Serum levels of transforming growth factor beta1 in patients with breast cancer

HYPOTHESIS: Transforming growth factor beta1 (TGF-beta1) may be related to breast cancer progression. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Sixty consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. The control group consisted of 14 patients with benign breast tumors (7 with fibrocystic disease and 7 with fibroadenoma). INTERVENTION: Venous blood samples were collected before the surgery. Sera were obtained by centrifugation and stored at -70 degrees C until assayed. Serum concentrations of TGF-beta1 were measured by quantitative sandwich enzyme immunoassay. Data on primary tumor stage, age, estrogen receptor status, lymph node status, distant metastases, and TNM staging (according to the Union Internationale Contre le Cancer) were reviewed and recorded. MAIN OUTCOME MEASURES: Measurements of preoperative serum TGF-beta1 levels in patients with breast cancer. RESULTS: The mean +/- SD value of serum TGF-beta1 in patients with invasive breast cancer was 498.7 +/- 249.7 pg/mL and in the control group was 495.2 +/- 225.5 pg/mL (P =.96). However, there were significantly higher serum levels of TGF-beta1 in patients with more advanced lymph node status (P =.04), more advanced TNM stage (P =.005), and poorer histological grade (P =.02). In multivariate analysis, TNM staging (P =.02) was demonstrated to be the independent factor related to significantly higher serum levels of TGF-beta1. CONCLUSIONS: Patients with more advanced TNM stages were shown to have higher serum TGF-beta1 levels. Thus, serum TGF-beta1 levels may reflect the severity of invasive breast cancer.     

Potential value of soluble intercellular adhesion molecule-1 in the serum of patients with bladder cancer

INTRODUCTION: The potential value of serum levels of intercellular adhesion molecule-1 (ICAM-1) in the staging and pathological nature of bladder cancer was investigated in this study. MATERIALS AND METHODS: A total of 90 patients (mean age 64.5 +/- 7.1) having transitional cell carcinoma of the bladder and 30 control patients (mean age 64.0 +/- 5.5) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery, at the same hour of the day. RESULTS: The preoperative sICAM-1 levels were found to be 46.2 +/- 14.7 and 28.0 +/- 7.8 ng/ml in the tumor group and the control group respectively, which is significantly higher (p = 0.00). The ICAM-1 levels were not different in the invasive tumor group (36 patients) and the superficial tumor group (54 patients; 47.3 +/- 13.8 ng/ml in the invasive group and 45.5 +/- 15.3 ng/ml in the superficial tumor group; p = 0.520). The serum levels of sICAM-1 were significantly higher in grade III tumors than grade I and II tumors (62.0 +/- 8.7, 38.4 +/- 11.9 and 42.2 +/- 8.2 ng/ml respectively; p = 0.000). The mean serum sICAM-1 levels in tumors >3 cm and <3 cm were found to be 52.6 +/- 15.8 and 40.7 +/- 11.0 ng/ml respectively which is statistically significant (p = 0.000). CONCLUSIONS: In this study, serum ICAM-1 levels were found to be related to tumor presence, grade and size. Larger series are needed for the thorough understanding of the role of ICAM-1 in bladder cancer.     

The 1992 TNM classification of T2 prostate cancer predicts pathologic stage and prognosis better than the revised 1997 classification

PURPOSE: In the 1997 the TNM staging system for prostate cancer was changed, reclassifying, T2 cancers from 3 groups (T2a, less than one half of one lobe; T2b, one lobe; and T2c, both lobes) to 2 groups (T2a, one lobe; and T2b, both lobes), combining the 1992 T2a and T2b into the 1997 T2a subclassification. We investigated the pathological stage and prognosis of cancers in the 1992 and 1997 subclassification to determine whether this change was warranted. MATERIAL AND METHODS: We studied a consecutive series of 555 patients with clinical stage T2 prostate cancer treated with radical prostatectomy (RP) between 1983 and 1998. We analyzed the clinical, pathological features and PSA non-progression rate after prostatectomy for patients classified according to the 1992 and the 1997 TNM system. Median follow-up was 51.3 months. RESULTS: In the 1992 TNM system T2a tumors were more likely to have a low PSA (5.8 versus 7.2 and 8.1 ng/ml, p = 0.034, p = 0.012), be confined to the prostate (67% versus 45% and 40%, p < 0.001 for both), be poorly differentiated (48% versus 63% and 66%, p = 0.002 for both) and have a low cancer volume (1.22 versus 2.27 and 2.63 cm3, p = 0.005 for both) than T2b and T2c tumors. But there were no significant differences between T2b and T2c. Reflecting these results, the patients with T2a cancer had a significantly better prognosis with 82 +/- 4% PSA non-progression rate at 5 years compared to 68 +/- 4% of patients with T2b and 73 +/- 4% of patients with T2c (p = 0.007, p = 0.048, respectively). In the 1997 TNM system T2a tumors were also different from T2b tumors in terms with the frequency of confined cancer (54% versus 40%, p = 0.006) and cancer volume (1.78 versus 2.63 cm3, p = 0.013). However, the those differences were smaller than those in 1992 system. There were no significant differences between 1997 T2a and T2b cancers in the serum PSA level and the frequency of a poorly differentiated cancer. In fact, the 5-years recurrence-free survival rate for patients with T2a (73 +/- 3%) was identical to that for T2b cancer. In a Cox proportional hazard regression analysis, however, neither the 1992 nor the 1997 TNM staging subclassifications of T2 cancers were independent predictor of PSA non-progression when the age of patient, serum PSA level and biopsy Gleason grade were included in the analysis. CONCLUSION: Since a palpable tumor less than half of one lobe (1992 T2a) has a distinctly different pathological and prognostic significance compared to T2b and T2c cancers, the T2a subclassification should be retained in future revisions of TNM staging system. However, because the digital rectal examination provides limited information, both PSA results and histological grade in a biopsy specimen should be incorporated into future revision of the TNM staging system.     

Serum levels of soluble E-selectin in women with breast cancer

BACKGROUND: Increasing evidence suggests that E-selectin contributes to tumour growth and metastasis, possibly by increasing angiogenesis and the adhesion of tumour cells to endothelial cells at distant sites. This study aimed to examine the relationship between preoperative levels of circulating soluble E-selectin and breast cancer. METHODS: Sixty-four consecutive women undergoing surgery for invasive breast cancer were studied prospectively. Venous blood samples were collected before the operation. A control group consisted of 16 patients with a benign breast tumour (eight with fibrocystic disease and eight with fibroadenoma). Serum concentrations of soluble E-selectin were measured by the quantitative sandwich enzyme immunoassay technique and compared with clinicopathological information. RESULTS: The mean (s.d.) serum level of soluble E-selectin in patients with invasive breast cancer was 73.7 (20.9) ng/ml, compared with 36.3 (5.6) ng/ml in the control group (P < 0.001). Furthermore, the serum levels of soluble E-selectin were significantly higher in women with oestrogen receptor-negative tumours (P = 0.001), poorly differentiated tumours (P < 0.001), more advanced primary tumour stage (P < 0.001), involved lymph nodes (P < 0.001), distant metastases (P < 0.001) and more advanced tumour node metastasis (TNM) stage (P < 0.001). On multivariate analysis, TNM stage (P < 0.001) was found to be an independent factor with regard to higher serum levels of soluble E-selectin. CONCLUSION: Preoperative serum levels of soluble E-selectin might reflect the severity of invasive breast cancer; further evaluation is warranted.     

Predicting Axillary Nodal Positivity in 1,787 Patients with Invasive Breast Carcinoma

Abstract: Axillary lymph node status continues to be the single most important prognostic variable regarding breast cancer survival in spite of the development of numerous new tumor markers. All patients with invasive breast cancer who underwent axillary lymph node dissection as part of their treatment were stratified by the primary lesion's T category (TNM staging system) and whether or not the lesion was clinically palpable. Laboratory parameters and breast cancer specific survival were stratified by palpability and T category. Six hundred and forty-two of 1,787 (36%) axillary node dissections contained metastases. Overall, the probability of axillary node involvement was higher for all palpable lesions versus all nonpalpable lesions (42% versus 13%, p = 0.00001). Palpable lesions were less likely to be ER or PgR positive. They had a lower percentage of favorable histologic patterns, were less likely to be diploid, and were more likely to overexpress HER2/neu, have a high S-phase, exhibit high nuclear grade, and microscopically reveal lymphatic tumor emboli or vascular invasion. When tumors were stratified by size, the probability of nodal involvement was higher within each T category for palpable lesions when compared with nonpalpable lesions. The 10-year Kaplan-Meier survival for patients with palpable invasive breast cancer was 75% compared with 90% for patients with nonpalpable lesions (p = 0.00001). Palpability is a poor prognostic sign.     

Microvascular Transplantation of Adipose Tissue and Serum Level of Adipocyte Products

Microvascular transplantation of subcutaneous adipose tissue is an essential step in reconstructive surgery after breast carcinoma. Serum levels of adipose tissue products may serve as indicators for transplant function. This study aimed to determine serum leptin and tumor necrosis factor (TNF)-alpha plasma levels pre-, intra-, and postoperatively in 20 patients undergoing reconstructive breast surgery and in 7 women undergoing abdominoplasty operation. In the patients undergoing reconstructive breast surgery, the serum leptin levels decreased intraoperatively from 14.5 +/- 13.1 to 9.1 +/- 7.3 ng/ml, a decrease of 63%. An increase in serum leptin levels to 13.5 +/- 12.7 ng/ml (93% of the initial value) was found on postoperative day 1. This was paralleled by similar changes in the plasma levels of TNF-alpha (preoperatively, 20 +/- 7.3 pg/ml; intraoperatively, 17 +/- 11.4 pg/ml; postoperatively, 21 +/- 10.8 pg/ml). In the patients undergoing abdominoplasty, plasma leptin and TNF-alpha levels decreased intraoperatively (20% and 27%, respectively) and postoperatively (44% and 27%, respectively). The results of our pilot study indicate that a postoperative increase in the level of serum leptin after reconstructive breast surgery may be related to successful transplant function.     

IL-8, IL-6 and ICAM-1 in serum of paediatric patients undergoing cardiopulmonary bypass with and without cardiocirculatory arrest

BACKGROUND: The aim of the present study was to evaluate the systemic inflammatory response to CPB in paediatric patients undergoing surgical correction of congenital heart diseases. METHODS: Experimental design: comparative investigation. Setting: paediatric cardiology hospital Intervention: ICAM-1, IL-8, and IL-6 production were analysed before and during CPB, and after surgery in 9 paediatric patients, submitted to cardiocirculatory arrest (Group A); and in 11 without cardiocirculatory arrest (Group B). Measures: ICAM-1, IL-8, and IL-6 production were analysed from arterial samples before and during CPB, and after surgery. RESULTS: In group A vs group B a significant increase of IL-8 was detected during (297+/-250 vs 11+/-19 pg x ml(-1), p<0.001) and after (100+/-230 vs n.d. pg x ml(-1)) surgery and was correlated with the duration of operation (r=0.759; p=0.0001) and clamping time (r=0.738; p<0.05). After surgery in group A, IL-6 levels (35+/-43 pg x ml) were higher than those in group B (2+/-5 pg x ml), and a good correlation was observed between IL-6 and duration of aortic clamping (r=0.714; p=0.048), cardiac arrest, (r=0.714; p=0.048), and length of surgery (r=0.867; p=0.04). CONCLUSIONS: In children who underwent CPB with cardiocirculatory arrest cytokine production seems related to duration of operation and amplified by ischemia-reperfusion phenomena.     

Presurgical assessment of the tumor burden of familial medullary thyroid carcinoma by calcitonin testing

BACKGROUND: Early diagnosis of familial medullary thyroid carcinoma (MTC) is currently done by genetic analysis. These techniques have replaced calcitonin stimulation testing, which was previously used for this purpose. Some studies suggest a relationship between MTC spread and calcitonin levels. The aim of this study was to assess whether the tumor burden of MTC associated with multiple endocrine neoplasia type 2A (MEN 2A) syndrome can be estimated from the plasma calcitonin values before surgery. STUDY DESIGN: We retrospectively studied the relationship of basal and peak calcitonin values before thyroidectomy with histopathologic findings in 53 patients with MEN 2A syndrome from 14 families. The MTC was classified according to TNM staging. Analysis of variance was used for statistical analysis complemented with equality contrasts for pairs of means by the least significant difference method with a Student's t-test and with the Bonferroni's adjustment. RESULTS: A positive association was found between tumor stage and basal and peak calcitonin levels. There were significant differences between the following: mean basal concentrations of patients with C cell hyperplasia (CCH) (34.3 pg/mL) and TNM stage II (1,097.4 pg/mL), p < 0.01; CCH and TNM stage III (2,940.8 pg/mL), p < 0.001; TNM stage I (165.3 pg/mL) and stage II (1,097.4 pg/mL), p < 0.01, and between TNM stages I and III, p < 0.001. Poststimulation mean concentrations were different between CCH (48.7 pg/mL) and TNM I (514.2 pg/mL), p < 0.001. CONCLUSIONS: Preoperative calcitonin testing may be useful for assessing tumor spread and should be considered when deciding the extent of surgery for MEN 2A MTC.     

IGF-II serum levels increase discrimination between benign prostatic hyperplasia and prostate cancer and improve the predictive value of PSA in clinical staging

PURPOSE: IGF-I serum levels have been demonstrated as being associated with prostate cancer (PCa) and can serve as a predictive factor for the risk of PCa development. However, the role of IGF-II in PCa and its importance as a predictive marker is still unclear. Our aim was to determine PSA and IGF-II serum levels in patients with PCa and benign prostatic hyperplasia (BPH) and to analyse the value of IGF-II as an additional predictive factor in the diagnostics of PCa. METHODS: 112 patients who underwent surgery for BPH or PCa (no hormonal treatment, no further malignancies) were included in this study ((I) 38 PCa, PSA < or = 15 ng/ml; (II) 34 PCa, PSA > 15 ng/ml; (III) 40 BPH). Preoperative serum levels of total PSA and total IGF-II were determined by ELFA and ELISA, respectively. RESULTS: PSA levels were (I) 5.7+/-1.9 ng/ml; (II) 25.0+/-11.5 ng/ml and (III) 4.0+/-2.8 ng/ml. (II) was statistically associated with a high grading (2b/3; p = 0.0182), a high Gleason sum score (7-10; p = 0.0049) and a non-organ confined tumor (T3/4; p = 0.0009) compared to (I), all Chi2 test. IGF-II levels were significantly higher in PCa (I+II) compared to BPH (833.8+/-238.9 ng/ml vs. 633.3+/-141.4 ng/ml, p < 0.0001, t-test). Both PSA and IGF-II were associated with tumor staging (p = 0.0097, p = 0.0308; t-test). No significant correlation was observed between PSA and IGF-II levels. Logistic regression analysis revealed that the combination of PSA and IGF-II improves the prediction of tumor staging in PCa (p = 0.0175 and p = 0.0459, Wald test). Additionally, the combination of PSA and IGF-II can significantly increase discrimination between BPH and PCa; each p < 0.0001, Wald test. CONCLUSIONS: This study provides evidence that IGF-II serum levels may serve as an additional parameter for (a) improved determination of tumor staging and (b) better discrimination between BPH and PCa.     

Axillary regional recurrence after sentinel lymph node biopsy for breast cancer

The accuracy of sentinel lymph node biopsy (SLNB) staging in breast cancer has been demonstrated in studies comparing it with axillary dissection. There is a 5 per cent false-negative rate, but this does not always correlate with axillary recurrence. Our purpose was to determine the rate of axillary lymphatic recurrence in breast cancer patients who had a negative SLNB. We conducted a cohort study of breast cancer patients who underwent SLNB between 2001 and 2005. Only patients who had a negative SLNB were included. Patient demographics and tumor factors were reviewed. Outcomes measured were axillary and systemic recurrence and survival. Eighty-nine patients with a mean age of 54.4 +/- 9.9 years were included. Eighty-nine per cent of cases had infiltrating ductal carcinoma histology. Mean tumor size was 19 +/- 14 mm. Breast conservation surgery was done in 65 cases and mastectomy in 24. A mean of 2.3 +/- 2.4 SLN were found. After a median follow-up of 2.15 years, 1 (1%) patient developed a lymphatic recurrence in the axilla. SLNB provides accurate staging of breast cancer. Patients with negative SLNB do not require axillary dissection.     

术后采用人参皂甙Rg3联合丝裂霉素加呋喃尿嘧啶方案对进展期胃癌的疗效

目的探讨人参皂甙Rg3(Rg3)联合丝裂霉素加呋喃尿嘧啶(MF)化疗方案(Rg3 MF)对进展期胃癌术后的治疗效果。方法将71例进展期胃癌术后患者随机分为对照组(33例)和观察组(38例),前者用MF方案,后者用Rg3加MF方案治疗。检测血清血管内皮生长因子(VEGF)水平,并对预后进行对比分析。结果进展期胃癌患者血清VEGF含量[(297.8±129.6) pg/ml]明显高于正常组[(212.3±67.5)pg/ml](P<0.01),且与胃癌患者肿瘤的浸润深度、淋巴结转移、肿瘤大于4cm及TMN分期有关(均P<0.05)。术后14周时检测血清VEGF水平,观察组已明显低于术前(P<0.05)、而接近正常组水平,对照组仅降至术前水平。观察组、对照组中位生存时间分别为40和25个月。观察组的术后累计生存率高于对照组(P=0.047)。结论进展期胃癌患者术后采用MF方案联合Rg3治疗可明显降低血清VEGF含量,提高生存率。     

Determinants of cardiovascular stability during abdominal aortic aneurysmectomy (AAA)

Patients undergoing abdominal aortic aneurysmectomy (AAA) develop depressed cardiac function during aortic clamping. The importance of volume status and thromboxane (Tx) mediated declines in cardiac contractility in determining this event was studied. In a blinded fashion, patients received the cyclo-oxygenase inhibitor ibuprofen 12 mg/kg by mouth (n = 11) or a placebo (n = 15), 1.5 hours prior to surgery. In the placebo group levels of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin (PGI2) rose from 20 +/- 10 to 1170 +/- 80 pg/ml (p less than 0.05) soon after incision. Concentrations of TxB2, the stable hydrolysis product of TxA2, were unchanged until 30 minutes after the aorta was clamped when arterial TxB2 concentrations rose from 90 +/- 20 to 230 +/- 30 pg/ml (mean +/- SEM) (p less than 0.05). A pulmonary source for PGI2 and TxA2 was indicated by the observation that arterial 6-keto-PGF1 alpha and TxB2 levels exceeded those in pulmonary arterial blood by 180 +/- 50 and 110 +/- 30 pg/ml, respectively (p less than 0.05). Levels of TxB2 in circulating platelets remained unchanged from baseline in the placebo group. During aortic clamping, cardiac index (CI) fell 0.7 +/- 0.2 1/min X m2 (p less than 0.05) in placebo treated patients, and there was a 6% decline in plasma contractility as bioassayed with a rat papillary muscle (p less than 0.05). Placebo patients entered surgery with a PAWP greater than or equal to 10 mmHg (mean 13 mm). Ibuprofen suppressed production of TxB2, such that 30 minutes after aortic clamping TxB2 was 70 +/- 30 pg/ml, a value lower than control patients (p less than 0.05). Further, plasma no longer depressed contractility of the papillary muscle. Five patients given ibuprofen had an initial pulmonary arterial wedge pressure (PAWP) of 10 mmHg or greater (mean 12 mmHg). During aortic clamping there was an insignificant decrease in CI of 0.2 +/- 0.1 1/min X m2. This was in contrast to the CI decrease in six other ibuprofen treated patients of 0.9 +/- 0.2 1/min X m2 whose PAWP at the start of surgery was less than 10 mmHg (mean 6 mmHg) (p less than 0.05), and to placebo patients whose initial PAWP was greater than or equal to 10 (p less than 0.05). Platelet counts fell from 185,000 to 121,000/mm3 in placebo patients (p less than 0.05), but did not fall when ibuprofen was given. Creatinine concentrations were unaffected by ibuprofen. Blood replacement in placebo and ibuprofen patients was similar, 1.90 +/- 0.20 and 0.65 +/- 0.15 1, respectively. Results indicate that CI will not decrease during AAA if sufficient volume is given before surgery to increase PAWP above 10 mmHg, and secondly, if TxB2 synthesis is inhibited.     

Is the TNM Staging System for Breast Cancer Still Relevant in the Era of Biomarkers and Emerging Personalized Medicine for Breast Cancer – An Institution's 10‐year Experience

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).     

A study on the vascular proliferation in tissues around the tumor in breast cancer

In order to study the vascular proliferation in human breast cancer, blood vessels were counted, per square millimeter, in the tissue immediately around tumors. Mastectomized specimens of 84 patients with breast cancer and specimens from 10 patients with benign mammary diseases were stained by hematoxylin eosin and, where required, by the avidin biotin peroxidase complex method for laminin staining. The vascular density around the breast cancer tissue was 20.35 +/- 8.40/mm2, which was significantly higher than the value of 13.44 +/- 5.85/mm2 for noncancerous mammary tissues (p less than 0.001) or the value of 12.65 +/- 4.12/mm2 for benign mammary disease tissues (p less than 0.01). Among the breast cancers, noninvasive carcinoma had a higher vascular density (28.44 +/- 6.15/mm2) than invasive carcinoma (19.73 +/- 8.22/mm2, p less than 0.02). According to the Japan Mammary Cancer Society Classification of invasive ductal carcinoma, vascularity was higher in the papillotubular type of cancer than in the solid-tubular or scirrhous types of cancer (p less than 0.02), although the papillotubular type had the lowest rate of nodal metastasis and vascular invasion as compared with the scirrhous and solid-tubular types. The vascular density around the tumors did not change in association with an increase in tumor size and it was suggested that blood vessels around a tumor would increase almost in proportion to the square of the tumor diameter.     

Addition of dextran sulfate to blood cardioplegia attenuates reperfusion injury in a porcine model of cardiopulmonary bypass

Objective: Contact of blood with artificial surfaces and air as well as ischemia/reperfusion injury to the heart and lungs mediate systemic and local inflammation during cardiopulmonary bypass (CPB). Activation of complement and coagulation cascades leads to and accompanies endothelial cell damage. Therefore, endothelial-targeted cytoprotection with the complement inhibitor and endothelial protectant dextran sulfate (DXS, MW 5000) may attenuate CBP-associated myocardial and pulmonary injury. Methods: Eighteen pigs (DXS, n=10; phosphate buffered saline [PBS], n=8) underwent standard cardiopulmonary bypass. After aortic cross-clamping, cardiac arrest was initiated with modified Buckberg blood cardioplegia (BCP), repeated after 30 and 60min with BCP containing either DXS (300mg/10ml, equivalent to 5mg/kg) or 10ml of PBS. Following 30min reperfusion, pigs were weaned from CPB. During 2h of observation, cardiac function was monitored by echocardiography and invasive pressure measurements. Inflammatory and coagulation markers were assessed regularly. Animals were then sacrificed and heart and lungs analyzed. Results: DXS significantly reduced CK-MB levels (43.4+/-14.8ng/ml PBS, 35.9+/-11.1ng/ml DXS, p=0.042) and significantly diminished cytokine release: TNFalpha (1507.6+/-269.2pg/ml PBS, 222.1+/-125.6pg/ml DXS, p=0.0071), IL1beta (1081.8+/-203.0pg/ml PBS, 110.7+/-79.4pg/ml DXS, p=0.0071), IL-6 (173.0+/-91.5pg/ml PBS, 40.8+/-19.4pg/ml DXS, p=0.002) and IL-8 (304.6+/-81.3pg/ml PBS, 25.4+/-14.2pg/ml DXS, p=0.0071). Tissue endothelin-1 levels were significantly reduced (6.29+/-1.90pg/100mg PBS, 3.55+/-1.15pg/100mg DXS p=0.030) as well as thrombin-anti-thrombin formation (20.7+/-1.0mug/ml PBS, 12.8+/-4.1mug/ml DXS, p=0.043). Also DXS reduced cardiac and pulmonary complement deposition, neutrophil infiltration, hemorrhage and pulmonary edema (measured as lung water content, 81+/-3% vs 78+/-3%, p=0.047), indicative of attenuated myocardial and pulmonary CPB-injury. Diastolic left ventricular function (measured as dp/dt(min)), pulmonary artery pressure (21+/-3mmHg PBS, 19+/-3mmHg DXS, p=0.002) and right ventricular pressure (21+/-1mmHg PBS, 19+/-3mmHg DXS p=0.021) were significantly improved with the use of DXS. Conclusions: Addition of DXS to the BCP solution ameliorates post-CPB injury and to a certain extent improves cardiopulmonary function. Endothelial protection in addition to myocyte protection may improve post-CPB outcome and recovery.     

紧密连接蛋白claudin-1与乳腺肿瘤的相关性研究

目的探讨紧密连接蛋白claudin-1在乳腺肿瘤组织中的表达及其与乳腺癌发生、发展的关系。方法应用组织芯片技术和免疫组织化学法研究89例乳腺癌和37例乳腺良性病变中claudin-1的表达情况,并统计分析其与乳腺癌淋巴结转移、TNM分期和肿块最大径以及组织学分级间的关系。结果 claudin-1在乳腺癌组织中的表达强度明显弱于乳腺良性病变者(χ2=19.20,P=0.000 2)。在有淋巴结转移的乳腺癌组织中claudin-1表达强度明显弱于无淋巴结转移者(χ2=3.85,P=0.049 7);TNM分期为Ⅲ期的乳腺癌组织中claudin-1表达强度分别弱于Ⅰ期(χ2=5.29,P=0.021 4)和Ⅱ期(χ2=7.46,P=0.006 3)。claudin-1表达强度在肿块最大径各组间(χ2=1.58,P=0.453 8)及组织学各分级之间(χ2=1.02,P=0.600 5)比较差异均无统计学意义。结论乳腺癌的发生、发展及转移可能与claudin-1的表达强度有关,可作为判断乳腺癌淋巴结转移和估计预后的参考指标之一。     

The effect of subarachnoid hemorrhage on blood and CSF atrial natriuretic factor

Atrial natriuretic factor (ANF) is a diuretic natriuretic peptide hormone produced by both the heart and brain which has been postulated to play a role in the hemodynamic and sodium instability that frequently follows subarachnoid hemorrhage (SAH). Levels of ANF were measured in 12 patients with nontraumatic SAH and nine control patients with unruptured cerebral aneurysms. At surgery, the mean plasma ANF level (+/- standard deviation) of the SAH group was significantly higher than that of the control group (158.1 +/- 83.8 vs. 57.8 +/- 45.3 pg/ml, respectively; p = 0.01). There was no significant difference in serum sodium concentration, blood pressure, or central venous pressure between these groups. Nine patients with SAH due to aneurysm rupture had plasma ANF levels similar to those in three patients with SAH due to other causes. Four patients with moderate to severe SAH had significantly higher mean cerebrospinal fluid (CSF) ANF values (17.7 +/- 12.8 pg/ml) than five patients with minimal SAH (0.6 +/- 0.9 pg/ml) or the control group of nine patients (3.7 +/- 1.3 pg/ml) (p less than 0.05). Five patients with moderate to severe SAH had significantly higher plasma ANF values (202.6 +/- 72.2 pg/ml) than five with minimal SAH (86.8 +/- 29.2 pg/ml) or the control group (57.8 +/- 45.3 pg/ml) (p less than 0.05). Plasma ANF values were substantially higher than CSF ANF content in the SAH group (p less than 0.01) and in the control group (p = 0.05). From these data it is concluded that: 1) plasma ANF is elevated significantly after SAH; 2) this rise appears unrelated to the cause of hemorrhage, serum sodium concentration, blood pressure, or central venous pressure, but is related to the extent of the hemorrhage; 3) ANF concentrations in the CSF are significantly lower than in plasma, and are elevated after moderate to severe SAH; and 4) the source of CSF ANF is probably the plasma, and the source of plasma ANF is likely the heart.     

Serum keratinocyte growth factor measurement in patients with prostate cancer

PURPOSE: Keratinocyte growth factor (KGF) is a stromally derived growth factor important in mediating androgen induced activities in benign prostatic hyperplasia (BPH) and prostate cancer. We assessed whether serum KGF could be used as a molecular marker in patients with prostate cancer. MATERIALS AND METHODS: Using a modified double sandwich enzyme-linked immunosorbent assay, we measured serum KGF in 56 men with prostate cancer and 81 men with BPH. Comparative analyses were made with total serum prostate specific antigen (PSA), disease stage and clinical grade. RESULTS: Following optimization, a sensitive and reproducible assay for serum KGF measurement was developed. Serum KGF levels tend to be higher in men with BPH compared to those with prostate cancer (1,242 and 828 pg./ml., respectively). A weak but significant linear relationship between PSA and KGF (p = 0.034) was found in patients with BPH. There was no association between KGF and tumor grade or stage but there was a strong positive linear relationship between PSA and KGF (p = 0.006, R(2) = 68.3%) in low grade tumors. In those men with serum PSA less than 10 ng./ml. KGF levels were significantly higher in BPH compared to prostate cancer cases (965 +/- 245 and 133 +/- 61.3 pg./ml., respectively, p = 0.0058). Using a KGF threshold range of 500 to 900 pg./ml., specificity for detecting BPH was 88% to 100% and the positive predictive value was 92% to 100%. CONCLUSIONS: We have optimized a reproducible and sensitive enzyme-linked immunosorbent assay system for the measurement of serum KGF. Overall KGF levels tend to be lower in patients with prostate cancer than with BPH. In patients with serum PSA less than 10 ng./ml. serum KGF levels were significantly higher in the BPH compared to the prostate cancer group. A large prospective study is indicated to assess the role of serum KGF measurement in patients with prostate cancer.     

术中腹腔游离癌细胞检测用于胃癌TNM分期

目的 探讨术中腹腔游离癌细胞的检测在胃癌TNM分期中的应用.方法 用实时荧光RT-PCR方法检测胃癌患者术中腹腔游离癌细胞(free cancer cell,FCC),并进行5年的随访.用MedCalc软件分析FCC最佳阳性判定值,大于此值表示FCC的存在,标记为FCC(+),然后把FCC(+)当作远处转移(M1)重新进行分期,并作新的生存曲线图.结果 (1)在最佳阳性判定值为31.21拷贝/ml时约登指数最高;(2)把FCC(+)当作M1重新进行分期,各分期之间的5年生存曲线显示:Ⅰ～Ⅱ期P=0.134;Ⅱ～Ⅲ期P=0.004;Ⅲ～Ⅳ期P=0.022.新分期各分期的5年生存率分别为Ⅰ期100%(18/18),Ⅱ期88%(7/8),Ⅲ期24%(4/17),Ⅳ期9%(2/22).结论 (1)FCC最佳阳性判定值为31.21拷贝/ml;(2)现行TNM分期中加入FCC检测结果则可使其更加完善,能更准确地评估进展期胃癌患者的手术预后.     

The role of tumor necrosis factor in allograft rejection. I. Evidence that elevated levels of tumor necrosis factor-alpha predict rejection following orthotopic liver transplantation

Plasma levels of tumor necrosis factor-alpha were measured in 50 adult patients following orthotopic liver transplantation. The mean (+/- SEM) plasma concentration of TNF-alpha was significantly higher in patients experiencing a rejection episode (941 +/- 83 pg/ml) than in those with a stable clinical course (240 +/- 6 pg/ml; P = 0.0001). Peak levels of TNF-alpha were usually found at the time of clinically diagnosed rejection, although elevated levels were observed 1-2 days earlier. First-week peak TNF-alpha levels were significantly higher in patients who suffered graft loss (2146 +/- 788 pg/ml) than in those who were discharged from the hospital without clinical evidence of rejection (581 +/- 93 pg/ml; P = 0.004). TNF-alpha levels were not correlated with white blood cell count (r2 = 0.004), cyclosporine levels (0.01), serum creatinine (0.002), serum bilirubin (0.05), serum SGOT (0.03), or SGPT (0.05). TNF-alpha levels were not elevated in four cases of viral hepatitis occurring after transplantation. We conclude that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. First-week TNF-alpha levels are also useful predictors of long-term graft outcome. Further investigation is required to determine whether this monokine is important in the actual pathogenesis of allograft rejection.