Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation

Willett, Christopher G.; Hagan, Michael P.; Daley, William; Warland, Gretchen; Shellito, Paul C.; Compton, Carolyn C.

doi:10.1007/bf02236897

Cited by 20 publications

(9 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PCNA immunostaining has proven to be a simple and useful method for the estimation of cell proliferation within tumors [24]. Our results agree with those of Willett et al [25, 26], indicating that proliferating cells are more responsive to radiation damage. The presence of a high PCNA index was statistically associated with a higher probability of a significant histologic tumor response to preoperative chemoradiotherapy.…”

Section: Discussionsupporting

confidence: 83%

Preoperatively Irradiated Rectal Carcinoma: Analysis of the Histopathologic Response and Predictive Value of Proliferating Cell Nuclear Antigen Immunostaining

Díez¹,

Ramos

Medrano

et al. 2003

Oncology

View full text Add to dashboard Cite

Objectives: To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53. Methods: Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy. Results: Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07–26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy. Conclusion: High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy.

show abstract

Section: Discussionsupporting

confidence: 83%

Preoperatively Irradiated Rectal Carcinoma: Analysis of the Histopathologic Response and Predictive Value of Proliferating Cell Nuclear Antigen Immunostaining

Díez¹,

Ramos

Medrano

et al. 2003

Oncology

View full text Add to dashboard Cite

show abstract

“…9 Ki-67 proliferative activity is probably associated with the downstaging of highly proliferative tumors and the greater populations of quiescent cells in tumors resistant to downstaging. Willet et al 4 reported that tumor downstaging is influenced by growth fractions, such as PCNA (proliferative cell nuclear antigen) or Ki-67 staining. Moreover, rectal cancer with evidence of high growth fraction was found to be more likely to be downstaged.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, molecular genetic studies have been used to identify some of the genetic factors related to the wide spectrum of tumor radioresponsiveness. Willet et al 4 observed that tumor components with a low proliferative index do not respond well and that highly proliferative tumors generally show good response. Recently, the tumor suppressor genes, p53 and p21, which regulate the cell cycle and apoptosis, have been proposed to play major roles in tumor response to radiotherapy and chemotherapy.…”

mentioning

confidence: 98%

p53, BCL-2, and Ki-67 Expression According to Tumor Response After Concurrent Chemoradiotherapy for Advanced Rectal Cancer

et al. 2001

View full text Add to dashboard Cite

show abstract

“…However, the benefit from preoperative radiation varies significantly in trials with a substantially wide pCR (9%-37%) [6][7][8][9][10] . Patients who achieve a pCR have better outcomes compared to patients who do not [11] .…”

Section: Introductionmentioning

confidence: 99%

Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

Ramzan¹

2014

WJGO

View full text Add to dashboard Cite

Due to a wide range of clinical response in patients undergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of treatment. Despite extensive research in this field, the exact mechanisms still remain elusive. Data raging from DNA-repair to specific molecules leading to cell survival as well as resistance to apoptosis have been investigated. Individually, or in combination, there is no single pathway that has become clinically applicable to date. In the following review, we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer. Key words: Ionizing radiation; DNA double-strand break; Non-homologous end-joining pathway; DNA-PKcs; Ku proteins; Complete pathological response; Radiation therapy; Apoptosis; Angiogenesis Core tip: Treatment of locally advanced rectal cancer stage Ⅱ and Ⅲ includes neoadjuvant chemo-radiation followed by surgery if clinically feasible. A strategy of observing patients without an operation has been proposed by some surgeons, but this is still the center of much debate. Moreover, the therapeutic effect of ionizing radiation in treatment of rectal cancer varies significantly from one person to another. This has led investigators to identify the molecular targets and pathways in rectal tumors resistant to ionizing radiation in a bid to improve the therapeutic effect of radiation by advanced biomedical and genetic engineering.Ramzan Z, Nassri AB, Huerta S. Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer.

show abstract

Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation

Cited by 20 publications

References 15 publications

Preoperatively Irradiated Rectal Carcinoma: Analysis of the Histopathologic Response and Predictive Value of Proliferating Cell Nuclear Antigen Immunostaining

Preoperatively Irradiated Rectal Carcinoma: Analysis of the Histopathologic Response and Predictive Value of Proliferating Cell Nuclear Antigen Immunostaining

p53, BCL-2, and Ki-67 Expression According to Tumor Response After Concurrent Chemoradiotherapy for Advanced Rectal Cancer

Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

Contact Info

Product

Resources

About