Search results for: targeted axillary dissection

Authors: Madeleine Gadd, Rose How, Edward Mathews, John Buchanan, Vicky Cottrell, Andre Coetzee, Karuna Katti

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Introduction: Triphallia, a congenital anomaly describing the presence of three distinct penile shafts, has been reported only once in the literature. This case report describes the serendipitous discovery of the first reported human case of partial orthotopic triphallia during cadaveric dissection. Case Summary: Despite the normal appearance of external genitalia on examination, the dissection of a 78-year-old male revealed a remarkable anatomical variation: two small supernumerary penises situated in a transverse orientation postero inferiorly to the primary penis. The main and the larger supernumerary penile shafts displayed their own corpora cavernosa and glans penis, sharing a single urethra, which coursed through the secondary penis prior to its passage through the primary penis. The smallest of the supernumerary penises was similar in dimension to the secondary penis, at 3.7cm long and 1.2cm wide (compared to the secondary penis at 3.8cm long and 1.3cm wide). However, it lacked a urethra and a typical arrangement of the corpora cavernosa and spongiosum, making this a case of partial triphallia rather than true triphallia. Conclusion: This case report provides a comprehensive anatomical description of partial triphallia in a cadaver, shedding light on the morphology, embryology, and clinical implications of this anomaly. This case report underscores the importance of meticulous anatomical dissections, particularly since, without dissection, this anatomical variation would have remained undiscovered. Although we can only speculate the functional implications of this condition, understanding such anatomical variations contributes to both knowledge of human anatomy and clinical management, should the condition be encountered in living individuals.

Keywords: triphallia, diphallia, congenital abnormalities, genitourinary abnormalities, urology

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Authors: Aihong Zhao, Priya Sastry, Mark L Field, Mohamad Bashir, Arvind Singh, David Richens

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Objectives: Intramural haematoma (IMH) is one of the pathologies, along with acute aortic dissection, that present as Acute Aortic Syndrome (AAS). Evidence suggests that unlike aortic dissection, some intramural haematomas may regress with medical management. However, intramural haematomas have been traditionally managed like acute aortic dissections. Given that some of these pathologies may regress with conservative management, it would be useful to be able to identify which of these may not need high risk emergency intervention. A computational aortic model was used in this study to try and identify intramural haematomas with risk of progression to aortic dissection. Methods: We created a computational model of the aorta with luminal blood flow. Reports in the literature have identified 11 mm as the radial clot thickness that is associated with heightened risk of progression of intramural haematoma. Accordingly, haematomas of varying sizes were implanted in the modeled aortic wall to test this hypothesis. The model was exposed to physiological blood flows and the stresses and strains in each layer of the aortic wall were recorded. Results: Size and shape of clot were seen to affect the magnitude of aortic stresses. The greatest stresses and strains were recorded in the intima of the model. When the haematoma exceeded 10 mm in all dimensions, the stress on the intima reached breaking point. Conclusion: Intramural clot size appears to be a contributory factor affecting aortic wall stress. Our computer simulation corroborates clinical evidence in the literature proposing that IMH diameter greater than 11 mm may be predictive of progression. This preliminary report suggests finite element modelling of the aortic wall may be a useful process by which to examine putative variables important in predicting progression or regression of intramural haematoma.

Keywords: intramural haematoma, acute aortic syndrome, finite element analysis,

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Christen Kutz

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Objective: The aim of this study is to review a case series of 4 high-level Olympic and Division 1 wrestlers who experienced debilitating posterior circulation ischemic strokes during or after a competitive wrestling event and to identify risk factors, etiology and outcomes of stroke in young, healthy elite wrestlers. Background: Stroke occurs in one in 10,000 people under age 64. In young adults, the most common causes of stroke are cardiac embolism, hypercoagulable state, and vasculopathy. One-third of these strokes occur in young, fit individuals. There is little published literature about ischemic strokes that occur in wrestlers. Based on the nature of wrestling, the risk of injury or dissection to neurovascular structures may be a possible theory, but very few case reports exist. Methodology: 4 wrestlers under the age of 44 with a known history of ischemic stroke participated in individual interviews either in person or virtually. Each of the wrestlers provided their demographic information, wrestling background, clinical presentation at the time of stroke, imaging results, identification of potential risk factors, acute treatment and recovery. Results: 3 white male Division 1 wrestlers (2 Lehigh University, 1 Lock Haven University) and 1 black male 2008 Olympian experienced posterior circulation strokes. Case #1 felt a “pop” while wrestling (lateral medullary infarct, possible vertebral artery dissection); Case #2 awoke with severe vertigo, sweating, and vomiting after wrestling the previous day (left cerebellar infarct, (+) protein S deficiency); Case #3 severe vertigo, ataxia, and sensation of impending doom after wrestling earlier that week (left cerebellar infarct, hypoplastic left vertebral artery (+) anti-cardiolipin antibodies). Case #4 severe dizziness, confusion (left cerebellar stroke, vertebral artery dissection, small PFO). Conclusion: 3 wrestlers were started on anti-platelet therapy, risk factors were modified, and returned to their sport. 1 wrestler was placed on anti-coagulation and retired from competition.

Keywords: stroke, wrestling, Olympic, posterior circulation

Procedia PDF Downloads 43

Authors: Li Chun Zhao, Zhi Chao Hu, Xi Qiang Liu, Man Lai Lee, Chak Shing Yeung, Man Fei Xu, Yuen Yee Kwan, Alan H. M. Ho, Nickie W. K. Chan, Bin Deng, Zhong Zhen Zhao, Min Xu

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Background: Chuangxiong Rhizoma (Chuangxion, CX) is one of the most frequently used herbs in Chinese medicine because of its wide therapeutic effects such as vasorelaxation and anti-inflammation. Aim: The purposes of this study are (1) to perform non-targeted / targeted analyses of CX methanol extract and water extract, and compare the present data with previously LC-MS or GC-MS fingerprints; (2) to examine the difference between CX methanol extract and water extract for preliminarily evaluating whether current compound markers of methanol extract from crude CX materials could be suitable for quality control of CX water extract. Method: CX methanol extract was prepared according to the Hong Kong Chinese Materia Medica Standards. DG water extract was prepared by boiling with pure water for three times (one hour each). UHPLC-Q-TOF-MS/MS fingerprint analysis was performed by C18 column (1.7 µm, 2.1 × 100 mm) with Agilent 1290 Infinity system. Experimental data were analyzed by Agilent MassHunter Software. A database was established based on 13 published LC-MS and GC-MS CX fingerprint analyses. Total 18 targeted compounds in database were selected as markers to compare present data with previous data, and these markers also used to compare CX methanol extract and water extract. Result: (1) Non-targeted analysis indicated that there were 133 compounds identified in CX methanol extract, while 325 compounds in CX water extract that was more than double of CX methanol extract. (2) Targeted analysis further indicated that 9 in 18 targeted compounds were identified in CX methanol extract, while 12 in 18 targeted compounds in CX water extract that showed a lower lose-rate of water extract when compared with methanol extract. (3) By comparing CX methanol extract and water extract, Senkyunolide A (+1578%), Ferulic acid (+529%) and Senkyunolide H (+169%) were significantly higher in water extract when compared with methanol extract. (4) Other bioactive compounds such as Tetramethylpyrazine were only found in CX water extract. Conclusion: Many new compounds in both CX methanol and water extracts were found by using UHPLC Q-TOF MS/MS analysis when compared with previous published reports. A new standard reference including non-targeted compound profiling and targeted markers functioned especially for quality control of CX water extract (herbal decoction) should be established in future. (This project was supported by Hong Kong Baptist University (FRG2/14-15/109) & Natural Science Foundation of Guangdong Province (2014A030313414)).

Keywords: Chuanxiong rhizoma, fingerprint analysis, targeted analysis, quality control

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Authors: Abla A. Ali, Heba A. Abd El Razik, Nadia A. Kotb, Amany A. Bayoumi, Laila A. Rashed

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The detection of human skin through mRNA-based profiling is a very useful tool for forensic investigations. The aim of this study was definitive identification of human skin at different time intervals using an mRNA marker late cornified envelope gene 1C. Ten middle-aged healthy volunteers of both sexes were recruited for this study. Skin samples controlled with blood samples were taken from the candidates to test for the presence of our targeted mRNA marker. Samples were kept at dry dark conditions to be tested at different time intervals (24 hours, one week, three weeks and four weeks) for detection and relative quantification of the targeted marker by RT PCR. The targeted marker could not be detected in blood samples. The targeted marker showed the highest mean value after 24 hours (11.90 ± 2.42) and the lowest mean value (7.56 ± 2.56) after three weeks. No marker could be detected at four weeks. This study verified the high specificity and sensitivity of mRNA marker in the skin at different storage times up to three weeks under the study conditions.

Keywords: human skin, late cornified envelope gene 1C, mRNA marker, time intervals

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Authors: Öykü Barutçu, Mehmet Özgür Kuzdan

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Aim: Laparoscopy is very risky in patients undergoing, multiple open abdominal surgeries. The aim of this study, to define a safe method for the first trocar placement in children with a history of multiple open abdominal surgeries. Methods: Children who underwent laparoscopic surgery between March 2019 and April 2020 with a history of three or more open abdominal surgeries were included in the retrospective study. Patient information was obtained from the hospital automation system. Ultrasonography was used to determine the location of adhesions preoperatively. The first trocar was placed according to ultrasonography findings, using the Hasson technique to create an air pocket with finger dissection. The patient's preoperative, perioperative, and postoperative findings are reported. Results: A total of 10 patients were included in the study. The median number of operations before laparoscopy was three. The most common site for the first trocar entry was Palmer's point (40%). No mortality or morbidity was observed amongst any patients. The average number of adhesions detected by USG and observed on laparoscopy were significantly positively correlated. Conclusion: In children with a history of multiple abdominal surgeries, abdominal wall ultrasonography for visualization of adhesions and finger dissection for the formation of an air pocket appears to be a safe method for the first trocar insertion.

Keywords: abdominal wall, child, laparoscopy, ultrasonography

Procedia PDF Downloads 82

Authors: John Joseph S. Martis, Rohanchandra R. Gatty, Aaron Jose Fernandes, Rahul P. Nambiar

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Introduction: Surgery for breast cancer is either mastectomy or breast conservation surgery. The most commonly used incision for modified radical mastectomy is the transverse Stewart incision. But this incision may have the disadvantage of causing disparity between the closure lines of superior and inferior skin flaps in mastectomy and can cause overhanging of soft tissue below and behind the axilla. The curvizigzag incision, on principle, may help in this regard and can prevent scar migration beyond the anterior axillary line. This study aims to compare the two incisions in this regard. Methods: 100 patients with cancer of breast were included in the study after satisfying inclusion and exclusion criteria. They underwent surgery at Father Muller Medical College, Mangalore, India, between November 2019 to September 2021. The patients were divided into two groups. Group A patients were subjected to modified radical mastectomy with curvizigzag incision and group B patients with transverse Stewart incision. Results: Seroma on postoperative day1, day 2 was 0% in both the groups. Seroma on postoperative day 30 was present in 14% of patients in group B. 60% of patients in group B had sag of soft tissue below and behind the axilla, and none of the patients in group A had this problem. In 64% of the patients in group B, the incision crossed the anterior axillary fold, 64% of the patients in group B had tension in the incision site while approximation of the skin flaps. Conclusion: Curvizigzag incision is statistically better with lesser complications when compared to the transverse Stewart incision for modified radical mastectomy for carcinoma breast.

Keywords: breast cancer, curvizigzag incision, transverse Stewart incision, seroma, modified radical mastectomy

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Authors: Alexander Rodríguez-Hernández, Arnulfo Rojas-Perez, Liz Diaz-Vazquez

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The rise in consumerism over the past century has resulted in the creation of higher amounts of plasticizers, personal care products and other chemical substances, which enter and accumulate in water systems. Other sources of pollutants in Neotropical regions experience large inputs of nutrients with these pollutants resulting in eutrophication of water which consume large quantities of oxygen, resulting in high fish mortality. This dilemma has created a need for the development of targeted detection in complex matrices and remediation of emerging contaminants. We have synthesized carbon nanoparticles from macro algae (Ulva fasciata) by oxidizing the graphitic carbon network under extreme acidic conditions. The resulting material was characterized by STEM, yielding a spherical 12 nm average diameter nanoparticles, which can be fixed into a polysaccharide aerogel synthesized from the same macro algae. Spectrophotometer analyses show a pH dependent fluorescent behavior varying from 450-620 nm in aqueous media. Heavily oxidized edges provide for easy functionalization with enzymes for a more targeted analysis and remediation technique. Given the optical properties of the carbon base nanoparticles and the numerous possibilities of functionalization, we have developed a selective and robust targeted bio-detection and bioremediation technique for the treatment of emerging contaminants in complex matrices like estuarine embayment.

Keywords: aerogels, carbon nanoparticles, fluorescent, targeted analysis

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Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

Procedia PDF Downloads 150

Authors: Wisam Ismail, Chole Wright, Elizabeth Baker, Cathy Tait, Mohamed Salhab, Richard Linforth

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Background: Post-mastectomy breast reconstruction is an important treatment option for women with breast cancer with psychosocial, emotional and quality of life benefits. Despite this, Asian patients are one-fifth as likely as Caucasian patients to undergo reconstruction after mastectomy. Aim: This study aimed to assess the difference in breast reconstruction rates between Asian and Caucasian patients treated at Bradford Teaching Hospitals between May 2011 – December 2015.The long-term goal is to equip healthcare professionals to improve breast cancer treatment outcome by increasing breast reconstruction rates in this sub-population. Methods: All patients undergoing mastectomy were identified using a prospectively collected departmental database. Further data was obtained via retrospective electronic case note review. Bradford city population is about 530.000 by the end of 2015, with 67.44% of the city's population was White ethnic groups and 26.83% Asian Ethnic Groups (UK population consensus). The majority of Asian population speaks Urdu, hence an Urdu speaking breast care nurse was appointed to facilitate communications and deliver a better understanding of the reconstruction options and pathways. Statistical analysis was undertaken using the SAS program. Patients were stratified by age, self-reported ethnicity, axillary surgery and reconstruction. Relative odds were calculated using univariate and multivariate logistic regression analyses with adjustment for known confounders. An Urdu speaking breast care nurse was employed throughout this period to facilitate communication and patient decision making. Results: 506 patients underwent Mastectomy over 5 years. 72 (14%) Asian v. 434 (85%) Caucasian. Overall median age is 64 years (SD1.1). Asian median age is 62 (SD0.9), versus Caucasian 65 (SD1.2). Total axillary clearance rate was 30% (42% Asian v.30% Caucasian). Overall reconstruction rate was 126 patients (28.9%).Only 6 of 72 Asian patients (<1%) underwent breast reconstruction versus 121of 434 Caucasian (28%) (p < 0.04), Odds ratio 0.68, (95% confidence interval 0.57-0.79). Conclusions: There is a significant difference in post-mastectomy reconstruction rates between Asian and Caucasian patients. This difference is likely to be multi-factorial. Higher rates of axillary clearance in Asian patients might suggest later disease presentation and/or higher rates of subsequent adjuvant therapy, both of which, can impact on the suitability of breast reconstruction. Strategies aimed at reducing racial disparities in breast reconstruction should include symptom awareness to enable earlier presentation and facilitated communication to ensure informed decision-making.

Keywords: aesthetic, Asian, breast, reconstruction

Procedia PDF Downloads 253

Authors: S. M. P Manjula, Ishara Amarathunga, Aryan Nath Koura, Jaideepraj Rao

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Background: Laparoscopic D2 Gastrectomy for non metastatic advanced Gastric cancer (AGC) has become a controversial topic as there are confronting ideas from experts in the field. Lack of consensus are mainly due to non feasibility of the dissection and safety and efficacy. Method: Data from all D2 Gastrectomies performed (both Subtotal and Total Gastrectomies) in our unit from 2009 December to 2013 December were retrospectively analysed. Computor database was prospectively maintained. Pathological stage two A (iiA) and above considered advanced Gastric cancers, who underwent curative intent D2 Gastrectomy were included for analysis(n=46). Four patients excluded from the study as peritoneal fluid cytology came positive for cancer cells and one patient exempted as microscopic resection margin positive(R1) after curative resection. Thirty day morbidity and mortality, operative time, lymph nodes harvest and survival (disease free and overall) analyzed. Results: Complete curative resection achieved in 40 patients. Mean age of the study population was 62.2 (32-88) and male to female ratio was 23: 17. Thirty day mortality (1/40) and morbidity (6/40). Average operative time 203.7 minutes (185- 400) and average lymphnodes harvest was 40.5 (18-91). Disease free survival of the AGC in this study population was 16.75 months (1-49). Average hospital stay was 6.8 days (3-31). Conclusion: Laparoscopic dissection is effective feasible and safe in AGC.

Keywords: laparoscopy, advanced gastric cancer, safety, efficacy

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Authors: Shazia Bano

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

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Andrii Shalaginov, Katrin Franke, Xiongwei Huang

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One of the leading problems in Cyber Security today is the emergence of targeted attacks conducted by adversaries with access to sophisticated tools. These attacks usually steal senior level employee system privileges, in order to gain unauthorized access to confidential knowledge and valuable intellectual property. Malware used for initial compromise of the systems are sophisticated and may target zero-day vulnerabilities. In this work we utilize common behaviour of malware called ”beacon”, which implies that infected hosts communicate to Command and Control servers at regular intervals that have relatively small time variations. By analysing such beacon activity through passive network monitoring, it is possible to detect potential malware infections. So, we focus on time gaps as indicators of possible C2 activity in targeted enterprise networks. We represent DNS log files as a graph, whose vertices are destination domains and edges are timestamps. Then by using four periodicity detection algorithms for each pair of internal-external communications, we check timestamp sequences to identify the beacon activities. Finally, based on the graph structure, we infer the existence of other infected hosts and malicious domains enrolled in the attack activities.

Keywords: malware detection, network security, targeted attack, computational intelligence

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Authors: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: Arindam Pramanik, Parimal Karmakar

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We have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group (like curcumin) in metallorganic compound “Copper acetylacetonate” (CuAA). The cytotoxicity mechanism of CuAA complex was evaluated on various cancer cell lines in vitro. Among these, reactive oxygen species (ROS), glutathione level (GSH) in the cell was found to increase. Further mitochondrial membrane damage was observed. The fate of cell death was found to be induced by apoptosis. For application purpose, we have developed a novel biodegradable, non-toxic polymer-based nanoparticle which has hydrophobically modified core for loading of the CuAA. Folic acid is conjugated on the surface of the polymer (chitosan) nanoparticle for targeting to cancer cells for minimizing toxicity to normal cells in-vivo. Thus, this novel drug CuAA has an efficient anticancer activity which has been targeted specifically to cancer cells through polymer nanoparticle.

Keywords: anticancer, apoptosis, copper nanoparticle, targeted drug delivery

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Authors: Ankita Shukla, Tiratha Raj Singh

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Colorectal cancer (CRC) imposes serious mortality burden worldwide and it has been increasing for past consecutive years. Continuous efforts have been made so far to diagnose the disease condition and to identify the root cause for it. In this study, we performed the pathway level as well as the differential gene expression studies for CRC. We analyzed the gene expression profile GSE24514 from Gene Expression Omnibus (GEO) along with the gene pathways involved in the CRC. This analysis helps us to understand the behavior of the genes that have shown differential expression through their targeted pathways. Pathway analysis for the targeted genes covers the wider area which therefore decreases the possibility to miss the significant ones. This will prove to be beneficial to expose the ones that have not been given attention so far. Through this analysis, we attempt to understand the various neighboring genes that have close relationship to the targeted one and thus proved to be significantly controlling the CRC. It is anticipated that the identified hub and neighboring genes will provide new directions to look at the pathway level differently and will be crucial for the regulatory processes of the disease.

Keywords: mismatch repair, microsatellite instability, carcinogenesis, morbidity

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Authors: Madhu Gupta, Vikas Sharma, Suresh P. Vyas

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CD13 receptors are abundantly overexpressed in tumor cells as well as in neovasculature. The CD13 receptors were selected as a targeted site and polymeric nanoparticles (NPs) as a targeted delivery system. By combining these, a cyclic NGR (cNGR) peptide ligand was coupled on the terminal end of polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) and prepared the dual targeted-NPs (cNGR-PEG-PTX-NPs) to enhance the intracellular delivery of anticancer drug to tumor cells and tumor endothelial cells via ligand-receptor interaction. In-vitro cytotoxicity studies confirmed that the presence of cNGR enhanced the cytotoxic efficiency by 2.8 folds in Human Umbilical Vein Endothelial (HUVEC) cells, while cytotoxicity was improved by 2.6 folds in human fibrosarcoma (HT-1080) cells as compared to non-specific stealth NPs. Compared with other tested NPs, cNGR-PEG-PTX-NPs revealed more cytotoxicity by inducing more apoptosis and higher intracellular uptake. The tumor volume inhibition rate was 59.7% in case of cNGR-PEG-PTX-NPs that was comparatively more with other formulations, indicating that cNGR-PEG-PTX-NPs could more effectively inhibit tumor growth. As a consequence, the cNGR-PEG-PTX-NPs play a key role in enhancing tumor therapeutic efficiency for treatment of CD13 receptor specific solid tumor.

Keywords: cyclic NGR, CD13 receptor, targeted polymeric NPs, solid tumor, intracellular delivery

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Authors: Beom-Seok Ko, Yoo-Seok Kim, Woo-Sung Lim, Ku-Sang Kim, Hyun-Ah Kim, Jin-Sun Lee, An-Bok Lee, Jin-Gu Bong, Tae-Hyun Kim, Sei-Hyun Ahn

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Background: Breast conserving surgery (BCS) followed by radiation therapy is today standard therapy for early breast cancer. It is safe therapeutic procedure in early breast cancers, because it provides the same level of overall survival as mastectomy. There are a number of different types of incisions used to BCS. Avoiding scars on the breast is women’s desire. Numerous minimal approaches have evolved due to this concern. Periareolar incision is often used when the small tumor relatively close to the nipple. But periareolar incision has a disadvantages include limited exposure of the surgical field. In plastic surgery, various methods such as zigzag incisions have been recommended to achieve satisfactory esthetic results. Periareolar zigzag incision has the advantage of not only good surgical field but also contributed to better surgical scars. The purpose of this study was to evaluate the oncological safety of procedures by studying the status of the surgical margins of the excised tumor specimen and reduces the need for further surgery. Methods: Between January 2016 and September 2016, 148 women with breast cancer underwent BCS or mastectomy by the same surgeon in ASAN medical center. Patients with exclusion criteria were excluded from this study if they had a bilateral breast cancer or underwent resection of the other tumors or taken axillary dissection or performed other incision methods. Periareolar zigzag incision was performed and excision margins of the specimen were identified frozen sections and paraffin-embedded or permanent sections in all patients in this study. We retrospectively analyzed tumor characteristics, the operative time, size of specimen, the distance from the tumor to nipple. Results: A total of 148 patients were reviewed, 72 included in the final analysis, 76 excluded. The mean age of the patients was 52.6 (range 25-19 years), median tumor size was 1.6 cm (range, 0.2-8.8), median tumor distance from the nipple was 4.0 cm (range, 1.0-9.0), median excised specimen sized was 5.1 cm (range, 2.8-15.0), median operation time was 70.0 minute (range, 39-138). All patients were discharged with no sign of infection or skin necrosis. Free resection margin was confirmed by frozen biopsy and permanent biopsy in all samples. There were no patients underwent reoperation. Conclusions: We suggest that periareolar zigzag incision can provide a good surgical field to remove a relatively large tumor and may provide cosmetically good outcomes.

Keywords: periareolar zigzag incision, breast conserving surgery, breast cancer, resection margin

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Authors: Ching-Yi Huang, Pi-Fen Cheng, Hui-Zhu Chen, Shi Ting Huang, Heng-Hua Wang

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This is a case of oral cancer after extensive resection and modified right lateral neck lymph node dissection followed by reconstruction with a skin flap. The nursing period lasted From September 25 to October 3, 2017, through observation, interview, physical assessment, and medical record review, the author identified the following nursing problems: acute pain, impaired oral mucous membrane, and body image change. During the nursing period, the author provided individual and overall nursing care and established mutual trust through the use of empathy. Author listened and eased the patient's physical indisposition, such as wound pain, we use medications and acupuncture massage to relieve pain. However, for oral mucosa change caused by surgery, provide continuous and complete oral care and oral exercise training to improve oral mucosal healing and restore swallowing function. In the body-image changes, guided him to express his feeling after the body-image change, and enhanced support and from the family, and encouraged him to attend head and neck cancer survivor alliance which allowed the patient to accept the altered body image and reaffirm self-worth. Hopefully, through sharing this nursing experience will help to the nursing care quality of nursing care for oral cancer patients after extensive resection and modified right lateral neck lymph node dissection followed by reconstruction with a skin flap.

Keywords: oral cancer, acute pain, impaired oral mucous membrane, body image change

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Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

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Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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Authors: Balaji Devanathan, Gokul G., Abilash S., Abhishek Yadav, Sudhir K. Gupta

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Background: As an alternative to the traditional autopsy, a virtual autopsy is carried out using scanning and imaging technologies, mainly post-mortem computed tomography (PMCT). This facility aims to supplement traditional autopsy results and reduce or eliminate internal dissection in subsequent autopsies. For emotional and religious reasons, the deceased's relatives have historically disapproved such interior dissection. The non-invasive, objective, and preservative PMCT is what friends and family would rather have than a traditional autopsy. Additionally, it aids in the examination of the technologies and the benefits and drawbacks of each, demonstrating the significance of contemporary imaging in the field of forensic medicine. Results: One hundred falls resulting in fatalities was analysed by the writers. Before the autopsy, each case underwent a PMCT examination using a 16-slice Multi-Slice CT spiral scanner. By using specialised software, MPR and VR reconstructions were carried out following the capture of the raw images. The accurate detection of fractures in the skull, face bones, clavicle, scapula, and vertebra was better observed in comparison to a routine autopsy. The interpretation of pneumothorax, Pneumoperitoneum, pneumocephalus, and hemosiuns are much enhanced by PMCT than traditional autopsy. Conclusion. It is useful to visualise the skeletal damage in fall from height cases using a virtual autopsy based on PMCT. So, the ideal tool in traumatising patients is a virtual autopsy based on PMCT scans. When assessing trauma victims, PMCT should be viewed as an additional helpful tool to traditional autopsy. This is because it can identify additional bone fractures in body parts that are challenging to examine during autopsy, such as posterior regions, which helps the pathologist reconstruct the victim's life and determine the cause of death.

Keywords: PMCT, fall from height, autopsy, fracture

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Authors: Mai Ashraf Talaat

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Bullying is an aggressive behavior and a serious issue that should be addressed by everyone and should be avoided at all costs. It is very common among adolescents and schoolchildren and the effects can be devastating and long-lasting. Students are most commonly bullied about physical appearance, race, gender, disability, ethnicity, religion, and sexual orientation. Appearance-targeted bullying is a form of bullying that targets an aspect of a person's appearance, which includes facial and dental features. Deviation from accepted dentofacial aesthetics leads to elevated incidences of bullying in schoolchildren. The aim of this review article is to assess the prevalence of bullying due to dentofacial characteristics and evaluate the importance of dentofacial appearance on perceived social attractiveness based on multiple studies.

Keywords: dentofacial features, orthodontics, malocclusion, adolescents, bullying

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Authors: Sharmi Mukherjee, Anindita Chakraborty

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Cellular irradiation incites complex responses including arrest of cell cycle progression. This article accentuates the effects of radiation on cell cycle status of radiation non-targeted cells. Human Hepatoma HepG2 cells were exposed to increasing doses of γ radiations (1, 2, 4, 6 Gy) and their cell culture media was transferred to non-targeted HepG2 cells cultured in other Petri plates. These radiation non-targeted cells cultured in the ICCM (Irradiated cell conditioned media) were the bystander cells on which cell cycle analysis was performed using flow cytometry. An apparent decrease in the distribution of bystander cells at G0/G1 phase was observed with increased radiation doses upto 4 Gy representing a linear relationship. This was accompanied by a gradual increase in cellular distribution at G2/M phase. Interestingly the number of cells in G2/M phase at 1 and 2 Gy irradiation was not significantly different from each other. However, the percentage of G2 phase cells at 4 and 6 Gy doses were significantly higher than 2 Gy dose indicating the IC50 dose to be between 2 and 4 Gy. Cell cycle arrest is an indirect indicator of genotoxic damage in cells. In this study, bystander stress signals through the cell culture media of irradiated cells disseminated the radiation induced DNA damages in the non-targeted cells which resulted in arrest of the cell cycle progression at G2/M phase checkpoint. This implies that actual radiation biological effects represent a penumbra with effects encompassing a larger area than the actual beam. This article highlights the existence of genotoxic damages as bystander effects of γ rays in human Hepatoma cells by cell cycle analysis and opens up avenues for appraisal of bystander stress communications between tumor cells. Contemplation of underlying signaling mechanisms can be manipulated to maximize damaging effects of radiation with minimum dose and thus has therapeutic applications.

Keywords: bystander effect, cell cycle, genotoxic damage, hepatoma

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Authors: Segun Steven Bodunde

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Mudlogging is the continuous analysis of rock cuttings and drilling fluids to ascertain the presence or absence of oil and gas from the formation penetrated by the drilling bit. This research highlighted a case study of Well BSS-99ST from ‘Bisas Field’, Niger Delta, with depth extending from 1950m to 3640m (Measured Depth). It was focused on identifying the lithologies encountered at specified depth intervals and to accurately delineate the targeted potential reservoir on the field and prepare the lithology and Master log. Equipment such as the Microscope, Fluoroscope, spin drier, oven, and chemicals, which includes: hydrochloric acid, chloroethene, and phenolphthalein, were used to check the cuttings for their calcareous nature, for oil show and for the presence of Cement respectively. Gas analysis was done using the gas chromatograph and the Flame Ionization Detector, which was connected to the Total Hydrocarbon Analyzer (THA). Drilling Parameters and Gas concentration logs were used alongside the lithology log to predict and accurately delineate the targeted reservoir on the field. The result showed continuous intercalation of sand and shale, with the presence of small quantities of siltstone at a depth of 2300m. The lithology log was generated using Log Plot software. The targeted reservoir was identified between 3478m to 3510m after inspection of the gas analysis, lithology log, electric logs, and the drilling parameters. Total gas of about 345 units and five Alkane Gas components were identified in the specific depth range. A comparative check with the Gamma ray log from the well further confirmed the lithologic sequence and the accurate delineation of the targeted potential reservoir using mudlogging.

Keywords: mudlogging, chromatograph, drilling fluids, calcareous

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Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Samuel P. Prahlow, Anthony Sciuva, Katherine Bombly, Emily Wilson, Shiv Dhiman, Savita Arya

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A prevalence cohort study of atherosclerotic lesions within cadavers was performed to better understand and characterize the prevalence of atherosclerosis among Georgia residents within body donors in the Philadelphia College of Osteopathic Medicine (PCOM) - Georgia body donor program. We procured specimens from cadavers used for medical students, physical therapy students, and biomedical science students cadaveric anatomical dissection at PCOM - South Georgia and PCOM - Georgia. Tissues were prepared using hematoxylin and eosin (H&E) stainas histological slides by Colquitt Regional Medical Center Laboratory Services. One section from each of the following arteries was taken after cadaveric dissection at the site of most calcification palpated grossly (if present): left anterior descending coronary artery, left internal carotid artery, abdominal aorta, splenic artery, and hepatic artery. All specimens were graded and categorized according to the American Heart Association’s Modified and Conventional Standards for Atherosclerotic Lesions using x4, x10, x40 microscopic magnification. Our study cohort included 22 cadavers, with 16 females and 6 males. The average age was 72.54, and the median age was 72, with a range of 52 to 90 years old. The cause of death determination listing vascular and/or cardiovascular causes was present on 6 of the 22 death certificates. 19 of 22 (86%) cadavers had at least a single artery grading > 5. Of the cadavers with at least a single artery graded at greater than 5, only 5 of 19 (26%) cadavers had a vascular or cardiovascular cause of death reported. Malignancy was listed as a cause of death on 7 (32%) death certificates. The average atherosclerosis grading of the common hepatic, splenic and left internal carotid arteries (2.15, 3.05, and 3.36 respectively) were lower than the left anterior descending artery and the abdominal aorta (5.16 and 5.86 respectively). This prevalence study characterizes atherosclerosis found in five medium and large systemic arteries within cadavers from the state of Georgia.

Keywords: pathology, atherosclerosis, histology, cardiovascular

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Temesgen Geremew

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Functionalized nanoparticles have emerged as a revolutionary platform for drug delivery, offering significant advantages over traditional methods. By strategically modifying their surface properties, these nanoparticles can be designed to target specific tissues and cells, significantly reducing off-target effects and enhancing therapeutic efficacy. This targeted approach allows for lower drug doses, minimizing systemic exposure and potential side effects. Additionally, functionalization enables controlled release of the encapsulated drug, improving drug stability and reducing the frequency of administration, leading to improved patient compliance. This work explores the immense potential of functionalized nanoparticles in revolutionizing drug delivery, addressing limitations associated with conventional therapies and paving the way for personalized medicine with precise and targeted treatment strategies.

Keywords: nanoparticles, drug, nanomaterials, applications

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Authors: Susmita Roy, Madhavan Nallani

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In recent years' polymersomes, self-assembled polymeric vesicles emerge from block copolymers, have been widely investigated due to their enhance stability and unique advantageous properties compared to their phospholipid counterpart, liposomes, dendrimers, and micelles. It provides a distinctive platform for advanced therapeutics and the creation of complex (bio) catalytically active systems for research in Nanomedicine and synthetic biology. Inspired by nature, where compartmentalization of biological components is all ubiquitous, we are interested in developing a platform technology of self-assembled multifunctional compartments with applications in areas from targeted drug/gene delivery, biosensing, pharmaceutical to cosmetics. Polymersome surfaces can be a proper choice of derivatization with a controlled amount of functional groups. To achieve site-specific targeting of polymersomes, biological recognition motives can be attached to the polymersomes surface by standard bioconjugation techniques, (like esterification, amidation, thiol-maleimide coupling, click-chemistry routes or other coupling methods). Herein, we are developing easy going, one-step bioconjugation strategies for site-specific surface functionalized biodegradable polymeric and/or polymer-lipid hybrid vesicles for targeted drug delivery. Biodegradable polymer, polycaprolactone-b-polyethylene glycol (PCL-PEG), polylactic acid-b-polyethylene glycol (PLA-PEG) and phospholipid, 1-palmitoyl-2- oleoyl-sn-glycero-3-phosphocholine (POPC) has been widely used for numerous vesicle formulations. Some of these drug-loaded formulations are being tested on mice for controlled release. These surface functionalized polymersomes are also appropriate for membrane protein reconstitution/insertion, antibodies conjugation and various bioconjugation with diverse targeted molecules for controlled drug delivery.

Keywords: drug delivery, membrane protein, polymersome, surface modification

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