Levofloxacin combined with azithromycin is more effective than azithromycin monotherapy in treating cervicitis. The combination significantly reduces inflammatory responses and recurrence rates without increasing adverse effects, making it a valuable option for clinical use.

Multidisciplinary consultation recommended initiation of systemic chemotherapy with cisplatin and etoposide. This case underscores the aggressive nature and poor prognosis associated with malignant insulinomas, particularly those with high proliferative indices. It highlights the complexities of managing refractory hypoglycemia in the context of widespread metastatic disease and emphasizes the urgent need for effective therapeutic strategies to improve patient outcomes.

Combination studies indicated that DSG synergized with the conventional chemotherapeutic agent doxorubicin to suppress MCF-7 cell migration, as confirmed by wound-healing and transwell assays. Collectively, these findings suggest that DSG may serve as a potential agent for inhibiting breast cancer cell metastasis by decreasing FN1 expression.

In conclusion, HO has an inhibitory effect on NASH fibrosis. This effect is mediated by targeting upregulation of hepatocyte FXR, which in turn attenuates hepatocyte apoptosis and thus indirectly inhibits the activation of HSCs.

Δ9 was downregulated in all senescence-induced cell lines compared to control cells, in both the lipidomic analysis and when measuring protein levels via western blotting. Hence, our findings demonstrate that the study of membrane lipid composition and the expression levels of Δ9 could potentially form the basis for future applications investigating the state of cellular senescence.

Molecular docking, molecular dynamics (MD) simulations, and MM/GBSA calculations further confirmed the stable binding of voreloxin to both c-Myc and Bcl-2 G4s, primarily driven by π-π stacking and hydrogen bonding interactions. These findings provide valuable insights for the development of G4-targeting drugs for cancer therapy.

Nerol plays a positive role in alleviating DOX-induced heart failure in rats, possibly by inhibiting cardiomyocyte apoptosis. These findings provide novel evidence and potential targets for developing new cardioprotective drugs.

Therefore, p53 target genes-Fas, DR-5, Puma, and PIDD-were transcriptionally upregulated, leading to activation of the caspase-3-GSDME axis and promoting etoposide-induced pyroptosis in various tumor cells. This study demonstrates a previously uncharacterized association between O-GlcNAcylation and chemotherapy-induced pyroptosis, offering potential therapeutic interventions for pyroptosis-related diseases.

Notable activities of linichlorin B, cynaropicrin, and aguerin B (with IC50 values of 13.67 μg/ml, 6.79 μg/ml, and 3.46 μg/ml, respectively) were detected in the PC-3 cell line; aguerin B demonstrated activity most comparable to the standard anticancer agent doxorubicin. Likewise, linichlorin B, aguerin B, and cynaropicrin demonstrated notable efficacy in the HeLa and MCF-7 cell lines, as reported by the American National Cancer Institute. Aguerin B, linichlorin B, and cynaropicrin are projected to serve as promising novel chemotherapeutic agents for cancer therapy.

The protein-crowning polymeric GO nanoparticles could give multimodal shielding and triple-responsive release of doxorubicin and Snail-targeted siRNA...The findings witness the targeted accumulation and potent cytotoxicity of the hybrid nanoparticles for M2 TAMs and tumor cells; especially, elimination of M2 TAMs in tumor microenvironment holds back Snail-enhancing transforming growth factor (TGF)-β signal pathway, which collaborates with Snail silencing in tumor cells to reverse epithelial mesenchymal transition (EMT) and metastasis-promoting niche. Collectively, the synergistic targeting therapeutic platform could provide a promising solution for metastatic tumor treatment.

Carbonic anhydrase IX inhibitor, protoporphyrin IX (Por) complexed with Fe and epirubicin (EPI) are grafted to hyaluronic acid (HA) via disulfide bonds to obtain HSPFE and loaded xCT inhibitor SAS for fabricating SAS@HSPFE which is actively targeted to deep hypoxic tumor cells, and explosively releasing EPI, Por-Fe complex and SAS due to at high GSH concentration...SAS@HSPFE NPs revealed highly efficient antitumor effect in vivo study. This study provides a novel approach to cancer treatment by targeting redox imbalance.

P2, N=55, Active, not recruiting, Chinese University of Hong Kong | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

In addition, THL attenuated DOX-induced myocardial hypertrophy and cardiac fibrosis in mice, in conjunction with attenuation of DOX-induced upregulation of C-caspase3, Bax, NLRP3, C-caspase-1/Pro-caspase, GSDMD-N/GSDMD, IL-1β, and IL-18 in heart or serum samples. In conclusion, our data supported that THL alleviates the cardiotoxic effects of DOX and suppresses NLRP3 inflammasome in the mouse model, suggesting that THL as a potential drug for DOXIC.

D/P@ZUCO is synthesized using ZnFe2O4 and NH2-UiO66 (Cu/Zr) through an in situ growth method, followed by loading with doxorubicin (DOX) and primaquine (PQ), and functionalization with oxidized hyaluronic acid (OHA). The targeted drug delivery of D/P@ZUCO is facilitated by magnetic guidance and interactions between OHA and CD44 receptors. D/P@ZUCO demonstrates effective cancer treatment by triggering multiple cell death pathways through a synergistic combination of enzymatic actions, serving as a paradigm for systemic activation of multiple enzymes in triple-negative breast cancer therapy.

P2, N=88, Not yet recruiting, Virginia Commonwealth University

Oral mucositis risk and severity in a pediatric population being treated for OS with HDMTX, doxorubicin, and cisplatin were associated with genes in the ABC family (ABCA3, ABCC2, and ABCC6 genes).

P=N/A, N=15, Active, not recruiting, University of Sao Paulo General Hospital | Recruiting --> Active, not recruiting

The results of this study suggested that TQ can decrease oxidative stress levels and DOX-induced cardiotoxicity by activating the Nrf2/HO-1 signaling pathway to alleviate ferroptosis in murine cardiomyocytes.

Furthermore, in vivo experiments demonstrated that blocking CCL20 effectively restores the sensitivity of AML cells to daunorubicin chemotherapy. Collectively, these findings underscore the complex interplay between M2 macrophages, CCL20 signaling, and chemotherapy resistance in AML, highlighting potential therapeutic avenues for intervention.

To address these challenges, we developed polysaccharide hyaluronic acid (HA)-functionalized ruthenium nanoaggregates (Ru NAs) to enhance the chemotherapy of doxorubicin (DOX) for OS. These NAs, comprising Ru nanoparticles (NPs) and alendronate-modified HA (HA-ALN), effectively load DOX, resulting in DOX@Ru-HA-ALN NAs...They can bidirectionally overcome drug resistance of DOX via downregulation of resistance-related factors including multi-drug resistant associate protein, P-glycoprotein, heat shock factor 1, etc. The integration of cascade targeting with bidirectional modulation of drug resistance positions Ru-HA-ALN NAs to substantially enhance DOX chemotherapy for OS. Therefore, the present work highlights the potential of polysaccharide-functionalized nanomaterials in advancing tumor chemotherapy by addressing challenges of both delivery efficiency and drug resistance.

Standard systemic chemotherapy for these tumors includes doxorubicin (DOX)...In vivo experiments demonstrated that TPA inhibited tumor growth in nu/nu mice with relapsed DOX-treated fibrosarcoma 7-fold and led to improved overall (2-fold) survival. In an experimental metastatic model, the combination of TPA with DOX treatment extended overall survival 3-fold, suggesting that targeting CSC can become an effective strategy in the treatment of refractory/relapse fibrosarcoma.

This study presents the important role of FLT3-ITD mutation via its downstream signaling (PI3K/AKT) in the outcome of D3A7 induction therapy. The FLT3-ITD mutation plays an important role in the 12-month survival of AML patients after D3A7 therapy. However, the outcome of D3A7 therapy and FLT3-ITD mutation were not associated with leukemia stem cells.

The nanoparticles also inhibited Proteus mirabilis (ZOI = 1.9 cm) and exhibited promising effects on the gut microbiome of treated animals. Altogether, ETP-CS-LF-MLT-NPs hold great potential for targeted colorectal cancer therapy, improving drug delivery, tumor targeting, bioavailability, and reducing systemic toxicity.

Cisplatin (CP) and doxorubicin (DOX) are common CT drugs indicated to induce ferroptosis in vitro and in vivo. Systematic investigations are, therefore, needed to unfold the roles of ginger, 6G and ZG on ferroptosis involved in CT side effect toxicity, as they are potential natural agents for the prevention of CT toxicity. This review reveals the ferroptotic and non-ferroptotic toxicity mechanisms of CT and the protective mechanisms of ginger, 6G and ZG against CT-induced, ferroptotic and non-ferroptotic organ toxicities.

Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.

Network pharmacological analysis further shows that SII downregulates P53 protein expression by activating the AKT/MDM2 signaling pathway, thus attenuating DIC. In conclusion, this study confirms that SII mitigates DIC through downregulation of the AKT/MDM2/P53 signaling pathway, suggesting a promising therapeutic strategy for alleviating DIC.

The co-culture system revealed a synergistic effect of free DOX on cancer cells while simultaneously mitigating the toxic effects of DOX on normal cells. This study suggests that EXO-DOX has promising potential as a targeted drug delivery system that could potentially improve therapeutic efficacy and minimize off-target toxicity.

P=N/A, N=24, Active, not recruiting, Fox Chase Cancer Center | Trial completion date: Oct 2024 --> Oct 2027 | Trial primary completion date: Jun 2021 --> Oct 2026

Doxorubicin-induced cytotoxicity is associated with autophagy flux in breast cancer. The lysosomal gene ATP6AP1 facilitates autolysosome acidification and contributes to doxorubicin resistance in breast cancer.

IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II.

Moreover, YKL-06-061 effectively enhanced the antiproliferation of gemcitabine or doxorubicin in pancreatic cancer cells in a synergistic manner. Collectively, these findings implicate YKL-06-061 as a promising therapeutic agent for patients with pancreatic cancer.

The reference drug (Doxorubicin) showed a higher toxicity against Vero CCL-81(IC50: 0.41 μg/mL) and DU-145 (IC50: 0.28 μg/mL) cells and a lower selectivity index of 1.46. The DU-145 cells treated with the studied plant extracts exhibited notable upregulation of ar and bcl2, and normalization of caspase 3, cdk1 and p53 expression. The studied plant extracts possess in vitro anti-prostate cancer properties and could be promising candidates for further preclinical studies aimed at developing novel botanical-based therapies for the management of prostate cancer.

P2, N=108, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting

Doxorubicin enhances bortezomib-induced cell death in MM by inhibiting aggresome formation and amplifying ER/Golgi stress and apoptosis. This study highlights the potential therapeutic benefits of combining bortezomib with doxorubicin for MM treatment.

The ethyl acetate stem bark extract of B. coriacea demonstrates significant antioxidant and anticancer activities, potentially through modulation of apoptosis and cell cycle pathways. The presence of bioactive compounds supports its potential as a therapeutic agent, warranting further investigation for developing novel treatments for prostate cancer and oxidative stress-related conditions.

P1, N=50, Completed, Tan Tock Seng Hospital

P1, N=12, Terminated, Swiss Group for Clinical Cancer Research | N=30 --> 12 | Trial completion date: Oct 2024 --> Dec 2023 | Recruiting --> Terminated; The premature termination is based on the unexpectedly low patient accrual to the clinical trial and the strategic considerations in the development of the TLD-1 after having included 13 out of 14 patients in the comparative PK part.

P2, N=20, Active, not recruiting, Shaare Zedek Medical Center | Recruiting --> Active, not recruiting | Trial completion date: Mar 2027 --> Sep 2028 | Trial primary completion date: Mar 2024 --> Sep 2028

Overall, our investigation demonstrated that nigericin and dactinomycin play therapeutic roles in tumours by promoting RMS cell pyroptosis. Interference with GEFT and drug combination can exert a great inhibitory effect on tumours.

Mechanistically, we found that PA inhibited the expression of divalent metal transporter protein 1 (DMT1), suppressed Fe2+ overload in cardiomyocytes, and inhibited ferroptosis, thereby alleviating DIC. Our study demonstrated the feasibility of high-throughput screening targeting the Fe2+ concentration, and elucidated the role and mechanism of PA in alleviating DIC, which provides a new possibility.

In cancer cells exposed to interferon -γ, tumor necrosis factor -α, and etoposide, XAF1 is elevated and actively secreted through the unconventional endo-lysosomal trafficking pathway and the zinc finger 4 domain of XAF1 plays an essential for this secretion...XAF1 expression is associated with overall survival in T cell-enriched cancer patients and also correlates with prognosis in T cell-based immunotherapies. Together, our study identifies XAF1 as a novel secretory immune-modulatory tumor suppressor, illuminating the mechanistic consequence of its inactivation in tumorigenesis.

These results revealed that in FAT1-L AML cells, inhibiting autophagy by CQ enhances the cytotoxic effect of IDA, but leads to immune escape, resulting in AML recurrence. Our study supports the use of a combination of autophagy and PD-L1 inhibitors with IDA to increase the cytotoxic effect of IDA while inhibiting AML recurrence.