Anticancer Research Articles

Hydrophilic Metal-Organic Frameworks Regulated by Biomineralized Protein for Enhanced Stability and Drug Delivery.

For bridging the gap between biological and synthetic materials, the fusion of Metal-Organic Frameworks (MOFs) with biological entities has emerged as a revolutionary strategy in functional materials. In this context, our study introduces a novel structure wherein Bovine Serum Albumin (BSA), a robust and versatile protein, encapsulates zeolitic imidazolate framework-8 (ZIF-8), forming a protein-caged MOF. Highlighting the advantages of this innovative design, the protein-encapsulation enhances the stability and dispersity of ZIF-8, and aids in the synthesis of smaller-sized nanoparticles, crucial for size-impact performance applications. Additionally, the BSA-caged ZIF-8 structure showcases potential in drug delivery applications, especially in the controlled delivery of chemotherapeutic drugs. The study thus elucidates the multifaceted applicability of this novel structure, marking a significant stride in the convergence of biological and synthetic materials.

LncRNA SNHG14 Facilitates Cisplatin Resistance Through Upregulating Notch2 via Binding to U2AF2 in Nasopharyngeal Carcinoma.

Cisplatin (DDP) is one of the commonly used chemotherapeutic drugs for nasopharyngeal carcinoma (NPC) patients, and the resistance of tumor cells to cisplatin is main obstacle for NPC treatment. This study explored effect and possible mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on drug resistance of NPC cells to cisplatin. Levels of SNHG14 and Notch2 in NPC tissues and cells were confirmed using RT-qPCR. Western blot detected Notch2 and ABCB1 expression in NPC cells. IC50 of cisplatin-treated NPC cells was tested utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell proliferation and apoptosis were evaluated utilizing colony formation experiment and flow cytometry, respectively. RNA immunoprecipitation (RIP) assay was utilized to validate the target genes of U2AF2. Notch2 mRNA stability was tested using actinomycin D. SNHG14 level was increased in both cisplatin-resistant NPC tissues and cell lines. SNHG14 silencing in HNE1/DDP cells resulted in inhibition of chemoresistance to cisplatin. Conversely, upregulation of SNHG14 in HNE1 cells enhanced their resistance to cisplatin. SNHG14 exhibited an interaction with U2AF2, leading to stabilization of Notch2 mRNA. Finally, Notch2 was involved in SNHG14-mediated cisplatin resistance in NPC cells. Our findings demonstrate SNHG14 plays a significant role in promoting chemoresistance of NPC cells to cisplatin through U2AF2/Notch2 axis. These results highlight potential therapeutic targets for NPC treatment.

A wearable osmotic microneedle patch provides high-capacity sustained drug delivery in animal models.

The maintenance of stable plasma drug concentrations within a therapeutic window can be critical for drug efficacy. Here, we developed a wearable osmotic microneedle (OMN) patch to support sustained drug dosing for at least 24 hours without the use of electronic components. The OMN patch uses an osmotic pressure driving force to deliver drug solution into the skin through three hollow microneedles with diameters of less than 200 micrometers. The rate of drug release was related to the composition and concentration of the osmogen and drug and to the physical properties of the semipermeable membrane separating the low- and high-solute compartments. The OMN patch released the peptide drug exenatide in rats and mice for 24 hours, whereas subcutaneous injection resulted in a burst release and rapid decline in the plasma drug concentration. OMN release of exenatide improved glycemic control in a diabetic mouse model consistent with a sustained effective plasma concentration of the drug. Continuous release of the small-molecule chemotherapeutic drug cytarabine reduced the progression of acute myeloid leukemia in mice more effectively than subcutaneous injection. Further evaluation of the OMN patch in canines demonstrated continuous dosing of cytarabine up to 225 milligrams for 24 hours, satisfying clinical requirements (150 to 300 milligrams daily). OMN patches were well tolerated in human participants with minimal pain or irritation of the skin and a stated preference over other administration routes. This wearable drug delivery system could provide a platform for stable high-dose drug release with convenience and safety.

Clinical study of different interventional treatments for primary hepatocellular carcinoma based on propensity-score matching

BACKGROUND Transcatheter arterial chemoembolization (TACE) is the main treatment for patients with primary hepatocellular carcinoma (PHC) who miss the opportunity to undergo surgery. Conventional TACE (c-TACE) uses iodized oil as an embolic agent, which is easily washed by blood and affects its efficacy. Drug-eluting bead TACE (DEB-TACE) can sustainably release chemotherapeutic drugs and has a long embolization time. However, the clinical characteristics of patients before the two types of interventional therapies may differ, possibly affecting the conclusion. Only a few studies have compared these two interventions using propensity-score matching (PSM). AIM To analyze the clinical effects of DEB-TACE and c-TACE on patients with PHC based on PSM. METHODS Patients with PHC admitted to Dangyang People’s Hospital (March 2020 to March 2024) were retrospectively enrolled and categorized into groups A (DEB-TACE, n = 125) and B (c-TACE, n = 106). Sex, age, Child-Pugh grade, tumor-node-metastasis stage, and Eastern Cooperative Oncology Group score were selected for 1:1 PSM. Eighty-six patients each were included post-matching. Clinical efficacy, liver function indices (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin), tumor serum markers, and adverse reactions were compared between the groups. RESULTS The objective response and disease control rates were significantly higher in group A (80.23% and 97.67%, respectively) than in group B (60.47% and 87.21%, respectively) (P < 0.05). Post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin were lower in group A than in group B (P < 0.05), whereas post-treatment levels of albumin in group A were comparable to those in group B (P > 0.05). Post-treatment levels of tumor serum markers were significantly lower in group A than in group B (P < 0.05). Patients in groups A and B had mild-to-moderate fever and vomiting symptoms, which improved with conservative treatment. The total incidence of adverse reactions was significantly higher in group B (22.09%) than in group A (6.97%) (P < 0.05). CONCLUSION DEB-TACE has obvious therapeutic effects on patients with PHC. It can improve liver function indices and tumor markers of patients without increasing the rate of liver toxicity or adverse reactions.

Role of solute carrier transporters in ovarian cancer (Review).

Solute carrier (SLC) transporters are involved in various biological processes associated with metabolic reprogramming and cancer, supporting the increased requirement of nutrients and energy. Over the past decade, there have been significant advancements in understanding the expression and function of SLCs in ovarian cancer (OC). This gynecological condition has a high mortality rate and limited treatment options; thus, early diagnosis remains a target clinically. OC exhibits complexity and heterogeneity, resulting in different clinical characteristics, resistance to chemotherapy drugs and poor prognosis. Additionally, SLCs have a different expression pattern between healthy and tumor tissue, and consequently, their inhibition or activation could modify signaling pathways involved in the tumor growth process, such as cell proliferation, apoptosis and drug accumulation. The present review aims to consolidate current data to provide a comprehensive understanding of the potential importance of SLCs in OC. Additionally, it seeks to offer guidance for further research on utilizing SLCs as prognostic biomarkers and therapeutic targets.

Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer.

Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing and post-transcriptional modifications are often altered in cancer to support cellular transformation. In conditions of limiting levels of amino acids, this deregulated control of protein synthesis leads to aberrant protein production in the form of ribosomal frameshifting or misincorporation of non-cognate amino acids. Here, we studied leucine, an essential amino acid coded by six different codons. Surprisingly, we found that leucine deprivation leads to ribosomal stalling and aberrant protein production in various cancer cell types, predominantly at one codon, UUA. Similar effects were observed after treatment with chemotherapeutic agents, implying a shared mechanism controlling the downstream effects on mRNA translation. In both conditions, a limitation in the availability of tRNALeu(UAA) for protein production was shown to be the cause for this dominant effect on UUA codons. The induced aberrant proteins can be processed and immune-presented as neoepitopes and can direct T-cell killing. Altogether, we uncovered a novel mode of interplay between DNA damage, regulation of tRNA availability for mRNA translation and aberrant protein production in cancer that could be exploited for anti-cancer therapy.

Liposomal Codelivery of Doxorubicin and Curcumin Sensitizes Antitumor Activity and Reduces Tumor Metastasis.

Multidrug resistance (MDR) is a major obstacle to traditional cancer treatment using chemotherapeutic agents like doxorubicin (DOX). MDR affects drug dosage regimens and enables the recurrence and metastasis of cancer. Because DOX causes severe side effects at high dosages, it is important to use an MDR modulator to make cancer cells sensitive to DOX. This work focused on a liposome-based codelivery system containing curcumin (CUR) and DOX, focusing on CUR as an MDR modulator. The synergistic effect was maximized when the ratio of DOX and CUR was 1:1, and the synthesis of liposomal drugs was successfully verified. In addition, a successful MDR reversal effect was demonstrated through rhodamine 123 assay, Western blotting, and immunofluorescence. Compared to the conventional DOX treatment, the dual-drug treatment exhibits a significantly improved anticancer effect. In the murine metastasis 4T1 IP tumor model, the dual-drug-encapsulating liposomes successfully suppressed tumor growth and reversed the tumoral effect (omental tumor metastasis, fat, and muscle weight loss) into a normal state.

PD-L1 antibody conjugated dihydrotanshinone I-loaded polymeric nanoparticle for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death

PurposeCombination immune checkpoint inhibitors (ICI) with chemotherapeutic agents has proven to be highly promising in cancer therapy. However, low response rate, immune-related adverse events, and lack of effectively targeted co-delivery strategy are still major hurdles to overcome for this combination therapeutic regimen. Herein, programmed death-L1 (PD-L1) antibody modified and dihydrotanshinone I (DHT) loaded nanoparticle was prepared for tumor targeting drug delivery, thus achieving immune checkpoint blockade (ICB) and immunogenic cell death (ICD) synergistic anti-tumor effects. MethodsThe DHT-loaded nanoparticle (DHT NP) was prepared by the emulsion solvent diffusion method. Atezolizumab (ATEZO) was thiolated with 2-iminothiolane and conjugated to the surface of DHT NP to prepare the ATEZO DHT NP. The drug encapsulation efficiency, drug loading, particle size and drug release were determined. The in vitro cellular uptake, cell proliferation inhibition and apoptosis were evaluated on the HGC-27 tumor cell. The in vivo tumor targeting, anti-tumor efficiency and immune regulation were assessed on tumor bearing mice. ResultsThe optimized ATEZO DHT NP was a spherical nanoparticle of about 250 nm with a continuous drug release profile. It was selectively taken up by the tumor cells through PD-L1 receptor-mediated endocytosis, which resulted in enhanced cytotoxicity and cell apoptosis. In vivo imaging further demonstrated its superior tumor tissue targeting ability. When tumor bearing mice were treated with the ATEZO DHT NP, its synergistic anti-tumor effect was much stronger than that of a single drug. Moreover, the tumor targeting delivery of DHT caused tumor necrosis and initiated ICD with release of tumor-associated antigens, which efficiently up-regulated the population of CD4+ and CD8+ T cells. Notably, there were no obvious system toxicity or tissue damage occur during the whole treatment period. ConclusionThe ATEZO DHT NP could specifically target to tumor and enhance treatment efficiency through combination of PD-L1 blockade with ICD effect.

Newly Synthesized Citral Derivatives Serve as Novel Inhibitor in HepG2 Cells.

2H-pyran compound 1 synthesized from 6-methylpyridine-2,4-diol and citral, has been used for Cu-catalyzed N-arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC50 value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.5 μM). Meanwhile, the cell-cycle arrest of HepG2 cells occurred in the S phase, and the apoptosis of HepG2 cells was significantly increased with increasing drug concentration. In addition, real-time fluorescence quantification PCR and Western blotting experiments showed that the expression of apoptotic protein BAX was increased, while the expression of anti-apoptotic protein BCL2 was inhibited in a dose-dependent fashion. The results of these experiments indicated that apoptosis was promoted in HepG2 cells via apoptotic signaling pathway activated by 3 h. Furthermore, 3 h effectively decreased the phosphorylation levels of PI3 K, ATK and ERK, resulting in the inhibitions of MAPK/ERK and PI3 K/ATK signaling pathways. Briefly, 3 h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells and may be used as anti-cancer drug in the future.

Fungal Influences on Cancer Initiation, Progression, and Response to Treatment.

Fungal dysbiosis is increasingly recognized as a key factor in cancer, influencing tumor initiation, progression, and treatment outcomes. This review explores the role of fungi in carcinogenesis, with a focus on mechanisms such as immunomodulation, inflammation induction, tumor microenvironment remodeling, and interkingdom interactions. Fungal metabolites are involved in oncogenesis, and antifungals can interact with anticancer drug, including eliciting potential adverse effects and influencing immune responses. Furthermore, mycobiota profiles have potential as diagnostic and prognostic biomarkers, emphasizing their clinical relevance. The interplay between fungi and cancer therapies can impact drug resistance, therapeutic efficacy, and risk of invasive fungal infections associated with targeted therapies. Finally, emerging strategies for modulating mycobiota in cancer care are promising approaches to improve patient outcomes.

L-Cystine-Based Polyurethane as a Drug-Delivery Vehicle in Targeted Cancer Therapy and Biomedical Applications.

Controlled and sustained drug release is a critical aspect of drug-delivery systems (DDSs) that can be used in chemotherapy while ensuring therapy effectiveness and biosafety. Hence, polyurethane (PU) is modified using a biomolecule Cystine (CYS) for protracted drug release, aiming to enhance cancer treatment efficacy while minimizing adverse side effects in tumor patients. To confirm the formation of a polymer structure, characterization techniques such as NMR and FTIR are used, and the morphology is determined using SEM. Biocompatibility of the synthesized polymers is evaluated through cellular assessments, including MTT assay, cell adhesion, and antibacterial assay along with drug release using an anticancer drug, Paclitaxel (PTX). Notably, the incorporation of PTX in the polymer matrix results in minimal mortality (85% viable cells) rates in healthy cells (3T3), in contrast to a 56% mortality rate observed with the pure drug. While PTX shows a burst release and kills cancer cells only for the first 24 h, PU loaded with the drug shows sustained release and kills the cancer cells for 3 days. This vehicle selectively kills 59% of SiHA cells after a consecutive study of 3 days, which highlights the potential of this newly designed vehicle for effective drug delivery, particularly in anticancer treatments. Moreover, cystine's antibacterial property adds up with PU; hence, PU shows antibacterial activity against Staphylococcus aureus (MIC, 20 μg/mL) and also acts as a reductive oxygen species scavenger. Therefore, modifying PU with CYS has shown sustained release of PTX along with a selective effect on cells, underscoring its significance as a superior delivery agent and supported by a shred of convincing evidence.

Synthesis, characterization, X-ray structure, and DFT calculations of Zn complex encompassing HLN2O ligand: Relevance in cytotoxicity and antifungal photodynamic therapy.

This article presents the synthesis, characterization, and X-ray crystallographic features of one new Zn complex derived from a Salen-type tridentate ligand (HLN2O). A single-crystal diffraction study determined the complex crystal structure, which confirms that it crystallizes in the orthorhombic space group P212121. The single-crystal structure is constructed using the unique mononuclear component [ZnLN2°] and supramolecular CH∙∙∙π type interaction, resulting in a 1D structure. The IR, HRMS, and NMR study also support the complex structure. The Zn metal centre has a distorted square pyramidal geometry with τ value of 0.49. The Hirshfeld surfaces and 2D fingerprint confirm predominant H…H (77.9 %) interactions, with minor H…O, H…C, and H…N (5.0 %, 4.9 %, and 0.2 %). DFT calculations employed the B3LYP-D3/Lanl2DZ class of theory. FMO/MEP explains the complex reactivity perspective, while IP (4.71 eV) and low EA (1.11 eV) suit biological applications. The bonding gateway was analysed using NBO/QTAIM-NCI and ELF-LOL plots. Cytotoxicity was assessed using the Trypan blue exclusion method and tested against the DLA cell line, showing effectiveness against the DLA cell and suggesting complex potential as an anticancer agent. Antifungal photodynamic therapy (APDT) explored that ligand and Zn complex have significant activity against C. albicans. Finally, molecular docking simulations substantiate the experimental findings.

In Silico Evaluation of Some Computer-Designed Fluoroquinolone–Glutamic Acid Hybrids as Potential Topoisomerase II Inhibitors with Anti-Cancer Effect

Background/Objectives: Fluoroquinolones (FQs) are topoisomerase II inhibitors with antibacterial activity, repositioned recently as anti-cancer agents. Glutamic acid (GLA) is an amino acid that affects human metabolism. Since an anti-cancer mechanism of FQs is human topoisomerase II inhibition, it is expected that FQ-GLA hybrids can act similarly. Methods: We designed 27 hypothetical hybrids of 6 FQs and GLA through amide bonds at the 3- and 7-position groups of FQs or via ethylenediamine/ethanolamine linkers at the carboxyl group of the FQ. Hydroxamic acid derivatives were also theoretically formulated. Computational methods were used to predict their physicochemical, pharmacokinetic, or toxicological properties and their anti-cancer activity. For comparison, etoposide was used as an anti-cancer agent inhibiting topoisomerase II. Molecular docking assessed whether the hybrids could interact with the human topoisomerase II beta in the same binding site and interaction sites as etoposide. Results: All the hybrids acted as potential topoisomerase II inhibitors, demonstrating possible anti-cancer activity on several cancer cell lines. Among all the proposed hybrids, MF-7-GLA would be the ideal candidate as a lead compound. The hybrid OF-3-EDA-GLA and the hydroxamic acid derivatives also stood out. Conclusions: Both FQs and GLA have advantageous structures for obtaining hybrids with favourable properties. Improvements in the hybrids’ structure could lead to promising results.

A sulfonimide derivative of bezafibrate as a dual inhibitor of cyclooxygenase-2 and PPARα

BackgroundPPARα and cyclooxygenase (COX)-2 are overexpressed in certain types of cancer. Thus, developing a dual inhibitor that targets both could be more effective as an anticancer agent than single inhibitors. We have previously shown that an analog of the bezafibrate named AA520 is a PPARα antagonist. Herein, we report the identification of AA520 as a potent COX-2 inhibitor using in silico approaches. In addition, we performed a thorough pharmacological characterization of AA520 towards COX-1 and COX-2 in different in vitro models.MethodsAA520 was characterized for inhibiting platelet COX-1 and monocyte COX-2 activity in human whole blood (HWB) and for effects on lipidomics of eicosanoids using LC-MS/MS. The kinetics of the interaction of AA520 with COX-2 was assessed in the human colon cancer cell line, HCA-7, expressing only COX-2, by testing the COX-2 activity after extensive washing of the cells. The impact of AA520 on cancer cell viability, metabolic activity, and cytotoxicity was tested using the MTT reagent.ResultsIn HWB, AA520 inhibited in a concentration-dependent fashion LPS-stimulated leukocyte prostaglandin (PG) E2 generation with an IC50 of 0.10 (95% CI: 0.05–0.263) μM while platelet COX-1 was not affected up to 300 μM. AA520 did not affect LPS-induced monocyte COX-2 expression, and other eicosanoids generated by enzymatic and nonenzymatic pathways. AA520 inhibited COX-2-dependent PGE2 generation in the colon cancer cell line HCA7. Comparison of the inhibition of COX-2 and its reversibility by AA520, indomethacin (a time-dependent inhibitor), acetylsalicylic acid (ASA) (an irreversible inhibitor), and ibuprofen (a reversible inhibitor) showed that the compound is acting by forming a tightly bound COX-2 interaction. This was confirmed by docking and molecular dynamics studies. Moreover, AA520 (1 μM) significantly reduced MTT in HCA7 cells.ConclusionWe have identified a highly selective COX-2 inhibitor with a unique scaffold. This inhibitor retains PPARα antagonism at the same concentration range. It has the potential to be effective in treating certain types of cancer, such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), where COX-2 and PPARα are overexpressed.

Toxicity of bioactive compounds from Halocnemum strobilaceum against A549 lung cancer cells

This study investigates the toxicity of bioactive compounds isolated from the halophytic plant Halocnemum strobilaceum against A549 lung cancer cells. Sequential extraction using petroleum ether, chloroform, and methanol yielded various fractions, with the petroleum ether extract demonstrating the highest cytotoxicity. Through bioassay-guided fractionation and isolation techniques, including vacuum liquid chromatography and column chromatography, three compounds were identified: (1) Di(2-ethylhexyl) phthalate, (2) isorhamnetin-3-glucoside, and (3) quercetin-3-glucoside. The cytotoxic effects of these compounds were assessed using the MTT assay, revealing significant toxicity on A549 cells, with quercetin-3-glucoside exhibiting 78% cytotoxicity and isorhamnetin-3-glucoside showing 69% cytotoxicity at a concentration of 100 μg/mL. These findings suggest that the toxic effects of H. strobilaceum may be attributed to the presence of bioactive compounds, such as flavonoids and polyphenols, known for their antioxidant and free-radical scavenging capabilities. This highlights the potential of H. strobilaceum as a source of novel anti-cancer agents, warranting further studies to elucidate the mechanisms of action and explore therapeutic applications.

Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells

IntroductionCannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.MethodsHerein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.ResultsTwo CBD piperazinyl derivatives (19 and 21) showed augmented antiproliferative effects with an IC50 of 5.5 and 4.1 µM, respectively, compared to CBD’s IC50 of 22.9 µM. Further studies suggest that modulation of apoptosis and ferroptosis may contribute to the cytotoxic effects of CBD and its derivatives. In addition, CBD and its derivatives (19 and 21) were explored for their potential synergistic antiproliferative effects in combination with chemotherapeutic agent cisplatin. Compounds 19 or 21 (5 µM) combined with cisplatin (1 µM) showed a synergistic effect with a combination index of 0.23 and 0.72, respectively. This effect was supported by elevated levels of reactive oxygen species in Caov-3 cells treated with cisplatin combined with 19 or 21.DiscussionFindings from this study suggest that CBD derivatives with enhanced antiproliferative effects may exert synergistic effects with chemotherapeutic drugs, providing insight into the development of cannabinoid-based adjuvant agents for the management of ovarian cancer.

Colorectal Cancer in Elderly Patients: Insights into Presentations, Prognosis, and Patient Outcomes

Background and Objectives: Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and is the third leading cause of cancer-related deaths. In 2020 alone, there were over 1.9 million new cases of CRC and nearly 0.9 million deaths worldwide. The incidence and outcomes of CRC exhibit significant geographical and temporal variations, largely influenced by diverse risk factors among populations. Recognizing the prognostic factors and the presenting symptoms of CRC, a leading global cancer with high mortality, can enhance early detection and thereby improve clinical outcomes. Materials and Methods: This retrospective, observational study analyzed 724 CRC elderly patients aged 70 and over (median age 80, 53.17% male), treated at a single center. Data on demographics, clinical characteristics, and outcomes were collected. Overall survival was analyzed using Kaplan–Meier curves, with stratification based on tumor location, disease staging, lymph node involvement, and family history. Results: Our study encompassed all CRC cases treated with surgery and systemic therapies (chemotherapy or biological agents) from July 2002 to September 2020. We focused on comparing prognosis between left-sided and right-sided CRC, as well as rectal cancer. We found that left-sided CRC demonstrated a superior prognosis compared to rectal cancer (p = 0.0022). Furthermore, among patients with CRC, tumors originating in the rectum were associated with worse outcomes compared to those arising in both the right and left colon, regardless of disease stage (p = 0.0049). Additionally, a family history of CRC was associated with poorer prognosis, impacting both metastatic (p = 0.0022) and localized disease (p = 0.035). The main symptoms prompting patients to start an investigation of CRC were abdominal pain (31.49%), anemia (18.08%), rectal bleeding (hematochezia) (17.82%), change in bowel habits (9.94%), and weight loss (7.60%). Conclusions: This study provides valuable insights into the symptoms prompting initial investigation and the prognostic factors associated with CRC in an elderly population with varied characteristics. It underscores the need for increased vigilance in recognizing key symptoms and the importance of personalized treatment strategies tailored to these prognostic factors.

Enhancing the Cytotoxic Effects of Carboplatin and Cisplatin on Liposomes in Oral Cancer Cells with Curcumin

Background: Oral squamous cell carcinoma remains challenging to treat effectively with conventional chemotherapy, leading researchers to explore synergistic combinations to enhance therapeutic outcomes. Combining curcumin with platinum-based drugs, such as cisplatin and carboplatin, has demonstrated potential in enhancing cytotoxic effects. However, limited studies have explored these combinations’ efficacy and sustained release profile in liposomal form specifically for oral cancer. This study investigates the enhanced cytotoxic effects of cisplatin-curcumin and carboplatin-curcumin nanoliposome formulations on CAL 27 oral cancer cells. Methods and Materials: Nanoliposomes encapsulating cisplatin or carboplatin with curcumin were formulated and characterized by particle size, zeta potential, and polydispersity index (PDI) to ensure optimized delivery properties. Particle sizes of the cisplatin and carboplatin nanoliposomes ranged from 175 to 187 nm, with a zeta potential greater than -30 mV, indicating good stability, and PDI values less than 0.48, suggesting uniform particle size distribution. In vitro cytotoxicity was assessed using the MTT assay at 24, 48, and 96 hours across different curcumin concentrations. Results: Cisplatin-curcumin and carboplatin-curcumin nanoliposome formulations demonstrated significantly increased cytotoxicity in CAL 27 cells compared to control groups. Drug release studies indicated a sustained release profile, with approximately 22% of cisplatin and 28% of carboplatin released over 52 hours, which may prolong therapeutic effects by maintaining drug availability within the cancer cells. Conclusion: The findings suggest that cisplatin-curcumin and carboplatin-curcumin nanoliposomal formulations enhance the cytotoxic effects of these chemotherapeutic agents while providing a stable, sustained release profile.

Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells

Abstract This research examines the cytotoxic consequences of thymoquinone-loaded bovine serum albumin nanoparticles (TQ-BSA NPs) on the A549 lung cancer cell line. UV-visible (UV–Vis) spectroscopy, Fourier transform infrared spectrophotometer (FT-IR), scanning electron microscopy (SEM), and dynamic light scattering (DLS) were employed to verify the biogenic TQ-BSA NPs’ size, shape, and distribution. UV–Vis spectrophotometry indicated peaks at 200–300 nm, 500–600 nm, and a prominent peak at 700–800 nm, confirming the presence of TQ-BSA NPs. The polydispersity index, as confirmed by DLS, indicated a solvent distribution in water, accompanied by a zeta potential value of 126.2 ± 46.8 mV. The average size of TQ-BSA NPs was confirmed to be 187 ± 8 nm by SEM. TQ-BSA NPs reduce colony formation in the A549 lung cancer cell line in a dose-dependent manner relative to the control group. Protein expression analysis indicated that TQ-BSA NPs promoted programmed cell death by increasing pro-apoptotic levels and decreasing anti-apoptotic levels. TQ-BSA NPs demonstrated inhibition of cancer cell proliferation and promotion of apoptosis and exhibited significant efficacy against cancer cells at low concentrations. As a result, they have the makings of a promising chemotherapeutic agent for low-dose, long-term administration.

The Protective Effects of Carvacrol Against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.

Doxorubicin (DOX) is a remarkable chemotherapeutic agent, however, its adverse effect on DOX-induced cardiotoxicity (DIC) is a rising concern. Recent research has identified carvacrol (CAR), an antioxidant and anti-inflammatory agent, as a promising natural compound for protecting against DIC. This study aims to investigate the potential cardioprotective effects properties of CAR in vitro and in vivo. The cardioprotective effect of CAR was assessed by pretreating H9c2 cells with non-toxic CAR for 24h, followed by co-treatment with DOX (10μM) for an additional 24h. The cell viability was determined using an MTT assay. For the in vivo study, male Sprague-Dawley rats (200-250g) were randomly divided into three groups: control, cardiotoxicity (DOX), and treatment (CAR + DOX) groups. CAR (50mg/kg, BW) was administered orally to the CAR + DOX groups for 14days. Then, a single dose of DOX (15mg/kg/i.p, BW) was administered on day 15 for DOX and CAR + DOX groups. The rats were allowed to recover for 3days before being sacrificed. Our results demonstrated that DOX (10µM) significantly reduced H9c2 cell viability by 50% (p < 0.0001), and CAR (0.067µM) protected H9c2 cells from DIC (p = 0.0045). In the rat model, CAR pretreatment effectively mitigated DOX-induced reductions in systolic pressure (p = 0.0007), pulse pressure (p = 0.0213), hypertrophy (p = 0.0049), and cardiac fibrosis (p = 0.0006). However, the pretreatment did not alter the heart function, oxidative stress, and antioxidant enzymes. In conclusion, our results indicate that CAR could potentially serve as an adjuvant to reduce cardiotoxicity by ameliorating myocardial fibrosis and hypertrophy.