Search results for: anti cancer drug

Authors: Naima Nur, Safa Islam, Saeema Islam, Faridul Alam

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Background: Drug-resistant pulmonary tuberculosis (DR-PTB), particularly multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant (pre-XDR), is a major challenge in effectively controlling TB, especially in developing. This study aimed to identify the strains of M. tuberculosis complex (MTC) and drug resistance patterns among the pulmonary tuberculosis patients. Methods: The study used a cross-sectional design, and 815 patients were recruited randomly in three study periods. In the first-period, 210 treated PTB patients, who were completed their treatment, received their diagnoses using light microscopy, fluorescence microscopy and cultured on Lowenstein-Jensen (L-J) slant, and then strains were identified as MTC by biochemical tests, and then sensitivity test in National Institute of Diseases of the Chest and Hospital. In the second-period, 220 re-treated PTB patients, who were completed their treatment, received their diagnoses using culture on L-J slant, line probe assay (LPA), and GeneXpert in the same hospital. In the last-period, during treatment, 385 MDR-PTB patients received their diagnoses using culture on L-J slant and LPA in the same hospital. Results: Among sixty-two (29.5%) PTB patients, 13% were sensitive to all first-line anti-TB drugs, 26% were MDR-TB patients, and 14.2% were pre-XDR-TB among 14 MDR-TB patients. After three years, 31% were MDR-TB among 220 re-treated PTB patients. After five years, 16.4% was pre-XDR-TB among 385 MDR-TB patients. Compared to females, male patients were significantly higher at all times. Conclusion: The current study demonstrated that in three study periods, the proportions of DR-TB, MDR-TB, and pre-XDR patients were an alarming issue and increasing daily.

Keywords: multi-drug resistant, drug-resistant, pre-extensive drug resistant, pulmonary tuberculosis

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Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Mohsina Akhter

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Cancer has become a wide spread disease around the globe and takes many lives every year. Different treatments are being practiced but all have potential side effects with somewhat less specificity towards target sites. Pseudomonas aeruginosa is known to secrete a protein azurin with special anti-cancer function. It has unique cell penetrating peptide comprising of 18 amino acids that have ability to enter cancer cells specifically. Reported function of Azurin is to stabilize p53 inside the tumor cells and induces apoptosis through Bax mediated cytochrome c release from mitochondria. At laboratory scale, we have made recombinant azurin through cloning rpTZ57R/T-azu vector into E.coli strain DH-5α and subcloning rpET28-azu vector into E.coli BL21-CodonPlus (DE3). High expression was ensured with IPTG induction at different concentrations then optimized high expression level at 1mM concentration of IPTG for 5 hours. Purification has been done by using Ni+2 affinity chromatography. We have concluded that azurin can be a remarkable improvement in cancer therapeutics if it produces on a large scale. Azurin does not enter into the normal cells so it will prove a safe and secure treatment for patients and prevent them from hazardous anomalies.

Keywords: azurin, pseudomonas aeruginosa, cancer, therapeutics

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Authors: Syed Asif Hassan, Syed Atif Hassan

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Multidrug-resistant Tuberculosis (MDR-TB) is an infection caused by the resistant strains of Mycobacterium tuberculosis that do not respond either to isoniazid or rifampicin, which are the most important anti-TB drugs. The increase in the occurrence of a drug-resistance strain of MTB calls for an intensive search of novel target-based therapeutics. In this context LprG (Rv1411c) a lipoprotein from MTB plays a pivotal role in the immune evasion of Mtb leading to survival and propagation of the bacterium within the host cell. Therefore, a machine learning method will be developed for generating a computational model that could predict for a potential anti LprG activity of the novel antituberculosis compound. The present study will utilize dataset from PubChem database maintained by National Center for Biotechnology Information (NCBI). The dataset involves compounds screened against MTB were categorized as active and inactive based upon PubChem activity score. PowerMV, a molecular descriptor generator, and visualization tool will be used to generate the 2D molecular descriptors for the actives and inactive compounds present in the dataset. The 2D molecular descriptors generated from PowerMV will be used as features. We feed these features into three different classifiers, namely, random forest, a deep neural network, and a recurring neural network, to build separate predictive models and choosing the best performing model based on the accuracy of predicting novel antituberculosis compound with an anti LprG activity. Additionally, the efficacy of predicted active compounds will be screened using SMARTS filter to choose molecule with drug-like features.

Keywords: antituberculosis drug, classifier, machine learning, molecular descriptors, prediction

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Authors: Nusaiba Al-Nemrawi, Belal Al-Husein

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Methotrexate (MTX) is a stoichiometric inhibitor of dihydrofolate reductase, which is essential for DNA synthesis. MTX is a chemotherapeutic agent used for treating many types of cancer cells. However, cells’ resistant to MTX is very common and its pharmacokinetic behavior is highly problematic. of MTX within tumor cells, we propose encapsulation of antitumor drugs in nanoparticulated systems. Chitosan (CS) is a naturally occurring polymer that is biocompatibe, biodegradable, non-toxic, cationic and bioadhesive. CS nanoparticles (CS-NPs) have been used as drug carrier for targeted delivery. Titanium dioxide (TiO2), a natural mineral oxide, which is used in biomaterials due to its high stability and antimicrobial and anticorrosive properties. TiO2 showed a potential as a tumor suppressor. In this study a new formulation of MTX loaded in CS NPs (CS-MTX NPs) and coated with Titanium oxide (TiO2) was prepared. The mean particle size, zeta potential, polydispersity index were measured. The interaction between CS NPs and TiO2 NPs was confirmed using FTIR and XRD. CS-MTX NPs was studied in vitro using the tumor cell line MCF-7 (human breast cancer). The results showed that CS-MTX has a size around 169 nm and as they were coated with TiO2, the size ranged between and depending on the ratio of CS-MTX to TiO2 ratio used in the preparation. All NPs (uncoated and coated carried positive charges and were monodispersed. The entrapment efficacy was around 65%. Both FTIR and XRD proved that TiO2 interacted with CS-MTX NPs. The drug invitro release was controlled and sustained over days. Finally, the studied in vitro using the tumor cell line MCF-7 suggested that combining nanomaterials with anticancer drugs CS-MTX NPs may be more effective than free MTX for cancer treatment. In conclusion, the combination of CS-MTX NPs and TiO2 NPs showed excellent time-dependent in vitro antitumor behavior, therefore, can be employed as a promising anticancer agent to attain efficient results towards MCF-7 cells.

Keywords: Methotrexate, Titanium dioxide, Chitosan nanoparticles, cancer

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Authors: Filipa Vasconcelos

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The administration of endoplasmic reticulum amino peptidases (ERAP1 or ERAP2) inhibitors can be used for therapeutic approaches against cancer and auto-immune diseases. However, one of the main shortcomings of drug delivery systems (DDS) is associated with the drug off-target distribution, which can lead to an increase in its side effects on the patient’s body. To overcome such limitations, the encapsulation of four representative compounds of ERAP inhibitors into Polycaprolactone (PCL), Polyvinyl-alcohol (PVA), crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes is proposed as a safe and controlled drug release system. The use of electrospun fibrous meshes as a DDS allows efficient solvent evaporation giving limited time to the encapsulated drug to recrystallize, continuous delivery of the drug while the fibers degrade, prevention of initial burst release (sustained release), tunable dosages, and the encapsulation of other agents. This is possible due to the fibers' small diameters and resemblance to the extracellular matrix (confirmed by scanning electron microscopy results), high specific surface area, and good mechanical strength/stability. Furthermore, release studies conducted on PCL, PVA, crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes with each of the ERAP compounds encapsulated demonstrated that they were capable of releasing >60%, 50%, 40%, and 45% of the total ERAP concentration, respectively. Fibrous meshes with ERAP_E compound encapsulated achieved higher released concentrations (75.65%, 62.41%, 56.05%, and 65.39%, respectively). Toxicity studies of fibrous meshes with encapsulated compounds are currently being accessed in vitro, as well as pharmacokinetics and dynamics studies. The last step includes the implantation of the drug-loaded fibrous meshes in vivo.

Keywords: drug delivery, electrospinning, ERAP inhibitors, liposomes

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Authors: Hyekyung Woo, Gwihyun Kim

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mHealth, which encompasses mobile health technologies and interventions, is rapidly evolving in various medical specialties, and its impact is evident in oncology. This review describes current trends in research addressing the integration of mHealth into the management of breast cancer by examining evaluations of mHealth and its contributions across the cancer care continuum. Mobile technologies are perceived as effective in prevention and as feasible for managing breast cancer, but the diagnostic accuracy of these tools remains in doubt. Not all phases of breast cancer treatment involve mHealth, and not all have been addressed by research. These drawbacks in the application of mHealth to breast cancer management call for intensified research to strengthen its role in breast cancer care.

Keywords: mobile application, breast cancer, content analysis, mHealth

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Authors: Abdelhadi Adam Salih Denei

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Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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Authors: Meltem Koray, Arda Ozgon, Duygu Ofluoglu, Mehmet Yaltirik

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Oral ulcerations can be seen as a side effect of different drugs. These ulcers usually appear within a few weeks following drug treatment. In most of cases, these ulcers resist to conventional treatments, such as anesthetics, antiseptics, anti-inflammatory agents, cauterization, topical tetracycline and corticosteroid treatment. The diagnosis is usually difficult, especially in patients receiving multiple drug therapies. Hyaluronan or hyaluronic acid (HA) is a biomaterial that has been introduced as an alternative approach to enhance wound healing and also used for oral ulcer treatment. The aim of this report is to present the treatment of drug-induced oral ulceration on maxillary mucosa with HA gel. 60-year-old male patient was referred to Department of Oral and Maxillofacial Surgery complaining of oral ulcerations during few weeks. He had received chemotherapy and radiotherapy in 2014 with the diagnosis of nasopharyngeal carcinoma, and he has accompanying systemic diseases such as; cardiological, neurological diseases and gout. He is medicated with Escitalopram (Cipralex® 20mg), Quetiapine (Seroquel® 100mg), Mirtazapine (Zestat® 15mg), Acetylsalicylic acid (Coraspin® 100mg), Ramipril-hydrochlorothiazide (Delix® 2.5mg), Theophylline anhydrous (Teokap Sr® 200mg), Colchicine (Colchicum Dispert® 0.5mg), Spironolactone (Aldactone® 100mg), Levothyroxine sodium (Levotiron® 50mg). He had painful oral ulceration on the right side of maxillary mucosa. The diagnosis was 'drug-induced oral ulceration' and HA oral gel (Aftamed® Oral gel) was prescribed 3 times a day for 2 weeks. Complete healing was achieved within 3 weeks without any side effect and discomfort. We suggest that HA oral gel is a potentially useful local drug which can be an alternative for management of drug-induced oral ulcerations.

Keywords: drug-induced, hyaluronic acid, oral ulceration, maxillary mucosa

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Authors: Rashini Maduka, C. R. Wijesinghe, A. R. Weerasinghe

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Drug-drug interactions (DDIs) can happen when two or more drugs are taken together. Today DDIs have become a serious health issue due to adverse drug effects. In vivo and in vitro methods for identifying DDIs are time-consuming and costly. Therefore, in-silico-based approaches are preferred in DDI identification. Most machine learning models for DDI prediction are used chemical and biological drug properties as features. However, some drug features are not available and costly to extract. Therefore, it is better to make automatic feature engineering. Furthermore, people who have diabetes already suffer from other diseases and take more than one medicine together. Then adverse drug effects may happen to diabetic patients and cause unpleasant reactions in the body. In this study, we present a model with a graph convolutional autoencoder and a graph decoder using a dataset from DrugBank version 5.1.3. The main objective of the model is to identify unknown interactions between antidiabetic drugs and the drugs taken by diabetic patients for other diseases. We considered automatic feature engineering and used Known DDIs only as the input for the model. Our model has achieved 0.86 in AUC and 0.86 in AP.

Keywords: drug-drug interaction prediction, graph embedding, graph convolutional networks, adverse drug effects

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Authors: M. Sai Veerendra

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Today, money laundering (ML) poses a serious threat not only to financial institutions but also to the nation. This criminal activity is becoming more and more sophisticated and seems to have moved from the cliché of drug trafficking to financing terrorism and surely not forgetting personal gain. Most of the financial institutions internationally have been implementing anti-money laundering solutions (AML) to fight investment fraud activities. However, traditional investigative techniques consume numerous man-hours. Recently, data mining approaches have been developed and are considered as well-suited techniques for detecting ML activities. Within the scope of a collaboration project on developing a new data mining solution for AML Units in an international investment bank in Ireland, we survey recent data mining approaches for AML. In this paper, we present not only these approaches but also give an overview on the important factors in building data mining solutions for AML activities.

Keywords: data mining, clustering, money laundering, anti-money laundering solutions

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Authors: Salvana P. M. Costa, Tarcyla A. Gomes, Giovanna C. R. M. Schver, Leslie R. M. Ferraz, Cristovão R. Silva, Magaly A. M. Lyra, Danilo A. F. Fonte, Larissa A. Rolim, Amanda C. Q. M. Vieira, Miracy M. Albuquerque, Pedro J. Rolim-neto

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Efavirenz (EFV) is considered one of the most widely used anti-HIV drugs. However, it is classified as a drug class II (poorly soluble, highly permeable) according to the biopharmaceutical classification system, presenting problems of absorption in the gastrointestinal tract and thereby inadequate bioavailability for its therapeutic action. This study aimed to overcome these barriers by developing and obtaining solid dispersions (SD) in order to increase the EFZ bioavailability. For the development of SD with EFV, theoretical and practical studies were initially performed. Thus, there was a choice of a carrier to be used. For this, it was analyzed the various criteria such as glass transition temperature of the polymer, intra- and intermolecular interactions of hydrogen bonds between drug and polymer, the miscibility between the polymer and EFV. The choice of the obtainment method of the SD came from the analysis of which method is the most consolidated in both industry and literature. Subsequently, the choice of drug and carrier concentrations in the dispersions was carried out. In order to obtain DS to present the drug in its amorphous form, as the DS were obtained, they were analyzed by X-ray diffraction (XRD). SD are more stable the higher the amount of polymer present in the formulation. With this assumption, a SD containing 10% of drug was initially prepared and then this proportion was increased until the XRD showed the presence of EFV in its crystalline form. From this point, it was not produced SD with a higher concentration of drug. Thus, it was allowed to select PVP-K30, PVPVA 64 and the SOLUPLUS formulation as carriers, once it was possible the formation of hydrogen bond between EFV and polymers since these have hydrogen acceptor groups capable of interacting with the donor group of the drug hydrogen. It is worth mentioning also that the films obtained, independent of concentration used, were presented homogeneous and transparent. Thus, it can be said that the EFV is miscible in the three polymers used in the study. The SD and Physical Mixtures (PM) with these polymers were prepared by the solvent method. The EFV diffraction profile showed main peaks at around 2θ of 6,24°, in addition to other minor peaks at 14,34°, 17,08°, 20,3°, 21,36° and 25,06°, evidencing its crystalline character. Furthermore, the polymers showed amorphous nature, as evidenced by the absence of peaks in their XRD patterns. The XRD patterns showed the PM overlapping profile of the drug with the polymer, indicating the presence of EFV in its crystalline form. Regardless the proportion of drug used in SD, all the samples showed the same characteristics with no diffraction peaks EFV, demonstrating the behavior amorphous products. Thus, the polymers enabled, effectively, the formation of amorphous SD, probably due to the potential hydrogen bonds between them and the drug. Moreover, the XRD analysis showed that the polymers were able to maintain its amorphous form in a concentration of up to 80% drug.

Keywords: amorphous form, Efavirenz, solid dispersions, solubility

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Authors: Regina R. Gunawan, Indwiani Astuti, H. Raden Danarto

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Cancer is the leading cause of death worldwide. Cancer is caused by mutations that alter the function of normal human genes and give rise to cancer genes. MicroRNA (miRNA) is a small non-coding RNA that regulates the gen through complementary bond towards mRNA target and cause mRNA degradation. miRNA works by either promoting or suppressing cell proliferation. miRNA level expression in cancer may offer another value of miRNA as a biomarker in cancer diagnostic. miRNA-21 is believed to have a role in carcinogenesis by enhancing proliferation, anti-apoptosis, cell cycle progression and invasion of tumor cells. Hsa-miR-21-5p marker has been identified in Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) patient’s urine. This research planned to explore the diagnostic performance of miR-21 to differentiate PCa and BPH patients. In this study, urine samples were collected from 20 PCa patients and 20 BPH patients. miR-21 relative expression against the reference gene was analyzed and compared between the two. miRNA expression was analyzed using the comparative quantification method to find the fold change. miR-21 validity in identifying PCa patients was performed by quantifying the sensitivity and specificity with the contingency table. miR-21 relative expression against miR-16 in PCa patient and in BPH patient has 12,98 differences in fold change. From a contingency table of Cq expression of miR-21 in identifying PCa patients from BPH patient, Cq miR-21 has 100% sensitivity and 75% specificity. miR-21 relative expression can be used in discriminating PCa from BPH by using a urine sample. Furthermore, the expression of miR-21 has higher sensitivity compared to PSA (Prostate specific antigen), therefore miR-21 has a high potential to be analyzed and developed more.

Keywords: benign prostate hyperplasia, biomarker, miRNA-21, prostate cancer

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Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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Authors: Fakhrosadat Sajjadian

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The majority of deaths in cancer patients are caused by distant metastasis. Breast cancer shows a unique spread pattern, often affecting bone, liver, lung, and brain. Breast cancer can be categorized into various subtypes according to gene expression patterns, and these subtypes exhibit specific preferences for organs where metastasis occurs. Breast tumors with luminal characteristics have a preference for spreading to the bone, whereas basal-like breast cancer (BLBC) shows a tendency to metastasize to the lungs. Still, the mechanisms behind this particular pattern of metastasis in organs have yet to be fully understood. In this evaluation, we will outline the latest progress in molecular signaling pathways and treatment methods for breast cancer lung metastasis.

Keywords: lung cancer, liver cancer, diagnosis, BLBC, metastasis

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Amir Ghasemlouei, Alireza Khalaj

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In women, cancer of the breast is one of the most common incident cancer and cause of death from cancer .we reviewed the prevalence of obesity and its association with breast cancer. In this study, a total of 25 articles regarding the subject matter of the article have been presented in which 640 patients were examined that 320 patients with breast cancer and 320 were controls. The distribution of breast cancer patients and controls with respect to their anthropometric indices in patients with higher weight, which was statistically significant (60.2 ± 10.2 kg) compared with control group (56.1 ± 11.3 kg). The body mass index of patients was (26.06+/-3.42) and significantly higher than the control group (24.1+/-1.7). Obesity leads to increased levels of adipose tissue in the body that can be stored toxins and carcinogens to produce a continuous supply. Due to the high level of fat and the role of estrogen in a woman is endogenous estrogen of the tumor and regulate the activities of growth steroids, obesity is a risk factor for breast cancer is confirmed. Our study and other studies show that obesity is a risk factor for breast cancer. And with a weight loss intervention for breast cancer can be prevented in the future.

Keywords: breast cancer, review study, obesity, overweight

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Authors: Corina Muscurel, Irina Stoian, Laura Gaman, Valeriu Atanasiu

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Chronic inflammation predisposes cells to neoplastic transformation and is associated with angiogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) give rise to anti-inflammatory metabolites and decrease some inflammatory cytokines. The aim of the study was to analyze the effect of n-3 PUFAs intake on patients with tumors in early-stage (without regional or distant metastasis). There were two groups of patients: one group with colon tumors and one group with lung tumors. All patients took for 60 days daily supplements from fish-oil containing 600 mg eicosapentaenoic acid and 400 mg docosahexaenoic acid. The plasma markers were evaluated before and after PUFAs intake: ceruloplasmin (using p-phenylenediamine oxidase method), plasma total thiol groups (using dithiobis-nitrobenzoic acid method) and CEA (carcinoembryonic antigen using electrochemiluminescent immunoassay). The results reflect ceruloplasmin decrease (p < 0.05), plasma total thiol groups increase (not statistically significant) and CEA decrease (p < 0.05) after n-3 PUFAs intake. Conclusions: n-3 PUFAs intake is favorable in premalignant lesions or in early tumor stage and dietary fish-oil has anti-inflammatory effects and can contribute to reduce cancer progression.

Keywords: cancer, fish-oil, inflammation, n-3 polyunsaturated fatty acids

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Authors: Rini Jarial, Puranjan Mishra, Lakhveer Singh, Sveta Thakur, A. W. Zularisam, Mimi Sakinah

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The aim of the present study was to assess the biological properties of Camellia sinensis and to identify its functional compounds. The methanolic leaves-extract (MLE) of commercial green tea (Camellia sinensis) was assessed for anti-bacterial activities by measuring inhibition zones against a panel of pathogenic bacterial strains using agar diffusion method. The flavonoid (5.0 to 8.0 mg/ml) and protein content (10 to 15 mg/ml) of the MLE were recorded. MLE at a concentration of 25 μg/ml showed marked anti-bacterial activity against all bacterial strains (11-30 mm zone of inhibition) and was maximum against Staphylococcus aureus (30 mm). The MLE of Camellia sinensis had the best MIC values of 2.25 and 0.56 mg/ml against S. aureus and Enterobacter sp., respectively. The MLE also possessed good anti-lipolytic activity (65%) against a Porcine pancreatic lipase (PPL) and cholesterol oxidase inhibition (79%). The present study provided strong experimental evidences that the MLE of Camellia sinensis is not only a potent source of natural anti-oxidants and anti-bacterial activity but also possesses efficient cholesterol degradation and anti-lipolytic activities that might be beneficial in the body weight management.

Keywords: anti-oxidant, anti-bacterial activity, anti-lipolytic activity, Camellia sinensis, phyto-chemicals

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Authors: Sachinkumar Patil, Sonali Patil, Shitalkumar Patil

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Nanoparticles played important role in the biomedicine. New advanced methods having great potential apllication in the diagnosis and therapy of cancer. Now a day’s magnetic nanoparticles used in cancer therapy. Cancer is the major disease causes death. Magnetic nanoparticles show response to the magnetic field on the basis of this property they are used in cancer therapy. Cancer treated with hyperthermia by using magnetic nanoparticles it is unconventional but more safe and effective method. Magnetic nanoparticles prepared by using different innovative techniques that makes particles in uniform size and desired effect. Magnetic nanoparticles already used as contrast media in magnetic resonance imaging. A magnetic nanoparticle has been great potential application in cancer diagnosis and treatment as well as in gene therapy. In this review we will discuss the progress in cancer therapy based on magnetic nanoparticles, mainly including magnetic hyperthermia, synthesis and characterization of magnetic nanoparticles, mechanism of magnetic nanoparticles and application of magnetic nanoparticles.

Keywords: magnetic nanoparticles, synthesis, characterization, cancer therapy, hyperthermia, application

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Authors: Ikram Mohamed Eltayeb Elsiddig, Yacouba Amina Djamila, Amna El Hassan Hamad

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Hyperglycemia and diabetes have been treated with several medicinal plants for a long time, meanwhile reduce associated side effects than the synthetic ones. Therefore, the search for more effective and safer anti-diabetic agents derived from plants has become an interest area of active research. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol, and high blood pressure. The present study was carried out to investigate the anti-hyperglycemic effect of the extracts of A. sativum bulb growing in Sudan on glucose-loaded Wistar albino rats. A. sativum bulbs were collected from local vegetable market at Khourtoum/ Sudan in a fresh form, identified and authenticated by taxonomist, then dried, and extracted with solvents of increasing polarity: petroleum ether, chloroform, ethyl acetate and methanol by using Soxhlet apparatus. The effect of the extracts on glucose uptake was evaluated by using the isolated rats hemidiaphgrams after loading the fasting rats with glucose, and the anti-hyperglycemic effect was investigated on glucose-loaded Wistar albino rats. Their effects were compared to control rats administered with the vehicle and to a standard group administered with Metformin standard drug. The most active extract was analyzed chemically using GC-MS analysis compared to NIST library. The results showed significant anti-diabetic effect of extracts of A. sativum bulb growing in Sudan. Addition to the hypoglycemic activity of A. sativum extracts was found to be decreased with increase in the polarity of the extraction solvent; this may explain the less polarity of substance responsible for the activity and their concentration decreased with polarity increase. The petroleum ether extract possess anti-hyperglycemic activity more significant than the other extracts and the Metformin standard drug with p-value 0.000** of 400mg/kg at 1 hour, 2 hour and four hour; and p-value 0.019*, 0.015* and 0.010* of 200mg/kg at 1 hour, 2 hour and four hour respectively. The GC-MS analysis of petroleum ether extract, with highest anti -diabetes activity showed the presence of Methyl linolate (42.75%), Hexadecanoic acid, methyl ester (10.54%), Methyl α-linolenate (8.36%), Dotriacontane (6.83), Tetrapentacontane (6.33), Methyl 18-methylnonadecanoate (4.8), Phenol,2,2’-methylenebis[6-(1,1-dimethylethyl)-4-methyl] (3.25), Methyl 20-methyl-heneicosanoate (2.70), Pentatriacontane (2.13) and many other minor compounds. The most of these compounds are well known for their anti-diabetic activity. The study concluded that A. sativum bulbs extracts were found to enhanced the reuptake of glucose in the isolated rat hemidiaphragm and have antihyperglycemic effect when evaluated on glucose-loaded albino rats with petroleum ether extract activity more significant than the Metformin standard drug.

Keywords: Allium, anti-hyperglycemic, bulbs, sativum

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Authors: Sharjeel Abid, Tanveer Hussain, Ahsan Nazir, Abdul Zahir, Nabyl Khenoussi

Abstract:

Localized application of drug has various advantages and fewer side effects as compared with other methods. Burn patients suffer from swear pain and the major aspects that are considered for burn victims include pain and infection management. Nano-fibers (NFs) loaded with drug, applied on local wound area, can solve these problems. Therefore, this study dealt with the fabrication of drug loaded NFs for better pain management. Two layers of NFs were fabricated with different drugs. Contact layer was loaded with Gabapentin (a nerve painkiller) and the second layer with acetaminophen. The fabricated dressing was characterized using scanning electron microscope, Fourier Transform Infrared Spectroscopy, X-Ray Diffraction and UV-Vis Spectroscopy. The double layered based NFs dressing was designed to have both initial burst release followed by slow release to cope with pain for two days. The fabricated nanofibers showed diameter < 300 nm. The liquid absorption capacity of the NFs was also checked to deal with the exudate. The fabricated double layered dressing with dual drug loading and release showed promising results that could be used for dealing pain in burn victims. It was observed that by the addition of drug, the size of nanofibers was reduced, on the other hand, the crystallinity %age was increased, and liquid absorption decreased. The combination of fast nerve pain killer release followed by slow release of non-steroidal anti-inflammatory drug could be a good tool to reduce pain in a more secure manner with fewer side effects.

Keywords: pain management, burn wounds, nano-fibers, controlled drug release

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Authors: Ramandeep Kaur, Gurjit Singh Bhathal

Abstract:

Cancer diagnosis is very difficult task. Magnetic resonance imaging (MRI) scan is used to produce image of any part of the body and provides an efficient way for diagnosis of cancer or tumor. In existing method, fuzzy clustering mean (FCM) is used for the diagnosis of the tumor. In the proposed method FCM is used to diagnose the cancer of the foot. FCM finds the centroids of the clusters of the foot cancer obtained from MRI images. FCM thresholding result shows the extract region of the cancer. Morphological operations are applied to get extracted region of cancer.

Keywords: magnetic resonance imaging (MRI), fuzzy C mean clustering, segmentation, morphological operations

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Authors: Sudhir Kumar, V. R. Sinha

Abstract:

Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: S. S. Patil, B. U. Janugade, S. V. Patil

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Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery thus increasing patient compliance. These systems are designed according to the circadian rhythm of the body. Chronotherapeutics is the discipline concerned with the delivery of drugs according to inherent activities of a disease over a certain period of time. It is becoming increasingly more evident that the specific time that patients take their medication may be even more significant than was recognized in the past. The tradition of prescribing medication at evenly spaced time intervals throughout the day, in an attempt to maintain constant drug levels throughout a 24-hour period, may be changing as researcher’s report that some medications may work better if their administration is coordinated with day-night patterns and biological rhythms. The potential benefits of chronotherapeutics have been demonstrated in the management of a number of diseases. In particular, there is a great deal of interest in how chronotherapy can particularly benefit patients suffering from allergic rhinitis, rheumatoid arthritis and related disorders, asthma, cancer, cardiovascular diseases, and peptic ulcer disease.

Keywords: pulsatile drug delivery, chronotherapeutics, circadian rhythm, asthma, chronobiology

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Authors: Farzad Jalilian, Mehdi Mirzaei Alavijeh, Fazel Zinat Motlagh

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Social support is an important benchmark of health for people in avoidance conditions. The main goal of this study was to determine the three kinds of social support (family, friend and other significant) to drug cessation among male addicts, in Kermanshah, the west of Iran. This cross-sectional study was conducted among 132 addicts, randomly selected to participate voluntarily in the study. Data were collected from conduct interviews based on standard questionnaire and analyzed by using SPSS-18 at 95% significance level. The majority of addicts were young (Mean: 30.4 years), and with little education. Opium (36.4%), Crack (21.2%), and Methamphetamine (12.9%) were the predominant drugs. Inabilities to reject the offer and having addict friends are the most often reasons for drug usage. Almost, 18.9% reported history of drug injection. 43.2% of the participants already did drug cessation at least once. Logistic regression showed the family support (OR = 1.110), age (OR = 1.106) and drug use initiation age (OR = 0.918) was predicting drug cessation. Our result showed; family support is a more important effect among types of social support in drug cessation. It seems that providing educational program to addict’s families for more support of patients at drug cessation can be beneficial.

Keywords: drug cessation, family support, drug use, initiation age

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Authors: Temesgen Geremew

Abstract:

Functionalized nanoparticles have emerged as a revolutionary platform for drug delivery, offering significant advantages over traditional methods. By strategically modifying their surface properties, these nanoparticles can be designed to target specific tissues and cells, significantly reducing off-target effects and enhancing therapeutic efficacy. This targeted approach allows for lower drug doses, minimizing systemic exposure and potential side effects. Additionally, functionalization enables controlled release of the encapsulated drug, improving drug stability and reducing the frequency of administration, leading to improved patient compliance. This work explores the immense potential of functionalized nanoparticles in revolutionizing drug delivery, addressing limitations associated with conventional therapies and paving the way for personalized medicine with precise and targeted treatment strategies.

Keywords: nanoparticles, drug, nanomaterials, applications

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Authors: Umme Hani, Mohammed Rahmatulla, Mohammed Ghazwani, Ali Alqahtani, Yahya Alhamhoom

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Background and introduction: Neratinib is a potent anticancer drug used for the treatment of breast cancer. It is poorly soluble at higher pH, which tends to minimize the therapeutic effects in the lower gastrointestinal tract (GIT) leading to poor bioavailability. An attempt has been made to prepare and develop a gastro-retentive system of Neratinib to improve the drug bioavailability in the GIT by enhancing the gastric retention time. Materials and methods: In the present study a three-factor at two-level (23) factorial design based optimization was used to inspect the effects of three independent variables (factors) such as sodium alginate (A), sodium bicarbonate (B) and sodium citrate (C) on the dependent variables like in vitro gelation, in vitro floating, water uptake and percentage drug release. Results: All the formulations showed pH in the range 6.7 ±0.25 to 7.4 ±0.24, percentage drug content was observed to be 96.3±0.27 to 99.5 ±0.28%, in vitro gelation observed as gelation immediate remains for an extended period. Percentage of water uptake was in the range between 9.01±0.15 to 31.01±0.25%, floating lag time was estimated form 7±0.39 to 57±0.36 sec. F4 and F5 showed floating even after 12hrs. All formulations showed a release of around 90% drug release within 12hr. It was observed that the selected independent variables affect the dependent variables. Conclusion: The developed system may be a promising and alternative approach to augment gastric retention of drugs and enhances the therapeutic efficacy of the drug.

Keywords: neratinib, 2³ factorial design, sodium alginate, floating, in situ gelling system

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Authors: Angalabiri-Owei E. Bekekeme, Brambaifa Nelson

Abstract:

In view of the peculiar environment of the Niger Delta, access to modern health care is limited, hence the inhabitants especially those in the swampy areas resorts to sourcing for alternatives cure for their ailments using plants commonly found in this area without scientific evaluation. Rhizophora racemosa, G. F. Meyer (Rhizophoraceae) is the most abundant mangrove plant in the Niger Delta Area of Nigeria. The plant has been observed to be used for relief of a toothache and dysmenorrhoea among some Ijaw communities in the region. This work has revealed the likely potential of the plant in drug discovery and development. The crude methanol extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) were tested for analgesic effect using fresh egg albumin induced inflammatory pain and Randall–Sellito method to assess the pain threshold. The anti-inflammatory effect was also evaluated with the extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) using acute inflammatory model; fresh egg albumin induced paw oedema and assessed using Plethysmometer in rats. The methanol extracts 300 mg/kg and 600 mg/kg exhibited a significant (P < 0.001) and dose-dependent analgesic activity compared with the negative control and a standard drug diclofenac using ANOVA with Least Significant Difference post hoc test as evidenced by increased pain threshold. Also, the extract significantly (P < 0.001) reduced the rat paw oedema induced by the sub plantar injection of fresh egg albumin when compared with the negative control and a standard diclofenac using above statistical methods. This study revealed that the plant possesses analgesic and anti-inflammatory activities hence provide scientific bases for use as medicine.

Keywords: analgesic, anti-inflammatory, plethysmometer, Rhizophora racemosa

Procedia PDF Downloads 320