Search results for: ambulatory chemotherapy

Authors: Behzad Sinaei, Shahryar Sane, Behzad Kazemi Haki

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Children with different malignancies usually experience potential neurologic complications when treated with radiation therapy, especially if under frequent anesthesia. The aim of this study was to evaluate the neurologic problems associated with anesthesia in pediatrics treated with radiotherapy under anesthesia. The study was a cross-sectional experiment that consisted of 133 pediatric patients with different malignancies who needed anesthesia for performing radiotherapy and were referred to Omid Charity Hospital and Imam Khomeini University Hospital from 2014 to 2020 by the census. P-values less than 0.05 were considered statistically significant (P-value < 0.05). Anesthesia complications in this study were slight and insignificant. Some were due to the effects of the tumor on other important organs or either previous radiation therapy or chemotherapy. For safe anesthesia, considering the effects of tumors on body organs and the neurological complications they cause can greatly help reduce anesthesia complications in pediatrics under radiation therapy.

Keywords: anesthesia, neurologic complications, pediatrics, radiotherapy

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Rasime Kalkan, Emine Ikbal Atli, Ali Arslantaş, Muhsin Özdemir, Sevilhan Artan

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Glioblastoma (WHO grade IV), is the malignant form of brain tumor, the genetic background of the GBM is highly variable. The tumor mass of a GBM is multilayered and every tumor layer shows distinct characteristics with a different cell population. The treatment planning of GBM should be focused on the tumor genetic characteristics. We screened primary glioblastoma multiforme (GBM) in a population-based study for MGMT and RARβ methylation and IDH1 mutation correlated them with clinical data and treatment. There was no correlation between MGMT-promoter methylation and overall survival. The overall survival time of the patients with methylated RARβ was statically (OS;p<0,05) significance between the patients who were treated with chemotherapy and radiotherapy. Here we showed the status of IDH1 gene associatied with younger age. We demonstrated that the together with MGMT gene the RARβ gene should be used as a potantial treatment decision marker for GBMs.

Keywords: RARβ, primary glioblastoma multiforme, methylation, MGMT

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Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

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Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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Authors: Eghosa Morgan, Bourtarbouch Mahjouba, Heida El Ouahabi, Poluyi Edward, Diawarra Seylan

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Non-AIDS lymphoma, a type of primary central nervous system (CNS) lymphoma is an uncommon aggressive infiltrative malignant tumour involving several sites in the central nervous system, such as the periventricular region and leptomeninges. In this article, the authors presented a 26-year old man with painless progressive right exophthalmos and scalp swelling with no symptoms and signs of intracranial hypertension and hyperthyroidism. Magnetic resonance imaging (MRI) done revealed isointense masses with brilliant homogenous enhancement on contrast administration resembling a meningioma, with a dura tail – like attachment as seen in meningioma. He had surgery for the right orbital tumour and histopathological diagnosis confirmed our suspicion of lymphoma (B type). Steroid was given in the post-operative period which led to significant regression of the tumours, hence its description as ‘vanishing tumour’. He is presently receiving methotrexate-based chemotherapy and subsequently planned for radiotherapy.

Keywords: central nervous system (CNS), meningioma, non-aids lymphoma, orbital

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Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

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Authors: Nitin Dwivedi, Jigna Shah

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Brain tumor is metastatic neoplasm of central nervous system, in most of cases it is life threatening disease with low survival rate. Despite of enormous efforts in the development of therapeutics and diagnostic tools, the treatment of brain tumors and gliomas remain a considerable challenge in the area of neuro-oncology. The most reason behind of this the presence of physiological barriers including blood brain barrier and blood brain tumor barrier, lead to insufficient reach ability of therapeutic agents at the site of tumor, result of inadequate destruction of gliomas. So there is an indeed need empowerment of brain tumor imaging for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional different generations of dendrimer offer an improved effort for potentiate drug delivery at the site of brain tumor and gliomas. So this article emphasizes the innovative dendrimer approaches in tumor targeting, tumor imaging and delivery of therapeutic agent.

Keywords: blood brain barrier, dendrimer, gliomas, nanotechnology

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Authors: Ana L. Martins, Luis Orfão

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Healthcare systems have been subject to various research efforts aiming at process improvement under a lean approach. Another perspective, agility, has also been used, though in a lower scale, in order to analyse the ability of different hospital services to adapt to demand uncertainties. Both perspectives have a common denominator, the improvement of effectiveness and efficiency of the services in a healthcare setting context. Mixing the two approached allows, on one hand, to streamline the processes, and on the other hand the required flexibility to deal with demand uncertainty in terms of both volume and variety. The present research aims to analyse the impacts of the combination of both perspectives in the effectiveness and efficiency of an hospital service. The adopted methodology is based on a case study approach applied to the process of the ambulatory surgery service of Hospital de Lamego. Data was collected from direct observations, formal interviews and informal conversations. The analyzed process was selected according to three criteria: relevance of the process to the hospital, presence of human resources, and presence of waste. The customer of the process was identified as well as his perception of value. The process was mapped using flow chart, on a process modeling perspective, as well as through the use of Value Stream Mapping (VSM) and Process Activity Mapping. The Spaghetti Diagram was also used to assess flow intensity. The use of the lean tools enabled the identification of three main types of waste: movement, resource inefficiencies and process inefficiencies. From the use of the lean tools improvement suggestions were produced. The results point out that leagility cannot be applied to the process, but the application of lean and agility in specific areas of the process would bring benefits in both efficiency and effectiveness, and contribute to value creation if improvements are introduced in hospital’s human resources and facilities management.

Keywords: case study, healthcare systems, leagility, lean management

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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

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

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Authors: Qing Li, Maiko Kobayashi, Shigeyoshi Kumeda, Hiroko Ochiai, Toshiya Ochiai, Takashi Miura, Takahide Kagawa, Michiko Imai, Toshiaki Otsuka, Tomoyuki Kawada

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In the present study, we investigated the effects of a forest bathing program on cardiovascular and metabolic parameters. Nineteen healthy male subjects (mean age: 51.3 ± 8.8 years) were selected after obtaining informed consent. These subjects took day trips to a forest park named Akasawa Shizen Kyuyourin, Agematsu, Nagano Prefecture (situated in central Japan), and to an urban area of Nagano Prefecture as a control in August 2015. On both trips, they walked 2.6 km for 80 min each in the morning and afternoon on Saturdays. Blood and urine were sampled in the morning before and after each trip. Cardiovascular and metabolic parameters were measured. Blood pressure and pulse rate were measured by an ambulatory automatic blood pressure monitor. The Japanese version of the profile of mood states (POMS) test was conducted before, during and after the trips. Ambient temperature and humidity were monitoring during the trips. The forest bathing program significantly reduced pulse rate, and significantly increased the score for vigor and decreased the scores for depression, fatigue, and confusion in the POMS test. The levels of urinary noradrenaline and dopamine after forest bathing were significantly lower than those after urban area walking, suggesting the relaxing effect of the forest bathing program. The level of adiponectin in serum after the forest bathing program was significantly greater than that after urban area walking. There was no significant difference in blood pressure between forest and urban area trips during the trips.

Keywords: ambient temperature, blood pressure, forest bathing, forest therapy, human health, POMS, pulse rate

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Authors: Mthokozisi B. C. Simelane

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Despite the various efforts by governmental and non-governmental organizations aimed at eradicating the disease, malaria is said to kill a child every 30 seconds. Traditional healers use different concoctions prepared from medicinal plants to treat malaria. In the quest to bio-prospect plant-derived triterpenes for anti-malaria activity, we report here the in vivo antiplasmodial activity of ursolic acid acetate (ursolic acid isolated from dichloromethane extract of Mimusops caffra was chemically modified to its acetate derivative). The transdermal administration of ursolic acid acetate (UAA) dose dependently showed complete inhibition of the parasites’ growth at the highest concentration of 400 mg/kg after 15 days of Plasmodium berghei infection. UAA prevented the in vitro aggregation of MDH but did not prevent the expression of PfHsp 70 in E. coli XL1 blue cells. It, however, enhanced PfHsp70 ATPase activity with the specific activity of 65 units (amount of phosphate released 73.83 nmolPi/min.mg). Ursolic acid acetate prevented the formation of hemozoin (60 ± 0.02% at 6 mg/ml). The results suggest that Ursolic acid acetate possesses potential anti-malaria properties.

Keywords: Mimusops caffra, ursolic acid acetate, hemozoin, Malaria

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Authors: Yanling Li, Linying Ji, Zita Oravecz, Timothy R. Brick, Michael D. Hunter, Sy-Miin Chow

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Assessing several individuals intensively over time yields intensive longitudinal data (ILD). Even though ILD provide rich information, they also bring other data analytic challenges. One of these is the increased occurrence of missingness with increased study length, possibly under non-ignorable missingness scenarios. Multiple imputation (MI) handles missing data by creating several imputed data sets, and pooling the estimation results across imputed data sets to yield final estimates for inferential purposes. In this article, we introduce dynr.mi(), a function in the R package, Dynamic Modeling in R (dynr). The package dynr provides a suite of fast and accessible functions for estimating and visualizing the results from fitting linear and nonlinear dynamic systems models in discrete as well as continuous time. By integrating the estimation functions in dynr and the MI procedures available from the R package, Multivariate Imputation by Chained Equations (MICE), the dynr.mi() routine is designed to handle possibly non-ignorable missingness in the dependent variables and/or covariates in a user-specified dynamic systems model via MI, with convergence diagnostic check. We utilized dynr.mi() to examine, in the context of a vector autoregressive model, the relationships among individuals’ ambulatory physiological measures, and self-report affect valence and arousal. The results from MI were compared to those from listwise deletion of entries with missingness in the covariates. When we determined the number of iterations based on the convergence diagnostics available from dynr.mi(), differences in the statistical significance of the covariate parameters were observed between the listwise deletion and MI approaches. These results underscore the importance of considering diagnostic information in the implementation of MI procedures.

Keywords: dynamic modeling, missing data, mobility, multiple imputation

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: T. Nalowa, L. Foncha, S. Eposi

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Prostate enlargement, prostate cancer are major global health problems affecting many men as they advance in age. It is highly recommended to encourage older men to get Prostate Specific Antigen test screening frequently. Conventional treatments like radiation, chemotherapy are associated with many side effects. And this situation is a call for concern. Traditional medicine is affordable, easily prepared with little or no side effects and it contains many phytochemicals. The study aims to find the cure for prostate cancer and prostate enlargement by extracting products from plant tissues of specific herbs to determine anti-inflammatory, anti-cancer, and anti-hematuria properties. Descriptive statistical analysis was applied to describe the data process. The commonly used method of preparation was extraction. Overall, 40 patients were classified based on their medical conditions on their underlying user report. Rural communities in Fako are rich sources of plants with medicinal properties. The used plants consequently provide basic information and aid to investigate the cure of prostate cancer and prostate enlargement, with great significance.

Keywords: cancer, enlargement, metastases, prostate

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Conor Mccartney, Mark Lee

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Background: An essential component in ambulatory breast augmentation surgery is good analgesia. The demographic undergoing this operation is usually fit, low risk with few comorbidities. These patients do not require long-term hospitalization and do not want to spend excessive time in the hospital for financial reasons. Opiate analgesia can have significant side effects such as nausea, vomiting and sedation. Reducing volumes of postoperative opiates allows faster ambulation and discharge from day surgery. We have developed two targeted nerve blocks that can be applied by the operating surgeon in a matter of seconds under direct vision, not requiring imaging. Anecdotally we found that these targeted nerve blocks reduced opiate requirements and allowed accelerated discharge and faster return to normal activities. This was then tested in a prospective randomized, double-blind trial. Methods: 20 patients were randomized into saline (n = 10) or Ropivicaine adrenaline solution (n = 10). The operating surgeon and anesthetist were blinded to the solution. All patients were closely followed up and morphine equivalents were accurately recorded. Follow-up pain scores were recorded using the Overall Benefit of Analgesia pain questionnaire. Findings: The Ropivicaine nerve blocks significantly reduced opiate requirements postoperatively (p<0.05). Pain scores were significantly decreased in the study group (p<0.05). There were no side effects attributable to the nerve blocks. Conclusions: Intraoperative targeted nerve blocks significantly reduce postoperative opiate requirements in breast augmentation surgery. This results in faster recovery and higher patient satisfaction.

Keywords: breast augmentation, nerve block, postoperative recovery, opiate analgesia, inter pectoral block, sub serratus block

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Authors: Teodora Mocan, Matea Cristian, Cornel Iancu, Flaviu A. Tabaran, Florin Zaharie, Bartos Dana, Lucian Mocan

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Colon cancer (CC) a lethal human malignancy, is one of the most commonly diagnosed cancer. With its high increased mortality rate, as well as low survival rate combined with high resistance to chemotherapy CC, represents one of the most important global health issues. In the presented research, we have developed a distinct nanostructured colon carcinoma vaccine model based on a nano-biosystem composed of 39 nm gold nanoparticles conjugated to colon cancer epitopes. We prove by means of proteomic analysis, immunocytochemistry, flow cytometry and hyperspectral microscopy that our developed nanobioconjugate was able to contribute to an optimal prophylactic effect against CC by promoting major histocompatibility complex mediated (MHC) antigen presentation by dendritic cells. We may conclude that the proposed immunoprophylactic approach could be more effective than the current treatments of CC because it promotes recognition of the tumoral antigens by the immune system.

Keywords: anticancer vaccine, colon cancer, gold nanoparticles, tumor antigen

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Sanela Slavkovic, Congor Nad, Spela Golubovic

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Background: The diagnosis of multiple sclerosis (MS) is a major life challenge and has repercussions on all aspects of the daily functioning of those attained by it – personal activities, social participation, and quality of life. Regular follow-up of only the neurological status is not informative enough so that it could provide data on the sort of support and rehabilitation that is required. Objective: The aim of this study was to establish the current level of functioning of persons attained by MS and the factors that influence it. Methods: The study was conducted in Serbia, on a sample of 108 persons with relapse-remitting form of MS, aged 20 to 53 (mean 39.86 years; SD 8.20 years). All participants were fully ambulatory. Methods applied in the study include Expanded Disability Status Scale-EDSS and World Health Organization Disability Assessment Schedule, WHODAS 2.0 (36-item version, self-administered). Results: Participants were found to experience the most problems in the domains of Participation, Mobility, Life activities and Cognition. The least difficulties were found in the domain of Self-care. Symptom duration was the only control variable with a significant partial contribution to the prediction of the WHODAS scale score (β=0.30, p < 0.05). The total EDSS score correlated with the total WHODAS 2.0 score (r=0.34, p=0.00). Statistically significant differences in the domain of EDSS 0-5.5 were found within categories (0-1.5; 2-3.5; 4-5.5). The more pronounced a participant’s EDSS score was, although not indicative of large changes in the neurological status, the more apparent the changes in the functional domain, i.e. in all areas covered by WHODAS 2.0. Pyramidal (β=0.34, p < 0.05) and Bowel and bladder (β=0.24, p < 0.05) functional systems were found to have a significant partial contribution to the prediction of the WHODAS score. Conclusion: Measuring functioning and disability is important in the follow-up of persons suffering from MS in order to plan rehabilitation and define areas in which additional support is needed.

Keywords: disability, functionality, multiple sclerosis, rehabilitation

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

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

Keywords: endocrine therapy, alopecia, breast cancer, Tunisia

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Authors: Bhargavi Santebennur Dwarakanath, Praveen Vadakke Kamath, Savitha Janakiraman

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Cervical cancer is one of the leading causes of mortality in women and is the second most common malignancy worldwide. Lovastatin, a non polar, anticholesterol drug which also exerts antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties in human cervical cancer cell lines (HeLa). The growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cell lines were investigated by determining its influence on cytotoxicity, Mitochondrial Membrane Potential (MMP), DNA fragmentation and antioxidant property (Hydroxy radical scavenging effect and the levels of total reduced glutathione). Flow cytometry analysis by propidium iodide staining confirmed the induction of apoptotic cell death and revealed cell cycle arrest at G0/G1 phase. Results of the study give leads for anticancer effects of lovastatin and its potential efficacy in the chemotherapy of cervical cancer.

Keywords: apoptosis, Aspergillus terreus, cervical cancer, lovastatin

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Authors: Ç. Erdoğan, T. Turan

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Pediatric cancer patients experience multiple distressing, challenges, physical symptom such as fatigue, pain, sleep disturbance, and balance impairment that continue years after treatment completion. In recent years, yoga is often used in children with cancer to cope with these symptoms. Yoga practice is defined as a unique physical activity that combines physical practice, breath work and mindfulness/meditation. Yoga is an increasingly popular mind-body practice also characterized as a mindfulness mode of exercise. This study aimed to evaluate the impact of yoga intervention of children with cancer. This article planned searching the literature in this field. It has been determined that individualized yoga is feasible and provides benefits for inpatient children, improves health-related quality of life, physical activity levels, physical fitness. After yoga program, children anxiety score decreases significantly. Additionally, individualized yoga is feasible for inpatient children receiving intensive chemotherapy. As a result, yoga is an alternative and complementary medicine that can be safely used in children with cancer.

Keywords: cancer treatment, children, nursing, yoga

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Authors: Ines Zemni, Maher Slimane, Jamel Ben Hassouna, Khaled Rahal

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Background: Neurofibromatosis type 1 (NF1) is a genetic disease, which is associated with an increased risk of developing different malignancies including breast cancer. The association between NF1 band breast sarcoma is a rare entity. Herein we present a 25-year-old woman with NF1 who had fibrosarcoma of the left breast. Case presentation: The patient has multiple thoraco-abdominal 'café au lait' spots. Clinical examination showed a lump of the left breast measuring 9 cm of diameter, which was noticed for 6 months. There was a left inguinal mass of 6 cm of diameter. The patient underwent first a left lumpectomy. Histopathological exam revealed a high-grade fibrosarcoma of the left breast measuring 7.5 cm. Three months later, the patient underwent a left mastectomy and excision of the inguinal mass, which was a neurofibroma. An adjuvant chemotherapy and radiation therapy were indicated, but not applied because of the timeout. The patient is now alive after a follow up of 6 years, with no loco-regional recurrence or metastasis. Conclusion: The relationship between NF1 and breast cancer need to be more clarified by further studies. Establishing a specific screening program of these patients may help to make an earlier diagnosis of breast cancer.

Keywords: neurofibromatosis, breast, sarcoma, cancer

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Authors: Nabila N. El-Maraghy, Amany Essa, Yousra Abdel–Mottaleb, Nada Ismail

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The use of combination of chemotherapy and natural products to influence the cell death with low doses of chemotherapeutic agents and few side effects has recently emerged as a new method of cancer therapy. Aim: Evaluation the modulatory effect of Thymoquinone on HepG2 cells treated with Sorafenib. Methods: Hepatocellular Carcinoma HepG2 cell line was treated with Sorafenib and TQ individually and in combination. The effect of these treatments on cell viability (MTT assay), apoptosis (Expression of Caspase-3) and oxidative markers (GSH content and extent of lipid peroxidation) was determined. Results: When compared the effect of both agents alone and the combination of the IC50 of Sorafenib and the IC50 TQ, the combination resulted in reduction of cell inhibition and apoptosis and antagonize their actions on GSH content and extent of lipid peroxidation which are increased. This study showed potent anti-tumor activity of both TQ and Sorafenib separately on HepG2 but upon combination surprisingly they interacted and give antagonistic effect. Conclusion: Co-treatment resulted in antagonistic interaction between Sorafenib and Thymoquinone.

Keywords: antagonism, hepatocellular carcinoma, sorafenib, thymoquinone

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Authors: Javier Comes Fayos, Isabel Rodríguez Moreno, Sara Bressanutti, Marisol Lila, Angel Romero Martínez, Luis Moya Albiol

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Empathy is a cognitive-affective capacity whose deterioration is associated with aggressive behaviour. Deficient affective processing is one of the predominant risk factors in men convicted of intimate partner violence (IPV perpetrators), since it makes their capacity to empathize very difficult. The objective of this study is to compare the response of electrodermal activity (EDA), as an indicator of emotionality, to an empathic induction task, between IPV perpetrators and men without a history of violence. The sample was composed of 51 men who attended the CONTEXTO program, with penalties for gender violence under two years, and 47 men with no history of violence. Empathic induction was achieved through the visualization of 4 negative emotional-eliciting videos taken from an emotional induction battery of videos validated for the Spanish population. The participants were asked to actively empathize with the video characters (previously pointed out). The psychophysiological recording of the EDA was accomplished by the "Vrije Universiteit Ambulatory Monitoring System (VU-AMS)." An analysis of repeated measurements was carried out with 10 intra-subject measurements (time) and "group" (IPV perpetrators and non-violent perpetrators) as the inter-subject factor. First, there were no significant differences between groups in the baseline AED levels. Yet, a significant interaction between the “time” and “group” was found with IPV perpetrators exhibiting lower EDA response than controls after the empathic induction task. These findings provide evidence of a subdued EDA response after an empathic induction task in IPV perpetrators with respect to men without a history of violence. Therefore, the lower psychophysiological activation would be indicative of difficulties in the emotional processing and response, functions that are necessary for the empathic function. Consequently, the importance of addressing possible empathic difficulties in IPV perpetrator psycho-educational programs is reinforced, putting special emphasis on the affective dimension that could hinder the empathic function.

Keywords: electrodermal activity, emotional induction, empathy, intimate partner violence

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Authors: E.A. Kuchma

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Photodynamic therapy (PDT) is considered an alternative and minimally invasive cancer treatment modality compared to chemotherapy and radiation therapy. PDT includes three main components: a photosensitizer (PS), oxygen, and a light source. PS is injected into the patient's body and then selectively accumulates in the tumor. However, the light used in PDT (spectral range 400–700 nm) is limited to superficial lesions, and the light penetration depth does not exceed a few cm. The problem of PDT (poor visible light transmission) can be solved by using X-rays. The penetration depth of X-rays is ten times greater than that of visible light. Therefore, X-ray radiation easily penetrates through the tissues of the body. The aim of this work is to develop universal nanocomposites for X-ray photodynamic therapy of deep and superficial tumors using scintillation nanoparticles of gadolinium fluoride (GdF3), doped with Tb3+, coated with a biocompatible coating (PEG) and photosensitizer RB (Rose Bengal). PEG@GdF3:Tb3+(15%) – RB could be used as an effective X-ray, UV, and photoluminescent mediator to excite a photosensitizer for generating reactive oxygen species (ROS) to kill tumor cells via photodynamic therapy. GdF3 nanoparticles can also be used as contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI).

Keywords: X-ray induced photodynamic therapy, scintillating nanoparticle, radiosensitizer, photosensitizer

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Authors: Sameer Masood, Lucas Chartier

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Head injuries are a commonly encountered presentation in emergency departments (ED) and the Choosing Wisely Canada (CWC) campaign was released in June 2015 in an attempt to decrease imaging utilization for patients with minor head injuries. The impact of the CWC campaign on imaging utilization for head injuries has not been explored in the ED setting. In our study, we describe the characteristics of patients with head injuries presenting to a tertiary care academic ED and the impact of the CWC campaign on CT head utilization. This retrospective cohort study used linked databases from the province of Ontario, Canada to assess emergency department visits with a primary diagnosis of head injury made between June 1, 2014 and Aug 31, 2016 at the University Health Network in Toronto, Canada. We examined the number of visits during the study period, the proportion of patients that had a CT head performed before and after the release of the CWC campaign, as well as mode of arrival, and disposition. There were 4,322 qualifying visits at our site during the study period. The median presenting age was 44.12 years (IQR 27.83,67.45), the median GCS was 15 (IQR 15,15) and the majority of patients presenting had intermediate acuity (CTAS 3). Overall, 43.17% of patients arrived via ambulance, 49.24 % of patients received a CT head and 10.46% of patients were admitted. Compared to patients presenting before the CWC campaign release, there was no significant difference in the rate of CT heads after the CWC (50.41% vs 47.68%, P = 0.07). There were also no significant differences between the two groups in mode of arrival (ambulance vs ambulatory) (42.94% vs 43.48%, P = 0.72) or admission rates (9.85% vs 11.26%, P = 0.15). However, more patients belonged to the high acuity groups (CTAS 1 or 2) in the post CWC campaign release group (12.98% vs 8.11% P <0.001). Visits for head injuries make up a significant proportion of total ED visits and approximately half of these patients receive CT imaging in the ED. The CWC campaign did not seem to impact imaging utilization for head injuries in the 14 months following its launch. Further efforts, including local quality improvement initiatives, are likely needed to increase adherence to its recommendation and reduce imaging utilization for head injuries.

Keywords: choosing wisely, emergency department, head injury, quality improvement

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Authors: Ram Sharan Mehta

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The number of new cancer cases annually is estimated to rise from 10.9 million in 2002 to more than 16 million by 2020, if current trends continue. Much of this increase in absolute numbers derives from the ageing of populations worldwide. The objectives of this study were to find out the demographic characteristics of the admitted cancer patients in BPKIHS. It was hospital based descriptive cross-sectional study conducted reviewing all the records of admitted diagnosed cancer patients in BPKIHS from 15th October 2004 to 14th October 2012. Using total enumerative sampling technique all 1379 diagnosed cancer patients record were reviewed after obtaining the permission from concerned authorities. Using SPSS-15 software package data was analyzed. It was found that majority (71%) of cancer patients were of age more than 40 years and equal of both sexes. Most of the clients were form Sunsari (31.1%), Morang (16.6%) and Jhapa (17%) districts. The mean hospitalization day is 8.32 and very few patients (5.2%) were only cured. The numbers of cancer patients are markedly increases in BPKIHS, especially in advanced stage. It is mandatory to start the cancer information and education programme in eastern region of Nepal and proper management of cancer patients using chemotherapy, radiotherapy and surgery at BPKIHS for quality patient care.

Keywords: lung, cancer, patients, Nepal

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Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

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In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

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Authors: Rachel F. Ajayi, Unathi Sidwaba, Usisipho Feleni, Samantha F. Douman, Ezo Nxusani, Lindsay Wilson, Candice Rassie, Oluwakemi Tovide, Priscilla G.L. Baker, Sibulelo L. Vilakazi, Robert Tshikhudo, Emmanuel I. Iwuoha

Abstract:

Pyrazinamide (PZA) is among the first-line pro-drugs in the tuberculosis (TB) combination chemotherapy used to treat Mycobacterium tuberculosis. Numerous reports have suggested that hepatotoxicity due to pyrazinamide in patients is due to inappropriate dosing. It is therefore necessary to develop sensitive and reliable techniques for determining the PZA metabolic profile of diagnosed patients promptly and at point-of-care. This study reports the determination of PZA based on nanobiosensor systems developed from disuccinimidyl octanedioate modified Cytochrome P450-2E1 (CYP2E1) electrodeposited on gold substrates derivatised with (poly(8-anilino-1-napthalene sulphonic acid) PANSA/PVP-AgNPs nanocomposites. The rapid and sensitive amperometric PZA detection gave a dynamic linear range of 2 µM to 16 µM revealing a limit of detection of 0.044 µM and a sensitivity of 1.38 µA/µM. The Michaelis-Menten parameters; KM, KMapp and IMAX were also calculated and found to be 6.0 µM, 1.41 µM and 1.51 µA respectively indicating a nanobiosensor suitable for use in serum.

Keywords: tuberculosis, cytochrome P450-2E1, disuccinimidyl octanedioate, pyrazinamide

Procedia PDF Downloads 375