Current Insights on Neoplasms and Adequate Dental Care for Patients with Oral Cancer / Actualización sobre Neoplasmas y su Correcta Atención Odontológica en Pacientes con Cancer Oral

The present study aimed to review the literature on the main complications of antineoplastic therapies and the degree of knowledge of dental surgeons about these complications. A bibliographic search was conducted in the main health databases PUBMED (www.pubmed.gov) and Scholar Google (www.scholar.google.com.br), in which studies published from 1987 to 2023 were collected. Laboratory studies, case reports, systematic and literature reviews, which were developed in living individuals, about the main neoplastic genes and their relationship with the cells of individuals affected by neoplasms in the head and neck region, and studies on the care with this group of patients, were included. Therefore, articles that did not deal with neoplasm and the main complications of antineoplastic therapies were excluded. Neoplasm is a clonal disorder, caused by mutations, resulting from changes in the genetic structure of cells. Each healthy cell has instructions on how to grow and divi de. In the presence of any error in these instructions (mutation), it can result in a diseased cell that, when proliferating, may cause a tumor. Countless knowledge has been accumulated over the years on the main characteristics of neoplasms, whether they are cancer cell biology, carcinogenesis mechanism, neoplasms of the maxillofacial system and sequels of antineoplastic treatments. In this context, methods have been developed that offer a better quality of life for patients diagnosed with this pathology, as well as preventive vaccine models that may, in the not too distant future, contribute to this goal to be successfully achieved.

El presente estudio tuvo como objetivo revisar la literatura sobre las principales complicaciones de las terapias antineoplásicas y el grado de conocimiento de los odontólogos sobre este abordaje. Se realizó una búsqueda bibliográfica en las principales bases de datos de salud PUBMED (www.pubmed.gov) y Scholar Google (www.scholar.google.com.br), en la que se recopilaron estudios publicados entre 1987 y 2023. Fueron incluidos estudios de laboratorio, relatos de casos, revisiones de la literatura y revisiones sistemáticas, desarrolladas en individuos vivos, que incluyeran los principales genes neoplásicos y su relación con las células de individuos afectados por neoplasias en la cabeza y el cuello. También, se tuvieron en cuenta estudios relacionados con la atención a este grupo de pacientes. La neoplasia es un trastorno clonal, causado por mutaciones, como resultado de cambios en la estructura genética de las células. Cada célula sana tiene instrucciones sobre cómo crecer y dividirse. En presencia de cualquier error en estas instrucciones (mutación), puede provocar una célula alterada que, al proliferar, puede causar un tumor. Se han acumulado innumerables conocimientos a lo largo de los años sobre las principales características de las neoplasias, ya sea sobre biología de células cancerosas, el mecanismo de la carcinogénesis, la neoplasias del sistema maxilofacial y las diferentes secuelas de tratamientos antineoplásicos. En este contexto, se han desarrollado métodos que ofrecen una mejor calidad de vida para los pacientes diagnosticados con esta patología, así como modelos de vacunas preventivas que, en un futuro no muy lejano, pueden contribuir a alcanzar este objetivo con éxito.

The identification of lung cancer gene-drug module based on multiplex networks algorithm / 生物医学工程学杂志

Using modular identification methods in gene-drug multiplex networks to infer new gene-drug associations can identify new therapeutic target genes for known drugs. In this paper, based on the gene expression data and drug response data of lung cancer in the genomics of drug sensitivity in cancer (GDSC) database, a multiple network algorithm is proposed. First, a heterogeneous network of genes of lung cancer and drugs in different cell lines is constructed, and then a network module identification method based on graph entropy is used. In this heterogeneous network, network modules are identified, and five lung cancer gene-drug association modules are identified through iterative convergence. Compared with other methods, the algorithm has better results in terms of running time, accuracy and robustness, and the identified modules have obvious biological significance. The research results in this article have guiding significance for the medication and treatment of lung cancer, and can provide references for the treatment of other diseases with the same targeted genes.

Comprehensive Cancer Panel Sequencing Defines Genetic Diversity and Changes in the Mutational Characteristics of Pancreatic Cancer Patients Receiving Neoadjuvant Treatment

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDA) is associated with an extremely poor prognosis. This study assessed the genetic diversity among patients with PDA and compared their mutational profiles before and after treatment. METHODS: Tumors and matched blood samples were obtained from 22 PDA patients treated with neoadjuvant chemoradiation therapy. The somatic mutations were analyzed with comprehensive cancer gene panel (CCP). In addition, the biopsy samples obtained at diagnosis and the surgically resected samples after treatment were compared for seven patients. The CCP provided formalin-fixed paraffin-embedded sample-compatible multiplexed target selection for 409 genes implicated in cancer. RESULTS: Assessments of the MLH1, MLH3, MSH2, and PMS2 genes showed that the four patients with the highest relative burdens of mutations harbored somatic mutations in at least three of these genes. Genes in the histone-lysine N-methyltransferase 2 (KMT2) family, such as KMT2D, KMT2A, and KMT2C, were frequently mutated in tumor samples. Survival was worse in patients with ARID1A gene mutations than those without ARID1A gene mutations. Mutation patterns were compared between tissue samples before and after neoadjuvant treatment in seven patients who underwent surgical resection. The allelic fraction of mutations in KRAS codon 12 was lower in the surgically resected samples than in the endoscopic ultrasonography-guided fine needle aspiration biopsy samples of six patients. The number of mutant alleles of the histone lysine methyltransferase gene WHSC1 also decreased after treatment. CONCLUSIONS: These results indicate that tumor tissue from PDA patients is genetically diverse and suggest that ARID1A mutations may be a potential prognostic marker for PDA.

Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance. MATERIALS AND METHODS: A total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2–, luminal B and HR+/HER2+, HR–/HER2+ and HER2–enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS. RESULTS: In total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation–related discordant breast cancer including the VHL gene in the HR+/HER2– group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01). CONCLUSION: A substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.

Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model

PURPOSE: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.

Bioinformatics analysis of genes related to poor prognosis of human hepatocellular carcinoma and its clinical significance / 中国应用生理学杂志

OBJECTIVE@#To screen genes associated with poor prognosis of hepatocellular carcinoma (HCC) and to explore the clinical significance of these genes.@*METHODS@#The proper expression profile data of HCC was obtained from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified by differential expression analysis. The DAVID and String database were used for function enrichment analysis and to construct the protein-protein interaction (PPI) network respectively. The Cancer Genome Atlas (TCGA) database and the Cox Proportional Hazard Model were used for prognosis analysis of the DEGs.@*RESULTS@#A eligible human HCC data set (GSE84402) met the requirements. A total of 1141 differentially expressed genes were identified, including 720 up-regulated and 421 down-regulated genes. The results of function enrichment analysis and PPI network performed that CDK1、CDC6、CCNA2、CHEK1、CENPE 、PIK3R1、RACGAP1、BIRC5、KIF11 and CYP2B6 were prognosis key genes. And the prognosis analysis showed that the expressions of CDC6、PIK3R1、KIF11 and RACGAP1 were increased, and the expression of CENPE was decreased, which was closely related to prognosis of HCC.@*CONCLUSION@#CDC6、CENPE、PIK3R1、KIF11 and RACGAP1 may be closely related to poor prognosis of HCC, and can be used as molecular biomarkers for future research of HCC prognosis.

Síndrome de Lynch: aspectos genéticos, clínicos y diagnósticos / Lynch syndrome: genetic, clinical and diagnostic aspects

Esta revisión tiene como objetivo dar a conocer los aspectos genéticos, clínicos y diagnósticos del síndrome de Lynch, además de brindar la información más relevante acerca de la asesoría genética en estos pacientes y las recomendaciones actuales para su seguimiento.

This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.

GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers

Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers.

Construction and analysis of a breast cancer gene-drug network model / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a breast cancer gene-drug network model for extracting and predicting the correlations between breast cancer-related genes and drugs.</p><p><b>METHODS</b>We developed an algorithm based on the ABC principle and the association rules to obtain the correlations between the biological entities. For breast cancer, we constructed 3 different correlations (gene-gene, drug-drug and gene-drug) and used the R language to implement the associated network model. The reliability of the algorithm was verified by ROC curve.</p><p><b>RESULTS</b>We identified 185 breast cancer-associated genes and 98 associations between them, 97 drugs and 170 associations between them. The breast cancer genes-drugs network contained 127 genes and 77 drugs with 384 associations between them.</p><p><b>CONCLUSIONS</b>We identified a large number of different correlations between the breast cancer-related genes and drugs and close correlations between some biological entity pairs that have not yet been reported, which may provide a new strategy for experimental design for testing personalized breast cancer treatment.</p>

Association of polymorphism in the promoter region of PCA3 gene with risk of prosate cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the polymorphism in the promoter region of PCA3 gene and its relationship with risk of prostate cancer (PCa).</p><p><b>METHODS</b>The promoter region of PCA3 gene of the DNA of peripheral blood mononuclear cells was detected by sequence analysis in the 186 PCa and 141 BPH patients and 135 healthy control individuals. If the samples were detected with polymorphism of insection/deletion, clone sequence analysis was used with pBS-T carrier to verify it.</p><p><b>RESULTS</b>There were 5 polymorphisms. TAAA repeat times: 4, 5, 6, 7, 8, and 8 genotypes (TAAA 4/5, TAAA 4/6, TAAA 5/5, TAAA 5/6, TAAA 5/7, TAAA 5/8, TAAA 6/6, and TAAA 6/7) were detected in the promoter region of PCA3 gene. The eight genotypes were divided into three groups: ≤10TAAA, 11TAAA, ≥12TAAA. Unconditional logistic regression analysis models were used to analyze the relationship between different genotypes and cancer risks adjusted by sex and age. The type 11TAAA and ≥12TAAA was associated with higher relative risk for prostate cancer than the group ≤10TAAA [OR=1.74, 95% CI=1.06-2.87 (for type 11TAAA); OR=5.63, 95% CI=1.85-17.19 (for type ≥12TAAA)]. In the 186 PCa patients, there was 62.4% allele of PCA3 gene with AG/CA mutation found in the promoter 18-19 bp region of PCA3 gene and it had a close relation with the development of prostate cancer.</p><p><b>CONCLUSIONS</b>Short tandem repeats are found in the promoter region of the PCA3 gene in PCa patients, and the increase of TAAA repeat sequences highly enhance the relative risk of prostate cancer development. The occurrence of such STR might be related to the mutations in their upstream loci.</p>

Establishment of a comprehensive database for laryngeal cancer related genes and the miRNAs / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>By collecting and analyzing the laryngeal cancer related genes and the miRNAs, to build a comprehensive laryngeal cancer-related gene database, which differs from the current biological information database with complex and clumsy structure and focuses on the theme of gene and miRNA, and it could make the research and teaching more convenient and efficient.</p><p><b>METHODS</b>Based on the B/S architecture, using Apache as a Web server, MySQL as coding language of database design and PHP as coding language of web design, a comprehensive database for laryngeal cancer-related genes was established, providing with the gene tables, protein tables, miRNA tables and clinical information tables of the patients with laryngeal cancer.</p><p><b>RESULTS</b>The established database containsed 207 laryngeal cancer related genes, 243 proteins, 26 miRNAs, and their particular information such as mutations, methylations, diversified expressions, and the empirical references of laryngeal cancer relevant molecules. The database could be accessed and operated via the Internet, by which browsing and retrieval of the information were performed. The database were maintained and updated regularly.</p><p><b>CONCLUSION</b>The database for laryngeal cancer related genes is resource-integrated and user-friendly, providing a genetic information query tool for the study of laryngeal cancer.</p>

Renal cell carcinoma with t(6;11)(p21.2;q13)/MALAT1-TFEB fusion: a clinical and pathological analysis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion.</p><p><b>METHODS</b>A total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature.</p><p><b>RESULTS</b>The age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E-cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis.</p><p><b>CONCLUSIONS</b>TFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis.</p>

Role of hydatidiform mole-related gene F10 in the tumorigenicity of choriocarcinoma cell line JEG-3 / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of the hydatidiform mole-related gene F10 in the tumorigenicity of choriocarcinoma cell lines JEG-3 in nude mice.</p><p><b>METHODS</b>Choriocarcinoma JEG-3 cell lines with stable F10 gene over-expression and F10 gene silencing were established using cell transfection and RNA interference techniques, respectively. Thirty SPF nude mice (4-5 weeks old) were equally randomized into F10 over-expression group, control group, and F10 gene-silenced group for subcutaneous injection of 0.2 ml cell suspension (5 × 10⁷ cells) of F10 gene over-expressing JEG-3 cells, non-treated JEG-3 cells, and F10 gene-silenced JEG-3 cells, respectively. The mice were observed and weighed every 3-4 days, and the tumor formation time was recorded to draw the tumor growth curve and calculate the tumor formation rate.</p><p><b>RESULTS</b>The tumor formation rates were 100% in all the 3 groups. No significant difference was found in the tumor formation time among the F10 over-expression, F10-silenced and control groups (6.2 ± 0.78 vs 7 ± 2.49 vs 6.3 ± 0.67 days; F=0.781, P=0.468). A significantly greater tumor growth rate was noted in the F10 over-expression group compared with the other two groups (P<0.05), and the growth rate was significantly slower in F10-silenced group than in the control group (P<0.05). The subcutaneous tumor weight at 5 weeks after JEG-3 cell injection differed significantly among F10 over-expression, F10-silenced and control groups (571.1 ± 221.10 vs 136.2 ± 66.25 vs 354.5 ± 116.23 mg; F=21.199, P=0.000).</p><p><b>CONCLUSION</b>F10 gene plays a role in the regulation of choriocarcinoma JEG-3 cell proliferation and might enhance its tumorigenicity in nude mice.</p>

Mutation analysis of large tumor suppressor genes LATS1 and LATS2 supports a tumor suppressor role in human cancer

In recent years, human cancer genome projects provide unprecedented opportunities for the discovery of cancer genes and signaling pathways that contribute to tumor development. While numerous gene mutations can be identified from each cancer genome, what these mutations mean for cancer is a challenging question to address, especially for those from less understood putative new cancer genes. As a powerful approach, in silico bioinformatics analysis could efficiently sort out mutations that are predicted to damage gene function. Such an analysis of human large tumor suppressor genes, LATS1 and LATS2, has been carried out and the results support a role of hLATS1//2 as negative growth regulators and tumor suppressors.

Carcinogenesis Colorrectal. Nuevas perspectivas e implicancias clínicas para su detección / Colorectal Carcinogenesis. New perspectives and clinical implications for its detection

El cáncer colorrectal (CCR) es una de las principales causas de morbilidad y mortalidad a nivel mundial. Clásicamente se considera a los adenomas como las lesiones precursoras del CCR y se estipula un tiempo de 10 a 15 años para completar la secuencia adenoma-carcinoma. El CCR evoluciona a través de la acumulación progresiva de alteraciones genéticas y epigenéticas, las que conducen a la transformación de la mucosa colónica normal en cáncer invasivo. La identificación de diferentes vías moleculares de carcinogénesis colorrectal ha demostrado la naturaleza heterogénea del cáncer colónico. De reciente descripción, las lesiones aserradas muestran cambios moleculares y patológicos distintos a los adenomas tradicionales, estimándose que presentan un tiempo más acelerado de evolución hacia la malignidad. El objetivo de esta revisión es actualizar conocimientos sobre la génesis tumoral y sus bases biomoleculares a fin de posibilitar su aplicación a etapas clínicas concretas como la prevención y el tratamiento

Colorectal cancer (CRC) is one of the main causes of morbidity and mortality worldwide. Adenomas are classically regarded as precursor lesions of CRC and between 10 and 15 years is thought to elapse to complete the adenoma-carcinoma sequence. CRC evolves through the progressive accumulation of genetic and epigenetic alterations that lead to invasive cancer through the transformation of normal colonic mucosa. The identification of different molecular pathways of colorectal carcinogenesis has demonstrated the heterogeneous nature of colon cancer. Recent description of serrated lesions shows molecular and pathological changes other than traditional adenomas with an estimated faster time of progression to malignancy. The aim of this review is to update the knowledge about tumorigenesis and its biomolecular basis for clinical application in early stages providing firm ground for prevention and treatment

Terapia génica para el tratamiento del cáncer / Gene therapy for cancer treatment

El cáncer es una enfermedad compleja de etiología desconocida. Factores genéticos y epigenéticos se asocian al incremento en el riesgo de desarrollar esta enfermedad. A pesar del avance en los tratamientos tradicionales contra el cáncer, el pronóstico de los pacientes no ha mejorado significativamente. Estudios en la patogénesis molecular del cáncer han evidenciado la existencia de dianas moleculares con potencial terapéutico que permiten trasladar los conocimientos de la investigación básica a la clínica implementando nuevas terapias para el beneficio del paciente. El conocimiento del genoma viral, su función, replicación y los mecanismos de infección a la célula tumoral han permitido el desarrollo de la terapia génica viral que puede ser la herramienta ideal para el tratamiento del cáncer. Este artículo revisa diferentes metodologias desarrolladas para el diseno de una terapia génica contra el cáncer, abordada desde diferentes contextos biológicos, y su aplicación clínica para el tratamiento del cáncer.

Cancer is a complicated disease of unknown etiology. Genetic and epigenetic factors are associated with an increased risk for developing this disease. Despite the progress in the traditional cancer therapies, the prognosis of patients has not improved significantly. Studies on the molecular pathogenesis of cancer have demonstrated the existence of molecular targets with therapeutic potential. Furthermore, knowledge of the viral genome function and replication, as well as of the mechanisms of tumor cell infection, have made it possible to develop an ideal tool for gene therapy against cancer and thus, enable the transfer of knowledge from basic to clinical research for the benefit of patients. This article reviews different methodologies developed to design a cancer gene therapy and its clinical application for treating cancer, addressed from various biological contexts.

Application of improved locally linear embedding algorithm in dimensionality reduction of cancer gene expression data / 生物医学工程学杂志

Cancer gene expression data have the characteristics of high dimensionalities and small samples so it is necessary to perform dimensionality reduction of the data. Traditional linear dimensionality reduction approaches can not find the nonlinear relationship between the data points. In addition, they have bad dimensionality reduction results. Therefore a multiple weights locally linear embedding (LLE) algorithm with improved distance is introduced to perform dimensionality reduction in this study. We adopted an improved distance to calculate the neighbor of each data point in this algorithm, and then we introduced multiple sets of linearly independent local weight vectors for each neighbor, and obtained the embedding results in the low-dimensional space of the high-dimensional data by minimizing the reconstruction error. Experimental result showed that the multiple weights LLE algorithm with improved distance had good dimensionality reduction functions of the cancer gene expression data.

Altered Gene Expression Profile After Exposure to Transforming Growth Factor beta1 in the 253J Human Bladder Cancer Cell Line

PURPOSE: Transforming growth factor beta1 (TGF-beta1) inhibits the growth of bladder cancer cells and this effect is prominent and constant in 253J bladder cancer cells. We performed a microarray analysis to search for genes that were altered after TGF-beta1 treatment to understand the growth inhibitory action of TGF-beta1. MATERIALS AND METHODS: 253J bladder cancer cells were exposed to TGF-beta1 and total RNA was extracted at 6, 24, and 48 hours after exposure. The RNA was hybridized onto a human 22K oligonucleotide microarray and the data were analyzed by using GeneSpring 7.1. RESULTS: In the microarray analysis, a total of 1,974 genes showing changes of more than 2.0 fold were selected. The selected genes were further subdivided into five highly cohesive clusters with high probability according to the time-dependent expression pattern. A total of 310 genes showing changes of more than 2.0 fold in repeated arrays were identified by use of simple t-tests. Of these genes, those having a known function were listed according to clusters. Microarray analysis showed increased expression of molecules known to be related to Smad-dependent signal transduction, such as SARA and Smad4, and also those known to be related to the mitogen-activated protein kinase (MAPK) pathway, such as MAPKK1 and MAPKK4. CONCLUSIONS: A list of genes showing significantly altered expression profiles after TGF-beta1 treatment was made according to five highly cohesive clusters. The data suggest that the growth inhibitory effect of TGF-beta1 in bladder cancer may occur through the Smad-dependent pathway, possibly via activation of the extracellular signal-related kinase 1 and Jun amino-terminal kinases Mitogen-activated protein kinase pathway.