Search results for: cancer treatment

Authors: Nuhi Arslani, Stojan Potrc, Timotej Mikuljan

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Background: In Department of Abdominal and General Surgery of University Medical Centre Maribor, we treated 578 patients for rectal cancer between 2004 and 2014. During and after treatment we especially concentrated on monitoring local and systemic complications. Methods: For analysis, we used data gathered from preoperative diagnostic tests, reports gathered during operation, reports from the pathohistologic review, and reports on complications after surgery and follow up. Results: In the case of 573 (out of 578) patients (99.1%) we performed resection. R0 was achieved in 551 patients (96,1%). R1 was achieved in 8 patients (1,4%). R2 was achieved in 14 patients (2,4%). Local complications were reported in 78 (13.5%) patients and systemic complications were reported in 68 (11.7%). We would like to point out the low number of local and systemic complications. Conclusions: With advances in surgical techniques, with a multimodal-multidisciplinary approach and with the use of total mesorectal excision we experienced a significant improvement in reducing the number of local and systemic complications in patients with rectal cancer. However, there still remains the question for truly optimal care for each patient with rectal cancer and his quality of life after surgical treatment.

Keywords: local complications, rectal cancer, resection, systemic complications

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Authors: Marwa M. Abu-Serie, Marwa M. Eltarahony

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The search for reliable, effective, and safe nanoparticles (NPs) as a treatment for cancer is a pressing priority. In this study, Cu-NPs were fabricated by Streptomyces cyaneofuscatus through simultaneous bioreduction strategy of copper nitrate salt. The as-prepared Cu-NPs subjected to structural analysis; energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, transmission electron microscopy, and ζ-potential. These biological synthesized Cu-NPs were mixed with disulfiram (DS), forming a nanocomplex of Cu-DS with a size of ~135 nm. The prepared nanocomplex (nanoCu-DS) exhibited higher anticancer activity than that of free complex of DS-Cu, Cu-NPs, and DS alone. This was illustrated by the lowest IC50 of nanoCu-DS (< 4 µM) against human breast and liver cancer cell lines comparing with DS-Cu, Cu-NPs, and DS (~8, 22.98-33.51 and 11.95-14.86, respectively). Moreover, flow cytometric analysis confirmed that higher apoptosis percentage range of nanoCu-DS-treated in MDA-MB 231, MCF-7, Huh-7, and HepG-2 cells (51.24-65.28%) than free complex of Cu-DS ( < 4.5%). Regarding inhibition potency of liver and breast cancer cell migration, no significant difference was recorded between free and nanocomplex. Furthermore, nanoCu-DS suppressed gene expression of β-catenine, Akt, and NF-κB and upregulated p53 expression (> 3, >15, > 5 and ≥ 3 folds, respectively) more efficiently than free complex (all ~ 1 fold) in MDA-MB 231 and Huh-7 cells. Our finding proved this prepared nano complex has a powerful anticancer activity relative to free complex, thereby offering a promising cancer treatment.

Keywords: biologically prepared Cu-NPs, breast cancer cell lines, liver cancer cell lines, nanoCu- disulfiram

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: A. Dashti, M. Eskandari, L. Farahmand, P. Parvin, A. Jafargholi

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Breast Cancer is one of the most considerable diseases in the United States and other countries and is the second leading cause of death in women. Common breast cancer treatments would lead to adverse side effects such as loss of hair, nausea, and weakness. These complications arise because these cancer treatments damage some healthy cells while eliminating the cancer cells. In an effort to address these complications, laser radiation was utilized and tested as a targeted cancer treatment for breast cancer. In this regard, tissue engineering approaches are being employed by using an electrospun scaffold in order to facilitate the growth of breast cancer cells. Polycaprolacton (PCL) was used as a material for scaffold fabricating because of its biocompatibility, biodegradability, and supporting cell growth. The specific breast cancer cells have the ability to create a three-dimensional cell cluster due to the spontaneous accumulation of cells in the porosity of the scaffold under some specific conditions. Therefore, we are looking for a higher density of porosity and larger pore size. Fibers showed uniform diameter distribution and final scaffold had optimum characteristics with approximately 40% porosity. The images were taken by SEM and the density and the size of the porosity were determined with the Image. After scaffold preparation, it has cross-linked by glutaraldehyde. Then, it has been washed with glycine and phosphate buffer saline (PBS), in order to neutralize the residual glutaraldehyde. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor (MTT) results have represented approximately 91.13% viability of the scaffolds for cancer cells. In order to create a cluster, Michigan Cancer Foundation-7 (MCF-7, breast cancer cell line) and Michigan Cancer Foundation-10A (MCF-10A, human mammary epithelial cell line) cells were cultured on the scaffold in 24 well plate for five days. Then, we have exposed the cluster to the laser diode 808 nm radiation to investigate the effect of laser on the tumor with different power and time. Under the same conditions, cancer cells lost their viability more than the healthy ones. In conclusion, laser therapy is a viable method to destroy the target cells and has a minimum effect on the healthy tissues and cells and it can improve the other method of cancer treatments limitations.

Keywords: breast cancer, electrospun scaffold, polycaprolacton, laser diode, cancer treatment

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Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

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Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

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Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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Authors: Leah Ning

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This paper discusses the development of a machine learning algorithm that accurately detects metastatic breast cancer (cancer has spread elsewhere from its origin part) in selected images that come from pathology scans of lymph node sections. Being able to develop an accurate artificial intelligence (AI) algorithm would help significantly in breast cancer diagnosis since manual examination of lymph node scans is both tedious and oftentimes highly subjective. The usage of AI in the diagnosis process provides a much more straightforward, reliable, and efficient method for medical professionals and would enable faster diagnosis and, therefore, more immediate treatment. The overall approach used was to train a convolution neural network (CNN) based on a set of pathology scan data and use the trained model to binarily classify if a new scan were benign or malignant, outputting a 0 or a 1, respectively. The final model’s prediction accuracy is very high, with 100% for the train set and over 70% for the test set. Being able to have such high accuracy using an AI model is monumental in regard to medical pathology and cancer detection. Having AI as a new tool capable of quick detection will significantly help medical professionals and patients suffering from cancer.

Keywords: breast cancer detection, AI, machine learning, algorithm

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Authors: Hossain A., Miah S., Ray P. K.

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Introduction: Single channel and tri-channel applicators are used in the traditional treatment of cervical cancer. Total reference air kerma (TRAK) and treatment outcomes in high-dose-rate brachytherapy for cervical cancer using single-channel and tri-channel applicators were the main objectives of this retrospective study. Material and Methods: Patients in the radiotherapy division who received brachytherapy, chemotherapy, and external radiotherapy (EBRT) using single and tri-channel applicators were the subjects of a retrospective cohort study from 2016 to 2020. All brachytherapy parameters, including TRAK, were calculated in accordance with the international protocol. The Kaplan Meier method was used to analyze survival rates using a log-rank test. Results and Discussions: Based on treatment times of 15.34 (10-20) days and 21.35 (6.5-28) days, the TRAK for the tri-channel applicator was 0.52 cGy.m² and for the single-channel applicator was 0.34 cGy.m². Based on TRAK, the rectum, bladder, and tumor had respective Pearson correlations of 0.082, 0.009, and 0.032. The 1-specificity and sensitivity were 0.70 and 0.30, respectively. At that time, AUC was 0.71. The log-rank test showed that tri-channel applicators had a survival rate of 95% and single-channel applicators had a survival rate of 85% (p=0.565). Conclusions: The relationship between TRAK and treatment duration and Pearson correlation for the tumor, rectum, and bladder suggests that TRAK should be taken into account for the proper operation of single channel and tri-channel applicators.

Keywords: single-channel, tri-channel, high dose rate brachytherapy, cervical cancer

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Authors: Marshal Rashid

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In Pakistan, one in nine women develops breast cancer at some stage of their lives. Every year thousands of females lose their lives due to lack of awareness, several women do not share their health issues with others and are shy to go for any kind of breast examination. An inductive approach was used to analyze the data which resulted in the emergence of eight subthemes under the umbrella of three major themes that delineate individual, socio-cultural and structural barriers to seek screening and treatment of breast cancer in Pakistan. Individual barriers included lack of awareness, hesitance in accepting social support, and spiritual healing. The identified socio-cultural factors included feminine sensitivity, stigmatization, and aversion to male doctors.

Keywords: breast, cancer, women, Pakistan

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Authors: Yusha'u Shu'aibu Baraya, Kah Keng Wong, Nik Soriani Yaacob

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Strobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‘Pecah kaca’ or ‘Jin batu’ which have demonstrated potent anticancer effects in both in vitro and in vivo models. In particular, S. crispus subfraction (SCS) significantly reduced tumor growth in N-methyl-N-Nitrosourea-induced breast cancer rat model. However, there is paucity of information on the effects of SCS in breast cancer metastasis. Thus, in this study, the antimetastatic effects of SCS (100 mg/kg) was investigated following 30 days of treatment in 4T1-induced mammary tumor (n = 5) model. The response to treatment was assessed based on the outcome of the tumour growth, body weight and hematological parameters. The results demonstrated that tumor bearing mice treated with SCS (TM-S) had significant (p<0.05) reduction in the mean tumor number and tumor volume as well as tumor weight compared to the tumor bearing mice (TM), i.e. tumor untreated group. Also, there was no secondary tumor formation or tumor-associated lesions in the major organs of TM-S compared to the TM group. Similarly, comparable body weights were observed among the TM-S, normal (uninduced) mice treated with SCS and normal (untreated/control) mice (NM) groups compared to the TM group (p<0.05). Furthermore, SCS administration does not cause significant changes in the hematological parameters as compared to the NM group, which indicates no sign of anemia and toxicity related effects. In conclusion, SCS significantly inhibited the overall tumor growth and metastasis in 4T1-induced breast cancer mouse model suggesting its promising potentials as therapeutic agent for breast cancer treatment.

Keywords: 4T1-cells, breast cancer, metastasis, Strobilanthes crispus

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Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

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Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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Authors: Shiva Shakori Poshteh

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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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Authors: Chuan Yin

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Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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Authors: Lin Feng, Ling-Ling E., Hong-Chen Liu

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The development of chemoresistance in patients represents a major challenge in cancer treatment. Lactate dehydrogenase‑A (LDHA) is one of the principle isoforms of LDH that is expressed in breast tissue, controlling the conversion of pyruvate to lactate and also playing a significant role in the metabolism of glucose. The aim of this study was to identify whether LDHA was involved in oral cancer cell resistance to Taxol and whether the downregulation of LDHA, as a result of cisplatin treatment, may overcome Taxol resistance in human oral squamous cells. The OECM‑1 oral epidermal carcinoma cell line was used, which has been widely used as a model of oral cancer in previous studies. The role of LDHA in Taxol and cisplatin resistance was investigated and the synergistic cytotoxicity of cisplatin and/or Taxol in oral squamous cells was analyzed. Cell viability was analyzed by MTT assay, LDHA expression was analyzed by western blot analysis and siRNA transfection was performed to knock down LDHA expression. The present study results showed that decreased levels of LDHA were responsible for the resistance of oral cancer cells to cisplatin (CDDP). CDDP treatments downregulated LDHA expression and lower levels of LDHA were detected in the CDDP‑resistant oral cancer cells compared with the CDDP‑sensitive cells. By contrast, the Taxol‑resistant cancer cells showed elevated LDHA expression levels. In addition, small interfering RNA‑knockdown of LDHA sensitized the cells to Taxol but desensitized them to CDDP treatment while exogenous expression of LDHA sensitized the cells to CDDP, but desensitized them to Taxol. The present study also revealed the synergistic cytotoxicity of CDDP and Taxol for killing oral cancer cells through the inhibition of LDHA. This study highlights LDHA as a novel therapeutic target for overcoming Taxol resistance in oral cancer patients using the combined treatments of Taxol and CDDP.

Keywords: cisplatin, Taxol, carcinoma, oral squamous cells

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Authors: Saman Khan, Imrana Naseem

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Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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Authors: Laura Elena De León Prado, Dora Alicia Cortés Hernández, Javier Sánchez

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Among the different cancer treatments that are currently used, hyperthermia has a promising potential due to the multiple benefits that are obtained by this technique. In general terms, hyperthermia is a method that takes advantage of the sensitivity of cancer cells to heat, in order to damage or destroy them. Within the different ways of supplying heat to cancer cells and achieve their destruction or damage, the use of magnetic nanoparticles has attracted attention due to the capability of these particles to generate heat under the influence of an external magnetic field. In addition, these nanoparticles have a high surface area and sizes similar or even lower than biological entities, which allow their approaching and interaction with a specific region of interest. The most used magnetic nanoparticles for hyperthermia treatment are those based on iron oxides, mainly magnetite and maghemite, due to their biocompatibility, good magnetic properties and chemical stability. However, in order to fulfill more efficiently the requirements that demand the treatment of magnetic hyperthermia, there have been investigations using ferrites that incorporate different metallic ions, such as Mg, Mn, Co, Ca, Ni, Cu, Li, Gd, etc., in their structure. This paper reports the synthesis of nanosized Mg_xMn_1-xFe₂O₄ (x = 0.3 and 0.4) ferrites by sol-gel method and their evaluation in terms of heating capability and in vitro hemolysis to determine the potential use of these nanoparticles as thermoseeds for the treatment of cancer by magnetic hyperthermia. It was possible to obtain ferrites with nanometric sizes, a single crystalline phase with an inverse spinel structure and a behavior near to that of superparamagnetic materials. Additionally, at concentrations of 10 mg of magnetic material per mL of water, it was possible to reach a temperature of approximately 45°C, which is within the range of temperatures used for the treatment of hyperthermia. The results of the in vitro hemolysis assay showed that, at the concentrations tested, these nanoparticles are non-hemolytic, as their percentage of hemolysis is close to zero. Therefore, these materials can be used as thermoseeds for the treatment of cancer by magnetic hyperthermia.

Keywords: ferrites, heating capability, hemolysis, nanoparticles, sol-gel

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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: Eddy K. Mukadi

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This work is a documentary and descriptive study devoted to the epidemiological, clinical, histopathological and therapeutic profile of breast cancer deals with the department of gynecology and obstetrics of the university clinics of Kinshasa during the period from 1 January 2014 to 31 December 2014. We have identified 56 cases of breast cancer. These cancers accounted for 45.2% of gynecological mammary cancers. The youngest in our series was 18 years old while the oldest was 74 years old; And the mean age of these patients was 43.4 years and mostly multiparous (35.7%). Brides (60.7%) and bachelors (26.8%) were the most affected by breast cancer. The reasons for consultation were dominated by nodules in the breast (48.2%) followed by pain (35.7%) and nipple discharge (14.3%). In 89.2% of the cases, it was the advanced clinical stage (stage 3 and 4) and the infiltrating ductal carcinoma was the most frequent histological type (75%) The malignant tumor was mainly in the left breast (55.3%), and chemotherapy with hormone therapy and patey was the most convenient treatment (42.8%), while patey mastectomy was performed in 12.5% of patients. Because of the high incidence of breast cancer identified in our study, some preventive measures must be taken into account to address this public health problem, including breast autopalpation once a month, Early detection system development of a national breast cancer policy and the implementation of a national breast cancer control program.

Keywords: breast cancer, histopathological profile, epidemiological profile, Kinshasa

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Authors: Faezah Shekh Abdullah, Mohd. Azizuddin Mohd. Yussof, Komathy Thiagarajan, Hasnoorina Husin, Noor Azreena Abd Aziz

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Polycystic ovary syndrome has been associated with multiple disorders such as endocrine disorder, metabolic syndrome, infertility, and endometrial cancer. Women with polycystic ovary syndrome (PCOS) are anticipated to develop three times more chances for endometrial cancer than women without PCOS. This study, therefore, was conducted to determine the association between polycystic ovary syndrome and endometrial cancer and to determine the cervical cytology features of PCOS. Patients attending the Subfertility Clinic of the National Population and Family Development Board were recruited and examined physically by medical practitioners. They were categorized into two groups; i) the PCOS group if they met Rotterdam Criteria 2004 and ii) the control group if they did not meet Rotterdam Criteria 2004. Cervical sampling was done on all patients via the Liquid-Based Cytology (LBC) method in the pre-and post-subfertility treatment. A total of 167 patients participated in the study, of which 79 belonged to the PCOS group and 88 to the control group. The findings showed no cervical and endometrial cancer cases in both groups. The Liquid-Based Cytology results in the PCOS group displayed more cases with cellular changes, i.e., benign inflammation, atrophic smear and Candida sp. infection. To conclude, no association was found between polycystic ovary syndrome and endometrial cancer. A more holistic study with a higher number of participants can further determine the association between endometrial cancer and PCOS. Furthermore, a longer duration between LBC pre- and post-subfertility treatment should be implied to observe changes in the cervical cells.

Keywords: endometrial cancer, liquid-based cytology, PCOS, polycystic ovary syndrome

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Authors: Vandana Gawande, Chandani Satija

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Gnidia glauca is a semi-woody herb of thymelaeaceae family traditionally used as fish poison in India. It is also found in Sri lanka and Africa. In the present study, potential anticancer effect of n-hexane and ethanolic extracts of Gnidia glauca in human breast cancer cells was investigated. Human breast cancer cells (MCF-7) were cultured as monolayers in RPMI 1640 medium. The cells were cultured for 48 hours to allow growth and achieve about 80% confluence in 96-well culture plates. The cells were treated with various concentrations of Gnidia glauca (0.1-100 mg/mL) for 72 hours. Percentage of viable cells after treatment was assessed using a sulforhodamine B colorimetric assay. Both n-hexane and ethanolic extract showed significant cytotoxic activity on MCF-7 cancer cells. This study supports the notion of using Gnidia glauca as a novel anticancer agent for breast cancer.

Keywords: 96 well plate, anticancer activity, Gnidia glauca, MCF-7

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Angel Champion, Sadia Kanwal, Rafat Siddiqui

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Harnessing phytochemicals from plant sources presents a novel opportunity to prevent or treat malignant diseases, including breast cancer. Chemotherapy lacks precision in targeting cancerous cells while sparing normal cells, but a phytopharmaceutical approach may offer a solution. Dandelion, a common weed plant, is rich in phytochemicals and provides a safer, more cost-effective alternative with lower toxicity than traditional pharmaceuticals for conditions such as breast cancer. In this study, an in-vitro experiment will be conducted using the ethanol extract of Dandelion on triple-negative MDA-231 breast cancer cell lines. The polyphenolic analysis revealed that the Dandelion extract, particularly from the root and leaf (both cut and sifted), had the most potent antioxidant properties and exhibited the most potent antioxidation activity from the powdered leaf extract. The extract exhibits prospective promising effects for inducing cell proliferation and apoptosis in breast cancer cells, highlighting its potential for targeted therapeutic interventions. Standardizing methods for Dandelion use is crucial for future clinical applications in cancer treatment. Combining plant-derived compounds with cancer nanotechnology holds the potential for effective strategies in battling malignant diseases. Utilizing liposomes as carriers for phytoconstituent anti-cancer agents offers improved solubility, bioavailability, immunoregulatory effects, advancing anticancer immune function, and reducing toxicity. This integrated approach of natural products and nanotechnology has significant potential to revolutionize healthcare globally, especially in underserved communities where herbal medicine is prevalent.

Keywords: apoptosis, antioxidant activity, cancer nanotechnology, phytopharmaceutical

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Authors: Fatima Abu Baker Hamad

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Anaemia is a public health problem that affects population in both rich and poor countries. Although the primary cause is iron deficiency, it is seldom present in isolation. More frequently it coexists with a number of other causes, such as malaria, parasitic infection, nutritional deficiencies and hemoglobin apathies. That was the people in Sudan suffered from it .Anaemia has a high prevalence in patients with cancer. The aim of this study was to find the incidence of anaemia in new cases of Sudanese female breast patients attending the National Cancer Institute (NCI), Gezira University, Sudan. The study was performed on 250 female breast cancer patients, the age range was (20-70) years and the mean age was 45.99±0.82. The hemoglobin level was measured by SYSMEX-KX2lM.As result 144(58.8) of patients presented with anaemia, between moderate to severe. Forty four (17.6%) of the patients were found to be under weight, 31 of them were anaemic. While 105(42%) of the patients were overweight and obese, 52 of them were anaemic. The incidence of anaemia in newly diagnosed Sudanese female breast cancer patients presented at NCI is association presentation with advance disease stage. Also it is related to age, state of nutrition and social economic factors. Early cancer detection which leads to effective treatment and reduced complication of diseases included anaemia is recommended.

Keywords: anaemia, breast cancer, stages of disease, malaria

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Authors: S. Valarmathi, P. B. Harathi, R. Sridhar, S. Balasubramanian

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Machine learning tools in medical diagnosis is increasing due to the improved effectiveness of classification and recognition systems to help medical experts in diagnosing breast cancer. In this study, ID3 chooses the splitting attribute with the highest gain in information, where gain is defined as the difference between before the split versus after the split. It is applied for age, location, taluk, stage, year, period, martial status, treatment, heredity, sex, and habitat against Very Serious (VS), Very Serious Moderate (VSM), Serious (S) and Not Serious (NS) to calculate the gain of information. The ranked histogram gives the gain of each field for the breast cancer data. The doctors use TNM staging which will decide the risk level of the breast cancer and play an important decision making field in fuzzy logic for perception based measurement. Spatial risk area (taluk) of the breast cancer is calculated. Result clearly states that Coimbatore (North and South) was found to be risk region to the breast cancer than other areas at 20% criteria. Weighted value of taluk was compared with criterion value and integrated with Map Object to visualize the results. ID3 algorithm shows the high breast cancer risk regions in the study area. The study has outlined, discussed and resolved the algorithms, techniques / methods adopted through soft computing methodology like ID3 algorithm for prognostic decision making in the seriousness of the breast cancer.

Keywords: ID3 algorithm, breast cancer, fuzzy logic, MATLAB

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Authors: Doaa Hashad, Amany Elbanna, Abeer Ibrahim, Gihan Khedr

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Background: H19 is one of the long non coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H119, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. Methods: A total of sixty-two participants were enrolled in the present study. The first group included thirty-two GC patients, while the second group was formed of thirty age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real time quantitative PCR technique. Results: H19 expression was up-regulated in GC patients with positive correlation to TNM cancer stages. Conclusions: Up-regulation of H19 is closely associated with gastric cancer and correlates well with tumor staging. Convenient, efficient quantification of H19 in plasma using real time PCR technique implements its role as a potential noninvasive prognostic biomarker in gastric cancer, that predicts patient’s outcome and most importantly as a novel target in gastric cancer treatment with better performance achieved on using both CEA and H19 simultaneously.

Keywords: biomarker, gastric, cancer, LncRNA

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Authors: Elyce Cardonick, Shistri Dhar, Linsdey Seidman

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Background: When breast cancer is diagnosed during pregnancy, the prognosis is comparable to non-pregnant women matched for prognostic indicators when pregnant women receive treatment without delay. Chemotherapy, including taxanes, can be given during pregnancy with normal neonatal development in exposed fetuses. Methods: Cases of primary breast cancer were extracted from the Cancer and Pregnancy Registry and longitudinal study at Cooper Medical School, which collects cases of pregnant women diagnosed and treated for cancer into a single database. Obstetrical, oncology and pediatric records were reviewed, including annual neonatal developmental, behavioral and medical assessments. Results: 270 pregnant women were diagnosed with primary breast cancer at a mean gestational age of 14.7+9weeks. Mean maternal age at diagnosis 34.5+4.5 years. Receptor status is comparable to non-pregnant women of reproductive age. Forty-nine women were advised to terminate. Two hundred two women underwent surgery;244 women received chemotherapy in pregnancy after the first trimester; the majority of Doxorubucin/Cytoxan; 81 of the cases included a taxane. At a mean of 90 months, follow up obtained on 255 newborns.192/255 newborns are meeting developmental milestones. Respiratory illnesses, including asthma, and bronchiolitis, were reported in 64 newborns, the most common medical condition reported. Thirty-one children are undergoing treatment for GERD, 11 for urinary tract infections, and 7 are undergoing treatment for anemia. Twenty-six children with expressive or articulation language delays, 21/26 are mild. Eleven children with gross/ 7 with fine motor delays. Eight children are treated for ADHD, 4 for anxiety and 4 have social skill impairment. The majority of children with developmental, language or motor delays were born preterm. Conclusion: After chemotherapy exposure in utero for breast cancer, the majority of newborns are meeting developmental milestones and are medically healthy. The goal for treating pregnant women with breast cancer is to aim for delivery close to the term.

Keywords: breast cancer, pregnancy, chemotherapy, newborn

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Authors: Ekhlas Al Gamal, Tony Long

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The impact on the parents of caring for a child with cancer was intense and wide-ranging. A high level of distress and low level or resilience remains during treatment. Even completion of treatment can be a time of increased anxiety and stress for parents particularly with worries about recurrence or relapse. The purpose of this study to examine the associations between parental satisfactions with healthcare provided for their child and the impact of being a caregiver for a child with cancer. Methodology: A descriptive, correlational and cross-sectional design was employed using data from Arabic versions of self-report questionnaires which were administered to 113 parents with children with cancer in Jordan during 2015. Findings: the result indicated that Family relationship functioning was ranked as the highest (better functioning) domain while daily activities were ranked as the lowest (poorer functioning) domain. Parents were generally satisfied with the health care provided, but their emotional needs were not met adequately. Parents with better social functioning were more satisfied in all areas of healthcare satisfaction other than emotional needs and communication. Parents who had a child with more emotional and behavioural problems were more likely to experience a negative impact on the family and a poor level of family functioning. Conclusion and Significance: Nurses and other health care providers should emphasis on family centred approach rather than child centred approach.

Keywords: parents, children, cancer, Jordan

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Authors: Maxime Moreau, Silvère Baron, Jean-Marc Lobaccaro, Karine Charlet, Sébastien Menecier, Frédéric Perisse

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Cold Atmospheric Plasma (CAP) is an ionized gas generated at atmospheric pressure with the temperature of heavy particles (molecules, ions, atoms) close to the room temperature. Recent studies have shown that both in-vitro and in-vivo plasma exposition to many cancer cell lines are efficient to induce the apoptotic way of cell death. In some other works, normal cell lines seem to be less impacted by plasma than cancer cell lines. This is called selectivity of plasma. It is highly likely that the generated RNOS (Reactive Nitrogen Oxygen Species) in the plasma jet, but also in the medium, play a key-role in this selectivity. In this study, two CAP devices will be compared to electrical power, chemical species composition and their efficiency to kill cancer cells. A particular focus on the action of hydrogen peroxide will be made. The experiments will take place as described next for both devices: electrical and spectroscopic characterization for different voltages, plasma treatment of normal and cancer cells to compare the CAP efficiency between cell lines and to show that death is induced by an oxidative stress. To enlighten the importance of hydrogen peroxide, an inhibitor of H2O2 will be added in cell culture medium before treatment and a comparison will be made between the results of cell viability in this case and those from a simple plasma exposition. Besides, H2O2 production will be measured by only treating medium with plasma. Cell lines will also be exposed to different concentrations of hydrogen peroxide in order to characterize the cytotoxic threshold for cells and to make a comparison with the quantity of H2O2 produced by CAP devices. Finally, the activity of catalase for different cell lines will be quantified. This enzyme is an important antioxidant agent against hydrogen peroxide. A correlation between cells response to plasma exposition and this activity could be a strong argument in favor of the predominant role of H2O2 to explain the selectivity of plasma cancer treatment by cold atmospheric plasma.

Keywords: cold atmospheric plasma, hydrogen peroxide, prostate cancer, selectivity

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Authors: Afrah Aladwani, Alexander Mullen, Mohammad AlRashidi, Omamah Alfarisi, Faisal Alterkit, Abdulwahab Aladwani, Asit Kumar, Emad Eldosouky

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Introduction: Trastuzumab is a HER-2 targeted humanized monoclonal antibody that significantly improves the therapeutic outcomes of metastatic and non-metastatic breast cancer. However, it is associated with increased risk of cardiotoxicity that ranges from mild decline in the cardiac ejection fraction to permanent cardiomyopathy. Concerns have been raised in treating eligible older patients. This study compares trastuzumab outcomes between two age cohorts in the Kuwait Cancer Control Centre (KCCC). Methods: In a prospective comparative observational study, 93 HER-2 positive breast cancer patients undergoing different chemotherapy protocols + trastuzumab were included and divided into two cohorts based on their age (˂60 and ≥60 years old). The baseline left ventricular ejection fraction (LVEF) was assessed and monitored every three months during trastuzumab treatment. Event of cardiotoxicity was defined as ≥10% decline in the LVEF from the baseline. The lower accepted normal limit of the LVEF was 50%. Results: The median baseline LVEF was 65% in both age cohorts (IQR 8% and 9% for older and younger patients respectively). Whereas, the median LVEF post-trastuzumab treatment was 51% and 55% in older and younger patients respectively (IQR 8%; p-value = 0.22), despite the fact that older patients had significantly lower exposure to anthracyclines compared to younger patients (60% and 84.1% respectively; p-value ˂0.001). 86.7% and 55.6% of older and younger patients, respectively, developed ≥10% decline in their LVEF from the baseline. Among those, only 29% of older and 27% of younger patients reached a LVEF value below 50% (p-value = 0.88). Statistically, age was the only factor that significantly correlated with trastuzumab induced cardiotoxicity (OR 4; p-value ˂0.012), but it did not increase the requirement for permanent discontinuation of treatment. A baseline LVEF value below 60% contributed to developing a post-treatment value below normal ranges (50%). Conclusion: Breast cancer patients aged 60 years and above in Kuwait were at 4-fold higher risk of developing ≥10% decline in their LVEF from the baseline than younger patients during trastuzumab treatment. Surprisingly, previous exposure to anthracyclines and multiple comorbidities were not associated with significant increased risk of cardiotoxicity.

Keywords: breast cancer, elderly, Trastuzumab, cardiotoxicity

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