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1.
World J Urol ; 42(1): 279, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693444

ABSTRACT

PURPOSE: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is associated with a 1-8% risk of post-biopsy sepsis (PBS). A recent study described an isopropyl alcohol needle washing protocol that significantly decreased PBS rates. The current study examined the efficacy of this technique in our clinic population. MATERIALS AND METHODS: Data were reviewed for 1250 consecutive patients undergoing TRUS-Bx at the Charlie Norwood VA Medical Center from January 2017 to January 2023. Needle washing was adopted in February 2021. Complications occurring within 30 days after TRUS-Bx were recorded. RESULTS: There were 912 patients in group 1 (without needle washing) and 338 in group 2 (with needle washing). Groups had equivalent demographic features, and men of African descent comprised 70% of patients. Standard 12 core biopsies were done in 83% and 82% in groups 1 and 2, respectively (p = 0.788). Total complication rates were 4% and 2% in groups 1 and 2, respectively (p = 0.077). There were 13 sepsis events in group 1 (1.4%) and none in group 2 (p = 0.027). Clavien-Dindo Grade I-III complications occurred in 25 (2.7%) and 7 (2.1%) patients in groups 1 and 2, respectively (p = 0.505). Standard antibiotic prophylaxis (PO fluoroquinolone and IM gentamicin) was given in 80% and 86% of patients in groups 1 and 2, respectively (p = 0.030). Subset analysis limited to patients who received standard prophylaxis showed a significant difference in sepsis rates (1.5% vs 0%; p = 0.036). CONCLUSIONS: Adoption of isopropyl alcohol needle washing was associated with a significant decrease in PBS events.


Subject(s)
2-Propanol , Image-Guided Biopsy , Prostate , Sepsis , Humans , Male , Sepsis/prevention & control , Aged , Prostate/pathology , Middle Aged , 2-Propanol/administration & dosage , Retrospective Studies , Image-Guided Biopsy/methods , Prostatic Neoplasms/pathology , Ultrasonography, Interventional , Needles , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology
2.
S D Med ; 77(3): 129-133, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38990797

ABSTRACT

Sotos syndrome is an uncommon congenital overgrowth syndrome characterized by excessive growth in childhood, learning disabilities, and distinct facial features. We present the case of a young male who appeared to have the classic presentation of Sotos syndrome despite a normal genetic workup. Additionally, we present a brief review of overgrowth syndromes in order to highlight potential challenges differentiating these syndromes in clinical practice. Many overgrowth disorders often have similar presentation to Sotos syndrome, so it is important to recognize and identify specific clinical features and perform genetic testing to rule out other disorders, confirm a diagnosis, and choose the appropriate management for patients.


Subject(s)
Sotos Syndrome , Humans , Male , Sotos Syndrome/diagnosis , Sotos Syndrome/genetics , Diagnosis, Differential
3.
S D Med ; 76(1): 28-30, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36897787

ABSTRACT

Statin drugs are commonly used to decrease levels of triglycerides and cholesterol. Common side effects of this medication class are generally mild and include headache, nausea, diarrhea, and myalgia. Rarely, statins have been associated with autoimmune disease resulting in a potentially serious inflammatory myopathy known as statininduced immune-mediated necrotizing myopathy (IMNM). Here, we describe a case of statin-induced IMNM in a 66-year-old man placed on atorvastatin several months prior to CABG surgery. We review the relevant laboratory results, imaging, immunologic, histopathologic findings and treatment strategy of this important disorder.


Subject(s)
Autoimmune Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Muscular Diseases , Myositis , Male , Humans , Aged , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Muscular Diseases/chemically induced , Muscular Diseases/pathology , Autoantibodies/adverse effects , Myositis/chemically induced , Muscles/pathology
4.
S D Med ; 76(2): 86-90, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36898077

ABSTRACT

Focal peripheral neuropathies (FPN) will be encountered by clinical practitioners in all disciplines. While bedside exam skills are greatly beneficial in the diagnostic approach, new options are improving diagnostic accuracy. A variety of management options are available to assist patients with these diverse disorders. Ten less common focal neuropathies are featured in this review.


Subject(s)
Peripheral Nervous System Diseases , Humans , Peripheral Nervous System Diseases/diagnosis
5.
Conserv Biol ; 35(2): 654-665, 2021 04.
Article in English | MEDLINE | ID: mdl-32537779

ABSTRACT

Collisions with buildings cause up to 1 billion bird fatalities annually in the United States and Canada. However, efforts to reduce collisions would benefit from studies conducted at large spatial scales across multiple study sites with standardized methods and consideration of species- and life-history-related variation and correlates of collisions. We addressed these research needs through coordinated collection of data on bird collisions with buildings at sites in the United States (35), Canada (3), and Mexico (2). We collected all carcasses and identified species. After removing records for unidentified carcasses, species lacking distribution-wide population estimates, and species with distributions overlapping fewer than 10 sites, we retained 269 carcasses of 64 species for analysis. We estimated collision vulnerability for 40 bird species with ≥2 fatalities based on their North American population abundance, distribution overlap in study sites, and sampling effort. Of 10 species we identified as most vulnerable to collisions, some have been identified previously (e.g., Black-throated Blue Warbler [Setophaga caerulescens]), whereas others emerged for the first time (e.g., White-breasted Nuthatch [Sitta carolinensis]), possibly because we used a more standardized sampling approach than past studies. Building size and glass area were positively associated with number of collisions for 5 of 8 species with enough observations to analyze independently. Vegetation around buildings influenced collisions for only 1 of those 8 species (Swainson's Thrush [Catharus ustulatus]). Life history predicted collisions; numbers of collisions were greatest for migratory, insectivorous, and woodland-inhabiting species. Our results provide new insight into the species most vulnerable to building collisions, making them potentially in greatest need of conservation attention to reduce collisions and into species- and life-history-related variation and correlates of building collisions, information that can help refine collision management.


Correlaciones de las Colisiones de Aves contra Edificios en Tres Países de América del Norte Resumen Las colisiones contra los edificios causan hasta mil millones de fatalidades de aves al año en los Estados Unidos y en Canadá. Sin embargo, los esfuerzos por reducir estas colisiones se beneficiarían con estudios realizados a grandes escalas espaciales en varios sitios de estudio con métodos estandarizados y considerando las variaciones relacionadas a la historia de vida y a la especie y las correlaciones de las colisiones. Abordamos estas necesidades de investigación por medio de una recolección coordinada de datos sobre las colisiones de aves contra edificios en los Estados Unidos (35), Canadá (3) y México (2). Recolectamos todos los cadáveres y los identificamos hasta especie. Después de retirar los registros de cadáveres no identificados, las especies sin estimaciones poblacionales a nivel distribución y las especies con distribuciones traslapadas en menos de diez sitios, nos quedamos con 269 cadáveres de 64 especies para el análisis. Estimamos la vulnerabilidad a colisiones para 40 especies con ≥2 fatalidades con base en la abundancia poblacional para América del Norte, el traslape de su distribución entre los sitios de estudio y el esfuerzo de muestreo. De las diez especies que identificamos como las más vulnerables a las colisiones, algunas han sido identificadas previamente (Setophaga caerulescens), y otras aparecieron por primera vez (Sitta carolinensis), posiblemente debido a que usamos una estrategia de muestreo más estandarizada que en los estudios previos. El tamaño del edificio y el área del vidrio estuvieron asociados positivamente con el número de colisiones para cinco de ocho especies con suficientes observaciones para ser analizadas independientemente. La vegetación alrededor de los edificios influyó sobre las colisiones solamente para una de esas ocho especies Catharus ustulatus). Las historias de vida pronosticaron las colisiones; el número de colisiones fue mayor para las especies migratorias, insectívoras y aquellas que habitan en las zonas boscosas. Nuestros resultados proporcionan una nueva perspectiva hacia las especies más vulnerables a las colisiones contra edificios, lo que las pone en una necesidad potencialmente mayor de atención conservacionista para reducir estas colisiones y de estudio de las variaciones relacionadas con la especie y la historia de vida y las correlaciones de las colisiones contra edificios, información que puede ayudar a refinar el manejo de colisiones.


Subject(s)
Conservation of Natural Resources , Songbirds , Animals , Canada , Mexico , North America , United States
6.
Opt Express ; 28(22): 32239-32248, 2020 Oct 26.
Article in English | MEDLINE | ID: mdl-33114915

ABSTRACT

Resonant biosensors are attractive for diagnostics because they can detect clinically relevant biomarkers with high sensitivity and in a label-free fashion. Most of the current solutions determine their detection limits in a highly stabilised laboratory environment, which does, however, not apply to real point-of-care applications. Here, we consider the more realistic scenario of low-cost components and an unstabilised environment and consider the related design implications. We find that sensors with lower quality-factor resonances are more fault tolerant, that a filtered LED lightsource is advantageous compared to a diode laser, and that a CMOS camera is preferable to a CCD camera for detection. We exemplify these findings with a guided mode resonance sensor and experimentally determine a limit of detection of 5.8 ± 1.7×10-5 refractive index units (RIU), which is backed up by a model identifying the various noise sources. Our findings will inform the design of high performance, low cost biosensors capable of operating in a real-world environment.


Subject(s)
Biosensing Techniques/economics , Refractometry/economics , Surface Plasmon Resonance/instrumentation , Biosensing Techniques/instrumentation , Equipment Design , Equipment Failure Analysis , Limit of Detection , Refractometry/instrumentation , Reproducibility of Results , Sensitivity and Specificity , Transducers
7.
S D Med ; 73(4): 178-180, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32445306

ABSTRACT

In this report, we present a case of acquired copper deficiency which initially presented as progressive pain and numbness in the patient's lower extremities. The acquired copper deficiency is attributed to a previous bariatric surgery exacerbated by zinc toxicity. A 42-year-old female with a past medical history of type 2 diabetes mellitus, anemia, hypertension, bipolar disorder, attention deficit disorder, pulmonary embolus, fibromyalgia, migraine headaches, and chronic pain as well as a remote past surgical history of gastric bypass procedure presented with progressive pain and numbness in her lower extremities. The patient reported chronic use of zinc supplements. Clinical evaluation revealed abnormal neurologic exam consistent with a myeloneuropathy and anemia. A cervical spine MRI showed increased signal intensity primarily affecting the posterior columns from C2-C6. Laboratory studies confirmed low copper, low ceruloplasmin, and elevated zinc levels. This case is an example of acquired copper deficiency due to previous bariatric surgery exacerbated by zinc ingestion. With an increased prevalence of bariatric surgery, it is important to monitor patients postoperatively for neurologic symptoms potentially due to copper deficiency.


Subject(s)
Bariatric Surgery , Copper , Diabetes Mellitus, Type 2 , Nervous System Diseases , Zinc , Adult , Copper/deficiency , Female , Humans , Nervous System Diseases/etiology , Neurologic Examination , Zinc/administration & dosage , Zinc/adverse effects
8.
J Arthroplasty ; 34(4): 735-742, 2019 04.
Article in English | MEDLINE | ID: mdl-30665832

ABSTRACT

BACKGROUND: Wound complications associated with soft tissue defects following total knee arthroplasty present challenges for the orthopedic surgeon. The scale of early complications include less morbid problems, such as quickly resolving drainage and small superficial eschars, to persistent drainage and full-thickness tissue necrosis, which may require advanced soft tissue coverage. METHODS: This review outlines current wound management strategies and provides an algorithm to help guide treatment and clinical decision-making. CONCLUSION: A surgeon's understanding of soft tissue coverage options is essential in protecting the knee prosthesis from a deep infection and to obtain an optimal functional outcome.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Postoperative Complications/therapy , Skin Transplantation , Surgical Flaps , Algorithms , Debridement , Drainage , Humans , Necrosis , Negative-Pressure Wound Therapy , Wound Healing
9.
S D Med ; 72(9): 393-395, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31581374

ABSTRACT

Glossopharyngeal neuralgia is an underreported condition characterized by discomfort elicited through involvement of the ninthcranial nerve. Triggering phenomena and associated vagal nerve involvement creates the potential for an unexpected clinical presentation. In this case report, we present a 60-year-old male who described a shock-like pain throughout his neck and jaw. The patient initially responded to carbamazepine but the clinical course was complicated by cardiac pauses with syncope requiring pacemaker implantation. Failure of pharmacologic treatment led to surgical intervention.


Subject(s)
Analgesics, Non-Narcotic , Carbamazepine , Glossopharyngeal Nerve Diseases , Neuralgia , Analgesics, Non-Narcotic/therapeutic use , Carbamazepine/therapeutic use , Glossopharyngeal Nerve , Glossopharyngeal Nerve Diseases/diagnosis , Glossopharyngeal Nerve Diseases/drug therapy , Humans , Male , Middle Aged , Pacemaker, Artificial , Syncope
10.
Proc Natl Acad Sci U S A ; 111(40): 14436-41, 2014 Oct 07.
Article in English | MEDLINE | ID: mdl-25246544

ABSTRACT

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is recruited to the TNF receptor 1 to mediate proinflammatory signaling and to regulate TNF-induced cell death. RIPK1 deficiency results in postnatal lethality, but precisely why Ripk1(-/-) mice die remains unclear. To identify the lineages and cell types that depend on RIPK1 for survival, we generated conditional Ripk1 mice. Tamoxifen administration to adult RosaCreER(T2)Ripk1(fl/fl) mice results in lethality caused by cell death in the intestinal and hematopoietic lineages. Similarly, Ripk1 deletion in cells of the hematopoietic lineage stimulates proinflammatory cytokine and chemokine production and hematopoietic cell death, resulting in bone marrow failure. The cell death reflected cell-intrinsic survival roles for RIPK1 in hematopoietic stem and progenitor cells, because Vav-iCre Ripk1(fl/fl) fetal liver cells failed to reconstitute hematopoiesis in lethally irradiated recipients. We demonstrate that RIPK3 deficiency partially rescues hematopoiesis in Vav-iCre Ripk1(fl/fl) mice, showing that RIPK1-deficient hematopoietic cells undergo RIPK3-mediated necroptosis. However, the Vav-iCre Ripk1(fl/fl) Ripk3(-/-) progenitors remain TNF sensitive in vitro and fail to repopulate irradiated mice. These genetic studies reveal that hematopoietic RIPK1 deficiency triggers both apoptotic and necroptotic death that is partially prevented by RIPK3 deficiency. Therefore, RIPK1 regulates hematopoiesis and prevents inflammation by suppressing RIPK3 activation.


Subject(s)
Apoptosis/physiology , Bone Marrow/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/deficiency , Animals , Apoptosis/drug effects , Apoptosis/genetics , Bone Marrow/pathology , Cells, Cultured , Cytokines/blood , Epithelial Cells/cytology , Epithelial Cells/metabolism , Estrogen Antagonists/pharmacology , Flow Cytometry , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Inflammation Mediators/blood , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Necrosis , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Spleen/cytology , Spleen/metabolism , Tamoxifen/pharmacology , Thymus Gland/cytology , Thymus Gland/metabolism , Tumor Necrosis Factor-alpha/pharmacology
11.
Sci Rep ; 14(1): 2816, 2024 02 02.
Article in English | MEDLINE | ID: mdl-38307935

ABSTRACT

Neuroendocrine prostate cancer (NEPC) is a highly lethal variant of castration-resistant prostate cancer (CRPC) with poor survival rates. Current treatment options for NEPC are limited to highly toxic platinum drugs highlighting the urgent need for new therapies. This study aimed to develop a novel therapeutic approach using engineered exosomes against NEPC. Exosomes were modified to target CEACAM5, an NEPC surface antigen, by attaching CEACAM5 antibodies to HEK293T exosomes. These exosomes were loaded with drugs inhibiting EZH2 and the androgen receptor (AR) as recent research shows a persistent role of AR in NEPC wherein it plays a concerted role with EZH2 in driving neuronal gene programs. In vitro experiments with NEPC cell lines demonstrated that CEACAM5-targeted exosomes were specifically taken up by NEPC cells, leading to reduced cellular viability and decreased expression of neuronal markers. Further in vivo tests using a NEPC patient-derived xenograft model (LuCaP145.1) showed significant tumor regression in mice treated with engineered exosomes compared to control mice receiving IgG-labeled exosomes. These results suggest that CEACAM5-engineered exosomes hold promise as a targeted therapy for NEPC. Importantly, our exosome engineering strategy is versatile and can be adapted to target various surface antigens in prostate cancer and other diseases.


Subject(s)
Exosomes , Prostatic Neoplasms , Male , Humans , Animals , Mice , Exosomes/metabolism , HEK293 Cells , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Cell Line, Tumor
12.
J Surg Case Rep ; 2024(2): rjae064, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370595

ABSTRACT

Rezum is a relatively new, minimally invasive approach that utilizes vaporized water to ablate prostatic tissue surrounding the proximal urethra in patients with benign prostatic hyperplasia. However, of the many notable studies involving Rezum's effectiveness in men, none have documented use of Rezum in the transgender community. With a growing population of transgender patients in the USA, prostate treatments will be offered for transgender women on a more regular basis. To the best of our knowledge, we introduce the first case of Rezum being utilized to treat benign prostatic hyperplasia in a patient self-identifying as a woman.

13.
J Urol ; 189(1): 36-42, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23164381

ABSTRACT

PURPOSE: We introduce the concept of trifecta outcomes during robotic/laparoscopic partial nephrectomy, in which the 3 key outcomes of negative cancer margin, minimal renal functional decrease and no urological complications are simultaneously realized. We report serial trifecta outcomes in patients treated with robotic/laparoscopic partial nephrectomy for tumor in a 12-year period. MATERIALS AND METHODS: A total of 534 patients had complete data available and were retrospectively divided into 4 chronologic eras, including the discovery era--139 from September 1999 to December 2003, conventional hilar clamping era--213 from January 2004 to December 2006, early unclamping era--104 from January 2007 to November 2008 and anatomical zero ischemia era--78 from March 2010 to October 2011. Renal functional decrease was defined as a greater than 10% reduction in the actual vs volume predicted postoperative estimated glomerular filtration rate. RESULTS: Across the 4 eras tumors trended toward larger size (2.9, 2.8, 3.1 and 3.3 cm, p = 0.08) and yet the estimated percent of kidney preserved was similar (89%, 90%, 90% and 88%, respectively, p = 0.3). Recent eras had increasingly complex tumors that were more often 4 cm or greater (p = 0.03), centrally located (p <0.009) or hilar (p <0.0001). Nevertheless, with significant technical refinement warm ischemia time decreased serially (36, 32, 15 and 0 minutes, respectively, p <0.0001). Renal functional outcomes were superior in recent eras with fewer patients experiencing a decrease (p <0.0001). Uniquely, actual estimated glomerular filtration rate outcomes exceeded volume predicted estimated glomerular filtration rate outcomes only in the zero ischemia cohort in regard to other eras (-9.5%, -11%, -0.9% and 4.2%, respectively, p <0.001). Positive cancer margins were uniformly low at less than 1%. Urological complications trended lower in recent eras (p = 0.01). Trifecta outcomes occurred more commonly in recent eras (45%, 44%, 62% and 68%, respectively, p = 0.0002). CONCLUSIONS: Trifecta should be a routine goal during partial nephrectomy. Despite increasing tumor complexity, trifecta outcomes of robotic/laparoscopic partial nephrectomy improved significantly in the last decade.


Subject(s)
Kidney Neoplasms/surgery , Laparoscopy , Nephrectomy/methods , Robotics , Humans , Retrospective Studies , Treatment Outcome , Warm Ischemia
14.
J Urol ; 189(5): 1638-42, 2013 May.
Article in English | MEDLINE | ID: mdl-23159462

ABSTRACT

PURPOSE: Renal parenchymal volume decrease after partial nephrectomy is associated with late functional outcomes. We examined the relative effects of resection related and atrophy related volume change on late kidney function. MATERIALS AND METHODS: Data were analyzed from a cohort of 187 patients who underwent open, laparoscopic or robotic partial nephrectomy between 2009 and 2011. Total change in kidney size after surgery was expressed as percent functional volume preservation measured using the cylindrical volume ratio method. Renal atrophy was expressed as parenchymal thickness preservation, and was assessed by measuring parenchymal thickness before and after partial nephrectomy in regions of the operated kidney distant from the site of resection. Standard statistical analyses were conducted to assess relationships among variables. RESULTS: Mean (± SD) percent functional volume preservation was 92% (± 8%), which correlated with a late percent glomerular filtration rate preservation of 91% (± 12%). Mean parenchymal thickness preservation for the cohort was 99% (± 4%). Minimal atrophy was observed in patients with warm ischemia time less than 40 minutes (parenchymal thickness preservation range 98% to 100%). Atrophy was more pronounced in patients with warm ischemia time greater than 40 minutes (parenchymal thickness preservation 96%). Multivariate regression analysis showed correlation of percent functional volume preservation with atrophy; correlation of warm ischemia time, diameter-axial-polar nephrometry score and atrophy with percent functional volume preservation; and correlation of Charlson score and diameter-axial-polar nephrometry score with percent decrease in glomerular filtration rate. CONCLUSIONS: In most patients with warm ischemia time less than 40 minutes the incidence of parenchymal atrophy was minimal, suggesting that the kidney volume decrease after partial nephrectomy was predominantly resection related. Kidney volume decrease after partial nephrectomy in patients with warm ischemia time greater than 40 minutes appeared to be due to a combination of resection related and atrophy related changes.


Subject(s)
Kidney/pathology , Nephrectomy/adverse effects , Nephrectomy/methods , Warm Ischemia , Atrophy/etiology , Female , Humans , Male , Middle Aged , Prospective Studies
15.
Ann Surg Oncol ; 20(5): 1456-61, 2013 May.
Article in English | MEDLINE | ID: mdl-23184291

ABSTRACT

PURPOSE: Adrenocortical carcinoma (ACC) is a rare and clinically aggressive cancer. Previous studies reported increased recurrence rates associated with laparoscopic adrenalectomy (LA). We evaluated a single-center experience of LA versus open adrenalectomy (OA) for the management of ACC. METHODS: Between 1993 and 2011, 44 consecutive patients with primary ACC were treated at our institution. Baseline patient characteristics and surgical and pathological outcomes were compared between OA and LA groups. Multivariable Cox proportional hazards analysis was used to estimate the association between OA versus LA with recurrence-free and overall survival. RESULTS: Eighteen and 26 patients underwent LA and OA, respectively. Patients who underwent OA had larger tumors and more advanced clinical stage compared with LA group. During a median follow-up of 22 months, 22 recurrences and 26 deaths were observed. The 2-year, recurrence-free and overall survivals for OA and LA were 60 vs. 39 % (P = 0.7) and 54 vs. 58 % (P = 0.6), respectively. After adjusting for clinical stage, OA was associated with lower risk of recurrence (hazard ratio (HR) 0.4; 95 % confidence interval (CI) 0.2-1.2; P = 0.099) and improved overall survival (HR 0.5; 95 % CI 0.2-1.2; P = 0.122) compared with LA, although differences were not statistically significant. CONCLUSIONS: A nonstatistically significant increase in recurrence and death was observed among patients undergoing LA versus OA after adjusting for clinical stage. The rarity of this disease limits the ability to assess for significant differences in a single-institution series. Patients with suspected ACC should be considered for OA.


Subject(s)
Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Carcinoma/surgery , Neoplasm Recurrence, Local , Adrenal Gland Neoplasms/pathology , Adult , Aged , Carcinoma/secondary , Disease-Free Survival , Female , Hospitals, High-Volume , Humans , Kaplan-Meier Estimate , Laparoscopy , Male , Middle Aged , Multivariate Analysis , Neoplasm, Residual , Proportional Hazards Models , Treatment Outcome
16.
Sci Rep ; 13(1): 12427, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37528206

ABSTRACT

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms affect a large percentage of the male population and places a substantial burden on the world health system. Current therapies include 5-alpha reductase inhibitors and alpha-blockers that are only partially effective and pose a huge economic burden, emphasizing the urgent need for effective, economical therapies. We isolated nanovesicles from pomegranate juice (Punica Granatum) (referred to as 'POM-NVs') and report to our knowledge for the first time, that these vesicles possess therapeutic potential against BPH. Following extensive characterization of POM-NVs, we tested their therapeutic potential in vitro using BPH1 cell line and identified a potential anti-proliferative and pro-apoptotic effect. We further tested these vesicles using a clinically relevant xenograft mouse BPH model derived from human BPH tissues. Remarkably, POM-NVs could reverse the BPH phenotype conferred by TGF-ß mediated signaling and induced epithelial-to-mesenchymal (EMT) reversal, leading to the restoration of prostate epithelial states in vivo and in vitro. Furthermore, these vesicles attenuated bone morphogenic protein 5 (BMP5) signaling, a cardinal alteration that is instrumental in driving BPH. Considering the large incidences of BPH and its associated economic burdens, our study has important implications and can potentially improve the clinical management of BPH.


Subject(s)
Pomegranate , Prostatic Hyperplasia , Humans , Male , Mice , Animals , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism , Mice, Nude , Heterografts , Prostate/metabolism
17.
Cancers (Basel) ; 16(1)2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38201476

ABSTRACT

The molecular basis of prostate cancer (PCa) progression from the primary disease to metastatic castration-resistant prostate cancer (CRPC) followed by therapy-induced neuroendocrine prostate cancer is not fully understood. In this study, we elucidate the role of miR-410, a little-studied microRNA located on chromosome 14q32.31 within the DLK1-DIO3 cluster, in PCa. miR-410 expression analyses in primary and metastatic PCa tissues and cell lines show that its levels are decreased in initial stages and increased in advanced PCa. Functional studies were performed in a series of PCa cell lines. In LNCaP cells, miR-410 overexpression led to decreases in cellular viability, proliferation, invasiveness, and migration. On the other hand, miR-410 overexpression in PC3 and C42B cells led to increased viability, proliferation, and invasiveness. Our data suggest that miR-410 represses epithelial-to-mesenchymal transition (EMT) in LNCaP cells by directly repressing SNAIL. However, it promotes EMT and upregulates PI3K/Akt signaling in PC3 and C42B cells. In vivo studies with PC3 xenografts support an oncogenic role of miR-410. These data suggest that miR-410 acts as a tumor suppressor in the initial stages of PCa and play an oncogenic role in advanced PCa. Our findings have important implications in understanding the molecular basis of PCa progression with potential translational implications.

18.
Breast Cancer Res ; 14(5): R126, 2012 Sep 19.
Article in English | MEDLINE | ID: mdl-22992387

ABSTRACT

INTRODUCTION: NOTCH activation has been recently implicated in human breast cancers, associated with a poor prognosis, and tumor-initiating cells are hypothesized to mediate resistance to treatment and disease relapse. To address the role of NOTCH1 in mammary gland development, transformation, and mammary tumor-initiating cell activity, we developed a doxycycline-regulated mouse model of NOTCH1-mediated mammary transformation. METHODS: Mammary gland development was analyzed by using whole-mount analysis and by flow cytometry in nulliparous transgenic mice maintained in the presence/absence of doxycycline (or intracellular NOTCH1). Mammary tumors were examined histologically and immunophenotyped by staining with antibodies followed by flow cytometry. Tumors were transplanted into mammary fat pads under limiting dilution conditions, and tumor-initiating cell frequency was calculated. Mammary tumor cells were also plated in vitro in a tumorsphere assay in the presence/absence of doxycycline. RNA was isolated from mammary tumor cell lines cultured in the presence/absence of doxycycline and used for gene-expression profiling with Affymetrix mouse arrays. NOTCH1-regulated genes were identified and validated by using quantitative real-time polymerase chain reaction (PCR). Mammary tumor-bearing mice were treated with doxycycline to suppress NOTCH1 expression, and disease recurrence was monitored. RESULTS: Similar to published studies, we show that constitutive expression of human intracellular NOTCH1 in the developing mouse mammary gland inhibits side branching and promotes luminal cell fate. These mice develop mammary adenocarcinomas that express cytokeratin (CK) 8/18. In vivo limiting-dilution analyses revealed that these mammary tumors exhibit functional heterogeneity and harbor a rare (1/2,978) mammary tumor-initiating cell population. With this dox-regulated NOTCH1 mammary tumor model, we demonstrate that NOTCH1 inhibition results in mammary tumor regression in vivo and prevents disease recurrence in four of six tumors tested. Consistent with the in vivo data, NOTCH1 inhibition reduces mammary tumorsphere activity in vitro. We also identify the embryonic stem cell transcription factor Nanog as a novel NOTCH1-regulated gene in tumorspheres and in mouse and human breast cancer cell lines. CONCLUSIONS: These data indicate that NOTCH1 inhibition results in mammary tumor regression in vivo and interferes with disease recurrence. We demonstrate that NOTCH1-transformed mouse mammary tumors harbor a rare mammary tumor-initiating population and that NOTCH1 contributes to mammary tumor-initiating activity. This work raises the possibility that NOTCH therapeutics may target mammary tumor-initiating cells in certain human breast cancer subtypes.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Receptor, Notch1/metabolism , Animals , Apoptosis/genetics , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Transformation, Neoplastic , Disease Models, Animal , Disease Progression , Female , Gene Expression , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Male , Mice , Mice, Transgenic , Nanog Homeobox Protein , Neoplasm Recurrence, Local , Neoplastic Stem Cells/metabolism , Receptor, Notch1/genetics , Spheroids, Cellular , Tumor Cells, Cultured
19.
J Urol ; 188(2): 384-90, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22698624

ABSTRACT

PURPOSE: The R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) and centrality index nephrometry scores enable systematic, objective assessment of anatomical tumor features. We systematically compared these systems using item analysis test theory to optimize scoring methodology. MATERIALS AND METHODS: Analysis was based on 299 patients who underwent partial nephrectomy from 2007 to 2011 and met study inclusion criteria. Percent functional volume preservation, and R.E.N.A.L. and centrality index scores were measured. Late percent glomerular filtration rate preservation was calculated as the ratio of the late to the preoperative rate. Interobserver variability analysis was done to assess measurement error. All data were statistically analyzed. RESULTS: A novel scoring method termed DAP (diameter-axial-polar) nephrometry was devised using a data based approach. Mean R.E.N.A.L., centrality index and DAP scores for the cohort were 7.3, 2.5 and 6 with 84%, 90% and 95% interobserver agreement, respectively. The DAP sum score and all individual DAP scoring components were associated with the clinical outcome, including percent functional volume preservation, warm ischemia time and operative blood loss. DAP scoring criteria allowed for the normalization of score distributions and increased discriminatory power. DAP scores showed strong linear associations with percent functional volume preservation (r(2) = 0.97) and late percent glomerular filtration rate preservation (r(2) = 0.81). Each 1 unit change in DAP score equated to an average 4% change in kidney volume. CONCLUSIONS: DAP nephrometry integrates the optimized attributes of the R.E.N.A.L. and centrality index scoring systems. DAP scoring was associated with simplified methodology, decreased measurement error, improved performance characteristics, improved interpretability and a clear association with volume loss and late function after partial nephrectomy.


Subject(s)
Kidney Neoplasms/pathology , Kidney/pathology , Nephrectomy , Organ Sparing Treatments , Adult , Aged , Cohort Studies , Female , Glomerular Filtration Rate/physiology , Humans , Kidney Neoplasms/surgery , Laparoscopy , Male , Middle Aged , Organ Size , Predictive Value of Tests , Robotics , Tumor Burden
20.
J Urol ; 188(1): 39-44, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22578726

ABSTRACT

PURPOSE: Functional volume preservation after partial nephrectomy is a primary determinant of kidney function. We identified tumor features, including R.E.N.A.L. (radius for tumor size as maximal diameter, exophytic/endophytic tumor properties, nearness of deepest portion of tumor to collecting system or sinus, anterior/posterior descriptor and location relative to polar line) and centrality index nephrometry scores, associated with volume loss after partial nephrectomy. MATERIALS AND METHODS: A chart and imaging review was done for 237 patients who underwent partial nephrectomy from 2007 to 2010 and met study inclusion criteria. R.E.N.A.L. and centrality index nephrometry scores were measured in all patients. Percent functional volume preservation was estimated a median of 1.4 years after surgery using the cylindrical volume ratio method. Statistical analysis was done to study associations. RESULTS: Independent tumor features associated with percent functional volume preservation included tumor diameter (p < 0.001) and the distance from tumor periphery to kidney center (p = 0.02). R.E.N.A.L. and centrality index scores were associated with percent functional volume preservation (each p < 0.001). Nephrometry scores were also associated with nadir and late percent glomerular filtration rate preservation. Tumors classified as highly complex, with a centrality index score of 1.5 or less and a R.E.N.A.L. score of 10 or greater, were associated with an average 28% to 30% functional parenchymal volume loss of operated kidneys. A mean 8% difference in percent functional volume preservation was observed among low, intermediate and high tumor complexity categories for R.E.N.A.L. and centrality index scores. CONCLUSIONS: R.E.N.A.L. and centrality index nephrometry scores were associated with changes in the percent functional volume preservation and the perioperative functional decrease. Nephrometry scores performed better than diameter alone on statistical analysis. Nephrometry scores may be useful to estimate the likelihood of operative volume loss and by proxy the functional outcome.


Subject(s)
Kidney Neoplasms/diagnostic imaging , Kidney/physiology , Nephrectomy/methods , Organ Size/physiology , Recovery of Function , Tomography, X-Ray Computed/methods , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Kidney Neoplasms/physiopathology , Kidney Neoplasms/surgery , Male , Middle Aged , Postoperative Period , Prognosis , Retrospective Studies
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