Search results for: thyroid cancer

Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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

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

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

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Authors: Nusrat Praween, Krishna Thej Pammi Guru, Palash Kumar Basu

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Designing non-invasive biosensors for cancer diagnosis is essential for developing an affordable and specific tool to measure cancer-related exosome biomarkers. Exosomes, released by healthy as well as cancer cells, contain valuable information about the biomarkers of various diseases, including cancer. Despite the availability of various isolation techniques, ultracentrifugation is the standard technique that is being employed. Post isolation, exosomes are traditionally exposed to detergents for extracting their proteins, which can often lead to protein degradation. Further to this, it is very essential to develop a sensing platform for the quantification of clinically relevant proteins in a wider range to ensure practicality. In this study, exosomes were immobilized on the Au Screen Printed Electrode (SPE) using EDC/NHS chemistry to facilitate binding. After immobilizing the exosomes on the screen-printed electrode (SPE), we investigated the impact of the electric field by applying various voltages to induce exosome lysis and release their contents. The lysed solution was used for sensing TSG101, a crucial biomarker associated with various cancers, using both faradaic and non-faradaic electrochemical impedance spectroscopy (EIS) methods. The results of non-faradaic and faradaic EIS were comparable and showed good consistency, indicating that non-faradaic sensing can be a reliable alternative. Hence, the non-faradaic sensing technique was used for label-free quantification of the TSG101 biomarker. The results were validated using ELISA. Our electrochemical immunosensor demonstrated a consistent response of TSG101 from 125 pg/mL to 8000 pg/mL, with a detection limit of 0.125 pg/mL at room temperature. Additionally, since non-faradic sensing is label-free, the ease of usage and cost of the final sensor developed can be reduced. The proposed immunosensor is capable of detecting the TSG101 protein at low levels in healthy serum with good sensitivity and specificity, making it a promising platform for biomarker detection.

Keywords: biosensor, exosomes isolation on SPE, electric field lysis of exosome, EIS sensing of TSG101

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Authors: Dalwinder Singh, Amandeep Verma, Manpreet Kaur, Birmohan Singh

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The detection of pre-cancerous changes using a Pap smear test of cervical cell is the important step for the early diagnosis of cervical cancer. The Pap smear test consists of a sample of human cells taken from the cervix which are analysed to detect cancerous and pre-cancerous stage of the given subject. The manual analysis of these cells is labor intensive and time consuming process which relies on expert cytotechnologist. In this paper, a computer assisted system for the automated analysis of the cervical cells has been proposed. We propose a morphology based approach to the nucleus detection and segmentation of the cytoplasmic region of the given single or multiple overlapped cell. Further, various texture and region based features are calculated from these cells to classify these into normal and abnormal cell. Experimental results on public available dataset show that our system has achieved satisfactory success rate.

Keywords: cervical cancer, cervical tissue, mathematical morphology, texture features

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

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

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

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Authors: Carolina L. Cerdeira, Julia V. F. Cortes, Maria E. V. Amarante, Gersika B. Santos

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Skin cancer is the most common cancer in several parts of the world; in a tropical country like Brazil, the situation isn’t different. The Brazilian population is exposed to high levels of solar radiation, increasing the risk of developing cutaneous carcinoma. Aimed at encouraging prevention measures and the early diagnosis of these tumors, a study was carried out that analyzed data on cutaneous melanomas, basal cell, and epidermoid carcinomas, using as primary data source the medical records of 161 patients registered in one pathology service, which performs skin biopsies in a city of Minas Gerais, Brazil. All patients diagnosed with skin cancer at this service from January 2015 to December 2019 were included. The incidence of skin carcinoma cases was correlated with the identification of histological type, sex, age group, and topographic location. Correlation between variables was verified by Fisher's exact test at a nominal significance level of 5%, with statistical analysis performed by R® software. A significant association was observed between age group and type of cancer (p=0.0085); age group and sex (0.0298); and type of cancer and body region affected (p < 0.01). Those 161 cases analyzed comprised 93 basal cell carcinomas, 66 epidermoid carcinomas, and only two cutaneous melanomas. In the group aged 19 to 30 years, the epidermoid form was most prevalent; from 31 to 45 and from 46 to 59 years, the basal cell prevailed; in 60-year-olds or over, both types had higher frequencies. Associating age group and sex, in groups aged 18 to 30 and 46 to 59 years, women were most affected. In the 31-to 45-year-old group, men predominated. There was a gender balance in the age group 60-year-olds or over. As for topography, there was a high prevalence in the head and neck, followed by upper limbs. Relating histological type and topography, there was a prevalence of basal cell and epidermoid carcinomas in the head and neck. In the chest, the basal cell form was most prevalent; in upper limbs, the epidermoid form prevailed. Cutaneous melanoma affected only the chest and upper limbs. About 82% of patients 60-year-olds or over had head and neck cancer; from 46 to 59 and 60-year-olds or over, the head and neck region and upper limbs were predominantly affected; the distribution was balanced in the 31-to 45-year-old group. In conclusion, basal cell carcinoma was predominant, whereas cutaneous melanoma was the rarest among the types analyzed. Patients 60-year-olds or over were most affected, showing gender balance. In young adults, there was a prevalence of the epidermoid form; in middle-aged patients, basal cell carcinoma was predominant; in the elderly, both forms presented with higher frequencies. There was a higher incidence of head and neck cancers, followed by malignancies affecting the upper limbs. The epidermoid type manifested significantly in the upper limbs. Body regions such as the thorax and lower limbs were less affected, which is justified by the lower exposure of these areas to incident solar radiation.

Keywords: basal cell carcinoma, cutaneous melanoma, skin cancer, squamous cell carcinoma, topographic location

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Authors: Bernat-Carles Serdà Ferrer, Arantza Del Valle Gómez

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The Quality of Life (QoL) paradigm is multidimensional, dynamic and modular and its definition differs across the cancer continuum. The challenge in the interpretation of QoL data in clinical research is that QoL is influenced by psychological phenomena such as adaptation to illness. This research aims to obtain a valid and sensitive assessment of QoL change over the continuum disease, and to evaluate a rehabilitation programme aimed at inverting the observed decrease in QoL when patients return to daily living activities. The sample comprised 66 men. Patients were first assessed to establish a baseline (P1-diagnosis). This was followed by a post-test (P2-discharge) and a then-test measurement (P3-retrospective evaluation) and after returning home patients were randomized in experimental and control groups. The experimental group attended a rehabilitation programme over 24 weeks (P4). Results show that from baseline to post-test, QoL decreased significantly. The recalibration then-test confirmed a low QoL in all periods evaluated. Significant differences between the experimental and control groups prove the positive effect of the Exercise Rehabilitation Programme (ERP) on QoL. Understanding the real dynamic of QoL over time would help to adapt rehabilitation programmes by improving sensitivity and efficacy and provide professionals with a more accurate perception of the impact of treatment and side effects on patients’ QoL. Our results underline the importance of changing the approach adopted by health professionals towards one of watchful waiting on patients’ QoL until their complete recovery in daily life.

Keywords: exercise, prostate cancer, quality of life, rehabilitation programme, response shift

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Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

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Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

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Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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

Abstract:

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

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

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Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

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Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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Authors: S. Sakhri

Abstract:

Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.

Keywords: HER2+, RH+, breast cancer, tyrosine kinase

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Authors: Aparajita Bhattacharya, Mousumi Dutta, Zakir Husain, Dionne Sequeira, Asima Mukhopadhyay

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Background: Tata Medical Centre (TMC), Kolkata is a major cancer referral centre in Eastern India and neighbouring countries providing state of the art facilities; however, it is a non-profit organisation with patients requiring to pay at subsidised rates. Although a system for social assessment and applying for governmental/ non-governmental (NGO) funds is in place, access is challenging. Amongst gynaecological cancers (GC), ovarian cancer (OC) is associated with the highest treatment cost; majority of which is required at the beginning when complex surgery is performed and funding arrangements cannot be made in time. We therefore appointed a dedicated Medical Social Worker (MSW) in 2016, supported by NGO for GC patients in order to assist patients/family members to access/avail these funds more readily and assist in economic evaluation for both direct and opportunity costs. Objectives: To reflect on our experience and challenges in collecting data on economic evaluation of cancer patients and compare success rates in achieving fund mobilization after introduction of MSW. Methods: A Retrospective survey. Patients with OC and their relatives were seen by the MSW during the initial outpatients department visit and followed though till discharge from the hospital and during follow-up visits. Assistance was provided in preparing the essential documents/paperwork/contacts for the funding agencies including both governmental (Chief-Minister/Prime-Minister/President) and NGO sources. In addition, a detailed questionnaire was filled up for economic assessment of direct/opportunity costs during the entire treatment and 12 months follow up period which forms a part of the study called HEPTROC (Health economic evaluation of primary treatment for ovarian cancer) developed in collaboration with economics departments of Universities. Results: In 2015, 102 patients were operated for OC; only 16 patients (15.68 %) had availed funding of a total sum of INR 1640000 through the hospital system for social assessment. Following challenges were faced by majority of the relatives: 1. Gathering important documents/proper contact details for governmental funding bodies and difficulty in following up the current status 3. Late arrival of funds. In contrast in 2016, 104 OC patients underwent surgery; the direct cost of treatment was significantly higher (median, INR 300000- 400000) compared to other GCs (n=274). 98/104 (94.23%) OC patients could be helped to apply for funds and 90/104(86.56%) patients received funding amounting to a total of INR 10897000. There has been a tenfold increase in funds mobilized in 2016 after the introduction of dedicated MSW in GC. So far, in 2017 (till June), 46/54(85.18%) OC patients applied for funds and 37/54(68.51%) patients have received funding. In a qualitative survey, all patients appreciated the role of the MSW who subsequently became the key worker for patient follow up and the chief portal for patient reported outcome monitoring. Data collection quality for the HEPTROC study was improved when questionnaires were administered by the MSW compared to researchers. Conclusion: Introduction of cancer specific MSW can expedite the availability of funds required for cancer patients and it can positively impact on patient satisfaction and outcome reporting. The economic assessment will influence fund allocation and decision for policymaking in ovarian cancer. Acknowledgement: Jivdaya Foundation Dallas, Texas.

Keywords: economic evaluation, funding, medical social worker, ovarian cancer

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Authors: Diya Kohli, Amalia Ardeljan, Lexi Frankel, Jose Garcia, Lokesh Manjani, Omar Rashid

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Gonorrhea is the second most common sexually transmitted disease (STDs) in the United States of America. Gonorrhea affects the urethra, rectum, or throat and the cervix in females. Lymphoma is a cancer of the immune network called the lymphatic system that includes the lymph nodes/glands, spleen, thymus gland, and bone marrow. Lymphoma can affect many organs in the body. When a lymphocyte develops a genetic mutation, it signals other cells into rapid proliferation that causes many mutated lymphocytes. Multiple studies have explored the incidence of cancer in people infected with STDs such as Gonorrhea. For instance, the studies conducted by Wang Y-C and Co., as well as Caini, S and Co. established a direct co-relationship between Gonorrhea infection and incidence of prostate cancer. We hypothesize that Gonorrhea infection also increases the incidence of Lymphoma in patients. This research study aimed to evaluate the correlation between Gonorrhea infection and the incidence of Lymphoma. The data for the research was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. This database was utilized to evaluate patients infected with Gonorrhea versus the ones who were not infected to establish a correlation with the prevalence of Lymphoma using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for academic research. Standard statistical methods were applied throughout. Between January 2010 and December 2019, the query was analyzed and resulted in 254 and 808 patients in both the infected and control group, respectively. The two groups were matched by Age Range and CCI score. The incidence of Lymphoma was 0.998% (254 patients out of 25455) in the Gonorrhea group (patients infected with Gonorrhea that was Lymphoma Positive) compared to 3.174% and 808 patients in the control group (Patients negative for Gonorrhea but with Lymphoma). This was statistically significant by a p-value < 2.210-16 with an OR= 0.431 (95% CI 0.381-0.487). The patients were then matched by antibiotic treatment to avoid treatment bias. The incidence of Lymphoma was 1.215% (82 patients out of 6,748) in the Gonorrhea group compared to 2.949% (199 patients out of 6748) in the control group. This was statistically significant by a p-value <5.410-10 with an OR= 0.468 (95% CI 0.367-0.596). The study shows a statistically significant correlation between Gonorrhea and a reduced incidence of Lymphoma. Further evaluation is recommended to assess the potential of Gonorrhea in reducing Lymphoma.

Keywords: gonorrhea, lymphoma, STDs, cancer, ICD

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Authors: M. Sulieman, H. Arabiyat, H. Ali, K. Potiszil, I. Abbas, R. English, P. King, I. Brown, P. Drew

Abstract:

Introduction: The incidence of breast ductal Carcinoma in Situ (DCIS) has been increasing; it currently represents up 20-25% of all breast carcinomas. Some aspects of DCIS management are still controversial, mainly due to the heterogeneity of its clinical presentation and of its biological and pathological characteristics. In DCIS, histological diagnosis obtained preoperatively, carries the risk of sampling error if the presence of invasive cancer is subsequently diagnosed. The mammographic extent over than 4–5 cm and the presence of architectural distortion, focal asymmetric density or mass on mammography are proven important risk factors of preoperative histological under staging. Intracystic papillary cancer (IPC) is a rare form of breast carcinoma. Despite being previously compared to DCIS it has been shown to present histologically with invasion of the basement membrane and even metastasis. SLNB – Carries the risk of associated comorbidity that should be considered when planning surgery for DCIS and IPC. Objectives: The aim of this Audit was to better define a ‘high risk’ group of patients with pre-op diagnosis of non-invasive cancer undergoing breast conserving surgery, who would benefit from sentinel node biopsy. Method: Retrospective data collection of all patients with ductal carcinoma in situ over 5 years. 636 patients identified, and after exclusion criteria applied: 394 patients were included. High risk defined as: Extensive micro-calcification >40mm OR any mass forming DCIS. IPC: Winpath search from for the term ‘papillary carcinoma’ in any breast specimen for 5 years duration;.29 patients were included in this group. Results: DCIS: 188 deemed high risk due to >40mm calcification or a mass forming (radiological or palpable) 61% of those had a mastectomy and 32% BCS. Overall, in that high-risk group - the number with invasive disease was 38%. Of those high-risk DCIS pts 85% had a SLN - 80% at the time of surgery and 5% at a second operation. For the BCS patients - 42% had SLN at time of surgery and 13% (8 patients) at a second operation. 15 (7.9%) pts in the high-risk group had a positive SLNB, 11 having a mastectomy and 4 having BCS. IPC: The provisional diagnosis of encysted papillary carcinoma is upgraded to an invasive carcinoma on final histology in around a third of cases. This has may have implications when deciding whether to offer sentinel node removal at the time of therapeutic surgery. Conclusions: We have defined a ‘high risk’ group of pts with pre-op diagnosis of non-invasive cancer undergoing BCS, who would benefit from SLNB at the time of the surgery. In patients with high-risk features; the risk of invasive disease is up to 40% but the risk of nodal involvement is approximately 8%. The risk of morbidity from SLN is up to about 5% especially the risk of lymphedema.

Keywords: breast ductal carcinoma in Situ (DCIS), intracystic papillary carcinoma (IPC), sentinel node biopsy (SLNB), high-risk, non-invasive, cancer disease

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

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

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

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

Abstract:

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: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

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Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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Authors: Shangerganesh Lingeshwaran

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In this presentation, we have performed numerical simulations for a reaction-diffusion equation with various nonlinear density-dependent diffusion operators and proliferation functions. The mathematical model represented by parabolic partial differential equation is considered to study the invasion of gliomas (the most common type of brain tumors) and to describe the growth of cancer cells and response to their treatment. The unknown quantity of the given reaction-diffusion equation is the density of cancer cells and the mathematical model based on the proliferation and migration of glioma cells. A standard Galerkin finite element method is used to perform the numerical simulations of the given model. Finally, important observations on the each of nonlinear diffusion functions and proliferation functions are presented with the help of computational results.

Keywords: glioma invasion, nonlinear diffusion, reaction-diffusion, finite eleament method

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Authors: Estefania Ponce-Amaya, Ana Lidia Arellano-Ortiz, Cecilia Diaz-Hernandez, Jose Alberto Lopez-Diaz, Antonio De La Mora-Covarrubias, Claudia Lucia Vargas-Requena, Mauricio Salcedo-Vargas, Florinda Jimenez-Vega

Abstract:

Cervical Cancer (CC) is the second leading cause of death among women worldwide and it had been associated with a persistent infection of human papillomavirus (HPV). The goal of the current study was to identify the prevalence of HPV infection in women with abnormal Pap smear who were attended at Dysplasia Clinic of Ciudad Juarez, Mexico. Methods: Cervical samples from 146 patients, who attended the Colposcopy Clinic at Sanitary Jurisdiction II of Cd Juarez, were collected for histopathology and molecular study. DNA was isolated for the HPV detection by Polymerase Chain Reaction (PCR) using MY09/011 and GP5/6 primers. The associated risk factors were assessed by a questionnaire. The statistical analysis was performed by ANOVA, using EpiINFO V7 software. Results: HPV infection was present in 142 patients (97.3 %). The prevalence of HPV infection was distributed in a 96% of all evaluated groups, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HISIL) and CC. We found a statistical significance (α = <0.05) between gestation and number of births as risk factors. The median values showed an ascending tend according with the lesion progression. However, CC showed a statistically significant difference with respect to the pre-carcinogenic stages. Conclusions: In these Mexican patients exists a high prevalence of HPV infection, and for that reason, we are studying the most prevalent HPV genotypes in this population.

Keywords: cervical cancer, HPV, prevalence hpv, squamous intraepithelial lesion

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Authors: Karol Rodriguez-Peña, Martha L. Macias-Rubalcava, Leticia Rocha-Zavaleta, Sergio Sanchez

Abstract:

A bioassay-guided study for anti-cancer compounds from endophytes of the Mexican medicinal plant Amphipteryygium adstringens resulted in the isolation of a streptomycete capable of producing a group of compounds with high cytotoxic activity. Microorganisms from surface sterilized samples of various sections of the plant were isolated and all the actinomycetes found were evaluated for their potential to produce compounds with cytotoxic activity against cancer cell lines MCF7 (breast cancer) and HeLa (cervical cancer) as well as the non-tumoural cell line HaCaT (keratinocyte). The most active microorganism was picked for further evaluation. The identification of the microorganism was carried out by 16S rDNA gene sequencing, finding the closest proximity to Streptomyces scabrisporus, but with the additional characteristic that the strain isolated in this study was capable of producing colorful compounds never described for this species. Crude extracts of dichloromethane and ethyl acetate showed IC50 values of 0.29 and 0.96 μg/mL for MCF7, 0.51 and 1.98 μg/mL for HeLa and 0.96 and 2.7 μg/mL for HaCaT. Scaling the fermentation to 10 L in a bioreactor generated 1 g of total crude extract, which was fractionated by silica gel open column to yield 14 fractions. Nine of the fractions showed cytotoxic activity. Fraction 4 was chosen for subsequent purification because of its high activity against cancerous cell lines, lower activity against keratinocytes. HPLC-UV-MS/ESI was used for the evaluation of this fraction, finding at least 10 different compounds with high values of m/z (≈588). Purification of the compounds was carried out by preparative thin-layer chromatography. The prevalent compound was Steffimycin B, a molecule known for its antibiotic and cytotoxic activities and also for its low solubility in aqueous solutions. Along with steffimycin B, another five compounds belonging to the steffimycin family were isolated and at this moment their structures are being elucidated, some of which display better solubility in water: an attractive property for the pharmaceutical industry. As a conclusion to this study, the isolation of endophytes resulted in the discovery of a strain capable of producing compounds with high cytotoxic activity that need to be studied for their possible utilization.

Keywords: amphipterygium adstringens, cytotoxicity, streptomyces scabrisporus, steffimycin

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Authors: Mariam Khaled, Noha Farag, Ghada Mohamed Abdel Salam, Khaled Abu-Aisha, Mohamed El-Azizi

Abstract:

Gastric and colorectal cancers are among the most frequent causes of cancer-associated mortalities in Africa. They have been considered as a global public health concern, as nearly one million new cases are reported per year. IL-1β is a pro-inflammatory cytokine-produced by activated macrophages and monocytes- and a member of the IL-1 family. The inactive IL-1β precursor is cleaved and activated by caspase-1 enzyme, which itself is activated by the assembly of intracellular structures defined as NLRP3 (Nod Like receptor P3) inflammasomes. Activated IL-1β stimulates the Interleukin-1 receptor type-1 (IL-1R1), which is responsible for the initiation of a signal transduction pathway leading to cell proliferation. It has been proven that the IL-1β gene is a highly polymorphic gene in which single nucleotide polymorphisms (SNPs) may affect its expression. It has been previously reported that SNPs including base transitions between C and T at positions, -511 (C-T; dbSNP: rs16944) and -31 (C-T; dbSNP: rs1143627), from the transcriptional start site, contribute to the pathogenesis of gastric and colorectal cancers by affecting IL-1β levels. Altered production of IL-1β due to such polymorphisms is suspected to stimulate an amplified inflammatory response and promote Epithelial Mesenchymal Transition leading to malignancy. Allele frequency distribution of the IL-1β-31 and -511 SNPs, in different populations, and their correlation to the incidence of gastric and colorectal cancers, has been intriguing to researchers worldwide. The current study aims to investigate allele distributions of the IL-1β SNPs among gastric and colorectal cancers Egyptian patients. In order to achieve to that, 89 Biopsy and surgical specimens from the antrum and corpus mucosa of chronic gastritis subjects and gastric and colorectal carcinoma patients was collected for DNA extraction followed by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The amplified PCR products of IL-1β-31C > T and IL-1β-511T > C were digested by incubation with the restriction endonuclease enzymes ALu1 and Ava1. Statistical analysis was carried out to determine the allele frequency distribution in the three studied groups. Also, the effect of the IL-1β -31 and -511 SNPs on nuclear factor binding was analyzed using Fluorescence Electrophoretic Mobility Shift Assay (EMSA), preceded by nuclear factor extraction from gastric and colorectal tissue samples and LPS stimulated monocytes. The results of this study showed that a significantly higher percentage of Egyptian gastric cancer patients have a homozygous CC genotype at the IL-1β-31 position and a heterozygous TC genotype at the IL-1β-511 position. Moreover, a significantly higher percentage of the colorectal cancer patients have a homozygous CC genotype at the IL-1β-31 and -511 positions as compared to the control group. In addition, the EMSA results showed that IL-1β-31C/T and IL-1β-511T/C SNPs do not affect nuclear factor binding. Results of this study suggest that the IL-1β-31 C/T and IL-1β-511 T/C may be correlated to the incidence of gastric cancer in Egyptian patients; however, similar findings couldn’t be proven in the colorectal cancer patients group for the IL-1β-511 T/C SNP. This is the first study to investigate IL-1β -31 and -511 SNPs in the Egyptian population.

Keywords: colorectal cancer, Egyptian patients, gastric cancer, interleukin-1β, single nucleotide polymorphisms

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Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

Abstract:

Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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Authors: Ankita Shukla, Tiratha Raj Singh

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Colorectal cancer (CRC) imposes serious mortality burden worldwide and it has been increasing for past consecutive years. Continuous efforts have been made so far to diagnose the disease condition and to identify the root cause for it. In this study, we performed the pathway level as well as the differential gene expression studies for CRC. We analyzed the gene expression profile GSE24514 from Gene Expression Omnibus (GEO) along with the gene pathways involved in the CRC. This analysis helps us to understand the behavior of the genes that have shown differential expression through their targeted pathways. Pathway analysis for the targeted genes covers the wider area which therefore decreases the possibility to miss the significant ones. This will prove to be beneficial to expose the ones that have not been given attention so far. Through this analysis, we attempt to understand the various neighboring genes that have close relationship to the targeted one and thus proved to be significantly controlling the CRC. It is anticipated that the identified hub and neighboring genes will provide new directions to look at the pathway level differently and will be crucial for the regulatory processes of the disease.

Keywords: mismatch repair, microsatellite instability, carcinogenesis, morbidity

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Authors: Fereydoon Bondarian, Samira Shaygan

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Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

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Authors: Khusboo Agrawal, S. Saraf

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Quercetin, a flavonol provides a cellular protection against UV induced oxidative damages due to its excellent free radical scavenging activity and direct pro-apoptopic effect on tumor cells. However, its topical use is limited due to its unfavorable physicochemical properties. The present study was aimed to evaluate the potential of mesoporous silica nanoparticles as topical carrier system for quercetin delivery. Complexes of quercetin with mesoporous silica was prepared with different weight ratios and characterized by thermo gravimetric analysis, X-ray diffraction, high resolution TEM, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry The protective effect of this vehicle on UV-induced degradation of the quercetin was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated by using Franz diffusion cells. The immobilization of Quercetin in mesoporous silica nanoparticles (MSNs) increased the stability without undermining the antioxidant efficacy.

Keywords: cancer, MSNs, quercetin, topical delivery

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

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Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

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Authors: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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