High Serum Levels of Soluble IL-2 Receptor, Cytokines, and C Reactive Protein Correlate with Impairment of T Cell Response in Patients with Advanced Epithelial Ovarian Cancer

The serum levels of interleukin-(IL-)1α, IL-1β, IL-2, IL-6, TNFα, and sIL-2R and the proliferative response of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), anti-CD3 monoclonal antibody (mAb), recombinant IL-2 (rIL-2), and the combination of PHA or anti-CD3 mAb with rIL-2 were studied and correlated with serum levels of C-reactive protein (CRP) in women with advanced epithelial ovarian cancer. The expression of CD25 and CD122 subunities of membrane-bound IL-2R on PHA- or anti-CD3 mAb-stimulated PBMC was also studied. In comparisons with the controls, PBMC response to PHA, anti-CD3 mAb, and rIL-2 was significantly lower in the cancer patients. The addition of exogenous rIL-2 to the PBMC cultures increased response in both controls and patients but did not modify the significance of the differences. After stimulation with PHA or anti-CD3 mAb, the percentage of PBMC CD25⁺or CD122⁺was significantly lower in patients. The serum levels of IL-1α, IL-1β, IL-6, TNFα, sIL-2R, and CRP were significantly increased in patients compared to the controls. Instead, no differences were observed for serum levels of IL-2. A strong association was found between high serum levels of the above-mentioned cytokines, sIL-2R, and CRP. The results of our study on advanced stage (IIIb–IV) ovarian cancer patients are consistent with the previously reported hypothesis that high IL-6 and/or CRP serum levels may represent an important and independent prognostic factor of the likely outcome in cancer patients.     

血清MIA检测在恶性黑素瘤诊断中的临床价值

探讨血清黑素抑制蛋白（ｍｅｌｏｎｏｍａ－ｉｎｈｉｂｉｔｉｎｇ ａｃｔｉｖｉｔｙ ｐｒｏｔｅｉｎ,ＭＩＡ）在恶性黑素瘤诊断中的价值。方法：采用ＥＬＩＳＡ方法,检测不同临床分期的黑素瘤及其他恶性肿瘤患者,以及正常人血清ＭＩＡ浓度。结果正常成人（ｎ＝２０）和肺癌（ｎ＝１０）、肝癌、（ｎ＝１２）结肠癌（ｎ＝１２）患者血清ＭＩＡ浓度全部低于正常（６．５ｎｇ／ｍｌ）水平,黑素瘤患者血清ＭＩＡ浓度明显升高,阳性     

白血病细胞线粒体超微结构及其蛋白质双向电泳分析

探讨白血病细胞线粒体（mt）形态、结构和功能的异常与mt蛋白组分变化间的可能的关系。方法采用离心法分离纯化了可移植性小鼠腹水型白血病细胞（L7811）及正常615纯系小鼠胸腺细胞线粒体，对其超微结构进行了电镜观察。结果对它们各自蛋白质双向电泳图谱分析后发现在PH4．5～6．5，MW15～35KD范围内正常对照有8个蛋白质斑点在L7811l白血病细胞线粒体电泳图谱相应位置未观察到，而在PH6左右、MW10～17KD区域内白血病样品有3个蛋白质斑点，在正常对照的电泳图谱相应区域也未观察到。结论白血病细胞与正常对照细胞相比线粒体在超微结构和蛋白质组成上均有明显差异。     

Haptoglobin-related protein as a serum marker in malignant lymphoma

A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin’s lymphoma (n=58) and Hodgkin’s disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430xl0³ u/ml, range 0-4000xl0³) were significantly higher than in the control group (median 68xl0³ u/ml, range 0-180xl0³) (p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), “B” symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma. This work is dedicated to the memory of Dr. Arie H. Bartal, a dedicated oncologist and friend. This work was supported by Chemotech Thechnologies Ltd., by grant no. 3676 from the Chief Scientist’s Office of the Ministry of Health, Israel, and by the Fund for Promotion of Research in the Technion.     

P53 fusion protein expression in prokaryote and preparation of monoclonal antibody to P53

Objective: Conventional immunohistochemistry (IHC) is available to assess P⁵³ mutations, and expensive imported anti-P⁵³ monoclonal antibody has been used in China, it is necessary to study a new monoclonal antibody. Methods: The P⁵³ DNA fragment enconding N-terminal 180 amiao acide was obtained by PCR and was cloned into P^GEX-2T plasmid expressing glutathione S-transferase (GST). The P⁵³-GST fusion protein expressed by JM109 was used for immunizing BALB/C mice. We have raised one hybridoma strain secreting McAb to human P⁵³ (named M126). Results: The IHC analysis of 52 paraffin-embedded sections from human breast cancer with M126 and P_AB1801 (Zymed Co.) has showed that the positive immunoreactions were 25 cases (48%) and 22 cases (42.3%) respectively. The staining of M126 was stronger and preferable to P_AB1801. Conclusion: M126 can be instead of P_AB1801 for studying immunohistochemical analysis on P⁵³ protein.     

Advanced glycosylation end products, protein kinase C and renal alterations in diabetic rats

Objective To study the relationship between advanced glycosylation end products (AGE) an d protein kinase C (PKC), and their effects on renal alteration in diabetic rats .
Methods Insulin or aminoguanidine was administered to diabetic rats. Blood glucose, hem oglobin A_1C (HbA_1C), glomerular tissue extracts AGE (GTE-AGE), PKC, glomerular basement membrane thickness (GBMT) and urine protein/creatinine ( Pr/Cr) ratio in diabetic rats were measured and analysed.
Results Levels of blood glucose, HbA_1C and AGE, PKC activity, the Pr/Cr ratio an d GBMT were all significantly increased (P values all less than 0.01) in di abetic rats. Insulin could decrease the formation of HbA_1C and AGE, and improve PKC activity. Aminoguanidine had no influence on PKC activity (P >0.05) although it decreased the formation of AGE. Both drugs could delay t he increase of urine Pr/Cr ratio and GBMT (P<0.05 or P<0.01).
Conclusions Chronic hyperglycemia may lead to an increase of PKC activity. HbA_1Cand AGE may not directly contribute to alterations of PKC activity, but the increa se of PKC activity could promote the action of AGE on GBM thickening. It is imp ortant t o inhibit the formation of AGE and reduce the PKC activity so as to prevent or d elay the development of diabetic nephropathy.     

The effect of soy isoflavones on the development of intestinal neoplasia in Apc mouse

Data from epidemiological studies suggest that isoflavones in soy may have a protective effect on the development of colon cancer in humans. Therefore, we have investigated whether soy isoflavones will inhibit intestinal tumour development in Apc^Min mice. The mice were fed a Western-type high risk diet (high fat, low fibre and calcium) containing two different isolates of soy protein as a protein source. For the control and test groups this resulted in the administration of about 16 and 475 mg of total isoflavones per kg diet, respectively. As a positive control, a third group of mice was administered a low isoflavone diet supplemented with 300 ppm sulindac. No significant differences in the incidence, multiplicity, size and distribution of intestinal tumours were observed between Min mice fed low and high isoflavone-containing diets. However, a clear reduction in the number of small intestinal tumours was observed for the sulindac diet. Thus, in contrast to epidemiological studies, our results demonstrate that high amounts of soy isoflavones present in a Western-type high risk diet do not protect against intestinal tumour development in a relevant animal model such as the Min mice.