Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis

CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40-9.00) and 3.10 (range 0.90-8.00), respectively. Kaplan-Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFbeta1 and TGFbeta3 together with the receptor-ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFbeta1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFbeta1 level was noted in patients with carcinoma over the controls. Furthermore, TGFbeta3 and CD105/TGFbeta3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFbeta1 was expressed in cancer cells but TGFbeta3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFbeta1, TGFbeta3 and CD105/TGFbeta complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.     

Thalidomide in relapsed or refractory multiple myeloma: how much and for how long?

The optimum dose and duration of treatment with thalidomide for relapsed or refractory multiple myeloma are not known. Long term responses were seen in 5 patients given low doses of thalidomide (100-200 mg) with or without pulsed dexamethasone, for between 48 and 108 weeks. The responses were sustained for between 23 and 67 weeks after stopping treatment. We recommend that the lowest effective dose (LED) and optimum duration of therapy with thalidomide should be determined within the framework of a well conducted clinical trial in order to answer these important questions.     

Biallelic inactivation of the APC gene is associated with hepatocellular carcinoma in familial adenomatous polyposis coli

BACKGROUND: Certain primary hepatic tumors have been associated with familial adenomatous polyposis (FAP), a condition caused by germline mutations of the adenomatous polyposis coli (APC) gene. However, a genetic association between FAP and hepatocellular carcinoma (HCC) has not been shown. This study tested the hypothesis that biallelic inactivation of the APC gene contributed to the development of HCC in a patient with FAP and a known germline mutation of the APC gene at codon 208, but no other risk factors for HCC. METHODS: Total RNA and genomic DNA were isolated from the tumor, and in vitro synthesized protein assay and DNA sequencing analysis were used to screen for a somatic mutation in the APC gene. RESULTS: A somatic one-base pair deletion at codon 568 was identified in the wild-type allele of the APC gene. CONCLUSIONS: To the authors' knowledge, this study provides the first evidence that biallelic inactivation of the APC gene may contribute to the development of HCC in patients with FAP.     

Presumed prevalence analysis on suspected and highly suspected breast cancer lesions in S?o Paulo using BIRADS criteria.

CONTEXT AND OBJECTIVE: Breast cancer screening programs are critical for early detection of breast cancer. Early detection is essential for diagnosing, treating and possibly curing breast cancer. Since there are no data on the incidence of breast cancer, nationally or regionally in Brazil, our aim was to assess women by means of mammography, to determine the prevalence of this disease. DESIGN AND SETTING: The study protocol was designed in collaboration between the Department of Diagnostic Imaging (DDI), Institute of Diagnostic Imaging (IDI) and S?o Paulo Municipal Health Program. METHODS: A total of 139,945 Brazilian women were assessed by means of mammography between April 2002 and September 2004. Using the American College of Radiology (ACR) criteria (Breast Imaging Reporting and Data System, BIRADS), the prevalence of suspected and highly suspected breast lesions were determined. RESULTS: The prevalence of suspected (BIRADS 4) and highly suspected (BIRADS 5) lesions increased with age, especially after the fourth decade. Accordingly, BIRADS 4 and BIRADS 5 lesions were more prevalent in the fourth, fifth, sixth and seventh decades. CONCLUSION: The presumed prevalence of suspected and highly suspected breast cancer lesions in the population of S?o Paulo was 0.6% and it is similar to the prevalence of breast cancer observed in other populations.     

Racial differences in prostate-specific antigen levels and prostate-specific antigen densities in patients with prostate cancer

To compare serum prostate-specific antigen (PSA) levels and PSA density (PSAD) among African American (AA), white, and Hispanic men with prostate cancer (PC) seen in an urban, equal-access urology clinic. Between January 1988 and January 1993, 1,105 men were screened for PC at Cook County Hospital in Chicago, Illinois. A total of 529 men underwent transrectal ultrasound-guided prostate gland biopsies for abnormal digital rectal examination, suspect transrectal ultrasound, elevated PSA, or any combination of these abnormalities. PC was found in 246 patients (204 AAs, 22 whites, and 20 Hispanics). We analyzed the differences in PSA and PSAD among the three racial groups using univariate and multivariate analyses adjusting for race, age, clinical stage, and grade. AAs have a higher mean serum PSA levels (21.56 ng/ml) than whites (mean PSA of 10.96 ng/ml) and Hispanics (mean PSA of 8.25 ng/ml) (p = 0.04). The mean PSAD also was higher in AAs than in the other two groups (0.68 versus 0.34 for whites and 0.31 for Hispanics, p = 0.05). On a multivariate analysis, the PC stage and grade were overwhelmingly significant, whereas the race and age lost their statistical significance. AAs have higher serum PSA and PSAD than whites or Hispanics in an equal-access healthcare environment. Race is a significant factor in determining PSA and PSAD on univariate but not on multivariate analysis. Preliminary studies suggest that these differences are due to sociological, not biologic causes. These findings warrant a large, prospective study to investigate the extent and the causes of the racial differences in PSA and PSAD.     

Prognostic relevance of microvessel density in colorectal tumours.

The importance of angiogenesis as a prognostic marker has been examined in 111 colorectal cancer patients with a minimum follow-up of 5 years. Tumour sections were immunostained with pan-endothelial antibody to CD31. Microvessels were identified and counted in 5 separate areas of highest vascularity (). Analysis of the data showed that the survival was not significantly affected by tumour site, size, grade, patients' age or gender. However, a statistically significant correlation was found between microvessel density (MVD) and survival: patients with an increased number of microvessels survived longer than those with a low number of microvessels (p=0.0007). Therefore, paradoxically, unlike other tumour types, in colorectal cancer MVD appears to be an indicator of good prognosis. The reasons that MVD correlates with good or poor prognosis are likely to vary in different tumours. For instance a frequent difficult issue in colon cancer is the presence of ulceration and adjacent severe inflammation which by itself can increase vascularity. Furthermore, overall prognosis will also depend on other factors, such as oncogenes, extracellular matrix components, adhesion molecules, growth factors, degree of apoptosis and the mode of metastatic spread.     

Pathophysiological variability of different genotypes of human <Emphasis Type="Italic">Blastocystis hominis</Emphasis> Egyptian isolates in experimentally infected rats

The genotyping of Blastocystis hominis clinical isolates obtained from 28 gastrointestinal symptomatic patients and 16 asymptomatic individuals were identified by polymerase chain reaction using sequenced-tagged site (STS) primers. Then, pathophysiological variability between different B. hominis genotypes was evaluated in experimentally infected rats. Only four B. hominis subtypes (1, 2, 3, and 4) were detected (18.2%, 9.1%, 54.5%, and 18.2%, respectively) in human isolates. In symptomatic isolates, subtypes 1, 3, and 4 were detected in 8 (28.6%), 16 (57.1%), and 4 (14.3%) patients, respectively. In asymptomatic isolates, subtypes 2, 3, and 4 were identified in 4 (25%), 8 (50%), and 4 (25%), respectively. Subtype 3 was the commonest in humans. Different degrees of pathological changes were found among infected rats by symptomatic subtypes compared with asymptomatic subtypes. The moderate and severe degrees of pathological changes were found only in symptomatic subtypes infected rats while mild degree was found only in asymptomatic subtypes infected rats. Only subtype 1 induced mortality rate with 25% among infected rats. On evaluation of the intestinal cell permeability in the Ussing chamber, a prominent increase in short circuit current (ΔIsc) was found in symptomatic subtype 1 compared to symptomatic subtypes 3 and 4 infected rats. Minimal effects were found in the asymptomatic and control groups. The results proved that subtype 1 was clinically and statistically highly relevant to the pathogenicity of B. hominis while subtype 2 was irrelevant. Also, the results suggest the presence of pathogenic and nonpathogenic strains among subtypes 3 and 4.