Search results for: breast cancer cell lines

Authors: Sutinon Yuchomsuk, Satchachon Changthom, Pruet Areesawangvong, Monsiri Jinapen

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Background: Esophageal squamous cell carcinoma can be presented with many symptoms, such as dysphagia or weight loss. However, in some circumstances, rare presentations can be found, e.g., dyspnea, which is more common in pulmonary malignancy. And dyspnea is also one of the most common presentations of COVID-19 infection. So, in this case, we can learn from many points in patient symptoms and findings leading to the diagnosis of esophageal squamous cell carcinoma. Method: This research is a case-report study including one patient from Mahasarakham Hospital, Thailand. Data were collected during December 2021. Result: A 55-year-old Thai male patient with an unknown past medical history presented with dyspnea and shortness of breath for the duration of three days prior to admission. His symptom also included cough, fever, and sore throat. Laboratory results indicated that the patient had COVID-19 pneumonia. Further investigation showed that he had cardiac tamponade and suspected pulmonary/esophageal cancer. Lung biopsy and pericardiocentesis were done, which were positive for carcinoma from pericardial effusion but negative for malignancy from the lung biopsy. Later esophagogastroduodenoscopy was done with endoscopic tissue biopsy; the result was positive for squamous cell carcinoma of the esophagus. Conclusion: Most commonly, esophageal cancer is presented with dysphagia or weight loss. However, in some rare cases, patients can also be presented with dyspnea due to cardiac tamponade. And in recent years, COVID-19 has become a pandemic all over the world, sometimes masking symptoms of other diseases. Such as in this case, the patient didn’t improve after the pneumonia was resolved, which led to the final diagnosis of metastatic esophageal cancer.

Keywords: esophageal cancer, cardiac tamponade, metastatic squamous cell carcinoma, COVID-19 infection

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Authors: Khalid Al Saleh, Najlaa AlSayed

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Background: Palliative care is changing from just ‘end of life care’ to care delivered earlier in the disease course. Metanalysis showed that Palliative Performance Scale (PPS) is associated with increased length of survival. The Palliative Care Center (PCC) in Kuwait is the only stand-alone center in Eastern Mediterranean Region with a capacity of 92 beds. We compared clinical characteristics between patients referred from the Specialized Cancer Center and general hospitals in Kuwait to PCC. Method: A cross Sectional survey was conducted since the opening of PCC in January 2011 to June 2013. Patients’ data on demographics, type of the cancer, PPS score and referring hospital were collected and analyzed. Results: Total number of the patients was 142. Mean age was 61.05±14.79 years, 66 patients (47.1%) were males and 74 (52.9%) were females. The most common cancers in males were lung (n=18, 27.3%) followed by head and neck cancers (n=8, 12.1%) and brain tumors (n=7, 10.6%) while in females, the most common cancers were breast cancer (n=12, 16.7%) followed by ovarian cancer (n=10, 13.9%) and Cancer Colon (n=8, 11.1%). Patients with PPS score 30% were 27.9% (n=39), 40% in 40.7% (n=57), and 50% in 17.1% (n=24) respectively. Patients referred from the Specialized Cancer Center had significantly higher portion of patients with PPS score > 30% (73.4%, n=94), compared to patients coming from general hospitals (33.3%, n=4), P value= 0.007. Conclusion: There is significant difference in PPS scores between patients referred from the Specialized Cancer Center compared to patients referred from general hospitals. We encourage that all cancer patients should be treated in Specialized Cancer Centers and earlier involvement of Palliative Care Centers to achieve better survival. Training workshops are needed for health care professionals working in general hospitals to raise awareness about earlier referral of patients to palliative care services.

Keywords: palliative care, kuwait, performance scale differences, pps score, specialized hospitals

Procedia PDF Downloads 279

Authors: Achitphol Chookaew, Paramee Thongsukhsai, Patamarerk Engsontia, Narongwit Nakwan, Pritsana Raugrut

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Lung cancer is one of the most common malignancies and primary cause of death due to cancer worldwide. Non-small cell lung cancer (NSCLC) is the main subtype in which majority of patients present with advanced-stage disease. Herein, we analyzed differentially expressed genes to find potential biomarkers for lung cancer diagnosis as well as prognostic markers. We used transcriptome data from our 2 NSCLC patients and public data (GSE81089) composing of 8 NSCLC and 10 normal lung tissues. Differentially expressed genes (DEGs) between NSCLC and normal tissue and between early-stage and late-stage NSCLC were analyzed by the DESeq2. Pairwise correlation was used to find the DEGs with false discovery rate (FDR) adjusted p-value £ 0.05 and |log2 fold change| ³ 4 for NSCLC versus normal and FDR adjusted p-value £ 0.05 with |log2 fold change| ³ 2 for early versus late-stage NSCLC. Bioinformatic tools were used for functional and pathway analysis. Moreover, the top ten genes in each comparison group were verified the expression and survival analysis via GEPIA. We found 150 up-regulated and 45 down-regulated genes in NSCLC compared to normal tissues. Many immnunoglobulin-related genes e.g., IGHV4-4, IGHV5-10-1, IGHV4-31, IGHV4-61, and IGHV1-69D were significantly up-regulated. 22 genes were up-regulated, and five genes were down-regulated in late-stage compared to early-stage NSCLC. The top five DEGs genes were KRT6B, SPRR1A, KRT13, KRT6A and KRT5. Keratin 6B (KRT6B) was the most significantly increased gene in the late-stage NSCLC. From GEPIA analysis, we concluded that IGHV4-31 and IGKV1-9 might be used as diagnostic biomarkers, while KRT6B and KRT6A might be used as prognostic biomarkers. However, further clinical validation is needed.

Keywords: differentially expressed genes, early and late-stages, gene ontology, non-small cell lung cancer transcriptomics

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Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Ga-Young Lee, Hyun-Man Kim

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

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

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Authors: Aref Zribi, Sonia Ben Nasr, Sana Fendri, Mahdi Balti, Abderazzek Haddaoui

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Background: Despite their benefit, Endocrine therapies (ET) are known to have substantial adverse events (AEs) such as hot flashes, mood disorders and osteoarticular pain. ET induced alopecia(EIA) is less frequently noted by patients and is less reported in the literature. The aim of our study was to report ET alopecia characteristics and their influence on patient and treatment observance. Method: We conducted a retrospective study including luminal BC patients treated in the oncology department of the military hospital of Tunis between January 2015 and December 2020. Patients treated with previous chemotherapy-inducing alopecia were excluded. Results: 145 female patients were included. The median age was 59 years. EIA was reported in 44% of cases. Alopecia was attributed to aromatase inhibitors in 53% and tamoxifen in 21%. Severity was grade 1 in 80% and grade 2 in the remaining cases. ET discontinuation because of alopecia was noted in 6.5 % of patients. Moderate improvement of alopecia was observed with topical minoxidil and Thallium metallicum 9CH homeopathy during ET in 60% of patients. Conclusions: EIA is frequent in BC patients and should be considered to improve treatment observance and patients’ quality of life.

Keywords: endocrine therapy, alopecia, breast cancer, Tunisia

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Authors: Anil Koklu, Amin Mansoorifar, Ali Beskok

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Dielectric spectroscopy (DS) is a noninvasive, label free technique for a long term real-time measurements of the impedance spectra of biological cells. DS enables characterization of cellular dielectric properties such as membrane capacitance and cytoplasmic conductivity. We have developed a lab-on-a-chip device that uses an electro-activated microwells array for loading, DS measurements, and unloading of biological cells. We utilized from dielectrophoresis (DEP) to capture target cells inside the wells and release them after DS measurement. DEP is a label-free technique that exploits differences among dielectric properties of the particles. In detail, DEP is the motion of polarizable particles suspended in an ionic solution and subjected to a spatially non-uniform external electric field. To the best of our knowledge, this is the first microfluidic chip that combines DEP and DS to analyze biological cells using electro-activated wells. Device performance is tested using two different cell lines of prostate cancer cells (RV122, PC-3). Impedance measurements were conducted at 0.2 V in the 10 kHz to 40 MHz range with 6 s time resolution. An equivalent circuit model was developed to extract the cell membrane capacitance and cell cytoplasmic conductivity from the impedance spectra. We report the time course of the variations in dielectric properties of PC-3 and RV122 cells suspended in low conductivity medium (LCB), which enhances dielectrophoretic and impedance responses, and their response to sudden pH change from a pH of 7.3 to a pH of 5.8. It is shown that microfluidic chip allowed online measurements of dielectric properties of prostate cancer cells and the assessment of the cellular level variations under external stimuli such as different buffer conductivity and pH. Based on these data, we intend to deploy the current device for single cell measurements by fabricating separately addressable N × N electrode platforms. Such a device will allow time-dependent dielectric response measurements for individual cells with the ability of selectively releasing them using negative-DEP and pressure driven flow.

Keywords: microfluidic, microfabrication, lab on a chip, AC electrokinetics, dielectric spectroscopy

Procedia PDF Downloads 129

Authors: Ayush Shrivastava, Arpit Chaudhary, Devang Kulshreshtha, Vibhav Prakash Singh, Rajeev Srivastava

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Early diagnosis of breast cancer can improve the survival rate by detecting cancer at an early stage. Breast region segmentation is an essential step in the analysis of digital mammograms. Accurate image segmentation leads to better detection of cancer. It aims at separating out Region of Interest (ROI) from rest of the image. The procedure begins with removal of labels, annotations and tags from the mammographic image using morphological opening method. Pectoral Muscle Sliding Window Algorithm (PMSWA) is used for removal of pectoral muscle from mammograms which is necessary as the intensity values of pectoral muscles are similar to that of ROI which makes it difficult to separate out. After removing the pectoral muscle, Dispersed Region Growing Algorithm (DRGA) is used for segmentation of mammogram which disperses seeds in different regions instead of a single bright region. To demonstrate the validity of our segmentation method, 322 mammographic images from Mammographic Image Analysis Society (MIAS) database are used. The dataset contains medio-lateral oblique (MLO) view of mammograms. Experimental results on MIAS dataset show the effectiveness of our proposed method.

Keywords: CAD, dispersed region growing algorithm (DRGA), image segmentation, mammography, pectoral muscle sliding window algorithm (PMSWA)

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Authors: Seyhan Karaçavuş, Bülent Yılmaz, Ömer Kayaaltı, Semra İçer, Arzu Taşdemir, Oğuzhan Ayyıldız, Kübra Eset, Eser Kaya

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In this study, our goal was to perform tumor staging and subtype determination automatically using different texture analysis approaches for a very common cancer type, i.e., non-small cell lung carcinoma (NSCLC). Especially, we introduced a texture analysis approach, called Law’s texture filter, to be used in this context for the first time. The 18F-FDG PET images of 42 patients with NSCLC were evaluated. The number of patients for each tumor stage, i.e., I-II, III or IV, was 14. The patients had ~45% adenocarcinoma (ADC) and ~55% squamous cell carcinoma (SqCCs). MATLAB technical computing language was employed in the extraction of 51 features by using first order statistics (FOS), gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), and Laws’ texture filters. The feature selection method employed was the sequential forward selection (SFS). Selected textural features were used in the automatic classification by k-nearest neighbors (k-NN) and support vector machines (SVM). In the automatic classification of tumor stage, the accuracy was approximately 59.5% with k-NN classifier (k=3) and 69% with SVM (with one versus one paradigm), using 5 features. In the automatic classification of tumor subtype, the accuracy was around 92.7% with SVM one vs. one. Texture analysis of FDG-PET images might be used, in addition to metabolic parameters as an objective tool to assess tumor histopathological characteristics and in automatic classification of tumor stage and subtype.

Keywords: cancer stage, cancer cell type, non-small cell lung carcinoma, PET, texture analysis

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Authors: Loai AbdAllah, Mahmoud Kaiyal

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Missing values in real-world datasets are a common problem. Many algorithms were developed to deal with this problem, most of them replace the missing values with a fixed value that was computed based on the observed values. In our work, we used a distance function based on Bhattacharyya distance to measure the distance between objects with missing values. Bhattacharyya distance, which measures the similarity of two probability distributions. The proposed distance distinguishes between known and unknown values. Where the distance between two known values is the Mahalanobis distance. When, on the other hand, one of them is missing the distance is computed based on the distribution of the known values, for the coordinate that contains the missing value. This method was integrated with Wikaya, a digital health company developing a platform that helps to improve prevention of chronic diseases such as diabetes and cancer. In order for Wikaya’s recommendation system to work distance between users need to be measured. Since there are missing values in the collected data, there is a need to develop a distance function distances between incomplete users profiles. To evaluate the accuracy of the proposed distance function in reflecting the actual similarity between different objects, when some of them contain missing values, we integrated it within the framework of k nearest neighbors (kNN) classifier, since its computation is based only on the similarity between objects. To validate this, we ran the algorithm over diabetes and breast cancer datasets, standard benchmark datasets from the UCI repository. Our experiments show that kNN classifier using our proposed distance function outperforms the kNN using other existing methods.

Keywords: missing values, incomplete data, distance, incomplete diabetes data

Procedia PDF Downloads 200

Authors: Waqas Ahmad, Eisha Tahir, Shahper Aqeel, Imran Khalid Niazi, Amjad Iqbal

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Background: Breast conservation surgery applies a number of techniques for accurate localization of lesions. Wire localization remains the method of choice in non-palpable breast cancers post-neoadjuvant chemotherapy. Objective: The aim of our study was to determine the accuracy of wire localization procedures in our department and compare it with internationally set protocols as per the Royal College of Radiologists. Post wire mammography, as well as the margin status of the postoperative specimen, assessed the accuracy of the procedure. Methods: We retrospectively reviewed the data of 225 patients who presented to our department from May 2014 to June 2015 post neoadjuvant chemotherapy with non-palpable cancers. These patients are candidates for wire localized lumpectomies either under ultrasound or stereotactic guidance. Metallic marker was placed in all the patients at the time of biopsy. Post wire mammogram was performed in all the patients and the distance of the wire tip from the marker was calculated. The presence or absence of the metallic clip in the postoperative specimen, as well as the marginal status of the postoperative specimen, was noted. Results: 157 sonographic and 68 stereotactic wire localization procedures were performed. 95% of the wire tips were within 1 cm of the metallic marker. Marginal status was negative in 94% of the patients in histopathological specimen. Conclusion: Our audit report declares more than 95% accuracy of image guided wire localization in successful excision of non-palpable breast lesions.

Keywords: breast, cancer, non-palpable, wire localization

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Authors: Sajjad Jafari, Reza Akbari

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Background and Aim: Chrysin, a flavonoid compound found in medicinal plants, honey, and propolis, has potential biological activities that make it an important perspective in the treatment of infectious and cancer diseases. The aim of this review study is to evaluate the biological activities of chrysin in the treatment of infectious and cancer diseases. Material and Methods: The present study is a review study that searched reputable scientific databases such as PubMed, Google Scholar, Scopus, and Web of Science from 2000 to 2023 using keywords such as antimicrobial, antifungal, chrysin, anticancer, antioxidants, and infectious diseases. The researchers examined 25 articles to determine the biological activities of chrysin. Results: Chrysin has high inhibitory or lethal activities on gram-positive and gram-negative bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Enterococcus faeces. It also has anti-biofilm effects and antifungal effects on strains such as Aspergillus niger and Candida albicans. Chrysin also has anticancer effects on various cancers, including colorectal cancer, pancreatic cancer, breast cancer, and MCF-7 cancer, which have been confirmed in vitro and in vivo. Conclusion: Chrysin has the potential as an important therapeutic option in the treatment of infectious and cancer diseases. Its high antimicrobial and anticancer activities, combined with its low toxicity in nanoparticle form, make it a promising candidate for further clinical trials. The production of anti-microbial and anti-cancer drugs from natural substances, such as chrysin, is a valuable contribution to the field of medicine.

Keywords: chrysin, antimicrobial, anticancer, infectious diseases

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Authors: Itee Chowdhury, Shikha Modi

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Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

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Authors: Muhammad Umar Hassan

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Renal cell carcinoma is a subset of kidney cancer that arises in the lining of DCT and is present in parenchymal tissue. Diagnosis is based on lab reports, including urinalysis, renal function tests (RFTs), and electrolyte balance, along with imaging techniques. Organ failure and other complications have been commonly observed in these cases. Over the years, the presentation of patients has varied, so carcinoma was classified on the basis of site, shape, and consistency for detailed analysis. Lifestyle patterns and occupational history were inquired about and recorded. Methods: Data from 100 patients presenting to the oncology and nephrology department of Mayo Hospital in the year 2015-2020 were included in this retrospective study on a random basis. The study was specifically focused on three risk factors. Smoking, occupational exposures, and Hakim medicine are taken by the patient for any cause. After procurement of data, follow-up contacts of these patients were established, resulting in a detailed analysis of lifestyle. Conclusion: The inference drawn is a direct causal link between smoking, industrial workplace exposure, and Hakim medicine with the development of Renal Cell Carcinoma. It was shown in the majority of the patients and hence confirmed our hypothesis.

Keywords: renal cell carcinoma, kidney cancer, clear cell carcinoma

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Authors: Arpita Roy, Navneeta Bharadvaja

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Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

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Authors: Parul Grover, K. A. Suri, Raj Kumar, Gulshan Bansal

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Background: Nyctanthes arbortristis Linn is traditionally used as anticancer herb in Indian system of medicine, but its introduction into modern system of medicine is still awaited due to lack of systematic scientific studies. Objective: The objective of the present study was to isolate and characterize anticancer phytoconstituents from N. arbortristis L. leaves based on bioactivity guided fractionation. Method: Different extracts of the leaves of the plant were prepared by Soxhlet extractor. Each extract was evaluated for anticancer activity against HL-60 cell lines. Chloroform and HA extract showed potent anticancer activity and hence were selected for fractionation. Fraction C1 from chloroform extract was found to be most potent amongst all when tested against three cell lines (HL-60, A-549, and HCT-116) and thus was selected for further fractionation and a pure compound CP-01 was isolated. RP-HPLC method has been developed for quantification of isolated compound by using Kinetex C-18 column with gradient elution at 0.7 mL/min using mobile phase containing potassium dihydrogen phosphate (0.01 M, pH 3.0) with acetonitrile. The wavelength of maximum absorption (λₘₐₓ) selected was 210 nm. Results: The structure of potent anticancer CP-01 was determined on the basis spectroscopic methods like IR, 1H-NMR, ¹³C-NMR and Mass Spectrometry and it was characterized as 1,1,2-tris(2’,4’-di-tert-butylbenzene)-4,4-dimethyl-pent-1-ene. The content of CP-01 was found to be 0.88 %w/w of chloroform extract and 0.08 %w/w of N.arbortristis leaves. Conclusion: The study supports the traditional use of N. arbortristis as anticancer herb & the identified compound CP-01 can serve as an excellent lead to develop potent and safe anticancer drugs.

Keywords: anticancer, HL-60 cell lines, Nyctanthes arbor-tristis, RP-HPLC

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

Procedia PDF Downloads 135

Authors: Geovanna dos Santos Romeiro, Polintia Rayza Brito da Silva, Luis Henrique Moura, Izadora Moreira Do Amaral, Marília Vitória Pinto Milhomem

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Introduction: The nose is one of the most likely sites for the appearance of malignancy on the face. This can be associated with its unique position of exposure to environmental damage, lack of photoprotection and because it is an area susceptible to greater sun exposure. It is already known that the most common type of nasal tumor is basal cell carcinoma. Squamous cell carcinoma is less common but considerably more aggressive, with a tendency to grow rapidly and metastasize. Nasal skin cancer can have a good prognosis, regardless of the type of treatment chosen, i.e., surgery, radiotherapy or electrodissection. However, tumors that are not diagnosed and treated quickly can be harmful and have a greater chance of metastasizing. When curative surgery is performed, therapies and reconstructive surgical procedures are usually required. Objective: The objective is to review the literature on nasal skin tumors and their types and specific locations. Forty-four articles published in Pubmed related to the location of skin cancer in the specific nasal areas region were analyzed. Twelve were excluded for being prior to the year 2000, three with inconclusive results, and one with unbiased conclusions. Results and Conclusion: Regarding the prevalence of types of nasal tumors, basal cell carcinoma comprises the majority, occurring predominantly in the ala, tip and root; squamous cell carcinoma, on the other hand, is more common in the lateral borders and columella. Even so, 2 articles report that the prevalence of metastasis has a higher incidence in squamous cell carcinomas. All of this points to the importance of early location, including regions that are often overlooked in the examination if the patient is wearing glasses. This topic needs further investigation for a greater correlation between anatomy and clinical-surgical implications.

Keywords: skin cancer, melanoma, non-melanoma, surgery

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Authors: Nawal Al Musayeib, Musarat Amina, Perwez Alam

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Plectranthus barbatus Andrews (Lamiaceae) is the most common species of genus Plectranthus. It is used for treating various ailments. In this study, two rare diterpenes 11,14-dihydroxy-8,11,13-abietatrien-7-one (1) and 12-hydroxyabieta-8(14),9(11),12-trien-7-one (2) were isolated for the first time from P. barbatus. Their chemical structures were verified utilizing various spectroscopic experiments. The effect of diterpenes against undifferentiated/anaplastic thyroid cancer cell line (FRO) was evaluated and they were quantitatively analysed using HPTLC method. The two diterpenes were found to be cytotoxic, however compound 1 showed significant cytotoxic effects where 95% reduction in the cell viability was observed in different time intervals. The quantity of compound 1 and compound 2 in PBCE were found to be 2.04 and15.97 μg/mg, respectively of dried weight of the extract.

Keywords: abietatrien, cancer, diterpenes, Plectranthus barbatus

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Abdulkareem M. Hamid, Yaseen Elhebshi, Adam Daïch

Abstract:

Luotonins and its derivatives (Isoluotonins) are alkaloids from the aerial parts of Peganum nigellastrum Bunge that display three major skeleton types. Luotonins A, B, and E are pyrroloquinazolinoquinoline alkaloids. A few methods were known for the sysnthesis of Isoluotonin. All luotonins have shown promising cytotoxicities towards selected human cancer cell lines, especially against leukemia P-388 cells. Luotonin A is the most active one, with its activity stemming from topoisomerase I-dependent DNA-cleavage. Such intriguing biological activities and unique structures have led not only to the development of synthetic methods for the efficient synthesis of these compounds, but also to interest in structural modifications for improving the biological properties. Recent progress in the study of luotonins is covered.

Keywords: luotonin A, isoluotonin, pyrroloquiolines, alkaloids

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Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

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In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

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Authors: Shangqing Song, Bin Xu, Yajun Cheng, Zhong Wang

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miRNAs derived from exosomes exist in a body fluid such as urine were regarded as potential biomarkers for various human cancers diagnosis and prognosis, as mature miRNAs can be steadily preserved by exosomes. However, its potential value in clear cell renal cell carcinoma (ccRCC) diagnosis and prognosis remains unclear. In the present study, differentially expressed miRNAs from urinal exosomes were identified by next-generation sequencing (NGS) technology. The 16 differentially expressed miRNAs were identified between ccRCC patients and healthy donors. To explore the specific diagnosis biomarker of ccRCC, we validated these urinary exosomes from 70 early-stage renal cancer patients, 30 healthy people and other urinary system cancers, including 30 early-stage prostate cancer patients and 30 early-stage bladder cancer patients by qRT-PCR. The results showed that urinary exosome miR-30c-5p could be stably amplified and meanwhile the expression of miR-30c-5p has no significant difference between other urinary system cancers and healthy control, however, expression level of miR-30c-5p in urinary exosomal of ccRCC patients was lower than healthy people and receiver operation characterization (ROC) curve showed that the area under the curve (AUC) values was 0.8192 (95% confidence interval was 0.7388-0.8996, P= 0.0000). In addition, up-regulating miR-30c-5p expression could inhibit renal cell carcinoma cells growth. Lastly, HSP5A was found as a direct target gene of miR-30c-5p. HSP5A depletion reversed the promoting effect of ccRCC growth casued by miR-30c-5p inhibitor, respectively. In conclusion, this study demonstrated that urinary exosomal miR-30c-5p is readily accessible as diagnosis biomarker of early-stage ccRCC, and miR-30c-5p might modulate the expression of HSPA5, which correlated with the progression of ccRCC.

Keywords: clear cell renal cell carcinoma, exosome, HSP5A, miR-30c-5p

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Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

Abstract:

In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: H. S. Niroshani, W. M. Ediri Arachchi, R. Tudugala, U. J. M. A. L. Jayasinghe, U. M. U. J. Jayasekara, P. B. Hewavithana

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Mammography is used as a screening tool for early diagnosis of breast cancer. It is also useful in refining the diagnosis of breast cancer either by assessment or work up after a suspicious area in the breast has been detected. In order to detect breast cancer accurately and at the earliest possible stage, the image must have an optimum contrast to reveal mass densities and spiculated fibrous structures radiating from them. In addition, the spatial resolution must be adequate to reveal the suffusion of micro calcifications and their shape. The above factors can be optimized by implementing an effective QA programme to enhance the accurate diagnosis of mammographic imaging. Therefore, the radiographer’s knowledge on QA is greatly instrumental in routine mammographic practice. The aim of this study was to assess the radiographer’s knowledge on Quality Assurance and Quality Control programmes in relation to mammographic procedures. A cross-sectional study was carried out among all radiographers working in each mammography setting in Sri Lanka. Pre-tested, anonymous self-administered questionnaires were circulated among the study population and duly filled questionnaires returned within a period of three months were taken into the account. The data on demographical information, knowledge on QA programme and associated QC tests, overall knowledge on QA and QC programmes were obtained. Data analysis was performed using IBM SPSS statistical software (version 20.0). The total response rate was 59.6% and the average knowledge score was 54.15±11.29 SD out of 100. Knowledge was compared on the basis of education level, special training of mammography, and the years of working experience in a mammographic setting of the individuals. Out of 31 subjects, 64.5% (n=20) were graduate radiographers and 35.5% (n=11) were diploma holders while 83.9% (n=26) of radiographers have been specially trained for mammography and 16.1% (n=5) have not been attended for any special training for mammography. It is also noted that 58.1% (n=18) of individuals possessed their experience of less than one year and rest 41.9% (n=13) of them were greater than that. Further, the results found that there is a significant difference (P < 0.05) in the knowledge of QA and overall knowledge on QA and QC programme in the categories of education level and working experience. Also, results imply that there was a significant difference (P < 0.05) in the knowledge of QC test among the groups of trained and non-trained radiographers. This study reveals that education level, working experience and the training obtained particularly in the field of mammography have a significant impact on their knowledge on QA and QC in mammography.

Keywords: knowledge, mammography, quality assurance, quality control

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Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

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A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

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Authors: Shaista Suhail

Abstract:

As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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Authors: Shamim Mushtaq, Moazzam Shahid

Abstract:

Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

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Authors: Nicole Ramlachan, Samuel Mark West

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Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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