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The coronavirus disease 2019 (COVID-19) has various presentations, of which immune dysregulation or the so-called cytokine storm syndrome (COVID-CSS) is prominent. Even though cytokines are vital regulators of body immunoinflammatory responses, their exaggerated release can be harmful. This hyperinflammatory response is more commonly observed during severe COVID-19 infections, caused by the excessive release of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, IL-8, tumour necrosis factor, granulocyte-macrophage colony-stimulating factor, and interferon-gamma, making their blockers and antagonists of great interest as therapeutic options in this condition. Thus, the pathophysiology of excessive cytokine secretion is outlined, and their most important blockers and antagonists are discussed, mainly focussing on tocilizumab, an interleukin-6 receptor blocker approved to treat severe COVID-19 infections.
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COVID-19 , Humanos , Citocinas , SARS-CoV-2RESUMO
Since the start of the pandemic, thrombotic events have been a well-known and severe complication associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nevertheless, the initiation of vaccination programs brought another rare yet highly fatal thrombotic event, vaccine-induced immune thrombotic thrombocytopaenia, which has caused extensive debate regarding the safety of vaccines. This review defines the thromboembolic events following infection and vaccination, identifies their risk factors, describes their pathophysiology, and discusses their management, treatment, and prevention.
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Vacinas contra COVID-19 , COVID-19 , Trombocitopenia , Trombose , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombose/induzido quimicamente , Vacinação/efeitos adversos , Vacinas ViraisRESUMO
INTRODUCTION: Disturbance in the lymphatic drainage during D2 dissection is associated with significant morbidity. We aimed to assess the effect of fibrin glue on the reduction of postoperative lymphatic leakage. METHODS: Prospective double-blinded randomized clinical trial with forty patients in each study arm was conducted. All patients diagnosed, staged, and became a candidate for D2 dissection based on NCCN 2019 guideline for gastric cancer. The intervention group received 1 cc of IFABOND® applied to the surgical bed. RESULTS: The difference between study groups regarding age, gender, tumor stage was insignificant. (All p-values > 0.05). The median daily drainage volume was 120 ml with the first and the third interquartile being 75 and 210 ml, respectively for the intervention group. The control group had median, the first, and the third interquartile of 350, 290, and 420 ml. The difference between daily drainage volumes was statistically significant (p-value < 0.001). The length of hospital stay was significantly different between the two groups. Notably, the intervention group was discharged sooner (median of 7 Vs 9 days, p-value: 0.001). CONCLUSION: This study showed the possible role of fibrin glue in reducing postoperative lymphatic leakage after gastrectomy and D2 dissection. Registration trial number: IRCT20200710048071N1, 2020.08.16.
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Adesivo Tecidual de Fibrina/uso terapêutico , Gastrectomia/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/prevenção & controle , Neoplasias Gástricas/cirurgia , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Chylothorax (CT) is a rare yet serious complication after esophagectomy. Identification of the thoracic duct (TD) during esophagectomy is challenging due to its anatomical variation. Real-time identification of TD may help to prevent its injury. Near infra-red imaging with Indocyanine green (ICG) is a novel technique that recently has been used to overcome this issue. METHODS: Patients who underwent minimally invasive esophagectomy for esophageal cancer were divided into two groups with and without ICG. We injected ICG into bilateral superficial inguinal lymph nodes. Identification of TD and its injuries during the operation was evaluated and compared with the non-ICG group. RESULTS: Eighteen patients received ICG, and 18 patients underwent surgery without ICG. Each group had one (5.5%) TD ligation. In the ICG group injury was detected intraoperative, and ligation was done at the site of injury. In all cases, the entire thoracic course of TD was visualized intraoperatively after a mean time of 81.39 min from ICG injection to visualization. The Mean extra time for ICG injection was 11.94 min. In the ICG group, no patient suffered from CT. One patient in the non-ICG group developed CT after surgery that was managed conservatively. According to Fisher's exact test, there was no significant association between CT development and ICG use, possibly due to the small sample size. CONCLUSIONS: This study confirms that ICG administration into bilateral superficial inguinal lymph nodes can highlight the TD and reduce its damage during esophagectomy. It can be a standard method for the prevention of postoperative CT.
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Quilo , Verde de Indocianina , Humanos , Ducto Torácico/diagnóstico por imagem , Ducto Torácico/cirurgia , Ducto Torácico/patologia , Esofagectomia/efeitos adversos , FluorescênciaRESUMO
Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.
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Cancer treatment often involves excisional surgery, but this approach may leave behind minimal residual disease, leading to tumor regrowth. Proinflammatory cytokines and their role in altering residual cancerous cells postsurgery have garnered attention. The study examines how mild intraoperative cooling affects cancer cells and their gene expression. It aims to discover strategies for reducing tumor growth after surgery. Nine cases of solid tumor were included in the study, nine samples were cooled with the Peltier-Seebeck device down to12°C, and cooled and noncooled regions of tumors were analyzed using reverse transcription-polymerase chain reaction. Key transcriptomes, including neural-cadherin, cadherins (CDH), 70-kDa Heat Shock Protein (HSP70), hypoxia-inducible factor (HIF), Y-Box-binding protein 1 (YB-1), matrix metalloproteinase 9 (MMP9), and matrix metalloproteinase 2 (MMP2), were measured to assess the impact of mild hypothermia on cancer cell metabolism and cold shock responses. Analysis of cooled and noncooled regions revealed reduced MMP2/9 levels in cooled regions in five out of seven cases, indicating potential suppression of tumor invasion and metastasis. CDH-1 expression was detected in five cases, with decreased levels observed in cooled regions in most cases, suggesting a role in tumor aggressiveness. YB-1 expression was increased in six out of eight samples, possibly correlating with local recurrence and reduced overall survival times. N-Cad expression was increased in all five samples where it was detected, indicating its potential involvement in tumor cell motility and invasion. HSPs showed a mild increase in four out of five cases following cooling, potentially contributing to tumor cell resistance to cooling-induced apoptosis. Intraoperative mild cooling resulted in the downregulation of key proteins playing a role in invasion and metastasis. However, Elevated YB-1 and N-Cad expression limits cooling's universal application. Further research is necessary to comprehend cooling-related transcriptome changes and their impact on patient outcomes.
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Background: The surgery for a breast imaging-reporting and data system (BIRADS) IV lesions needs imaging or pathology supporting data. The roll of breast scintigraphy for this purpose is unclear. Materials and Methods: In a prospective design, 16 patients with 25 BIRADS IV lesions who were scheduled for surgery were included. Before the surgery, breast scintigraphy was done using a nondedicated dual head gamma camera in the prone position employing a shaped foam pad providing imaging at breast pendulous position. Twenty mCi99m Tc methoxy-isobutyl-isonitrile was injected and two 15 and 60-min delayed imaging were done (anterior, bilateral, and single photon emission computed tomography [SPECT] projections). Pathology reports were collected and tumor to nontumor uptake ratio (T/NT) was analyzed, accordingly. Results: Out of all lesions, 12 were malignant (invasive ductal and lobular carcinoma ductal carcinoma in situ). At 15 min, T/NT was insignificantly higher in the malignant compared to benign lesions (22.8 ± 23.9 vs. 10.1 ± 10.1; P = 0.109). The optimal T/NT cutoff for discrimination of malignant and benign lesions was 20. Only 1 out of 13 benign lesions presented uptake >20 (7.7%; false-positive rate; P = 0.047). The diagnostic accuracy, sensitivity, and specificity for T/NT calculated at 0.68, 0.42, and 0.92, respectively. The T/NT at 60 min remained unchanged for either benign or malignant lesions (22.3 ± 30.2 vs. 11.7 ± 17.1; P = 0.296). Conclusions: Breast scintigraphy with general purpose gamma camera employing SPECT imaging may assist the selection of BIRADS IV lesions in need for surgery. All uptake positive cases should undergo surgery and decision for uptake negative cases should be made based on other data.
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Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there have been multiple peaks of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus virus 2) infection, mainly due to the emergence of new variants, each with a new set of mutations in the viral genome, which have led to changes in the pathogenicity, transmissibility, and morbidity. The Omicron variant is the most recent variant of concern (VOC) to emerge and was recognized by the World Health Organization (WHO) on 26 November 2021. The Omicron lineage is phylogenetically distinct from earlier variants, including the previously dominant Delta SARS-CoV-2 variant. The reverse transcription-polymerase chain reaction (RT-PCR) test, rapid antigen assays, and chest computed tomography (CT) scans can help diagnose the Omicron variant. Furthermore, many agents are expected to have therapeutic benefits for those infected with the Omicron variant, including TriSb92, molnupiravir, nirmatrelvir, and their combination, corticosteroids, and interleukin-6 (IL-6) receptor blockers. Despite being milder than previous variants, the Omicron variant threatens many lives, particularly among the unvaccinated, due to its higher transmissibility, pathogenicity, and infectivity. Mounting evidence has reported the most common clinical manifestations of the Omicron variant to be fever, runny nose, sore throat, severe headache, and fatigue. This review summarizes the essential features of the Omicron variant, including its history, genome, transmissibility, clinical manifestations, diagnosis, management, and the effectiveness of existing vaccines against this VOC.
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Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS-CoV-2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro- or macro-vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID-19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life-threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID-19-induced hypercoagulable state and the use of anticoagulants to treat SARS-CoV-2 infections in different patient groups, as well as their pros and cons.
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Transtornos da Coagulação Sanguínea , COVID-19 , Trombose , Humanos , COVID-19/complicações , SARS-CoV-2 , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/complicações , Trombose/tratamento farmacológico , Trombose/etiologia , Trombose/prevenção & controleRESUMO
Melanoma is a destructive skin disease with few therapeutic options in the developed stage and therefore there is a critical need for reliable biomarkers for early diagnosis. In this context, microRNAs could play an important role as diagnostic biomarkers. Three datasets with accession numbers GSE31568, GSE61741 and GSE20994 were downloaded from the Gene Expression Omnibus (GEO) database. MATLAB software was used to analyze differentially expressed miRNAs between cutaneous melanoma plasma samples and normal plasma samples (control). Plasma levels of miR-193b, miR-146b-3p and miR-483-3p were evaluated by the RT-PCR method. Furthermore, linear regression followed by receiver operating characteristic analyses was performed to estimate whether selected plasma miRNAs were able to distinguish between cases and controls. Finally, the data were analyzed by unpaired Mann-Whitney U test using Graph pad prism 8 computer software. Specifically, miR-193b and miR-146b-3p were downregulated in the plasma of melanoma patients compared with control groups which were decreased 5 × [Formula: see text]-fold in miR-193b and 58-fold in miR-146b-3p, while miR-483-3p was upregulated 3.5-fold. After receiver operating characteristic (ROC) curve analysis, miR-193b with the most area under the curve (AUC: 1.00, 95% confidence interval 1.00-1.00, p < 0.0001) had the best discriminatory power, and miR-146b-3p had the large area under the curve (AUC: 0.96, 95% confidence interval 0.96-1.00, p < 0.0001) and consequently the high discriminatory power. Between these three miRNAs, miR-193b and miR-146b-3p had a high capacity to distinguish between melanoma patients and control groups that are appropriate to be applied in melanoma diagnosis as an early and noninvasive method.
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BACKGROUNDS: Total Pelvic Exenteration (TPE) is a radical operation for malignancies in which all of the organs inside the pelvic cavity, including the female reproductive organs, the lower urinary tract, and a part of the rectosigmoid are removed. In this study, we aimed to conduct a systematic review to assess the overall survival (OS) and disease-free survival (DFS) following TPE. METHODS: This systematic review is composed of a comprehensive review of PubMed and Scopus databases with various related keywords to synthesis the overall survival and disease-free survival following TPE. The Synthesis Without Meta-analysis guideline was used to summarize the results. RESULTS: We included the results of 39 primary studies and the results revealed that one-year OS of gynecological cancer in patients who have undergone TPE ranged from 50.0% to 72.0% and the 5-years OS ranged from 6.0% to 64.6%. The one-year survival rate of colorectal cancer patients was reported to be over 80% in almost all studies. The 3-year survival rate of patients varied from 25% to 75% and the lowest 5-year survival rate was 8% and the highest survival rate was 92%. To synthesis the disease-free survival rate in colorectal cancer, ten studies were included and one-year recurrence rate was 9.1% and the one-year DFS was reported as 61.0%. Three-year recurrence rate study was 20.4% and 3 and 5-year DFS ranged from 22.0% to 78.0%. CONCLUSIONS: The results suggested that DFS in primary advanced cancers is higher than locally recurrence tumors. This review showed that patient overall survival and disease-free survival rates have increased over time, especially at high volume centers that are more experienced and possibly better equipped. Therefore, it can be suggested that the attitude towards PE as a palliative surgery can be turned into curative surgery.
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Neoplasias Colorretais , Exenteração Pélvica , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Exenteração Pélvica/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the common subtypes of kidney cancer. Circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) to affect the expression of microRNAs (miRNAs), and hence the expression of genes involved in the development and progression of ccRCC. However, these interactions have not been sufficiently explored. METHODS: The differential expression of circRNAs (DEC) was extracted from the GEO database, and the expression of circRNAs was analyzed by the Limma R package. The interaction of miRNAs with circRNAs was predicted using (cancer-specific circRNA database) CSCD and circinteractome database. The genes affected by the miRNAs were predicted by miRwalk version 3, and the differential expression was retrieved using TCGA. Functional enrichment was assessed and a PPI network was created using DAVID and Cytoscape, respectively. The genes with significant interactions (hub-genes) were screened, and the total survival rate of ccRCC patients was extracted from the Gene Expression Profiling Interactive Analysis (GEPIA) database. To confirm the expression of OS genes we used the Immunohistochemistry (IHC) data and TCGA database. The correlation between gene expression and immune cell infiltration was investigated using TIMER2.0. Finally, potential drug candidates were predicted by the cMAP database. RESULTS: Four DECs (hsa_circ_0003340, hsa_circ_0007836, hsa_circ_0020303, and hsa_circ_0001873) were identified, along with 11 interacting miRNAs (miR-1224-3p, miR-1294, miR-1205, miR-1231, miR-615-5p, miR-940, miR-1283, and miR-1305). These miRNAs were predicted to affect 1282 target genes, and function enrichment was used to identify the genes involved in cancer biology. 18 hub-genes (CCR1, VCAM1, NCF2, LAPTM5, NCKAP1L, CTSS, BTK, LILRB2, CD53, MPEG1, C3AR1, GPR183, C1QA, C1QC, P2RY8, LY86, CYBB, and IKZF1) were identified from a PPI network. VCAM1, NCF2, CTSS, LILRB2, MPEG1, C3AR1, P2RY8, and CYBB could affect the survival of ccRCC patients. The hub-gene expression was correlated with tumor immune cell infiltration and patient prognosis. Two potantial drug candidates, naphazoline and lithocholic acid could play a role in ccRCC therapy, as well other cancers. CONCLUSION: This bioinformatics analysis brings a new insight into the role of circRNA/miRNA/mRNA interactions in ccRCC pathogenesis, prognosis, and possible drug treatment or immunotherapy.
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Carcinoma de Células Renais , Redes Reguladoras de Genes , Neoplasias Renais , MicroRNAs , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Humanos , Neoplasias Renais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genéticaRESUMO
A novel coronavirus, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the causative agent of coronavirus disease 2019 (COVID-19). In early 2020, the World Health Organization declared COVID-19 the sixth public health emergency of international concern. The COVID-19 pandemic has substantially affected many groups within the general population, but particularly those with extant clinical conditions, such as having or being treated for cancer. Cancer patients are at a higher risk of developing severe COVID-19 since the malignancy and chemotherapy may negatively affect the immune system, and their immunocompromised condition also increases the risk of infection. Substantial international efforts are currently underway to develop specific methods for diagnosing and treating COVID-19. However, cancer patients' risk profiles, management, and outcomes are not well understood. Thus, the main objective of this review is to discuss the relevant evidence to understand the prognosis of COVID-19 infections in cancer patients more clearly, as well as helping to improve the clinical management of these patients.
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COVID-19/etiologia , Neoplasias/imunologia , SARS-CoV-2 , Antineoplásicos/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Neoplasias/complicações , Neoplasias/terapia , Oncologistas , Fatores de Risco , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Telemedicina , Tratamento Farmacológico da COVID-19RESUMO
Aim: MiRNA's-143 and -206 are powerful apoptotic regulators in cancer cells. This study aimed to use miRNA-143- and 206-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles conjugated with folic acid to induce apoptosis in the EL4 cancer cells. Materials & methods: The therapy was conducted in six groups: treatment with both miRNAs simultaneously (mixed miRNAs), miRNA-206 treatment, miRNA-143 treatment, blank PLGA, blank polyethylenimine (PEI) and complex PEI-miRNAs. Results: In terms of viability, in mixed miRNAs no synergistic effect was observed on EL4 cell elimination. However, in the single miRNA-206 group, a stronger apoptotic effect was observed than the mixed miRNAs group and single miRNA-143 group alone. Conclusion: MiRNAs' apoptotic induction effects in cancer cells were found to be remarkable.
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MicroRNAs , Nanopartículas , Neoplasias , Ácido Fólico , Humanos , Ácido Láctico , Masculino , MicroRNAs/genética , Polietilenoimina , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Espermatogônias , Células-TroncoRESUMO
The nuclear factor kappa B (NF-kB) family of transcription factors plays an essential role as stressors in the cellular environment, and controls the expression of important regulatory genes such as immunity, inflammation, death, and cell proliferation. NF-kB protein is located in the cytoplasm, and can be activated by various cellular stimuli. There are two pathways for NF-kB activation, as the canonical and non-canonical pathways, which require complex molecular interactions with adapter proteins and phosphorylation and ubiquitinase enzymes. Accordingly, this increases NF-kB translocation in the nucleus and regulates gene expression. In this study, the concepts that emerge in different cellular systems allow the design of NF-kB function in humans. This would not only allow the development for rare diseases associated with NF-kB, but would also be used as a source of useful information to eliminate widespread consequences such as cancer or inflammatory/immune diseases.
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Hippo Tumor Suppressor Pathway is the main pathway for cell growth that regulates tissue enlargement and organ size by limiting cell growth. This pathway is activated in response to cell cycle arrest signals (cell polarity, transduction, and DNA damage) and limited by growth factors or mitogens associated with EGF and LPA. The major pathway consists of the central kinase of Ste20 MAPK (Saccharomyces cerevisiae), Hpo (Drosophila melanogaster) or MST kinases (mammalian) that activates the mammalian AGC kinase dmWts or LATS effector (MST and LATS). YAP in the nucleus work as a cofactor for a wide range of transcription factors involved in proliferation (TEA domain family, TEAD1-4), stem cells (Oct4 mononuclear factor and SMAD-related TGFß effector), differentiation (RUNX1), and Cell cycle/apoptosis control (p53, p63, and p73 family members). This is due to the diverse roles of YAP and may limit tumor progression and establishment. TEAD also coordinates various signal transduction pathways such as Hippo, WNT, TGFß and EGFR, and effects on lack of regulation of TEAD cancerous genes, such as KRAS, BRAF, LKB1, NF2 and MYC, which play essential roles in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. However, RAS signaling is a pivotal factor in the inactivation of Hippo, which controls EGFR-RAS-RAF-MEK-ERK-mediated interaction of Hippo signaling. Thus, the loss of the Hippo pathway may have significant consequences on the targets of RAS-RAF mutations in cancer.
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INTRODUCTION: Neuroendocrine tumors (NET) of common bile duct are rare. There have been less than 100 cases reported worldwide. PRESENTATION OF CASE: A 37-year-old female patient was referred to our center after six months of abdominal pain with no definite diagnosis. At initial presentation, she complained of increased abdominal pain, nausea, vomiting, oral intolerance to food and icteric sclera. Physical examination and laboratory tests were indicative of pancreatitis. At day four, she took retrograde cholangiopancreatography (ERCP) and a mid CBD stenosis or impacted stone was found. In order to locally investigate the lesion, Endoscopic Ultrasound (EUS) examination was performed which reported 16 × 12 mm isoechoic tumoral lesion at the middle of the CBD. In this regard we decided to perform ERCP-guided brushing biopsy of the lesion. The pathology report was highly suggestive for malignancy. She underwent resection of the mid portion of the CBD with Roux-en-Y hepaticojejunostomy, cholecystectomy and portahepatis lymph node dissection. The pathology report indicated that the CBD lesion was well-differentiated neuroendocrine tumor grade II. DISCUSSION: The exact etiology of developing NET in the bile duct tissues is not clear however cholelithiasis and congenital malformation of the biliary tract has been proposed to cause chronic inflammation with subsequent metaplasia which ultimately transforms into NET. CONCLUSION: As there are very few cases of NETs of the CBD, no definite surgical or medical treatment is proposed. Currently, combination of radical surgical resection and lymph node dissection followed by chemotherapy is the treatment of choice.
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INTRODUCTION: Colorectal cancer (CRC) is a type of cancer in humans that leads to high mortality and morbidity. CD166 and CD326 are immunoglobulins that are associated with cell migration. These molecules are included in tumorigenesis of CRC and serve a great marker of CRC stem cells. In the present study, we devised a novel chimeric protein including the V1-domain of the CD166 and two epitopes of CD326 to use in diagnostic or therapeutic applications. METHODS: In silico techniques were launched to characterize the properties and structure of the protein. We have predicted physicochemical properties, structures, stability, MHC class I binding properties and ligand-receptor interaction of this chimeric protein by means of computational bioinformatics tools and servers. The sequence of chimeric gene was optimized for expression in prokaryotic host using online tools and cloned into pET-28a plasmid. The recombinant pET28a was transformed into the E. coli BL21DE3. Expression of recombinant protein was examined by SDS-PAGE and Western blotting. RESULTS: The designed chimeric protein retained high stability and the same immunogenicity as of the original proteins. Bioinformatics data indicated that the epitopes of the synthetic chimeric protein might induce B-cell- and T-cell-mediated immune responses. Furthermore, a gene was synthesized using the codon bias of a prokaryotic expression system. This synthetic gene expressed a bacterial expression system. The recombinant protein with molecular weights of 27kDa was expressed and confirmed by anti-his Western blot analysis. CONCLUSION: The designed recombinant protein may be useful as a CRC diagnostic tool and for developing a protective vaccine against CRC.
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Antígenos CD/análise , Moléculas de Adesão Celular Neuronais/análise , Neoplasias Colorretais/genética , Simulação por Computador , Molécula de Adesão da Célula Epitelial/análise , Proteínas Fetais/análise , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Antígenos CD/genética , Moléculas de Adesão Celular Neuronais/genética , Clonagem Molecular , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Biologia Computacional , Molécula de Adesão da Célula Epitelial/genética , Proteínas Fetais/genética , Humanos , Engenharia de Proteínas , Proteínas Recombinantes/análise , Proteínas Recombinantes/genéticaRESUMO
The importance of blood serum testing in most medical diagnosis has led researchers to seek for a reliable analysis method. Raman spectroscopy is a potential tool for probing serum components due to its real-time and non-destructive measurements without need to any additional reagents. So, Raman spectroscopy for the analysis and discrimination of human serum of healthy and gastric cancer subjects is investigated in this work. In order to find the correlation between Raman spectra and enzymatic test results of glucose, cholesterol, HDL, LDL and triglycerides of serum samples, the partial least squares regression (PLSR) method is utilized. Moreover, the Raman spectroscopy is used to distinguish between serum samples of healthy people and gastric cancer patients using partial least square discriminant analysis (PLS-DA) method. Correlation results reveal that for all serum components, the correlation coefficients between Raman spectra and all enzymatic test results are above 94% significantly. Discrimination results of healthy subjects and gastric cancer patients show that 87.5⯱â¯2.5% of healthy and gastric cancer subjects are diagnosed properly. Our preliminary results can confirm the Raman method in analysis of serum and also as a diagnostic tool in screening of gastric cancer.
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Soro/química , Neoplasias Gástricas/diagnóstico , Adulto , Análise Química do Sangue/métodos , Glicemia/análise , Colesterol/sangue , Análise Discriminante , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise Espectral Raman/métodos , Neoplasias Gástricas/sangue , Triglicerídeos/sangueRESUMO
Cancer is one of the most complex diseases that has resulted in multiple genetic disorders and cellular abnormalities. Globally, cancer is the most common health concern disease that is affecting human beings. Great efforts have been made over the past decades in biology with the aim of searching novel and more efficient tools in therapy. Thus, small interfering RNAs (siRNAs) have been considered one of the most noteworthy developments which are able to regulate gene expression following a process known as RNA interference (RNAi). RNAi is a post-transcriptional mechanism that involves the inhibition of gene expression through promoting cleavage on a specific area of a target messenger RNA (mRNA). This technology has shown promising therapeutic results for a good number of diseases, especially in cancer. However, siRNA therapeutics have to face important drawbacks in therapy including stability and successful siRNA delivery in vivo. In this regard, the development of effective siRNA delivery systems has helped addressing these issues by opening novel therapeutic windows which have allowed to build up important advances in Nanomedicine. In this review, we discuss the progress of siRNA therapy as well as its medical application via nanoparticle-mediated delivery for cancer treatment.