Animal models of spinal cord injury for evaluation of tissue engineering treatment strategies.

Tissue engineering approaches to spinal cord injury (SCI) treatment are attractive because they allow for manipulation of native regeneration processes involved in restoration of the integrity and function of damaged tissue. A clinically relevant spinal cord regeneration animal model requires that the model mimics specific pathologic processes that occur in human SCI. This manuscript discusses issues related to preclinical testing of tissue engineering spinal cord regeneration strategies from a number of perspectives. This discussion includes diverse causes, pathology and functional consequences of human SCI, general and species related considerations, technical and animal care considerations, and data analysis methods.

Current perspectives of bispecific antibody-based immunotherapy.

The field of bispecific antibodies is an evolving field of research that has increasing clinical appeal. The fusion of two antibodies or antibody fragments introduced a new way to override natural specificity of T cell and induce effector responses against tumor targets in MHC-unrestricted manner. Initial experiences with bispecific antibodies demonstrate both the promise for and limitations of this anti-cancer strategy. Significant body of work has shown that bispecific antibodies have potential to induce T cell mediated anti-tumor responses in pre-clinical models. However, immunotherapy with bispecific antibodies in humans has yet to prove its value in clinical settings. In addition, the production of high-quality bispecific antibodies for clinical applications, the optimal size and avidity of bispecific antibodies, and in vivo T cell pre-activation remain critical issues. In this review, we summarize recent progress in bispecific antibody-based immunotherapy and address essential aspects of this anti-cancer strategy.

Laparoscopic colon and rectal surgery.

There are disparate variables available to appraise the quality of the laparoscopic colorectal surgery. Currently available data suggest that laparoscopic colectomy can be completed safely in most cases. It is feasible and offers patient-related benefits similar to those described for other laparoscopic procedures. The framework, within which the quality of laparoscopic colon and rectum surgery is appraised and judged, is discussed with an emphasis on diverse outcomes used to measure quality.

Significance of pre-treatment immunological parameters in colorectal cancer patients with unresectable metastases to the liver.

BACKGROUND/AIMS: In this study, we have compared the profiles of peripheral blood lymphocyte (PBL) subsets and serum cytokine levels of healthy individuals with those of patients with unresectable liver metastases from colorectal carcinoma before starting regional chemoimmunotherapy. Since the therapeutic responses are limited only to a subset of patients, we hypothesize that the initial status of immunity and individual immune response to a tumor might be significant to the therapeutic outcome. METHODOLOGY: Cellular and humoral immunological parameters were compared between 10 patients with colorectal cancer metastases to the liver responding and non-responding to regional intra-arterial chemo-immunotherapy, and 5 healty individuals. Analyses included a flow cytometric immunophenotyping of peripheral blood mononuclear cells (CD3, CD4, CD8, CD19, CD25, CD28, CD56, CD57, CD80 and HLA.DR), estimation of serum cytokine levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and other immunological parameters are soluble IL-2 receptor (sIL-2), carcinoembryonic antigen (CEA), gastrointestinal cancer-associated antigen (CA 19-9), and C-reactive acute phase protein (CRP). A significantly lower proportion of CD8 lymphocytes and a trend for decreased CD19, CD28 and CD80 was detected among colorectal cancer patients before liver-directed chemotherapy compared to healthy controls. RESULTS: The cancer patients showed a significantly increased population of peripheral NK cells as detected by both CD56+ and CD57+ phenotypes. Elevated serum levels of CRP, IL-4 and TNF-alpha, sIL-2R, but not IL-2, were also demonstrated in cancer patients as compared to controls. Activated CD25+ lymphocytes correlated negatively with CD28+ lymphocytes (r = -0.68, p < 0.01) and less significantly with CD4+ lymphocytes (r = -0.56, p < 0.05). The CD8+ cytotoxic cell subset might be negatively influenced by serum IL-4 (r = -0.57, p < 0.05). Positive correlation was found between sIL-2R and CRP (r = -0.78, p < 0.01), and between sIL-2R and TNF-alpha (r = 0.64, p < 0.05) serum levels in patients with progressive disease during the course of therapy, the initial proportions of CD4+, CD19+ and CD28+ lymphocytes were significantly lower than those among responders. Among humoral parameters, only sIL-2R showed a marginal correlation with therapeutic response, being more elevated among non-responding patients. Pre-treatment serum levels of CEA and CA 19-9 showed correlation with neither therapeutic response nor with any of the cellular or humoral immunological parameters analyzed. CONCLUSIONS: The results may serve as an initial guideline to open a discussion on the rationale of such a panel of tests, hopefully leading to standardized laboratory pre-selection and monitoring of patients treated with regional chemoimmunotherapy.

Detection of Bronchial Neoplasia in Uranium Miners by Autofluorescence Endoscopy (SAFE-1000).

The increase in the detection rate for premalignant changes of bronchial epithelium was studied in 56 symptom-free volunteers from the risk group of Czech uranium miners (mean age 50.69 years, mean WLM 21.06 (1 Working Level Month is equal to the absorption of latent energy of 2.08 x 10(-5) J/m(3) in one month, i.e. 170 working hours)) by the additional employment of the System of Autofluorescence Endoscopy (SAFE-1000 Pentax) to conventional white-light bronchoscopy, comparing results with those of bronchial biopsy histopathology examination. Histopathology using hematoxylin and eosin staining confirmed intraepithelial neoplasias in 15 areas in 10 persons. White-light bronchoscopy sensitivity was 21.05%, and specificity 93.7% which an autofluorescence bronchoscopy sensitivity was 78.95% and specificity 81.89%.

[Cytokines in regional immunochemotherapy of liver tumors]. / Cytokiny v regionální imunochemoterapii nádoru jater.

Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve, as compared with the little effective systemic chemotherapy, a higher percentage of therapeutic responses. The objective of regional chemoimmunotherapy, i.e. the use of cytokines, in particular interferon alpha (IFN-a) and interleukin-2 (IL-2) in the therapeutic regimens is to improve the survival of patients with malignant liver tumours. One of the main prerequisites of the effect of locally administered cytokines is activation of hepatic lymphocytes (LAL)-liver associated lymphocytes, effectors with specific phenotype and potential anti-tumourous effect directly in the target area. Although in regional monotherapy the effectiveness of cytokines is low, regimens combining the administration of cytostatics with IL-2 achieve a 50-70% therapeutic response. The authors summarize basic data on the regional administration of cytokines and present an review of combined regimens of regional chemoimmunotherapy, including their own protocol of the Masaryk Oncological Institute in Brno.

Biomarkers for predicting response to regional chemo-immunotherapy in liver metastases from colorectal carcinoma.

Differences in therapeutic outcomes after regional chemotherapy or chemo-immunotherapy in liver metastases from colorectal carcinoma cannot be explained only by variations in the regimens of treatment. This study was undertaken to assess the potential of several tumor-associated markers of biological behavior (biomarkers) to predict therapeutic response in order to pre-select the best candidates for this demanding treatment. In a group of 21 patients, flow cytometric DNA ploidy provided the most accurate prediction, with a response rate of 88% in 8 DNA diploid tumors compared to 31% in 13 DNA aneuploid cases (P = 0.017) and a difference in overall survival of nine months (20.4 vs 11.3, P = 0.041). Only a slight trend towards improved response rate was observed when we immunohistochemically detected p53 anti-oncoprotein expression in 11 (52%) p53-positive tumors (P = 0.063). Other immunohistochemical biomarkers as P-glycoprotein (p170), p21/WAF, mdm2, c-erbB-2, and proliferative activity of tumor (detected either by anti-PCNA and anti-Ki67 monoclonal antibodies or as a flow cytometric proliferation index) were unrelated to the outcome of treatment. DNA ploidy and expression of p53 protein are potential biomarkers for predicting the response to regional chemotherapy of liver metastases from colorectal carcinoma.