Search results for: breast cancer cell lines

Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

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Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

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Authors: Mrinal Kanti Bhowmik, Kakali Das Jr., Barin Kumar De, Debotosh Bhattacharjee

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Breast cancer is the most common cancer and a leading cause of death for women in the 35 to 55 age group. Early detection of breast cancer can decrease the mortality rate of breast cancer. Mammography is considered as a ‘Gold Standard’ for breast cancer detection and a very popular modality, presently used for breast cancer screening and detection. The screening of digital mammograms often leads to over diagnosis and a consequence to unnecessary traumatic & painful biopsies. For that reason recent studies involving the use of thermal imaging as a screening technique have generated a growing interest especially in cases where the mammography is limited, as in young patients who have dense breast tissue. Tumor is a significant sign of breast cancer in both mammography and thermography. The tumors are complex in structure and they also exhibit a different statistical and textural features compared to the breast background tissue. Fractal geometry is a geometry which is used to describe this type of complex structure as per their main characteristic, where traditional Euclidean geometry fails. Over the last few years, fractal geometrics have been applied mostly in many medical image (1D, 2D, or 3D) analysis applications. In breast cancer detection using digital mammogram images, also it plays a significant role. Fractal is also used in thermography for early detection of the masses using the thermal texture. This paper presents an overview of the recent aspects and initiatives of fractals in breast cancer detection in both mammography and thermography. The scope of fractal geometry in automatic breast cancer detection using digital mammogram and thermogram images are analysed, which forms a foundation for further study on application of fractal geometry in medical imaging for improving the efficiency of automatic detection.

Keywords: fractal, tumor, thermography, mammography

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Authors: Ahmad Jawad Fardin

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Over 60% of patients with breast cancer in Afghanistan present late with advanced stage III and IV, a major cause for the poor survival rate. The objectives of this study were to identify the contributing factors for the diagnosis and treatment delay and its outcome. This cross-sectional study was conducted on 318 patients with histologically confirmed breast cancer in the oncology department of Jamhoriat hospital, which is the first and only national cancer center in Afghanistan; data were collected from medical records and interviews conducted with women diagnosed with breast cancer, linear regression and logistic regression were used for analysis. Patient delay was defined as the time from first recognition of symptoms until first medical consultation and doctor form first consultation with a health care provider until histological confirmation of breast cancer. The mean age of patients was 49.2+_ 11.5years. The average time for the final diagnosis of breast cancer was 8.5 months; most patients had ductal carcinoma 260.7 (82%). Factors associated with delay were low education level 76% poor socioeconomic and cultural conditions 81% lack of cancer center 73% lack of screening 19%. The stage distribution was as follows stage IV 4 22% stage III 44.4% stage II 29.3% stage I 4.3%. Complex associated factors were identified to delayed the diagnosis of breast cancer and increased adverse outcomes consequently. Raising awareness and education in women, the establishment of cancer centers and providing accessible diagnosis service and screening, training of general practitioners; required to promote early detection, diagnosis and treatment.

Keywords: delayed diagnosis and poor outcome, breast cancer in Afghanistan, poor outcome of delayed breast cancer treatment, breast cancer delayed diagnosis and treatment in Afghanistan

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Authors: Nadia H. Mohammed, Anmar Al-Taie, Fadia H. Al-Sultany

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Although breast cancer prevalence continues to increase, mortality has been decreasing as a result of early detection and improvement in adjuvant systemic therapy. Nevertheless, this disease required further efforts to understand and identify the associated potential risk factors that could play a role in the prevalence of this malignancy among Iraqi women. The objective of this study was to assess the perception of certain predictive risk factors on the prevalence of breast cancer types among a sample of Iraqi women diagnosed with breast cancer. This was a retrospective observational study carried out at National Cancer Research Center in College of Medicine, Baghdad University from November 2017 to January 2018. Data of 100 patients with breast cancer whose biopsies examined in the National Cancer Research Center were included in this study. Data were collected to structure a detailed assessment regarding the patients’ demographic, medical and cancer records. The majority of study participants (94%) suffered from ductal breast cancer with mean age 49.57 years. Among those women, 48.9% were obese with body mass index (BMI) 35 kg/m². 68.1% of them had positive family history of breast cancer and 66% had low parity. 40.4% had stage II ductal breast cancer followed by 25.5% with stage III. It was found that 59.6% and 68.1% had positive oestrogen receptor sensitivity and positive human epidermal growth factor (HER2/neu) receptor sensitivity respectively. In regard to the impact of prediction of certain variables on the incidence of ductal breast cancer, positive family history of breast cancer (P < 0.0001), low parity (P< 0.0001), stage I and II breast cancer (P = 0.02) and positive HER2/neu status (P < 0.0001) were significant predictive factors among the study participants. The results from this study provide relevant evidence for a significant positive and potential association between certain risk factors and the prevalence of breast cancer among Iraqi women.

Keywords: Ductal Breast Cancer, Hormone Sensitivity, Iraq, Risk Factors

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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: Nouf A. Aldarmahi, Nesrin I. Tarbiah, Nuha A. Alkhattabi, Huda F. Alshaibi

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Nigella sativa which is known as dark cumin is a well-known example for a widely applicable herbal medicine. Nigella sativa can be effective in a variety of diseases such as hypertension, diabetes, bronchitis, gastrointestinal upset, and cancer. The anticancer effect of Nigella sativa appeared to be mediated by immune-modulatory effect through stimulating human natural killer (NK) cells. This is a type of lymphocytes which is part of the innate immunity, also known as the first line of defense in the body against pathogens. This study investigated the effect of thymoquinone as a major component of Nigella sativa on the molecular cytotoxic pathway of NK cell and the role of thymoquinone therapeutic effect on NK cells. NK cells were cultured with breast tumor cells in different ways and cultured media was collected and the concentration of perforin, granzyme B and interferon-α were measured by ELISA. The cytotoxic effect of NK cells on breast tumor cells was enhanced in the presence of thymoquinone, with increased activity of perforin in NK cells. This improved anticancer effect of thymoquinone on breast cancer cells.

Keywords: breast cancer, cancer cells, natural killer cells, thymoquinone

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Karthik Mittal

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This study performs an unsupervised machine learning analysis to find clusters of related SNPs which highlight biological pathways that are important for the biological mechanisms of breast cancer. Studying genetic variations in isolation is illogical because these genetic variations are known to modulate protein production and function; the downstream effects of these modifications on biological outcomes are highly interconnected. After extracting the SNPs and their effect on different types of breast cancer using the MRBase library, two unsupervised machine learning clustering algorithms were implemented on the genetic variants: a k-means clustering algorithm and a hierarchical clustering algorithm; furthermore, principal component analysis was executed to visually represent the data. These algorithms specifically used the SNP’s beta value on the three different types of breast cancer tested in this project (estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer, and breast cancer in general) to perform this clustering. Two significant genetic pathways validated the clustering produced by this project: the MAPK signaling pathway and the connection between the BRCA2 gene and the ESR1 gene. This study provides the first proof of concept showing the importance of unsupervised machine learning in interpreting GWAS summary statistics.

Keywords: breast cancer, computational biology, unsupervised machine learning, k-means, PCA

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Authors: Najeeb Ullah Khan

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Background: The receptor activator NF-κβ ligand (RANKL) and Osteoprotegerin (OPG) polymorphisms have been associated with the progression of breast cancer to bone metastasis. Here, we aimed to investigate the association of RANKL and OPG gene polymorphism with breast to bone metastasis in the Pashtun population, Pakistan. Methods: Genomic DNA was obtained from all the study subjects (106 breast cancer, 58 breast to bone metastasis, and 51 healthy controls). RANKL (rs9533156) and OPG (rs2073618, rs3102735) polymorphisms were genotyped using Tetra-ARMS PCR. Results: Our results indicated that the frequencies of OPG (rs3102735) risk allele and genotypes carrying risk allele in breast cancer vs healthy control (C- p=0.005; CC- p=0.0208; TC- p=0.0181), bone metastasis vs healthy control (C- p=0.0211; CC- p=0.0153; TC- p=0.0775), and breast cancer vs breast to bone metastasis (C- p=0.0001; CC- p=0.0001; TC- p=0.001) were found significantly associated with disease risk. However, there was no significant association observed for OPG (rs2073618) risk allele and risk allele containing genotypes in all study groups. Similarly, RANKL (rs9533156) risk alleles and corresponding genotypes in breast cancer vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.0084), bone metastasis vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.5593), and breast cancer vs breast to bone metastasis (C- p=0.0185; CC- p=0.6077; TC- p=0.1436) showed significant association except for the risk allele carrying genotypes in breast cancer to bone metastasis (TC, p=0.1436; CC, p=0.6077). Conclusion: OPG (rs3102735) and RANKL (rs9533156) showed significant association with breast to bone metastasis, while OPG (rs2073618) didn’t show a significant association with breast to bone metastasis in Pashtun population of Pakistan. However, more investigation will be required to disseminate the results while gene sequencing or whole-exome sequencing.

Keywords: breast cancer, bone metastasis, OPG, RANKL, polymorphism

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Authors: Ya-Ching Wang, Yi-Maun Subeq

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Background: There is a lack of evidence to understand differences in risk for developing breast cancer between sexual minority women and heterosexual women in Taiwan. The purpose of this study is to compare differences in risk for developing breast cancer between the two groups of Taiwanese women. Methods: An online cross-sectional survey was used to collect data. A total of 238 Taiwanese women (mean age 30.69 years old, SD=8.231, range 20-60) were recruited between December 2016 and February 2017, including 115 heterosexual women and 123 sexual minority women. Results: There were no significant differences between heterosexual women and sexual minority women in body mass index, history of non-malignant breast disease, age at menarche and menopause, use of hormone replacement therapy, use of hormone replacement therapy, nor the prevalence of breast cancer. The sexual minority women had higher rates of current drinking, smoking and using breast-bindings and also reported exercise more a week; the heterosexual women had higher rates of pregnancy, children, breastfeed, miscarriages, abortion and use of birth control pills. Discussion/Conclusion: There were significant differences between heterosexual women and sexual minority women in reproductive factors and behavioral risk factors for the development of breast cancer. In particular, the finding that the sexual minority women had higher rate of using breast-bindings (56.6%) than the heterosexual women (4.7%) should be further explore, in order to understand whether long-term breast compression is associated with the development of breast cancer.

Keywords: breast cancer, risk, sexual orientation, Taiwan

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Authors: Suzan Ghaddar, Aline Pinon, Manuel Gallardo-villagran, Mona Diab-assaf, Bruno Therrien, Bertrand Liagre

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Colorectal cancer (CRC) is the third most common cancer and exhibits a consistently rising incidence worldwide. Despite notable advancements in CRC treatment, frequent occurrences of side effects and the development of therapy resistance persistently challenge current approaches. Eventually, innovations in focal therapies remain imperative to enhance the patient’s overall quality of life. Photodynamic therapy (PDT) emerges as a promising treatment modality, clinically used for the treatment of various cancer types. It relies on the use of photosensitive molecules called photosensitizers (PS), which are photoactivated after accumulation in cancer cells, to induce the production of reactive oxygen species (ROS) that cause cancer cell death. Among commonly used metal-based drugs in cancer therapy, ruthenium (Ru) possesses favorable attributes that demonstrate its selectivity towards cancer cells and render it suitable for anti-cancer drug design. In vitro studies using distinct arene-Ru complexes, encapsulating porphin PS, are conducted on human HCT116 and HT-29 colorectal cancer cell lines. These studies encompass the evaluation of the antiproliferative effect, ROS production, apoptosis, cell cycle progression, molecular localization, and protein expression. Preliminary results indicated that these complexes exert significant photocytotoxicity on the studied colorectal cancer cell lines, representing them as promising and potential candidates for anti- cancer agents.

Keywords: colorectal cancer, photodynamic therapy, photosensitizers, arene-ruthenium complexes, apoptosis

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Authors: Bhargavi Santebennur Dwarakanath, Praveen Vadakke Kamath, Savitha Janakiraman

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Cervical cancer is one of the leading causes of mortality in women and is the second most common malignancy worldwide. Lovastatin, a non polar, anticholesterol drug which also exerts antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties in human cervical cancer cell lines (HeLa). The growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cell lines were investigated by determining its influence on cytotoxicity, Mitochondrial Membrane Potential (MMP), DNA fragmentation and antioxidant property (Hydroxy radical scavenging effect and the levels of total reduced glutathione). Flow cytometry analysis by propidium iodide staining confirmed the induction of apoptotic cell death and revealed cell cycle arrest at G0/G1 phase. Results of the study give leads for anticancer effects of lovastatin and its potential efficacy in the chemotherapy of cervical cancer.

Keywords: apoptosis, Aspergillus terreus, cervical cancer, lovastatin

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Authors: Abuelquasim. M. Hassan, Namarig .S. Mohammed, Samah F. Mohammed, Wafaa. A. Mohammed, Wafaa M. Edriss, Amel A. Ahmed, Elfadil M. Abass

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Introduction: Cytomegalovirus (CMV), a common virus, usually causes asymptomatic infections in immunocompetent hosts; however, it may lead to serious complications especially in cancer patients. Objectives: This study was conducted to determine the seroprevalence of human cytomegalovirus (HCMV) among leukemia, breast and prostate cancer patients attending at Radiation Isotope-Center-Khartoum (RICK) from April to August 2016. Material and Methods: A total of 91 subjects were included: 30 leukemic, 22 breast cancer and 29 prostate cancer patients.10 of them were healthy and used as control group, serum samples were collected and tested for CMV IgG & IgM using enzyme-linked immune sorbent assay (ELISA). Result: Of the control group, 9/10 (9.9%) were seropositive for CMV IgG and 1/10 (1.09%) were sero positive for IgM. Also, all cancer groups demonstrated presence of IgG antibody classes as: The percentage of positive results in prostate, breast cancer and leukemia were 35.8 %, 37.2%, and 35.3% respectively. Conclusion: There was no significant correlation between leukemia, breast, prostate and HCMV.

Keywords: cytomegalovirus, serodiagnostic, breast cancer, leukemia

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Authors: Tolulope Allo, Mofoluwake P. Ajayi, Adenike E. Idowu, Emmanuel O. Amoo, Fadeke Esther Olu-Owolabi

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Breast cancer which was more prevalent in Europe and America in the past is gradually being mirrored across the world today with greater economic burden on low and middle income countries (LMCs). Breast cancer is the most common cancer among women globally and current studies have shown that a woman dies with the diagnosis of breast cancer every thirteen minutes. The economic cost of breast cancer is overwhelming particularly for developing economies. While it causes billion of dollar in losses of national income, it pushes millions of people below poverty line. This study examined the economic burden of breast cancer on Nigerian women, its impacts on their standard of living and its effects on Nigeria’s socio economic development. The study adopts a qualitative research approach using the in-depth interview technique to elicit valuable information from respondents with cancer experience from the Southern part of Nigeria. Respondents constituted women in their reproductive age (15-49 years) that have experienced and survived cancer and also those that are currently receiving treatment. Excerpts from the interviews revealed that the cost of treatment is one of the major factors contributing to the late presentation of breast cancer incidences among women as many of them could not afford to pay for their own treatment. The study also revealed that many women prefer to explore other options such as herbal treatments and spiritual consultations which is less expensive and affordable. The study therefore concludes that breast cancer diagnosis and treatment should be subsidized by the government in order to facilitate easy access and affordability thereby promoting early detection and reducing the economic burden of treatment on women.

Keywords: breast cancer, development, economic burden, women

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Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

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Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4, and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.

Keywords: hsa-miRNA-326 (miR-326), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Jaewoo Choi, Ki-Tae Hwang, Eunyoung Ko

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Backgrounds/Aims: Patients with breast cancer are currently classified according to TNM stage. Nevertheless, the actual volume would be mis-estimated, and it would bring on inappropriate diagnosis. Tridimensional volume-stage derived from the ellipsoid formula was presented as useful measure. Methods: The medical records of 480 consecutive breast cancer between January 2001 and March 2013 were retrospectively reviewed. All patients were divided into three groups according to tumor volume by receiver operating characteristic analysis, and the ranges of each volume-stage were that V1 was below 2.5 cc, V2 was exceeded 2.5 and below 10.9 cc, and V3 was exceeded 10.9 cc. We analyzed outcomes of volume-stage and compared disease-free survival (DFS) and overall survival (OS) between size-stage and volume-stage with variant intrinsic factor. Results: In the T2 stage, there were patients who had a smaller volume than 4.2 cc known as maximum value of T1. These findings presented that patients in T1c had poorer DFS than T2-lesser (mean of DFS 48.7 vs. 51.8, p = 0.011). Such is also the case in OS (mean of OS 51.1 vs. 55.3, p = 0.006). The cumulative survival curves for V1, V2 compared T1, T2 showed similarity in DFS (HR 1.9 vs. 1.9), and so did it for V3 compared T3 (HR 3.5 vs. 2.6) significantly. Conclusion: This study demonstrated that tumor volume had good feasibility on the prognosis of patients with breast cancer. We proposed that volume-stage should be considered for an additional stage indicator, particularly in early breast cancer.

Keywords: breast cancer, tridimensional volume of tumor, TNM stage, volume stage

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Authors: S. Subramaniam, J. S. A. Rao, P. Ramdas, K. R. Selvaduray, N. M. Han, M. K. Kutty, A. K. Radhakrishnan

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Immune system is a complex system where the immune cells have the capability to respond against a wide range of immune challenges including cancer progression. However, in the event of cancer development, tumour cells trigger immunosuppressive environment via activation of myeloid-derived suppressor cells and T regulatory (Treg) cells. The Treg cells are subset of CD4+ T lymphocytes, known to have crucial roles in regulating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Dysregulation of these mechanisms could lead to cancer progression and immune suppression. Recently, there are many studies reporting on the effects of natural bioactive compounds on immune responses against cancer. It was known that tocotrienol-rich-fraction consisting 70% tocotrienols and 30% α-tocopherol is able to exhibit immunomodulatory as well as anti-cancer properties. Hence, this study was designed to evaluate the effects of gamma-tocotrienol (G-T3) supplementation on T-reg cells in a syngeneic mouse model of breast cancer. In this study, female BALB/c mice were divided into two groups and fed with either soy oil (vehicle) or gamma-tocotrienol (G-T3) for two weeks followed by inoculation with tumour cells. All the mice continued to receive the same supplementation until day 49. The results showed a significant reduction in tumour volume and weight in G-T3 fed mice compared to vehicle-fed mice. Lung and liver histology showed reduced evidence of metastasis in tumour-bearing G-T3 fed mice. Besides that, flow cytometry analysis revealed T-helper cell population was increased, and T-regulatory cell population was suppressed following G-T3 supplementation. Moreover, immunohistochemistry analysis showed that there was a marked decrease in the expression of FOXP3 in the G-T3 fed tumour bearing mice. In conclusion, the G-T3 supplementation showed good prognosis towards breast cancer by enhancing the immune response in tumour-bearing mice. Therefore, gamma-T3 can be used as immunotherapy agent for the treatment of breast cancer.

Keywords: breast cancer, gamma tocotrienol, immune suppression, supplement

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Authors: Mahsa Taghavi

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In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

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Authors: Ines Zemni, Maher Slimane, Jamel Ben Hassouna, Khaled Rahal

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Background: Neurofibromatosis type 1 (NF1) is a genetic disease, which is associated with an increased risk of developing different malignancies including breast cancer. The association between NF1 band breast sarcoma is a rare entity. Herein we present a 25-year-old woman with NF1 who had fibrosarcoma of the left breast. Case presentation: The patient has multiple thoraco-abdominal 'café au lait' spots. Clinical examination showed a lump of the left breast measuring 9 cm of diameter, which was noticed for 6 months. There was a left inguinal mass of 6 cm of diameter. The patient underwent first a left lumpectomy. Histopathological exam revealed a high-grade fibrosarcoma of the left breast measuring 7.5 cm. Three months later, the patient underwent a left mastectomy and excision of the inguinal mass, which was a neurofibroma. An adjuvant chemotherapy and radiation therapy were indicated, but not applied because of the timeout. The patient is now alive after a follow up of 6 years, with no loco-regional recurrence or metastasis. Conclusion: The relationship between NF1 and breast cancer need to be more clarified by further studies. Establishing a specific screening program of these patients may help to make an earlier diagnosis of breast cancer.

Keywords: neurofibromatosis, breast, sarcoma, cancer

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Authors: Shaik Asha Begum, S. Joshna Rani, Shaik Abdul Rahaman

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INTRODUCTION: Breast cancer is a disease that creates in breast cells. "KAP" study estimates the Knowledge, Attitude, and Practices of a local area. More than 1.5 million ladies (25% of all ladies with malignancy) are determined to have bosom disease consistently all through the world. Understanding the degrees of Knowledge, Attitude and Practice will empower a more effective cycle of mindfulness creation as it will permit the program to be custom-made all the more properly to the necessities of the local area. OBJECTIVES: The objective of this study is to assess the knowledge on signs and symptoms, risk factors, provide awareness on the practicing of the early detection techniques of breast cancer and provide knowledge on the overall breast cancer including preventive techniques. METHODOLOGY: This is an expressive cross-sectional investigation. This investigation of KAP was done in the Nirmala Educational Institutions from January to April 2021. A total of 300 participants are included from women students in pharmacy graduates & lecturers, and also from graduates other than the pharmacy. The examiners are taken from the BCAM (Breast Cancer Awareness Measure), tool compartment (Version 2). RESULT: According to the findings of the study, the majority of the participants were not well informed about breast cancer. A lump in the breast was the most commonly mentioned sign of breast cancer, followed by pain in the breast or nipple. The percentage of knowledge related to the breast cancer risk factors was also very less. The correct answers for breast cancer risk factors were radiation exposure (58.20 percent), a positive family history (47.6 percent), obesity (46.9 percent), a lack of physical activity (43.6 percent), and smoking (43.2 percent). Breast cancer screening, on the other hand, was uncommon (only 30 and 11.3 percent practiced clinical breast examination and mammography respectively). CONCLUSION: In this study, the knowledge on the signs and symptoms, risk factors of breast cancer - pharmacy graduates have more knowledge than the non-pharmacy graduates but in the preventive techniques and early detective tools of breast cancer -had poor knowledge in the pharmacy and non-pharmacy graduate. After the awareness program, pharmacy and non-pharmacy graduates got supportive knowledge on the preventive techniques and also practiced the early detective techniques of breast cancer.

Keywords: breast cancer, mammography, KAP study, early detection

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Authors: Huma Naqeeb

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Epidemiological studies have shown the robust link between breast cancer and dietary pattern. There has been no previous study conducted in Pakistan, which specifically focuses on dietary patterns among breast cancer women. This study aims to examine the association of breast cancer with dietary patterns among Pakistani women. This case-control research was carried in multiple tertiary care facilities. Newly diagnosed primary breast cancer patients were recruited as cases (n = 408); age matched controls (n = 408) were randomly selected from the general population. Data on required parameters were systematically collected using subjective and objective tools. Factor and Principal Component Analysis (PCA) techniques were used to extract women’s dietary patterns. Four dietary patterns were identified based on eigenvalue >1; (i) veg-ovo-fish, (ii) meat-fat-sweet, (iii) mix (milk and its products, and gourds vegetables) and (iv) lentils - spices. Results of the multiple regressions were displayed as adjusted odds ratio (Adj. OR) and their respective confidence intervals (95% CI). After adjusted for potential confounders, veg-ovo-fish dietary pattern was found to be robustly associated with a lower risk of breast cancer among women (Adj. OR: 0.68, 95%CI: (0.46-0.99, p<0.01). The study findings concluded that attachment to the diets majorly composed of fresh vegetables, and high quality protein sources may contribute in lowering the risk of breast cancer among women.

Keywords: breast cancer, dietary pattern, women, principal component analysis

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Authors: Alaa M. M. Badr Eldin, Marwa I. Ezzat, Mohammed S. Sedeek, Manal S. Afifi, Omar M. Sabry

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Cytotoxic activity of the total methanol extract against breast cancer cell line MCF-7 was amazing IC50 at 54 ug/ml. 130 polyphenolic compounds were tentatively identified in pomegranate peel (Punica granatum L.) methanol extract using HPLC-MS/MS technique. The antiestrogenic activity of the polyphenolic constituents found in pomegranate extract was confirmed experimentally in-vitro and by the in-silico molecular docking using gallagic acid, ellagic acid, and Punicalagin as these are considered model compounds confirmed in pomegranate peel extract. The methanolic extract was found to suppress ER, TGF-β, and NF-kB in-vitro gene expression strongly, and that was verified by qPCR and Western Blot gel electrophoresis techniques.

Keywords: HPLC-MS/MS, pomegranate, breast cancer, ovarian cancer, ER, TGF-β, NF-kB

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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: Rana F. Obeidat, Suzanne S. Dickerson, Gregory G. Homish, Nesreen M. Alqaissi, Robin M. Lally

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Background: Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early stage breast cancer and surgical treatment. Objective: To gain understanding of the diagnosis and surgical treatment experience of Jordanian women diagnosed with early stage breast cancer. Methods: An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Results: Fear had a profound effect on Jordanian women’s stories of diagnosis and surgical treatment of early stage breast cancer. Women’s experience with breast cancer and its treatment was shaped by their pre-existing fear of breast cancer, the disparity in the quality of care at various health care institutions, and sociodemographic factors (e.g., education, age). Conclusions: Early after the diagnosis, fear was very strong and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the health care system, surgeons, family, friends, and/or neighbors, and often accepted treatment offered by their surgeons without questioning. Implications for practice: Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and support necessary to help them cope with their illness.

Keywords: breast cancer, early stage, Jordanian, experience, phenomenology

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Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

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Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

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Authors: Li Hoon Lim, Nur Farhanah Said, Katie Simmons, Eric Pei Ping Pang, Sharon Mei Mei Wong

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Background and Purpose: Research regarding the sexual impact of breast cancer treatment on Asian women is both sensitive and scarce. This study aims to assess and evaluate the sexual health needs and concerns of breast cancer radiotherapy patients. It is hoped that awareness will be increased and an appropriate intervention can be developed to address the needs of future breast cancer patients. Methods: 110 consecutive unselected breast cancer patients were recruited prospectively. Questionnaires were administered once for patient undergoing radiotherapy to the breast. This study employed an anonymous questionnaire; any breast radiotherapy patient who can read English can voluntarily receive and complete the survey. The questionnaire consisted of items addressing demographics, potential informational needs, and educational preferences. Results: Patients’ interest to address sexual concerns decreases with age (p=0.024). Coherently, sexual concerns of patients are reported to decrease with age (p=0.015) where 70% of all respondents below age 50 [age 20-29 (60%); 30-39 (56.3%); 40-49(55.1%)] have started to have sexual concerns regarding their treatment effects on their sexual health. Patients who underwent breast conservation surgery (42.2%) and reconstruction surgery (83.3%) were more likely to have concerns about sexual health versus patients who underwent mastectomy (36.7%) (p=0.032). 74.2% of patients with sexual concern regardless of age would initiate conversation with their healthcare providers (p < 0.001). Conclusions: The results showed a staggering interest of female patients wanting information on this area which would not only boost their confidence and body image but also address concerns of the effect of breast radiotherapy on sexual health during their treatment.

Keywords: breast cancer, breast radiotherapy, sexual health, sexual impact

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Authors: Kabange Kasumbwe, Viresh Mohanlall, Bharti Odhav, Venu Narayanaswamy

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Coumarins are naturally occurring plant metabolites known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological and biochemical properties and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1-CMRN7 were synthesized and evaluated for their anticancer activity. The cytotoxicity potential of the test compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer) and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay keeping doxorubicin as standard drug. The apoptotic potential of the coumarin compounds was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential; pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. The synthetic coumarin has strongly suppressed the cell proliferation of UACC-62 (Melanoma) and MCF-7 (Breast) Cancer cells, the higher toxicity of these compounds against UACC-62 (Melanoma) and MCF-7 (Breast) were CMRN3, CMRN4, CMRN5, CMRN6. However, compounds CMRN1, CMRN2, and CMRN7 had no significant inhibitory effect. Furthermore the active compounds CMRN3, CMRN4, CMRN5, CMRN6 exerted antiproliferative effects through apoptosis induction against UACC-62 (Melanoma), suggesting their potential could be considered as attractive lead molecules in the future for the development of potential anticancer agents since one of the important criteria in the development of therapeutic drugs for cancer treatment is to have high selectivity and less or no side-effects on normal cells and these compounds had no inhibitory effect against the PBMC cells.

Keywords: coumarin, MTT, apoptosis, cytotoxicity

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Authors: Hamza Assiry, Gamal A. Mohamed, Sabrin R. M. Ibrahim, Hossam M. Abdallah

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Chemical investigation of the aerial parts of Barleria trispinosa(Forssk.) Vahl. resulted in isolation of four major iridoids that were identified as 6,8-O,O-diacetylshanhiside methyl ester (acetyl barlerin) (1), 8-O-acetylshanzhiside methyl ester (barlerin) (2), shanzhiside methyl ester (3), and 6- ⍺ -L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester (4). The isolated compounds were confirmed by detailed one and two-dimensional NMR. Isolated compounds were tested for their cytotoxic activity on breast cancer (MCF-7, MDA-MB-231) and colon cancer (LS174T) cell linesusing sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards MDA-MB-231 cell line with IC5016.7 ± 2.7µg / mL compared to doxorubicin whereas compounds 2, showed moderate cytotoxic potential with IC5021.2 ± 1.9µg / mL on MCF-7. The other compounds showed moderate activity on the tested cell lines.

Keywords: acanthaceae, cytotoxicity, metabolites, barleria trispinosa

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Authors: Sajadian Akram, Tavasoli F.

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Breast cancer is the second most common cancer in the world and certainly the most frequent cancer mostly among women. This study was aimed to compare the effectiveness of individual counseling and group narrative therapy on female patients' life expectancy afflicted by breast cancer. The present study is a pre-test-post-test clinical trial. Fifty-five patients with breast cancer were randomly selected in the follow-up period and after their active medical treatment completion. Then, they were randomly divided into two groups: individual counseling and group counseling. Herth hope index (HHI) was used to measure the patients' hope level. Data were analyzed using t-test and SPSS software. hope rate was statistically significant in both groups receiving individual and group narrative therapy in the post-test compared to the pre-test (P <00000). Moreover, the comparative evaluation of hope in both groups (individual & group counseling) in the post-test showed that group narrative counseling is more effective than individual narrative counseling (P <00000). Conclusion: Narrative therapy promotes hope in breast cancer patients effectively. Due to the nature of breast cancer and its psychological effects in the post-treatment period, providing narrative group therapy can improve life quality. Patients' life quality changes in tandem with changes in hope.

Keywords: hope, narrative therapy, counseling, breast cancer

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Authors: Lauren Zammerilla Westcott, Ronald C. Jones, James W. Fleshman

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The surgical treatment of breast cancer has rapidly evolved over the past 50 years, progressing from Halsted’s radical mastectomy to a public campaign of surgical options, aesthetic reconstruction, and patient empowerment. This article examines the happenings that led to the transition of breast surgery as a subset of general surgery to its own specialized field. Sparked by the research of Dr. Bernard Fisher and the first National Surgical Adjuvant Breast and Bowel Project trial in 1971, the field of breast surgery underwent significant growth over the next several decades, enabling general surgeons to limit their practices to the breast. High surgical volumes eventually led to the development of the first formal breast surgical oncology fellowship in a large community-based hospital at Baylor University Medical Center in 1982. The establishment of the American Society of Breast Surgeons, as well several landmark clinical trials and public campaign efforts, further contributed to the advancement of breast surgery, making it the specialized field of the current era.

Keywords: breast cancer, breast fellowship, breast surgery, surgical history

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