Simulations of centriole of polarized centrosome as a monopole antenna in immune and viral synapses.

The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules. We are extending this prior hypothesis of the endogenous electromagnetic field in the cell postulating that polarized centriole in immune and viral synapse could serve as a monopole antenna. This is an addition to our hypothesis that primary cilium could serve as a monopole antenna. We simulated the distribution of electric field of centriole of polarized centrosome as a monopole antenna in immune and viral synapse. Very weak electromagnetic field of polarized centriole of CD8+ T lymphocyte in IS can contribute to the transport of cytolytic granules into the attacked (cancer) cell. Analogically, very weak electromagnetic field of polarized centriole in viral synapse of infected CD4 cells can aid the transport of viruses (human immunodeficiency virus) to non-infected CD4 cells. We hypothesized that healthy organisms need these monopole antennas. If, during the neoplastic transformation, healthy cells lose monopole antennas in form of primary cilia, the IS aims to replace them by monopole antennas of polarized centrioles in IS to restore homeostasis.

The changes of tumour vascular endothelial growth factor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma.

AIM OF THE STUDY: The aim was to examine the effects of neoadjuvant chemoradiotherapy on VEGF expression in patients with locally advanced rectal cancer. MATERIALS AND METHODS: A total of 53 patients with locally advanced rectal cancer were retrospectively studied. Neoadjuvant treatment comprised external beam radiation (50.4 Gy/28 fractions) with continuous infusion of 5-fluorouracil. Four to 6 weeks after the chemoradiotherapy, the patients underwent surgical resection. Immunohistochemistry was performed to assess VEGF expression in the pretreatment biopsies and in resected specimens. RESULTS: Resection with microscopic residual tumour (R1) was performed in two patients while in the remaining 51 patients radical resection with microscopically negative margins (R0) was possible. Downstaging after preoperative chemoradiotherapy was observed in 34 patients (64%). After chemoradiotherapy 24 patients (45%) had decreased VEGF expression, in 20 patients (38%) there was no change, and in two patients it was not possible to assess the dynamics of VEGF expression due to pathologic complete response after chemoradiotherapy. The five-year overall survival (OS) rate was 56% (95% CI: 43-70%). Although the median OS was 2.5 times shorter in patients who experienced decreased VEGF expression during therapy, this difference did not reach statistical significance. VEGF expression was not significant in Cox regression analysis or log-rank test. VEGF expression decreased after neoadjuvant chemoradiotherapy in most patients with rectal adenocarcinoma examined. This decrease was associated with a trend of inferior prognosis. CONCLUSIONS: VEGF expression decreased after neoadjuvant chemoradiotherapy in most patients examined. This decrease was associated with a trend of inferior prognosis.

Transient and Non-Transient Intussusceptions of the Large Bowel in Adults: Two Case Reports.

BACKGROUND: Intussusception of the large bowel in adults is a very rare pathological condition. However, it has its clinical importance because intussusception is very often associated with an intraluminal lesion. CASE REPORT: We report two cases of the large bowel intussusception, ileocolic and colorectal. Both intussusceptions were associated with a malignant tumor. However, the clinical presentation was different. One of the intussusceptions was of non-transient character, while the second one resolved spontaneously before operation. Both patients underwent surgery and malignant tumors were found and removed. RESULTS: The purpose of the article is to draw attention to intussusception and emphasize that intussusception, either transient or non-transient, should be further examined. CONCLUSIONS: The intussusception may be the first and the only signal of the existence of a malignant tumor, very often colorectal carcinoma.

Dissociated invasively growing cancer cells with NF-kappaB/p65 positivity after radiotherapy: a new marker for worse clinical outcome in rectal cancer? Preliminary data.

Objectives Nuclear factor-kappaB (NF-kappaB), especially p65 subunit, seems to be associated with origin and progression of cancer. The aim of the study was to determine expression of NF-kappaB/p65 in rectal cancer patients before and after radiotherapy as well as to assess the relationship between NF-kappaB/p65 expression, other tumor characteristics, and disease progression. Further aim was to evaluate whether expression of NF-kappaB/p65 in tumor tissue may serve as a predictive marker of patient outcome. Patients and methods Twenty-five patients with rectal cancer undergoing pre-operative radiotherapy were included in the study. Unirradiated rectal cancer specimens were obtained from diagnostic colonoscopy. Irradiated rectal cancer specimens were obtained from surgically removed part of the rectum with the tumor. NF-kappaB/p65 expression was determined by immunohistochemistry. Results Cytoplasmic positivity in cancer cells and nuclear positivity in lymphocytes were detected. In post-radiotherapy specimens single tumor cells or small clones of them deeply infiltrating the wall of the rectum, that were characterized by high NF-kappaB/p65 expression, were found. Patients with presence of these cells in post-radiotherapy specimens have worse clinical outcome in terms of overall survival and disease-free interval. Conclusion While the NF-kappaB/p65 positive staining of the epithelial cells did not have any clinical implications in this study, it may be of clinical significance in the future. Residual invasively growing cancer cells with high NF-kappaB/p65 positivity found in specimens after radiotherapy and surgery may be used to find what patients have a worse outcome. Thus, patients being at risk of cancer progression and requiring more aggressive anti-cancer therapy may be identified.

Intraluminal high dose rate brachytherapy of tumorous esophageal stenoses.

BACKGROUND/AIMS: The prognosis of inoperable carcinomas of esophagus is poor, and therapeutic efforts are generally limited to palliation. The aim of this study was to retrospectively evaluate the effectiveness of intraluminal high dose rate brachytherapy in the palliative treatment of tumorous esophageal stenoses. METHODOLOGY: Between February 1997 and July 2002 intraluminal brachytherapy was performed in 19 patients with inoperable esophageal carcinoma (squamous cell carcinoma in 14 cases and adenocarcinoma in 5 cases). All patients had dysphagia at presentation. Brachytherapy was performed using high dose rate afterloading system. RESULTS: Dysphagia was improved in all patients. The mean survival was 248 days. No mechanical complications were observed during introduction of the applicator. CONCLUSIONS: Our experience indicates that intraluminal brachytherapy is an effective and safe method of palliation of dysphagia caused by malignant esophageal stenosis.

Survival of patients with colorectal cancer liver metastases treated by regional chemotherapy.

BACKGROUND/AIMS: Liver is the most common site of metastatic disease in colorectal cancer. Superior response rate was demonstrated in trials comparing hepatic arterial administration of cytotoxic agents with systemic chemotherapy. METHODOLOGY: Records of 109 consecutive patients with colorectal carcinoma metastatic to the liver treated by regional chemotherapy, who underwent implantation of a port system into hepatic artery or portal vein tributaries between 1991 and 1999, were reviewed and survival was evaluated using the log-rank test and multivariate analysis (Cox's proportional hazard regression). RESULTS: The median survival from diagnosis was 24 months. Survival was significantly longer for patients treated by radical resection, and patients treated in 1997-1999. On multivariate analysis, treatment by 6 or more chemotherapy cycles, stage 1 liver metastases, treatment with irinotecan and radical resection were associated with better survival, while the presence of extrahepatic disease had an adverse effect on the risk of death. Extrahepatic spread was subsequently detected in almost half of the patients who had originally isolated liver metastases. CONCLUSIONS: Patients treated by liver resection had the best outcome, while patients with extrahepatic diseases had poor prognosis. The prognosis of patients treated by regional chemotherapy improved significantly with the advent of irinotecan and better selection.

Regional chemotherapy in patients with breast carcinoma liver metastases.

BACKGROUND/AIMS: Although liver is a common site of metastases in breast cancer, isolated liver metastases in patients with disseminated breast cancer are rare. The role of liver-directed therapies in these patients is based on data derived from retrospective analysis of case series. METHODOLOGY: We have reviewed the records of 8 patients with liver metastases and a history of breast cancer treated at our institution over a period of 11 years with regional chemotherapy administered through surgically implanted port systems. RESULTS: Three of the patients also had a history of second primary colorectal carcinoma. One patient had evidence of extrahepatic spread. All patients were treated by regimens based on the combination of 5-fluorouracil and folinic acid. Three patients were also treated by cytoreductive procedures. The median survival times from the diagnosis and port systems implantation were 34 months and 31 months, respectively. CONCLUSIONS: Our data support the use of regional intraarterial chemotherapy in patients with metastatic breast cancer limited to the liver.

Blood supply of metastatic liver tumors: an experimental study.

Based on experiments with 18 female mice with induced secondary liver tumors, the entire liver metastasis blood circulation including characterization of efferent drainage system is described. The center of liver metastases is supplied from capillaries originated from branches of the hepatic artery. From the capillaries, blood is led to the superficial venous network of the metastases and further to intrahepatic veins. The portal vein system is essential for small metastases nutrition. The surface of large metastases is also nourished by the portal vein. Based on these findings, it is suggested that, in human surgery, the catheter for locoregional chemotherapy for liver tumors should be optimally implanted into both the hepatic artery and the portal vein at the same time. Thus, anticancer treatment can reach the whole tumor mass including its periphery, ie, its growth zone.

Hepatic arterial infusion chemotherapy in sarcoma liver metastases: a report of 6 cases.

AIMS AND BACKGROUND: Liver metastases in patients with sarcoma are rare and associated with a poor prognosis. The experience with liver-directed therapies, eg hepatic arterial infusion, in these patients is limited. METHODS: Six patients with sarcoma metastatic to the liver (4 patients with gastrointestinal stromal tumors and 2 patients with leiomyosarcoma) were treated by hepatic arterial infusion in our center over a 12-year period. Since the experience was limited, a pooled analysis of reports with data on survival of 22 individual patients was performed. RESULTS: None of the 5 assessable patients responded to the therapy, and liver metastases progressed in all patients. The median survival was 20 months. In the pooled analysis, partial response was observed in 10 of 21 assessable patients (48%) and median survival was 20 months. The survival was significantly longer in responding patients compared to nonresponders (35 vs 14 months; logrank test, P = 0.009). CONCLUSIONS: Hepatic arterial infusion has little efficacy in the treatment of sarcoma metastatic to the liver. More promising results have been reported for chemoembolization. The survival of responding patients seems to be better compared to non-responders.

Hepatic arterial infusion chemotherapy in gastric cancer: a report of four cases and analysis of the literature.

AIMS AND BACKGROUND: Gastric cancer is associated with high mortality. Although the liver is a common site of metastases in this tumor, the experience with liver-directed therapies is limited. METHODS: We report a single-center experience involving four patients with liver metastases from gastric cancer treated by hepatic arterial infusion (HAI). In addition, we performed a search for reports on HAI in gastric cancer metastatic to the liver and used the studies with data on survival of individual patients for a pooled analysis. RESULTS: Among three valuable patients, one had a complete response, one had stable disease and one had progressive disease. The patient with complete response is still alive 41 months after the diagnosis of liver metastases, while the other patients died 6, 22 and 31 months after the diagnosis. Objective responses were observed in 48% of the 25 patients in the pooled analysis. Objective response and limited hepatic involvement were independent predictors of survival in these patients. CONCLUSIONS: Although isolated liver involvement in metastatic gastric cancer is rare, HAI seems to be similarly effective in these patients as in patients with liver metastases from colorectal cancer. The prognosis is significantly better in gastric cancer patients who have limited hepatic involvement and attain an objective response after HAI.

Successful treatment of infected vascular prosthetic grafts in the groin using conservative therapy with povidone-iodine solution.

Four cases of infected vascular prosthetic graft in the groin successfully treated with povidone-iodine solution using a conservative approach are described here. In all patients the same technique was used. After complete debridement, the prosthetic graft in the groin was completely exposed. The wound was cleansed with hydrogen peroxide and then dressed with gauze soaked in 1:10 sterile water-diluted povidone-iodine solution. The dressings were changed twice a day. The patients were supplemented by systemic therapy of an appropriate antibiotic. All patients were observed in the intensive care unit. In all patients this treatment method led to control of infection and healing of the wound. Thus, it was not necessary to remove the prosthetic graft and patients were spared a major surgical intervention. At follow-up, the prosthetic grafts remain patent without any signs of recurrence of infection.

Inhibition of NF-kappa B augments sensitivity to 5-fluorouracil/folinic acid in colon cancer.

BACKGROUND: 5-fluorouracil (5-FU), the most common antimetabolite used for the treatment of colorectal cancer, exerts its cytotoxic effects through the induction of apoptosis. Folinic acid potentiates the effect of 5-FU. Drug activity is currently limited as a result of inducible chemoresistance. Limited research suggests that the transcription factor nuclear factor kappa-B (NF-kappaB), which has antiapoptotic properties, may play a major role in inducible chemoresistance. MATERIALS AND METHODS: SW48 colon cancer cells were used for all experiments. Cell growth was determined by cell proliferation assay. Apoptosis was assessed by measuring caspase 3 activity. Activation of NF-kappaB was ascertained by electrophoretic mobility shift assay, luciferase reporter assay, and Western blot analysis. RESULTS: Treatment with 5-FU (0.001-10 mm), not only inhibited growth and induced apoptosis but significantly activated NF-kappaB in SW48 cells. Folinic acid alone (0.01-100 mg/L) did not inhibit growth but improved the cytotoxic effect of 5-FU in a dose-dependent manner. Likewise, folinic acid alone did not activate NF-kappaB or induce apoptosis but enhanced 5-FU-mediated NF-kappaB activation and cell apoptosis. Transfection with adenovirus IkappaBalpha super-repressor strongly inhibited constitutive activation of NF-kappaB and significantly enhanced 5-FU and 5-FU/Folinic acid-mediated growth inhibition (P < 0.05). CONCLUSIONS: Treatment with 5-FU activates NF-kappaB. Folinic acid enhances 5-FU-mediated activation of NF-kappaB. Inhibition of NF-kappaB enhances the cytotoxic effect of 5-FU with or without Folinic acid in colon cancer cells.