[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.

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.

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).

[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.

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.

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).

[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.

[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.

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.

Acquired resistance of pulmonary adenocarcinoma to initially successful targeted therapy due to EGFR mutation T790M.

According to previous reports in the literature, the T790M mutation indicates an acquired resistance to tyrosine kinase inhibitors. The initial positive effect of combination chemotherapy with erlotinib as the first line of treatment correlates with several positive predictors including the type of carcinoma, non-smoking status, occurrence of rash and the presence of exon 19 EGFR gene mutation. The case of a 32-year-old, non-smoker with non-contributory history patient, who was diagnosed with adenocarcinoma in the left lung T4N0M0 stage IIIB is reported. The patient underwent 6 cycles of chemotherapy with erlotinib, gemcitabine and cisplatin, followed by complete remission. Fifteen months after commencing therapy, disease recurred over subsequent therapy with erlotinib and then gefitinib. During that time, bone and cerebral metastases with pericardial effusion were detected. The patient died 7 months later. Genetic examination of tumour tissue collected at the beginning of therapy revealed activating exon 19 mutation in the EGFR gene. Later, during the relapse, the same mutation was still present and, in addition, a T790M mutation in exon 20 of EGFR was found. The subsequently acquired resistance against both erlotinib, as well as gefitinib was most likely a result of tumor cells acquiring the T790M mutations and escaping the drug effect. The authors recommend testing for T790M mutation presence in selected patients prior to targeted therapy with tyrosine kinase inhibitors.

The importance of prognostic factors in premenopausal women with breast cancer.

BACKGROUND: Basic conventional prognostic factors for breast cancer include the age of the patient, tumor grade, regional lymph nodes status, and estrogen (ER) and progesterone (PR) receptor status. Positivity of the HER2 receptor (c-erbB-2) seems to be a new prognostic and predictive factor. Prognostic factors seem to be more important in the high-risk group of the premenopausal females. We evaluated individual prognostic factors (age, histology, TNM classification, ER, PR, CA 15-3, CEA, HER2) and their impact on disease-free survival (DFS) and overall survival (OS) during the 5-year follow-up period. PATIENTS AND METHODS: Forty-two patients were monitored after standard oncology treatment for a period of at least 5 years. The statistical significance of the individual prognostic parameters was evaluated in relationship to the time to progression (DFS and OS). RESULTS: The following were evaluated as statistically significant prognostic parameters for DFS: PR positivity (p = 0.0036), proliferative marker MIB1 (p = 0.0108), pre-operative level of CA 15-3 (p = 0.0425), ER negativity (p = 0.0507). The following were evaluated as statistically significant prognostic parameters for OS: PR positivity (p = 0.0003), MIB1 (p = 0.0005), ER (p = 0.0440), pre-operative level of CEA (p = 0.0495). Positivity of immunohistochemically performed test of c-erbB-2 was not statistically significant for DFS os OS (p = 0.6361 and 0.9323, respectively). CONCLUSION: The statistically significant prognostic importance of the levels of tumor markers CA 15-3 and CEA for prognosis in breast cancer of premenopausal females was proven. So far, these factors have been underestimated. The prognostic parameters of ER, PR and MIB1 were statistically significant. While no prognostic importance was confirmed for c-erbB-2 positivity; this factor cannot be evaluated in premenopausal females separately from the other prognostic factors due to the predictive value in relation to the adjuvant therapy (patients with HER+, ER+, PR-).

Clinicopathological assessment and quantitative estimation of the matrix metalloproteinases MMP-2 and MMP-7 and the inhibitors TIMP-1 and TIMP-2 in colorectal carcinoma tissue samples.

BACKGROUND: The matrix metalloproteinases (MMP) are a family of proteolytic enzymes involved in tumor growth and in the process of invasion. The aim of our study was to test the levels of MMP-2, MMP-7, and the MMP inhibitors TIMP-1 and TIMP-2 mRNA in colorectal carcinoma tissue samples with the clinicopathological status of the disease. PATIENTS AND METHODS: Colorectal carcinoma tissue samples were obtained from 38 patients who underwent resection of colorectal carcinoma. The expression levels of mRNA of MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene were quantified in these tissue samples using the method of reverse transcription real-time PCR. RESULTS: It was found that the levels of mRNA expression of MMP-2, TIMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples than in the normal colorectal tissue (p < 0.0020, p < 0.0467, p < 0.0007 and p < 0.0003 respectively). The level of mRNA expression of MMP-2, MMP-7, TIMP-2 and TIMP-1 did not correlate with the stage of the disease, localization of the tumor, metastatic spread or with disease-free survival (DFI). We recorded a statistically significant inverse negative correlation (r = -0.85; p < 0.0001) between the levels of MMP-7 mRNA and TIMP-2 mRNA. Correlations between the values of mRNA MMP-7 vs. TIMP-1, MMP-2 vs. TIMP-2, MMP-2 vs. TIMP-1 and MMP-2 vs. MMP-7 were not statistically significant. CONCLUSION: We found that there were statistically significant differences in the levels of MMP-2, MMP-7, TIMP-1, TIMP-2 mRNA between normal colorectal tissue and tumor tissue, but we did not find any statistically significant correlation between mRNA levels of MMP-2, MMP-7, TIMP-1, TIMP-2 expression and localization of tumor, clinical stage or course of disease. We found an inverse negative statistically significant correlation between mRNA levels of MMP-7 and TIMP-2. On the basis of these results the clinical use of this approach to the determination of a prognosis is ambiguous.

Dynamic monitoring of cardio-specific markers and markers of thyroid gland function in cancer patients--a pilot study.

BACKGROUND: With the increased effectiveness of anticancer therapy, much more attention is being paid to the monitoring of the side-effects of chemotherapy, which often constitute a limiting factor in anticancer therapy. In this pilot study, the results of our monitoring of changes in cardio-specific markers and thyroid gland parameters in patients with colorectal carcinoma in the course of adjuvant and palliative chemotherapy are presented. PATIENTS AND METHODS: A total of 42 patients with colorectal carcinoma were monitored (median age 52 years, range 34-82 years); in these patients a post-operative adjuvant or palliative chemotherapy was applied (de Gramont's or FOLFIRI regimen). In all of these patients, the cardio-specific markers brain natriuretic peptide (BNP) and troponin I were assessed, as well as markers of thyroid gland function, TSH and FT4. RESULTS: In the course of chemotherapy, more than half of the patients showed laboratory signs of coronary ischemia; in 6 of these (14%) coronary ischemia was manifested with troponin I levels above 0.3 microg/L. Twenty patients (48%) had laboratory signs of heart failure in the course of adjuvant or palliative chemotherapy. A more frequent incidence of elevated cardio-specific enzymes was observed in continual regimens than in bolus application of fluorouracil. Reduced TSH values were observed in the course of chemotherapy in 9 patients (21%), without changes in FT4 values. An increase in TSH values was observed in 4 patients (10%), again without changes in FT4 values. CONCLUSION: The pilot study demonstrated that in patients undergoing treatment for colorectal carcinoma by adjuvant or palliative chemotherapy on the basis of 5-fluorouracil, it is advisable to check for possible cardiotoxicity and simultaneously to monitor thyroid gland functions. This systematic monitoring may improve the quality of life in cancer patients.

Tumor markers as useful predictors of survival rate after exploratory laparotomy for liver malignancies.

BACKGROUND: Tumor markers are used for the prediction of relapse and in determining the effect of postoperative or post-oncological therapy as a standard component of follow-up. Metastatic processes of the liver and primary malignancies of the liver and gall bladder are very common in the European population. The aim of this study was to demonstrate the behaviour of malignancy in patients who have not undergone surgical therapy and to study serum levels of the monitored tumor markers in relation to the life expectancy of these patients. PATIENTS AND METHODS: The Log-rank test and Wilcoxon test were used for statistical evaluation. Survival was computed using the Kaplan-Meier method. Serum levels of the tumor markers conventionally used in clinical practice in patients with gastrointestinal tumors (CEA, CA19-9, C724) and the markers of the proliferation activity in malignancy (TK, TPA, TPS) were studied. RESULTS: One hundred and nine patients who underwent exploratory laparotomy without any surgical therapy between September 1999 and June 2005 were studied. For patients with a serum level of CEA, CA19-9 and CA72-4 that was higher than the calculated cut-off hazard ratios of early death were respectively 3-, 5- and 9-fold higher than for patients with serum levels of the same tumor markers below the calculated cut-off. Preoperative serum levels of proliferative tumor markers (TK, TPA and TPS) were not statistically significant for the prediction of early death. CONCLUSION: The results of the pilot study suggest the importance of tumor markers for the prediction of the short-term survival rate. These markers could be used to supplement classic clinical, laboratory and radiodiagnostic parameters. It would be very helpful for the planning of palliative oncological therapy for patients with liver malignancies who cannot be treated by surgical therapy.

Prognostic importance of thymidine kinase in colorectal and breast cancer.

BACKGROUND: Thymidine kinase (TK) plays an essential role in the processing of thymidine within the cell and therefore it is an important marker of proliferation, particularly in tumor cells. The aim of our study was to determine the diagnostic, prognostic and predictive importance of TK measurement in cancer. PATIENTS AND METHODS: TK was measured using radioreceptor analysis (RRA) with Immunotech assay kits. The serum level of TK was measured in 1087 patients with malignant disease (355 patients with hematology malignancies and 732 patients with solid tumors). RESULTS: Serum levels of TK were significantly elevated in inflammatory and immunological diseases in comparison with healthy individuals. Malignant diseases were associated with elevated serum levels of TK only in particular cases (e.g. hematological malignancies, cervical cancer). This marker has a high sensitivity for use as a primary diagnostic tool. It also has a high sensitivity during the follow-up period in breast and colorectal cancer for the prediction of relapse at the time of primary diagnosis and 3 months earlier than the diagnosis of relapse by imaging methods. CONCLUSION: TK represents a secondary tumor marker which is particularly useful for cancer disease monitoring. Interpretation of this marker must be performed only in association with evaluation of clinical status since all other possible non-specific causes (inflammatory or immunological diseases) of elevated serum levels must be excluded.

Expression of mRNA MMP-7 and mRNA TIMP-1 in non-small cell lung cancer.

BACKGROUND: Destruction of the extracellular matrix is a necessary precondition for metastasis and invasion of tumour cells. Metalloproteinases (MMPs) are involved in this process, matrilysin being one of them (MMP-7). The results of our pilot study with patients operated on for non-small cell lung carcinoma (NSCLC), with the assessment of MMP-7 and the tissue inhibitor of matrix metalloproteinase (TIMP-1), are presented here. PATIENTS AND METHODS: The group consisted of 34 patients who had been operated on in the course of 2005. Messenger RNA MMP- 7 and TIMP-1 were assessed in 20 cases (58%). Tissue samples were frozen to -70 degrees C, total RNA was subsequently isolated and a reverse transcription was performed from it. The quantitative assessment itself was performed using a real-time PCR method. The resulting expression level was determined as the expression ratio of the assessed gene and the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RESULTS: A higher expression of mRNA MMP-7 was found in the NSCLC tissue than in non-tumourous lung tissue. On the other hand, a higher expression of mRNA TIMP-1 in the non-tumourous surrounding lung tissue was demonstrated. The expression of mRNA MMP-7 and TIMP-1 was higher in adenocarcinoma than in the epidermoid form of NSCLC. CONCLUSION: The value of our results should not be overestimated since we had only a small group of patients and assessed only one of the whole range of metalloproteinases (MMP-7). We consider the assessment and ratio quantification of metallorpoteinases in normal lung and NSCLC to be the first step in a further application of these parameters.