Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.     

20q13.2 Amplification in intraductal hyperplasia adjacent to in situ and invasive ductal carcinoma of the breast

The 20q13 region harboring recently described putative oncogenes is frequently amplified in invasive ductal carcinoma (IDC). The aim of this study was to examine the 20q13 copy number in intraduct hyperplasia (IH), atypical duct hyperplasia (ADH), and ductal carcinoma in situ (DCIS) adjacent to IDC. In 5 patients, comparative genomic hybridization (CGH) after laser microdissection revealed 20q13 amplification in four of five cases of IH, in all of three cases of IH with atypia, all five of DCIS, and all five of IDC. Fluorescence in situ hybridization (FISH) confirmed the amplification at 20q13.2 in IH in the two specimens analyzed. The amplification rate, however, was higher in DCIS and IDC. In phenotypically normal ductal epithelium normal values were found for 20q13 copy number by FISH (n=2) and CGH (n=5). Although the number of cases presented here is small, our results suggest that mutations in the 20q13.2 region in IH may be associated with accelerated proliferation and hyperplasia of the ductal epithelium. Progression to DCIS and ICD is accompanied by a further increase in the 20q13.2 copy number. Received: 17 March 1999 / Accepted: 22 June 1999     

Tumor necrosis factor-mediated interactions between inflammatory response and tumor vascular bed

Summary: Solid tumor therapy with chemotherapeutics greatly depends on the efficiency with which drugs are delivered to tumor cells. The typical characteristics of the tumor physiology promote but also appose accumulation of blood-borne agents. The leaky tumor vasculature allows easy passage of drugs. However, the disorganized vasculature causes heterogeneous blood flow, and together with the often-elevated interstitial fluid pressure, this state results in poor intratumoral drug levels and failure of treatment. Manipulation of the tumor vasculature could overcome these barriers and promote drug delivery. Targeting the vasculature has several advantages. The endothelial lining is readily accessible and the first to be encountered after systemic injection. Second, endothelial cells tend to be more stable than tumor cells and thus less likely to develop resistance to therapy. Third, targeting the tumor vasculature can have dual effects: (i) manipulation of the vasculature can enhance concomitant chemotherapy, and (ii) subsequent destruction of the vasculature can help to kill the tumor. In particular, tumor necrosis factor α is studied. Its action on solid tumors, both directly through tumor cell killing and destruction of the tumor vasculature and indirectly through manipulation of the tumor physiology, is complex. Understanding the mechanism of TNF and agents with comparable action on solid tumors is an important focus to further develop combination immunotherapy strategies.     

Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data

Cryptorchidism and hypospadias share possible risk factors, such as intrauterine growth retardation. According to the data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS), apparently increasing trends in the incidence of hypospadias were found in Sweden during the 1960s, and in Norway, Denmark, England and Hungary during the 1970s. In Norway and Denmark, the increase continued in the 1980s, while in the USA it has continued from the 1970s to the 1990s. Finland has shown a lower reported rate of hypospadias than other Nordic countries. However, it is difficult to make comparisons between countries because of variable inclusion criteria. Furthermore, the reliability of the data depends on correct ascertainment and reporting of the cases. The ICBDMS has also collected data on cryptorchidism, but these appear to be unreliable because of a discrepancy with the data from cohort studies. According to two comparable English studies, the incidence of cryptorchidism in full-term boys approximately doubled between the 1950s and the 1980s. Regionally there are large differences: e.g. in Finland the incidence of cryptorchidism is clearly lower than in Denmark. Regional and temporal trends may help to identify environmental factors that might be associated with these disorders.     

Diagnostic utility of serum dipeptidyl peptidase (DPP- IV) /CD26 as a serum marker in Egyptian patients with colorectal cancer

ABSTRACT

Background

Colorectal cancer (CRC) is considered a major cause of morbidity and mortality in Egypt. Colonoscopy is the standard for detection of lesions. The combination of screening methods is effective. Decrease and loss of DPP-IV/CD26 expression and activity are found in microenvironments of specific tumors which are related to impaired immune functions.     

Loss of claudin-1 expression induces epithelial-mesenchymal transition through nuclear factor-κB activation in colorectal cancer

Objective

The aim of this study was to elucidate the clinicopathological significance and prognostic role of loss of claudin-1 in colorectal cancer (CRC).

Incidence of cancer in children born after in-vitro fertilization

Evaluation of the long-term health of children born using in-vitro fertilization (IVF) provides important information to clinicians and consumers. Until very recently, there have been no published data on the incidence of cancer in children conceived as a result of IVF, despite a number of case reports of neuroblastoma in children conceived using fertility drugs. This study used a record-linkage cohort design to investigate the incidence of cancer in children born after IVF. The study included all conceptions using assisted reproductive technologies between 1979 and 1995 at two clinics in Victoria, Australia that resulted in a live birth. Data on births were linked with a population-based cancer registry to determine the number of cases of cancer that occurred. The standardized incidence ratio (SIR) was calculated by comparing the observed number of cases to the expected number of cases. The final cohort included 5249 births. The median length of follow-up was 3 years, 9 months (range 0-15 years). In all, 4.33 cases of cancer were expected and six were observed, giving a SIR of 1.39 (95% CI 0.62-3.09). This study found that children conceived using IVF and related procedures did not have a significantly increased incidence of cancer in comparison to the general population.     

Simultaneous detection of fluorescent in situ hybridization and in vivo incorporated BrdU in a human bladder tumour

We have used fluorescent in situ hybridization and simultaneous in vivo bromodeoxyuridine labelling of a solid bladder cancer to examine tumour cell subsets for possible proliferative growth differences. In this dual-labelled preparation, most tumour cell nuclei exhibited monosomy 9, consistent with reported karyotypes of bladder cancer. Incorporated bromodeoxyuridine was visualized with a fluoresceinated antibody in 5-6 per cent of the tumour cells, concordant with S-phase estimates by cell cycle analysis of the flow cytometric DNA histogram. A majority of the bromodeoxyuridine-positive cells also carried the monosomy 9 chromosome abnormality. This is the first report to demonstrate the feasibility of combined in situ hybridization and detection of bromodeoxyuridine incorporated in vivo in human tumour cells in order to provide information on the growth rate of specific subsets of tumour cells identified by chromosomal constitution.     

胃癌患者血清CEA、CA19—9及CA72—4联检的临床价值探讨

目的：探讨血清CEA、CA19—9及CA72—4联检在胃癌诊断、病情监测及疗效观察中的价值。方法：采用电化学发光技术检测36例正常对照组、42例良性胃病、55例胃癌患者血清CEA、CA19—9、CA72—4的含量，并对胃癌患者进行治疗前后三种肿瘤标志物的含量变化监测随防。结果：胃癌患者血清CEA、CA19—9、CA72—4的阳性率明显高于正常对照组及良性胃病组，差异有显著性（P〈0．01）。胃癌患者治疗后三种肿瘤标志物含量及阳性率较治疗前有明显下降，差异有显著性（P〈0．01）。三者联检的敏感性、准确性均显著提高（P〈0．01）。结论：血清CEA、CA19-9、CA72—4联检有助于提高胃癌诊断的敏感性、同时对疗效观察及术后监测有重要意义。