Antinuclear antibody reduces the pregnancy rate in the first IVF-ET treatment cycle but not the cumulative pregnancy rate without specific medication

PROBLEM: It has been shown that the presence of antinuclear antibody (ANA) might reduce pregnancy rates after in vitro fertilization-embryo transfer (IVF-ET). However, the mechanism of implantation failure by ANA has not yet been clarified. This study was performed to investigate the impact of ANA on pregnancy rates after IVF-ET, and the necessity of specific medication for infertile women who have ANA in their sera. METHOD OF STUDY: A total of 108 infertile women were treated by IVF-ET or intracytoplasmic sperm injection (ICSI)-ET. ANA was examined by an indirect fluorescent antibody procedure. Data from women under 40 years old were analyzed retrospectively. RESULTS: The implantation rates per embryo transferred in the first treatment cycles were 14.8% (eight of 54) and 32.4% (33 of 102), in women with and without ANA, respectively. There was a significant difference in the implantation rates between the two groups (P < 0.05). The pregnancy rates per ET in the first treatment cycles were 28% (seven of 25) and 54.2% (26 of 48), respectively. There was also a significant difference in the pregnancy rates between the two groups (P < 0.05). Afterwards, treatments with IVF-ET or ICSI-ET were repeatedly performed for unsuccessful patients, without any specific medication for ANA. The average ET cycles were 1.80 +/- 1.13 and 1.27 +/- 0.54, in women with and without ANA, respectively. The cumulative pregnancy rates per patient were 68% (17 of 25) and 55.6% (35 of 63), respectively. There was no significant difference in the overall pregnancy rates between the two groups. CONCLUSIONS: These findings suggest that ANA might have an impact on implantation failure in women treated by IVF-ET or ICSI-ET. ANA reduced the pregnancy rates in the first IVF-ET or ICSI-ET cycles but not the cumulative pregnancy rates without medication. This indicates that the mechanisms of implantation failure by ANA could be solved, and effective and safe medication should be developed for better implantation rates, especially in the first treatment cycle.     

Participation of the matrix metalloproteinase inhibitor in Thy-1 nephritis

What influence would be shown in Thy‐1 glomerulonephritis when the synthetic matrix metalloproteinase (MMP) inhibitor SI‐27 is administered? Five groups of 80 male Wistar rats were studied: healthy group; treated healthy group; nephritic group; pretreated nephritic group; and post‐treated nephritic group. SI‐27 treatment of nephritic animals was initiated either 2 days before or 2 days after anti‐Thy‐1.1 antibody injection. On days 7, 14, 26 and 42 after disease induction, we examined renal histology, extracellular matrix (ECM) constituent, and MMP activity. SI‐27 treated Thy‐1 groups resulted in significant reduction of glomerular cells including α‐smooth muscle actin (α‐SMA) positive mesangial cells and suppressed expression of type IV collagen at 7 days. Moreover, type I collagen was also decreased by SI‐27 at 42 days. However, glomerular cell numbers did not show any significant changes at 14, 26 and 42 days. In gelatin zymography, the gelatinolytic band for MMP‐9 was expressed in SI‐27 treated Thy‐1 nephritis groups, although it was not expressed in the nephritic group at day 7. However, the expression of MMP‐9 was no longer seen at 14, 26 and 42 days. The bands for an active form of MMP‐2 were expressed throughout the experimental period in the Thy‐1 nephritic groups. These results suggest that MMP plays an important role in the development of Thy‐1 nephritis, and even if the synthetic MMP inhibitor intercepts the initial increase of glomerular cells and matrices, it does not inhibit recovery to normal glomerular capillary structures in Thy‐1 nephritis.     

基质金属蛋白酶1、3,基质金属蛋白酶组织抑制剂1和miR-29在大鼠肺纤维化中及活性维生素D3处理后的表达与作用

目的:探讨大鼠肺纤维化发生发展中基质金属蛋白酶1(MMP1)、MMP3、基质金属蛋白酶组织抑制剂1(TIMP1)及miR-29的表达和作用以及活性维生素D3[1,25(OH)_2D_3]处理对这些基因表达的影响。方法:雄性SD大鼠随机分为预防组和治疗组。预防组分为对照组Ⅰ、模型组Ⅰ和给药组Ⅰ,治疗组分为对照组Ⅱ、模型组Ⅱ和给药组Ⅱ。模型组Ⅰ/Ⅱ和给药组Ⅰ/Ⅱ经气管注入博莱霉素,对照组Ⅰ/Ⅱ经气管注入生理盐水。预防组和治疗组分别于术后第2和14天腹腔注射给药,给药组给予活性维生素D3,模型组给予活性维生素D3溶剂,对照组给予生理盐水。预防组的各组分别于术后第14、21、28天处死大鼠取材,治疗组的各组分别于术后第21和28天处死大鼠取材。实时定量PCR检测大鼠肺组织中miR-29a及TIMP1 mRNA表达水平,免疫组织化学检测组织中MMP1、MMP3和TIMP1的表达水平。结果:模型组Ⅰ/Ⅱ和给药组Ⅰ/Ⅱ中的MMP1、MMP3和TIMP1的表达均明显高于相同时间点对照组Ⅰ/Ⅱ中的表达,而miR-29a的表达明显低于相应的对照组Ⅰ/Ⅱ;给药组Ⅰ/Ⅱ中MMP1、MMP3和TIMP1的表达均低于相应时间点的模型组Ⅰ/Ⅱ的表达,而给药组Ⅰ/Ⅱ中miR-29a的表达则高于模型组Ⅰ/Ⅱ中的表达。结论:MMP1、MMP3、TIMP1和miR-29在大鼠肺纤维化发生发展中具有重要作用,活性维生素D3可以促进miR-29表达,抑制MMP1、MMP3、TIMP1的表达;可能是通过miR-29调节包括MMP1、MMP3、TIMP1在内的多种靶基因来发挥抑制纤维化的作用。     

Increased expression of matrix metalloproteinase-9 in the eutopic endometrial tissue of women with endometriosis

BACKGROUND: Endometriosis is a disease where endometrial tissue implants in ectopic locations. Remodelling of the extracellular matrix (ECM) is a prerequisite for the implantation of this tissue to be possible. METHODS: In this study, we detected immunoreactive matrix metalloproteinase-9 (MMP-9) throughout endometrial tissue and identified von Willebrand factor (vWF)-positive endothelial cells, CD45-positive leukocytes, CD3-positive T lymphocytes and CD68-positive macrophages as cells expressing MMP-9 in the stroma. RESULTS: We found an increased expression of MMP-9 in the uterine endometrial tissue of women with endometriosis, as assessed by zymography and enzyme-linked immunosorbent assay (ELISA) (P < 0.05). However, RT-PCR did not show a statistically significant increase in MMP-9 mRNA expression in these tissues (P = 0.14). There was no significant difference between women with and without endometriosis in the expression of tissue inhibitor of MMPs (TIMP)-1, a known natural inhibitor of the pro- and active forms of MMP-9, whether tested by ELISA or by RT-PCR (P = 0.46 and 0.37, respectively). Interestingly, the ratio of MMP-9/TIMP-1 expression was significantly higher in women with endometriosis than in normal women both at the protein and the mRNA levels (P < 0.05). CONCLUSION: These findings make plausible the involvement of MMP-9/TIMP-1 imbalance in the invasiveness of the endometrial tissue of patients with endometriosis and the ectopic development of the disease.     

The matrix metalloproteinase/tissue inhibitor of matrix metalloproteinase profile in colorectal polyp cancers

Aims:  The matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) system has a major role in tumour invasion and metastasis. Roles in pathways involved in early tumour development are also being identified for this system, and the aim of this study was to define the expression profile of the major MMPs and TIMPs in colorectal polyp cancers.
Methods and results:  The expression and cellular localization of individual MMPs and TIMPs was determined in colorectal polyp cancers by immunohistochemistry. All the MMPs and TIMPs showed immunoreactivity in carcinomatous epithelium. MMP1 ( P  < 0.001), MMP2 ( P  = 0.003), MMP3 ( P  = 0.004), TIMP1 ( P  = 0.01) and TIMP2 ( P  < 0.001) showed significant increases in immunoreactivity in carcinomatous epithelium compared with adenomatous epithelium. MMP7 showed immunoreactivity in carcinomatous epithelium, but showed no immunoreactivity in either normal epithelium or adenomatous epithelium. MMP and TIMP expression was limited in normal epithelium to MMP1, MMP2 and TIMP3.
Conclusions:  This study defines the expression profile of MMPs and TIMPs in colorectal polyp cancers and shows that the increased expression of MMPs and TIMPs occurs at an early stage of colorectal neoplasia. It provides evidence to support the hypothesis that these molecules have a key involvement in the early stages of tumour development.     

Relationship between matrix metalloproteinases MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinases-1 and IL-5, IL-8 in nasal polyps

BACKGROUND: Nasal polyps (NP), a subgroup of chronic rhinosinusitis, are characterized by interleukin 5 (IL-5) mediated infiltration of eosinophils in sinus mucosa, leading to pseudostratified ciliated columnar epithelium, thickening of the epithelial basement membrane and tissue edema. Matrix metalloproteinases (MMP) constitute a large group of Zn2+ dependent endopeptidases with the ability to degrade extracellular matrix and are possibly responsible for the development of tissue edema in chronic sinusitis. OBJECTIVE: The aim of this study was to determine the expression of MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) mRNA and to locate the distribution of MMP-2, MMP-9 and TIMP-1 by immunohistochemistry in ethmoid sinus mucosa in NP. Furthermore the correlation between IL-5 or IL-8 and MMP-2, MMP-9 or TIMP-1 is examined. METHODS: Nasal polyps of 33 patients and 18 specimens of inferior turbinate mucosa were examined by real time RT-PCR for MMP-2, MMP-9, TIMP-1, IL-5 and IL-8 mRNA expression. Immunohistochemical labeling for MMP-2, MMP-9 and TIMP-1 was performed. RESULTS: Differences between both locations were detectable for MMP-9 (P < 0.001) and IL-5 (P=0.003) but not for MMP-2 (P=0.278), TIMP-1 (P=0.515) and IL-8 (P=0.386). Correlation was detected only between TIMP-1 and IL-5 (r=0.422, P =0.014). Cytoplasmic staining of MMP-2 was present in the apical part of the ciliated cells, submucosal glands and in smooth muscle cells. Matrix metalloproteinase-9 was expressed in surface epithelium, in seromucous glands and in polymorphonuclear cells. CONCLUSIONS: Expression of MMP-9 and IL-5 mRNA are associated with NP. The correlation between IL-5 and TIMP-1 indicates the role of TIMP-1 in maintaining the homeostasis in NP.     

蜕膜组织MMP-9/TIMP-3水平与自然流产关系

目的研究蜕膜组织中MMP-9／TIMP-3之间的平衡与自然流产发生的关系。方法用免疫组化S-P法测定30例自然流产患者与20例正常妊娠者蜕膜组织中MMP-9／TIMP-3的表达。结果研究组蜕膜细胞MMP-9表达阳性率为76．7％，高于对照组(55．0％，P-0．02)，两组蜕膜细胞TIMP-3的表达差异无显著性。结论自然流产患者蜕膜组织中MMP-9的表达增高，TIMP-3表达正常所导致的MMP-9／TIMP-3比例升高，在自然流产的发生中起重要作用。     

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer: implications for tumour progression

AIMS: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors. METHODS AND RESULTS: A study of 11 normal skin, 29 Bowen's disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell carcinoma (BCC) samples for MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out using immunohistochemistry and in situ hybridization. The expression of all metalloproteinases was greater in tumours than in normal skin. MMP-2 and MMP-9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP-1 expression was greater in the stroma of BCC than of SCC or BD and TIMP-2 expression was greater in the stroma of SCC than of BD. There was a correlation between increased metalloproteinase expression and depth of lesion (MMP-2 and TIMP-2), inflammation (MMP-2, MMP-9, TIMP-1 and TIMP-2) and microvessel density (MMP-2, MMP-9 and TIMP-2). CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 play an important role in the pathogenesis of non-melanoma skin cancer, but differ significantly in their expression levels between the tumour types examined. The immunoexpression of these proteins may be useful indicators of cutaneous cancer invasion and progression.     

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas

The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low-grade malignant chondrosarcoma and a benign growing enchondroma.     

MMP-3和TIMP-3在卵巢癌中的表达及其意义

目的探讨MMP-3和TIMP-3在卵巢癌的表达及其意义。方法本文采用光镜、透射电镜和免疫组化方法对27例卵巢癌组织中的MMP-3及TIMP-3表达进行检测。结果结果表明,临床分期为晚期的卵巢癌组织中MMP-3阳性细胞的数密度和面密度明显高于早期,而TIMP-3则低于早期。电镜下,早期淋巴细胞和树突状细胞浸润较多,癌细胞没有穿过基底膜;晚期淋巴细胞和树突状细胞浸润较少,可见癌细胞穿基底膜。结论MMP-3和TIMP-3的表达程度及MMP-3/TIMP-3的比值,可作为判断卵巢癌病程的指标。     

Study of matrix metalloproteinases and their tissue inhibitors in ductal in situ carcinomas of the breast

Aims: To analyse the expression of metalloproteinases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ of the breast (DCIS). Methods and results: An immunohistochemical study was performed in 56 patients with pure DCIS, in 39 with DCIS adjacent to invasive carcinoma (IDC) and 63 patients with T1 IDC, using tissue microarrays and specific antibodies against MMPs and TIMPs. Immunohistochemical results were categorized using a specific software program. The data were analysed by unsupervised hierarchical cluster analysis by each cellular type. IDC showed a higher expression rate of MMP‐7 and TIMP‐1 than pure DCIS, as well as a higher expression rate of MMP‐9 and TIMP‐3 than the DCIS component of mixed cases, whereas pure DCIS showed a higher rate of expression of MMP‐9 and ‐11 and TIMP‐3 than in the DCIS component of mixed cases. Pure DCIS with a periductal inflammatory infiltrate showed significantly higher MMP‐2, ‐14 and TIMP‐1. Dendograms identified two cluster groups with distinct MMP/TIMP expression profiles in neoplastic cells and fibroblastic or mononuclear inflammatory cells surrounding the neoplastic ducts of pure DCIS. Conclusions: The results indicate the distinct variability in MMP/TIMP expression by DCIS, which may be of potential biological and clinical interest in breast cancer.     

Infiltrative capacity of T leukemia cell lines: A distinct functional property coupled to expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1)

Infiltrative capacity was found to distinguish separate T leukemia cell lines. Of seven T-cell lines four exhibited capacity to infiltrate Matrigel. Analysis of infiltration was performed at the single-cell level throughout the Matrigel using a depth meter. Further, we examined differences in migration capacity and metalloproteinase production between infiltrating and non-infiltrating T-cell lines. The capacity to infiltrate was not directly correlated to the capacity to adhere to the Matrigel or to migrate on/to extracellular matrix components. It is concluded that infiltration capacity does not simply reflect capacity to migrate but represents a distinct functional property. The production of metalloproteinases and their inhibitors by the separate T-cell lines was analyzed using rt PCR, biosynthetic labelling, zymography, immunoprecipitation and ELISA. All T-cell lines with capacity to infiltrate produced matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) while non-infiltrating cell lines did not express MMP-9. Expression of MMP-1, 2, 3, 10, 14 and 17 showed no correlation to capacity to infiltrate. Analysis of infiltration in the presence of a metalloprotease inhibitor showed an increased number of cells within the gel. This enhancement of infiltration suggests that the function of MMPs and/or their inhibitors in lymphocyte infiltration is more complex than previously thought. This revised version was published online in July 2006 with corrections to the Cover Date.     

Matrix metalloproteinases 2, 3, 13 and their type 2 tissue inhibitor in tumors and plasma of patients with colorectal cancer

Enzyme immunoassay studies revealed increased content of matrix metalloproteinases 2, 3 and 13 in tumors compared to the adjacent histologically unchanged mucosa in 70–90% patients with colorectal cancer, while the increase in the content of type 2 metalloproteinase tissue inhibitor did not reach the level of statistic significance. Plasma concentrations of these proteins did not correlate with the corresponding values in the tumors and did not surpass the normal levels, while their decrease after removal of the primary tumor was observed only in patients with initially high levels of this parameter. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 337–341, March, 2008     

基质金属蛋白酶-2、3及其组织抑制剂TIMP-1在子宫内膜异位症中的表达

目的探讨基质金属蛋白酶(MMP-2、MMP-3)及其抑制剂(TIMP-1)在子宫内膜异位症发生及发展中的作用.方法采用免疫组化SP法分别测定MMP-2、MMP-3 、TIMP-1在卵巢子宫内膜异位症异位内膜60例(A组),子宫腺肌症异位内膜40例(B组),子宫肌瘤子宫内膜30例(对照组C)的表达强度.结果 A、B组中MMP-2、MMP-3的表达强度明显高于对照组(P<0.05)而TIMP-1的表达明显低于对照组(P<0.05);A、B组间MMP-2、MMP-3 、TIMP-1 的表达无明显差异(P>0.05).结论在子宫内膜异位症中MMP-2、MMP-3的过度表达及TIMP-1的低表达可能与内异症的发生与发展有关.     

The matrix metalloproteinase inhibitor batimastat inhibits angiogenesis in liver metastases of B16F1 melanoma cells

Matrix metalloproteinases (MMPs) have been shown to contribute functionally to tumor metastasis. MMP inhibitors are thus being assessed for clinical utility as anti-metastatic therapeutics. Batimastat (BB-94) is a synthetic MMP inhibitor that has been shown to inhibit tumor growth and metastasis in mice. Here we assessed the ability of batimastat to inhibit liver metastases of murine B16F1 cells, after injection of cells in mice via mesenteric vein to target the liver. We then determined which of the sequential steps in metastasis were affected by batimastat, in order to identify its mechanism of action in vivo. Intravital videomicroscopy was used to assess the effect on extravasation, and a cell accounting procedure was used to determine the effect on initial survival of cells. Stereological quantification of functional blood vessels was used to determine the effect on tumor vascularity, thereby avoiding problems associated with immunohistochemical detection of liver sinusoidal endothelial cells. We found that batimastat (50 mg/kg i.p. 5 h prior to and after cell injection, daily thereafter) resulted in a 23% reduction in mean diameter of liver metastases (equivalent to a 54% reduction in tumor volume), while not reducing the number of metastases. Extravasation of cells from the liver circulation was not affected: at 8, 24 and 48 h after injection of cells, the same proportion of cells had extravasated from treated vs. control mice. Batimastat also did not inhibit early survival of cells. However, batimastat-treated mice had a significantly reduced percentage vascular volume within liver metastases, indicating inhibition of angiogenesis. This study demonstrates in vivo that the mechanism by which batimastat limits growth of B16F1 metastases in liver is not by affecting extravasation, but by inhibiting angiogenesis within metastases. This finding suggests that MMP inhibitors may be appropriate for use in patients with metastatic cells that have already extravasated in secondary sites.     

不同类型不明原因不孕患者的体外受籼胎移植助孕结局探讨

目的：探讨不同类型不明原因不孕（UI）夫妇接受IVF-ET助孕治疗的结局。方法：共纳入212个因UI接受IVF-ET助孕的周期进行回顾性分析。所有周期均采用短时受精,在IVF受精后6h,对低受精率（〈30％）和IVF完全受精失败周期中未出现第二极体的成熟卵立即进行早期补救ICSI。结局按原发不孕（A1组,139例）及继发不孕（A2,组73例）分组进行比较。并将所有获得成熟卵的周期再分为IVF受精（B1组,181例）与补救ICSI受精（B2组,26例）进行比较。结果：1．A1组较A2组年轻,但不孕年限更长,MII卵IVF受精率及2PN受精率较低,补救ICSI受精周期率明显较高（17.04％比4.17％,P值〈0.05）。A1组因异常受精、未受精、未卵裂或胚胎质量差导致的无可移植胚胎周期取消率明显高于A2组（11.79％比2.74％,P值〈0.05）,但两组移植周期种植率、临床妊娠率及活产率无显著差异（P值〉0.05）。2．Bl组比B2组MII卵受精率更高（93.82％比84.78％,P值〈0.05）,但其余指标比较无显著差异。结论：不明原因不孕夫妇中原发不孕者更容易出现IVF受精失败或低受精率。采用短时受精及补救ICSI受精后可以获得与继发不孕夫妇相当的IVF-ETII临床结局。     

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in thyroid C-cells and medullary thyroid carcinomas

Aims: Hyperplastic C-cells of the thyroid and medullary thyroid carcinomas (MTCs) were studied immunocytochemically for calcitonin, carcinoembryonic antigen (CEA), chromogranin A, matrix metalloproteinase (MMP)-2 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 and -2. Methods and results: Non-neoplastic C-cells were positive for all these substances whereas MTC tumour cells were relatively weaker stained, and thyroid follicular cells were negative for all the substances studied. We have recently reported that pancreatic islet cells and islet cell tumours were positive for MMPs and TIMPs, and, in addition, anterior pituitary cells and pituitary adenomas and parathyroid gland and its adenomas were also positively stained. The MMP- and TIMP-positive endocrine cells correspond to Pearse's APUD cells, derived from neural crest and endodermal cells. Conclusions: MMPs and TIMPs may well be added as newly recognized markers for neuroendocrine cells. The possible function of MMP-TIMP homeostasis in C-cells and MTCs is discussed.     

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in thyroid C-cells and medullary thyroid carcinomas

Aims : Hyperplastic C-cells of the thyroid and medullary thyroid carcinomas (MTCs) were studied immunocytochemically for calcitonin, carcinoembryonic antigen (CEA), chromogranin A, matrix metalloproteinase (MMP)-2 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 and -2. Methods and results : Non-neoplastic C-cells were positive for all these substances whereas MTC tumour cells were relatively weaker stained, and thyroid follicular cells were negative for all the substances studied. We have recently reported that pancreatic islet cells and islet cell tumours were positive for MMPs and TIMPs, and, in addition, anterior pituitary cells and pituitary adenomas and parathyroid gland and its adenomas were also positively stained. The MMP- and TIMP-positive endocrine cells correspond to Pearse's APUD cells, derived from neural crest and endodermal cells. Conclusions : MMPs and TIMPs may well be added as newly recognized markers for neuroendocrine cells. The possible function of MMP-TIMP homeostasis in C-cells and MTCs is discussed.     

Matrix metalloproteinases 7 and 9 and their types 1 and 4 tissue inhibitors in tumors and plasma of patients with colorectal cancer

Enzyme immunoassays showed significantly elevated content of matrix metalloproteinase 7 and type 1 tissue inhibitor of metalloproteinases in tumors compared to adjacent histologically unchanged mucosa of patients with colorectal cancer; the levels of metalloproteinase 9 and type 4 tissue inhibitor of metalloproteinases were virtually the same in the tumors and mucosa. Plasma concentrations of the studied proteins did not correlate with their levels in the tumor, did not surpass the normal, and did not decease after removal of the primary tumor in the majority of patients. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 4, pp. 438–441, April, 2007