Search results for: malignant mixed mullerian tumor

Authors: Chao Wu

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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Mounir Zili

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We will introduce a new extension of the Brownian motion, that could serve to get a good model of many natural phenomena. It is a linear combination of a finite number of sub-fractional Brownian motions; that is why we will call it the mixed sub-fractional Brownian motion. We will present some basic properties of this process. Among others, we will check that our process is non-markovian and that it has non-stationary increments. We will also give the conditions under which it is a semi-martingale. Finally, the main features of its sample paths will be specified.

Keywords: fractal dimensions, mixed gaussian processes, sample paths, sub-fractional brownian motion

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Authors: Gregor Bouville, Celine Schmidt

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This article presents a French case study on lean production drawing on a mixed method design which has received little attention in French management research-especially in French human resources research. The purpose is to show that using a mixed method approach in this particular case overstep the limitations of previous studies in lean production studies. The authors use the embedded design as a special articulation of mixed method to analyse and understand the effects of three organizational practices on job satisfaction and workers’ health. Results show that low scheduled autonomy, quality management, time constraint have deleterious effects on job satisfaction. Furthermore, these three practices have ambivalent effects on health work. Interest in the subjects of mixed method has been growing up among French health researchers and practioners, also recently among French management researchers. This study reinforces and refines how mixed methods may offer interesting perspectives in an integrated framework included human resources, management, and health fields. Finally, potentials benefits and limits for those interdisciplinary researches programs are discussed.

Keywords: lean production, mixed method, work organization practices, job satisfaction

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Mohamed Khalifa Zayet, Salma Belal Eiid, Mushira Mohamed Dahaba

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Introduction: Malignant tumors may not be easily detected by traditional radiographic techniques especially in an anatomically complex area like maxillofacial region. At the same time, the advent of biological functional MRI was a significant footstep in the diagnostic imaging field. Objective: The purpose of this study was to define the malignant metabolic profile of maxillofacial lesions using diffusion MRI and magnetic resonance spectroscopy, as adjunctive aids for diagnosing of such lesions. Subjects and Methods: Twenty-one patients with twenty-two lesions were enrolled in this study. Both morphological and functional MRI scans were performed, where T1, T2 weighted images, diffusion-weighted MRI with four apparent diffusion coefficient (ADC) maps were constructed for analysis, and magnetic resonance spectroscopy with qualitative and semi-quantitative analyses of choline and lactate peaks were applied. Then, all patients underwent incisional or excisional biopsies within two weeks from MR scans. Results: Statistical analysis revealed that not all the parameters had the same diagnostic performance, where lactate had the highest areas under the curve (AUC) of 0.9 and choline was the lowest with insignificant diagnostic value. The best cut-off value suggested for lactate was 0.125, where any lesion above this value is supposed to be malignant with 90 % sensitivity and 83.3 % specificity. Despite that ADC maps had comparable AUCs still, the statistical measure that had the final say was the interpretation of likelihood ratio. As expected, lactate again showed the best combination of positive and negative likelihood ratios, whereas for the maps, ADC map with 500 and 1000 b-values showed the best realistic combination of likelihood ratios, however, with lower sensitivity and specificity than lactate. Conclusion: Diffusion weighted imaging and magnetic resonance spectroscopy are state-of-art in the diagnostic arena and they manifested themselves as key players in the differentiation process of orofacial tumors. The complete biological profile of malignancy can be decoded as low ADC values, high choline and/or high lactate, whereas that of benign entities can be translated as high ADC values, low choline and no lactate.

Keywords: diffusion magnetic resonance imaging, magnetic resonance spectroscopy, malignant tumors, maxillofacial

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Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

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Authors: Nicole Ramlachan, Samuel Mark West

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

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

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Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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Authors: Mohammed Althobiti, Patrick Booms, Dorota Fiszer, Philip Hopkins

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Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. MH results from anaesthetics induced breakdown of calcium homeostasis. RYR1 and CACN1AS mutations represent the aetiology in ~70% of the MH population. Previous studies indicate that up to 25% of MH patients carry no variants in these genes. Therefore, the aim of this study is to investigate the relationships between MH susceptibility and genes encoding skeletal muscle Ca2+ channels as well as accessory proteins. The JSRP, encoding JP-45, was previously sequenced and novel genetic variants were identified. The variant p.P108L (c.323C > T) was identified in exon 4 and encodes a change from a proline at amino acid 108 to leucine residue. The variant P108L was detected in two patients out of 50 with 4% frequency in the sample population. The alignment of DNA sequences in different species indicates highly conserved proline sequences involved in the substitution of the P108L variant. In this study, the variant P108L co-segregates with the SNP p.V92A (c.275T > C) at the same exon, both variants being inherited in the same two patients only. This indicates that the two variants may represent a haplotype. Therefore, a set of single nucleotide polymorphisms and statistical analysis will be used to investigate the effects of haplotypes on MH susceptibility. Furthermore, investigating the effect of the P108L variant in combination with RYR1 mutations or other genetic variants in other genes as a combination of two or more genetic variants, haplotypes may then provide stronger genetic evidence indicating that JSRP1 is associated with MH susceptibility. In conclusion, these preliminary results lend a potential modifier role of the variant P108L in JSRP1 in MH susceptibility and further investigations are suggested to confirm these results.

Keywords: JSRP1, malignant hyperthermia, RyR1, skeletal muscle

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Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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Authors: Md Abdullah Al Mashud, M. Tariquzzaman, M. Jahangir Alam, Tapan Kumar Godder, M. Mahbubur Rahman

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This paper presents a Monte Carlo (MC) method-based dose distributions on lung tumor for 6 MV photon beam to improve the dosimetric accuracy for cancer treatment. The polystyrene which is tissue equivalent material to the lung tumor density is used in this research. In the empirical calculations, TRS-398 formalism of IAEA has been used, and the setup was made according to the ICRU recommendations. The research outcomes were compared with the state-of-the-art experimental results. From the experimental results, it is observed that the proposed based approach provides more accurate results and improves the accuracy than the existing approaches. The average %variation between measured and TPS simulated values was obtained 1.337±0.531, which shows a substantial improvement comparing with the state-of-the-art technology.

Keywords: lung tumour, Monte Carlo, polystyrene, Elekta synergy, Monaco planning system

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Authors: Anuar Ishak

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The mixed convection stagnation point flow toward a vertical plate is investigated. The external flow impinges normal to the heated plate and the surface temperature is assumed to vary linearly with the distance from the stagnation point. The governing partial differential equations are transformed into a set of ordinary differential equations, which are then solved numerically using MATLAB routine boundary value problem solver bvp4c. Numerical results show that dual solutions are possible for a certain range of the mixed convection parameter. A stability analysis is performed to determine which solution is linearly stable and physically realizable.

Keywords: dual solutions, heat transfer, mixed convection, stability analysis

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: S. Oudjemia, F. Alim, S. Seddiki

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This paper shows the application of multifractal analysis for additional help in cancer diagnosis. The medical image processing is a very important discipline in which many existing methods are in search of solutions to real problems of medicine. In this work, we present results of multifractal analysis of brain MRI images. The purpose of this analysis was to separate between healthy and cancerous tissue of the brain. A nonlinear method based on multifractal detrending moving average (MFDMA) which is a generalization of the detrending fluctuations analysis (DFA) is used for the detection of abnormalities in these images. The proposed method could make separation of the two types of brain tissue with success. It is very important to note that the choice of this non-linear method is due to the complexity and irregularity of tumor tissue that linear and classical nonlinear methods seem difficult to characterize completely. In order to show the performance of this method, we compared its results with those of the conventional method box-counting.

Keywords: irregularity, nonlinearity, MRI brain images, multifractal analysis, brain tumor

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Authors: Rida Ahmad, Areej S. Habib, Sohail A. Dogar, Saqib H. Qazi

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Transverse testicular ectopia is a rare congenital disorder involving mal descent and mal-positioning of the testes, reported in the medical literature about 300 times. Many theories attempt to explain the failure of the testes to migrate to their correct location. While the age at presentation can vary; most cases present in early adolescents or late adulthood. It is often an incidental discovery made during an operative intervention, most commonly during hernia exploration. It can be isolated or present with a plethora of anomalies. We present the case of a 2-year-old male with transverse testicular ectopia who presented with vague abdominal pain. He was managed successfully with the Modified Ombredanne procedure and good outcome 6 months after the procedure.

Keywords: cryptorchidism, persistent Mullerian duct syndrome, transverse testicular ectopia, testicular mal-descent

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Authors: Yung-Chih Kuo, I-Hsuan Lee

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Solid lipid nanoparticles (SLNs) conjugated with aprotinin (Apr) and melanotransferrin antibody (Anti-MTf) were used to carry doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) chemotherapy. Dox-entrapped SLNs with grafted Apr and Anti-MTf (Apr-Anti-MTf-Dox-SLNs) were applied to a cultured monolayer comprising human brain-microvascular endothelial cells (HBMECs) with regulation of human astrocyte (HAs) and to a proliferated colony of U87MG cells. Based on the average particle diameter, zeta potential, entrapping efficiency of Dox, and grafting efficiency of Apr and Anti-MTf, we found that 40% (w/w) 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in lipids were appropriate for fabricating Apr-Anti-MTf-Dox-SLNs. In addition, Apr-Anti-MTf-Dox-SLNs could prevent Dox from fast dissolution and did not induce a serious cytotoxicity to HBMECs and HAs when compared with free Dox. Moreover, the treatments with Apr-Anti-MTf-Dox-SLNs enhanced the ability of Dox to infuse the BBB and to inhibit the growth of GBM. The current Apr-Anti-MTf-Dox-SLNs can be a promising pharmacotherapeutic preparation to penetrate the BBB for malignant brain tumor treatment.

Keywords: solid lipid nanoparticle, glioblastoma multiforme, blood–brain barrier, doxorubicin

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Authors: Shuko Takeshita

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This study investigates the identity formation of mixed-race children in Japan. From the latter half of the 1980s to the mid-2000s, Japan experienced an 'intermarriage boom,' which was soon followed by a fairly significant number of children born to these unions. These children are now coming of age. Among mixed-race children, some embraced both cultural traditions, while others chose a monocultural path despite exposure to two cultural traditions as they grew up. What factors are involved in shaping the identity of mixed-race children? How does identity formation actually occur in these children? This study addresses these questions through an interview survey of 139 cross-cultural families since 1999, including 23 Pakistani-Japanese families, 20 Turkish-Japanese families, 26 families comprising other international Muslim husbands and Japanese wives, 33 Filipino-Japanese families, and 37 Brazilian-Japanese families. The results of this two-decade-long study reveal that in cases where one cannot tell at first glance that children are mixed race, there is a tendency for them to hide their mixed background due to fear of bullying at school, as well as for their parents to encourage them to do this. To pass as a Japanese is one strategy for avoiding discrimination and prejudice, and it can provide a measure of ethnic security or a way of coping with social intolerance. Certainly, among my informants, there are some children who were bullied or teased at school, and as a result, they stopped attending or transferred to other schools. But the mixed-race experience is not always a negative thing in Japan. There is clearly a double standard involved in that mixed-race children of a Caucasian parent are more readily accepted by society than those of a non-Caucasian parent. The perceived social status of mixed-race individuals is usually understood in relation to the hierarchical positionings of monoracial groups. Mixed-race children could be guaranteed the right to enjoy the benefit of maintaining and developing an identity as a Japanese, in addition to one more identity. We need to encourage a new awareness of the children as agents for a transition from a monocultural system to a multicultural system in Japanese society.

Keywords: identity formation, intermarriage, mixed race, multicultural children

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Authors: Anoosh Eghdami

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Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

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Authors: Sujeet Poudyal

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Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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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: Po-Chin Liang, Yung-Chu Chen, Chi-Feng Chiang, Yun-Ping Lin, Wen-Yuan Hsieh, Win-Li Lin

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The aim of this study was to develop super paramagnetic iron oxide (SPIO) nano-particles comprised of a magnetic Fe3O4 core and a shell of aqueous stable self-doped polyethylene glycol (PEG) with a high loading of doxorubicin (SPIO-PEG-D) for tumor theranostics. The in-vivo MRI study showed that there was a stronger T2-weighted signal enhancement for the group under a magnetic field, and hence it indicated that this group had a better accumulation of SPIO-PEG than the group without a magnetic field. In the anticancer evaluation of SPIO-PEG-D, the group with a magnetic field displayed a significantly smaller tumor size than the group without. The overall results show that SPIO-PEG-D nanoparticles have the potential for the application of MRI/monitoring chemotherapy and the therapy can be locally enhanced by applying an external magnetic field.

Keywords: super paramagnetic iron oxide nano particles, doxorubicin, chemotherapy, MRI, magnetic fields

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Authors: Dalia M. Abouelfadl, Noha N. Yassen, Marwa E. Shabana

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Background: The evolution of immune therapy motivated many to study the relation between immune response and progression of cancer. Little is known about expression of PD-L1 (a newly evolving immunotherapeutic drug) in papillary thyroid carcinoma (PTC) arising de-novo and PTC arising on top of autoimmune thyroiditis (Hashimoto's (HT) and lymphocytic thyroiditis (LT)). The aim of this work is to study the alteration of expression of PD-L1 in PTCs arising from de-novo or on top of HT OR LT using immunohistochemistry and image analyser system. Method: 100 paraffin blocks for PTC cases were collected retrospectively for staining using PD-L1 rabbit monoclonal antibody (BIOCARE-ACI 3171 A, C). The antibody expression is measured digitally using Image Analyzer Leica Qwin 3000, and the membranous and cytoplasmic expression of PD-L1 in tumor cells was considered positive. The results were correlated with tumor grade, size, and LN status. Results: The study samples consisted of 41 cases of PTC arising De novo, 36 cases on top of HT, and 23 on top of LT. Expression of PD-L1 was highest among the PTC-HL group (25 case-69%) followed by PTC-TL group (14 case-60.8%) then de-novo PTC (19 case-46%) with P Value < 0.05. PD-L1 expression correlated with nodal metastasis and was not relevant to tumor size or grade. Conclusion: The severity of the immune response in tumor microenvironment directly influences PTC prognosis. The anti PD-L1 Ab can be a very successful therapeutic agent for PTC arising on top of HT.

Keywords: carcinoma, Hashimoto's, lymphocytic, papillary, PD-L1, thyroiditis

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Authors: Sepehr Moradi, Mehdi Asadi Rad

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The aim of this study is to evaluate and compare live weight of pure and mixed races Tizpar 30-day pigeons to investigate about their sex, race, and some auxiliary variables. In this paper, 70 pieces of pigeons as 35 male and female pairs with equal age are studied randomly. A natural incubation was done from each pair. All produced chickens were weighted at 30 days age before and after hunger by a scale with one gram precision. A covariance analysis was used since there were many auxiliary variables and unequal observations. SAS software was used for statistical analysis. Mean weight of live in pure race (Tizpar-Tizpar) with 12 records, 182.3±60.9 gr and mixed races of Tizpar-Kabood, Tizpar-Parvazy, Tizpar-Namebar, Kabood-Tizpar, Namebar-Tizpar, and Parvazy-Tizpar with 10, 10, 8, 6, 12, and 12 records were 114.3±71.6, 210.6±71.7, 353.2±86, 520.8±81.5, 288.3±65.6, and 382.6±70.4 gr, respectively. Effects of sex, race and some auxiliary variables were also significant in 1% level (P < 0.01). Difference live weight of 30-day of Tizpar-Tizpar race with Tizpar-Namebar and Parvazi-Tizpar mixed races was significant in 5% level (P < 0.05) and with Kabood-Tizpar mixed races was significant in 1% level (P < 0.01) but with Tizpar-Kabood, Nmaebar-Tizpar and Tizpar-Parvazy mixed races was not significant. The results showed that most and least weights of live belonged to Kabood-Tizpar and Tizpar-Kabood.

Keywords: squabs, Tizpar race, 30-day live weight, pigeons

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Authors: Mohamed A. Morsy, Azza A. K. El-Sheikh, Abdulla Y. Al-Taher

Abstract:

The aim of the present study is to investigate the effect of resveratrol (RES) on methotrexate (MTX)-induced testicular damage. RES (10 mg/kg/day) was given for 8 days orally and MTX (20 mg/kg i.p.) was given at day 4 of experiment, with or without RES in rats. MTX decreased serum testosterone, induced histopathological testicular damage, increased testicular tumor necrosis factor-α level and expression of nuclear factor-κB and cyclooxygenase-2. In MTX/RES group, significant reversal of these parameters was noticed, compared to MTX group. Testicular expression of multidrug resistance protein (Mrp) 3 was three- and five-folds higher in RES- and MTX/RES-treated groups, respectively. In vitro, using prostate cancer cells, each of MTX and RES alone induced cytotoxicity with IC50 0.18 ± 0.08 and 20.5 ± 3.6 µM, respectively. RES also significantly enhanced cytotoxicity of MTX. In conclusion, RES appears to have dual beneficial effect, as it promotes MTX tumor cytotoxicity, while protecting the testes, probably via up-regulation of testicular Mrp3 as a novel mechanism.

Keywords: resveratrol, methotrexate, multidrug resistance protein 3, tumor necrosis factor-α, nuclear factor-κB, cyclooxygenase-2

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Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani

Abstract:

Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.

Keywords: antitumor, honey, sider, tumor cell lines

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Authors: Simeon Mayala, Ida Herdlevær, Jonas Bull Haugsøen, Shamundeeswari Anandan, Sonia Gavasso, Morten Brun

Abstract:

In this paper, we propose a minimum spanning tree-based method for segmenting brain tumors. The proposed method performs interactive segmentation based on the minimum spanning tree without tuning parameters. The steps involve preprocessing, making a graph, constructing a minimum spanning tree, and a newly implemented way of interactively segmenting the region of interest. In the preprocessing step, a Gaussian filter is applied to 2D images to remove the noise. Then, the pixel neighbor graph is weighted by intensity differences and the corresponding minimum spanning tree is constructed. The image is loaded in an interactive window for segmenting the tumor. The region of interest and the background are selected by clicking to split the minimum spanning tree into two trees. One of these trees represents the region of interest and the other represents the background. Finally, the segmentation given by the two trees is visualized. The proposed method was tested by segmenting two different 2D brain T1-weighted magnetic resonance image data sets. The comparison between our results and the standard gold segmentation confirmed the validity of the minimum spanning tree approach. The proposed method is simple to implement and the results indicate that it is accurate and efficient.

Keywords: brain tumor, brain tumor segmentation, minimum spanning tree, segmentation, image processing

Procedia PDF Downloads 96

Authors: Mohamad Ahrari, Kayvan Sadri, Mahmoud Reza Jafari

Abstract:

PEGylated liposomes have a smaller volume of distribution and decreased clearance, consequently, due to their more prolonged presence in bloodstream and maintaining their stability during this period, these liposomes can be applied for imaging tumoral sites. The purpose of this study is to develop an appropriate radiopharmaceutical agent in long-term imaging for improved diagnosis and evaluation of tumors. In this study, liposomal formulations encapsulating albumin is synthesized by solvent evaporation method along with homogenization, and their characteristics were assessed. Then these liposomes labeled by Philips method and the rate of stability of labeled liposomes in serum, and ultimately the rate of biodistribution and gamma scintigraphy in C26-colon carcinoma tumor-bearing mice, were studied. The result of the study of liposomal characteristics displayed that capable of accumulating in tumor sites based of EPR phenomenon. these liposomes also have high stability for maintaining encapsulated albumin in a long time. In the study of biodistribution of these liposomes in mice, they accumulated more in the kidney, liver, spleen, and tumor sites, which, even after clearing formulations in the bloodstream, they existed in high levels in these organs up to 96 hours. In gamma scintigraphy also, organs with high activity accumulation from early hours up to 96 hours were visible in the form of hot spots. concluded that PEGylated liposomal formulation encapsulating albumin can be labeled with In-Oxine, and obtained stabilized formulation for long-term imaging, that have more favorable conditions for the evaluation of tumors and it will cause early diagnosis of tumors.

Keywords: nano liposome, 111In-oxine, imaging, biodistribution, tumor

Procedia PDF Downloads 72

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Martin Van, Mohammed Javed, Sarah Hemington-Gorse

Abstract:

Aim: Our aim was to determine the effect of size and tumor depth of basal cell carcinomas (BCCs) on surgical margin clearance. Methods: A retrospective study was conducted at the Welsh Centre for Burns and Plastic Surgery (WCBPS), Morriston Hospital between 1 Jan 2016 – 31 July 2016. Only patients with confirmed BCC on histopathological analysis were included. Patient data including anatomical region treated, lesion size, histopathological clearance margins and histological sub-types were recorded. An independent T-test was performed determine statistical significance. Results: A total of 228 BCCs were excised in 160 patients. Eleven lesions (4.8%) were incompletely excised. The nose area had the highest rate of incomplete excision. The mean diameter of incompletely excised lesions was 11.4mm vs 11.5mm in completely excised lesions (p=0.959) and the mean histological depth of incompletely excised lesions was 4.1mm vs. 2.5mm for completely excised BCCs (p < 0.05). Conclusions: BCC tumor depth of > 4.1 mm was associated with high rate of incomplete margin clearance. Hence, in prospective patients, a BCC tumor depth (>4 mm) on tissue biopsy should alert the surgeon of potentially higher risk of incomplete excision of lesion.

Keywords: basal cell carcinoma, excision margins, plastic surgery, treatment

Procedia PDF Downloads 211