[Relationship between the mutation of leptin receptor gene and tumorigenesis of breast cancer].

OBJECTIVE: The aim of this study was to investigate the relationship of the mutations of leptin receptor gene exon 4, exon 6, exon9, and exon20 with the tumorigenesis of breast cancer. METHODS: Genomic DNA was extracted from breast cancer tissues of 155 patients, benign lesions of 56 patients and normal tissues and blood samples from 100 health control subjects. The leptin receptor genes were assayed with polymerase chain reaction (PCR) amplification and direct sequence analysis. RESULTS: Nucleotide substitutions no mutations were found at exon 4, and nucleotide substitutions occurred at codon 1029 in exon 9, no significant difference among the three groups (P = 0.574). The nucleotide substitutions at codon 668 in exon 6 resulted in Gln223Arg polymorphisms. The occurring frequencies of GG, GA, AA in breast cancer, breast benign lesions tissues and health tissues control group were 70.9% and 17.4%, 12.3%; 80.4%, 14.3% and 5.4%; and 81.0%, 16.0%, and 3.0%, respectively. Alleles of G and A in the three groups were 79.1% and 20.8%, 87.5% and 12.5%, and 89.0% and 11.0%, respectively. Compared the Gln223Arg genotype with the three allele groups, there were significant differences (χ(2) = 16.11, P < 0.005 and χ(2) = 11.41, P < 0.01), respectively. The nucleotide substitutions at codon 3057 in exon 20 resulted in Pro1019Pro polymorphisms. The occurrence frequencies of GG, GA, AA in the breast cancer, benign disease and health control groups were 11.6%, 30.3% and 56.1%; 32.1%, 44.0% and 28.5%; and 32.0%, 45.0% And 23.0%, respectively. Alleles of G and A in the three groups were 26.8% and 73.2%, 51.8% and 48.2%, and 54.5% and 45.5%, respectively. There are significant differences among the three groups (χ(2) = 6.56, P < 0.03 and χ(2) = 5.45, P < 0.05), respectively. Nucleotide substitutions occurred at relatively high frequencies at exon 6 and exon 20 in obese and overweight breast cancer patients compared with those in normal weight breast cancer patients, there were significant differences (P < 0.05 and P < 0.01). CONCLUSIONS: Our findings show that there is no relationship between the variations of leptin receptor gene exon 9 and tumorigenesis of breast cancer. The variation rate of leptin receptor gene exon 6 and exon 20 are significantly increased in the obese and overweight breast cancer patients.

[Expression and clinical significance of nuclear matrix protein 22 and cytokeratin 18 in transitional cell carcinoma of the bladder].

OBJECTIVE: To evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder. METHODS: Urinary NMP22 and CK18 levels of 293 patients with transitional cell carcinoma of the bladder, 400 patients with non-transitional cell carcinoma of the bladder, and 105 bladder benign disease were analysed by enzyme-linked-immunosorbent assay (ELISA). RESULTS: The levels of urinary NMP22 and CK18 in the patients with transitional cell carcinoma of the bladder (M = 17.3 U/ml, M(CK18) = 484.2 U/L) were significantly higher than those in the non-transitional cell carcinoma of the bladder (M = 6.8 U/ml, M(CK18) = 156.0 U/L) and the benign disease group (M(NMP22) = 2.3 U/ml, M(CK18) = 66.6 U/L) (P < 0.001). The sensitivity and specificity of urinary NMP22 and CK18 were 79.2%, 88.6% and 78.2%, 82.9%, respectively, for transitional cell carcinoma of the bladder before any treatment. The joint sensitivity of the two markers was 91.7%. The NMP22 and CK18 levels were significantly lower in the recovered patients after surgical operation (P < 0.01), while in patients with recurrence or metastasis the levels of the markers were significantly higher (P < 0.01). There was a significant relationship between NMP22 and CK18, (r = 0.689, P < 0.01). The levels of urinary nmp22 and CK18 were significantly different among pathological grade G1, G2, G3, and stage Ta, T1, T2, T3 (P < 0.01). CONCLUSION: NMP22 and CK18 are useful tumor marker for diagnosis of transitional cell carcinoma of the bladder and for monitoring the state of illness. The joint use of the two markers can improve the sensitivity of cancer detection. NMP22 and CK18 may become a new class of tumor markers, and to be the basis for development of a new assay with an increased efficacy for the detection and treatment of bladder cancer.

[Testosterone induces different-featured prostate hyperplasia in castrated and uncastrated mice].

OBJECTIVE: To study the different features of hyperplasia in castrated and uncastrated mice after testosterone (T) treatment. METHODS: Forty-eight BALB/c mice were randomly divided into 6 groups of 8 in each: castrated (A), uncastrated (B) , castrated + low T (C), uncastrated + low T (D), castrated + high T (E), uncastrated + high T (F). Groups C and D were treated with testosterone solution at the dose of 12.5 mg/(kg d) and Groups E and F at 125 mg/(kg d) for 20 consecutive days, while Groups A and B received saline only. All the mice were sacrificed on the 21st day, their ventral and dorsal prostate glands weighed and their pathological features studied. RESULTS: Atrophic prostates were observed in Group A, but normal in Group B; prostatic hyperplasia was found in both Group C and D, but more obvious in the latter (P <0.05); and a slightly higher degree of hyperplasia was noted in Groups E and F than in C and D. There was an increase in serum T and vascular endothelial growth factor (VEGF) concentration and a decrease in serum estrogen (E2) concentration in the testosterone treated groups. CONCLUSION: Both castrated and uncastrated mice develop prostate hyperplasia after short-term testosterone treatment, although in different degrees and with different features, which may help further the studies on the association of castration and androgen with prostate diseases.

[Pre- and post-chemotherapy expressions of Th1 and Th2 type cytokines and their clinical significance in gastric cancer patients].

OBJECTIVE: To investigate the pre- and post-chemotherapy expression levels of Th1 and Th2 type cytokines in peripheral blood CD4(+) T lymphocytes, the changes of Th1/Th2 ratio and their clinical significance in patients with gastric cancer. METHODS: The levels of specific cytokines in 60 gastric cancer patients were detected by flow cytometry before and after chemotherapy with FOLFOX4. RESULTS: The level of IFN-gamma from peripheral blood CD4(+) T lymphocytes after chemotherapy in the whole group of gastric cancer patients was 11.4% +/- 5.0%, significantly higher than that (9.5% +/- 3.4%) before chemotherapy (P < 0.05). The level of IL-10 after chemotherapy was 3.6% +/- 1.2%, significantly lower than that (4.2% +/- 1.8%) before chemotherapy (P < 0.05). The ratio of Th1/Th2 (IFN-gamma/IL-4) after chemotherapy was 3.4 +/- 1.0 versus 3.4 +/- 1.6 before chemotherapy, without significant difference (P > 0.05). Interestingly, the levels of IFN-gamma and TNF-alpha of peripheral blood CD4(+) T lymphocytes in 15 gastric cancer patients who achieved partial response (PR) after chemotherapy were 14.8% +/- 8.0% and 5.9% +/- 2.0%, respectively, both were higher than that (6.9% +/- 2.5% and 4.2% +/- 1.3%) before chemotherapy (both P < 0.05). Furthermore, the ratio of Th1/Th2 (IFN-gamma/IL-4) after chemotherapy was 4.0 +/- 1.5, significantly higher than 2.5 +/- 1.2 before chemotherapy (P < 0.01). CONCLUSION: Effective chemotherapy may reduce the tumor burden and relieve the shift of Th1/Th2 ratio. Improvement in immune function may be a very important therapeutic measure due to poor response of chemotherapy in gastric cancer patients.

[The diagnosis and monitoring of transitional cell cancer of the urinary tract through nuclear matrix protein 22].

OBJECTIVE: To evaluate the urinary nuclear matrix protein (NMP22) as an adjuvant diagnostic index for transitional cell carcinoma of urinary tract and monitoring the state of disease. METHODS: Urinary samples were collected from 262 patients with transitional cell carcinoma, 198 non-transitional cell carcinoma of the urinary tract and 65 patients with benign diseases. Urinary NMP22 concentration was determined through enzyme linked immunosorbent assay (ELISA). RESULTS: The urinary NMP22 concentration had significant difference among the three groups (Kruskal Wallis, chi(2) = 197.17 P < 0.001). The detection sensitivity and specificity of urinary NMP22 to transitional cell carcinoma were 71.37% and 87.69% respectively. The NMP22 concentration showed significant difference among three groups divided according to the pathological grade (Kruskal-Wallis test, chi(2) = 34.06 P < 0.01). The NMP22 concentration was significant lower in the recovery patients after the operation than the peoples of pre-operation and recurrence (Kruskal-Wallis test, chi(2) = 37.53, P < 0.001). CONCLUSION: MP22 is a helpful tumor marker for the diagnosis of transitional cell carcinoma and monitoring the state of illness with increased efficacy.

[Detection and clinical study of serum tumor markers in patients with colorectal cancer].

OBJECTIVE: To investigate the diagnostic value and clinical significance of serum tumor markers CEA, CA19-9 and CA242 in patients with colorectal cancer. METHODS: The serum levels of CEA, CA19-9 and CA242 were determined by ELISA before surgery in 134 patients with colorectal cancer and in 200 healthy people as a control. RESULTS: The CEA, CA19-9 and CA242 levels in patients were significantly higher than those in controls (P < 0.01, respectively). The sensitivity of CEA and CA242 for colorectal cancer diagnosis was higher than that of CA19-9, and the combined sensitivity of CEA + CA242 and CEA + CA242 + CA19-9 were higher than that of single item or the other two combinations (CEA + CA19-9 and CA19-9 + CA242). In Dukes stages A, B, C and D, serum levels and sensitivity of the three tumor markers were significantly and successively increased. In the cases with lymph node metastasis, levels of the three tumor markers were significantly increased. The markers levels were also significantly and successively increased along with the extent of cancer infiltration. CONCLUSION: The results indicate that the combined use of CEA and CA242 or the three markers is an useful adjuvant diagnostic measure for colorectal cancer, and is helpful in the evaluation of lymph node metastasis, degree of invasion and Dukes staging in cancer treatment.

Characteristic Trend Analysis of Cancer Patients Hospitalized in Shanxi Tumor Hospital for the First Time during 2001 and 2010.

UNLABELLED: To observe and analyze the characteristic trend of cancer patients hospitalized for the first time in Shanxi Tumor Hospital from 2001 to 2010, clinical data including case number, age, gender, and frequency of different tumor occurrences were collected and statistically analyzed. RESULTS: (i) From 2001 to 2010, the number of cancer patients hospitalized for the first time increased by 1.3-fold; (ii) The patient overall average age also increased from 51.8 to 54.4, for males from 55.5 to 58.7 and females from 48.4 to 51.1, respectively. (iii) Male patients accounted for 43-48% and females accounted for 52-57% of the total. The percentage of female patients was higher than that of male patients in every year and showed an upward trend over the years, while that of the males showed a downward trend (χ2 =7.031, p=0.008); (iv) Among the top 6 most common cancers, lung, cervical, esophageal, colorectal and breast cancers tended to increase over the years (p<0.05), but not gastric cancer (p=0.423). CONCLUSIONS: (i) The number of cancer patients hospitalized for the first time during the past 10 years increased year by year, and was higher for female than male; (ii) the average age of patients increased year after year and was greater for male than female; (iii) the number of patients with lung cancer, cervical cancer, esophageal cancer, colorectal cancer and breast cancer increased over years.

Lipid levels in serum and cancerous tissues of colorectal cancer patients.

AIM: To investigate the correlations between lipid metabolism disorder and the occurrence and development of colorectal cancer by monitoring the alterations in lipid levels in cancerous tissue and serum in patients with colorectal cancer. METHODS: The levels of total and free cholesterol (TCH and FCH), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), apolipoprotein A1 (ApoA-1) and ApoB in serum of 206 patients with colorectal cancer, 70 patients with benign colorectal disease and 300 healthy participants, and in the cancerous tissue and paracancerous tissue of 152 patients with colorectal cancer were measured with an Olympus 600 auto-biochemical analyzer. The obtained data were statistically analyzed. RESULTS: Serum FCH level was significantly higher (1.9 ± 0.4 mmol/L vs 1.3 ± 0.3 mmol/L, 1.9 ± 0.4 mmol/L vs 1.2 ± 0.4 mmol/L, P < 0.05), whereas serum levels of TCH, LDL-C, ApoA-I and ApoB were significantly lower in patients with colorectal cancer than in patients with benign colorectal disease and healthy controls. The levels of FCH and TG in cancerous tissue were significantly lower (14.5 ± 9.6 µmol/g vs 19.3 ± 13.9 µmol/g, P < 0.05; 16.3 ± 19.8 µmol/g vs 44.1 ± 38.1 µmol/g, P < 0.05), whereas HDL-C level was significantly higher (7.9 ± 4.5 µmol/g vs 5.7 ± 3.9 µmol/g, P < 0.01) in cancerous tissue than in paracancerous tissue. The levels of TCH and TG in serum and the levels of TCH and HDL-C in cancerous tissue in patients with colorectal cancer were significantly correlated with TNM stage. The levels of TCH and LDL-C in serum were significantly lower, whereas HDL-C level in cancerous tissue was significantly higher in patients with lymph node metastasis than in patients without lymph node metastasis. The levels of TCH, FCH, TG, HDL-C and LDL-C in cancerous tissue were not significantly different from those in paracancerous tissue. The serum levels of FCH and TG were significantly higher, whereas serum HDL-C levels were significantly lower in patients with rectum cancer than in patients with colon cancer. CONCLUSION: The disordered and abnormally altered levels of lipids in cancerous tissue and serum of patients with colorectal cancer may be correlated with the occurrence and development of colorectal cancer.

Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer.

To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer.

AIM: To investigate the roles of serum insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding proteins (IGFBPs) in the initiation and progression of colorectal cancer. METHODS: We determined serum insulin, IGF-1 and IGFBPs levels in 615 colorectal cancer patients and 650 control healthy donors by enzyme-linked immunosorbent assay (ELISA). In the meantime, their body mass index (BMI) and waist-to-hip ratio (WHR) were measured. RESULTS: Serum levels of insulin and IGF-1 as well as IGF-1/IGFBP-3 ratio in pre-operation patients were significantly elevated, but the level of IGFBP-3 was significantly decreased compared with normal controls and post-operation patients (P < 0.05 and P < 0.001, respectively). There is no significant difference (P > 0.05) in the levels of insulin, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 between the patients with and without hepatic as well as distal abdominal metastases. WHR and BMI of colon cancer patients were positively and significantly correlated with the levels of insulin and IGF-1/IGFBP-3. In contrast, WHR and BMI were negatively correlated with IGFBP-3 level. CONCLUSION: The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease.

[Association of insulin, insulin-like growth factor and insulin-like growth factor binding proteins with the risk of colorectal cancer].

OBJECTIVE: To study the association of the changes of serum insulin, insulin-like growth factor (IGF-1), insulin-like growth factor binding proteins(IGFBPs), body mass index (BMI), waist and hip circumference ratio(WHR) with the genesis of colorectal cancer. METHODS: Sera from 244 colorectal cancer patients before operation, 371 patients after operation and 150 healthy subjects were assayed for insulin, leptin, IGF-1, IGFBP-1 and IGFBP-3 by the enzyme-linked immunosorbent assay. SPSS 13.0 statistics software was applied to analyze the data. RESULTS: The serum levels of insulin, IGF-1 and the ratio of IGF-1/ IGFBP-3 in colorectal cancer patients before and after surgical treatment were significantly higher than those in controls. The serum levels of IGFBP-3 in patients before and after operation were significantly lower than those in controls, and the differences were significant(P=0.015,P=0.001, respectively). The BMI in colorectal carcinoma patients was not significantly different to the healthy controls(P>0.05). The WHR in colorectal carcinoma patients was higher than that in healthy subjects, and the difference was significant(P=0.003, P=0.035 respectively). The WHR in colon cancer patients was different to that in rectal cancer patients(P=0.046). The WHR and BMI in colon carcinoma patients were positively correlated with the serum insulin level and the value of IGF/IGFBP3. The WHR and BMI were negatively correlated with IGFBP3. The WHR and BMI were not correlated with IGF-1 and IGFBP1. CONCLUSIONS: The serum insulin, IGF-1 levels and the value of IGF-1/IGFBP-3 are significantly increased in colorectal cancer patients, and serum IGFBP-3 level is markedly decreased, which may be related to the genesis of colorectal cancer, but are not correlated with the progress and improvement of colorectal cancer. Central adipositas may be a risk factor for the genesis of colon cancer.

Associations among lipids, leptin, and leptin receptor gene Gin223Arg polymorphisms and breast cancer in China.

We evaluated the relationship among the leptin receptor (LEPR) gene Gln223Arg polymorphism, body mass index (BMI), waist and hip circumference ratio (WHR), dietary structure, lifestyle, and other biomarkers with breast cancer and determined whether they could be effective for the prevention and treatment of breast cancer. The Gln223Arg polymorphisms in the LEPR gene were investigated in blood deoxyribonucleic acid (DNA) available for 240 breast cancer cases and 500 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Leptin, insulin were determined by enzyme-linked immunosorbent assays. We found that the serum levels of leptin, insulin, triglyceride (TG), free cholesterol (FCH), apolipoprotain (APO) A1, and BMI were significantly higher in breast cancer cases than the controls, while physical activity was clearly less in breast cancer cases (P < 0.02 approximately P < 0.001, respectively). Moreover, there were significant association between the Gln223Arg genotype and breast cancer risk; homozygotes for AA and heterozygotes for AG,AG + GG genotypes had been proved to increase the risk of breast cancer, and their corresponding odds ratio were 7.14 (95% confidence interval [CI] = 1.92-25.64), 1.33(95% CI = 1.03-2.70), and 2.04 (95% CI = 1.09-3.82). Interestingly, logistic regression analysis showed that LEPR gene Gln223Arg polymorphism and elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB increased the risk of developing breast cancer, respectively. And, it also suggested that LEPR gene Gln223Arg polymorphisms, elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB should play a major role in the development of breast cancer.

[Association among lipids, leptin and leptin receptor polymorphisms with risk of breast cancer].

OBJECTIVE: To evaluate the association between serum level of leptin and leptin receptor gene (LEPR) polymorphism and patients with breast cancer. METHODS: LEPR G1n223Arg polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 94 patients with breast cancer and 128 healthy controls. The level of leptin were analyzed by enzyme linked immunosorbent assay. RESULTS: In univariate regression analyses, we found serum level of leptin and LEPR Gin223Arg genotype polymorphism were significantly higrer than those of the controls (P < 0.05-0.001, respectively). Through multivariable analyses, we found that increased risk estimates for breast cancer were among those with leptin level (OR = 1.53, 95% CI: 1.13-2.07, P = 0.006), LEPR Gin223Arg genotype (OR = 4.87, 95%CI:1.30-18.22, P = 0.019), WHR (OR = 3.68, 95% CI: 1.34-10.11, P = 0.011). CONCLUSION: Results from this study suggested that LEPR Gln233Agr polymorphism, the elevated WHR and serum level of leptin might be correlated with increased risk of breast cancer.