Therapy For Treatment Of Cancer Research Articles

Metformin Impairs Linsitinib Anti-Tumor Effect on Ovarian Cancer Cell Lines

Ovarian cancer (OC) remains one of the leading causes of cancer-related mortality among women. Targeting the insulin-like growth factor 1 (IGF-1) signaling pathway has emerged as a promising therapeutic strategy. Linsitinib, an IGF-1 receptor (IGF-1R) inhibitor, has shown potential in disrupting this pathway. Additionally, metformin, commonly used in the treatment of type 2 diabetes, has been studied for its anti-cancer properties due to its ability to inhibit metabolic pathways that intersect with IGF-1 signaling, making it a candidate for combination therapy in cancer treatments. This study explores the anti-cancer effects of linsitinib and metformin on OVCAR3 cells by the suppression of the IGF-1 signaling pathway by siRNA-mediated IGF-1 gene silencing. The goal is to evaluate their efficacy as therapeutic agents and to emphasize the critical role of this pathway in OC cell proliferation. Cellular viability was evaluated by resazurin-based assay, and apoptosis was assessed by flux cytometry. The results of this study indicate that the combination of linsitinib and metformin exhibits an antagonistic effect (obtained by SynergyFinder 2.0 Software), reducing their anti-neoplastic efficacy in OC cell lines. Statistical analyses were performed using ordinary one-way or two-way ANOVA, followed by Tukey’s or Šídák’s multiple comparison tests. While linsitinib shows promise as a therapeutic option for OC, further research is needed to identify agents that could synergize with it to enhance its therapeutic efficacy, like the combination with standard chemotherapy in OC (carboplatin and paclitaxel).

Nanotechnology‐Based Systems for Enhancing the Efficacy of Sonodynamic Therapy in Cancer Treatment

AbstractSonodynamic therapy (SDT) is a minimally invasive cancer therapeutic modality that utilizes low‐intensity ultrasound to activate sensitizers for the production of cytotoxic reactive oxygen species (ROS) and the site‐specific ablation of tumors. Compared to conventional cancer treatments, SDT has no adverse side effects, has been shown to radically reduce tumor volume, and has the potential to raise antitumor immune response. Ever‐increasing studies have demonstrated that nanotechnology can significantly enhance the efficacy of SDT against certain cancers and improve its therapeutic effects. Nanosystems are developed that can improve the intratumoral delivery and cellular uptake of sensitizers, can reduce intrinsic cancer defenses against ROS, can act synergistically for the production of ROS and can tackle cancer immune tolerance. In this review, the various strategies to enhance SDT performance with the assistance of nanotechnology, and the outstanding research outcomes, are discussed.

Skrining fitokimia tumbuhan potensi obat kanker kolorektal Begonia medicinalis Ardi & D.C. Thomas

Cancer is a condition in which cells or tissues undergo abnormal progressive growth. Colorectal cancer is cancer that occurs in the colon to rectum organs of humans. Alternative therapy for colorectal cancer treatment is the use of herbs such as Begonia medicinalis Ardi & D.C. Thomas. This study aimed to screen the bioactive compounds in the Begonia medicinalis Ardi & D.C. Thomas. extract and its potential as a colorectal cancer drug. This research consists of two stages, namely the extraction stage using the maceration method and the screening stage. The results showed that the extract of Begonia medicinalis Ardi & D.C. Thomas. positively contains flavonoids, alkaloids, and saponins. These bioactive compounds have potential activity as preventive and curative agents for colorectal cancer through several mechanisms, including suppressing oxidative stress, inhibiting CDK activity, suppressing intestinal inflammation, and increasing floranormal diversity and probiotic barrier activity in the intestine.

Photophysical characterization of xanthene dyes

The growing interest in using photodynamic therapy for cancer treatment and antimicrobial applications has prompted the search for different classes of dyes. In general, the protocols of these studies are different, making it difficult to compare their efficiency directly. Here, we apply a controlled protocol to analyze the photophysical properties of Erythrosin B, Eosin Y, and Rose Bengal using a set of optical techniques. The results show that Erythrosine has the best singlet oxygen generation capacity. This result, added to the well-known low toxicity of Erythrosine, makes it a good choice among the xanthenes for health applications.

Unlocking nature’s pharmacy: an in-depth exploration of phytochemicals as potential sources of anti-cancer and anti-inflammatory molecules

Phytochemicals, the bioactive compounds derived from plants, play a significant role in modulating pathways leading to cancer and inflammation, rendering themselves promising candidates for therapeutic interventions. This review explores the multifaceted potential of various phytochemicals in modulating key mechanisms involved in the development and progression of cancer and inflammation. The diverse array of phytochemicals discussed here encompasses polyphenols, flavonoids, alkaloids, terpenoids, and many others, each with distinct molecular targets and modes of action. This review is an attempt to elucidate and correlate the regulatory role of phytochemicals on cellular signaling pathways implicated in oncogenesis and inflammatory responses, highlighting the significance and potential of phytochemical-based therapies for cancer prevention and treatment, as well as for managing inflammatory conditions. By exploring the promising potential of phytochemical-based remedies for cancer prevention, treatment, and inflammatory conditions and emphasizing their diverse roles in modulating critical regulatory mechanisms, this review addresses the current research landscape, challenges, and future directions in utilizing phytochemicals as effective agents against cancer and inflammation.

Clownselling: an in-depth narrative review on the therapeutic influence of clowning therapy in paediatric and adult cancer treatment and palliative care

Cancer and its treatments impose substantial physical and psychological burdens on patients, underscoring the need for innovative and holistic interventions. This narrative review explores the evolving role of clownselling in paediatric and adult cancer care, tracing its historical progression from entertainment to a therapeutic modality. Recognizing the potential of clowning therapy to address emotional, psychological, and existential challenges, the review systematically assesses its impact on treatment adherence, quality of life, and contributions in palliative care settings. By elucidating the therapeutic process, principles, and goals, it provides a comprehensive understanding of the foundations of clowning therapy. Given its positive influence on well-being, the integration of clowning therapy into interdisciplinary care teams and institutional policies is advocated. Future directions include diversified research, technology integration, standardized protocols and awareness campaigns, ensuring the sustained evolution of clowning therapy in fostering holistic well-being within the intricate tapestry of cancer care.

Hollow Magnetic Nanocarrier-Based Microrobot Swarms for NIR-Responsive Targeted Drug Delivery and Synergistic Therapy.

Nanocarriers are frequently used for drug delivery due to their large surface area, biocompatibility, and photothermal effects. However, they face the problem of premature drug leakage during drug transport. To address this challenge, we developed near-infrared light (NIR)-responsive hollow magnetic nanocarriers (HMC) by incorporating a chitosan-based molecular valve onto hollow magnetic nanocarriers (CHMC) to enable NIR-triggered drug release. Despite this advancement, this material still encounters the challenge of inadequate targeting. Recognizing the efficacy of magnetically driven micro/nanorobot swarms in remote wireless control, targeted motion, and efficient transport, we merged CHMC with magnetically controlled micro/nanorobot swarms. We evaluated their performance under programmable magnetic fields, which can be precisely controlled in biological fluid and directed toward targeting cells. Additionally, they demonstrated the ability to execute a responsive drug release under NIR irradiation. Ultimately, we confirmed their capacity for targeted delivery, responsive drug release, and photothermal therapy for liver cancer treatment in vivo. This approach heralds new possibilities for responsive drug therapy facilitated by micro/nanorobot swarms, offering promising advancements in medical treatment.

Human transforming growth factor β type I receptor in complex with kinase inhibitor SB505124.

The crystal structure of the intracellular domain of transforming growth factor β type I receptor (TβR1) in complex with the competitive inhibitor SB505124 is presented. The study provides insights into the structure and function of TβR1 in complex with SB505124, and as such offers molecular-level understanding of the inhibition of this critical signalling pathway. The potential of SB505124 as an avenue for therapy in cancer treatment is discussed on basis of the results.

Computational approach for counting of SISH amplification signals for HER2 status assessment

The human epidermal growth factor receptor 2 (HER2) gene is a critical biomarker for determining amplification status and targeting clinical therapies in breast cancer treatment. This study introduces a computer-aided method that automatically measures and scores HER2 gene status from invasive tissue regions of breast cancer using whole slide images (WSI) through silver in situ hybridization (SISH) staining. Image processing and deep learning techniques are employed to isolate untruncated and non-overlapping single nuclei from cancer regions. The Stardist deep learning model is fine-tuned on our HER2-SISH data to identify nuclei regions, followed by post-processing based on identified HER2 and CEP17 signals. Conventional thresholding techniques are used to segment HER2 and CEP17 signals. HER2 amplification status is determined by calculating the HER2-to-CEP17 signal ratio, in accordance with ASCO/CAP 2018 standards. The proposed method significantly reduces the effort and time required for quantification. Experimental results demonstrate a 0.91% correlation coefficient between pathologists manual enumeration and the proposed automatic SISH quantification approach. A one-sided paired t-test confirmed that the differences between the outcomes of the proposed method and the reference standard are statistically insignificant, with p-values exceeding 0.05. This study illustrates how deep learning can effectively automate HER2 status determination, demonstrating improvements over current manual methods and offering a robust, reproducible alternative for clinical practice.

Association Between Chemotherapy-Induced Peripheral Neuropathy and Low Anterior Resection Syndrome

Introduction: Low anterior resection syndrome (LARS) can be a debilitating condition that develops after undergoing sphincter-preserving surgery for rectal cancer. Chemotherapy-induced peripheral neuropathy is a common side effect of platinum-based chemotherapy agents used as systemic therapy for rectal cancer treatment. The purpose of this study was to determine the potential relationship between CIPN and LARS. Methods: This was a retrospective review of patients who underwent a low anterior resection for rectal cancer and received systemic therapy contacted at least six months from the most recent surgery. Eligible patients were called and completed the relevant surveys over the phone or email. Results: There was a total of 42 patients who completed the surveys with 33 (79%) having major LARS. Presence of a diverting ileostomy was the only significantly differentcharacteristic in those with major LARS versus those without. CIPN was independently associated with LARS (p = 0.046) on linear regression when controlling for neoadjuvant chemoradiation, diverting ileostomy and tumor distance from the anal verge. Conclusions: Developing severe CIPN is associated with developing LARS. Further studies evaluating the etiology behind this relationship should be conducted.

Astragalus membranaceus: A Traditional Chinese Medicine with Multifaceted Impacts on Breast Cancer Treatment

Breast cancer, the most prevalent malignant tumor among women globally, remains a critical area of focus for researchers striving to refine therapeutic approaches. As an important component of traditional Chinese medicine, Astragalus membranaceus (AM) has demonstrated potential for multifaceted impacts on breast cancer treatment through various mechanisms. To guide clinical practice and further explore the under-researched field of AM in breast cancer treatment, this paper mainly reviews the regulatory roles of AM-derived compounds and extracts on breast cancer cell proliferation, migration, invasion, and chemoresistance. Furthermore, this study delves into the synergistic effects observed when AM is co-administered with chemotherapeutic agents, including the enhancement of chemosensitivity, mitigation of toxic side effects, and reversal of drug resistance. This review indicates that AM holds promise not only as a therapy in breast cancer treatment but also paves the way for innovative integrated treatment approaches that combine the benefits of traditional medicine with modern pharmaceuticals. Nevertheless, future research endeavors are also urged to elucidate the in vivo pharmacological effects and underlying mechanisms of AM to inform more effective clinical treatment strategies.

Targeting the transcription factor YY1 is synthetic lethal with loss of the histone demethylase KDM5C.

An understanding of the enzymatic and scaffolding functions of epigenetic modifiers is important for the development of epigenetic therapies for cancer. The H3K4me2/3 histone demethylase KDM5C has been shown to regulate transcription. The diverse roles of KDM5C are likely determined by its interacting partners, which are still largely unknown. In this study, we screen for KDM5C-binding proteins and show that YY1 interacts with KDM5C. A synergistic antitumor effect is exerted when both KDM5C and YY1 are depleted, and targeting YY1 appears to be a vulnerability in KDM5C-deficient cancer cells. Mechanistically, KDM5C promotes global YY1 chromatin recruitment, especially at promoters. Moreover, an intact KDM5C JmjC domain but not KDM5C histone demethylase activity is required for KDM5C-mediated YY1 chromatin binding. Transcriptional profiling reveals that dual inhibition of KDM5C and YY1 increases transcriptional repression of cell cycle- and apoptosis-related genes. In summary, our work demonstrates a synthetic lethal interaction between YY1 and KDM5C and suggests combination therapies for cancer treatments.

Targeting the Renin-angiotensin-aldosterone System (RAAS) for Cardiovascular Protection and Enhanced Oncological Outcomes: Review.

The renin-angiotensin-aldosterone system (RAAS) is a crucial regulator of the cardiovascular system and a target for widely used therapeutic drugs. Dysregulation of RAAS, implicated in prevalent diseases like hypertension and heart failure, has recently gained attention in oncological contexts due to its role in tumor biology and cardiovascular toxicities (CVTs). Thus, RAAS inhibitors (RAASi) may be used as potential supplementary therapies in cancer treatment and CVT prevention. Oncological treatments have evolved significantly, impacting patient survival and safety profiles. However, they pose cardiovascular risks, necessitating strategies for mitigating adverse effects. The main drug classes used in oncology include anthracyclines, anti-HER2 therapies, immune checkpoint inhibitors (ICIs), and vascular endothelial growth factor (VEGF) signaling pathway inhibitors (VSPI). While effective against cancer, these drugs induce varying CVTs. RAASi adjunctive therapy shows promise in enhancing clinical outcomes and protecting the cardiovascular system. Understanding RAAS involvement in cancer and CVT can inform personalized treatment approaches and improve patient care.

Functional Assessments of Gynecologic Cancer Models Highlight Differences Between Single-Node Inhibitors of the PI3K/AKT/mTOR Pathway and a Pan-PI3K/mTOR Inhibitor, Gedatolisib

Background/Objectives: The PI3K/AKT/mTOR (PAM) pathway is frequently activated in gynecological cancers. Many PAM inhibitors selectively target single PAM pathway nodes, which can lead to reduced efficacy and increased drug resistance. To address these limitations, multiple PAM pathway nodes may need to be inhibited. Gedatolisib, a well-tolerated panPI3K/mTOR inhibitor targeting all Class I PI3K isoforms, mTORC1 and mTORC2, could represent an effective treatment option for patients with gynecologic cancers. Methods: Gedatolisib and other PAM inhibitors (e.g., alpelisib, capivasertib, and everolimus) were tested in endometrial, ovarian, and cervical cancer cell lines by using cell viability, cell proliferation, and flow cytometry assays. Xenograft studies evaluated gedatolisib in combination with a CDK4/6 inhibitor (palbociclib) or an anti-estrogen (fulvestrant). A pseudo-temporal transcriptomic trajectory of endometrial cancer clinical progression was computationally modeled employing data from 554 patients to correlate non-clinical studies with a potential patient group. Results: Gedatolisib induced a substantial decrease in PAM pathway activity in association with the inhibition of cell cycle progression and the decreased cell viability in vitro. Compared to single-node PAM inhibitors, gedatolisib exhibited greater growth-inhibitory effects in almost all cell lines, regardless of the PAM pathway mutations. Gedatolisib combined with either fulvestrant or palbociclib inhibited tumor growth in endometrial and ovarian cancer xenograft models. Conclusions: Gedatolisib in combination with other therapies has shown an acceptable safety profile and promising preliminary efficacy in clinical studies with various solid tumor types. The non-clinical data presented here support the development of gedatolisib combined with CDK4/6 inhibitors and/or hormonal therapy for gynecologic cancer treatment.

Copaiba Essential Oil: Composition, Therapeutic Actions, and Methods of Use for Health and Well-Being

Essential oils, known for their complex mixture of bioactive compounds, have long been used in traditional medicine and have shown potential in treating various diseases, including cancer. Recent studies highlight their anticancer properties, such as cytotoxic, antiproliferative, and antimetastatic effects. Essential oils contain molecules like terpenes and phenylpropanoids, which induce apoptosis in cancer cells by interfering with cellular signaling pathways. For instance, frankincense oil induces programmed cell death in breast cancer cells, while compounds like curcumin and thymol inhibit the proliferation of colorectal cancer cells. Additionally, certain essential oils prevent metastasis by inhibiting the migration and invasion of cancer cells. Despite promising preclinical results, the effectiveness and safety of essential oils in cancer treatment require further validation through human clinical trials. This review discusses the potential of essential oils as complementary therapies in cancer treatment, emphasizing the need for cautious application under professional supervision due to their concentrated nature and possible adverse effects. The therapeutic promise of essential oils lies in their ability to induce apoptosis, inhibit cell proliferation, and prevent metastasis, underscoring the importance of rigorous research to ensure their safe and effective use in oncology.

Nanotechnology-based platforms for effective and versatile sonodynamic therapy in cancer treatment.

Nanotechnology-based platforms for effective and versatile sonodynamic therapy in cancer treatment.

Small particle drug-eluting beads-transarterial chemoembolization combined with targeted therapy in the clinical treatment of unresectable liver cancer.

Liver cancer is a highly malignant tumor with significant clinical impact. Chemotherapy alone often yields suboptimal outcomes in both the short and long term, characterized by high rates of local recurrence and distant metastasis, leading to a poor long-term prognosis. To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization (DEB-TACE) combined with targeted therapy for the treatment of unresectable liver cancer. We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020. Based on the different treatment regimens administered, patients were divided into the control (36 patients receiving sorafenib alone) and joint (38 patients receiving small particle DEB-TACE combined with sorafenib) groups. We compared liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB)] and serum tumor markers [alpha fetoprotein (AFP)] before and after treatment in both groups. Short-term efficacy measures [complete response (CR), partial response, progression disease, stable disease, objective response rate (ORR), and disease control rate (DCR)] were assessed post-treatment. Long-term follow-up evaluated median overall survival (OS), progression-free survival (PFS), and adverse reaction rates between the two groups. One month post-treatment, the joint group demonstrated significantly higher rates of CR, ORR, and DCR compared to the control group (P < 0.05). Three days after treatment, the joint group showed elevated levels of ALT, AST, and TBIL but reduced levels of ALB and AFP compared to the control group (P < 0.05). The median OS was 18 months for the control group and 25 months for the joint group, while the median PFS was 15 months for the control group and 22 months for the joint group, with significant differences observed (log-rank: χ 2 = 7.824, 6.861, respectively; P = 0.005, 0.009, respectively). The incidence of adverse reactions was not significantly different between the groups (P > 0.05). The combination of small particle DEB-TACE and sorafenib significantly improves both short- and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.

Utilizing Carbon Nanomaterials for Enhanced Photothermal Therapy in Breast Cancer Treatment

Breast cancer is the most often diagnosed cancer in women and the second largest cause of cancer mortality worldwide. Photothermal therapy (PTT) has emerged as a viable cancer treatment that uses near-infrared (NIR) light-absorbing chemicals to selectively heat and destroy tumor cells while sparing healthy tissue. PTT has advantages such as high specificity, little invasiveness, and efficient tumor ablation. Recent advances include developing imageable photothermal agents to aid in therapy planning. This review focuses on the function of carbon nanoparticles in PTT, investigating their processes and advantages and analysing in vitro and in vivo investigations. Carbon nanomaterials like carbon nanotubes (CNTs) and graphene have a large surface area, great electrical conductivity, and biocompatibility, making them ideal for PTT. Carbon nanomaterials absorb NIR light, enabling deep tissue penetration and targeted heating of tumor tissues, resulting in necrosis and apoptosis. Carbon nanomaterials also increase tumor vascular permeability, which promotes chemotherapeutic drug accumulation and improves treatment results. Repurposing carbon nanomaterials for increased PTT is a potential method because of its capacity to target various pathways, select cytotoxicity against cancer cells, and synergistic effects with other anticancer drugs.

Hydrogen Sulfide (H2S)activatable Photodynamic Therapy Against Colon Cancer by tunable FRET Effect.

Developing activatable photodynamic agents is becoming a promising mode for realizing selective photodynamic therapy (PDT) in cancer treatment. However, till now only a few H2S-activatable photodynamic agents have been involved in this field. Here, we fabricated H2S-activatable nano-assemblies (P@TPPCY) for the treatment of colon cancer containing high concentration H2S. The H2S-activatable photosensitizer (TPPCY) was synthesized by covalent conjugation between tetraphenylporphyrin (TPP) and heptamethine cyanine (Cy7), and then TPPCY was encapsulated by an amphiphilic polymer DSPE-mPEG to form P@TPPCY nano-assemblies. We demonstrated that the photosensitizing effect of TPP was efficiently quenched by Cy7 with strong absorption in the NIR region via fluorescence resonance energy transfer (FRET) effect. Interestingly, the FRET effect between Cy7 and TPP was attenuated by the decrease of absorption of Cy7 in the NIR region after the Cy7 reacted with H2S, and then the photosensitizing effect of TPP in P@TPPCY was activated. Strikingly, the P@TPPCY showed efficient H2S-activatable photodynamic therapy (PDT) in vitro against HCT116 cells (human colon carcinoma cell line), thus this work provides a new method for realizing accurate treatment of colon cancer in virtue of high H2S concentration microenvironment.

Preparation of dual drug-loaded polymer nanoconjugate to enhance treatment efficacy for ovarian cancer cells

Ovarian cancer is the deadliest gynecological malignancy, representing 2.5 % of all female cancers and accounting for 5 % of female cancer-related fatalities. Despite numerous strategies in its treatment, the disease shows a high recurrence rate and a low survival rate. Consequently, there is a growing focus on targeted therapies in ovarian cancer treatment. It is well-known that VEGFR and LPA pathways undergo alterations in ovarian cancer and stimulate survival, adhesion, migration, invasion, tumor growth and angiogenesis. Cabozantinib (CBZ) is a multi-receptor tyrosine kinase inhibitor that effectively targets MET, VEGFR-1, 2, 3, FLT3, c-KIT, and RET. Ki16425 is a selective inhibitor of LPA receptors 1, 2, and 3. Therefore, targeting LPA receptors and combining with VEGFR inhibitor is a strategic approach for ovarian cancer treatment. In this study, it was aimed to prepare polymer-drug nanoconjugate for both VEGFR and LPAR inhibition. For this, O-(2-Carboxyethyl) polyethylene glycol (PEG5000) which advantages are known in cancer studies, was chosen as the carrier system, and a nanoconjugate containing Ki16425 and CBZ (Ki-PEG-CBZ) was synthesized and its potential was evaluated. Initially, CBZ and Ki16425 were conjugated to the PEG5000 through pH-sensitive hydrazone and ester bonds. After nanoconjugate characterization, in vitro release and its ovarian cancer treatment potential were evaluated on A2780, OVCAR3 and SKOV3 ovarian cancer cell lines. A nanoconjugate was obtained with a particle size of 169 ± 15.23 nm, a zeta potential of −13.5 ± 1.21 mV, and a release profile lasting 48 h, containing CBZ and Ki16425 with drug loading efficiencies of 73.71 ± 0.53 % and 77.72 ± 2.51 %, respectively. In vitro studies have demonstrated that Ki-PEG-CBZ is highly effective against ovarian cancer. We suggest that the developed polymer-drug nanoconjugate is an effective and safe nanoconjugate for the treatment of ovarian cancer.