Search results for: glomus jugulare tumor excision
Commenced in January 2007
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Edition: International
Paper Count: 848

Search results for: glomus jugulare tumor excision

428 Biosynthesis of a Nanoparticle-Antibody Phthalocyanine Photosensitizer for Use in Targeted Photodynamic Therapy of Cervical Cancer

Authors: Elvin P. Chizenga, Heidi Abrahamse

Abstract:

Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

Procedia PDF Downloads 107
427 Effects of Renin Angiotensin Pathway Inhibition on Efficacy of Anti-PD-1/PD-L1 Treatment in Metastatic Cancer

Authors: Philip Friedlander, John Rutledge, Jason Suh

Abstract:

Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

Procedia PDF Downloads 55
426 Antiangiogenic and Pro-Apoptotic Properties of Shemamruthaa: An Herbal Preparation in Experimental Mammary Carcinoma-Bearing Rats and Breast Cancer Cell Line In vitro

Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

Abstract:

Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

Procedia PDF Downloads 235
425 Enhanced Wound Healing Efficacy of Cordycepin-Melittin Nanoconjugate in Excised Wounds of Diabetic Rats

Authors: Mohammed Flaih Alotaibi, Rasheed Ahemad Shaik, Mohammed Z. Nasrullah

Abstract:

Diabetic foot ulcers are the foremost global healthcare burden. Hyperglycemia in diabetics is incriminating in impeding wound healing and it can allow for more severe medical issues. The study was intended to establish a nanoconjugate of cordycepin-melittin (COR-MEL) and evaluate its healing effects in wounded diabetic rats. Diabetes induced by injecting streptozotocin intraperitoneally (50 mg/kg, body weight). Therefore, animals were classified into various groups; diabetic untreated, vehicle-treated, COR alone, MEL alone, and COR-MEL nanoconjugate treated, respectively. Animals with diabetes were exposed to excision and treated with Vehicle, COR, MEL, or COR-MEL nanoconjugate topically. After 14 days, the wounded skin was sliced and subjected to histological and biochemical assessments. The formulated nanoconjugate has a particle size of 253.5± 17.4 nm by a polydispersity index of 0.36 ± 0.05, and a zeta potential of 1.72 ± 0.3 mV. The study demonstrated an accelerated wound contraction in COR-MEL-treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde and exhaustion of superoxide dismutase and glutathione peroxidase enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of proinflammatory cytokines (IL-6 and TNF-α). Additionally, the nanoconjugate exhibits a strong expression of growth factors (TGF-β1, VEGF-A, and PDGFR-β), indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1. Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Keywords: diabetic wounds, cordycepin, melittin, nanoconjugate, wound healing

Procedia PDF Downloads 65
424 Treatment of Papillary Thyroid Carcinoma Metastasis to the Sternum: A Case Report

Authors: Geliashvili T. M., Tyulyandina A. S., Valiev A. K., Kononets P. V., Kharatishvili T. K., Salkov A. G., Pronin A. I., Gadzhieva E. H., Parnas A. V., Ilyakov V. S.

Abstract:

Aim/Introduction: Metastasis (Mts) to the sternum, while extremely rare in differentiated thyroid cancer (DTC) (1), requires a personalized, multidisciplinary treatment approach. In aggressively growing Mts to the sternum, which rapidly become unresectable, a comprehensive therapeutic and diagnostic approach is particularly important. Materials and methods: We present a clinical case of solitary Mts to the sternum as first manifestation of a papillary thyroid microcarcinoma in a 55-year-old man. Results: 18F-FDG PET/CT after thyroidectomy confirmed the solitary Mts to the sternum with extremely high FDG uptake (SUVmax=71,1), which predicted its radioiodine-refractory (RIR). Due to close attachment to the mediastinum and rapid growth, Mts was considered unresectable. During the next three months, the patient received targeted therapy with the tyrosine kinase inhibitor (TKI) Lenvatinib 24 mg per day. 1st course of radioiodine therapy (RIT) 6 GBq was also performed, the results of which confirmed the RIR of the tumor process. As a result of systemic therapy (targeted therapy combined with RIT and suppressive hormone therapy with L-thyroxine), there was a significant biochemical response (decrease of serum thyroglobulin level from 50,000 ng/ml to 550 ng/ml) and a partial response with decrease of tumor size (from 80x69x123 mm to 65x50x112 mm) and decrease of FDG accumulation (SUVmax from 71.1 to 63). All of this made possible to perform surgical treatment of Mts - sternal extirpation with its replacement by an individual titanium implant. At the control examination, the stimulated thyroglobulin level was only 134 ng/ml, and PET/CT revealed postoperative areas of 18F-FDG metabolism in the removed sternal Mts. Also, 18F-FDG PET/CT in the early (metabolic) stage revealed two new bone Mts (in the area of L3 SUVmax=17,32 and right iliac bone SUVmax=13,73), which, as well as the removed sternal Mts, appeared to be RIRs at the 2nd course of RIT 6 GBq. Subsequently, on 02.2022, external beam radiation therapy (EBRT) was performed on the newly identified oligometastatic bone foci. At present, the patient is under dynamic monitoring and in the process of suppressive hormone therapy with L-thyroxine. Conclusion: Thus, only due to the early prescription of targeted TKI therapy was it possible to perform surgical resection of Mts to the sternum, thereby improve the patient's quality of life and preserve the possibility of radical treatment in case of oligometastatic disease progression.

Keywords: differentiated thyroid cancer, metastasis to the sternum, radioiodine therapy, radioiodine-refractory cancer, targeted therapy, lenvatinib

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423 Ytterbium Advantages for Brachytherapy

Authors: S. V. Akulinichev, S. A. Chaushansky, V. I. Derzhiev

Abstract:

High dose rate (HDR) brachytherapy is a method of contact radiotherapy, when a single sealed source with an activity of about 10 Ci is temporarily inserted in the tumor area. The isotopes Ir-192 and (much less) Co-60 are used as active material for such sources. The other type of brachytherapy, the low dose rate (LDR) brachytherapy, implies the insertion of many permanent sources (up to 200) of lower activity. The pulse dose rate (PDR) brachytherapy can be considered as a modification of HDR brachytherapy, when the single source is repeatedly introduced in the tumor region in a pulse regime during several hours. The PDR source activity is of the order of one Ci and the isotope Ir-192 is currently used for these sources. The PDR brachytherapy is well recommended for the treatment of several tumors since, according to oncologists, it combines the medical benefits of both HDR and LDR types of brachytherapy. One of the main problems for the PDR brachytherapy progress is the shielding of the treatment area since the longer stay of patients in a shielded canyon is not enough comfortable for them. The use of Yb-169 as an active source material is the way to resolve the shielding problem for PDR, as well as for HRD brachytherapy. The isotope Yb-169 has the average photon emission energy of 93 KeV and the half-life of 32 days. Compared to iridium and cobalt, this isotope has a significantly lower emission energy and therefore requires a much lighter shielding. Moreover, the absorption cross section of different materials has a strong Z-dependence in that photon energy range. For example, the dose distributions of iridium and ytterbium have a quite similar behavior in the water or in the body. But the heavier material as lead absorbs the ytterbium radiation much stronger than the iridium or cobalt radiation. For example, only 2 mm of lead layer is enough to reduce the ytterbium radiation by a couple of orders of magnitude but is not enough to protect from iridium radiation. We have created an original facility to produce the start stable isotope Yb-168 using the laser technology AVLIS. This facility allows to raise the Yb-168 concentration up to 50 % and consumes much less of electrical power than the alternative electromagnetic enrichment facilities. We also developed, in cooperation with the Institute of high pressure physics of RAS, a new technology for manufacturing high-density ceramic cores of ytterbium oxide. Ceramics density reaches the limit of the theoretical values: 9.1 g/cm3 for the cubic phase of ytterbium oxide and 10 g/cm3 for the monoclinic phase. Source cores from this ceramics have high mechanical characteristics and a glassy surface. The use of ceramics allows to increase the source activity with fixed external dimensions of sources.

Keywords: brachytherapy, high, pulse dose rates, radionuclides for therapy, ytterbium sources

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422 Mammotome Vacuum-Assisted Breast Biopsy versus Conventional Open Surgery: A Meta-Analysis

Authors: Dylan Shiting Lu, Samson Okello, Anita Chunyan Wei, Daniel Xiao Li

Abstract:

Mammotome vacuum-assisted breast biopsy (MVB) introduced in 1995 can be used for the removal of benign breast lesions. Whether or not MVB is a better option compared to conventional open surgery is inconclusive. We aim to compare the clinical and patient-related outcomes between MVB and open surgery to remove benign breast tumors less than 5 cm in women. We searched English and Chinese electronic databases with the keywords of Mammotome, clinical trial (CT), vacuum-assisted breast biopsy for studies comparing MVB and open surgery until May 2021. We performed a systematic review and random-effects meta-analysis to compare incision size, operation time, intraoperative blood loss, healing time, scar length, patient satisfaction, postoperative hematoma rate, wound infection rate, postoperative ecchymosis, and postoperative sunken skin among those who have Mammotome and those who have surgery. Our analysis included nine randomized CTs with 1155 total patients (575 Mammotome, 580 surgery) and mean age 40.32 years (standard deviation 3.69). We found statistically significant favorable outcomes for Mammotome including blood loss (ml) [standardized mean difference SMD -5.03, 95%CI (-7.30, -2.76)], incision size (cm) [SMD -12.22, 95%CI (-17.40, -7.04)], operation time (min) [SMD -6.66, 95%CI (-9.01, -4.31)], scar length (cm) [SMD -7.06, 95%CI (-10.76, -3.36)], healing time (days) [SMD -6.57, 95%CI (-10.18, -2.95)], and patient satisfaction [relative risk RR 0.38, 95%CI (0.13, 1.08)]. In conclusion, Mammotome vacuum-assisted breast biopsy compared to open surgery shows better clinical and patient-related outcomes. Further studies should be done on whether or not MVB is a better option for benign breast tumors excision.

Keywords: clinical and patient outcomes, open surgery, Mammotome vacuum-assisted breast biopsy, meta-analysis

Procedia PDF Downloads 194
421 Rare Case of Three Metachronous Cancers Occurring over the Period of Three Years: Clinical Importance of Investigating Neoplastic Growth Discovered during Follow-Up

Authors: Marin Kanarev, Delyan Stoyanov, Ivanna Popova, Nadezhda Petrova

Abstract:

Thanks to increased survival rates in patients bearing oncological malignancies due to recent developments in anti-cancer therapies and diagnostic techniques, observation of clinical cases of metachronous cancers is more common and can provide more in-depth knowledge of their development and, as a result, help clinicians apply suitable therapy. This unusual case of three metachronous tumors presented the opportunity to follow their occurrence, progression, and treatment thoroughly. A 77-year-old male presented with carcinoma ventriculi of the pylorus region, which was surgically removed via upper subtotal stomach resection, a lateral antecolical gastro-enteroanastomosis, and a subsequent Braun anastomosis. An EOX chemotherapy regimen followed. A CT scan four months later showed no indication of recurrence or dissemination. The same scan, performed as a part of the follow-up plan two years later, showed an indication of neoplastic growth in the urinary bladder. After the patient had been directed to a urologist, the suspicion was confirmed, and the growth was histologically diagnosed as a carcinoma of the urinary bladder. An immunohistochemistry test showed an expression of PDL1 of less than 5%, which resulted in treatment with GemCis chemotherapy regimen that led to full remission. Two years and seven months after the first surgery, a CT scan showed again that the two carcinomas were gone. However, four months later, elevated tumor markers prompted a PET/CT scan, which showed data indicative of recurring neoplastic growth in the region of the stomach cardia. It was diagnosed as an adenocarcinoma infiltrating the esophagus. Preoperative chemotherapy with the ECF regimen was completed in four courses, and a CT scan showed no progression of the disease. In less than a month after therapy, the patient underwent laparotomy, debridement, gastrectomy, and a subsequent mechanical terminal-lateral esophago-jejunoanasthomosis. It was verified that the tumor originated from metastasis from the carcinoma ventriculi, which was located in the pylorus. In conclusion, this case report highlights the importance of patient follow-up and studying recurring neoplastic growth. Despite the absence of symptoms, clinicians should maintain a high level of suspicion when evaluating the patient data and choosing the most suitable therapy.

Keywords: carcinoma, follow-up, metachronous, neoplastic growth, recurrence

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420 Anti-Neuroinflammatory and Anti-Apoptotic Efficacy of Equol, against Lipopolysaccharide Activated Microglia and Its Neurotoxicity

Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

Abstract:

Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

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419 Automatic Segmentation of 3D Tomographic Images Contours at Radiotherapy Planning in Low Cost Solution

Authors: D. F. Carvalho, A. O. Uscamayta, J. C. Guerrero, H. F. Oliveira, P. M. Azevedo-Marques

Abstract:

The creation of vector contours slices (ROIs) on body silhouettes in oncologic patients is an important step during the radiotherapy planning in clinic and hospitals to ensure the accuracy of oncologic treatment. The radiotherapy planning of patients is performed by complex softwares focused on analysis of tumor regions, protection of organs at risk (OARs) and calculation of radiation doses for anomalies (tumors). These softwares are supplied for a few manufacturers and run over sophisticated workstations with vector processing presenting a cost of approximately twenty thousand dollars. The Brazilian project SIPRAD (Radiotherapy Planning System) presents a proposal adapted to the emerging countries reality that generally does not have the monetary conditions to acquire some radiotherapy planning workstations, resulting in waiting queues for new patients treatment. The SIPRAD project is composed by a set of integrated and interoperabilities softwares that are able to execute all stages of radiotherapy planning on simple personal computers (PCs) in replace to the workstations. The goal of this work is to present an image processing technique, computationally feasible, that is able to perform an automatic contour delineation in patient body silhouettes (SIPRAD-Body). The SIPRAD-Body technique is performed in tomography slices under grayscale images, extending their use with a greedy algorithm in three dimensions. SIPRAD-Body creates an irregular polyhedron with the Canny Edge adapted algorithm without the use of preprocessing filters, as contrast and brightness. In addition, comparing the technique SIPRAD-Body with existing current solutions is reached a contours similarity at least 78%. For this comparison is used four criteria: contour area, contour length, difference between the mass centers and Jaccard index technique. SIPRAD-Body was tested in a set of oncologic exams provided by the Clinical Hospital of the University of Sao Paulo (HCRP-USP). The exams were applied in patients with different conditions of ethnology, ages, tumor severities and body regions. Even in case of services that have already workstations, it is possible to have SIPRAD working together PCs because of the interoperability of communication between both systems through the DICOM protocol that provides an increase of workflow. Therefore, the conclusion is that SIPRAD-Body technique is feasible because of its degree of similarity in both new radiotherapy planning services and existing services.

Keywords: radiotherapy, image processing, DICOM RT, Treatment Planning System (TPS)

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418 Effect of Sodium Arsenite Exposure on Pharmacodynamic of Meloxicam in Male Wistar Rats

Authors: Prashantkumar Waghe, N. Prakash, N. D. Prasada, L. V. Lokesh, M. Vijay Kumar, Vinay Tikare

Abstract:

Arsenic is a naturally occurring metalloid with potent toxic effects. It is ubiquitous in the environment and released from both natural and anthropogenic sources. It has the potential to cause various health hazards in exposed populations. Arsenic exposure through drinking water is considered as one of the most serious global environmental threats including Southeast Asia. The aim of present study was to evaluate the modulatory role of subacute exposure to sodium (meta) arsenite on the antinociceptive, anti-inflammatory and antipyretic responses mediated by meloxicam in rats. Rats were exposed to arsenic as sodium arsenite through drinking water for 28 days. A single dose of meloxicam (2 mg/kg b. wt.) was administered by oral gavage on the 29th day. The exact time of meloxicam administration depended on the type of test. Rats were divided randomly into 5 groups (n=6). Group I served as normal control and received arsenic free drinking water, while rats in group II were maintained similar to Group I but received meloxicam on 29th day. Groups III, IV and V were pre-exposed to arsenic through drinking water at 0.5, 5.0 and 50 ppm, respectively, for 28 days and was administered meloxicam next day and; pain and inflammation carried out by using formalin-induced nociception and carrageenan-induced inflammatory model(s), respectively by using standard protocol. For assessment of antipyretic effects, one more additional group (Group VI) was taken and given LPS @ 1.8 mg/kg b. wt. for induction of pyrexia (LPS control). Higher dose of arsenic inhibited the meloxicam mediated antinociceptive, anti-inflammatory and antipyretic responses. Further, meloxicam inhibited the arsenic induced level of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 and COX2 mediated prostaglandin E2 in hind paw muscle. These results suggest a functional antagonism of meloxicam by arsenic. This may relate to arsenic mediated local release of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 releases COX2 mediated prostaglandin E2. Based on the experimental study, it is concluded that sub-acute exposure to arsenic through drinking water aggravate pyrexia, inflammation and pain at environment relevant concentration and decrease the therapeutic efficacy of meloxicam at higher level of arsenite exposure. Thus, the observation made has clinical relevance in situations where animals are exposed to arsenite epidemic geographical locations.

Keywords: arsenic, analgesic activity, meloxicam, Wistar rats

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417 Botulinum Toxin a in the Treatment of Late Facial Nerve Palsy Complications

Authors: Akulov M. A., Orlova O. R., Zaharov V. O., Tomskij A. A.

Abstract:

Introduction: One of the common postoperative complications of posterior cranial fossa (PCF) and cerebello-pontine angle tumor treatment is a facial nerve palsy, which leads to multiple and resistant to treatment impairments of mimic muscles structure and functions. After 4-6 months after facial nerve palsy with insufficient therapeutic intervention patients develop a postparalythic syndrome, which includes such symptoms as mimic muscle insufficiency, mimic muscle contractures, synkinesis and spontaneous muscular twitching. A novel method of treatment is the use of a recent local neuromuscular blocking agent– botulinum toxin A (BTA). Experience of BTA treatment enables an assumption that it can be successfully used in late facial nerve palsy complications to significantly increase quality of life of patients. Study aim. To evaluate the efficacy of botulinum toxin A (BTA) (Xeomin) treatment in patients with late facial nerve palsy complications. Patients and Methods: 31 patients aged 27-59 years 6 months after facial nerve palsy development were evaluated. All patients received conventional treatment, including massage, movement therapy etc. Facial nerve palsy developed after acoustic nerve tumor resection in 23 (74,2%) patients, petroclival meningioma resection – in 8 (25,8%) patients. The first group included 17 (54,8%) patients, receiving BT-therapy; the second group – 14 (45,2%) patients continuing conventional treatment. BT-injections were performed in synkinesis or contracture points 1-2 U on injured site and 2-4 U on healthy side (for symmetry). Facial nerve function was evaluated on 2 and 4 months of therapy according to House-Brackman scale. Pain syndrome alleviation was assessed on VAS. Results: At baseline all patients in the first and second groups demonstrated аpostparalytic syndrome. We observed a significant improvement in patients receiving BTA after only one month of treatment. Mean VAS score at baseline was 80,4±18,7 and 77,9±18,2 in the first and second group, respectively. In the first group after one month of treatment we observed a significant decrease of pain syndrome – mean VAS score was 44,7±10,2 (р<0,01), whereas in the second group VAS score was as high as 61,8±9,4 points (p>0,05). By the 3d month of treatment pain syndrome intensity continued to decrease in both groups, but, the first group demonstrated significantly better results; mean score was 8,2±3,1 and 31,8±4,6 in the first and second group, respectively (р<0,01). Total House-Brackman score at baseline was 3,67±0,16 in the first group and 3,74±0,19 in the second group. Treatment resulted in a significant symptom improvement in the first group, with no improvement in the second group. After 4 months of treatment House-Brockman score in the first group was 3,1-fold lower, than in the second group (р<0,05). Conclusion: Botulinum toxin injections decrease postparalytic syndrome symptoms in patients with facial nerve palsy.

Keywords: botulinum toxin, facial nerve palsy, postparalytic syndrome, synkinesis

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416 One Year Follow up of Head and Neck Paragangliomas: A Single Center Experience

Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

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Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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415 Impact of Simulated Brain Interstitial Fluid Flow on the Chemokine CXC-Chemokine-Ligand-12 Release From an Alginate-Based Hydrogel

Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

Abstract:

The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

Procedia PDF Downloads 66
414 Pterygium Recurrence Rate and Influencing Factors for Recurrence of Pterygium after Pterygium Surgery at an Eastern Thai University Hospital

Authors: Luksanaporn Krungkraipetch

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Pterygium is a frequent ocular surface lesion that begins in the limbal conjunctiva within the palpebral fissure and spreads to the cornea. The lesion is more common in the nasal limbus than in the temporal, and it has a wing-like aspect. Indications for surgery, in decreasing order of significance, are growth over the corneal center, decreased vision due to corneal deformation, documented growth, sensations of discomfort, and esthetic concerns. The aim of this study is twofold: first, to determine the frequency of pterygium recurrence after surgery at the mentioned hospital, and second, to identify the factors that influence the recurrence of pterygium. The research design is a retrospective examination of 164 patient samples in an eastern Thai university hospital (Code 13766). Data analysis is descriptive statistics analysis, i.e., basic data details about pterygium surgery and the risk of recurrent pterygium, and for factor analysis, the inferential statistics chi-square and ANOVA are utilized. Twenty-four of the 164 patients who underwent surgery exhibited recurrent pterygium. Consequently, the incidence of recurrent pterygium after surgery was 14.6%. There were an equal number of men and women present. The participants' ages ranged from 41 to 60 years (62, 8 percent). According to the findings, the majority of patients were female (60.4%), over the age of 60 (51.2%), did not live near the beach (83.5%), did not have an underlying disease (92.1%), and 95.7% did not have any other eye problems. Gender (X² = 1.26, p = .289), age (X² = 5.86, p = .119), an address near the sea (X² = 3.30, p = .081)), underlying disease (X² = 0.54, p = .694), and eye disease (X² = 0.00, p = 1.00) had no effect on pterygium recurrence. Recurrences occurred in 79.1% of all surgical procedures and 11.6% of all patients using the bare sclera technique. The recurrence rate for conjunctival autografts was 20.9% for all procedures and 3.0% for all participants. Mitomycin-C and amniotic membrane transplant techniques had no recurrence following surgery. Comparing the surgeries done on people with recurrent pterygium did not show anything important (F = 1.13, p = 0.339). In conclusion, the prevalence of pterygium recurrence following pterygium, 14.6%, does not differ from earlier research. Underlying disease, other eye conditions, and surgical procedures such as pterygium recurrence are unaffected by pterygium surgery.

Keywords: pterygium, recurrence pterygium, pterygium surgery, excision pterygium

Procedia PDF Downloads 51
413 Radiofrequency Ablation: A Technique in the Management of Low Anal Fistula

Authors: R. Suresh, C. B. Singh, A. K. Sarda

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Background: Over the decades, several surgical techniques have been developed to treat anal fistulas with variable success rates and complications. Large amount of work has been done in radiofrequency excision of the fistula for several years but no work has been done for ablating the tract. Therefore one can consider for obliteration ofanal fistula by Radiofrequency ablation (RFA). Material and Methods: A randomized controlled clinical trial was conducted at Lok Nayak Hospital, where a total of 40 patients were enrolled in the study and they were randomly assigned to Group I (fistulectomy)(n=20) and Group II (RFA) (n=20). Aim of the study was to compare the efficacy of RFA of fistula versus fistulectomy in the treatment of a low anal fistula and to evaluate RFA as an effective alternative to fistulectomy with respect to time taken for wound healing as primary outcome and post-operative pain, time taken to return to work as secondary outcomes. Patients with simple low anal fistulas, single internal and external opening, not more than two secondary tracts were included. Patients with high complex fistula, fistulas communicating with cavity, fistula due to condition like tuberculosis, Crohn's, malignancy were excluded from the study. Results: Both groups were comparable with respect to age, sex ratio, type of fistula. Themean healing time was significantly shorter in group II (41.02 days) than in group I(62.68 days).The mean operative time was significantly shorter in groupII (21.40 min) than in group I(28.50 min). The mean time taken to return to work was significantly shorter in group II(8.30 days)than in group I(12.01 days).There was no significant difference in the post operative hospital stay, mean postoperative pain score, wound infection and recurrence between the two groups. Conclusion: The patients who underwent RFA of fistula had shorter wound healing time, operative time and time taken to return to work when compared to those who underwent fistulectomy and therefore RFA shows outcome comparable to fistulectomy in the treatment of low anal fistula.

Keywords: fistulectomy, low anal fistula, radio frequency ablation, wound healing

Procedia PDF Downloads 333
412 Angiomotin Regulates Integrin Beta 1-Mediated Endothelial Cell Migration and Angiogenesis

Authors: Yuanyuan Zhang, Yujuan Zheng, Giuseppina Barutello, Sumako Kameishi, Kungchun Chiu, Katharina Hennig, Martial Balland, Federica Cavallo, Lars Holmgren

Abstract:

Angiogenesis describes that new blood vessels migrate from pre-existing ones to form 3D lumenized structure and remodeling. During directional migration toward the gradient of pro-angiogenic factors, the endothelial cells, especially the tip cells need filopodia to sense the environment and exert the pulling force. Of particular interest are the integrin proteins, which play an essential role in focal adhesion in the connection between migrating cells and extracellular matrix (ECM). Understanding how these biomechanical complexes orchestrate intrinsic and extrinsic forces is important for our understanding of the underlying mechanisms driving angiogenesis. We have previously identified Angiomotin (Amot), a member of Amot scaffold protein family, as a promoter for endothelial cell migration in vitro and zebrafish models. Hence, we established inducible endothelial-specific Amot knock-out mice to study normal retinal angiogenesis as well as tumor angiogenesis. We found that the migration ratio of the blood vessel network to the edge was significantly decreased in Amotec- retinas at postnatal day 6 (P6). While almost all the Amot defect tip cells lost migration advantages at P7. In consistence with the dramatic morphology defect of tip cells, there was a non-autonomous defect in astrocytes, as well as the disorganized fibronectin expression pattern correspondingly in migration front. Furthermore, the growth of transplanted LLC tumor was inhibited in Amot knockout mice due to fewer vasculature involved. By using MMTV-PyMT transgenic mouse model, there was a significantly longer period before tumors arised when Amot was specifically knocked out in blood vessels. In vitro evidence showed that Amot binded to beta-actin, Integrin beta 1 (ITGB1), Fibronectin, FAK, Vinculin, major focal adhesion molecules, and ITGB1 and stress fibers were distinctly induced by Amot transfection. Via traction force microscopy, the total energy (force indicater) was found significantly decreased in Amot knockdown cells. Taken together, we propose that Amot is a novel partner of the ITGB1/Fibronectin protein complex at focal adhesion and required for exerting force transition between endothelial cell and extracellular matrix.

Keywords: angiogenesis, angiomotin, endothelial cell migration, focal adhesion, integrin beta 1

Procedia PDF Downloads 217
411 Radiomics: Approach to Enable Early Diagnosis of Non-Specific Breast Nodules in Contrast-Enhanced Magnetic Resonance Imaging

Authors: N. D'Amico, E. Grossi, B. Colombo, F. Rigiroli, M. Buscema, D. Fazzini, G. Cornalba, S. Papa

Abstract:

Purpose: To characterize, through a radiomic approach, the nature of nodules considered non-specific by expert radiologists, recognized in magnetic resonance mammography (MRm) with T1-weighted (T1w) sequences with paramagnetic contrast. Material and Methods: 47 cases out of 1200 undergoing MRm, in which the MRm assessment gave uncertain classification (non-specific nodules), were admitted to the study. The clinical outcome of the non-specific nodules was later found through follow-up or further exams (biopsy), finding 35 benign and 12 malignant. All MR Images were acquired at 1.5T, a first basal T1w sequence and then four T1w acquisitions after the paramagnetic contrast injection. After a manual segmentation of the lesions, done by a radiologist, and the extraction of 150 radiomic features (30 features per 5 subsequent times) a machine learning (ML) approach was used. An evolutionary algorithm (TWIST system based on KNN algorithm) was used to subdivide the dataset into training and validation test and to select features yielding the maximal amount of information. After this pre-processing, different machine learning systems were applied to develop a predictive model based on a training-testing crossover procedure. 10 cases with a benign nodule (follow-up older than 5 years) and 18 with an evident malignant tumor (clear malignant histological exam) were added to the dataset in order to allow the ML system to better learn from data. Results: NaiveBayes algorithm working on 79 features selected by a TWIST system, resulted to be the best performing ML system with a sensitivity of 96% and a specificity of 78% and a global accuracy of 87% (average values of two training-testing procedures ab-ba). The results showed that in the subset of 47 non-specific nodules, the algorithm predicted the outcome of 45 nodules which an expert radiologist could not identify. Conclusion: In this pilot study we identified a radiomic approach allowing ML systems to perform well in the diagnosis of a non-specific nodule at MR mammography. This algorithm could be a great support for the early diagnosis of malignant breast tumor, in the event the radiologist is not able to identify the kind of lesion and reduces the necessity for long follow-up. Clinical Relevance: This machine learning algorithm could be essential to support the radiologist in early diagnosis of non-specific nodules, in order to avoid strenuous follow-up and painful biopsy for the patient.

Keywords: breast, machine learning, MRI, radiomics

Procedia PDF Downloads 256
410 Neuroendocrine Tumors of the Oral Cavity: A Summarized Overview

Authors: Sona Babu Rathinam, Lavanya Dharmendran, Therraddi Mutthu

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Objectives: The purpose of this paper is to provides an overview of the neuroendocrine tumors that arise in the oral cavity. Material and Methods: An overview of the relevant papers on neuroendocrine tumors of the oral cavity by various authors was studied and summarized. Results: On the basis of the relevant studies, this paper provides an overview of the classification and histological differentiation of the neuroendocrine tumors that arise in the oral cavity. Conclusions: The basis of classification of neuroendocrine tumors is largely determined by their histologic differentiation. Though they reveal biologic heterogeneity, there should be an awareness of the occurrence of such lesions in the oral cavity to enable them to be detected and treated early.

Keywords: malignant peripheral nerve sheath tumor, olfactory neuroblastoma, paraganglioma, schwannoma

Procedia PDF Downloads 64
409 Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition Inhibits by INT3 & Quercetin in MCF7 Cell Lines

Authors: D. Pradhan, G. Tripathy, S. Pradhan

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Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

Procedia PDF Downloads 291
408 The Contribution of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Vascular Endothelial Growth Factor into the Unfavorable Clinical Course of Ulcerative Colitis

Authors: Y. I. Tretyakova, S. G. Shulkina, T. Y. Kravtsova, A. A. Antipova, N. Y. Kolomeets

Abstract:

The research aimed to assess the functional significance of tumor necrosis factor-alpha (TNF-α) gene polymorphism at the -308G/A (rs1800629) region and vascular endothelial growth factor A (VEGFA) gene polymorphism at the -634G/C (rs 2010963) region in the development of ulcerative colitis (UC), focusing on patients from the Perm region, Russia. We examined 70 UC patients and 50 healthy donors during the active phase of the disease. Our focus was on TNF-α and VEGF concentration in the blood serum, as well as TNF-α and VEGFA gene polymorphisms at the -308G/А and -634G/C regions, respectively. We found that TNF-α and VEGF levels were significantly higher in patients with severe UC and high endoscopic activity compared to those with milder forms of the disease and low endoscopic activity. These tests could serve as additional non-invasive markers for assessing mucosal damage in the large intestine of UC patients. The frequency of allele variations in the TNF-α gene -308G/A (rs1800629) revealed a significantly higher occurrence of the unfavorable homozygote AA in UC patients compared to donors. Additionally, the major allele G and the allele pair GG were more frequent in patients with mild to moderate disease and 1-2 degree of endoscopic activity than in those with severe UC and 3-4 degree of endoscopic activity (χ2=14.19; p=0.000). We also observed a mutant allele A and the unfavorable homozygote AA associated with severe progressive UC. The occurrence of the mutant allele increased the risk of severe UC by 5 times (OR 5.03; CI 12.07-12.21). We did not find any significant differences in the frequency of the CC homozygote (χ2=1.02; p=0.6; OR=1.32) and the mutant allele C of the VEGFA gene -634G/C (rs 2010963) (χ2=0.01; p=0.913; OR=0.97) between groups of UC patients and healthy individuals. However, we detected that the mutant allele C and the unfavorable homozygote CC of the VEGFA gene were associated with more severe endoscopic changes in the colonic mucosa of UC patients (χ2=25,76; р=0,000; OR=0,15). The presence of the mutant allele increased the risk of severe UC by 6 times (OR 6,78; CI 3,13–14,7). We found a direct correlation between TNF-α and VEGFA gene polymorphisms, increased production of the same factors, disease severity, and endoscopic activity (р=0.000). Therefore, the presence of the mutant allele A and homozygote AA of the TNF-α gene at the -308G/A region and the mutant allele C and homozygote CC of the VEGFA gene at the -634G/C region are associated with risks related to an unfavorable clinical course of UC, frequent recurrences, and rapid progression. These findings should be considered when making prognoses regarding the clinical course of the disease and selecting treatment strategies. The presence of the homozygote AA in the TNF-α gene (rs1800629) is considered a sign of genetic predisposition to UC.

Keywords: gene polymorphism, TNF-α, ulcerative colitis, VEGF

Procedia PDF Downloads 58
407 Induction of Adaptive Response in Yeast Cells under Influence of Extremely High Frequency Electromagnetic Field

Authors: Sergei Voychuk

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Introduction: Adaptive response (AR) is a manifestation of radiation hormesis, which deal with the radiation resistance that may be increased with the pretreatment with small doses of radiation. In the current study, we evaluated the potency of radiofrequency EMF to induce the AR mechanisms and to increase a resistance to UV light. Methods: Saccharomyces cerevisiae yeast strains, which were created to study induction of mutagenesis and recombination, were used in the study. The strains have mutations in rad2 and rad54 genes, responsible for DNA repair: nucleotide excision repair (PG-61), postreplication repair (PG-80) and mitotic (crossover) recombination (T2). An induction of mutation and recombination are revealed due to the formation of red colonies on agar plates. The PG-61 and T2 are UV sensitive strains, while PG-80 is sensitive to ionizing radiation. Extremely high frequency electromagnetic field (EHF-EMF) was used. The irradiation was performed in floating mode and frequency changed during exposure from 57 GHz to 62 GHz. The power of irradiation was 100 mkW, and duration of exposure was 10 and 30 min. Treatment was performed at RT and then cells were stored at 28° C during 1 h without any exposure but after that they were treated with UV light (254nm) for 20 sec (strain T2) and 120 sec (strain PG-61 and PG-80). Cell viability and quantity of red colonies were determined after 5 days of cultivation on agar plates. Results: It was determined that EHF-EMF caused 10-20% decrease of viability of T2 and PG-61 strains, while UV showed twice stronger effect (30-70%). EHF-EMF pretreatment increased T2 resistance to UV, and decreased it in PG-61. The PG-80 strain was insensitive to EHF-EMF and no AR effect was determined for this strain. It was not marked any induction of red colonies formation in T2 and PG-80 strain after EHF or UV exposure. The quantity of red colonies was 2 times more in PG-61 strain after EHF-EMF treatment and at least 300 times more after UV exposure. The pretreatment of PG-61 with EHF-EMF caused at least twice increase of viability and consequent decrease of amount of red colonies. Conclusion: EHF-EMF may induce AR in yeast cells and increase their viability under UV treatment.

Keywords: Saccharomyces cerevisiae, EHF-EMF, UV light, adaptive response

Procedia PDF Downloads 304
406 Case Report of Intramural Pregnancy

Authors: S. Woźniak, J. Rybka, T. Paszkowski, P. Milart

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A 30-year-old patient, who was pregnant for her second 9 weeks, was admitted to the hospital due to a suspected incomplete miscarriage. A fetal egg was found in the uterine cavity near the mouth of the fallopian tube. The patient was qualified for dilatation and curettage. The histopathological examination revealed fragments of the trophoblast. Two months later, the patient was re-admitted to the hospital due to vaginal bleeding and elevated levels of beta-hCG. Additional tests were performed. An intramural pregnancy was suspected. The patient was qualified for embolization of the uterine arteries and then treatment with methotrexate. Three weeks later, during a routine gynecological examination, a detached tumor 4 cm in diameter was found in the vagina. The material was sent for histopathological examination, which showed the presence of trophoblastic cells.

Keywords: ectopic pregnancy, intramural pregnancy, uterine artery embolization, methotrexate

Procedia PDF Downloads 86
405 Comparison of Conjunctival Autograft versus Amniotic Membrane Transplantation for Pterygium Surgery

Authors: Luksanaporn Krungkraipetch

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Currently, surgery is the only known effective treatment for pterygium. In certain groups, the probability of recurrence after basic sclera excision is very significant. Tissue grafting is substantially more time-consuming and challenging than keeping the sclera uncovered, but it reduces the chance of recurrence. Conjunctival autograft surgery is older than amniotic membrane graft surgery. The purpose of this study was to compare pterygium surgery with conjunctival autograft against an amniotic membrane transplant. In the study, a randomized controlled trial was used. Four cases were ruled out (two for failing to meet inclusion criteria and the other for refusing to participate). Group I (n = 40) received the intervention, whereas Group II (n = 40) served as the control. Both descriptive and inferential statistical approaches were used, including data analysis and data analysis statistics. The descriptive statistics analysis covered basic pterygium surgery information as well as the risk of recurrent pterygium. As an inferential statistic, the chi-square was used. A p-value of 0.05 is statistically significant. The findings of this investigation were the majority of patients in Group I were female (70.0%), aged 41–60 years, had no underlying disease (95.0%), and had nasal pterygium (97.5%). The majority of Group II patients were female (60.0%), aged 41–60 years, had no underlying disease (97.5%) and had nasal pterygium (97.5%). Group I had no recurrence of pterygium after surgery, but Group II had a 7.5% recurrence rate. Typically, the recurrence time is twelve months. The majority of pterygium recurrences occur in females (83.3%), between the ages of 41 and 60 (66.7%), with no underlying disease. The recurrence period is typically six months (60%) and a nasal pterygium site (83.3%). Pterygium recurrence after surgery is associated with nasal location (p =.002). 16.7% of pterygium surgeries result in complications; one woman with nasal pterygium underwent autograft surgery six months later. The presence of granulation tissue at the surgical site is a mild complication. A pterygium surgery recurrence rate comparison of conjunctival autograft and amniotic membrane transplantation revealed that conjunctival autograft had a higher recurrence rate than amniotic membrane transplantation (p =.013).

Keywords: pterygium, pterygium surgery, conjunctival autograft, amniotic membrane transplantation

Procedia PDF Downloads 52
404 Tumor Detection Using Convolutional Neural Networks (CNN) Based Neural Network

Authors: Vinai K. Singh

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In Neural Network-based Learning techniques, there are several models of Convolutional Networks. Whenever the methods are deployed with large datasets, only then can their applicability and appropriateness be determined. Clinical and pathological pictures of lobular carcinoma are thought to exhibit a large number of random formations and textures. Working with such pictures is a difficult problem in machine learning. Focusing on wet laboratories and following the outcomes, numerous studies have been published with fresh commentaries in the investigation. In this research, we provide a framework that can operate effectively on raw photos of various resolutions while easing the issues caused by the existence of patterns and texturing. The suggested approach produces very good findings that may be used to make decisions in the diagnosis of cancer.

Keywords: lobular carcinoma, convolutional neural networks (CNN), deep learning, histopathological imagery scans

Procedia PDF Downloads 117
403 Systematic Identification of Noncoding Cancer Driver Somatic Mutations

Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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402 Preservation of Endocrine Function after Central Pancreatectomy without Anastomoses for a Mid Gland Pancreatic Insulinoma: A Case Report

Authors: Karthikeyan M., Paul M. J.

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This abstract describes a case of central pancreatectomy (CP) for a 50-year-old woman with a neuroendocrine tumor in the mid-body of the pancreas. CP, a parenchyma-sparing surgical option, preserves the distal pancreas and spleen, reducing the risk of pancreatic endocrine and exocrine insufficiency compared to traditional resections. The patient, initially misdiagnosed with transient ischemic attack, presented with hypoglycemic symptoms and was found to have a pancreatic lesion. Post-operative results were positive, with a reduction in pancreatic drain volume and normalization of blood sugar levels. This case highlights CP's efficacy in treating centrally located pancreatic lesions while maintaining pancreatic function.

Keywords: central pancreatectomy without anastomosis, no endocrine deficiency on follow-op, less post-op hospital stay, less post-op complications

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401 Investigation of the Function of Chemotaxonomy of White Tea on the Regulatory Function of Genes in Pathway of Colon Cancer

Authors: Fereydoon Bondarian, Samira Shaygan

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Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

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400 Effect of Chronic Exposure to Diazinon on Glucose Homeostasis and Oxidative Stress in Pancreas of Rats and the Potential Role of Mesna in Ameliorating This Effect

Authors: Azza El-Medany, Jamila El-Medany

Abstract:

Residential and agricultural pesticide use is widespread in the world. Their extensive and indiscriminative use, in addition with their ability to interact with biological systems other than their primary targets constitute a health hazards to both humans and animals. The toxic effects of pesticides include alterations in metabolism; there is a lack of knowledge that organophosphates can cause pancreatic toxicity. The primary goal of this work is to study the effects of chronic exposure to Diazinon an organophosphate used in agriculture on pancreatic tissues and evaluate the ameliorating effect of Mesna as antioxidant on the toxicity of Diazinon on pancreatic tissues.40 adult male rats, their weight ranged between 300-350 g. The rats were classified into three groups; control (10 rats) was received corn oil at a dose of 1 0 mg/kg/day by gavage once a day for 2 months. Diazinon (15 rats) was received Diazinon at a dose of 10 mg/kg/day dissolved in corn oil by gavage once a day for 2 months. Treated group (15 rats), were received Mesna 180mg/kg once a week by gavage 15 minutes before administration of Diazinon for 2 months. At the end of the experiment, animals were anesthetized, blood samples were taken by cardiac puncture for glucose and insulin assays and pancreas was removed and divided into 3 portions; first portion for histopathological study; second portion for ultrastructural study; third portion for biochemical study using Elisa Kits including determination of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), myeloperoxidase activity (MPO), interleukin 1β (IL-1β). A significant increase in the levels of MDA, TNF-α, MPO activity, IL-1β, serum glucose levels in the toxicated group with Diazinon were observed, while a significant reduction was noticed in GSH in serum insulin levels. After treatment with Mesna a significant reduction was observed in the previously mentioned parameters except that there was a significant rise in GSH in insulin levels. Histopathological and ultra-structural studies showed destruction in pancreatic tissues and β cells were the most affected cells among the injured islets as compared with the control group. The current study try to spot light about the effects of chronic exposure to pesticides on vital organs as pancreas also the role of oxidative stress that may be induced by them in evoking their toxicity. This study shows the role of antioxidant drugs in ameliorating or preventing the toxicity. This appears to be a promising approach that may be considered as a complementary treatment of pesticide toxicity.

Keywords: Diazinon, reduced glutathione, myeloperoxidase activity, tumor necrosis factor α, Mesna

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399 The Influence of Nutritional and Immunological Status on the Prognosis of Head and Neck Cancer

Authors: Ching-Yi Yiu, Hui-Chen Hsu

Abstract:

Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35%, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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