Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancer
Abstract Background The tumoricidal complex alpha1‐oleate targets bladder cancer cells, triggering rapid, apoptosis‐like tumor cell death. Clinical effects of alpha1‐oleate were recently observed in patients with non‐muscle invasive bladder cancer (NMIBC), using a randomized, placebo‐controlled stud...
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| Format: | Article |
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Wiley
2024-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70149 |
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| author | Farhan Haq Samudra Sabari Jaromir Háček Antonín Brisuda Ines Ambite Michele Cavalera Parisa Esmaeili Murphy Lam Yim Wan Shahram Ahmadi Marek Babjuk Catharina Svanborg |
| author_facet | Farhan Haq Samudra Sabari Jaromir Háček Antonín Brisuda Ines Ambite Michele Cavalera Parisa Esmaeili Murphy Lam Yim Wan Shahram Ahmadi Marek Babjuk Catharina Svanborg |
| author_sort | Farhan Haq |
| collection | DOAJ |
| description | Abstract Background The tumoricidal complex alpha1‐oleate targets bladder cancer cells, triggering rapid, apoptosis‐like tumor cell death. Clinical effects of alpha1‐oleate were recently observed in patients with non‐muscle invasive bladder cancer (NMIBC), using a randomized, placebo‐controlled study protocol. Aims To investigate if there are dose‐dependent effects of alpha1‐oleate. Materials and Methods Here, patients with NMIBC were treated by intravesical instillation of increasing concentrations of alpha1‐oleate (1.7, 8.5, or 17 mM) and the treatment response was defined relative to a placebo group. Results Strong, dose‐dependent anti‐tumor effects were detected in alpha1‐oleate treated patients for a combination of molecular and clinical indicators; a complete or partial response was detected in 88% of tumors treated with 8.5 mM compared to 47% of tumors treated with 1.7 mM of alpha1‐oleate. Uptake of alpha1‐oleate by the tumor triggered rapid shedding of tumor cells into the urine and cell death by an apoptosis‐like mechanism. RNA sequencing of tissue biopsies confirmed the activation of apoptotic cell death and strong inhibition of cancer gene networks, including bladder cancer related genes. Drug‐related side effects were not recorded, except for local irritation at the site of instillation. Discussion and Conclusions These dose‐dependent anti‐tumor effects of alpha1‐oleate are promising and support the potential of alpha1‐oleate treatment in patients with NMIBC. |
| format | Article |
| id | doaj-art-b5d29c498cd44e9d837e274d4f7f27ed |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-b5d29c498cd44e9d837e274d4f7f27ed2025-02-07T09:08:08ZengWileyCancer Medicine2045-76342024-09-011317n/an/a10.1002/cam4.70149Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancerFarhan Haq0Samudra Sabari1Jaromir Háček2Antonín Brisuda3Ines Ambite4Michele Cavalera5Parisa Esmaeili6Murphy Lam Yim Wan7Shahram Ahmadi8Marek Babjuk9Catharina Svanborg10Division of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenDivision of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenDepartment of Pathology and Molecular Medicine Motol University Hospital, 2nd Faculty of Medicine, Charles University Praha Prague Czech RepublicDepartment of Urology Motol University Hospital, 2nd Faculty of Medicine, Charles University Praha Prague Czech RepublicDivision of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenDivision of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenDivision of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenDivision of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenDivision of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenDepartment of Urology Motol University Hospital, 2nd Faculty of Medicine, Charles University Praha Prague Czech RepublicDivision of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Faculty of Medicine Lund University SwedenAbstract Background The tumoricidal complex alpha1‐oleate targets bladder cancer cells, triggering rapid, apoptosis‐like tumor cell death. Clinical effects of alpha1‐oleate were recently observed in patients with non‐muscle invasive bladder cancer (NMIBC), using a randomized, placebo‐controlled study protocol. Aims To investigate if there are dose‐dependent effects of alpha1‐oleate. Materials and Methods Here, patients with NMIBC were treated by intravesical instillation of increasing concentrations of alpha1‐oleate (1.7, 8.5, or 17 mM) and the treatment response was defined relative to a placebo group. Results Strong, dose‐dependent anti‐tumor effects were detected in alpha1‐oleate treated patients for a combination of molecular and clinical indicators; a complete or partial response was detected in 88% of tumors treated with 8.5 mM compared to 47% of tumors treated with 1.7 mM of alpha1‐oleate. Uptake of alpha1‐oleate by the tumor triggered rapid shedding of tumor cells into the urine and cell death by an apoptosis‐like mechanism. RNA sequencing of tissue biopsies confirmed the activation of apoptotic cell death and strong inhibition of cancer gene networks, including bladder cancer related genes. Drug‐related side effects were not recorded, except for local irritation at the site of instillation. Discussion and Conclusions These dose‐dependent anti‐tumor effects of alpha1‐oleate are promising and support the potential of alpha1‐oleate treatment in patients with NMIBC.https://doi.org/10.1002/cam4.70149alpha1‐oleate complexcell sheddingcellular uptakegene expressionnon‐muscle invasive bladder cancer |
| spellingShingle | Farhan Haq Samudra Sabari Jaromir Háček Antonín Brisuda Ines Ambite Michele Cavalera Parisa Esmaeili Murphy Lam Yim Wan Shahram Ahmadi Marek Babjuk Catharina Svanborg Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancer Cancer Medicine alpha1‐oleate complex cell shedding cellular uptake gene expression non‐muscle invasive bladder cancer |
| title | Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancer |
| title_full | Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancer |
| title_fullStr | Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancer |
| title_full_unstemmed | Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancer |
| title_short | Clinical and molecular response to alpha1‐oleate treatment in patients with bladder cancer |
| title_sort | clinical and molecular response to alpha1 oleate treatment in patients with bladder cancer |
| topic | alpha1‐oleate complex cell shedding cellular uptake gene expression non‐muscle invasive bladder cancer |
| url | https://doi.org/10.1002/cam4.70149 |
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