ABSTRACT
The aim of this study was to explore baseline data, laboratory and molecular analyses to determine if any could serve as potential prognostic marker(s) for treatment response to second line tuberculosis regimens. Of a total number of 50 multi-drug resistant tuberculosis (MDR-TB) patients starting second-line drug MDR-TB treatment in Iraq, only 21 showed treatment adherence and thus, included in this study. Response to treatment was monitored for 11 months by sputum microscopy and culture. We explored baseline data, laboratory and molecular analyses to determine if any could serve as potential prognostic marker(s) for treatment response. Highly signifi cant association (P = 0.019) was detected between mutations in katG315 codon and good response to second-line anti-TB drugs. Spoligotyping and mycobacterial interspersed repetitive unit variable number tandem repeat confi rmed that katG315-mutatnt isolates were genotypically unrelated. The katG315 mutation is a potential prognostic marker for treatment response to second-line anti-tuberculosis drugs. One possible explanation of our results is that the katG315-mutants are sensitive to bacterial killing by “oxidative killing.”
ABSTRACT
Context: Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) preferentially degrade the basement membrane, a key step in tumor invasion, metastases, and induction of vascularization of tumor tissue. Aim: To determine MMP-2 and MMP-9 in situ mRNA expressions in colorectal adenocarcinomas from Iraqi patients. Materials and Methods: Forty archived paraffin-embedded colorectal adenocarcinoma samples and their resection margins were enrolled in our study. Thin paraffin embedded sections (3-5 μm thick) of both tumor and resection margins were prepared for each respective biopsy and were used to detect MMP-2 and MMP-9 in situ mRNA expressions based on in situ hybridization technique. Statistical Analysis: Statistical analyses were conducted to describe different variables and parameters in this research, and to describe relationships with each other as well. For the comparisons, the t test of significance was used. The associations were found by chi-square (χ2 ) and analysis of variance (ANOVA) tests, or as appropriate, as well as 95% confidence interval. The correlations were calculated using correlation coefficient (r). Statistical significance was defined as P < 0.05. Results: Based on the current outcome, there were significant differences in MMP-2 and MMP-9 in situ mRNA expressions when each tumor sample were compared to its respective resection margin (P < 0.001 and P < 0.001, respectively). When tumor samples were analyzed based on their depth of invasion, means of in situ mRNA expressions of both MMP-2 and MMP-9 were significantly increased in the group in which tumor invaded submucosa into muscularis properia (SMP) compared to that of tumor in serosa (SE) group and tumor invading other organs (OR) group (P < 0.05 and P < 0.05, respectively). Furthermore, when tumor lymph node metastases were questioned, exclusively, MMP-2 in situ mRNA expression was significantly differentiated among N0, N1, and N2 groups (P < 0.05). Regarding the possible correlation between the two investigated parameters with respect to various histopathological variables, both MMP-2 and MMP-9 in situ mRNA expressions have significant positive correlation in tumor samples (r = 0.88), whereas in resection margins, this correlation was absent. Interestingly, MMP-2 and MMP-9 in situ mRNA expressions were found to correlate positively as well as significantly within tumor differentiation [well-differentiated (WD) adenocarcinoma: r = 0.78; moderately differentiated (MD) adenocarcinoma: r = 0.90; and poorly differentiated (PD) adenocarcinoma: r = 0.91], tumor stage (A-B: r = 0.70 and C-D: r = 0.95), depth of invasion (SMP: r = 0.77; SE: r = 0.87; and OR: r = 0.97), lymph node metastasis (N0: r = 0.82; N1: r = 0.92; and N2: r = 0.96), and tumor size (<3 mm 3 : r = 0.76 versus ≥3 mm3: r = 0.94). Conclusions: Overexpression of MMP-2 and MMP-9 are often associated with increased invasive metastatic potential of colorectal adenocarcinoma. However, their activities are essential during the early stages of tumor progression.
ABSTRACT
Context: Counting of newly formed microvessel may prove to be a useful tool in the early detection of metastatic potential and selection of patients for whom antiangiogenesis drugs might be beneficial. Aims: We designed this study to assess the significance of microvessel quantification in colorectal cancer with respect to different clinicopathological variables. Materials and Methods: Forty archived paraffin-embedded colorectal adenocarcinoma samples and their resection margins were enrolled in our study. Thin paraffin-embedded sections (3-5 ΅m thick) of both tumor and resection margins were prepared for each respective biopsy and were used to detect endothelial cell (EC) surface expression of PECAM-1 and vWF by immunohistochemistry technique. Statistical Analysis: For the comparison between tumor and resection margin regarding the investigated parameters, the t-test of significance was conducted. The association between surface expression of PECAM-1 and vWF along with tumor differentiation, depth of invasion and lymph node metastasis was performed by Chi-square (χ2 ) and ANOVA test as well as 95% confidence interval. On the other hand, the association between the investigated parameters and tumor stage as well as tumor size was performed by student t-test. The correlations between the two investigated parameters in respect to various clinicopathological parameters were calculated by correlation coefficient (r). Statistical significance was defined as P < 0.05. All statistical analyses were performed using SPSS statistical package for social and medical science version 15.0. Results: Based on the current outcome, there were significant differences in microvessel density based on PECAM-1 or vWF immunostaining when each tumor sample was compared to its respective resection margin (P < 0.001 and P < 0.001, respectively). In addition, tumors ≥3 mm 3 in size demonstrated a significant increase in their microvessel density compared to their counterparts whether PECAM-1 or vWF immunostaining was applied (P < 0.001 and P < 0.001, respectively). Moreover, when tumor samples were analyzed based on their depth of invasion, for intratumoral microvessel count, exclusively, vWF immunostaining analysis demonstrated significant differences among the three groups: submucosa into muscularis propria (SMP), tumor reaches serosa (SE) and tumors invade other organs (OR), since the latter came up with the highest microvessel count (P < 0.05). When tumor lymph node metastases were questioned, exclusively, vWF immunostaining were significantly differentiated among N0, N1 and N2 groups (P < 0.05). Concerning the possible correlations between the two investigated parameters in respect to various histopathological variables, both PECAM-1 and vWF immunostaining demonstrated significant positive correlations in tumor samples (r = 0.37), whereas in resection margins, these correlations were absent. Although, PECAM-1 and vWF immunostaining revealed significant and positive correlations within tumor differentiation (WD: r = 0.56, MD: r = 0.57 and PD: r = 0.89) as well as with tumor stage (A-B: r = 0.39 and C-D: r = 0.31), still, they seem to correlate significantly and exclusively within SE group (r = 0.74), tumors <3 mm 3 in size (r = 0.66), N0 (r = 0.36) and N1 (r = 0.85) groups. However, PECAM-1 and vWF immunostaining revealed significant but negative correlation exclusively within N2 group (r = -0.38). Conclusion: In conclusion, microvessel count could be useful as a predictor for tumor metastases in patients with colorectal adenocarcinoma. Possible interpretations of the current outcome are explained thoroughly in the text.
ABSTRACT
Context: Rheumatoid arthritis (RA) has a heterogeneous course, spanning from mild forms tending to remission and reacting well to treatment, to aggressive forms resistant to classical therapeutic measures. Reliable predictive parameters of the disease course in RA are needed. Raised levels of Rheumatoid Factors (RFs) are associated with RA and that this RF is found in IgM, IgA and IgG classes (isotypes). Aims: To figure out the value of RF isotypes titers as predictors for RA processes and outcomes. Materials and Methods: Fifty three RA patients were enrolled in this study. The patients were diagnosed based on ACR criteria. Blood sample was taken from each patient at time of attending; sera were separated immediately and kept frozen at -70oC until used. Disease Activity Score (DAS) was calculated using DAS28-3 formula. Radiographs were read by expert radiologists. Sandwich Enzyme-linked Immunosorbent Assay (ELISA) was used for the separate quantitative detection of RF of the IgG, IgM and IgA classes in serum. Statistical Analysis Used: Chi-square, Pearson's correlation coefficient and ROC statistical analyses was performed using SPSS version 15.0. Results: Among the 53 RA patients who were enrolled in this study, there were statistically significant positive correlations between the presence of radiological joint changes with serum levels of IgG-RF, IgM-RF and IgA-RF as measured by calculation of area under curve (0.772, 0.703 and 0.769, respectively). However, no correlation could be found between those RF isotypes with any of other disease processes and outcomes. Conclusions: These results may indicate the importance of the titers of those isotypes as good predictors of erosive RA and may reflect a causal relationship between their titers and joint damage during the course of RA.