miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215.

BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer. METHOD: We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis. RESULTS: We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis. CONCLUSION: Our analysis showed that miRNAs are altered in metastatic RCCs and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.

Involved-field radiotherapy alone for early-stage non-small-cell lung cancer.

PURPOSE: To describe the outcome of involved-field radiotherapy in patients with early-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A written policy for the radical treatment of early-stage NSCLC with involved-field radiotherapy was adopted at our center in 1986. The sites of known disease were treated to a dose of 52.5 Gy in 20 daily fractions over 4 weeks without elective irradiation of radiologically uninvolved regional nodes. We have reviewed the outcome of this policy in 102 patients treated with radiotherapy alone between 1986 and 1995. RESULTS: The patients' median age was 71.5 years. The stage distribution was as follows: T1, 33.3%; T2, 56.9%; T3, 8.8%; and T4, 1.0%. Only 5 cases were N1; the remainder were N0. Most patients (76.5%) were not surgical candidates because of co-morbidity. Ninety-three percent had a CT of the thorax as part of their initial staging, while mediastinoscopy was performed in only 16.7%. Overall survival was 35% at 3 years and 16% at 5 years. Recurrence free survival was 23.9% at 3 years and 13. 9% at 5 years. Cause-specific survival was 43.5% at 3 years and 26. 8% at 5 years. Of those who recurred, 68.9% had a local component of failure at initial relapse, and 49.2% failed locally without evidence of regional or distant metastases. Isolated regional nodal relapse at initial failure occurred in only 6.6% of recurrences. There were no treatment interruptions due to acute toxicity and no treatment-related deaths. CONCLUSION: Involved-field radiotherapy alone cures a small but significant number of patients with early-stage NSCLC. This approach is recommended in patients who are unfit for surgery and who have severely compromised pulmonary function that would preclude the use of wide-field radiotherapy. The dose used in this study was well tolerated, but produced suboptimal local control rates.

A prospective trial of short-course radiotherapy plus chemotherapy for palliation of dysphagia from advanced esophageal cancer.

PURPOSE: Between 1994 and 1997, 22 patients with dysphagia from advanced incurable esophageal cancer were enrolled in a phase I/II prospective study to assess the palliative benefit and toxicity of a short course of radiotherapy with chemotherapy. METHODS: The study population included 17 men and five women with a median age of 69 (range 43-84). Patients were treated with 30 Gy in ten fractions to the mediastinum with a concurrent single course of chemotherapy (5-FU, 1000 mg/m(2), days 1-4 and mitomycin-C 10 mg/m(2), day 1). Swallowing ability was recorded each day on a self-administered diary card using the five point dysphagia index of the MRC (UK). The median baseline MRC swallowing score was 4 (cannot swallow solids). RESULTS: Treatment was generally well tolerated, but seven (32%) patients had transient worsening of dysphagia scores immediately following treatment because of esophagitis; fifteen (68%) achieved a complete response (score 1: no difficulty on swallowing) with a median time to normalization of swallowing of 5 weeks. For these patients, the median dysphagia-free interval from time of onset of improvement was 11 weeks (range 1-131 weeks) and 11 (73%) remained dysphagia-free until death. The remaining patients had no or marginal improvement. Univariate analysis showed no difference between responders and non-responders with respect to age, gender, or histology. Median survival for the entire study population was 20 weeks (range 3-135 weeks). CONCLUSIONS: This prospective trial shows that a short course of radiotherapy plus chemotherapy may produce complete relief of swallowing difficulties in a substantial proportion of patients with acceptable toxicity.

A real-time audit of radiation therapy in a regional cancer center.

PURPOSE: To report the development, structure, and implementation of a real-time clinical radiotherapy audit of the practice of radiation oncology in a regional cancer center. METHODS AND MATERIALS: Radiotherapy treatment plans were audited by a real-time peer-review process over an 8-year period (1989-1996). The overall goal of the audit was to establish a process for quality assurance (QA) of radiotherapy planning and prescription for individual patients. A parallel process was developed to audit the implementation of intervention-specific radiotherapy treatment policies. RESULTS: A total of 3052 treatment plans were audited. Of these, 124 (4.1%) were not approved by the audit due to apparent errors in radiation planning. The majority of the nonapproved plans (79%) were modified prior to initiating treatment; the audit provided important clinical feedback about individual patient care in these instances. Most of the remaining nonapproved plans were deviations from normal practice due to patient-specific considerations. A further 110 (3.6% of all audited plans) were not approved by the audit due to deviations from radiotherapy treatment policy. A minority of these plans (22%) were modified prior to initiating treatment and the remainder provided important feedback for continuous quality improvement of treatment policies. CONCLUSION: A real-time audit of radiotherapy practice in a regional cancer center setting proved feasible and provided important direct and indirect patient benefits.

Heterosis, maternal and direct effects for postweaning growth traits and carcass performance in rabbit crosses.

SUMMARY: A crossbreeding experiment was carried out in Egypt using a local breed (Baladi Red, BR) and New Zealand White (NZ) to estimate direct heterosis, maternal additive effects and direct sire effects on some growth and carcass traits in rabbits. Data of body weight (at 5, 6, 8, 10, 12 weeks) and daily gains (at intervals of 5-6, 6-8, 8-10, and 10-12 weeks) on 2153 weaned rabbits were collected. Carcass performance at 12 weeks of age (weight and percentages of carcass, giblets, head, fur, blood and viscera) on 213 male rabbits was evaluated. Estimates of coefficients of variation (CV) for most growth and carcass traits were high and ranged from 10.0 to 40.2%. Sire-breed was of considerable importance in the variation of growth traits and some carcass traits, while dam-breed contributed little. Sire-breed × dam-breed interaction affected (P<0.01 or P<0.001) most body weights and gains studied, while it contributed little to the variation of carcass traits. The purebred NZ resulted in rabbits with heavier weights and carcass and with lighter non-edible carcass (blood and viscera) compared to the BR. Heterosis percentages for most growth traits were significant and ranged from 2.5% to 5.0% for body weights and from 0.7% to 9.5% for daily gains. Insignificant positive direct heterosis was observed for most carcass traits. Crossbred rabbits from NZ sires with BR dams were superior to from the reciprocals. Maternal-breed effects on most weights and gains were insignificant, while sire-breed contrasts for some weights and gains proved significant. Postweaning growth and carcass performances of BR-mothered rabbits generally surpassed the NZ mothered, while NZ-sired rabbits were superior at later ages. High edible carcass was observed for BR-sired rabbits, while more non-edible carcass wastes (blood and viscera) for NZ-sired rabbits. Maternal-breed effects appeared to be less important than paternal-breed effects in influencing most weights, gains and carcass traits studied. ZUSAMMENFASSUNG: Heterosis, maternale und direkte Wirkungen bei Wachstums- und Schlachtkörpermerkmalen in Kaninchenkreuzungen Der Kreuzungsversuch wurde mit lokalen ägyptischen Rassen (BR) und Neuseeland Weißen (NZ) zur Schätzung direkter Heterosis, maternaler additiver Wirkungen, direkter Vater-Wirkung auf einige Wachstums- und Schlachtkörpermerkmale von Kaninchen durchgeführt. Angaben über Körpergewicht (5, 6, 8, 10, 12 Wochen) und Zuwachs (Intervalle 5 bis 6, 6 bis 8, 8 bis 10, 10 bis 12 Wochen) wurden von 2153 abgesetzten Kaninchen gewonnen. Die Schlachtkörperleistungen bei 12 Wochen Alter (Gewicht und Anteil von Schlachtkörper, Kopf, Pelz, Blut und Innereien) stammen von 213 männlichen Kaninchen. Schätzungen der Variationskoeffizenten (CV) für meiste Wachstums- und Schlachtkörpermerkmale waren hoch und bewegten sich zwischen 10 und 40,2%. Vaterrasse hatte erheblichen Einfluß auf Unterschiede in Wachstumsrate und einige Schlachtkörpermerkmale, während die Mutterrasse weniger beigetragen hat. Interaktion zwischen beiden beeinflußte die meisten Körpergewichts- und Zuwacnsleistungen, während sie wenig zur Variabilität der Schlachtkörpermerkmale beigetragen hat. Reinrassige NZ waren schwerer und hatten weniger nicht nutzbare Schlachtkörperteile (Blut und Eingeweide) verglichen mit BR. Heterosis-Prozente für die meisten Wachstumsmerkmale waren signifikant und schwankten zwischen 2,5 und 5% für Körpergewicht, 0,7 bis 9,5% für Zuwachs. Insignifikante positive direkte Heterosis wurde für die meisten Schlachtkörpermerkmale beobachtet. Kreuzungskaninchen von NZ Vätern waren den reziproken überlegen. Maternale Wirkungen auf meiste Gewichtsmerkmale waren insignifikant, während Vaterrassenkontraste hierfür signifikant waren. Zuwachs- und Schlachtkörperleistung von BR gesäugten Kaninchen haben im allgemeinen die von NZ gesäugten übertroffen, während von NZ Böcken gezeugte in späteren Altersabschnitten überlegen waren. Hohe Werte für Schlachtkörper wurden für BR gesäugte Kaninchen gefunden, während mehr nicht verzehrbare Abfälle (Blut und Eingeweide) bei NZ gezeugten vorhanden war. Maternale Rassenwirkungen schienen weniger wichtig als paternale zu sein.