Recent developments in the synthesis and anti-cancer activity of acridine and xanthine-based molecules

Cancer is the uncontrolled growth and development of abnormal cells which is a major cause of death in both advanced and emerging countries. Although currently chemotherapy is most broadly used among an extensive range of anti-cancer therapies, it includes many demerits, such as highly toxic, side-effects, expensive and partial lack of targeting specificity. So the design and synthesis of new molecules that perform specifically on target proteins in tumor cells is a focus of contemporary research. So many researchers aim for new drugs that will be more efficient, more selective, and less toxic. Because of the interesting structures and significant biological profile, naturally occurring acridines and xanthines as well as their analogues have attracted considerable interest in researchers and technologists. Natural and synthetic acridine derivatives form a significant category of heterocycles having nitrogen that is of considerable interest for organic chemists and biological communities due to their attractive anti-cancer activity. Another important class of therapeutic agents with diverse biological properties including cytotoxic effects is xanthine derivatives which are collectively called xanthines (a group of alkaloids). Among many significant molecules based on the structure of the purine, there is a group of natural xanthines, involving theobromine, caffeine, and theophylline and analogues of xanthine display anti-cancer activity. Hence the present chapter wishes to concentrate the attention on the synthesis and anti-cancer activity of acridine and xanthine-based compounds brilliantly.

Oral Hygiene Considerations in Adult Patients with Leukemia during a Cycle of Chemotherapy

The oral cavity is the place where the first symptoms of systemic diseases may appear. Leukemia is the malignancy of the hematopoietic system in which abnormal leukocytes are produced in the bone marrow and these cells spread to the peripheral blood. It is classified clinically on the basis of the duration and nature of the disease (acute or chronic), the type of cell involved (myeloid, lymphoid, or monocytes), and a rise in the number of abnormal cells in the blood. The study aimed to assess and compare the oral hygiene and periodontium status based on the indices in leukemic patients before and after one cycle of chemotherapy and whether the therapy had an impact on the change of these parameters. Dental indices used in clinical diagnostics were calculated: API (approximal plaque index), SBI (sulcus bleeding index), and CPI (community periodontal index). The research project was conducted at the Clinic of Hematooncology and Bone Marrow Transplantation of the Independent Public Clinical Hospital No. 1 in Lublin. The target population consisted of 102 adults with leukemia who were over 18 years of age. The time since diagnosis of the disease ranged from 1 to 10 years. The data were evaluated in the Statistica 12 software with the respective tests. In the majority of patients, both before and after chemotherapy, improper oral hygiene and severe generalized periodontitis were confirmed. The cycle of chemotherapy that was used did not correlate with the change of patients’ oral hygiene and periodontium state. Unsatisfactory oral hygiene and periodontal health has to be addressed with urgent dental treatment to avoid systemic complications in leukemic patients.

Preoperative AI-Driven Fluorescence Diagnosis of Non-Melanoma Skin Cancer

The diagnosis and treatment of non-melanoma skin cancer remain urgent problems. Histological examination of biopsy material—the gold standard of diagnosis—is an invasive procedure that requires a certain amount of time to perform. The ability to detect abnormal cells using fluorescence spectroscopy (FS) has been shown in many studies. This technique is rapidly expanding due to its safety, relative cost-effectiveness, and efficiency. However, skin lesion FS-based diagnosis is challenging due to a number of single overlapping spectra emitted by fluorescent molecules, making it difficult to distinguish changes in the overall spectrum and the molecular basis for it. We applied deep learning (DL) algorithms to quantitatively assess the ability of FS to differentiate between pathologies and normal skin. A total of 137 patients with various forms of primary and recurrent basal cell carcinoma (BCC) were observed by a multispectral laser-based device with a built-in neural network (NN) “DSL-1”. We measured the fluorescence spectra of suspected non-melanoma skin cancers and compared them with “normal” skin spectra. These spectra were input into DL algorithms to determine whether the skin is normal, pigmented normal, benign, or BCC. The preoperative differential AI-driven fluorescence diagnosis method correctly predicted the BCC lesions. We obtained an average sensitivity of 62% and average specificity of 83% in our experiments. Thus, the presented “DSL-1” diagnostic device can be a viable tool for the real-time diagnosis and guidance of non-melanoma skin cancer resection.

Dual Role of p73 in Cancer Microenvironment and DNA Damage Response

Understanding the mechanisms that regulate cancer progression is pivotal for the development of new therapies. Although p53 is mutated in half of human cancers, its family member p73 is not. At the same time, isoforms of p73 are often overexpressed in cancers and p73 can overtake many p53 functions to kill abnormal cells. According to the latest studies, while p73 represses epithelial–mesenchymal transition and metastasis, it can also promote tumour growth by modulating crosstalk between cancer and immune cells in the tumor microenvironment, M2 macrophage polarisation, Th2 T-cell differentiation, and angiogenesis. Thus, p73 likely plays a dual role as a tumor suppressor by regulating apoptosis in response to genotoxic stress or as an oncoprotein by promoting the immunosuppressive environment and immune cell differentiation.

In silico Molecular Docking Analysis of Imatinib to Target the Marker Proteins of Breast Cancer

Cancer is an uncontrolled over growth of abnormal cells elsewhere in the body. It is the second leading cause of death globally due to non communicable disease. Among the various types of cancers, the incidence of breast cancer is next to lung cancer. The most commonly used drugs to treat breast cancer are namely, Anastrozole, Arimidex, Letrozol, Imatinib, Tamoxifen, Raloxifene, Toremifene and so on. The hope is to establish the specificity of the drug Imatinib towards the selective potential breast cancers such as mammalian target of rapamycin, (mTOR), human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), poly (ADP-Ribose) polymerase (PARP) and phosphoprotein 53 (p53). To identify the promising target, the Schrodinger software was utilized for the study. The study helped to evaluate the pharmacokinetic properties and binding efficiency of Imatinib towards the breast cancer proteins. The results of study showed that the Imatinib exhibited better binding affinities to mTOR and HER2 as compared to ER, PARP and P53 proteins. The present study will be more useful to rationalize the anticancer therapy based on the expression levels of the target protein in the cancer microenvironment.

Cytotoxicity of Mangrove Leaves (Rhizophora) Ethanolic Extract on Cancer Cells

Cancer is a disease that can attack any part of the body when the abnormal cells begin to grow uncontrollably beyond the limit, then attack the connected parts of the body and spread to other organs. The mangrove (Rhizophora) is a herbal plant that can be used as a treatment for various diseases, one of which is cancer. The mangrove (Rhizophora) plant contains phytochemicals ranging from fruit, seeds, leaves and roots. This review article aims to examine the cytotoxicity effects of mangrove (Rhizophora) plants on cancer cells. The library sources in this article review use the Google Scholar and PubMed databases. The inclusion criteria used were articles containing the cytotoxic test of mangrove (Rhizophora) with the last 10 years of publication (2011-2020), original research, there were results of anticancer activity in the form of IC50 and research using mangrove (Rhizophora). plant extracts. The exclusion criteria used were articles that did not contain a full text, used plants with different genus, did not have an IC50 value and were not original research. From the journals that have been analyzed, it can be said that the extract of the mangrove (Rhizophora) plant can be developed for cancer treatment. The mangrove (Rhizophora) plant has cytotoxic activity because it contains active compounds in the form of phenolic, flavonoids and terpenoids. Based on the results of the cytotoxic test of mangrove (Rhizophora) extract, the plant parts that have the strongest cytotoxic effect are fruit.

1-(4-Methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one: A Diphenyl Chalcone Derivative with Potent Antitumor Activity Via Up-Regulation of p21 Gene

Background and Aim: Cancer is a disease of complex aetiology and is characterised by uncontrolled growth of abnormal cells. It is a major worldwide health problem. Many natural and synthetic chalcone or their derivatives showed anticancer activities. The aim of the present study is to evaluate the anticancer activity of novel chalcone derivatives and also to establish possible mechanism of action. Materials and Methods: A series of chalcones 3-(3-phenoxyphenyl)-1-phenylprop-2-en-1-one (2a); 1-(4-chlorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one (2b); 1-(4-fluorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one (2c); 1-(4-Nitro-phenyl)-3-(3-phenoxy-phenyl)prop-2-en-1-one (2d); 1-(4-methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one(2e) were evaluated for the cytotoxic activity both in vitro and in vivo. The in vivo antitumor activity of these compounds was estimated on Daltons Ascites Lymphoma induced solid tumor model. The effect of promising compound was further analysed by flow cytometer and RT- PCR analysis. Results and Conclusion: 1-(4-methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one and 1-(4- chlorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one was showed in vitro cytotoxic activity, DNA damage and antiproliferative activity. DLA induced solid tumor model suggested that 1-(4-methoxyphenyl)-3-(3- phenoxy phenyl) prop-2-en-1-one significantly reduced the tumor volume, increase the percentage tumor inhibition and reverse the haematological parameters. Flow cytometry analysis concluded that the compound induces cell cycle arrest at G0/G1 phase due to the over expression of p21. 1-(4-methoxyphenyl)-3-(3- phenoxy phenyl) prop-2-en-1-one may be a potential agent for cancer treatment.

The Interactions between Nanoparticles and the Innate Immune System from a Nanotechnologist Perspective

The immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, the immune system can detect molecular and cellular structures with a spatial resolution of a few nm, which allows for detecting molecular patterns expressed in a great variety of pathogens, including viral and bacterial proteins and bacterial nucleic acid sequences. Such patterns are also expressed in abnormal cells. In this context, it is expected that nanostructured materials in the size range of proteins, protein aggregates, and viruses with different molecular coatings can engage in a sophisticated interaction with the immune system. Nanoparticles can be recognized or passed undetected by the immune system. Once detected, they can be tolerated or induce defensive (inflammatory) or anti-inflammatory responses. This paper describes the different modes of interaction between nanoparticles, especially inorganic nanoparticles, and the immune system, especially the innate immune system. This perspective should help to propose a set of selection rules for nanosafety-by-design and medical nanoparticle design.

Inefficient exploitation of accessory receptors reduces the sensitivity of chimeric antigen receptors.

Chimeric antigen receptors (CARs) can re-direct T cells to target abnormal cells but their activity is limited by a profound defect in antigen sensitivity, the source of which remains unclear. Here, we show that CARs have a > 100-fold lower antigen sensitivity compared to the TCR when antigen is presented on antigen-presenting-cells, but nearly identical sensitivity when antigen is presented as purified protein in isolation. Given that the TCR uses other, accessory, receptors to achieve high sensitivity, we screened prominent accessory receptors by presenting their purified ligands together with antigen. We found that ligating the adhesion receptor CD2 or LFA-1 improved antigen sensitivity for the TCR by > 100-fold, whereas for CARs the improvement was < 10-fold. We reproduced these findings using target cells where the CD2 and/or LFA-1 interaction were abrogated. Sensitivity can be partially restored by fusing the CAR variable domains to the TCR CD3ϵ subunit (also known as a TRuC) and fully restored when exchanging the TCRαβ variable domains for those of the CAR (also known as a STAR). Our study localises the defect in CAR sensitivity to inefficient use of accessory receptors and suggests approaches to increase sensitivity.

Fulfillment Of Activity Daily Living (ADL) In Breast Cancer Patients Undergoing Chemotherapy At Haji Adam Malik Hospital Medan

Breast cancer arises as a result of abnormal cells forming in the breast at an uncontrolled and irregular rate. There are several types of treatment for breast cancer patients and one of them is chemotherapy. The frequency of chemotherapy can cause several effects that can worsen the patient's functional status. Functional status is an ability to perform daily tasks that include work, self-care, and maintenance of family or social roles. This study aims to identify ADL compliance in breast cancer patients undergoing chemotherapy. This study used a descriptive design, the sample was taken using a non-probability sampling method, namely accidental sampling and the instrument used was a questionnaire compiled using a Likert scale. The reliability test of this study used a Cronbach Alpha of 0.917. Data collection was carried out from September 2015 to August 2016. The description of ADL fulfillment of breast cancer patients undergoing chemotherapy was described to determine the frequency and percentage. The results showed that the fulfillment of ADL in breast cancer patients undergoing chemotherapy was independent (20 people, 54.1%), partial dependence (10 people, 27%), and total dependence (7 people, 18.9%). It can be concluded that most breast cancer patients undergoing chemotherapy can carry out their Activity Daily Living with an independent level of ability. The description of ADL fulfillment of breast cancer patients undergoing chemotherapy is described to determine the frequency and percentage. The results showed that the fulfillment of ADL in breast cancer patients undergoing chemotherapy was independent (20 people, 54.1%), partial dependence (10 people, 27%), and total dependence (7 people, 18.9%). It can be concluded that most breast cancer patients undergoing chemotherapy can carry out their Activity Daily Living with an independent level of ability. The description of ADL fulfillment of breast cancer patients undergoing chemotherapy is described to determine the frequency and percentage. The results showed that the fulfillment of ADL in breast cancer patients undergoing chemotherapy was independent (20 people, 54.1%), partial dependence (10 people, 27%), and total dependence (7 people, 18.9%). It can be concluded that most breast cancer patients undergoing chemotherapy can carry out their Activity Daily Living with an independent level of ability.