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Kidney Structure01:45

Kidney Structure

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The kidneys are two large bean-shaped organs located in the upper abdomen. They filter the blood several times a day to remove toxins and rebalance water and electrolytes of the circulatory system via the renal veins. The kidneys receive blood directly from the heart via the renal arteries. These arteries enter the kidney at the hilum, the concave surface of the bean, where they branch and divide into smaller vessels and capillaries.
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External Anatomy of the Kidney01:21

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The kidneys are a pair of bean-shaped organs in the human body that play a critical role in maintaining overall health. They filter out waste products from the blood, regulate blood pressure, maintain electrolyte balance, and stimulate the production of red blood cells.
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Internal Anatomy of the Kidney01:12

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The kidneys are essential organs in the human body, performing a myriad of tasks that maintain homeostasis and overall health.
Anatomical Position and Dimensions
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A kidney transplant is a surgical approach that involves replacing a non-functioning kidney with a healthy one from a donor. This procedure is often a treatment option for end-stage renal disease (ESRD) patients. The method requires careful recipient selection, including evaluating various medical and psychosocial factors. These criteria vary between transplant centers but generally include assessments of the patient's overall health, adherence to medical recommendations, and lifestyle...
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Anatomy of the Genitourinary System I: Kidneys and Ureters01:11

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The upper urinary system comprises two kidneys and two ureters, which are crucial in filtering blood and forming urine.KidneysLocation and Structure:The kidneys are two bean-shaped organs positioned behind the peritoneum on either side of the spine.Kidneys are between the 12th thoracic (T12) and the 3rd lumbar (L3) vertebrae.The position of the liver causes the right kidney to sit slightly lower than the left.Protective Layers:Each kidney is enveloped in a tough, fibrous membrane called the...
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Acute Kidney Injury I: Introduction01:22

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Introduction:Acute Kidney Injury (AKI) describes a swift decrease in kidney function occurring over hours to days, characterized by the kidneys' failure to remove waste products from the bloodstream. This leads to dangerous complications like metabolic acidosis, fluid overload, and electrolyte imbalances, such as hyperkalemia, which can cause life-threatening arrhythmias. AKI is common in both hospital and outpatient settings, often triggered by dehydration, sepsis, or exposure to nephrotoxic...
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Related Experiment Video

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Targeting CDK11 in Rhabdoid Tumor of the Kidney.

Yuki Murakami1,2, Kamhung Lam1, Shinsuke Fukui1

  • 1Department of Pediatrics, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Cancers
|January 28, 2026
PubMed
Summary

Cyclin-dependent kinase 11 (CDK11) inhibition effectively targets rhabdoid tumor of the kidney (RTK) by halting cell cycle progression and RNA splicing. This approach shows promise for treating pediatric cancers with SMARCB1 loss.

Keywords:
CDK11 inhibitorRNA splicingapoptosiscell cyclerhabdoid tumor

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Rhabdoid tumor of the kidney (RTK) is an aggressive pediatric cancer linked to SMARCB1 loss, MYC pathway activation, and cell cycle dysregulation.
  • MYC-activated tumors exhibit vulnerabilities in RNA splicing, suggesting potential therapeutic targets like splicing inhibitors.

Purpose of the Study:

  • To investigate cyclin-dependent kinase 11 (CDK11) as a therapeutic target in RTK, given its role in cell cycle and RNA splicing.
  • To evaluate the efficacy of the CDK11 inhibitor OTS964 in preclinical RTK models.

Main Methods:

  • Analyzed CDK11A/B expression in RTK using the TARGET-RT database.
  • Assessed OTS964's therapeutic efficacy in RTK cell lines and a xenograft mouse model.
  • Examined cytotoxicity, apoptosis, cell cycle, and RNA splicing using various assays (SRB, immunoblotting, flow cytometry, RT-PCR).

Main Results:

  • CDK11B was upregulated in RTK and correlated with poor survival; CDK11A was not.
  • OTS964 demonstrated potent in vitro cytotoxicity (IC50: 33.1 nM, 19.3 nM) and significantly prolonged survival in vivo (p < 0.01) with minimal toxicity.
  • OTS964 induced G2/M cell cycle arrest, p53 upregulation, disrupted RNA splicing via SF3B1 dephosphorylation, and triggered apoptosis.

Conclusions:

  • CDK11 inhibition by OTS964 effectively suppresses RTK growth via cell cycle arrest and RNA splicing inhibition, culminating in apoptosis.
  • OTS964 exhibits potent anti-tumor activity and good tolerability, establishing CDK11 as a promising therapeutic target for RTK and SMARCB1-deficient cancers.