Search results for: De novo malignancy

Authors: Wissam Saliba, Mandy Nicholson

Abstract:

Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Raquel Mateo Mendaza, Carmen Novo Urraca

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The current paper presents the elaboration of a corpus database that aligns two different corpora in order to simplify the search of information both for researchers and students of Old English. This database comprises the information contained in two main reference corpora, namely the Dictionary of Old English Corpus (DOEC), compiled at the University of Toronto, and the York-Toronto-Helsinki Parsed Corpus of Old English (YCOE). The first one provides information on all surviving texts written in the Old English language. The latter offers the syntactical and morphological annotation of several texts included in the DOEC. Although both corpora are closely related, as the YCOE includes the DOE source text identifier, the main problem detected is that there is not an alignment of texts that allows for the search of whole fragments to be further analysed in terms of morphology and syntax. The database proposed in this paper gathers all this information and presents it in a simple, more accessible, visual, and educational way. The alignment of fragments has been done in an automatized way. However, some problems have emerged during the creating process particularly related to the lack of correspondence in the division of fragments. For this reason, it has been necessary to revise the whole entries manually to obtain a truthful high-quality product and to carefully indicate the gaps encountered in these corpora. All in all, this database contains more than 60,000 entries corresponding with the DOE fragments annotated by the YCOE. The main strength of the resulting product is its research and teaching implications in the study of Old English. The use of this database will help researchers and students in the study of different aspects of the language, such as inflectional morphology, syntactic behaviour of given words, or translation studies, among others. By means of the search of words or fragments, the annotated information on morphology and syntax will be automatically displayed, automatizing, and speeding up the search of data.

Keywords: alignment, corpus database, morphosyntactic analysis, Old English

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Authors: Vandana Singh, Subash Singh

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Introduction: Oral squamous cell carcinoma is the most common malignant tumor of the oral cavity. Normally the death of cell and the growth are active processes and depend not only on external factors but also on the expression of genes like Bcl-2, which activate and inhibit apoptosis. The term Bcl-2 is an acronym for B-cell lymphoma/ leukemia -2 genes. Objectives: An attempt was made to evaluate Bcl-2 oncoprotein expression in patients with oral precancer and cancer and to assess possible correlation between Bcl-2 oncoprotein expression and clinicopathological features of oral precancer and cancer. Material and Methods: This is a selective prospective clinical and immunohistochemical study. Clinicopathological examination is correlated with immunohistochemical findings. The immunolocalization of Bcl-2 protein is performed using the labeled streptavidin biotin (LSAB) method. To visualize the reaction, 3, 3-diaminobenzidine (DAB) is used. Results: Bcl-2 expression was positive in 11 [36.66 %, low Bcl-2 expression 3 (10.00 %), moderate Bcl-2 expression 7 (23.33 %), and high Bcl-2 expression 1 (3.33 %)] oral cancer cases and in 14 [87.50 %, low expression 8 (50 %), moderate expression 6 (37.50 %)] precancer cases. Conclusion: On the basis of the results of our study we conclude that positive Bcl-2 expression may be an indicator of poor prognosis in oral cancer and precancer. Relevance: It has been reported that there is deregulation of Bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. It can be used for revealing progression of epithelial dysplasia to malignancy and as a prognostic marker in oral precancer and cancer.

Keywords: BcL-2, immunohistochemistry, oral cancer, oral precancer

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Authors: Roland Benedict Reyes, Marc Edsel Ayes, Regina Berba, Cybele Lara Abad

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Background: Three AIDS-defining malignancies have been associated with the human immunodeficiency virus (HIV): Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical carcinoma. However, new cases of non-AIDS defining malignancies also have been increasingly associated with HIV. One of these is a rare intracranial malignancy, meningeal hemangiopericyotma. Case Description: A 32-year old HIV-positive male, not on highly active antiretroviral therapy, was admitted to our hospital due to generalized weakness and sudden onset hearing loss. Cranial MRI was done, which revealed a temporal nodule with the following considerations: granuloma, meningioma or metastases. A craniotomy was performed and the mass excised. Results from the biopsy showed meningeal hemangiopericytoma. The patient was then started on antiretroviral therapy (Lamivudine, Tenofovir, and Efavirenz) and was discharged for radiation therapy and metastatic work-up as an outpatient. On follow-up seven months later, metastatic work up revealed multiple hepatic foci not previously documented suggestive of metastasis short of biopsy sampling. Conclusions: This case of an intracranial hemangiopericytoma in an HIV-positive patient is the second case thus far presented, based on our systematic and extensive search of the literature.

Keywords: Hemangiopericytoma, Human Immunodeficiency Virus, Meningeal hemangiopericytoma, Neoplasm

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Authors: A. F. Suleimanov, A. B. Saduakassova, V. S. Pokrovsky, D. V. Vinnikov

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Relevance: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with relapse occurring in about 70% of advanced cases with poor prognoses. The aim of the study was to evaluate functional visceral fat activity (VAT) evaluated by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) as a predictor of metastases in epithelial ovarian cancer (EOC). Materials and methods: We assessed 53 patients with histologically confirmed EOC who underwent ¹⁸F-FDG PET/CT after a surgical treatment and courses of chemotherapy. Age, histology, stage, and tumor grade were recorded. Functional VAT activity was measured by maximum standardized uptake value (SUVₘₐₓ) using ¹⁸F-FDG PET/CT and tested as a predictor of later metastases in eight abdominal locations (RE – Epigastric Region, RLH – Left Hypochondriac Region, RRL – Right Lumbar Region, RU – Umbilical Region, RLL – Left Lumbar Region, RRI – Right Inguinal Region, RP – Hypogastric (Pubic) Region, RLI – Left Inguinal Region) and pelvic cavity (P) in the adjusted regression models. We also identified the best areas under the curve (AUC) for SUVₘₐₓ with the corresponding sensitivity (Se) and specificity (Sp). Results: In both adjusted-for regression models and ROC analysis, ¹⁸F-FDG accumulation in RE (cut-off SUVₘₐₓ 1.18; Se 64%; Sp 64%; AUC 0.669; p = 0.035) could predict later metastases in EOC patients, as opposed to age, sex, primary tumor location, tumor grade, and histology. Conclusions: VAT SUVₘₐₓ is significantly associated with later metastases in EOC patients and can be used as their predictor.

Keywords: ¹⁸F-FDG, PET/CT, EOC, predictive value

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Authors: C. A. Ologunde

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Escherichia coli have been a major microorganisms associated with, and isolated from feacal samples either in adult or children all over the world. Strains of these organisms are resistant to cephalosporins and fluoroquinolone (FQ) antimicrobial agents among hospitalized patients and FQs are the most frequently prescribed antimicrobial class in hospitals, and the level of resistant of E. coli to these antimicrobial agents is a risk factor that should be assessed. Hence, this study was conducted to determine the prevalence and risk factors for colonization with fluoroquinolone (FQ)-resistant E. coli in hospitalized patients in Ado-Ekiti. Rectal swabs were obtained from patients in hospitals in the study area and FQ-resistant E. coli were isolated and identified by means of Nalidixic acid multi-disk and a 1-step screening procedure. Species identification and FQ resistance were confirmed by automated testing (Vitek, bioMerieux, USA). Individual colonies were subjected to pulse-field gel electrophoresis (PAGE) to determine macro-restriction polymorphism after digestion of chromosomal DNA. FQ-resistant E. coli was detected in the stool sample of 37(62%) hospitalized patient. With multivariable analyses, the use of FQ before hospitalization was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures for the 3-12 months of study. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified conal spread of 1(one) strain among 18 patients. Loss (9 patients) or acquisition (10 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. It was concluded that FQ-resistant E. coli carriage was associated with clonal spread. The differential effects of individual fluoroquinolone on antimicrobial drug resistance are an important area for future study, as hospitals manipulate their formularies with regard to use of individual fluoroquinolone, often for economic reasons.

Keywords: E. coli, fluoroquinolone, risk factors, feacal carriage, hospitalized patients, Ado-Ekiti

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: Lamis Naddaf, Yuval Tabach

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In this research, we identified the missense genetic variants that have the potential to enhance resistance against cancer. Such field has not been widely explored, as researchers tend to investigate mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution, and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and can have significant implications on improved risk estimation, diagnostics, prognosis and even for personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and picked up the alleles that showed a correlation with the species’ cancer resistance. We predicted 250 protecting variants (PVs) with a 0.01 false discovery rate and more than 20 thousand PVs with a 0.25 false discovery rate. Cancer resistance in Mammals and reptiles was significantly predicted by the number of PVs a species has. Moreover, Genes enriched with the protecting variants are enriched in pathways relevant to tumor suppression like pathways of Hedgehog signaling and silencing, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are more abundant in healthy people compared to cancer patients within different human races.

Keywords: comparative genomics, machine learning, cancer resistance, cancer-protecting alleles

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Authors: Marzieh Jafarzadeh, Fatemeh Rezaee

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Introduction: The effect of ionizing radiation on human health can be effective for genomic integrity and cell viability. It also increases the risk of cancer and malignancy. Therefore, X-ray behavior and absorption dose calculation are considered. One of the applicable tools for calculating and evaluating the absorption dose in human tissues is Monte Carlo simulation. Monte Carlo offers a straightforward way to simulate and integrate, and because it is simple and straightforward, Monte Carlo is easy to use. The Monte Carlo BEAMnrc code is one of the most common diagnostic X-ray simulation codes used in this study. Method: In one of the understudy hospitals, a certain number of CT scan images of patients who had previously been imaged were extracted from the hospital database. BEAMnrc software was used for simulation. The simulation of the head of the device with the energy of 0.09 MeV with 500 million particles was performed, and the output data obtained from the simulation was applied for phantom construction using CT CREATE software. The percentage of depth dose (PDD) was calculated using STATE DOSE was then compared with international standard values. Results and Discussion: The ratio of surface dose to depth dose (D/Ds) in the measured energy was estimated to be about 4% to 8% for bone and 3% to 7% for bone marrow. Conclusion: MC simulation is an efficient and accurate method for simulating bone marrow and calculating the absorbed dose.

Keywords: Monte Carlo, absorption dose, BEAMnrc, bone marrow

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Authors: Salwa Hagag Abdelaziz, Dorria Salem, Hoda Zaki, Suzan Atteya

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Early detection of breast cancer saves many thousands of lives each year via application of mammography and genetic screening and many more lives could be saved if nurses are involved in breast care screening practices. So, the aim of the study was to identify nurse's role in early detection of breast cancer through mammography and genetic screening and its impact on patient's outcome. In order to achieve this aim, 400 women above 40 years, asymptomatic were recruited for mammography and genetic screening. In addition, 50 nurses and 6 technologists were involved in the study. A descriptive analytical design was used. Five tools were utilized: sociodemographic, mammographic examination and risk factors, women's before, during and after mammography, items relaying to technologists, and items related to nurses were also obtained. The study finding revealed that 3% of women detected for malignancy and 7.25% for fibroadenoma. Statistically, significant differences were found between mammography results and age, family history, genetic screening, exposure to smoke, and using contraceptive pills. Nurses have insufficient knowledge about screening tests. Based on these findings the present study recommended involvement of nurses in breast care which is very important to in force population about screening practices.

Keywords: mammography, early detection, genetic screening, breast cancer

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Authors: Manjunath A. P., Al-Ajmi G. M., Al Shukri M., Girija S

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Introduction: This study aimed to compare the ability of hysteroscopy and ultrasonography to diagnose uterine polyps. To correlate the ultrasonography and hystroscopic findings with various clinical factors and histopathology of uterine polyps. Methods: This is a retrospective study conducted at the Department of Obstetrics and Gynaecology at Sultan Qaboos University Hospital from 2014 to 2019. All women undergoing hysteroscopy for suspected uterine polyps were included. All relevant data were obtained from the electronic patient record and analysed using SPSS. Results: A total of 77 eligible women were analysed. The mean age of the patients was 40 years. The clinical risk factors; obesity, hypertension, and diabetes mellitus, showed no significant statistical association with the presence of uterine polyps (p-value>0.005). Although 20 women (52.6%) with uterine polyps had thickened endometrium (>11 mm), however, there is no statistical association (p-value>0.005). The sensitivity and specificity of ultrasonography in the detection of uterine polyp were 39% and 65%, respectively. Whereas for hysteroscopy, it was 89% and 20%, respectively. The prevalence of malignant and premalignant lesions were 1.85% and 7.4%, respectively. Conclusion: This study found that obesity, hypertension, and diabetes mellitus were not associated with the presence of uterine polyps. There was no association between thick endometrium and uterine polyps. The sensitivity is higher for hysteroscopy, whereas the specificity is higher for sonography in detecting uterine polyps. The prevalence of malignancy was very low in uterine polyps.

Keywords: endometrial polyps, hysteroscopy, ultrasonography, premalignant, malignant

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Authors: Lamis Naddaf, Yuval Tabach

Abstract:

We identified missense genetic variants with the potential to enhance resistance against cancer. Such a field has not been widely explored as researchers tend to investigate the mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and have significant implications for improved risk estimation, diagnostics, prognosis, and even personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and selected the alleles that showed a correlation with the species’ cancer resistance. Interestingly, we found several amino acids that are more generally preferred (like the Proline) or avoided (like the Cysteine) by the resistant species. Furthermore, Cancer resistance in mammals and reptiles is significantly predicted by the number of the predicted protecting variants (PVs) a species has. Moreover, PVs-enriched-genes are enriched in pathways relevant to tumor suppression. For example, they are enriched in the Hedgehog signaling and silencing pathways, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are mostly more abundant in healthy people compared to cancer patients within different human races.

Keywords: cancer resistance, protecting variant, naked mole rat, comparative genomics

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Authors: Michael Aupetit, Mahmoud Al-ismail, Khaled Mohamed

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Cancer is a major public health problem all over the world. Breast cancer has the highest incidence rate over all cancers for women in Qatar making its study a top priority of the country. Human cancer is a dynamic disease that develops over an extended period through the accumulation of a series of genetic alterations. A Darwinian process drives the tumor cells toward higher malignancy growing the branches of a progression tree in the space of genes expression. Although it is not possible to track these genetic alterations dynamically for one patient, it is possible to reconstruct the progression tree from the aggregation of thousands of tumor cells’ genetic profiles from thousands of different patients at different stages of the disease. Analyzing the progression tree is a way to detect pivotal molecular events that drive the malignant evolution and to provide a guide for the development of cancer diagnostics, prognostics and targeted therapeutics. In this work we present the development of a Visual Analytic web platform CanVis enabling users to upload gene-expression data and analyze their progression tree. The server computes the progression tree based on state-of-the-art techniques and allows an interactive visual exploration of this tree and the gene-expression data along its branching structure helping to discover potential driver genes.

Keywords: breast cancer, progression tree, visual analytics, web platform

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Authors: Roudabeh Vakil Monfared, Farhad Mashayekhi

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Breast cancer is the most common malignancy type among women with about 1 million new cases each year. The immune system plays an important role in the breast cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a member of the tumor necrosis factor super family binds to its receptor OX40 and this co-stimulation has a crucial role in T-cell proliferation, survival and cytokine release. Due to the importance of the T-cells in anti-tumor activities of OX40L we studied the association of rs3850641 (T→C) polymorphism of OX40L gene with breast cancer. The study included 123 women with breast cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was extracted from blood leucocytes. Genotype and allele frequencies were determined in patients and control cases with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the analysis was performed by Med Calc. The prevalence of genotype frequencies of TT, CT and CC were 60.9%, 30.08% and 8.9 % in patients with breast cancer and 74.6 %, 18.25 % and 7.14 % in healthy volunteers while the T and C allelic frequency was 76.01% and 23.98 % in patients and 83.73% and 16.26% in healthy controls. Respectively Statistical analysis has shown no significant difference from the comparison of either genotype (P=0.06). According to these results, the rs3850641 SNP has no association with the susceptibility of breast cancer in a population in northern Iran. However, further studies in larger populations including other genetic and environmental factors are required to achieve conclusion.

Keywords: OX40L, gene, polymorphism, breast cancer

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Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

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Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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Authors: Abhishikta Ghosh Roy

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Breast cancer is the most common malignancy among women globally, including India. Human breast cancer results from the genetic and environmental interaction. The present study attempts to understand the molecular heterogeneity of BRCA1 and BRCA2 genes, as well as to understand the association of various lifestyle and reproductive variables for the Breast Cancer risk. The study was conducted amongst 110 patients and 128 controls with total DNA sequencing of flanking and coding regions of BRCA1 BRCA2 genes that revealed ten Single Nucleotide Polymorphisms (SNPs) (6 novels). The controls selected for the study were age, sex and ethnic group matched. After written and informed consent biological samples were collected from the subjects. After detailed molecular analysis, significant (p < 0.005) molecular heterogeneity is revealed in terms of SNPs in BRCA1 (4 Exonic & 1 Intronic) and BRCA2 (2exonic and 3 Intronic) genes. The augmentation study investigated significant (p < 0.05) association with positive family history, early age at menarche, irregular menstrual periods, menopause, prolong contraceptive use, nulliparity, history of abortions, consumption of alcohol and smoking for breast cancer risk. To the best of authors knowledge, this study is the first of its kind, envisaged that the identification of the SNPs and modification of the lifestyle factors might aid to minimize the risk among the Bengalee Hindu females.

Keywords: breast cancer, BRCA, lifestyle, India

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Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

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Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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Authors: Zohra Salim

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Objective: To access the relationship of primary tumor thickness with cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa. Methodology: A cross-sectional observational study was carried out on 80 Patients with biopsy-proven oral squamous cell carcinoma of buccal mucosa at Dow University of Health Sciences. All the study participants were treated with wide local excision of the primary tumor with elective neck dissection. Patients with prior head and neck malignancy or those with prior radiotherapy or chemotherapy were excluded from the study. Data was entered and analyzed on SPSS 21. Chi-squared test with 95% C.I and 80% power of the test was used to evaluate the relationship of tumor depth with cervical lymph nodes. Results: 50 participants were male, and 30 patients were female. 30 patients were in the age range of 20-40 years, 36 patients in the range of 40-60 years, while 14 patients were beyond age 60 years. Tumor size ranged from 0.3cm to 5cm with a mean of 2.03cm. Tumor depth ranged from 0.2cm to 5cm. 20% of the participants reported with tumor depth greater than 2.5cm, while 80% of patients reported with tumor depth less than 2.5cm. Out of 80 patients, 27 reported with negative lymph nodes, while 53 patients reported with positive lymph nodes. Conclusion: Our study concludes that relationship exists between the depth of primary tumor and cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa.

Keywords: squamous cell carcinoma, tumor depth, cervical lymphadenopathy, buccal mucosa

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Authors: Roni Rachel Mendelson, Caileigh Pudela

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Bacillus cereus is a toxin-producing, facultatively anaerobic gram-positive bacterium that is widely distributed environmentally. It can quickly multiply at room temperature with an abundantly present preformed toxin. When ingested, this toxin can cause gastrointestinal illness, which is the commonly known manifestation of the disease. Bacillus cereus sepsis is a disease that is mostly concerning in the population of the immunocompromised patients. One of them is acute lymphoblastic leukemia’s patients during induction. Pediatric acute lymphoblastic leukemia is a common pediatric hematologic malignancy. It is characterized by the rapid proliferation of poorly differentiated lymphoid progenitor cells inside the bone marrow. We present here a 21-month-old boy undergoing induction chemotherapy for acute lymphoblastic leukemia who developed bacillus sepsis bacteremia and, as a result, multi organ failure leading to seizures and multiple strokes. Our case report highlights the extensive overall and neurological damage that can be caused because of bacillus cereus bacteremia, which can lead to higher mortality rate and decreased in survivorship in a highly curable disease. It is very subtle and difficult to recognize and appears to be deteriorating extremely fast. There should be a low threshold for work up and empiric coverage for neutropenic patients during acute lymphoblastic leukemia induction therapy.

Keywords: acute lymphoblastic leukemia, bacillus cereus, immunocompromised, sepsis

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Authors: Aadil Khan, Yasser Chomayil, P. P. Venugopalan

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Background: Budd-Chiari syndrome is caused by thrombosis of the hepatic veins and/or the thrombosis of the intrahepatic or suprahepatic IVC. The etiology remains idiopathic in 16% -35% of cases. Malignancy, rheumatological disorder, myeloproliferative disease, inheritable coagulopathy, infection or hyperestrogen state can be identified in many cases. Methodology: Review of case records of the patient presented to Aster Medcity, Emergency Department, Cochin. Introduction:17 years old female was presented to ED with fever, jaundice and abdominal distention since 1 week. O/E: Pallor+, icterus+. Abdomen- gross distension+, shifting dullness+, generalized anasarca+. USG abdomen showed hepatomegaly with mild coarse echotexture and moderate to gross ascites. CT abdomen and chest showed hepatomegaly with thrombosis of all three hepatic vein and moderate ascites suggestive of Budd-Chiari syndrome. Patient was taken for catheter vein thrombolysis. Venogram done the next day revealed almost > 50% opening of the right hepatic vein. Concurrent doppler showed colour and doppler signals in middle hepatic veins. She gradually improved and was discharged home on anticoagulant and adviced regular follow up. Conclusion: Being a rare disease in this young population, high suspicion is required when evaluating young patients with abdominal pain and jaundice.

Keywords: Budd-Chiari syndrome, rare disease, abdominal pain, India

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Authors: Sakeh N. Mohd, Bahari M. N. Abdul, Abdullah S. N. Akmar

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Oil palm production generates high export earnings to many countries especially in Southeast Asian region. Infection by necrotrophic fungus, Ganoderma boninense on oil palm results in basal stem rot which compromises oil palm production leading to significant economic loss. There are no reliable disease treatments nor promising resistant oil palm variety has been cultivated to eradicate the disease up to date. Thus, understanding molecular mechanisms underlying early interactions of oil palm with Ganoderma boninense may be vital to promote preventive or control measure of the disease. In the present study, four months old oil palm seedlings were infected via artificial inoculation of Ganoderma boninense on rubber wood blocks. Roots of six biological replicates of treated and untreated oil palm seedlings were harvested at 0, 3, 7 and 11 days post inoculation. Next-generation sequencing was performed to generate high-throughput RNA-Seq data and identify differentially expressed genes (DEGs) during early oil palm-Ganoderma boninense interaction. Based on de novo transcriptome assembly, a total of 427,122,605 paired-end clean reads were assembled into 30,654 unigenes. DEGs analysis revealed upregulation of 173 transcription factors on Ganoderma boninense-treated oil palm seedlings. Sixty-one transcription factors were categorized as DEGs according to stringent cut-off values of genes with log2 ratio [Number of treated oil palm seedlings/ Number of untreated oil palm seedlings] ≥ |1.0| (corresponding to 2-fold or more upregulation) and P-value ≤ 0.01. Transcription factors in response to biotic stress will be screened out from abiotic stress using reverse transcriptase polymerase chain reaction. Transcription factors unique to biotic stress will be verified using real-time polymerase chain reaction. The findings will help researchers to pinpoint defense response mechanism specific against Ganoderma boninense.

Keywords: Ganoderma boninense, necrotrophic, next-generation sequencing, transcription factors

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Authors: Abraham J. Rizkalla, Joanne F. Irons, Christopher Q. Cao

Abstract:

Purpose: Lobectomy was considered the standard of care for early-stage non-small lung cancer (NSCLC) after the Lung Cancer Study Group trial demonstrated increased locoregional recurrence for sublobar resections. However, there has been heightened interest in segmentectomies for selected patients with peripheral lesions ≤2cm, as investigated by the JCOG0802 and CALGB140503 trials. Minimally invasive robotic surgery facilitates segmentectomies with improved maneuverability and visualization of intersegmental planes using indocyanine green. We hereby present a patient who underwent robotic lingulectomy for an undiagnosed ground-glass opacity. Methodology: This video demonstrates a robotic portal lingulectomy using three 8mm ports and a 12mm port. Stereoscopic direct vision facilitated the identification of the lingula artery and vein, and intra-operative bronchoscopy was performed to confirm the lingula bronchus. The intersegmental plane was identified by indocyanine green and a near-infrared camera. Thorough lymph node sampling was performed in accordance with international standards. Results: The 18mm lesion was successfully excised with clear margins to achieve R0 resection with no evidence of malignancy in the 8 lymph nodes sampled. Histopathological examination revealed lepidic predominant adenocarcinoma, pathological stage IA. Conclusion: This video presentation exemplifies the standard approach for robotic portal lingulectomy in appropriately selected patients.

Keywords: lung cancer, robotic segmentectomy, indocyanine green, lingulectomy

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Authors: Alka Yadav, Mayank Jain, Rajan Saxena, Niraj Kumari, Narendra Krishnani, Ashok Kumar

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Purpose: To study the mismatch repair (MMR) protein expression and its clinicopathological correlation in colorectal cancer patients in North India. Methods: A prospective study was conducted on histologically proven 52 (38 males and 14 females) patients with adenocarcinoma of colorectum. MMR protein loss was determined by using immunohistochemistry for MLH1, MSH2, PMS2 and MSH6. Results: 52 patients (38 males and 14 females) underwent resection for colorectal cancer with the median age of 52 years (16-81 years). 35% of the patients (n=18) were younger than 50 years of the age. 3 patients had associated history of malignancy in the family. 29 (56%) patients had right colon cancer, 9 (17%) left colon cancer and 14 (27%) rectal cancer. 2 patients each had synchronous and metachronous cancer. Histology revealed well-differentiated tumour in 16, moderately differentiated in 10 and poorly differentiated tumour in 26 patients. MMR protein loss was seen in 15 (29%) patients. Seven (46%) of these patients were less than 50 years of age. Combined loss of MSH2 and MSH6 was seen most commonly and it was found in 6 patients. 12 (80%) patients with MMR protein loss had tumour located proximal to the splenic flexure compared to 3 (20%) located distal to the splenic flexure. There was no difference in MMR protein loss based on patients' age, gender, degree of tumour differentiation, stage of the disease and tumour histological characteristics. Conclusions: This study revealed that there was less than 30% MMR protein loss in colorectal cancer patients. The loss was most commonly seen in right sided colon cancer than left. A larger study is further required to validate these findings.

Keywords: colorectal cancer, mismatch repair protein, immunohitochemistry, clinicopathological correlation

Procedia PDF Downloads 197

Authors: Wadha Alqahtani

Abstract:

In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

Procedia PDF Downloads 91

Authors: Veronika Zivicova, Petr Broz, Zdenek Fik, Alzbeta Mifkova, Jan Plzak, Zdenek Cada, Herbert Kaltner, Jana Fialova Kucerova, Hans-Joachim Gabius, Karel Smetana Jr.

Abstract:

The possibility to determine genome-wide expression profiles of cells and tissues opens a new level of analysis in the quest to define dysregulation in malignancy and thus identify new tumor markers. Toward this long-term aim, we here address two issues on this level for head and neck cancer specimen: i) defining profiles in different regions, i.e. the tumor, the transition zone and normal control and ii) comparing complete data sets for seven individual patients. Special focus in the flanking immunohistochemical part is given to adhesion/growth-regulatory galectins that upregulate chemo- and cytokine expression in an NF-κB-dependent manner, to these regulators and to markers of differentiation, i.e. keratins. The detailed listing of up- and down-regulations, also available in printed form (1), not only served to unveil new candidates for testing as marker but also let the impact of the tumor in the transition zone become apparent. The extent of interindividual variation raises a strong cautionary note on assuming uniformity of regulatory events, to be noted when considering therapeutic implications. Thus, a combination of test targets (and a network analysis for galectins and their downstream effectors) is (are) advised prior to reaching conclusions on further perspectives.

Keywords: galectins, genome scale sequencing, squamous cell carcinoma, transition zone

Procedia PDF Downloads 208

Authors: Matheesha Herath, Ned Kinnear, Bridget Heijkoop, Eliza Bramwell, Alannah Frazetto, Amy Noll, Prajay Patel, Derek Hennessey, Greg Otto, Christopher Dobbins, Tarik Sammour, James Moore

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Background: Important incidental pathology requiring further action is commonly found during appendicectomy, macro- and microscopically. It is unknown whether the acute surgical unit (ASU) model affects the management and disclosure of these findings. Methods: An ASU model was introduced at our institution on 01/08/2012. In this retrospective cohort study, all patients undergoing appendicectomy 2.5 years before (traditional group) or after (ASU group) this date were compared. The primary outcomes were rates of appropriate management of the incidental findings and communication of the findings to the patient and to their general practitioner (GP). Results: 1,214 patients underwent emergency appendicectomy; 465 in the traditional group and 749 in the ASU group. 80 (6.6%) patients (25 and 55 in each respective period) had important incidental findings. There were 24 patients with benign polyps, 15 with neuro-endocrine tumour, 11 with endometriosis, 8 with pelvic inflammatory disease, 8 Enterobius vermicularis infection, 7 with low grade mucinous cystadenoma, 3 with inflammatory bowel disease, 2 with diverticulitis, 2 with tubo-ovarian mass, 1 with secondary appendiceal malignancy and none with primary appendiceal adenocarcinoma. One patient had dual pathologies. There was no difference between the traditional and ASU group with regards to communication of the findings to the patient (p=0.44) and their GP (p=0.27), and there was no difference in the rates of appropriate management (p=0.21). Conclusions: The introduction of an ASU model did not change rates of surgeon-to-patient and surgeon-to-GP communication nor affect rates of appropriate management of important incidental pathology during an appendectomy.

Keywords: acute care surgery, appendicitis, appendicectomy, incidental

Procedia PDF Downloads 118

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

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

Keywords: breast cancer, molecular biology, ecology, environment

Procedia PDF Downloads 349

Authors: Rossana Taravella, Gilberto M. Cellura, Giuseppe Cirrincione, Salvatore Asciutto, Marco Caruso, Massimo Benedetto, Renato Ciofalo, Giuliana Pace, Salvatore Novo

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Objectives: This retrospective analysis sought to evaluate 1-month outcomes and therapy effectiveness of a population of patients treated with MitraClip therapy. We describe in this article the preliminary results of primary effectiveness endpoint. Background: Percutaneous Mitral Repair is being developed to treat severe mitral regurgitation (MR), with increasing real-world cases of functional MR (FMR). In the EVEREST (Endovascular Valve Edge-to-Edge Repair Study)II trial, the percutaneous device showed superior safety but less reduction in MR at 1year. 4-year outcomes from EVEREST II trial showed no difference in the prevalence of moderate-severe and severe MR or mortality at 4years between surgical mitral repair and percutaneous approach. Methods: We analysed retrospectively collected data from one center experience in Italy enrolled from January 2011 to December 2016. The study included 62 patients [mean age 74±11years, 43 men (69%)] with MR of at least grade3+. Most of the patients had functional MR, were in New York Heart Association (NYHA) functional class III or IV, with a large portion (78%) of mild-to-moderate Tricuspid Regurgitation (TR). One or more clips were implanted in 67 procedures (62 patients). Results and Conclusions: Severity of MR was reduced in all successfully treated patients,54(90%) were discharged with MR≤2+ (primary effectiveness endpoint). Clinical 1-month follow-up data showed an improvement in NYHA functional class (42 patients (70%) in NYHA class I-II). 60 of 62 (97 %) successfully treated patients were free from death and mitral valve surgery at 1-month follow-up. MitraClip therapy reduces functional MR with acute MR reduction to <2+ in the great majority of patients, with a large freedom from death, surgery or recurrent MR in a great portion of patients.

Keywords: MitraClip, mitral regurgitation, heart valves, catheter-based therapy

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Authors: Abdullah Saeidi, Aydin Gülses, Christan Flörke

Abstract:

Skin cancer of the face region is the most common type of malignancy and surgical excision is the preferred approach. However, the clinical long term results reported in the literature are still controversial. Objectives: To describe; 1. Demographical characteristics 2. Affected site, distribution and TNM classification regarding tumor type 3. Surgical aspects • Surgical removal: excision principles, safety margins, the need for secondary resection, primary reconstruction/ defect closure, anesthesia protocol, duration of hospital stay (if any) • Secondary intervention for defect closure/reconstruction: Flap technique, anesthesia protocol, duration of hospital stay (if any), postoperative wound management etc. 4. Tumor recurrences 5. Clinical outcomes 6. Studying the possible therapy approach throw Biostatistical relation and correlation between multiple Histological, diagnostics and clinical Faktors. following surgical ablation of the skin cancer of the head and neck region. Methods: Selection and statistical analysis of medical records of patients who had admitted to the Department of Oral and Maxillofacial Surgery, Universitätsklinikum Schleswig Holstein, Campus Kiel during the period of 2015-2019 will be retrospectively evaluated. Data will be collected via ORBIS Information-Management-System (ORBIS AG, Saarbrücken, Germany).

Keywords: non melanoma skin cancer, face skin cancer, skin reconstruction, non melanoma skin cancer recurrence, non melanoma skin cancer metastases

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Authors: Vivian A. Panes, Raymond John S. Rebong, Miel Q. Diaz

Abstract:

Moringa oleifera Lam. is known mainly for its high nutritional value and medicinal properties contributing to its popular reputation as a 'miracle plant' in the tropical climates where it usually grows. The main objective of this study is to discover the genes and gene products involved in abiotic stress-induced activity that may impact the M. oleifera Lam. mature seeds as well as their corresponding functions. In this study, RNA-sequencing and de novo transcriptome assembly were performed using two assemblers, Trinity and Oases, which produced 177,417 and 120,818 contigs respectively. These transcripts were then subjected to various bioinformatics tools such as Blast2GO, UniProt, KEGG, and COG for gene annotation and the analysis of relevant metabolic pathways. Furthermore, FPKM analysis was performed to identify gene expression levels. The sequences were filtered according to the 'response to stress' GO term since this study dealt with stress response. Clustered Orthologous Groups (COG) showed that the highest frequencies of stress response gene functions were those of cytoskeleton which make up approximately 14% and 23% of stress-related sequences under Trinity and Oases respectively, recombination, repair and replication at 11% and 14% respectively, carbohydrate transport and metabolism at 23% and 9% respectively and defense mechanisms 16% and 12% respectively. KEGG pathway analysis determined the most abundant stress-response genes in the phenylpropanoid biosynthesis at counts of 187 and 166 pathways for Oases and Trinity respectively, purine metabolism at 123 and 230 pathways, and biosynthesis of antibiotics at 105 and 102. Unique and cumulative GO term counts revealed that majority of the stress response genes belonged to the category of cellular response to stress at cumulative counts of 1,487 to 2,187 for Oases and Trinity respectively, defense response at 754 and 1,255, and response to heat at 213 and 208, response to water deprivation at 229 and 228, and oxidative stress at 508 and 488. Lastly, FPKM was used to determine the levels of expression of each stress response gene. The most upregulated gene encodes for thiamine thiazole synthase chloroplastic-like enzyme which plays a significant role in DNA damage tolerance. Data analysis implies that M. oleifera stress response genes are directed towards the effects of climate change more than other stresses indicating the potential of M. oleifera for cultivation in harsh environments because it is resistant to climate change, pathogens, and foreign invaders.

Keywords: stress response, genes, Moringa oleifera, transcriptomics

Procedia PDF Downloads 117