Search results for: malignant mesothelioma

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: Alexandru Grigorescu, Alexandra Protesanu

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Background: Approximately 34-67 percent of cancer patients experience an episode of uncontrolled pain during the course of their disease, depending on the stage. The aim is to provide evidence-based data for pain prevalence, diagnosis and treatment recommendations on an integrative model of medical oncology and palliative care for patients with cancer diagnostic in a day hospital. Patients and method: Consultation registers and electronic records of 166 Patients (Pts) were studied from April 2022 to March 2023. Pts with pain syndrome were selected. The pain was objectified by the visual pain scale. To elucidate the causes of the pain, investigations were carried out: bone scintigraphy, CT scan, and PET-CT. The analgesic treatments were represented by weak and strong morphine, radiotherapy, and bisphosphonates. Result: During the mentioned period, 166 oncological patients (74 women and 92 men) were treated in the oncology day hospitalization service. There were 1,500 consultations, 40 of which were only for pain. The neoplastic locations were: gynecological, malignant melanoma, breast, gastric, bronchopulmonary, colorectal, liver, pancreatic, bladder, and kidney. 70 Pts presented pain syndrome. The causes of the pain were represented by bone metastases, compressive tumors, and post-surgical status. Drug treatment: Tramadol 47 Pts, of which 10 switched to a major opioid (Oxycodonum, Morphine sulfate), 20 Pts were treated with Oxycodonum as the first intention. In 5 patients ry to rotated morphine, 20 Pts received palliative radiotherapy, 10 Pts were treated with bisphosphonates. 2 Pts required neurosurgery consultation for an antalgic intervention. 5 Pts had important adverse reactions to morphine. All patients and their families were advised by a medical oncologist and psychologist for a lifestyle change. Conclusions: The prevalence of pain was similar to that described in the literature. In most cases, the pain could be managed in the day hospital. Weak and strong morphine represented the main pain therapy. Palliative radiotherapy was the second most effective therapy. Treatment with bisphosphonates was useful. Surgical interventions were rarely indicated. Discussions with patients and their families regarding the lifestyle change were important.

Keywords: cancer pain, opioids, medical oncology, palliative care

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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

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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

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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

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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

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

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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

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

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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

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

Keywords: synchronous, colon, tumor, adenocarcinoma

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

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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

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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

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

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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

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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

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

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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: Shashi Sharma, V. K. Katiyar, Uaday Singh

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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.

Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling

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Authors: Rammah Abdlbagi, Egmen Tazcan, Kiriti Tripathi, Vinayagam Sudhakar, Thomas Swallow, Aakash Pai

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Introduction and Objectives: MRI has an increasing role in the diagnosis and staging of prostate cancer. Multiparametric MRI includes multiple sequences, including T2 weighting, diffusion weighting, and dynamic contrast enhancement (DCE). Administration of DCE is expensive, time-consuming, and requires medical supervision due to the risk of anaphylaxis. Biparametric MRI (bpMRI), without DCE, overcomes many of these issues; however, there is conflicting data on its accuracy. Furthermore, data on the concordance between bpMRI lesion and pathology specimen, as well as the rates of cancer stage upgrading after surgery, is limited within the available literature. This study aims to examine the diagnostic test accuracy of bpMRI in the diagnosis of prostate cancer and radiological assessment of prostate cancer staging. Specifically, we aimed to evaluate the ability of bpMRI to accurately localise malignant lesions to better understand its accuracy and application in MRI-targeted biopsies. Materials and Methods: One hundred and forty patients who underwent bpMRI prior to radical prostatectomy (RP) were retrospectively reviewed from a single institution. Histological grade from the prostate biopsy was compared with surgical specimens from RP. Clinically significant prostate cancer (csPCa) was defined as Gleason grade group ≥2. bpMRI staging was compared with RP histology. Results: Overall sensitivity of bpMRI in diagnosing csPCa independent of location and staging was 98.87%. Of the 140 patients, 29 (20.71%) had their prostate biopsy histology upgraded at RP. 61 (43.57%) patients had csPca noted on RP specimens in areas that were not identified on the bpMRI. 55 (39.29%) had upstaging after RP from the original staging with bpMRI. Conclusions: Whilst the overall sensitivity of bpMRI in predicting any clinically significant cancer was good, there was notably poor concordance in the location of the tumour between bpMRI and eventual RP specimen. The results suggest that caution should be exercised when using bpMRI for targeted prostate biopsies and validates the continued role of systemic biopsies. Furthermore, a significant number of patients were upstaged at RP from their original staging with bpMRI. Based on these findings, bpMRI results should be interpreted with caution and can underestimate TNM stage, requiring careful consideration of treatment strategy.

Keywords: biparametric MRI, Ca prostate, staging, post prostatectomy histology

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Giselle Tran, Ralitza Parina, Phuong T. Nguyen

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Background/Aims: Pancreatic cysts (PC) have recently become an increasingly common entity, often diagnosed as incidental findings on cross-sectional imaging. Clinically, management of the lesions is difficult because of uncertainties in their potential for malignant degeneration. Prior series have reported that carcinoembryonic antigen (CEA), a biomarker collected from cyst fluid aspiration, has a high diagnostic accuracy for discriminating between mucinous and non-mucinous lesions, at the patient’s initial presentation. To the author’s best knowledge, no prior studies have reported PC CEA levels obtained from endoscopic ultrasound fine-needle aspiration (EUS-FNA) over years of serial EUS surveillance imaging. Methods: We report a consecutive retrospective series of 624 patients who underwent EUS evaluation for a PC between 11/20/2009 and 11/13/2018. Of these patients, 401 patients had CEA values obtained at the point of entry. Of these, 157 patients had two or more CEA values obtained over the course of their EUS surveillance. Of the 157 patients (96 F, 61 M; mean age 68 [range, 62-76]), the mean interval of EUS follow-up was 29.7 months [3.5-128]. The mean number of EUS procedures was 3 [2-7]. To assess CEA value fluctuations, we defined an appreciable increase in CEA as "spikes" – two-times increase in CEA on a subsequent EUS-FNA of the same cyst, with the second CEA value being greater than 1000 ng/mL. Using this definition, cysts with a spike in CEA were compared to those without a spike in a bivariate analysis to determine if a CEA spike is associated with poorer outcomes and the presence of high-risk features. Results: Of the 157 patients analyzed, 29 had a spike in CEA. Of these 29 patients, 5 had a cyst with size increase >0.5cm (p=0.93); 2 had a large cyst, >3cm (p=0.77); 1 had a cyst that developed a new solid component (p=0.03); 7 had a cyst with a solid component at any time during surveillance (p=0.08); 21 had a complex cyst (p=0.34); 4 had a cyst categorized as "Statistically Higher Risk" based on molecular analysis (p=0.11); and 0 underwent surgical resection (p=0.28). Conclusion: With serial EUS imaging in the surveillance of PC, an increase in CEA level defined as a spike did not predict poorer outcomes. Most notably, a spike in CEA did not correlate with the number of patients sent to surgery or patients with an appreciable increase in cyst size. A spike in CEA did not correlate with the development of a solid nodule within the PC nor progression on molecular analysis. Future studies should focus on the selected use of CEA analysis when patients undergo EUS surveillance evaluation for PCs.

Keywords: carcinoembryonic antigen (CEA), endoscopic ultrasound (EUS), fine-needle aspiration (FNA), pancreatic cyst, spike

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Authors: Gurbanova J., Majidova N., Ali-Zade S., Hasanova A., Mikailzade P.

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Currently, the problem of oncogynecological diseases is widespread and remains relevant in terms of quantitative growth. It is known that due to the increase in the number of benign diseases of the cervix, the development of precancerous conditions occurs. Benign diseases of the cervix represent the most common gynecological problem, which are often precursors of malignant neoplasms, especially cervical cancer. According to statistics, benign diseases of the cervix cover 25-45% of all gynecological diseases. Among women's oncogynecological diseases, cervical cancer ranks second in the world after breast cancer and ranks first in the mortality rate among oncological diseases in economically underdeveloped countries. We performed a comprehensive clinical and laboratory examination of 130 women aged 18 to 73 with benign cervical diseases. 59 (38.5%) women of reproductive age, as well as 39 (30%) premenopausal and 41 (31.5%) menopausal patients, participated in the study. Detailed anamnesis was collected from all patients, objective and gynecological examination was performed, laboratory and instrumental examinations (USM, IPV DNA, smear microscopy, and PCR bacteriological examination of sexually transmitted infections), simple and extended colposcopy, liquid-based РАР-smear smear and РАР-classic smear examinations were conducted. As a result of the research, the following nosological forms were found in women with benign diseases of the cervix: non-specific vaginitis in 10 (7.7%) cases; ectopia, endocervicitis - 60(46.2%); cervical ectropion - 7(5.4%); cervical polyp - 9(6.9%); cervical leukoplakia - 15(11.5%); atrophic vaginitis - 7(5.4%); condyloma - 12(9.2%); cervical stenosis - 2(1.5%); endometriosis of the cervix - was noted in 8 (6.2%) cases (p<0.001), respectively. Characteristics of the menstrual cycle among the examined women: normal cycle in 97 (74.6%) cases; oligomenorrhea – 23 (17.7%); polymenorrhea – 4(3.1%); algomenorrhea – noted in 6 (4.6%) cases (p<0.001). Cytological examination showed that: the specificity of liquid-based cytology was 76.2%, and the traditional PAP test was set at 70.6%. The overall diagnostic value was calculated to be 86% in liquid-based cytology and 78.5% in conventional PAP tests. Treatment of women with benign diseases of the cervix was carried out by diathermocoagulation method and "FOTEK EA 141M" device. It should be noted that 6 months after the treatment, after treatment with the "FOTEK EA 141M" device, there was no relapse in any patient. Recurrence was found in 23.7% of patients after diathermoelectrocoagulation. Thus, it is clear from the above that the study of cervical pathologies, the determination of optimal examinations, and effective treatment methods is one of the urgent problems facing obstetrics and gynecology.

Keywords: cervical cancer, cytological examination, PAP-smear, non-specific vaginitis

Procedia PDF Downloads 117

Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: A. P. Pashkov

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The number of environmental factors that adversely affect children's health is growing every year; their combination in each territory is different. The contribution of socio-economic factors to the health status of the younger generation is increasing. It is the child’s body that is most sensitive to changes in environmental conditions, responding to this with a deterioration in health. Over the past years, scientists have determined the influence of environmental factors and the incidence of children. Currently, there is a tendency to study regional characteristics of the interaction of a combination of environmental factors with the child's body. The aim of the work was to identify trends in the primary non-infectious morbidity of the children of the Altai Territory as a unique region that combines territories with different levels of environmental quality indicators, as well as to assess the effect of atmospheric air, drinking water and socio-economic indicators on the incidence of children in the region. An unfavorable tendency has been revealed in the region for incidence of such nosological groups as neoplasms, including malignant ones, diseases of the endocrine system, including obesity and thyroid disease, diseases of the circulatory system, digestive diseases, diseases of the genitourinary system, congenital anomalies, and respiratory diseases. Between some groups of diseases revealed a pattern of geographical distribution during mapping and a significant correlation. Some nosologies have a relationship with socio-economic indicators for an integrated assessment: circulatory system diseases, respiratory diseases (direct connection), endocrine system diseases, eating disorders, and metabolic disorders (feedback). The analysis of associations of the incidence of children with average annual concentrations of substances that pollute the air and drinking water showed the existence of reliable correlation in areas of critical and intense degree of environmental quality. This fact confirms that the population living in contaminated areas is subject to the negative influence of environmental factors, which immediately affects the health status of children. The results obtained indicate the need for a detailed assessment of the influence of environmental factors on the incidence of children in the regional aspect, the formation of a database, and the development of automated programs that can predict the incidence in each specific territory. This will increase the effectiveness, including economic of preventive measures.

Keywords: incidence of children, regional features, socio-economic factors, environmental factors

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Authors: Maha Atout, Pippa Hemingway, Jane Seymour

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Background: A mixed method systematic review was undertaken in order to explore issues related to the experiences of health care providers and parents in the care of children with palliative care needs. The aims of this systematic review were to identify existing evidence about the experiences of communication in the care of children with palliative care needs, to appraise the research conducted in this area and to identify gaps in the literature in order to recommend for future related studies. Method: A mixed method systematic review of research on the experience of communication in the care of children with palliative care needs, conducted with parents and health professionals was undertaken. The electronic databases of CINAHL, Cochrane, PubMed, OVID, Social Care Online, Web of Science, Scopus, and ProQuest were searched for the period of 2000-2016. Inclusion was limited to studies of communication experience in the care of children with palliative care needs. Result: Thirty-eight studies were found. The studies were conducted in a variety of countries: Uganda, Jordan, USA, UK, Taiwan, Turkey, Ireland, Poland, Brazil, Australia, Switzerland, Sweden, Netherland, Lebanon, Spain, Greece, and China. The current review shows that parents tend to protect their children when they are discussing their illnesses with them, particularly where they have a life-threatening or life-limiting condition. The approach of parents towards the discussion of sensitive issues concerning death with their children is significantly affected by the cultural background of the families. Conservative cultures encourage collusion behaviours which tend to keep children unaware of the incurable nature of the disease. The major communication challenges reported by health professionals are facing difficulties in judging how much information should be given to parents, responding to difficult questions, conflicts with families and inadequate skills to support grieving families. Conclusion: It is probably significant for the future studies to consider the change of parent-child communication experience over time in order to understand how the parents could change their interaction styles with their children according to the different stages of their children’s disease. Moreover, further studies are required to investigate the experience of communication of parents of children with non-malignant life-threatening and life-limiting illnesses.

Keywords: children with life-threatening or life- limiting illnesses, end of life, experience of communication, healthcare care providers, paediatric palliative care

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Authors: Ugo Rovigatti

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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

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Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: Sandra Adarve, Jhon Osorio

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Uncertainty has been studied in patients with different types of cancer, except in patients with hematologic cancer and undergoing transplantation. The purpose of this study was to identify factors associated with uncertainty in adults patients with malignant hemato-oncology diseases who are scheduled to undergo hematopoietic stem cell transplantation based on Merle Mishel´s Uncertainty theory. This was a cross-sectional study with an analytical purpose. The study sample included 50 patients with leukemia, myeloma, and lymphoma selected by non-probability sampling by convenience and intention. Sociodemographic and clinical variables were measured. Mishel´s Scale of Uncertainty in Illness was used for the measurement of uncertainty. A bivariate and multivariate analyses were performed to explore the relationships and associations between the different variables and uncertainty level. For this analysis, the distribution of the uncertainty scale values was evaluated through the Shapiro-Wilk normality test to identify statistical tests to be used. A multivariate analysis was conducted through a logistic regression using step-by-step technique. Patients were 18-74 years old, with a mean age of 44.8. Over time, the disease course had a median of 9.5 months, an opportunity was found in the performance of the transplantation of < 20 days for 50% of the patients. Regarding the uncertainty scale, a mean score of 95.46 was identified. When the dimensions of the scale were analyzed, the mean score of the framework of stimuli was 25.6, of cognitive ability was 47.4 and structure providers was 22.8. Age was identified to correlate with the total uncertainty score (p=0.012). Additionally, a statistically significant difference was evidenced between different religious creeds and uncertainty score (p=0.023), education level (p=0.012), family history of cancer (p=0.001), the presence of comorbidities (p=0.023) and previous radiotherapy treatment (p=0.022). After performing logistic regression, previous radiotherapy treatment (OR=0.04 IC95% (0.004-0.48)) and family history of cancer (OR=30.7 IC95% (2.7-349)) were found to be factors associated with the high level of uncertainty. Uncertainty is present in high levels in patients who are going to be subjected to bone marrow transplantation, and it is the responsibility of the nurse to assess the levels of uncertainty and the presence of factors that may contribute to their presence. Once it has been valued, the uncertainty must be intervened from the identified associated factors, especially all those that have to do with the cognitive capacity. This implies the implementation and design of intervention strategies to improve the knowledge related to the disease and the therapeutic procedures to which the patients will be subjected. All interventions should favor the adaptation of these patients to their current experience and contribute to seeing uncertainty as an opportunity for growth and transcendence.

Keywords: hematopoietic stem cell transplantation, hematologic diseases, nursing, uncertainty

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Authors: Yung-Chih Kuo, I-Hsin Wang

Abstract:

Catanionic solid lipid nanoparticles (CASLNs) with surface wheat germ agglutinin (WGA) and lactoferrin (Lf) were formulated for entrapping and releasing etoposide (ETP), crossing the blood–brain barrier (BBB), and inhibiting the growth of glioblastoma multiforme (GBM). Microemulsified ETP-CASLNs were modified with WGA and Lf for permeating a cultured monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and for treating malignant U87MG cells. Experimental evidence revealed that an increase in the concentration of catanionic surfactant from 5 μM to 7.5 μM reduced the particle size. When the concentration of catanionic surfactant increased from 7.5 μM to 12.5 μM, the particle size increased, yielding a minimal diameter of WGA-Lf-ETP-CASLNs at 7.5 μM of catanionic surfactant. An increase in the weight percentage of BW from 25% to 75% enlarged WGA-Lf-ETP-CASLNs. In addition, an increase in the concentration of catanionic surfactant from 5 to 15 μM increased the absolute value of zeta potential of WGA-Lf-ETP-CASLNs. It was intriguing that the increment of the charge as a function of the concentration of catanionic surfactant was approximately linear. WGA-Lf-ETP-CASLNs revealed an integral structure with smooth particle contour, displayed a lighter exterior layer of catanionic surfactant, WGA, and Lf and showed a rigid interior region of solid lipids. A variation in the concentration of catanionic surfactant between 5 μM and 15 μM yielded a maximal encapsulation efficiency of ETP ata 7.5 μM of catanionic surfactant. An increase in the concentration of Lf/WGA decreased the grafting efficiency of Lf/WGA. Also, an increase in the weight percentage of ETP decreased its encapsulation efficiency. Moreover, the release rate of ETP from WGA-Lf-ETP-CASLNs reduced with increasing concentration of catanionic surfactant, and WGA-Lf-ETP-CASLNs at 12.5 μM of catanionic surfactant exhibited a feature of sustained release. The order in the viability of HBMECs was ETP-CASLNs ≅ Lf-ETP-CASLNs ≅ WGA-Lf-ETP-CASLNs > ETP. The variation in the transendothelial electrical resistance (TEER) and permeability of propidium iodide (PI) was negligible when the concentration of Lf increased. Furthermore, an increase in the concentration of WGA from 0.2 to 0.6 mg/mL insignificantly altered the TEER and permeability of PI. When the concentration of Lf increased from 2.5 to 7.5 μg/mL and the concentration of WGA increased from 2.5 to 5 μg/mL, the enhancement in the permeability of ETP was minor. However, 10 μg/mL of Lf promoted the permeability of ETP using Lf-ETP-CASLNs, and 5 and 10 μg/mL of WGA could considerably improve the permeability of ETP using WGA-Lf-ETP-CASLNs. The order in the efficacy of inhibiting U87MG cells was WGA-Lf-ETP-CASLNs > Lf-ETP-CASLNs > ETP-CASLNs > ETP. As a result, WGA-Lf-ETP-CASLNs reduced the TEER, enhanced the permeability of PI, induced a minor cytotoxicity to HBMECs, increased the permeability of ETP across the BBB, and improved the antiproliferative efficacy of U87MG cells. The grafting of WGA and Lf is crucial to control the medicinal property of ETP-CASLNs and WGA-Lf-ETP-CASLNs can be promising colloidal carriers in GBM management.

Keywords: catanionic solid lipid nanoparticle, etoposide, glioblastoma multiforme, lactoferrin, wheat germ agglutinin

Procedia PDF Downloads 237

Authors: Maierhaba Mijiti

Abstract:

Objective：The aim is to understand the relationship between the expression level of the long-non-coding RNA LINC AC008063 and the clinicopathological parameters of patients with head and neck squamous cell carcinoma (HNSCC), and to clarify the biological function of LINC AC008063 in HNSCC cells. Moreover, it provides a potential biomarker for the diagnosis, treatment, and prognosis evaluation of HNSCC. Methods: The expression level of LINC AC008063 in the HNSCC was analyzed using transcriptome sequencing data from the TCGA (The cancer genome atlas) database. The expression levels of LINC AC008063 in human embryonic lung diploid cells 2BS, human immortalized keratinocytes HACAT, HNSCC cell lines CAL-27, Detroit562, AMC-HN-8, FD-LSC-1, FaDu and WSU-HN30 were determined by real-time quantitative PCR (qPCR). RNAi (RNA interference) was introduced for LINC AC008063 knockdown in HNSCC cell lines, the localization and abundance analysis of LINC AC008063 was determined by RT-qPCR, and the biological functions were examined by CCK-8, clone formation, flow cytometry, transwell invasion and migration assays, Seahorse assay. Results: LINC AC008063 was upregulated in HNSCC tissue (P<0.001), and verified b CCK-8, clone formation, flow cytometry, transwell invasion and migration assays, Seahorse assayy qPCR in HNSCC cell lines. The survival analysis revealed that the overall survival rate (OS) of patients with high LINC AC008063 expression group was significantly lower than that in the LINC AC008063 expression group, the median survival times for the two groups were 33.10 months and 61.27 months, respectively (P=0.002). The clinical correlation analysis revealed that its expression was positively correlated with the age of patients with HNSCC (P<0.001) and positively correlated with pathological state (T3+T4＞T1+T2, P=0.03). The RT-qPCR results showed that LINC AC008063 was mainly enriched in cytoplasm (P=0.01). Knockdown of LINC AC008063 inhibited proliferation, colony formation, migration and invasion; the glycolytic capacity was significantly decreased in HNSCC cell lines (P＜0.05). Conclusion: High level of LINC AC008063 was associated with the malignant progression of HNSCC as well as promoting the important biological functions of proliferation, colony formation, migration and invasion; in particular, the glycolytic capacity was decreased in HNSCC cells. Therefore, LINC AC008063 may serve as a potential biomarker for HNSCC and a distinct molecular target to inhibit glycolysis.

Keywords: head and neck squamous cell carcinoma, oncogene, long non-coding RNA, LINC AC008063, invasion and metastasis

Procedia PDF Downloads 12