Search results for: occult breast cancer

Authors: Godwin Dennison, Edwin Cooper, George Theobald, Richard Dalton

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We report an unusual case of giant filiform polyposis in a patient with ulcerative colitis, causing a large stricture in the colon. A 62-year-old man was referred to the Bowel Cancer Screening Programme with a positive Faecal Immunochemical Test (FIT). He was known to have UC for 30 years. A CT scan showed a 9 cm stricture in the transverse colon suspicious of malignancy. A colonoscopy was attempted three times, and biopsies confirmed features of ulcerative colitis. A laparoscopic assisted transverse colectomy (Left hemicolectomy) was performed, and the histology revealed giant filiform polyposis. This should be considered in a UC patient presenting with signs of obstruction mimicking a carcinoma. Whilst it is a benign condition, because of the size of the lesion, it often causes obstruction, and surgery is indicated to relieve symptoms.

Keywords: giant inflammatory polyposis, filiform polyposis, ulcerative colitis, inflammatory bowel disease

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Authors: Tedman Cheuk-Yiu Chau, Xavier Harvey, Hung Nguyen

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Defunctioning ileostomies are frequently used as an adjunct to low anterior resection in the surgical treatment of rectal cancer. Despite reducing the rate of clinically relevant anastomotic leak, the burden of defunctioning ileostomy is significant, with up to two-thirds of patients reporting stoma-related morbidity. International data have demonstrated an increased risk of bowel dysfunction and lower quality of life in patients with delayed closure (greater than six months post-surgery). While timely reversal is safe and cost-effective, the time to the reversal in Australian and New Zealand public hospitals is not described in the published literature. Thus, it is important to assess the current timeliness of ileostomy closure in the Australian regional context and examine the reasons for the delay. A retrospective analysis of ileostomy closure in Launceston General Hospital (LGH) patients treated with low/ultra low anterior resection for rectal cancer between 2012 and 2019 was undertaken. 94 cases of rectal adenocarcinoma undergoing ultralow anterior resection were examined over the years between 2012-2019. Amongst these, 21 cases (22.3%) were not reversed due to disease progress, death prior to reversal, or surgical complication. Demographics, disease status, surgical technique, and hospital inpatient events of these cases were examined. An average waiting time of 213.2 days was noted. Reasons for the delay include non-specified/prolonged hospital waiting time (54%), delayed or complicated chemotherapy course (13%), surgical complication (11%), advanced age, and frailty(5%). Complication of a delayed ileostomy reversal includes post-operation ileus and the development of an incisional hernia. We conclude that a delayed reversal of ileostomy can contribute to a higher incidence of stoma-related co-morbidities and contribute to a longer hospital stay and therefore use of public hospital resources.

Keywords: anterior resection, colorectal surgery, ileostomy reversal, rectal cancer

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Authors: Mona Nada, Fahmy Fahmy

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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

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Authors: Min Ju Kim, Beom Jin Park, Deuk Jae Sung, Na Yeon Han, Kichoon Sim

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Purpose: The purpose of this study is to determine the significant magnetic resonance (MR) imaging factors of lateral pelvic lymph node (LPLN) on the assessment of survival outcomes of neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with mid/low rectal cancer. Materials and Methods: The institutional review board approved this retrospective study of 63 patients with mid/low rectal cancer who underwent MR before and after CRT and patient consent was not required. Surgery performed within 4 weeks after CRT. The location of LPLNs was divided into following four groups; 1) common iliac, 2) external iliac, 3) obturator, and 4) internal iliac lymph nodes. The short and long axis diameters, numbers, shape (ovoid vs round), signal intensity (homogenous vs heterogenous), margin (smooth vs irregular), and diffusion-weighted restriction of LPLN were analyzed on pre- and post-CRT images. For treatment response using size, lymph node groups were defined as group 1) short axis diameter ≤ 5mm on both MR, group 2) > 5mm change into ≤ 5mm after CRT, and group 3) persistent size > 5mm before and after CRT. Clinical findings were also evaluated. The disease-free survival and overall survival rate were evaluated and the risk factors for survival outcomes were analyzed using cox regression analysis. Results: Patients in the group 3 (persistent size >5mm) showed significantly lower survival rates than the group 1 and 2 (Disease-free survival rates of 36.1% and 78.8, 88.8%, p < 0.001). The size response (group 1-3), multiplicity of LPLN, the level of carcinoembryonic antigen (CEA), patient’s age, T and N stage, vessel invasion, perineural invasion were significant factors affecting disease-free survival rate or overall survival rate using univariate analysis (p < 0.05). The persistent size (group 3) and multiplicity of LPLN were independent risk factors among MR imaging features influencing disease-free survival rate (HR = 10.087, p < 0.05; HR = 4.808, p < 0.05). Perineural invasion and T stage were shown as independent histologic risk factors (HR = 16.594, p < 0.05; HR = 15.891, p < 0.05). Conclusion: The persistent size greater than 5mm and multiplicity of LPLN on both pre- and post-MR after CRT were significant MR factors affecting survival outcomes in the patients with mid/low rectal cancer.

Keywords: rectal cancer, MRI, lymph node, combined chemoradiotherapy

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia AbdulMajid, Maryam Zahedifard

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Colon cancer is one of the most prevalent cancers in the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. New schiff based compounds are reported to exhibit a wide spectrum of biological activities of therapeutic importance. To evaluate inhibitory properties of CdCl2(C14H21N3O2) complex on colonic aberrant crypt foci, five groups of 7-week-old male rats were used. Control group was fed with 10% Tween 20 once a day, cancer control group was intra-peritoneally injected with 15 mg/kg Azoxymethan, drug control group was injected with 15 mg/kg azoxymethan and 5-Flourouracil, experimental groups were fed with 2.5 and 5 mg/kg CdCl2(C14H21N3O2) compound each once a day. Administration of compound were found to be effectively chemoprotective. Andrographolide suppressed total colonic ACF formation up to 72% to 74%, respectively, when compared with control group. The results also showed a significant increase in glutathione peroxidase, superoxide dismutase, catalase activities and a decrease in malondialdehyde level. Immunohistochemical staining demonstrated down-regulation of PCNA protein. According to the Western blot comparison analysis, COX-2 and Bcl2 is up-regulated whilst the Bax is down-regulated. according to these data, this compound plays promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, Schiff based compound, aberrant crypt foci (ACF), immunohistochemical staining

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Authors: Lucian Mocan, Flaviu Tabaran, Teodora Mocan, Cristian Matea, Cornel Iancu

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We present method of Gold Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinoma cell line), based on a simple gold nanoparticle carrier system, such as serum albumin (BSA), and demonstrate its selective therapeutic efficacy. Hyperspectral, contrast phase, and confocal microscopy combined immunochemical staining were used to demonstrate the selective internalization of HSA-GNPs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. We examined the ability of laser-activated carbon nanotubes to induce Hsp70 expression using confocal microscopy. Hep G2 cells heat-shocked (laser activated BSA-GNPs) to 42°C demonstrated an up-regulation of Hsp70 compared with control cells (BSA-GNPs treated cells without laser), which showed no detectable constitutive expression of Hsp70. We observed a time-dependent induction in Hsp70 expression in Hep G2 treated with BSA-GNPs and LASER irradiated. The post-irradiation apoptotic rate of HepG2 cells treated with HSA-GNPs ranged from 88.24% (for 50 mg/L) at 60 seconds, while at 30 minute the rate increased to 92.34% (50 mg/L). These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: gold nanoparticles, liver cancer, albumin, laser irradiation

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Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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Authors: Tomohiro Uchida, Noriaki Satake, Toshimichi Nakaho, Akira Inoue, Hidemitsu Saito

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In this study, we assessed the bereavement risk of family caregivers of patients with cancer. In the palliative care unit of Tohoku University Hospital, we conducted a family psychoeducation session to support the family caregivers of patients with cancer. A total of 50 participants (8 males and 42 females; mean age = 62.98 years, SD = 11.10) were assessed after the session for bereavement risk using the Japanese version of the Bereavement Risk Assessment Tool (BRAT-J). According to the BRAT-J scores, eight participants were considered to be having no known risk (Level 1), seventeen had minimal risk (Level 2), twenty had a low risk (Level 3), four had a moderate risk (Level 4), and one had a high risk (Level 5). Of these participants, seven participants had completed the follow-up postal survey that assessed their psychological distress (the Kessler Psychological Distress Scale: K6) to compare the bereavement risk. According to the K6 scores, three-fourth of the individuals, who were considered to be at Level 3 on the BRAT-J, scored higher than the cutoff point (>10) for the detection of depressive disorder. On the other hand, one-third of the individuals, who were considered to be at Level 2 on the BRAT-J, scored higher than the cutoff point. Therefore, it appears that the BRAT-J can predict the likelihood of difficulties or complications in bereaved family caregivers. This research was approved by the Ethics Committee of Tohoku University Graduate School of Medicine and Tohoku University Hospital.

Keywords: palliative care, family caregivers, bereavement risk, BRAT, post-loss psychological distress

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Authors: Chodidjah, Edi Dharmana, Hardhono, Sarjadi

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Breast cancer treatment options including surgery, radiation therapy, chemotherapy, and immunotherapy have not been effective. Besides, they have side effects. Keladi Tikus (Typhonium flagelliforme) has been shown to improve immune system, suppress tumor growth and induce apoptosis. One of the parameters for immune system, tumor growth and apoptosis is IFNγ (Interferon γ), VEGF (Vascular Endothelial Growth Factor) and Caspase 3 respectively. The aim of this study was to examine the effect of the administration of Keladi Tikus tuber extract at the dose of 200 mg/kgBW, 400 mg/KgBW, and 800 mg/kgBW on the level of IFNγ, VEGF and caspase 3 expression. In this experimental study using post test randomized control group design, 24 CH3 mice with tumor were randomly divided into 4 groups including control group and treated groups: Treated with 0.2 cc extract of Keladi Tikus at the dose of 200 mg/kgBW, 400 mg/kgBW, 800 mg/kgBW, respectively for 30 days. On day 31 the lymphatic tissue was taken and evaluated for its level of IFNγ, using ELISA. The tumor tissue was taken and subjected to immunohistochemistry staining for VEGF and caspase 3 expression evaluation. The data on IFNγ, VEGF and Caspase 3 expression were analyzed using One Way Anova with significant level of 0.05. One Way Anova resulted in p<0.05. LSD test showed that the level of IFNγ and Caspase 3 for control group was different from that of treated groups. There was no significant different between the treated group of 400 mg/KgBW and 800mg/KgBW. VEGF expressions for all the treated groups were significant. In conclusion, the oral administration of ethanolic extract of Keladi Tikus (Typhonium flagelliforme) at the dose of 200mg/kgBW, 400 mg/kgBW,800 mg/kgBW increases IFNγ, Caspase 3 and decreases VEGF expression in C3H mice with adenocarsinoma mamma.

Keywords: Typhonium flagelliforme, IFNγ, caspase 3, VEGF

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Authors: Mualla McManus, Jenna Luche Thaye

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World Health Organisation International Classification of Disease codes were created to define disease including infections in order to guide and educate diagnosticians. Most infectious diseases such as syphilis are clearly defined by their ICD 10 codes and aid/help to educate the clinicians in syphilis diagnosis and treatment globally. However, current ICD 10 codes for relapsing fever Borreliosis and Lyme disease are less clearly defined and can impede appropriate diagnosis especially if the clinician is not familiar with the symptoms of these infectious diseases. This is despite substantial number of scientific articles published in peer-reviewed journals about relapsing fever and Lyme disease. In the USA there are estimated 380,000 people annually contacting Lyme disease, more cases than breast cancer and 6x HIV/AIDS cases. This represents estimated 0.09% of the USA population. If extrapolated to the global population (7billion), 0.09% equates to 63 million people contracting relapsing fever or Lyme disease. In many regions, the rate of contracting some form of infection from tick bite may be even higher. Without accurate and appropriate diagnostic codes, physicians are impeded in their ability to properly care for their patients, leaving those patients invisible and marginalized within the medical system and to those guiding public policy. This results in great personal hardship, pain, disability, and expense. This unnecessarily burdens health care systems, governments, families, and society as a whole. With accurate diagnostic codes in place, robust data can guide medical and public health research, health policy, track mortality and save health care dollars. Better defined ICD codes are the way forward in educating the diagnosticians about relapsing fever and Lyme diseases.

Keywords: WHO ICD codes, relapsing fever, Lyme diseases, World Health Organisation

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Authors: Sarah K. Hagi, Majdi Alnowaimi

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In the last decade, there were immense advancements in the medical imaging modalities. These advancements can scan a whole volume of the lung organ in high resolution images within a short time. According to this performance, the physicians can clearly identify the complicated anatomical and pathological structures of lung. Therefore, these advancements give large opportunities for more advance of all types of lung cancer treatment available and will increase the survival rate. However, lung cancer is still one of the major causes of death with around 19% of all the cancer patients. Several factors may affect survival rate. One of the serious effects is the breathing process, which can affect the accuracy of diagnosis and lung tumor treatment plan. We have therefore developed a semi automated algorithm to localize the 3D lung tumor positions across all respiratory data during respiratory motion. The algorithm can be divided into two stages. First, a lung tumor segmentation for the first phase of the 4D computed tomography (CT). Lung tumor segmentation is performed using an active contours method. Then, localize the tumor 3D position across all next phases using a 12 degrees of freedom of an affine transformation. Two data set where used in this study, a compute simulate for 4D CT using extended cardiac-torso (XCAT) phantom and 4D CT clinical data sets. The result and error calculation is presented as root mean square error (RMSE). The average error in data sets is 0.94 mm ± 0.36. Finally, evaluation and quantitative comparison of the results with a state-of-the-art registration algorithm was introduced. The results obtained from the proposed localization algorithm show a promising result to localize alung tumor in 4D CT data.

Keywords: automated algorithm , computed tomography, lung tumor, tumor localization

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Authors: Nurunnahar Akter, Elena Kulinskaya, Nicholas Steel, Ilyas Bakbergenuly

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Although Hormone Replacement Therapy (HRT) is an effective treatment in ameliorating menopausal symptoms, it has mixed effects on different health outcomes, increasing, for instance, the risk of breast cancer. Because of this, many symptomatic women are left untreated. Untreated menopausal symptoms may result in other health issues, which eventually put an extra burden and costs to the health care system. All-cause mortality analysis may explain the net benefits and risks of the HRT therapy. However, it received far less attention in HRT studies. This study investigated the impact of HRT on all-cause mortality using electronically recorded primary care data from The Health Improvement Network (THIN) that broadly represents the female population in the United Kingdom (UK). The study entry date for this study was the record of the first HRT prescription from 1984, and patients were followed up until death or transfer to another GP practice or study end date, which was January 2017. 112,354 HRT users (cases) were matched with 245,320 non-users by age at HRT initiation and general practice (GP). The hazards of all-cause mortality associated with HRT were estimated by a parametric Weibull-Cox model adjusting for a wide range of important medical, lifestyle, and socio-demographic factors. The multilevel multiple imputation techniques were used to deal with missing data. This study found that during 32 years of follow-up, combined HRT reduced the hazard ratio (HR) of all-cause mortality by 9% (HR: 0.91; 95% Confidence Interval, 0.88-0.94) in women of age between 46 to 65 at first treatment compared to the non-users of the same age. Age-specific mortality analyses found that combined HRT decreased mortality by 13% (HR: 0.87; 95% CI, 0.82-0.92), 12% (HR: 0.88; 95% CI, 0.82-0.93), and 8% (HR: 0.92; 95% CI, 0.85-0.98), in 51 to 55, 56 to 60, and 61 to 65 age group at first treatment, respectively. There was no association between estrogen-only HRT and women’s all-cause mortality. The findings from this study may help to inform the choices of women at menopause and to further educate the clinicians and resource planners.

Keywords: hormone replacement therapy, multiple imputations, primary care data, the health improvement network (THIN)

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Ripon Sarkar, Kabita Chaterjee, Ananya Barui

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Smoking is one of the leading causes of oral cancer. Cigarette smoke affects various cellular parameters and alters molecular metabolism of cells. Epithelial cells losses their cytoskeleton structure, membrane integrity, cellular polarity that subsequently initiates the process of epithelial cells to mesenchymal transition due to long exposure of cigarette smoking. It changes the normal cellular metabolic activity which induces oxidative stress and enhances the reactive oxygen spices (ROS) formation. Excessive ROS and associated oxidative stress are considered to be a driving force in alteration in cellular phenotypes, polarity distribution and mitochondrial metabolism. Noninvasive assessment of such parameters plays essential role in development of routine screening system for early diagnosis of oral cancer. Electrical cell-substrate impedance sensing (ECIS) is one of such method applied for detection of cellular membrane impedance which can be correlated to cell membrane integrity. Present study intends to explore the alteration in cellular impedance along with the expression of cellular polarity molecules and cytoskeleton distributions in oral epithelial cells of habitual smokers and to correlate the outcome to that of clinically diagnosed oral leukoplakia and oral squamous cell carcinoma patients. Total 80 subjects were categorized into four study groups: nonsmoker (NS), cigarette smoker (CS), oral leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC). Cytoskeleton distribution was analyzed by staining of actin filament and generation of ROS was measured using assay kit using standard protocol. Cell impedance was measured through ECIS method at different frequencies. Expression of E-cadherin and protease-activated receptor (PAR) proteins were observed through immune-fluorescence method. Distribution of actin filament is well organized in NS group however; distribution pattern was grossly varied in CS, OLPK and OSCC. Generation of ROS was low in NS which subsequently increased towards OSCC. Expressions of E-cadherin and change in cellular electrical impedance in different study groups indicated the hallmark of cancer progression from NS to OSCC. Expressions of E-cadherin, PAR protein, and cell impedance were decreased from NS to CS and farther OSCC. Generally, the oral epithelial cells exhibit apico-basal polarity however with cancer progression these cells lose their characteristic polarity distribution. In this study expression of polarity molecule and ECIS observation indicates such altered pattern of polarity among smoker group. Overall the present study monitored the alterations in intracellular ROS generation and cell metabolic function, membrane integrity in oral epithelial cells in cigarette smokers. Present study thus has clinical significance, and it may help in developing a noninvasive technique for early diagnosis of oral cancer amongst susceptible individuals.

Keywords: cigarette smoking, early oral cancer detection, electric cell-substrate impedance sensing, noninvasive screening

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Authors: Anas Al-Ali, Mohammed Suleiman, Ayman Hussein

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Sulfur is an important element has many practical applications in present as nanoparticles. Nanosize sulfur particles also have many important applications like in pharmaceuticals, medicine, syn-thesis of nano-composites for lithium batteries, modification of carbon nano tubes. Different methods were used for nano-sized particle synthesis; among those, chemical precipitation, electrochemical method, micro emulsion technique, composing of oil, surfactant, co-surfactant, aqueous phases with the specific compositions and ultrasonic treatment of sulfur-cystine solution. In this work Sulfur nanoparticles (S NPs) were prepared by a quick precipitation method with and without using a surfactant to stabilize the formed S NPs. The synthesized S NPs were characterized by XRD, SEM and TEM in order to confirm their sizes and structures.Application of nanotechnology is suggested for diag-nosis and treatment of cancer. The anticancer activity of the prepared S NPs has been tested on various types of cancer cell clones including leukemia, kidney and colon cancers.

Keywords: sulfur nanoparticles (S-NPs), TEM, SEM, XRD

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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

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Authors: Soumya Sajjan

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Liver cancer is the most common cancer disease worldwide in men and women, and is one of the few cancers still on the rise. Liver disease is the 4th leading cause of death. According to new NHS (National Health Service) figures, deaths from liver diseases have reached record levels, rising by 25% in less than a decade; heavy drinking, obesity, and hepatitis are believed to be behind the rise. In this study, we focus on Development of Diagnostic Classifier for Ultrasound liver lesion. Ultrasound (US) Sonography is an easy-to-use and widely popular imaging modality because of its ability to visualize many human soft tissues/organs without any harmful effect. This paper will provide an overview of underlying concepts, along with algorithms for processing of liver ultrasound images Naturaly, Ultrasound liver lesion images are having more spackle noise. Developing classifier for ultrasound liver lesion image is a challenging task. We approach fully automatic machine learning system for developing this classifier. First, we segment the liver image by calculating the textural features from co-occurrence matrix and run length method. For classification, Support Vector Machine is used based on the risk bounds of statistical learning theory. The textural features for different features methods are given as input to the SVM individually. Performance analysis train and test datasets carried out separately using SVM Model. Whenever an ultrasonic liver lesion image is given to the SVM classifier system, the features are calculated, classified, as normal and diseased liver lesion. We hope the result will be helpful to the physician to identify the liver cancer in non-invasive method.

Keywords: segmentation, Support Vector Machine, ultrasound liver lesion, co-occurance Matrix

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Authors: Vanitha Varadharaj, Vijalakshmi Krishnamurthy

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Annona squamosa Linn, commonly known as Sugar apple, belonging to the family Annonaceae, is said to show varied medicinal effects, including insecticide, antiovulatory and abortifacient. The alkaloid and flavonoids present in Annona squamosa leaf has proved to have antioxidant activity. The present work has been planned to investigate the effect of ethanolic leaf extract of Annona squamosa leaf on Den Induced wistar albino rats. The study was carried out to analyze the biochemical Parmeters like Total Proteins, Bilirubin, Enzymatic and Non –Enzymatic enzymes, Marker enzymes and Tumor markers in serum and also the histopathological studies in liver is carried out in control and DEN induced rats. Supplementation of ELAS (Ethanolic Leaf Extract Of Annona squamosa) reduced the liver weight and also reduced the tumour incidence. Chemoprevention group showed near normal values of bilirubin when compared with the control rats. Total protein was decreased in the cancer bearing group and on treatment with the extract the levels of protein were restored. Both in pre and post treatment group, the activities of enzymatic antioxidants such as superoxide dismutase, catalase, and Glutathione peroxidase were increased but in pre treated animals it was more effective than post treated animals. The non- enzymatic antioxidants such as vitamin C and vitamin E were brought back to normal level significantly in post and pre treated animals. Activities of marker enzymes such as SGOT, SGPT, ALP, γ GT were significantly elevated in the serum of cancer animals and the values returned to normal after treatment with the extract suggesting the hepato protective effect of the extract. Lipid peroxide was found to be elevated in the cancer induced group. This condition was brought back to the normal in the pre and post treated animals with ELAS. Histological examination also confirmed the anti- carcinogenic potential of ELAS, Cancer induced groups had a triple fold increase in their AFP values when compared to other groups. DEN treatment increased the level of AFP expression while ELAS partially counteracted the effect of it. So the scientific validation obtained from this study may pave way to many budding scientists to find new drugs from Annona squamosa for various ailments.

Keywords: annona squamosa, biochemical parmeters, cancer, leaf extract

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Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

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Authors: Kedir Teji Roba, Thomas P. O’Connor, Tefera Belachew, Nora M. O’Brien

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Micronutrient deficiencies of ferritin, zinc and haemoglobin are prevalent among the mothers and their infants in developing countries. But little attention has been given to these vulnerable groups. No study has been done on co-existence of the deficiencies among lactating mothers and their breast feeding infants in two different agro-ecological zones of rural Ethiopia. Methods: Data were collected from 162 lactating mothers and their breast feeding infants (aged 6-23 months) who were living in two different agro-ecological zones. The data were collected via a structured interview, anthropometric measurements, and blood test for Zinc, ferritin and anaemia. Correlation and Chi square test were used to determine the association among nutritional status and agro ecological zones. Results: Iron deficiency was found in 44.4% of the infants and 19.8% of the mothers. Zinc deficiency was found in 72.2% of the infants and 67.3% of the mothers. Of the study subject 52.5% of the infants and 19.1% of the mothers were anaemic, and 29.6% of the infants and 10.5% of the mothers had iron deficiency anaemia. Among the mothers with iron deficiency, 81.2% and 56.2% of their children were deficient in zinc and iron respectively. Similarly, among the zinc deficient mothers, 75.2% and 45.3% of their children were deficient in zinc and iron. There was a strong correlation between the micronutrient status of the mothers and the infants on status of ferritin, zinc and anaemia (P < 0.001). There is also statistically significant association between micronutrient deficiency and agro-ecological zones among the mothers (p < 0.001) but not with their infants. Deficiency in one, two, or three, micronutrients was observed in 48.1%, 16.7% and 9.9% of the mothers and 35.8%, 29.0%, and 23.5%, of their infants respectively. Conclusion: This study shows that iron and zinc deficiencies are the prevalent micronutrient deficiencies among the lactating mothers and their infants, with variation of the magnitude across the agro-ecological zones. This finding calls for a need to design effective preventive public health nutrition programs to address both the mothers’ and their infants’ needs.

Keywords: ferritin/iron, zinc, anaemia, agroecology, malnutrition

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Authors: Godwin Dennison, C. E. Boulind, O. Gould, B. de Lacy Costello, J. Allison, P. White, P. Ewings, A. Wicaksono, N. J. Curtis, A. Pullyblank, D. Jayne, J. A. Covington, N. Ratcliffe, N. K. Francis

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Background: Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. Methods: A prospective, multi-centre, observational feasibility study was performed across three sites. Patients referred on NHS fast-track pathways for potential CRC provided a urine sample which underwent Gas Chromatography Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS) and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. Results: 558 patients participated with 23 (4.1%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity=0.878, specificity=0.882, AUROC=0.884). Conclusion: Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified therefore suggesting VOC analysis may have future utility as a triage tool. Acknowledgment: Funding: NIHR Research for Patient Benefit grant (ref: PB-PG-0416-20022).

Keywords: colorectal cancer, volatile organic compound, gas chromatography mass spectrometry, field asymmetric ion mobility spectrometry, selected ion flow tube mass spectrometry

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Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

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Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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Authors: Fadzil Ahmad, Noor Ashidi Mat Isa

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This study introduces an improved genetic algorithm procedure that focuses search around near optimal solution corresponded to a group of elite chromosome. This is achieved through a novel crossover technique known as Segmented Multi Chromosome Crossover. It preserves the highly important information contained in a gene segment of elite chromosome and allows an offspring to carry information from gene segment of multiple chromosomes. In this way the algorithm has better possibility to effectively explore the solution space. The improved GA is applied for the automatic and simultaneous parameter optimization and feature selection of artificial neural network in pattern recognition of medical problem, the cancer and diabetes disease. The experimental result shows that the average classification accuracy of the cancer and diabetes dataset has improved by 0.1% and 0.3% respectively using the new algorithm.

Keywords: genetic algorithm, artificial neural network, pattern clasification, classification accuracy

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Authors: Yasuyuki Takahashi, Hirotaka Shimada, Kyoko Saito

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Bone scintigraphy is widely used as a screening tool for bone metastases. However, the 180 to 240 minutes (min) waiting time after the intravenous (i.v.) injection of the tracer is both long and tiresome. To solve this shortcoming, a bone scan with a shorter waiting time is needed. In this study, we applied the Maximum Intensity Projection (MIP) and triple energy window (TEW) scatter correction to a whole body bone SPECT (Merged SPECT) and investigated shortening the waiting time. Methods: In a preliminary phantom study, hot gels of 99mTc-HMDP were inserted into sets of rods with diameters ranging from 4 to 19 mm. Each rod set covered a sector of a cylindrical phantom. The activity concentration of all rods was 2.5 times that of the background in the cylindrical body of the phantom. In the human study, SPECT images were obtained from chest to abdomen at 30 to 180 min after 99mTc- hydroxymethylene diphosphonate (HMDP) injection of healthy volunteers. For both studies, MIP images were reconstructed. Planar whole body images of the patients were also obtained. These were acquired at 200 min. The image quality of the SPECT and the planar images was compared. Additionally, 36 patients with breast cancer were scanned in the same way. The delectability of uptake regions (metastases) was compared visually. Results: In the phantom study, a 4 mm size hot gel was difficult to depict on the conventional SPECT, but MIP images could recognize it clearly. For both the healthy volunteers and the clinical patients, the accumulation of 99mTc-HMDP in the SPECT was good as early as 90 min. All findings of both image sets were in agreement. Conclusion: In phantoms, images from MIP with TEW scatter correction could detect all rods down to those with a diameter of 4 mm. In patients, MIP reconstruction with TEW scatter correction could improve the detectability of hot lesions. In addition, the time between injection and imaging could be shortened from that conventionally used for whole body scans.

Keywords: merged SPECT, MIP, TEW scatter correction, 99mTc-HMDP

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Authors: Heeba A. Gurku

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Introduction: Cone Beam CT(CBCT) images play an integral part in proper patient positioning in cancer patients undergoing radiation therapy treatment. But these images are low in quality. The purpose of this study is to generate high-quality synthetic CT images from CBCT using generative models. Material and Methods: This study utilized two datasets from The Cancer Imaging Archive (TCIA) 1) Lung cancer dataset of 20 patients (with full view CBCT images) and 2) Pancreatic cancer dataset of 40 patients (only 27 patients having limited view images were included in the study). Cycle Generative Adversarial Networks (GAN) and its variant Attention Guided Generative Adversarial Networks (AGGAN) models were used to generate the synthetic CTs. Models were evaluated by visual evaluation and on four metrics, Structural Similarity Index Measure (SSIM), Peak Signal Noise Ratio (PSNR) Mean Absolute Error (MAE) and Root Mean Square Error (RMSE), to compare the synthetic CT and original CT images. Results: For pancreatic dataset with limited view CBCT images, our study showed that in Cycle GAN model, MAE, RMSE, PSNR improved from 12.57to 8.49, 20.94 to 15.29 and 21.85 to 24.63, respectively but structural similarity only marginally increased from 0.78 to 0.79. Similar, results were achieved with AGGAN with no improvement over Cycle GAN. However, for lung dataset with full view CBCT images Cycle GAN was able to reduce MAE significantly from 89.44 to 15.11 and AGGAN was able to reduce it to 19.77. Similarly, RMSE was also decreased from 92.68 to 23.50 in Cycle GAN and to 29.02 in AGGAN. SSIM and PSNR also improved significantly from 0.17 to 0.59 and from 8.81 to 21.06 in Cycle GAN respectively while in AGGAN SSIM increased to 0.52 and PSNR increased to 19.31. In both datasets, GAN models were able to reduce artifacts, reduce noise, have better resolution, and better contrast enhancement. Conclusion and Recommendation: Both Cycle GAN and AGGAN were significantly able to reduce MAE, RMSE and PSNR in both datasets. However, full view lung dataset showed more improvement in SSIM and image quality than limited view pancreatic dataset.

Keywords: CT images, CBCT images, cycle GAN, AGGAN

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Authors: Nusrat Masood, Vijaya Dubey, Suaib Luqman

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Caspase 3, a member of cysteine-aspartic acid protease family, is an imperative indicator for cell death particularly when substantiating apoptosis. Thus, caspase 3 is an interesting target for the discovery and development of anticancer agent. We adopted a four level assessment of both terpenoids and flavonoids and thus experimentally performed the enzymatic assay in cell free system as well as in cancer cell line which was validated through real time expression and molecular interaction studies. A significant difference was observed with both the class of natural products indicating terpenoids as better activators of caspase 3 compared to flavonoids both in the cell free system as well as in cell lines. The expression analysis, activation constant and binding energy also correlate well with the enzyme activity. Overall, terpenoids had an unswerving effect on caspase 3 in all the tested system while flavonoids indirectly affect enzyme activity.

Keywords: Caspase 3, terpenoids, flavonoids, activation constant, binding energy

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Authors: Arfaoui Emna, Nouira Mariem

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Background and aims: Breastfeeding is the reference feeding for a child, especially during the first months of life. It is not widespread in many countries due to many factors. There has been a decline in exclusive breastfeeding (EB) practice, particularly in the middle- and low-income countries, i.e., Tunisia. The aim of our study was to describe the knowledge, attitudes, and practice of a sample of Tunisian mothers toward breastfeeding. Methods: It was a descriptive cross-sectional study conducted during the year 2022 over a period of two months in three health structures in the north of Tunisia among mothers of infants aged 2 to 18 months. Levels of mothers’ knowledge (low/moderate/high) were determined using a score ranging from 0 to 11 points. EB was defined as the proportion of infants who were exclusively breastfed during the first six months of life. Results: A total of 180 women with a mean age of 33±4.9 years were included. The average knowledge score was equal to 6.4 ±1.5 points, with extremes ranging from 3 to 11 points. Most of the respondents had a moderate knowledge level (44.4%). More than half of surveyed mothers (66.1%) thought that breastfeeding deforms breasts, and 16.7% thought that breastfeeding is specific to women who do not work. Breastfeeding experience during the first week of life was considered difficult in 70% of cases. The prevalence of EB up to 6 months of age was equal to 16.4% [10.8-23.2]. The main reported obstacles during breastfeeding practice were having an insufficient quantity of breast milk (18.3%) and child difficulties with sucking (12.8%), and having pain in the breast while breastfeeding (12.80%). Conclusion: Our results highlighted the insufficient level of knowledge and a low prevalence of EB in our study population. Improving mothers’ knowledge and promoting EB practice is needed. Implementing health education strategies involving healthcare workers, who represent a main actor in education and breastfeeding promotion, is very important to reach a satisfactory frequency for EB.

Keywords: breastfeeding, practices, knowledge, Tunisia

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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

Procedia PDF Downloads 326

Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

Abstract:

Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

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

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

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

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