The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase (<it>MMP</it>) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of <it>MMP-1 </it>and <it>MMP-3 </it>with susceptibility to oral squamous cell carcinoma (OSCC).</p> <p>Methods</p> <p>We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of <it>MMP-1 </it>and <it>MMP-3</it>.</p> <p>Results</p> <p>The frequency of the <it>MMP-1 </it>2G allele was higher and that of the 1G homozygote was lower in the OSCC cases (<it>p </it>= 0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47-fold) risk of OSCC (95%CI 1.47–4.14, <it>p </it>= 0.0006), and those carrying the <it>MMP-1 </it>2G allele had a 2.30-fold risk (95%CI 1.15–4.58, <it>p </it>= 0.018), indicating independent involvement of these factors in OSCC. One of the key discoveries of this research is the apparent reduction of the <it>MMP-1 </it>1G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.</p> <p>Conclusion</p> <p>Since the 2G allele is a majority of the <it>MMP-1 </it>genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the <it>MMP-1 </it>2G allele in the early onset OSCC.</p

Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma.

Therapeutic drug monitoring (TDM) is used in certain clinically selected cases and in research settings to optimize the response to antiretroviral therapy. Plasma of blood is commonly used for TDM, but blood sampling is invasive and at risk for transmission of infectious agents. On the other hand, saliva sampling is noninvasive, safe, cheap, and easily performed compared to blood. Dolutegravir (DTG) is now widely prescribed as a key component of antiretroviral therapy for HIV infection. In this study, we examined the relationship between DTG concentrations in plasma and saliva of treated patients to explore the possibility of using saliva as an alternative body fluid of TDM. A total of 17 pairs of blood and saliva samples were obtained from 15 consented HIV-1-infected subjects treated with DTG containing regimens for more than one month. Both blood and saliva samples were collected within 1 h of each other. Drug concentrations were determined by liquid chromatography-tandem mass spectrometry using DTG-d5 as an internal standard. The LLOQ was 0.5 ng/mL. The calibration curves were prepared with pooled plasma or saliva containing DTG in a range of 0.5-100 ng/mL with precision of <14.4% and accuracy within ±14.7%. The DTG concentrations in the plasma and saliva were significantly correlated (Pearson's correlation coefficient r = 0.76, p < 0.001). The median ratio of the drug concentration in saliva to those in plasma was 0.0056, which is close to the rate of non-protein-bound DTG in plasma (0.70%), suggesting that only free DTG in plasma is transported to the salivary glands and secreted into saliva. The present study demonstrates that DTG concentration in saliva reflects the pharmacologically active drug concentration in plasma and may provide an easily accessible alternative for monitoring effective antiretroviral treatment

Application of stem-cell media to explant culture of human periosteum: An optimal approach for preparing osteogenic cell material

As part of our clinical tests on bone regeneration using cultured periosteal sheets, here, we prepared cultured periosteal sheets in two types of stem-cell culture media, STK1 and STK3. Human periosteum was expanded either in 1% human serum–supplemented STK1 for 28 days, in 1% human serum–supplemented STK1 for 14 days followed by 1% human serum–supplemented STK3 for 14 days (1% human serum–supplemented STK1+3), or in 10% fetal bovine serum–supplemented Medium 199 for 28 days (control). Cultured periosteal sheet diameter and DNA content were significantly higher, and the multilayer structure was prominent in 1% human serum–supplemented STK1 and 1% human serum–supplemented STK1+3. The messenger RNA of osteoblastic markers was significantly upregulated in 1% human serum–supplemented STK1+3. Osteopontin-immunopositive staining and mineralization were evident across a wide area of the cultured periosteal sheet in 1% human serum–supplemented STK1+3. Subcutaneous implantation in nude mice following expansion in 1% human serum–supplemented STK1+3 produced the highest cultured periosteal sheet osteogenic activity. Expansion in 1% human serum–supplemented STK1+3 successfully induced cultured periosteal sheet growth while retaining osteogenic potential, and subsequent osteoblastic induction promoted the production of homogeneous cell material

Central hemangioma of the maxilla: Report of a case with an exophytic growth

A case of intraosseous hemangioma occuring in the maxilla of a 74 year-old-female is described. A radiolucent lesion in the maxilla pointed out by her dentist grew rapidly in a month. CT examination revealed an intraosseous mass lesion with scalloping margins and rapid enhancement with contrastive media. MRI indicated a well-demarcated and exophytic lesion with high T2-weight signals. The lesion, measuring 20 x 38 x 58 mm in size, was clinically suspected of malignancy and surgically resected together with the right half of the maxillary bone. Histopathologically, the lesion was a fibrous granulation tissue absorbing the maxillary bone and expanding into the oral mucosa. It was largely occupied with blood coagulae in the center and contained many dilated blood vessels with single-layered endothelial linings in the periphery including the bone. This is the first case report of central hemangioma with an exophytic growth. © 2004 Elsevier Ltd. All rights reserved.Link_to_subscribed_fulltex