Evidence map›Paper›PMID 37268911›Full record

ArticleBMC cancer2023

A cisplatin conjugate with tumor cell specificity exhibits antitumor effects in renal cancer models.

Stefan Mrdenovic, Yanping Wang, Lijuan Yin, Gina Chia-Yi Chu, Yan Ou, Michael S Lewis, Marija Heffer, Edwin M Posadas, Haiyen E Zhau, Leland W K Chung and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Stefan MrdenovicDivision of Hematology, Department of Internal Medicine, University Hospital Osijek, Osijek, Croatia.
Yanping WangDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Lijuan YinDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Gina Chia-Yi ChuDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Yan OuDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Michael S LewisDepartments of Pathology, Cedars-Sinai Medical Center and the VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Marija HefferDepartment of Medical Biology and Genetics, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
Edwin M PosadasDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Haiyen E ZhauDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Leland W K ChungDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Mouad EdderkaouiDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Stephen J PandolDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ruoxiang WangDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Yi ZhangBiomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis 3059, 90048, Los Angeles, CA, USA. yi.zhang@cshs.org.
Cedars-Sinai Medical Center · USUniversity of Osijek · HRVA Greater Los Angeles Healthcare System · US

Funding

ROS Targeted Therapy for Lethal Prostate CancerR21CA256419 · NCI · CEDARS-SINAI MEDICAL CENTER · PI WANG, RUOXIANG, ZHANG, YI · 2021 to 2022
$425k
NCI NIH HHS R21 CA256419NIH HHS R21CA256419
6 · The paper itself

Abstract

backgroundClear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and is notorious for its resistance to both chemotherapy and small-molecule inhibitor targeted therapies. Subcellular targeted cancer therapy may thwart the resistance to produce a substantial effect.

methodsWe tested whether the resistance can be circumvented by subcellular targeted cancer therapy with DZ-CIS, which is a chemical conjugate of the tumor-cell specific heptamethine carbocyanine dye (HMCD) with cisplatin (CIS), a chemotherapeutic drug with limited use in ccRCC treatment because of frequent renal toxicity.

resultsDZ-CIS displayed cytocidal effects on Caki-1, 786-O, ACHN, and SN12C human ccRCC cell lines and mouse Renca cells in a dose-dependent manner and inhibited ACHN and Renca tumor formation in experimental mouse models. Noticeably, in tumor-bearing mice, repeated DZ-CIS use did not cause renal toxicity, in contrast to the CIS-treated control animals. In ccRCC tumors, DZ-CIS treatment inhibited proliferation markers but induced cell death marker levels. In addition, DZ-CIS at half maximal inhibitory concentration (IC50) sensitized Caki-1 cells to small-molecule mTOR inhibitors. Mechanistically, DZ-CIS selectively accumulated in ccRCC cells' subcellular organelles, where it damages the structure and function of mitochondria, leading to cytochrome C release, caspase activation, and apoptotic cancer cell death.

conclusionsResults from this study strongly suggest DZ-CIS be tested as a safe and effective subcellular targeted cancer therapy.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsAnimalsApoptosisCell DeathCell Line, TumorCell ProliferationCisplatinHumansMiceCisplatinCell deathCisplatinConjugateHeptamethine carbocyanine dyeKidney cancer

Identifiers

PMID37268911
PMCPMC10236852
OpenAlexW4379197505

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.