Oral carcinogenesis is a complex process involving multiple genes. However, the genetic changes involved in this process are not apparent in identical oral squamous cell carcinomas (OSCCs). According to pathological characteristics, samples of normal tissue, oral dysplastic lesions (ODLs), and invasive cancers were obtained from identical OSCCs using laser microdissection (LMD). Large‐scale gene expression profiling was carried out on 33 samples derived from 11 OSCCs. We analyzed genes differentially expressed in normal tissues vs. ODLs and in ODLs vs. invasive tumors and identified 15 candidate genes with continuously increasing or decreasing expression during oral carcinogenesis. One of these genes, ISG15, was chosen for further characterization. Real‐time quantitative reverse transcription‐polymerase chain reaction and immunohistochemical analysis confirmed that ISG15 expression consistently increased during oral tumorigenesis. An ISG15 high‐expression level was significantly associated with poor prognosis (p = 0.027). In addition, patients with high‐expression tumors had a poorer 5‐year survival rate than patients with low expression levels (p = 0.019). In conclusion, we identified 15 genes with continuously increasing or decreasing expression during oral carcinogenesis. One of these, ISG15, is likely to be associated with both dysgenesis and tumorigenesis and may be a potential prognostic marker for oral cancer.
In order to breed Brassica napus-Raphanus sativus monosomic addition lines (MALs), hybridizations between two synthetic amphidiploid (RRAA and RRCC) and B. napus (AACC) were performed. Two allooctoploids (RRAAAACC and AACCRRCC) were produced from each F 1 hybrid by chromosome doubling. From successive backcrosses to B. napus, MAL plants were first obtained in BC 2 generation and the R. sativus-derived chromosome was identified by genomic in situ hybridization (GISH). The nine chromosomes of R-genome in the MAL plants were clearly classified by each chromosome-specific RAPD markers. As a result, alloplasmic (radish cytoplasm) B. napus-R. sativus MAL having 8 types (a-i, except for h-type) and autoplasmic (rape cytoplasm) MAL with complete 9 types (a-i) were obtained in BC 3 and BC 4 generations. These alloplasmic and autoplasmic MAL plants were showed differences in their morphological, physiological and cytogenetical characters. From the survey of favorable traits, it was suggested that the a-type had fertility restoring gene(s) for male sterility in alloplasmic line and the g-type had a gene controlling white color petal. These two MALs are useful materials for exploring agronomic traits located on each chromosome of radish and for promoting the introgression of promising radish gene(s) to B. napus.
Abstract. The prognosis of oral squamous cell carcinoma (OSCC) is significantly dependent on the existence of cervical lymph node metastasis (LNM), with the overall survival rate being much lower in patients with LNM. Primary causes and molecular mechanisms of LNM are still largely unclear. We hypothesized that factors related with cancer progress and/or prognosis in OSCC are revealed by genome-wide investigation of DNA copy number aberrations (CNAs). In order to find biomarkers for occult LNM of OSCC, we comprehensively investigated genomic DNAs from 60 OSCC patients using Affymetrix mapping arrays and statistically analyzed correlations between CNAs of genes and the presence of occult LNM in the patients. The genome-wide CNA study indicated significant correlations between the presence of occult LNM and CNAs of certain genes. Through a literature survey, we narrowed down the candidates and focused on loss of NKX3-1, which is a homeodomain-containing transcription factor. NKX3-1 is known as a tumor suppressor gene in prostate cancer but has never been reported in OSCC. Quantitative RT-PCR and immunohistochemistry (IHC) analyses also showed significantly lower expression of NKX3-1 in the cases with occult LNM, which was further validated by IHC analysis in independent cases. The survival analyses indicated that NKX3-1 loss is a significant risk factor to decrease the diseasefree survival (DFS) and the overall survival (OS) rates. This is the first time that the significant association of NKX3-1 loss and occult LNM was indicated in OSCC. The present results suggest that loss of NKX3-1 may be a potential biomarker for occult LNM of OSCC. IntroductionOral squamous cell carcinoma (OSCC) is the most common head and neck carcinoma, accounting for more than 260,000 cases worldwide each year (1). Although therapies for OSCC have recently been improved, only slight progress has been observed in the mortality rates over the last two decades (2). The most important prognostic factor in OSCC is the presence of lymph node metastasis (LNM). In fact, the 5-year overall survival rate in patients with LNM is approximately 25% lower than in patients without LNM (3). Especially, nodal metastasis diagnosed after surgical resection of a primary tumor site is more severe for survival and known as occult LNM even when the patient is diagnosed without cervical LNM (N0 neck) at the first visit. Therefore, the appropriate management of occult LNM is required and currently two major approaches are applied to manage the N0 neck in OSCCs; an elective neck dissection of cervical lymph node(s) and a 'wait-and-see' policy (4,5). In a case of stage N0 neck with a risk of occult LNM greater than 20%, neck dissection is a standard procedure for elective treatment (6). The risk of metastatic potential can vary according to the site, size, histopathological and genetic features of a primary tumor. Much controversy exists over the decision of the treatment with or without a preventive lymphadenectomy based on accurate risk stratification of potentia...
In the present work, simonkolleite powder consisting of Zn5(OH)8Cl2·H2O composition was proposed as a new candidate material for the healing of deep wounds in a moist environment. The powder was synthesized using a solution process and evaluated for wound-healing effects in rats. The pH value of physiological saline at 37 °C using the simonkolleite powder was 7.27, which was the optimal pH value for keratinocyte and fibroblast proliferation (range: 7.2–8.3). The amount of Zn2+ ions sustainably released from simonkolleite powder into physiological saline was 404 mmol/L below cytotoxic ion concentrations (<500 mmol/L), and the rhombohedral simonkolleite was accordingly converted to monoclinic Zn5(OH)10·2H2O. To evaluate the wound-healing effect of simonkolleite powder, the powder was applied to a full-thickness surgical wound reaching the subcutaneous tissue in the rat’s abdomen. The histological analysis of the skin tissues collected after 1, 2, and 4 weeks found that angiogenesis, collagen deposition, and maturation were notedly accelerated due to the Zn2+ ions released from simonkolleite powder. The simonkolleite regenerated collagen close to autologous skin tissue after 4 weeks. The hair follicles, one of the skin appendages, were observed on the regenerative skin in the simonkolleite group at 4 weeks but not in the control group. Therefore, simonkolleite was hypothesized to stimulate the early regeneration of skin tissue in a moist environment, compared with commercial wound dressing material. These results suggested that simonkolleite could offer great potential as new wound dressing material.
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