Search results for: nonsmall cell lung cancer

Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

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Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

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Authors: Williams A. Adu, Cynthia A. Danquah, Paul P. S. Ossei, Selase Ativui, Michael Ofori, James Asenso, George Owusu

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Background Silicosis is an occupational disease of the lung that is caused by chronic exposure to silica dust. There is a higher frequency of co-existence of silicosis with tuberculosis (TB), ultimately resulting in lung fibrosis and respiratory failure. Chronic intake of synthetic drugs has resulted in undesirable side effects. Diosgenin is a steroidal saponin that has been shown to exert a therapeutic effect on lung injury. Therefore, we investigated the ability of diosgenin to reduce the susceptibility of silica-induced TB in rats. Method Silicosis was induced by intratracheal instillation of 50 mg/kg crystalline silica in Sprague Dawley rats. Different doses of diosgenin (1, 10, and 100 mg/kg), Mycobacterium smegmatis and saline were administered for 30 days. Afterwards, 5 of the rats from each group were sacrificed, and the 5 remaining rats in each group, except the control, received Mycobacterium smegmatis. Treatment of diosgenin continued until the 50th day, and the rats were sacrificed at the end of the experiment. The result was analysed using a one-way analysis of variance (ANOVA) with a Graph-pad prism Result At a half-maximal inhibition concentration of 48.27 µM, diosgenin inhibited the growth of Mycobacterium smegmatis. There was a marked decline in the levels of immune cell infiltration and cytokines production. Lactate dehydrogenase and total protein levels were significantly reduced compared to control. There was an increase in the survival rate of the treatment group compared to the control. Conclusion Diosgenin ameliorated silica-induced pulmonary tuberculosis by declining the levels of inflammatory and pro-inflammatory cytokines and, in effect, significantly reduced the susceptibility of rats to pulmonary TB.

Keywords: silicosis, tuberculosis, diosgenin, fibrosis, crystalline silica

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Authors: Neha Singh

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Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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Authors: Ragini Verma, J. Ponmozhi

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The oral cavity is home to a wide variety of microorganisms that lead to various diseases and even oral cancer. Despite advancements in the diagnosis and detection at the initial phase, the situation hasn’t improved much. Saliva-on-a-chip is an innovative point-of-care platform for early diagnosis of oral cancer and other oral diseases in live and dead cells using a microfluidic device with a current perspective. Some of the major challenges, like real-time imaging of the oral cancer microbes, high throughput values, obtaining a high spatiotemporal resolution, etc. were faced by the scientific community. Integrated microfluidics and microscopy provide powerful approaches to studying the dynamics of oral pathology, microbe interaction, and the oral microenvironment. Here we have developed a saliva-on-chip (salivary microbes) device to monitor the effect on oral cancer. Adhesion of cancer-causing F. nucleatum; subsp. Nucleatum and Prevotella intermedia in the device was observed. We also observed a significant reduction in the oral cancer growth rate when mortality and morbidity were induced. These results show that this approach has the potential to transform the oral cancer and early diagnosis study.

Keywords: microfluidic device, oral cancer microbes, early diagnosis, saliva-on-chip

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Authors: Amy Pullen, Samantha Rodrigues, David Kieser, Brian Shaw

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The aim of the study was to determine if a projectile interacting with the lungs increases the severity of injury in comparison to a projectile interacting with the ribs or intercostal muscle. This comparative study employed a 10% gelatine based model with either porcine ribs or balloons embedded to represent a lung. Four sample groups containing five samples were evaluated; these were control (plain gel), intercostal impact, rib impact, and lung impact. Two ammunition natures were evaluated at a range of 10m; these were 5.56x45mm and 7.62x51mm. Aspects of projectile behavior were quantified including exiting projectile weight, location of yawing, projectile fragmentation and distribution, location and area of the temporary cavity, permanent cavity formation, and overall energy deposition. Major findings included the cavity showing a higher percentage of the projectile weight exit the block than the intercostal and ribs, but similar to the control for the 5.56mm ammunition. However, for the 7.62mm ammunition, the lung was shown to have a higher percentage of the projectile weight exit the block than the control, intercostal and ribs. The total weight of projectile fragments as a function of penetration depth revealed large fluctuations and significant intra-group variation for both ammunition natures. Despite the lack of a clear trend, both plots show that the lung leads to greater projectile fragments exiting the model. The lung was shown to have a later center of the temporary cavity than the control, intercostal and ribs for both ammunition types. It was also shown to have a similar temporary cavity volume to the control, intercostal and ribs for the 5.56mm ammunition and a similar temporary cavity to the intercostal for the 7.62mm ammunition The lung was shown to leave a similar projectile tract than the control, intercostal and ribs for both ammunition types. It was also shown to have larger shear planes than the control and the intercostal, but similar to the ribs for the 5.56mm ammunition, whereas it was shown to have smaller shear planes than the control but similar shear planes to the intercostal and ribs for the 7.62mm ammunition. The lung was shown to have less energy deposited than the control, intercostal and ribs for both ammunition types. This comparative study provides insights into the influence of the lungs on thoracic gunshot trauma. It indicates that the lungs limits projectile deformation and causes a later onset of yawing and subsequently limits the energy deposited along the wound tract creating a deeper and smaller cavity. This suggests that lung impact creates an altered pattern of local energy deposition within the target which will affect the severity of trauma.

Keywords: ballistics, lung, trauma, wounding

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Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

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Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma

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Authors: Shenghui Wu, Patricia Chalela, Amelie G. Ramirez

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Background: Cervical cancer (CC), colorectal cancer (CRC), and breast cancer (BC) are diseases that can be prevented/detected through early test. Through educational programs, individuals can become better informed about these cancers and understand the importance of screening and early detection. A community-based educational program was developed to improve knowledge and awareness toward the screening of the three cancer types in a South Texas underserved population. Methods: Residents living in Laredo, Texas were invited to participate in the present study. From January 2020 to April 2021, participants were recruited using social media and flyer distributions in general community. Participants received a free live web cancer education presentation delivered by bilingual community health educators, and online pre- and post-education surveys for CC, CRC, and BC separately. Pre-post changes in knowledge for individual items were compared using McNemar’s chi-squared tests. Results: Overall, participants demonstrated increases in CC (n=237), CRC (n=59), and BC (n=56) screening knowledge and awareness after receiving the cancer screening education (Ps<0.05). After receiving the cancer screening education, 85-97% of participants had an intent to talk to a healthcare provider about CC/CRC/BC screening, 88-97% had an intent to get a CC/CRC/BC screening test in the next 12 months or at the next routine appointment, and 90-97% had an intent to talk about CC/CRC/BC with their family members or friends. Conclusion: A community-based educational program can help increase knowledge and awareness about cervical, colorectal, and breast cancer screening, promote positive changes in population's knowledge and awareness about the benefits of cancer screening.

Keywords: cervical cancer, colorectal cancer, breast cancer, educational program, health knowledge, awareness, Hispanics, screening, health education

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Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

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Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

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Authors: Rubina Ghani, Sehrish Zia, Afifa Fatima Rafique, Shaista Emad

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Background: Cancer is a leading cause of death worldwide, with breast cancer being the most common cancer in women. Pakistan has the highest rate of breast cancer cases among Asian countries. Early and accurate diagnosis is crucial for treatment outcomes and quality of life. Method: It is a case-control study with a sample size of 150. There were 100 suspected cancer cases, 25 healthy controls, and 25 diagnosed cancer cases. To analyze SSAT-1 mRNA expression in whole blood, Zymo Research Quick-RNA Miniprep and Innu SCRIPT—One Step RT-PCR Syber Green kits were used. Patients were divided into three groups: 100 suspected cancer cases, 25 controls, and 25 confirmed breast cancer cases. Result: The total mRNA was isolated, and the expression of SSAT-1 was measured using RT-qPCR. The threshold cycle (Ct) values were used to determine the amount of each mRNA. Ct values were then calculated by taking the difference between the CtSSAT-1 and Ct GAPDH, and further Ct values were calculated with the median absolute deviation for all the samples within the same experimental group. Samples that did not correlate with the results were taken as outliers and excluded from the analysis. The relative fold change is shown as 2^-Ct values. Suspected cases showed a maximum fold change of 32.24, with a control fold change of 1.31. Conclusion: The study reveals an overexpression of SSAT-1 in breast cancer. Furthermore, we can use SSAT-1 as a diagnostic, prognostic, and therapeutic marker for early diagnosis of cancer.

Keywords: breast cancer, spermidine/spermine, qPCR, mRNA

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Authors: Pakakrong Thongdeeying, Srisopa Ruangnoo, Arunporn Itharat

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The rhizomes of Smilax corbularia Kunth have long been used as common ingredients in anticancer preparations. Thus, the objective of this study is to investigate cytotoxicity of S. corbularia and its ingredients against cholangiocarcinoma cell line (KKU-M156) by SRB assay. Ethanolic and water extracts of S. corbularia rhizomes were obtained using the procedures followed by Thai traditional doctors. Bioassay guided isolation was used to isolate cytotoxic compounds. The results revealed that the ethanolic extract of S. corbularia exhibited activity against KKU-M156 cell line with an IC50 value of 84.53±1.62 µg/ml, but the water extract showed no cytotoxic activity. Three flavonoid compounds [astilbin (1), engeletin (2), and quercetin (3)] were isolated from the ethanolic extract. Compound 3 exhibited the strongest activity against KKU-M156 cell line (IC50 = 8.14 ± 1.15 µg/ml), but 1 and 2 showed no cytotoxic activity (IC50 > 100 µg/ml). In conclusion, quercetin showed the highest efficacy against cholangiocarcinoma. These results support the traditional use of this plant by Thai traditional doctors for cancer treatment.

Keywords: cholangiocarcinoma, cytotoxicity, flavonoid, Smilax corbularia

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: Allulu Yousef Alturki, Raghad Abdullah Alshafi, Sara Abdulaziz Alghashem, Sahar Saleh Alghamdi, Rasha Saad Suliman, Zeyad Alehaideb, Rizwan Ali

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Cancer is recognized as a worldwide public health concern. Therefore, there is a continuous quest to discover new effective medications with less side-effects. In recent years, researchers have shown an increased interest in medicinal plants as several plant species have shown promising biological activities. Thus, we seek to investigate three medicinal herbs that are commonly-found in the Middle Easternregion and yet have not been explored in depth, including plants belonging to the Rhamnaceae, Polygonaceae, and Apocynaceaeplant families. Initially, we investigated using three types of cancer cell lines for breast, colorectal, and liver cancers. We performed high Content Imaging (HCI)-Apoptosis Assay and ApoTox-Glo™ Triplex Assay on KAIMRC2 and HCT8 cell lines. The highest activity of HCI-Apoptosis Assay was with Calligonumcomosum and Ziziphusnummularia in ethanol, followed by Calotropis procera and Ziziphusnummularia in ethyl acetate. The IC50values for the families of Rhamnaceae, Polygonaceae, and Apocynaceae in HepG2 and HCT8 cell lines ranged from 0.089 to 9.84mg/mL and 0.080to 15.08mg/mL, respectively. Further screening was conducted on an additional two cell lines, namely the MDA-MB-231 and KAIMRC2, for selected seven extracts with the highest activity having IC50values ranged from 0.058 to0.51mg/mL and 0.029 to0.19mg/mL, respectively. Continuous scientific investigations to isolate and characterize the potent bioactive phytochemical(s) are warranted. Funding: The authors acknowledge financial support from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. Institutional Review Board Statement: The study was approved by the Institutional Review Board of the Institutional Review Board of King Abdullah International Medical Research Center (SP21R/463/12, 24 January 2022). Acknowledgments: The authors want to express their gratitude to the College of Pharmacy (COP) at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and King Abdullah International Medical Research Center (KAIMRC) for their continued support.

Keywords: rhamnaceae, polygonaceae, apocynaceae, natural products

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Authors: Sanjeewa Seneviratne, Ian Campbell, Nina Scott, Ross Lawrenson

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Introduction: Indigenous Māori women experience a 60% higher breast cancer mortality rate compared with European women in New Zealand. We explored the impact of difference in the rate of screen detected breast cancer between Māori and European women on more advanced disease at diagnosis and lower survival in Māori women. Methods: All primary in-situ and invasive breast cancers diagnosed in screening age women (as defined by the New Zealand National Breast Cancer Screening Programme) between 1999 and 2012 in the Waikato area were identified from the Waikato Breast Cancer Register and the national screening database. Association between screen versus non-screen detection and cancer stage at diagnosis and survival were compared by ethnicity and socioeconomic deprivation. Results: Māori women had 50% higher odds of being diagnosed with more advance staged cancer compared with NZ European women, a half of which was explained by the lower rate of screen detected cancer in Māori women. Significantly lower breast cancer survival rates were observed for Māori compared with NZ European and most deprived compared with most affluent socioeconomic groups for symptomatically detected breast cancer. No significant survival differences by ethnicity or socioeconomic deprivation were observed for screen detected breast cancer. Conclusions: Low rate of screen detected breast cancer appears to be a major contributor for more advanced stage disease at diagnosis and lower breast cancer survival in Māori compared with NZ European women. Increasing screening participation for Māori has the potential to substantially reduce breast cancer mortality inequity between Māori and NZ European women.

Keywords: breast cancer, screening, ethnicity, inequity

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Authors: Devendra Gupta, S. P. Ambesh, P. K Singh

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Introduction: Minimally invasive coronary artery bypass grafting (MICABG) is a less invasive method of performing surgical revascularization. Minimally invasive direct coronary artery bypass (MIDCAB) provides many anesthetic challenges including one lung ventilation (OLV), managing myocardial ischemia, and pain. We present an early and midterm result of the use of this technique with OLV. Method: We enrolled 62 patients for analysis operated between 2008 and 2012. Patients were anesthetized and left endobronchial tube was placed. During the procedure left lung was isolated and one lung ventilation was maintained through right lung. Operation was performed utilizing off pump technique of coronary artery bypass grafting through a minimal invasive incision. Left internal mammary artery graft was done for single vessel disease and radial artery was utilized for other grafts if required. Postoperative ventilation was done with single lumen endotracheal tube. Median follow-up is 2.5 years (6 months to 4 years). Results: Median age was 58.5 years (41-77) and all were male. Single vessel disease was present in 36, double vessel in 24 and triple vessel disease in 2 patients. All the patients had normal left ventricular size and function. In 2 cases difficulty were encounter in placement of endobronchial tube. In 1 case cuff of endobronchial tube was ruptured during intubation. High airway pressure was developed on OLV in 1 case and surgery was accomplished with two lung anesthesia with low tidal volume. Mean postoperative ventilation time was 14.4 hour (11-22). There was no perioperative and 30 day mortality. Conversion to median sternotomy to complete the operation was done in 3.23% (2 out of 62 patients). One patient had acute myocardial infarction postoperatively and there were no deaths during follow-up. Conclusion: MICABG is a safe and effective method of revascularization with OLV in low risk candidates for coronary artery bypass grafting.

Keywords: MIDCABG, one lung ventilation, coronary artery bypass grafting, endobronchial tube

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Authors: Viviane A. O. Silva, Angela M. Costa, Glaucia N. M. Hajj, Ana Preto, Aline Tansini, Martin Roffé, Peter Jordan, Rui M. Reis

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Autophagy is a recycling and degradative system suggested to be a major cell death pathway in cancer cells. Autophagy pathway is interconnected with the endocytosis pathways sharing the same ultimate lysosomal destination. Lysosomes are crucial regulators of cell homeostasis, responsible to downregulate receptor signalling and turnover. It seems highly likely that derailed endocytosis can make major contributions to several hallmarks of cancer. WNK2, a member of the WNK (with-no-lysine [K]) subfamily of protein kinases, had been found downregulated by its promoter hypermethylation, and has been proposed to act as a specific tumour-suppressor gene in brain tumors. Although some contradictory studies indicated WNK2 as an autophagy modulator, its role in cancer cell death is largely unknown. There is also growing evidence for additional roles of WNK kinases in vesicular traffic. Aim: To evaluate the role of WNK2 in autophagy and endocytosis on glioma context. Methods: Wild-type (wt) A172 cells (WNK2 promoter-methylated), and A172 transfected either with an empty vector (Ev) or with a WNK2 expression vector, were used to assess the cellular basal capacities to promote autophagy, through western blot and flow-cytometry analysis. Additionally, we evaluated the effect of WNK2 on general endocytosis trafficking routes by immunofluorescence. Results: The re-expression of ectopic WNK2 did not interfere with autophagy-related protein light chain 3 (LC3-II) expression levels as well as did not promote mTOR signaling pathway alteration when compared with Ev or wt A172 cells. However, the restoration of WNK2 resulted in a marked increase (8 to 92,4%) of Acidic Vesicular Organelles formation (AVOs). Moreover, our results also suggest that WNK2 cells promotes delay in uptake and internalization rate of cholera toxin B and transferrin ligands. Conclusions: The restoration of WNK2 interferes in vesicular traffic during endocytosis pathway and increase AVOs formation. This results also suggest the role of WNK2 in growth factor receptor turnover related to cell growth and homeostasis and associates one more time, WNK2 silencing contribution in genesis of gliomas.

Keywords: autophagy, endocytosis, glioma, WNK2

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Authors: Buse Bahitli, Samiye Mete

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The aim of the study was to evaluate the quality of sexual life of women with diagnosed gynecological cancer and receive treatment. The study was a descriptive and cross-sectional type, and it was carried out with 276 women. Information Form and Sexual Quality of Life Scale-Female (SQOL) form was used in the study. The data was evaluated using Mann-Whitney U and Kruskal-Wallis test. In the study, Sexual Quality of Life Scale-Female average score was 68.83 ± 21.17. The %43.1 of women was endometrial cancer, %30.8 was cervical cancer, %24.6 was ovarian cancer, and %1.4 was vulvar cancer. The average time to diagnosis of patients is 41.80 ± 47.64 months. There was no significant difference mean SQOL according to individual/sociodemographic characteristics like age, education. Gynecological cancer-related characteristics like gynaecological cancer type, treatment type, surgery type were found not to affect the mean score of SQOL. However, it was found that the difference was due to the higher SQOL score in the group with a diagnosis time of 25 months and over (X²KW= 6.356, p= 0.046). The reason of significant difference means SQOL according to diagnosis over time might be that women adapted to cancer diagnosis. While women with gynaecologic cancer are evaluating their sexual lives, it is necessary to evaluate them with good evaluation tools.

Keywords: gynecological cancers, sexuality, quality of sexual life, SQOL

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Authors: Meryem Saban Guler, Saniye Bilici

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Malnutrition is a problem that significantly affects patients with cancer throughout the course of their illness, and it may be present from the moment of diagnosis until the end of treatment. We searched electronic databases using key terms such as ‘malnutrition in cancer patients’ or ‘nutritional status in cancer’ or ‘nutritional screening tools’ etc. Decline in nutritional status and continuing weight loss are associated with an increase in number and severity of complications, impaired quality of life and decreased survival rate. Nutrition is an important factor in the treatment and progression of cancer. Cancer patients are particularly susceptible to nutritional depletion due to the combined effects of the malignant disease and its treatment. With increasing incidence of cancer, identification and management of nutritional deficiencies are needed. Early identification of malnutrition, is substantial to minimize or prevent undesirable outcomes throughout clinical course. In determining the nutritional status; food consumption status, anthropometric methods, laboratory tests, clinical symptoms, psychosocial data are used. First-line strategies must include routine screening and identification of inpatients or outpatients at nutritional risk with the use of a simple and standardized screening tool. There is agreement among international nutrition organizations and accredited health care organizations that routine nutritional screening should be a standard procedure for every patient admitted to a hospital. There are f management of all cancer patients therefore routine nutritional screening with validated tools can identify cancer patients at risk.

Keywords: cancer, malnutrition, nutrition, nutritional screening

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Authors: Abobaker Mohammed Qasem Farhan, Shangming Yang, Mohammed Al-Nehari

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Pneumonia is a kind of lung disease that creates congestion in the chest. Such pneumonic conditions lead to loss of life of the severity of high congestion. Pneumonic lung disease is caused by viral pneumonia, bacterial pneumonia, or Covidi-19 induced pneumonia. The early prediction and classification of such lung diseases help to reduce the mortality rate. We propose the automatic Computer-Aided Diagnosis (CAD) system in this paper using the deep learning approach. The proposed CAD system takes input from raw computerized tomography (CT) scans of the patient's chest and automatically predicts disease classification. We designed the Hybrid Deep Learning Algorithm (HDLA) to improve accuracy and reduce processing requirements. The raw CT scans have pre-processed first to enhance their quality for further analysis. We then applied a hybrid model that consists of automatic feature extraction and classification. We propose the robust 2D Convolutional Neural Network (CNN) model to extract the automatic features from the pre-processed CT image. This CNN model assures feature learning with extremely effective 1D feature extraction for each input CT image. The outcome of the 2D CNN model is then normalized using the Min-Max technique. The second step of the proposed hybrid model is related to training and classification using different classifiers. The simulation outcomes using the publically available dataset prove the robustness and efficiency of the proposed model compared to state-of-art algorithms.

Keywords: CT scan, Covid-19, deep learning, image processing, lung disease classification

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Authors: Simin Shahvazi, Sepideh Soltani, Seyed Mehdi Ahmadi, Russell J. De Souza, Amin Salehi-Abargouei

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Background and Objectives: Vitamin D has received attention for its potential to disrupt cancer processes such as attenuating cell proliferation and exacerbating differentiation and apoptosis. However, whether there exists a role for vitamin D in the treatment of prostate cancer specifically remains controversial. We systematically review the literature to assess whether supplementation with vitamin D influences PSA response and overall survival in patients with prostate cancer. Methods: We searched PubMed, Scopus, ISI Web of Science and Google scholar from inception through up to 10 September 2017 for both before-and-after and randomized trials that evaluated the effect of vitamin D supplementation on the prostate specific antigen (PSA) response rate in participants with prostate cancer. The DerSimonian and Laird, inverse-weighted random-effects model was used to pool effect estimates from the studies. Heterogeneity and potential publication bias were evaluated. Subgroup analyses were also performed. Results: Twenty-two studies (16 before-after and 6 randomized controlled trials) were found and included in meta-analysis. The analysis on controlled clinical trials revealed that PSA change from baseline [weighted mean difference (WMD) = -1.66 ng/ml, 95%CI: -0.69, 0.36, P= 0.543)], PSA response (RR=1.18, 95%CI: 0.97, 1.45, P=0.104) and mortality rate (risk ratio (RR) = 1.05, 95% CI: 0.81-1.36; P=0.713) was not significantly different between vitamin D supplementation and placebo groups. Single arm trials revealed that vitamin D supplementation had had a modest effect on PSA response rate: 19% of those enrolled had at least a 50% reduction in PSA by the end of treatment (95% CI: 7% to 31%; p=0.002). Conclusion: We found that vitamin D modestly increases the PSA response rate in single arm studies. No effect on serum PSA levels, PSA response and mortality was seen in randomized controlled clinical trials. It does not seem patients with prostate cancer benefit from vitamin D supplementation.

Keywords: mortality, prostatic neoplasms, PSA response, vitamin D

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Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini

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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.

Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry

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Authors: Nikfarid Lida, Maryam Rassouli, Leili Borimnejad, Hamid Alavi Majd

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Purpose: Chronic sorrow is experienced by mothers of children with cancer. It is a multidimensional concept and is experienced by mothers in different ways depends on their various contexts. Little is known about the concept of chronic sorrow in mothers of children with cancer living in Iran. This study aimed to clarify the concept and explain lived experiences of chronic sorrow in Iranian mothers of children with cancer. Methods: In this hermeneutic phenomenological study, 8 mothers of children with cancer participated in semi structured in-depth interviews about their experiences of chronic sorrow. Interviews continued until data saturation was reached. All interviews were recorded, transcribed, analyzed, and interpreted using 7 steps of the Dickelman et al’s phenomenological approach. Results: Three main themes emerged from mothers’ experiences of chronic sorrow related to child’s cancer. These main themes were ‘climbing up shaky rocks,’ ‘fear and hope,’ and ‘continuous role changing.’ Each of these themes consisted of several subthemes. Conclusion: There are similarities in experiencing chronic sorrow by mothers of children with chronic diseases in different societies. However some experiences are unique in Iranian mothers of children with cancer.

Keywords: cancer, children, mothers, Iran, phenomenology

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Authors: Kapoor Anurag, Sharma Pradeep, Mittal K Kailash, Kumar Ajai, Jawad Kalbe, Amit Kumar Singh

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Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumour on a global scale. Limited research has been conducted on tumour markers in oral cancer, and additional evaluation is required for several tumour producers that show clinical promise. The present study aimed to find out the co-relation of β-2 Microglobulin and Lipid Bound Sialic Acid in oral carcinoma patients. Methodology: The present case-control study was carried out on 35 patients with histopathologically confirmed OSCC and 35 age-matched controls. Serum concentrations of 2-Microglobulin and Total Sialic Acid (TSA) in the participants were determined via ELISA and spectrophotometric technique, respectively. Results: The OSCC group consisted of 20 males and 15 females, with an average age of 58 years, while the control group comprised 18 males and 17 females, with an average age of 55 years. Elevated levels of β2-microglobulin (3.87±0.12) and LSA (73.57±2.42) were observed in OSCC patients compared to controls (2.25±0.18; 65.21±2.06, respectively). Further examination based on smoking status revealed a significant increase in both β2-microglobulin and LSA levels among smokers compared to non-smokers (p < 0.05). Conclusion: The study suggests a notable association between higher levels of β2-microglobulin and LSA in oral squamous cell carcinoma (OSCC) patients who smoke compared to non-smokers. This observation leads to a hypothesis that this disparity could potentially serve as a significant contributing factor to the advancement of oral cancer.

Keywords: biochemistry human cancer, human, oral carcinoma, marker

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Authors: Stephanie A. Schauder, Gosia Sylwestrzak

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Overweight and obese women report avoiding preventive care due to fear of weight-related bias from medical professionals. Gynecological exams, due to their sensitive and personally invasive nature, are especially susceptible to avoidance. This research investigates the association between body mass index (BMI) and screening rates for breast and cervical cancer using claims data from 1.3 million members of a large health insurance company. Because obesity is associated with increased cancer risk, screenings for these cancers should increase as BMI increases. However, this paper finds that the distribution of cancer screening rates by BMI take an inverted U-shape with underweight and obese members having the lowest screening rates. For cervical cancer screening, those in the target population with a BMI of 23 have the highest screening rate at 68%, while Obese Class III members have a screening rate of 50%. Those in the underweight category have a screening rate of 58%. This relationship persists even after controlling for health and demographic covariates in regression analysis. Interestingly, there is no association between BMI and BRCA (BReast CAncer gene) genetic testing. This is consistent with the narrative that stigma causes avoidance because genetic testing does not involve any assessment of a person’s body. More work must be done to determine how to increase cancer screening rates in those who may feel stigmatized due to their weight.

Keywords: cancer screening, cervical cancer, breast cancer, weight stigma, avoidance of care

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Authors: Vassilena Dakova, Mariana Panayotova-Pencheva

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The present work focused on the study of pulmonary helminth-fauna of the stone marten in Bulgaria in terms of which the data are little. For the purpose, four stone martens were helminthologically necropsied according to the common technique. In addition, some of the injured lung parts were investigated after their boiling in lactic acid and subsequent compression. Four nematode species from different families of order Strongylida and Trichocephalida were found in the lungs. These were Crenosoma petrowi Morosov, 1939; Eucoleus aerophilus Creplin, 1839; Filaroides martis Werner, 1782 and Sobolevingylus petrowi Romanov, 1952. Some of the parasite structures with taxonomic importance were measured and described. According to our best knowledge, the species F. martis and S. petrowi are recorded for the first time as a part of the helminth-fauna of Southeast Europe and Bulgaria in particular.

Keywords: Bulgaria, Crenosoma petrowi, Eucoleus aerophilus, Filaroides martis, lung parasites, Sobolevingylus petrowi, stone martens

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Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh

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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.

Keywords: corchorus olitorius, melanoma, drug development, strophanthidin

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Authors: A. Alao Olumuyiwa

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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.

Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)

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Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: Razvan Mercut, Mihaela Ionescu, Vlad Parvanescu, Razvan Ghita, Tudor-Gabriel Caragea, Cristina Simionescu, Marius-Eugen Ciurea

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Introduction: Over the past years, the incidence of non-melanoma skin cancer (NMSC) has continuously increased, being one of the most commonly diagnosed carcinomasofthe cephalic extremity. NMSC regroups basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma, cutaneous lymphoma, and sarcoma. The most common forms are BCC and SCC, both still implying a significant level of morbidity due to local invasion (especially BCC), even if the overall death rates are declining. The objective of our study was the evaluation of clinical and histological aspects of NMSC for a group of patients with BCC and SCC, from Craiova, a south-western major city in Romania. Materialand method: Our study lot comprised 65 patients, with an almost equal distribution of sexes, and ages between 23-91 years old (mean value±standard deviation62.61±16.67), all treated within the Clinic of Plastic Surgery and Reconstructive Microsurgery, Clinical Emergency County Hospital Craiova, Romania, between 2019-2020. In order to determine the main morphological characteristics of both studied cancers, we used paraffin embedding techniques, with various staining methods:hematoxylin-eosin, Masson's trichrome stain with aniline blue, and Periodic acid-schiffAlcian Blue. The statistical study was completed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA), with XLSTAT (Addinsoft SARL, Paris, France). Results: The overall results of our study indicate that BCC accounts for 67.69% of all NMSC forms; SCC covers 27.69%, while 4.62% are representedby other forms. The most frequent site is the nose for BCC (27.69%, 18 patients), being followed by preauricular regions, forehead, and periorbital areas. For patients with SCC, tumors were mainly located at lips level (66.67%, 12 patients). The analysis of NMSC histological forms indicated that nodular BCC is predominant (45.45%, 20 patients), as well as ulcero-vegetant SCC (38.89%, 7 patients). We have not identified any topographic characteristics or NMSC forms significantly related to age or sex. Conclusions: The most frequent NMSC form identified for our study lot was BCC. The preferred location was the nose for BCC. For SCC, the oral cavity is the most frequent anatomical site, especially the lips level. Nodular BCC and ulcero-vegetant SCC were the most commonly identified histological types. Our findings emphasize the need for periodic screening, in order to improve prevention and early treatment for these malignancies.

Keywords: non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, histological

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Authors: Safa Safdar

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Breast cancer is a type of cancer which is developed by the formation of a tumor on the breast. This tumor invades and causes different electrolyte imbalance. The present study was designed to measure the serum calcium and inorganic phosphorous levels and to check the frequency of hypercalcemia and hypophosphatemia in breast cancer patients. Serum calcium and phosphorous levels of fifty breast cancer women of 18-70 years of age group and fifty healthy women of same age group were measured by using semi-automated chemistry analyzer ( Humalyzer 3000, Human, Germany ). Significant variation in these levels was observed. The mean calcium value in BC patients was higher 9.398 mg/dl as compared to controls which were 8.694 mg/dl. Whereas the mean value of inorganic phosphorus level was lower 4.060 mg/dl in BC patients as compared to controls having 4.456 mg/dl. In this study, the frequency of hypercalcemia in Breast cancer patients was 10% i.e. only 10 out of 50 Breast cancer patients were suffering from hypercalcemia. Whereas the frequency of hypophosphatemia in this study was only 2 % i.e. only 1 out of 50 patients was suffering from hypophosphatemia. Thus it is concluded that there is a significant change in serum calcium and inorganic phosphorous levels in Breast cancer patients as the disease progresses. So, this study will be helpful for the clinicians to maintain serum calcium and phosphorous levels in Breast cancer patients and also preventing them from further complications.

Keywords: serum analysis, calcium, inorganic phosphorus, hpercalcemia hypophosphatemia

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

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Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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