Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate (dRib-1-P). Although this reaction is reversible, the main metabolic function of TP is catabolic. TP is identical to the angiogenic factor platelet-derived endothelial-cell growth factor (PD-ECGF). TP is overexpressed in several human cancers in response to cellular stressful conditions like hypoxia, acidosis, chemotherapy and radiotherapy. TP has been shown to promote tumor angiogenesis, invasion, metastasis, evasion of the immuneresponse and resistance to apoptosis. Some of the biological effects of TP are dependent on its enzymatic activity, while others are mediated through cytokines like interleukin 10 (IL-10), basic fibroblast growth factor (bFGF) and tumour necrosis factor α (TNFα). Interestingly, TP also plays a role in cancer treatment through its role in the conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU. TP is a predictive marker for fluoropyrimidine response. Given its various biological functions in cancer progression, TP is a promising target in cancer treatment. Further translational research is required in this area.
16066 Background: Serum levels of the tumor marker CA125 and its relation to disease stage, grade, tumor volume, survival and prognosis have been studied with conflicting results. This study was conducted in a single center serving a population of 340,000. Methods: Newly diagnosed patients referred between Jan 1 2001 and Dec 31 2005 were included. Serum CA125 levels were recorded before and after optimal debulking surgery and before each cycle of chemotherapy. Patients received standard adjuvant or palliative chemotherapy. Disease was staged using the FIGO staging system. Tumors were graded by the Broders Classification. CT scan within 6 weeks of surgery was used to quantify residual disease. Disease status as of Dec 2006 was used for measurements of overall survival (OS). The relationships between preoperative CA125 and stage, grade and OS were retrospectively evaluated. Post surgical levels of CA125 were also analysed and correlated to the same parameters. The influence of age and bulk of residual disease on OS were also examined. Kaplan- Meier (univariate) analysis was applied for survival analysis and Spearman's method was used to study the correlation of CA125 and the multiple variables. Results: 91 newly diagnosed ovarian cancer referrals were received in the study period. This report is based on the 75 patients of this total group for whom full data was available. Length of follow up ranged from 2 to 71 months (median of 24, mean of 28.2 months). Preoperative CA125 level did not correlate significantly with stage, tumor grade or OS (p=0.08. p=0.113 and p=0.847 respectively). A strong correlation was seen however between postoperative CA125 level (recorded prior to commencement of chemotherapy) and stage, tumor grade and OS (p<0.0001, p<0.0001 and p<0.01respectively) OS for the total group was 37%, and OS for those with stage III and IV disease (n=43) was 17%. The mean age of the patients was 59.6 years. Older age at time of surgery (p=0.009) followed by bulk of residual disease (p=0.011) correlated strongly with shortened OS. Kaplan-Meier curves will be available for presentation. Conclusion: In our study, CA125 levels after optimal surgery correlated well with FIGO stage, tumor grade and overall survival. No correlation was seen with preoperative CA125 levels. No significant financial relationships to disclose.
Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.
We report a rapid early response to crizotinib as neoadjuvant therapy, enabling surgical excision of a large ALK-translocated IMT, which resulted in complete disease clearance. To the best of our knowledge, this is the first case in the literature of a patient with IMT in whom crizotinib was used successfully in the neoadjuvant or curative setting.
In prostate cancer patients, if bone scan demonstrates a solitary lesion in atypical area, this is possibly an indication of metastatic disease. Therefore, biopsy confirmation is required to determine the nature of the abnormality and therefore dictates further staging investigations and treatment options.
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