Background: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and ...disease-free survival.
Purpose: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy.
Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen.
Materials: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987–1990.
Results: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (
p = 0.03), with a trend toward improved disease-free survival (
p = 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates.
Conclusion: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.
Abstract
Chemokines are small cytokine-like secreted proteins with chemoattractant properties which function in the recruitment of leucocytes into inflamed tissue. Besides well studied roles in the ...immune system, chemokines and their receptors have also been shown to play critical roles in tumorigenesis. The present study focuses on C-X-C motif chemokine 10 (CXCL10), a potent chemoattractant for stimulated T-cells and NK-cells. Both CXCL10 and its receptor CXCR3 are expressed by breast tumor cells, and accumulating data suggests roles for this chemokine and its receptor in breast cancer development and proliferation. We have previously shown CXCL10 to be significantly upregulated in ER positive as well as negative breast cancer cell lines over-expressing 17β hydroxysteroid dehydrogenase 14 (17βHSD14). Using a validated anti-CXCL10 primary antibody, we examined the relationship between CXCL10 expression and clinicopathological features in tissue microarrays comprised of tumor material from 912 breast cancer patients participating in a randomized tamoxifen trial conducted in Stockholm, Sweden, 1976-1990. All patients had lymph node negative primary breast cancer and were postmenopausal at the time of diagnosis. Results were obtained from tumors of 793 patients, of which 6% were deemed negative, 23% weak, 28% moderate, and 42% strong. Staining intensity of CXCL10 was strongly correlated with expression of 17βHSD14 (p<0.0001), however no significant correlation was observed between CXCL10 and prognostic markers such as ER, PR or tumor size. No clear associations between CXCL10-expression levels and the clinical outcome of tamoxifen treatment were observed, and moreover no prognostic value of CXCL10 was seen in systemically untreated patients. In the present study we have investigated expression of CXCL10 in a breast tumour cohort. We have previously found a functional relationship between 17βHSD14 and CXCL10 suggesting a possible regulatory loop involving this 17βHSD enzyme. A strong association between CXCL10 and 17βHSD14 in this tumor cohort further strengthens this theory. We found CXCL10 to be ubiquitously expressed in the tumors however no significant relationship between CXCL10 expression and tamoxifen treatment prediction or prognosis among patients was noted. Previous data on the action of CXCL10 in cancer is conflicting as the chemokine has been suggested to act as a growth promoter as well as an inhibitor growth. The presence of two splice variants of the CXCL10 receptor CXCR3, of which CXCR3-A has been shown to promote proliferation and CXCR3-B- to induce apoptosis, has generally not been accounted for, and varying expression levels of these receptors may to some degree explain these conflicting findings. In order to elucidate the role of CXCL10 in breast cancer, tumoral distribution and expression levels of these two splice variants of the CXCL10 receptor need to be evaluated.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3142. doi:10.1158/1538-7445.AM2011-3142
Several cases with microscopically visible, terminal 6p deletions have been described, and a distinct clinical phenotype has emerged, including developmental delay, congenital heart malformations, ...ocular abnormalities, hearing loss and a characteristic facial appearance. We report a patient with a submicroscopic 6p deletion, detected by subtelomeric screening using fluorescence in situ hybridisation. This girl presented with typical facial dysmorphic features, hearing impairment, malformation of the anterior eye segment, an ASD and severe language impairment. However, her cognitive functions were within the normal range. Detailed FISH analysis with 20 BAC probes covering the distal 6p25 region estimated the size of the terminal deletion to 2.1 Mb, and thus this case narrows down the critical region for the 6p phenotype. The forkhead transcription factor gene FOXC1, involved in a spectrum of anterior eye chamber disorders, is deleted in this patient, together with several characterised and putative genes with yet unknown function.
Simian AIDS-related lymphomas (sARL) of cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied in relation to growth in severe combined immunodeficient (SCID) mice, ...karyotype abnormalities, and DNA sequence of the first noncoding region of the Bcl-6 gene. The tumors were diffuse large B cell lymphomas and expressed a simian homolog to Epstein-Barr virus (HVMF-1) in 12 of 13 primary tumors and corresponding cell lines. A tested cell line was tumorigenic in SCID mice. Tumors in the SCID mice showed cell growth features similar to those in the original lymphoma, suggesting that no subpopulation with growth advantage was selected for in the mice. Spectral karyotype analysis of sARL cell lines showed normal cytogenetic features except for a trisomy of monkey chromosome 2 (corresponding to human chromosomes 7 and 21) in two of five sARL lines, which was not recovered in SCID tumors established from the same cell line. Sequence analysis of a Bcl-6 gene fragment showed sequence variations indicative of population polymorphism(s) in 10 of 13 sARLs, and no evidence of Bcl-6 mutations. Thus Bcl-6 mutations in the first noncoding region are irrelevant for sARL development in cynomolgus monkeys and for tumorigenicity of sARL cell lines. We also demonstrate that no cytogenetic alterations are needed for the development of highly aggressive lymphomas in the SIV-immunosuppressed host.
Endometrios - en inflammatorisk kvinnosjukdom Bergqvist, Agneta; Bergquist, Christer; Nordenskjöld, Fredrik
Tidsskrift for den Norske Lægeforening,
2001, Letnik:
121, Številka:
21
Journal Article
PDF
