Search results for: cancer biomarker

Authors: L. Szymanski, S. Wiak, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

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There exist more than one hundred different types of cancer, and therefore no particular treatment is offered to people struggling with this disease. The character of treatment proposed to a patient will depend on a variety of factors such as type of the cancer diagnosed, advancement of the disease, its location in the body, as well as personal preferences of a patient. None of the commonly known methods of cancer-fighting is recognised as a perfect cure, however great advances in this field have been made over last few decades. Once a patient is diagnosed with cancer, he is in need of medical care and professional treatment for upcoming months, and in most cases even for years. Among the principal modes of treatment offered by medical centres, one can find radiotherapy, chemotherapy, and surgery. All of them can be applied separately or in combination, and the relative contribution of each is usually determined by medical specialist in agreement with a patient. In addition to the conventional treatment option, every day more complementary and alternative therapies are integrated into mainstream care. There is one promising cancer modality - hyperthermia therapy which is based on exposing body tissues to high temperatures. This treatment is still being investigated and is not widely available in hospitals and oncological centres. There are two kinds of hyperthermia therapies with direct and indirect heating. The first is not commonly used due to low efficiency and invasiveness, while the second is deeply investigated and a variety of methods have been developed, including ultrasounds, infrared sauna, induction heating and magnetic hyperthermia. The aim of this work was to examine possibilities of heating magnetic nanoparticles under the influence of electromagnetic field for cancer treatment. For this purpose, multiwalled carbon nanotubes used as nanocarriers for iron particles were investigated for its heating properties. The samples were subjected to an alternating electromagnetic field with frequency range between 110-619 kHz. Moreover, samples with various concentrations of carbon nanotubes were examined. The lowest frequency of 110 kHz and sample containing 10 wt% of carbon nanotubes occurred to influence the most effective heating process. Description of hyperthermia therapy aiming at enhancing currently available cancer treatment was also presented in this paper. Most widely applied conventional cancer modalities such as radiation or chemotherapy were also described. Methods for overcoming the most common obstacles in conventional cancer modalities, such as invasiveness and lack of selectivity, has been presented in magnetic hyperthermia characteristics, which explained the increasing interest of the treatment.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, ligands

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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: Daniela Prado, Lexi Frankel, Amalia Ardeljan, Lokesh Manjani, Matthew Cardeiro, Omar Rashid

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Background: Clostridium difficile (C. diff) is a gram-positive bacterium that is known to cause life-threatening diarrhea and severe inflammation of the colon. It originates as an alteration of the gut microbiome and can be transmitted through spores. Recent studies have shown a high association between the development of C. diff in cancer patients due to extensive hospitalization. However, research is lacking regarding C. diff’s association in the causation or prevention of cancer. The objective of this study was to therefore assess the correlation between Clostridium difficile infection (CDI) and the incidence of bone cancer. Methods: This retrospective analysis used data provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with C. diff using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Standard statistical methods were used. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 78863 patients in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bone cancer was 659 patients (0.835%) in the C. diff group compared to 1941 patients (2.461%) in the control group. The difference was statistically significant by a P-value < 2.2x10^-16 with an odds ratio (OR)= 0.33 (0.31-0.37) with a 95% confidence interval (CI). Treatment for CDI was analyzed for both C. diff infected and noninfected populations. 91 out of 16,676 (0.55%) patients with a prior C. diff infection and treated with antibiotics were compared to the control group were 275 out of 16,676 (1.65%) patients with no history of CDI and received antibiotic treatment. Results remained statistically significant by P-value <2.2x10-16 with an OR= 0.42 (0.37, 0.48). and a 95% CI. Conclusion: The study shows a statistically significant correlation between C. diff and a reduced incidence of bone cancer. Further evaluation is recommended to assess the potential of C. difficile in reducing bone cancer incidence.

Keywords: bone cancer, colitis, clostridium difficile, microbiome

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Sung Yong Kim, Byung Joo Song

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Background: Circulating 25-hydroxyvitamin D (25(OH)D) levels has been considered to be inversely related to breast cancer development, recurrence risk, and mortality. Mean vitamin D levels in Korean population is lower than western countries due to higher incidence of lactose intolerance and lower exposure to sunlight. The purpose of this study was to assess incidence of 25(OH)D deficiency at diagnosis and after adjuvant chemotherapy and to investigate the correlation serum 25(OH)D levels with clinicopathologic features. Methods: From December 2011 to October 2012, 280 breast cancer patients seen at a single tertiary cancer center were enrolled. Serum 25(OH)D was measured at the time of surgery and after completion of adjuvant chemotherapy. Statistical analyses used chi-square test, Fisher's exact test, t-test, and ANOVA. Results: Mean serum 25(OH)D was 18.5 ng/ml. The 25(OH)D levels were deficient (<20 ng/ml) in 190 patients (67.9%), insufficient (20-29 ng/ml) in 51 patients(18.2%), and sufficient (30-150 ng/ml) in 39 patients(13.9%). A notable decrease in 25(OH)D concentration was observed(p<0.001) after chemotherapy but was not related to chemotherapy regimens. It was found significant lower 25(OH)D levels at winter season(from October to March, p=0.030). Subjects with invasive carcinoma (IDC or ILC) had significantly lower circulating levels of 25(OH)D than those with ductal carcinoma in situ(DCIS) (p=0.010). Patients with larger tumor size tends to have lower serum 25(OH)D but there were no statistical significance. Conclusions: Most of the breast cancer patients showed deficient or insufficient serum 25(OH)D concentration. Incidence of vitamin D deficiency was higher in invasive carcinoma than DCIS. Serum 25(OH)D levels were decreased after chemotherapy. Consideration should be given to the supplement of vitamin D to those patients.

Keywords: breast neoplasms, vitamin D, Korean population, breast cancer

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Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from Khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, miR-146a rs2910164 polymorphism, p53 codon 72 polymorphism, tumors, pathology reports

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Authors: Nana Gorgiladze, Tamar Gaprindashvili, Mikheil Shavdia, Zurab Pagava

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Introduction/Purpose Chemotherapy is a common treatment for breast cancer, but it can also cause damage to the heart and blood vessels. This damage, known as cancer therapy-related cardiovascular toxicity (CTR-CVT), can increase the risk of heart failure and death in breast cancer patients. The left ventricle is often affected by CTR-CVT, but the right ventricle (RV) may also be vulnerable to CTR-CVT and may show signs of dysfunction before the left ventricle. The study aims to investigate how the RV function changes during chemotherapy for breast cancer by using conventional echocardiographic and global longitudinal strain (GLS) techniques. By measuring the GLS strain of the RV, researchers tend to detect early signs of CTR-CVT and improve the management of breast cancer patients. Methods The study was conducted on 28 women with low cardiovascular risk who received anthracycline chemotherapy for breast cancer. Conventional 2D echocardiography (LVEF, RVS’, TAPSE) and speckle-tracking echocardiography (STE) measurements of the left and right ventricles (LVGLS, RVGLS) were used to assess cardiac function before and after chemotherapy. All patients had normal LVEF at the beginning of the study. Cardiotoxicity was defined as a new LVEF reduction of 10 percentage points to an LVEF of 40-49% and/or a new decline in GLS of 15% from baseline, as proposed by the most recent cardio-oncology guideline. ResultsThe research found that the LVGLS decreased from -21.2%2.1% to -18.6%2.6% (t-test = -4.116; df = 54, p=0.001). The change in value LV-GLS was 2.6%3.0%. The mean percentage change of the LVGLS was 11,6%13,3%; p=0.001. Similarly, the right ventricular global longitudinal strain (RVGLS) decreased from -25.2%2.9% to -21.4%4.4% (t-test = -3.82; df = 54, p=0.001). The RV-GLS value of change was 3.8%3.6%. Likewise, the percentage decrease of the RVGLS was 15,0%14,3%, p=0.001.However, the measurements of the right ventricular systolic function (RVS) and tricuspid annular plane systolic excursion (TAPSE) were insignificant, and the left ventricular ejection fraction ( LVEF) remained unchanged.

Keywords: cardiotoxicity, chemotherapy, GLS, right ventricle

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Authors: E. Njuguna, S. Ilovi, P. Muiruri, K. Mutai, J. Kinuthia, P. Njoroge

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Introduction: Cervical cancer is the commonest cause of cancer-related morbidity and mortality among women in developing countries in Sub Saharan Africa. Screening for cervical cancer in all women regardless of HIV status is crucial for the early detection of cancer of the cervix when treatment is most effective in curing the disease. It is particularly more important to screen HIV infected women as they are more at risk of developing the disease and progressing faster once infected with HPV (Human Papilloma Virus). We aimed to determine the factors affecting the utilization of cervical cancer screenings among HIV infected women above 18 years of age at Kenyatta National Hospital (KNH) Comprehensive Care Center (CCC). Materials and Methods: A cross-sectional mixed quantitative and qualitative study involving randomly and purposefully selected HIV positive female respectively was conducted. Qualitative data collection involved 4 focus group discussions of eligible female participants while quantitative data were acquired by one to one interviewer administered structured questionnaires. The outcome variable was the utilization of cervical cancer screening. Data were entered into Access data base and analyzed using Stata version 11.1. Qualitative data were analyzed after coding for significant clauses and transcribing to determine themes arising. Results: We enrolled a total of 387 patients, mean age (IQ range) 40 years (36-44). Cervical cancer screening utilization was 46% despite a health care provider recommendation of 85%. The screening results were reported as normal in 72 of 81 (88.9%) and abnormal 7 of 81(8.6%) of the cases. Those who did not know their result were 2 of 81(2.5%). Patients were less likely to utilize the service with increasing number of years attending the clinic (OR 0.9, 95% CI 0.86-0.99, p-value 0.02), but more likely to utilize the service if recommendation by a staff was made (OR 10, 95% CI 4.2-23.9, p<0.001), and if cervical screening had been done before joining KNH CCC (OR 2.9, 95% CI 1.7-4.9, p < 0.001). Similarly, they were more likely to rate the services on cervical cancer screening as good (OR 5.0, 95% CI 1.7-3.4, p <0.001) and very good (OR 8.1, 95% CI 2.5-6.1, p<0.001) if they had utilized the service. The main barrier themes emerging from qualitative data included fear of screening due to excessive pain or bleeding, lack of proper communication on screening procedures and increased waiting time. Conclusions: Utilization of cervical cancer screening services was low despite health care recommendation. Patient socio-demographic characteristics did not influence whether or not they utilized the services, indicating the important role of the health care provider in the referral and provision of the service.

Keywords: cervical, cancer, HIV, women, comprehensive care center

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Authors: Patricia O. Carvalho, Marcia C. F. Messias, Laura Credidio, Carlos A. R. Martinez

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Lipidomic strategy can provide important information regarding cancer pathogenesis mechanisms and could reveal new biomarkers to enable early diagnosis of rectal adenocarcinoma (RAC). This study set out to evaluate lipoperoxidation biomarkers, and lipidomic signature by gas chromatography (GC) and electrospray ionization-qToF-mass spectrometry (ESI-qToF-MS) combined with multivariate data analysis in plasma from 23 RAC patients (early- or advanced-stages cancer) and 18 healthy controls. The most abundant ions identified in the RAC patients were those of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) while those of lisophosphatidylcholine (LPC), identified as LPC (16:1), LPC (18:1) and LPC (18:2), were down-regulated. LPC plasmalogen containing palmitoleic acid (LPC (P-16:1)), with highest VIP score, showed a low tendency in the cancer patients. Malondialdehyde plasma levels were higher in patients with advanced cancer (III/IV stages) than in the early stages groups and the healthy group (p<0.05). No differences in F2-isoprostane levels were observed between these groups. This study shows that the reduction in plasma levels of LPC plasmalogens associated to an increase in MDA levels may indicate increased oxidative stress in these patients and identify the metabolite LPC (P-16:1) as new biomarkers for RAC.

Keywords: biomarkers, lipidomic, plasmalogen, rectal adenocarcinoma

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: Youn Young Shim, Ji Hye Kim, Jae Youl Cho, Martin J. T. Reaney

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Flaxseed (Linum usitatissimum L.) is gaining popularity in the food industry as a superfood due to its health-promoting properties. The flax plant synthesizes an array of biologically active cyclic peptides or linusorbs (LOs, a.k.a. cyclolinopeptides) from three or more ribosome-derived precursors. [1–9-NαC]-linusorb B3 and [1–9-NαC]-linusorb B2, suppress immunity, induce apoptosis in human epithelial cancer cell line (Calu-3) cells, and inhibit T-cell proliferation, but the mechanism of LOs action is unknown. Using gene expression analysis in nematode cultures and human cancer cell lines, we have observed that LOs exert their activity, in part, through induction of apoptosis. Specific LOs’ properties include: 1) distribution throughout the body after flaxseed consumption; 2) induce heat shock protein (HSP) 70A production as an indicator of stress and address the issue in Caenorhabditis elegans (exposure of nematode cultures to [1–9-NαC]-linusorb B3 induced a 30% increase in production of the HSP 70A protein); 3) induce apoptosis in Calu-3 cells; and 4) modulate regulatory genes in microarray analysis. These diverse activities indicate that LOs might induce apoptosis in cancer cells or act as versatile platforms to deliver a variety of biologically active molecules for cancer therapy.

Keywords: flaxseed, linusorb, cyclic peptide, orbitides, heat shock protein, apoptosis, anti-cancer

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

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

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

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: L. M. Al-Harbi, A. M. Shokry, J. S. M. Sabir, A. Chaudhary, J. Manikandan, K. S. Saini

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Breast cancer is the second most common cause of cancer death worldwide and is the most common malignancy among Saudi females. During breast carcinogenesis, a wide-array of cytogenetic changes involving deletions, or amplification, or translocations, of part or whole of chromosome regions have been observed. Because of the limitations of various earlier technologies, newer tools are developed to scan for changes at the genomic level. Recently, Array Comparative Genomic Hybridization (aCGH) technique has been applied for detecting segmental genomic alterations at molecular level. In this study, aCGH was performed on twenty breast cancer tumors and their matching non-tumor (normal) counterparts using the Agilent 2x400K. Several regions were identified to be either amplified or deleted in a tumor-specific manner. Most frequent alterations were amplification of chromosome 1q, chromosome 8q, 20q, and deletions at 16q were also detected. The amplification of genetic events at 1q and 8q were further validated using FISH analysis using probes targeting 1q25 and 8q (MYC gene). The copy number changes at these loci can potentially cause a significant change in the tumor behavior, as deletions in the E-Cadherin (CDH1)-tumor suppressor gene as well as amplification of the oncogenes-Aurora Kinase A. (AURKA) and MYC could make these tumors highly metastatic. This study validates the use of aCGH in Saudi breast cancer patients and sets the foundations necessary for performing larger cohort studies searching for ethnicity-specific biomarkers and gene copy number variations.

Keywords: breast cancer, molecular biology, ecology, environment

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Monika Verma, Renuka Sharma, B. R. Gulati, Namita Singh

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In combination therapy, two chemotherapeutic agents work together in a collaborative action. It has appeared as one of the promising approaches to improve anti-cancer treatment efficacy. In the present investigation, piperine (P-NPS), paclitaxel (PTX NPS), and a combination of both, piperine-paclitaxel nanoparticle (Pip-PTX NPS), were made by the nanoprecipitation method and later characterized by PSA, DSC, SEM, TEM, and FTIR. All nanoparticles exhibited a monodispersed size distribution with a size of below 200 nm, zeta potential ranges from (-30-40mV) and a narrow polydispersity index (>0.3) of the drugs. The average encapsulation efficiency was found to be between 80 and 90%. In vitro release of drugs for nanoparticles was done spectrophotometrically. FTIR and DSC results confirmed the presence of the drug. The Pip-PTX NPS significantly inhibit cell proliferation as compared to the native drugs nanoparticles in the breast cancer cell line MCF-7. In addition, Pip-PTX NPS suppresses cells in colony formation and soft gel agar assay. Scratch migration and Transwell chamber invasion assays revealed that combined nanoparticles reduce the migration and invasion of breast cancer cells. Morphological studies showed that Pip-PTX NPS penetrates the cells and induces apoptosis, which was further confirmed by DNA fragmentation, SEM, and western blot analysis. Taken together, Pip-PTX NPS inhibits cell proliferation, anchorage dependent and anchorage independent cell growth, reduces migration and invasion, and induces apoptosis in cells. These findings support that combination therapy using Pip-PTX NPS represents a potential approach and could be helpful in the future for breast cancer therapy.

Keywords: piperine, paclitaxel, breast cancer, apoptosis

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Authors: Tayyaba Bibi, Jenny Ronan, Robert Hernan, Kathleen O’Rourke, Brendan McHugh, Evin McGovern, Michelle Giltrap, Gordon Chambers, James Wilson

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Sediment contamination is a major source of ecosystem stress and has received significant attention from the scientific community. Both the Water Framework Directive (WFD) and Marine Strategy Framework Directive (MSFD) require a robust set of tools for biological and chemical monitoring. For the MSFD in particular, causal links between contaminant and effects need to be assessed. Appropriate assessment tools are required in order to make an accurate evaluation. In this study, a range of recommended sediment bioassays and chemical measurements are assessed in a number of potentially impacted and lowly impacted locations around Ireland. Previously, assessment indices have been developed on individual compartments, i.e. contaminant levels or biomarker/bioassay responses. A number of assessment indices are applied to chemical and ecotoxicological data from the Seachange project (Project code) and compared including the metal pollution index (MPI), pollution load index (PLI) and Chapman index for chemistry as well as integrated biomarker response (IBR). The benefits and drawbacks of the use of indices and aggregation techniques are discussed. In addition to this, modelling of raw data is investigated to analyse links between contaminant and effects.

Keywords: bioassays, contamination indices, ecotoxicity, marine environment, sediments

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Authors: O. J. Akinsola, Yinan Zheng, Rose Anorlu, F. T. Ogunsola, Lifang Hou, Robert Leo-Murphy

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Cervical Cancer (CC) is the 2nd most common cancer among women living in low and middle-income countries, with no associated symptoms during formative periods. With the advancement and innovative medical research, there are numerous preventive measures being utilized, but the incidence of cervical cancer cannot be truncated with the application of only screening tests. The mortality associated with this invasive cervical cancer can be nipped in the bud through the important role of early-stage detection. This study research selected an array of different top features selection techniques which was aimed at developing a model that could validly diagnose the risk factors of cervical cancer. A retrospective clinic-based cohort study was conducted on 178 HIV-associated cervical cancer patients in Lagos University teaching Hospital, Nigeria (U54 data repository) in April 2022. The outcome measure was the automated prediction of the HIV-associated cervical cancer cases, while the predictor variables include: demographic information, reproductive history, birth control, sexual history, cervical cancer screening history for invasive cervical cancer. The proposed technique was assessed with R and Python programming software to produce the model by utilizing the classification algorithms for the detection and diagnosis of cervical cancer disease. Four machine learning classification algorithms used are: the machine learning model was split into training and testing dataset into ratio 80:20. The numerical features were also standardized while hyperparameter tuning was carried out on the machine learning to train and test the data. Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), and K-Nearest Neighbor (KNN). Some fitting features were selected for the detection and diagnosis of cervical cancer diseases from selected characteristics in the dataset using the contribution of various selection methods for the classification cervical cancer into healthy or diseased status. The mean age of patients was 49.7±12.1 years, mean age at pregnancy was 23.3±5.5 years, mean age at first sexual experience was 19.4±3.2 years, while the mean BMI was 27.1±5.6 kg/m2. A larger percentage of the patients are Married (62.9%), while most of them have at least two sexual partners (72.5%). Age of patients (OR=1.065, p<0.001**), marital status (OR=0.375, p=0.011**), number of pregnancy live-births (OR=1.317, p=0.007**), and use of birth control pills (OR=0.291, p=0.015**) were found to be significantly associated with HIV-associated cervical cancer. On top ten 10 features (variables) considered in the analysis, RF claims the overall model performance, which include: accuracy of (72.0%), the precision of (84.6%), a recall of (84.6%) and F1-score of (74.0%) while LR has: an accuracy of (74.0%), precision of (70.0%), recall of (70.0%) and F1-score of (70.0%). The RF model identified 10 features predictive of developing cervical cancer. The age of patients was considered as the most important risk factor, followed by the number of pregnancy livebirths, marital status, and use of birth control pills, The study shows that data mining techniques could be used to identify women living with HIV at high risk of developing cervical cancer in Nigeria and other sub-Saharan African countries.

Keywords: associated cervical cancer, data mining, random forest, logistic regression

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Shannon Hearney, Jeffrey Hoch

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Pancreatic cancer is a notoriously costly and deadly form of cancer. Many types of treatment centers exist for patients to seek care from, including high-volume centers which have shown promise to provide the highest quality of care. While it may be true that this type of center provides the best care it is unclear if that care is cost-effective. Studies in the US have confirmed that high-volume hospitals do provide higher quality of care but have shown inconsistencies in the cost-effectiveness of that care. Other studies, like those from Finland have shown that high-volume centers had lower mortality and lower costs than low-volume centers. This paper thus seeks to review the current scientific literature to better understand if high-volume centers are cost-effective in delivering care in both a European setting and in the US. A review of major reference databases such as Medline, Embase and PubMed will be conducted for cost-effectiveness studies on the surgical treatment of pancreatic cancer at high-volume centers. Possible MeSH terms to be included, but not limited to, are: “pancreatic cancer”, “cost analysis”, “cost-effectiveness”, “economic evaluation”, “pancreatic neoplasms”, “surgical”, and “high-volume”. Studies must also have been available in the English language. This review will encompass European scientific literature, as well as those in the US. Based on our preliminary findings, we anticipate high-volume hospitals to provide better care at greater costs. We anticipate that high-volume hospitals may be cost-effective in different contexts depending on the national structure of a healthcare system. Countries with more centralized and socialized healthcare may yield results that are more cost-effective. High-volume centers may differ in their cost-effectiveness of the surgical care of pancreatic cancer internationally especially when comparing those in the United States to others throughout Europe.

Keywords: cost-effectiveness analysis, economic evaluation, pancreatic cancer, scientific literature review

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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: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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Authors: Teklay Gebrecherkos, Mahmud Abdulkader, Tobias Rinke De Wit, Britta C. Urban, Feyissa Chala, Yazezew Kebede, Dawit Welday

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Background: C-reactive protein (CRP) levels are a reliable surrogate for interleukin-6 bioactivity that plays a pivotal role in the pathogenesis of cytokine storm associated with severe COVID-19. There is a lack of data on the role of CRP as a determinant of COVID-19 severity status in the African context. Methods: We determined the longitudinal kinetics of CRP levels on 78 RT-PCR-confirmed COVID-19 patients (49 non-severe and 29 severe cases) and 50 PCR-negative controls. Results: COVID-19 patients had overall significantly elevated CRP at baseline when compared to PCR-negative controls [median 11.1 (IQR: 2.0-127.8) mg/L vs. 0.9 (IQR: 0.5-1.9) mg/L; p=0.0004)]. Moreover, severe COVID-19 patients had significantly higher median CRP levels than non-severe cases [166.1 (IQR: 48.6-332.5) mg/L vs. 2.4 (IQR: 1.2-7.6) mg/L; p<0.00001)]. In addition, persistently elevated levels of CRP were exhibited among those with comorbidities and higher age groups. Area under receiver operating characteristic curve (AUC) analysis of CRP levels distinguished PCR-confirmed COVID-19 patients from the ones with PCR-negative non-COVID-19 individuals, with an AUC value of 0.77 (95% CI: 0.68-0.84; p=0.001). Moreover, it clearly distinguished severe from non-severe COVID-19 patients, with an AUC value of 0.83 (95% CI: 0.73-0.91). After adjusting for age and the presence of comorbidities, CRP levels above 30 mg/L were significantly associated with an increased risk of developing severe COVID-19 (adjusted relative risk 3.99 (95%CI: 1.35-11.82; p=0.013). Conclusions: Determining CRP levels in COVID-19 patients in African settings may provide a simple, prompt, and inexpensive assessment of the severity status at baseline and monitoring of treatment outcomes.

Keywords: CRP, COVID-19, SARS-CoV-2, biomarker

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Yong Seong Kim, Seongbin Hong, So Hun Kim, Moonsuk Nam

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Background: Patients who undergo thyroidectomy due to thyroid cancer often complain weight gain, although they are on suppressive thyroid hormone treatment. The aim of this study is to know whether thyroid cancer patients gain the weight after thyroidectomy and weight change is dependent on estrogen state or use of rhTSH. Material and Method: We performed a retrospective chart review of subjects receiving medical care at an academic medical center. Two hundred two patients who underwent total thyroidectomy were included. As a control group, patients with thyroid nodule and euthyroidism were matched for age, gender, menopausal status. The weight changes occurring over first one year and thyroid function were assessed. Results: Mean age was 51±12 years and patients was composed with 38% of premenopausal, 15 % perimenopausal women, 37% of postmenopausal women and 20% of men. Patients with thyroid cancer gained 2.2 kg during the first year. It’ was not significantly different with control. However, weigh change in perimenopausal and post menopausal women gained more weight than control (P <0.05). Age, baseline body weight and weight gain were not correlated. Discussion: Patient who had undergone thyroidectomy gained more weight than their control, especially in peri- and postmenopausal women. Patients in this age should be monitored for their weight carefully.

Keywords: weight gain, thyroidectomy, thyroid cancer, weight chance

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Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

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Background: Breast cancer (BC) is the most common cancer among women worldwide, and cases are continuing to increase in Sweden. Bone is the most common metastatic site in breast cancer patients, where > 65-75% of women with advanced breast cancer develop bone metastases during their disease. To prevent the skeletal-related events of metastases (e.g., pathological fractures, bone loss, cancer-induced bone pain, and hypercalcemia bone), two different classes of antiresorptive medications (AR), bisphosphonate and denosumab are typically administered every 3 to 4 weeks. Since 2015, adjuvant bisphosphonate treatment has been used every six months for three to five years in postmenopausal women for the prevention of skeletal metastases and improved survival. Methods: A case-control study was conducted to test the hypotheses that patients treated with high-dose AR are at higher risk of developing MRONJ than breast cancer patients with adjuvant bisphosphonate treatment at a lower dose. Medical and odontological data was collected between 2015-2020. Assessment of oral health and dental care before and during oncological treatment took place at the specialist clinic for Orofacial medicine linked to the specific hospital. Results: In total, 220 patients were included, 101 patients in the high-dose group and 119 patients in the adjuvant BP-treatment group. MRONJ was diagnosed in 13 patients (14%) in the high-dose group. The mandible was affected in most of the cases (84.6%), with a mean duration of high-dose treatment of 19.7 months. In 46.2% of cases, no dental cause of MRONJ could be identified. Overall, estrogen receptor-positive (ER+) BC was the most representative type in 172 patients (78.2%). However, this was 83.9% in the high-dose cases group. The most used drug was denosumab. Twenty-five patients (26.9%) switched their medication from ZOL to denosumab during their oncological treatment. Patients with ER+ breast cancer were reported in 88 patients (87.8%) in the adjuvant group that was treated with ZOL. Conclusions: MRONJ was diagnosed only in the high-dose AR group. Dental assessment and care of patients in the adjuvant group should be considered, with a recommendation to potentially prolong ZOL treatment from 3 to 5 years, with concomitant use of hormonal therapy in patients diagnosed with ER+ breast cancer to prevent bone loss induced by oncological treatment. A new referral for dental assessment is very important in the case of bone metastases when treatment with high dose AR will be required since it is associated with a higher risk of MRONJ.

Keywords: antiresorptive therapy, breast cancer, dental care, MRONJ

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Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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Authors: Shradha Parsekar, Suma Nair, Ajay Bailey, Binu V. S.

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Background: Concealing of cancer-related information is seen in many low-and-middle-income countries and may be associated with multiple factors. Comparatively, there is lack of information about, how breast cancers diagnosed women disclose cancer-related information to their social contacts and vice versa. To get more insights on the participant’s experience, opinions, expectations, and attitudes, a qualitative study is a suitable approach. Therefore, this study involving in-depth interviews was planned to lessen this gap. Methods: Interviews were conducted separately among breast cancer patients and their caregivers with semi-structured qualitative interview guide. Purposive and convenient sampling was being used to recruit patients and caregivers, respectively. Ethical clearance and permission from the tertiary hospital were obtained and participants were selected from the Udupi district, Karnataka, India. After obtaining a list of breast cancer diagnosed cases, participants were contacted in person and their willingness to take part in the study was taken. About 39 caregivers and 35 patients belonging to different breast cancer stages were recruited. Interviews were recorded with prior permission. Data was managed by Atlas.ti 8 software. The recordings were transcribed, translated and coded in two cycles. Most of the patients belonged to stage II and III cancer. Codes were grouped together into to whom breast cancer status was concealed to and underneath reason for the same. Main findings: followings are the codes and code families which emerged from the data. 1) Concealing the breast cancer status from social contacts other than close family members (such as extended family, neighbor and friends). Participants perceived the reasons as, a) to avoid questions which people probe (which doesn’t have answers), b) to avoid people paying courtesy visit (to inquire about the health as it is Indian culture to visit the sick person) making it inconvenient for patient and caregivers have to offer something and talk to them, c) to avoid people getting shocked (react as if cancer is different from other diseases) or getting emotional/sad, or getting fear of death d) to avoid getting negative suggestion or talking anything in front of patient as it may affect patient negatively, e) to avoid getting stigmatized, f) to avoid getting obstacle in child’s marriage. 2) Participant concealed the breast cancer status of young children as they perceived that it may a) affect studies, b) affect emotionally, c) children may get scared. 3) Concealing the breast cancer status from patients as the caregivers perceived that they have fear of a) worsening patient’s health, b) patient getting tensed, c) patient getting shocked, and d) patient getting scared. However, some participants stressed important in disclosing the cancer status to social contact/patient to make the people aware of the disease. Conclusion: The news of breast cancer spreads like electricity in the wire, therefore, patient or family avoid it for many reasons. Although, globally, due to physicians’ ethical obligations, there is an inclination towards more disclosure of cancer diagnosis and status of prognosis to the patient. However, it is an ongoing argument whether patient/social contacts should know the status especially in a country like India.

Keywords: breast cancer, concealing cancer status, India, qualitative study

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Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

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Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe₃O₄ nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: tumor tissue, antibody, magnetic nanoparticle, CTCs capturing

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