Rustin Massoudi, MD

All Publications

• Giant renal angiomyolipoma in a solitary kidney CANADIAN JOURNAL OF UROLOGY Sohlberg, E., Sun, A., Massoudi, R., Prado, K., Skinner, E. 2018; 25 (6): 9614–16

  View details for Web of Science ID 000454188000010

• Multiregion Quantification of Extracellular Signal-regulated Kinase Activity in Renal Cell Carcinoma. European urology oncology Hoerner, C. R., Massoudi, R., Metzner, T. J., Stell, L., O'Rourke, J. J., Kong, C. S., Liliental, J. E., Brooks, J. D., Sabatti, C., Leppert, J. T., Fan, A. C. 2018

  Abstract

  To personalize treatment for renal cell carcinoma (RCC), it would be ideal to confirm the activity of druggable protein pathways within individual tumors. We have developed a high-resolution nanoimmunoassay (NIA) to measure protein activity with high precision in scant specimens (eg, fine needle aspirates [FNAs]). Here, we used NIA to determine whether protein activation varied in different regions of RCC tumors. Since most RCC therapies target angiogenesis by inhibiting the vascular endothelial growth factor (VEGF) receptor, we quantified phosphorylation of extracellular signal-regulated kinase (ERK), a downstream effector of the VEGF signaling pathway. In 90 ex vivo FNA biopsies sampled from multiple regions of 38 primary clear cell RCC tumors, ERK phosphorylation differed among patients. In contrast, within individual patients, we found limited intratumoral heterogeneity of ERK phosphorylation. Our results suggest that measuring ERK in a single FNA may be representative of ERK activity in different regions of the same tumor. As diagnostic and therapeutic protein biomarkers are being sought, NIA measurements of protein signaling may increase the clinical utility of renal mass biopsy and allow for the application of precision oncology for patients with localized and advanced RCC. PATIENT SUMMARY: In this report, we applied a new approach to measure the activity of extracellular signal-regulated kinase (ERK), a key cancer signaling protein, in different areas within kidney cancers. We found that ERK activity varied between patients, but that different regions within individual kidney tumors showed similar ERK activity. This suggests that a single biopsy of renal cell carcinoma may be sufficient to measure protein signaling activity to aid in precision oncology approaches.

  View details for DOI 10.1016/j.euo.2018.09.011

  View details for PubMedID 31412000

• Preclinical Testing of a Combination Stone Basket and Ureteral Balloon to Extract Ureteral Stones JOURNAL OF ENDOUROLOGY Massoudi, R., Metzner, T. J., Bonneau, B., Ngo, T. C., Shinghal, R., Leppert, J. T. 2018; 32 (2): 96–99

  Abstract

  We have developed the Peralta Stone Extraction System to increase the safety of ureteral stone extraction. The device combines a nitinol stone basket and low-pressure balloon into a single device. After visualization, the stone is captured in the tipless nitinol basket and enveloped by a low-pressure balloon. We tested the performance of device prototypes in a porcine model using stone mimics with diameters ranging from 4.2 to 6.2 mm. Stones extracted with the device required less force when compared with stones in a standard ureteral stone basket. The force reduction was most pronounced for stones greater than 4.2 mm in diameter, and when traversing a ureteral stenosis model. In conclusion, a combination stone basket and balloon device may provide a new and safer way to extract ureteral stones.

  View details for PubMedID 29216731

• INTRA-TUMOR HETEROGENEITY IN RENAL CELL CARCINOMA: IMPLICATIONS FOR PROTEOMIC ANALYSIS OF RENAL MASS BIOPSIES Massoudi, R., Hoerner, C., Metzner, T., O'Rourke, J., Curtis, R., Stell, L., Sabatti, C., Brooks, J., Fan, A., Leppert, J. ELSEVIER SCIENCE INC. 2017: E496–E497

  View details for DOI 10.1016/j.juro.2017.02.1184

  View details for Web of Science ID 000398276602070

• Recovery of a Missile Embolus From the Right Ventricle. Annals of thoracic surgery Marshall, C. D., Ma, M. R., Park, J., Sheckter, C. C., Massoudi, R. A., Ligman, C. M., Jou, R. M., Ogden, W. D. 2017; 103 (1): e69-e71

  Abstract

  Missile embolism is a clinical entity in which a projectile object enters a blood vessel and is carried to a distant part of the body. We present a case of the discovery of an iliac vein to right ventricle missile embolus in a young man, with successful extraction through a right atriotomy. We provide a historical overview of the literature concerning missile embolism, and we argue that whereas acute embolized projectiles should be removed in almost all cases, it may be reasonable to simply observe an asymptomatic chronic missile embolus.

  View details for DOI 10.1016/j.athoracsur.2016.06.107

  View details for PubMedID 28007279

• Male Infertility: a Harbinger of Future Health Current Sex Health Reports Dallas, K., Massoudi, R., Eisenberg, M. 2016; 8 (3)
• What is the Incidence of Kidney Stones after Chemotherapy in Patients with Lymphoproliferative or Myeloproliferative Disorders? INTERNATIONAL BRAZ J UROL Mirheydar, H. S., Banapour, P., Massoudi, R., Palazzi, K. L., Jabaji, R., Reid, E. G., Millard, F. E., Kane, C. J., Sur, R. L. 2014; 40 (6): 772-780

  Abstract

  This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy.From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not.A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316). Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013), calcium (p<0.001)), and potassium (p=0.039) levels were higher in stone formers. Diabetes mellitus (p<0.001), hypertension (p=0.003), and hyperlipidemia (p<0.001) were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone.We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy.

  View details for DOI 10.1590/S1677-5538.IBJU.2014.06.08

  View details for Web of Science ID 000348607500008

  View details for PubMedID 25615245

• Exome Capture Reveals ZNF423 and CEP164 Mutations, Linking Renal Ciliopathies to DNA Damage Response Signaling CELL Chaki, M., Airik, R., Ghosh, A. K., Giles, R. H., Chen, R., Slaats, G. G., Wang, H., Hurd, T. W., Zhou, W., Cluckey, A., Gee, H. Y., Ramaswami, G., Hong, C., Hamilton, B. A., Cervenka, I., Ganji, R. S., Bryja, V., Arts, H. H., van Reeuwijk, J., Oud, M. M., Letteboer, S. J., Roepman, R., Husson, H., Ibraghimov-Beskrovnaya, O., Yasunaga, T., Walz, G., Eley, L., Sayer, J. A., Schermer, B., Liebau, M. C., Benzing, T., Le Corre, S., Drummond, I., Janssen, S., Allen, S. J., Natarajan, S., O'Toole, J. F., Attanasio, M., Saunier, S., Antignac, C., Koenekoop, R. K., Ren, H., Lopez, I., Nayir, A., Stoetzel, C., Dollfus, H., Massoudi, R., Gleeson, J. G., Andreoli, S. P., Doherty, D. G., Lindstrad, A., Golzio, C., Katsanis, N., Pape, L., Abboud, E. B., Al-Rajhi, A. A., Lewis, R. A., Omran, H., Lee, E. Y., Wang, S., Sekiguchi, J. M., Saunders, R., Johnson, C. A., Garner, E., Vanselow, K., Andersen, J. S., Shlomai, J., Nurnberg, G., Nurnberg, P., Levy, S., Smogorzewska, A., Otto, E. A., Hildebrandt, F. 2012; 150 (3): 533-548

  Abstract

  Nephronophthisis-related ciliopathies (NPHP-RC) are degenerative recessive diseases that affect kidney, retina, and brain. Genetic defects in NPHP gene products that localize to cilia and centrosomes defined them as "ciliopathies." However, disease mechanisms remain poorly understood. Here, we identify by whole-exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing NPHP-RC. All three genes function within the DNA damage response (DDR) pathway. We demonstrate that, upon induced DNA damage, the NPHP-RC proteins ZNF423, CEP164, and NPHP10 colocalize to nuclear foci positive for TIP60, known to activate ATM at sites of DNA damage. We show that knockdown of CEP164 or ZNF423 causes sensitivity to DNA damaging agents and that cep164 knockdown in zebrafish results in dysregulated DDR and an NPHP-RC phenotype. Our findings link degenerative diseases of the kidney and retina, disorders of increasing prevalence, to mechanisms of DDR.

  View details for DOI 10.1016/j.cell.2012.06.028

  View details for Web of Science ID 000307301400013

  View details for PubMedID 22863007

• Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers AMERICAN JOURNAL OF MEDICAL GENETICS PART A Zaki, M. S., Sattar, S., Massoudi, R. A., Gleeson, J. G. 2011; 155A (12): 3042-3049

  Abstract

  Disorders within the "ciliopathy" spectrum include Joubert (JS), Bardet-Biedl syndromes (BBS), and nephronophthisis (NPHP). Although mutations in single ciliopathy genes can lead to these different syndromes between families, there have been no reports of phenotypic discordance within a single family. We report on two consanguineous families with discordant ciliopathies in sibling. In Ciliopathy-672, the older child displayed dialysis-dependent NPHP whereas the younger displayed the pathognomonic molar tooth MRI sign (MTS) of JS. A second branch displayed two additional children with NPHP. In Ciliopathy-1491, the oldest child displayed classical features of BBS whereas the two younger children displayed the MTS. Importantly, the children with BBS and NPHP lacked MTS, whereas children with JS lacked obesity or NPHP, and the child with BBS lacked MTS and NPHP. Features common to all three disorders included intellectual disability, postaxial polydactyly, and visual reduction. The variable phenotypic expressivity in this family suggests that genetic modifiers may determine specific clinical features within the ciliopathy spectrum.

  View details for DOI 10.1002/ajmg.a.34173

  View details for Web of Science ID 000297200300023

  View details for PubMedID 22002901

• Nonviral gene vector formation in monodispersed picolitre incubator for consistent gene delivery LAB ON A CHIP Hsieh, A. T., Hori, N., Massoudi, R., Pan, P. J., Sasaki, H., Lin, Y. A., Lee, A. P. 2009; 9 (18): 2638-2643

  Abstract

  A novel picolitre incubator based microfluidic system for consistent nonviral gene carrier formulation is presented. A cationic lipid-based carrier is the most attractive nonviral solution for delivering plasmid DNA, shRNA, or drugs for pharmaceutical research and RNAi applications. The size of the cationic lipid and DNA complex (CL-DNA), or the lipoplex, is one of the important variations for consistency of gene transfection. CL-DNA size, in turn, may be controlled by factors such as the cationic lipid and DNA mixing order, mixing rate, and mixture incubation time. The Picolitre Microfluidic Reactor and Incubator (PMRI) system described here is able to control these parameters in order to create homogeneous CL-DNA. Compared with conventional CL-DNA preparation techniques involving hand-shaking or vortexing, the PMRI system demonstrates a greater ability to constantly and uniformly mix cationic lipids and DNA simultaneously. After mixing in the picolitre droplet reactors, the cationic lipid and DNA is incubated within the picolitre incubator to form CL-DNA. The PMRI generates a narrower size distribution band, while also turning the sample loading, mixing and incubation steps into an integrated process enabling the consistent formation of CL-DNA. The coefficient of variation (CV) of transfection efficiency is 0.05 and 0.30 for PMRI-based and conventional methods, respectively. In addition, this paper demonstrates that the gene transfection efficiency of lipoplex created in the PMRI is more reproducible.

  View details for DOI 10.1039/b823191e

  View details for Web of Science ID 000269289600004

  View details for PubMedID 19704978