Search results for: cancer therapeutics

Authors: A. Alao Olumuyiwa

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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.

Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)

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Authors: M. Pourshirazi, M. Esmaelifar, A. Aliahmadi, F. Yazdian, A. S. Hatamian Zarami, S. J. Ashrafi

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Medicinal fungi are the new potential source of drugs to improve the treatment of diseases with association to oxidative agents such as cancers. Monascus purpureus contains functional components potentially effective in improving human health. In the present work, ethanolic extract of Monascus purpureus (EEM) was evaluated for health improving potential mainly focusing on antioxidant and anticancer activities. Ferric ion reducing power (FRAP), scavenging of DPPH radicals and determining viability of breast carcinoma MCF-7 and cervical carcinoma HeLa cells with MTT assay were evaluated. Our data showed a significant antioxidant activity of EEM with 142.45 µg/ml inhibition concentration of 50% DPPH radicals and 2112.33 µg eq.Fe2+/mg extract of FRAP assay. These results might be caused by antioxidant components such as pigments and phenolic compounds. Further, the results demonstrated that EEM caused significant reduction in the viability of MCF-7 with IC50 of 7 µg/ml but not have good effect against viability of HeLa cells. Accordingly, Monascus purpureus is presented as a strong potential of breast cancer treatment. In further study, the mechanistic studies are needed to determine the mechanisms of anticancer activity of EEM.

Keywords: Monascus purpureus, antioxidant, cancer, ethanolic extract

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Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan

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Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.

Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA

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Authors: Iftikhar Tayubi, Tabrej Khan, Rayan Alsulmi, Abdulrahman Labban

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Spider produces a special kind of substance. This special kind of substance is called a toxin. The toxin is composed of many types of protein, which differs from species to species. Spider toxin consists of several proteins and non-proteins that include various categories of toxins like myotoxin, neurotoxin, cardiotoxin, dendrotoxin, haemorrhagins, and fibrinolytic enzyme. Protein Sequence information with references of toxins was derived from literature and public databases. From the previous findings, the Spider toxin would be the best choice to treat different types of tumors and cancer. There are many therapeutic regimes, which causes more side effects than treatment hence a different approach must be adopted for the treatment of cancer. The combinations of drugs are being encouraged, and dramatic outcomes are reported. Spider toxin is one of the natural cytotoxic compounds. Hence, it is being used to treat different types of tumors; especially its positive effect on breast cancer is being reported during the last few decades. The efficacy of this database is that it can provide a user-friendly interface for users to retrieve the information about Spiders, toxin and toxin protein of different Spiders species. SPIDTOXD provides a single source information about spider toxins, which will be useful for pharmacologists, neuroscientists, toxicologists, medicinal chemists. The well-ordered and accessible web interface allows users to explore the detail information of Spider and toxin proteins. It includes common name, scientific name, entry id, entry name, protein name and length of the protein sequence. The utility of this database is that it can provide a user-friendly interface for users to retrieve the information about Spider, toxin and toxin protein of different Spider species. The database interfaces will satisfy the demands of the scientific community by providing in-depth knowledge about Spider and its toxin. We have adopted the methodology by using A MySQL and PHP and for designing, we used the Smart Draw. The users can thus navigate from one section to another, depending on the field of interest of the user. This database contains a wealth of information on species, toxins, and clinical data, etc. This database will be useful for the scientific community, basic researchers and those interested in potential pharmaceutical Industry.

Keywords: siptoxd, php, mysql, toxin

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Authors: Magdalena Hałupka-Bryl, Magdalena Bednarowicz, Ryszard Krzyminiewski, Yukio Nagasaki

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Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles (PEG-PIONs/DOX) with chemotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer PEG-derivative (poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate). Complete physicochemical characterization was carried out (ESR, HRTEM, X-ray diffraction, SQUID analysis) to evaluate the magnetic properties of obtained PEG-PIONs/DOX. Nanoparticles were investigated also in terms of their stability, drug loading efficiency, drug release and antiproliferative effect on cancer cells. PEG-PIONs/DOX have been successfully used for the efficient delivery of an anticancer drug into the tumor region. Fluorescent imaging showed the internalization of PEG-PIONs/DOX in the cytoplasm. Biodistribution studies demonstrated that PEG-PIONs/DOX preferentially accumulate in tumor region via the enhanced permeability and retention effect. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery.

Keywords: targeted drug delivery, magnetic properties, iron oxide nanoparticles, biodistribution

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Authors: Muhammad Umar Hassan

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Renal cell carcinoma is a subset of kidney cancer that arises in the lining of DCT and is present in parenchymal tissue. Diagnosis is based on lab reports, including urinalysis, renal function tests (RFTs), and electrolyte balance, along with imaging techniques. Organ failure and other complications have been commonly observed in these cases. Over the years, the presentation of patients has varied, so carcinoma was classified on the basis of site, shape, and consistency for detailed analysis. Lifestyle patterns and occupational history were inquired about and recorded. Methods: Data from 100 patients presenting to the oncology and nephrology department of Mayo Hospital in the year 2015-2020 were included in this retrospective study on a random basis. The study was specifically focused on three risk factors. Smoking, occupational exposures, and Hakim medicine are taken by the patient for any cause. After procurement of data, follow-up contacts of these patients were established, resulting in a detailed analysis of lifestyle. Conclusion: The inference drawn is a direct causal link between smoking, industrial workplace exposure, and Hakim medicine with the development of Renal Cell Carcinoma. It was shown in the majority of the patients and hence confirmed our hypothesis.

Keywords: renal cell carcinoma, kidney cancer, clear cell carcinoma

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Authors: Harukuni Tokuda, Xu FengHao, Nobutaka Suzuki

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As part of an ongoing our projects to investigate the anti-tumor promoring properties (chemopreventive potency) of Gromwell seed, dry powder materials and its active compounds were carried out through useful test systems. Gromwell seed (Coix lachryma-jobi seed) (GS) is a grass crop that has long been used and played a role in traditional medicine as a nourishing food, and for the treatment of various aliments, paticularly cancer. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enable rapid and easy detection of naturally occurring substances(anti-tumor promoters chemo-preventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphblastoid cells. In addition, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA intiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. these results provide a basis for further development of these botanical supplements for human cancer chemoprevention and observations seem that this materials more extensively as one of the trials for the purpose of complementary and alternative medicine.

Keywords: chemoprevention, medicinal plant, mouse, carcinogenesis systems

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Authors: Varun Agarwal

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Introduction: With the advent of personalized medicine, histopathological review of whole slide images (WSIs) for cancer diagnosis presents an exceedingly time-consuming, complex task. Specifically, detecting metastatic regions in WSIs of sentinel lymph node biopsies necessitates a full-scanned, holistic evaluation of the image. Thus, digital pathology, low-level image manipulation algorithms, and machine learning provide significant advancements in improving the efficiency and accuracy of WSI analysis. Using Camelyon16 data, this paper proposes a deep learning pipeline to automate and ameliorate breast cancer metastasis localization and WSI classification. Methodology: The model broadly follows five stages -region of interest detection, WSI partitioning into image tiles, convolutional neural network (CNN) image-segment classifications, probabilistic mapping of tumor localizations, and further processing for whole WSI classification. Transfer learning is applied to the task, with the implementation of Inception-ResNetV2 - an effective CNN classifier that uses residual connections to enhance feature representation, adding convolved outputs in the inception unit to the proceeding input data. Moreover, in order to augment the performance of the transfer learning CNN, a stack of convolutional denoising autoencoders (CDAE) is applied to produce embeddings that enrich image representation. Through a saliency-detection algorithm, visual training segments are generated, which are then processed through a denoising autoencoder -primarily consisting of convolutional, leaky rectified linear unit, and batch normalization layers- and subsequently a contrast-normalization function. A spatial pyramid pooling algorithm extracts the key features from the processed image, creating a viable feature map for the CNN that minimizes spatial resolution and noise. Results and Conclusion: The simplified and effective architecture of the fine-tuned transfer learning Inception-ResNetV2 network enhanced with the CDAE stack yields state of the art performance in WSI classification and tumor localization, achieving AUC scores of 0.947 and 0.753, respectively. The convolutional feature retention and compilation with the residual connections to inception units synergized with the input denoising algorithm enable the pipeline to serve as an effective, efficient tool in the histopathological review of WSIs.

Keywords: breast cancer, convolutional neural networks, metastasis mapping, whole slide images

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Authors: Wadha Alqahtani

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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

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Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis

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Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.

Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis

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Authors: Sahar Heidary

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Radiography and radiotherapy have emerged as crucial pillars of modern medical practice, revolutionizing diagnostics and treatment for a myriad of health conditions. This abstract highlights the pivotal role of radiography and radiotherapy in favor of healthcare and society. Radiography, a non-invasive imaging technique, has significantly advanced medical diagnostics by enabling the visualization of internal structures and abnormalities within the human body. With the advent of digital radiography, clinicians can obtain high-resolution images promptly, leading to faster diagnoses and informed treatment decisions. Radiography plays a pivotal role in detecting fractures, tumors, infections, and various other conditions, allowing for timely interventions and improved patient outcomes. Moreover, its widespread accessibility and cost-effectiveness make it an indispensable tool in healthcare settings worldwide. On the other hand, radiotherapy, a branch of medical science that utilizes high-energy radiation, has become an integral component of cancer treatment and management. By precisely targeting and damaging cancerous cells, radiotherapy offers a potent strategy to control tumor growth and, in many cases, leads to cancer eradication. Additionally, radiotherapy is often used in combination with surgery and chemotherapy, providing a multifaceted approach to combat cancer comprehensively. The continuous advancements in radiotherapy techniques, such as intensity-modulated radiotherapy and stereotactic radiosurgery, have further improved treatment precision while minimizing damage to surrounding healthy tissues. Furthermore, radiography and radiotherapy have demonstrated their worth beyond oncology. Radiography is instrumental in guiding various medical procedures, including catheter placement, joint injections, and dental evaluations, reducing complications and enhancing procedural accuracy. On the other hand, radiotherapy finds applications in non-cancerous conditions like benign tumors, vascular malformations, and certain neurological disorders, offering therapeutic options for patients who may not benefit from traditional surgical interventions. In conclusion, radiography and radiotherapy stand as indispensable tools in modern medicine, driving transformative improvements in patient care and treatment outcomes. Their ability to diagnose, treat, and manage a wide array of medical conditions underscores their favor in medical practice. As technology continues to advance, radiography and radiotherapy will undoubtedly play an ever more significant role in shaping the future of healthcare, ultimately saving lives and enhancing the quality of life for countless individuals worldwide.

Keywords: radiology, radiotherapy, medical imaging, cancer treatment

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Authors: Soodabeh Shahid Sales, Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Kazem Anvari, Mohammad Sadegh Khorrami, Saeideh Ahmadi Simab, Ali Moradi, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A. Ferns, Amir Avan

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Background Esophageal cancer has been reported as the eighth most common cancer universal and the seventh cause of cancer-related death in men .recent studies have revealed that cytochrome P450, family 1, subfamily B, polypeptide 1, which plays a role in metabolizing xenobiotics, is associated with different cancers. Therefore in the present study, we investigated the impact of CYP1B1-rs1056836 on esophagus squamous cell carcinoma (ESCC) patients. Method: 317 subjects, with and without ESCC were recruited. DNA was extracted and genotyped via Real-time PCR-Based Taq Man. Kaplan Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between patients clinicopathological data, genotypic frequencies, disease prognosis, and patients survival, Pearson chi-square and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. Results: the genotypic frequency for GG, GC, and CC are respectively 58.6% , 29.8%, 11.5% in the healthy group and 51.8%, 36.14% and 12% in ESCC group. With respect to the recessive genetic inheritance model, an association between the GG genotype and stage of ESCC were found. Also, statistically significant results were not found for this variation and risk of ESCC. Patients with GG genotype had a decreased risk of nodal metastasis in comparison with patients with CC/CG genotype, although this link was not statistically significant. Conclusion: Our findings illustrated the correlation of CYP1B1-rs1056836 as a potential biomarker for ESCC patients, supporting further studies in larger populations in different ethnic groups. Moreover, further investigations are warranted to evaluate the association of emerging marker with dietary intake and lifestyle.

Keywords: Cytochrome P450, esophagus squamous cell carcinoma, dietary intake, lifestyle

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Authors: Ting-I Lin

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Purpose: This article explores the care experience of a 34-year-old female breast cancer patient who was admitted to the intensive care unit after undergoing a modified radical mastectomy. The patient discovered a lump in her right breast during a self-examination and, after mammography and ultrasound-guided biopsy, was diagnosed with a malignant tumor in the right breast. The tumor measured 1.5 x 1.4 x 2 cm, and the patient underwent a modified radical mastectomy. Postoperatively, she exhibited feelings of inferiority due to changes in her appearance. Method: During the care period, we engaged in conversations, observations, and active listening, using Gordon's Eleven Functional Health Patterns for a comprehensive assessment. In collaboration with the critical care team, a psychologist, and an oncology case manager, we conducted an interdisciplinary discussion and reached a consensus on key nursing issues. These included pain related to postoperative tumor excision and disturbed body image due to changes in appearance after surgery. Result: During the care period, a private space was provided to encourage the patient to express her feelings about her altered body image. Communication was conducted through active listening and a non-judgmental approach. The patient's anxiety level, as measured by the depression and anxiety scale, decreased from moderate to mild, and she was able to sleep for 6-8 hours at night. The oncology case manager was invited to provide education on breast reconstruction using breast models and videos to both the patient and her husband. This helped rebuild the patient's confidence. With the patient's consent, a support group was arranged where a peer with a similar experience shared her journey, offering emotional support and encouragement. This helped alleviate the psychological stress and shock caused by the cancer diagnosis. Additionally, pain management was achieved through adjusting the dosage of analgesics, administering Ultracet 37.5 mg/325 mg 1# Q6H PO, along with distraction techniques and acupressure therapy. These interventions helped the patient relax and alleviate discomfort, maintaining her pain score at a manageable level of 3, indicating mild pain. Conclusion: Disturbance in body image can cause significant psychological stress for patients. Through support group discussions, encouraging patients to express their feelings, and providing appropriate education on breast reconstruction and dressing techniques, the patient's self-concept was positively reinforced, and her emotions were stabilized. This led to renewed self-worth and confidence.

Keywords: breast cancer, modified radical mastectomy, acupressure therapy, Gordon's 11 functional health patterns

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Authors: Iris W. A. Boot, Anke Wesselius, Maurice P. Zeegers

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Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus , thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk. Individual dietary data were pooled from three cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose–response relationships (Model 1) were examined using a nonparametric test for trend. In total, 2,871 cases and 522,364 non-cases were included in the analyses. The present study showed an overall increased BC risk for high dietary vitamin D intake (HR: 1.14, 95% CI: 1.03-1.26). A similar increase BC risk with high vitamin D intake was observed among women and for the non-muscle invasive BC subtype, (HR: 1.41, 95% CI: 1.15-1.72, HR: 1.13, 95% CI: 1.01-1.27, respectively). High calcium intake decreased the BC risk among women (HR: 0.81, 95% CI: 0.67-0.97). A combined inverse effect on BC risk was observed for low vitamin D intake and high calcium intake (HR: 0.67, 95% CI: 0.48-0.93), while a positive effect was observed for high vitamin D intake in combination with low, moderate and high phosphorus (HR: 1.31, 95% CI: 1.09-1.59, HR: 1.17, 95% CI: 1.01-1.36, HR: 1.16, 95% CI: 1.03-1.31, respectively). Combining all nutrients showed a decreased BC risk for low vitamin D intake, high calcium and moderate phosphor intake (HR: 0.37, 95% CI: 0.18-0.75), and an increased BC risk for moderate intake of all the nutrients (HR: 1.18, 95% CI: 1.02-1.38), for high vitamin D and low calcium and phosphor intake (HR: 1.28, 95% CI: 1.01-1.62), and for moderate vitamin D and calcium and high phosphorus intake (HR: 1.27, 95% CI: 1.01-1.59). No significant dose-response analyses were observed. The findings of this study show an increased BC risk for high dietary vitamin D intake and a decreased risk for high calcium intake. Besides, the study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.

Keywords: bladder cancer, nutritional oncology, pooled cohort analysis, vitamin D

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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

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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

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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

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Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: Lavinia Ruta, Ileana Farcasanu

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The yeast surface display (YSD) technique enables the expression of proteins on yeast cell surfaces, facilitating the identification and isolation of proteins with targeted binding properties, such as nanobodies. Nanobodies, derived from camelid species, are single-domain antibody fragments renowned for their high affinity and specificity towards target proteins, making them valuable in research and potentially in therapeutics. Their advantages include a compact size (~15 kDa), robust stability, and the ability to target challenging epitopes. The project endeavors to establish and validate a platform for producing Green Fluorescent Protein (GFP) and mCherry nanobodies using the yeast surface display method. mCherry, a prevalent red fluorescent protein sourced from coral species, is commonly utilized as a genetic marker in biological studies due to its vibrant red fluorescence. The GFP-nanobody, a single variable domain of heavy-chain antibodies (VHH), exhibits specific binding to GFP, offering a potent means for isolating and engineering fluorescent protein fusions across various biological research domains. Both GFP and mCherry nanobodies find specific utility in cellular imaging and protein analysis applications.

Keywords: YSD, nanobodies, GFP, Saccharomyces cerevisiae

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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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