Serial values of hematologic variables and deep venous thrombosis: Red cell distribution width is associated with deep venous thrombosis

Abstract Introduction As 30 to 50% of deep venous thrombosis (DVT) cases remain idiopathic, an increased focus on hematologic variables may therefore reveal novel correlates of DVT. Very few studies have investigated the association of hematological parameters with DVT and the causal relationship between them is still to be elucidated. Therefore, we aimed to investigate the association between serial values of hematologic variables and DVT. Methods Complete blood count parameters were serially measured at baseline and then at approximately 3-month intervals for 12 months in 152 adults with the first episode of DVT and 152 age- and sex-matched controls. The odds ratio (OR) with the 95% confidence interval (95%CI) was calculated as a measure of association between hematological parameters and DVT. Results The red cell distribution width (RDW) was the only hematologic variable which showed an independent and consistent association with DVT at all time points (multivariable-adjusted OR [95%CI] 3.38 [1.28 - 8.91] at baseline, 2.24 [0.85 - 5.92] at 3 months and 2.12 [0.81 - 5.55] at 12 months for RDW > 14.0%). This association was higher for provoked DVT than unprovoked DVT and for DVT plus pulmonary embolism than DVT alone. No significant correlation was found between the high RDW and classical thrombotic risk factors, except malignancy. Conclusions We demonstrated an independent and consistent association of the high RDW with the first episode of DVT in adult patients. The study was probably underpowered to evaluate the association between the high RDW and recurrent DVT. Further large studies with long follow-up are needed to confirm this association.

Over Expression of Cancer Stem Cell Marker CD44 and Its Clinical Significance in Patients with Oral Squamous Cell Carcinoma.

Cancer stem cell marker CD44 is a cell-surface glycoprotein which is involved in various cellular functions such as cell-cell interactions, cell adhesion, haematopoiesis and tumour metastasis. The CD44 gene transcription is partly activated by beta-catenin and Wnt signalling pathway, the later pathway being linked to tumour development. However, the role of CD44 in oral squamous cell carcinoma (OSCC) is not well understood. We investigated the expression of CD44 in peripheral circulation, tumour tissues of oral cancer patients and oral squamous cell carcinoma cell lines by ELISA and quantitative (q)-RTPCR. Relative CD44s mRNA expression was significantly higher in peripheral circulation (p = 0.04), tumour tissues (p = 0.049) and in oral cancer cell lines (SCC4, SCC25 p = 0.02, SCC9 p = 0.03). Circulating CD44total protein levels were also significantly (p < 0.001) higher in OSCC patients that positively correlated with increasing tumour load and loco-regional spread of the tumour. The circulating tumour stem cell marker CD44 appears to be a potent indicator of tumour progression and may be useful for developing suitable therapeutics strategies for patients with oral squamous cell carcinoma.

Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma-A Review.

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The current review provides a detailed overview of the strategies, targets, and candidates for therapeutic vaccination in HNSCC. The classical principle of inducing a potent, antigen-specific, cell-mediated cytotoxicity targeting a specific tumor antigen seems to be the most effective mechanism of therapeutic vaccination, particularly against the human papilloma virus positive subset of HNSCC. However, approaches such as countering the immunosuppressive tumor microenvironment of HNSCC and immune co-stimulatory mechanisms have also been explored recently, with encouraging results.

Serial values of hematologic variables and deep venous thrombosis: Red cell distribution width is associated with deep venous thrombosis.

INTRODUCTION: As 30 to 50% of deep venous thrombosis (DVT) cases remain idiopathic, an increased focus on hematologic variables may therefore reveal novel correlates of DVT. Very few studies have investigated the association of hematological parameters with DVT and the causal relationship between them is still to be elucidated. Therefore, we aimed to investigate the association between serial values of hematologic variables and DVT. METHODS: Complete blood count parameters were serially measured at baseline and then at approximately 3-month intervals for 12 months in 152 adults with the first episode of DVT and 152 age- and sex-matched controls. The odds ratio (OR) with the 95% confidence interval (95%CI) was calculated as a measure of association between hematological parameters and DVT. RESULTS: The red cell distribution width (RDW) was the only hematologic variable which showed an independent and consistent association with DVT at all time points (multivariable-adjusted OR [95%CI] 3.38 [1.28 - 8.91] at baseline, 2.24 [0.85 - 5.92] at 3 months and 2.12 [0.81 - 5.55] at 12 months for RDW > 14.0%). This association was higher for provoked DVT than unprovoked DVT and for DVT plus pulmonary embolism than DVT alone. No significant correlation was found between the high RDW and classical thrombotic risk factors, except malignancy. CONCLUSIONS: We demonstrated an independent and consistent association of the high RDW with the first episode of DVT in adult patients. The study was probably underpowered to evaluate the association between the high RDW and recurrent DVT. Further large studies with long follow-up are needed to confirm this association.

Serum Survivin in Oral Submucosal Fibrosis and Squamous Cell Carcinoma.

Survivin, an inhibitor of apoptosis protein is a biomarker of significance in prognostication of many malignancies. In the current study we investigated the serum survivin levels in patients with oral submucosal fibrosis (OSMF) and squamous cell carcinoma (OSCC). Serum was isolated from, peripheral blood collected of clinically and histopathologically confirmed OSMF and OSCC patients. Circulating level of survivin was measured in patients and control subjects by ELISA and analyzed further using Kruskal-Wallis test and two-sample Wilcoxon rank-sum (Mann-Whitney) test. Serum Survivin levels were significantly reduced in the OSCC group as compared to the control group. No significant correlation was noted between the serum survivin level and various clinicopathological characteristics of OSCC and OSMF patients. Our study suggests that free, wild form of circulating survivin probably has no role in predicting the prognosis of oral cancer or the malignant transformation potential of oral submucosal fibrosis.

The Holistic Review on Occurrence, Biology, Diagnosis, and Treatment of Oral Squamous Cell Carcinoma.

A prevalent head and neck cancer type is oral squamous cell carcinoma (OSCC). It is widespread and associated with a high death rate of around 50% in some regions of the world. We discuss the likelihood of developing OSCC and the impact of age in this review. Prior to examining the vast array of diagnostic indicators, a brief explanation of the biology of the disease is addressed. Finally, the therapeutic strategies for OSCC are listed. The complete literature for this study was compiled by searching Google Scholar and PubMed using the terms "OSCC," "oral squamous cell carcinoma," "diagnosis of OSCC," "oral cancer," and "biomarkers and OSCC." The research finds that OSCC has several critical parameters with a lot of room for additional in-depth study.

Cinnamomum zeylanicum Extract and its Bioactive Component Cinnamaldehyde Show Anti-Tumor Effects via Inhibition of Multiple Cellular Pathways.

Cinnamomum zeylanicum is a tropical plant with traditional medicinal significance that possesses antimicrobial, antifungal, anti-parasitic, and anti-tumor properties. Here, we have elucidated the anti-tumor effects of Cinnamomum zeylanicum extract (CZE) and its bioactive compound cinnamaldehyde (CIN) on oral cancer and elucidated underlying molecular mechanisms. Anti-tumor activities of CZE and CIN were demonstrated by various in vitro experiments on oral cancer cells (SCC-4, SCC-9, SCC-25). The cell proliferation, growth, cell cycle arrest, apoptosis, and autophagy were analyzed by MTT, clonogenic assay, propidium iodide, annexin-V-PI, DAPI, and acridine orange staining, respectively. The binding affinity of CIN towards dihydrofolate reductase and p38-MAP kinase alpha was analyzed by molecular docking. Western blot assay was performed to assess the alteration in the expression of various proteins. CZE and CIN treatment significantly inhibited the growth and proliferation of oral cancer cells in a dose-dependent manner. These treatments further induced apoptosis, cell cycle arrest, and autophagy. CZE and CIN inhibited the invasion and cytoplasmic translocation of NF-κB in these cell lines. CIN showed a high affinity to MAP kinase P38 alpha and dihydrofolate reductase with binding affinities of -6.8 and -5.9 kcal/mol, respectively. The cancer cells showed a decreased expression of various PI3k-AKT-mTOR pathways related to VEGF, COX-2, Bcl-2, NF-κB, and proteins post-treatment.

Circulating Vimentin Over-Expression in Patients with Oral Sub Mucosal Fibrosis and Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common (90%) types of oral carcinomas in the world. It is the 2nd most common and 3rd deadliest cancer in India. The lack of early detection marker is one of the major causes of worst prognosis. The vimentin belongs to intermediate filament family proteins which plays significant role in maintaining cellular integrity. Over-expression of vimentin has been widely reported in many epithelial cancers however the information regarding its prevalence in the oral cancers still needs further scientific intervention. The expression level of circulating vimentin protein in serum samples (n = 30) of oral submucous fibrosis (OSMF), OSCC patients and healthy controls were measured by performing ELISA. The serum level of vimentin was significantly higher in OSMF (p < 0.01) and OSCC (p < 0.003) patients as compared to healthy subjects. The circulating vimentin levels showed a gradual increase with increasing disease status (normal < OSMF < OSCC). Circulatory levels of vimentin may ba useful indicator of disease progression and as a suitable target for therapeutic intervention of oral submucous fibrosis and oral carcinoma.

Drug repurposing for breast cancer therapy: Old weapon for new battle.

Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed.

Epoxyazadiradione exhibit activities in head and neck squamous cell carcinoma by targeting multiple pathways.

The head and neck squamous cell carcinoma (HNSCC) constitute about 90% of all head and neck cancers. HNSCC falls in the top 10 cancers in men globally. Epoxyazadiradione (EPA) and Azadiradione (AZA) are the limonoids derived from the medicinal plant Azadirachta indica (popularly known as Neem). Whether or not the limonoids exhibit activities against HNSCC and the associated mechanism remains elusive. Herein, we demonstrate that EPA exhibits stronger activity in HNSCC in comparison to AZA. The limonoids obeyed the Lipinski's rule of 5. EPA exhibited activities in a variety of HNSCC lines like suppression of the proliferation and the induction of apoptosis. The limonoid suppressed the level of proteins associated with anti-apoptosis (survivin, Bcl-2, Bcl-xL), proliferation (cyclin D1), and invasion (MMP-9). Further, the expression of proapoptotic Bax and caspase-9 cleavage was induced by the limonoid. Exposure of EPA induced reactive oxygen species (ROS) generation in the FaDu cells. N-acetyl-L-cysteine (ROS scavenger) abrogated the down-regulation of tumorigenic proteins caused by EPA exposure. EPA induced NOX-5 while suppressing the expression of programmed death-ligand 1 (PD-L1). Further, hydrogen peroxide induced NF-κB-p65 nuclear translocation and EPA inhibited the translocation. Finally, EPA modulated the expression of lncRNAs in HNSCC lines. Overall, these results have shown that EPA exhibit activities against HNSCC by targeting multiple cancer related signalling molecules. Currently, we are evaluating the efficacy of this molecule in mice models.

Clinico-pathological peculiarities of human papilloma virus driven head and neck squamous cell carcinoma: A comprehensive update.

AIMS: The current article provides a detailed account of the current understanding of molecular and clinico-pathological aspects of Human papilloma virus (HPV) driven head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The literature review included most of the landmark trials and clinical studies related to the HPV driven HNSCC. KEY FINDINGS: HPV positive HNSCC differ distinctly from HPV negative tobacco-related HNSCC, especially in oropharyngeal region. Therefore, the American joint committee on cancer`s latest manual for classification and staging of cancer suggests a separate staging system for HPV positive oropharyngeal cancers. Despite the younger patients being affected and the high propensity for cervical metastasis, the HPV positive oropharyngeal cancers respond much better to the treatment. The association with wild type TP53 and low EGFR expression confers the favorable prognosis in HPV driven HNSCC. Since the association is not universal, we suggest checking for p53 and EGFR expression status before considering de-intensification of therapy. In addition, the presence of matted lymph nodes and five or more nodes could mean relatively poorer prognosis, and are not suitable for de-intensification of therapy. The same is also true probably with higher T stage and co-existing tobacco use. The methods for the detection of p16, HPV DNA, HPV E6/E7 mRNA, anti-E6/E7 antibodies, in tissue, in serum and in saliva of patients, along with their clinical implications are also discussed. SIGNIFICANCE: This article provides latest developments on the HPV driven HNSCC. 'Diagnosis of transcriptionally active HPV infection,' 'Modalities for surveillance,' 'Implication of de-escalation of therapy' are some of the critical issues that could serve the medical, the research as well as the patient communities.

Targeted disruption of PI3K/Akt/mTOR signaling pathway, via PI3K inhibitors, promotes growth inhibitory effects in oral cancer cells.

PURPOSE: The phosphoinositide-3-kinase (PI3K) pathway is the frequently altered in human cancer. This has led to the development and study of novel PI3K inhibitors for targeted therapy and also to overcome resistance to radiotherapy. METHOD: The anti-tumour effects of PI3K inhibitors (PI-828, PI-103 and PX-866) in terms of cell proliferation, colony formation, induction of apoptosis, cell cycle arrest, invasion, autophagy, and pNF-κB/p65 translocation in SCC-4, SCC-9 and SCC-25 cells were studied by performing MTT, clonogenic, DAPI staining, propidium iodide staining, annexin-V binding, matrigel invasion, acridine orange staining and immuno-fluorescence assay. Western blot assay was performed to assess the alteration in the expression of various proteins. RESULT: PI-828 and PI-103 treatment exhibited dose-dependent inhibition of growth and proliferation of OSCC cells with a concomitant induction of apoptosis, altered cell cycle regulation and decreased invasiveness (p < 0.01). PX-866 induced apoptosis, cell cycle arrest, autophagy and a significant decrease in the invasiveness of oral cancer cells as compared to untreated cells (p < 0.01). These compounds significantly reduced expression of COX-2, cyclin-D1 and VEGF in the treated cells besides cytoplasmic accumulation of pNF-κB/p65 protein. In addition to PI3Kα, inactivation of downstream components, i.e. Akt and mTOR was seen. CONCLUSION: PI3K inhibitors such as PI-103, PI-828 and PX-866 may be developed as potential therapeutic agents for effective treatment of oral squamous cell carcinoma (OSCC) patients, associated with activated PI3K/Akt pathway.

Inflammation, a Double-Edge Sword for Cancer and Other Age-Related Diseases.

Increasing evidence from diverse sources during the past several years has indicated that long-term, low level, chronic inflammation mediates several chronic diseases including cancer, arthritis, obesity, diabetes, cardiovascular diseases, and neurological diseases. The inflammatory molecules and transcription factors, adhesion molecules, AP-1, chemokines, C-reactive protein (CRP), cyclooxygenase (COX)-2, interleukins (ILs), 5-lipooxygenase (5-LOX), matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) are molecular links between inflammation and chronic diseases. Thus, suppression of inflammatory molecules could be potential strategy for the prevention and therapy of chronic diseases. The currently available drugs against chronic diseases are highly expensive, minimally effective and produce several side effects when taken for long period of time. The focus of this review is to discuss the potential of nutraceuticals derived from "Mother Nature" such as apigenin, catechins, curcumin, ellagic acid, emodin, epigallocatechin gallate, escin, fisetin, flavopiridol, genistein, isoliquiritigenin, kaempferol, mangostin, morin, myricetin, naringenin, resveratrol, silymarin, vitexin, and xanthohumol in suppression of these inflammatory pathways. Thus, these nutraceuticals offer potential in preventing or delaying the onset of chronic diseases. We provide evidence for the potential of these nutraceuticals from pre-clinical and clinical studies.

Dynamics of regulatory T cells (Tregs ) in patients with oral squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The immune dysfunction in oral squamous cell carcinoma (OSCC) patients is one of the major factors for growth and dissemination of tumor affecting disease-free survival. METHODS: The phenotypic and functional characteristics of Regulatory T (Treg ) CD4+ CD25+ FoxP3+ subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-ß) by Western blot and qRT-PCR. RESULTS: An increased (P < 0.05) prevalence of Treg phenotypes (CD4+ CD25+ , CD4+ FoxP3+ , CD8+ FoxP3+ , CD4+ CD25+ FoxP3+ ) was observed in the peripheral circulation of OSCC patients that positively correlated with clinicopathological features. The increased frequency of CD4+ CD8+ CD25+ FoxP3+ , a unique T cell subset, CTLA-4+ , GITR+ , NrP1+ , HLA-DR+ , CD127+ , Tbet+ , TGF-ß+ , and granzyme B+ (GzmB) Tregs also showed a significantly higher prevalence in OSCC patients. Functionally, CD4+ FoxP3+ Tregs showed skewed expression of IL-2, IL-10, and IL-35 in patients as compared with the normal controls. Further, enhanced expression of CCR5 and CCR7 on Tregs with up regulation of their ligands (CCL5, CCL19, and CCL21) in tumor cells indicates efficient recruitment and trafficking of Tregs to the tumor site. CONCLUSION: It seems reasonable to assume that modulation of functional dynamics of selective Treg subsets may be useful in developing immunotherapeutic strategy for OSCC patients.

Operculina turpethum extract inhibits growth and proliferation by inhibiting NF-κB, COX-2 and cyclin D1 and induces apoptosis by up regulating P53 in oral cancer cells.

OBJECTIVES: Herbal drugs are popularly emerging as complementary and alternative medicines in cancer patients because of their cost effectiveness and minimal side-effects. The extract of Operculina turpethum (OT) is known to have antipyretic, anti-inflammatory and purgative properties. Since it is popularly known have antiinflammatory activity, we investigated its anti-tumor activity on four oral squamous cell carcinoma cell lines (OSCC) namely, (SCC-4, KB, SCC-9 and SCC-25). DESIGN: Antitumor activities of Operculina turpathum extract (OTE) was investigated by MTT and clonogenic assay, effect on cell cycle and apoptosis induction by Annexin-V/propidium iodide (PI) staining and flow cytometry and invasive potential of the tumor was determined by matrigel assay. The expression of various proteins involved in these mechanisms was analysed by western blotting. RESULTS: OTE specifically inhibited the growth and colony formation of OSCC cells in a dose-dependent manner via inhibiting NF-κB and its downstream target COX-2. It further arrested cell cycle at G0/G1 phase by inhibiting cyclin-D1 and induced early apoptosis by up-regulating P53 in OSCC cells. It also limits the invasion capacity of OSCC cells by up to 55-60%. CONCLUSIONS: OTE shows antitumor activities in OSCC cells by inhibiting NF-κB, COX-2 and cyclin D1 and upregulation of p53 expression. It may be developed as a safe and promising alternative chemopreventive/chemotherapeutic agent for oral cancer.

6-Gingerol Mediates its Anti Tumor Activities in Human Oral and Cervical Cancer Cell Lines through Apoptosis and Cell Cycle Arrest.

6-Gingerol, a potent nutraceutical, has been shown to have antitumor activity in different tumors, although its mechanism of action is not well understood. In this study, we evaluated antitumor activities of 6-gingerol on human oral (SCC4, KB) and cervical cancer (HeLa) cell lines with or without wortmannin, rapamycin, and cisplatin. Tumor cell proliferation was observed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt assay, cell cycle analysis by propidium iodide labeling and flow cytometry, apoptosis by Annexin-V binding assay, and caspase activity by chemiluminescence assay. 6-Gingerol showed dose-dependent cytotoxicity in all three cell lines. Combinations of 6-gingerol with wortmannin and cisplatin showed additive effects, while with rapamycin, it showed 50% cytotoxicity that was equivalent to IC50 of 6-gingerol alone. Treatment with 6-gingerol resulted in G2-phase arrest in KB and HeLa cells and S-phase arrest in SCC4 cells. 6-Gingerol, wortmannin, and rapamycin treatment showed almost two-fold higher expression of caspase 3 in all cell lines. The results imply that 6-gingerol either alone or in combination with PI-3 K inhibitor and cisplatin may provide better therapeutic effects in oral and cervical carcinoma. Thus, 6-gingerol appears to be a safe and potent chemotherapeutic/chemopreventive compound acting through cell cycle arrest and induction of apoptosis in human oral and cervical tumor cells.

Garcinol inhibits tumour cell proliferation, angiogenesis, cell cycle progression and induces apoptosis via NF-κB inhibition in oral cancer.

Garcinol, a polyisoprenylated benzophenone is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Its ability to inhibit tumour growth has been demonstrated in certain cancers. In this study, we evaluated the potential anti-tumour effects of garcinol on oral squamous cell carcinoma (OSCC) cells. Three OSCC cell lines (SCC-4, SCC-9 and SCC-25) were treated with garcinol for 48 h and its effect on growth and proliferation, clonogenic survival, cell cycle and apoptosis was studied by MTT, clonogenic assay, propidium iodide (PI) staining and annexin-V binding assay, respectively. The alteration in expression of NF-κB and COX-2 was studied by western blot analysis and that of VEGF by ELISA. Garcinol treatment significantly (p < 0.001) inhibited the growth and proliferation and colony formation of OSCC cells with a concomitant induction of apoptosis and cell cycle arrest. It did not show toxic effect on normal cells. It significantly (p < 0.05) reduced the expression of NK-κB and COX-2 expression in treated cells as compared to untreated controls besides inhibiting VEGF expression. It appears that garcinol exerts anti-proliferative, pro-apoptotic, cell-cycle regulatory and anti-angiogenic effects on oral cancer cells through inhibition of NF-κB and COX-2. Thus, garcinol may be developed as a potential chemopreventive and/or chemotherapeutic agent for treatment of oral squamous cell carcinoma.

Galectin-1 and galectin-3: plausible tumour markers for oral squamous cell carcinoma and suitable targets for screening high-risk population.

BACKGROUND: Galectins are a family of carbohydrate binding proteins that regulate several cellular functions such as growth, migration, adhesion and apoptosis. METHODS: We investigated the expression of galectin (gal)-1 and galectin (gal)-3 in patients with oral squamous cell carcinoma (OSCC) and observed their effects on growth and survival of OSCC cell lines. RESULTS: OSCC patients expressed significantly higher levels of gal-1 and gal-3 in circulation (p<0.0001) and at the tumour sites (p<0.01) as compared to controls. Patients with higher tumour load showed significantly higher expression of both galectins than those with lower tumour load. In ROC analysis, serum levels of gal-1 and gal-3 at cut-off values of 4.875 and 0.871ng/ml respectively, discriminated between healthy subjects and patients with more than 80% sensitivity and specificity. Similarly, logistic regression analysis revealed about 3-times higher risk of OSCC in subjects over expressing these proteins. Further, exogenous gal-1 and gal-3 significantly increased survival, proliferation and angiogenesis in OSCC cell lines. CONCLUSIONS: Serum levels of gal-1 and gal-3 may serve as plausible markers for oral squamous cell carcinoma and may be useful in screening population at a higher risk.

Expression of vascular endothelial growth factor (VEGF) in patients with oral squamous cell carcinoma and its clinical significance.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an important angiogenic cytokine that plays an important role in growth, development and progression of the tumour. We investigated expression of VEGF in oral cancer patients and its effect on proliferation of OSCC cell lines. METHODS: Cell and tissue expression of VEGF was determined by qRT-PCR, western blot and immunofluorescence assay while serum level of VEGF was determined by ELISA. Tumour cell proliferation was assessed by MTT assay. RESULTS: Serum VEGF levels were significantly higher in oral cancer patients (p<0.0001) as compared to normal controls that further showed an increasing trend with clinical stage and lymph node involvement. In ROC analysis serum VEGF level distinguished between patients and normal subjects with a higher sensitivity (65.71%) and specificity (66.67%). It was significantly upregulated in tumour tissues and in OSCC cell lines. Exogenous VEGF treatment significantly enhanced proliferation of SCC-4 and SCC-9 cell lines. CONCLUSION: It seems therefore that serum VEGF level may be a reliable biomarker and may be a potential target for development of chemopreventive and chemotherapeutic strategies for patients with tobacco-related oral carcinoma.