Search results for: colorectal carcinoma

Authors: Angelis P. Barlampas, Ghita Bianca-Andreea

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A case of a prostatic midline cyst is presented, which was found during a routine general ultrasound examination in an otherwise healthy young man. The incidence of prostatic cysts discovered in suprapubic ultrasound examination has constantly been rising over the previous decades. Despite the fact that the majority of them are benign, a significant amount is related to symptoms, such as pain, dysuria, infertility, and even cancer. The wide use of ultrasound examination and the increasing availability of high-resolution ultrasound systems have rendered new diagnostic challenges. Once upon a time a suprapubic ultrasound was only useful for measuring only the size and the dimensions of the prostatic gland. It did not have the ability to analyze and resolve structures such as cystic or solid nodules. The current machine equipment has managed to depict the imaging characteristics of lesions with high acuity that compares of an intrarectal ultrasound. But the last one is a specialized examination, which demands expertise and good knowledge. Maybe the time has come for the general radiologist and, especially the one who uses suprapubic ultrasound, to pay more attention to the examination of the prostate gland and to take advantage of the superb abilities and the high resolution of the new ultrasound systems. That is exactly, what this case is emphasizing. The incidental discovery of prostatic cysts, and the relatively little available literature about managing them turns them into an interesting theme for exploring and studying. The prostatic cysts are further divided into midline and paramidline cysts, with the first being usually utricle cysts. A more precise categorization is as follows: A midline cystic lesion usually regards a Mullerian duct cyst, a prostatic utricle cyst, an ejaculatory duct cyst, a prostatic cystadenoma, a ductus deferens cyst, and a TURP. On the other hand, a lateral cystic lesion usually refers to a cystic degeneration of benign prostatic hyperplasia, a prostatic retention cyst, a seminal vesicle cyst, diverticular prostatitis, a prostatic abscess, cavitatory prostatitis from chronic prostatitis, a parasitic prostatic cyst, a cystic prostatic carcinoma, e.t.c.

Keywords: prostatic cyst, radiology, benign prostatic lesions, prostatic cancer, suprapubic prostatic ultrasound

Procedia PDF Downloads 32

Authors: Aisling Eves, Andrew Pieri, Ross McLean, Nerys Forester

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Background: DCIS accounts for 20% of malignancies diagnosed by the breast screening programme and is primarily managed by surgical excision. There is variable guidance on defining excision margins, and adjuvant treatments vary widely. This study aimed to investigate the clinical outcomes for patients following surgical excision of small volume DCIS. Methods: This single-centreretrospective cohort study of 101 consecutive breast screened patients diagnosed with DCIS who underwent surgical excision. All patients diagnosed with DCIS had radiological abnormalities <15mm. Clinical, radiological, and histological data were collected from patients who had been diagnosed within a 5 year period, and ASCO guidelines for margin involvement of <2mm was used to guide the need for re-excision. Outcomes included re-excision rates, radiotherapy usage, and the presence of invasive cancer. Results: Breast conservation surgery was performed in 94.1% (n=95). Following surgical excision, 74(73.27%)patients had complete DCIS excision (>2mm margin), 4(4.0%) had margins 1-2mm, and 17(16.84%)had margins <1mm. The median size of DCIS in the specimen sample was 4mm. In 86% of patients with involved margins (n=18), the mammogram underestimated the DCIS size by a median of 12.5mm (range: 1-42mm). Of the patients with involved margins, 11(10.9%)had a re-excision, and 6 of these (50%) required two re-excisions to completely excise the DCIS. Post-operative radiotherapy was provided to 53(52.48%)patients. Four (3.97%) patients were found to have invasive ductal carcinoma on surgical excision, which was not present on core biopsy – all had high-grade DCIS. Recurrence of DCIS was seen in the same site during follow-up in 1 patient (1%), 1 year after their first DCIS diagnosis. Conclusion: Breast conservation surgery is safe in patients with DCIS, with low rates of re-excision, recurrence, and upstaging to invasive cancer. Furthermore, the median size of DCIS found in the specimens of patients who had DCIS fully removed in surgery was low, suggesting it may be possible that total removal through VAE was possible for these patients.

Keywords: surgical excision, breast conservation surgery, DCIS, Re-excision, radiotherapy, invasive cancer

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: Head and neck cancers (HNC) are often associated with the development of non-HNC primaries, as the risk factors that predispose patients to HNC are often risk factors for other cancers. Aim: We sought to evaluate whether there was an increased risk of smoking and alcohol-related cancers and also other cancers in HNC patients and to evaluate whether there is a difference between the rates of non-HNC primaries in Aboriginal compared with non-Aboriginal HNC patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single center in Western Australia, identifying 80 Aboriginal and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, treatments, outcomes, and past and subsequent HNCs and non-HNC primaries. Results: In the overall study population, there were 86 patients (26.9%) with a metachronous or synchronous non-HNC primary. Non-HNC primaries were actually significantly more common in the non-Aboriginal population compared with the Aboriginal population (30% vs. 17.5%, p=0.02); however, half of these were patients with cutaneous squamous or basal cell carcinomas (cSCC/BCC) only. When cSCC/BCCs were excluded, non-Aboriginal patients had a similar rate as Aboriginal patients (16.7% vs. 15%, p=0.73). There were clearly more cSCC/BCCs in non-Aboriginal patients compared with Aboriginal patients (16.7% vs. 2.5%, p=0.001) and more patients with melanoma (2.5% vs. 0%, p value not significant (p=NS). Rates of most cancers were similar between non-Aboriginal and Aboriginal patients, including prostate (2.9% vs. 3.8%), colorectal (2.9% vs. 2.5%), kidney (1.2% vs. 1.2%), and these rates appeared comparable to Australian Age Standardised Incidence Rates (ASIR) in the general community. Oesophageal cancer occurred at double the rate in Aboriginal patients (3.8%) compared with non-Aboriginal patients (1.7%), which was far in excess of ASIRs which estimated a lifetime risk of 0.59% in the general population. Interestingly lung cancer rates did not appear to be significantly increased in our cohort, with 2.5% of Aboriginal patients and 3.3% of non-Aboriginal patients having lung cancer, which is in line with ASIRs which estimates a lifetime risk of 5% (by age 85yo). Interestingly the rate of Glioma in the non-Aboriginal population was higher than the ASIR, with 0.8% of non-Aboriginal patients developing Glioma, with Australian averages predicting a 0.6% lifetime risk in the general population. As these are small numbers, this finding may well be due to chance. Unsurprisingly, second HNCs occurred at an increased incidence in our cohort, in 12.5% of Aboriginal patients and 11.2% of non-Aboriginal patients, compared to an ASIR of 17 cases per 100,000 persons, estimating a lifetime risk of 1.70%. Conclusions: Overall, 26.9% of patients had a non-HNC primary. When cSCC/BCCs were excluded, Aboriginal and non-Aboriginal patients had similar rates of non-HNC primaries, although non-Aboriginal patients had a significantly higher rate of cSCC/BCCs. Aboriginal patients had double the rate of oesophageal primaries; however, this was not statistically significant, possibly due to small case numbers.

Keywords: head and neck cancer, synchronous and metachronous primaries, other primaries, Aboriginal

Procedia PDF Downloads 43

Authors: Luciano Tarantino, Emanuele Balzano, Paolo Tarantino, Riccardo Aurelio Nasto, Aurelio Nasto

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Liver transplantation (OLT) is contraindicate in Portal Vein tumor Thrombosis (PVTT) from Hepatocellular Carcinoma at hepatic hilum(pH-HCC) Surgery,Thermal ablation and chemotherapy show poorer outcomes Electrochemotherapy (ECT) has been successfully used in patients with pH-HCC with PVTT. We report the results of ECT as downstaging aimed to definitive cure by OLT. F.P. 53 years HBV related Cirrhosis Child-Pugh B7 class; EGDS F2 aesophageal Varices. Diabetes. April 2016 : Enhanced Computed Tomography (CT) detected HCC(n.3 nodules in VII-VIII-VI;diameter range=25 cm) and PVTT of right portal vein. The patient was considered ineligible for OLT. May 2016: first ablation session with percutaneous Radiofrequency-ablation(RFA) of 3 HCC-nodules . August 2016: second ablation session with ECT of PVTT. CT october 2016: disappearance of PVTT and patent right portal vein. No intraparenchymal recurrence. CT march 2017: No recurrence in portal vein and in the left lobe. local recurrence in the VII-VIII segments. May 2017 : transarterial chemoembolization (TACE) of right lobe recurrences. CT October 2017: patent right portal vein. No recurrence. The patient was reconsidered for OLT. He underwent OLT in April 2018. At 36-months follow-up , no intrahepatic recurrence of HCC occurred. March 2021: enhanced CT and PET/CT detected a single small nodule (1.5 cm) uptaking tracer in the left upper pulmonary lobe, no hepatic recurrence . CT-guided FNB showed metastasis from HCC . June 2021: left lung upper lobectomy . At the current time the patient is alive and recurrence-free at 64 months follow-up. ECT Could be aneffective technique as pre-OLT dowstaging in HCC with PVTT.

Keywords: liver tumor ablation, interventional ultrasound, electrochemotherapy, liver transplantation

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Authors: Nighat Bakhtiar, Ali Raza Khan, Shahid Khan Khattak, Aamir Ali Syed

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Introduction: Chemoradiation followed by resection has been the standard therapy for resectable (cT1-4aN0-3M0) esophageal carcinoma. The optimal surgical approach remains a matter of debate. Therefore, the purpose of this study was to share our experiences of minimal invasive esophagectomies concerning morbidity, mortality and oncological quality. This study aims to enlighten the world about the surgical outcomes after minimally invasive esophagectomy at Shaukat Khanum Hospital Lahore. Objective: The purpose of this study is to review an institutional experience of Surgical outcomes of Minimal Invasive esophagectomies for esophageal cancer. Methodology: This retrospective study was performed after ethical approval at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) Pakistan. Patients who underwent Minimal Invasive esophagectomies for esophageal cancer from March 2018 to March 2023 were selected. Data was collected through the human information system (HIS) electronic database of SKMCH&RC. Data was described using mean and median with minimum and maximum values for quantitative variables. For categorical variables, a number of observations and percentages were reported. Results: A total of 621 patients were included in the study, with the mean age of the patient was 39 years, ranging between 18-58 years. Mean Body Mass Index of patients was 21.2.1±4.1. Neo-adjuvant chemoradiotherapy was given to all patients. The mean operative time was 210.36 ± 64.51 minutes, and the mean blood loss was 121 milliliters. There was one mortality in 90 days, while the mean postoperative hospital stay was 6.58 days with a 4.64 standard deviation. The anastomotic leak rate was 4.2%. Chyle leak was observed in 12 patients. Conclusion: The minimal invasive technique is a safe approach for esophageal cancers, with minimal complications and fast recovery.

Keywords: minimal invasive, esophagectomy, laparscopic, cancer

Procedia PDF Downloads 42

Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

Procedia PDF Downloads 109

Authors: Praveen Adusumilli, Meher Lakshmi Konatam, Sadashivudu Gundeti, Stalin Bala

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The invention of trastuzumab has changed the treatment of breast cancer and lives of many patients all over the world. Despite many patients getting benefitted from the drug, it is out of reach for most of the patients. There is very limited real world data regarding the epidemiology and clinical outcome of Her2neu positive breast cancer patients. Materials and Methods: This is a retrospective analysis of breast cancer patients presenting to a tertiary care cancer centre in Southern India from 2007 to2013. All early and locally advanced breast cancer patients, who were Her2neu 3+ on IHC are included in the study and evaluated in terms of epidemiology, 3-year disease free survival (DFS)and 5-year overall survival(OS). Chemotherapy regimens used were-FAC 6 cycles or AC 4 cycles followed by 12 cycles of weekly paclitaxel . Trastuzumab was given after 6 cycles of FAC or weekly with paclitaxel followed by 3weekly maintenance until 1 year. Results: Over the period of this study there were 885 newly diagnosed cases of carcinoma breast, of which 242 (27%) were Her2neu positive, 360(40%) were hormone receptor positive, and 212(24%) were triple negative. A total of 71(8%) were Her2neu equivocal of which only 10 patients got FISH test done. Of the 212 newly diagnosed patients, only 74 (29%) opted to have standard of care therapy with trastuzumab at our centre, out of which 52(24%), 8(3%), received under insurance, paying basis respectively. 14(9%) patients received the care as part of clinical trial program (ALTTO trial). 7 (9.72%) patients developed decrease of ejection fraction by greater than 10%, requiring stoppage of trastuzumab out of which 5 were restarted in 2 months. Patients receiving trastuzumab along with chemotherapy had longer 3year DFS 92% vs. 60% (p value<0.0001) when compared to chemotherapy alone. 5 year OS was 87% vs 44% (p-value <0.0001) compared to chemotherapy alone. Conclusion: Trastuzumab with chemotherapy improves the DFS and OS in Her2neu positive patients. The biggest constraint is the cost of the treatment and absence of universal health security net to treat all patients with this diagnosis.

Keywords: breast cancer, Her 2 neu positive, real world data, Trastuzumab

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Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

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Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

Procedia PDF Downloads 228

Authors: Allulu Yousef Alturki, Raghad Abdullah Alshafi, Sara Abdulaziz Alghashem, Sahar Saleh Alghamdi, Rasha Saad Suliman, Zeyad Alehaideb, Rizwan Ali

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Cancer is recognized as a worldwide public health concern. Therefore, there is a continuous quest to discover new effective medications with less side-effects. In recent years, researchers have shown an increased interest in medicinal plants as several plant species have shown promising biological activities. Thus, we seek to investigate three medicinal herbs that are commonly-found in the Middle Easternregion and yet have not been explored in depth, including plants belonging to the Rhamnaceae, Polygonaceae, and Apocynaceaeplant families. Initially, we investigated using three types of cancer cell lines for breast, colorectal, and liver cancers. We performed high Content Imaging (HCI)-Apoptosis Assay and ApoTox-Glo™ Triplex Assay on KAIMRC2 and HCT8 cell lines. The highest activity of HCI-Apoptosis Assay was with Calligonumcomosum and Ziziphusnummularia in ethanol, followed by Calotropis procera and Ziziphusnummularia in ethyl acetate. The IC50values for the families of Rhamnaceae, Polygonaceae, and Apocynaceae in HepG2 and HCT8 cell lines ranged from 0.089 to 9.84mg/mL and 0.080to 15.08mg/mL, respectively. Further screening was conducted on an additional two cell lines, namely the MDA-MB-231 and KAIMRC2, for selected seven extracts with the highest activity having IC50values ranged from 0.058 to0.51mg/mL and 0.029 to0.19mg/mL, respectively. Continuous scientific investigations to isolate and characterize the potent bioactive phytochemical(s) are warranted. Funding: The authors acknowledge financial support from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. Institutional Review Board Statement: The study was approved by the Institutional Review Board of the Institutional Review Board of King Abdullah International Medical Research Center (SP21R/463/12, 24 January 2022). Acknowledgments: The authors want to express their gratitude to the College of Pharmacy (COP) at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC) for their continued support.

Keywords: rhamnaceae, polygonaceae, apocynaceae, natural products

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Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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Authors: Vincent Murray

Abstract:

The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

Procedia PDF Downloads 94

Authors: Anne N. Heirman, Song Duimel, Rob van Son, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Julia van Weert, Michiel W.M. van den Brekel

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Objectives: Treatments for head-neck cancer are drastic and often significantly impact the quality of life and appearance of patients. Shared decision-making (SDM) beholds a collaboration between patient and doctor in which the most suitable treatment can be chosen by integrating patient preferences, values, and medical information. SDM has a lot of advantages that would be useful in making difficult treatment choices. The objective of this study was to determine the current level of SDM among patients and head-and-neck surgeons. Methods: Consultations of patients with a non-cutaneous head-and-neck malignancy facing a treatment decision were selected and included. If given informed consent, the consultation was recorded with an audio recorder, and the patient and surgeon filled in a questionnaire immediately after the consultation. The SDM level of the consultation was scored objectively by independent observers who judged audio recordings of the consultation using the OPTION5-scale, ranging from 0% (no SDM) to 100% (optimum SDM), as well as subjectively by patients (using the SDM-Q-9 and Control preference scale) and clinicians (SDM-Q-Doc, modified control preference scale) percentages. Preliminary results: Five head-neck surgeons have each at least seven recorded conversations with different patients. One of them was trained in SDM. The other four had no experience with SDM. Most patients were male (74%), and oropharyngeal carcinoma was the most common diagnosis (41%), followed by oral cancer (33%). Five patients received palliative treatment of which two patients were not treated recording guidelines. At this moment, all recordings are scored by the two independent observers. Analysis of the results will follow soon. Conclusion: The current study will determine to what extent there is a discrepancy between the objective and subjective level of shared decision-making (SDM) during a doctor-patient consultation in Head-and-Neck surgery. The results of the analysis will follow shortly.

Keywords: head-and-neck oncology, patient involvement, physician-patient relations, shared decision making

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Authors: Farahnaz Amini, Woo Yun Kin, Lazwani Kolandaiveloo

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Availability of different genetic tests after completion of Human Genome Project increases the physicians’ responsibility to keep themselves update on the potential implementation of these genetic tests in their daily practice. However, due to numbers of barriers, still many of physicians are not either aware of these tests or are not willing to offer or refer their patients for genetic tests. This study was conducted an anonymous, cross-sectional, mailed-based survey to develop a primary data of Malaysian physicians’ level of knowledge and perception of gene profiling. Questionnaire had 29 questions. Total scores on selected questions were used to assess the level of knowledge. The highest possible score was 11. Descriptive statistics, one way ANOVA and chi-squared test was used for statistical analysis. Sixty three completed questionnaires was returned by 27 general practitioners (GPs) and 36 medical specialists. Responders’ age range from 24 to 55 years old (mean 30.2 ± 6.4). About 40% of the participants rated themselves as having poor level of knowledge in genetics in general whilst 60% believed that they have fair level of knowledge. However, almost half (46%) of the respondents felt that they were not knowledgeable about available genetic tests. A majority (94%) of the responders were not aware of any lab or company which is offering gene profiling services in Malaysia. Only 4% of participants were aware of using gene profiling for detection of dosage of some drugs. Respondents perceived greater utility of gene profiling for breast cancer (38%) compared to the colorectal familial cancer (3%). The score of knowledge ranged from 2 to 8 (mean 4.38 ± 1.67). Non-significant differences between score of knowledge of GPs and specialists were observed, with score of 4.19 and 4.58 respectively. There was no significant association between any demographic factors and level of knowledge. However, those who graduated between years 2001 to 2005 had higher level of knowledge. Overall, 83% of participants showed relatively high level of perception on value of gene profiling to detect patient’s risk of disease. However, low perception was observed for both statements of using gene profiling for general population in order to alter their lifestyle (25%) as well as having the full sequence of a patient genome for the purpose of determining a patient’s best match for treatment (18%). The lack of clinical guidelines, limited provider knowledge and awareness, lack of time and resources to educate patients, lack of evidence-based clinical information and cost of tests were the most barriers of ordering gene profiling mentioned by physicians. In conclusion Malaysian physicians who participate in this study had mediocre level of knowledge and awareness in gene profiling. The low exposure to the genetic questions and problems might be a key predictor of lack of awareness and knowledge on available genetic tests. Educational and training workshop might be useful in helping Malaysian physicians incorporate genetic profiling into practice for eligible patients.

Keywords: gene profiling, knowledge, Malaysia, physician

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Authors: Maximo Cozzetti

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The aim is to evaluate the capability of the 'Siberian Husky' (FCI-Standard Nº 270) breed of the common dog (Canis lupus familiaris) to detect terminally-ill human patients undergoing palliative care. A total of 49 such patients that fulfill the 'National Scientific and Technical Research Council–Ethical Principles for the Behavior of the Scientific and Technical Investigator' policy, (mainly affected with Stage IV Hodgkin lymphoma or Stage IV Carcinoma, though various other terminal diseases were present) and 49 controls were enrolled. A total of 13 specimens of Siberian Huskies (Canis lupus familiaris FCI – Standard Nº 270) were selected. After a conditioning training regime in which the canines were rewarded when identifying terminally ill patients and excluding the control subjects, a double-blind experiment was conducted in which the canines were presented with a previously unknown patient through an olfactory-proof plexiglass window for 2-minute intervals. The test subjects correctly identified 89.80% of the humans as either ‘ill’ or ‘healthy’. It is important to note that both groups of humans were selected considering and preventing confounding and self-identifying factors such as age, ethnicity, clothing, posture, skin color, alopecia (chemotherapy-induced or otherwise), etc. The olfactory-proofing of the test area rules out the use of the sense of smell to detect distinctive drugs or bodily odors that may be associated with terminal diseases. Thus, the Siberian Husky breed of the common dog shows the visual capability to detect and identify terminally ill patients undergoing palliative care regardless of age, posture, and quantity of hair. Though the capability of the breed of dog to detect terminally-ill patients was observed thoroughly during the course of the experiments, the exact process by which the canines identify the test subjects remains unknown and further research is encouraged.

Keywords: Canis lupus familiaris, Siberian Husky, visual identification of terminall illness, FCI-Standard Nº270

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Authors: Ahlam H. Mahmoud, Samir F. Zohny, Ibrahim H. Boraia, Faten S. Bayoumic, Eman Eissa

Abstract:

Hepatocellular carcinoma is one of the most common cancers worldwide and is known to be resistant to conventional chemotherapy. Therefore, we aimed to assess the Salsola inermis extract as a novel chemopreventive and/or therapeutic agent against N-nitrosodiethylamine (DNE)/phenobarbital (PB)-induced hepatocarcinogenesis in rats. Adult male Wistar albino rats were divided into five groups: group1 rats were served as normal controls; group 2 rats were injected intraperitoneally with S. inermis extract (100 mg/kg body weight/day) for 20 weeks; group 3 rats were subjected to two-phase hepatocarcinogenic regimen (initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of DEN at a dose of 200 mg/kg body weight, 2 weeks later, the carcinogenic effect was promoted by supplementation of rats with 0.05% PB for 16 weeks); group 4 rats were injected intraperitoneally with S. inermis extract 2 weeks prior to the injection of DEN, the daily injection of S. inermis extract was then continued for 18 weeks along with two-phase hepatocarcinogenic regimen (chemoprevention group); and group 5 rats were subjected to the two-phase hepatocarcinogenic regimen, and then, the animals were injected intraperitoneally with S. inermis extract for 4 weeks (treatment group). The activities of serum liver enzymes and levels of total bilirubin, conjugated bilirubin, α-fetoprotein, vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were decreased in chemopreventive and treated rats compared with DEN/PB-administered rats. Interestingly, the serum levels of total protein and albumin were normalized in chemopreventive and treated rats. Moreover, the majority of chemopreventive and treated rats showed an almost normal histological pattern of liver. In conclusion, S. inermis extract possessed chemopreventive and therapeutic activities against hepatocarcinogenesis in rats partially through the inhibition of VEGF and sICAM-1.

Keywords: Salsola inermis extract, hepatocarcinogenesis, α–fetoprotein, VEGF, sICAM-1

Procedia PDF Downloads 345

Authors: Anne N. Heirman, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Michiel W.M. van den Brekel

Abstract:

Background: Due to the rising incidence of oropharyngeal squamous cell cancer (OPSCC), many patients are challenged with choosing between transoral(robotic) surgery and radiotherapy, with equal survival and oncological outcomes. Also, functional outcomes are of little difference over the years. With this study, the wants and needs of patients and caregivers are identified to develop a comprehensible patient decision aid (PDA). Methods: The development of this PDA is based on the International Patient Decision Aid Standards criteria. In phase 1, relevant literature was reviewed and compared to current counseling papers. We interviewed ten post-treatment patients and ten doctors from four head and neck centers in the Netherlands, which were transcribed verbatim and analyzed. With these results, the first draft of the PDA was developed. Phase 2 beholds testing the first draft for comprehensibility and usability. Phase 3 beholds testing for feasibility. After this phase, the final version of the PDA was developed. Results: All doctors and patients agreed a PDA was needed. Phase 1 showed that 50% of patients felt well-informed after standard care and 35% missed information about treatment possibilities. Side effects and functional outcomes were rated as the most important for decision-making. With this information, the first version was developed. Doctors and patients stated (phase 2) that they were satisfied with the comprehensibility and usability, but there was too much text. The PDA underwent text reduction revisions and got more graphics. After revisions, all doctors found the PDA feasible and would contribute to regular counseling. Patients were satisfied with the results and wished they would have seen it before their treatment. Conclusion: Decision-making for OPSCC should focus on differences in side-effects and functional outcomes. Patients and doctors found the PDA to be of great value. Future research will explore the benefits of the PDA in clinical practice.

Keywords: head-and-neck oncology, oropharyngeal cancer, patient decision aid, development, shared decision making

Procedia PDF Downloads 124

Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala

Abstract:

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.

Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker

Procedia PDF Downloads 80

Authors: Mona Nada, Fahmy Fahmy

Abstract:

Background: Pleomorphic dermal sarcoma is a rare form of skin cancer affecting cutaneous layer and, in some cases associated with recurrence and metastasis, very commonly to seen in elderly patient affecting the area of head and neck. Pleomorphic dermal sarcoma rises in ultraviolet light exposed areas. The symptoms and severity of this kind of skin cancer varies according to histological factors. The differentiation of Pleomorphic dermal sarcoma needs extensive immunohistochemistry, as the diagnosis depends mainly on exclusion to rule out other malignancy like poorly differentiated squamous cell carcinoma, melanoma, angiosarcoma and leiomyosarcoma. Objective: assessing the management of Pleomorphic dermal sarcoma in our unit and compared to the updated guidelines. Design: Retrospective study Collection of patient data from medical records at countess of Chester plastic surgery unit of the last 5 years, all histologically confirmed Pleomorphic dermal sarcoma (2017-2023). Data were collected confirmed to be Pleomorphic dermal sarcoma were included in the study. The data collected: clinical description of the lesions at first presentation, operation time, multidisciplinary team discussion, plan, referral as well as second operation and investigation done. With comparison of histological examination, immunohistochemistry staining, the excision and rate of recurrence. Results: data collected N19 from (2017-2023) showed the disease predominantly affecting males and the lesion mainly in head and neck, the diagnosis needed extensive immunohistochemistry to differentiate between other malignancy. recurrence present in numbers of the cases which managed after multidisciplinary team discussion either by excision or radiotherapy. Conclusion: Pleomorphic dermal sarcoma is a rare malignancy which needs more understanding and avoid missing as it is aggressive form of skin cancer, there is a chance of metastasis and recurrence which makes it very important to understand the process of development of the cancer and frequent review of the management guidelines.

Keywords: pleomorphic dermal sarcoma, recurrence, radiotherapy, surgical

Procedia PDF Downloads 47

Authors: Arjun Prakash, Samanvitha H.

Abstract:

BACKGROUND: Breast cancer is the commonest malignancy among women globally, with an estimated incidence of 2.3 million new cases as of 2020, representing 11.7% of all malignancies. As per Globocan data 2020, it accounted for 13.5% of all cancers and 10.6% of all cancer deaths in India. Early diagnosis and treatment can improve the overall morbidity and mortality, which necessitates the importance of differentiating benign from malignant breast masses. OBJECTIVE: The objective of the present study was to evaluate and compare the role of Digital Mammography (DM), B mode Ultrasound (USG), Shear Wave Elastography (SWE) and Strain Elastography (SE) in differentiating benign and malignant breast masses (ACR BI-RADS 3 - 5). Histo-Pathological Examination (HPE) was considered the Gold standard. MATERIALS & METHODS: We conducted a cross-sectional study on 53 patients with 64 breast masses over a period of 10 months. All patients underwent DM, USG, SWE and SE. These modalities were individually assessed to know their accuracy in differentiating benign and malignant masses. All Digital Mammograms were done using the Fujifilm AMULET Innovality Digital Mammography system and all Ultrasound examinations were performed on SAMSUNG RS 80 EVO Ultrasound system equipped with 2 to 9 MHz and 3 – 16 MHz linear transducers. All masses were subjected to HPE. Independent t-test and Chi-square or Fisher’s exact test were used to assess continuous and categorical variables, respectively. ROC analysis was done to assess the accuracy of diagnostic tests. RESULTS: Of 64 lesions, 51 (79.68%) were malignant and 13 (20.31%) (p < 0.0001) were benign. SE was the most specific (100%) (p < 0.0001) and USG (98%) (p < 0.0001) was the most sensitive of all the modalities. E max, E mean, E max ratio, E mean ratio and Strain Ratio of the malignant masses significantly differed from those of the benign masses. Maximum SWE value showed the highest sensitivity (88.2%) (p < 0.0001) among the elastography parameters. A combination of USG, SE and SWE had good sensitivity (86%) (p < 0.0001). CONCLUSION: A combination of USG, SE and SWE improves overall diagnostic yield in differentiating benign and malignant breast masses. Early diagnosis and treatment of breast carcinoma will reduce patient mortality and morbidity.

Keywords: digital mammography, breast cancer, ultrasound, elastography

Procedia PDF Downloads 79

Authors: Nadia Akbarpour

Abstract:

Pancreatic ductal adenocarcinoma is a forceful and obliterating illness, which is portrayed by intrusiveness, fast movement, and significant protection from treatment. Advances in neurotic arrangement and malignant growth hereditary qualities have worked on our illustrative comprehension of this infection; be that as it may, significant parts of pancreatic disease science remain ineffectively comprehended. A superior comprehension of pancreatic disease science should lead the way to more viable medicines. In the course of the most recent couple of years, there have been significant advances in the sub-atomic and organic comprehension of pancreatic malignancy. This included comprehension of the genomic intricacy of the illness, the job of pancreatic malignant growth undifferentiated organisms, the importance of the growth microenvironment, and the one-of-a-kind metabolic transformation of pancreas disease cells to acquire supplements under hypoxic climate. Endeavors have been made towards the advancement of the practical answer for its treatment with compelled achievement due to its complicated science. It is grounded that pancreatic malignancy undifferentiated cells (CSCs), yet present in a little count, contribute extraordinarily to PC inception, movement, and metastasis. Standard chemo and radiotherapeutic choices, notwithstanding, grow general endurance, the connected aftereffects are a huge concern. In the midst of the latest decade, our understanding with regards to atomic and cell pathways engaged with PC and the job of CSCs in its movement has expanded massively. By and by, the center is to target CSCs. The natural items have acquired a lot of thought as of late as they, generally, sharpen CSCs to chemotherapy and target atomic flagging engaged with different cancers, including PC. Some arranged investigations have demonstrated promising outcomes recommending that assessments in this course bring a ton to the table for the treatment of PC. Albeit preclinical investigations uncovered the significance of natural items in lessening pancreatic carcinoma, restricted examinations have been led to assess their part in centers. The current survey gives another knowledge to late advances in pancreatic malignancy science, treatment, and the current status of natural items in its expectation.

Keywords: pancreatic, genomic, organic, cancer

Procedia PDF Downloads 115

Authors: Asma Zaib, Saeed Khan, Ayaz Ahmed Noonari, Sehrish Bint-e-Mohsin

Abstract:

Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.

Keywords: angiogenesis, anti-cytoproliferative, molecular docking, resveratrol

Procedia PDF Downloads 297

Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

Abstract:

To investigate the chemoprotective potential of NBRIQU16 chemotype isolated from Argyreia speciosa (Family: Convolvulaceae) on N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and NaCl-induced gastric carcinomas in Wistar rats. Forty-six male 6-week-old Wistar rats were divided into two groups. Thirty rats in group A were fed with a diet supplemented with 8 % NaCl for 20 weeks and simultaneously given N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in drinking water at a concentration of 100 ug/ml for the first 17 weeks. After administration of the carcinogen, 200 and 400 mg/kg of NBRIQU16 were administered orally once a day throughout the study. From week 18, these rats were given normal water. From week 21, these rats were fed with a normal diet for 15 weeks. Group B containing 16 rats was fed standard diet for thirty-five days. It served as control. Ten rats from group A were sacrificed after 20 weeks. Scarification of remaining animals was conducted after 35 weeks. Entire stomach and some part of the duodenum were incised parallel to the greater curvature, and the samples were collected. After opening the stomach location and size of tumors were recorded. The number of tumors with their locations and sizes were recorded. Expression of survivin was examined by recording the Immunohistochemistry of the specimens. The treatment with NBRIQU16 significantly reduced the nodule incidence and nodule multiplicity in the rats after MNNG administration. Surviving expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and NBRIQU16 treated tissues adjacent to tumor were 0, 42.0 %, 79.3%, and 36.4 %, respectively. Expression of survivin was significantly different as compared to the normal rats. Histological observations of stomach tissues too correlated with the biochemical observations.These finding powerfully supports that NBRIQU16 chemopreventive effect by suppressing the tumor burden and restoring the activities of gastric cancer marker enzymes on MNNG and NaCl-induced gastric carcinomas in Wistar rats.

Keywords: Argyreia speciosa, gastric carcinoma, immunochemistry, NBRIQU16

Procedia PDF Downloads 260

Authors: Eman Abdullah Morsi, Hend Okasha, Heba Abdel Hady, Mortada El-Sayed, Mohamed Abbas Shemis

Abstract:

Context: Linum usitatissimum (Linn), known as Flaxseed, is one of the most important medicinal plants traditionally used for various health as nutritional purposes. Objective: Estimation of total phenolic and flavonoid contents as well as evaluate the antioxidant using α, α-diphenyl-β-picrylhydrazyl (DPPH), 2-2'azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and total antioxidant capacity (TAC) assay and investigation of anti-inflammatory by Bovine serum albumin (BSA) and anticancer activities of hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF7) have been applied on hexane, ethyl acetate, n-butanol and methanol extracts and also, fractions of methonal extract (hexane, ethyl acetate and n-butanol). Materials and Methods: Phenolic and flavonoid contents were detected using spectrophotometric and colorimetric assays. Antioxidant and anti-inflammatory activities were estimated in-vitro. Anticancer activity of extracts and fractions of methanolic extract were tested on (HepG2) and (MCF7). Results: Methanolic extract and its ethyl acetate fraction contain higher contents of total phenols and flavonoids. In addition, methanolic extract had higher antioxidant activity. Butanolic and ethyl acetate fractions yielded higher percent of inhibition of protein denaturation. Meanwhile, ethyl acetate fraction and methanolic extract had anticancer activity against HepG2 and MCF7 (IC50=60 ± 0.24 and 29.4 ± 0.12µg.mL⁻¹) and (IC50=94.7 ± 0.21 and 227 ± 0.48µg.mL⁻¹), respectively. In Gas chromatography-mass spectrometry (GC-MS) analysis, methanolic extract has 32 compounds, whereas; ethyl acetate and butanol fractions contain 40 and 36 compounds, respectively. Conclusion: Flaxseed contains totally different biologically active compounds that have been found to possess good variable activities, which can protect human body against several diseases.

Keywords: phenolic content, flavonoid content, HepG2, MCF7, hemolysis-assay, flaxseed

Procedia PDF Downloads 100

Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

Abstract:

Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 84

Authors: Amina Aloui, Jalila Ben Salah-Abbès, Abdellah Zinedine, Amar Riba, Noel Durand, Catherine Brabet, Didier Montet, Samir Abbès

Abstract:

Mycotoxin contamination of food and feed-isa globaconcern, both economically and for public health. Aflatoxin M1 (AFM1) is the principal hydroxylated metabolite of aflatoxin B1. It is frequently found in milk and other dairy products. It is responsible for the development of hepatocellular carcinoma and immunotoxic in humans and animals. The reduction of its bioavailabilitybecomesa great demand in order to protect human and animal health. The use of probiotic bacteria and clay are demonstrated to be able to bind AFM1 in vitro. This study aimed to investigate, in vivo, the activity of two-component mixture: L. rhamnosusGAF06 (LR) and bentonite for reducing the oxidative stress and the histological alterationsinduced by AFM1 in the liver andkidneys. For the experiment, male mice were divided into 7 groups (6 mice/group) and treated, orally, by AFM1, alone or in combination with LR and/or bentonite, for 10 days as follows: group 1 control, group 2 treated with LR alone (2.108 CFU/ml), group 3 treated with bentonite alone (1g/kg), group 4 treated with AFM1 alone (100μg/kg), group 5 co-treated with LR+AFM1, group 6 co-treated with bentonite+AFM1, group 7 co-treated with bentonite+LR+AFM1. At the end of the treatment, the mice were sacrificed, and the livers and kidneys were collected for histological assays. Intracellular antioxidant activities and lipid peroxidation were also studied. The results showed that AFM1causeddamage in liver and kidney tissues, being evidence of hepatotoxicity and nephrotoxicity marked by necrotic cells. It increased the MDA level and decreased the antioxidant enzyme activities (SOD) in both organs. In contrast, the co-treatment with AFM1 plus LR and/or bentonitesignificantly improved the hepatic and renal tissues, regulated kidney, and liver antioxidant enzyme activities. This improvement was more remarkable with the administration of LR-bentonite mixture with AFM1.LR and bentonite alone showed to be safe during the treatment. This mixture can be a promising candidate for future applications in biotechnological processes that aimed to detoxify AFM1in food and feed.

Keywords: aflatoxin M1, bentonite, L. rhamnosus GAF06, oxidative stress, prevention

Procedia PDF Downloads 149

Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, p53, miR-146a, rs2910164, polymorphism

Procedia PDF Downloads 447

Authors: Hossein Rassi, Marjan Moradi fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human Papillomavirus (HPV) infection is the leading risk factor for Cervical Intraepithelial Neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33, and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, miR-146a rs2910164 polymorphism, p53 polymorphism, intraepithelial, neoplasia, HPV

Procedia PDF Downloads 378

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

Abstract:

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

Procedia PDF Downloads 291

Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, HPV18, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism

Procedia PDF Downloads 431