C-kit is a trans-membrane receptor tyrosine kinase (RTK) encoded by the proto-oncogene KIT located at 4q11-12. Gain-of-function mutations arising to c-kit activation independent of its ligand were observed in various tumors related to germ cells, mast cells, and interstitial cells of Cajal. C-kit also participates in melanocyte development; hence, its involvement in oral mucosal melanoma (OMM) tumorigenesis was investigated. Immunohistochemistry and mutation analysis were performed using 18 cases of human primary OMM. Results revealed 16 cases positive to c-kit protein. Atypical melanocytes expressed c-kit. All in situ components expressed c-kit, but only four cases exhibited intense expression in the invasive component. Missense mutations were observed in four cases, and two of those correlated with increased protein expression. C-kit expression in atypical melanocytes suggests the role of c-kit in the early stage of OMM tumorigenesis. C-kit protein expression correlated with activating mutations indicating the pertinent role of the proto-oncogene KIT in the tumorigenesis of OMM.

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Nitric oxide (NO) has been implicated to play a role in the pathogenesis of depressive disorders. Adrenomedullin (AM) induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of NO. AM immune reactivity is present in the brain, consistent with a role as neurotransmitter. Therefore, it is suggested that these two molecules may play a role together in the brain. We aimed to examine AM and NO in bipolar affective disorder (BPAD). Forty-four patients with BPAD and 21 healthy control subjects were included in this study. DSM-IV diagnosis of bipolar affective disorder (type I, manic episodes) was independently established by two psychiatrists and the Turkish version of the Bech-Rafaelson Mania Scale was administered. Also, a semistructured form was used to ascertain several sociodemographic and clinical variables of the patients. AM and NO were studied in plasma. The mean value of plasma NO levels in the BPAD group of 46.58 ± 13.97 µmol/l was significantly higher than that of controls (31.81 ± 8.14 µmol/l) (z = –4.15, p = 0.000). Mean plasma AM levels were found to be increased in patients with BPAD (35.13 ± 5.26 pmol/l) compared to controls (16.22 ± 3.02 pmol/l) (z = –6.16, p = 0.000). AM levels of BPAD patients were approximately 2-fold higher than controls. AM levels were positively correlated with the duration of hospitalization for the current episode and negatively correlated with the total duration of illness. Both NO and AM may have a pathophysiological role in BPAD (type I, manic episodes) and the clinical symptomatology and prognosis of BPAD.

We analysed the loss of heterozygosity (LOH) of long arm of chromosome 2 by using 16 polymorphic microsatellite markers in 39 matched oral normal and cancer tissues, and defined the deletional mapping of the region with putative tumor suppressor genes. LOH was detected at least one location in 33 of 39 (85%) tumor tissues. Frequent deletions were detected at the locations of microsatellite markers, D2S2304 (35%), D2S111 (40%), D2S155 (35%), D2S1327 (29%), D2S164 (29%), D2S125 (68%) and D2S140 (32%). Three preferentially deleted regions at 2q21-24, 2q33-35 and 2q37.3 were observed. Several candidate tumor suppressor genes in these regions such as LRP1B, CASP8, CASP10, BARD1, ILKAP, PPP1R7, and ING5, are located. Further molecular analysis of each gene should be performed to clarify their roles in oral carcinogenesis.

The aim of the present study was to compare the effectiveness of four different laser wavelengths (660, 810, 980, and 1,064 nm) used for low-level laser therapy (LLLT) on the healing of mucositis in an animal model of wound healing by investigating the expression of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), and blood-derived fibroblast growth factor (bFGF). Thirty-five male Wistar albino rats with a weight of 250-300 g body mass and 5 months old were used in the study. All animals were intraperitoneally injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tip of an 18-gauge needle was used in order to develop a superficial scratching on the left cheek pouch mucosa by dragging twice in a linear movement on third and fifth days. After ulcerative mucositis were clinically detected on the animals' left cheek pouch mucosa, the laser therapy was started. Four different laser wavelengths (660 nm, HELBO, Bredent; 810 nm, Fotona XD, Fotona; 980 nm, ARC Fox; and 1,064 nm, Fidelis Plus 3, Fotona) used for LLLT at ED 8 J/cm(2) daily from the first to the fourth days. Oval excisional biopsy was taken from the site of the wound, and the expression of PDGF, TGF-β, and bFGF was evaluated. The obtained data were analyzed by one2-way ANOVA, and then Tukey HSD tests were used for pairwise comparisons among groups (α = 0.05). The one-way ANOVA test indicated that expression values of the growth factors, PDGF and bFGF, were significantly affected by irradiation of different wavelengths of lasers (p < 0.001). However, expression value of the TGF-β was not affected by irradiation of different wavelengths of lasers (p > 0.05). The highest PDGF expression was detected in neodymium-doped yttrium aluminum garnet (Nd:YAG) laser group (p < 0.05), and there were no statistically significant differences among the other groups (p > 0.05). The highest bFGF expression was detected in 980-nm diode and Nd:YAG laser groups (p < 0.05), and there were no statistically significant differences among the other groups (p > 0.05). These findings suggest that low-level Nd:YAG and 980-nm diode laser therapy accelerate the wound healing process by changing the expression of PDGF and bFGF genes responsible for the stimulation of the cell proliferation and fibroblast growth.

Our previous study showed high frequency of allelic loss at chromosome 2q37 region in oral cancer. This location contains several candidate tumor suppressor genes such as PPP1R7, ILKAP, DTYMK and ING5. We previously showed 3 members of inhibitor of growth (ING) family, ING1, ING3 and ING4 as tumor suppressor gene in head and neck cancer. As ING5 shows high homology with other members of ING genes including highly conserved carboxy-terminal plant homeodomain and nuclear localization signal, we first picked up ING5 and examined it as a possible tumor suppressor in oral cancer. For this aim, mutation and mRNA expression status of ING5 in paired normal and oral squamous cell carcinoma samples were examined by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. Three missense mutations located within leucine zipper like (LZL) finger and novel conserved region (NCR) domains in ING5 protein were detected, probably abrogating its normal function. We also found 5 different alternative splicing variants of ING5. Then, we examined mRNA level of ING5 by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) analysis, which demonstrated decreased expression of ING5 mRNA in 61% of the primary tumors as compared to the matched normal samples. In conclusion, tumor-specific mutation and downregulation of ING5 mRNA suggested it as a tumor suppressor gene in oral squamous cell carcinoma.Oral and oropharyngeal squamous cell carcinoma is the 6th most frequently occurring cancer worldwide, with $400,000 new cases diagnosed each year. 1 Similar to other type of cancer, oral squamous cell carcinoma (OSCC) is the result of accumulation of multiple genetic events in the cell. Among these events, inactivation of tumor suppressor genes (TSG) is considered to be an important step in carcinogenesis. Thus, localization and identification of TSG are of great interest for a better comprehension of cancer and development of molecular diagnostics as well as therapies.TSG are referred as genetic elements with negative influence on cell proliferation and growth. 2 Inactivation of TSG causes cells to display one or more phenotypes of neoplastic growth. Knudson's definition of a classical TSG requires inactivation of both alleles of a candidate gene in tumors. 3 Inactivation of these classical TSG usually occurs through deletion of one of its allele and mutation in the rest of the allele. However, a new class of TSG with haploid insufficiency, in which one allele is lost and the remaining allele is haploinsufficient, has been described recently, and these hemizygous TSG show a tumor-prone phenotype when challenged with carcinogens. 4,5 One of the critical steps for the identification of TSG is loss of heterozygosity (LOH) analysis. By using LOH analysis, we recently showed high frequency of allelic loss on chromosomes 13q34, 7q31 and 12p13 in oral, and head and neck cancer. Our continuous effort for detailed analysis of these regions resulted in identification of various inhibitor of growth (ING) tumor s...

Our findings suggest a metastasis model proposing accumulation of a subtype of cancer cells with high metastatic capacity within heterogenous primary tumor cell population.

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. Material and Methods: In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. Results: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. Conclusions: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues.