Search results for: tumor infiltrating lymphocytes

Authors: M. Ouassaf, S. Belaidi

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Aromatase is an estrogen biosynthetic enzyme belonging to the cytochrome P450 family, which catalyzes the limiting step in the conversion of androgens to estrogens. As it is relevant for the promotion of tumor cell growth. A set of thirty 1,2,3-triazole derivatives was used in the quantitative structure activity relationship (QSAR) study using regression multiple linear (MLR), We divided the data into two training and testing groups. The results showed a good predictive ability of the MLR model, the models were statistically robust internally (R² = 0.982) and the predictability of the model was tested by several parameters. including external criteria (R²pred = 0.851, CCC = 0.946). The knowledge gained in this study should provide relevant information that contributes to the origins of aromatase inhibitory activity and, therefore, facilitates our ongoing quest for aromatase inhibitors with robust properties.

Keywords: aromatase inhibitors, QSAR, MLR, 1, 2, 3-triazole

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Authors: Simona Perga, Chiara Beltramo, Floriana Fruscione, Isabella Martini, Federica Cavallo, Federica Riccardo, Paolo Buracco, Selina Iussich, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari, Paola Modesto

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Introduction: Human and canine melanoma have common clinical, histologic characteristics making dogs a good model for comparative oncology. The identification of specific genes and a better understanding of the genetic landscape, signaling pathways, and tumor–microenvironmental interactions involved in the cancer onset and progression is essential for the development of therapeutic strategies against this tumor in both species. In the present study, the differential expression of genes in spontaneously occurring canine melanoma and in paired normal tissue was investigated by targeted RNAseq. Material and Methods: Total RNA was extracted from 17 canine malignant melanoma (CMM) samples and from five paired normal tissues stored in RNA-later. In order to capture the greater genetic variability, gene expression analysis was carried out using two panels (Qiagen): Human Immuno-Oncology (HIO) and Mouse-Immuno-Oncology (MIO) and the miSeq platform (Illumina). These kits allow the detection of the expression profile of 990 genes involved in the immune response against tumors in humans and mice. The data were analyzed through the CLCbio Genomics Workbench (Qiagen) software using the Canis lupus familiaris genome as a reference. Data analysis were carried out both comparing the biologic group (tumoral vs. healthy tissues) and comparing neoplastic tissue vs. paired healthy tissue; a Fold Change greater than two and a p-value less than 0.05 were set as the threshold to select interesting genes. Results and Discussion: Using HIO 63, down-regulated genes were detected; 13 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Eighteen genes were up-regulated, 14 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Using the MIO, 35 down regulated-genes were detected; only four of these were down-regulated, also comparing neoplastic sample vs. paired healthy tissue. Twelve genes were up-regulated in both types of analysis. Considering the two kits, the greatest variation in Fold Change was in up-regulated genes. Dogs displayed a greater genetic homology with humans than mice; moreover, the results have shown that the two kits are able to detect different genes. Most of these genes have specific cellular functions or belong to some enzymatic categories; some have already been described to be correlated to human melanoma and confirm the validity of the dog as a model for the study of molecular aspects of human melanoma.

Keywords: animal model, canine melanoma, gene expression, spontaneous tumors, targeted RNAseq

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Authors: Abdol-Hassan Doulah

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In this research, some of the inorganic complexes of uranyl with N- donor ligands were synthesized. Complexes were characteriezed by FT-IR and UV spectra, ¹HNMR, ¹³CNMR and some physical properties. The uranyl unit (UO2) is composed of a center of uranium atom with the charge (+6) and two oxygen atom by forming two U=O double bonds. The structure is linear (O=U=O, 180) and usually stable. So other ligands often coordinate to the U atom in the plane perpendicularly to the O=U=O axis. The antitumor activity of some of ligand and their complexes against a panel of human tumor cell lines (HT29: Haman colon adenocarcinoma cell line T47D: human breast adenocarcinoma cell line) were determined by MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay. These data suggest that some of these compounds provide good models for the further design of potent antitumor compounds.

Keywords: inorganic, uranyl complex-donor ligands, Schiff bases, anticancer activity

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Authors: Ilirian Laçi, Alketa Spahiu

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Modality of treatment in hepatocellular carcinoma (HCC) patients depends on the stage of the disease. The Barcelona Clinic Liver Cancer Classification (BCLC) is the preferred staging system. There are many patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. The differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Because of these differences, not all patients benefit equally from TACE. Several tools have been devised to aid the decision-making process, which have shown promising initial results but have failed external evaluation and have not been translated to the clinic aspects. Criteria for treatment decisions in daily clinical practice are needed in all stages of the disease.

Keywords: hepatocellular carcinoma, transarterial chemoembolization, TACE, liver

Procedia PDF Downloads 96

Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Abdul Aziz, Muhammad Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam

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Introduction: The most common endocrine tumor is thyroid cancer. Follicular Thyroid Carcinoma (FTC) accounts for 5%–10% of all thyroid cancers. Patients with FTC frequently present with more advanced stage diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery, while radioactive iodine therapy is the main adjuvant therapy as per ATA guidelines. In many developing countries, surgical facilities and radioactive iodine are in short supply; therefore, understanding follicular thyroid cancer trends may help developing countries plan and use resources more effectively. Methodology: It was a retrospective observational study of FTC patients of age 18 years and above conducted at Aga Khan University Hospital, Karachi, from 1st January 2010 to 31st December 2019. Results: There were 404 patients with thyroid carcinoma, out of which forty (10.1%) were FTC. 50% of the patients were in the 41-60 years age group, and the female to male ratio was 1.5: 1. Twenty-four patients (60%) presented with complain of neck swelling followed by metastasis (20%) and compressive symptoms (20%). The most common site of metastasis was bone (87.5%), followed by lung (12.5%). The pre-operative thyroglobulin level was done in six out of eight metastatic patients (75%) in which it was elevated. This emphasizes the importance of checking thyroglobulin level in unusual presentation (bone pain, fractures) of a patient having neck swelling also to help in establishing the primary source of tumor. There was no complete documentation of ultrasound features of the thyroid gland in all the patients, which is an important investigation done in the initial evaluation of thyroid nodule. On FNAC, 50% (20 patients) had Bethesda category III-IV nodules, while 10% ( 4 patients ) had Bethesda category II. In sixteen patients, FNAC was not done as they presented with compressive symptoms or metastasis. Fifty percent had a total thyroidectomy and 50% had subtotal followed by completion thyroidectomy, plus ten patients had lymph node dissection, out of which seven had histopathological lymph node involvement. On histopathology, twenty-three patients (57.5%) had minimally invasive, while seventeen (42.5%) had widely invasive follicular thyroid carcinoma. The capsular invasion was present in thirty-three patients (82.5%); one patient had no capsular invasion, but there was a vascular invasion. Six patients' histopathology had no record of capsular invasion. In contrast, the lymphovascular invasion was present in twenty-six patients (65%). In this study, 65 % of the patients had clinical stage 1 disease, while 25% had stage 2 and 10% had clinical stage 4. Seventeen patients (42.5%) had received RAI 30-100 mCi, while ten patients (25%) received more than 100 mCi. Conclusion: FTC demographic and clinicopathological presentation are the same in Pakistan as compared to other countries. Surgery followed by RAI is the mainstay of treatment. Thus understanding the trend of FTC and proper planning and utilization of the resources will help the developing countries in effectively treating the FTC.

Keywords: thyroid carcinoma, follicular thyroid carcinoma, clinicopathological features, developing countries

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Authors: Angelis P. Barlampas

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Introduction: The term phantom lung mass describes the ovoid collection of fluid within the interlobular fissure, which initially creates the impression of a mass. The problem of correct differential diagnosis is great, especially in plain radiography. A case is presented with three nodular pulmonary foci, the shape, location, and density of which, as well as the presence of chronic loculated pleural effusions, suggest the presence of multiple phantom tumors of the lung. Purpose: The aim of this paper is to draw the attention of non-experienced and non-specialized physicians to the existence of benign findings that mimic pathological conditions and vice versa. The careful study of a radiological examination and the comparison with previous exams or further control protect against quick wrong conclusions. Methods: A hospitalized patient underwent a non-contrast CT scan of the chest as part of the general control of her situation. Results: Computed tomography revealed pleural effusions, some of them loculated, increased cardiothoracic index, as well as the presence of three nodular foci, one in the left lung and two in the right with a maximum density of up to 18 Hounsfield units and a mean diameter of approximately five centimeters. Two of them are located in the characteristical anatomical position of the major interlobular fissure. The third one is located in the area of the right lower lobe’s posterior basal part, and it presents the same characteristics as the previous ones and is likely to be a loculated fluid collection, within an auxiliary interlobular fissure or a cyst, in the context of the patient's more general pleural entrapments and loculations. The differential diagnosis of nodular foci based on their imaging characteristics includes the following: a) rare metastatic foci with low density (liposarcoma, mucous tumors of the digestive or genital system, necrotic metastatic foci, metastatic renal cancer, etc.), b) necrotic multiple primary lung tumor locations (squamous epithelial cancer, etc. ), c) hamartomas of the lung, d) fibrotic tumors of the interlobular fissures, e) lipoid pneumonia, f) fluid concentrations within the interlobular fissures, g) lipoma of the lung, h) myelolipomas of the lung. Conclusions: The collection of fluid within the interlobular fissure of the lung can give the false impression of a lung mass, particularly on plain chest radiography. In the case of computed tomography, the ability to measure the density of a lesion, combined with the provided high anatomical details of the location and characteristics of the lesion, can lead relatively easily to the correct diagnosis. In cases of doubt or image artifacts, comparison with previous or subsequent examinations can resolve any disagreements, while in rare cases, intravenous contrast may be necessary.

Keywords: phantom mass, chest CT, pleural effusion, cancer

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Authors: Sudhir Kumar Sharma, Abiy D. Woldetsadik, Mazin Magzoub, Ramesh Jagannathan

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It is well known that bioactive ceramics exhibit specific biological affinities, especially in the area of tissue re-generation. In this context, we report the development of an eminently scalable, novel, supercritical CO₂ based process for the fabrication of hierarchically porous 'soft' CaCO₃ scaffolds. Porosity at the macro, micro, and nanoscales was obtained through process optimization of the so-called 'coffee-ring effect'. Exposure of these CaCO₃ scaffolds to monocytic THP-1 cells yielded negligible levels of tumor necrosis factor-alpha (TNF-α) thereby confirming the lack of immunogenicity of the scaffolds. ECM protein treatment of the scaffolds showed enhanced adsorption comparable to standard control such as glass. In vitro studies using osteoblast precursor cell line, MC3T3, also demonstrated the cytocompatibility of hierarchical porous CaCO₃ scaffolds.

Keywords: supercritical CO2, CaCO3 scaffolds, coffee-ring effect, ECM proteins

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Nabil Abu-Heakal, Ismail Abo-Ghanema, Basma Hamed Merghani

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The aim of this investigation is to study the effect of seasonal variations in Egypt on hematological parameters, reproductive and metabolic hormones of Egyptian buffalo-cows. This study lasted one year extending from December 2009 to November 2010 and was conducted on sixty buffalo-cows. Group of 5 buffalo-cows at estrus phase were selected monthly. Then, after blood sampling through tail vein puncture in the 2nd day after natural service, they were divided in two samples: one with anticoagulant for hematological analysis and the other without anticoagulant for serum separation. Results of this investigation revealed that the highest atmospheric temperature was in hot summer 32.61±1.12°C versus 26.18±1.67°C in spring and 19.92±0.70°C in winter season, while the highest relative humidity % was in winter season 43.50±1.60% versus 32.50±2.29% in summer season. The rise in temperature-humidity index from 63.73±1.29 in winter to 78.53±1.58 in summer indicates severe heat stress which is associated with significant reduction in total red blood cell count (3.20±0.15×106), hemoglobin concentration (8.83±0.43 g/dl), packed cell volume (30.73±0.12%), lymphocytes % (40.66±2.33 %), serum progesterone hormone concentration (0.56±0.03 ng/mll), estradiol17-B concentration (16.8±0.64 ng/ml), triiodothyronin (T3) concentration (2.33±0.33 ng/ml) and thyroxin hormone (T4) concentration (21.66±1.66 ng/ml), while hot summer resulted in significant increase in mean cell volume (96.55±2.25 fl), mean cell hemoglobin (30.81±1.33 pg), total white blood cell count (10.63±0.97×103), neutrophils % (49.66±2.33%), serum prolactin hormone (PRL) concentration (23.45±1.72 ng/ml) and cortisol hormone concentration (4.47±0.33 ng/ml) compared to winter season. There was no significant seasonal variation in mean cell hemoglobin concentration (MCHC). It was concluded that in Egypt there was a seasonal variation in atmospheric temperature, relative humidity, temperature humidity index (THI) and the rise in THI above the upper critical level (72 units), which, for lactating buffalo-cows in Egypt is the major constraint on buffalo-cows' hematological parameters and hormonal secretion that affects animal reproduction. Hence, we should improve climatic conditions inside the dairy farm to eliminate or reduce summer infertility.

Keywords: buffalo, climate change, Egypt, physiological parameters

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Authors: Amr A. Fouad, Hamed A. Alwadaani, Iyad Jresat

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The present study investigated the protective effect of thymoquinone (TQ), against cadmium-induced kidney injury in rats. Cadmium chloride (1.2 mg Cd/kg/day, s.c.), was given for nine weeks. TQ treatment (40 mg/kg/day, p.o.) started on the same day of cadmium administration and continued for nine weeks. TQ significantly decreased serum creatinine, renal malondialdehyde and nitric oxide, and significantly increased renal reduced glutathione in rats received cadmium. Histopathological examination showed that TQ markedly minimized renal tissue damage induced by cadmium. Immunohistochemical analysis revealed that TQ markedly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, and caspase-3 in renal tissue. It was concluded that TQ significantly protected against cadmium nephrotoxicity in rats, through its antioxidant, antiinflammatory, and antiapoptotic actions.

Keywords: thymoquinone, cadmium, kidney, rats

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Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

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Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) is above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) cytogenetic analysis of peripheral blood lymphocytes was used. Gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistic analysis the Mann-Whitney U-test was used. The mean Cr level in blood of exposed group was 0.095 µmol/l (0.019 min - max 0.504). No value exceeds the average normal value. The mean value Cr in urine was 7.9 µmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs. 0.80% and CSA-type 0.96% vs. 0.90%). In the number of total CA statistical difference was observed between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44% <1.82% <2.13%). A statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups was observed (1.22% vs. 0.59%, P <0.05). The work place is usually higher source of exposure to harmful factors. Workers need consistent and frequent health control. In assessing the risk of adverse effects of metals it is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: CCND1, genotoxicity, polymorphism, stainless steel, welders

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Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

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The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Keywords: hesperidin, cyclophosphamide, liver, rats

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Authors: Beth Taylor, Kojima Mituaki, Atsushi Senda, Koji Morishita, Yasuhiro Otomo

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Intestinal ischaemia-reperfusion injury drives systemic inflammation and organ failure following trauma/haemorrhagic shock (T/HS), through the release of pro-inflammatory mediators into the mesenteric lymph (ML). However, changes in the biological function of ML are not fully understood, and therefore, a specific model of intestinal ischaemia-reperfusion injury is required to obtain ML for the study of its biological function upon inflammatory cells. ML obtained from a model of intestinal ischaemia-reperfusion injury was used to assess biological function upon inflammatory cells and investigate changes in the biological function of individual ML components. An additional model was used to determine the effect of vagal nerve stimulation (VNS) upon biological function. Rat ML was obtained by mesenteric lymphatic duct cannulation before and after occlusion of the superior mesenteric artery (SMAO). ML was incubated with human polymorphonuclear neutrophils (PMNs), monocytes and lymphocytes, and the biological function of these cells was assessed. ML was then separated into supernatant, exosome and micro-vesicle components, and biological activity was compared in monocytes. A model with an additional VNS phase was developed, in which the right cervical vagal nerve was exposed and stimulated, and ML collected for comparison of biological function with the conventional model. The biological function of ML was altered by intestinal ischaemia-reperfusion injury, increasing PMN activation, monocyte activation, and lymphocyte apoptosis. Increased monocyte activation was only induced by the exosome component of ML, with no significant changes induced by the supernatant or micro-vesicle components. VNS partially attenuated monocyte activation, but no attenuation of PMN activation was observed. Intestinal ischaemia-reperfusion injury induces changes in the biological function of ML upon both innate and adaptive inflammatory cells, supporting the role of intestinal ischaemia-reperfusion injury in driving systemic inflammation following T/HS. The exosome component of ML appears to be critical to the transport of pro-inflammatory mediators in ML. VNS partially attenuates changes in innate inflammatory cell biological activity observed, presenting possibilities for future novel treatment development in multiple organ failure patients.

Keywords: exosomes, inflammation, intestinal ischaemia, mesenteric lymph, vagal stimulation

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Authors: L. Mallesha, C. S. Karthik, P. Mallu

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A series of new [1-(substituted-benzoyl)-piperidin-4-yl]-(2,4-difluoro-phenyl)-methanone oxime derivatives, 3(a-f) were synthesized and characterized by different spectral studies. All compounds were evaluated for their in vitro antibacterial activity against bacterial strains. These compounds were screened for their antioxidant activity by DPPH• and Fe2+ chelating assay. Antiproliferative effects were evaluated using the MTT assay method against two human cancer cell lines and one astrocytoma brain tumor cell line. Compound 3b exhibited moderate antibacterial activity when compared with other compounds. All the compounds showed antioxidant activity, where compound 3f was the best radical scavenger and Fe2+ ion scavenger. Compounds, 3b, and 3d showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.

Keywords: Piperidine, antibacterial, antioxidant, antiproliferative

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Authors: Diya Kohli, Amalia Ardeljan, Lexi Frankel, Jose Garcia, Lokesh Manjani, Omar Rashid

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Gonorrhea is the second most common sexually transmitted disease (STDs) in the United States of America. Gonorrhea affects the urethra, rectum, or throat and the cervix in females. Lymphoma is a cancer of the immune network called the lymphatic system that includes the lymph nodes/glands, spleen, thymus gland, and bone marrow. Lymphoma can affect many organs in the body. When a lymphocyte develops a genetic mutation, it signals other cells into rapid proliferation that causes many mutated lymphocytes. Multiple studies have explored the incidence of cancer in people infected with STDs such as Gonorrhea. For instance, the studies conducted by Wang Y-C and Co., as well as Caini, S and Co. established a direct co-relationship between Gonorrhea infection and incidence of prostate cancer. We hypothesize that Gonorrhea infection also increases the incidence of Lymphoma in patients. This research study aimed to evaluate the correlation between Gonorrhea infection and the incidence of Lymphoma. The data for the research was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. This database was utilized to evaluate patients infected with Gonorrhea versus the ones who were not infected to establish a correlation with the prevalence of Lymphoma using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for academic research. Standard statistical methods were applied throughout. Between January 2010 and December 2019, the query was analyzed and resulted in 254 and 808 patients in both the infected and control group, respectively. The two groups were matched by Age Range and CCI score. The incidence of Lymphoma was 0.998% (254 patients out of 25455) in the Gonorrhea group (patients infected with Gonorrhea that was Lymphoma Positive) compared to 3.174% and 808 patients in the control group (Patients negative for Gonorrhea but with Lymphoma). This was statistically significant by a p-value < 2.210-16 with an OR= 0.431 (95% CI 0.381-0.487). The patients were then matched by antibiotic treatment to avoid treatment bias. The incidence of Lymphoma was 1.215% (82 patients out of 6,748) in the Gonorrhea group compared to 2.949% (199 patients out of 6748) in the control group. This was statistically significant by a p-value <5.410-10 with an OR= 0.468 (95% CI 0.367-0.596). The study shows a statistically significant correlation between Gonorrhea and a reduced incidence of Lymphoma. Further evaluation is recommended to assess the potential of Gonorrhea in reducing Lymphoma.

Keywords: gonorrhea, lymphoma, STDs, cancer, ICD

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Authors: Sai Maniveer Adapa, Sai Guptha Perla, Adithya Reddy P.

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Thyroid nodules can often be diagnosed with ultrasound imaging, although differentiating between benign and malignant nodules can be challenging for medical professionals. This work suggests a novel approach to increase the precision of thyroid nodule identification by combining machine learning and deep learning. The new approach first extracts information from the ultrasound pictures using a deep learning method known as a convolutional autoencoder. A support vector machine, a type of machine learning model, is then trained using these features. With an accuracy of 92.52%, the support vector machine can differentiate between benign and malignant nodules. This innovative technique may decrease the need for pointless biopsies and increase the accuracy of thyroid nodule detection.

Keywords: thyroid tumor diagnosis, ultrasound images, deep learning, machine learning, convolutional auto-encoder, support vector machine

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Authors: Himanshu Kushwah, Nidhi Sandal, Meenakshi K. Chauhan, Gaurav Mittal

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Excessive bleeding is the primary factor of avoidable death in both civilian trauma centers as well as the military battlefield. Hundreds of Indian troops die every year due to blood loss caused by combat-related injuries. These deaths are avoidable and can be prevented to a large extent by making available a suitable hemostatic dressing in an emergency medical kit. In this study, natural gums were evaluated as potential hemostatic agents in combination with calcium gluconate. The study compares the hemostatic activity of Gum Tragacanth (GT), Guar Gum (GG), Xanthan Gum (XG) and Gum Acacia (GA) by carrying out different in-vitro and in-vivo studies. In-vitro studies were performed using the Lee-White method and Eustrek method, which includes the visual and microscopic analysis of blood clotting. MTT assay was also performed using human lymphocytes to check the cytotoxicity of the gums. The in-vivo studies were performed in Sprague Dawley rats using tail bleeding assay to evaluate the hemostatic efficacy of the gums and compared with a commercially available hemostatic sponge, Surgispon. Erythrocyte agglutination test was also performed to check the interaction between blood cells and the natural gums. Other parameters like blood loss, adherence strength of the developed hemostatic dressing material incorporating these gums, re-bleeding, and survival of the animals were also studied. The data obtained from the MTT assay showed that Guar gum, Gum Tragacanth, and Gum Acacia were not significantly cytotoxic, but substantial cytotoxicity was observed in Xanthan gum samples at high concentrations. Also, Xanthan gum took the least time with its minimum concentration to achieve hemostasis, (approximately 50 seconds at 3mg concentration). Gum Tragacanth also showed efficient hemostasis at a concentration of 35mg at the same time, but the other two gums tested were not able to clot the blood in significantly less time. A sponge dressing made of Tragacanth gum was found to be more efficient in achieving hemostasis and showed better practical applicability among all the gums studied and also when compared to the commercially available product, Surgispon, thus making it a potentially better alternative.

Keywords: cytotoxicity, hemostasis, natural gums, sponge

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Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

Abstract:

Introduction: Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) in steel was above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. Materials and Methods: The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) was used cytogenetic analysis of peripheral blood lymphocytes, gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistical analysis was used the Mann-Whitney U-test. Results: The mean Cr level in exposed group was 0.095 mmol/l (0.019 min-max 0.504). No value does exceed the average normal value. The average value Cr in urine was 7.9 mmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs 0.80% and CSA-type 0.96% vs 0.90%). In the number of total CA was observed statistical difference between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44%<1.82%<2.13%). There was observed a statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups (1.22% vs. 0.59%, P<0.05). Discussion and conclusions: The work place is usually higher source of exposure to harmful factors. Workers need consistently and checked frequently health control. In assessing the risk of adverse effects of metals is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: genotoxicity, chromium, stainless steels, welders

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Authors: Sourita Ghosh, Falguni Pati, Suhanya Duraiswamy

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Spheroid, a simple three-dimensional cellular aggregate, allows us to simulate the in-vivo complexity of cellular signaling and interactions in greater detail than traditional 2D cell culture. It can be used as an in-vitro model for drug toxicity testing, tumor modeling and many other such applications specifically for cancer. Our work is focused on the development of an affordable, user-friendly, robust, reproducible, high throughput microfluidic device for water in oil droplet production, which can, in turn, be used for spheroids manufacturing. Here, we have investigated the droplet breakup between two non-Newtonian fluids, viz. silicone oil and decellularized liver matrix, which acts as our extra cellular matrix (ECM) for spheroids formation. We performed some biochemical assays to characterize the liver ECM, as well as rheological studies on our two fluids and observed a critical dependence of capillary number (Ca) on droplet breakup and homogeneous drop formation

Keywords: chip less, droplets, extracellular matrix, liver spheroid

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Authors: Behzad Sinaei, Shahryar Sane, Behzad Kazemi Haki

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Children with different malignancies usually experience potential neurologic complications when treated with radiation therapy, especially if under frequent anesthesia. The aim of this study was to evaluate the neurologic problems associated with anesthesia in pediatrics treated with radiotherapy under anesthesia. The study was a cross-sectional experiment that consisted of 133 pediatric patients with different malignancies who needed anesthesia for performing radiotherapy and were referred to Omid Charity Hospital and Imam Khomeini University Hospital from 2014 to 2020 by the census. P-values less than 0.05 were considered statistically significant (P-value < 0.05). Anesthesia complications in this study were slight and insignificant. Some were due to the effects of the tumor on other important organs or either previous radiation therapy or chemotherapy. For safe anesthesia, considering the effects of tumors on body organs and the neurological complications they cause can greatly help reduce anesthesia complications in pediatrics under radiation therapy.

Keywords: anesthesia, neurologic complications, pediatrics, radiotherapy

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Authors: Mansi Patel, Priti Mehta

Abstract:

Background: Ionizing radiations have detrimental effects on humans, and the growing technological encroachment has increased human exposure to it enormously. So, the safety issues have emphasized researchers to develop radioprotector from natural resources having minimal toxicity. A substance having anti-inflammatory, antioxidant, and immunomodulatory activity can be a potential candidate for radioprotection. One such plant with immense potential i.e. Bamboo was selected for the present study. Purpose: The study aims to evaluate the potential of Indian bamboo leaves for protection against the clastogenic effect of gamma radiation. Methods: The protective effect of bamboo leaf extract against gamma radiation-induced genetic damage in human peripheral blood lymphocytes (HPBLs) was evaluated in vitro using Cytokinesis blocked micronuclei assay (CBMN). The blood samples were pretreated with varying concentration of extract 30 min before the radiation exposure (4Gy & 6Gy). The reduction in the frequency of micronuclei was observed for the irradiated and control groups. The effect of various concentration of bamboo leaf extract (400,600,800 mg/kg) on the development of radiation induced sickness and altered mortality in mice exposed to 8 Gy of whole-body gamma radiation was studied. The developed symptoms were clinically scored by multiple endpoints for 30 days. Results: Treatment of HPBLs with varying concentration of extract before exposure to a different dose of γ- radiation resulted in significant (P < 0.0001) decline of radiation induced micronuclei. It showed dose dependent and concentration driven activity. The maximum protection ~ 70% was achieved at nine µg/ml concentration. Extract treated whole body irradiated mice showed 50%, 83.3% and 100% survival for 400, 600, and 800mg/kg with 1.05, 0.43 and 0 clinical score respectively when compared to Irradiated mice having 6.03 clinical score and 0% survival. Conclusion: Our findings indicate bamboo leaf extract reduced the radiation induced cytogenetic damage. It has also increased the survival ratio and reduced the radiation induced sickness and mortality when exposed to a lethal dose of gamma radiation.

Keywords: bamboo leaf extract, Cytokinesis blocked micronuclei (CBMN) assay, ionizing radiation, radio protector

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

Abstract:

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.

Keywords: X inactivate-specific transcript; hsa-miRNA-34a-5p, miR-34a-5p; E2F3, nasopharyngeal carcinoma, tumorigenesis

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Authors: Anthony S. Machi, Joseph Minardi

Abstract:

We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Shazia Bano

Abstract:

Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

Abstract:

Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

Abstract:

N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

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Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.

Abstract:

Most conventional chemotherapeutic agents which are used for the treatment of cancers not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that leads to severe pancytopenia during treatment. Therefore, a need exists for novel approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential new chemotherapeutic agent for the treatment of many cancers such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: In this study, 24 samples of bone marrow and cord blood were collected with consent, and mononuclear cells were separated using density gradient separation. These cells were then exposed to various concentrations of PTL for 24 hours. Cell viability after culture was determined using 7ADD in a flow cytometry test. Additionally, the impact of PTL on hematopoietic stem cells (HSCs) was evaluated using a colony forming unit assay (CFU). Furthermore, the levels of NFҝB expression were assessed by using a PE-labelled anti-pNFκBP65 antibody. Results: this study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4) on the other hand was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Discussion &Conclusion: At concentrations ≤25 μM PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs. This could be due to the higher percentage of T-lymphocytes, which are resistant to PTL, in CB samples (85% in CB vs. 56% in BM. Additionally, CB samples contained a higher proportion of CD34+ cells, with 14.5% of brightly CD34+ cells compared to only 1% in normal BM. These bright CD34+ cells in CB were mostly negative for early-stage stem cell maturation antigens, making them young and resilient to oxidative stress and high concentrations of PTL.

Keywords: stem cell, parthenolide, NFKB, CLL

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Authors: David J. Foran, Nhan Do, Samuel Ajjarapu, Wenjin Chen, Tahsin Kurc, Joel H. Saltz

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The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers.

Keywords: clinical data warehouse, decision support, data-mining, intelligent databases, machine-learning.

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Authors: Zainab Shaikh, Yusuf Miyanji

Abstract:

Pilomatrixoma is a benign neoplasm of the hair follicle matrix that is not commonly diagnosed in general practice. This is a case report of a 9-year-old boy who presented with a one-year history of a 19mm x 11 mm swelling in the left infra-orbital region. This was previously undiagnosed in Spain, where the patient resided at the time of initial presentation, due to the language barrier the patient’s family encountered. An ultrasound and magnetic resonance imaging gave useful information regarding surrounding structures for complete tumor excision and indicated that the risk of facial nerve palsy is low. The lesion was surgically excised and a definitive diagnosis was made after histopathology. Pilomatrixoma, although not rare in its occurrence, is rarely this large at the time of excision due to early presentation. This case highlights the importance of including pilomatrixoma in the differential diagnosis of dermal and subcutaneous lesions in the head and neck region, as it is often misdiagnosed due to the lack of awareness of its clinical presentation.

Keywords: pilomatrixoma, swelling, infra-orbital, facial swelling

Procedia PDF Downloads 141