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Background: The treatment alternatives for bladder cancer (BLCA), the 10th most prevalent cancer in the world, need to be further investigated, and many active substances like Puerarin in herbal medicine were found to be effective in treating BLCA. The purpose of this study was to investigate the potential treating mechanisms of Puerarin on BLCA. Methods: The cell counting kit 8 assay and flow cytometry were performed to confirm Puerarin’s ability to suppress BLCA. The differentially expressed proteins (DEPs) were obtained by Tandem Mass Tags technology and functional enrichment analysis performed by Rstudio. The most enriched pathways were selected for study and the DEPs were screened out. Protein-protein interaction network maps were created using String and Cyto scape and key proteins, which will be analyzed for survival, expression, and upstream transcription factor prediction, were screened out using the cyto Hubba plugin. CHEA3 was used to obtain upstream transcription factor validated by molecular docking and western blotting experiments. Results: Cell counting kit 8 showed that Puerarin inhibited BLC Acells, with 50% inhibitory concentration of 218 µmol/L in T24 and 198 µmol/L in 5637. Flow cytometry reveals that Puerarin blocks T24 and 5637 cells in G1 phase. 1,385 DEPs were obtained and the enrichment analysis revealed that cell cycle and DNA replication were the two main areas in which DEPs were enriched. Cyclin-B-cyclin dependent kinase 1 (CDK1), cyclin B1 (CCNB1), and polo-like kinase 1 (PLK1) were identified as key proteins, and their up stream transcription factor was predicted to be centromere protein A (CENPA). Puerarin’s binding energy to CENPA was determined by molecular docking to be −6.3 kcal/mol, indicating a strong binding interaction. Western blot showed that Puerarin significantly reduced the expression of CENPA. Conclusion: We hypothesize that Puerarin may inhibit the proliferation of bladder cancer cells by inhibiting CENPA expression to regulate PLK1and CCNB1 expression, thereby affecting cell cycle. [ABSTRACT FROM AUTHOR]

Photothermal therapy is an alternative cancer therapy that uses a photothermal agent with light irradiation to induce fatal hyperthermia in cancer cells. In a previous study, we found that ex vivo photothermal (PT) treatment induced expression of heat shock proteins (HSPs), such as HSP70, HSP27, and HSP90, in cancer cells; moreover, immunization with lysates from PT-treated tumor cells resulted in significant tumor growth inhibition in tumor-bearing mice. In this study, we hypothesized that sublethal PT treatment of antigen-presenting cells regulates their immunogenicity. We observed the upregulation of expression of intracellular HSP70 and surface activation markers, such as CD40, CD80, CD86, and MHC class II, in sublethal PT-treated cells. The protumoral activity of myeloid-derived suppressor cells (MDSCs) was reduced by sublethal hyperthermia. Furthermore, poorly immunogenic MDSCs were converted into immunogenic antigen-presenting cells by PT treatment. The differences in immunogenicity between MDSCs untreated or treated with the PT technique were evaluated using the Student's t-test or Mann–Whitney rank sum test. Collectively, direct hyperthermic treatment resulted in phenotypic changes and the functional regulation of immune cells. [ABSTRACT FROM AUTHOR]

Despite recent medical progress, cervical cancer remains a major global health concern for women. Current standard treatments have limitations such as non-specific toxicity that necessitate development of safer and more effective therapeutic strategies. This research evaluated the combinatorial effects of olive leaf extract (OLE), rich in anti-cancer polyphenols, and the oncolytic Newcastle disease virus (NDV) against human cervical cancer cells. OLE was efficiently encapsulated (>94% loading) within MF59 lipid nanoparticles and nanostructured lipid carriers (NLCs; contains Precirol as NLC-P, contains Lecithin as NLC-L) to enhance stability, bioavailability, and targeted delivery. Physicochemical analysis confirmed successful encapsulation of OLE within nanoparticles smaller than 150 nm. In vitro cytotoxicity assays demonstrated significantly higher toxicity of the OLE-loaded nanoparticle formulations on HeLa cancer cells versus HDF normal cells (P<0.05). MF59 achieved the highest encapsulation efficiency, while NLC-P had the best drug release profile. NDV selectively infected and killed HeLa cells versus HDF cells. Notably, combining NDV with OLE-loaded nanoparticles led to significantly enhanced synergistic cytotoxicity against cancer cells (P<0.05), with NLC-P (OLE) and NDV producing the strongest effects. Apoptosis and cell cycle analyses confirmed the increased anti-cancer activity of the combinatorial treatment, which induced cell cycle arrest. This study provides evidence that co-delivery of OLE-loaded lipid nanoparticles and NDV potentiates anti-cancer activity against cervical cancer cells in vitro through a synergistic mechanism, warranting further development as a promising alternative cervical cancer therapy. [ABSTRACT FROM AUTHOR]

Microwave ablation has become a viable alternative for cancer treatment for patients who cannot undergo surgery. During this procedure, a single‐slot coaxial antenna is employed to effectively deliver microwave energy to the targeted tissue. The success of the treatment was measured by the amount of ablation zone created during the ablation procedure. The significantly large blood vessel placed near the antenna causes heat dissipation by convection around the blood vessel. The heat sink effect could result in insufficient ablation, raising the risk of local tumor recurrence. In this study, we investigated the heat loss due to large blood vessels and the relationship between blood velocity and temperature distribution. The hepatic artery, with a diameter of 4 mm and a height of 50 mm and two branches, is considered in the computational domain. The temperature profile, localized tissue contraction, and ablation zones were simulated for initial blood velocities 0.05, 0.1, and 0.16 m/s using the 3D Pennes bio‐heat equation, temperature–time dependent model, and cell death model, respectively. Temperature‐dependent blood velocity is modeled using the Navier–Stokes equation, and the fluid–solid interaction boundary is treated as a convective boundary. For discretization, we utilized HcurlΩ elements for the wave propagation model, H1Ω elements for the Pennes bio‐heat model, and H1Ω3×L02Ω elements for the Navier–Stokes equation, where Ω represents the computational domain. The simulated results show that blood vessels and blood velocity have a significant impact on temperature distribution, tissue contraction, and the volume of the ablation zone. [ABSTRACT FROM AUTHOR]

The gut microbiota dysbiosis that often occurs in cancer therapy requires more efficient treatment options to be developed. In this concern, the present research approach is to develop drug delivery systems based on magnetite nanoparticles (MNPs) as nanocarriers for bioactive compounds. First, MNPs were synthesized through the spraying-assisted coprecipitation method, followed by loading bee pollen or bee bread extracts and an antitumoral drug (5-fluorouracil/5-FU). The loaded-MNPs were morphologically and structurally characterized through transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Dynamic Light Scattering (DLS), and thermogravimetric analysis. UV-Vis spectroscopy was applied to establish the release profiles and antioxidant activity. Furthermore, the antibacterial and antitumoral activity of loaded-MNPs was assessed. The results demonstrate that MNPs with antioxidant, antibacterial, antiproliferative, and prebiotic properties are obtained. Moreover, the data highlight the improvement of 5-FU antibacterial activity by loading on the MNPs' surface and the synergistic effects between the anticancer drug and phenolic compounds (PCs). In addition, the prolonged release behavior of PCs for many hours (70–75 h) after the release of 5-FU from the developed nanocarriers is an advantage, at least from the point of view of the antioxidant activity of PCs. Considering the enhancement of L. rhamnosus MF9 growth and antitumoral activity, this study developed promising drug delivery alternatives for colorectal cancer therapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most prominent cancer worldwide, and the second leading cause of cancer death. Poor outcomes and limitations of current treatments fuel the search for new therapeutic options. Curcumin (CUR) is often presented as a safer alternative for cancer treatment with a staggering number of molecular targets involved in tumor initiation, promotion, and progression. Despite being promising, its therapeutic potential is hindered due to its hydrophobic nature. Hence, the ongoing development of optimal delivery strategies based on nanotechnology, such as polymeric micelles (PMs), to overcome issues in CUR solubilization and delivery to tumor cells. In this sense, this study aimed to optimize the development and stability of CUR-loaded P123:F127:TPGS PMs (PFT:CUR) based on the thin-film approach and evaluate their therapeutic potential in CRC. Overall, the results revealed that the solubility of CUR was improved when room temperature was used to hydrate the film. The PFT–CUR hydrated at room temperature presents an average hydrodynamic diameter of 15.9 ± 0.3 nm with a polydispersity index (PDI) of 0.251 ± 0.103 and a zeta potential of −1.5 ± 1.9 mV, and a 35.083 ± 1.144 encapsulation efficiency (EE%) and 3.217 ± 0.091 drug loading (DL%) were observed. To ensure the stability of the optimized PFT–CUR nanosystems, different lyophilization protocols were tested, the use of 1% of glycine (GLY) being the most promising protocol. Regarding the critical micellar concentration (CMC), it was shown that the cryoprotectant and the lyophilization process could impact it, with an increase from 0.064 mg/mL to 0.119 mg/mL. In vitro results showed greater cytotoxic effects when CUR was encapsulated compared to its free form, yet further analysis revealed the heightened cytotoxicity could be attributed to the system itself. Despite challenges, the developed CUR-loaded PM shows potential as an effective therapeutic agent for CRC. Nonetheless, the system must undergo refinements to enhance drug entrapment as well as improve overall stability. [ABSTRACT FROM AUTHOR]

Breast cancer represents the most prevalent form of cancer and the leading cause of cancer-related mortality among females worldwide. It has been reported that several risk factors contribute to the appearance and progression of this disease. Despite the advancements in breast cancer treatment, a significant portion of patients with distant metastases still experiences no cure. The extracellular matrix represents a potential target for enhanced serum biomarkers in breast cancer. Furthermore, extracellular matrix degradation and epithelial–mesenchymal transition constitute the primary stages of local invasion during tumorigenesis. Additionally, the microbiome has a potential influence on diverse physiological processes. It is emerging that microbial dysbiosis is a significant element in the development and progression of various cancers, including breast cancer. Thus, a better understanding of extracellular matrix and microbiome interactions could provide novel alternatives to breast cancer treatment and management. In this review, we summarize the current evidence regarding the intricate relationship between breast cancer with the extracellular matrix and the microbiome. We discuss the arising associations and future perspectives in this field. [ABSTRACT FROM AUTHOR]

To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST's dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion's diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended. [ABSTRACT FROM AUTHOR]

Background: Paraptosis is a programmed cell death characterized by cytoplasmic vacuolation, which has been explored as an alternative method for cancer treatment and is associated with cancer resistance. However, the mechanisms underlying the progression of paraptosis in cancer cells remain largely unknown. Methods: Paraptosis-inducing agents, CPYPP, cyclosporin A, and curcumin, were utilized to investigate the underlying mechanism of paraptosis. Next-generation sequencing and liquid chromatography-mass spectrometry analysis revealed significant changes in gene and protein expressions. Pharmacological and genetic approaches were employed to elucidate the transcriptional events related to paraptosis. Xenograft mouse models were employed to evaluate the potential of paraptosis as an anti-cancer strategy. Results: CPYPP, cyclosporin A, and curcumin induced cytoplasmic vacuolization and triggered paraptosis in cancer cells. The paraptotic program involved reactive oxygen species (ROS) provocation and the activation of proteostatic dynamics, leading to transcriptional activation associated with redox homeostasis and proteostasis. Both pharmacological and genetic approaches suggested that cyclin-dependent kinase (CDK) 7/9 drive paraptotic progression in a mutually-dependent manner with heat shock proteins (HSPs). Proteostatic stress, such as accumulated cysteine-thiols, HSPs, ubiquitin-proteasome system, endoplasmic reticulum stress, and unfolded protein response, as well as ROS provocation primarily within the nucleus, enforced CDK7/CDK9–Rpb1 (RNAPII subunit B1) activation by potentiating its interaction with HSPs and protein kinase R in a forward loop, amplifying transcriptional regulation and thereby exacerbating proteotoxicity leading to initiate paraptosis. The xenograft mouse models of MDA-MB-231 breast cancer and docetaxel-resistant OECM-1 head and neck cancer cells further confirmed the induction of paraptosis against tumor growth. Conclusions: We propose a novel regulatory paradigm in which the activation of CDK7/CDK9–Rpb1 by nuclear proteostatic stress mediates transcriptional regulation to prime cancer cell paraptosis. [ABSTRACT FROM AUTHOR]

Rarely has a chemical elicited as much controversy as dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product, then a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects on experimental animals. These publications showed contradictory results in vivo and in vitro such that a thorough consideration of this compound's in cancer is merited. Despite 50 years of experimentation, DCA's future in therapeutics is uncertain. Without adequate clinical trials and health authorities' approval, DCA has been introduced in off-label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are few thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA's benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in it. [ABSTRACT FROM AUTHOR]

Key clinical message: Ayurveda Rasayana Therapy (ART) may serve as a safe and effective alternative treatment option for chemo‐intolerance high‐grade stage IV follicular lymphoma patients for increasing survival and tumor regression. Follicular lymphoma (FL), also called follicle center lymphoma/nodular lymphoma, observed in the B lymphocytes (B‐cells). Available therapeutic options for follicular lymphoma are associated with various side effects and, patients with co‐morbidities can seldom tolerate the chemotherapy regimens. Rasayana therapy not only resulted in tumor regression and improved survival but also dealt with the adverse effects of previous chemotherapy drugs. Herein, we present a case of a 74‐year‐old female diagnosed with Follicular lymphoma who had undergone three cycles of chemotherapy with unresolved disease outcome and serious adverse events. The patient refused to undergo further cycles of chemotherapy. Her family decided to start Ayurveda treatment for her as an alternative therapy for cancer care. On thorough case taking considering the Ayurveda parameters personalized Rasayana therapy as planned for the patient with an aim for improvement in Quality of Life (QoL), increasing survival, and optimizing body's immune response to fight the tumor. After treatment of 8 months, this case demonstrated partial tumor response as evidenced by PET‐CT‐scan. Quality of Life as evaluated using FACT‐G was also seen improved besides significant improvement in physical performance status evaluated using ECOG. The patient showed a survival of 3.5 years after starting Ayurveda Rasayana Therapy (ART). Rasayana therapy was well tolerated by the patient. This case report indicates the potential role of ART as a therapeutic option in geriatric cancer patients who are not eligible for cytotoxic interventions. Case warrants further systematic investigation to evaluate the potential role of ART in the treatment of geriatric cancer patients. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma affects the uterine lining. Endogenous activity, intrinsic targeting, and ability to engage with a host defence system make exosomal vehicles (EVs) a viable cancer treatment alternative. Due to these benefits, mesenchymal stem cell (MSC)-derived EVs loaded with carboplatin and paclitaxel could resemble immune cells to fight cancer. This study found that Car-Pac@EVs downregulated endometrial cancer (EC) cells relative to normal endometrium. Car-Pac@EVs' effects on ECC-1 and HEC-1A EC cells at different doses were examined in vitro. To detect cancer, MTT, flow cytometry, and transwell assays were used. Protein expression was measured by Western blotting and qRT-PCR. Car-Pac@EVs were affected by time- and dose-dependent EC cell proliferation reductions. In EC cells, Car-Pac@EVs triggered apoptosis. Car-Pac@EVs formulation reduced EC cell migration and invasion by reducing MMP-2 expression via Rac1/NF-κB signalling. The results indicated that Car-Pac@EVs may be an effective EC diagnosis and treatment target. [ABSTRACT FROM AUTHOR]

Cancer immunology offers a new alternative to traditional cancer treatments, such as radiotherapy and chemotherapy. One notable alternative is the development of personalized vaccines based on cancer neoantigens. Moreover, Transformers are considered a revolutionary development in artificial intelligence with a significant impact on natural language processing (NLP) tasks and have been utilized in proteomics studies in recent years. In this context, we conducted a systematic literature review to investigate how Transformers are applied in each stage of the neoantigen detection process. Additionally, we mapped current pipelines and examined the results of clinical trials involving cancer vaccines. [ABSTRACT FROM AUTHOR]

The discovery of new therapeutic alternatives for cancer treatment is essential for improving efficacy and specificity, overcoming resistance, and enabling a more personalized approach for each patient.We investigated the antitumor activity of the crude ethanolic extract of the fungus Trichoderma asperelloides (ExtTa) and its interaction with chemotherapeutic drugs. It was observed, byMTT cytotoxicity assay, that ExtTa significantly reduced cell viability in breast adenocarcinoma, glioblastoma, lung carcinoma, melanoma, colorectal carcinoma, and sarcomas cell lines. The highest efficacy and selectivity of ExtTa were found against glioblastoma T98G and colorectal HCT116 cell lines. ExtTa is approximately four times more cytotoxic to those tumor cells than to non-cancer cell lines. A synergistic effect between ExtTa and doxorubicin was found in the treatment of osteosarcoma Saos-2 cells, aswell as with 5-fluorouracil in the treatment of HCT116 colorectal carcinoma cells using CompuSyn software. Our data unravel the presence of bioactive compounds with cytotoxic effects against cancer cells present in T. asperelloides ethanolic crude extract, with the potential for developing novel anticancer agents. [ABSTRACT FROM AUTHOR]

Prostate cancer remains a significant global health challenge, necessitating the exploration of novel therapeutic approaches. Androgen receptor (AR) signaling plays a critical role in prostate cancer progression and is a primary target for therapy. This study investigates the potential of phytochemicals from Capsicum annuum (Bell pepper) along with two common standand drugs (Apalutamide and Enzalutamide) as inhibitors of the human androgen receptor (AR) and prostate-specific membrane antigen (PSMA). Utilizing computer-aided drug design techniques, molecular docking studies were conducted to evaluate the binding affinities of selected ligands against AR (PDB ID: 1XOW) and PSMA (PDB ID: 2XEI), their ADMET properties, drug-likeness, oral bioavailability, and bioactivity profiles were also examined. Coumaroylquinic acid and 5-O-caffeoylquinic acid methyl-ester emerged as top-performing ligands, demonstrating strong binding affinities of −9.4 kcal/mol and −9.2 kcal/mol, respectively, against PSMA. Additionally, molecular dynamics simulations provided insights into the stability of protein-ligand complexes, with Coumaroylquinic acid exhibiting a stable binding conformation throughout the simulation. These findings suggest the potential of C. annuum phytochemicals, particularly Coumaroylquinic acid and 5-O-caffeoylquinic acid methyl-ester, as promising inhibitors of PSMA. Moreover, other ligands (Caffeoylglucoside and 1-O-galloyl-beta-d-glucose) identified in the study demonstrate interactions with AR, highlighting a multifaceted approach to prostate cancer treatment. Overall, this study underscores the potential of C. annuum phytochemicals as a source of novel therapeutic agents for prostate cancer, laying the groundwork for further lead optimization efforts. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common invasive neoplasm and the leading cause of cancer death in women worldwide. The main cause of mortality in cancer patients is invasion and metastasis, where the epithelial-mesenchymal transition (EMT) is a crucial player in these processes. Pharmacological therapy has plants as its primary source, including isoflavonoids. Brazilin is an isoflavonoid isolated from Haematoxilum brasiletto that has shown antiproliferative activity in several cancer cell lines. In this study, we evaluated the effect of Brazilin on canonical markers of EMT such as E-cadherin, vimentin, Twist, and matrix metalloproteases (MMPs). By Western blot, we evaluated E-cadherin, vimentin, and Twist expression and the subcellular localization by immunofluorescence. Using gelatin zymography, we determined the levels of secretion of MMPs. We used Transwell chambers coated with matrigel to determine the in vitro invasion of breast cancer cells treated with Brazilin. Interestingly, our results show that Brazilin increases 50% in E-cadherin expression and decreases 50% in vimentin and Twist expression, MMPs, and cell invasion in triple-negative breast cancer (TNBC) MDA-MB-231 and to a lesser extend in MCF7 ER+ breast cancer cells. Together, these findings position Brazilin as a new molecule with great potential for use as complementary or alternative treatment in breast cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Due to multidrug resistance and the high risk of recurrence, effective and less toxic alternative pancreatic cancer treatments are urgently needed. Pancreatic cancer cells are highly resistant to apoptosis but sensitive to ferroptosis. In this study, an innovative nanoplatform (AsIr@PDA) was developed by electrostatic adsorption of a cationic iridium complex (IrFN) onto two‐dimensional (2D) arsenene nanosheets. This nanoplatform exhibits superior ferroptosis‐inducing effects with high drug loading capacity and, importantly, excellent anti‐cancer immune activation function, leading to efficient elimination of pancreatic tumors with no observable side effects. Interestingly, AsIr@PDA significantly prevents the recurrence of pancreatic cancer in vivo when compared with a cisplatin‐loaded nanoplatform. This designed nanoplatform demonstrated superior therapeutic efficacy by synergistic ferroptosis‐induced chemotherapy with immunotherapy via an all‐in‐one strategy, providing new insights for future pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

As the global cancer burden escalates, the search for alternative therapies becomes increasingly vital. Natural products, particularly plant-derived compounds, have emerged as promising alternatives to conventional cancer treatments due to their diverse bioactivities and favorable biosafety profiles. Here, we investigate Paucatalinone A, a newly discovered geranylated flavanone derived from the fruit of Paulownia Catalpifolia Gong Tong, notable for its significant anti-cancer properties. We revealed the capability of Paucatalinone A to induce apoptosis in osteosarcoma cells and deciphered its underlying mechanisms. Our findings demonstrate that Paucatalinone A substantially augments apoptosis, inhibits cell proliferation, and demonstrates a pronounced anti-tumor effect in a murine model of osteosarcoma. Mechanistically, Paucatalinone A disrupts calcium homeostasis and exacerbates intracellular reactive oxygen species accumulation, leading to mitochondrial impairment, cytoskeletal collapse, and caspase-dependent apoptotic cell death. This study underscores the potential of Paucatalinone A in initiating apoptosis in cancer cells and highlights the therapeutic efficacy of plant-derived agents in treating osteosarcoma, offering a viable approach for managing other intractable cancers. [ABSTRACT FROM AUTHOR]

In order to reduce the side effects of traditional chemotherapy in the treatment of colorectal cancer (CRC), a new drug delivery system has been developed in this work, based on exosomes that can host two drugs that act synergistically: farnesol (that stops the cell cycle) and paclitaxel (prevents microtubule system depolymerization). Firstly, exosomes were isolated from different cell cultures (from colorectal cancer and from fibroblast as example of normal cell line) by different methods and characterized by western blot, TEM and DLS, and results showed that they express classical protein markers such as CD9 and HSP-70 and they showed spherical morphology with sizes from 93 nm to 129 nm depending on the source. These exosomes were loaded with both drugs and its effect was studied in vitro. The efficacy was studied by comparing the viability of cell cultures with a colorectal cancer cell line (HCT-116) and a normal cell line (fibroblast HS-5). Results showed that exosomes present a specific effect with more reduction in cell viability in tumour cultures than healthy ones. In summary, exosomes are presented in this work as a promising strategy for colorectal cancer treatment. [Display omitted] • Comparation between two exosomes isolation methods from cell culture: with the commercial ExoQuick-TC Ultra kit o by ultracentrifugation. • Exosomes isolated from CRC cell culture were used to load with non-water-soluble anticancer drugs: farnesol (FOH) and paclitaxel (PTX). • Effectivity comparation between cyclodextrins and exosomes as drug delivery system. • The use of exosomes as a promising alternative for colorectal cancer treatment based on the regulation of metabolic pathways. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from natural sources, such as certain vegetables containing a variety of secondary metabolites with beneficial effects on the body and that play a crucial role in the fight against cancer, is essential. Among the compounds with the greatest efficacy in controlling this disease, those with antioxidant activity, particularly phenolic com-pounds, stand out. A remarkable example of this group is protocatechuic acid (PCA), which has been the subject of various revealing research on its activities in different areas. These studies sustain that protocatechuic acid has anti-inflammatory, antimutagenic, antidiabetic, antiulcer, antiviral, antifibrogenic, antiallergic, neuroprotective, antibacterial, anticancer, antiosteoporotic, anti-aging, and analgesic properties, in addition to offering protection against metabolic syndrome and con-tributing to the preservation of hepatic, renal, and reproductive functionality. Therefore, this paper aims to review the biological activities of PCA, focusing on its anticancer potential and its in-volvement in the control of various molecular pathways involved in tumor development, sup-porting its option as a promising alternative for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Breast Cancer continues to rank among all cancer types as the most dangerous malignancies, accounting for a significant portion of cancer-associated mortalities among women globally. Additionally, the number of breast cancer cases that are identified each year is rising globally. After surgery or radiation, the typical therapies entail chemotherapy which is followed by endocrine therapy. However, breast cancer is extremely resistant to therapies, which causes it to recur. As a result, emphasis is being placed on the development of complementary medicines with fewer adverse effects that are obtained from plants. An isoquinoline alkaloid, Protopine, possesses an array of biological properties, including anti-tumor efficacy against several malignancies. Materials and Methods: In this work, the anti-carcinogenic property of Protopine against the MDA-MB-231 cells has been investigated. The impact of Protopine on cell growth, apoptosis, ROS accumulation, and apoptotic marker levels was investigated. Doxorubicin was employed as the positive control drug in the studies. Results: The effect of Protopine on cell growth demonstrated its cytotoxic property was elevated dose-dependently and IC50 concentration was selected for additional work. The AO/EB and DAPI staining was performed to examine morphological alterations concerning apoptotic cell death. Additionally, Protopine augmented the ROS accumulation and induced DNA damage in Protopine-treated cells. The caspase levels were also increased upon Protopine treatment. Discussion and Conclusion: The outcomes highlight that Protopine remarkably inhibited cell growth by augmenting the ROS levels, inducing DNA fragmentation and apoptosis, leading to cell death by caspase-dependent pathway. Thus, Protopine could be possibly employed as an effective anti-cancer alternative for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that natives of Southeast Asia have been consuming Prismatomeris glabra for decades for a variety of health benefits, research on this species is not as extensive as that on other species due to its limited distribution. The purpose of this study was to determine the cytotoxicity and identify the bioactive compounds of P. glabra crude leaf extracts against the MCF-7 cell line. Results: We first examined the potential cytotoxic activity of P. glabra using the MTT assay against the MCF-7 cell line to determine the IC50 of the plant extracts at various concentrations at three time points (24 h, 48 h, and 72 h). Across all time points, the MTT assay revealed that the aqueous extract exhibited the lowest IC50 values (p < 0.05) compared to the ethanol and methanol extracts. All plant extracts exerted the ability to induce cell death in the MCF-7 cell line at all time points, and the optimal time for P. glabra to manifest its antiproliferative activities and promote cell death was 48 h. LC–MS analysis was conducted to reveal the components in plant extracts. Forty compounds were discovered in P. glabra's extracts, with the majority being flavonoids and triterpenoids. Five similar compounds were present in all three extracts. Further research should be conducted on these compounds to unveil a compound that fulfils the criteria as a promising anticancer agent. This research is of the utmost importance, as it provides a fundamental framework for the identification of alternative therapies for breast cancer and contributes implicitly to the development of new drugs. Conclusions: This study discovered that P. glabra crude leaf extracts have the potential to inhibit the MCF-7 cell line by inducing cell death. [ABSTRACT FROM AUTHOR]

In seeking alternative cancer treatments, antimicrobial peptides (AMPs), sourced from various life forms, emerge as promising contenders. These endogenous peptides, also known as host defense peptides (HDPs), play crucial roles in immune defenses against infections and exhibit potential in combating cancers. With their diverse defensive functions, plant-derived AMPs, such as thionins and defensins, offer a rich repertoire of antimicrobial properties. Insects, amphibians, and animals contribute unique AMPs like cecropins, temporins, and cathelicidins, showcasing broad-spectrum activities against bacteria, fungi, and viruses. Understanding these natural peptides holds significant potential for developing effective and targeted therapies against cancer and infectious diseases. Antimicrobial peptides (AMPs) exhibit diverse structural characteristics, including α-helical, β-sheet, extended, and loop peptides. Environmental conditions influence their structure, connecting to changes in cell membrane hydrophobicity. AMPs' actions involve direct killing and immune regulation, with additional activities like membrane depolarization. In this review, we focus on antimicrobial peptides that act as anticancer agents and AMPs that exhibit mechanisms akin to antimicrobial activity. Buforin AMPs, particularly Buforin I and II, derived from histone H2A, demonstrate antibacterial and anticancer potential. Buforin IIb and its analogs show promise, with selectivity for cancer cells. Despite the challenges, AMPs offer a unique approach to combat microbial resistance and potential cancer treatment. In various cancer types, including HeLa, breast, lung, ovarian, prostate, and liver cancers, buforins demonstrate inhibitory effects and apoptosis induction. To address limitations like stability and bioavailability, researchers explore buforin-containing bioconjugates, covalently linked with nanoparticles or liposomes. Bioconjugation enhances specificity-controlled release and combats drug resistance, presenting a promising avenue for targeted cancer treatment. Clinical translation awaits further evaluation through in vivo studies and future clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence (1). Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results (2, 3). We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. Methods: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. Results: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p < 0.001). Some RCT's had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. Conclusions: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer continue to be a leading cause of cancer-related death for women. The current anticancer drugs remain inefficient due to the lack of specificity to inhibit the cancer cells growth. Plant-based drugs with potent anticancer should add to the efforts in finding drugs with lesser side effects but great potential to increase survival. Hence, this study sought to determine the tumour growth inhibition of standardized fraction (SF1) from Clinacanthus nutans as a potential alternative treatment for cervical cancer. Methods: SF1 was isolated from a series of bioassay-guided fractionation of C.nutans leaves. Female nude mice were xenografted with human cervical cancer cell line, SiHa, subcutaneously. When the tumour volume reached 100mm3, SF1 was intraperitoneally injected once daily for 28 days. Body weight and tumour volume were recorded every 3 days. Tumour and liver were fixed for hematoxylin and eosin staining and immunohistochemistry using caspase-3 antibody. Blood was collected by cardiac puncture for assessment of liver enzymes level, AST and ALT. Results: SF1 has a great tumour inhibition with more than 50% inhibition rate compared to the negative control group (DMSO). ALT and AST levels in SF1-treated mice were maintained in normal ranges compared to the positive control group, cisplatin indicating no sign of toxicities. SF1-treated group revealed no indication of liver toxicity. The number of tumour mitosis was reduced and caspase-3, a critical mediator of apoptosis was overexpressed in SF1-treated group. Conclusion: SF1 demonstrated potent anticancer activity by inhibiting the tumour growth with less toxic effects, suggesting a promising candidate for preventing cancer progression. [ABSTRACT FROM AUTHOR]

Background: ZEB1, a core transcription factor involved in epithelial-mesenchymal transition (EMT), is associated with aggressive cancer cell behavior, treatment resistance, and poor prognosis across various tumor types. Similarly, the expression and activity of CD73, an ectonucleotidase implicated in adenosine generation, is an important marker of tumor malignancy. Growing evidence suggests that EMT and the adenosinergic pathway are intricately linked and play a pivotal role in cancer development. Therefore, this study focuses on exploring the correlations between CD73 and ZEB1, considering their impact on tumor progression. Methods: We employed CRISPR/Cas9 technology to silence CD73 expression in cell lines derived from papillary thyroid carcinoma. These same cells underwent lentiviral transduction of a reporter of ZEB1 non-coding RNA regulation. We conducted studies on cell migration using scratch assays and analyses of cellular speed and polarity. Additionally, we examined ZEB1 reporter expression through flow cytometry and immunocytochemistry, complemented by Western blot analysis for protein quantification. For further insights, we applied gene signatures representing different EMT states in an RNA-seq expression analysis of papillary thyroid carcinoma samples from The Cancer Genome Atlas. Results: Silencing CD73 expression led to a reduction in ZEB1 non-coding RNA regulation reporter expression in a papillary thyroid carcinoma-derived cell line. Additionally, it also mitigated ZEB1 protein expression. Moreover, the expression of CD73 and ZEB1 was correlated with alterations in cell morphology characteristics crucial for cell migration, promoting an increase in cell polarity index and cell migration speed. RNA-seq analysis revealed higher expression of NT5E (CD73) in samples with BRAF mutations, accompanied by a prevalence of partial-EMT/hybrid state signature expression. Conclusions: Collectively, our findings suggest an association between CD73 expression and/or activity and the post-transcriptional regulation of ZEB1 by non-coding RNA, indicating a reduction in its absence. Further investigations are warranted to elucidate the relationship between CD73 and ZEB1, with the potential for targeting them as therapeutic alternatives for cancer treatment in the near future. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant therapy constitutes a valuable modality for diminishing tumor volume prior to surgical resection. Nonetheless, its application encounters limitations in the context of recurrent tumors, which manifest resistance to conventional treatments. Silver nanoparticles (AgNPs) have emerged as a promising alternative for cancer treatment owing to their cytotoxic effects. Methods: Cellular viability was assessed by Alamar blue assay in 4T1 breast cancer cell line. Silver biodistribution was detected by an inductively coupled plasma optical emission spectrometer in an in vivo mice model. For neoadjuvant evaluation, mice were randomized and treated intratumoral with AgNPs-G or intraperitoneally with doxorubicin (DOX) as a control. Recurrence was determined after 170 days by counting lung metastatic nodules (dyed with Bouin solution) with histological confirmation by H&E. Masson's stain, Ki67 immunohistochemistry, and a TUNEL assay were performed in lungs from treated mice. Results: AgNPs-G reduced 4T1 cell viability and in an ex vivo assay the AgNPs-G decreased the tumor cell viability. After intravenous administration of AgNPs-G were detected in different organs. After intratumor administration, AgNPs-G are retained. The AgNPs-G treatment significantly reduced tumor volume before its surgical resection. AgNPs-G reduced the development of lung metastatic nodules and the expression of Ki67. TUNEL assay indicated that AgNPs-G didn't induce apoptosis. Conclusions: We concluded that intratumor administration of AgNPs-G reduced tumor volume before surgical resection, alongside a reduction in lung metastatic nodules, and Ki67 expression. These findings provide valuable insights into the AgNPs-G potential for intratumor and neoadjuvant cancer therapies. However, further research is needed to explore their full potential and optimize their use in clinical settings. [ABSTRACT FROM AUTHOR]

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a photochemical‐based treatment approach that involves using light to activate photosensitizers (PSs). Attractively, PDT is one of the alternative cancer treatments due to its noninvasive technique. By utilizing the heavy atom effect, this work modified a class of formazan dyes to improve intersystem crossing (ISC) to improve reactive oxygen species (ROS) generation for PDT treatment. Two methods were used to observe the ROS generation enhanced by ISC of the synthesized complexes including, (1) recording DPBF decomposition caused by the ROS, and (2) calculating the potential energy curves for photophysical mechanisms of BF2‐formazanate dyes using the DFT and nudged elastic band (NEB) methods. The photophysical properties of the dyes were studied using spectroscopic techniques and X‐ray crystallography, as well as DFT calculations. The experimental and theoretical results and in vitro cellular assays confirmed the potential use of the newly synthesized iodinated BF2‐formazanate dyes in PDT. [ABSTRACT FROM AUTHOR]

Photodynamic cancer therapy circumvents the major side effects associated with the conventional cancer treatment methods, such as chemotherapy, surgery and exposure to radiation. Experimental measurement of photosensitizer quantum yield (PQY) singlet production of oxygen through either sensitive laser spectroscopy or luminescence detection at the wavelength of 1270 nm is costly; time consuming and intensive while unreliability of chemical traps experimental approach is of serious concern. Quantitative structure-activity relationship (QSAR) computational method proposed in the literature for computing PQY of singlet oxygen production has characteristics deviation from the measured values. PQY singlet oxygen production of twenty-nine pteridines photosensitizer compounds is modeled and predicted in this present contribution using extreme learning machine (ELM) and support vector regression (SVR) with hybridized particle swarm optimization (PSO) method for ensuring combinatory parameter selection. The performances of the developed SVR-PSO computational method are assessed using mean absolute error (MAE), correlation coefficient (CC), root mean square error (RMSE) and mean absolute percentage deviation (MAPD). The developed SVR-PSO model outperforms QSAR (2016) model with performance superiority of 34.78%, 3.65%, 17.64% and 42.16% on the basis of RMSE, CC, MAE and MAPD performance measuring parameters, respectively. The developed ELM-SINE (with sine activation function) and ELM-SIG (with sigmoid activation function) respectively outperform the existing QSAR (2016) model with improvement of 6.54% and 4.70% using R-squared metric. The demonstrated outstanding performance of the present predictive models is immensely meritorious in strengthening the potentials of alternative cancer therapy and circumventing the experimental challenges of PQY singlet oxygen production determination. [ABSTRACT FROM AUTHOR]

Cancer death cases have increased yearly, and there are estimated to be 21.6 million cancer cases in 2030. Studies of herbal compounds for cancer treatment alternatives are essential because cancer treatment is relatively expensive and has adverse effects. Phyllanthus niruri (Pn) and Catharanthus roseus (Cr) are plants that are known as herbal medicines. Combining the two plants is expected to prevent and enhance the immune system in breast cancer cases. This study aims to analyze the anti-cancer and immunomodulatory effects of P. niruri and C. roseus extract (PCE) in modulating macrophage polarization in breast cancer mice. Experimental animals are divided into six groups and there is healthy control (normal mice), cancer (DMBA-induced mice), cancer mice with cisplatin administration, cancer mice with PCE administration with three different doses, including dose 1 (500 mg/kg Pn + 15 mg/kg Cr), dose 2 (1000 mg/kg Pn + 75 mg/kg Cr), and dose 3 (2000 mg/kg Pn + 375 mg/kg Cr). The mice were injected with DMBA once a week for six weeks to induce cancer in mice. The breast cancer mice model was administered with PCE orally for 14 days. The expression of CD11b+IL-10+ and CD11b+IFN-γ+ demonstrated macrophage polarization. The results showed that breast cancer induction using DMBA increased the level of IL-10 and decreased the level of IFN-γ significantly compared to the normal group (p < 0.05). In specific doses, administration of PCE could reduce IL-10 levels and increase the level of IFN-γ significantly (p < 0.05). PCE can modulate the polarization of macrophages by suppressing the M2-like macrophage and increasing the M1-like macrophage. The ability of PCE to modulate macrophage polarization indicates that the combination of P. niruri and C. roseus has activity as an anti-cancer. [ABSTRACT FROM AUTHOR]

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Background: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. Methods: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. Results: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. Conclusions: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Phenolic compounds present in plants have demonstrated several biological properties such as antioxidant, antitumor, cardioprotective, and antiproliferative. On the other hand, doxorubicin, a chemotherapeutic widely used to treat breast cancer, usually exhibits chronic cardiotoxicity associated with oxidative stress. Therefore, we aimed to study the effects of phenolic compound‐enriched extract (PCEE) with doxorubicin in breast cancer. To achieve this, after an SPE‐C18‐column purification process of crude extracts obtained from pecan nutshells (Carya illinoinensis), the resulting PCEE was used to evaluate the cytotoxicity and antioxidant properties against the human breast cancer cell line MDA‐MB‐231 and the normal‐hamster ovary cell line CHO‐K1. PCEE was selectively cytotoxic against both cell lines, with an IC50 value (≈26.34 mg/L) for MDA‐MB‐231 lower than that obtained for CHO‐K1 (≈55.63 mg/L). As a cytotoxic mechanism, PCEE inhibited cell growth by G2/M cell cycle arrest in MDA‐MB‐231 cells. Simultaneously, the study of the antioxidant activity showed that PCEE had a cytoprotective effect, evidenced by reduced ROS production in cells with oxidative stress caused by doxorubicin. The results highlight PCEE as a potential antitumor agent, thus revaluing it as an agro‐industrial residue. Significance statement: The selective and antiproliferative effect of a phenolic compound‐enriched extract (PCEE) on the human breast cancer cell line (MDA‐MB‐231) was investigated. By evaluating the antiproliferative effects of the PCEE together with the chemotherapeutic doxorubicin, we have demonstrated the antioxidant and modulatory activities of these bioactive compounds as a novel insight in the field. It provides an experimental basis for further studies on the biological activity of polyphenols and also highlights the potential value of a waste generated through agro‐industrial activities, paving the way for sustainable‐driven alternatives to obtain bioactive molecules. Furthermore, biopharmacotherapy with chemotherapeutic agents in cancer is a source of interest in the topic of adjuvant therapy and therefore, the obtained results could provide the potential application of PCEE as an alternative therapy for breast cancer in the functional food industry. We acknowledge that further preclinical and clinical trials will be necessary to gain deeper insights into the potential therapies that can be developed using these natural compounds. [ABSTRACT FROM AUTHOR]

As an alternative treatment in cancer therapy, there has been a growing interest in using helminths, such as Trichinella spiralis (T. spiralis), Echinococcus granulosus (E. granulosus), Toxocara canis (T. canis), and Taenia solium (T. solium). This study aimed to investigate the antigens and mechanisms that contribute to the anticancer properties of helminths, providing insights into how helminths may be used as a new and innovative treatment modality for cancer. The current review analyzed preclinical and clinical studies published between 2000 and 2023. The present study sought to obtain information on helminths, such as E. granulosus, T. spiralis, T. canis, and T. solium, to treat cancers of the breast, pancreas, melanoma, and leukemia by exploring databases, such as PubMed, Google Scholar, and Scopus. Studies focusing on helminth therapy against particular cancer types for in vitro and animal models were included. Several studies have shown the possibility of inhibiting breast, colon, melanoma, and leukemia tumor growth, inducing apoptosis, and modulating the tumor microenvironment with E. granulosus, T. spiralis, T. canis, and T. solium based on in vitro and animal models studies. Some studies have indicated that helminth therapy can improve survival rates, reduce tumor growth, and stimulate the immune system in cancer patients. A potential improvement in treatment outcomes can be used for combination therapies, such as antigen selection, immune profiling, and individualized approaches based on helminth therapy. Helminth therapy is an additional option for cancer treatment, emphasizing T. spiralis, E. granulosus, T. canis, and T. solium. These helminth antigens could modulate immune responses and directly cause cytotoxicity in cancer cells. [ABSTRACT FROM AUTHOR]

The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota‐mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field. [ABSTRACT FROM AUTHOR]

[Display omitted] Immunotherapy has revolutionized cancer therapy, using chemical or biological agents to reinvigorate the immune system. However, most of these agents have poor tumor penetration and inevitable side effects that complicate therapeutic outcomes. Electrical stimulation (ES) is a promising alternative therapy against cancers that does not involve chemical or biological agents but is limited in the fabrication and operation of complex micrometer-scale ES devices. Here, we present an optically microprinted flexible interdigital electrode with a gold-plated polymer microneedle array to generate alternating electric fields for cancer treatment. A flexible microneedle-array-integrated interdigital electrode (FMIE) was fabricated by combining optical 3D microprinting and electroless plating processes. FMIE-mediated ES of cancer cells induced necrotic cell death through mitochondrial Ca2+ overload and increased intracellular reactive oxygen species (ROS) production. This led to the release of damage-associated molecular patterns that activated the immune response and potentiated immunogenic cell death (ICD). FMIE-based ES has an excellent safety profile and systemic anti-tumor effects, inhibiting the growth of primary and distant tumors as well as melanoma lung metastasis. FMIE-based ES-driven cancer immunomodulation provides a new pathway for drug-free cancer therapy. [ABSTRACT FROM AUTHOR]

We analyzed a quantitative multiscale model that describes the epigenetic dynamics during the growth and evolution of an avascular tumor. A gene regulatory network (GRN) formed by a set of ten genes that are believed to play an important role in breast cancer development was kinetically coupled to the microenvironmental agents: glucose, estrogens, and oxygen. The dynamics of spontaneous mutations was described by a Yule-Furry master equation whose solution represents the probability that a given cell in the tissue undergoes a certain number of mutations at a given time. We assumed that the mutation rate is modified by a spatial gradient of nutrients. The tumor mass was simulated by means of cellular automata supplemented with a set of reaction diffusion equations that described the transport of microenvironmental agents. By analyzing the epigenetic state space described by the GRN dynamics, we found three attractors that were identified with cellular epigenetic states: normal, precancer and cancer. For two-dimensional (2D) and three-dimensional (3D) tumors we calculated the spatial distribution of the following quantities: (i) number of mutations, (ii) mutation of each gene and, (iii) phenotypes. Using estrogen as the principal microenvironmental agent that regulates cells proliferation process, we obtained tumor shapes for different values of estrogen consumption and supply rates. It was found that he majority of mutations occurred in cells that were located close to the 2D tumor perimeter or close to the 3D tumor surface. Also, it was found that the occurrence of different phenotypes in the tumor are controlled by estrogen concentration levels since they can change the individual cell threshold and gene expression levels. All results were consistently observed for 2D and 3D tumors. Author summary: We introduce and analyze in detail a 2D and 3D quantitative multiscale model that describes the growth and epigenetic evolution of an avascular breast tumor. We obtain series of microarrays that describe the activation/inhibit levels of a group of genes that respond to the occurrence of oxygen and estrogen concentration gradients. We identify three cell phenotypes: normal, precancer and cancer, that are crucial to understand the tumor structure, the spatial distribution of mutations and the tumor heterogeneity. Finally, we found that the estrogen concentration gradients are related to the variation of gene expression levels and phenotypes occurrence. These findings strongly suggest that it is possible to develop epigenetic cancer treatment alternatives to either stop or reverse tumor evolution. [ABSTRACT FROM AUTHOR]

Thermal ablation is a promising alternative treatment for lung cancer. It disintegrates cancer cells and releases antigens, followed by the remodeling of local tumor immune microenvironment and the activation of anti-tumor immune responses, enhancing the overall effectiveness of the treatment. Biomarkers can offer insights into the patient’s immune response and outcomes, such as local tumor control, recurrence, overall survival, and progression-free survival. Identifying and validating such biomarkers can significantly impact clinical decision-making, leading to personalized treatment strategies and improved patient outcomes. This review provides a comprehensive overview of the current state of research on potential biomarkers for predicting immune response and outcomes in lung cancer patients undergoing thermal ablation, including their potential role in lung cancer management, and the challenges and future directions. [ABSTRACT FROM AUTHOR]

The process of ferroptosis has become an alternative therapy to fight cancer. As a continuation of previous work, a non-autonomous model was developed for avascular and vascular tumor growth under periodic perturbations that simulate the application of a chronotherapeutically modulated treatment based on triggering the ferroptosis process. It was found that for critical amplitude and a perturbation frequency of twice the autonomous frequency in vascular growth, less complex and therefore less robust states are reached, and the tumor population decreases. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of mortality worldwide, and conventional cancer therapies such as chemotherapy and radiotherapy often result in undesirable and adverse effects. Natural products have emerged as a promising alternative for cancer treatment, with comparatively fewer side effects reported. Opuntia ficus-indica (L.) Mill., a member of the Cactaceae family, contains a diverse array of phytochemicals, including flavonoids, polyphenols, betalains, and tannins, which have been shown to exhibit potent anticancer properties. Various parts of the Opuntia plant, including the fruits, stems/cladodes, and roots, have demonstrated cytotoxic effects against malignant cell lines in numerous studies. This review comprehensively summarizes the anticancer attributes of the phytochemicals found in Opuntia ficus-indica (L.) Mill., highlighting their potential as natural cancer prevention and treatment agents. Bibliometric metric analysis of PubMed and Scopus-retrieved data using VOSviewer as well as QDA analysis provide further insights and niche to be explored. Most anticancer studies on Opuntia ficus-indica and its purified metabolites are related to colorectal/colon cancer, followed by melanoma and breast cancer. Very little attention has been paid to leukemia, thyroid, endometrial, liver, and prostate cancer, and it could be considered an opportunity for researchers to explore O. ficus-indica and its metabolites against these cancers. The most notable mechanisms expressed and validated in those studies are apoptosis, cell cycle arrest (G0/G1 and G2/M), Bcl-2 modulation, antiproliferative, oxidative stressmediated mechanisms, and cytochrome c. We have also observed that cladodes and fruits of O. ficus-indica have been more studied than other plant parts, which again opens the opportunity for the researchers to explore. Further, cell line-based studies dominated, and very few studies were related to animal-based experiments. The Zebrafish model is another platform to explore. However, it seems like more in-depth studies are required to ascertain clinical utility of this biosustainable resource O. ficus-indica. [ABSTRACT FROM AUTHOR]

Drug resistance is a serious challenge for platinum anticancer drugs. Platinum complexes may get over the drug resistance via a distinct mechanism of action. Cholesterol is a key factor contributing to the drug resistance. Inhibiting cellular cholesterol synthesis and uptake provides an alternative strategy for cancer treatment. Platinum(IV) complexes FP and DFP with fenofibric acid as axial ligand(s) were designed to combat the drug resistance through regulating cholesterol metabolism besides damaging DNA. In addition to producing reactive oxygen species and active platinum(II) species to damage DNA, FP and DFP inhibited cellular cholesterol accumulation, promoted cholesterol efflux, upregulated peroxisome proliferator‐activated receptor alpha (PPARα), induced caspase‐1 activation and gasdermin D (GSDMD) cleavage, thus leading to both apoptosis and pyroptosis in cancer cells. The reduction of cholesterol significantly relieved the drug resistance of cancer cells. The double‐acting mechanism gave the complexes strong anticancer activity in vitro and in vivo, particularly against cisplatin‐resistant cancer cells. [ABSTRACT FROM AUTHOR]

Targeted protein degradation has emerged as an alternative therapy against cancer, offering several advantages over traditional inhibitors. The new degrader drugs provide different therapeutic strategies: they could cross the phospholipid bilayer membrane by the addition of specific moieties to extracellular proteins. On the other hand, they could efficiently improve the degradation process by the generation of a ternary complex structure of an E3 ligase. Herein, we review the current trends in the use of TAC-based technologies (TACnologies), such as PROteolysis TArgeting Chimeras (PROTAC), PHOtochemically TArgeting Chimeras (PHOTAC), CLIck-formed Proteolysis TArgeting Chimeras (CLIPTAC), AUtophagy TArgeting Chimeras (AUTAC), AuTophagosome TEthering Compounds (ATTEC), LYsosome-TArgeting Chimeras (LYTAC), and DeUBiquitinase TArgeting Chimeras (DUBTAC), in experimental development and their progress towards clinical applications. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the most lethal cancer in gynaecology. Surgery, chemotherapy, and radiotherapy are the most often used cancer-fighting strategies. Post-surgery infection is fairly prevalent, especially among people with insufficient immunity. Zinc oxide nanoparticles (ZnOnps) have amazing biomedical features as anticancer and antibacterial agents. Methods: We investigated the behaviour of ZnOnps synthesized by green methods on ovarian cancers using established human ovarian cancer cell lines, besides the antibacterial action toward models of gram + ve and gram -ve bacteria. The cytotoxic effect of ZnOnps was calculated using a Sulforhodamine B (SRB) trial. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were tested as models for gram + ve and gram -ve bacteria. The selected bacteria were subjected to concentrations of 20, 40, 80, and 100 μg/ml. Results: The synthesized ZnOnps induced 50% inhibitory concentration (IC50) at a concentration of 27.45 μg/ml. The diameter of inhibition ranged between 20.16 ± 0.16 and 27 ± 0.57 mm for S. aureus and 25.66 ± 0.33 to 31 ± 0.33 mm for E. coli. ZnOnps antagonistic effect statistically differed with neomycin, cefaclor, and cefadroxil. Conclusions: Green synthesis of ZnOnps is easily prepared, low cost, non-toxic, and eco-friendly. Their cytotoxic action on SKOV3 cells and their antibacterial characteristics pave the way to be an alternative therapy for ovarian cancer and S. aureus and E. coli infection. [ABSTRACT FROM AUTHOR]

This article explores the impact of menopause on women's health, focusing on the increased risk of age-related diseases such as cardiovascular disease, osteoporosis, and dementia. It discusses the potential benefits and risks of hormone replacement therapy (HRT), specifically the administration of estrogen, in mitigating these risks. The timing and duration of HRT use are important considerations, as starting HRT early and in the absence of certain risk factors appears to be more beneficial. The article also highlights the need for more research on alternative treatments for breast cancer patients and the importance of including women in clinical trials to better understand the effects of drugs and treatments on menopausal women. Additionally, it suggests the need for improved diagnostic methods for menopause and the potential benefits of mandating regular ovarian reserve testing for women. Overall, the article emphasizes the importance of recognizing menopause as more than just the loss of fertility and the need for tailored therapies to address the specific health risks associated with menopause. [Extracted from the article]

Oestrogen synthesis pathway is one of the bottom line steps for breast cancer advancement; involving, aromatase enzyme (Cyp450), which transform androgens to oestrogens. Thus endocrine-based therapies comprising of human aromatase blockage is the most necessary way in order to decrease the oestrogen levels and thereafter prohibiting the chances of breast cancer commencement. In recent years, limelight on drug discovery from green sources has been growing for their less toxicity and cost effectiveness. Our present course of study aims at searching of new antagonist/s from a common dietary source "Citrus species". Molecular docking along with In-silico evaluation their pharmacokinetics (ADME) properties and toxicity were employed to fulfill the aim. Result shows that, all the five Citrus compounds have reasonable affinity towards cytochrome p450. However, Hesperidin shows highest affinity towards its target receptor protein i.e. -9.7 kcal/mol, followed by Chalcone that shows the lowest affinity towards its target protein i.e. -7.4 kcal/mol. Hence, bioactive components of Citrus species can be green alternatives for breast cancer therapy. [ABSTRACT FROM AUTHOR]