Blood serum levels of E-cadherin in patients with colorectal cancer.

INTRODUCTION: Colorectal cancer is the second most common cancer in terms of incidence in Poland. It is also the second most common cause of cancer deaths in men and the third women. In 75-80% of cases, depending on sources, it is of an occasional nature, and in the remaining 20-25% it has a hereditary character. AIM: To compare the levels of E-cadherin in blood serum with some histopathological and clinical features. E-cadherin is an adhesion molecule, loss of function of which is suspected to influence both cancer progression and metastasis. MATERIAL AND METHODS: The study group comprised 48 patients diagnosed with colorectal cancer treated surgically in the Second Department of General and Gastroenterological Surgery, Medical University Hospital in Bialystok. RESULTS: As has been shown here, there is no statistically significant relationship between the levels of E-cadherin in blood serum and the possible prognosis to the progression of colorectal cancer. However, it was indicated that there appears to be a statistically significant relationship between blood serum E-cadherin levels and the levels of alanine aminotransferase and aspartate aminotransferase in patients with colorectal cancer. CONCLUSIONS: The authors suggest that this significance may require further study.

Large pancreatic pseudocyst penetrating into posterior mediastinum.

We report a rare case of a large mediastinal pancreatic pseudocyst compressing the left atrium and the esophagus and causing dyspnea, palpitations, and emesis. Chest radiograph was non-diagnostic, esophagogastroduodenoscopy showed diffuse extrinsic compression of the distal esophagus and gastric corpus, but a definitive diagnosis was confirmed by computed tomography. We decided to perform surgery due to the recurrence of the pancreatic pseudocyst, a history of unsuccessful radiologically guided external drainage a few years earlier, and a very large diameter of the pseudocyst causing acute cardio-pulmonary distress syndrome.

Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is a rare neoplasm that affects the gastrointestinal system, and is characterized by a high mortality rate. It has been demonstrated that apoptosis has a significant role in the regulation of cancer cells. Therefore, the aim of the present study was to immunohistochemically assess the expression of proteins belonging to the caspase family, namely caspase-8, pro-caspase-3 and cleaved (active) caspase-3 in pancreatic cancer. The study group consisted of 29 patients exhibiting PDAC. Protein expression was evaluated by immunohistochemical methods. The expression of caspase-8 in normal cells was negative in 17.2% of cases and positive in 82.8% of cases. All cases demonstrated pro-caspase-3 expression in normal pancreatic cells, compared with 93.1% of cancer cells. Staining for activated caspase-3 was positive in 27 normal tissue cases, compared with positivity in only 10 cancer cases. Caspase-8 expression positively correlated with cleaved caspase-3 expression in the cytoplasm of cancer cells (P<0.002). Caspase-3 expression was identified to correlate with inflammatory peritumoral infiltration (P<0.015). No correlation was observed between caspase expression and any other clinicopathological parameters. The results of the present study demonstrated aberrant initiation of cancer cell apoptosis in PDAC via a decrease in caspase-8 expression, which may lead to disorders in the activation of effector caspase-3.

Dysfunctions in the Mature Dendritic Cells Are Associated with the Presence of Metastases of Colorectal Cancer in the Surrounding Lymph Nodes.

Dendritic cells play a key role in the antigen presentation and T cell activation. The aim of this study was a detailed analysis of the presence of mature dendritic cells (CD 83 positive) in colorectal cancer in correlation with selected clinicopathological parameters. The presence of mature dendritic cells (mDCs) was determined immunohistochemically using the anti-CD83 antibody. The morphometric analysis of the mDCs was performed in the normal colon wall adjacent to the cancerous tumor as well as in the front of the tumor and in the main mass of the cancerous tumor. Decrease in mDCs in the front and in the main tumor mass was observed. The increase in the number of mDCs in both of these locations was associated with the presence of metastases in the nearby lymph nodes (p < 0.05 and p < 0.01). Furthermore, the increase in the proportion of mDCs in the main tumor mass was associated with the presence of the invasion of tumor cells into the blood and lymph vessels (p < 0.01). The increase in the amount of mDCs in the cancerous tumor is associated with the invasiveness of the tumor and especially with the metastasis to the surrounding lymph nodes.

Expression of apoptotic proteins in human colorectal cancer and metastatic lymph nodes.

PURPOSE: The aim of this study was to determine the expression of Bak, Bax, Bcl-2, Bcl-xl and procaspase-3 proteins in colorectal tumor and regional lymph nodes, as well as to investigate the correlation between them and with clinicopathologic parameters. METHODS: Expression of the examined proteins was evaluated by immunohistochemical study. RESULTS: No significant correlation was revealed between Bcl-2, Bcl-xl, Bak, Bax and procaspase-3 expressions and age, gender, location or size of primary tumor and grade in the main tumor mass or in lymph nodes. Additionally, the only association we found was between Bak protein in primary tumor and in adjacent metastatic lymph nodes. CONCLUSION: Bcl-2 protein seems to exert substantial effects prevention of apoptosis in pT3 CRC with positive lymph node involvement, while lower expressions of Bcl-xl proteins suggest that it does not play a significant part in the inhibition of apoptosis.

High Fas expression in gastric carcinoma cells as a factor correlating with the occurrence of metastases to regional lymph nodes.

PURPOSE: The aim of this study was to evaluate the correlation of the expression of Fas and Fas-L proteins in gastric carcinoma cells on the occurrence of metastases to regional lymph nodes. MATERIAL/METHODS: The study included 89 patients treated surgically for gastric carcinoma. The evaluated clinicomorphological parameters were verified based on both histopathological material collected at surgery and intraoperative image. Fas and Fas-L expression was evaluated immunohistochemically in the neoplastic tissue of the removed gastric tumors. RESULTS: A statistically significant positive correlation between Fas expression in gastric carcinoma cells and the number of regional lymph nodes affected by metastases was observed (p<0.05). No such correlation was noticed with respect to Fas-L. A statistically significant correlation between the depth of neoplastic infiltration of the stomach wall (T feature) and the number of affected lymph nodes was observed (p<0.05). No statistically significant correlations in the other examined clinicomorphological features and the number of metastatic lymph nodes was observed. CONCLUSION: A positive Fas expression correlates with more frequent occurrence of metastases to regional lymph nodes. Determination of this protein expression in cancer cells prior to surgery may be helpful for planning the surgical procedure, especially with respect to the extent of lymph node excision.

PRL-3 and E-cadherin show mutual interactions and participate in lymph node metastasis formation in gastric cancer.

E-cadherin, a transmembrane adhesion molecule, and phosphatase of regenerating liver 3 (PRL-3) protein, a member of the family of tyrosine phosphatases, seem to be responsible for cancer cell migration. Therefore, the study objective was to determine a correlation between PRL-3 and E-cadherin, to assess their expression in neoplastic tissue and normal mucosa of the stomach, to analyze their effect on cancer advancement, and to evaluate their potential as prognostic markers in gastric cancer. The expressions of PRL-3 and E-cadherin were assessed immunohistochemically in 71 patients with gastric cancer. Positive expression of PRL-3 was observed in 42.2 % of gastric cancer cases, whereas E-cadherin expression was abnormal in 38 % of cases. The study revealed that the positive PRL-3 expression and abnormal E-cadherin expression were associated with mucinous gastric carcinoma and lymph node involvement. The former was also related to the infiltrating type of tumor and abnormal E-cadherin expression. The expression of PRL-3, but not of E-cadherin, was associated with shorter survival of patients. PRL-3 and E-cadherin exhibit interactions in gastric cancer and are involved in the formation of lymph node metastases. The PRL-3 protein can be an independent predictive factor of overall survival in gastric cancer patients.

Bax protein may influence the invasion of colorectal cancer.

AIM: To evaluate the expression of Bcl-xL, Bak, and Bax proteins in correlation with particular clinico-histopathological parameters, including tumor invasion front, in patients with colorectal cancer. METHODS: The expression of these proteins was evaluated with the use of the immunohistochemical method in 50 primary tumors. RESULTS: According to observations, a low expression of Bax and Bak proteins is related to the localization of the tumor in the rectum (P < 0.05 and P < 0.05 respectively), which may explain an increased incidence of colorectal cancer in this area. A positive expression of Bax protein also correlates with the presence of cancer cell infiltration to lymph and blood vessels (P < 0.05), which may suggest the participation of this protein in the early stages of colorectal cancer progression. Moreover, a positive expression of Bcl-xL protein correlated with a positive expression of Bak protein. This may suggest a greater participation of Bcl-xL protein in the inhibition of the proapoptotic Bak protein, but not the Bax protein. CONCLUSION: Bax protein is probably very significant in the cancerogenesis mechanism in the large intestine.

Immunohistochemical expression of MMP-7 protein and its serum level in colorectal cancer.

The study objective was to determine the presence of MMP-7 in cancer tissue in correlation with its serum level in patients diagnosed with colorectal cancer (CRC). In 45 patients with CRC, MMP-7 expression was assessed immunohistochemically on FFPE slides in tumours (N = 37) and in the corresponding surgical margin sample. MMP-7 serum level was measured preoperatively. The expression of MMP-7 in cancer tissue was much stronger as compared to the normal intestinal mucosa. Also the level of MMP-7 in the serum of CRC patients was higher than in healthy subjects (N = 24) (p < 0.01). The tumour located in the colon showed higher expression of MMP-7 than CRCs located in the rectum (p < 0.05), whereas the higher MMP-7 serum level showed correlation with older age (p = 0.005), tumour size less than 5 cm (p < 0.05), higher Dukes' stage (p < 0.05) and distant metastases (p < 0.05). The increased serum level of MMP-7 in CRC patients may indicate the presence of distant metastases.

Increased concentration of metronidazole and its hydroxy metabolite in colon cancer in women.

BACKGROUND: Metronidazole (MTZ) is indicated in the prevention of infections during surgical procedures. However, some data have shown that metronidazole has carcinogenic potential. METHODS: In the present work, we determined concentrations of metronidazole and its hydroxy metabolite (MTZOH) in colorectal cancer patients. MTZ and MTZOH were measured in tumor tissue and surrounding healthy tissue by LC-ESI-MS-MS method. RESULTS: We found different concentration of MTZ and MTZOH in colorectal cancer and healthy tissue. Interestingly, we noted a higher level of the above substances in women vs. men, both in healthy and cancerous gut. CONCLUSION: We suggest that women are more exposed to a potential carcinogenic effect of metronidazole than men.

Determination of the activity of CD134 (OX-40) and CD137 (4-1BB) adhesive molecules by means of flow cytometry in patients with colorectal cancer metastases to the liver.

UNLABELLED: Colorectal carcinoma (CRC) is one of the most common reasons of mortality in patients diagnosed with neoplasms. In nearly 20% of patients with colorectal carcinoma metastatic lesions are diagnosed. In general, survival of patients with metastatic lesions to the liver and other organs is poor. Conventional therapy of colorectal carcinoma is based on the surgical excision of the tumor, chemotherapy, and radiotherapy. THE AIM OF THE STUDY: was to determine the expression of CD134 and CD137 molecules inside the tumor, at the border of the tumor, in the healthy tissue, and peripheral blood, considering patients with colorectal carcinoma metastases to the liver. MATERIAL AND METHODS: The study group comprised 39 patients subject to surgical treatment at the Department of General and Gastroenterological Surgery, due to colorectal carcinoma with liver metastases. CD134 and CD137 adhesive molecule levels were determined inside the tumor, at the border of the tumor, and in the healthy margins of the surgical incision. Additionally, the authors evaluated the peripheral blood level of the above-mentioned molecules on the day of the surgical procedure, and 10 days, thereafter. RESULTS: The mean CD134 levels were the highest inside the tumor, significantly decreasing towards the direction of healthy tissues. The average peripheral blood molecule levels were four-fold higher on the day of the surgical procedure, as compared to values obtained on the tenth postoperative day. This dependency also concerned the remaining statistical measures.The mean CD137 levels showed no significant difference, regardless their location. The authors observed significant, peripheral blood, CD137 level differences, considering the day of the surgical procedure and tenth postoperative period. The mean CD137 peripheral blood level was several times higher on the day of the surgical procedure, as compared to the postoperative period. CONCLUSIONS: The determination of the activity of CD134 and CD137 molecules might create opportunities to plan treatment and predict prognosis in case of colorectal carcinoma. Proper immuno-therapeutic management which is based on the expression of the above-mentioned molecules might help determine the risk of metastases, preventing from their development. In advanced cases treatment of liver metastases might be possible.

Relationships between insulin-like growth factor i and selected clinico-morphological parameters in colorectal cancer patients.

UNLABELLED: Insulin Like Growth Factor (IGF I) as the one of the strongest growth factors which can affect cancers development including colorectal cancer. IGF I induces processes of the cells growth and division. It regulates cells cycle and inhibits apoptosis. There is limited data about correlation between IGF I and staging of the tumor. The aim of the study was estimation of the clinical usefulness of IGF I concentration in the serum of the patients with colorectal cancer. MATERIAL AND METHODS: We have examined 125 individuals with colorectal cancer. The age range was 36 to 92 years. They have been operated in the 2nd Departament of The Gastrointestinal Surgery of the Medical University in Bialystok. Serum concentration of the IGF I have been estimated using immunoassay ELISA before and after operation. Correlation between serum level of IGF I and clinicopathologic features: age, gender, localisation of the primary tumor, TNM stage of tumor, histological type and histological grade (G) of the cancer have been estimated. RESULTS: Our study revealed statistically significant increased serum concentration of IGF I in patients with locally advanced colorectal cancer (pT3 and pT4) comparing to less advanced (pT2) The investigations showed higher serum concentration of IGF I in patients with poorly differentiated cancers (G3) than in moderately differentiated. Similarly higher serum concentration of IGF I were found in male, in patients older than 60 years and in mucigenous colorectal cancers. CONCLUSIONS: Our results indicated that IGF I can be one of the factors of the prognosis in colorectal cancer development.

Correlation between Fas and FasL proteins expression in normal gastric mucosa and gastric cancer.

The study's objective was to assess the expressions of Fas and FasL proteins in gastric cancer in correlation with chosen clinicohistological parameters. Fas and FasL expression was analyzed in 68 patients with gastric cancer, using the immunohistochemical method. The expression of Fas was found to be lower in gastric cancer cells than in healthy mucosa, both in the lining epithelium and in glandular tubes (28% vs. 48% and 44%; p < 0.001). The expression of FasL was also markedly lower in cancer cells than in glandular tubes, yet higher than in the lining epithelium (51% vs. 73% and 14%; p < 0.01). Positive expressions of FasL and Fas were lower in less advanced gastric cancer cells (T1, T2), than in more advanced tumors (T3, T4), but only in the case of FasL was this difference statistically significant (p < 0.05). Our findings seem to confirm the theory of the impact of apoptotic disorders at the level of Fas receptor and FasL protein in the process of gastric cancer formation and growth, which is manifested in the varied expressions of these proteins in gastric cancer and in the normal lining and glandular epithelium of the stomach. However, the lack of significant differences in the expressions of Fas and FasL in correlation to other clinicohistological parameters indicates the existence of mechanisms that have a greater impact on the process of differentiation of gastric cancers. This in our opinion eliminates these proteins as prognostic factors.

Assessment of activity of an adhesion molecule CD134 and CD137 in colorectal cancer patients.

UNLABELLED: Epidemiological studies prove that incidence of colorectal cancer is increasing. The first line therapy of colorectal cancer is surgical resection of the primary tumor and elimination of regional and remote metastases. THE AIM OF THE STUDY was to determine expression of adhesion molecules CD134 and CD137 in the peripheral blood in colorectal cancer patients, depending on clinical cancer stage, size and invasion of the tumor. MATERIAL AND METHODS: The study enrolled 72 patients with primary colorectal adenocarcinoma. An average patient age was 64.55 years. Clinical tumor stage was assessed using two scales: Dukes: A and Astler-Coller scale. Expression of adhesion molecules was determined in the peripheral blood collected on the day of the procedure and 10 days after the procedure. RESULTS: An average activity of CD134 molecules (12.66%) was significantly higher than that of CD137 (6.26%) (p<0.001). Clinical tumor stage was assessed on Dukes scale and was unrelated to CD134 activity, while activity of CD137 was related to clinical cancer stage. CONCLUSIONS: CD137 activity is directly proportional to colorectal cancer stage. Surgical resection of the tumor results in increased CD134 and CD137 expression. Long term studies, enrolling larger groups of patients, including their subdivision to colon and rectal cancer, are required to utilize CD134 and CD137 in immune therapy of colorectal cancer.