ABSTRACT
BACKGROUND: Almost 30% of the sunitinib-treated patients for metastatic renal carcinoma (mRCC) do not receive a clinical benefit. Convincing evidences demonstrated a cross talk between the VEGF and CXCR4 pathways. It was hypothesized that CXCR4 expression in primary renal cancer could predict sunitinib responsiveness. PATIENTS AND METHODS: In this exploratory study sixty-two mRCC patients receiving sunitinib as first-line treatment were evaluated for CXCR4 expression through immunohistochemistry (IHC). Correlations between CXCR4 expression, baseline patients and tumour characteristics were studied by contingency tables and the chi-square test. Univariable analysis was performed with the log-rank test, and the Cox model was applied for multivariable analysis. RESULTS: The objective response rate of sunitinib first-line therapy was 35.5% (22/62) with a disease control rate (response and stable disease) of 62.9% (39/62). CXCR4 expression was absent/low in 30 (48.4%), moderate in 17 (27.4%), and high in 15 (24.2%) tumors respectively. Low or absent CXCR4 expression predicted response to sunitinib therapy. Moreover, Fuhrman grading and concomitant, CXCR4 and Fuhrman grading, strongly predicted sunitinib first line therapy responsiveness on progression-free survival and overall survival. CONCLUSIONS: High CXCR4 expression correlates with sunitinib poor response in metastatic renal cancer.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/immunology , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/immunology , Pyrroles/therapeutic use , Receptors, CXCR4/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Cell Line, Tumor , Chi-Square Distribution , Disease-Free Survival , Female , Humans , Immunohistochemistry , Italy , Kaplan-Meier Estimate , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Predictive Value of Tests , Proportional Hazards Models , RNA, Messenger/metabolism , Receptors, CXCR4/genetics , Risk Assessment , Risk Factors , Sunitinib , Time Factors , Treatment OutcomeABSTRACT
CXCR4 is a chemokine receptor implicated in the metastatic process. The CXCR4 ligand, CXCL12, was shown to bind also the CXCR7 receptor, a recently deorphanized chemokine receptor whose signalling pathway and function are still controversial. This study was conducted to determine patients clinic-pathological factors and outcome according to the expressions of CXCR4 and CXCR7 in renal cell carcinoma (RCC). CXCR4 and CXCR7 expression was evaluated in 223 RCC patients through immunohistochemistry; moreover CXCR4 and CXCR7 was detected in 49 others consecutive RCC patients trough RT- PCR. CXCR4 expression was low in 42/223 RCC (18.8%), intermediate in 71/223 (31.9%) and high in 110/223 (49.3%). CXCR7 expression was low in 44/223 RCC patients (19.8%), intermediate in 65/223 (29.1%) and high in 114/223 (51.1%). High CXCR4 and high CXCR7 expression predicted shorter disease free survival. In multivariate analysis, high CXCR4 expression (p= 0.0061), high CXCR7 (p= 0.0194) expression and the concomitant high expression of CXCR4 and CXCR7 (p= 0.0235) are independent prognosis factors. Through RT-PCR, CXCR4 was overexpressed in 36/49 and CXCR7 in 33/49 samples correlating with symptoms at diagnosis and lymph nodes status. So we can hypothesize that CXCR4 and CXCR7, singularly evaluated and in combination, are valuable prognostic factors in RCC patients.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , Receptors, CXCR4/metabolism , Receptors, CXCR/metabolism , Aged , Aging , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/secondary , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kidney/metabolism , Kidney/pathology , Kidney Neoplasms/pathology , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , RNA, Messenger/metabolism , Receptors, CXCR/genetics , Receptors, CXCR4/genetics , Reverse Transcriptase Polymerase Chain Reaction , Survival AnalysisABSTRACT
The diffusion of peritoneal dialysis (PD) at home is somewhat restricted by the difficulty of transport and storage of a large amount of dialytic solutions. This problem is exacerbated in the case of hemodialysis. With the aim of producing pure water to be used in preparing the solution for peritoneal dialysis, or for hemodialysis in general, as one example, we purified the spent dialysate solution from PD. Experiments were carried out with 24 dialysate solutions taken from 8 patients. Pure water was obtained by means of a thermodialysis process in a hollow fiber reactor operating under nonisothermal conditions. Results show that the yield of the nonisothermal process is dependent on the temperature difference applied across the hydrophobic membranes. The production of pure water per square meter of membrane and per hour was equal to 0.55 or 1.2 or 2.0 liters, with a temperature difference of 11 degrees C or 21 degrees C or 28 degrees C, respectively. These results encourage the use of the thermodialysis process in the production of pure water for clinical uses.
