3 research outputs found
Inter- and intra-tumoral relationships between vasculature characteristics, GLUT1 and budding in colorectal carcinoma
Vascular characteristics, hypoxia and tumor
budding are features that have been implied in the
biology and prognosis of colorectal cancer. Internal
relationships and the inter- and intra-tumoral variation of
these tumor properties remain to be determined. In the
current study we have characterized blood vessel status
in different areas of CRC and in the peritumoral
fibroblastic stroma. Analyses of these characteristics
have been supplemented by characterization of budding
and hypoxia.
Analyses revealed significantly lower values of
vessel perimeter (VP) and vessel lumen area (VL) at the
invasive front and surrounding stroma as compared to
the tumor center. Also, the number of vessels (VN) in
the peritumoral stroma was higher than in the center.
Thus, tumor center displays larger and fewer vessels as
compared to the tumor periphery.
GLUT1 expression was correlated directly with VN
(r=0.351, p=0.028) and inversely with VL and VP (r=-
0.432, p=0.006 and r=-0.484, p=0.002) at the invasive
front. Moreover, GLUT1 expression, VP at the invasive
front, and VN in the surrounding peritumoral stroma,
were associated with budding score (r=0.574, p<0.000,
r=-0.340, p=0,034 and r=-0,389, p=0.025 respectively).
Furthermore, GLUT1, budding score, vessel number
in peritumoral stroma, and vessel size in the invasive
front, were significantly different in tumors with or
without lymph node metastasis.
This study reports previously unrecognized
relationships between localization-specific vascular
characteristics, hypoxia and tumor budding. The findings
suggest potential functional relationships, which should
be further explored, and also highlight the inter-tumoral
variations in vasculature, which is highly relevant for
ongoing efforts to identify vessel-based biomarkers
Over-Expression of βII-Tubulin and Especially Its Localization in Cell Nuclei Correlates with Poorer Outcomes in Colorectal Cancer
Tubulin is a heterodimer of α and β subunits, both existing as isotypes differing in amino acid sequence encoded by different genes. Specific isotypes of tubulin have associations with cancer that are not well understood. Previous studies found that βII-tubulin is expressed in a number of transformed cells and that this isotype is found in cell nuclei in non-microtubule form. The association of βII expression and its nuclear localization with cancer progression has not previously been addressed. We here used a monoclonal antibody to βII to examine patients with colorectal cancer and found that patients whose tumors over-express βII have a greatly decreased life expectancy which is even shorter in those patients with nuclear βII. Our results suggest that βII-tubulin may facilitate cancer growth and metastasis and, to accomplish this, may not need to be in microtubule form. Furthermore, βII expression and localization could be a useful prognostic marker. We also found that βII appears in the nuclei of otherwise normal cells adjacent to the tumor. It is possible therefore that cancer cells expressing βII influence nearby cells to do the same and to localize βII in their nuclei by an as yet uncharacterized regulatory pathway
Analysis of thyroid malignant pathologic findings identified during 3 rounds of screening (1997-2008) of a cohort of children and adolescents from belarus exposed to radioiodines after the Chernobyl accident.
BACKGROUND: Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear.
METHODS: A cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression.
RESULTS: In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1;
CONCLUSIONS: I-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness