Current Cancer Drug Targets - Online First

Historically, there has been a lack of focus on the mortality rates of individuals with both diabetes and Bladder Bancer (BC). Our study aimed to identify the risk factors associated with death from Diabetes Mellitus (DM) in BC patients.

Data was gathered from the SEER database on individuals who were diagnosed with BC between the years 2000 and 2017. Calculation of the Standardized Mortality Ratio (SMR) was performed to determine the mortality rate of DM in patients from BC. Potential risk factors for DM mortality were identified by a multivariate competing risk model. Hazard Ratios (HR), with 95% confidence intervals (95% CI) were used to indicate the degree of associated risk.

A total of 217,230 BC patients' data were collected from the SEER database for analysis. Among them, 98,880 patients passed away, and 1,783 patients encountered DM mortality. The overall SMR for DM mortality in BC patients was 3.32 (95% CI: 3.17-3.48). Results indicated that SMR increased with increasing years but decreased with increasing follow-up time. Multivariate competing risk analysis shows that BC patients with the following factors were at higher risk of developing DM mortality: advanced age, male, black, in situ tumor stage, early year of diagnosis, pathology type of transitional cell carcinoma, without chemotherapy or radiation therapy, and absence of spouse (including separated, divorced, widowed, and unmarried).

Individuals diagnosed with BC are at a considerably elevated risk of mortality from DM compared to the general population. It is of the utmost importance to identify high-risk groups and implement effective interventions for DM in order to enhance the survival rate among this patient population.

Quinoline derivatives, often incorporating other heterocyclic structures, have shown a wide range of therapeutic potential, especially in the treatment of cancer. These compounds have demonstrated significant anticancer activity against various cell lines, including HeLa (human cervical cancer) and MDA-MB-435 (melanoma), exhibiting strong inhibitory effects.

In this study, arylhydrazonopyrazole derivatives (3a-c) were employed in a series of multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinoline and pyran derivatives. Pyrazolo[1,5-a]quinoline derivatives, due to their structural properties, are considered valuable scaffolds for the development of novel drugs targeting similar biological pathways, with the potential for improved therapeutic efficacy. This study aimed to demonstrate the use of simple arylhydrazonopyrazole derivatives in multicomponent reactions with cyclic ketones and aromatic aldehydes. The resulting compounds were then assessed for their cytotoxic and antiproliferative activities. Following these reactions, further heterocyclization processes were conducted, incorporating the quinoline moiety into the final structures. These findings underscore the potential of pyrazolo[1,5-a]quinoline derivatives as promising candidates for drug discovery, offering new avenues for targeting diseases with related molecular mechanisms.

The key starting compound in this study was 3,5-dimethyl-4-(2-phenylhydrazono)-4H-pyrazole, which has been utilized in numerous heterocyclization reactions. These reactions, involving various reagents, such as cyclic ketones and diketones in the presence of aromatic aldehydes, led to the formation of fused tetracyclic compounds. Arylhydrazonopyrazole derivatives (5a-c) were employed in multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinoline and pyran derivatives. The reactions were carried out using both conventional catalysts and ionic liquid-immobilized catalysts. Notably, the use of ionic liquid-immobilized catalysts resulted in higher yields of the desired compounds.

In this study, new compounds were synthesized, characterized, and evaluated for their cytotoxicity against six cancer cell lines: A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Additionally, the cytotoxic effects of the synthesized compounds were assessed against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cell lines. Morphological studies of selected compounds were also conducted to further understand their effects on the cancer cells. Moreover, the cytotoxicity of the selected compounds was tested against seventeen different cancer cell lines, categorized by disease type. Morphological analyses of these selected compounds were also performed to gain deeper insights into their potential as anticancer agents.

The inhibition assays of the tested compounds demonstrated significant activity against c-Met enzymatic activity, with IC50 values ranging from 0.25 to 10.30 nM. Additionally, potent inhibition was observed in the prostate PC-3 cell line, with IC50 values ranging from 0.19 to 8.62 µM. These promising results highlight the potential of these compounds and encourage further research to explore their therapeutic applications in the future.

Lenvatinib is an oral tyrosine kinase inhibitor that selectively inhibits receptors involved in tumor angiogenesis and tumor growth. It is an emerging first-line treatment agent for hepatocellular carcinoma (HCC). However, there is no intravenous administration of Lenvatinib.

This study aimed to construct nanocomposites that can efficiently support Lenvatinib and target liver cancer tissues and cells.

In this study, ferric oxide-viral-like mesoporous silica nanoparticles-folic acid (Fe3O4-vMSN-FA) nanocomposites loaded with Lenvatinib were constructed, and their anti-hepatocellular carcinoma effects were evaluated.

The hydrothermal method was used to synthesize ferric oxide (Fe3O4). Ferric oxide-viral-like mesoporous silica nanoparticles (Fe3O4-vMSN) were synthesized using a two-phase method. Then, Fe3O4-vMSN was modified with folic acid (Fe3O4-vMSN-FA) to better target tumor cells.

The experimental data showed that Fe3O4-vMSN-FA nanocomposites were successfully synthesized and could be loaded with Lenvatinib (Len@ Fe3O4-vMSN-FA). Fe3O4-vMSN-FA had good stability and biocompatibility, and it can release the loaded Lenvatinib faster in an acidic environment (pH 5.5). CCK8 assay and flow cytometry showed that HepG2 cells in the Len@ Fe3O4-vMSN group had the lowest cell viability and the highest apoptosis rate, confirming the anticancer properties of Len@ Fe3O4-vMSN-FA in vitro. In addition, transwell experiments showed that the migration and invasion ability of HepG2 cells in the Len@ Fe3O4-vMSN-FA group were significantly inhibited. In vivo fluorescence imaging in mice confirmed the enhanced tumor-targeting ability of Fe3O4-vMSN-FA. The tumor volume of the Len@ Fe3O4-vMSN-FA group was significantly reduced, and there was no significant effect on body weight. Moreover, serum liver function index (ALT and AST) and HE staining showed that Len@ Fe3O4-vMSN-FA did not cause obvious damage to organ tissue.

Len@ Fe3O4-vMSN-FA has a good anti-liver cancer effect. Fe3O4-vMSN-FA can be used as an alternative platform for drug delivery, providing more options for cancer therapy.

There is a relative lack of real-world data regarding the treatment of advanced squamous cell lung cancer (SqCLC) with anlotinib.

This study aimed to investigate the clinical efficacy and safety of combining anlotinib with ICIs for the treatment of advanced SqCLC.

Sixty patients with advanced SqCLC from December, 2017 to December, 2022, were retrospectively recruited in the final analysis. The overall survival (OS), adverse events (AEs), and short-term clinical effectiveness, including complete remission (CR), partial remission (PR), stable disease (SD), and progression disease (PD) of the study populations, were observed. Objective response rate (ORR) was defined as the combined percentage of CR and PR in all patients. Disease control rate (DCR) was defined as the combined percentage of CR, PR, and SD in all patients. Subgroups were classified based on age (<65 or ≥65), sex (female or male), and the eastern cooperative oncology group (ECOG) score (0-1 or 1-2).

The median age of the study population was 65 years, and 41 (68.3%) of the participants were male. ORR was 21.67%, and DCR was 83.33%. The median PFS and OS were 7.5 and 19.5 months, respectively. Furthermore, the Kaplan-Meier curves demonstrated no significant difference (P >0.05) in PFS and OS between different age groups, sex, and ECOG scores. Bone marrow suppression was the most common AE, followed by immune pneumonia.

The findings of this study confirmed the effectiveness and safety of anlotinib and ICIs for advanced SqCLC.

Ferroptosis, a regulated cell death initiated by Fe-dependent lipoperoxidation, is closely linked to the development of lung adenocarcinoma (LUAD). LncRNA human leukocyte antigen complex P5 (HCP5) has been confirmed as oncogenic in LUAD, but its function in ferroptosis is unknown.

Based on the previous bioinformatics mining of the ceRNA (competitive endogenous RNA) network HCP5/miR-17-5p/ Homeobox A7 (HOXA7) related to ferroptosis in LUAD, in this study, we characterized the cell-based experiments to validate the binding between the HCP5/miR-17-5p/HOXA7 axis and ferroptosis.

The HCP5/miR-17-5p/HOXA7 linkage was identified by a two-luciferase reporter. Cell Counting Kit-8 (CCK-8) and Transwell assay were employed for the detection of viability, invasion, and migration of A549 cells, respectively. ACSL4 and SLC7A11 were associated with ferroptosis, MMP 9, vimentin, and E-cadherin, which were associated with migration and invasion and were assessed by WB and qRT-PCR. Fe2+ and malondialdehyde (MDA) were analyzed using kits.

Over-expression of HCP5 enhances the growth, invasion, and migration of A549 cells by adjusting miR-17-5P to increase the expression of HOXA7. In addition, the knockdown of HCP5 elevated miR-17-5p, which inhibited HOXA7 expression and suppressed ferroptosis and EMT in A549 cells.

HCP5/miR-17-5p/HOXA7 can affect ferroptosis as well as the biological behavior of A549 cells.