Search results for: borderline ovarian tumor

Authors: Katalin Gocze, Gabriella Kiss, Zsuzsanna Gurdan, Krisztian Kvell, Attila Trabert

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Introduction: On a worldwide scale running has become an increasingly popular leisure time activity during the past decade. Since the participation rate of women has risen significantly the aim of our study was to analyze the mental status, sleeping habits and the prevalence of depression among female runners. Methods: Cross-sectional analysis included the use of validated and globally used surveys for the comprehensive evaluation of insomnia (AIS), depression (BDI), exercise dependence (EDS) and exercise addiction (EAI). Recreational and amateur female runners participating at half-marathon events in Hungary were asked to take part in our pilot study. Results: Participants mean age was 42.03±9.03 years. The prevalence of imsomnia was 18.87%. 60.34% has worries regarding their weight and 43.1% think that they have an actual weight problem. 77.6% stated that their body weight has an influence on their mood. 2.7% displayed borderline clinical depression, the prevalence of mild mood disorders was 10.81%. 17.2% had previously problems with disordered eating. Participants had a mean total EDS score of 46.94±15.55 and a mean total of 13.49±3.80 on EAI. Component scores were the highest for tolerance (a need for increased amounts of exercise to achieve the desired effect or a diminished effect occurs with continued use of the same amount of exercise). Conclusion: Even tough running can help improve mental health, tackle depression and overcome adversity, athletes are at risk of experiencing psychological difficulties which have an impact on their physical perfomance as well. Further research can help initiate targeted educational and screening programs to ensure that female athletes find a path to emotional well-being.

Keywords: depression, eating disorder, exercise addiction, exercise dependence, insomnia, running

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Authors: Belaynesh Tsegay Beyene, Teklay Gebrecherkos, Atsebaha Gebrekidan Kahsay, Mahmud Abdulkader

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Background: Hepatitis B and C viruses are of important health and socioeconomic problem of the globe with remarkable diseases and deaths in Sub-Saharan African countries. The burden of hepatitis is unknown in the prison settings of Tigrai. Therefore, we aimed to describe the seroprevalence and associated factors of hepatitis B and C viruses among prisoners of Tigrai, Ethiopia. Methods: A cross-sectional study was carried out from February 2020 to May 2020 at the prison facilities of Tigrai. Demographics and associated factors were collected from 315 prisoners prospectively. Five milliliter of blood was collected and tested using rapid tests kits of HBsAg (Zhejiang orient Gene Biotech Co., Ltd., China) and HCV antibodies (Volkan Kozmetik Sanayi Ve Ticaret Ltd. STI, Turkey). Positive samples were confirmed using enzyme-linked immunosorbent assay (ELISA) (Beijing Wantai Biological Pharmacy Enterprise Co. Ltd). Data were analyzed using Statistical Package for Social Sciences (SPSS) version 20 and p < 0.05 was considered statistically significant. Results: The overall seroprevalence of HBV and HCV were 25 (7.9%) and 1(0.3%), respectively. The majority of hepatitis B viral infections were identified from the age groups of 18-25 years (10.7%) and unmarried prisoners (11.8%). Prisoners greater than 100 per cell [AOR =3.95, 95% CI= (1.15, 13.6, p =0.029)] and having history of alcohol consumption [AOR =3.01, 95% CI= (1.17, 7.74, p =0.022)] were significantly associated with HBV infections. Conclusions: The seroprevalence of HBV among prisoners was nearly high or borderline (7.9%) with a very low HCV prevalence (0.3%). HBV was most prevalent among young adults, large number of prisoners per cell and those who had history of alcohol consumption. This study recommends that there should be prison-focused intervention including regular health education by emphasis on the mode of transmission and introducing HBV screening policy for prisoners especially when they enter to the prison.

Keywords: seroprevalence, HBV, HCV, prisoners, Tigrai

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

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

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

Procedia PDF Downloads 144

Authors: Buse Bahitli, Samiye Mete

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The aim of the study was to evaluate the quality of sexual life of women with diagnosed gynecological cancer and receive treatment. The study was a descriptive and cross-sectional type, and it was carried out with 276 women. Information Form and Sexual Quality of Life Scale-Female (SQOL) form was used in the study. The data was evaluated using Mann-Whitney U and Kruskal-Wallis test. In the study, Sexual Quality of Life Scale-Female average score was 68.83 ± 21.17. The %43.1 of women was endometrial cancer, %30.8 was cervical cancer, %24.6 was ovarian cancer, and %1.4 was vulvar cancer. The average time to diagnosis of patients is 41.80 ± 47.64 months. There was no significant difference mean SQOL according to individual/sociodemographic characteristics like age, education. Gynecological cancer-related characteristics like gynaecological cancer type, treatment type, surgery type were found not to affect the mean score of SQOL. However, it was found that the difference was due to the higher SQOL score in the group with a diagnosis time of 25 months and over (X²KW= 6.356, p= 0.046). The reason of significant difference means SQOL according to diagnosis over time might be that women adapted to cancer diagnosis. While women with gynaecologic cancer are evaluating their sexual lives, it is necessary to evaluate them with good evaluation tools.

Keywords: gynecological cancers, sexuality, quality of sexual life, SQOL

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Authors: Marina Shurupova, Victor Anisimov, Alexander Latanov

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Background: The cerebellar lesions inevitably provoke oculomotor impairments in patients of different age. Symptoms of subtentorial tumors, particularly medulloblastomas, include static and dynamic coordination disorders (ataxia, asynergia, imbalance), hypo-muscle tonus, disruption of the cranial nerves, and within the oculomotor system - nystagmus (fine or gross). Subtentorial tumors can also affect the areas of cerebellum that control the oculomotor system. The noninvasive eye-tracking technology allows obtaining multiple oculomotor characteristics such as the number of fixations and their duration, amplitude, latency and velocity of saccades, trajectory and scan path of gaze during the process of the visual field navigation. Eye tracking could be very useful in clinical studies serving as convenient and effective tool for diagnostics. The aim: We studied the dynamics of oculomotor system functioning in patients undergoing remission from cerebellar tumors removal surgeries and following neurocognitive rehabilitation. Methods: 38 children (23 boys, 15 girls, 9-17 years old) that have recovered from the cerebellar tumor-removal surgeries, radiation therapy and chemotherapy and were undergoing course of neurocognitive rehabilitation participated in the study. Two tests were carried out to evaluate oculomotor performance - gaze stability test and counting test. The monocular eye movements were recorded with eye tracker ArringtonResearch (60 Hz). Two experimental sessions with both tests were conducted before and after rehabilitation courses. Results: Within the final session of both tests we observed remarkable improvement in oculomotor performance: 1) in the gaze stability test the spread of gaze positions significantly declined compared to the first session, and 2) the visual path in counting test significantly shortened both compared to the first session. Thus, neurocognitive rehabilitation improved the functioning of the oculomotor system in patients following the cerebellar tumor removal surgeries and subsequent therapy. Conclusions: The experimental data support the effectiveness of the utilization of the eye tracking technique as diagnostic tool in the field of neurooncology.

Keywords: eye tracking, rehabilitation, cerebellar tumors, oculomotor system

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Authors: Hurtado Zuñiga Yonel Marcos, Ferreira Joao Tiago

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Introduction: Leiomyoma is a benign smooth muscle tumor. It is predominantly found between 40-49 years with a small prevalence in men. It is commonly found in the uterus, stomach, and in areas with smooth muscle. It presents as nodular, solitary, variable size, slow growing, and asymptomatic. It is classified into solid, vascular, and epithelioid leiomyoma. Vascular leiomyoma is the most common in the oral cavity. Oral leiomyomas are very rare because a smooth muscle in the oral cavity isn’t common. The most frequent areas of this pathologyaretongue, lip, buccal mucosa, and palate. It may be derived from the vascular walls or excretory ducts of the salivary glands. The diagnosis is made by histologically analysis. The treatment of choice is complete excision. Recurrence is rare. Objective: To report the case of a solid leiomyoma on the dorsum of the tongue and review the literature. Case description: A 78-year-old female patient presented a nodular (ovoid) elevation of 8x6mm, brownish color, with irregular limits and firm consistency located in the dorsal part of the tongue with slight symptoms. An excisional biopsy was performed, photographic record, and 3 weeks post-surgical follow-up. Result: The surgical specimen was submitted to an anatomopathological analysis, resulting in a benign nodule with defined limits compatible with solid leiomyoma of the tongue. Discussion: It is a pathology that presents in a solitary, nodular, well-defined, asymptomatic form; in the oral cavity, leiomyomas are found in the tongue, lip, buccal mucosa, and palate; as in our patient, it was nodular and, in the tongue, with a difference only in the symptomatology. The most prevalent age is 40-49 years and with small predominance in men, unlike our female patient with 78 years. Conclusions: Oral leiomyoma is a rare benign lesion that presents as a solitary nodular nodule; for its diagnosis, an anatomopathological analysis should be performed, and the treatment of choice is total excision with little recurrence.

Keywords: tongue, bening tumor, oral leiomyoma, leiomyoma

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Authors: Nir Schreiber, Reuven Cohen, Simi Haber

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The Potts model has been widely explored in the literature for the last few decades. While many analytical and numerical results concern with the traditional two site interaction model in various geometries and dimensions, little is yet known about models where more than two spins simultaneously interact. We consider a ferromagnetic four site interaction Potts model on the square lattice (FFPS), where the four spins reside in the corners of an elementary square. Each spin can take an integer value 1,2,...,q. We write the partition function as a sum over clusters consisting of monochromatic faces. When the number of faces becomes large, tracing out spin configurations is equivalent to enumerating large lattice animals. It is known that the asymptotic number of animals with k faces is governed by λᵏ, with λ ≈ 4.0626. Based on this observation, systems with q < 4 and q > 4 exhibit a second and first order phase transitions, respectively. The transition nature of the q = 4 case is borderline. For any q, a critical giant component (GC) is formed. In the finite order case, GC is simple, while it is fractal when the transition is continuous. Using simple equilibrium arguments, we obtain a (zero order) bound on the transition point. It is claimed that this bound should apply for other lattices as well. Next, taking into account higher order sites contributions, the critical bound becomes tighter. Moreover, for q > 4, if corrections due to contributions from small clusters are negligible in the thermodynamic limit, the improved bound should be exact. The improved bound is used to relate the critical point to the finite correlation length. Our analytical predictions are confirmed by an extensive numerical study of FFPS, using the Wang-Landau method. In particular, the q=4 marginal case is supported by a very ambiguous pseudo-critical finite size behavior.

Keywords: entropic sampling, lattice animals, phase transitions, Potts model

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Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Ndou Rembuluwani Moddy, Daniel Ter Goon, Takalani Grace Tshitangano, Lindelani Fhumudzani Mushaphi

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Obesity is a global public health problem. The study aimed to determine the risk factors associated with and the consequences of obesity among residents of Tshikota, Makhado Municipality, Limpopo Province, South Africa. A cross-sectional study involving 318 randomly selected adults aged 18-45 years residing at Tshikota, Makhado Local Municipality, South Africa. Sociodemographic information includes age, gender, educational level, occupation, behavioral lifestyle, environmental, psychological, and family history. Anthropometric, blood pressure, and blood glucose measurements followed standard procedure. The prevalence of obesity and overweight was 35.5% and 28.6%, respectively. About 75.2% of obese do not engage in physical activity. Most participants (63.5%) take meals three times a day, and 19.2% do not skip breakfast. Most participants do not have access to fruits and vegetables. Participants who were pre-hypertensive were 92(28.9%) and 32(10.1%) were in Stage 1 hypertension. Of the participants with Class 1 obesity, 40.9% were pre-hypertensive, and 15.2% were in Stage 1 hypertension. In Class 2 obesity, 37.8% were pre-hypertensive, and 26.7% were in Stage 1 hypertension. There was a significant difference between BMI and blood pressure among participants (p=0.00). About 6.1% of the participants in Class 1 obesity were at high risk, and 3.0% were at very high risk of glucose levels. Regarding cholesterol levels, 65 (20.4%) were at borderline, and 17(5.3%) were at high risk. There was no significant difference in BMI and cholesterol levels among participants (p= 0.20). The prevalence of obesity and overweight was high among residents of this setting. Age, marital and educational status, and employment were significantly associated with obesity. An obesity awareness campaign is crucial, and the availability of supermarkets and full-service grocery stores would provide accessibility to healthy food such as fruits and vegetables.

Keywords: obesity, overweight, risk factors, adults.

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Authors: Mehrdad Shafiei Dizaji, Hoda Azari

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The research explores the pioneering integration of Physics-Informed Neural Networks (PINNs) into the domain of Ground-Penetrating Radar (GPR) data prediction, akin to advancements in medical imaging for tracking tumor progression in the human body. This research presents a detailed development framework for a specialized PINN model proficient at interpreting and forecasting GPR data, much like how medical imaging models predict tumor behavior. By harnessing the synergy between deep learning algorithms and the physical laws governing subsurface structures—or, in medical terms, human tissues—the model effectively embeds the physics of electromagnetic wave propagation into its architecture. This ensures that predictions not only align with fundamental physical principles but also mirror the precision needed in medical diagnostics for detecting and monitoring tumors. The suggested deep learning structure comprises three components: a CNN, a spatial feature channel attention (SFCA) mechanism, and ConvLSTM, along with temporal feature frame attention (TFFA) modules. The attention mechanism computes channel attention and temporal attention weights using self-adaptation, thereby fine-tuning the visual and temporal feature responses to extract the most pertinent and significant visual and temporal features. By integrating physics directly into the neural network, our model has shown enhanced accuracy in forecasting GPR data. This improvement is vital for conducting effective assessments of bridge deck conditions and other evaluations related to civil infrastructure. The use of Physics-Informed Neural Networks (PINNs) has demonstrated the potential to transform the field of Non-Destructive Evaluation (NDE) by enhancing the precision of infrastructure deterioration predictions. Moreover, it offers a deeper insight into the fundamental mechanisms of deterioration, viewed through the prism of physics-based models.

Keywords: physics-informed neural networks, deep learning, ground-penetrating radar (GPR), NDE, ConvLSTM, physics, data driven

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Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

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The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

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Authors: Shoukat Ali, Amjad Hussain, Latif-ur-Rehman, Sehrish Inam

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Radiotherapy plays an important role in the management of cancer patients. Approximately 50% of the cancer patients receive radiotherapy at one point or another during the course of treatment. The entire radiotherapy treatment of curative intent is divided into different phases, depending on the histology of the tumor. The established protocols are useful in deciding the total dose, fraction size, and numbers of phases. The objective of this study was to evaluate the dosimetric differences between the conventional treatment protocols and the three-dimensional conformal simultaneously integrated boost (SIB) plans for three different tumors sites (i.e. bladder, breast, and brain). A total of 30 patients with brain, breast and bladder cancers were selected in this retrospective study. All the patients were CT simulated initially. The primary physician contoured PTV1 and PTV2 in the axial slices. The conventional doses prescribed for brain and breast is 60Gy/30 fractions, and 64.8Gy/36 fractions for bladder treatment. For the SIB plans biological effective doses (BED) were calculated for 25 fractions. The two conventional (Phase I and Phase II) and a single SIB plan for each patient were generated on Eclipse™ treatment planning system. Treatment plans were compared and analyzed for coverage index, conformity index, homogeneity index, dose gradient and organs at risk doses.In both plans 95% of PTV volume received a minimum of 95% of the prescribe dose. Dose deviation in the optic chiasm was found to be less than 0.5%. There is no significant difference in lung V20 and heart V30 in the breast plans. In the rectum plans V75%, V50% and V25% were found to be less than 1.2% different. Deviation in the tumor coverage, conformity and homogeneity indices were found to be less than 1%. SIB plans with three dimensional conformal radiotherapy technique reduce the overall treatment time without compromising the target coverage and without increasing dose to the organs at risk. The higher dose per fraction may increase the late effects to some extent. Further studies are required to evaluate the late effects with the intention of standardizing the SIB technique for practical implementation.

Keywords: coverage index, conformity index, dose gradient, homogeneity index, simultaneously integrated boost

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Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

Abstract:

In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

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Authors: Umair Riaz, Mudassar Iqbal, Umer Farooq, Farah Ali, Musadiq Idris

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The present work was designed to establish biometrical norms for ovaries, oviducts and crevices of one humped camels (Camelus dromedarius) and the diseases associated thereof in various age groups viz. calves (< 2 years, n=15), heifers (2-4 years, n=34) and adults (> 4 years, n=81). The genitalia were attained from Lahore Abbatoir, Punjab, Pakistan. Ovaries, oviducts and cervices of experimental genitalia were assessed for their length, width, thickness and weight. Statistically, there was no difference in the length and width of both left and right ovaries which however, increased with the advancement of age of camel. Similar results were noticed regarding the width of oviducts. The mean length of cervices of female camels correlated well with the number of cervical annular rings amongst the age groups. Regarding the abnormalities of ovaries and cervices in the 3 age groups, camel calves did not have any of the abnormalities. However, ovarian hypoplasia in heifers (2.94%) and follicular cyst in adult female camels (1.23%) were revealed in the present study. Mucocervix in heifers (2.96%) and cervicitis 1.23% in adult camels was also noticed. The present work presents a preliminary data on biometrical analysis for one humped camels and envisages a broader study with increased population and sample size.

Keywords: camelus dromedarius, pathology, biometry, female genital tract

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Authors: L. Szymanski, Z. Kolacinski, Z. Kamiński, G. Raniszewski, J. Fraczyk, L. Pietrzak

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In the article the development and demonstration of method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nano containers. Methodology of the production carbon - ferromagnetic nanocontainers includes: the synthesis of carbon nanotubes, chemical and physical characterization, increasing the content of ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Folic acid is ligand of folate receptors which is overexpresion in tumor cells. The presence of ligand should ensure the specificity of the interaction between ferromagnetic nanocontainers and tumor cells. The chemical functionalization contains several step: oxidation reaction, transformation of carboxyl groups into more reactive ester or amide groups, incorporation of spacer molecule (linker), attaching folic acid. Activation of carboxylic groups was prepared with triazine coupling reagent (preparation of superactive ester attached on the nanocontainers). The spacer molecules were designed and synthesized. In order to ensure biocompatibillity of linkers they were built from amino acids or peptides. Spacer molecules were synthesized using the SPPS method. Synthesis was performed on 2-Chlorotrityl resin. The linker important feature is its length. Due to that fact synthesis of peptide linkers containing from 2 to 4 -Ala- residues was carried out. Independent synthesis of the conjugate of foilic acid with 6-aminocaproic acid was made. Final step of synthesis was connecting conjugat with spacer molecules and attaching it on the ferromagnetic nanocontainer surface. This article contains also information about special CVD and microvave plasma system to produce nanotubes and ferromagnetic nanocontainers. The first tests in the device for hyperthermal RF generator will be presented. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz.

Keywords: synthesis of carbon nanotubes, hyperthermia, ligands, carbon nanotubes

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Authors: Amal Abo El-Maaty, Amira Mohamed, Nashwa Abu-Aita, Hisham Morgan

Abstract:

For estimating markers of overweight or obesity of brood mares used for riding and training, 17 mares of different body conditions were subjected to blood sampling and ultrasound examination to measure rump fat thickness and monitor ovulation for six consecutive weeks. Also length (L), heart girth (G) and withers height (H) were measured to estimate body weight (BW), body fat %, body fat mass (BFM) and body mass index (BMI). Mares were classified into three groups according to both body condition score (BCS) and rump back fat (BF). Overweight mares (O) were having BCS > 7 and BF thickness >7mm, moderate body condition (M) mares were having BCS >3and ≤7and BF <3and <7mm, and emaciated mares (E) were having BCS ≤3 and BF ≤3mm. glucose, triglycerides, nitric oxide, ovarian, thyroid, insulin, insulin like growth factor-I (IGF-1), and leptin hormones were measured. Results revealed that BCS, G, L, L*G*H, BW, BF, fat %, BFM were significantly (P<0.0001) decreasing linearly from O to E. T4 concentrations of E were significantly high (P=0.04) compared to M and O but T3 concentrations tended to decrease in E (P>0.05). Insulin and IGF-1 concentrations tended to be high in O (P>0.05) and decrease with the decrease of body condition. M had (P=0.007) the highest leptin, but E mares had the lowest P4 concentrations (P=0.01). Concentrations of glucose and NO decreased with the decrease of BCS and BF but triglycerides of O were insignificantly high. In conclusion, exercise could prevent the development of metabolic syndrome in horses and back fat and morphometric measurements were the easiest and simple assessment of overweight and deviation to obesity.

Keywords: body condition score, insulin, leptin, mares, rump fat

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Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

Abstract:

Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Jiri Kysucan, Dusan Klos, Katherine Vomackova, Pavel Koranda, Martin Lovecek, Cestmir Neoral, Roman Havlik

Abstract:

Aim: The prognosis of patients with pancreatic cancer is poor. The median of survival after establishing diagnosis is 3-11 months without surgical treatment, 13-20 months with surgical treatment depending on the disease stage, 5-year survival is less than 5%. Radical surgical resection remains the only hope of curing the disease. Early diagnosis with valid establishment of tumor resectability is, therefore, the most important aim for patients with pancreatic cancer. The aim of the work is to evaluate the contribution and define the role of 18F-FDG PET/CT in preoperative staging. Material and Methods: In 195 patients (103 males, 92 females, median age 66,7 years, 32-88 years) with a suspect pancreatic lesion, as part of the standard preoperative staging, in addition to standard examination methods (ultrasonography, contrast spiral CT, endoscopic ultrasonography, endoscopic ultrasonographic biopsy), a hybrid 18F-FDG PET/CT was performed. All PET/CT findings were subsequently compared with standard staging (CT, EUS, EUS FNA), with peroperative findings and definitive histology in the operated patients as reference standards. Interpretation defined the extent of the tumor according to TNM classification. Limitations of resectability were local advancement (T4) and presence of distant metastases (M1). Results: PET/CT was performed in a total of 195 patients with a suspect pancreatic lesion. In 153 patients, pancreatic carcinoma was confirmed and of these patients, 72 were not indicated for radical surgical procedure due to local inoperability or generalization of the disease. The sensitivity of PET/CT in detecting the primary lesion was 92.2%, specificity was 90.5%. A false negative finding in 12 patients, a false positive finding was seen in 4 cases, positive predictive value (PPV) 97.2%, negative predictive value (NPV) 76,0%. In evaluating regional lymph nodes, sensitivity was 51.9%, specificity 58.3%, PPV 58,3%, NPV 51.9%. In detecting distant metastases, PET/CT reached a sensitivity of 82.8%, specificity was 97.8%, PPV 96.9%, NPV 87.0%. PET/CT found distant metastases in 12 patients, which were not detected by standard methods. In 15 patients (15.6%) with potentially radically resectable findings, the procedure was contraindicated based on PET/CT findings and the treatment strategy was changed. Conclusion: PET/CT is a highly sensitive and specific method useful in preoperative staging of pancreatic cancer. It improves the selection of patients for radical surgical procedures, who can benefit from it and decreases the number of incorrectly indicated operations.

Keywords: cancer, PET/CT, staging, surgery

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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

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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

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

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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

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Authors: Conchita Martin de Bustamante, Christopher S. Kung, Brianne Lacy, Eunsol Park, Hien Piotrowski, Mustafa Husain, Waseem Ahmed

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Objective: To explore the comorbidity of mental health conditions (major depressive disorder, borderline personality disorder, generalized anxiety disorder, and schizophrenia) with opioid use disorder in people incarcerated at a large urban jail. Background Schizophrenia, depression, bipolar disorder, and anxiety are all serious mental health conditions that are highly prevalent amongst incarcerated patients. However, it is seldom the only disorder these patients are suffering from. According to the US Department of Justice, about half of US prisoners, both at the state and federal level, suffer from substance use disorders. Although the opioid epidemic has been studied greatly in the recent years amongst the general population, little has been explored on how the opioid crisis has affected incarcerated patients in local jails, particularly regarding which of these patients are most susceptible. Method The cohort consisted of 507 people incarcerated at a large county jail who were evaluated by mental health providers in December 2020. A retrospective review was performed to evaluate associations between mental health diagnoses, substance use disorder, and other demographic variables. Results Participants had been diagnosed with various mental health conditions, including MDD (22.6%, n = 115), GAD (33.7%, n = 171), Schizophrenia (15.2%, n = 77) and BPD (27%, n = 137). Preliminary Chi square tests were conducted for these conditions against marijuana, alcohol, cocaine, opioid, methamphetamine, benzodiazepines, and sedative use disorders. The results showed significant associations between Schizophrenia (p = 0.013), GAD (p M 0.001), and MDD (p = 0.029) with opioid use disorders. Conclusions Determining the extent of these comorbid substance use and mental health disorders within an incarcerated population can help influence treatment plans for future incarcerated patients. Many federal and state jail systems lack pharmacological substance use intervention and the prevalence of these co-morbid conditions can shed light on the importance of treating conditions concurrently upon intake.

Keywords: mental health conditions, opioids, substance use disorder, comorbidity

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Authors: Nidesh Sapkota, Garima Pudasaini, Dikshya Agrawal, Binav Baral, Umesh Bhagat, Dharanidhar Baral

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Background: Medical and Dental students are vulnerable to higher levels of Psychological distress than other age matched peers. Many studies reveals that there is high prevalence of psychoactive substance use and Psychiatric co-morbidities among them. Objectives: -To study the prevalence of substance use among medical and dental students of a Medical University. -To study the prevalence of depression and anxiety in medical and dental students of a Medical University. Materials and Method: A cross-sectional descriptive study in which simple random sampling was done. Semi-structured questionnaire, AUDIT for alcohol use, Fagerstrom test for Nicotine dependence, Cannabis screening test (CAST), Beck’s Depression Inventory (BDI), Beck’s Anxiety Inventory (BAI) were used for the assessment. Results: Total sample size was 588 in which the mean age of participants was 22±2years. Among them the prevalence of alcohol users was 47.75%(281) in which 32%(90) were harmful users. Among 19.55%(115) nicotine users 56.5%(65), 37.4%(43), 6.1%(7) had low, low to moderate and moderate dependence respectively. The prevalence of cannabis users was 9%(53) with 45.3%(24), 18.9%(10) having low and high addiction respectively. Depressive symptoms were recorded in 25.3%(149) out of which 12.6%(74), 6.5%(38), 5.3%(31), 0.5%(3), 0.5%(3) had mild, borderline, moderate, severe and extreme depressive symptoms respectively. Similarly anxiety was recorded among 7.8%(46) students with 42 having moderate and 4 having severe anxiety symptoms. Among them 6.3%(37) had suicidal thoughts and 4(0.7%) of them had suicide attempt in last one year. Statistically significant association was noted with harmful alcohol users, Depression and suicidal attempts. Similar association was noted between Depression and suicide with moderate use of nicotine. Conclusion: There is high prevalence of Psychoactive substance use and psychiatric co-morbidities noted in the studies sample. Statistically significant association was noted with Psychiatric co-morbidities and substance use.

Keywords: alcohol, cannabis, dependence, depression, medical students

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Authors: Azza Gaber Antar Farag, Eman Abd El Fatah Badr, Wesam Ahmed Tawfik Hasssan Abdel Aal, Mustafa Elsayed Elshaib

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Background: Female Sexual Dysfunction (FSD) represents recurrent and persistent problems that distress women and/or strain their relationships with their partners. Dopamine can affect sexual function and interacts with ovarian hormones in the ventromedial area in the hypothalamus. Objective: To investigate the possible role of dopamine in FSD. Method: This prospective case-control study was carried on 100 women having FSD and 100 healthy volunteer females. They were recruited from the Al-Menoufia governorate. All included women were subjected to the questionnaire to assess their demographic and gynecological data as well as sexual function. They were investigated for serum levels of dopamine, estradiol, progesterone and DHEA hormones. Results: Dopamine serum levels were significantly lower in females having sexual dysfunction (6.68±4.14) than controls (57.97±26.26) (P>0.001). This decreased dopamine level was of a significant positive correlation with the arousal domain and significant negative correlation regarding the pain domain (r=-0.19, p=0.01). Also, estradiol serum levels were significantly lower (P>0.001), but progesterone and DHEA serum levels were significantly higher in the FSD group than controls (P>0.001). There was a significant negative correlation between dopamine and DHEA serum levels (r= -0.45, p <0.001). Conclusions: Decreased dopamine serum levels may have an active role in the pathophysiology of FSD, impacting mainly arousal and pain domains, and its targeting should be considered during FSD management.

Keywords: dopamine, estradiol, progesterone, DHEA, females sexual dysfunction

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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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Authors: Hajar Hosseini Khorami

Abstract:

Porphyrins are organic, aromatic compounds found in heme, cytochrome, cobalamin, chlorophyll , and many other natural products with essential roles in biological processes that their cationic forms have been used as groups of favorable non-viral vectors recently. Cationic porphyrins are self-chromogenic reagents with a high capacity for modifications, great interaction with DNA and protection of DNA from nuclease during delivery of it into a cell with low toxicity. In order to have high efficient gene transfection into the cell while causing low toxicity, genetically manipulations of the non-viral vector, cationic porphyrin, would be useful. In this study newly modified cationic porphyrin derivative, 5, 10-dihexyl-15, 20bis (N-methyl-4-pyridyl) porphyrin was applied. Cytotoxicity of synthesized cationic porphyrin on Chinese Hamster Ovarian (CHO) cells was evaluated by using MTT assay. This cationic derivative is dose-dependent, with low cytotoxicity at the ranges from 100 μM to 0.01μM. It was uptake by cells at high concentration. Using direct non-viral gene transfection method and different concentration of cationic porphyrin were tested on transfection of CHO cells by applying derived transfection reagent with X-tremeGENE HP DNA as a positive control. However, no transfection observed by porphyrin derivative and the parameters tested except for positive control. Results of this study suggested that applying different protocol, and also trying other concentration of cationic porphyrins and DNA for forming a strong complex would increase the possibility of efficient gene transfection by using cationic porphyrins.

Keywords: cationic porphyrins, gene delivery, non-viral vectors, transfection reagents

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