Biomedical subjects

Kenji Sugio

Publications and source records attributed to Kenji Sugio.

64 records · Page 4Linked to original sources

PubMedDate not supplied

A case-case study comparing the usefulness of serum trace elements (Cu, Zn and Se) and tumor markers (CEA, SCC and SLX) in non-small cell lung cancer patients.

UNLABELLED: Serum copper (Cu), zinc (Zn) the Cu/Zn ratio (Cu/Zn) and selenium (Se) were evaluated in 84 patients with non-small cell lung cancer (NSCLC) before surgery. Serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and sialyl Lewis X-i antigen (SLX) levels were also determined in the same cases. The cut-off values of Cu, Zn and Se were established to create two categories with equal numbers of patients. We investigated the clinical and prognostic usefulness of assays of serum trace elements (Cu, Zn, Cu/Zn and Se) and compared levels of serum trace elements and serum tumor markers (CEA, SCC and SLX) in NSCLC patients. Furthermore, we evaluated the usefulness of serum trace elements, when compared with tumor markers, in assessing prognosis for NSCLC. IN CONCLUSION: (1) a preoperative increase in Cu/Zn level predicted tumor progression more effectively than changes in Cu or Zn levels; (2) Se levels seemed to vary with age, but there was no relationship between Se level and disease stage; (3) the measurement of Cu/Zn was useful for assessing both prognosis and extent of the disease in NSCLC patients, similar to the measurement of serum tumor markers such as CEA; and (4) the measurement of the Cu/Zn had prognostic significance, but was inferior to disease stage in predicting outcome. Cu and Zn in serum are storable and the determination of Cu/Zn level is so simple and inexpensive that it can be helpful in determining clinical stages and predicting the prognoses of NSCLC patients.

Adult↗

PubMedDate not supplied

Evidence-based prevention (EBP): approach to lung cancer prevention based on cytochrome 1A1 and cytochrome 2E1 polymorphism.

Now that the human genome has been sequenced, we consider that combinations of 3 to 10 million polymorphic loci scattered throughout the genome contribute to individual differences. Genetic polymorphism analysis is useful for the made-to-order medical treatment of patients and the prevention of disease onset in normal healthy individuals. Individually-tailored disease prevention based on findings such as genetic polymorphism analysis results can be grasped by the concept of evidence-based prevention (EBP). In this paper we outline cytochrome P450 (CYP) 1A1 and 2E1 polymorphism-related differences in metabolic activation of carcinogens in relation to the risk of lung cancer, and explain single nucleotide polymorphism (SNP). We also compare the reports to date on SNP types in CYP1A1 and CYP2E1 in relation to the risk of lung cancer with our study results, examine survival rates of lung cancer patients by CYP1A1 or CYP2E1 genotype and discuss the applicability of SNP research to EBP.

Cytochrome P-450 CYP1A1↗

PubMedDate not supplied

Molecular genetic tumor markers in non-small cell lung cancer.

Not only serum tumor markers, such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and carbohydrate antigen (CA) 125, but also serum growth factors have been examined to evaluate tumor stages and to predict the recurrence and metastasis in patients with non-small cell lung cancer (NSCLC) (1-5). In recent years, the analysis of the genome and proteome has advanced remarkably. An array of molecular genetic tumor markers (MGTMs) have been identified based on the biological characterization of tumors, such as tumor development, growth, invasion and metastasis. Molecular genetic tumor marker research has also entered a new era, since comprehensive gene profile analysis using cDNA microarrays and comprehensive protein expression analysis using proteomics technology have been developed. On the other hand, the frequency of lung cancer patients with which various tumor markers are associated is increasing in Japan (6-8). This paper reviews MGTMs characteristic of lung cancer and clarifies the clinical usefulness and applications of MGTM for cancer treatment.

Biomarkers, Tumor↗

PubMedDate not supplied

Y-box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer.

Transcription factor Y-box-binding protein 1 (YB-1), which binds to the inverted CCAAT box, is not only involved in the transcription of various genes, but also in cell proliferation and DNA repair. The aim of this study was to detect YB-1 and p53 expression and their relationship to proliferating cell nuclear antigen (PCNA) in non-small cell lung cancer (NSCLC) using immunohistochemical (IHC) staining, and to evaluate the relationship between their expression levels and the prognosis of patients with NSCLC. Positive expressions of YB-1, p53 and PCNA were detected in NSCLC cells in 43 (45.7%), 33 (35.0%) and 45 (47.9%) out of 94 patients, respectively. No significant differences were observed between YB-1 expression and the patients' gender, age at surgery, pathological stage, pathological T status, pathological N status, or pathological M status. The mean PCNA-labelling index (LI) for cells was 40.7+/-2.6. Also, a significant correlation between YB-1 and PCNA-LI was found (p<0.01), but none was found between p53 expression and PCNA. The positive expression of YB-1 was associated with squamous cell carcinoma and large cell carcinoma, compared with adenocarcinomas (p<0.01), and higher levels of PCNA-LI were associated with large cell carcinoma compared with adenocarcinomas and squamous cell carcinoma (p<0.01). These results suggest that YB-1 expression is correlated with PCNA expression in NSCLC. In addition, the DNA repair pathway and tumor proliferation mediated by YB-1 linking to PCNA may be responsible for controlling the growth of NSCLC.

Adult↗

PubMedDate not supplied

Expression of deltaNp63 in squamous cell carcinoma of the esophagus.

BACKGROUND: The p63 gene is present as two isoforms, namely TAp63 and deltaNp63. The biological role of deltaNp63 in the progression of esophageal cancer is still controversial. PATIENTS AND METHODS: The expression of deltaNp63, as well as that of p63, was immunohistochemically examined in 61 resected specimens of squamous cell carcinoma of the esophagus. RESULTS: The incidences of a positive deltaNp63 expression were 32 and 64% in carcinomas with and without adventitial invasion, respectively, and 37 and 65% in those with and without lymph node metastasis, respectively (p<0.05). The prognosis was significantly better in the positive deltaNp63 group than in the negative group (p<0.01). However, a multivariate analysis revealed deltaNp63 not to be an independent prognostic factor. Regarding p63, diminished expression was more frequently observed in advanced carcinomas, however, there were no statistically significant differences. CONCLUSION: The impaired deltaNp63 reflects the progression of squamous cell carcinoma of the esophagus.

Adult↗

PubMedDate not supplied

P53R2, p53 inducible ribonucleotide reductase gene, correlated with tumor progression of non-small cell lung cancer.

p53R2 plays a crucial role in supplying dNTPs for DNA repair. The expression of p53R2 is induced by DNA-damaging agents in a p53-dependent manner and p53R2 translocates to the nucleus upon DNA damage. Immunohistochemistry was used to analyze the protein expression of p53R2 in paraffin-embedded tumor samples from 130 well-characterized non-small cell lung cancer (NSCLC) patients and the expression level of p53R2, clinical variables and survival outcome were compared. A positive expression of p53R2 was detected in the cytoplasm of tumor cells in 61 of the 130 patients (46.2%) with NSCLC. The positive ratio was significantly higher in the patients with pathological stage II/III, pathological T3-4 and pathological N1-3 than in those with stage I, T1-2 and N0, respectively. No significant difference was observed between the p53R2 expression and the gender, age at operation, histological type or p53 expression. Though our findings do not support that the p53R2 immunocytochemical marker alone plays an important prognostic role in NSCLC, the DNA repair pathway mediated by p53R2 may be responsible for controlling the growth of lung cancer.

Adult↗

PubMedDate not supplied

Expression of FHIT in esophageal epithelium and carcinoma: reference to drinking, smoking and multicentric carcinogenesis.

BACKGROUND: Both alcohol consumption and cigarette smoking are risk factors for esophageal cancer. The purpose of this study was to clarify whether the fragile histidine triad (FHIT) is their target gene in esophageal carcinogenesis as well as in multicentric carcinogenesis. PATIENTS AND METHODS: The expression of FHIT was immunohistochemically examined in the squamous cell carcinoma as well as in the normal esophageal epithelium of 55 cases with esophageal cancer. RESULTS: The median drinking indices (DIs) were 546 and 1092 (p<0.01) in cases with positive FHIT expression and those with a diminished expression in the esophageal epithelium, respectively. Furthermore, the incidences of intra-esophageal multiple cancer were 44% and 13%, respectively (p<0.05). Regarding the expression in cancer lesions, the median DIs were 280 and 721 in positive and diminished cases, respectively (p=0.081). CONCLUSION: A loss of FHIT expression is associated not only with alcohol-induced esophageal carcinogenesis, but also with multicentric carcinogenesis.

Acid Anhydride Hydrolases↗

PubMedDate not supplied

Expression of the p53 family in lung cancer.

BACKGROUND: p53 is mutated in about 50% of various malignant diseases including lung cancer. The p53 family consists of p53, p73 and p63. Although transactivating protein isoforms display p53-like functions, the deltaNp73 or deltaNp63 isoforms act toward p53 in a dominantly negative way. The aim of this study was to detect p53, deltaNp73 and deltaNp63 expressions in lung cancer and to evaluate the relationship between the expression levels of the proteins and the prognosis of patients with resectable lung cancer. MATERIALS AND METHODS: Immunohistochemistry was employed to analyze the protein expression of p53, deltaNp73 and deltaNp63 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients. The correlation among the expression levels of p53, deltaNp73 and deltaNp63, clinical variables and survival outcome was analyzed. RESULTS: Positive expressions of p53, deltaNp73 and deltaNp63 were detected in the tumor cells in 52, 77 and 44 of the 132 patients, respectively (39.4%, 58.3% and 33.3%) with lung cancer. The incidence of p53 positive expression was 54.5% and 27.6% in patients with squamous cell carcinoma and adenocarcinoma, respectively (p = 0.03). The incidence of a positive expression of deltaNp73 was 64.5% and 43.6% in male and female patients, respectively (p = 0.03). The incidence of deltaNp63 positive expression was 68.2% and 15.8% in the patients with squamous cell carcinoma and adenocarcinoma, respectively (p < 0.0001). The expressions of p53 and deltaNp63 were not found to significantly affect survival. However, lung cancer patients with a positive deltaNp73 expression had a poorer prognosis than those with a negative deltaNp73 expression. In addition, multivariate analysis indicated that a positive expression of deltaNp73 was a significantly independent factor for predicting a poor prognosis (p < 0.0001, risk ratio = 3.38). CONCLUSION: Clinical evidence that the p53 family is frequently overexpressed in lung cancer specimens, especially deltaNp63 in squamous cell carcinoma, was provided. The expression of deltaNp73 may be a useful marker for predicting a poor prognosis in resectable lung cancer. Understanding how groups of lung cancer cell genes are coordinately expressed in response to physiological, immunological and micro-environmental stimuli remains an important goal. A better understanding of the gene expression profiles of tumors may help to identify molecular targets, such as deltaNp73, for effective therapy.

Adult↗

PubMedDate not supplied

Effect of IgG produced by tumor-infiltrating B lymphocytes on lung tumor growth.

BACKGROUND: Tumor-infiltrating B lymphocytes (TIB) are often observed in lung cancer. The role of TIB in tumor growth has not been well investigated. MATERIALS AND METHODS: Forty-four surgically-resected human lung cancer tissues were xenotransplanted into SCID mice. Their blood was collected and the volume of the transplanted tumors was measured regularly. The correlations between the IgG titer in the sera and the growth of the transplanted tumors according to the clinicopathological variables were examined. RESULTS: Human IgG production from TIB was observed in the all xenotransplanted mice. Twenty-seven out of the 44 tumors regressed gradually. The average serum human IgG level of the tumor regressors (n = 10) was significantly higher than that of the progressors (n = 9) in squamous cell carcinoma (p = 0.02), while there was no significant difference in the other histological groups. CONCLUSION: IgG produced by TIB might play a crucial role in preventing tumor growth in squamous cell carcinoma.

Animals↗

PubMedDate not supplied

Antigens recognized by IgG derived from tumor-infiltrating B lymphocytes in human lung cancer.

BACKGROUND: Lung cancer tissues are often infiltrated by B lymphocytes, but it is not clear whether these infiltrations represent tumor-specific immune response or a nonspecific reaction. MATERIALS AND METHODS: The serological analysis of recombinant cDNA expression libraries (SEREX) were previously modified using a severe combined immunodeficient (SCID) mice model engrafted with fresh human lung cancer. Here, a panel of antigens recognized by tumor-infiltrating B lymphocytes (TIB) in human lung cancer were characterized. RESULTS: The modified SEREX analysis identified 22 distinct antigens in a large cell carcinoma of the lung. Sequence analysis and real time-PCR analysis showed that 55% of isolated antigens were overexpressed in tumor tissues and 9% had mutation. CONCLUSION: The results of this study indicate that the humoral immune response of TIB in lung cancer patients can be detected in the xenotransplanted SCID mouse model and our modification shows high sensitivity and specificity for identification of tumor antigens.

Animals↗