 81 healthy controls were recruited. Expression levels of LCN2, MMP-9, and LCN2/MMP-9 were determined with immunoenzymatic assays. RESULTS: Patients with OSCC exhibited significantly higher levels of LCN2, MMP-9, and LCN2/MMP-9 compared with healthy controls (LCN2: P < 0.001; MMP-9: P < 0.001; LCN2/MMP-9: P < 0.01). Plasma levels of LCN2, MMP-9, and LCN2/MMP-9 in patients with OSCC were significantly correlated with each other and were associated with more-advanced clinical stages (P < 0.05) and/or a larger tumor size (P < 0.05), but were not associated with positive lymph-node metastasis or distal metastasis. CONCLUSION: Our results suggest that plasma levels of LCN2 and the LCN2/MMP-9 complex may be useful in non-invasively monitoring OSCC progression, while supporting their potential role as biomarkers of oral cancer disease status.

Survivin SNP-carcinogen interactions in oral cancer.

UNLABELLED: In Taiwan, oral cancer is causally associated with environmental carcinogens. Survivin is an anti-apoptotic protein and is generally considered a marker of malignancy. The current study explored the combined effect of survivin gene polymorphisms and environmental carcinogens on the risk and clinico-pathological development of oral cancer. Five single-nucleotide polymorphisms (SNPs) of survivin genes from 439 male patients with oral cancer and 424 male control participants (who did not have cancer) were analyzed. The survivin -31GG, +9194 GG, and +9809 TT homozygotes exhibited higher risk for oral cancer compared with the corresponding ancestral genotype, after adjustment for related confounders. The survivin -31, +9194, and +9809 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. The distribution frequency of the -31 G: +9194 A: +9809 T haplotype was significantly higher in oral cancer patients than in control participants. These results suggest that survivin gene polymorphisms and their interactions with environmental carcinogens may increase susceptibility to oral cancer in Taiwanese men. ABBREVIATIONS: AOR, adjusted odds ratio; CI, confidence intervals; PCR, polymerase chain-reaction; SNP, single-nucleotide polymorphisms.

Impact of interleukin-8 gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan.

OBJECTIVES: Interleukin-8 (IL-8), which is an angiogenic chemokine with a high expression level in tumor tissues, plays important roles in developing many human malignancies including oral squamous cell carcinoma (OSCC). This study was designed to examine the association of IL-8 gene polymorphisms with the susceptibility and clinicopathological characteristics of OSCC. METHODS: A total of 270 patients with OSCC and 350 healthy control subjects were recruited. Four single nucleotide polymorphisms (SNPs) of IL-8 genes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis. RESULTS: Results showed that four IL-8 SNPs (-251 T/A, +781 C/T, +1633 C/T, and +2767 A/T) were not associated with oral cancer susceptibility as well as clinicopathological parameters. But among 345 smokers, IL-8 polymorphisms carriers with betel quid chewing were found to have a 17.41- to 23.14-fold risk to have oral cancer compared to IL-8 wild-type carriers without betel quid chewing. Among 262 betel quid chewers, IL-8 polymorphisms carriers with smoking have a 10.54- to 20.44-fold risk to have oral cancer compared to those who carried wild type without smoking. CONCLUSIONS: Our results suggest that the combination of IL-8 gene polymorphisms and environmental carcinogens might be highly related to the risk of oral cancer.