Search results for: malignant melanoma

Authors: Akram Boubakri, Fethi Choubani, Tan Hoa Vuong, Jacques David

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Nowadays, microwave hyperthermia is considered as an effective treatment for the malignant tumors. This microwave treatment which comes to substitute the chemotherapy and the surgical intervention enables an in-depth tumor heating without causing any diseases to the sane tissue. This technique requires a high precision system, in order to effectively concentrate the heating just in the tumor, without heating any surrounding healthy tissue. In the hyperthermia treatment, the temperature in cancerous area is typically raised up to over 42◦C and maintained for one hour in order to destroy the tumor sufficiently, whilst in the surrounding healthy tissues, the temperature is maintained below 42◦C to avoid any damage. Metamaterial lenses are widely used in medical applications like microwave hyperthermia treatment. They enabled a subdiffraction resolution thanks to the amplification of the evanescent waves and they can focus electromagnetic waves from a point source to a point image. Metasurfaces have been used to built metamaterial lenses. The main mechanical advantages of those structures over three dimensional material structures are ease of fabrication and a smaller required volume. Here in this work, we proposed a metasurface based lens operating at the frequency of 6 GHz and designed for microwave hyperthermia. This lens was applied and showed good results in focusing and heating the tumor inside a breast tissue with an increased and maintained temperature above 42°C. The tumor was placed in the focal distance of the lens so that only the tumor tissue will be heated. Finally, in this work, it has been shown that the hyperthermia area within the tissue can be carefully adjusted by moving the antennas or by changing the thickness of the metamaterial lenses based on the tumor position. Even though the simulations performed in this work have taken into account an ideal case, some real characteristics can be considered to improve the obtained results in a realistic model.

Keywords: focusing, hyperthermia, metamaterial lenses, metasurface, microwave treatment

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Authors: J. Vinay , Kusumbati Besra, Niharika Pattnaik, Shivaram Prasad Singh, Manjusha Dixit

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Gallbladder cancer (GBC) is rare but highly malignant cancer; its prevalence is more in certain geographical regions and ethnic groups, which include the Northern and Eastern states of India. Previous studies in India have reported genetic predisposition as one of the risk factors in GBC pathogenesis. Although the matrix metalloproteinase-14 (MMP14) is a well-known modulator of the tumor microenvironment and tumorigenesis and TCGA data also suggests its upregulation yet, its role in the genetic predisposition for GBC is completely unknown. We elucidated the role of MMP14 promoter variants as genetic risk factors and their implications in expression modulation. We screened MMP14 promoter variants association with GBC using Sanger’s sequencing in approximately 300 GBC and 300 control subjects and 26 GBC tissue samples of Indian ethnicity. The immunohistochemistry was used to check the MMP14 protein expression in GBC tissue samples. The role of promoter variants on expression levels was elucidated using a luciferase reporter assay. The variants rs1004030 (p-value = 0.0001) and rs1003349 (p-value = 0.0008) were significantly associated with gallbladder cancer. The luciferase assay in two different cell lines, HEK-293 (p = 0.0006) and TGBC1TKB (p = 0.0036) showed a significant increase in relative luciferase activity in the presence of risk alleles for both the single nucleotide polymorphisms (SNPs). Similarly, genotype-phenotype correlation in patients samples confirmed that the presence of risk alleles at rs1004030 and rs1003349 increased MMP14 expression. Overall, this study unravels the genetic association of MMP14 promoter variants with gallbladder cancer, which may contribute to pathogenesis by increasing its expression.

Keywords: gallbladder cancer, matrix metalloproteinase-14, single nucleotide polymorphism, case control study, genetic association study

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Authors: Ghada Esheba, Ebtisam Aljerayan, Afnan Al-Ghamdi, Atheer Alsharif, Hanan alzahrani

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Background: Primary ovarian neoplasms comprise a heterogeneous group of tumors of three main subtypes: surface epithelial, germ cell, and sex cord-stromal. The wide morphological variation within and between these groups can result in diagnostic difficulties. Gonadal sex cord-stromal tumors (SCST) represent one of the most heterogeneous categories of human neoplasms, because they may contain various combinations of different gonadal sex cord and stromal element. Aim: The aim of this work is to highlight the clinicopathological characteristics of SCST and to assess the value of alpha-inhibin and calretinin in the distinction between SCST and their mimics. Material and methods: This study was carried out on 100 cases using full tissue sections; 70 cases were SCST and 30 cases were histological mimics of SCST. The cases were studied using immunohistochemically using alpha-inhibin. In addition, an ovarian tissue microarray containing 170 benign and malignant ovarian neoplasms was also studied immunohistochemically for calretinin expression. The ovarian microarray included 14 SCST, 59 ovarian serous borderline tumors, 17 mucinous borderline tumors, 10 mucinous adenocarcinomas, 32 endometrioid adenocarcinomas, 34 clear cell carcinomas, and 4 germ cell tumors. Results: 99% of SCST examined using full tissue sections exhibited positive cytoplasmic staining for inhibin. On the contrary, only 7% of the histological mimics (P value < 0.0001). 86% of SCST in the tissue microarray were positive for calretinin with nuclear and/or cytoplasmic staining compared to only 7% of the other tumor types (P value < 0.0001). Conclusions: SCST have characteristic clinicopathological and immunohistochemical features and their recognition is crucial for proper diagnosis and treatment. Alpha-inhibin and calretinin are of great help in the diagnosis of sex cord-stromal tumors.

Keywords: calretinin, granulosa cell tumor, inhibin, sex cord-stromal tumors

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Authors: Lukman Ahmad Jamil, Heather M. Wallace

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Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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Authors: Mujahid Ali, Wasif Mohammed Ali, Meraj Ahmad

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Background: Perforation peritonitis is the most common surgical emergency encountered by surgeons all over the world as well as in India. The etiology of perforation peritonitis in India continues to be different from its western counterparts. The aim of this study is to evaluate the spectrum of cases of perforation peritonitis at our hospital. Methods: A prospective study conducted includes three hundred thirtysix patients of perforation peritonitis at J. N. Medical College from October 2015 to July 2017. The patients were admitted, resuscitated and underwent emergency laparotomy. Data were collected in terms of demographic profile, clinical presentations, site of perforations, causes and surgical outcomes. Results: In this study, the most common cause of perforation peritonitis was peptic ulcer disease (43%), followed by enteric perforation (12.8%), tubercular perforation (12.5%), traumatic perforation (11.9%), appendicular perforation (9.8%), amoebic caecal perforation (3%), malignant perforation (1.5%), etc. The sites of perforations were stomach in majority (38.3%), ileum (31%), appendix (8%), duodenum (5.%), caecum (4.4%) ,colon (3%), jejunum (8.5%) and gall bladder (2%). The overall mortality was 21% in our study. Age >50 years (p= <0.0001, OR= 3.9260, CI= 2.2 to 6.9), organ failure (p= <0.0001, OR= 29.2, CI= 14.8 to 57.6), shock (p=<0.0001, OR=20.20, CI= 10.56 to 38.6), diffuse peritonitis (p<0.0015, OR= 6.8810, CI= 2.09 to 22.57) and faecal exudates (p<0.0001) were found to be significant factors affecting mortality. The most common complication associated was superficial wound infection (40%), followed by burst abdomen seen in 21% cases, intra-abdominal sepsis in 18% cases, electrolyte imbalances in 15% cases, anastomotic leak in 6% cases. Conclusion: In this study, stomach is the most common site of perforation with peptic ulcer disease being the most common etiology. Older age, presence of shock, organ failure and faecal peritonitis were the risk factors affecting the mortality of the patients. Early recognition, adequate resuscitation and referral of patients can influence outcome and reduces mortality as well as morbidity.

Keywords: etiology, mortality, perforation, spectrum

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

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

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

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: Muñiz-Lino Marcos Agustín, Vazquez Borbolla Jessica, Licéaga-Escalera Carlos

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The ectomesenchymal tissues involved in tooth development and their remnants are the origin of different odontogenic lesions, including tumors and cysts of the jaws, with a wide range of clinical behaviors. Dentigerous cyst (DC) represents approximately 20% of all cases of odontogenic cysts, and it has been demonstrated that it can develop benign and malignant odontogenic tumors. DC is characterized by bone destruction of the area surrounding the crown of a tooth which has not erupted and it contain is liquid. The treatment of odontogenic tumors and cysts usually are partial or total removal of the jaw, causing important secondary co-morbidities. However, molecules implicated in DC pathogenesis as well in its development to odontogenic tumors remains unknown. A cellular model may be useful to study these molecules, but that model has not been established yet. Here, we reported the establishment of a cell culture derived from a dentigerous cyst. This cell line was named DeCy-1. In spite of its ectomesenchymal morphology, DeCy-1 cells express epithelial markers such as cytokeratins 5, 6, and 8. Furthermore, these cells express the ODAM protein, which is present in odontogenesis and in dental follicle, indicating that DeCy-1 cells derived from odontogenic epithelium. Analysis by electron microscopy of this cell line showed that it has a high vesicular activity, suggesting that DeCy-1 could secrete molecules that may be involved in DC pathogenesis. Thus, secreted proteins were analyzed by PAGE-SDS, where we observed approximately 11 bands. In addition, the capacity of these secretions to degrade proteins was analyzed by gelatin substrate zymography. A degradation band of about 62 kDa was found in these assays. Western blot assays suggested that the matrix metalloproteinase 2 (MMP-2) is responsible of this protease activity. Thus, our results indicate that the establishment of a cell line derived from DC is a useful in vitro model to study the biology of this odontogenic lesion and its participation in the development of odontogenic tumors.

Keywords: dentigerous cyst, MMP20, cancer, cell culture

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Authors: J. J. Mathew

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Pulmonary tuberculosis is highly prevalent in the Indian subcontinent. Most cases of pulmonary tuberculosis are diagnosed with sputum examinations and the vast majority of these are undertaken by the government run establishments. However, mycobacterial cultures are not routinely done, unless drug resistance is detected based on clinical response. Modern diagnostic tests like bronchoscopy and Genexpert are not routinely employed in the government institutions for the diagnosis of pulmonary tuberculosis, but have been accepted widely by good private institutions. The utility of these investigations in the private sector is not yet well recognized. This retrospective study aims to assess the usefulness of bronchoscopy and Genexpert in the diagnosis of pulmonary tuberculosis in quaternary care private hospital in India. 30 patients with respiratory symptoms raising the possibility of tuberculosis based on clinical and radiological features, but without any significant sputum production, were subject to bronchoscopy and BAL samples taken for microbiological studies, including Genexpert. 6 out of the 30 patients were found to be Genexpert positive and none of them showed Rifampicin resistance. All the 6 cases had upper zone predominant disease. One of the 6 cases of tuberculosis had another co-existent bacterial infection according to the routine culture studies. 6 other cases were proven to be due to other bacterial infections alone, 2 had a malignant diagnosis and the remaining cases were thought to be non-infective pathologies. The Genexpert results were made available within 48 hours in the 6 positive cases. All of them were commenced on standard anti-tuberculous regimen with excellent clinical response. The other infective cases were also managed successfully based on the drug susceptibilities. The study has shown the usefulness of these investigations as early intervention enabled diagnosis facilitating treatment and prevention of any clinical deterioration. The study lends support to early bronchoscopy and Genexpert testing in suspected cases of pulmonary tuberculosis without significant sputum production, in a high prevalence country which normally relies on sputum examination for the diagnosis of pulmonary tuberculosis.

Keywords: pulmonary, tuberculosis, bronchoscopy, genexpert

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Authors: Fathi Kallel, Abdulelah Alabd Uljabbar, Abdulrahman Aldukhail, Abdulaziz Alomran

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The brain is an important organ in our body since it is responsible about the majority actions such as vision, memory, etc. However, different diseases such as Alzheimer and tumors could affect the brain and conduct to a partial or full disorder. Regular diagnosis are necessary as a preventive measure and could help doctors to early detect a possible trouble and therefore taking the appropriate treatment, especially in the case of brain tumors. Different imaging modalities are proposed for diagnosis of brain tumor. The powerful and most used modality is the Magnetic Resonance Imaging (MRI). MRI images are analyzed by doctor in order to locate eventual tumor in the brain and describe the appropriate and needed treatment. Diverse image processing methods are also proposed for helping doctors in identifying and analyzing the tumor. In fact, a large Computer Aided Diagnostic (CAD) tools including developed image processing algorithms are proposed and exploited by doctors as a second opinion to analyze and identify the brain tumors. In this paper, we proposed a new advanced CAD for brain tumor identification, classification and feature extraction. Our proposed CAD includes three main parts. Firstly, we load the brain MRI. Secondly, a robust technique for brain tumor extraction is proposed. This technique is based on both Discrete Wavelet Transform (DWT) and Principal Component Analysis (PCA). DWT is characterized by its multiresolution analytic property, that’s why it was applied on MRI images with different decomposition levels for feature extraction. Nevertheless, this technique suffers from a main drawback since it necessitates a huge storage and is computationally expensive. To decrease the dimensions of the feature vector and the computing time, PCA technique is considered. In the last stage, according to different extracted features, the brain tumor is classified into either benign or malignant tumor using Support Vector Machine (SVM) algorithm. A CAD tool for brain tumor detection and classification, including all above-mentioned stages, is designed and developed using MATLAB guide user interface.

Keywords: MRI, brain tumor, CAD, feature extraction, DWT, PCA, classification, SVM

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Authors: Saman Khan, Imrana Naseem

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Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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Authors: Kathryn L. Duncan, Charles A. Kuntz, James O. Simcock

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A surgical approach to the cranium for treatment of frontal lobe and olfactory bulb neoplasia in dogs is described in this report, which provided excellent access for visualisation and removal of gross neoplastic tissue. An 8-year-old spayed female Shih Tzu crossbreed dog (dog 1) and a 13-year-old neutered male Miniature Fox Terrier (dog 2) were evaluated for removal of neoplasms involving both the frontal lobe and olfactory bulb. Both dogs presented with abnormal neurological clinical signs, decreased menace responses, and behavioural changes. Additionally, dog 2 presented with compulsive circling and generalized tonic-clonic seizure activity. Computed tomography was performed in both dogs, and MRI was also performed in dog 1. Imaging was consistent with frontal lobe and olfactory bulb neoplasia. A transorbital frontal bone craniectomy, with orbital ligament desmotomy and ventrolateral retraction of the globe, was performed in both cases without complication. Dog 1 had a focal area of lysis in the frontal bone adjacent to the neoplasm in the frontal lobe. The presence of the bone defect provided part of the impetus for this approach, as it would permit resection of the lytic bone. In addition, the neoplasms would be surgically accessible without encountering interposed brain parenchyma, reducing the risk of iatrogenic injury. Both dogs were discharged from the hospital within 72 hours post-operatively, both with normal mentation. Case 1 had a histopathologic diagnosis of malignant anaplastic neoplasm. The tumour recurred 101d postoperatively, and the patient was euthanized. Case 2 was diagnosed with a meningioma and was neurologically normal at 294d postoperatively. This transorbital surgical approach allowed successful removal of the intracranial frontal lobe and olfactory bulb neoplasms in 2 dogs. This approach should be considered for dogs with lateralized frontal lobe and olfactory bulb neoplasms that are closely associated with the suborbital region of the frontal bone.

Keywords: neurosurgery, small animal surgery, surgical oncology, veterinary neurology

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.

Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle

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Authors: Mostafa Sefidgar, Sohrab Zendehboudi, Hossein Bazmara, Madjid Soltani

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Based on findings from clinical applications, most drug treatments fail to eliminate malignant tumors completely even though drug delivery through systemic administration may inhibit their growth. Therefore, better understanding of tumor formation is crucial in developing more effective therapeutics. For this purpose, nowadays, solid tumor modeling and simulation results are used to predict how therapeutic drugs are transported to tumor cells by blood flow through capillaries and tissues. A solid tumor is investigated as a porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multi scale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. In this work, the mathematical model in our previous studies is developed by considering two model of momentum equation for porous media: Darcy and Brinkman. The mathematical method involves processes such as fluid flow through solid tumor as porous media, extravasation of blood flow from vessels, blood flow through vessels and solute diffusion, convective transport in extracellular matrix. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model does.

Keywords: solid tumor, porous media, Darcy model, Brinkman model, drug delivery

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Authors: Mary Abigail T. Ty, Mary Jocelyn Yu-Laygo, Jocelyn Z. Mariano

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This is a case of L.S.T., a 61 year old, G6P4 (3124) who presented with a one month history of intermittent, brownish, watery, non foul smelling vaginal discharge. There were no other accompanying symptoms. On rectovaginal examination, a palpable adnexal mass on the left was appreciated, with the lower border measuring 3 cm. The mass was non-tender, had irregular borders and solid areas. On transvaginal sonography, it revealed a left pelvic mass measuring 3 x 4 x 2 cm, with a Sassone score of 9. It had vascularization. The primary consideration was Ovarian Newgrowth, probably malignant in nature. CA-125 results were slightly elevated at 43.2 u/ml (NV: 0-35 u/ml). After intraoperative evaluation, the left fallopian tube was converted into a 9 x 4.5 x 3 cm bulbous cystic mass with solid areas. On cut section, the ampullary portion of the fallopian tube contained necrotic and friable looking tissues. Specimen was sent for frozen section and results revealed adenocarcinoma of the left fallopian tube. Patient subsequently underwent complete surgical staging with unremarkable post-operative course. The Surg Ico pathologic diagnosis was G6P4 (3124) Fallopian tube serous cystadenocarcinoma stage 1. The mean incidence of PFTC is 3.6 per million women yearly. This is associated with a generally low survival rate. The primary diagnosis is very difficult to establish because only 0–10% of patients suffering from PFTC are diagnosed pre-operatively. Symptoms play a very important role in the discovery of this disease, because there will be no presentation to the hospital without symptoms. The most common of which may be vaginal bleeding, abdominal pain, a palpable mass and ascites. A conglomerate of manifestations may be encountered, but not at all times. This is termed hydrops tubae profluens where there is presence of colicky pain with relief from intermittent passage of serosanguinous vaginal discharge. The significance of this report is to emphasize the rarity of the case and how the dilemma in the diagnosis is almost always present despite ancillary procedures.

Keywords: fallopian tube carcinoma, prognosis, rare, risk factors

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Authors: Yousef Reda

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Pancreatic cancer has an overall dismal prognosis. CT, MRI and Endoscopic Ultrasound are most often used to establish the diagnosis. We present a case of a patient found on abdominal CT and MRI to have an 8 mm cystic lesion within the head of the pancreas which was thought to be a benign intraductal papillary mucinous neoplasm (IPMN). Further evaluation by EUS demonstrated a 1 cm predominantly solid mass that was proven to be an adenocarcinoma by EUS-guided FNA. The patient underwent a Whipple procedure. The final pathology confirmed a 1 cm pT1 N0 pancreatic ductal adenocarcinoma. Case: A 63-year-old male presented with left upper quadrant pain and an abdominal CT demonstrated an 8 mm lesion within the head of the pancreas that was thought to represent a side branch IPMN. An MRI also showed similar findings. Four months later due to ongoing symptoms an EUS was performed to re-evaluate the pancreatic lesion. EUS revealed a predominantly solid hypoechoic, homogeneous mass measuring 12 mm x 9 mm. EUS-guided FNA was performed and was positive for adenocarcinoma. The patient underwent a Whipple procedure that confirmed it to be a ductal adenocarcinoma, pT1N0. The solid mass was noted to be adjacent to a cystic dilation with no papillary architecture and scant epithelium. The differential diagnosis resided between cystic degeneration of a primary pancreatic adenocarcinoma versus malignant degeneration within a side-branch IPMN. Discussion: The reported sensitivity of CT for pancreatic cancer is approximately 90%. For pancreatic tumors, less than 3 cm the sensitivity of CT is reduced ranging from 67-77%. MRI does not significantly improve overall detection rates compared to CT. EUS, however is superior to CT in the detection of pancreatic cancer, in particular among lesions smaller than 3 cm. EUS also outperforms CT and MRI in distinguishing neoplastic from non-neoplastic cysts. In this case, both MRI and CT failed to detect a small pancreatic adenocarcinoma. The addition of EUS and FNA to abdominal imaging can increase overall accuracy for the diagnosis of neoplastic pancreatic lesions. It may be prudent that when small lesions although appearing as a benign IPMN should further be evaluated by EUS as this would lead to potentially identifying earlier stage pancreatic cancers and improve survival in a disease which has a dismal prognosis.

Keywords: IPMN, MRI, EUS, CT

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: The mortality gap in Aboriginal Head and Neck Cancer is well known, but the reasons for poorer survival are not well established. Aim: We aimed to evaluate the locoregional and metastatic involvement, and stage at diagnosis, in Aboriginal compared with non-Aboriginal patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, regions involved, stage at diagnosis, treatment history, and survival and relapse patterns, including sites of metastatic and locoregional involvement. Results: Aboriginal patients had a significantly higher incidence of lung metastases (26.3% versus 13.7%, p=0.009). Aboriginal patients also had a numerically but non-statistically significant higher incidence of thoracic nodal involvement (10% vs 5.8%) and malignant pleural effusions (3.8% vs 2.5%). Aboriginal patients also had a numerically but not statistically significantly higher incidence of adrenal and bony involvement. Interestingly, non-Aboriginal patients had an increased rate of cutaneous (2.1% vs 0%) and liver metastases (4.6% vs 2.5%) compared with Aboriginal patients. In terms of locoregional involvement, Aboriginal patients were more than twice as likely to have contralateral neck involvement (58.8% vs 24.2%, p<0.00001), and 30% more likely to have ipsilateral neck lymph node involvement (78.8% vs 60%, p=0.002) than non-Aboriginal patients. Aboriginal patients had significantly more advanced disease at diagnosis (p=0.008). Aboriginal compared with non-Aboriginal patients were less likely to present with stage I (7.5% vs 22.5%), stage II (11.3% vs 13.8%), or stage III disease (13.8% vs 17.1%), and more likely to present with more advanced stage IVA (42.5% vs 34.6%), stage IVB (15% vs 7.1%), or stage IVC (10% vs 5%) disease (p=0.008). Number of regions of disease involvement was higher in Aboriginal patients (median 3, mean 3.64, range 1-10) compared with non-Aboriginal patients (median 2, mean 2.80, range 1-12). Conclusion: Aboriginal patients had a significantly higher incidence of lung metastases, and significantly more frequent involvement of ipsilateral and contralateral neck lymph nodes. Aboriginal patients also had significantly more advanced disease at presentation with a higher stage at diagnosis. We are performing further analyses to investigate explanations for these findings.

Keywords: head and neck cancer, Aboriginal, metastases, locoregional, pattern of relapse, sites of disease

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Authors: Hala M. El-hanbuli, Mohammed F. Darweesh

Abstract:

The incidence rates of any tumor vary hugely with geographical location. Basal Cell Carcinoma (BCC) is one of the most common skin cancer that has many histopathologic subtypes. Objective: The aim was to study the histopathological features of BCC cases that were received in the Pathology Department, Kasr El-Aini hospital, Cairo University, Egypt during the period from Jan 2004 to Dec 2013 and to evaluate the clinical characters through the patient data available in the request sheets. Methods: Slides and data of BCC cases were collected from the archives of the pathology department, Kasr El-Aini hospital. Revision of all available slides and histological classification of BCC according to WHO (2006) was done. Results: A total number of 310 cases of BCC representing about 65% from the total number of malignant skin tumors examined during the 10-years duration in the department. The age ranged from 8 to 84 years, the mean age was (55.7 ± 15.5). Most of the patients (85%) were above the age of 40 years. There was a slight male predominance (55%). Ulcerated BCC was the most common gross picture (60%), followed by nodular lesion (30%) and finally the ulcerated nodule (10%). Most of the lesions situated in the high-risk sites (77%) where the nose was the most common site (35%) followed by the periocular area (22%), then periauricular (15%) and finally perioral (5%). No lesion was reported outside the head. The tumor size was less than 2 centimeters in 65% of cases, and from 2-5 centimeters in the lesions' greatest dimension in the rest of cases. Histopathological reclassification revealed that the nodular BCC was the most common (68%) followed by the pigmented nodular (18.75%). The histologic high-risk groups represented (7.5%) about half of them (3.75%) being basosquamous carcinoma. The total incidence for multiple BCC and 2nd primary was 12%. Recurrent BCC represented 8%. All of the recurrent lesions of BCC belonged to the histologic high-risk group. Conclusion: Basal Cell Carcinoma is the most common skin cancer in the 10-year survey. Histopathological diagnosis and classification of BCC cases are essential for the determination of the tumor type and its biological behavior.

Keywords: basal cell carcinoma, high risk, histopathological features, statistical analysis

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Authors: Aliseydi Bozkurt

Abstract:

Objectives: Benign prostatic hyperplasia (BPH) is the most common benign disease, and prostate cancer (PC) is malign disease of the prostate gland. Transrectal ultrasound-guided biopsy (TRUS-bx) is one of the most important diagnostic tools in PC diagnosis. Identifying men at increased risk for having a biopsy detectable prostate cancer should consider prostate specific antigen density (PSAD), f/t PSA Ratio, an estimate of prostate volume. Method: We retrospectively studied 269 patients who had a prostate specific antigen (PSA) score of 4 or who had suspected rectal examination at any PSA level and received TRUS-bx between January 2015 and June 2018 in our clinic. TRUS-bx was received by 12 experienced urologists with 12 quadrants. Prostate volume was calculated prior to biopsy together with TRUS. Patients were classified as malignant and benign at the end of pathology. Age, PSA value, prostate volume in transrectal ultrasonography, corpuscle biopsy, biopsy pathology result, the number of cancer core and Gleason score were evaluated in the study. The success rates of PV, PSAD, and f/tPSA were compared in all patients and those with PSA 2.5-10 ng/mL and 10.1-30 ng/mL tp foresee prostate cancer. Result: In the present study, in patients with PSA 2.5-10 ng/ml, PV cut-off value was 43,5 mL (n=42 < 43,5 mL and n=102 > 43,5 mL) while in those with PSA 10.1-30 ng/mL prostate volüme (PV) cut-off value was found 61,5 mL (n=31 < 61,5 mL and n=36 > 61,5 mL). Total PSA values in the group with PSA 2.5-10 ng/ml were found lower (6.0 ± 1.3 vs 6.7 ± 1.7) than that with PV < 43,5 mL, this value was nearly significant (p=0,043). In the group with PSA value 10.1-30 ng/mL, no significant difference was found (p=0,117) in terms of total PSA values between the group with PV < 61,5 mL and that with PV > 61,5 mL. In the group with PSA 2.5-10 ng/ml, in patients with PV < 43,5 mL, f/t PSA value was found significantly lower compared to the group with PV > 43,5 mL (0.21 ± 0.09 vs 0.26 ± 0.09 p < 0.001 ). Similarly, in the group with PSA value of 10.1-30 ng/mL, f/t PSA value was found significantly lower in patients with PV < 61,5 mL (0.16 ± 0.08 vs 0.23 ± 0.10 p=0,003). In the group with PSA 2.5-10 ng/ml, PSAD value in patients with PV < 43,5 mL was found significantly higher compared to those with PV > 43,5 mL (0.17 ± 0.06 vs 0.10 ± 0.03 p < 0.001). Similarly, in the group with PSA value 10.1-30 ng/mL PSAD value was found significantly higher in patients with PV < 61,5 mL (0.47 ± 0.23 vs 0.17 ± 0.08 p < 0.001 ). The biopsy results suggest that in the group with PSA 2.5-10 ng/ml, in 29 of the patients with PV < 43,5 mL (69%) cancer was detected while in 13 patients (31%) no cancer was detected. While in 19 patients with PV > 43,5 mL (18,6%) cancer was found, in 83 patients (81,4%) no cancer was detected (p < 0.001). In the group with PSA value 10.1-30 ng/mL, in 21 patients with PV < 61,5 mL (67.7%) cancer was observed while only in10 patients (32.3%) no cancer was seen. In 5 patients with PV > 61,5 mL (13.9%) cancer was found while in 31 patients (86.1%) no cancer was observed (p < 0.001). Conclusions: Identifying men at increased risk for having a biopsy detectable prostate cancer should consider PSA, f/t PSA Ratio, an estimate of prostate volume. Prostate volume in PC was found lower.

Keywords: prostate cancer, prostate volume, prostate specific antigen, free/total PSA ratio

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Authors: R. Alramyan, S. Alsalamah, R. Alrashed, R. Alakel, F. Altheyeb, M. Alessa

Abstract:

Background: Nutritional support with total parenteral nutrition (TPN) is usually commenced with hematopoietic stem cell transplantation (HSCT) patients. However, it has its benefits and risks. Complications related to central venous catheter such as infections, and metabolic disturbances, including abnormal liver function, is usually of concern in such patients. Methods: A retrospective charts review of all pediatric patients who underwent HSCT between the period 2015-2018 in a tertiary hospital in Riyadh, Saudi Arabia. Patients' demographics, types of conditioning, type of nutrition, and patients' outcomes were collected. Statistical analysis was conducted using SPSS version 22. Frequencies and percentages were used to describe categorical variables. Mean, and standard deviation were used for continuous variables. A P value of less than 0.05 was considered as statically significant. Results: a total of 162 HSCTs were identified during the period mentioned. Indication of allogenic transplant included hemoglobinopathy in 50 patients (31%), acute lymphoblastic leukemia in 21 patients (13%). TPN was used in 96 patients (59.30%) for a median of 14 days, nasogastric tube feeding (NGT) in 16 (9.90%) patients for a median of 11 days, and 71 of patients (43.80%) were able to tolerate oral feeding. Out of the 96 patients (59.30%) who were dependent on TPN, 64 patients (66.7%) had severe mucositis in comparison to 17 patients (25.8%) who were either on NGT or tolerated oral intake. (P-value= 0.00). Sinusoidal obstruction syndrome (SOS) was seen in 14 patients (14.6%) who were receiving TPN compared to none in non-TPN patients (P=value 0.001). Moreover, majority of patients who had SOS received myeloablative conditioning therapy for non-malignant disease (hemoglobinopathy). However, there were no statistically significant differences in Graft-vs-Host Disease (both acute and chronic), bacteremia, and patient outcome between both groups. Conclusions: Nutritional support using TPN is used in majority of patients, especially post-myeloablative conditioning associated with severe mucositis. TPN was associated with VOD, especially in hemoglobinopathy patients who received myeloablative therapy. This may emphasize on use of preventative measures such as fluid restriction, use of diuretics, or defibrotide in high-risk patients.

Keywords: hematopoeitic stem cell transplant, HSCT, stem cell transplant, sinusoidal obstruction syndrome, total parenteral nutrition

Procedia PDF Downloads 127

Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

Abstract:

Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

Procedia PDF Downloads 112

Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

Abstract:

Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) is above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) cytogenetic analysis of peripheral blood lymphocytes was used. Gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistic analysis the Mann-Whitney U-test was used. The mean Cr level in blood of exposed group was 0.095 µmol/l (0.019 min - max 0.504). No value exceeds the average normal value. The mean value Cr in urine was 7.9 µmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs. 0.80% and CSA-type 0.96% vs. 0.90%). In the number of total CA statistical difference was observed between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44% <1.82% <2.13%). A statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups was observed (1.22% vs. 0.59%, P <0.05). The work place is usually higher source of exposure to harmful factors. Workers need consistent and frequent health control. In assessing the risk of adverse effects of metals it is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: CCND1, genotoxicity, polymorphism, stainless steel, welders

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Authors: Mohamed Shafi Bin Mahboob Ali

Abstract:

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

Keywords: synchronous, colon, tumor, adenocarcinoma

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

Abstract:

Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Yu-Mei Hsueh, Cheng-Shiuan Tsai, Chao-Yuan Huang

Abstract:

Prostate Cancer (PC) is a malignant tumor originated in prostate and is a second common male’s cancer in the world. Incidence of PC in Asia countries, have still been rising over the past few decades. As an antioxidant, selenium can slow down prostate cancer tumor progression, but the association between plasma selenium levels and risk of aggressive prostate cancer may be modified by different genotype of selenoprotein. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinaty total arsenic, and prostate cancer. Two hundred ninety five pathologically-confirmed cases of PC and 295 cancer-free controls were individually matched to case subjects by age (± 5 years) were recruited from Department of Urology of National Taiwan University Hospital, Taipei Municipal Wan Fang Hospital and Taipei Medical University Hospital. Personal interview and biospeciment of urine and blood collection from participants were conducted by well-trained interviewers after participants’ informed consent was obtained. Plasma selenium was measured by an inductively coupled plasma mass. Urinary arsenic concentration was detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of SEPP1rs3797310 and SEP15 rs5859 were determined using polymerase chain reaction-restriction fragment length polymorphism method. The higher plasma selenium was the lower OR of PC with a dose-response relationship. Prostate cancer patients with high plasma selenium had low tumor stage and grade. Participants carried SEPP1rs3797310 CT+TT genotype compared to those with CC genotype had a lower OR of PC in crude model; then this relationship was disappeared after confounder was adjusted. Prostate cancer patients with high urinary total arsenic concentration had high tumor stage and grade. Urinary total arsenic concentration was significantly positively related with plasma selenium and prostate specific antigen concentration. Participants with lower plasma selenium concentration and higher urinary total arsenic concentration compared to those with higher plasma selenium concentration and lower urinary total arsenic concentration had a higher OR of PC with a dose-response relationship.

Keywords: prostate cancer, plasma selenium concentration, urinary arsenic concentration, prostate specific antigen

Procedia PDF Downloads 437

Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

Abstract:

Introduction: Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) in steel was above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. Materials and Methods: The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) was used cytogenetic analysis of peripheral blood lymphocytes, gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistical analysis was used the Mann-Whitney U-test. Results: The mean Cr level in exposed group was 0.095 mmol/l (0.019 min-max 0.504). No value does exceed the average normal value. The average value Cr in urine was 7.9 mmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs 0.80% and CSA-type 0.96% vs 0.90%). In the number of total CA was observed statistical difference between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44%<1.82%<2.13%). There was observed a statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups (1.22% vs. 0.59%, P<0.05). Discussion and conclusions: The work place is usually higher source of exposure to harmful factors. Workers need consistently and checked frequently health control. In assessing the risk of adverse effects of metals is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: genotoxicity, chromium, stainless steels, welders

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Authors: Priyal Chikhaliwala, Sudeshna Chandra

Abstract:

Liver cancer is one of the most common malignant tumors with poor prognosis. This is because liver cancer does not exhibit any symptoms in early stage of disease. Increased serum level of AFP is clinically considered as a diagnostic marker for liver malignancy. The present diagnostic modalities include various types of immunoassays, radiological studies, and biopsy. However, these tests undergo slow response times, require significant sample volumes, achieve limited sensitivity and ultimately become expensive and burdensome to patients. Considering all these aspects, electrochemical biosensors based on dendrimer-magnetic nanoparticles (MNPs) was designed. Dendrimers are novel nano-sized, three-dimensional molecules with monodispersed structures. Poly-amidoamine (PAMAM) dendrimers with eight –NH₂ groups using ethylenediamine as a core molecule were synthesized using Michael addition reaction. Dendrimers provide added the advantage of not only stabilizing Fe₃O₄ NPs but also displays capability of performing multiple electron redox events and binding multiple biological ligands to its dendritic end-surface. Fe₃O₄ NPs due to its superparamagnetic behavior can be exploited for magneto-separation process. Fe₃O₄ NPs were stabilized with PAMAM dendrimer by in situ co-precipitation method. The surface coating was examined by FT-IR, XRD, VSM, and TGA analysis. Electrochemical behavior and kinetic studies were evaluated using CV which revealed that the dendrimer-Fe₃O₄ NPs can be looked upon as electrochemically active materials. Electrochemical immunosensor was designed by immobilizing anti-AFP onto dendrimer-MNPs by gluteraldehyde conjugation reaction. The bioconjugates were then incubated with AFP antigen. The immunosensor was characterized electrochemically indicating successful immuno-binding events. The binding events were also further studied using magnetic particle imaging (MPI) which is a novel imaging modality in which Fe₃O₄ NPs are used as tracer molecules with positive contrast. Multicolor MPI was able to clearly localize AFP antigen and antibody and its binding successfully. Results demonstrate immense potential in terms of biosensing and enabling MPI of AFP in clinical diagnosis.

Keywords: alpha-fetoprotein, dendrimers, electrochemical biosensors, magnetic nanoparticles

Procedia PDF Downloads 117

Authors: Saniya Ablatt, Matthew Jacobsson, Jamie Whisler, Austin Forbes

Abstract:

Postoperative pancreatic fistula (POPF) is a complication that occurs in up to 41% of patients after pancreaticoduodenectomy. Although certain characteristics such as individual patient anatomy are known risk factors for POPF, the effect of barbed suture techniques remains underexplored. This study examines whether the use of Stratafix barbed suture versus PDS impacts the risk of developing POPF. After obtaining IRB exemption, a retrospective chart review was initiated involving patients who underwent pancreaticoduodenectomy for the treatment of malignant or premalignant lesions of the pancreas at our institution between April 1st 2020 and April 30th 2022. Patients were stratified into 2 groups respective to the technique used to suture the pancreatico-jejunal anastomosis: Group 1 was composed to patients in which 4.0 Stratafix® suture was used n=41. Group 1 was composed to patients in which 4.0 PDS suture was used n=42. Data regarding patient age, sex, BMI, presence or absence of biochemical leak, presence or absence of grade B & C postoperative pancreatic fistulas, rate and type of in hospital complication, rate of reoperation, 30 day readmission rate, 90 day mortality, and total mortality were compared between groups. 83 patients were included in our study with 42 receiving Stratafix and 41 receiving PDS (50.6% vs 49.4%). Stratafix patients had less biochemical leaks (0.0% vs 4.8%, p=0.19) and higher rates of POPF but this was not statistically significant (7.2% vs 2.4%, p=0.26). Additionally, there was no difference between the use of stratafix versus PDS on the risk of clinically relevant grade B or C POPF (p=0.26, OR=3.25 [CI= 0.74-16.43]). Of the independent variables including age, race, sex, BMI, and ASA class, BMI greater than 25 increased the risk of clinically relevant POPF by 7.7 times compared to patients with BMI less than 25 (p=0.03, OR=7.79 [1.04-88.51]). Despite no significant difference in primary outcomes, the Stratafix group had lower rates of secondary outcomes including 90-day mortality; bleeding, cardiac, and infectious complications; reoperation; and 30-day readmission. On statistical analysis, Stratafix decreased the risk of 30-day readmission (p=0.04, OR=0.21, CI=0.04-0.97) and had a marginally significant effect on the risk of reoperation (p=0.08, OR=0.24, CI=0.04-1.26). There was no difference between the use of Stratafix versus PDS on the risk of POPF (p=0.26). However, Stratafix decreased the risk of 30-day readmission (p=0.04) and BMI greater than 25 increased the risk of clinically relevant POPF (p=0.03).

Keywords: pancreas, hepatobiliary surgery, hepatobiliary, pancreatic leak, biochemical leak, fistula, pancreatic fistula

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

Abstract:

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

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

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