An Analysis of Risk Factors of Recipient Site Temporary Effluvium After Follicular Unit Excision: A Single-Center Retrospective Study.

BACKGROUND: Temporary hair loss at the recipient site after hair restoration surgery is called shock loss (SL). This study analyzed the risk factors for SL among patients who received follicular unit excision. MATERIALS AND METHODS: This study included 621 patients (554 males and 67 females). Twenty-three patients had SL (9 males and 14 females with a mean age of 40.8 years). The prevalence of SL was analyzed in relation to sex, age, graft follicular units, cause of alopecia, diabetes mellitus, smoking, drinking alcohol, and local anesthesia agent. RESULTS: Sex was identified as a risk factor for SL (odds ratio [OR]: 30.18; 95% confidence interval [CI] 9.43-96.55; p<0.001). Among female patients, age was identified as a risk factor for SL (OR:1.07; 95% CI 1.00-1.15; p=0.039). Over 40 years, the female pattern hair loss group had a significantly higher risk for SL than a female cosmetic group younger than 39 years. CONCLUSION: Sex was the only risk factor found for SL in this study. In addition, age was identified as a risk factor for SL among female patients. We believe our results provide information and risk factors for SL, not only for hair transplant surgeons, but also patients who will receive follicular unit excision. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Treatment of Linear and Narrow Scar after Craniotomy Using the Follicular Unit Excision.

Background The scar alopecia after cranioplasty (SAC) may decrease the patient's quality of life. We have treated SAC using follicular unit extraction (FUE). The aim of this study was to discuss that efficacy of FUE and how much hair follicular unit (FU) should be transplanted intraoperatively for the treatment of SAC. Methods We treated 10 patients (4 men and 6 women) who had SAC using FUE. Results The average age, alopecia size, and intraoperative hair density on the graft area were 29.8 ± 12.1 years, 29.8 ± 44.5 cm 2 , and 34.6 ± 11.8 FU/cm 2 , respectively. One year postoperatively, the average hair survival rate on the graft area was 66.3 ± 6.1%. Hair appearance was rated as good in six, fair in three, and poor in one. Among patients whose 1-year postoperative hair density was ≥ 20 FU/cm 2 , five of six patients achieved good results. However, among patients whose 1-year postoperative hair density was < 20 FU/cm 2 , all four patients achieved fair or poor results. The postoperative hair density was significantly higher in patients whose 1-year postoperative hair density was ≥ 20 FU/cm 2 than in patients whose 1-year postoperative hair density was < 20 FU/cm 2 . The rate of achieving fair or poor results was significantly higher if the postoperative hair density was < 20 FU/cm 2 than if it was ≥ 20 FU/cm 2 ( p = 0.047). Conclusions FU excision is useful for the treatment of scar alopecia after craniotomy. Our results suggest that the 1-year postoperative hair density should exceed 20 FU/cm 2 to achieve good outcomes.

Immuno-cell therapy with antecedent surgery has superior actuarial survival to immuno-cell therapy without antecedent surgery for advanced cancers.

BACKGROUND: Immuno-cell therapy using activated lymphocytes (ALs) and/or dendritic cells (DCs) is considered one of the less toxic supportive therapies compared with conventional chemotherapy and radiotherapy, especially for the treatment for advanced cancers. To improve the efficacy of immuno-cell therapy for such cancer, clinical data were analyzed in this preliminary study. PATIENTS AND METHODS: The clinical data of 38 consecutive patients with advanced cancer who underwent at least one course of treatment with ALs and/or matured DCs, with or without antecedent surgery or additional conventional chemotherapy and/or radiotherapy, were evaluated. RESULTS: Of the 23 patients who received surgery before immuno-cell therapy, 2 (8.7%) showed a complete response (CR) and 15 (65%) showed a partial response (PR) or prolonged stable disease (SD). Of the 15 remaining patients who did not undergo antecedent surgery, there was no CR but 7 (46%) showed PR or prolonged SD. Actuarial survival is one of the important indices for the evaluation of anticancer therapies that present longer durable efficacy of immunotherapy compared with conventional anticancer chemotherapy and radiotherapy, and actuarial survival analysis revealed that immuno-cell therapy with antecedent surgery afforded significantly longer survival than immuno-cell therapy without antecedent surgery (P < 0.001). CONCLUSION: Antecedent surgical resection of tumors is advisable for obtaining better efficacy of immuno-cell therapy, even in advanced cancer patients.

Donor site of follicular unit excision hair transplantation: the relationship between appearance and actual hair density, and hair diameter.

Donor site morbidity is an important consideration for follicular unit excision (FUE). We examined 103 male patients with adult androgenic alopecia. Patients were divided into three groups (Good, Fair, and Poor) based on visual assessment of the donor site. Hair density and hair diameter were measured using digital photography. A total of 72, 21 and 10 patients were classified into the Good, Fair and Poor appearance groups. The average hair density of each group was 127.8 ± 22.6 hair/cm2, 114.8 ± 23.1 hair/cm2 and 94.9 ± 25.4 hair/cm2. The hair density of the Good group was significantly higher than that of the Poor group (p = 0.003). The average hair diameter of each group was 0.0968 ± 0.0267 mm, 0.0754 ± 0.0299 mm and 0.0473 ± 0.0158 mm. The hair diameter of the Good group was significantly higher than that of the Poor group (p = 0.001). Thirty-three of 72 patients whose hair density was >130 hair/cm2 belonged to the Good group. Seven of 10 patients whose hair density was <105.0 hair/cm2 belonged to the Poor group, while 31 of 72 patients whose hair diameter was <0.101 mm were included in the Good group. Eight of 10 patients whose hair diameter was less than 0.070 mm were in the Poor group. Donor sites rated Good on appearance had both high hair density and thick hair diameter. To maintain a good appearance after FUE, donor site hair density should not be less than 105.0 hair/cm2.

Novel technique of follicular unit extraction hair transplantation with a powered punching device.

BACKGROUND: A follicular unit extraction (FUE) method has been developed as one type of follicular unit transplantation (FUT) surgery that is a widely accepted hair restoration technique. Although FUE is considered to be more time consuming, depending on the operator's skill, and there are restrictions on patient candidacy, FUE has many advantages, including a small donor wound, less pain, and a slender graft without extra surrounding tissue. OBJECTIVE: To propose a novel powered FUE (P-FUE) technique. MATERIALS AND METHODS: To compare harvesting time and graft transection rate, FUE surgery was performed by manual FUE and P-FUE on male patients with alopecia. RESULTS: The P-FUE method had a shorter harvesting time (6.0 minutes for 100 grafts; 14.2 minutes for manual FUE) and lower graft transection rate (5.4% vs 17.3% with manual FUE). For 40 P-FUE cases, mean harvesting time for 100 grafts was 8.9+/-1.3 minutes. In 10 validated cases, the transection rate was 5.5%. Although there were limitations on patient selection with manual FUE, there were no restrictions on patient candidacy with the P-FUE method. CONCLUSION: The P-FUE method is a novel FUE procedure with many advantages over the conventional FUE technique.

Overexpression of human X-box binding protein 1 (XBP-1) in colorectal adenomas and adenocarcinomas.

BACKGROUND: Human X-box binding protein 1 (XBP-1) is a transcription factor essential for hepatocyte growth, as well as for plasma cell differentiation. Recently, overexpression of XBP-1 has been reported in breast cancer including non-invasive carcinomas, and was suggested to play an important role in breast carcinogenesis. To investigate the involvement of XBP-1 in colorectal tumorigenecity, the expression of XBP-1 was examined in four colon cancer cell lines, six colorectal polyps and five colorectal carcinomas. MATERIALS AND METHODS: The study population consisted of eleven patients who had undergone resection for colorectal cancer or adenoma from 2000 to 2002. Four colon cancer cell lines, DLD1, SW480, HCT15 and WiDr, were also analyzed for expression of XBP-1. Reverse transcription-polymerase chain reaction was performed using eleven primary colon tumors. XBP-1 expression was then investigated using an immunohistochemical method for archived paraffin-embedded sections. RESULTS: The XBP-1 gene was overexpressed in four cases out of five primary colorectal carcinomas and in four cases out of six colorectal adenomas. Also all four cancer cell lines expressed XBP-1 mRNA. Immunohistochemical staining demonstrated that XBP-1 protein was strongly stained in the cytoplasms of cancer cells, whereas it was unreactive in the normal colon epithelial cells and stromal cells. CONCLUSION: These data indicate that increased expression of XBP-1 gene may play some role in human colon carcinogenesis through impairment of cell differentiation regulation.

Down-regulation of transcription elogation factor A (SII) like 4 (TCEAL4) in anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and appears to arise mainly from transformation of pre-existing differentiated thyroid cancer (DTC). However, the carcinogenic mechanism of anaplastic transformation remains unclear. Previously, we investigated specific genes related to ATC based on gene expression profiling using cDNA microarray analysis. One of these genes, transcription elongation factor A (SII)-like 4 (TCEAL4), encodes a member of the transcription elongation factor A (SII)-like gene family. The detailed function of TCEAL4 has not been described nor has any association between this gene and human cancers been reported previously. METHODS: To investigate the role of TCEAL4 in ATC carcinogenesis, we examined expression levels of TCEAL4 in ACLs as well as in other types of thyroid cancers and normal human tissue. RESULTS: Expression of TCEAL4 was down-regulated in all 11 ACLs as compared to either normal thyroid tissues or papillary and follicular thyroid cancerous tissues. TCEAL4 was expressed ubiquitously in all normal human tissues tested. CONCLUSION: To our knowledge, this is the first report of altered TCEAL4 expression in human cancers. We suggest that loss of TCEAL4 expression might be associated with development of ATC from DTC. Further functional studies are required.

Growth-suppressive function of phosphatidylethanolamine-binding protein in anaplastic thyroid cancer.

BACKGROUND: A cDNA microarray analysis of anaplastic thyroid cancer cell lines (ACL) was recently performed and the down-regulation of phosphatidylethanolamine-binding protein (PBP) [RAF kinase inhibitor protein (RKIP)] in ACL compared to normal thyroid tissues was identified. MATERIALS AND METHODS: The expression levels of PBP in primary anaplastic and papillary thyroid cancer, thyroid cancer cell lines (anaplastic, papillary and follicular) and several normal human organs were examined. To examine the function of PBP, cell-growth assays were performed. RESULTS: PBP expression was reduced in anaplastic thyroid cancers, compared to either normal thyroid tissues or differentiated thyroid cancers. PBP was expressed ubiquitously in normal human tissues. Exogenous PBP expression suppressed ACL growth, and suggested a tumor suppressive function of PBP in ACL. CONCLUSION: This is the first report demonstrating that PBP may be a tumor suppressor whose loss is associated with development of anaplastic thyroid cancer from differentiated thyroid cancer.

Dissimilarity in gene expression profiles of lung adenocarcinoma in Japanese men and women.

BACKGROUND: Although clinical differences in lung cancer between men and women have been noted, few studies have examined the sex dissimilarity using gene expression analysis. OBJECTIVE: The purpose of this study was to determine the different molecular carcinogenic mechanisms involved in lung cancers in Japanese men and women. METHODS: Patients who received surgery for stage I lung adenocarcinoma were included. RNA was extracted from cancerous and normal tissue, and gene expression was then examined with oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was performed. RESULTS: In a microarray analysis of tissue from 13 men and 6 women, 12 genes were under-expressed and 24 genes were overexpressed in lung adenocarcinoma in women compared with men. Genes related to cell cycle were present in underexpressed genes, and genes related to apoptosis, ubiquitination, and metabolism were observed in overexpressed genes. Of interest among the selected genes were WAP four-disulfide core domain 2 (WFDC2) and major histocompatibility complex, class II, DM alpha (HLA-DMA); these genes were classified into 2 groups by hierarchical clustering analysis. Expression of WFDC2 in nonsmokers was significantly higher than that in smokers (P=0.023). However, there was no significant difference in HLA-DMA expression between smokers and nonsmokers. CONCLUSION: Thirty-six genes that characterize lung adenocarcinoma by sex were selected. This information may contribute to the development of novel diagnostic techniques and treatment modalities that consider sex differences in lung adenocarcinoma.

Expansion of microsatellite in the thyroid hormone receptor-alpha1 gene linked to increased receptor expression and less aggressive thyroid cancer.

PURPOSE: The purpose of this study was to determine whether the length of the THRA1 microsatellite, which resides in a noncoding portion of the thyroid hormone receptor-alpha1 gene, affects receptor expression and is linked to clinicopathological parameters in thyroid cancer. EXPERIMENTAL DESIGN: In 30 cases of surgically resected sporadic thyroid cancer, the length of the THRA1 microsatellite was determined by DNA sequence analysis, and expression of thyroid hormone receptor-alpha1 was assessed immunohistochemically in thin sections cut from tumor blocks. The length of THRA1 and expression of thyroid hormone receptor-alpha1 were also assessed in seven cancer cell lines. Regression analysis was used to gauge the correlation between the size of THRA1 and receptor expression. Multivariate analysis was used to test for links to the clinical parameters of gender, age, histology, stage, nodal involvement, distant metastasis, extrathyroidal invasion and tumor-node-metastasis (TNM) classification. RESULTS: A statistically significant correlation between the length of THRA1 and thyroid hormone receptor-alpha1 expression was observed in both cell lines and primary thyroid cancers. Thyroid tumors that displayed higher than average thyroid hormone receptor-alpha1 expression had expanded THRA1 microsatellites and were less aggressive as judged by TNM ranking. A statistically significant correlation was also found between low thyroid hormone receptor-alpha1 expression and more aggressive thyroid cancer, as judged by extrathyroidal invasion and nodal involvement. CONCLUSIONS: Less aggressive thyroid cancer was found to be linked to increased thyroid hormone receptor-alpha1 expression and an expanded THRA1 microsatellite.

Upregulation and overexpression of DVL1, the human counterpart of the Drosophila dishevelled gene, in prostate cancer.

AIMS AND BACKGROUND: The Wnt/beta-catenin signaling pathway is one of the main carcinogenic mechanisms in human malignancies including prostate cancer. Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta-catenin signaling pathway. In addition, alterations of the DVL1 gene have been reported in breast and cervical cancer. The abnormality of beta-catenin in prostate cancer has been well studied, so the examination of the DVL1 gene in prostate cancer is appealing. METHODS: We investigated DVL1 messenger RNA alterations by semiquantitative PCR (SQ-PCR) in 20 primary prostate cancers and assessed the protein expression by immunohistochemical analysis in the same samples. In addition, DVL1 and beta-catenin protein expression was evaluated with a new validated set of 20 prostate cancers. RESULTS: SQ-PCR revealed significant overexpression of DVL1 in prostate cancer (65%). Upregulation of the DVL1 gene product in prostate cancer was confirmed by immunostaining. With SQ-PCR and immunostaining, none of the cases showed underexpression or downregulation of DVL1. In addition, the data showed correlations between DVL1 mRNA and protein expression. Interestingly, the expression level of DVL1 increased with worsening histological grade. In addition, a correlation between DVL1 expression and beta-catenin expression was confirmed. CONCLUSIONS: DVL1 was overexpressed in prostate cancer and its overexpression might be related to prostate cancer progression through the Wnt/beta-catenin pathway.

Gene expression patterns as marker for 5-year postoperative prognosis of primary breast cancers.

PURPOSE: To establish the novel prognostic markers for breast cancer, gene expression profile was examined genome-wide. METHODS: We used cDNA microarray consisting of 18,432 human genes to compare genome-wide expression profiles of eight primary breast cancers, four from patients who died of breast cancer within 5 years after surgery (5D group) and four who survived disease-free for more than 5 years (5S group). RESULTS: We identified 21 genes whose expression was greater in tumors from the 5D group than in 5S tumors, and 23 with higher expression in the 5S group than in the 5D group. We established a Prognostic Index (PI) for prediction of postoperative prognosis, based on the aberrant expression profiles of ten of those genes. Among 20 additional cases chosen blindly, ten presented with high prognostic scores (>7, good) according to the PI; the remaining ten cases revealed scores <7 (poor). The PI predicted the actual 5-year clinical outcomes of these 20 cases with 100% accuracy. CONCLUSION: Our PI system is reliable in clinical settings for predicting postoperative risk for breast cancer. The extensive list of genes provides valuable information about progression of breast cancer and suggests potential target molecules for treating this disease.

Telomeric repeat-length alterations in colorectal carcinoma are associated with loss of heterozygosity and point mutation in p53 gene.

The telomere, the terminal region of eukaryotic chromosomes, plays an important role in the stability of DNA replication and in the protection of chromosomal ends. To investigate whether the two-stage mechanism of cellular aging and immortalization in vitro is involved in the carcinogenesis and immortalization of human colorectal carcinomas, we examined for genetic alterations in the telomeres and in the p53, Rb, and K-ras genes. Based on our results, we discuss the effects that these genetic changes might have on mechanisms, such as the mortality stage 1 (M1), that normally prevent immortalization in carcinoma cells. Telomeric repeat-lengths (TRL) were measured by Southern blot analysis, and p53 Rb and K-ras gene variants were detected by PCR based assays. Thirty-six primary colorectal carcinomas were examined. Telomere alterations were found in 19 of 36 (52.8%) cases, while mutations of the p53 gene were observed in 15 of 36 (41.7%) cases and LOH involving p53 observed in 14 of 36 (38.9%) cases. Twelve of 15 (80%) cases with p53 mutations also showed altered TRL, so that p53 mutations were positively associated with TRL alterations (p=0.008). Ten of 14 (71.4%) cases with LOH of p53 also showed alteration in TRL, also revealing a positive association with TRL (p=0.09). The six cases with both p53 mutation and LOH all showed altered TRL. K-ras gene mutations and LOH involving the Rb gene were not associated with alterations in TRL. These results suggest that inactivation of p53 is one of the factors that promotes immortalization and overcomes M1 in colorectal carcinoma.

Upregulation and overexpression of human X-box binding protein 1 (hXBP-1) gene in primary breast cancers.

BACKGROUND: Human X-box binding protein 1 (hXBP-1) is a transcription factor essential for hepatocyte growth as well as for plasma cell differentiation. hXBP-1 also binds to cis-elements of human T cell leukemia virus and human major histocompatibility complex genes. In order to clarify the role of XBP-1 in breast cancer, here we investigated the expression of XBP-1 in 11 primary breast cancers and 5 breast cancer cell lines. MATERIALS AND METHODS: The study population consisted of eleven patients who were underwent surgery for breast cancer from 2000 to 2002. Five breast cancer cell lines (MDA-MB-453, CRL1500, YMB-1-E, MCF7 and HBL100) were analyzed for XBP-1 expression. Reverse transcription polymerase chain reaction was performed on 6 primary breast cancers. Then we investigated XBP-1 expression by immunohistochemically on archived paraffin-embedded sections. RESULTS: hXBP-1 mRNA expression was increased in all 11 primary breast cancers we examined, as well as 5 breast cancer cell lines, but hardly detectable in non-cancerous breast tissue. Immunohistochemical staining demonstrated that hXBP-1 protein stained strongly in the cytoplasm of cancer cells but was unreactive in the normal breast ductal epithelial and myoepithelial cells. CONCLUSIONS: These data indicate that increased expression of the hXBP-1 gene may play some role in human breast carcinogenesis through impairment of cell differentiation regulation.

Genetic prognostic index influences patient outcome for node-positive breast cancer.

PURPOSE: To establish a novel genetic prognostic index among node-positive breast cancer patients. METHODS: Using a cDNA microarray, the gene expression profiles of 20 primary breast cancers that had metastasis to four or more axillary lymph nodes were examined. Ten patients survived disease-free for more than 5 years (5S), while ten patients died of breast cancer within 5 years of surgery (5D). RESULTS: A set of genes characterizing each group was identified. Sixteen genes were underexpressed in 5D compared to 5S, and 15 genes were underexpressed in 5S in comparison to 5D. The prognostic index (PI) was established, which could predict the postoperative outcome with five genes that were commonly underexpressed in the 5D group; these genes encoded granulin (GRN), heat shock 90 kDa protein 1 beta (HSPCB), large tumor suppressor homolog 1 (LATS1), valosin-containing protein (VCP), and LIM-and-SH3 protein1 (LASP1). CONCLUSION: These five genes might play an important role in deciding the behavior of node-positive breast cancer. The PI system could thus predict the prognosis of node-positive breast cancer, and might therefore be able to provide valuable information for the prognosis of breast cancer patients.

Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), alpha-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.

Overexpressed in anaplastic thyroid carcinoma-1 (OEATC-1) as a novel gene responsible for anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most fulminant human malignancies. However, the molecular carcinogenic mechanisms of ATC are understood poorly. Recently, the authors performed a cyclic DNA (cDNA) microarray analysis with 11 anaplastic thyroid carcinoma cell lines (ACLs) and discovered several novel responsible genes for ACLs and ATC. From the extended list, they focused on hypothetical and anonymous genes and investigated a novel gene, named the overexpressed in anaplastic thyroid carcinoma-1 (OEATC-1) gene. METHODS: To investigate the role of the OEATC-1 gene in ATC carcinogenesis, first, the expression levels of OEATC-1 in ACLs, in various types of carcinoma cell lines, and in normal human tissues were examined with reverse transcriptase-polymerase chain reaction analysis. To explore the effect of OEATC-1 in ATC development, a cell-growth assay was performed with KTA2 cells under OEATC-1 gene silencing using small-interfering RNA (siRNA). RESULTS: OEATC-1 was overexpressed significantly in ACLs and in other types of carcinoma cell lines with various expression levels. Conversely, in normal human tissues, OEATC-1 was expressed weakly in placenta, kidney, spleen, thymus, small intestine, and thyroid gland. To evaluate the effects of OEATC-1 on tumor cell growth, gene silencing was caused by transfecting the plasmid-generating siRNA effect to KTA2 cells. Consequently, the silencing of OEATC-1 significantly suppressed the cell growth compared with controls. CONCLUSIONS: The current results indicated that OEATC-1 may have some oncogenic or cell growth-promoting function in ACL. OEATC-1 is considered a novel responsible gene in ATC.

Up-regulation of CC chemokine, CCL3L1, and receptors, CCR3, CCR5 in human glioblastoma that promotes cell growth.

Human CC ligand 3-like protein 1 (CCL3L1), a member of the CC chemokine family, that induces MCP1 and RANTES, exhibits a variety of proinflammatory activities including chemotaxis, and functional and proliferative activation of leukocytes, lymphocytes and macrophages. Its signal is transmitted through transmembrane receptors, CC chemokine receptors, CCR1, CCR3 and CCR5. To examine gene expression of chemokine, CCL3L1, and its receptors, CCR1, CCR3 and CCR5, we analyzed tumor tissues from 21 patients with several types of primary gliomas. CCL3L1, CCR3 and CCR5 gene exhibited over-expression in 70% (7/10), 60% (6/10), and 60% (6/10) of glioblastoma, in comparison with lower frequencies seen in lower-grade gliomas. Transfection of CCL3L1-expression vector to glioblastoma cell line enhanced proliferation of the tumor cells. These data suggest that increased expression of the CCL3L1, CCR3 and CCR5 chemokine-receptors system is involved in brain tumorigenesis, especially in the progression of glioblastoma.

Down-regulation of members of glycolipid-enriched membrane raft gene family, MAL and BENE, in cervical squamous cell cancers.

Persistent human papillomavirus infections cause infected epithelial cells to lose cellular polarity leading to cell transformation. Glycolipid-enriched membrane (GEM) rafts are implicated in polarized sorting of apical membrane proteins in epithelial cells and even in signal transduction. The MAL and BENE are essential component of the GEM raft's machinery for apical sorting of membrane proteins. In this study we demonstrated down-regulation of MAL and BENE mRNA in over two-thirds of primary cervical squamous cell cancers (14 and 15 of 20 cases, for MAL and BENE, respectively) when compared to corresponding non-cancerous uterine squamous cells. Allelic loss or hyper-methylation was not accompanied by MAL or BENE mRNA down-expression in human primary cervical cancers in microsatellite allelic analysis and HpaII-PCR-based methylation analysis of the MAL and BENE genomic region. In addition, we note down-regulation of these genes in established cervical cancer cell lines. These results suggest that down-regulation of MAL and BENE genes, which are essential components of the cellular polarized sorting system, play an important role in human cervical squamous cell cancer development.

Characterization of liver-cirrhosis nodules by analysis of gene-expression profiles and patterns of allelic loss.

To disclose genetic mechanisms involved in development or progression of hepatocellular carcinoma (HCC), we used a genome-wide cDNA microarray consisting of 8,448 genes to compare gene-expression profiles among 12 liver-cirrhosis nodules (LCNs) and five specimens of HCC excised from a single patient and carefully prepared by laser-capture microdissection (LCM). The expression patterns enabled us to identify 72 genes that were frequently upregulated and 57 that were downregulated specifically in the LCN specimens as compared to the HCCs. We also documented upregulation of 31 genes and downregulation of seven others in both HCC and LCN tissues. Several types of intracellular kinase, including receptor-type kinase, were upregulated in LCNs. Expression patterns of HCCs and LCNs generally represented two genetically distinct groups when subjected to a hierarchical clustering analysis, although expression profiles of two of the LCNs resembled the HCC pattern. Analysis of allelic losses at microsatellite loci revealed that LCNs showed frequent loss of heterozygosity (LOH) (33%) in chromosomal regions 6q and 22q; over half of the LCNs had lost an allele for at least one of the 28 loci examined. The presence of early genetic changes among LCNs, with additional genetic changes occurring during formation of HCCs, suggests that hepatocellular carcinogenesis follows the multistep model established for colon cancers and that some LCNs may be precancerous lesions.