Relationship between the mutation of leptin receptor gene and tumorigenesis of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Testosterone induces different-featured prostate hyperplasia in castrated and uncastrated mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the different features of hyperplasia in castrated and uncastrated mice after testosterone (T) treatment.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Expression and clinical significance of nuclear matrix protein 22 and cytokeratin 18 in transitional cell carcinoma of the bladder / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Association of insulin, insulin-like growth factor and insulin-like growth factor binding proteins with the risk of colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Pre- and post-chemotherapy expressions of Th1 and Th2 type cytokines and their clinical significance in gastric cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>The levels of specific cytokines in 60 gastric cancer patients were detected by flow cytometry before and after chemotherapy with FOLFOX4.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

The diagnosis and monitoring of transitional cell cancer of the urinary tract through nuclear matrix protein 22 / 中华预防医学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>MP22 is a helpful tumor marker for the diagnosis of transitional cell carcinoma and monitoring the state of illness with increased efficacy.</p>

Association among lipids, leptin and leptin receptor polymorphisms with risk of breast cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the association between serum level of leptin and leptin receptor gene (LEPR) polymorphism and patients with breast cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Detection and clinical study of serum tumor markers in patients with colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the diagnostic value and clinical significance of serum tumor markers CEA, CA19-9 and CA242 in patients with colorectal cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Estrogen receptor gene polymorphisms and risk of women's malignant tumor related to estrogen / 肿瘤研究与临床

Estrogen receptors(ER)has two subtype alpha and beta.It is a kind of glycoprotein which can bond to estrogen(E).They distribute all kinds of organs and tissues,especially in procreation organs and breast tissue.Study showed that estrogen receptor gene polymorphisms had been associated with the risk of carcinogenesis of endometrial cancer,ovarian cancer and breast cancer.We reviewed the molecule structure, function,gene polymorphisms of ER,and the relationship with endometrial cancer,ovarian cancer and breast cancer.