Context Pediatric patients with solid tumors can have a significant symptom burden that impacts quality of life and end-of-life care needs. Objectives We evaluated outcomes and symptoms in children with solid tumors, and compared patterns of end-of-life care after implementation of a dedicated institutional pediatric palliative care service. Methods We performed a retrospective cohort study of children with solid tumors treated at St. Jude Children’s Research Hospital, before and after implementation of the institutional Quality of Life/Palliative Care (QoL/PC) Service in January 2007. Patients who died between July 2001- February 2005 (historical cohort; n=134) were compared to those who died between January 2007- January 2012 (QoL/PC cohort; n=57). Results Median time to first QoL/PC consultation was 17.2 months (range, 9–33 months). At consultation, 60% of children were not receiving or discontinued cancer-directed therapy. Within the QoL/PC cohort, 54 patients had documented symptoms; 94% required intervention for ≥ 3 symptoms; 76% received intervention for ≥ 5 symptoms. Eighty-three percent achieved their preferred place of death. Compared to the historical cohort, the QoL/PC cohort had more end-of-life discussions per patient (median, 12 vs. 3; P<0.001), earlier end-of-life discussions, with longer times before do-not-resuscitate orders (median, 195 vs. 2 days; P<0.001), and greater hospice enrollment (71% vs. 46%, P=0.002). Conclusion Although children with solid tumor malignancies may have significant symptom burden towards end of life, positive changes were documented in communication and in places of care and death following implementation of a pediatric palliative care service.
RCC accounts for 9 out of 10 cases of kidney cancer. Approximately 65,150 new cases and 13,680 deaths are expected from this disease in 2013. There is urgent clinical need for better treatment options as RCC responds poorly to current chemotherapy. A major limitation to developing new treatments is that the molecular mechanisms responsible for inappropriate cell survival and chemoresistance are unknown. One pathway suggested to be involved in vitro is the JAK2/STAT. We hypothesized that there would be altered expression of the members and regulators of the JAK/STAT pathways in RCC. We utilized samples from normal (n=14), benign (n=6), and histological Fuhrman grades: Grade 1 (n=3), Grade 2 (n=10), Grade 3 (n=14), and Grade 4 (n=3). We analyzed 31 human RCC samples as well as the normal and benign samples with Affymetrix human gene microarrays and Western Blot technology. The samples were all clear cell renal carcinomas verified by a Beaumont Hospital pathologist. We analyzed 22,148 genes and altered gene expression was then detected by ANOVA taking into account histological stage. We found 170 genes that were differentially expressed in all grades compared to both normal and benign kidney samples. We found both JAK1 and JAK2 mRNA to be highly expressed in the RCC samples compared to the controls. We did not observe any decrease in the mRNA levels or protein expression of the regulatory proteins SOCS1, SOCS3 or SHP‐1. We did find an increase in SHP‐1 serine phosphorylation which is inhibitory in the RCC samples. These data suggest that altered function of the regulators not expression may be involved in RCC. Grant Funding Source: Zafarna Foundation
Diabetes is characterized by vascular and kidney damage. Accumulating evidence suggests that vasoactive substances such as 5‐HT stimulate these pathological processes and plasma levels of 5‐HT are elevated in diabetes. In recent clinical studies 5‐HT2A receptor antagonists substantially decreased albuminuria in type 2 diabetic patients suggesting 5‐HT is mediating pathological processes in vivo. The molecular mechanisms behind the role of 5‐ HT and expression of 5‐HT receptors in vivo in normal and diabetic conditions are currently unknown. Utilizing male Sprague‐ Dawley rats in a type I model of diabetes we used Western blot and immunohistochemical (IHC) analyses to show a significant increase in the expression of 5‐HT2B and 5‐HT2A receptor proteins but not the 5‐HT2C receptor in the diabetic rat kidney. Furthermore, our ex vivo myograph data suggests an increase in the activation of the 5‐HT‐induced intracellular signaling that can stimulate a potentiated contractile response in both thoracic aorta and renal artery in type‐1 diabetic rats which may lead to cardiovascular complications. Investigating both the mechanisms of 5‐HT‐induced intracellular signaling, functional consequences and the expression of 5‐HT receptors, is critical because targeted inhibition may reduce the risk of both kidney damage and vascular abnormality; critical in the treatment for chronic diabetic patients. (NHLBI R00 AKLB)
There is urgent clinical need for better treatment options as RCC responds poorly to chemotherapy and currently has no early detection biomarkers available. We previously demonstrated increased activity of Janus Kinase (JAK2) pathway.We hypothesized that increased JAK2 activity resulted in increased levels of MAP7, linked to chemoresistance, and decreased levels of Uromodulin, a secreted protein linked to renal protection, measurable in the urine. We utilized samples from normal (n=14), benign (n=6), and histological Fuhrman grades: Grade 1 (n=3), Grade 2 (n=10), Grade 3 (n=14), and Grade 4 (n=3). We analyzed samples with Affymetrix human gene microarrays and Western Blot technology. The samples were all clear cell renal carcinomas verified by a pathologist. Altered gene and protein expression was detected by ANOVA taking into account histological stage. We found MAP7 mRNA to be highly expressed in the RCC samples compared to the controls and benign and it increased with severity of the cancer stage. Uromodulin mRNA levels were increased in the benign samples compared to control and were undetectable in all stages of the RCC samples. We saw corresponding changes in the protein levels of both MAP7 and Uromodulin. We also performed an ELISA to measure Uromodulin in the urine and found a significant decreases in stage 3 and 4 RCC samples compared to normal and benign. There were significant increases in Uromodulin in benign, stage 1 and 2 RCC samples compared to control. These data suggest that altered function of these protein may be involved in RCC. Zafarna Fund
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