Treatment Of Cancer Research Articles

Possibilities and prospects of artificial intelligence in the treatment of colorectal cancer (review)

AIM: to study modern approaches to the application of machine learning and deep learning technologies for the management of patients with colorectal cancer.MATERIALS AND METHODS: after screening 398 publications, 112 articles were selected and the full text of the works was studied. After studying the full texts of the articles, the works were selected, machine learning models in which showed an accuracy of more than 80%. The results of 41 original publications were used to write this review.RESULTS: several areas have been identified that are the most promising for the use of artificial intelligence technologies in the management of patients with colorectal cancer. They are predicting the response to neoadjuvant treatment, predicting the risks of metastasis and recurrence of the disease, predicting the toxicity of chemotherapy, assessing the risks of leakage of colorectal anastomoses. As the most promising factors that can be used to train models, researchers consider clinical parameters, the immune environment of the tumor, tumor RNA signatures, as well as visual pathomorphological characteristics. The models for predicting the risk of liver metastases in patients with stage T1 (AUC = 0.9631), as well as models aimed at assessing the risk of 30-day mortality during chemotherapy (AUC = 0.924), were characterized with the greatest accuracy. Most of the technologies discussed in this paper are software products trained on data sets of different quality and quantity, which are able to suggest a treatment scenario based on predictive models, and, in fact, can be used as a doctor’s assistant with very limited functionality.CONCLUSION: the current level of digital technologies in oncology and in the treatment of colorectal cancer does not allow us to talk about a strong AI capable of making decisions about the treatment of patients without medical supervision. Personalized treatment based on the microbiotic and mutation spectrum and, for example, personal pharmacokinetics, so far look fantastic, but certainly promising for future developments.

Two-dimensional MXene-based nano-prodrug for synergistic chemo-photothermal therapy on cancer treatment

In cancer treatment, although prodrugs have been developed to overcome obstacles such as undesirable pharmacokinetic performance and serious off-target toxicity of most chemotherapeutics, the combination of prodrugs with nanotechnology could be used to overcome the shortcomings of conventional prodrug strategies and facilitate more efficient drug delivery and accumulation of anticancer prodrugs at specific sites/tissues. Phototherapy is a method that uses near-infrared (NIR) light to achieve local and non-invasive tumor therapy. The combination of chemotherapy and phototherapy has shown many therapeutic advantages, including synergistic therapeutic effects and the reduction of toxic and side effects of drugs through dose reduction. In this work, a hydrazone linkage was reported to conjugate Ti3C2Tx MXene nanosheets with doxorubicin hydrochloride (DOX) and methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) through a chemical surface modification to form a two-dimensional (2D) nano-prodrug Ti3C2Tx-DOX/PEG (TDP) for synergistic chemo-photothermal therapy. First, hydrazide functionalized Ti3C2Tx was obtained. Then, the carbonyl group of DOX and the aldehyde group of mPEG-CHO can form a pH-responsive hydrazone bond with hydrazide-functionalized Ti3C2Tx. The high surface area of Ti3C2Tx could overcome the reduced drug loading caused by conjugation. Aqueous stability and biocompatibility were enhanced by the introduction of PEG, making the material capable of prolonged circulation in the body’s bloodstream. By achieving excellent antitumor results with this nano-prodrug, we have added another brick to the edifice of Ti3C2Tx MXene as an anticancer drug carrier, and given new vitality to the study of anticancer prodrugs combined with nanotechnology.

Review on Paclitaxel Derivatization: Enhanced Anticancer Action

Background: The United States Food and Drug Administration (FDA) has authorized paclitaxel for the treatment of numerous types of cancer, including breast, lung, ovarian, and Kaposi's sarcoma. It possesses all the characteristics of BCS class IV medications, including low bioavailability, low water solubility, poor permeability, unpredictable and poor absorption, and inter- and intrasubject variability. Objective: The purpose of this research was to evaluate previous efforts done to derivatize paclitaxel for greater effectiveness. Methods: A systematic literature review was conducted from a variety of sources, including published research, review articles, and patents, that mainly focus on the derivatization of paclitaxel that has been done in the last 10 years to enhance its solubility, permeability, and bioavailability. Different forms of derivatization were done in order to improve the drug's ability to be absorbed by the body, as well as its solubility and bioavailability. Results: This article explores the current and future strategies for increasing the anti-cancer efficacy of paclitaxel by enhancing its bioavailability, solubility, and penetration efficacy. Some examples are lipidbased delivery systems, polymer-based nanocarriers, crystal engineering (nanocrystals and co-crystals), liquidsolid technologies, and self-emulsifying solid dispersions. Other strategies are also discussed in this article. Conclusion: It is quite likely that this review article will contain perfect fragments of evidence for building a new model for the application of paclitaxel in the treatment of cancer.

Effects of sintilimab plus chemotherapy as first-line treatment on health-related quality of life in patients with advanced esophageal squamous cell carcinoma: results from the randomized phase 3 ORIENT-15 study

In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC. From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134. As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P=0.0170), pain (-2.24, 95% CI:-4.30 to-0.17; P=0.0337), fatigue (-2.24, 95% CI:-4.46 to-0.02; P=0.0479), constipation (-3.27, 95% CI-5.49 to-1.05; P=0.0039), QLQ-OES18 pain (-1.77, 95% CI-3.11 to-0.43; P=0.0097), trouble swallowing saliva (-2.09, 95% CI:-3.77 to-0.42; P=0.0146), and choked when swallowing (-3.23, 95% CI:-5.60 to-0.86; P=0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94, P=0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35-0.67, P<0.0001). Improved OS were observed in patients with better performance in several functioning and symptom scales of QLQ-C30 and QLQ-QES18. The statistically significant differences of several HRQoL scales and improvements in delayed deterioration observed in our study further support the use of sintilimab plus chemotherapy as first-line treatment for advanced ESCC. This study was funded by Innovent Biologics and was co-funded by Eli Lilly.

Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is a major health concern due to its prevalence, impact on well-being, high mortality rate, economic burden, and potential for prevention and early detection. GI cancer research has made remarkable strides in understanding biology, risk factors, and treatment options. An emerging area of research is the gut microbiome's role in GI cancer development and treatment response. The gut microbiome, vital for digestion, metabolism, and immune function, is increasingly linked to GI cancers. Dysbiosis and alterations in gut microbe composition may contribute to cancer development. Scientists study how specific bacteria or microbial metabolites influence cancer progression and treatment response. Modulating the gut microbiota shows promise in enhancing treatment efficacy and preventing GI cancers. Gut microbiota dysbiosis can impact GI cancer through inflammation, metabolite production, genotoxicity, and immune modulation. Microbes produce metabolites like short-chain fatty acids, bile acids, and secondary metabolites. These affect host cells, influencing processes like cell proliferation, apoptosis, DNA damage, and immune regulation, all implicated in cancer development. This review explores the latest research on gut microbiota metabolites and their molecular mechanisms in GI cancers. The hope is that this attempt will help in conducting other relevant research to unravel the precise mechanism involved, identify microbial signatures associated with GI cancer, and develop targets.

Cancer registration in Iceland for 70 years - incidence, mortality and survival

The Icelandic Cancer Registry (ICR) was founded seventy years ago by the Icelandic Cancer Society. In 2007 the ICR became one of the health registers of the Directorate of Health. In this paper we present cancer incidence, mortality, and survival in Iceland over 70 years. The ICR receives information on cancer diagnoses from histopathological laboratories, the Hospital Discharge Registry and the Cause of Death Registry. Iceland participates in the Nordic cancer database NORDCAN. Because of the small population size, random variation in numbers is very prominent. Therefore, data from ICR are published as five-year averages. For all malignancies combined, age-standardized incidence (ASI) in men rose steadily until around 15 years ago when a decline started. This is in line with prostate- and lung cancer incidence trends. In women, the ASI was lower than in men, but it is still on the rise despite declining lung cancer incidence. ASI for breast cancer, the most common cancer in women, is increasing. Simultaneously, cancer mortality for both sexes has declined in recent years and cancer survival is improving. Population-based cancer registration for over 70 years makes it possible to monitor the epidemiology of cancer in Iceland and compare with other countries. The changes in trends in ASI are in line with changes of cancer risk factors and diagnostic policy. The decline in cancer mortality and improvement in survival reflects advances in cancer treatment as well as effects of early detection and prevention.

Crosstalk between Oxidative Stress and Inflammation Induced by Ionizing Radiation in Healthy and Cancerous Cells.

Radiotherapy (RT) is a unique modality in cancer treatment with no replacement in many cases and uses a tumoricidal dose of various ionizing radiation types to kill cancer cells. It causes oxidative stress through reactive oxygen species (ROS) production or the destruction of antioxidant systems. On the other hand, RT stimulates the immune system both directly and indirectly by releasing danger signals from stress-exposed and dying cells. Oxidative stress and inflammation are two reciprocal and closely related mechanisms, one induced and involved by the other. ROS regulates the intracellular signal transduction pathways, which participate in the activation and expression of pro-inflammatory genes. Reciprocally, inflammatory cells release ROS and immune system mediators during the inflammation process, which drive the induction of oxidative stress. Oxidative stress or inflammation-induced damages can result in cell death (CD) or survival mechanisms that may be destructive for normal cells or beneficial for cancerous cells. The present study has focused on the radioprotection of those agents with binary effects of antioxidant and anti-inflammatory mechanisms in ionizing radiation (IR)-induced CD.

Combining Cisplatin with Pinellia pedatisecta Schott Lipid-Soluble Extract Induces Tumor Immunogenic Cell Death in Cervical Cancer

BackgroundPinellia pedatisecta Schott extract (PE) is extracted from Pinellia pedatisecta Schott (PPS), a traditional Chinese medicinal plant with the potential for direct anticancer effects or eliciting an anti-tumor response by activating the immune system. PurposeTo explore PE's ability and mechanism to reconstruct cisplatin's immunogenicity. MethodsCervical cancer cells were treated with cisplatin (CDDP) and/or PE. The exposure of calreticulin (CRT) on cell membrane was investigated by flow cytometry. The extracellular of ATP and HMGB1 was investigated by Western blot analysis, immunofluorescence and ELISA assay. Changes in immune profiles were using flow cytometry in vaccination and anti-tumor assays in vivo. Lastly, the mechanism of PE influenced the ROS/ERS pathway was examined by ROS assay kit, flow cytometry and Western blotting. ResultsPE treatment induced translocation of CRT from the endoplasmic reticulum to the cell membrane of tumor cells, concomitantly triggering immunogenic cell death (ICD). In terms of mechanisms, endoplasmic reticulum (ER) stress relievers could impede the ability of PE to induce immunogenicity. This indicates that PE is activated by ER stress, leading to subsequent induction of ICD. Upon analyzing RNA-seq data, it was observed that PE primarily induces programmed cell death in tumors by impeding upstream antioxidant mechanisms. Additionally, it transforms dying tumor cells into vaccines, activating a series of immune responses. ConclusionsThis study observed for the first time that PE-induced CRT exposure on the membrane of cervical cancer cells compensates for the defect of nonimmunogenic cell death inducer CDDP thereby stimulating potent ICD. This ability restores the immunogenicity of CDDP through ER stress induced by the ROS signal. ROS played a role in PE's ability to induce ICD, leading to increased expression of ER stress-related proteins, including ATF3 and IRE-1α. PE exerted anti-cancer effects by increasing the ROS levels, and ROS/ERS signaling may be a potential avenue for cervical cancer treatment. Hence, the synergistic use of PE and CDDP holds potential for enhancing immunochemotherapy in cancer treatment.

Pediatric and Adolescent Hodgkin Lymphoma: Paving the Way for Standards of Care and Shared Decision Making.

Hodgkin lymphoma (HL) is a treatable cancer with an incidence peak in adolescent and young adult years. Treatment strategies have been developed to balance the intensity of therapy needed to maintain disease-free survival while simultaneously preserving overall survival. Risk-based, response-adapted frontline therapy has long used a combination of chemotherapy and radiotherapy (RT). Successive clinical trials over the past three decades have safely reduced cumulative alkylator, anthracycline, and RT exposures for many patients. The advent of checkpoint inhibitors and the CD30-targeted antibody drug conjugate, brentuximab vedotin, has provided new options for de-escalation of conventional therapies associated with late effects in survivors treated at a young age. The ability to evaluate novel agents has been accelerated in collaborative trials inclusive of children and adolescents within the US National Clinical Trials Network and between the Children's Oncology Group and the EuroNet Pediatric Hodgkin Lymphoma Consortium. With numerous treatment options, patients with HL and their clinicians have an opportunity for shared decision making from diagnosis, through cancer treatment, and into survivorship. Given excellent survival outcomes, decisions about treatment in classic HL should be collaborative and attention to long-term survivorship needs should remain a high priority. Patient-reported outcomes remain an important tool to aid clinicians working with survivors to optimize health status and related quality of life for decades after HL therapy.

Investigating the Effects of Dorema hyrcanum Root Extracts on Selective Induction of Programmed Cell Death in Glioblastoma, Ovarian Cancer and Breast Cancer Cell Lines.

Despite remarkable advances, cancer has remained the second cause of death, which shows that more potent novel compounds should be found. Ethnobotanical compounds have a long history of treating diseases, and several approved chemotherapeutic compounds were isolated from plants. The research aimed to evaluate the cytotoxic effects of Dorema hyrcanum root extract on ovarian, breast, and glioblastoma cells while examining its selectivity towards normal cells. Additionally, the study is directed to investigate cell death mechanisms, delineate modes of cell death, and explore intracellular ROS production. Cytotoxic effects of alcoholic, dichloromethane, and petroleum ether fractions of Dorema hyrcanum were investigated on cancer and normal cells by using MTT assay, and the concentration around IC50 values was used for flow cytometric assessment of apoptosis, evaluation of the expression of selected genes via RT-qPCR and production of ROS. Methanolic extract exhibited the highest cytotoxicity, impacting A2780CP and MDA-MB-231. All fractions showed comparable effects on U251 cells. Notably, extracts displayed higher IC50 values in normal HDF cells, indicating cancer cell specificity. Flow cytometry revealed induction of apoptosis and non-apoptotic death in all three cancer cell lines. QPCR results showed upregulation of related genes, with RIP3K prominently increased in U251 glioblastoma. The DCFH-DA assay demonstrated ROS induction by the PE fraction exclusively in A2780CP cells after 30 minutes and up to 24 hours. Dorema hyrcanum root extracts exhibited potent anti-tumor effects against all studied cell lines. The methanolic extract demonstrated the highest cytotoxicity, particularly against A2780CP and MDA-MB-231 cells. Importantly, all fractions displayed selectivity for cancer cells over normal HDF cells. Unique modes of action were observed, with the petroleum ether fraction inducing significant non-apoptotic cell death. These findings suggest promising therapeutic potential for Dorema hyrcanum in cancer treatment with subject to further mechanistic studies.

Updates in the Use of Targeted Therapies for Gynecologic Cancers.

Targeted therapies have changed the treatment landscape in gynecologic cancer. Studies released over the past year have led to the incorporation of immunotherapy (IO) into the treatment for all patients with endometrial and cervical cancers at some point during their disease course. Poly(ADP-ribose) polymerase (PARP) inhibitors continue to play a role in women with ovarian carcinoma, particularly in homologous repair deficient tumors. Furthermore, the benefit of PARP inhibitors in challenging subgroups continues to be elucidated. Biomarker identification has led to the approval or compendium listing of several antibody-drug conjugates (ADCs). This review will update on IO, ADCs, and PARP inhibition for the treatment of gynecologic cancers.

MiR-26a is a Key Therapeutic Target with Enormous Potential in the Diagnosis and Prognosis of Human Disease.

MicroRNA-26a (miR-26a) belongs to small non-coding regulatory RNA molecules emerging as fundamental post-transcriptional regulators inhibiting gene expression that plays vital roles in various processes of human diseases such as depression, renal ischemia and reperfusion injury, liver injury and some refractory cancer. In this review, we expound on the results of studies about miR-26a with emphasis on its function in animal models or in vitro cell culture to simulate the most common human disease in the clinic. Furthermore, we also illustrate the underlying mechanisms of miR-26a in strengthening the antitumor activity of antineoplastic drugs. Importantly, dysregulation of miR-26a has been related to many chronic and malignant diseases, especially in neurological disorders in the brain such as depression and neurodegenerative diseases as well as cancers such as papillary thyroid carcinoma, hepatocellular carcinoma and so on. It follows that miR-26a has a strong possibility to be a potential therapeutic target for the treatment of neurological disorders and cancers. Although the research of miRNAs has made great progress in the last few decades, much is yet to be discovered, especially regarding their underlying mechanisms and roles in the complex diseases of humans. Consequently, miR-26a has been analyzed in chronic and malignant diseases, and we discuss the dysregulation of miR-26a and functional roles in the development and pathogenesis of these diseases, which is very helpful for understanding their mechanisms as new biomarkers for diagnosing and curing diseases in the near future.

Sensitive and selective electrochemical sensor for palbociclib, a highly selective CDK4/6 inhibitor, based on molecularly imprinted polymer

In this research, a molecularly imprinted polymer (MIP)-based electrochemical sensor was developed for the first time to determine palbociclib (PLB), an oral, selective Cyclin Dependent Kinase (CDK4 and CDK6) inhibitor used in the treatment of breast cancer. Acrylamide (ACR) was selected as the functional monomer to fabricate the proposed sensor (ACR-PLB-MIP/GCE), and polymerization was performed by photopolymerization. To improve the efficiency of the MIP-based electrode for PLB measurement, several factors, including monomer ratio, removal time, removal agent, and rebinding time, were carefully optimized. Under optimal conditions and using the differential pulse voltammetry (DPV) technique, the limit of detection (LOD) of 1.35 × 10−12 M and the limit of quantification (LOQ) of 4.48 × 10−12 M were calculated for PLB analysis using ACR-PLB-MIP/GCE in standard solution. Application of the ACR-PLB-MIP/GCE sensor to commercial serum samples resulted in LOD and LOQ values of 3.33 × 10−12 M and 1.11 × 10−11 M, respectively. The sensor was also applied to the tablet sample for the detection of PLB and a satisfactory RSD% (0.95) was obtained. The results of interference studies confirmed the high selectivity of the electrode for PLB analysis. These results clearly demonstrated that the molecular imprinting approach for the detection of PLB in the novel sensor system is a highly efficient approach.

Naringenin-induced Oral Cancer Cell Apoptosis Via ROS-mediated Bid and Bcl-xl Signaling Pathway.

Oral cancer is a malignant tumor with a high impact and poor prognosis. Naringenin, a flavonoid found in citrus fruits and its anti-inflammatory and antioxidant properties offer potential therapeutic benefits. However, limited studies have been conducted on the impact of naringenin on human tongue carcinoma CAL-27 cells. This study aims to elucidate the correlation between naringenin and tongue cancer, thereby identifying a potential therapeutic candidate for drug intervention against tongue cancer. The effect of naringenin on the apoptosis of CAL-27 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-- FITC apoptosis detection, cell cycle, and apoptosis analysis, Reactive Oxygen Species assay and Western blot. The results showed that naringenin significantly induced apoptosis in CAL-27 cells in a dose-dependent manner. Mechanistically, naringenin-induced apoptosis was mediated through the upregulation of Bid and downregulation of Bcl-xl, which led to increased generation of ROS. The findings suggested that naringenin may represent a promising candidate for the treatment of oral cancer by inducing apoptotic cell death via modulation of the Bid and Bcl-xl signaling pathways.

A Scoping Review on Recent Progress on Purpurin and its Derivatives

Background: Purpurin is being used as a red dye for many decades. But recently, due to its pharmacological properties, purpurin and its derivatives have attracted a lot of researchers for the treatment of various ailments, such as cancer, Alzheimer’s disease, depression, etc. Objectives: The objective of this study is to provide an overview of its pharmacological properties, pharmacokinetic studies, synthesis, isolation, quality assurance, and patent studies. Method: A systemic scoping review was undertaken. Three databases (Pubmed, Scopus, and Google Scholar) and patent websites were searched using relevant words (e.g., purpurin, purpurin derivatives, anticancer, toxicity, etc.). All outcomes for studies that met the inclusion criteria were included in the review. Extracted data were accumulated using tables, figures, and accompanying narrative descriptive summaries. The review was reported using the preferred reporting items for scoping review (PRISMAScR) guidelines. Sixty-eight studies and eighty-six patents met the inclusion criteria, mostly preclinical (in vitro, in vivo, and in silico) studies performed in rats, mice, dogs, and zebrafish, followed by one clinical trial study. Results: The potent antioxidant nature of purpurin is the main reason behind its vast pharmacological properties. It acts by decreasing mitochondrial stress and by acting on the endoplasmic reticulum. It also crosses the BBB barrier, has high GI absorption, and follows the Lipinski rule, which makes it a good drug for various neurodegenerative disorders. It inhibits various CYP-450, CYP 1A2, and CYP 3A4 enzymes, which are responsible for causing mutations. It gets photosensitized by UV light and causes ROSdependent apoptosis in cancer cells. Conclusion: This scoping review highlights purpurin and its derivatives as highly prized moieties in the treatment of various neurological conditions and cancer. The unique nature of purpurin is responsible for its pharmacological properties, which are due to the presence of hydroxyl and keto groups at specific positions. It gets photosensitized by UV and laser light and acts as an anticancer drug. But the lack of robust evaluation in clinical studies is another major concern. Purpurin can be seen in the prescription in the future, although a lot of work still needs to be done.

Focal high-intensity focused ultrasound therapy for localized prostate cancer: An interim analysis of the multinational FASST study.

High-intensity focused ultrasound (HIFU) emerged as a novel approach for the treatment of localized prostate cancer (PCa). However, prospective studies on HIFU-related outcomes and predictors of treatment failure (TF) remain scarce. We conducted a multinational prospective cohort study among patients undergoing HIFU therapy for localized, low- to intermediate-risk PCa. Follow-up data on serial prostate specific antigen (PSA), multi-parametric magnetic resonance imaging (mpMRI), targeted/systematic biopsies, adverse events and functional outcomes were collected. The primary endpoint was TF, defined as histologically confirmed PCa requiring whole-gland salvage treatment. Uni- and multi-variable adjusted hazard ratios (HRs) were calculated using Cox proportional hazard regression models. At baseline, mean (standard deviation) age was 64.14 (7.19) years, with the majority of patients showing T-stage 1 (73.9%) and International Society of Urological Pathology grading system Grade 2 (58.8%). PSA nadir (median, 1.70 ng/mL) was reached after 6 months. Of all patients recruited, 16% had clinically significant PCa, as confirmed by biopsy, of which 13.4% had TF. Notably, T-stage and number of positive cores at initial biopsy were independent predictors of TF during follow-up (HR [95% CI] 1.27 [1.02-1.59] and 5.02 [1.80-14.03], respectively). Adverse events were minimal (17% and 8% early and late adverse events, respectively), with stable or improved functional outcomes in the majority of patients. This interim analysis of a multinational study on HIFU therapy for the management of low-to-intermediate-risk PCa reveals good functional outcomes, minimal adverse events and low incidence of TF over the short-term. Data on long-term outcomes, specifically as it relates to oncological outcomes, are awaited eagerly.

Moving Immunotherapy Into the Treatment of Resectable Non-Small Cell Lung Cancer.

Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non-small cell lung cancer (NSCLC) to add to the treatment of early-stage or resectable NSCLC. Although completed randomized trials supported the approvals of some ICIs as perioperative therapies (ie, adjuvant, neoadjuvant, or neoadjuvant followed by adjuvant), ongoing trials are evaluating other anti-PD-(L)1 antibodies for similar indications, or in combination with stereotactic body radiotherapy (SBRT). The incorporation of immunotherapy brings potential to improve outcomes of patients with resectable NSCLC, but these advances have also increased the complexity of the treatment landscape and created important knowledge gaps. This article reviews the current standards for local therapies in NSCLC, describes the clinical trials exploring the combination of ICIs to SBRT, and explains the recent approvals of ICIs as perioperative therapies. A discussion follows to highlight three important areas of uncertainty: (1) the contribution of ICIs given in each treatment phase (neoadjuvant and adjuvant) to the overall effect of neoadjuvant chemoimmunotherapy followed by adjuvant ICIs; (2) the selection of regimens to serve as comparators in future randomized trials of perioperative therapies; and (3) the role of pathologic complete response as an intermediate end point and aid for selection of patients for adjuvant therapy. Moving forward, stakeholders will need to engage in concerted research efforts to address the relevant clinical questions regarding the optimal management of resectable NSCLC.

Computational Study of Lactucine and its Derivatives to Investigate its Anti-cancerous Properties Targeting Apoptosis-inducing Protein

Background: Lactucine is related to the sesquiterpene lactone group of naturally occurring compounds and has a variety of pharmacological effects including anticancer properties found in Chicory, Wormwood, Laurus nobilis, Pyrethrum, Chamomile, etc. Lactucine has an anticancer effect which may induce apoptosis in cancerous cells and protect other cells from getting infected. Objective: In this study, Lactucine and its derivatives were screened, and performed their in silico docking study with the proteins involved in the apoptosis-inducing effect in human leukemia cancer. Methods: The three-dimensional structure of lactucine and its derivatives were retrieved in the SDF format. Active sites of protein structures were determined by Sitemap. LigPrep module was used for geometrical refining of chemical structures of lactucine and its derivatives. The protein preparation wizard of Maestro (Schrodinger) was used for protein preparation. From the receptor-complex structure, the cocrystallized ligands were removed from the active site position of the receptor chain. All ligands were docked using default Glide settings for a grid centered on the ligand and structure. Flexible docking was performed using the extra precision (XP) feature of Glide module. The best docking poses for the lactucine and their derivatives were selected based on their docking score. The ADMET properties of lactucine 15- oxalate have been predicted by admetSAR software. Results: Proteins and ligands three-dimensional structures were retrieved from PDB and Pubchem databases, respectively. All lactucine derivatives suitably docked on the apoptosis-inducing proteins with ample Glide scores Lactucin 15-oxalate interacts with proteins which are responsible for apoptosis with a maximum of six H-bonds. Other types of interactions are also involved, like Pi-cation, Pi-Pi stacking, salt bridges, and halogen bonds. Protein CDK-4 has shown the highest number of H-bond (LYS142 salt bridges), ALA16, VAL14, ASP99, LYS35, TYR17, and ASN145) with the Lactucin 15-oxalate. ADMET properties of lactucin 15-oxalate met with the criteria of being eligible to be a novel drug for the treatment of human leukemia cancer. The Dock score of both the Dasatinib drug and the lactucine-15-oxalate with the apoptosis-inducing protein stipulates that the selected ligand has equitable interaction with the target proteins. Conclusion: In this study, lactucine derivatives were docked with apoptosis-inducing proteins for the prediction of its anticancer effect. Lactucin15-oxalate has shown the highest binding affinity for the CDK-4 target and can be used as a lead compound for cancer treatment. Glide and Dock score for docking of lactucin 15-oxalate with CDK-4, well as the number of hydrogen bonding, is in agreement to use this ligand for study. These in silico results are valuable to proceed with the in vitro and in vivo studies related to the anti-cancer role of lactucin 15-oxalate.

Targeted delivery of 5-fluorouracil and shikonin by blended and coated chitosan/pectin nanoparticles for treatment of colon cancer

Herein, 5-fluorouracil and shikonin (extracted from Fusarium tricinctum) were loaded in chitosan/pectin nanoparticle (CS/PEC-NPs), prepared by blending (B-CS/PEC-NPs) and coating (C-CS/PEC-NPs) methods. The nanoparticles characterized by Fourier Transform Infrared (FTIR), X-ray diffraction (XRD), Energy-dispersive X-ray (EDX), Scanning Electron Microscope (SEM) and Differential Light Scattering (DLS). Then, some properties of the nanoparticles such as drug release rate and the nanoparticles cytotoxicity were studied. The FTIR, XRD, EDX, SEM and DLS results showed that the nanoparticles synthesized properly with an almost spherical morphology, an average size of 82–93 nm for B-CS/PEC-NPs, an average diameter of below 100 nm (mostly 66–89 nm) for C-CS/PEC-NPs, and hydrodynamic diameter of 310–817 nm. The drug release results indicated the lower release rate of drugs for B-CS/PEC-NPs relative to C-CS/PEC-NPs at different pHs, high release rate of drugs for the nanoparticles in the simulated large intestinal fluids containing pectinase, and Korsmeyer-Peppas model for release of the drugs. The results showed more cytotoxicity of B-CS/PEC-NPs containing drugs, especially B-CS/PEC-NPs containing both drugs (B-CS/PEC/5-FU/SHK-NPs) after treating with pectinase (IC50 of 18.6 μg/mL). In conclusion, despite the limitation of C-CS/PEC-NPs for simultaneous loading of hydrophilic and hydrophobic drugs, B-CS/PEC-NPs showed suitable potency for loading and targeted delivery of the drugs.

Cancer on motors: How kinesins drive prostate cancer progression?

Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.