Decreases in Paraoxonase-1 Activities Promote a Pro-inflammatory Effect of Lipids Peroxidation Products in Non-smoking and Smoking Patients with Acute Pancreatitis.

Aim: The study investigated the extent to which tobacco smoke exposure causes changes in lipids biochemistry through measurement blood concentrations of: paraoxonase-1 (PON-1) activities as lipid-bound enzyme into cell membrane, concentration of malonyldialdehyde (MDA), protein adducts of 4-hydroxynonenal (HNE-adducts), oxidized low density lipoproteins (oxLDL), total cholesterol (CH) and high-density lipoprotein cholesterol (HDL). Additionally, the activity of P isoform of glutathione S-transferase (GST-π) was measured. Methods: Investigations were performed in the blood of patients with acute pancreatitis (AP) on the 1st, 3rd and 7th day of hospitalization and in healthy volunteers. The activities of PON-1 forms, GST-π were determined spectrophotometrically. Concentrations of PON-1, MDA, HNE-adducts, oxLDL, HDL, CH were measured using commercial tests. Results: Near 2-fold higher concentrations of MDA, HNE-adducts, oxLDL, correlating with inflammatory markers in AP patients compared to healthy subjects were demonstrated, which were accompanied by gradually increasing CH/HDL ratio during hospitalization. During hospital treatment, decreased activities of all PON-1 subtypes were observed in AP patients compared to healthy subjects, more pronounced in tobacco smokers. A decreased PON-1 phosphotriesterase activity in non-AP control group smokers compared to non-smokers was noted. In non-smoking AP patients GST-π activity normalized during hospitalization in contrast to smokers. Conclusions: GST-π and PON-1 phosphotriesterase activities seem to be a sensitive marker of pro/antioxidative imbalance in smokers. Lipids peroxidation products generated during AP can intensify preexisting inflammation. Increasing stay in the hospital was associated with worsening of lipids peroxidation markers and the parameters of lipid profile, in both non-smoking and smoking AP patients, what can indicate that the oxidative-inflammatory process are not extinguished.

Relationship between somatostatin and interleukin-6: A cross-sectional study in patients with acute pancreatitis.

OBJECTIVES: The aim of the analysis is to determine dynamic changes in somatostatin (SS) and interleukin-6 (IL-6) concentrations during in acute pancreatitis (AP). METHODS: The influence of tobacco smoking on IL-6 and SS levels in the serum of non-smoking (n = 10) and smoking (n = 27) patients with diagnosed AP and control group: non-smoking (n = 44), smoking (n = 42) and passive smoking (n = 29) healthy persons was proved. The concentration of IL-6 and SS was determined by means of ELISA. Differences between the groups analyzed were tested using the U Mann Whitney test. The Spearman rank correlation analysis was used to evaluate the correlations. RESULTS: The concentrations of IL-6 and SS were significantly higher in smoking patients with AP and healthy persons when compared with non-smoking population on every day (1 day: p = 0.0002, p = 0.015; 3 day: p = 0.005, p = 0.001 and 7 day: p = 0.025, p = 0.038). Dynamic changes in concentrations of IL-6 and SS in the serum of patients with AP were demonstrated in the ensuing days of the disease. In case of non-smoking and smoking patients, significant positive correlations between IL-6 and SS was observed. CONCLUSIONS: These findings suggest that some of the antiinflammatory effects of SS against acute pancreatitis may be mediated by reducing the local proinflammatory cytokine secretion in the pancreas.

Resistin as a Prooxidant Factor and Predictor of Endothelium Damage in Patients with Mild Acute Pancreatitis Exposed to Tobacco Smoke Xenobiotics.

OBJECTIVES: The study was aimed to assess the influence of tobacco smoke exposure on the intensity of inflammation measured by IL-6, α1-antitripsin (AAT) and α1-acid glycoprotein (AGP) concentrations, and Cd level and oxidative stress intensity measured by advanced oxidation protein product (AOPP) concentration in the blood of healthy subjects and AP patients during hospitalization. Endothelin-1 (ET-1) and resistin concentrations, markers of endothelium injury, were determined. RESULTS: An increased IL-6 concentration in healthy smokers compared to nonsmokers and AP patients compared to controls was shown. An increased AAT and AGP concentrations during hospitalization of AP patients were noted, in both smokers (AAT, AGP) and nonsmokers (AAT). In comparison to control groups, in AP patients, a 2-fold increased resistin concentration correlating with ET-1 concentration and decreased albumin concentration accompanied by increased AOPP concentration were demonstrated. AOPP concentration was higher in smokers with AP compared to nonsmokers and gradually enhanced during their hospitalization. CONCLUSIONS: Tobacco smoke exposure can have a proinflammatory effect in both healthy subjects and AP patients. Increased resistin concentration in AP patients negatively correlating with albumin concentration has prooxidative effect on this protein resulting in enhanced AOPP level. Increased resistin concentration can intensify AAT and AGP production during AP.

The Association Between HSP90/topoisomerase I Immunophenotype and the Clinical Features of Colorectal Cancers in Respect to KRAS Gene Status.

AIM: The aim of this study was to investigate heat shock protein 90 (HSP90) and topoisomerase I (Topo I) expression and the association between both proteins and clinicopathological parameters of colorectal cancer (CRC), in order to describe their role in tumor biology regarding to Kirsten Ras (KRAS) - positive/negative cases. MATERIALS AND METHODS: Expression of HSP90 and Topo I, and KRAS gene mutations were estimated in primary CRCs. RESULTS: HSP90/Topo I immunophenotype correlated with gender, Duke staging, tumor grade and lymph node metastasis (p<0.01). Positive correlation was found between KRAS mutation and HSP90 expression (p=0.02). HSP90, Topo I expression, and co-expression of HSP90/Topo I correlated with unfavorable parameters of CRCs in respect to KRAS gene status (p<0.001). CONCLUSION: Our results revealed that cooperation between HSP90 and Topo I expression exists in CRCs, independently of KRAS gene status, suggesting that co-expression of both proteins might be considered as a double target on individual tumor cells.

K-ras gene mutation as an early prognostic marker of colon cancer.

UNLABELLED: Due to increased colorectal cancer incidence there is a necessity of seeking new both prognostic and prediction factors that will allow to evolve new diagnostic tests. K-ras gene seems to be such a factor and its mutations are considered to be an early marker of progression of colorectal cancer. The aim of the study was to find a correlation between K-ras gene mutation in patients with diagnosed colorectal cancer and selected clinical parameters. MATERIAL AND METHODS: A total of 104 patients (41 women and 63 men) with diagnosed colorectal cancer were included in this study. The average age of male group was 68.3 and in female group - 65.9. Samples were taken from paraffine blocks with tissue from diagnosed patients and K-ras gene mutation were identified. Afterwards the statistical analysis was made seeking the correlation between K-ras gene mutation incidence and clinical TNM staging system, tumour localisation, histological type, sex, age. RESULTS: K-ras gene mutations were detected in 20.1% of all colorectal cancers. Significantly higher rate of K-ras gene mutations were diagnosed among patients classified at stage I (40%), stage IIC (50%) and stage IV (50%) according to the TNM classification. CONCLUSIONS: The results of our study are compatible with other studies and indicate the correlation between K-ras gene mutation and colorectal cancer incidence. Identification of K-ras gene mutation may complement other diagnostic methods at early stage of colorectal cancer.

Expression of Androgen Receptor in Estrogen Receptor-positive Breast Cancer.

OBJECTIVES: The aim of the study was to estimate the implications of androgen receptor (AR) expression in estrogen receptor (ER)-positive subset of invasive breast carcinoma patients. PATIENTS AND METHODS: We assessed the AR expression in a subset of 96 predominantly ER-positive invasive breast carcinomas and correlated this expression pattern with several clinical and pathologic parameters: histologic type and grade, tumor size, lymph node status, progesterone receptor (PgR) status, and human epidermal growth factor receptor type 2 (HER2) overexpression and evaluated the association of these parameters with 10-year survival using univariate and multivariate analyses. Data used for analysis were derived from medical records. Immunohistochemical analysis for AR, ER, PgR, and HER2 were carried out and semiquantitative evaluation of stainings was performed. RESULTS: AR expression was demonstrated in 43.7% of patients. AR was significantly related to well-differentiated tumors and positive PgR/HER2 status. No statistical difference was demonstrated in AR expression in relation to tumor size, lymph node status, menopausal status, and tumor histologic type. AR expression was not an independent prognostic factor related to 10-year survival in ER-positive cancers. In multivariate analyses, older age at diagnosis, larger tumor size, and positive lymph node status were significantly associated with poorer 10-year survival. CONCLUSIONS: AR expression is significantly associated with ER/PgR/HER2 status and positively related to well-differentiated tumors. Although AR status in ER-positive cancers is not an independent prognostic factor, it might provide important additional information on prognosis and become a promising object for targeted therapy.

Surgical site infection--the authors' own prospective research.

UNLABELLED: Surgical site infection is a common complication in surgery, which increases treatment cost, extends hospitalization time and can lead to septic complications. The aim of the study was analysis of postoperative infections in own material and finding significant risk factors with preserving the obligatory procedures in the clinic. MATERIAL AND METHODS: Prospective analysis of 270 consecutively operated patients aged from 18 to 101 was performed with observation of early infection until 7th day postoperatively. Factors judged included: age, sex, BMI, operation type: elective or urgent, physical preparation for surgery, antibiotic prophylaxis, length and type of surgery. Wound observation card was used. Data were analysed statistically (t-Student's test, chi2 test, U Mann Whitney test and logistic regression analysis). RESULTS: Wound infection was observed in 33 patients (12.22% of the entire group). In 24 (8.88%) it was a superficial infection and in 9 (3.33%) deep infection. Statistically significant risk factors were age, presence of diabetes, operation time and operations on large bowel. The average age of patients with present infection was 61.2. In the group without infection there were 6,3% patients with diabetes and 20.8% in the group with infection. In our study diabetes increased the risk of infection four times. The longer the operation time the higher was the risk of deep infection (without complications 76.2 minutes, superficial 94.9 minutes, deep 148.9 minutes). Operations on large bowel were performed in 11.9%of all study patients. In the group of 33 patients with surgical wound infection, 39.4% had colon surgery, 39.4% of all deep infections and 29.2% of all superficial infections. CONCLUSIONS: In own study material significant risk factors of surgical wound infection were: age, presence of diabetes, length of operation, large bowel surgery. In preoperative course risk factors should be identified to perform certain prophylactic procedures to lower the risk of infectious complications.

Caspases and their role in gastric cancer.

Caspases (Cysteine Aspartate Specific Proteases) are a group of cysteine-containing proteolytic enzymes produced by the cells of living organisms. They participate in immunological functions, proliferation, cell migration and organization. Caspases also influence the secretion of various regulative factors. Moreover, they are responsible for cellular maturation and reconstruction, and for regulating the number and quality of cells initiating the apoptosis of old cells or those that cannot play their normal role due to abnormalities. Multiple pathological processes are associated with disorders in the activity of caspases. Changes in expression of individual caspases have been observed in gastric cancer. The expression of some caspases is also correlated with particular histological traits and the frequency of metastases, which suggests their possible use as a prognostic factor. It has also been discovered that some somatic mutations in caspase coding genes might lead to inhibition of apoptosis and the progression of the disease. Gene polymorphism may be a gastric cancer risk factor, but may also play a protective function. Considering the less than satisfactory effects of conventional therapeutic methods, the search for alternative ways to activate apoptosis - through gene therapy or selective activation of individual elements of the apoptotic pathways - constitutes a promising direction for studies of new therapeutic strategies. Caspases, enzymes playing a central role in the process of programmed cellular death, may possibly be a key to the development of a more effective anti-cancer therapy.

Intermediate- and low-methylation epigenotypes do not correspond to CpG island methylator phenotype (low and -zero) in colorectal cancer.

BACKGROUND: Most recent genome-wide studies on the CpG island methylation in colorectal cancer (CRC) have led to the discovery of at least 3 distinct methylation clusters. However, there remains an uncertainty whether the CRC clusters identified in these studies represent compatible phenotypes. METHODS: We carried out comprehensive genome-scale DNA methylation profiling by Illumina Infinium HumanMethylation27 of 21 DNA pools that represent 84 CRC samples divided according to their high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively) and 70 normal-adjacent colonic tissues. We have also examined the relationship among 3 epigenotypes and chromosomal gains and deletions (assessed by Comparative Genomic Hybridization) in a group of 100 CRC samples. RESULTS: The HME subgroup showed features associated with CpG island methylator phenotype - high (CIMP-high) including methylation of specific CpG sites (CpGs) as well as significantly lower mean number of chromosomal imbalances when compared with other epigenotypes. The IME subgroup displayed the lowest number of methylated CpGs (717 vs. 2,399 and 2,679 in HME and LME, respectively) and highest mean number of chromosomal imbalances when compared with HME (P, 0.001) and LME (P, 0.004). A comparison between the methylation profiles of 3 epigenotypes revealed more similarities between the HME and LME (1,669 methylated CpGs overlapped) than HME and IME (673 methylated CpGs overlapped). CONCLUSION: Our results provide evidence that IME and LME CRCs show opposite features to those that have been previously attributed to CIMP-low and CIMP-0 CRCs. IMPACT: These discrepancies should be considered when interpreting the data from a particular epigenotyping method.

High density of peritumoral lymphatic vessels measured by D2-40/podoplanin and LYVE-1 expression in gastric cancer patients: an excellent prognostic indicator or a false friend?

BACKGROUND: One of the most important prognostic indicators in gastric cancer is the presence of metastases in lymph nodes. Even now, little is known about lymphangiogenesis in neoplastic tissue, and little is also known about the transmission of a neoplastic cell from the tumor mass into a lymphatic vessel. METHODS: This study examined the relationships between the density of lymphatic vessels (LVD) stained immunohistochemically with lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and D2-40 (podoplanin) antibodies, the expression of vascular endothelial growth factor (VEGF)-C/D, selected clinical and pathomorphological factors, and the 5-year overall survival of gastric cancer patients. RESULTS: Statistical analysis showed no impact of increased intratumoral or peritumoral LVD on gastric cancer patient survival, irrespective of the protein used to stain lymphatic vessels. Analysis showed that the probability of overall survival was decreased in the cases with enhanced VEGF-D immunoreactivity (P = 0.0045). CONCLUSION: The study showed that the studied markers cannot be used to determine the required extent of the surgical procedure, as they have no statistically significant correlation with the degree of progression of the cancer, the stage of the disease assessed according to the TNM 5th classification of malignant tumors, clinicopathological features, and patient survival. VEGF-D is the only marker that can be regarded as an unfavorable prognostic indicator for patients with advanced gastric cancer.

The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual's susceptibility to sporadic colorectal cancer.

Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of "minor impact genes" such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors. We focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (-4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911C (Lys751Gln), XPF Arg415Gln, XPG Asp1104His, ERCC1 C118T]; homologous recombination repair [NBS1 Glu185Gln, Rad51 135G/C, XRCC3 C18067 (Thr241Met)]. The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher's exact test with a Bonferroni correction for multiple testing was used. We found that: (i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391, 3.7782) P=0.038], (ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR=0.4497, (95% CI 0.2215, 0.9131) P=0.031] for an individual with at least one A allele at this locus. (1) The XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer. (2) The NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC.

Assessment of three epigenotypes in colorectal cancer by combined bisulfite restriction analysis.

Recent investigations have demonstrated the clear heterogeneity of sporadic colorectal cancer (CRC) with regard to CpG island methylation. Two unsupervised cluster analyses revealed that CRCs form three distinct DNA methylation subsets, which are referred to as the high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively). A recent study by Yagi et al. found a fairly sensitive and specific identification of HME, IME, and LME using two marker panels analyzed by MALDI-TOF mass spectrometry (MassARRAY). However, the expensive equipment required for this method substantially increases the cost and complexity of the assay. In this article, we demonstrate the assessment of HME, IME, and LME in a group of 233 sporadic CRCs using seven markers proposed by Yagi et al. The DNA methylation of each marker was quantified using combined bisulfite restriction analysis (COBRA) and analyzed along with various genetic factors associated with CRC [the BRAF and KRAS mutations, MLH1 methylation and microsatellite instability (MSI)]. The baseline methylation of each marker was generated from pooled DNA isolated from 50 normal colon tissues. We demonstrate that the correlation of HME, IME, and LME epigenotyped by COBRA using different molecular classifiers is similar to that achieved by MassARRAY. Therefore, epigenotyping CRCs using COBRA is a simple, specific, and cost-effective method that has the potential to be widely used in CRC research.

Control of active B and L cathepsins in tissues of colorectal cancer using cystatins isolated from chicken egg proteins: in vitro studies.

The activity of cysteine peptidases (cathepsins B and L) was estimated in homogenates of tissues sampled during surgery from 60 patients operated due to colorectal tumors. The results were compared to those obtained using tissues in which histopathology disclosed no tumorous cells, obtained from 20 patients of the same group, treated as a control. Activity of the enzymes was inhibited using cysteine peptidase inhibitors isolated from chicken egg proteins. Application of the inhibitors was found to inhibit activity of the enzymes which play a key role in tumor development. It is suggested that in future the inhibitors may provide a component of new generation drugs in the so-called inhibitor therapy.

Cysteine peptidases and their inhibitors in breast and genital cancer.

Cysteine proteinases and their inhibitors probably play the main role in carcinogenesis and metastasis. The metastasis process need external proteolytic activities that pass several barriers which are membranous structures of the connective tissue which includes, the basement membrane of blood vessels. Activities of the proteinases are regulated by endogenous inhibitors and activators. The imbalance between cysteine proteinases and cystatins seems to be associated with an increase in metastatic potential in some tumors. It has also been reported that proteinase inhibitors, specific antibodies for these enzymes and inhibition of the urokinase receptor may prevent cancer cell invasion. Some proteinase inhibitor could serve as agents for cancer treatment.

Polymorphisms in methyl-group metabolism genes and risk of sporadic colorectal cancer with relation to the CpG island methylator phenotype.

BACKGROUND: The CpG island methylator phenotype (CIMP), together with extensive promoter methylation, is regarded as one of the mechanisms involved in colorectal carcinogenesis. The mechanisms underlying CIMP in sporadic colorectal cancer are poorly understood. Genes involved in methyl-group metabolism are likely to affect DNA methylation and thereby influence an individual's risk of CIMP. The aim of the present study was to evaluate whether polymorphisms in the genes encoding methyl-group metabolism pathway predispose to CIMP+ and/or CIMP- CRC. METHODS: We examined the potential association between the polymorphisms of MTHFR 677C>T, TS 5'UTR 2R/3R, TS 3'UTR 1494del6, DeltaDNMT3B -149C>T and DNMT3B -283T>C in a group of 46 CIMP+ CRC cases, 140 CIMP- CRC cases and 140 healthy controls. The CIMP status of the CRC cases was determined by MS-PCR in tumor tissue by a panel of five markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1), which was also followed by analyzing hMLH1 methylation and BRAF V600E mutation. RESULTS: The variant allele homozygote genotype for the DeltaDNMT3B -283T>C polymorphism was associated with a decreased risk for CIMP+ CRC (OR: 0.31, 95%CI: 0.09-0.73, p=0.009). Individuals with TS 3R/3R had an increased risk of CIMP- CRC (OR: 2.21, 95%CI: 1.23-4.91, p=0.01). Moreover, the carriers of 3R allele had an increased risk of CIMP- CRC (OR: 1.45, 95%CI: 1.10-2.13, p=0.01). CONCLUSION: This study provides support to the hypothesis that methyl-group metabolism plays a role in the etiology of both CIMP+ and CIMP- colorectal cancers but has a different impact on a distinct molecular subgroups of colorectal cancer.

Androgen receptors as a prognostic and predictive factor in breast cancer.

Many theoretical and experimental models indicate that androgen receptors can play an important role as prognostic factors in breast cancer. The aim of this study was to evaluate the correlations between the presence of androgen receptors on cancer cells and other selected prognostic and predictive factors with established clinical significance in women with breast cancer after radical surgical treatment. 488 adult females were included in the study, who underwent primary radical surgery for breast cancer. 428 patients (87.7%) had Patey's conservative radical mastectomy and 60 (12.3%) Halsted's radical mastectomy. The mean age at operation was 54.3, ranging from 32 to 79. The mean length of hospitalization was 7.2 days for the patients after Patey's mastectomy and 9.8 days for those after Halsted's mastectomy. The androgen receptor is the most frequently detected steroid receptor on breast cancer cells. Therapeutic efficacy of adjuvant hormone therapy was higher in the group of androgen receptor-positive patients than in androgen receptor-negative ones. The prognosis for androgen receptor-positive patients who underwent adjuvant hormone therapy was better than for those androgen receptor-positive patients who did not receive hormone therapy after primary radical surgery for breast cancer. Assessment of androgen receptor levels on cancer cells should become a routine procedure with patients undergoing primary radical surgery for breast cancer, as it seems to be an important predictive factor.

Immunohistochemical evaluation of metallothionein, Mcm-2 and Ki-67 antigen expression in tumors of the adrenal cortex.

BACKGROUND: The aim of this study was to assess the metallothionein (MT), maintenance protein 2 (Mcm-2) and Ki-67 expressions in adrenocortical adenomas and carcinomas in comparison to normal tissue and evaluate the correlations between these markers of proliferation and between these markers and tumor diameter. MATERIALS AND METHODS: The expression of MT, Mcm-2 and Ki-67 was assessed by immunochemistry in forty-eight adrenocortical adenomas, six adrenocortical carcinomas and eleven normal adrenal cortex tissue samples. RESULTS: The expressions of MT, Mcm-2 and Ki-67 in the adrenocortical carcinomas were significantly higher than in the adenomas and normal tissue (p<0.05). The levels of Mcm-2 were also higher in the adrenocortical adenomas compared to the normal tissue (p<0.05). The Mcm-2 expression showed a positive correlation to the expression of MT in the adrenocortical carcinomas (r=0.773; p<0.05) and to the expression of Ki-67 in the adrenocortical adenomas (r=0.432; p<0.05). The malignant tumor diameter was positively correlated with the MT and Mcm-2 expressions (r=0.766, p<0.05 and r=0.620, p<0.05, respectively). CONCLUSION: The assessment of Mcm-2 expression seems to be of special importance as a marker of adrenocortical dysplasia and a reliable indicator of malignancy in suspicious masses of the adrenal cortex.

The CpG island methylator phenotype correlates with long-range epigenetic silencing in colorectal cancer.

The CpG island methylator phenotype (CIMP), characterized by an exceptionally high frequency of methylation of discrete CpG islands, is observed in 18% to 25% of sporadic colorectal cancers. Another hypermethylation pattern found in colorectal cancers, termed long-range epigenetic silencing, is associated with DNA/histone methylation in three distinct gene clusters at chromosome 2q14.2, showing that DNA hypermethylation can span larger chromosomal domains and lead to the silencing of flanking, unmethylated genes. We investigated whether these two phenotypes are interrelated in colorectal cancers. The CIMP status of 148 sporadic colorectal cancers was determined by methylation-specific PCR. We determined the BRAF V600E mutation by mutant allele-specific PCR amplification. The methylation status of the MLH1 gene and of three CpG islands (EN1, SCTR, and INHBB), corresponding to three distinct clusters along 2q14.2, was determined by methylation-specific PCR. The average number of sites showing methylation in CIMP+ tumors was 2.21, compared with 1.22 for CIMP- individuals, and this difference was highly significant (P = 3.6 x 10(-8), Mann-Whitney test). Moreover, all CIMP+ tumors showed hypermethylation of at least one of these loci, in contrast to CIMP- tumors, where 18 (16%) samples remained unmethylated. The mean number of simultaneously hypermethylated CpG islands at 2q14.2 differs significantly between CIMP- and CIMP+ tumors, suggesting varying effects of domain silencing in this region. Given that the number of hypermethylated loci at 2q14.2 likely affects the range of silenced flanking genes, high frequency of simultaneous hypermethylation of three CpG islands (EN1, SCTR, and INHBB) may have potential influence on specific characteristics of CIMP+ colorectal cancers.

Molecular markers (c-erbB-2, p53) in breast cancer.

The aim of our study was to evaluate the correlation between clinical characteristics, histopatologic features and c-erbB-2 as well as p53 expression in cancer tissues. Breast cancer tissue was obtained from 184 female subjects with primary breast cancer. According to hormonal status patients were divided into two groups - 64 belonged to the premenopausal group and 120 to postmenopausal group. Each patient underwent mammectomy and axillary lymphadenectomy. c-erbB-2 protooncogene was detected in 54% cases, and was correlated with infiltrating type of cancer growth, as well as larger tumor size. The presence of p53 antioncogene was observed only in 33% of cases, mainly in infiltrating duct carcinomas. The incidence of c-erbB-2 and p53 positive cases was higher among subjects, whose ultrasound and mammography revealed malignancy. There was no correlation found between of c-erbB-2 expression and axillary lymph nodes involvement It seems probable, that c-erbB-2 and p53 status of cancer tissue may prove to be useful in assessment of the level of biological aggressiveness in breast carcinomas and hence can be used as a prognostic factor.

[Postoperative complications of curative treatment for rectal cancer in males with sphincter-preserving total mesorectal excision]. / Powiklania leczenia u mezczyzn raka odbytnicy metoda calkowitego wyciecia mezorektum z zaoszczedzeniem zwieraczy.

UNLABELLED: Cancer of the rectum is an important problem for public health in Poland due to increasing incidence rate and still not satisfying treatment outcomes. Surgical management remains the mainstay of therapy. Because of introduction of the total mesorectal excision technique (TME) better locoregional control can be achieved. The value of the treatment method for clinical practice is associated with oncological effectiveness but it is also related to the risk of mortality and morbidity. THE AIM OF THIS STUDY: To assess the risk of mortality and morbidity of the curative anterior resection with TME in male patients and to evaluate the association between the incidence of postoperative complications and patient-, tumour- and treatment-related variables. MATERIAL AND METHODS: Consecutive 65 patients with histologically confirmed rectal cancer operated on with sphincter-saving TME method were studied prospectively RO resection was achieved in all cases. All anastomoses were constructed with end to end double-stapling technique. Adjuvant therapy was administered for 54% patients (in stages UICC II i III). 19% of patients received preoperative radiation with high-dose fractions to 25 Gy (5 x 5 Gy) and postoperative chemotherapy with 5-fluorouracil and leucovorin in six courses. In 35% of patients combined adjuvant radiotherapy to the total dose 50.4 Gy and chemotherapy scheduled as above was used. RESULTS: There was no postoperative mortality. Early complications were noticed in 23% of patients: in 9.2% prolonged wound healing caused by superficial infection, in 6.9% anastomosis leakage (surgical treatment was performed in one patient), in 4.6% prolonged bowel paralysis, in 2.3% acute postoperative bleeding requiring relaparotomy. Late complications occurred in 16% of patients: in 6.9% anterior resection syndrome with bowel dysfunction (in one case defunctioning stoma was constructed), in 4.6% bladder dysfunction (nycturia with dysuria and urinary incontinence in 2.3% each), in 2.3% moderate benign anastomosis stricture and also in 2.3% complete sexual impotence. In patients with postoperative complications following factors were present: older age (> 75 years), obesity (BMI > 30), diabetes, preoperative radiotherapy and ultra low site of tumour (< 6 cm from the anal verge). CONCLUSIONS: Anterior resection with TME technique is a safe procedure in male patients. The incidence of early and late postoperative complications seems to be acceptable especially considering the oncological advantages of this method. The risk of morbidity increases in older patients with obesity, diabetes, ultra low-sited tumours and after preoperative radiation therapy