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

Abstract: 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

Expression of the apoptotic markers in normal breast epithelium, benign mammary dysplasia and in breast cancer

Apoptosis and proliferation are processes associated with the development and progression of breast cancer. The sensitivity of tumour cells to the induction of apoptosis depends on the balance between pro- and anti-apoptotic proteins. The expression of Bak and Bcl-2 was examined using an immunohistochemical method in 71 primary breast cancers. Furthermore, Bcl-2 and Bak were assessed in the normal mammary gland as well as in benign mammary dysplasia adjacent to breast cancer. Positive immunostaining for Bcl-2 was observed in 77.8% of cases of normal breast epithelium (NBE), 93% of benign dysplasia without intraductal proliferation (BBD) as well as in 94% of intraductal proliferative lesions of the breast (BIPL). Expression of Bak was detected in 39% of cases of NBE, 45% of BBD and in 67% of BIPL. In breast cancer Bcl-2 and Bak expression was found in 83% and 70% of the cases studied, respectively. Increased Bcl-2 expression in primary tumours significantly correlated with favourable prognostic factors, namely pT1, G2 and lack of metastases to the regional lymph nodes (p < 0.01, p < 0.03, p < 0.02, respectively). There were no relationships between Bak and the clinicopathological features studied, but our results indicate changes in the expression of Bak during breast cancer development and progression. It would appear to be important to assess and compare pro- and anti-apoptotic proteins between normal mammary gland, benign mammary dysplasia and the primary tumours of breast cancer. This knowledge should be helpful in understanding breast cancer development and progression

Double‐needle yamane technique using flanged haptics in ocular trauma—a retrospective survey of visual outcomes and safety

To evaluate visual outcomes and safety of the double‐needle technique using flanged haptics (Yamane technique) in patients with aphakia caused by ocular trauma at a trauma referral center. Retrospective: Consecutive interventional case series of 30 patients who underwent the Yamane technique due to posttraumatic aphakia. The double‐needle technique using flanged haptics was combined with anterior vitrectomy (group A) in 14 patients, and with pars plana vitrectomy (PPV) (group B) due to retinal detachment, nucleus dislocation into the vitreous cavity, or intraocular lens (IOL) displacement in 16 patients. No intraoperative complications were noted. There was significant improvement in the visual acuity in both groups at the second postoperative visit. However, the visual acuity was significantly worse in the group treated with the Yamane technique combined with PPV. Silicone oil tamponade in PPV group was associated with worse visual acuity, whereas post lensectomy status was associated with poor visual function result in the anterior vitrectomy group. There was one case of slight IOL decentration and one retinal detachment during the postoperative follow‐up period in the group with PPV. In this case series, the Yamane technique applied in traumatized eyes was found to be an efficacious and safe procedure. Combining the Yamane technique with PPV due to posterior segment ocular trauma was associated with worse functional results in the follow‐up at three months. Further studies with longer follow‐up evaluations are required to verify long‐term complications

Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer

BACKGROUND: Gap junctions are intercellular channels composed of connexins, which mediate the direct passage of small molecules between neighbouring cells. They are involved in regulation of cell cycle, cell signalling, and differentiation, and probably invasion and metastasis. The role of connexins in the metastatic process is controversial, because some studies indicate that connexin expression is inversely correlated with metastatic capacity. In contrast, others demonstrate that connexins may be involved in metastasis. In addition, connexin status in breast cancer metastasis has not been widely studied. METHODS: We evaluated by immunohistochemistry the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in primary breast tumours (PTs) and matched paired metastases to lymph nodes (MLNs). RESULTS: In PTs, we observed predominantly cytoplasmic localisation of evaluated connexins, indicating alterations in connexin expression in breast cancer cells. We demonstrated that expression of Cx26 and Cx43 was increased in MLNs compared with PTs (p<0.00001 and p<0.001, for CX26 and Cx43, respectively). In addition, Cx26 and Cx43 negative PTs developed Cx26 and Cx43 positive MLNs. Furthermore, besides increased cytoplasmic staining, enhanced membranous localisation of Cx43, typical of normal cells, was found in MLNs. Additionally, membranous Cx26 expression appeared only in metastatic breast cancer cells. CONCLUSIONS: These findings suggest that connexins may contribute to the efficient metastasising of breast cancer to the lymph nodes