Search results for: cancer survivor

Authors: Sarah Iaquinta, Christophe Blanquart, Elena Ishow, Sylvain Freour, Frederic Jacquemin, Shahram Khazaie

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Nanoparticles have recently emerged as a possible cancer treatment tool. Several formulations have been used to enhance the uptake of these nanoparticles by cancer cells and avoid their immediate clearance when administrated in vivo. Most of the previous studies focus on the investigation of the influence of the mechanical properties of the cell membrane and the particle. However, these studies do not account for the variation of adhesion and tension during the wrapping of the nanoparticle by the membrane. These couplings should be considered since the cell adapts to the interaction with the nanoparticle by, e.g., increasing the number of interactions (consequently leading to an increase of the cell membrane/nanoparticle adhesion) and by reorganizing its cytoskeleton, leading to the releasing of the tension of the cell membrane. The main contribution of this work is the proposal of a novel model for representing the cellular uptake of rigid circular nanoparticles based on an energetic model tailored to take into account the adaptation of the nanoparticle/cell membrane adhesion and of the membrane stress during wrapping. Several coupling models using sigmoidal functions are considered and compared. The study calculations revealed that the results considering constant parameters underestimated the final wrapping degree of the particle by up to 50%.

Keywords: adhesion, cellular adaptation, cellular uptake, mechanical properties, tension

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Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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Authors: Shivayogi Charantimath

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Radiotherapy and chemotherapy are effective for treating malignancies but are associated with side effects like oral mucositis. Chlorhexidine gluconate is one of the most commonly used mouthwash in prevention of signs and symptoms of mucositis. Evidence shows that chlorhexidine gluconate has side effects in terms of colonization of bacteria, bad breadth and less healing properties. Thus, it is essential to find a suitable alternative therapy which is more effective with minimal side effects. Curcumin, an extract of turmeric is gradually being studied for its wide-ranging therapeutic properties such as antioxidant, analgesic, anti-inflammatory, antitumor, antimicrobial, antiseptic, chemo sensitizing and radio sensitizing properties. The present study was conducted to evaluate the efficacy and safety of topical curcumin gel on radio-chemotherapy induced oral mucositis in cancer patients. The aim of the study is to evaluate the efficacy and safety of curcumin gel in the management of oral mucositis in cancer patients undergoing radio chemotherapy and compare with chlorhexidine. The study was conducted in K.L.E. Society’s Belgaum cancer hospital. 40 oral cancer patients undergoing the radiochemotheraphy with oral mucositis was selected and randomly divided into two groups of 20 each. The study group A [20 patients] was advised Cure next gel for 2 weeks. The control group B [20 patients] was advised chlorhexidine gel for 2 weeks. The NRS, Oral Mucositis Assessment scale and WHO mucositis scale were used to determine the grading. The results obtained were calculated by using SPSS 20 software. The comparison of grading was done by applying Mann-Whitney U test and intergroup comparison was calculated by Wilcoxon matched pairs test. The NRS scores observed from baseline to 1^st and 2^nd week follow up in both the group showed significant difference. The percentage of change in erythema in respect to group A was 63.3% for first week and for second week, changes were 100.0% with p = 0.0003. The changes in Group A in respect to erythema was 34.6% for 1^st week and 57.7% in second week. The intergroup comparison was significant with p value of 0.0048 and 0.0006 in relation to group A and group B respectively. The size of the ulcer score was measured which showed 35.5% [P=0.0010] of change in Group A for 1^st and 2^nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1^st week and 53.6% for 2^nd week follow up. The intergroup comparison with Wilcoxon matched pair test was significant with p=0.0001 in group A. The result obtained by WHO mucositis score in respect to group A shows 29.6% [p=0.0004] change in first week and 75.0% [p=0.0180] change in second week which is highly significant in comparison to group B. Group B showed minimum changes i.e. 20.1% in 1^st week and 33.3% in 2^nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1^st week follow up and 0.000 for 2^nd week follow up. Curcumin gel appears to an effective and safer alternative to chlorhexidine gel in treatment of oral mucositis.

Keywords: curcumin, chemotheraphy, mucositis, radiotheraphy

Procedia PDF Downloads 351

Authors: Najla M. Salkho, Vinod Paul, Pierre Kawak, Rute F. Vitor, Ana M. Martin, Nahid Awad, Mohammad Al Sayah, Ghaleb A. Husseini

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Liposomes are popular lipid bilayer nanoparticles that are highly efficient in encapsulating both hydrophilic and hydrophobic therapeutic drugs. Liposomes promote a low risk controlled release of the drug avoiding the side effects of the conventional chemotherapy. One of the great potentials of liposomes is the ability to attach a wide range of ligands to their surface producing ligand-mediated active targeting of cancer tumour with limited adverse off-target effects. Ultrasound can also aid in the controlled and specified release of the drug from the liposomes by breaking it apart and releasing the drug in the specific location where the ultrasound is applied. Our research focuses on the synthesis of PEGylated liposomes (contain poly-ethylene glycol) encapsulated with the model drug calcein and studying the effect of low frequency ultrasound applied at different power densities on calcein release. In addition, moieties are attached to the surface of the liposomes for specific targeting of the cancerous cells which over-express the receptors of these moieties, ultrasound is then applied and the release results are compared with the moiety free liposomes. The results showed that attaching these moieties to the surface of the PEGylated liposomes not only enhance their active targeting but also stimulate calcein release from these liposomes.

Keywords: active targeting, liposomes, moieties, ultrasound

Procedia PDF Downloads 602

Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

Procedia PDF Downloads 331

Authors: Chia-Hui Chen, Chien-Kuo Wang

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Background: Full field digital mammography (FFDM) is widely used in diagnosis of breast cancer. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Hence, the radiation dose delivered to the patients involved in an imaging protocol is of utmost concern. Aim: To compare the surface radiation dose (ESD) of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) by using breast phantoms. Method: We analyzed the average entrance surface dose (ESD) of FFDM and DBT by using breast phantoms. Optically Stimulated luminescent Dosimeters (OSLD) were placed in a tissue-equivalent Breast phantom at difference sites of interest. Absorbed dose measurements were obtained after digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) exposures. Results: An automatic exposure control (AEC) is proposed for surface dose measurement during DBT and FFDM. The mean ESD values for DBT and FFDM were 6.37 mGy and 3.51mGy, respectively. Using of OSLD measured for surface dose during DBT and FFDM. There were 19.87 mGy and 11.36 mGy, respectively. The surface exposure dose of DBT could possibly be increased by two times with FFDM. Conclusion: The radiation dose from DBT was higher than that of FFDM and the difference in dose between AEC and OSLD measurements at phantom surface.

Keywords: full-field digital mammography, digital breast tomosynthesis, optically stimulated luminescent dosimeters, surface dose

Procedia PDF Downloads 420

Authors: Mohamed Shafi Bin Mahboob Ali

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Introduction: Synchronous tumor is defined as the presence of more than one primary malignant lesion in the same patient at the indexed diagnosis. It is a rare occurrence, especially in the spectrum of colorectal cancer, which accounts for less than 4%. The underlying pathology of a synchronous tumor is thought to be due to a genomic factor, which is microsatellite instability (MIS) with the involvement of BRAF, KRAS, and the GSRM1 gene. There are no specific sites of occurrence for the synchronous colorectal tumor, but many studies have shown that a synchronous tumor has about 43% predominance in the ascending colon with rarity in the sigmoid colon. Case Report: We reported a case of a young lady in the middle of her 30's with no family history of colorectal cancer that was diagnosed with a synchronous adenocarcinoma at the descending colon and rectosigmoid region. The lady's presentation was quite perplexing as she presented to the district hospital initially with simple, uncomplicated hemorrhoids and constipation. She was then referred to our center for further management as she developed a 'football' sized right gluteal swelling with a complete intestinal obstruction and bilateral lower-limb paralysis. We performed a CT scan and biopsy of the lesion, which found that the tumor engulfed the sacrococcygeal region with more than one primary lesion in the colon as well as secondaries in the liver. The patient was operated on after a multidisciplinary meeting was held. Pelvic exenteration with tumor debulking and anterior resection were performed. Postoperatively, she was referred to the oncology team for chemotherapy. She had a tremendous recovery in eight months' time with a partial regain of her lower limb power. The patient is still under our follow-up with an improved quality of life post-intervention. Discussion: Synchronous colon cancer is rare, with an incidence of 2.4% to 12.4%. It has male predominance and is pathologically more advanced compared to a single colon lesion. Down staging the disease by means of chemoradiotherapy has shown to be effective in managing this tumor. It is seen commonly on the right colon, but in our case, we found it on the left colon and the rectosigmoid. Conclusion: Managing a synchronous colon tumor could be challenging to surgeons, especially in deciding the extent of resection and postoperative functional outcomes of the bowel; thus, individual treatment strategies are needed to tackle this pathology.

Keywords: synchronous, colon, tumor, adenocarcinoma

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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: Pei-Chih Wu, Hsin-Chih Lai, Yung-Lung Lee, Yun-Yao Chi, Ching-Yi Horng, Hsien-Chang Wang

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The impact of climate change to health has always been well documented. Amongst them, water-borne infectious diseases, chronic adverse effects or cancer risks due to chemical contamination in flooding or drought events are especially important in river basin. This study therefore utilizes GIS and different models to integrate demographic, land use, disaster prevention, social-economic factors, and human health assessment in the Erren River basin. Therefore, through the collecting of climatic, demographic, health surveillance, water quality and other water monitoring data, potential risks associated with the Erren River Basin are established and to understand human exposure and vulnerability in response to climate extremes. This study assesses the temporal and spatial patterns of melioidosis (2000-2015) and various cancer incidents in Tainan and Kaohsiung cities. The next step is to analyze the spatial association between diseases incidences, climatic factors, land uses, and other demographic factors by using ArcMap and GeoDa. The study results show that amongst all melioidosis cases in Taiwan, 24% cases (115) residence occurred in the Erren River basin. The relationship between the cases and in Tainan and Kaohsiung cities are associated with population density, aging indicator, and residence in Erren River basin. Risks from flooding due to heavy rainfall and fish farms in spatial lag regression are also related. Through liver cancer, the preliminary analysis in temporal and spatial pattern shows an increases pattern in annual incidence without clusters in Erren River basin. Further analysis of potential cancers connected to heavy metal contamination from water pollution in Erren River is established. The final step is to develop an assessment tool for human exposure from water contamination and vulnerability in response to climate extremes for the second year.

Keywords: climate change, health impact, health adaptation, Erren River Basin

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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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: Nasrin Hosseinzad

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Troxerutin, a trihydroxyethylated derived of rutin, is a flavonoid existing in tea, coffee, cereal grains, various fruits and vegetables have been conveyed to display radioprotective, antithrombotic, nephron-protective and hepato-protective possessions. Troxerutin, has been well-proved to utilize hepatoprotective assets. Troxerutin could upturn the resistance of hippocampal neurons alongside apoptosis by lessening the action of AChE and oxidative stress. Consequently, troxerutin may have advantageous properties in the administration of Alzheimer's disease and cancer. Troxerutin has been testified to have several welfares and medicinal stuffs. It could shelter the mouse kidney against d-gal-induced damage by refining renal utility, decreasing histopathologic changes, dropping ROS construction, reintroducing the activities of antioxidant enzymes and reducing DNA oxidative destruction. The DNA cleavage study clarifies that troxerutin showed DNA protection against hydroxyl radical persuaded DNA mutilation. Troxerutin uses anti-cancer effect in HuH-7 hepatocarcinoma cells conceivably through synchronized regulation of the molecular signalling pathways, Nrf2 and NF-κB. DNA binding at slight channel by troxerutin may have donated to feature breaks leading to improved radiation brought cell death. Furthermore, the mechanism principal the observed variance in the antioxidant activities of troxerutin and its esters was qualified to equally their free radical scavenging capabilities and dissemination on the cell membrane outward.

Keywords: troxerutin, DNA, oxidative stress, antioxidant, free radical

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Manjusha R. Vagal, Shyam K. Shrivastava, Umesh Mahantshetty, Sudeep Gupta, Supriya Chopra, Reena Engineer, Amita Maheshwari, Atul Buduk

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Vaginal stenosis is a common side effect associated with pelvic radiotherapy in cervical cancer patients which contributes negatively to woman’s health and prevents adequate vaginal/cervical examination. Vaginal dilation with a dilator is routine practice and is internationally advocated as a prophylactic measure to preserve vaginal patency. This retrospective study was carried out with the aim to know the usefulness of vaginal dilation following pelvic radiation therapy in cervical cancer patients in India. Data from medical records of 183 cervical cancer patients, which met the study criteria, were collected related to the stage of the disease, treatment received, commencement period of dilation post radiation therapy, sexual status and side effects associated to dilation practice. Data related to vaginal dimensions as per the length of insertion of a small, medium and large dilator were collected on regular follow-ups until 36 months and/or more. Vaginal dimensions as measured with the length of medium dilator insertion were used for analysis of dilation therapy results using paired t-test. Patients who underwent vaginal dilation with dilator maintained vaginal patency, also the mean vaginal length significantly increased, from 8.02 cm ± 2.69 to 9.96 ± 2.89 cm with a p value <0.001. There was no significant difference found on vaginal patency with different intervals of initiation of dilation therapy. At the third year and more following dilation therapy, significant increase in vaginal length observed with a p value of 0.0001 in both sexually active and inactive patients. Compilation of vaginal dosage during brachytherapy was inadequate, and hence, the secondary objective of the study to determine the effect of radiotherapy on the outcome of rehabilitation intervention was not studied in detail. This retrospective study has found that dilation therapy with vaginal dilators post pelvic radiotherapy is effective in preventing vaginal stenosis and improving vaginal patency and cannot be substituted with vaginal intercourse. Sexual quality of life assessment in the Indian population needs much attention.

Keywords: dilator, sexually active, vaginal dilation, vaginal stenosis

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Authors: Sabine Danzinger, Nora Hielscher, Miriam Izso, Johanna Metzler, Carmen Trinkl, Christian Pfeifer, Kristina Tendl-Schulz, Christian F. Singer

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The objective of this study is to analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors. Methods: We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC). Results: Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (þ), have a lower proliferation rate (Ki67 <14%), and a higher patholog- ical T stage (pT2–4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ERþ, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1–3) was significantly more frequent with ILC versus IDC. Conclusions: Our data suggests that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.

Keywords: breast cancer, lobular histology, tumor biology, hormone receptor, ki67

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Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Khalid A. Salman, Shereen Wagih, Tariq Munshi, Musaed Almalki, Safwan Zatari, Zahid Khan

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Aim: To measure exposure levels to family members and caregivers of Saudi patients treated with low dose I131 therapy, and household radiation exposure rate to predict different factors that can affect radiation exposure. Patients and methods: All adult self dependent patients with hyperthyroidism or cancer thyroid referred for low dose radioactive I131 therapy on outpatient basis are included. Radiation protection procedures are given to the participant and family members in details. TLD’s were dispensed to each participant in sufficient quantity for his/her family members living in the household. TLD’s are collected at fifth days post-dispense from patients who agreed to have a home visit during which the household is inspected and level of radiation contamination of surfaces was measured. Results: Thirty-two patients were enrolled in the current study, with a mean age of 43.1± 17.1 years Out of them 25 patients (78%) are females. I131 therapy was given in twenty patients (63%) for cancer thyroid of and for toxic goiter in the remaining twelve patients (37%), with an overall mean I131 dose of 24.1 ± 7.5mCi that is relatively higher in the former. The overall number of household family members and helpers of patients are 139, out of them77 are females (55.4%) & 62 are males (44.6%) with a mean age of 29.8± 17.6. The mean period of contact with the patient is 7.6 ±5.6hours. The cumulative radiation exposure shows that radiation exposure to all family members is below the exposure constraint (1mSv), with a range of 109 to 503uSv, and a mean value of 220.9±91 uSv. Numerical data shows a little higher exposure rate for family members of those who receive higher dose of I131 (patients with thyroid cancer) and household members who spent longer time with the patient, yet, the difference is statistically insignificant (P>0.05). Besides, no significant correlation was found between the degree of cumulative exposure of the family members to their gender, age, socioeconomic standard, educational level and residential factors. In the 21 home visits all data from bedrooms, reception areas and kitchens are below hazardous limits (0.5uSv/h) apart from bathrooms that give a slightly higher reading of 0.57±0.39 uSv/h in those with cancer thyroid who receive a higher radiation dose. A statistically significant difference was found between radiation exposure rate in bathrooms used by the patient versus those used by family members only, with a mean value of exposure rate of 0.701±0.21 uSv/h and 0.17±0.82 uSv/h respectively, with a p-value of 0.018 (<0.05). Conclusion: Family members of patients treated with low dose I131 on outpatient basis have a good compliance to radiation protection instruction if given properly with a cumulative radiation exposure rate evidently beyond the radiation exposure constraints of 1 mSv. Given I131 dose, hours spent with the patient, age, gender, socioeconomic standard, educational level and residential factors have no significant correlation with the cumulative radiation exposure. The patient bathroom exhibits more radiation exposure rate, needing more strict instructions for patient bathroom use and health hygiene.

Keywords: family members, radiation exposure, radioactive iodine therapy, radiation safety

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Authors: W. J. Zhang, Y. Q. Du, M. L. Wang

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Noninvasive diagnostics of diseases via breath analysis has attracted considerable scientific and clinical interest for many years and become more and more promising with the rapid advancement in nanotechnology and biotechnology. The volatile organic compounds (VOCs) in exhaled breath, which are mainly blood borne, particularly provide highly valuable information about individuals’ physiological and pathophysiological conditions. Additionally, breath analysis is noninvasive, real-time, painless and agreeable to patients. We have developed a wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) for the detection of a number of physiological indicators in breath. Eight DNA sequences were used to functionalize SWNT sensors to detect trace amount of methanol, benzene, dimethyl sulfide, hydrogen sulfide, acetone and ethanol, which are indicators of heavy smoking, excessive drinking, and diseases such as lung cancer, breast cancer, cirrhosis and diabetes. Our tests indicated that DNA functionalized SWNT sensors exhibit great selectivity, sensitivity, reproducibility, and repeatability. Furthermore, different molecules can be distinguished through pattern recognition enabled by this sensor array. Thus, the DNA-SWNT sensor array has great potential to be applied in chemical or bimolecular detection for the noninvasive diagnostics of diseases and health monitoring.

Keywords: breath analysis, diagnosis, DNA-SWNT sensor array, noninvasive

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Authors: András Fülöp, Lejla Heilmann, Zsolt Szabó, Ákos Koós

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Microbial fuel cells (MFCs) present a sustainable biotechnological solution to future energy demands. The aim of this study was to construct soil based, single cell, membrane-less MFC systems, operated without treatment to continuously power on-site monitoring and control systems during the soil bioremediation processes. Our Pseudomonas aeruginosa 541 isolate is an ideal choice for MFCs, because it is able to produce pyocyanin which behaves as electron-shuttle molecule, furthermore, it also has a significant antimicrobial effect. We tested several materials and structural configurations to obtain long term high power output. Comparing different configurations, a proton exchange membrane-less, 0.6 m long with 0.05 m diameter MFC tubes offered the best long-term performances. The long-term electricity production were tested from starch, yeast extract (YE), carboxymethyl cellulose (CMC) with humic acid (HA) as a mediator. In all cases, 3 kΩ external load have been used. The two best-operated systems were the Pseudomonas aeruginosa 541 containing MFCs with 1 % carboxymethyl cellulose and the MFCs with 1% yeast extract in the anode area and 35% hydrogel in the cathode chamber. The first had 3.3 ± 0.033 mW/m2 and the second had 4.1 ± 0.065 mW/m2 power density values. These systems have operated for 230 days without any treatment. The addition of 0.2 % HA and 1 % YE referred to the volume of the anode area resulted in 1.4 ± 0.035 mW/m2 power densities. The mixture of 1% starch with 0.2 % HA gave 1.82 ± 0.031 mW/m2. Using CMC as retard carbon source takes effect in the long-term bacterial survivor, thus enable the expression of the long term power output. The application of hydrogels in the cathode chamber significantly increased the performance of the MFC units due to their good water retention capacity.

Keywords: microbial fuel cell, bioremediation, Pseudomonas aeruginosa, biotechnological solution

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Authors: P. Narrima, C. Y. Looi, M. A. Mohd, H. M. Ali

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Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Keywords: antiproliferative, apoptosis, MCF-7 human breast cancer, Persea declinata

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Authors: J. Visser, C. Driver, T. Ebenhan

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[¹⁸F]-FDG (fluorodeoxyglucose) is a radiopharmaceutical compound that is used for non-invasive cancer tumor imaging through positron emission tomography (PET). This radiopharmaceutical is used to visualise the metabolic processes in tumour tissues, which can be applied for the diagnosis and prognosis of various types of cancer. [¹⁸F]-FDG has widespread use in both clinical and pre-clinical research settings. Imaging using [¹⁸F]-FDG results in representative normal tissue distribution as well as visualisation of hypermetabolic lesions ([¹⁸F]-FDG avid foci). The metabolic tissue concentration of these lesions following [¹⁸F]-FDG administration can be quantified using Standard Uptake Values (SUV). Standard uptake values of [¹⁸F]-FDG-based Positron Emission Tomography can be influenced by various biological and technical handling factors. Biological factors that affect [¹⁸F]-FDG uptake include the blood glucose levels of subjects, normal physiological variants between subjects and administration of certain pharmaceutical agents. Technical factors that can have an effect include the route of radiopharmaceutical or pharmaceutical agents administered and environmental conditions such as ambient temperature and lighting. These factors influencing tracer uptake need to be investigated to improve the robustness of the imaging protocol, which will achieve reproducible image acquisition across various research projects, optimised tumor visualisation and increased data validity and reliability.

Keywords: fluorodeoxyglucose, tumour imaging, Rodent, Blood Glucose, PET/CT Imaging

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Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Naila Sher, Mushtaq Ahmed, Nadia Mushtaq, Rahmat Ali Khan

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In cancer therapy, nanoparticles (NPs) shall be applied possibly by inoculation in the veins of humans. This action will connect them with white (WBCs) and red blood cells (RBCs) in the bloodstream before they reach their main targeted cancer cells. However, possible effects of silver, gold, and silver/gold bimetallic NPs (Ag, Au, and Ag/Au BNPs) on baby hamster kidney-21 (BHK-21) cells were studied by MTT assay. Here, Ag, Au, and their Ag/Au BNPs (bimetallic nanoparticles) were synthesized by using Hippeastrum hybridum (HH) extract. These NPs were characterized by UV-visible spectroscopy, FT-IR, XRD, and EDX, and SEM analysis. XRD analysis conferring the crystal structure with an average size of 13.3, 10.72, and 8.34nm of Ag, Au, and Ag/Au BNPs, respectively. SEM showed that Ag, Au, and Ag/Au BNPs had irregular morphologies, with nano measures calculated sizes of 40, 30, and 20 nm respectively. EDX spectrometers confirmed the presence of elemental Ag signal of the AgNPs with 22.75%, Au signal of the AuNPs with 48.08%, Ag signal with 12%, and Au signal with 38.26% of the Ag/Au BNPs. The BHK-21cells were incubated in the existence of doxorubicin, plant extract, Ag, Au, and Ag/Au BNPs. The cytotoxic effects could be observed in a dose-dependent mode; doxorubicin and Ag/Au BNPs were more toxic than plant extract, Ag, and Au NPs. It is demonstrated that NPs interact with BHK-21cells and significantly reduce cell viability in a concentration-dependent manner. However, to reduce the potential threats of NPs further studies are recommended.

Keywords: hippeastrum hybridum, nanoparticle, BHK-21cells

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Sima Parvizi Omran, Rezvan Tavakoli, Mahnaz Safari, Mohammadreza Aghasadeghi, Abolfazl Fateh, Pooneh Rahimi

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Background: SARS-CoV-2, a single-stranded RNA betacoronavirus causes the global outbreak of coronavirus disease 2019 (COVID-19). Several clinical and scientific concerns are raised by this pandemic. Genetic factors can contribute to pathogenesis and disease susceptibility. There are single nucleotide polymorphisms (SNPs) in many of the genes in the immune system that affect the expression of specific genes or functions of some proteins related to immune responses against viral infections. In this study, we analyzed the impact of polymorphism in the interferon alpha and beta receptor subunit 2 (IFNAR2) and dipeptidyl peptidase 9 (Dpp9) genes and clinical parameters on the susceptibility and resistance to Coronavirus disease (COVID-19). Methods: A total of 330- SARS-CoV-2 positive patients (188 survivors and 142 nonsurvivors) were included in this study. All single-nucleotide polymorphisms (SNPs) on IFNAR2 (rs2236757) and Dpp9 (rs2109069) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In survivor patients, the frequency of the favourable genotypes of IFNAR2 SNP (rs2236757 GC) was significantly higher than in nonsurvivor patients, and also Dpp9 (rs2109069 AT) genotypes were associated with the severity of COVID-19 infection. Conclusions: This study demonstrated that the severity of COVID- 19 patients was strongly associated with clinical parameters and unfavourable IFNAR2, Dpp9 SNP genotypes. In order to establish the relationship between host genetic factors and the severity of COVID-19 infection, further studies are needed in multiple parts of the world.

Keywords: SARS-CoV-2, COVID-19, interferon alpha and beta receptor subunit 2, dipeptidyl peptidase 9, single-nucleotide polymorphisms

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Authors: Iman Nazari, Behrouz Shaabani, Ali Ramouz

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Regarding to the dramatic rise of cancer prevalence of cancers in Iran and also base on the investigations around environmental factors which causes cancer, The air and water pollution is in high level in Iran’s capital city this issue motivated us to start an investigation on concentration of heavy metals and nitrate in Tehran’s Tap water, additionally we investigated the effects of this contaminations on public health, it is clear that heavy metals and also nitrate are causes cancers directly and indirectly, we divided the city to four districts: (1) North, (2) East, (3) West, (4) South and totally collected over 30 samples from noted districts, we obvious difference in concentrations, after a study we founded the reasons of this difference, the old distribution system, non-standard sewage disposal system, travel up from contaminated rains, releasing industrial wastes waters without any pretreatment, the most important one is the old distribution system, Tehran is an old city hence distribution system is old too we know that the old water pipes were built from alloys which containing several of this harmful heavy metals, releasing of this heavy metals from pipes to the tap water is one of the most Important reasons, as the result we presented the concentrations by districts and the alternatives to decreasing the level of this contaminations.

Keywords: water quality, heavy metals, drinking water, environmental toxinology

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Authors: Hussein Alahmer, Amr Ahmed

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Liver cancer is one of the common diseases that cause the death. Early detection is important to diagnose and reduce the incidence of death. Improvements in medical imaging and image processing techniques have significantly enhanced interpretation of medical images. Computer-Aided Diagnosis (CAD) systems based on these techniques play a vital role in the early detection of liver disease and hence reduce liver cancer death rate.  This paper presents an automated CAD system consists of three stages; firstly, automatic liver segmentation and lesion’s detection. Secondly, extracting features. Finally, classifying liver lesions into benign and malignant by using the novel contrasting feature-difference approach. Several types of intensity, texture features are extracted from both; the lesion area and its surrounding normal liver tissue. The difference between the features of both areas is then used as the new lesion descriptors. Machine learning classifiers are then trained on the new descriptors to automatically classify liver lesions into benign or malignant. The experimental results show promising improvements. Moreover, the proposed approach can overcome the problems of varying ranges of intensity and textures between patients, demographics, and imaging devices and settings.

Keywords: CAD system, difference of feature, fuzzy c means, lesion detection, liver segmentation

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Authors: Christos Lampropoulos, Maria Konsta, Ifigenia Apostolou, Vicky Dradaki, Tamta Sirbilatze, Irini Dri, Christina Kordali, Vaggelis Lambas, Kostas Argyros, Georgios Mavras

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Objectives: Mediterranean diet has been associated with lower incidence of cardiovascular disease and cancer. The purpose of our study was to examine the hypothesis that Mediterranean diet may protect against mortality and reduce admission duration in elderly, hospitalized patients. Methods: Sample population included 150 patients (78 men, 72 women, mean age 80±8.2). The following data were taken into account in analysis: anthropometric and laboratory data, dietary habits (MedDiet score), patients’ nutritional status [Mini Nutritional Assessment (MNA) score], physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission, compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and admission duration difference respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 30% per each unit increase of MedDiet score (OR=0.7, 95% CI:0.6-0.8, p < 0.0001). Patients with cancer-related admission were 37.7 times more likely to die, compared to those with infection (OR=37.7, 95% CI:4.4-325, p=0.001). According to multivariate linear regression analysis, admission duration was inversely related to Mediterranean diet, since it is decreased 0.18 days on average for each unit increase of MedDiet score (b:-0.18, 95% CI:-0.33 - -0.035, p=0.02). Additionally, the duration of current admission increased on average 0.83 days for each previous hospital admission (b:0.83, 95% CI:0.5-1.16, p<0.0001). The admission duration of patients with cancer was on average 4.5 days higher than the patients who admitted due to infection (b:4.5, 95% CI:0.9-8, p=0.015). Conclusion: Mediterranean diet adequately protects elderly, hospitalized patients against mortality and reduces the duration of hospitalization.

Keywords: Mediterranean diet, malnutrition, nutritional status, prognostic factors for mortality

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Authors: AliAkbar Hafezi, Jamshid Abedi, Jalal Taherian, Behnam Kadkhodaei, Mahsa Elahi

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Background. Peripheral neuropathy is a common side effect of the administration of neurotoxic chemotherapy agents. This adverse effect is a major dose-limiting factor of many commonly used chemotherapy drugs. Currently, there are no Food and Drug Administration (FDA) approved medications for the prevention or treatment of chemotherapy-induced peripheral neuropathy. Therefore, this study was performed to investigate the efficacy and safety of metformin on paclitaxel-induced peripheral neuropathy (PIPN). Methods. In this randomized clinical trial, cancer patients who were candidates for chemotherapy with paclitaxel referred to the radiation oncology departments in Iran from 2022 to 2023 were studied. Patients were randomly divided into two groups; 1- Case group (n = 30) received metformin 500 mg orally twice a day after meals during chemotherapy with paclitaxel, and 2- Control group (30 people) received chemotherapy without metformin or any additional medication. Patients were visited in terms of numbness or other neurological symptoms two weeks before chemotherapy, 1-2 days before and weekly during chemotherapy, and at the end of the study. They were assessed by nerve conduction study (NCS) before intervention and one week after the end of chemotherapy. The primary outcome was the efficacy in reducing PIPN and the secondary outcome was adverse effects. Eventually, the outcomes were compared between the two groups of patients. Results. A total of 60 female cancer patients receiving chemotherapy with paclitaxel were evaluated in two groups. The groups were matched in terms of age, body mass index, fasting blood sugar, smoking, pathologic stage, and creatinine levels. The results showed that 18 patients (60.0 %) in the case group and 23 patients (76.6 %) in the control group had PIPN clinically (P = 0.267), and NCS showed 11 patients (36.6 %) in the case group and 15 patients (50.0 %) in the control group suffered from PIPN which no significant difference was observed between the two groups (P = 0.435). Diarrhea (n = 3; 10.0 %) and nausea (n = 3; 10.0 %) were the most common side effects of metformin in the case group and no serious side effects (lactic acidosis and anemia) were found in these patients. Conclusion. This study indicated that metformin did not significantly prevent PIPN in cancer patients receiving chemotherapy, although the frequency of peripheral neuropathy in the case group was lower than in the control group. The use of metformin in the patients had acceptable safety and no serious side effects were reported.

Keywords: peripheral neuropathy, chemotherapy, paclitaxel, metformin

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Authors: Ayubova Nargiza Mirzabixulaevna, Kiryakov Dmitriy Andreyevich

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Relevance: According to experts from the World Health Organization, in 80% of cases, the causes of skin cancer are external factors: polluted air, radioactive substances, solar flares, and free radicals. In dermatology, one of the most common related to obligate diseases is actinic keratosis. Actinic keratosis (AC) is an area of abnormal proliferation and differentiation of keratinocytes, which carry the risk of progression into invasive squamous cell carcinoma of the skin. The purpose of the study is to study the prevalence of various forms of actinic keratosis among the population of Uzbekistan. Materials and methods of research: The study is based on the observation and clinical laboratory examination of 96 patients who were divided by gender and age. Women made up 45% and men made up 55%. The youngest patient was 43 years old, and the oldest was 92 years old. The control group consisted of 40 patients. The following clinical signs were evaluated: peeling, hyperkeratosis, erythema, pigmentation, atrophy. Results: Studies have shown that of all forms of actinic keratosis, erythematous (36%), hyperkeratotic (27%), pigmented (12%), cutaneous horn (7.0%), atrophic (7.0%), Actinic cheilitis (6%), lichenoid (5%) are common. Conclusion: Thus, the data we have obtained indicate that the main and pronounced clinical sign in the erythematous form is erythema and the hyperkeratic form is often found. With cutaneous horn, there is a sharp hyperkeratosis of the epidermis.

Keywords: actinic keratosis, patient, skin cancer, obligate diseases

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