Search results for: rectal cancer surgery

Authors: C. S. Marques, M. J. Reis Lima, J. Oliveira, E. Teixeira-Lemos

Abstract:

The growing concerns for physical wellbeing and health have been reflected in the way we choose food in our table. Nowadays, we are all more informed consumers and choose healthier foods. On the other hand, stroke, cancer and atherosclerosis may be somehow minimized by the intake of some bioactive compounds present in food, the so-called nutraceuticals and functional foods. The aim of this work was to make a revision of the published studies about the effects of some bioactive compounds, namely lycopene in human health, in the prevention of diseases, thus playing the role of a functional food. Free radical in human body can induce cell damage and consequently can be responsible for the development of some cancers and chronic diseases. Lycopene is one of the most powerful antioxidants known, being the predominant carotenoid in tomato. The respective chemistry, bioavailability, and its functional role in the prevention of several diseases will be object of this work. On the other hand the inclusion of lycopene in some foods can also be made by biotechnology and represents a way to recover the wastes in the tomato industry with nutritional positive effects in health.

Keywords: tomato, lycopene, bioavailability, functional foods, carotenoids, cancer and antioxidants

Procedia PDF Downloads 612

Authors: Hyun-jin Kim, Gumgyung Gu, Dae-Hyun Ko, Woochang Lee, Sail Chun, Won-Ki Min

Abstract:

Background: Ovarian carcinoma is the fourth most common cause of cancer-related death in women worldwide. HE4, a novel marker for ovarian cancer could be used for monitoring recurrence or progression of disease in patients with invasive epithelial ovarian carcinoma. It is further intended to be used in conjunction with CA 125 to estimate the risk of epithelial ovarian cancer in women presenting with an adnexal mass. In this study, we aim to evaluate the analytical performance and clinical utility of HE4 assay using Architect i 2000SR(Abbott Diagnostics, USA). Methods: The precision was evaluated according to Clinical and Laboratory Standards Institute(CLSI) EP5 guideline. Three levels of control materials were analyzed twice a day in duplicate manner over 20 days. We calculated within run and total coefficient of variation (CV) at each level of control materials. The linearity was evaluated based on CLSI EP6 guideline. Five levels of calibrator were prepared by mixing high and low level of calibrators. For 43 women with adnexal masses, HE4 and CA 125 were measured and Risk of ovarian malignancy (ROMA) scores were calculated. The patients’ medical records were reviewed to determine the clinical utility of HE4 and ROMA score. Results: In a precision study, the within-run and total CV were 2.0 % and 2.3% for low level of control material, 1.9% and 2.4% for medium level and 0.5 % and 1.1% for high level, respectively. The linear range of HE4 was 14.63 to 1475.15pmol/L. Of the 43 patients, two patients in pre-menopausal group showed the ROMA score above the cut-off level (7.3%). One of them showed CA 125 level within the reference range, while the HE4 was higher than the cut-off. Conclusion: The overall analytical performance of HE4 assay using Architect showed high precision and good linearity within clinically important range. HE4 could be an useful marker for managing patients with adnexal masses.

Keywords: HE4, CA125, ROMA, evaluation, performance

Procedia PDF Downloads 336

Authors: Nicholas McNamara, John Brookes, Michael Williams, Manish Mathew, Elizabeth Brookes, Tristan Yan, Paul Bannon

Abstract:

Objective: Pericardial effusions are an uncommon but potentially fatal complication after cardiac surgery. The goal of this study was to describe the incidence and risk factors associated with the development of pericardial effusion requiring drainage after coronary artery bypass graft surgery (CABG). Methods: A retrospective analysis was undertaken using prospectively collected data. All adult patients who underwent CABG at our institution between 1st January 2017 and 31st December 2018 were included. Pericardial effusion was diagnosed using transthoracic echocardiography (TTE) performed for clinical suspicion of pre-tamponade or tamponade. Drainage was undertaken if considered clinically necessary and performed via a sub-xiphoid incision, pericardiocentesis, or via re-sternotomy at the discretion of the treating surgeon. Patient demographics, operative characteristics, anticoagulant exposure, and postoperative outcomes were examined to identify those variables associated with the development of pericardial effusion requiring drainage. Tests of association were performed using the Fischer exact test for dichotomous variables and the Student t-test for continuous variables. Logistic regression models were used to determine univariate predictors of pericardial effusion requiring drainage. Results: Between January 1st, 2017, and December 31st, 2018, a total of 408 patients underwent CABG at our institution, and eight (1.9%) required drainage of pericardial effusion. There was no difference in age, gender, or the proportion of patients on preoperative therapeutic heparin between the study and control groups. Univariate analysis identified preoperative atrial arrhythmia (37.5% vs 8.8%, p = 0.03), reduced left ventricular ejection fraction (47% vs 56%, p = 0.04), longer cardiopulmonary bypass (130 vs 84 min, p < 0.01) and cross-clamp (107 vs 62 min, p < 0.01) times, higher drain output in the first four postoperative hours (420 vs 213 mL, p <0.01), postoperative atrial fibrillation (100% vs 32%, p < 0.01), and pleural effusion requiring drainage (87.5% vs 12.5%, p < 0.01) to be associated with development of pericardial effusion requiring drainage. Conclusion: In this study, the incidence of pericardial effusion requiring drainage was 1.9%. Several factors, mainly related to preoperative or postoperative arrhythmia, length of surgery, and pleural effusion requiring drainage, were identified to be associated with developing clinically significant pericardial effusions. High clinical suspicion and low threshold for transthoracic echo are pertinent to ensure this potentially lethal condition is not missed.

Keywords: coronary artery bypass, pericardial effusion, pericardiocentesis, tamponade, sub-xiphoid drainage

Procedia PDF Downloads 159

Authors: Damião Sousa, Hasan Turkez, Ozlem Tozlu, Tamires Lima

Abstract:

Glioblastoma (GBM) is an aggressive cancer from the brain and with high prevalence and significant morbimortality. Therefore, it is necessary to investigate new therapeutic options against this pathology. Thus, the purpose of this study was to evaluate the antitumor activity from Mentha crispa essential oil (MCEO), its major constituent rotundifolone (ROT) and a series of six analogues on human U87MG glioblastoma cell line. The antitumor effects of the compounds on human U87MG-GBM cell line were assessed using in vitro cell viability assays. In addition, biosafety tests were performed on cultured human blood cells. The data show that MCEO, 1,2-perillaldehyde epoxide (EPER1) and perillaldehyde (PALD) were the most cytotoxic compounds against the U87MG cells, with IC50 values of 16.263, 15.087 and 14.888 μg/mL, respectively. The treatment with MCEO, EPER1 and PALD did not lead to damage in blood cells. These chemical analogues may be useful as prototypes for development of novel antitumor drugs due to their promising activities and toxicological safety.

Keywords: antitumor activity, cancer, natural products, terpenes

Procedia PDF Downloads 146

Authors: Thampi Rawther, Sean O’Brien, Kamala Kanta Das

Abstract:

Background: Intussusception in the adult is rarely from a benign cause and is almost always pathological. Causes include carcinomas, polyps, Meckel's diverticulum, or colonic diverticulum. Common symptoms include abdominal pain, intestinal obstruction, palpable abdominal mass, GI bleeding, and anemia. Sarcomatoid carcinoma is a rare type of small intestinal malignancy exhibiting carcinomatous and sarcomatous features. It primarily affects older patients, mean age 57, and is 1.5 times more prevalent in men. Method: This is an interesting case report of a patient presenting with intussusception secondary to a sarcomatoid tumor of the small bowel. Conclusion: Surgery is the treatment of choice in adults with intussusception due to the high malignancy potential. Furthermore, surgical resection of the affected bowel is the definitive form of therapy as small bowel sarcomatoid tumors are not responsive to chemotherapy and radiotherapy. Early surgical intervention helps reduce mortality as it allows for early staging, treatment, and monitoring of the tumor. The patient was fortunate to have presented with intussusception, facilitating early surgical intervention, and was found to have a low disease stage.

Keywords: general surgery, small bowel tumour, imaging, unique

Procedia PDF Downloads 78

Authors: Kabange Kasumbwe, Viresh Mohanlall, Bharti Odhav, Venu Narayanaswamy

Abstract:

Coumarins are naturally occurring plant metabolites known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological and biochemical properties and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1-CMRN7 were synthesized and evaluated for their anticancer activity. The cytotoxicity potential of the test compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer) and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay keeping doxorubicin as standard drug. The apoptotic potential of the coumarin compounds was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential; pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. The synthetic coumarin has strongly suppressed the cell proliferation of UACC-62 (Melanoma) and MCF-7 (Breast) Cancer cells, the higher toxicity of these compounds against UACC-62 (Melanoma) and MCF-7 (Breast) were CMRN3, CMRN4, CMRN5, CMRN6. However, compounds CMRN1, CMRN2, and CMRN7 had no significant inhibitory effect. Furthermore the active compounds CMRN3, CMRN4, CMRN5, CMRN6 exerted antiproliferative effects through apoptosis induction against UACC-62 (Melanoma), suggesting their potential could be considered as attractive lead molecules in the future for the development of potential anticancer agents since one of the important criteria in the development of therapeutic drugs for cancer treatment is to have high selectivity and less or no side-effects on normal cells and these compounds had no inhibitory effect against the PBMC cells.

Keywords: coumarin, MTT, apoptosis, cytotoxicity

Procedia PDF Downloads 236

Authors: Nima Samie, Sekaran Muniandy, Zahurin Mohamed, M. S. Kanthimathi

Abstract:

Although number of indole containing compounds have been reported to have anticancer properties in vitro but only a few of them show potential as anticancer compounds in vivo. The current study was to evaluate the mechanism of cytotoxicity of selected indolic compound in vivo and in vitro. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, human monocyte/macrophage CRL-9855, and B lymphocyte CCL-156 cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content, measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results displayed a potent suppressive effect on HT-29 and WiDr after 24 h of treatment with IC50 value of 2.52±0.34 µg/ml and 2.13±0.65 µg/ml respectively. This cytotoxic effect on normal, monocyte/macrophage and B-cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the compound. Activation of this pathway was further evidenced by significant activation of caspase-9 and 3/7. The compound was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. These findings were further investigated for inhibitory efficiency of the compound on colonic aberrant crypt foci in male rats. Rats were divided in to 5 groups: vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of compounds for 10 weeks. Administration of compound suppressed total colonic ACF formation up to 73.4%. The results also showed that treatment with the compound significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. The outcome of this study suggest sthat the indolic compound is a potent anti-cancer agent against colon cancer and can be further evaluated by animal trial.

Keywords: indolic compound, chemoprevention, crypt, azoxymethane, colon cancer

Procedia PDF Downloads 347

Authors: Soheil Zorofchian Moghadamtousi, Habsah Abdul Kadir, Mohammadjavad Paydar, Elham Rouhollahi, Hamed Karimian

Abstract:

The present study was designed to evaluate the molecular mechanisms of Annona muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards A549 cells. Treatment of A549 cells with AMEAE significantly elevated the reactive oxygen species formation, followed by attenuation of mitochondrial membrane potential via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G1 phase. Our data showed for the first time that AMEAE inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway.

Keywords: Annona muricata, lung cancer, apoptosis, mitochondria

Procedia PDF Downloads 321

Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin

Abstract:

Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.

Keywords: breast cancer, metastasis, PPI networks, protein conformational changes

Procedia PDF Downloads 243

Authors: Ssembatya Joseph Mary

Abstract:

Introduction: Cryptococcal infection in the Central Nervous System (CNS) is frequently seen in human immunodeficiency virus (HIV) patients and others with low immunity as an opportunistic fungal infection. However, CNS cryptococcal granuloma (cryptococcoma) in immunocompetent patients is rare. We present a case of CNS cryptococcoma in an immunocompetent patient and review the literature to illustrate the diagnosis and treatment of such lesions. Case presentation: A 62-year-old, HIV-negative, immunocompetent female patient with no known chronic illness presented with 5 months history of a progressive headache associated with on and off episodic generalized tonic-clonic convulsions. She had been to several hospitals before she was referred to our center with a diagnosis of a brain tumor. Before referral and despite a negative CSF analysis result, she had received treatment for bacterial meningitis with no success. At Mbarara Regional Referral Hospital (MRRH), she had surgery with an excision biopsy which showed features consistent with cryptococcosis on histology. The patient had a successful adjuvant treatment with antifungal drugs following surgery. Conclusion: The diagnosis of a parasitic CNS infection, particularly cryptococcal infection mimicking neoplastic lesions in an immunocompetent patient, was unusual. Surgical management of such lesions from different reports has a bad outcome and management remains totally conservative.

Keywords: Cryptococcal meningitis, immunocompetent patient, Uganda, low resource setting

Procedia PDF Downloads 84

Authors: Nasim Nosoudi, Amir Zadeh, Hunter White, Joshua Conrad, Joon W. Shim

Abstract:

De novo Malignancy has become one of the major causes of death after transplantation, so early cancer diagnosis and detection can drastically improve survival rates post-transplantation. Most previous work focuses on using artificial intelligence (AI) to predict transplant success or failure outcomes. In this work, we focused on predicting de novo malignancy after liver transplantation using AI. We chose the patients that had malignancy after liver transplantation with no history of malignancy pre-transplant. Their donors were cancer-free as well. We analyzed 254,200 patient profiles with post-transplant malignancy from the US Organ Procurement and Transplantation Network (OPTN). Several popular data mining methods were applied to the resultant dataset to build predictive models to characterize de novo malignancy after liver transplantation. Recipient's bilirubin, creatinine, weight, gender, number of days recipient was on the transplant waiting list, Epstein Barr Virus (EBV), International normalized ratio (INR), and ascites are among the most important factors affecting de novo malignancy after liver transplantation

Keywords: De novo malignancy, bilirubin, data mining, transplantation

Procedia PDF Downloads 104

Authors: Ugo Rovigatti

Abstract:

Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

Procedia PDF Downloads 99

Authors: Mohammad H. Yarmohammadian, Masoud Ferdosi, Abbas Haghshenas, Fatemeh Rezaei

Abstract:

Surgical procedures aim at preserving human life and improving quality of their life. However, there are many potential risk sources that can cause serious harm to patients. For centuries, managers believed that technical competence of a surgeon is the only key to a successful surgery. But over the past decade, risks are considered in terms of process-based safety procedures, teamwork and inter departmental communication. Aims: This study aims to determine how the process- biased surgical risk management should be done in terms of project management tool named ABS (Activity Breakdown Structure). Settings and Design: This study was conducted in two stages. First, literature review and meeting with professors was done to determine principles and framework of surgical risk management. Next, responsible teams for surgical patient journey were involved in following meeting to develop the process- biased surgical risk management. Methods and Material: This study is a qualitative research in which focus groups with the inductive approach is used. Sampling was performed to achieve representativeness through intensity sampling biased on experience and seniority. Analysis Method used: context analysis of interviews and consensus themes extracted from FDG meetings discussion was the analysis tool. Results: we developed the patient journey process in 5 main phases, 24 activities and 108 tasks. Then, responsible teams, transposition and allocated places for performing determined. Some activities and tasks themes were repeated in each phases like patient identification and records review because of their importance. Conclusions: Risk management of surgical departments is significant as this facility is the hospital’s largest cost and revenue center. Good communication between surgical team and other clinical teams outside surgery department through process- biased perspective could improve safety of patient under this procedure.

Keywords: risk management, activity breakdown structure (ABS), surgical department, medical sciences

Procedia PDF Downloads 301

Authors: Farida Eid, Hala Nasseif, Hana Mokhtar, Labib Riachi, Mudhar Hasan

Abstract:

Bladder Endometriosis is a rare form of endometriosis and is defined as the presence of endometriotic tissue in the detrusor muscle of the bladder, either in full or partial thickness. Women typically present with dysuria, urinary frequency, hematuria, and recurrent urinary tract infections. Bladder endometriosis is typically found at the bladder base and bladder dome. Transvaginal ultrasound is considered first-line imaging, and the condition is typically managed with laparoscopic partial cystectomy. A 33-year-old nulliparous woman presented with chronic pelvic pain, severe dysmenorrhea, and metrorrhagia. The patient was previously diagnosed with bladder endometriomas two years ago with multiple recurrences. MRI revealed urinary bladder endometriosis measuring 3 x 2 x 1.5 cm. Accordingly, the patient underwent a cystoscopy-guided robotic-assisted excision of the endometriotic implant in the bladder with cystotomy and repair of the bladder mucosa. The operation was tolerated well, and the postoperative period was uneventful. Bladder Endometriosis (BE) typically presents with urinary symptoms and can be mistaken for a bladder tumor upon further imaging. The case was successfully managed with cystoscopy-guided, robotic-assisted excision and fulguration of the endometriotic implant in the bladder.

Keywords: endometriosis, bladder endometriosis (BE), urinary tract endometriosis (UTE), robotic-assisted surgery

Procedia PDF Downloads 28

Authors: Marlin Mubarak

Abstract:

Background: Endometriosis is a complex disabling disease affecting young females in the reproductive period mainly. The aim of this project is to generate a diagnostic model to predict severity and stage of endometriosis prior to Laparoscopic surgery. This will help to improve the pre-operative diagnostic accuracy of stage 3 & 4 endometriosis and as a result, refer relevant women to a specialist centre for complex Laparoscopic surgery. The model is based on the British Society of Gynaecological Endoscopy (BSGE) pain questionnaire, clinical examination and ultrasound scan. Design: This is a prospective, observational, study, in which women completed the BSGE pain questionnaire, a BSGE requirement. Also, as part of the routine preoperative assessment patient had a routine ultrasound scan and when recto-vaginal and deep infiltrating endometriosis was suspected an MRI was performed. Setting: Luton & Dunstable University Hospital. Patients: Symptomatic women (n = 56) scheduled for laparoscopy due to pelvic pain. The age ranged between 17 – 52 years of age (mean 33.8 years, SD 8.7 years). Interventions: None outside the recognised and established endometriosis centre protocol set up by BSGE. Main Outcome Measure(s): Sensitivity and specificity of endometriosis diagnosis predicted by symptoms based on BSGE pain questionnaire, clinical examinations and imaging. Findings: The prevalence of diagnosed endometriosis was calculated to be 76.8% and the prevalence of advanced stage was 55.4%. Deep infiltrating endometriosis in various locations was diagnosed in 32/56 women (57.1%) and some had DIE involving several locations. Logistic regression analysis was performed on 36 clinical variables to create a simple clinical prediction model. After creating the scoring system using variables with P < 0.05, the model was applied to the whole dataset. The sensitivity was 83.87% and specificity 96%. The positive likelihood ratio was 20.97 and the negative likelihood ratio was 0.17, indicating that the model has a good predictive value and could be useful in predicting advanced stage endometriosis. Conclusions: This is a hypothesis-generating project with one operator, but future proposed research would provide validation of the model and establish its usefulness in the general setting. Predictive tools based on such model could help organise the appropriate investigation in clinical practice, reduce risks associated with surgery and improve outcome. It could be of value for future research to standardise the assessment of women presenting with pelvic pain. The model needs further testing in a general setting to assess if the initial results are reproducible.

Keywords: deep endometriosis, endometriosis, minimally invasive, MRI, ultrasound.

Procedia PDF Downloads 352

Authors: M. Abuqebitah, H. Tanyildizi, N. Yeyin, I. Cavdar, M. Demir, L. Kabasakal

Abstract:

Aim: Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for wide range of cancers. Presently dosimetry is highly required either to plan treatment or to ascertain the absorbed dose delivered to critical organs during treatment. Methods and Materials: The study comprised 7 patients suffered from prostate cancer with progressive disease and candidate to undergo Lu-177-DOTA-617 therapy following to PSMA- PET/CT imaging for all patients. (5.2±0.3 mCi) was intravenously injected. To evaluate bone marrow absorbed dose 2 cc blood samples were withdrawn in short variable times (3, 15, 30, 60, 180 minutes) after injection. Furthermore, whole body scans were performed using scintillation gama camera in 4, 24, 48, and 120 hours after injection and in order to quantify the activity taken up in the body, kidneys , liver, right parotid, and left parotid the geometric mean of anterior and posterior counts were determined through ROI analysis, after that background subtraction and attenuation correction were applied using patients PSMA- PET/CT images taking in a consideration: organ thickness, body thickness, and Hounsfield unites from CT scan. OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. Findings: Absorbed doses of bone marrow, left kidney, right kidney, liver, left parotid, right parotid, total body were 1.28±0.52, 32.36±16.36, 32.7±13.68, 10.35±3.45, 38.67±21.29, 37.55±19.77, 2.25±0.95 (mGy/mCi), respectively. Conclusion: Our first results clarify that Lu-177-DOTA-617 is safe and reliable therapy as there were no complications seen. In the other hand, the observable variation in the absorbed dose of the critical organs among the patients necessitate patient-specific dosimetry approach to save body organs and particularly highly exposed kidneys and parotid gland.

Keywords: Lu-177-PSMA, prostate cancer, radionuclide therapy

Procedia PDF Downloads 479

Authors: Lucian Mocan

Abstract:

We present method of Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinomacell line), using gold nanoparticles combuned with a specific growth factor and demonstrate its selective therapeutic efficacy usig ex vivo specimens. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Ab bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of Ab bound to GNPs into tumor cells following ex-vivo intravascular perfusion. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: HepG2 cells, gold nanoparticles, nanoparticle functionalization, laser irradiation

Procedia PDF Downloads 366

Authors: Shokooh Moghadam, Mohammad Taghi Khorasani, Sajjad Seifi Mofarah, M. Daliri

Abstract:

Through the recent two decades, the use of magnetic-property materials with the aim of target cell’s separation and eventually cancer treatment has incredibly increased. Numerous factors can alter the efficacy of this method on curing. In this project, the effect of magnetic field on adhesion of PDL and L929 cells on nanocomposite of iron oxide/PHB with different density of iron oxides (1%, 2.5%, 5%) has been studied. The nanocamposite mentioned includes a polymeric film of poly hydroxyl butyrate and γ-Fe2O3 particles with the average size of 25 nanometer dispersed in it and during this process, poly vinyl alcohol with 98% hydrolyzed and 78000 molecular weight was used as an emulsion to achieve uniform distribution. In order to get the homogenous film, the solution of PHB and iron oxide nanoparticles were put in a dry freezer and in liquid nitrogen, which resulted in a uniform porous scaffold and for removing porosities a 100◦C press was used. After the synthesis of a desirable nanocomposite film, many different tests were performed, First, the particles size and their distribution in the film were evaluated by transmission electron microscopy (TEM) and even FTIR analysis and DMTA test were run in order to observe and accredit the chemical connections and mechanical properties of nanocomposites respectively. By comparing the graphs of case and control samples, it was established that adding nano particles caused an increase in crystallization temperature and the more density of γ-Fe2O3 lead to more Tg (glass temperature). Furthermore, its dispersion range and dumping property of samples were raised up. Moreover, the toxicity, morphologic changes and adhesion of fibroblast and cancer cells were evaluated by a variety of tests. All samples were grown in different density and in contact with cells for 24 and 48 hours within the magnetic fields of 2×10^-3 Tesla. After 48 hours, the samples were photographed with an optic and SEM and no sign of toxicity was traced. The number of cancer cells in the case of sample group was fairly more than the control group. However, there are many gaps and unclear aspects to use magnetic field and their effects in cancer and all diseases treatments yet to be discovered, not to neglect that there have been prominent step on this way in these recent years and we hope this project can be at least a minimum movement in this issue.

Keywords: nanocomposite, cell attachment, magnetic field, cytotoxicity

Procedia PDF Downloads 257

Authors: Mahesh Pal, Tripti Mishra, Chandana Rao, Dalip Upreti

Abstract:

Cancer has been considered to be a very dreadful disease. Holmskioldia sanguinea is a large climbing shrub found in the Himalayas at an altitude of 5,000 ft and preliminary investigation showed the excellent yield of andrographolide and subjected for the anticancer activity. Protective effect of Holmskioldia sanguinea leaf ethanolic extract has been investigated against Ehrlich ascites carcinoma (EAC) and Daltons ascites lymphoma (DAL) in Swiss albino mice to evaluate the possible mechanism of action. The enzymatic antioxidant status was studied on tumor bearing mice, which shows the potential of the compound to possess significant free radical scavenging property and revealed significant tumor regression and prolonged survival time. The isolated bioactive molecule andrographolide from Holmskioldia sanguinea yields (2.5%) in subject to HPTLC/HPLC analysis. The cellular defense system constituting the superoxide dismutase, catalyses was enhanced whereby the lipid peroxidation content was restricted to a larger extent. The Holmskioldia sanguinea is a new source of andrographolide and demonstrated the potency in treatment of cancer.

Keywords: Holmskioldia sanguinea, tumor, mice, andrographolide

Procedia PDF Downloads 262

Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

Abstract:

DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

Procedia PDF Downloads 214

Authors: Aref Zribi, Sonia Ben Nasr, Sana Fendri, Mahdi Balti, Abderazzek Haddaoui

Abstract:

Background: Despite their benefit, Endocrine therapies (ET) are known to have substantial adverse events (AEs) such as hot flashes, mood disorders and osteoarticular pain. ET induced alopecia(EIA) is less frequently noted by patients and is less reported in the literature. The aim of our study was to report ET alopecia characteristics and their influence on patient and treatment observance. Method: We conducted a retrospective study including luminal BC patients treated in the oncology department of the military hospital of Tunis between January 2015 and December 2020. Patients treated with previous chemotherapy-inducing alopecia were excluded. Results: 145 female patients were included. The median age was 59 years. EIA was reported in 44% of cases. Alopecia was attributed to aromatase inhibitors in 53% and tamoxifen in 21%. Severity was grade 1 in 80% and grade 2 in the remaining cases. ET discontinuation because of alopecia was noted in 6.5 % of patients. Moderate improvement of alopecia was observed with topical minoxidil and Thallium metallicum 9CH homeopathy during ET in 60% of patients. Conclusions: EIA is frequent in BC patients and should be considered to improve treatment observance and patients’ quality of life.

Keywords: endocrine therapy, alopecia, breast cancer, Tunisia

Procedia PDF Downloads 122

Authors: Sahar Nasr, Lin Li, Edwin Wang

Abstract:

Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

Procedia PDF Downloads 153

Authors: Samar Mousa, Ryan Kerstein, Mohanad Adam

Abstract:

Regional anaesthesia has been associated with favourable outcomes in patients undergoing a wide range of surgeries. Beneficial effects have been demonstrated in terms of postoperative respiratory and cardiovascular endpoints, 7-day survival, time to ambulation and hospital discharge, and postoperative analgesia. Our project aimed at assessing the regional anaesthesia practice in the plastic surgery department of Buckinghamshire trust and finding out ways to improve the service in collaboration with the anaesthesia team. It is a retrospective study associated with a questionnaire filled out by plastic surgeons and anaesthetists to get the full picture behind the numbers. The study period was between 1/3/2022 and 23/5/2022 (12 weeks). The operative notes of all patients who had an operation under plastic surgery, whether emergency or elective, were reviewed. The criteria of suitable candidates for the regional block were put by the consultant anaesthetists as follows: age above 16, single surgical site (arm, forearm, leg, foot), no drug allergy, no pre-existing neuropathy, no bleeding disorders, not on ant-coagulation, no infection to the site of the block. For 12 weeks, 1061 operations were performed by plastic surgeons. Local cases were excluded leaving 319 cases. Of the 319, 102 patients were suitable candidates for regional block after applying the previously mentioned criteria. However, only seven patients had their operations under the regional block, and the rest had general anaesthesia that could have been easily avoided. An online questionnaire was filled out by both plastic surgeons and anaesthetists of different training levels to find out the reasons behind the obvious preference for general over regional anaesthesia, even if this was against the patients’ interest. The questionnaire included the following points: training level, time taken to give GA or RA, factors that influence the decision, percentage of RA candidates that had GA, reasons behind this percentage, recommendations. Forty-four clinicians filled out the questionnaire, among which were 23 plastic surgeons and 21 anaesthetists. As regards the training level, there were 21 consultants, 4 associate specialists, 9 registrars, and 10 senior house officers. The actual percentage of patients who were good candidates for RA but had GA instead is 93%. The replies estimated this percentage as between 10-30%. 29% of the respondents thought that this percentage is because of surgeons’ preference to have GA rather than RA for their operations without medical support for the decision. 37% of the replies thought that anaesthetists prefer giving GA even if the patient is a suitable candidate for RA. 22.6% of the replies thought that patients refused to have RA, and 11.3% had other causes. The recommendations were in 5 main accesses, which are protocols and pathways for regional blocks, more training opportunities for anaesthetists on regional blocks, providing a separate block room in the hospital, better communication between surgeons and anaesthetists, patient education about the benefits of regional blocks.

Keywords: regional anaesthesia, regional block, plastic surgery, general anaesthesia

Procedia PDF Downloads 83

Authors: Mohamed Moussaoui

Abstract:

A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

Procedia PDF Downloads 46

Authors: Aishik Deb, Rituparna Sinha

Abstract:

We have developed an algorithm to detect the abnormal segment/"structural variation in the genome across a number of samples. We have worked on simulated as well as real data from the BAM Files and have designed a segmentation algorithm where abnormal segments are detected. This algorithm aims to improve the accuracy and performance of the existing CNV-CH algorithm. The next-generation sequencing (NGS) approach is very fast and can generate large sequences in a reasonable time. So the huge volume of sequence information gives rise to the need for Big Data and parallel approaches of segmentation. Therefore, we have designed a map-reduce approach for the existing CNV-CH algorithm where a large amount of sequence data can be segmented and structural variations in the human genome can be detected. We have compared the efficiency of the traditional and map-reduce algorithms with respect to precision, sensitivity, and F-Score. The advantages of using our algorithm are that it is fast and has better accuracy. This algorithm can be applied to detect structural variations within a genome, which in turn can be used to detect various genetic disorders such as cancer, etc. The defects may be caused by new mutations or changes to the DNA and generally result in abnormally high or low base coverage and quantification values.

Keywords: cancer detection, convex hull segmentation, map reduce, next generation sequencing

Procedia PDF Downloads 135

Authors: Donghee Kang

Abstract:

Background: Cancer pain is very difficult to control as the mechanism of pain is varied, and the patient has several co-morbidities. The use of Intravenous Patient-Controlled Analgesia (IV-PCA) can effectively control underlying pain and breakthrough pain. Ketamine is used in many pain patients due to its unique analgesic effect. In this study, it was checked whether there was a difference in the amount of analgesic usage, pain control degree, and side effects between patients who controlled pain with fentanyl-based IV-PCA and those who added Ketamine for pain control. Methods: Among the patients referred to this department for cancer pain, IV-PCA was applied to patients who were taking sufficient oral analgesics but could not control them or had blood clotting disorders that made the procedure difficult, and this patient group was targeted. In IV-PCA, 3000 mcg of Fentanyl, 160 mg of Nefopam, and 0.3 mg of Ramosetrone were mixed with normal saline to make a total volume of 100 ml. Group F used this IV-PCA as it is, and group K mixed 250 mg of Ketamine with normal saline to make a total volume of 100 ml. For IV-PCA, the basal rate was 0.5ml/h, the bolus was set to 1ml when pressed once, and the lockout time was set to 15 minutes. If pain was not controlled after IV-PCA application, 500 mcg of Fentanyl was added, and if excessive sedation or breathing difficulties occurred, the use was stopped for one hour. After that, the degree of daily pain control, analgesic usage, and side effects were investigated for seven days using this IV-PCA. Results: There was no difference between the two groups in the demographic data. Both groups had adequate pain control. Initial morphine milligram equivalents did not differ between the two groups, but the total amount of Fentanyl used for seven days was significantly different between the two groups [p=0.014], and group F used more Fentanyl through IV-PCA. In addition, the amount of sleeping pills used during the seven days was higher in Group F [p<0.01]. Overall, there was no difference in the frequency of side effects between the two groups, but the nausea was more frequent in Group F [p=0.031]. Discussion: When the two groups were compared, pain control was good in both groups. This seems to be because Fentanyl-based IV-PCA showed an adequate pain control effect. However, there was a significant difference in the total amount of opioid (Fentanyl) used, which is thought to be the opioid-sparing effect of Ketamine. Also, among the side effects, nausea was significantly less, which is thought to be possible because the amount of opioids used in the Ketamine group was small. The frequency of requesting sleeping pills was significantly less in the group using Ketamine, and it seems that Ketamine also helped improve sleep quality. In conclusion, using Ketamine with an opioid to control pain seems to have advantages. IV-PCA, which can be used effectively when other procedures are difficult, is more effective and safer when used together with Ketamine than opioids alone.

Keywords: cancer pain, intravenous patient-controlled analgesia, Ketamine, opioid

Procedia PDF Downloads 81

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

Abstract:

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

Procedia PDF Downloads 112

Authors: Eun Ho Kim

Abstract:

Innovations have conjured up a mode of treating GBM cancer cells in the newly diagnosed patients in a period of 4.9 months at an improved median OS, which brings along only a few minor side effects in the phase III of the clinical trial. This mode has been termed the Alternating Electric Fields (AEF). The study at hand is aimed at determining whether the AEF treatment is beneficial in sensitizing the GBM cancer cells through the process of increasing the AEF –induced senescence. The methodology to obtain the findings for this research ranged across various components, such as obtaining and testing SA-β-gal staining, flow cytometry, Western blotting, morphology, and Positron Emission Tomography (PET) / Computed Tomography (CT), immunohistochemical staining and microarray. The number of cells that displayed a senescence-specific morphology and positive SA-ß-Gal activity gradually increased up to 5 days. These results suggest that p16, p21 and p27 are essential regulators of AEF -induced senescence via NF-κB activation. The results showed that the AEF treatment is functional in enhancing the AEF –induced senescence in the GBM cells via an apoptosis- independent mechanism. This research concludes that this mode of treatment is a trustworthy protocol that can be effectively employed to overcome the limitations of the conventional mode of treatment on GBM.

Keywords: alternating electric fields, senescence, glioblastoma, cell death

Procedia PDF Downloads 90

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

Abstract:

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

Procedia PDF Downloads 141

Authors: Chaoran Liu

Abstract:

Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

Procedia PDF Downloads 232