Does bilateral Wilms' tumor involving the collecting system in children have a worse prognosis?

BACKGROUND: The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms' tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. METHODS: Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. RESULTS: Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). CONCLUSIONS: To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.

Can digital finance development drive green transformation in manufacturing? Evidence from China.

Digital finance is a product of emerging technology-enabled innovation in financial services and has a critical impact on the green transformation of the manufacturing industry. We propose a new efficiency measurement model based on the slacks-based measure (SBM) to measure the efficiency of green transformation on regional manufacturing. Chinese interprovincial data from 2010 to 2019 were obtained for the study. In addition, we estimated the effect of digital finance on green transformation of manufacturing using a benchmark panel model. Finally, considering the regional heterogeneity and spatial effects of green transformation efficiency in the manufacturing industry, we constructed a spatial Durbin model based on an economic-geographic nested spatial weight matrix to analyze the spatial influence of digital finance on green transformation in the manufacturing industry. The results show that the green transformation of the manufacturing industry has significant positive spatial spillover effects owing to the existence of competition, demonstration, and economic correlation effects among regions.

A flexible wearable self-supporting hybrid supercapacitor device based on hierarchical nickel cobalt sulfide@C electrode.

A flexible wearable electrode consisting of nickel-cobalt sulfide (NCS) nanowires was fabricated in this study. Self-supporting NCS was grown in situ on porous carbon nanofibers without a binder as a novel material for supercapacitor electrodes. The NCS nanowires were grown using cyclic voltammetry electrodeposition, which proved to be a fast and environmentally friendly method with good controllability of the material structure. One-dimensional carbon nanofibers (C) have high surface-area-to-volume ratios, short ion transmission distances, excellent mechanical strengths, and remarkable flexibilities. Moreover, the NCS@C flexible electrode exhibited a synergetic effect with the active compounds, and the dense active sites were uniformly distributed across the entire surface of the carbon fibers, enabling rapid electron transport and enhancing the electrochemical properties of the NCS@C nanowires. The NCS@C achieved specific capacitances of 334.7 and 242.0 mAh g-1 at a current density of 2 A g-1 and high current densities (up to 40 A g-1), respectively, corresponding to a 72.3% retention rate. An NCS@C-nanofilm-based cathode and an activated-carbon-based anode were used to fabricate a flexible asymmetric supercapacitor. The device exhibited high energy and power densities of 12.91 Wh kg-1 and 358 W kg-1, respectively.

A radiomics nomogram for preoperative prediction of nephron-sparing surgery in patients with bilateral Wilms tumor.

Background: Bilateral Wilms tumor (BWT) is a relatively rare malignant renal tumor in children. Nephron-sparing surgery (NSS) is the preferred surgical approach for treating BWT, but lacks uniform surgical indications worldwide. This study aimed to summarize the clinical and imaging features of BWT children, establish a radiomics nomogram, and predict the feasibility of NSS for improving outcomes. Methods: A 12-year retrospective single-center review was conducted on clinical data and preoperative imaging features of BWT patients. The tumor kidneys were divided into NSS and non-NSS groups. Logistic regression analysis was performed to identify independent predictors and develop a prediction model of the feasibility of NSS in BWT patients. A radiomics nomogram was constructed and internally validated by the parametric bootstrapping method. Results: A total of 58 BWT patients (115 renal units) were included in this study. After evaluations based on preoperative imaging and clinical data, 94 renal units underwent NSS with negative resection margins and were included in the NSS group, whereas 16 renal units with positive resection margins, macroscopic residual, or total nephrectomies were included in the non-NSS group. Tumor size [odds ratio (OR): 0.540, 95% confidence interval (CI): 0.308-0.945], relationship with the collecting system (OR: 0.013, 95% CI: 0.0004-0.370), and remaining renal parenchyma (RRP) proportion (OR: 71.23, 95% CI: 1.632-3108.8) were identified as independent predictors for NSS. A nomogram was constructed based on these factors, which demonstrated great consistency between the predicted and observed feasibility of NSS. The model presented with good discriminative ability [area under the curve (AUC), 0.982]. The decision curve analysis (DCA) revealed the clinical usefulness of the model. Conclusions: This study analyzed the clinical and preoperative imaging data of BWT patients and identified three independent predictors for the feasibility of NSS, including tumor size, relationship with the collecting system, and residual renal parenchyma proportion. The radiomics nomogram established in this study can provide individualized predictions to assist clinicians in making better decisions and improving patient outcomes.

Treatment of bilateral Wilms' tumor in children: how to improve the application of nephron-sparing surgery.

PURPOSE: To summarize the experience of nephron-sparing surgery (NSS) for bilateral Wilms tumors (BWT) in children. METHODS: This study included children with BWT admitted to our hospital between January 2008 and June 2022. The details of the treatments and outcomes were analyzed. RESULTS: In all, 70 patients (39 males and 31 females) were enrolled, including 66 patients with synchronous tumors and 4 patients with metachronous tumors. The median age at diagnosis was 13 (3-75) months. Overall, 59 patients received preoperative chemotherapy and 45.8% (54/118) of the 118 sides of WT achieved a partial response (PR). Of the 70 patients, 48 (68.6%) underwent bilateral NSS and 22 (31.4%) underwent unilateral NSS and contralateral total nephrectomy. The proportion of bilateral NSS in the preoperative chemotherapy group was significantly higher than in the non-chemotherapy group (P = 0.031). Additionally, there were 26, 25, 14, and 5 cases of stage I, stage II, stage III, and stage IV, respectively. Among the 70 children, 16 had a recurrence, and 8 died. The 4 years EFS and OS were 67.9% and 89.3%, respectively. CONCLUSIONS: The long-term survival rates of patients with BWT improved. Hence, preoperative chemotherapy should be administered to enhance the use of NSS in BWT.

Hydronephrosis in pediatric horseshoe kidneys: a comparative analysis of open and laparoscopic pyeloplasty and the influence of obstruction causes.

Background: Horseshoe kidney (HSK) represents a unique challenge for performing pyeloplasty due to its anomalous anatomy. Our study aimed to report our results in treating children with hydronephrosis in HSK and to investigate the differences in prognosis based on the cause of obstruction and the surgical approach. We also aimed to share our experiences by characterizing the success rates and complications after surgery. Methods: We retrospectively reviewed the clinical data of hydronephrosis patients with HSK who were treated with pyeloplasty from August 2009 to June 2022. The patients were grouped according to different surgical methods and causes of obstruction, and then the clinical characteristics and outcomes were analyzed. Results: Thirty-one patients were included in this retrospective cohort observational study, and surgical success was achieved in 80.6% (25/31) of patients. There was no significant difference in complications between open pyeloplasty (OP) and laparoscopic pyeloplasty (LP) groups (2/16 vs. 4/15, P=0.374). At 6 and 12 months postoperatively, both OP and LP groups experienced a decrease in anteroposterior pelvic diameter (APD) and the ratio of APD to the thickness of renal parenchyma (P/C ratio), accompanied by an increase in renal parenchymal thickness. Two patients of reobstruction were caused by missed crossing vessels in primary operation. The success rate of patients with crossing vessels (62.5%) was significantly lower than that of patients without crossing vessels (100%) (P=0.018). Conclusions: Our study found that intrinsic obstruction, crossing vessels, and high insertion were the main causes of hydronephrosis in HSK, with missed crossing vessels being the primary cause of reobstruction. Our results demonstrate that both OP and LP are safe and effective in treating hydronephrosis in HSK patients.

Phenotype expansion of variants affecting p38 MAPK signaling in hypospadias patients.

BACKGROUND: Hypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias. RESULTS: A novel BRAF variant (NM_004333.6: c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohort of sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias. CONCLUSION: Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.

Quantitative assessment of renal perfusion in children with UPJO by contrast enhanced ultrasound: A pilot study.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a new potential modality for the quantitative evaluation of the microvascular perfusion of a parenchymal organ. OBJECTIVE: To prospectively and quantitatively analyse the role of CEUS in evaluating renal perfusion for assessing renal function in children with ureteropelvic junction obstruction (UPJO). METHODS: The study protocol was approved by the local ethics committee, and written informed consent was obtained from the patients' parents or guardians. Ultrasonography, CEUS, and radioisotope renography were performed for 51 children (42 boys, 9 girls; mean age, 6.75 ± 4.14 years) with unilateral UPJO. The slope of the ascending curve (A), time to peak (TTP), peak intensity (PI), and area under the curve (AUC) were recorded during CEUS; quantitative data were calculated by QLab system (semiautomated border tracking, Philips Healthcare) software. Sensitivity and specificity values were determined for CEUS with respect to radioisotope renography. RESULTS: CEUS was used to evaluate 102 kidneys in 51 patients, for which the perfusion time-intensity curve (TIC) was determined. The TIC of renal cortical perfusion in all groups showed an asymmetrical single-peak curve, which could be clearly distinguished between the experimental group and the control group. Compared with the control group, the experimental group showed a markedly prolonged TTP but a significantly decreased A (P < 0.05). There was no significant correlation between the AUC, PI and differential renal function (DRF), but the correlation coefficient between TTP, A and DRF remained significant (p < 0.001).The receiver operating characteristic (ROC) curves drawn to differentiate DRF using the TTP value yielded an area under the ROC curve (AUROC) of 0.86. For a quantitative assessment of DRF less than 40% by CEUS, the sensitivity and specificity values were 92.86% and 76.14%, respectively. DISCUSSION: Unlike in previous studies, no significant difference in the AUC or PI was found between the control group and the experimental group in this study (P > 0.05). Renal blood perfusion could not be evaluated overall by CEUS. Parenchymal thinning may be considered a limitation to CEUS. CONCLUSIONS: This preliminary experience represents the first report of evaluating the diagnostic value of CEUS in assessing renal function in children with UPJO. CEUS is a highly sensitive, rapid, and cost-effective diagnostic imaging modality for detecting and monitoring renal function noninvasively.

Synthesis and Biological Evaluation of (2S,2'S)-Lomaiviticin A.

(-)-Lomaiviticin A (1) is a genotoxic C2-symmetric metabolite that arises from the formal dimerization of two bis(glycosylated) diazotetrahydrobenzo[b]fluorenes. Here we present a synthesis of the monomer 17 and its coupling to form (2S,2'S)-lomaiviticin A (4), an unnatural diastereomer of 1. (2S,2'S)-Lomaiviticin A (4) is significantly less genotoxic, a result we attribute to changes in the orientation of the diazofluorene and carbohydrate residues, relative to 1. These data bring the importance of the configuration of the conjoining bond to light and place the total synthesis of 1 itself within reach.

Testis-Preserving Tumor Enucleation Is Applicable in Children with Immature Testicular Teratoma.

INTRODUCTION: This study investigated the biological characteristics of immature testicular teratoma in children and explored the feasibility of testis-preserving tumor enucleation. METHODS: We retrospectively reviewed the cases of 23 children who received a pathologic diagnosis of immature testicular teratoma between January 2005 and December 2018. Ages ranged from 16 days to 13 months (mean: 6 months and 5 days). Painless testicular enlargement was the main clinical manifestation, and the course of disease ranged from 20 days to 4 months (mean: 1.4 months). The tumor volume ranged from 1.5 × 1.2 × 0.5 to 6 × 5 × 4.5 cm. Elevated levels of alpha-fetoprotein were measured in 21 patients. Preoperative ultrasound examination showed a cystic/solid mass with calcification. RESULTS: Excision of the affected testis was done in 10 patients and testis-preserving tumor excision in 13 patients. Postoperative chemotherapy was not employed. Nineteen patients were followed up for 1-10 years, and all showed disease-free survival without recurrence or metastasis. CONCLUSION: Immature testicular teratoma is found predominantly in children aged <1 year, and its biological characteristics are different from those in adults. Immature testicular teratoma is largely benign in children and can be managed by testis-preserving tumor enucleation, as for other benign tumors (such as mature teratoma). Postoperative monitoring and follow-up are necessary.

Chinese herb feed additives improved the growth performance, meat quality, and nutrient digestibility parameters of pigs.

BACKGROUND: Since the use of antibiotics in animal feed has become a critical concern worldwide due to severe threats to human health and environment, we are in need of finding alternatives to antibiotics in pig breeding, maintaining the health of pigs, and getting high-quality pork. As traditional Chinese herbs (TCH) are rich natural resources in China and show great benefits to human health we propose to transfer this abundant resource into animal production industry as additives. METHODS: Three groups of Chinese herbs (groups A, B, and C) were used as feed additives in the diet for pigs. In total 32 pigs were arranged in four groups (groups A, B, C, and control group, NC), fed in the same facility, eight pigs (one group) in each colony, free drinking, for 120 days. The feed:gain ratio (F/G), meat quality, total protein, and amino acid concentration of muscle were checked in the experiments. RESULTS: After 120 days of feeding, the feed:gain ratio (F/G) of pigs in groups A, B, and C was decreased 17.56%, 9.31%, and 13.86% compared with NC treatment, respectively. The diets supplemented with Chinese herbs improved meat quality, increased loin eye area (especially group A and C showed significant difference, P < .001), the total protein (increased ratio vs NC was A = 4.54%, B = 0.38% and C = 3.53%), amino acid concentration of muscle, increased the villus height:crypt depth ratio, and induced positive effects on serum biochemical parameters and immune function (serum TC and TG concentrations were significantly lower than those in the NC group, P < .05.). CONCLUSIONS: The use of Chinese herbal feed additives can reduce the cost of pig breeding and produce high-quality pock. The combination of these effects would contribute to better absorption ability of the intestinal tract and yield a better growth performance.

Coix seed improves growth performance and productivity in post-weaning pigs by reducing gut pH and modulating gut microbiota.

Coix seed has traditionally been used in traditional Chinese medicine to fortify the spleen and inhibit dampness, and has shown anticancer effects in humans. However, it is not known whether coix seed improves post-weaning growth performance and productivity, and the mechanism of interaction between coix seed and gut microbiota remains unknown. In this study, we established four groups: (i) control, (ii) antibiotic-fed, (iii) coix seed powder-fed, and (iv) coix seed extract-fed. The feeding experiment was conducted for 4 weeks. Coix seed extract significantly increased average weight gain and reduced the feed/meat ratio in weaned pigs, in addition to reducing the pH of their gastric juice. Further assays demonstrated that coix seed promotes an increase in the density and length of the gastrointestinal villi. Next, 16s sequencing of gut microbiota showed that coix seed significantly increased the abundance of phylum Bacteroidetes and genus Lactobacillus (p < 0.05) and reduced the abundance of phylum Prevotella (p < 0.05) in the gut microbiota. In contrast, the abundance of phylum Bacteroidetes and genus Lactobacillus decreased in the control group and antibiotic group, whereas the abundance of phylum Prevotella increased. Our findings indicate that coix seed improves growth performance and productivity in post-weaning pigs by reducing the pH value of gastric juice, increasing the density and length of gastrointestinal villi, and modulating gut microbiota. Thus, coix seed has good potential for use as a feed supplement in swine production.

Congenital pulmonary airway malformation mimicking lung cancer: A case report.

RATIONALE: Congenital pulmonary airway malformation (CPAM) is a rare developmental deformity of the lower respiratory tract. The disease occurs more in newborns. However, on rare occasions, CPAM can be found in adults. Radiologic features of CPAM include cystic or solid mass pattern. In an elderly patient, CPAM can be easily misdiagnosed as lung cancer. PATIENT CONCERNS: A 66-year old woman was admitted with complaints of chronic cough, expectoration. Her past history was unremarkable with no history of tuberculosis or smoking. Physical examination was normal. Computerized tomography of the chest showed an irregular cystic lesion in right lower lobe. DIAGNOSIS: Histopathological results confirmed the diagnosis of CPAM. INTERVENTION: The right pulmonary wedge resection was performed via thoracoscopic surgery. OUTCOMES: On follow up 1 year later, the patient is asymptomatic. LESSONS: CPAM is rare in adults, and imaging cannot accurately distinguish CPAM from thin-walled cystic lung cancer. Hence, histopathology is mandatory to confirm the diagnosis.

Englerins: A Comprehensive Review.

In the decade since the discovery of englerin A (1) and its potent activity in cancer models, this natural product and its analogues have been the subject of numerous chemical, biological, and preclinical studies by many research groups. This review summarizes published findings and proposes further research directions required for entry of an englerin analogue into clinical trials for kidney cancer and other conditions.

Synthesis of a stable and orally bioavailable englerin analogue.

Synthesis of analogues of englerin A with a reduced propensity for hydrolysis of the glycolate moiety led to a compound which possessed the renal cancer cell selectivity of the parent and was orally bioavailable in mice.

Structural basis for DNA cleavage by the potent antiproliferative agent (-)-lomaiviticin A.

(-)-Lomaiviticin A (1) is a complex antiproliferative metabolite that inhibits the growth of many cultured cancer cell lines at low nanomolar-picomolar concentrations. (-)-Lomaiviticin A (1) possesses a C2-symmetric structure that contains two unusual diazotetrahydrobenzo[b]fluorene (diazofluorene) functional groups. Nucleophilic activation of each diazofluorene within 1 produces vinyl radical intermediates that affect hydrogen atom abstraction from DNA, leading to the formation of DNA double-strand breaks (DSBs). Certain DNA DSB repair-deficient cell lines are sensitized toward 1, and 1 is under evaluation in preclinical models of these tumor types. However, the mode of binding of 1 to DNA had not been determined. Here we elucidate the structure of a 1:1 complex between 1 and the duplex d(GCTATAGC)2 by NMR spectroscopy and computational modeling. Unexpectedly, we show that both diazofluorene residues of 1 penetrate the duplex. This binding disrupts base pairing leading to ejection of the central AT bases, while placing the proreactive centers of 1 in close proximity to each strand. DNA binding may also enhance the reactivity of 1 toward nucleophilic activation through steric compression and conformational restriction (an example of shape-dependent catalysis). This study provides a structural basis for the DNA cleavage activity of 1, will guide the design of synthetic DNA-activated DNA cleavage agents, and underscores the utility of natural products to reveal novel modes of small molecule-DNA association.

Bone morphogenetic protein-10 induces cardiomyocyte proliferation and improves cardiac function after myocardial infarction.

Heart disease is among the leading causes of death worldwide, and the limited proliferation of mammalian cardiomyocytes prevents heart regeneration in response to injury. Bone morphogenetic protein-10 (BMP10) exerts multiple roles in various developmental events; however, the effect of BMP10 and the underlying mechanism involved in cardiac repair remains unclear. After stimulation with the recombinant BMP10, an obvious dose-dependent cardiomyocyte proliferation and reentry of differentiated mammalian cardiomyocytes into the cell cycle was observed. Furthermore, BMP10 stimulation strikingly enhanced Tbx20 expression. Further analysis demonstrated that T-box 20 (Tbx20) was involved in BMP10-induced proliferation of differentiated cardiomyocytes as preconditioning with Tbx20 siRNA significantly attenuated BMP10-induced DNA synthesis. In vivo, BMP10 induced rat cardiomyocyte DNA synthesis and cytokinesis. After myocardial infarction (MI), BMP10 stimulated cardiomyocyte cell-cycle reentry and mitosis, resulting in the decrease of infarct size and improvement of cardiac repair. Taken together, these data indicated that BMP10 stimulated cardiomyocyte proliferation and repaired cardiac function after heart injury. Consequently, BMP10 may be a potential target for innovative strategies against heart failure.

The cytotoxicity of (-)-lomaiviticin A arises from induction of double-strand breaks in DNA.

The metabolite (-)-lomaiviticin A, which contains two diazotetrahydrobenzo[b]fluorene (diazofluorene) functional groups, inhibits the growth of cultured human cancer cells at nanomolar-picomolar concentrations; however, the mechanism responsible for the potent cytotoxicity of this natural product is not known. Here we report that (-)-lomaiviticin A nicks and cleaves plasmid DNA by a pathway that is independent of reactive oxygen species and iron, and that the potent cytotoxicity of (-)-lomaiviticin A arises from the induction of DNA double-strand breaks (dsbs). In a plasmid cleavage assay, the ratio of single-strand breaks (ssbs) to dsbs is 5.3 ± 0.6:1. Labelling studies suggest that this cleavage occurs via a radical pathway. The structurally related isolates (-)-lomaiviticin C and (-)-kinamycin C, which contain one diazofluorene, are demonstrated to be much less effective DNA cleavage agents, thereby providing an explanation for the enhanced cytotoxicity of (-)-lomaiviticin A compared to that of other members of this family.

Recombinant AAV-PR39-mediated hypoxia-inducible factor 1α gene expression attenuates myocardial infarction.

PR39 is an angiogenic masterswitch protein, belonging to the second generation of angiogenic growth factors. However, the role of recombinant adeno-associated virus (AAV) carrying the PR39 fusion gene (AAV-PR39) in acute myocardial infarction remains unclear. Therefore, in this study, we investigated the role of AAV-PR39 in an experimental animal model of acute myocardial infarction. The PR39 gene was fused with the transmembrane peptide, TAT, 6xHis­tag and NT4 signal sequences. AAV-PR39 was then obtained by calcium phosphate co-precipitation. A total of 18 healthy Chinese mini pigs were randomly divided into an experimental groups (the AAV-PR39-treated group) and a control group [phosphated-buffered saline (PBS)-treated group]. Following the induction of myocardial infarction, enhanced 3.0T MR imaging was performed to observe the changes in myocardial signal intensity at 0 h, 1, 2 and 3 weeks. The expression of hypoxia-inducible factor­1α (HIF-1α) in the myocardial tissues was determined by SABC immunohistochemistry. In addition, in vitro experiments using CRL-1730 endothelial cells transfected with AAV vector containing NT4-TAT-His-PR39 revealed that the AAV-PR39-treated group had a significantly higher expression of HIF-1α compared with the control group. Moreover, PR39 regulated the HIF-1α-induced expression of angiogenic growth factors. Under hypoxic conditions, the anti-apoptotic effects in the AAV-PR39 group were more pronounced than those observed in the control (PBS-treated) group. In vivo, the enforced expression of recombinant PR39 elevated the level of HIF-1α under hypoxic conditions and decreased the size of the infarcted areas by upregulating the expression of HIF-1α in the areas surrounding the infarct area. Taken together, our data demonstrate that the recombinant AAV-PR39-mediated HIF-1α expression attenuates myocardial infarction, indicating that AAV-PR39 may serve as a novel therapeutic agent for the treatment of myocardial infarction.

Englerin a selectively induces necrosis in human renal cancer cells.

The number of renal cancers has increased over the last ten years and patient survival in advanced stages remains very poor. Therefore, new therapeutic approaches for renal cancer are essential. Englerin A is a natural product with a very potent and selective cytotoxicity against renal cancer cells. This makes it a promising drug candidate that may improve current treatment standards for patients with renal cancers in all stages. However, little is known about englerin A's mode of action in targeting specifically renal cancer cells. Our study is the first to investigate the biological mechanism of englerin A action in detail. We report that englerin A is specific for renal tumor cells and does not affect normal kidney cells. We find that englerin A treatment induces necrotic cell death in renal cancer cells but not in normal kidney cells. We further show that autophagic and pyroptotic proteins are unaffected by the compound and that necrotic signaling in these cells coincided with production of reactive oxygen species and calcium influx into the cytoplasm. As the first study to analyze the biological effects of englerin A, our work provides an important basis for the evaluation and validation of the compound's use as an anti-tumor drug. It also provides a context in which to identify the specific target or targets of englerin A in renal cancer cells.