Anticancer Research Articles

Biocompatible supramolecular hydrogels based on polysaccharide-modified hyaluronic acid for targeted delivering of doxorubicin

ABSTRACT In this paper, Biocompatible supramolecular hydrogels, composed of β-cyclodextrin-modified hyaluronic acid, pluronic F127, α-cyclodextrin and doxorubicin, were constructed, which can be employed for targeted delivery system. The chemical composition and rheological properties of the obtained hydrogels were fully characterised. Considering the controlled complexation between DOX and the hydrogel skeletons, the controlled release of hydrogel G[5, 10, 5] was investigated to exhibit a better pH- and temperature-controlled release behavior. The data of DOX release kinetic was fitted well with Higuchi and Korsmeyer-Peppas models. Moreover, the cellular toxicity experiments indicated that the hydrogel DOX@G[5, 10, 5] exhibited a similar anticancer ability in comparison with free DOX. Due to the hyaluronic acid-targeted effects, the cytotoxicity of the hydrogel DOX@G[5,10,5] to HepG2 cells was lower than that to SKOV-3 cells upon increasing the concentration. Therefore, these hydrogels may act as a potential prospect for the targeting release of anticancer drugs.

Flavonoids as Chemosensitizers in Leukemias.

Flavonoids, a diverse group of natural compounds abundant in plants, fruits, and seeds, are not only responsible for the vibrant colors, fragrances, and flavors found in nature but also possess significant health benefits. Representing a secondary metabolite, these phytonutrients contribute to overall well-being. They have garnered considerable interest due to their diverse biological roles, encompassing antioxidant, anti-inflammatory, and anticancer properties. Flavonoids exert anticancer properties by interfering with different signaling pathways and molecules. Also, they have been demonstrated to exert chemosensitization features, where flavonoids may enhance the effectiveness of chemotherapy, and hold promise for improving cancer treatment outcomes as they have been discovered to make cancer cells more responsive to treatment. Understanding their influence on the regulation of cellular signaling provides a foundation for exploring their potential in combination with different chemotherapy agents and their possible single use for cancer treatment. Besides, they are believed to present a cost-effective approach to cancer therapeutics with possible implications for reducing the side effects of the current chemotherapy regimens, which can be a great therapeutic strategy for treating cancer types, including leukemia. This chapter explores potential approaches for creating anticancer treatments, focusing on leukemia, through integrating flavonoid nutraceuticals with traditional chemotherapy agents.

The Chemistry and Pharmacological Properties of the Constituents of Toussaintia Orientalis - An Endangered Treasure of Biomedical Agents.

Toussaintia orientalis Verdc. (Annonaceae) is a medicinal plant species endemic to Tanzania. It is classified under the International Union for Conservation of Nature (IUCN) as an extremely endangered species threatened with extinction. The review covers the phytochemistry of this plant species and the pharmacological properties of the compounds obtained therefrom. The chemistry of this plant species entails natural products with different structures including uncommon cinnamoyl tetraketide derivatives, aristolactam alkaloids, and flavonoids. The review identifies 27 compounds belonging to different subclasses of natural products obtained from this species for the past fourteen years (2010-2024). These compounds are discussed along with other 13 related natural products. T. orientalis derived compounds exhibit varied potential pharmacological applications as antibacterial, anticancer, anti-inflammatory, antiviral, and neuroprotective agents. Some of the reported compounds displayed pharmacological properties corroborating the use of this plant species in traditional medicine. This review provides baseline data as one comprehensive compilation that will ignite interest and guide future research and development of therapeutic agents inspired by the chemodiversity presented by this plant species while at the same time attracting the attention of plant conservationists to initiate efforts to conserve this highly endangered biomedical treasure.

Optical and structural characterization of Au@ZnO core–shell nanoparticles prepared by pulsed laser ablation as anticancer agents for skin cancer

Optical and structural characterization of Au@ZnO core–shell nanoparticles prepared by pulsed laser ablation as anticancer agents for skin cancer

Early Endocrine and Metabolic Complications in Childhood Cancer Survivors—Experience from a Tertiary Care Pediatric Oncology Center in South India

Background Endocrine abnormalities and metabolic complications remain one of the common late effects after cancer therapy in children. Data on the incidence and pattern of complications would help to guide appropriate monitoring and treatment of childhood cancer survivors. Methods, Aims, and Objectives Purpose of study is to determine endocrine and metabolic effects in childhood cancer survivors including both hematological malignancies and solid tumors due to cancer per se and treatment-related, including different chemotherapeutic agents and radiotherapy. Results Among 97 participants, 84 children (84.5%) had at least one endocrine or metabolic complication; 41 children (42.3%) had more than two endocrine/metabolic complications. Common endocrine complications included precocious puberty (6.2%), short stature (6.2%), and hypothyroidism (5.1%). Among metabolic complications, dyslipidemia was the highest with an incidence of 68%, followed by fasting hyperinsulinism (32%), diastolic hypertension (18.6%), systolic hypertension (11.3%), obesity (8.8%), and metabolic syndrome (8.2%) and impaired fasting glucose (4.1%).Among endocrine complications, there was a significant increase in incidence of hypothyroidism among children receiving radiotherapy (odds ratio [OR]: 7.13, 95% confidence interval [CI]: 1.1–46.2), and among metabolic complications, a significant increase in incidence of metabolic syndrome in children treated with L-asparaginase compared with those not treated with L-asparaginase was observed (OR: 5.61, 95% CI: 1.07–29.5). There was no significant difference between incidence of observed endocrine and metabolic complications based on type of tumor, gender, and puberty status of study participants. Conclusion This study suggests that there is significant incidence of endocrine and metabolic complications in childhood cancer survivors, hence timely and appropriate recognition of these complications by appropriate screening recommendations and pursuing further endocrine evaluation rationally is needed.

DNA damage-induced EMT controlled by the PARP dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells.

Epithelial-to-mesenchymal transition (EMT) allows cancer cells to metastasize while acquiring resistance to apoptosis and chemotherapeutic agents with significant implications for patients' prognosis and survival. Despite its clinical relevance, the mechanisms initiating EMT during cancer progression remain poorly understood. We demonstrate that DNA damage triggers EMT and that activation of PARP and the PARP-dependent chromatin remodeler ALC1 (CHD1L) was required for this response. Our results suggest that this activation directly facilitates access to the chromatin of EMT transcriptional factors (TFs) which then initiate cell reprogramming. We also show that EMT-TFs bind to the RAD51 promoter to stimulate its expression and to promote DNA repair by homologous recombination (HR). Importantly, a clinically relevant PARP inhibitor reversed or prevented EMT in response to DNA damage while resensitizing tumor cells to other genotoxic agents. Overall, our observations shed light on the intricate relationship between EMT, DNA damage response, and PARP inhibitors, providing potential insights for in cancer therapeutics.

A case of methotrexate toxicity in induced abortion

Background: Methotrexate is an anticancer drug from the antimetabolite class which is being used in cases of unruptured ectopic pregnancy and as an abortifacient as well. Giving correct dosage according to the body weight and body surface area is of utmost importance to avoid the complications.Case: A 29-year-old, G4P3L3 at 8+3 weeks of gestation with previous three cesarean sections, presented to our hospital with complaints of fever, abdominal pain, multiple episodes of diarrhea and vomiting and oral ulcers for two days. On enquiring, it was found that she received two doses of injection methotrexate (75 and 50 mg) as an abortifacient for an unwanted intrauterine pregnancy from a local doctor nearby. On presentation, her general condition was poor, she was dehydrated, temperature was 101.3°F, pulse rate was 130 beats/minute, blood pressure was 102/64mmHg, respiratory rate was 25/minute and SPO2 was 99% on room air. Her body weight was 55 kgs. Skin pigmentation and multiple oral ulcers were present. Per speculum and per vaginal examination was suggestive of minimal spotting and bulky uterus. Initial blood investigations revealed a hemoglobin level of 8.8 gm/dl, TLC of 1000/mm3, platelet count of 1.45L, INR of 1.37, and normal liver and renal function tests. A provisional diagnosis of methotrexate toxicity was made. Management of the patient was started in consultation with medical oncologist along with supportive treatment. She received IV fluids, antibiotics, and blood products (2-unit PCV and 12-RDP). She received oral leucoverin 15 mg QID and two doses of 300 mg granulocyte stimulating factor each. Gradually, her condition improved and thereafter tablet misoprostol was given for abortion. She was discharged after 13 days of hospital stay with contraceptive advice.Conclusion: The successful management of this case who presented with a constellation of symptoms and deteriorating hematological parameters exhibits the significance of a multidisciplinary approach and vigilant monitoring. Strategies to reduce the side effects and their early recognition include a safety checking procedure like SMART (safety of methotrexate therapy by assessing risks and toxicity) and determining plasma methotrexate concentrations.

Amide Functionalized Novel Pyrrolo-pyrimidine Derivative as Anticancer Agents: Synthesis, Characterization and Molecular Docking Studies.

The development of new therapies targeting crucial kinases involved in cancer progression is a promising area of research. Pyrazolo pyrimidine derivatives have emerged as potential candidates for this purpose. This study aims to synthesize pyrazolo pyrimidine derivatives (5a-5r), evaluate their molecular docking against key kinases, and assess their anticancer activity. The synthesis involved a multi-step procedure starting with the cyclization of 6-amino-2- methylpyrimidin-4(3H)-one (1) to form 2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-4-ol (2). This was followed by chlorination to yield 4-chloro-2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine (3) and nucleophilic substitution to produce 2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-4-amine (4). The final derivatives (5a-5r) were synthesized through amide bond formation with various carboxylic acids using DCC and DMAP. Structural elucidation was confirmed via NMR, mass spectrometry, and HRMS. Molecular docking studies were conducted against Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), and cyclin-dependent kinase 4 (CDK4). Anticancer activity was evaluated against MCF-7, SET-2, and HCT-116 cell lines. Structural elucidation confirmed the successful synthesis of the derivatives. Molecular docking studies revealed promising binding affinities for selected derivatives, particularly those with heterocyclic substitutions. Anticancer activity evaluation showed diverse potency profiles, with several derivatives demonstrating IC50 values comparable to the reference drug, doxorubicin. Derivatives featuring nitro and heterocyclic moieties exhibited significant anticancer activity. The synthesized pyrazolo pyrimidine derivatives showed potential as lead compounds for further development due to their promising binding affinities and significant anticancer activity, particularly those with nitro and heterocyclic moieties.

Spatio-temporal localization of P21-activated kinase in endometrial cancer.

Endometrial cancer is the sixth most common gynecologic cancer, and has been reported as a malignancy arising due to the idiopathic effects of certain anticancer agents. Tamoxifen is the drug of choice in ER-positive breast cancer, and several studies have shown better disease-free survival in these patients. However, the long-term usage of tamoxifen has been associated with resistance and risk for endometrial malignancy. A direct mechanistic basis for tamoxifen-induced endometrial tumorigenesis is still unclear. Hyperactivation of PAK1 in endometrial cancer correlates with poor overall survival. The present study demonstrates that tamoxifen treatment induces nuclear localization of PAK1 in endometrial carcinoma cells. This nuclear transit is mediated through JAK2 phosphorylation of PAK1 and binding of β-PIX. In addition, a computational approach involving molecular modeling and simulation of phosphorylated and unphosphorylated forms of PAK1 was used to elucidate the dynamics of nuclear localization. Thus, PAK1 phosphorylation by JAK2 is a prerequisite for its nuclear localization and its tumorigenic effects on endometrial cancer cells.

Case report: High grade serous fallopian tube carcinoma with rare NRG1 gene fusion presenting as widespread peritoneal carcinomatosis

The discovery of gene fusions involving Neuregulin-1 (NRG1) within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. NRG1 fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed MYH10::NRG1 fusion. Moreover, we queried the whole transcriptome sequencing results of neoplasms analyzed by a commercial laboratory (Caris Life Sciences) to determine the overall incidence of NRG1 fusions in carcinomas of the ovary, fallopian tube, and peritoneum (0.18%). Twenty-five additional tumors were found to demonstrate NRG1 fusions, including 20 new genes partners that had not been previously identified in gynecologic carcinomas. Overall, NRG1 fusion events are rare in ovarian, fallopian tube, and primary peritoneal carcinomas, but they may carry diagnostic significance in the context of borderline/low grade serous tumors, which demonstrated exclusively CLU::NRG1 fusions, and could have important predictive implications for response to ERBB/ERBB2/ERBB3-directed therapies.

Development of Small Molecular Hyper-activators of Human Caseinolytic Peptidase P (hClpP) with a [1,8]-Naphthyridinone Scaffold as Novel Anti-cancer Agents.

Based on a clinical staged small molecular hClpP activator ONC201, a class of novel hClpP agonists with a [1,8]naphthyridinone scaffold were designed, synthesized and evaluated in a series of biochemical and biological assays. Mechanism studies for the representative compound F20 indicated that it can potently bind to and activate hClpP, efficiently promote the degradation of hClpP substrates, robustly induce ATF4/CHOP regulated integrated stress responses, strongly inhibit cell growth and effectively induce apoptosis in a subset of cancer cell lines. F20 showed good PK profiles when dosed by intravenous injection and exhibited moderate oral bioavailability in mice.

Construction and validation of a prognostic signature based on microvascular invasion and immune-related genes in hepatocellular carcinoma.

Microvascular invasion (MVI) is an independent risk factor of poor prognosis in hepatocellular carcinoma (HCC) and can be used to guide the diagnosis and treatment of HCC. The immune system serves as an integral role in the incidence and progression of HCC. However, the molecular biology correlation between MVI and tumor immunity and the value of combining the two parameters to predict patient prognosis and HCC response to treatment remain to be evaluated. In this study, we used univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to establish the MVI and immune-related gene index (MIRGPI) including eight genes. We demonstrated that the MIRGPI was an independent risk factor in predicting the prognosis of HCC. Subsequently, our research established a nomogram model combining pathologic characteristics and verified its good clinical application value. In addition, our study found that the TP53 gene had a higher mutation frequency and a lower degree of immune infiltration in the high-risk group. The low-risk group had higher sensitivity to immunotherapy, sorafenib, and TACE treatment, and the high-risk group had higher sensitivity to common chemotherapeutic agents. Finally, SEMA3C was found to facilitate the proliferation, migration and invasive ability of HCC by in vitro and in vivo experiments, and its mechanism may be associated with the activation of the NF-Κb/EMT signaling pathway. In summary, the MIRGPI signature we developed is a reliable marker for the prediction of prognosis and treatment response, and is important for the prognostic assessment and individualized treatment of HCC.

Novel Schiff bases of quinolin-4(1h)-one: Synthesis, antiproliferative evaluation, apoptosis, cell cycle, autophagy and molecular docking studies in human colon cancer cells

A green and efficient ultrasound-mediated protocol was developed for the synthesis of a series of novel Schiff bases derived from quinoline-4-one. The synthetic strategy involved the condensation of 4-oxo-1,4-dihydro-quinoline-3-carboxaldehyde with diverse anilines and heteroaryl amines. The synthesized compounds were characterized using spectroscopic techniques. A comprehensive in vitro cytotoxicity evaluation against HCT116 and HT-29 human colon cancer cell lines revealed that several compounds exhibited potent anticancer activity. Notably, compounds 3c and 3e demonstrated superior cytotoxicity compared to the clinical standard doxorubicin. Mechanistic studies indicated that these lead compounds induced apoptosis, necrosis, and cell cycle arrest at G1 and G2 phases. Furthermore, autophagy induction was observed. In silico ADMET predictions support the potential of compounds 3c and 3e as promising anticancer drug candidates. The molecular docking studies revealed that the Schiff bases 3c and 3e displayed good interaction with VEGFR-2 receptor. These findings underscore the quinoline-4-one scaffold as a valuable template for the development of novel antitumor agents.

In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II

Background: Sulfonamide acridine derivatives have garnered significant attention from medicinal chemists due to their diverse range of biological activities. Methods: In this study, eleven compounds were synthesized according to the literature, and their impact on cell growth inhibition, induction of apoptosis, and cell cycle distribution were assessed in three different cell lines. Their inhibitory effects on the topoisomerase (Topo) I and II were investigated in vitro. Molecular docking studies were conducted to predict the binding affinities of these compounds for crystallized downloaded topoisomerases. Results: The compounds were examined in vitro for their anticancer activity against human hepatic (HepG2) colon (HCT-8) and breast (MCF-7) carcinoma cell lines. Compound 8b was the most active against HepG2, HCT-116, and MCF-7 with IC50 14.51, 9.39, and 8.83 µM, respectively, compared to Doxorubicin as reference. In addition, it demonstrated the highest potency among the tested compounds against Topo-I, with an IC50 value of 3.41 µg/mL compared to the control camptothecin (IC50 of 1.46 μM). Compound 7c displayed a significant inhibitory effect on Topo-II, with an IC50 of 7.33 μM, compared to an IC50 value of 6.49 μM via Doxorubicin, the control. Compounds 7c and 8b were assessed against topoisomerases showing induction of apoptosis and a reduction in the S phase of the cell cycle. Molecular docking demonstrated interaction with the active site as with those exhibited by the co-crystallized ligands of the crystallized proteins in both topoisomerases. Conclusion: Compounds 7c and 8b hold promise as potential anticancer drugs due to their anti-proliferative and proapoptotic effects, which are mediated by their action on the topoisomerase enzyme, particularly Topo II.

Imbalance of redox homeostasis and altered cellular signaling induced by the metal complexes of terpyridine.

Compounds that can induce oxidative stress in cancer cells while remaining nontoxic to healthy cells are extremely promising for potential anticancer drugs. 2,2':6',2''-terpyridine-metal complexes possess these properties. The high level of activity (IC50 = 0.605 µM) of 2,2':6',2''-terpyridine-metal complexes on lung, breast, pancreatic, and glioblastoma multiforme cancer lines and their selectivity (SI > 41.32) on human normal fibroblasts were confirmed and presented in this paper. The mechanism of action of these compounds is associated with the generation of reactive oxygen species, which affects several cellular pathways and signals. The results demonstrate that 2,2':6',2''-terpyridine-metal complexes affect cell cycle inhibition in the G0/G1 phase as well as the activation of apoptosis and autophagy cell death. These results were confirmed in several independent studies, including experiments measuring the fluorescence levels of reactive oxygen species, flow cytometry, and gene and protein analysis.

A stimulus responsive microneedle-based drug delivery system for cancer therapy.

The intricate nature of the tumor microenvironment (TME) results in the inefficient delivery of anticancer drugs within tumor tissues, significantly compromising the therapeutic effect of cancer treatment. To address this issue, transdermal drug delivery microneedles (MNs) with high mechanical strength have emerged. Such MNs penetrate the skin barrier, enabling efficient drug delivery to tumor tissues. This approach enhances drug bioavailability, while also mitigating concerns such as liver and kidney toxicity associated with intravenous and oral drug administration. Notably, stimulus responsive MNs designed for drug delivery have the capacity to respond to various biological signals and pathological changes. This adaptability enables them to exert therapeutic effects within the TME, exploiting biochemical variations and tailoring treatment strategies to suit tumor characteristics. The present review surveys recent advancements in responsive MN systems. This comprehensive analysis serves as a valuable reference for the prospective application of smart MN drug delivery systems in cancer therapy.

Host-Guest Adduct as a Stimuli-Responsive Prodrug: Enzyme-Triggered Self-Assembly Process of a Short Peptide Within Mitochondria to Induce Cell Apoptosis.

To address the issue of nonspecific biodistribution of a chemotherapeutic drug, stable [2]pseudorotaxane complexes (PK@CAOPP and PR@CAOPP) are used to demonstrate a proof of concept. Cationic -PPh3 + moiety in CAOPP allows specific localization of the PK@CAOPP/ PR@CAOPP in the mitochondrial membrane (MM). Electrostatic interaction between the cationic LysinePK or ArgininePR moiety and the negatively charged phosphoesterCAOPP functionality in CAOPP favours strong adduct formation. The ALP-induced hydrolytic cleavage of the phosphoester moiety in cancer cells triggers dephosphorylation and releases PK/ PR moiety from PK@CAOPP/PR@CAOPP. PK or PR, derived from the Phe-Phe dipeptide, formed fibril-like molecular aggregates in the MM to induce dysfunction, depolarization, ROS generation and apoptotic MCF7 cell death. Such phenomena were not observed in ALP-negative HEK293 normal cells. These propositions were confirmed through control studies using NBDK and PE, other guest molecules. Smaller size and inclusion of the short peptides (PK or PR) within the hydrophobic interior of CAOPP, were attributed to their stability in blood serum. Thus, we have demonstrated the use of supramolecular adducts as a potential therapeutic option for treating cancer cells without affecting healthy cells. The efficacy was also established with an in-vivo MCF7 tumour xenograft model using Balb/c nude mice.

Combined Nabpaclitaxel pressurized intraPeritoneal aerosol chemotherapy with systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases: protocol of single-arm, open-label, phase II trial (Nab-PIPAC trial)

Abstract Objectives Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM. Methods The Nab-PIPAC trial is a single-center, prospective, open-label, phase II study (ClinicalTrials.gov identifier: NCT05371223). Its primary goal is to evaluate the antitumor activity of the combined treatment based on Disease Control Rate (DCR) using RECISTv.1.1 criteria. Secondary objectives include feasibility, safety, pathological response, progression-free and overall survival, nutritional status, quality of life, pharmacokinetics of NabPaclitaxel-PIPAC, and PM molecular evolution via translational research. The treatment protocol consists of three courses, each with two cycles of intravenous NabPaclitaxel-Gemcitabine and one cycle of NabPaclitaxel-PIPAC, with standard metastatic pancreatic cancer doses for the former and 112.5 mg/m2 for the latter. Sample size follows Simon’s two-stage design: 12 patients in stage one and 26 in stage two (80 % power, 0.1 alpha). Results Partial results will be available after first stage enrollment. Conclusions This trial aims to determine the antitumor efficacy and safety of combining NabPaclitaxel-PIPAC with systemic NabPaclitaxel-Gemcitabine in pancreatic cancer patients with PM.

Capturing Hydrophilic Chemotherapeutics Agents Into siRNA-Encapsulated Vesicle-Like Nanoparticles for Convenient ICB-Chemo Combination Therapy.

Clinical evidence has demonstrated that combining immune checkpoint blockade (ICB) therapy with chemotherapy significantly improves response rates to ICB therapy and therapeutic efficacy in various tumor types. However, a convenient method for achieving synergistic ICB therapy and chemotherapy with precise co-delivery of both agents is still highly desirable. In this study, a strategy for co-delivering small interfering RNA (siRNA) encapsulated in vesicle-like nanoparticles (VNPsiRNA) and chemotherapeutic drugs is aimed to develop. It is discovered that the hydrophilic chemotherapeutic drug mitoxantrone hydrochloride (MTO·2HCl) can be captured into VNPsiRNA. The resulting VNPsiRNACpMTO can simultaneously block immune checkpoints via RNA silencing and induce chemotherapeutic effects on tumor cells. The mechanism of MTO·2HCl is elucidates, captures, and demonstrates the superior therapeutic effect of VNPsiRNACpMTO through chemo-immunotherapy. This strategy can also be extended to deliver other hydrochloride anticancer drugs, such as doxorubicin hydrochloride (DOX·HCl), for achieving synergistic combination therapy. This study provides a facile strategy for enhancing combined ICB and chemotherapy via co-delivering siRNA and chemotherapeutic drugs, offering a promising approach to cancer treatment.

Cisplatin-Induced Renal Failure Measured by Glomerular Filtration Rate (GFR) with 99mTc-DTPA Scans in Cancer Patients: A Systematic Review and Meta-Analysis

Background: Cisplatin is a potent agent commonly used to treat cancer, but its effects pose a significant risk to renal function. Therefore, the present study aimed to evaluate the impact of cisplatin on renal function as measured by glomerular filtration rate (GFR) using diethyltriamine-penta-acetic acid (DTPA) renal scintigraphy. Methods: Extensive literature searches were performed using PRISMA guidelines that investigated cisplatin-induced renal failure by measuring GFR with DTPA. Eligible studies were included based on predefined criteria. Data on GFR, serum creatinine levels, and acute kidney injury (AKI) before and after cisplatin therapy were extracted and analyzed. A meta-analysis was performed utilizing RevMan 5.4 to determine the overall effect of cisplatin on GFR before and after treatment. For non-randomized controlled trials (RCTs), quality assessment was performed using the Newcastle–Ottawa Scale, while for RCT, the Cochrane risk of bias tool was utilized. Results: Initially, 1003 studies were searched from different databases, including ScienceDirect, PubMed, Scopus, Google Scholar, and The Cochrane Library, and after screening, 8 studies (PubMed, Scopus, and GoogleS cholar) with 489 patients were found eligible for inclusion in the present study. Cisplatin was administrated with varying doses ranging from 20 mg/m2 to 114.02 mg/m2. The findings underscore the nephrotoxic effects of cisplatin, a widely used chemotherapeutic agent, as demonstrated by the significant decline in GFR observed across multiple treatment cycles, and these findings were also supported by the findings of a meta-analysis that showed a significant (p < 0.01) difference between peri- and post-treatment GFR level with 37.06 (95% CI, 10.90–63.23) effect size and 96% heterogeneity. In addition, the included studies were found to be of high quality. Conclusions: Cisplatin significantly affects renal function, as evidenced by a decrease in GFR measured with DTPA. The findings underscore the importance of the routine monitoring of GFR to detect early renal injury and guide treatment modification. Future research should focus on strategies to reduce cisplatin-induced toxicity and explore alternative therapies with reduced renal risk.