Search results for: cancer cell type

Authors: Mutaz Dwairy

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Solid tumors have high interstitial fluid pressure (IFP), high mechanical stress, and low oxygen levels. Solid stresses may induce apoptosis, stimulate the invasiveness and metastasis of cancer cells, and lower their proliferation rate, while oxygen concentration may affect the response of cancer cells to treatment. Although tumors grow in a nonhomogeneous environment, many existing theoretical models assume homogeneous growth and tissue has uniform mechanical properties. For example, the brain consists of three primary materials: white matter, gray matter, and cerebrospinal fluid (CSF). Therefore, tissue inhomogeneity should be considered in the analysis. This study established a physical model based on convection-diffusion equations and continuum mechanics principles. The model considers the geometrical inhomogeneity of the brain by including the three different matters in the analysis: white matter, gray matter, and CSF. The model also considers fluid-solid interaction and explicitly describes the effect of mechanical factors, e.g., solid stresses and IFP, chemical factors, e.g., oxygen concentration, and biological factors, e.g., cancer cell concentration, on growing tumors. In this article, we applied the model on a brain tumor positioned within the white matter, considering the brain inhomogeneity to estimate solid stresses, IFP, the cancer cell concentration, oxygen concentration, and the deformation of the tissues within the neoplasm and the surrounding. Tumor size was estimated at different time points. This model might be clinically crucial for cancer detection and treatment planning by measuring mechanical stresses, IFP, and oxygen levels in the tissue.

Keywords: biomechanical model, interstitial fluid pressure, solid stress, tumor microenvironment

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Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

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Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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Authors: C. Panebianco, K. Adamberg, S. Adamberg, C. Saracino, M. Jaagura, K. Kolk, A. Di Chio, P. Graziano, R. Vilu, V. Pazienza

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Background/Aims: Despite recent advances in treatment options, a modest impact on the outcome of the pancreatic cancer (PC) is observed so far. Short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. However, diseased people may refuse to follow the fasting regimen and fasting may worsen the weight loss often occurring in cancer patients. Therefore, alternative approaches are needed. The aim of this study was to assess the effect of Engineered Low glycemic food ELGIF mimicking diet on growth of cancer cell lines in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in control and ELGIF mimicking diet culturing condition to evaluate the tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to ELGIF to assess the tumor volume and weight as compared to mice fed with control diet. Results: Pancreatic cancer cells cultured in ELGIF mimicking medium showed decreased levels of proliferation as compared to those cultured in the standard medium. Consistently, xenograft pancreatic cancer mice subjected to ELGIF diet displayed a significant decrease in tumor growth. Conclusion: A positive effect of ELGIF diet on proliferation in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

Keywords: functional food, microbiota, mouse model, pancreatic cancer

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Authors: Aliya Sekenova, Vyacheslav Ogay

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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

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Authors: Rahul Shrivastava, Manish Tripathi, Mohmmad Yasir, Shailesh Singh

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Life style changes and depletion in atmospheric ozone layer in recent decades lead to increase in skin cancer including both melanoma and nonmelanomas. Natural products which were obtained from different plant species have the potential of anti skin cancer activity. In regard of this, present study focuses the potential effect of Glycosmis pentaphylla against anti skin cancer activity. Different Phytochemical constituents which were present in the roots of Glycosmis pentaphylla were identified and were used as ligands after sketching of their structures with the help of ACD/Chemsketch. These ligands are screened for their anticancer potential with proteins which are involved in skin cancer effects with the help of pyrx software. After performing docking studies, results reveal that Noracronycine secondary metabolite of Glycosmis pentaphylla shows strong affinity of their binding energy with Ribosomal S6 Kinase 2 (2QR8) protein. Ribosomal S6 Kinase 2 (2QR8) has an important role in the cell proliferation and transformation mediated through by N-terminal kinase domain and was induced by the tumour promoters such as epidermal growth factor. It also plays a key role in the neoplastic transformation of human skin cells and in skin cancer growth. Noracronycine interact with THR-493 and MET-496 residue of Ribosomal S6 Kinase 2 protein with binding energy ΔG = -8.68 kcal/mole. Thus on the basis of this study we can say that Noracronycine which present in roots of Glycosmis pentaphylla can be used as lead compound against skin cancer.

Keywords: glycosmis pentaphylla, pyrx, ribosomal s6 kinase, skin cancer

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Authors: N. Zarghami, M. Mohammadinejad, A. Akbarzadeh, Y. Pilehvar-Soltanahmadi, F. Zarghami

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Breast cancer is known to be the most common cancer in women. Cyclin D1 is a proto-oncogene and over expression of cyclin D1 is directly associated with tumorgenesis. Cyclin D1 is overexpressed in more than 50% of breast cancer cases. Curcumin is derived from turmeric (curcuma longa) and chrysin is a component that could be extracted from many plants and honey. These two plants derived compounds are believed to assist in inhibition of the cancer cells growth and reducing cyclin D1 expression. In this work, the hypothesis is to combine curcumin and chrysin in order to analyze the potential synergistic effect in inhibition of cell proliferation and down regulation of cyclin D1. In addition, use of PLGA-PEG to improve bioavailability of pure curcumin and chrysin, while reinforcing the potential effect of this combination. PLGA-PEG nanoparticles were synthesized and characterized with FT-IR and 1HNMR methods. Although morphological features were analyzed by SEM. Afterward curcumin and chrysin were encapsulated with synthesized PLGA-PEG and MTT-assay was performed to measure cytotoxicity effect of these plant constitutes. T-47D cells were treated with proper concentration of these constituents and Real-time PCR was carried out to evaluate cyclin D1 expression levels. Curcumin, chrysin and combination of curcumin –chrysin in intact and nano-capsulated form affected T-47D cells in time and dose dependent manner and the combination of these compounds had synergistic effects. Real-time PCR results, revealed that curcumin, chrysin and combination of curcumin-chrysin in pure and encapsulated form inhibited cyclin D1 expression. Compared to pure components, different concentrations of nano-curcumin, nano chrysin and nano-combination caused further decline in cyclin D12 expression by 5-11%, 8-22% and 6-18% respectively. Our results demonstrated that, combination of chrysin-curcumin had synergistic effect and nano capsulated form of this component had grater inhibition on cyclin D1 expression.

Keywords: breast cancer, cyclin D1, curcumin, chrysin, nanoparticles

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Authors: Bahadir Batar, Elif Serdal, Berna Erdal, Hasan Ogul

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Micro-ribonucleic acids (miRNAs) are small short non-coding ribonucleic acid molecules about 22 nucleotides long. miRNAs play a key role in response to chemotherapeutic agents. WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor protein. Loss or reduction of Wwox protein is observed in many breast cancer cases. WWOX protein deficiency is increased in triple-negative breast cancer (TNBC). TNBC is a heterogeneous, highly aggressive, and difficult to treat tumor type. WWOX loss contributes to resistance to cisplatin therapy in patients with TNBC. Here, the aim of the study was to investigate the potential role of miRNAs in cisplatin therapy resistance of WWOX-deficient TNBC cells. This was a cell culture study. miRNA expression profiling was analyzed by LightCycler 480 system. miRNA Set Enrichment Analysis tool was used to integrate experimental data with literature-based biological knowledge to infer a new hypothesis. Increased miR-182 and decreased miR-214 were significantly correlated with cisplatin resistance in WWOX-deficient TNBC cells. miR-182 and miR-214 may involve in cisplatin resistance of WWOX-deficient TNBC cells by deregulating the DNA repair, apoptosis, or protein kinase B signaling pathways. These data highlight the mechanism by which WWOX regulates cisplatin resistance of TNBC and the potential use of WWOX as a predictor biomarker for cisplatin resistance.

Keywords: cisplatin, microRNA, triple-negative breast cancer, WWOX

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Authors: Imran Ali

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General chemotherapy for cancer treatment has many side and toxic effects. A new approach of targeting nano anti-cancer drug is under development stage and only few drugs are available in the market today. The unique features of these drugs are targeted action on cancer cells only without any side effect. Sometimes, these are called magic drugs. The important molecules used for nano anti-cancer drugs are cisplatin, carboplatin, bleomycin, 5-fluorouracil, doxorubicin, dactinomycin, 6-mercaptopurine, paclitaxel, topotecan, vinblastin and etoposide etc. The most commonly used materials for preparing nano particles carriers are dendrimers, polymeric, liposomal, micelles inorganic, organic etc. The proposed lecture will comprise the-of-art of nano drugs in cancer chemo-therapy including preparation, types of drugs, mechanism, future perspectives etc.

Keywords: cancer, nano-anti-cancer drugs, chemo-therapy, mechanism of action, future perspectives

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Authors: H. Al-Awaisi, M. H. Al-Azri, S. Al-Rasbi, M. Al-Moundhri

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Breast cancer is the most common cancer among females worldwide. It is also the most common cancer among females in Oman with 100 new breast cancer cases diagnosed every year. It has been found that breast cancer have a devastating effect on women’s life. Women diagnosed with breast cancer might develop negative attitudes towards the illness and their bodies. They might also suffer from psychological ailments such as depression. Despite the evidence on the impact of breast cancer diagnosis on women, there was no study found to explore the impact of breast cancer diagnosis among women in Oman. A phenomenological qualitative study was conducted to explore the impact of breast cancer diagnosis on Omani women. Data was collected through semi-structured individual interviews with 11 Omani women diagnosed with breast cancer. Interviews were transcribed verbatim and data were analyzed thematically. From the data, there are four main themes identified in relation to the impact of cancer diagnosis on Omani women. These are 'shock and disbelieve', 'a death sentence', “uncertain future” and “social stigma”. At the time of interviews, all participants had advanced breast cancer with some participants having metastatic disease. The impact of the word “cancer” had a profound and catastrophic effect on the women and their close relatives. In conclusion, breast cancer diagnosis was shocking and mainly perceived as a death sentence by Omani women with uncertain future and social stigma. Regardless of age, maternal status and education level, it is evident that Omani women participated in this study lacked awareness about breast cancer diagnosis, treatment and prognosis.

Keywords: breast cancer, coping, diagnosis, Oman, women

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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Authors: Fatemeh Zeinali Sehrig

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This study aimed to evaluate the expression of miR-299-3p, DNMT1, DNMT3A, and DNMT3B in breast cancer samples and investigate their diagnostic significance. Using the GSE40525 and GSE45666, the miR-299-3p expression level was studied in breast cancer tissues. Also, the expression levels of DNMT1, DNMT3A, and DNMT3B were investigated by analyzing GSE61725, GSE86374, and GSE37751 datasets. The target genes were studied in terms of biological processes of molecular functions and cellular components. Consistent with the in silico results, miR-299-3p expression was substantially decreased in breast cancer tissues, and the expression levels of DNMT1, DNMT3A, and DNMT3B were considerably upregulated in breast cancer samples. It was found that the expression levels of miR-299-3p and DNMT1, DNMT3A, and DNMT3B could be valuable diagnostic tools for detecting breast cancer. Also, miR-299-3p downregulation may play a role in DNMT1, DNMT3A, and DNMT3B upregulation in breast cancer.

Keywords: breast cancer, miR-299-3p, DNMTs, GEO database

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Authors: Mariola Głowacka

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Aim: The aim of this study was to present the assessment of dyspnea and anxiety in seniors staying in the hospice in the context of the nurse's tasks. Materials and methods: The presented research was carried out at the "Hospicjum Płockie" Association of St. Urszula Ledóchowska in Płock, in a stationary ward, for adults. The research group consisted of 100 people, women, and men. In the study described in this paper, the method of diagnostic survey, the method of estimation and analysis of patient records were used, and the research tools were the numerical scale of the NRS assessment, the modified Borg scale to assess dyspnea, the Trait Anxiety scale to test the intensity of anxiety and the sociodemographic assessment of the respondent. Results: Among the patients, the greatest number were people without dyspnoea (38 people) and with average levels of dyspnoea (26 people). People with lung cancer had a higher level of breathlessness than people with other cancers. Half of the patients included in the study felt anxiety at a low level. On average, men had a higher level of anxiety than women. Conclusion: 1) Patients staying in the hospice require comprehensive nursing care due to the underlying disease, comorbidities, and a wide range of medications taken, which aggravate the feeling of dyspnea and anxiety. 2) The study showed that in patients staying in the hospice, the level of dyspnea was of varying severity. The greatest number of people were without dyspnea (38) and patients with a low level of dyspnea (34). There were 12 people experiencing an average level of dyspnea and a high level of dyspnea 15. 3) The main factor influencing the severity of dyspnea in patients was the location of cancer. There was no significant relationship between the intensity of dyspnea and the age, gender of the patient, and time from diagnosis. 4) The study showed that in patients staying in the hospice, the level of anxiety was of varying severity. Most people experience a low level of anxiety (51). There were 16 people with a high level of anxiety, while there were 33 people experiencing anxiety at an average level. 5) The patient's gender was the main factor influencing the increase in anxiety intensity. Men had higher levels of anxiety than women. There was no significant correlation between the intensity of anxiety and the age of the respondents, as well as the type of cancer and time since diagnosis. 6) The intensity of dyspnea depended on the type of cancer the subjects had. People with lung cancer had a higher level of breathlessness than those with breast cancer and bowel cancer. It was not found that the anxiety increased depending on the type of cancer and comorbidities of the examined person.

Keywords: cancer, shortness of breath, anxiety, senior, hospice

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Authors: Harika Atmaca, Emir Bozkurt, Latife Merve Oktay, Selim Uzunoglu, Ruchan Uslu, Burçak Karaca

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Microarrays have been developed for highly parallel enzyme-linked immunosorbent assay (ELISA) applications. The most common protein arrays are produced by using multiple monoclonal antibodies, since they are robust molecules which can be easily handled and immobilized by standard procedures without loss of activity. Protein expression profiling with protein array technology allows simultaneous analysis of the protein expression pattern of a large number of proteins. Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate, Ecteinascidia turbinata, has been shown to have antitumor effects. Here, we used a novel proteomic approach to explore the mechanism of action of trabectedin in prostate cancer cell line PC-3 by apoptosis antibody microarray. XTT cell proliferation kit and Cell Death Detection Elisa Plus Kit (Roche) was used for measuring cytotoxicity and apoptosis. Human Apoptosis Protein Array (R&D Systems) which consists of 35 apoptosis related proteins was used to assess the omic protein expression pattern. Trabectedin induced cytotoxicity and apoptosis in prostate cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL R2/DR5, TNF R1/TNFRSF1A, FADD were significantly increased by 4.0-, 21.0-, 4.20- and 11.5-fold by trabectedin treatment in PC-3 cells. Moreover, mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, and Cleaved Caspase-3 expressions were induced by 2.68-, 2.07-, 2.8-, and 4.5-fold and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 3.5- and 5.2-fold in PC-3 cells. Proteomic (antibody microarray) analysis suggests that the mechanism of action of trabectedin may be exerted via the induction of both intrinsic and extrinsic apoptotic pathways. The antibody microarray platform can be utilised to explore the molecular mechanism of action of novel anticancer agents.

Keywords: trabectedin, prostate cancer, omic protein expression profile, apoptosis

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Authors: Mehrnaz Mostafavi

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Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

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Authors: T. Scattolin, E. Cavarzerani, F. Visentin, F. Rizzolio

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Organopalladium compounds have recently attracted attention for their high stability even under physiological conditions and, above all, for their remarkable in vitro cytotoxicity towards cisplatin-resistant cell lines. Among the organopalladium derivatives, those bearing at least one N-heterocyclic carbene ligand (NHC) and the Pd(II)-η³-allyl fragment have exhibited IC₅₀ values in the micro and sub-micromolar range towards several cancer cell lines in vitro and in some cases selectivity towards cancerous vs. non-tumorigenic cells. Herein, a selection of allyl and indenyl palladates were synthesized using a solvent-free method consisting of grinding the corresponding palladium precursors with different saturated and unsaturated azolium salts. All compounds have been fully characterized by NMR, XRD and elemental analyses. The intramolecular H, Cl interaction has been elucidated and quantified using the Voronoi Deformation Density scheme. Most of the complexes showed excellent cytotoxicity towards ovarian cancer cell lines, with I₅₀ values comparable to or even lower than cisplatin. Interestingly, the potent anticancer activity was also confirmed in a high-serous ovarian cancer (HGSOC) patient-derived tumoroid, with a clear superiority of this class of compounds over classical platinum-based agents. Finally, preliminary enzyme inhibition studies of the synthesized palladate complexes against the model TrxR show that the compounds have high activity comparable to or even higher than auranofin and classical Au(I) NHC complexes. Based on such promising data, further in vitro and in vivo experiments and in-depth mechanistic studies are ongoing in our laboratories.

Keywords: anticancer activity, palladium complexes, organoids, indenyl and allyl ligands

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Authors: Khalid Al Saleh, Najlaa AlSayed

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Background: Palliative care is changing from just ‘end of life care’ to care delivered earlier in the disease course. Metanalysis showed that Palliative Performance Scale (PPS) is associated with increased length of survival. The Palliative Care Center (PCC) in Kuwait is the only stand-alone center in Eastern Mediterranean Region with a capacity of 92 beds. We compared clinical characteristics between patients referred from the Specialized Cancer Center and general hospitals in Kuwait to PCC. Method: A cross Sectional survey was conducted since the opening of PCC in January 2011 to June 2013. Patients’ data on demographics, type of the cancer, PPS score and referring hospital were collected and analyzed. Results: Total number of the patients was 142. Mean age was 61.05±14.79 years, 66 patients (47.1%) were males and 74 (52.9%) were females. The most common cancers in males were lung (n=18, 27.3%) followed by head and neck cancers (n=8, 12.1%) and brain tumors (n=7, 10.6%) while in females, the most common cancers were breast cancer (n=12, 16.7%) followed by ovarian cancer (n=10, 13.9%) and Cancer Colon (n=8, 11.1%). Patients with PPS score 30% were 27.9% (n=39), 40% in 40.7% (n=57), and 50% in 17.1% (n=24) respectively. Patients referred from the Specialized Cancer Center had significantly higher portion of patients with PPS score > 30% (73.4%, n=94), compared to patients coming from general hospitals (33.3%, n=4), P value= 0.007. Conclusion: There is significant difference in PPS scores between patients referred from the Specialized Cancer Center compared to patients referred from general hospitals. We encourage that all cancer patients should be treated in Specialized Cancer Centers and earlier involvement of Palliative Care Centers to achieve better survival. Training workshops are needed for health care professionals working in general hospitals to raise awareness about earlier referral of patients to palliative care services.

Keywords: palliative care, kuwait, performance scale differences, pps score, specialized hospitals

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Authors: Leander Van Neste, Kirk Wojno

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The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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Authors: Maria Cristina B. Cabanag, Elijinese Marie S. Culangen

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Pregnancy is a period in a woman's life wherein the body may undergo different physiological changes. These changes can be attributed to the interplay of hormones in the body but can mask a more sinister type of disease such as malignancy on rare occasions. Colorectal cancer (CRC) in pregnancy is an epidemiologically rare disease worldwide. To our knowledge, no available studies were reported in the Philippines at the time of this writing, posing a dilemma for its appropriate diagnosis and management. Signs and symptoms of colorectal malignancy may camouflage a normal pregnancy and, when overlooked, impedes an appropriate approach. This case of a 38-year-old elderly primigravid who presented with hematochezia on her 25th week of gestation. She was diagnosed with rectal adenocarcinoma later in pregnancy which warranted a predicament regarding her appropriate care and management. This paper explores the repertoire of the different diagnostic and treatment approaches to colorectal cancer in the second trimester of pregnancy, with the least possible maternal and fetal hazards.

Keywords: cancer in pregnancy, chemotherapy in pregnancy, colorectal cancer, hematochezia in pregnancy

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Authors: Azza T. Tahera, Eman M. Ahmeda, Nadia A. Khalila, Yassin M. Nissanb

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New 3-(pyridin-4-yl)-[1,2,4] triazolo [4,3-b] pyridazine derivatives 2a-i, 4a,b and 6a,b were designed, synthesized and evaluated as cytotoxic agents. All compounds were investigated for their in vitro cytotoxicity at a single dose 10-5M concentration towards 60 cancer cell lines according to USA NCI protocol. The preliminary screening results showed that the majority of tested compounds exhibited remarkable activity against SR (leukemia) cell panel. Molecular docking for all synthesized compounds was performed on the active site of c-Met kinase. The most active compounds, 2f and 4a were further evaluated at a seven dose level screening and their IC50 as a c-Met kinase inhibitors were determined in vitro.

Keywords: triazolopyridazines, pyridazines, cytotoxic activity, cell panel

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Authors: Shittu Ahmed Tajudeen

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This study examines student-teachers’ attitude and intention towards cell-phone use for learning. The study involves one hundred and ninety (190) trainee teachers in one of the Institutes of Education in Nigeria. The data of the study was collected through a questionnaire on a rating of seven point likert-type Scale. The data collected was used to test the hypothesized model of the study using Structural Equation Modeling approach. The finding of the study revealed that Perceived Usefulness (PU), Perceived Ease of Use (PEU), Subjective Norm (SN) and Attitude significantly influence students’ intention towards adoption of cell-phone for learning. The study showed that perceived ease of use stands to be the strongest predictor of cell-phone use. The model of the study exhibits a good-fit with the data and provides an explanation on student- teachers’ attitude and intention towards cell-phone for learning.

Keywords: cell-phone, adoption, structural equation modeling, technology acceptance model

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Authors: Latife Merve Oktay, Berrin Tugrul

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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.

Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer

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Authors: Lukman Ahmad Jamil, Heather M. Wallace

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Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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Authors: Yu Chen, Seong-Jin Kim, Jaehoon Chung

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High throughput cells counting and sizing are often required for biomedical applications. Here we report design, fabrication and validating of a micro-machined Coulter counter device with multiple-channel to realize such application for low cost. Multiple vertical through-holes were fabricated on a silicon chip, combined with the PDMS micro-fluidics channel that serves as the sensing channel. In order to avoid the crosstalk introduced by the electrical connection, instead of measuring the current passing through, the potential of each channel is monitored, thus the high throughput is possible. A peak of the output potential can be captured when the cell/particle is passing through the microhole. The device was validated by counting and sizing the polystyrene beads with diameter of 6 μm, 10 μm and 15 μm. With the sampling frequency to be set at 100 kHz, up to 5000 counts/sec for each channel can be realized. The counting and enumeration of MCF7 cancer cells are also demonstrated.

Keywords: Coulter counter, cell enumeration, high through-put, cell sizing

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Authors: Sam Khozama, Ali M. Mayya

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Breast cancer is one of the most common types in women. Early prediction of breast cancer helps physicians detect cancer in its early stages. Big cancer data needs a very powerful tool to analyze and extract predictions. Machine learning and deep learning are two of the most efficient tools for predicting cancer based on textual data. In this study, we developed a fusion model of two machine learning and deep learning models. To obtain the final prediction, Long-Short Term Memory (LSTM) and ensemble learning with hyper parameters optimization are used, and score-level fusion is used. Experiments are done on the Breast Cancer Surveillance Consortium (BCSC) dataset after balancing and grouping the class categories. Five different training scenarios are used, and the tests show that the designed fusion model improved the performance by 3.3% compared to the individual models.

Keywords: machine learning, deep learning, cancer prediction, breast cancer, LSTM, fusion

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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Authors: Hossein Pourbashash

Abstract:

Recent experimental studies have shown that HIV can be transmitted directly from cell to cell when structures called virological synapses form during interactions between T cells. In this article, we describe a new within-host model of HIV infection that incorporates two mechanisms: infection by free virions and the direct cell-to-cell transmission. We conduct the local and global stability analysis of the model. We show that if the basic reproduction number R0 1, the virus is cleared and the disease dies out; if R0 > 1, the virus persists in the host. We also prove that the unique positive equilibrium attracts all positive solutions under additional assumptions on the parameters.

Keywords: HIV virus model, cell-to-cell transmission, global stability, Lyapunov function, second compound matrices

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Authors: Ben Nadler

Abstract:

Cell adhesion plays a vital role in many cell activities. The motivation to model cell adhesion is to study important biological processes, such as cell spreading, cell aggregation, tissue formation, and cell adhesion, which are very challenging to study by experimental methods alone. This study provides important insight into cell adhesion, which can lead to improve regenerative medicine and tissue formation techniques. In this presentation the biological cells adhesion is mediated by receptors–ligands binding and the diffusivity of the receptor on the cell membrane surface. The ability of receptors to diffuse on the cell membrane surface yields a very unique and complicated adhesion mechanism, which is exclusive to cells. The phospholipid bilayer, which is the main component in the cell membrane, shows fluid-like behavior associated with the molecules’ diffusivity. The biological cell is modeled as a fluid-like membrane with negligible bending stiffness enclosing the cytoplasm fluid. The in-plane mechanical behavior of the cell membrane is assumed to depend only on the area change, which is motivated by the fluidity of the phospholipid bilayer. In addition, the presence of receptors influences on the local mechanical properties of the cell membrane is accounted for by including stress-free area change, which depends on the receptor density. Based on the physical properties of the receptors and ligands the attraction between the receptors and ligands is modeled as a charged-nonpolar which is a noncovalent interaction. Such interaction is a short-range type, which decays fast with distance. The mobility of the receptor on the cell membrane is modeled using the diffusion equation and Fick’s law is used to model the receptor–receptor interactions. The resultant interaction force, which includes receptor–ligand and receptor–receptor interaction, is decomposed into tangential part, which governs the receptor diffusion, and normal part, which governs the cell deformation and adhesion. The formulation of the governing equations and numerical simulations will be presented. Analysis of the adhesion characteristic and properties are discussed. The roles of various thermomechanical properties of the cell, receptors and ligands on the cell adhesion are investigated.

Keywords: cell adhesion, cell membrane, receptor-ligand interaction, receptor diffusion

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