Monocyte-to-lymphocyte ratio as a prognostic factor in peripheral whole blood samples of colorectal cancer patients.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide. Therefore, it is critically important to identify new useful markers that can be easily obtained in routine practice. Inflammation is a crucial issue in the pathogenesis and development of cancer. AIM: To evaluate the prognostic value of absolute monocyte count, monocyte to lymphocyte ratio (MLR), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (NLR-PLR), and combined platelet and neutrophil-to-lymphocyte ratio (PLT-NLR) in peripheral blood samples of patients with colorectal cancer undergoing surgery. METHODS: We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery, and 42 healthy controls. The status of absolute monocyte count, MLR, NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery. Haematologic factors were examined in correlation with the type of tumour growth, tumour size, histological type, percentage of mucinous component, grade of malignancy, Tumour-Node-Metastasis stage, venous, lymphatic and perineural invasion of cancer cells, status of lymph node invasion and the presence of cancer cell deposits. The Kaplan-Meier method and the long-rank test were used to compare survival curves. To determine independent prognostic factors, univariate and multivariate Cox proportional hazards regression models were applied. RESULTS: The PLT-NLR status was correlated with tumour size and the presence of perineural invasion (P = 0.015; P = -0.174, P = 0.037). Moreover, high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component (NLR-PLR: P = 0.002; P = 0.009; PLR-NLR status: P = 0.002; P = 0.007). The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery [HR = 2.903, 95%CI: (1.368-6.158), P = 0.005] and the status of lymph node metastasis [HR = 0.813, 95%CI: (0.653-1.013), P = 0.050] were independent prognostic factors in colorectal cancer patients. CONCLUSION: The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.

Pre- and postoperative neutrophil and lymphocyte count and neutrophil-to-lymphocyte ratio in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification. The aim of the present study was to analyze the neutrophil and lymphocyte counts, as well as the neutrophil-to-lymphocyte ratio (NLR) in pre- and postoperative blood samples of patients with CRC in correlation with specific anatomical variables and disease- free survival (DFS). The variables pre- and postoperative neutrophil count (preNEU and postNEU, respectively), lymphocyte count and NLR were significantly higher in cancer patients than those noted in healthy subjects (all P<0.001). PreNEU count correlated with tumor size, necrosis and tumor budding (R=0.204, P=0.014; R=0.189, P=0.023; R=-0.174, P=0.036, respectively). Moreover, postNEU was associated only with the histological type (R=0.174; P=0.047). The PreLYMPH count was correlated with distant metastasis (R=-0.153, P=0.046). PreNLR and postNLR were associated with the expression of various histological markers of disease progression. Analysis of DFS indicated that the postNEU count in the low group exhibited a tendency to lower DFS duration, although the results were not significant (P=0.055). In conclusion, the present study indicated a significant correlation between the factors analyzed in blood samples of CRC patients and the disease progression markers.

Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression.

BACKGROUND: Despite effective prevention and screening methods, the incidence and mortality rates associated with colorectal cancer (CRC) are still high. Insulin receptor substrate 1 (IRS-1), a signaling molecule involved in cell proliferation, survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models. However, the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined. AIM: To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers, Bax, Bcl-xL and Ki-67 are related to clinicopathological features in human CRC. METHODS: The expression of IRS-1, Bax, Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods. The assays were performed using specific antibodies against IRS-1, Bax, Bcl-xL, Ki-67. The associations between the expression of IRS-1, Bax, Bcl-xL, Ki-67 were analyzed in relation to clinicopathological parameters, i.e., patient age, sex, primary localization of tumor, histopathological type, grading, staging and lymph node spread. Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P < 0.05. RESULTS: Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases. IRS-1 expression at any level in primary CRC was associated with tumor grade (69% in moderately differentiated tumors, G2 vs 31% in poorly differentiated tumors, G3) and with histological type (81.9% in adenocarcinoma vs 18.1% in adenocarcinoma with mucosal component cases). Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases (95.1%) and in moderately differentiated tumors (85.2%). We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined. The relationships between studied proteins were related to clinicopathological parameters of CRC. No significant correlation between the expression of IRS-1 and proliferation marker Ki-67, excluding early stage tumors, where the correlation was positive and on a high level (P = 0.043, r = 0.723). CONCLUSION: This study suggests that IRS-1 is co-expressed with both pro- and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.

Review of Potential Significance of Mutations of ADAMTS20, NF1 and PKHD1 Detected Using Next Generation Sequencing (NGS) in Dermal Fibrosarcoma Arising in Dermatofibrosarcoma Protuberans.

We examined a status of fibrosarcoma arising in dermatofibrosarcoma protuberans of 64-year-old male patient. A dermal, solid, grayish-yellow, desmin-negative trichrome-bluish tumor measured 1.5 cm in diameter pT1a (edition 8 pTNM). It was composed of spindle cells. It was consistent with dermatofibrosarcoma protuberans (ICD-O3: 8832/3) in areas of low mitotic activity, low atypia and sustained CD34 positivity. CD34-negative texture with high mitotic index and atypia was consistent with the high grade sarcoma apparently of fibrous origin, given category of poorly differentiated fibrosarcoma. The high grade component was graded (G3) and scored according to French Federation of Cancer Centers Sarcoma Group (FNCLCC): total score of 6 points: tumor differentiation: 3 points + Mitotic count: 3 points (up to 26 mitoses/ 10HPF in high-grade fields), + no necrosis: 0 points. In low grade sarcomatous component ADAMTS20 (NM_025003: c.1661C>T, p.P554L) NF1 (NM_001042492: c. 2173G>T, p.E725X) and PKHD1 (NM_138694: c. 11074C>T, p.R3692X) were revealed with following allelic frequencies: 25%, 27% and 17%. In high grade component allelic frequencies of the same mentioned mutations were 30%, 30% and 14% respectively. In the light of our findings, none of detected mutations can be regarded as a mutation that would definitely induce phenotype of high malignancy, because ADAMTS20, NF1 and PKHD1 mutations were detected both in high grade sarcoma and in low grade areas of dermatofibrosarcoma protuberans. It also points that these mutations appeared on early stages of tumor development.

Tumor-infiltrating lymphocytes in primary tumors of colorectal cancer and their metastases.

The presence of tumor cells in the large intestine stimulates hypoxia and local inflammatory mediators that activate numerous inflammatory cells, including a diverse lymphoid tumor cell population. The aim of the present study was to evaluate tumor-infiltrating lymphocytes (TILs) located in the invasive primary tumor, surrounding deposits of tumor cells and those present in distal metastatic cells in the liver of patients with colorectal cancer. Furthermore, the correlation of TILs with anatomical parameters was assessed. The study group included 123 patients with primary tumor colorectal cancer without distant metastasis, 25 cases with deposits of colorectal cancer cells and 15 cases of colorectal cancer liver metastasis. TILs were assessed in tissues stained with hematoxylin-eosin using light microscopy and evaluated by two independent pathologists blinded to the clinical information. Infiltration of TILs in the invasive front of primary tumor was stronger compared with those surrounding deposits of cancer cells and liver metastases (P<0.001). TILs in the invasive front of primary tumor masses were associated with various variables linked with tumor progression and inflammatory cell infiltrate. TILs distributed around the deposits of cancer cells were associated with postoperative treatment; however, those localized in the invasive front of liver metastases were correlated with preoperative therapy. In conclusion, TILs assessment in primary tumors of colorectal cancer, surrounding deposits of tumor cells and in the metastatic cells in the liver may be helpful in understanding the role of these cells in the organization of immune response.

Prognostic significance of inflammatory cell response in patients with colorectal cancer.

Cancer cells are characterized by a low antigenic immunogenicity, a rapid growth and an immunosuppressive effect on the extracellular matrix. These properties induce a weak immune response in colorectal cancer (CRC) carcinogenesis. It is therefore crucial to determine the composition of the inflammatory mass, including neutrophils, macrophages and eosinophils in the tumor tissue of patients with CRC, and to analyze other clinicopathological parameters. The present study included 144 patients diagnosed with CRC. Tissue samples obtained from routine histopathological diagnosis were stained with hematoxylin and eosin. Inflammatory cells were assessed in the invasive front and in the center of the tumor by light microscopy under a high-power magnification. The percentage of neutrophils in the invasive front was significantly higher compared with that in the center of the tumor mass (P<0.01). Macrophages and eosinophils were present in the invasive front and in the center of tumor mass in most cases. The presence of neutrophils, macrophages and eosinophils was correlated with various clinicopathological features. Patients with macrophages present in the center of tumor mass had longer disease-free survival time (P=0.041). In conclusion, the present study demonstrated that the inflammatory cell infiltrate served a significant role in the immune response of patients with CRC. It should be noted that the presence of macrophages localized in the stroma of the central part of the primary tumor mass was associated with the survival time of patients with CRC.

Features of the fetal gonad in androgen synthesis in the postpubertal testis are preserved in complete androgen insensitivity syndrome due to a novel genetic splice site donor variant in androgen receptor gene intron 1.

Mutations in the X-linked androgen receptor (AR) gene cause complete androgen insensitivity syndrome (CAIS). CAIS may cause congenital sexual development disorder, which frequently develops into testicular tumors. Here, we describe a novel splice-site intron 1 mutation in AR leading to improper splicing and AR protein absence in CAIS gonads. We characterized a patient's postpubertal gonadal steroidogenic enzyme expression profile. Localization of both CYP11A1 and CYP17A1 enzymes was restricted to both Leydig tumor cells and adjacent to tumor gonadal tissues. Sertoli cells of the CAIS gonad showed abundant HSD17B3 protein, which is an adult Leydig cell marker that enables the conversion of androstenedione to testosterone. Such HSD17B3 expression is typical for fetal-type Sertoli cells in rodents. The postpubertal CAIS gonad of our patient was completely devoid of androgen signaling pathway activity. Plausibly, the postpubertal Leydig cells consisted of two distinct cell populations: postpubertal fetal-type Leydig cells that persisted as androgen-independent cells and immature adult Leydig cells that failed to differentiate. Taken together, in this CAIS postpubertal testis, both Leydig and fetal-type Sertoli cells participated in testosterone production. Our results indicate the importance of molecular analysis as well as the characterization of steroidogenic enzyme profiling in the CAIS patient's gonad.

Squamous cell carcinoma of the breast as a clinical diagnostic challenge.

Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice.

Comparison of E-cadherin with STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different ER-alpha immunoprofile.

E-cadherin is a factor of good prognosis in endometrioid adenocarcinomas, while STAT3 is an oncogenic driver of carcinogenesis. E-cadherin, Bak, Bcl-xL and STAT3 were immunohistochemically detected in 78 human endometrioid adenocarcinomas. E-cadherin correlated with STAT3 (p <. 001, r = 0.537) as well as Bak (p = .005, r = 0.314) and Bcl-xL (p = .002, r = 0.340) in the whole study group. In G2 tumors, E-cadherin associated with Bak (p = .021, r = 0.319), Bcl-xL (p = .026, r = 0.309) and STAT3 (p <.001, r = 0.513) but not in G3 adenocarcinomas. E-cadherin correlated with Bak and Bcl-xL in both G1- and estrogen receptor (ER)-negative tumors with significant relation of E-cadherin and STAT3 in G1- and ER-negative tumors. Antigrowth synergy of expression was preserved for antiapoptotic Bak and proliferation-suppressing E-cadherin in IA adenocarcinomas (p = .031, r = 0.342) with no significance between Bak and E-cadherin or STAT3 and emerging correlation between E-cadherin and Bcl-xL in IB + II tumors instead (p = .003, r = 0.472). E-cadherin correlated with Bak and Bcl-xL in ER-positive adenocarcinomas (p = .002, r = 0.382 and p <.001, r = 0.439, respectively) but not in ER-negative tumors. In conclusion, expression deregulation of studied proteins is reflected in selective loss of correlation between suppressors of tumor growth (E-cadherin and Bak) presumably due to progressing impairment of growth-inhibitory properties of clone of neoplastic cells within higher staging and poorer differentiation.

Stromal and intraepithelial tumor-infiltrating lymphocytes in colorectal carcinoma.

The local mechanisms of antitumor immune defense determine the development and organization of the tumor microenvironment, and the composition and relative proportions of the inflammatory cell population affect the quality and characteristics of the immune response. The aim of the present study was to conduct a quantitative morphological evaluation of two types of tumor-infiltrating lymphocyte (TILs) populations, including those located in the stroma and intraepithelial cancer structures, in the invasive front and the center of the tumor in patients with colorectal cancer (CRC). The study included 160 patients with CRC who had undergone surgery. The tissue material was stained with hematoxylin and eosin, as used in routine histopathological diagnosis, and the two TIL populations were observed and counted with light microscopy. The relative extent of infiltration of stromal and intraepithelial TILs into the front and center of the primary tumors was similar. The extent of infiltration by stromal TILs was negatively correlated with the morphological features of tumor progression including the cancer infiltration of blood vessels (P=0.016), the invasion of lymph vessels (P=0.007), perineural invasion (P=0.036), lymph node involvement (P=0.047) and distant metastases (P=0.032). The infiltration by intraepithelial TILs was positively correlated with a desmoplastic reaction (P=0.002). Disease-free survival time was statistically shorter in patients without intraepithelial TILs in the center of the primary tumor mass (P=0.049; hazard ratio = 1.45). These results confirm that the infiltration of TILs into the invasive front and center of the tumor in patients with CRC serves an important role in the invasion and progression of the disease, and should be considered in routine histopathological examinations.

Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer.

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P<0.001) of the tumor, fibrosis (P<0.001), and the degree of desmoplasmic stroma (P=0.004). In contrast, inflammatory infiltration in the center of the tumor was associated with the tumor node metastasis stage (P=0.012), Dukes' stage (P=0.009), primary tumor stage (P=0.036), lymph node status (P=0.005), number of lymph nodes (P=0.006), invasion of lymph node pouches (P=0.021), size of lymph node metastasis (P=0.025) and the degree of desmoplasmic stroma (P=0.002). The low-group, who demonstrated an absent or weak inflammatory cell infiltrate in the invasive front of the tumor, had a statistically significant shorter disease-free survival (DFS) time (P=0.004). Inflammatory cell infiltrate in the invasive front was identified as an independent predictive factor in CRC (P=0.041). In conclusion, the degree of inflammatory cell infiltration in the invasive front of the primary tumor significantly affects various variables that determine disease progression and DFS rates of patients with CRC. Furthermore, the routine histopathological assessment of this parameter in tissue stained with H&E may have potential prognostic value.

Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma.

Estrogen receptor (ER) and progesterone receptor (PgR) accumulations lead to impairment of gap junctional intercellular communication in endometrial cancer. The task of this study was to explore relationships of Cx26 and Cx43 with anti-apoptotic protein Bcl-xL and proapoptotic agent Bak in ER-alpha and PgR negative or variably positive endometrioid adenocarcinomas. Cx26, Cx43, Bak, Bcl-xL, PgR and ER-alpha were detected in 78 endometrioid adenocarcinomas with immunohistochemistry. There was a remarkable cellular re-distribution of Cx26 and Cx43 from normally membranous location in normal endometrium to aberrantly cytoplasmic expression in endometrioid adenocarcinomas, thus suggesting the decrease of functional membranous gap junctions in the malignancy. Bak failed to correlate with Cx43 regardless of either PgR or ER-alpha status of tumors, while Bcl-xL positively correlated with Cx43 in ER-alpha positive tumors (p = 0.001, r = 0.427) and both PgR positive (p = 0.019, r = 0.312) and negative (p = 0.015, r = 0.509) cancers. Similarly, Bcl-xL significantly associated with Cx26 in ER-alpha positive tumors (p = 0.036, r = 0.267) and both PgR positive (p = 0.026, r = 0.297) and negative (p = 0.046, r = 0.429) cancers. On the contrary, Bak exclusively correlated with Cx26 only in ER-alpha negative tumors (p = 0.027, r = 0.551). ER-alpha status of endometrioid adenocarcinomas could restrict eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 in these tumors.

E-cadherin and ß-catenin adhesion proteins correlate positively with connexins in colorectal cancer.

The majority of solid cancers present with qualitative and quantitative aberrations of adhesion proteins, including E-cadherin and ß-catenin, and connexin (Cx) gap junction proteins, which is consistent with alterations in the expression and location of such proteins in neoplastic cells. Since there are no data on the correlation between adhesion proteins and Cxs in human colorectal cancer (CRC), the aim of the present study was to evaluate the expression and correlation between these proteins. Tissue specimens were obtained from 151 cases of surgically removed colorectal adenocarcinomas. The samples were examined by immunohistochemistry with the use of antibodies against E-cadherin, ß-catenin and the three Cxs: Cx26, Cx32 and Cx43. The aberrant expression of the studied adhesion proteins (primarily cytoplasmic for E-cadherin and cytoplasmic and/or nuclear for ß-catenin) was observed, whereas only a minority of cases revealed normal membranous distribution of the labeling. The present study is the first in the literature to reveal a correlation between the expression of E-cadherin and ß-catenin and the examined Cxs in CRC in humans. The positive correlation between the Cxs, particularly Cx26 and Cx32, and the adhesive proteins occurred in patients without lymph node metastases and in the moderately differentiated tumors (G2). Such a dependency was not observed in the analysis of the correlation between Cx43 and E-cadherin. However, a positive correlation between these proteins was observed in patients with lymph nodes metastases. Additionally, a link between the expression of these adhesion proteins was observed. The present study indicates, for the first time, that the expression of adhesion proteins, E-cadherin and ß-catenin, is closely associated with the expression of three studied Cxs in CRC, and that this correlation may improve an understanding of the carcinogenic process in this cancer.

Adenoid basal carcinoma-like tumor combined with invasive squamous cell carcinoma foci of uterine cervix - a case report of 55-year-old woman with literature review.

BACKGROUND: Adenoid basal carcinoma (ABC) of uterine cervix is an extraordinary example of carcinoma with both basal and glandular cell types. Here we present such a case of ABC combined with invasive squamous cell carcinoma (SCC) of 55-year-old woman. METHODS: The tumor was stained with Hematoxylin-Eosin (HE), Mucicarmine, PAS/Alcian Blue, CK AE1/AE3, CK7, CD117 and Ki67. RESULTS: The whitish-grey 1 cm in-depth infiltration of endocervix was composed of infiltrative coalescing areas of CK AE1/AE3 positive carcinoma with peripheral palisading of basal cell type with spaces lined by Mucicarmine- and Alcian Blue-positive benign looking, glandular epithelium. There were also foci of apparently malignant squamous epithelium with evident dyskeratosis. Thus, a lesion was diagnosed of adenoid basal carcinoma combined with invasive squamous cell carcinoma foci of uterine cervix. The tumor was further CD117 negative what favored diagnosis of ABC over adenoid cystic carcinoma (ACC). There were rare mitoses on HE slides but 60% of all tumor cells were positive for Ki67 that would partially contradict reported benign nature of ABC lesion. Moreover, tumor was CK7-positive and this finding was controversial and according to one report favored diagnosis of ABC-like adenosquamous carcinoma (ACC). Due to CK7 positivity and high index of Ki67, the neoplasm was re-classified as adenoid basal carcinoma-like tumor. CONCLUSIONS: It seems reasonable to treat the patient in the same manner as in case of pure simple invasive squamous cell carcinoma because much more aggressive, minor component of invasive SCC was found within ABC in our case.

Comparison of primarily diet-modifiable intestinal factors, connexin 43 and E-cadherin with TP53 and TGFB1 in colorectal cancer.

BACKGROUND/AIMS: Primarily, a diet (particularly dietary lipids and vitamins) can reversibly modify intestinal expressions of a few factors like connexin 43 (Cx43), E-cadherin (Cdh1), TP53 and TGFB1 with a special impact on immunity and mutagenesis. Malignant phenotype constitutes a diet-resistant signal streaming with engagement of these molecules which are generated in autonomous ways in colorectal cancer. METHODOLOGY: We aimed to compare adhesion proteins: (Cx43) and Cdh1 with TP53 and TGFB1 in colorectal adenocarcinomas. GJA1P1 and Cdh1 with TP53 and TGFB1 were detected with immunohistochemistry in the study of 106 colorectal adenocarcinomas. RESULTS: There was aberrant cytoplasmic expression instead of membranous one of Cx43 and Cdh1 reflecting constitutive destruction of intercellular ties while TP53 showed nuclear expression and TGFB1 accumulated in the cytoplasm. TP53 did not correlate with Cx43 (r=0.083, p=0.397) but correlated with Cdh1 (r=0.199, p=0.041). Cdh1 associated with TGFB1 reaching almost statistical significance (r=0.188, p=0.054), while TGFB1 correlated with Cx43 (r=0.359, p=0.001). CONCLUSIONS: The consequent and constant impairment of cancer intercellular communication seems to engage correlated with each other expressions of Cx43 and TGFB1 in colorectal cancer cells.

The relationships between hypoxia-dependent markers: HIF-1alpha, EPO and EPOR in colorectal cancer.

Hypoxia triggers production of several cytoprotective proteins. Hypoxia-inducible factor 1alpha (HIF-1α) is a powerful stimulator of transcription of many genes, including erythropoietin (EPO) in hypoxia-affected cells. Recent data have also implicated signaling by EPO receptor (EPOR) as a new factor influencing tumor progression. The aim of the study was to detect by immunohistochemistry the presence of HIF-1α, EPO and EPOR in colorectal cancer (CRC) in reference to clinicopathological variables. We found the presence of the studied proteins in specimens of all 125 CRC patients which is suggestive of the occurrence of hypoxia in colorectal cancer tissues. The expression of HIF-1α correlated significantly with the presence of EPO and EPOR in all samples (P < 0.001, r = 0.549 and P < 0.001, r = 0.536, respectively). Significant correlations (from P < 0.024 to P < 0.001) were found in the analyses of CRC subgroups such as histopathological type tumor, tumor grade, tumor stage and patients with lymph nodes metastases. The same high significant correlations (P < 0.001) were observed in group of sex, age and tumor location. However, the values of the correlation coefficients (r) which usually ranged from 0.5 to 0.6 suggest the existence of independent or concurrent mechanism stimulating generation of these proteins in colorectal cancer.

[Influence of the anti-inflammatory, anti-bacterial and anti-oxidative treatment combined with the dietary supplementation on sperm parameters]. / Wplyw skojarzonego leczenia przeciwzapalnego, przeciwbakteryjnego i antyoksydacyjnego oraz suplementacji zywieniowej mwzczyzn na jakosc nasienia.

UNLABELLED: The severe oligospermia and lukocytospermia is diagnosed among 25-40% of the infertile patients despite the absence of any clinical manifestation of the inflammatory process. The white blood cells are the main source of the free oxidative radicals, which can injure the cell membranes and the sperm DNA integrity influencing the reproductive potential of the male gametes. The aim of study was to assess the influence of the anti-inflammatory anti-bacterial and anti-oxidative treatment combined with the dietary supplementation on sperm parameters in the patients with severe oligospermia and lukocytospermia. MATERIALS AND METHODS: 100 patients with a severe oligospermia and leukocytospermia were qualified into the study. The anti-inflammatory anti-bacterial and anti-oxidative treatment combined with dietary supplementation was applied for 90 days. The sperm analysis was performed before and after the treatment. RESULTS: The mean volume of sperm samples and spermatozoa concentration were comparable before and after treatment. The leukocyte concentration was significantly lower after the therapy. There were significantly more spermatozoa in the fast and slow forward movement, less spermatozoa without movements and comparable concentration in spermatozoa in slow undirected movement after applied treatment. CONCLUSIONS: The present study demonstrated that the anti-inflammatory, anti-bacterial and anti-oxidative treatment combined with dietary supplementation in the patients with severe oligospermia and lukocytospermia improves the sperm movement parameters and reduces the inflammatory response. Therefore, it might be beneficial to patient suffering from the infertility.

[Gap junction intercellular communication in carcinogenesis of endometrial cancer]. / Komunikacja miedzykomórkowa z udzialem polaczen typu gap w karcinogenezie blony sluzowej trzonu macicy.

One of the mechanisms for direct cell to cell signaling is mediated by gap junctions. These junctions are formed by connexins, transmembrane proteins. Gap junction intercellular communication (GJIC) plays a critical role in tissue development, differentiation of cells, and regulation of tissue homeostasis. Cancer cells are characterized by growth and/or differentiation disorders. Endometrial cancer is the most common gynecological malignancy in developed countries. In this study we discuss the putative role of GJIC and adhesion molecules in the development of endometrial cancer The relationships of GJIC to the process of apoptosis and function of some adhesion proteins have also been underlined.