[The importance of early tumor shrinkage and deepness of response in assessing the efficacy of systemic anticancer treatment with metastatic colorectal cancer]. / Význam casné nádorové regrese a hloubky lécebné odpovedi pri hodnocení úcinnosti systémové lécby metastazujícího kolorektálního karcinomu.

BACKGROUND: The efficacy of anticancer therapy is regularly evaluated using the following indicators -  objective response rate, progression free survival and overall survival. The change in the tumor burden extent is assessed by the cumulative change in the size of target tumor lesions using imaging methods where WHO and RECIST criteria are most frequently used. The main problem of these criteria is that they use different definitions of response rate evaluation. Generally, existing results of these evaluations do not confirm a direct correlation between the objective response rate and survival (progression free survival or overall survival). Another problem of these methods is that the results of the assessment do not correlate with the bio-logical activity of tumor growth, since it is a static evaluation of clinical status. AIM: This review article provides an overview of results related to new possibilities for evaluating the efficacy of anticancer therapy using the concept of depth of response and the concept of early tumor shrinkage in patients with metastatic colorectal cancer. CONCLUSION: The results of numerous posthoc and exploratory analyses of clinical studies consistently suggest that early tumor shrinkage and depth of response are important variables in assessing the efficacy of systemic anticancer treatment.

Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

[Polyneuropathic pain therapy with a patient suffering from generalized castrate- resistant prostate cancer -  clinical case report]. / Lécba polyneuropatické bolesti u nemocného s generalizovaným, kastracne rezistentním karcinomem prostaty -  klinická kazuistika.

BACKGROUND: Tapentadol is a µâ€Š-opioid receptors agonist as well as an inhibitor of noradrenaline reuptake. This pharmacologic profile of tapentadol makes it a suitable drug of choice in nociceptive and neuropathic pain control. CASE REPORT: This clinical report pressents a 65year old man with poorly differentiated prostate cancer -  Gleason score 8 (4 + 4) with metastatic bone disease. Besides the initial application of bisphosphonates, the patient had been treated with androgen deprivation therapy (cyproterone acetate + leuprolide acetate) for the period of 18 months. This therapy was terminated due to an increase of PSA levels. Subsequently, the patient underwent palliative docetaxelbased chemotherapy. There were eight cycles applied with positive clinical and laboratory effect. However, the further application was limited by the averse effects, namely the peripheral neuropathy manifested by pain in arms and legs. The peripheral neuropathy had progressive tendency even after the end of chemotherapy, and supportive treatment with gabapentin and amitryptiline failed to succeed. Four months after zoledronic acid monotherapy, the patient was started on tapentadol in 50-mg dose b.i.d., consequently escalated to 100 mg b.i.d. (to this point, 25 µg of transdermal fentanyl were used for pain management). Significant relief from neuropathic discomfort was observed three weeks from the onset of tapentadol therapy. Patients state of health normalized within three months after the initiation of therapy. Consequently, the patient was able to receive docetaxel chemotherapy again, without any neuropathic pain exacerbation on the maintenance dose of tapentadol 50 mg b.i.d. CONCLUSION: Tapentadol administration resulted in stable and longtime relief from neuropathic pain which is a frequent side effect in the course of castrate-resistant prostate cancer therapy with taxanes.

[Chylous ascites as a serious complication of the neuroendocrine tumor of ileum -  case report]. / Chylózní ascites jako závazná komplikace neuroendokrinního tumoru ilea -  kazuistika.

BACKGROUND: Chylous ascites is a rare complication of the gastrointestinal neuroendocrine tumor. There are two mechanisms of its origin: mechanical obstruction by the tumor mass and fibrosis of the surrounding tissue due to overproduction of serotonin. Its presence restricts treatment options. CASE: We report a case of 66year old man suffering from recurrent diarrhoea and ascites. We found elevated tumor marker Chromogranin A and elevation of hydroxyindoleacetic acid (5- HIAA) in the urine. A subsequent whole body scintigraphy scan by octreoscan confirmed multinodal process with increased somatostatin receptors activity in the wall of the ileum, rectosigmoideum, lymph nodes of the retroperitoneum and mesenterium and left supraclavicular area. We performed bio-psy from the lymph node of supraclavicular area, and there was metastasis of the neuroendocrine tumor. Start of cytostatic therapy was repeatedly complicated by recurrent massive chylous ascites. The patient underwent only one series of palliative chemotherapy. Another procedure was again complicated by chylous ascites that caused hospitalization at the internal department, and the patient died four months after dia-gnosis. CONCLUSION: Chylous ascites is a very rare complication of gastrointestinal neuroendocrine tumor. It is not only a marker of poor prognosis, but also a complication that makes systemic treatment very difficult.

Immediately preoperative use of biological therapy does not influence liver regeneration after large resection--porcine experimental model with monoclonal antibody against epidermal growth factor.

BACKGROUND: The aim of this work was to study the influence of isolated biological therapy administered immediately before extended liver resection on liver function and regenerative capacity of future liver remnant (FLR) in a large-animal experiment. MATERIALS AND METHODS: Nineteen piglets were included in this study (10 in the control group and 9 in the experimental group). A port-a-cath was introduced into the superior caval vein. On days 11 and 4 before liver resection, cetuximab was administered via this port at 400 mg/m2 of piglet body surface. Physiological solution was applied to the control group. Resection of the left lateral, left medial and right medial hepatic lobes was followingly performed (reduction of 50-60% of liver parenchyma). Blood samples were collected at different times before the operation and after liver resection. Serum levels of bilirubin, urea, creatinine, alkaline phosphatase, gamma glutamyltransferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase, albumin, C-reactive protein and transforming growth factor-ß1 were assessed. The ultrasonographic examinations at different time points were performed pre-operatively and after liver resection in order to assess the liver volume. The biopsies from the liver parenchyma were examined for proliferative activity, binocluated hepatocytes, size of hepatocytes, and the length of the lobuli. The comparison of distribution of the studied parameters between the groups was carried out using the Wilcoxon test. The Spearman rank correlation co-efficient was used because of the non-Gaussian distribution of the parameter values. The whole development of the studied parameters over time was compared between the groups using ANOVA. RESULTS: There were no important complications of administration of biologic therapy during the operation or throughout the peri-operative period. There was no statistically significant difference in the regeneration of FLR nor were any differences in biochemical, immunoanalytical and histological parameters detected. CONCLUSION: The achieved results of comparable liver regeneration in both the experimental and control groups confirms the use of biological treatment with cetuximab in the pre-operative period for minimizing the recovery period.

Cytokeratin serum biomarkers in patients with colorectal cancer.

BACKGROUND: Circulating cytokeratins have shown to be important for management of patients with lung cancer. Here we investigated their role for differential diagnosis, therapy monitoring and prognosis in colorectal cancer (CRC). PATIENTS AND METHODS: Pretherapeutic levels of cytokeratin-19 fragments (CYFRA 21-1), carcino-embryonic antigen (CEA) and cancer antigen (CA) 19-9 were measured in 42 patients with CRC, 45 with benign colorectal diseases and 51 healthy controls. Furthermore, courses of CYFRA 21-1, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), M30-antigen, CEA and CA 19-9 were analyzed in prospectively collected sera of 15 patients with CRC during primary chemotherapy and were correlated with therapy response and overall survival (OS). RESULTS: Similar to CEA and CA 19-9, CYFRA 21-1 was significantly elevated in serum from patients with CRC (median 2.1 ng/ml) as compared with healthy (1.2 ng/ml; p<0.0001) and benign gastrointestinal controls (1.7 ng/ml; p=0.0178) and showed stage dependency in CRC (p=0.0118). CYFRA 21-1 correlated with CEA in benign diseases and CRC but not with CA 19-9. The best discrimination between healthy controls and patients with CRC was achieved by combination of CYFRA 21-1 and CA 19-9 (area under the curve; AUC=86.7%), while the combination of CEA and CA 19-9 discriminated best between benign diseases and CRC (AUC=73.9%). In CRC patients during primary chemotherapy, levels of cytokeratins CYFRA 21-1, TPA, TPS, CEA and CA 19-9 tended to be higher in patients with poor response to therapy and with poor prognosis. CONCLUSION: Cytokeratins are elevated in patients with CRC and show some association with response to primary therapy and prognosis.

Matrix metalloproteinases and their inhibitors in correlation to proliferative and classical tumour markers during surgical therapy of colorectal liver metastases.

OBJECTIVES: Classical and proliferative tumour markers and matrix metalloproteinases and their tissue inhibitors reflect the features of malignancy and are useful in prediction of prognosis in patients with colorectal liver metastases. There is very limited information about their physiological functions during regeneration and healing of liver parenchyma after any type of liver surgery for malignancy. METHODS: The presented study included the patients, who underwent following surgical procedures for CLM, benign liver lesions and inguinal hernias: Group A: 22 patients with inguinal hernias, Group B: 26 patients with benign liver lesions, Group C: 30 patients with colorectal liver metastases (CLM) who were treated by radiofrequency ablation, Group D: 41 patients with CLM who underwent a radical surgical therapy - resection, and Group E: 22 patients with inoperable CLM who underwent an explorative laparotomy without any surgical procedure. RESULTS: The preoperative and postoperative serum levels of CEA, CA 19-9, TK, TPA, TPS, MMP-2, MMP-9, TIMP-1, and TIMP-2 were statistically analyzed and compared within the groups to estimate the influence of a surgical procedure type. These results reflect the influence of surgical procedure on the serum levels of studied tumour markers during operation. CONCLUSIONS: It was the first description using these types of comparison to all metalloproteinases, their inhibitors, and proliferative and classical tumour markers. It could help us to estimate the critical relations of these tumour markers in prognoses of disease free survival or overall survival in patients after a surgical procedure for CLM (Tab. 5, Ref. 26).

The role of ABC transporters in progression and clinical outcome of colorectal cancer.

Worldwide, colorectal cancer (CRC) is the third most common cancer, with the highest mortality rates occurring in Central Europe. The use of chemotherapy to treat CRC is limited by the inter-individual variability in drug response and the development of cancer cell resistance. ATP-binding cassette (ABC) transporters play a crucial role in the development of resistance by the efflux of anticancer agents outside of cancer cells. The aim of this study was to explore transcript levels of all human ABCs in tumours and non-neoplastic control tissues from CRC patients collected before the first line of treatment by 5-fluorouracil (5-FU)-containing regimen. The prognostic potential of ABCs was evaluated by the correlation of transcript levels with clinical factors. Relations between transcript levels of ABCs in tumours and chemotherapy efficacy were also addressed. The transcript profile of all known human ABCs was assessed using real-time polymerase chain reaction with a relative standard curve. The majority of the studied ABCs were down-regulated or unchanged between tumours and control tissues. ABCA12, ABCA13, ABCB6, ABCC1, ABCC2 and ABCE1 were up-regulated in tumours versus control tissues. Transcript levels of ABCA12, ABCC7 and ABCC8 increased in direction from colon to rectum. Additionally, transcript levels of ABCB9, ABCB11, ABCG5 and ABCG8 followed the reverse significant trend, i.e. a decrease in direction from colon to rectum. The transcript level of ABCC10 in tumours correlated with the grade (P = 0.01). Transcript levels of ABCC6, ABCC11, ABCF1 and ABCF2 were significantly lower in non-responders to palliative chemotherapy in comparison with responders. The disease-free interval of patients treated by adjuvant chemotherapy was significantly shorter in patients with low transcript levels of ABCA7, ABCA13, ABCB4, ABCC11 and ABCD4. In conclusion, ABCC11 may be a promising candidate marker for a validation study on 5-FU therapy outcome.

Importance of miR-20a expression in prostate cancer tissue.

BACKGROUND: MicroRNAs (miRNAs), which are endogenously expressed regulatory noncoding RNAs, have an altered expression in tumor tissues. MiRNAs regulate cancer-related processes such as cell growth and tissue differentiation, and therefore, might function as oncogenes or tumor-suppressor genes. The aim of our study was to assess the expression of mir-20a, let-7a, miR-15a and miR-16 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) tissue and to investigate the relation between the expression of miRNAs and the clinicopathological features of PCa. PATIENTS AND METHODS: The study group comprised 138 patients: 85 patients with BPH and 53 patients with PCa. The total RNA was isolated from the tissue specimen core and miRNA expressions were quantified using a real-time RT-PCR method (TaqMan MicroRNA Assays). U6snRNA was used for the normalization of the miRNA expression. RESULTS: miR-20a expression was significantly higher in the group of patients with a Gleason score of 7-10 in comparison with the group of patients with a Gleason score of 0-6 (p=0.0082). We found no statistical differences in the miRNA expressions (mir-20a, let-7a, miR-15a and miR-16) in the PCa tissue samples in comparison with the BPH tissue samples. CONCLUSION: Our result shows that the more dedifferentiated PCa cells have a higher expression of miR-20a and this supports the oncogenic role of miR-20a in PCa carcinogenesis. The evaluation of miRNA expression could yield new information about PCa pathogenesis.

[Modern algorithms for diagnostics and treatment of anorectal fistulas in clinical practice--case reviews]. / Moderní algoritmy diagnostiky a lécby anorektálních pístelí na klinickém pracovisti--kazuistiky.

Authors present three case reports of perianal fistules with review of contemporary literature. The obligatory nature of this disease is defined by its behaviour, tendency to relace, a social taboos and handicap, that affects patients with perianal fistule. In introduction there is descripted aethiology, morphology, standard diagnostic procedures and therapy of anorectal fistules and fistule form of idiopatic bowel diseases. In discussion there is a review of the new trends of diagnostic and treatment procedures of these diseases, that reflect domestic and international expert literature. Standard procedures are summarized in conclusion.

Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis.

BACKGROUND: Early diagnosis of prostate cancer (PCa) in an organ-confined stage following radical treatment is the only potential curative approach in PCa. Prostatic-specific antigen (PSA) is very helpful in early diagnosis, but the main disadvantage is that it has a low positive predictive value in the range of the grey zone of 2.5-10 ng/mL, which results in a high number of needless biopsies. For this reason, new tests with better parameters are needed. One promising test is that for differential display code 3 (DD3(PCA3)), which is a prostate-specific non-coding mRNA that is highly overexpressed in prostate tumor cells. The aim of the present study was to evaluate the potential of DD3(PCA3) for mRNA in PCa diagnosis. PATIENTS AND METHODS: A total of 186 patients were examined. In a group of patients with suspected PCa, one tissue specimen core was collected for testing DD3(PCA3) expression. According to the histological verification there were 100 patients with benign prostatic hyperplasia, 12 patients with prostatic intraepithelial neoplasia and 74 patients with PCa. The total RNA was isolated and DD3(PCA3) and PSA expressions were quantified using quantitative RT real-time PCR method. The DD3(PCA3)/PSA mRNA ratio was determined for all groups. RESULTS: It was found that the levels of the mRNA expression of DD3(PCA3) were significantly higher (p<0.045) in patients with PCa than in patients with benign prostatic hyperplasia. No statistically significant differences in levels of mRNA expression of DD3(PCA3) between patients with organ-confined and those with advanced or metastatic disease, nor according to Gleason score, were found. CONCLUSION: DD3(PCA3) appears to be a promising marker for early detection of PCa and also for differential diagnosis between patients with benign prostate hyperplasia and those with PCa.

Significance of methylation status and the expression of RECK mRNA in lung tissue of patients with NSCLC.

OBJECTIVES: RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a glycoprotein which negatively regulates the activity of matrix metalloproteinases (MMPs). We analyzed differences in RECK mRNA expression in histological types of non-small cell lung cancer (NSCLC) and the relationship between promoter methylation status of RECK gene, level of RECK mRNA expression and clinicopathological values of patients with NSCLC. PATIENTS AND METHODS: Methylation status of the promoter and the expression of RECK mRNA were analyzed in paired tissue samples (tumor and control) of 50 patients with NSCLC. The methylation status of the RECK promoter was assessed using methylation-specific PCR. The level of RECK mRNA expression was measured using an RT real-time PCR method. RESULTS: Lower expression of RECK mRNA in NSCLC tissue was recorded compared to normal tissue (p=0.0032). Significantly lower expression of RECK in squamous cell carcinoma (SCC) tissue was observed in comparison with adenocarcinoma tissue (p=0.0051). Significant differences in expression of RECK in stages IB-IIIA were found in comparison with stage IA (p=0.0455). There was a significantly lower expression of RECK mRNA in NSCLC tissue in samples with positive RECK promoter methylation status in comparison with samples with negative promoter methylation status (p=0.0400). CONCLUSION: We showed that there were differences in expression between histological types of NSCLC (SCC, adenocarcinoma). There was a higher expression of RECK in stage IA in comparison with stages IB-IIIA. Our results indicate that RECK could be classified as a tumor suppressor gene and is an interesting target for further investigation of MMP inhibitors.

Cytokines and liver regeneration after partial portal vein ligation in porcine experimental model.

THE AIM OF STUDY: The limits of liver surgery are restricted today by the functional reserves of remnant parenchyma. The aim of this article was to acquaint the general surgical and medical public with the results of experimental liver regeneration stimulated by cytokines and thus to enhance their effort to carry on with implementing the research results in clinical practice. METHODS: Authors present their experimental model of liver regeneration after ligation of portal branches for caudate and right lateral, and right medial liver lobes. The regeneration was induced by application of TNF-alpha and IL-6 into the non-occluded portal branches, and compared with the results of other experimental teams. RESULTS AND CONCLUSION: The absolute volume of hypertrophic lobes increases after application of TNF-alpha more rapidly, whereas in the control group, practically no changes were recorded in hypertrophic liver lobes volumes in first three days. The achieved acceleration of growth of hypertrophic liver lobes after application of TNF-alpha and IL-6 confirmed the key role of studied pleiotropic cytokines in the priming of liver parenchyma regeneration after portal vein ligation (Fig. 3, Ref. 26).

Expression of MMP-7, MMP-9, TIMP-1 and TIMP-2 mRNA in lung tissue of patients with non-small cell lung cancer (NSCLC) and benign pulmonary disease.

UNLABELLED: The expression of matrix metallo-proteinases (MMP-7 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), which are involved in the degradation of the extracellular matrix (ECM) and tumor growth, was investigated in normal lung tissue, tissue of benign pulmonary diseases and non-small cell lung cancer (NSCLC) tissue. PATIENTS AND METHODS: Tumor tissue and surrounding carcinoma-free lung tissue samples were obtained from 91 patients with NSCLC who had undergone surgery in the years 2005-2007 as well as lung tissue from 12 patients operated on for 'benign' bullous emphysema or interstitial lung disease. The mRNA was isolated from the tissues and the expression of mRNA was assessed using a real-time RT PCR method. RESULTS: Significantly higher expression of MMP-7, MMP-9 and TIMP-1 mRNA was demonstrated in the NSCLC tissue in comparison with the normal lung tissue from the same patients (p=0.0003, p<0.0001 and p=0.0018, respectively). Similar results for MMP-7, MMP-9 and TIMP-1 were found in the histological subgroups: squamous cell lung cancer vs. normal tissue (p=0.0198, p=0.0015 and p=0.0366, respectively), and adenocarcinoma vs. normal tissue (p=0.0045, p<0.0001 and p=0.0140, respectively). The expression of MMP-7 was found to be significantly higher in tumor tissue vs. lung tissue of the benign diseases (p=0.0086) and similar results were also recorded in the histological subgroups: squamous cell lung cancer vs. benign tissue (p=0.0171) and adenocarcinoma vs. benign tissue (p=0.0135). The expression of MMP-9 was significantly higher only in the adenocarcinoma subgroup vs. the benign tissue (p=0.0412). No differences in the expression of mRNA between stage IA and stages IB-IIIB of NSCLC were recorded. CONCLUSION: Significantly higher expression of MMP-7 and MMP-9 in tumor tissue than in the surrounding tissue or in benign lung disease tissue supports the notion of an important role of these metalloproteinases in the growth of lung carcinoma. TIMP-1 expression is increased only in carcinoma, but not in benign lung disease.

Preoperative tumor markers as prognostic factors of colorectal liver metastases.

BACKGROUND/AIMS: Tumor recurrence develops in 45-80% of patients after liver surgery for colorectal liver metastases. To assess the significance of preoperative tumor marker levels for disease free interval (DFI) and patient survival (PS) after liver surgery. METHODOLOGY: Preoperative serum levels of carcinoembryonic antigen--CEA, CA 19-9, CA 72-4, thymidine kinase (TK), tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS) were evaluated in 173 patients operated on for colorectal liver metastases (CLM). Liver resection was performed on 114 patients and radiofrequency ablation on 59 patients. RESULTS: Preoperative serum levels of TPA (cut off level = 53 IU/L, Hazard ratio = 4.5, Wilcoxon test: p < 0.01, Log-Rank test: p < 0.03) and TPS (cut off level = 81 IU/L, Hazard ratio = 5.1, Wilcoxon test: p < 0.007, Log-Rank test: p < 0.009) were important for PS and DFI after liver resection (TPA: cut off level = 53 IU/L, Hazard ratio = 3.5, Wilcoxon test: n.s., Log-Rank test: n.s.; TPS: cut off level = 81 IU/l, Hazard ratio = 2.6, Wilcoxon test: p < 0.02, Log-Rank: p < 0.06). TPA serum levels were important for PS (Wilcoxon test--p < 0.003, Log-Rank test--p < 0.0002) and DFI after RFA (Wilcoxon test--p< 0.001, Log-Rank Test--p < 0.0001). TPS serum levels also correlated with PS (Wilcoxon test--p < 0.005, Log-Rank test--p < 0.003) and DFI after RFA (Wilcoxon test--p < 0.001, Log-Rank Test--p< 0.0001). CONCLUSIONS: TPA and TPS are important predictive markers for PS and DFI after liver resections and radiofrequency ablations for CLM.

[Significance of the TPS cytokeratin marker in the postoperative follow up of colorectal carcinoma patients]. / Význam cytokeratinového markeru TPS v pooperacním sledováiní nemocných s kolorektálním karcinomem.

AIM: Examination of tumour markers conducive to follow up of the patients with colorectal carcinoma. MATERIAL AND METHODS: The tumour markers were examined in the population of patients with primarily established and histologically verified colorectal adenocarcinoma. RESULTS: The resection therapy resulted in the decrease in post-operative CEA levels. There were no changes in pre- and post-operative CA 19-9 levels; unlike with post-operative TPS levels having been significantly increased, probably due to reparation processes resulting from the surgery. It can be concluded that pre- and post-operative CEA levels are the most suitable markers to check the effect of surgery. With a 95%-specificity for the establishment of recidives, the highest sensitivity was reached with TPS (83%); the sensitivities of the classical tumour markers CEA and CA 19-9 were significantly lower (41% and 25%, respectively). The results should be interpreted with caution due to a small number of relapses regarding a short follow up and rather local-regional character of the recidives. CONCLUSION: However, TPS seems to be a promising marker for the follow up of the patients with colorectal carcinoma. Thus, an ideal combination seems to be that of CEA and TPS.

[New aspects of tumor pathobiology]. / Nové aspekty patobiologie nádoru.

Several biological principles such as epigenetic changes, RNA interference, epithelial-mesenchymal transition, and cancer stem cell formation have been recently connected to the pathobiology of tumors. All these phenomena have, along with genetic changes, a significant impact on the neoplastic transformation and/or tumor progression. Authors report a review of the above mentioned "nongenetic" processes and their effect on the neoplastic transformation, and the appearance, behavior, prognosis, and therapy of tumors. Future diagnostic and therapeutic perspectives are also discussed.

Biological activity and clinical implications of the matrix metalloproteinases.

The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumour progression and the metastatic process by facilitating extracellular matrix degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by matrix metalloproteinase inhibitors have rapidly developed. Low molecular weight tissue inhibitors of matrix metalloproteinase (TIMPs) represent a new therapeutic approach for the treatment of individual types of cancer. This paper aims to briefly summarize current knowledge about the role of MMPs in select non- tumorous lesions, tumor invasion and metastasis. The perspectives in therapeutic intervention in cancer are also mentioned. The role of MMPs in diagnosis and prognosis of colorectal and thyroid cancer is discussed in detail.

Clinical relevance of the expression of mRNA of MMP-7, MMP-9, TIMP-1, TIMP-2 and CEA tissue samples from colorectal liver metastases.

BACKGROUND: Nowadays we know that survival rates do not differ between repeated and single liver resections for colorectal liver metastases (CLM). To be able to determine patients prone to early recurrence, the use of different markers with a better prognostic value than the routinely employed tumor markers is required. AIM OF STUDY: The aim of our study was to assess mRNA expression of MMP-7, MMP-9, TIMP-1, TIMP-2 and CEA in tissue samples from CLM and their relationship to disease-free interval (DFI) and overall survival (OS). PATIENTS AND METHODS: The liver tumor biopsies were obtained from 40 patients suffering from CLM treated with radical surgery. mRNA expression levels of CEA, MMPs and TIMPs and a housekeeping gene (GAPDH) were quantified using RT-PCR. RESULTS: The increased expression of CEA, MMP-9 and TIMP-1 in CLM was associated with a short DFI and a high tendency to early CLM recurrence. Statistical analysis confirmed CEA, MMP-9 and TIMP-1 expression as prognostic factors of survival. CONCLUSION: This study demonstrated the importance of CEA, MMP-9 and TIMP-1 in the prognostication of DFI and OS.

Dynamics of serum levels of tumour markers and prognosis of recurrence and survival after liver surgery for colorectal liver metastases.

BACKGROUND: The authors present a statistical analysis of the dynamics of tumour markers and compare these with single serum levels in patients before and after liver surgery for colorectal liver metastases (CLM). PATIENTS AND METHODS: The serum levels of tumor markers conventionally used in clinical practice (CA19-9, CEA, CA72-4) and markers informing of the proliferation activity of malignancy (TKI TPA, TPS) were statistically analysed. The authors studied 144 patients who underwent liver surgery for colorectal liver metastases between September 1999 and June 2005. Serum levels of tumor markers before surgery (maximally two weeks before the operation), after surgery (maximally one month after the operation - usually on the day of dismission), six months (+/- one month) and twelve months after the surgery (+/- one month) were determined. The Log Rank test and the Wilcoxon test were used for statistical evaluation. The survival rate and disease-free intervals (DFI) were computed using the Kaplan-Meier method. RESULTS: The statistical analysis of tumour marker dynamic after liver surgery (speed and power of recurrence) supported the dynamics of CA 19-9 and CEA as excellent prognostic factors of early recurrence of CLM in contrast to proliferative tumor markers. CONCLUSION: The results of the study suggest the importance of tumour markers for the prediction of a short survival rate or DFI. This approach would be very helpful for the planning of palliative oncological treatment for patients with liver malignancies that cannot be treated by surgical therapy. Current patients with a high tendency of recurrence of CLM after liver surgery should be followed up more thoroughly to increase the possibility of successful reoperation.