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1.
Sci Rep ; 14(1): 6977, 2024 03 23.
Article En | MEDLINE | ID: mdl-38521858

Radiation-induced renal fibrosis (RIRF) is a progressive, irreversible condition causing chronic kidney disease. Pentoxifylline (PTX) and vitamin E may mitigate radiation-induced damage and fibrosis. This study assesses their effectiveness. We used four groups, each with six rats: radiation therapy alone (RT-only), radiation therapy plus drug treatment (RT + drug), drug treatment alone (drug-only), and a control group. Rats were monitored for three months, with weight measurements every four weeks. Afterward, rats were analyzed biochemically and histologically, with blood and tissue samples taken for statistical comparison. No significant differences in serum creatinine levels and body weight were observed. RT-only group had more severe kidney tubule effects. Histomorphological, immunohistochemical, and TUNEL analyses showed significant RIRF mitigation in the RT + drug group. Our study highlighted molecular pathways (SMAD, TGF-beta, VEGF) and histological markers (collagens, a-SMA, fibronectin, metalloproteinases) associated with RIRF. PTX and vitamin E reduced ionizing radiation's impact on renal cells and mitigated radiation-induced kidney fibrosis. Further human studies are needed to confirm these findings.


Pentoxifylline , Rats , Humans , Animals , Pentoxifylline/pharmacology , Pentoxifylline/therapeutic use , Vitamin E/pharmacology , Vitamin E/therapeutic use , Antioxidants/pharmacology , Kidney/pathology , Fibrosis
2.
Oncol Res ; 31(3): 299-306, 2023.
Article En | MEDLINE | ID: mdl-37305394

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26-87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients' performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78-7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79-6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12-2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.


Carcinoma , Esophageal Neoplasms , Uterine Cervical Neoplasms , Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Esophageal Neoplasms/therapy , Chemoradiotherapy
3.
Breast ; 42: 10-14, 2018 Dec.
Article En | MEDLINE | ID: mdl-30121548

PURPOSE: Turkish Radiation Oncology Study Group investigated local recurrence rates and prognostic factors in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conservative surgery (BCS) followed by radiotherapy (RT) and Eastern Cooperative Oncology Group (ECOG) Study E5194 were compared with the original study. PATIENTS AND METHODS: Totally 252 patients were evaluated retrospectively. Prognostic factors that might influence local control (age, nuclear grade, comedo necrosis, surgical margins, tumor size, hormone receptor status) were compared. The eligibility criteria of ECOG 5194 were stratified into two groups as in the original study and were compared for local control. RESULTS: The median follow-up time was 59 (21-220) months. Local recurrence was observed in 9 patients (3.6%) who had invasive carcinoma (3 patients) and DCIS (6 patients). Ten years local control rates was 91.8% respectively. We found that the risk of ipsilateral breast recurrence was significantly higher in women younger than 50 years old (p = 0.016). In addition, a statistically significant trend was found in patients with tumor larger than 1 cm and HER2 positive tumors (p = 0.051, p = 0.068 respectively). When 12-year results were compared with the ECOG 5194, adjuvant RT produced an absolute difference of 11% in low-intermediate and 20% in high grade in local control. CONCLUSION: In our study, the 10-year local control rate was 92% and younger than 50 years old was the most important unfavorable prognostic factor for local recurrence. There was provided 20% absolute local control with adjuvant radiotherapy which eligibility criteria of ECOG 5194 high grade group.


Carcinoma, Intraductal, Noninfiltrating/radiotherapy , Carcinoma, Intraductal, Noninfiltrating/surgery , Neoplasm Recurrence, Local/epidemiology , Adult , Aged , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Disease-Free Survival , Female , Humans , Mastectomy, Segmental/statistics & numerical data , Middle Aged , Prognosis , Radiotherapy, Adjuvant/statistics & numerical data , Retrospective Studies , Turkey
4.
Radiother Oncol ; 127(1): 96-102, 2018 Apr.
Article En | MEDLINE | ID: mdl-29373196

BACKGROUND AND PURPOSE: The optimal treatment for adults with newly diagnosed medulloblastoma (MB) has not been defined. We report a large series of cases from the Rare Cancer Network. MATERIAL AND METHODS: Thirteen institutions enrolled 206 MB patients who underwent postoperative radiotherapy (RT) between 1976 and 2014. Log-rank univariate and Cox-modeled multivariate analyses were used to analyze data collected. RESULTS: Median patient age was 29 years; follow-up was 31 months. All patients had the tumor resected; surgery was complete in 140 (68%) patients. Postoperative RT was given in 202 (98%) patients, and 94% received craniospinal irradiation (CSI) and, usually, a posterior fossa boost. Ninety-eight (48%) patients had chemotherapy, mostly cisplatin and vincristine-based. The 10-year local control, overall survival, and disease-free survival rates were 46%, 51%, and 38%, respectively. In multivariate analyses, Karnofsky Performance Status (KPS) ≥80 and CSI were significant for disease-free and overall survival (P ≤ .04 for all); receiving chemotherapy and KPS ≥80 correlated with better local-control rates. CONCLUSIONS: Patients with high KPS who received CSI had better rates of disease-free and overall survival. Chemotherapy was associated with better local control. These results may serve as a benchmark for future studies designed to improve outcomes for adults with medulloblastoma.


Cerebellar Neoplasms/therapy , Medulloblastoma/therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cerebellar Neoplasms/mortality , Cerebellar Neoplasms/pathology , Cerebellar Neoplasms/surgery , Chemoradiotherapy, Adjuvant , Cisplatin/administration & dosage , Craniospinal Irradiation , Disease-Free Survival , Europe/epidemiology , Female , Humans , Male , Medulloblastoma/mortality , Medulloblastoma/pathology , Medulloblastoma/surgery , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Treatment Outcome , United States/epidemiology , Vincristine/administration & dosage , Young Adult
5.
Int J Radiat Oncol Biol Phys ; 67(1): 196-203, 2007 Jan 01.
Article En | MEDLINE | ID: mdl-17071013

PURPOSE: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. METHODS AND MATERIALS: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primary endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. RESULTS: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. CONCLUSIONS: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.


Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 9/analysis , Neoplasm Proteins/analysis , Rectal Neoplasms/chemistry , Tissue Inhibitor of Metalloproteinase-1/analysis , Tissue Inhibitor of Metalloproteinase-2/analysis , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/therapeutic use , Combined Modality Therapy/methods , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Logistic Models , Male , Middle Aged , Neoplasm Staging , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Retrospective Studies
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