Search results for: MCF7 breast cancer cells

Authors: Zaheer Ahmad, Afzal Shah

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pH responsive block copolymers consist of mPEG and glutamic acid units were syntheiszed in different formulations. The synthesized polymers were structurally investigated. Doxorubicin Hydrocholide (DOX-HCl) as a chemotherapy medication for the treatment of cancer was selected. DOX-HCl was loaded and their drug loading content and drug loading efficiency were determined. The nanocarriers were obtained in small size, well shaped and slightly negative surface charge. The release study was carried out both at pH 7.4 and 5.5 and it was revealed that the release was sustained and in controlled manner and there was no initial burst release. The in vitro release study was further carried out for different formulations with different glutamic acid moieties. Time dependent cell proliferation inhibition of the free drug and drug loaded nanoparticles against human breast cancer cell lines MCF-7 and Zr-75-30 was observed. Cellular uptakes and endocytosis were investigated by confocal laser scanning microscopy (CLSM) and flow cytometery. The biocompatibility, optimum size, shape and surface charge of the developed nanoparticles make the nanoparticles an efficient drug delivery carrier.

Keywords: doxorubicin, glutamic acid, cell proliferation inhibition, breast cancer cell

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Authors: Negar Zaheddoust, Negin Zaheddoust, Abbas Asoudeh-Fard

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Probiotic bacteria have been employed as a novel and less side-effect strategy for anticancer therapy. Since the oral cavity is a host for probiotic and pathogen bacteria to colonize, more investigation is needed to evaluate the effectiveness of this novel adjunctive treatment for oral cancer. We considered Lactobacillus plantarum as a probiotic and Streptococcus mutans as a pathogen bacterium in our study. The aim of this study is to examine the effect of Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT / PTEN, and MAPK signaling pathway, which is involved in apoptosis or survival of oral cancer KB cells. On the other hand, to study the effects of these bacteria on normal cells, we used HUVEC cells. The KB and HUVEC cell lines were co-cultured with Lactobacillus plantarum and Streptococcus mutans isolated from traditional Iranian dairy and dental plaque, respectively. The growth-inhibitory effects of these two bacteria on KB and HUVEC cells were determined by (3-(4, 5-dimethylthiazolyl-2)-2,5diphenyltetrazolium bromide) MTT assay. MTT results demonstrated that the proliferation of KB cells was affected in a time, dose, and strain-dependent manner. In the following, the examination of induced apoptosis or necrosis in co-cultured KB cells with the best IC50 concentration of the Lactobacillus plantarum and Streptococcus mutans will be analyzed by FACS flow cytometry, and the changes in gene expression of Casp3, AKT / PTEN, MAPK genes will be evaluated using real-time polymerase chain reaction.

Keywords: cancer therapy, induced apoptosis, oral cancer, probiotics

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Authors: Beom-Seok Ko, Yoo-Seok Kim, Woo-Sung Lim, Ku-Sang Kim, Hyun-Ah Kim, Jin-Sun Lee, An-Bok Lee, Jin-Gu Bong, Tae-Hyun Kim, Sei-Hyun Ahn

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Background: Breast conserving surgery (BCS) followed by radiation therapy is today standard therapy for early breast cancer. It is safe therapeutic procedure in early breast cancers, because it provides the same level of overall survival as mastectomy. There are a number of different types of incisions used to BCS. Avoiding scars on the breast is women’s desire. Numerous minimal approaches have evolved due to this concern. Periareolar incision is often used when the small tumor relatively close to the nipple. But periareolar incision has a disadvantages include limited exposure of the surgical field. In plastic surgery, various methods such as zigzag incisions have been recommended to achieve satisfactory esthetic results. Periareolar zigzag incision has the advantage of not only good surgical field but also contributed to better surgical scars. The purpose of this study was to evaluate the oncological safety of procedures by studying the status of the surgical margins of the excised tumor specimen and reduces the need for further surgery. Methods: Between January 2016 and September 2016, 148 women with breast cancer underwent BCS or mastectomy by the same surgeon in ASAN medical center. Patients with exclusion criteria were excluded from this study if they had a bilateral breast cancer or underwent resection of the other tumors or taken axillary dissection or performed other incision methods. Periareolar zigzag incision was performed and excision margins of the specimen were identified frozen sections and paraffin-embedded or permanent sections in all patients in this study. We retrospectively analyzed tumor characteristics, the operative time, size of specimen, the distance from the tumor to nipple. Results: A total of 148 patients were reviewed, 72 included in the final analysis, 76 excluded. The mean age of the patients was 52.6 (range 25-19 years), median tumor size was 1.6 cm (range, 0.2-8.8), median tumor distance from the nipple was 4.0 cm (range, 1.0-9.0), median excised specimen sized was 5.1 cm (range, 2.8-15.0), median operation time was 70.0 minute (range, 39-138). All patients were discharged with no sign of infection or skin necrosis. Free resection margin was confirmed by frozen biopsy and permanent biopsy in all samples. There were no patients underwent reoperation. Conclusions: We suggest that periareolar zigzag incision can provide a good surgical field to remove a relatively large tumor and may provide cosmetically good outcomes.

Keywords: periareolar zigzag incision, breast conserving surgery, breast cancer, resection margin

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Authors: X. Cervantes-López, C. Arriaga-Canon, L. Contreras Espinosa

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The goal of this study is to validate the overexpression of the lncRNA GATA3-AS1 associated with resistance to neoadjuvant chemotherapy of female patients with locally advanced mammary adenocarcinoma of luminal B subtype This study involved a cohort of one hundred thirty-seven samples for which total RNA was isolated from formalin fixed paraffin embedded (FFPE) tissue. Samples were cut using a Microtome Hyrax M25 Zeiss and RNA was isolated using the RNeasy FFPE kit and a deparaffinization solution, the next step consisted in the analysis of RNA concentration and quality, then 18 µg of RNA was treated with DNase I, and cDNA was synthesized from 50 ng total RNA, finally real-time PCR was performed with SYBR Green/ROX qPCR Master Mix in order to determined relative gene expression using RPS28 as a housekeeping gene to normalize in a fold calculation ΔCt. As a result, we validated by real-time PCR that the overexpression of the lncRNA GATA3-AS1 is associated with resistance to neoadjuvant chemotherapy in locally advanced breast cancer patients of luminal B subtype.

Keywords: breast cancer, biomarkers, genomics, neoadjuvant chemotherapy, lncRNAS

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Aisling Eves, Andrew Pieri, Ross McLean, Nerys Forester

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Background: DCIS accounts for 20% of malignancies diagnosed by the breast screening programme and is primarily managed by surgical excision. There is variable guidance on defining excision margins, and adjuvant treatments vary widely. This study aimed to investigate the clinical outcomes for patients following surgical excision of small volume DCIS. Methods: This single-centreretrospective cohort study of 101 consecutive breast screened patients diagnosed with DCIS who underwent surgical excision. All patients diagnosed with DCIS had radiological abnormalities <15mm. Clinical, radiological, and histological data were collected from patients who had been diagnosed within a 5 year period, and ASCO guidelines for margin involvement of <2mm was used to guide the need for re-excision. Outcomes included re-excision rates, radiotherapy usage, and the presence of invasive cancer. Results: Breast conservation surgery was performed in 94.1% (n=95). Following surgical excision, 74(73.27%)patients had complete DCIS excision (>2mm margin), 4(4.0%) had margins 1-2mm, and 17(16.84%)had margins <1mm. The median size of DCIS in the specimen sample was 4mm. In 86% of patients with involved margins (n=18), the mammogram underestimated the DCIS size by a median of 12.5mm (range: 1-42mm). Of the patients with involved margins, 11(10.9%)had a re-excision, and 6 of these (50%) required two re-excisions to completely excise the DCIS. Post-operative radiotherapy was provided to 53(52.48%)patients. Four (3.97%) patients were found to have invasive ductal carcinoma on surgical excision, which was not present on core biopsy – all had high-grade DCIS. Recurrence of DCIS was seen in the same site during follow-up in 1 patient (1%), 1 year after their first DCIS diagnosis. Conclusion: Breast conservation surgery is safe in patients with DCIS, with low rates of re-excision, recurrence, and upstaging to invasive cancer. Furthermore, the median size of DCIS found in the specimens of patients who had DCIS fully removed in surgery was low, suggesting it may be possible that total removal through VAE was possible for these patients.

Keywords: surgical excision, breast conservation surgery, DCIS, Re-excision, radiotherapy, invasive cancer

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Authors: Onmanee Prajuabjinda, Pakakrong Thondeeying, Jipisute Chunthorng-Orn, Bhanuz Dechayont, Arunporn Itharat

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A Thai medicinal preparation has been used for cancer treatment more than ten years ago in Khampramong Temple. Tectona grandis stem is one ingredient of this Thai medicinal remedy. The ethanolic extract of Tectona grandis stem showed the highest cytotoxic activities against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23) (IC50 = 3.92 and 7.78 µg/ml, respectively). It was isolated by bioassay-guided isolation method. Tectoquinone, a anthraquinone compound was isolated from this plant. This compound showed high specific cytotoxicity against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23)(IC50 =16.15 and 47.56 µg/ml or 72.67 and 214.00 µM, respectively). However, it showed less cytotoxic activity than the crude extract. In conclusion, tectoquinone as a main compound, is not the best cytotoxic compound from Tectona grandis, so there are more active cytotoxic compounds in this extract which should be isolated in the future. Moreover, tectoquinone displayed specific cytotoxicity against only human breast adenocarcinoma (MCF-7) which is a good criterion for cancer treatment.

Keywords: Tectona grandis, SRB assay, cytotoxicity, tectoquinone

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Authors: Mohamed Al-Badrashiny, Abdelghani Bellaachia

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This paper presents a classifier ensemble approach for predicting the survivability of the breast cancer patients using the latest database version of the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The system consists of two main components; features selection and classifier ensemble components. The features selection component divides the features in SEER database into four groups. After that it tries to find the most important features among the four groups that maximizes the weighted average F-score of a certain classification algorithm. The ensemble component uses three different classifiers, each of which models different set of features from SEER through the features selection module. On top of them, another classifier is used to give the final decision based on the output decisions and confidence scores from each of the underlying classifiers. Different classification algorithms have been examined; the best setup found is by using the decision tree, Bayesian network, and Na¨ıve Bayes algorithms for the underlying classifiers and Na¨ıve Bayes for the classifier ensemble step. The system outperforms all published systems to date when evaluated against the exact same data of SEER (period of 1973-2002). It gives 87.39% weighted average F-score compared to 85.82% and 81.34% of the other published systems. By increasing the data size to cover the whole database (period of 1973-2014), the overall weighted average F-score jumps to 92.4% on the held out unseen test set.

Keywords: classifier ensemble, breast cancer survivability, data mining, SEER

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Authors: Neha Singh

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Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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Authors: Salwa Hagag Abdelaziz, Naglaa Fathy Youssef, Nadia Abdellatif Hassan, Rasha Wesam Abdelrahman

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Breast cancer is considered as a substantial health concern and practicing mammography screening [MS] is important in minimizing its related morbidity. So it is essential to have a better understanding of breast cancer screening behaviors of women and factors that influence utilization of them. The aim of this study is to identify the factors that are linked to MS behaviors among the Egyptian women. A cross-sectional descriptive design was carried out to provide a snapshot of the factors that are linked to MS behaviors. A convenience sample of 311 women was utilized and all eligible participants admitted to the Women Imaging Unit who are 40 years of age or above, coming for mammography assessment, not pregnant or breast feeding and who accepted to participate in the study were included. A structured questionnaire was developed by the researchers and contains three parts; Socio-demographic data; Motivating factors associated with MS; and association between MS and model of behavior change. The analyzed data indicated that most of the participated women (66.6 %) belonged to the age group of 40-49.A high proportion of participants (58.1%) of group having previous MS influenced by their neighbors to practice MS, whereas 32.7 % in group not having previous MS were influenced by family members which indicated significant differences (P <0.05). Doctors and media are shown to be the least influence of others to practice MS. Women with intention to have a future mammogram had higher OR (1.404) for practicing MS compared with women with no intention. Further studies are needed to examine the relation between Trans-theoretical Model [TTM] and practicing MS.

Keywords: breast cancer, mammography, screening behaviors, morbidity

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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: Adriana C. Panayi, Riaz A. Agha, Brady A. Sieber, Dennis P. Orgill

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Background: Increased rates of both breast cancer and obesity have resulted in more women seeking breast reconstruction. These women may be at increased risk for perioperative complications. A systematic review was conducted to assess the outcomes in obese women who have undergone breast reconstruction following mastectomy. Methods: Cochrane, PUBMED and EMBASE electronic databases were screened and data was extracted from included studies. The clinical outcomes assessed were surgical complications, medical complications, length of postoperative hospital stay, reoperation rate and patient satisfaction. Results: 33 studies met the inclusion criteria for the review and 29 provided enough data to be included in the meta-analysis (71368 patients, 20061 of which were obese). Obese women were 2.3 times more likely to experience surgical complications (95 percent CI 2.19 to 2.39; P < 0.00001), 2.8 times more likely to have medical complications (95 percent CI 2.41 to 3.26; P < 0.00001) and had a 1.9 times higher risk of reoperation (95 percent CI 1.75 to 2.07; P < 0.00001). The most common complication, wound dehiscence, was 2.5 times more likely in obese women (95 percent CI 1.80 to 3.52; P < 0.00001). Sensitivity analysis confirmed that obese women were more likely to experience surgical complications (RR 2.36, 95% CI 2.22–2.52; P < 0.00001). Conclusions: This study provides evidence that obesity increases the risk of complications in both implant and autologous reconstruction. Additional prospective and observational studies are needed to determine if weight reduction prior to reconstruction reduces the perioperative risks associated with obesity.

Keywords: autologous reconstruction, breast cancer, breast reconstruction, literature review, obesity, oncology, prosthetic reconstruction

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Authors: Mojtaba Mirmontazemi, Habibollah Dadgar

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Bone is the most common metastasis site in some advanced malignancies, such as prostate and breast cancer. Bone metastasis generally indicates fewer prognostic factors in these patients. Different radiological and molecular imaging modalities are used for detecting bone lesions. Molecular imaging including computed tomography, magnetic resonance imaging, planar bone scintigraphy, single-photon emission tomography, and positron emission tomography as noninvasive visualization of the biological occurrences has the potential to exact examination, characterization, risk stratification and comprehension of human being diseases. Also, it is potent to straightly visualize targets, specify clearly cellular pathways and provide precision medicine for molecular targeted therapies. These advantages contribute implement personalized treatment for each patient. Currently, NaF PET/CT has significantly replaced standard bone scintigraphy for the detection of bone metastases. On one hand, 68Ga-PSMA PET/CT has gained high attention for accurate staging of primary prostate cancer and restaging after biochemical recurrence. On the other hand, FDG PET/CT is not commonly used in osseous metastases of prostate and breast cancer as well as its usage is limited to staging patients with aggressive primary tumors or localizing the site of disease. In this article, we examine current studies about FDG, NaF, and PSMA PET/CT images in bone metastases diagnostic utility and assess response to treatment in patients with breast and prostate cancer.

Keywords: skeletal metastases, fluorodeoxyglucose, sodium fluoride, molecular imaging, precision medicine, prostate cancer (68Ga-PSMA-11)

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Authors: Van Tran Thi Thuy, Cheol Won Lim, Dukjoon Kim

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A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazine (Hyd) segments on a PASPAM backbone. The hydrazine group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The mean diameter of the self - aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20 %. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX-loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatments.

Keywords: pH-sensitive, drug delivery, polyaspartamide, self-assembly, nano-aggregates

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Authors: Vinay Kumar Theendra

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The main objective of the study is to evaluate the effectiveness of hesperidin in the treatment of breast cancer and causing less (or) no bone marrow depression which is the major side effect of the present anticancer drugs treating breast cancer, also to evaluate the mechanisms through which these compounds are exerting their effect. Breast cancer is induced by administering N-methyl N-Nitrosourea (MNU) at a dose of 50mg/kg body weight. Upon the termination of the experiment, the animals were sacrificed by the method of cervical dislocation. The animals were dissected along the ventral midline and were grossly examined for the presence of tumors. Then the tumours were removed along with the stroma. Vascular endothelial growth factor (VEGF) levels were estimated by using ELISA method. The first occurrence of palpable tumors was eight weeks after carcinogen treatment and the final tumour incidence was 100% in the MNU alone and topical treated rats. Whereas in rats of other treatment groups there is decreased tumour incidence which might be due to their antitumour activity. Hesperidin therapy inhibited angiogenesis which can be evident from the significant reduction in serum as well as tumour VEGF concentrations in comparison to the untreated mammary carcinoma bearing rats. Hesperidin is promising agents that exert direct antitumor and also antiangiogenic, antiproliferative and anti-inflammatory activities. Even though the potency is little lesser than standard drug vincristine, it has been proved to be safe without effecting haematological count.

Keywords: hesperidin, VEGF, COX 2, N-methyl N-nitrosourea

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Authors: Kave Moloudi, Heidi Abrahamse, Blassan P. George

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Radiotherapy (RT) and photodynamic therapy (PDT) are both forms of cancer treatment that aim to kill cancer cells while minimizing damage to healthy tissue. The similarity between RT and PDT lies in their mechanism of action. Both treatments use energy to damage cancer cells. RT uses high-energy radiation to damage the DNA of cancer cells, while PDT uses light energy to activate a photosensitizing agent, which produces reactive oxygen species (ROS) that damage the cancer cells. Both treatments require careful planning and monitoring to ensure the correct dose is delivered to the tumor while minimizing damage to surrounding healthy tissue. They are also often used in combination with other treatments, such as surgery or chemotherapy, to improve overall outcomes. However, there are also significant differences between RT and PDT. For example, RT is a non-invasive treatment that can be delivered externally or internally, while PDT requires the injection of a photosensitizing agent and the use of a specialized light source to activate it. Additionally, the side effects and risks associated with each treatment can vary. In this review, we focus on generalizing the 6Rs of radiobiology in PDT, which can open a window for the clinical application of Radio-photodynamic therapy with minimum side effects. Furthermore, this review can open new insight to work on and design new radio-photosensitizer agents in Radio-photodynamic therapy.

Keywords: radiobiology, photodynamic therapy, radiotherapy, 6Rs in radiobiology, ROS, DNA damages, cellular and molecular mechanism, clinical application.

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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: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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Authors: Ga-Young Lee, Hyun-Man Kim

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The modulation of the cell-cell junction is critical in epithelial-mesenchymal transition during tumorigenesis. As RhoA activity is known to be up-regulated to dissociate cell-cell junction by contracting acto-myosin complex in various cancer cells, the present study investigated if RhoA activity was also associated with the disruption of the cell-cell junction of oral cancer cells. We studied SCC-25 cells which are established from oral squamous cell carcinoma if their E-cadherin junction (ECJ) was under control of RhoA. Interestingly, development of ECJ of SCC-25 cells depended on the amount of fibronectin (FN) coated on the culture dishes. Seeded cells promptly aggregated to develop ECJ on the substrates coated with a low amount of FN, whereas they were retarded in the development of ECJ on the substrates coated with a high amount of FN. However, it was an unexpected finding that total RhoA activity was lower in the dissociated cells on the substrates of high FN than in the aggregated cells on the substrates of low FN. Treating the dissociated cells on the substrates of high FN with LPA, a RhoA activator, promoted the development to ECJ. In contrast, treating the aggregated cells on the substrates of low FN with Clostridium botulinum C3, a toxin decreasing RhoA activity, dissociated cells concomitant with the disruption of ECJ. Genetical knockdown of RhoA expression by transfecting RhoA siRNA also down-regulated the development of ECJ in SCC-25 cells. Furthermore, PMA, an activator of protein kinase C (PKC), down-regulated the development of ECJ junction of SCC-25 cells on the substrates coated with low FN. In contrast, GO6976, a PKC inhibitor, up-regulated the development of ECJ of SCC-25 cells with the activation of RhoA on the substrates coated with high FN. In conclusion, in the present study, we demonstrated unexpected results that the activation of RhoA promotes the development of ECJ, whereas the inhibition of RhoA retards the development of ECJ in SCC-25 cells.

Keywords: E-cadherin junction, oral squamous cell carcinoma, PKC, RhoA, SCC-25

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Authors: Elyas Palantei, Dewiani, Farid Armin, Ardiansyah

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High precision of printed microwave sensor utilized for sensing and monitoring the potential breast cancer existed in women breast tissue was optimally computed. The single element of UWB printed sensor that successfully modeled through several numerical optimizations was multiple fabricated and incorporated with woman bra to form the spherical sensors array. One sample of UWB microwave sensor obtained through the numerical computation and optimization was chosen to be fabricated. In overall, the spherical sensors array consists of twelve stair patch structures, and each element was individually measured to characterize its electrical properties, especially the return loss parameter. The comparison of S11 profiles of all UWB sensor elements is discussed. The constructed UWB sensor is well verified using HFSS programming, CST programming, and experimental measurement. Numerically, both HFSS and CST confirmed the potential operation bandwidth of UWB sensor is more or less 4.5 GHz. However, the measured bandwidth provided is about 1.2 GHz due to the technical difficulties existed during the manufacturing step. The configuration of UWB microwave sensing and monitoring system implemented consists of 12 element UWB printed sensors, vector network analyzer (VNA) to perform as the transceiver and signal processing part, the PC Desktop/Laptop acting as the image processing and displaying unit. In practice, all the reflected power collected from whole surface of artificial breast model are grouped into several numbers of pixel color classes positioned on the corresponding row and column (pixel number). The total number of power pixels applied in 2D-imaging process was specified to 100 pixels (or the power distribution pixels dimension 10x10). This was determined by considering the total area of breast phantom of average Asian women breast size and synchronizing with the single UWB sensor physical dimension. The interesting microwave imaging results were plotted and together with some technical problems arisen on developing the breast sensing and monitoring system are examined in the paper.

Keywords: UWB sensor, UWB microwave imaging, spherical array, breast cancer monitoring, 2D-medical imaging

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Authors: Cho Ee Ng, Hazem Khout, Tarannum Fasih

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Acellular dermal matrices are increasingly used to reinforce the lower pole of the breast during implant breast reconstruction. There is no standard technique described in literature for the use of this product. In this article, we share our operative method of fixation.

Keywords: strattice, acellular dermal matric, breast reconstruction, implant

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Authors: K. Suresh, R. Arunkumar

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The objective of this study is to investigate the preparation of gramine nano suspension and protective effect of Gramine on the apoptosis of laryngeal cancer cells cell line (HEp-2 and KB). The growth inhibition rate of Hep-2 and KB cells in vitro were measured by MTT assay and apoptosis by, levels of reactive oxygen species, mitochondrial membrane potential, morphological changes and flowcytometry. Based on the results, we determined the effective doses of gramine as 127.23µm/ml for 24 hr and 119.81 µm/ml for 48hr in hep-2 cell line and 147.58 µm ml for 24 hr and 123.74µm µm/ml for 48hr in KB cell line. cytotoxicity effects of gramine were confirmed by treatment of HEp-2 cell and KB cell with IC50 concentration of gramine resulted in sequences of events marked by the enhance the apoptosis accompanied by loss of cell viability, modulation of reactive oxygen species and cell cycle arrest through the induction of G0/G1 phase arrest on HEp-2 cells. Our study suggests that the nanosuspension of gramine possesses the more cytotoxic effect of cancer cells and a novel candidate for cancer chemoprevention.

Keywords: apoptosis, HEp-2 cell line, KB cell line mitochondria, gramine, nanosuspension

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Authors: Ruqayya Naheed Khan, Awais Amjad Malik, Awais Naeem, Amina Khan, Asad Parvaiz

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Introduction: Axillary nodal status in breast cancer patients is a paramount prognosticator, next to primary tumor size and grade. It has been well established that patients with negative sentinel lymph node biopsy can safely avoid axillary lymph node dissection. A positive sentinel lymph node has traditionally required subsequent axillary dissection. According to ACOSOG Z11 trial, patients who underwent axillary dissection with 3 or more positive sentinel nodes or opted for observation in case of negative sentinel lymph node, did not find any difference in Overall Survival (OS) and Disease Free Survival (DFS). The Z11 trial included patients who underwent breast conserving surgery and excluded patients with mastectomies. The purpose of this study is to determine whether Z0011 can be applied to mastectomy patients as well in 1-3 positive sentinel lymph nodes and avoid unnecessary ALND. Methods: A retrospective review was conducted at Shaukat Khanam Memorial Cancer Hospital Pakistan from Jan 2015 to Dec 2017 including patients who were treated for invasive breast cancer and required upfront mastectomy. They were clinically node negative, so sentinel lymph node biopsy was performed. Patients underwent ALND with positive sentinel lymph node. A total of 156 breast cancer patients with mastectomies were reviewed. Results: 95% of the patients were female while 3% were male. Average age was 44 years. There was no difference in race, comorbidities, histology, T stage, N stage, and overall stage, use of adjuvant chemotherapy and radiation therapy. 64 patients underwent ALND for positive lymph node while 92 patients were spared of axillary dissection due to negative sentinel lymph node biopsy. Out of 64 patients, 38 patients (59%) had only 1 lymph node positive which was the sentinel node. 18 patients (28%) had 2 lymph nodes positive including the sentinel node while only 8 patients (13%) had 3 or more positive nodes. Conclusion: Keeping in mind the complications related to ALND, above results clearly show that ALND could have been avoided in 87% of patients in the setting of adjuvant radiation, possibly avoiding the morbidity associated with axillary lymphadenectomy although a prospective randomized trial needs to confirm these results.

Keywords: mastectomy, sentinel lymph node biopsy, axillary lymph node dissection, breast cancer

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Authors: B. Petrović, M. Petrović, L. Rutonjski, I. Djan, V. Ivanović

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Objective: Cardiac pacemakers are very sensitive to radiotherapy treatment from two sources: electromagnetic influence from the medical linear accelerator producing ionizing radiation- influencing electronics within the pacemaker, and the absorption of dose to the device. On the other hand, patients with cardiac pacemakers at the place of a tumor are rather rare, and single clinic hardly has experience with the management of such patients. The widely accepted international guidelines for management of radiation oncology patients recommend that these patients should be closely monitored and examined before, during and after radiotherapy treatment by cardiologist, and their device and condition followed up. The number of patients having both cancer and pacemaker, is growing every year, as both cancer incidence, as well as cardiac diseases incidence, are inevitably growing figures. Materials and methods: Female patient, age 69, was diagnozed with valvular cardiomyopathy and got implanted a pacemaker in 2005 and prosthetic mitral valve in 1993 (cancer was diagnosed in 2012). She was stable cardiologically and came to radiation therapy department with the diagnosis of right breast cancer, with the tumor in upper lateral quadrant of the right breast. Since she had all lymph nodes positive (28 in total), she had to have irradiated the supraclavicular region, as well as the breast with the tumor bed. She previously received chemotherapy, approved by the cardiologist. The patient was estimated to be with the high risk as device was within the field of irradiation, and the patient had high dependence on her pacemaker. The radiation therapy plan was conducted as 3D conformal therapy. The delineated target was breast with supraclavicular region, where the pacemaker was actually placed, with the addition of a pacemaker as organ at risk, to estimate the dose to the device and its components as recommended, and the breast. The targets received both 50 Gy in 25 fractions (where 20% of a pacemaker received 50 Gy, and 60% of a device received 40 Gy). The electrode to the heart received between 1 Gy and 50 Gy. Verification of dose planned and delivered was performed. Results: Evaluation of the patient status according to the guidelines and especially evaluation of all associated risks to the patient during treatment was done. Patient was irradiated by prescribed dose and followed up for the whole year, with no symptoms of failure of the pacemaker device during, or after treatment in follow up period. The functionality of a device was estimated to be unchanged, according to the parameters (electrode impedance and battery energy). Conclusion: Patient was closely monitored according to published guidelines during irradiation and afterwards. Pacemaker irradiated with the full dose did not show any signs of failure despite recommendations data, but in correlation with other published data.

Keywords: cardiac pacemaker, breast cancer, radiotherapy treatment planning, complications of treatment

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Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

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Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation

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Authors: May Fadheel Estephan, Richard Perks

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Context: Cancer is a serious health concern that affects millions of people worldwide. Early detection and treatment are essential for improving patient outcomes. However, current methods for cancer detection have limitations, such as low sensitivity and specificity. Research Aim: The aim of this study was to develop an optical sensor for cancer detection using elastic light scattering spectroscopy (ELSS). ELSS is a noninvasive optical technique that can be used to characterize the size and concentration of particles in a solution. Methodology: An optical probe was fabricated with a 100-μm-diameter core and a 132-μm centre-to-centre separation. The probe was used to measure the ELSS spectra of polystyrene spheres with diameters of 2, 0.8, and 0.413 μm. The spectra were then analysed to determine the size and concentration of the spheres. Findings: The results showed that the optical probe was able to differentiate between the three different sizes of polystyrene spheres. The probe was also able to detect the presence of polystyrene spheres in suspension concentrations as low as 0.01%. Theoretical Importance: The results of this study demonstrate the potential of ELSS for cancer detection. ELSS is a noninvasive technique that can be used to characterize the size and concentration of cells in a tissue sample. This information can be used to identify cancer cells and assess the stage of the disease. Data Collection: The data for this study were collected by measuring the ELSS spectra of polystyrene spheres with different diameters. The spectra were collected using a spectrometer and a computer. Analysis Procedures: The ELSS spectra were analysed using a software program to determine the size and concentration of the spheres. The software program used a mathematical algorithm to fit the spectra to a theoretical model. Question Addressed: The question addressed by this study was whether ELSS could be used to detect cancer cells. The results of the study showed that ELSS could be used to differentiate between different sizes of cells, suggesting that it could be used to detect cancer cells. Conclusion: The findings of this research show the utility of ELSS in the early identification of cancer. ELSS is a noninvasive method for characterizing the number and size of cells in a tissue sample. To determine cancer cells and determine the disease's stage, this information can be employed. Further research is needed to evaluate the clinical performance of ELSS for cancer detection.

Keywords: elastic light scattering spectroscopy, polystyrene spheres in suspension, optical probe, fibre optics

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Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

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Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

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Authors: Razieh Zareia, Hassan ZMB, Darush Moslemic, Amrollah Mostafa-Zaded

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Introduction: Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, at least, in vitro. The purpose of our research was to evaluate the immune-effectiveness on imbalance between IL-23/IL-17 axis, as an inflammatory pathway and TGF/Foxp3 T regulatory as a inhibitory pathway of commercial shark cartilage that is available as a non-common dietary supplement in IRAN. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23, IL-17, TGF-β, IL-4, and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: The simultaneously presented up-regulation IL-17A indicated, at least cytokine level without changing in TGF-β amount or CD4+CD25+Foxp3 T regulatory cells, that there are not a direct correlation between IL-23/IL-17 axis and Treg/TGF-β pathway in patients with gastric cancer treated by shark cartilage, but IL-23 was not expressed differentially in this group. So, accompany these changes, an imbalance between Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) evaluated in patients with gastric cancer treated by shark cartilage. Conclusion: On the basis of results, we propose that shark cartilage, by reducing IL-4, decreasing IL-17 a central cytokine in angiogenesis and increasing γ-IFN amplify anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4+CD25+Foxp3high T regulatory pathway, γ-IFN, IL-4, shark cartilage, gastric cancer

Procedia PDF Downloads 369