1.Expression of fragile histidine triad in endometriosis.
Gui-Dong SU ; Yan KE ; Yan-Hong YU ; Guang-Liang ZHANG
Journal of Southern Medical University 2009;29(7):1479-1481
OBJECTIVETo detect the expression of fragile histidine triad in endometriosis and investigate the pathogenesis of endometriosis.
METHODSimmunohistochemistry was used to examine the expression of Fhit in the eutopic and ectopic endometria of 58 patients with endometriosis and in the endometria in 15 patients with hysteromyoma.
RESULTSThe intensity of Fhit expression decreased in the order of normal endometrium, eutopic endometrium in endometriosis group, and ectopic endometrium. In patients with endometriosis, Fhit expression in the eutopic and ectopic endometria in proliferative phase showed no significant difference from that in secretory phase (P>0.05). Fhit expression in the ectopic endometrium showed significant difference between different r-AFS stages. MOD of ectopic endometrium in stages I-II was significantly higher than that in stages III-IV (P<0.05), but Fhit expression in the eutopic endometrium showed no significant difference (P>0.05). MOD of ovarian endometriosis showed no difference with that of adenomyosis.
CONCLUSIONSFhit may play an important role in the development of endometriosis.
Acid Anhydride Hydrolases ; metabolism ; Adult ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Proteins ; metabolism
2.Loss of fragile histidine triad expression in colorectal carcinoma.
Po ZHAO ; Yali LU ; Yingchuan HU ; Mei ZHONG ; Zhijun LI ; Xianghong LI
Chinese Journal of Pathology 2002;31(2):124-127
OBJECTIVETo investigate the expression of fragile histidine triad (FHIT) gene protein, FHIT and the possible relationship between FHIT expression and clinicopathological indices in colorectal carcinoma.
METHODSDetecting FHIT protein expression in 60 cases of formalin-fixed, paraffin-embedded colorectal carcinoma by citrate-microwave-SP immunohistochemical method, and analyzing its relationship to histological grade, Dukes' stage and 5-year survival rate.
RESULTS55% of the carcinomas showed a marked loss or absence of FHIT expression compared with their matched normal mucosa. Carcinomas with reduced expression of FHIT correlated with their histological grade, Dukes' stage (P < 0.05) and 5-year survival rate. The distribution of decreased expression of FHIT was 7/16 in grade I carcinoma, 14/30 in grade II, 12/14 in grade III, respectively. The correlation between decreased expression of FHIT and Dukes' staging was 5/11 in stage A, 12/28 in stage B, and 16/21 in stage C. The difference between stage A, B with no lymph nodes metastases and the stage C with lymph nodes metastases was of significance (P < 0.05). The follow-up data of 39 cases showed that in the 5-year survival group, 13/25 were of the low FHIT expression carcinomas, while in 5-year deceased group 12/14 were of the low FHIT expression carcinomas (P < 0.05).
CONCLUSIONSThe reduced expression of FHIT may be associated with decreasing differentiation, metastasis and 5-year survival rate in colorectal carcinoma. It is suggested that decreased FHIT expression plays an important role in the development and progression of the tumor, and thus may become a new prognostic marker in colorectal carcinoma.
Acid Anhydride Hydrolases ; Colorectal Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Proteins ; biosynthesis ; Neoplasm Staging ; Survival Analysis
3.Expression of Ki-67, galectin-3, fragile histidine triad, and parafibromin in malignant and benign parathyroid tumors.
Ou WANG ; Chun-Yan WANG ; Jie SHI ; Min NIE ; Wei-Bo XIA ; Mei LI ; Yan JIANG ; Heng GUAN ; Xun-Wu MENG ; Xiao-Ping XING
Chinese Medical Journal 2012;125(16):2895-2901
BACKGROUNDIt is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Our study aimed to investigate the differential expression of Ki-67, galectin-3, fragile histidine triad (FHIT) gene, and parafibromin in PC, parathyroid adenoma (PA), parathyroid hyperplasia (PH), and normal parathyroid (NP) tissues; then to assess these expression values for use in differential diagnosis of malignant and benign parathyroid tumors.
METHODSData of 15 cases with PC, 19 PAs, and 8 PHs were retrospectively analyzed for their clinical characteristics. The expression of Ki-67, galectin-3, FHIT, and parafibromin were detected via immunohistochemistry in the above-mentioned specimens and 6 NPs as control.
RESULTSComplete loss of parafibromin expression was seen in 9 of 15 (60%) carcinomas, and all normal parathyroid tissues and parathyroid benign tumors stained positive for parafibromin except for one (4%) adenoma. Galectin-3 staining was positive in 11 of 15 (73%) carcinomas, 5 of 19 (26%) adenomas, 1 of 8 (12%) hyperplasias, and 0 of 6 normal tissues. The Ki-67 proliferative index was high in 4 of 15 (27%) carcinomas, 1 of 19 (5%) adenomas, and none of the hyperplasia or normal tissues. FHIT expression did not differ appreciably among the tumor types. The combination of overexpression of galectin-3 or loss of parafibromin increased sensitivity for PC to 87%, while the specificity of both positive galectin-3 and positive Ki-67 could reach 100%.
CONCLUSIONSThese data suggested that loss of parafibromin and overexpression of galectin-3 and Ki-67 might help to distinguish parathyroid carcinoma from other parathyroid tumors. And the combination of two or three of these markers might produce better sensitivity and/or specificity for the diagnosis of parathyroid carcinoma.
Acid Anhydride Hydrolases ; metabolism ; Galectin 3 ; metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Neoplasm Proteins ; metabolism ; Parathyroid Neoplasms ; metabolism ; Tumor Suppressor Proteins ; metabolism
4.Expressions of FHIT and PTEN and their significance in prostate cancer.
Qin XIAO ; Xue-wen GU ; Ji-xin JIANG ; Cui-mei WANG ; Qing XU
National Journal of Andrology 2011;17(2):136-139
OBJECTIVETo investigate the expressions of the FHIT and PTEN genes and their significance in prostate cancer.
METHODSThe expressions of FHIT and PTEN were detected in 85 cases of prostate cancer and 30 cases of benign prostatic nodular hyperplasia by immunohistochemistry of PV-6000.
RESULTSThe positive expression rates of FHIT and PTEN were 34.1% and 42.4% in prostate cancer, significantly lower than 96.7% and 90.0% in benign prostatic nodular hyperplasia (P <0.01). Statistically significant differences were found in the positive expression rates of FHIT and PTEN among different Gleason grades, 44.4% and 55.6% in well differentiated, 38.9% and 44.4% in moderately differentiated, and 25.0% and 37.5% in lowly differentiated prostate cancer (P <0.05). But the expression of FHIT.
CONCLUSIONFHIT and PTEN may play a certain role in the was not correlated with that of PTEN in the prostate cancer tissue (P >0.05). development, progression and infiltration of prostate cancer.
Acid Anhydride Hydrolases ; metabolism ; Adenocarcinoma ; metabolism ; pathology ; Aged ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; PTEN Phosphohydrolase ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology
5.Expression of fragile histidine triad (FHIT) protein and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust.
Li BIAN ; Yong-Wen HE ; Hong-Mei FU ; Yong-Hua RUAN ; Qian GAO ; Chun-Yan WANG ; Ke-Wei JIN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2010;28(12):895-899
OBJECTIVETo study the expression and significance of fragile histidine triad (FHIT) and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust.
METHODSEvery second generation of immortalized human bronchial epithelial cells (BEAS-2B) and human embryo lung fibroblasts (WI-38) were exposed to 100 µg/ml Yunnan tin mine dust for 72 h, until the ninth generation. The cells were subsequently co-cultured from the 11th generation. Experimental setup: B group, B (W) group, B (W 100) group, B100 group, B100 (W) group, B100 (W100) group. The expressions of FHIT and Ki-67 in epithelial cells were determined by the method of immunocytochemistry at the 16th, 26th and 36th generation. The percentage of Ki-67 positive cells was calculated as proliferation index.
RESULTSThe expression of FHIT was observed in BEAS-2B cells. The expression levels of FHIT among B group, B (W) group and B (W 100) group had not instinctive difference. At the 16th generation, the expression of FHIT in the B100 group was decreased compared with that in the B group and the expression of FHIT between B100 (W) group and B100 (W100) group was lower than that in the B100 group. At the 26th generation, the expression of FHIT was decreased compared with that at the 16th generation in the B100, B100 (W) and B100 (W100) groups. However, At the 36th generation, positive expression were observed again in the B100, B100 (W) and B100 (W100) groups and the expression levels were in incremental order. At the 16th, 26th and 36th generation, the proliferation indexes of B group, B (W) group and B (W 100) group were all < 3%. The proliferation indexes of B100, B100 (W) and B100 (W100) were increased step by step with the generation elongation.
CONCLUSIONSFHIT could be a target at which Yunnan tin mine dust induces transformation of BEAS-2B cells. The proliferation activation of BEAS-2B cells can be improved by Yunnan tin mine dust.
Acid Anhydride Hydrolases ; metabolism ; Cell Line ; Cell Transdifferentiation ; China ; Dust ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Lung ; cytology ; Neoplasm Proteins ; metabolism ; Tin ; toxicity
6.Expression of FHIT gene protein in laryngeal carcinoma.
Litang CAO ; Xiaoming CHEN ; Binquan WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2008;22(3):122-123
OBJECTIVE:
To investigate the role and clinical significance of the expression of FHIT gene in development and progression of laryngeal squamous cell carcinoma(LSCC).
METHOD:
The expression FHIT protein was detected by immunohistochemistry method in the 52 cases with LSCC and 23 cases of adjacent cancer tissues and 10 cases of laryngeal normal mucosa. The expression of FHIT was analyzed in LSCC with different clinicopathological parameters.
RESULT:
The expression of FHIT in normal tissues (90.0%) and adjacent tissues (78.3%) was obvious higher than that in LSCC (46.2%), which had statistical significant difference (P < 0.01). There was a positive correlation between FHIT expression and TNM staging, lymph node metastasis; but not pathological grade.
CONCLUSION
The loss of FHIT expression may be correlated with the development and progression of laryngeal carcinoma. FHIT may be an important tumor suppressor gene in LSCC.
Acid Anhydride Hydrolases
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metabolism
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Adult
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Aged
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Carcinoma, Squamous Cell
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metabolism
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pathology
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Female
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Humans
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Laryngeal Neoplasms
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metabolism
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pathology
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Male
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Middle Aged
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Neoplasm Proteins
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metabolism
7.Aberrant expression and deletion of FHIT gene in leukemias.
Li WANG ; Lu-Jia DONG ; Fang TIAN ; Guang-Xian LIU ; Chun-Hai LI
Journal of Experimental Hematology 2003;11(2):153-160
FHIT (fragile histidine triad) gene at chromosome 3p14.2 usually expresses at a very low level in human tissue and cells. A high frequency of abnormalities in FHIT gene has been demonstrated in various cancers. FHIT is proposed as a putative tumor-suppressor gene. To evaluate the expression of the FHIT gene in various leukemias, bone marrow or peripheral blood samples from 98 leukemia patients were tested by RT-PCR: 38 from patients with AML-[M(2)(9), M(3)(12), M(4)(8), M(5)(9)], 16 with ALL, and 34 with CML-[CP(20), AP(4), BC(10)] of various FAB types, as well as 10 patients with other hematological malignancies. To detect a deletion in sequencing the FHIT gene, the representative aberrant PCR products were cloned and then sequenced. The results showed that 22/38 (58%) patients with AML, 9/16 (56%) patients with ALL and 19/34 (56%) patients with CML were detectable of aberrant FHIT mRNA transcripts or deletion of FHIT. In 6 (16%) AML patients, 3 (19%) ALL patients, and 5 (15%) CML patients, the wild-type product was absent. Some patient's samples - 6 (42%) AML, 6 (38%) ALL, and 14 (41%) CML revealed aberrant FHIT transcripts in addition to a normal-sized band. Samples from healthy donors (PB, n = 12; BM, n = 5) did not indicate any abnormal expression. Eleven isolated fragments from various patterns of FHIT gene expression were investigated using cDNA sequencing. Sequence analysis revealed deletion of exon 4-8, exon 5-8, and exon 5-6 in various leukemias, as well as the deletion of the full FHIT gene sequence. The fused transcripts included: exon 3 and exon 9, exon 3 and exon 7, exon 4 and exon 9, exon 5 and exon 7. Sequence analysis of aberrant fragments present in samples from an AML and a CML patients was detected for point mutations and insert mutations located in exons 2, 8 and 10, plus a variety of aberrant transcripts. Deletion or aberrant FHIT mRNA transcripts in 50/98 (51%) leukemia patients were found. All samples with aberrant FHIT lacked gene product. A Kaplan-Meier plot of survival in patients with AML in relation to FHIT expression revealed that aberrance or loss of FHIT gene significantly correlated with a low clinical remission rate and poor overall survival.
Acid Anhydride Hydrolases
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genetics
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Base Sequence
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Gene Deletion
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Humans
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Leukemia
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genetics
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metabolism
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Lymphocytes
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metabolism
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Molecular Sequence Data
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Mutation
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Neoplasm Proteins
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genetics
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Polymerase Chain Reaction
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RNA, Messenger
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analysis
8.Alteration of FHIT gene and p16 gene in malignant transformed cells induced by crystalline nickel sulfide.
Wei-dong JI ; Zhong-liang WU ; Jia-kun CHEN ; Fei YI ; Su-mei FENG
Chinese Journal of Oncology 2003;25(1):26-30
OBJECTIVETo detect the alteration of fragile histidine triad (FHIT) gene and p16 gene during malignant transformation of immortal human bronchial epithelial cell line (16HBE) induced by crystalline nickel sulfide, and study the molecular mechanism of nickel carcinogenesis.
METHODSMalignant transformed cells and tumorigenic cells were examined for the alteration of FHIT gene and p16 gene by RT-PCR, DNA sequencing and silver staining PCR-SSCP.
RESULTSCompared with those of control 16HBE, neither mutation of exon2 or exon2-3, abnormal expression in p16 gene nor mutation of FHIT exon5, 6, 7 and 8, exon1-4 or exon5-9 were observed in transformed cells and tumorigenic cells. But aberrant transcript or FHIT gene expression loss were observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in FHIT gene, the deletion of exon6, exon7 and exon8 and an insertion of 36 bp sequence replacing exon6-8, was confirmed by sequencing.
CONCLUSIONFHIT gene, not p16 gene, could play a definite role in nickel carcinogenesis. Alterations of FHIT gene induced by crystalline NiS could be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation, and FHIT gene could be one of the important target genes activated by exotic carcinogens.
Acid Anhydride Hydrolases ; Base Sequence ; Cell Transformation, Neoplastic ; chemically induced ; metabolism ; Cells, Cultured ; Gene Expression ; Genes, p16 ; physiology ; Humans ; Molecular Sequence Data ; Neoplasm Proteins ; genetics ; metabolism ; Nickel ; pharmacology
9.Impact of fragile histidine triad gene transfection on the proliferation and apoptosis of human colorectal cancer cell.
Jie CAO ; Li-yuan LIANG ; Ping YANG ; Yue-jun QIAN ; Hui WANG ; Zheng SUN ; Wang-lin LI ; Ming-hua TAN
Chinese Journal of Gastrointestinal Surgery 2010;13(9):691-694
OBJECTIVETo investigate the effect of fragile histidine triad (FHIT) gene transfection on human colorectal cancer cell line SW480 through up-regulation of caspase-8 expression.
METHODSThe eukaryotic expression plasmid containing FHIT, pRc/CMV2-FHIT was prepared and purified, and then identified by restrictive enzyme digestion. pRc/CMV2-FHIT was transfected into SW480 cells, and positive cell clones (SW480-FHIT, study group) were selected and amplified. Empty plasmid-transfected SW480 cells(SW480-pRc/CMV2, negative control) and normal SW480 cells (bland control) were used as control. Methyl thiazolyl tetrazolium (MTT) assay was used to test the changes in the proliferation of SW480 cells. Cell-cycle kinetics and apoptosis were analyzed by flow cytometry (FCM). The changes of pro-caspase-8, caspase-8 mRNA and caspase-8 relative activity were analyzed by Western blot, semi-quantitative RT-PCR and colorimetric assay with pan labeled substrate, respectively.
RESULTSAt 96 hours after transfection, cell inhibition rates of the study group and the negative control group were 71.7% and 16.9%. G0/G1 ratio was (63.2±3.5)% and (50.6±2.1)%, optical density of caspase-8 mRNA band 107 and 41, and relative activity of caspase-8 0.43 and 0.25, respectively. All the differences above were statistically significant (P<0.05). When FHIT inhibitor was added, the relative activity of caspase-8 decreased to 0.22, comparable to that in the control group.
CONCLUSIONSFHIT gene transfection can significantly inhibit the proliferation and induce G0/G1 arrest in human colon cancer cell line SW480. The mechanism is related to the up-regulation of caspase-8 expression.
Acid Anhydride Hydrolases ; genetics ; Apoptosis ; Caspase 8 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Colonic Neoplasms ; genetics ; pathology ; Humans ; Neoplasm Proteins ; genetics ; RNA, Messenger ; genetics ; Transfection
10.Interaction between folate deficiency and aberrant expression related to fragile histidine triad gene in the progression of cervical cancerization.
Xiao CHEN ; Jintao WANG ; Email: WANGJT59@163.COM. ; Lixia BAI ; Ling DING ; Tingting WU ; Lan BAI ; Juan XU ; Xuesong SUN
Chinese Journal of Epidemiology 2015;36(4):387-392
OBJECTIVETo explore the interaction between folate deficiency and aberrant expression related to fragile histidine triad (FHIT) gene in the progression of cervical cancerization.
METHODSA total number of 80 patients with histological diagnosis of cervix inflammation (CI), 55 cervical intraepithelial neoplasm I (CIN I), 55 cervical intraepithelial neoplasm II/III (CIN II/III) and 64 cervical squamous cell carcinoma (SCC) were included in this study. Levels of serum folate were detected by microbiological assay method and the methylation status of FHIT gene CpG islands was tested by methylation-specific PCR (MSP). FHIT protein levels were measured by Western blot. In vitro, cervical cancer cell lines CaSki (HPV16-positive) was treated with different concentrations of folate. Proliferation and apoptosis of cells, methylation of FHIT gene and the levels of FHIT protein expression were measured in each group. All analyses were performed with SPSS (version 17.0) statistical software. Differences among groups were assessed by chi-square test, Kruskal-Wallis test. Spearman correlation, and the interaction effects were evaluated by additive model.
RESULTSThe levels of serum folate (H = 59.08, P < 0.001) and FHIT protein expression (H = 50.93, P < 0.001) decreased gradually along with the severity of cervix lesions, while the methylation rates of FHIT gene CpG islands increased (trend χ² = 28.34, P < 0.001). Both levels of serum folate levels and FHIT protein expression were positively correlated (r = 0.213, P = 0.001), with an additive interaction seen between them in CIN I, CIN II/III, SCC groups. In vitro, both rates related to proliferation inhibition (r = 0.98, P < 0.001) and apoptosis (r = 0.99, P < 0.001) together with the levels of FHIT protein expression (r = 0.97, P < 0.001) were all increased gradually with the increase of folate concentration while the methylation status of FHIT gene CpG islands all changed from positive to negative gradually.
CONCLUSIONResults from our study revealed that both folate deficiency and FHIT protein aberrant low expression might increase the risk of developing cervical cancer and cervix precancerous lesions, and thus play a synergistic action in the progression of cervical cancerization.
Acid Anhydride Hydrolases ; metabolism ; Apoptosis ; Carcinoma, Squamous Cell ; pathology ; Cervical Intraepithelial Neoplasia ; pathology ; Disease Progression ; Female ; Folic Acid ; blood ; Folic Acid Deficiency ; epidemiology ; Human papillomavirus 16 ; Humans ; Neoplasm Proteins ; metabolism ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms ; pathology