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BACKGROUND: This study aims to investigate cell-free DNA (cfDNA) methylation of genes involved in some immune system targets as biomarkers of radioresistance in patients with non-metastatic rectal cancer. METHODS: Gene expression (GSE68204, GPL6480, and GSE15781) and DNA methylation profiles (GSE75548 and GSE139404) of rectal cancer patients were obtained from the Gene Expression Omnibus (GEO) database. GEO2R and FunRich software were first used to identify genes with significant expression differences. Enricher softwer was then used to analyze Gene Ontology and detect pathway enrichment of hub genes. Blood samples were then taken from 43 rectal cancer patients. After cfDNA extraction from samples, it was treated with bisulfite and analyzed by methylation-specific PCR. RESULTS: 1088 genes with high and 629 with low expression were identified by GEO2R and FunRich software. A total of five high-expression hub genes, including CDH24, FGF18, CCND1, IFITM1, UBE2V1, and three low-expression hub genes, including CBLN2, VIPR2, and IRF4, were identified from UALCAN and DNMIVD databases. Methylation-specific PCR indicated a significant difference in hub gene methylation between cancerous and non-cancerous individuals. Radiochemotherapy significantly affected hub gene methylation. There was a considerable difference in the methylation rate of hub genes between patients who responded to radiochemotherapy and those who did not. CONCLUSIONS: Evaluating gene methylation patterns might be an appropriate diagnostic tool to predict radiochemotherapy response and develop targeted therapeutic agents.
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Ácidos Nucleicos Livres , Quimiorradioterapia , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Retais , Humanos , Metilação de DNA/genética , Neoplasias Retais/genética , Neoplasias Retais/terapia , Masculino , Feminino , Quimiorradioterapia/métodos , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Pessoa de Meia-Idade , Idoso , Bases de Dados Genéticas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Sistema Imunitário , Ontologia Genética , Perfilação da Expressão GênicaRESUMO
BACKGROUND AND PURPOSE: Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. MATERIALS AND METHODS: A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. RESULTS: Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. CONCLUSION: There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.
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Neoplasias , Radioterapia (Especialidade) , Humanos , Irã (Geográfico)/epidemiologia , Neoplasias/epidemiologia , Neoplasias/radioterapia , Aceleradores de Partículas , Inquéritos e Questionários , Radioterapia/métodosRESUMO
INTRODUCTION/BACKGROUND: This study was designed to investigate the amount of time saved and the degree of contour difficulty between the two methods of contouring, mouse/keyboard, versus touch screen/stylus in radiotherapy. METHODS: Each of 94 patients consisting of 26 breast cancer cases, 24 lymph nodes cases, 25 rectal cancer cases, and 19 heart cases has been contoured twice. One with a mouse/keyboard, and the next one with the touch screen/stylus. Three radiation oncologists participated in this study. Contouring information including measured time, estimated time spent, volume of contour performed and organ contoured are recorded. To evaluate the differences between the contouring methods, the results regarding target volume and time to completion were analyzed using two-way robust ANOVA. Ease of use and contouring difficulty were compared for differences in distribution of the response choices between the groups using Pearson chi-square test. RESULTS: In this study, 94 clinical cases were studied. The average time required for contouring with the touch screen/stylus method was half the time needed for contouring patients with the mouse/keyboard method. The reduction in the time in breast cancer cases was the highest (48.2%) and the lowest in head and neck cancer cases (32.4%). In comparing the contoured volumes, no significant difference was observed between the two methods. the mean estimated time reported by the radiation oncologist in the mouse/keyboard method was 5.6 minutes longer and, in the touch screen/stylus method, was 3.9 minutes less than the actual measured time. CONCLUSIONS: All the measured and analyzed variables show the superiority of contouring with the touch screen/stylus method and reduced the time required for patient contouring by an average of 50%.
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Planejamento da Radioterapia Assistida por Computador , Humanos , Feminino , Planejamento da Radioterapia Assistida por Computador/métodos , Fatores de Tempo , Neoplasias/radioterapia , Neoplasias da Mama/radioterapia , MasculinoRESUMO
PURPOSE: Concurrent chemoradiation has been the mainstay of treatment for cervix cancer. We aimed to evaluate the non-inferiority of hypofractionated chemoradiation. METHODS: This study was designed as a phase 2, 1:1 randomized, investigator-blinded, controlled, non-inferiority trial and we report the interim results after 50% accrual. Cervical cancer patients with FIGO stages IIA-IIIC were recruited from April 2021 to September 2022. The intervention consisted of 40 Gy of 3D-conformal radiation therapy (RT) in 15 fractions over 3 weeks. In the control group, patients received standard chemoradiation of 45 Gy in 25 fractions over 5 weeks. Both groups received concurrent weekly cisplatin (40 mg/m2). Intravaginal brachytherapy of 28 Gy in 4 weekly fractions was delivered starting 1 week after the end of chemoradiation. The primary outcome was complete clinical response(CCR) at 3 months. Secondary outcomes included acute gastrointestinal (GI), genitourinary(GU), skin, and hematologic toxicities. A p value less than 0.05 was considered significant for analyses. RESULTS: 59 patients were randomized; 30 in the control group and 29 in the intervention group. 20/30 (66.7%) of the patients in the control group and 19/29 (65.5%) in the intervention group achieved a CCR (absolute difference of 0.011, 95% CI - 0.23 to 0.25, p value: 0.13). There was a significantly higher rate of acute grade ≥ 3 GI toxicity in the intervention group (27.6%) compared with the control group (6.7%) (p value 0.032). CONCLUSIONS: Despite an absolute difference of 1.1% in the 3-month CCR, our interim analysis failed to show the non-inferiority of the hypofractionated chemoradiation. Due to the higher GI toxicities, we will continue this trial using intensity-modulated radiation therapy. REGISTRATION NUMBER AND DATE: ClinicalTrials.gov: NCT04831437, 2021.4.1.
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Braquiterapia , Radioterapia Conformacional , Neoplasias do Colo do Útero , Feminino , Humanos , Braquiterapia/métodos , Quimiorradioterapia/métodos , Cisplatino/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapiaRESUMO
The CYLD gene is a tumor suppressor, reduced in many cancers. Here, we aimed to investigate CYLD protein level and NF-κß/TNF-α signaling pathway in rectal cancer patients with Lactobacillus acidophilus (L. acidophilus) consumption. One hundred ten patients with non-metastatic rectal cancer were randomly divided into L. acidophilus probiotic (500 mg, three times daily) and placebo groups for 13 weeks. The expression of CYLD, TNF-α, and NF-κB proteins and the genes involved in the NF-κß/TNF-α pathway were evaluated using ELISA and qPCR techniques. The survival rate was measured after five years. Unlike the placebo group, the results showed a significant increase in the expression of CYLD protein and tumor suppressor genes, including FOXP3, ROR-γ, Caspase3, GATA3, T-bet, and a considerable decrease in the expression of NF-Òß and TNF-α proteins and oncogenes, including STAT3, 4, 5, 6, and SMAD 3, in the probiotic group. A higher overall survival rate was seen after L. acidophilus consumption compared to the placebo group (P < 0.05). L. acidophilus consumption can reduce inflammation factors by affecting CYLD protein and its downstream signaling pathways. A schematic plot of probiotic consumption Effects on the CYLD protein in regulating the NF-Ä¸ß signaling pathway in colorectal cancer. NF-Ä¸ß can be activated by canonical and noncanonical pathways, which rely on IκB degradation and p100 processing, respectively. In the canonical NF-κß pathway, dimmers, such as p65/p50, are maintained in the cytoplasm by interacting with an IκBα protein. The binding of a ligand to a cell-surface receptor activates TRAF2, which triggers an IKK complex, containing -α, -ß, -g, which phosphorylates IKK-ß. It then phosphorylates IκB-α, leading to K48-ubiquitination and degradation of this protein. The p65/p50 protein freely enters the nucleus to turn on target genes. The non-canonical pathway is primarily involved in p100/RelB activation. It differs from the classical pathway in that only certain receptor signals activate this pathway. It proceeds through an IKK complex that contains two IKK-α subunits but not NEMO. Several materials including peptidoglycan, phorbol, myristate, acetate, and gram-positive bacteria such as probiotics inhibit NF-κB by inducing CYLD. This protein can block the canonical and noncanonical NF-κß pathways by removing Lys-63 ubiquitinated chains from activated TRAFs, RIP, NEMO, and IKK (α, ß, and γ). Moreover, TNF-α induces apoptosis by binding caspase-3 to FADD.
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Neoplasias , Probióticos , Humanos , Fator de Necrose Tumoral alfa , Enzima Desubiquitinante CYLD/genética , Lactobacillus acidophilus , NF-kappa B , Transdução de Sinais , Probióticos/farmacologia , Probióticos/uso terapêuticoRESUMO
Background & Objective: Iran is located in the esophageal cancer geographical belt. As multiple genetic alterations are responsible for the molecular pathogenesis of esophageal squamous cell cancer (ESCC), the role and frequency of HER2 expression, MMR deficiency, and PI3KCA mutation are not well defined. Methods: We carried out HER2/neu expression, dMMR/MSI high, and PI3KCA mutation analysis in specimens of patients with ESCC. We accessed archival tissue blocks related to specimens of 68 ESCC cases at the time of surgery following neoadjuvant chemoradiation. These patients underwent surgery during 2013-2018 at the Cancer Institute of Iran affiliated with the Tehran University of Medical Sciences in Tehran. Results: None of the patients showed HER2 expression, dMMR/MSI high, or PI3K mutations. Conclusion: dMMR/MSI-H and PI3KCA mutation and HER2 expression may not be reliable andfrequent targets for systemic therapy in patients with esophageal SCC.
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Introduction: The present study aimed to investigate the interaction of the common lncRNA-miRNA-mRNA network involved in signaling pathways in different stages of prostate cancer (PCa) by using bioinformatics and experimental methods. Methods: Seventy subjects included sixty PCa patients in Local, Locally Advanced, Biochemical Relapse, Metastatic, and Benign stages, and ten healthy subjects were entered into the current study. The mRNAs with significant expression differences were first found using the GEO database. The candidate hub genes were then identified by analyzing Cytohubba and MCODE software. Cytoscape, GO Term, and KEGG software determined hub genes and critical pathways. The expression of candidate lncRNAs, miRNAs, and mRNAs was then assessed using Real-Time PCR and ELISA techniques. Results: 4 lncRNAs, 5 miRNAs, and 15 common target genes were detected in PCa patients compared with the healthy group. Unlike the tumor suppressors, the expression levels of common onco-lncRNAs, oncomiRNAs, and oncogenes showed a considerable increase in patients with advanced stages; Biochemical Relapse and Metastatic, in comparison to the primary stages; Local and Locally Advanced. Additionally, their expression levels significantly increased with a higher Gleason score than a lower one. Conclusion: Identifying a common lncRNA-miRNA-mRNA network associated with prostate cancer may be clinically valuable as potential predictive biomarkers. They can also serve as novel therapeutic targets for PCa patients.
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Filgrastim, a recombinant type of granulocyte-colony stimulating factor (G-CSF), has a high potential to manage chemotherapy-induced leukopenia. It can increase stromal cell-derived factor 1 (SDF-1) which may stimulate C-X-C chemokine receptor type 4 (CXCR4) to migrate bone marrow-derived stem/progenitor cells to the bloodstream. Here, we aimed to investigate in vitro and in vivo effects of filgrastim on cell migration, invasion, and metastasis. A lentivirus vector of the anti-CXCR4 receptor was first used for the CXCR4 knockout. Effects of filgrastim on cell proliferation and migration were then investigated on 4T1 cells by Transwell migration and wound healing assay. At last, the effects of filgrastim on cell metastasis and the possible involved mechanisms have been investigated in a metastatic murine breast tumor. The knockout of the CXCR4 receptor could lead to a decrease in cell proliferation, migration, and invasion of the 4T1 cells. Filgrastim could directly target SDF-1 and upregulate the expression of the CXCR4 receptor. The knockout of the CXCR4 receptor reduced cell metastasis in an animal model of breast cancer. CXCR4 receptor stimulation by the filgrastim-affected pathways is a conserved evolutionary response that could increase cancer cell proliferation and consequent cell metastasis. Our results suggest that the activation of the CXCR4 receptor is a conserved evolutionary response that can increase cell proliferation, migration, and consequent metastasis. It seems that filgrastim may increase the chance of cancer cell metastasis in people continuously receiving it to increase the number of neutrophils. Filgrastim induces the SDF-1/CXCR4 axis on tumor cell growth. SDF-1 and its receptor CXCR4 are vital targets for filgrastim. The CXCR4 can stimulate the PI3K/AKT, NF-κB, and JAK/STAT signaling pathways. The SDF-1/CXCR4 pathway promotes cell chemotaxis and proliferation via MAPKs signaling. It also enhances cell survival, proliferation, and angiogenesis, increasing tumor cell metastasis. The STAT3-mediated inflammation is essential for tumorigenesis processes, and Akt, Wnt, STAT3, and CXCR4 signaling pathways are all correlated. CXCR4 = C-X-C chemokine receptor type 4, SDF-1 = stromal-derived-factor-1, MAPK = mitogen activated protein kinase; NF-κB = nuclear factor-κB, PI3K = phosphoinositide 3-kinase, JAK = Janus kinase, STAT = signal transducer and activator of transcription, PLC = phospholipase C, PKC = Protein kinase C, GRK = G protein-coupled receptor kinase.
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Quimiocina CXCL12 , NF-kappa B , Animais , Camundongos , Movimento Celular , Filgrastim , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Quimiocinas , Receptores CXCR4/genética , Receptores CXCR4/metabolismoRESUMO
PURPOSE: Peripheral neuropathy is a dose-limiting adverse effect of oxaliplatin. The aim of this study was to evaluate the efficacy and safety of duloxetine in the prevention of oxaliplatin-induced peripheral neuropathy (OIPN). METHOD: Cancer patients receiving oxaliplatin based chemotherapy were randomized into two arms. Duloxetine 60 mg capsule was given in the first 14 days of each chemotherapy cycle to one arm and placebo was similarly given to another. We compared the two arms based on the incidence of neuropathy and the results of the nerve conduction study (NCS). Grade of complained neuropathy was recorded according to Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Thirty-two patients mostly rectal cancer (90.6%) were randomized to duloxetine and placebo arms. Highest grade of neuropathy in each cycle was not significantly different between the two groups. Six weeks after treatment incidence of neuropathy of any grade was 52.9 in duloxetine arm compared to 76.9% in placebo arm (P: 0.26). Patients in the duloxetine arm had a lower percentage of chemotherapy cycles (mean) in which they reported distal paresthesia (51% vs. 84%, P = 0.01) and throat discomfort (37% vs. 69%, P = 0.01). Results of NCS were mostly comparable between the two arms except for the velocity in two of the examined nerve which was significantly higher in duloxetine group. Duloxetine was safe and well-tolerated. CONCLUSION: Although a definite conclusion might be difficult to draw but administering duloxetine for 14 days in each chemotherapy cycle could not decrease the incidence of acute OIPN based on CTCAE grading system.
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Doenças do Sistema Nervoso Periférico , Humanos , Oxaliplatina , Cloridrato de Duloxetina/uso terapêutico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Método Duplo-CegoRESUMO
BACKGROUND: Thyroid cancers are histologically classified into three types; differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). Among the several therapeutic strategies for treatment and management of thyroid cancer, surgical resection in combination with radioactive iodine therapy (RAI) is indicated for moderate to high-risk differentiated thyroid cancer (DTC) patients- according to current guidelines. However, external radiation therapy (EBRT) can be a viable alternative treatment option for these patients and scarce evidence is available regarding the efficacy and effectiveness of EBRT on thyroid cancer. AIM: This study aims at evaluating the role of EBRT in the management of thyroid carcinomas. METHODS AND RESULTS: In this retrospective cohort study, the records of 59 patients with thyroid cancer were accessed who were treated by EBRT from 2008 to 2016. The indications for EBRT included unresectable primary (definitive) or loco-regional recurrences (salvage) not suitable for RAI, palliation for local disease or metastatic foci (palliative), and the adjuvant treatment for suspected residual disease following resection. Progression-free survival (PFS) and overall survival (OS) were calculated for different types of cancer. PFS was measured from the start of EBRT to the last uneventful follow-up, recurrence, or death. Kaplan-Meier model was used for the survival analysis. Fifty-nine patients were evaluated. The histopathology of the tumors was differentiated and poorly-differentiated, medullary and anaplastic thyroid carcinomas in 22 and 6, 15 and 16 patients, respectively. Twenty-seven patients received external beam radiotherapy (EBRT) as adjuvant therapy and 18 of the cases as palliative therapy while the remaining received salvage or definitive primary EBRT. The stage of patients' cancer was as follows: stage II in 3 and III in 1, IVA in 18 and IVB in 18 and IVC in 19. Stage-based median overall survival was 26 months for IVA, 44 for IVB, and 29 for IVC. The median PFS was 18, 22 and 21 months for stages IVA, IVB and IVC, respectively. CONCLUSION: Based on our findings, EBRT may still play a role in the management of patients with thyroid carcinoma and should be considered in the armamentarium against thyroid cancers.
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Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Radioisótopos do Iodo/uso terapêutico , Irã (Geográfico)/epidemiologia , Terapia CombinadaRESUMO
PURPOSE: To identify pre-surgical imaging predictive value and factors associated with the clinicopathologic discrepancy for implication of definitive pelvic radiotherapy in clinically node-negative bladder cancer. METHOD: The documented data of bladder cancer patients who underwent radical cystectomy plus pelvic lymphadenectomy were collected retrospectively. Patients' characteristics, last imaging, pathology reports, disease-specific survival and overall survival were retrieved. RESULTS: From 142 patients, pre-surgical imaging had a sensitivity of 76.4%, specificity of 73.7%, positive predictive value (PPV) of 94.9%, and negative predictive value (NPV) of 32.6% (p value < 0.0001) for detection of muscle invasion. Also, for detection of positive lymph nodes, imaging had a sensitivity of 31.8%, specificity of 85.7%, PPV of 50%, and NPV of 73.7% (p value: 0.022). 44.4% of study population were upstaged after surgery (24.6% associated with N-upstaging) and 18.3% were downstaged (12% associated with N-downstaging). Receipt of neoadjuvant chemotherapy and T-stage were not correlated with N-upstaging. On multivariate analysis, lymphovascular invasion (LVI) maintained its significance for independent prediction of upstaging (OR 3.3, 95% CI 1.5-7.5, p value: 0.004) and inversely with downstaging (OR 0.34, 95% CI 0.12-0.96, p value: 0.04). Older age (OR 1.03, 95% CI 1.0-1.05, p value 0.047), positive margins (OR 2.1, 95% CI 1.2-3.8, p value 0.011), presence of LVI (OR 2.5, 95% CI 1.4-4.7, p value 0.003), perineural invasion (OR 2.0, 95% CI 1.2-3.4, p value 0.013), and lymph node ratio (OR 1.011, 95% CI 1.001-1.021, p value 0.03) were associated with worse survival. Also, N-upstaging independently predicted a worse survival after controlling for surgical pathology stage (OR 2.3, 95% CI 1.2-4.5, p value 0.011). CONCLUSIONS: The optimal target volume in definitive chemoradiotherapy of node-negative bladder cancer patients remains to be established. Since then, customizing the treatment is considered especially for positive LVI in TURBT specimen.
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Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia , Linfonodos/patologia , Excisão de Linfonodo , Quimiorradioterapia , Cistectomia/métodos , Músculos/patologiaRESUMO
BACKGROUND: Cervical cancer, the most common gynecological cancer, is a matter of concern, especially in developing countries. The present study investigates survival rates, associated factors, and post-treatment follow-up status in cervical cancer patients. STUDY DESIGN: A retrospective cohort study. METHODS: This study was conducted on 187 patients referred to an academic referral cancer center in Iran from 2014-2020. Overall survival (OS) and event-free survival (EFS) were evaluated using Kaplan Meyer analysis. The event was defined as recurrence, metastasis, or death. RESULTS: The patients came for post-treatment visits for a median of 36 months (interquartile range [IQR]: 18-51). The median OS and EFS were 24 and 18 months, respectively. The 1- and 3- year OS rates were 90% and 72%, respectively. The 1- and 3- year EFS rates were 76% and 61%, respectively. Stage ≥ III (hazard ratio [HR]: 3.1, 95% confidence interval [CI]: 1.5, 6.5, P < 0.001) and tumor size > 4 cm (HR: 2.5, 95% CI: 1.2, 4.9, P = 0.006) predicted lower OS. The most common histopathology was squamous cell carcinoma (SCC) (71.1%) with non-significant higher 3- year OS (HR: 0.62, 95% CI: 0.33, 1.16, P = 0.13). No significant difference in OS was found between adjuvant and definitive radiotherapy in both early and advance-staged patients (Log-rank = 0.7 P = 0.4, log-rank = 1.6, P = 0.2, respectively). CONCLUSION: As evidenced by the obtained results, the survival of patients was lower compared to that in developed countries. Higher stage and tumor size led to shorter survival. The histopathology and type of treatment in comparable stages did not have any significant impact on survival.
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Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Taxa de Sobrevida , Estadiamento de Neoplasias , Estudos Retrospectivos , PrognósticoRESUMO
BACKGROUND: The discovery of miRNA/mRNA interactions in several biological samples prompted the researchers to explore new biomarkers in tumors. OBJECTIVE: We aimed to investigate the interactions of miRNA/mRNA in response to radiotherapy in the plasma samples of rectal cancer patients. METHODS: Five microarray datasets related to cancerous and non-cancerous individuals were first used to construct networks. The databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze pathway enrichment. The plasma samples were then collected from 55 patients with recently diagnosed rectal cancer and 10 healthy subjects. For radiotherapy courses, the patients have consecutively received 30 sessions of local radiation for six weeks. At last, the expression of selected genes and miRNAs was experimentally measured before and after radiotherapy by qPCR, and the protein levels of the target genes were measured by ELISA assay. We evaluated the therapeutic responses based on the tumor regression grade of the Dworak classification. RESULTS: We identified 5 up-regulated and 5 down-regulated miRNAs and 8 up-regulated and 3 down-regulated genes of the databases. There was a significant increase in tumor suppressor miRNAs, including miR-101-3p, miR-145-5p, miR-26a-5p, miR-34a-5p, and a significant decrease in oncomiRs, including miR-221-3p and miR-17-5p, after radiotherapy compared to the pre-treatment. Moreover, the up-regulated miR-17-5p and miR-221-5p and the down-regulated miR-101-3p and miR-145-5p were directly related to rectal cancer through the interaction with the Wnt, RAS, PI3K, and TGF-ß signaling pathways. An analysis of receiver operating characteristics showed that miRNAs 221, 17, and 23 were response-related in locally advanced rectal cancer patients. CONCLUSIONS: It seems that monitoring the miRNA/mRNA interactions during radiotherapy can be an appropriate diagnostic tool to track the recovery process and respond to standard therapies.
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MicroRNAs , Neoplasias Retais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , MicroRNAs/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Retais/genética , Neoplasias Retais/radioterapiaRESUMO
PURPOSE: Post-surgery radiation can reduce the risk of loco-regional relapse in high-intermediate-risk endometrial cancer. High-dose-rate vaginal cuff brachytherapy (HDR-BRT) is an acceptable method of radiation in majority of endometrial cancer cases. Although 2D planning is frequently used for treatment based on physical examination without any imaging, measurement of the dose received by organs-at-risk (OARs) is not possible. Therefore, the present study was the first to compare dose delivered to target and OARs in 2D vs. 3D planning in patients treated with cobalt-60 source. MATERIAL AND METHODS: In this study, organs including vagina wall, bladder, rectum, and sigmoid were contoured on computed tomography (CT) scan images of 37 endometrial cancer patients, and doses delivered to organs were recorded. Statistics, such as D90, D99, V100, V150, V200, D0.1cc, D1cc, and D2cc were determined. RESULTS: D90 and D99 were lower in 3D treatment planning in comparison with 2D. Although V100 was more in 3D planning, V150 and V200 were less. Analyzing D0.1cc, D1cc, and D2cc of OARs revealed that doses given to rectum, sigmoid, and bladder were less in 3D planning compared to 2D. CONCLUSIONS: Comparison of 2D and 3D planning results showed that 3D planning could deliver an appropriate dose to the target while sparing more OARs.
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OBJECTIVES: Many patients with breast cancer (BC) require cardiotoxic anthracycline-based chemotherapy. We intended to assess the early cardiotoxic effects of doxorubicin utilizing cardiac magnetic resonance (CMR) imaging. MATERIAL AND METHODS: Forty-nine patients including 21 otherwise healthy females with BC at a mean age (±SD) of 47.62 ± 9.07 years and 28 normal controls at a mean age (±SD) of 45.18 ± 4.29 years were recruited. They underwent CMR and transthoracic echocardiography at baseline and 7 days after four biweekly cycles of doxorubicin and cyclophosphamide. Biventricular functional, volumetric, global strain, and tissue characterization findings were analyzed and compared with those of 28 controls. RESULTS: In post-chemotherapy CMR, 4 patients (19.04%), three symptomatic and one asymptomatic, exhibited evidence of doxorubicin cardiotoxicity. Significant differences in biventricular ejection fraction, left ventricular end-systolic volume index, and all 3D global strain values were noted after chemotherapy in comparison with the baseline (all P < 0.05). More than half of the study population showed a significant change in all right ventricular global strain values. One patient (4.76%) exhibited evidence of diffuse myocardial edema in post-chemotherapy CMR, and 3 patients (14.28%) showed myocardial fibrosis. The study participants were clinically followed up for 4-10 months (mean = 7 months). Overall, 8 patients (38.09%) complained of dyspnea on exertion and fatigue on follow-up. None of the CMR markers was associated with the development of symptoms. CONCLUSION: Our investigation revealed striking changes in CMR parameters in the follow-up of BC patients treated with cardiotoxic chemotherapy. These exclusive CMR features assist in the early initiation of preventive cardiac strategies.
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Multiple primary malignancies are exceedingly rare, but they may occur sequentially in a patient, so in the follow-up of patients with a history of malignancy, always pay attention to second and third primary malignancies as well.
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Follicular dendritic cell sarcoma responded dramatically to chemotherapy with gemcitabine and docetaxel.
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OBJECTIVES: The goal of this study is to examine the effect of contrast agent (CA) dose and diffusion coefficient on the estimation of vessel size index (VSI). MATERIALS AND METHODS: Three groups of four participants were enrolled in this study and two different experiments were performed. Different dose of CA, namely 0.1 mmol/kg and 0.05 mmol/kg were assessed in two groups of normal subjects. Diffusion coefficient effect was assessed in the third group with high-grade glioma. Imaging included gradient echo and spin-echo DSC and DTI on a 3-T MR Scanner. RESULTS: VSI estimation using half of standard dose of CA showed higher values compared to the application of standard, with a ratio of 2 for the WM and 1.5 for the GM. VSI estimates for tumor tissues (22 µm) were considerably higher compared to contra-lateral Normal-Appearing WM (NAWM, 4 µm, P < 0.01) and Normal-Appearing GM (NAGM, 8 µm, P < 0.04). DISCUSSION: Application of standard dose for CA injection and also taking into account the effect of diffusion coefficient can lead to a better correlation of VSI with previous theoretically predicted values and improvement of individual diagnostics in tumor evaluations.
Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Glioma/diagnóstico por imagem , Adulto , Barreira Hematoencefálica/efeitos dos fármacos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Espectroscopia de Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
Neuropathy is a dose limiting side effect of taxanes which may impact the quality of life and treatment outcomes. This randomized placebo-controlled double-blinded clinical trial was carried out to assess the efficacy of gabapentin in preventing chemotherapy induced neuropathy. Women with breast cancer were randomized into two groups of paclitaxel chemotherapy with gabapentin 300 mg/three times a day orally or placebo for 2 weeks started at day 1 of each paclitaxel cycle. Two groups were compared based on the relative frequency of neuropathy and change in nerve conducting velocity (NCV). Twenty women were assigned to each study arm. The majority of the neuropathy in gabapentin group was grade 1 in all of the four cycles with no event of ≥grade 3 neuropathy in this group. Compared to the placebo, the rate of 2nd and 3rd grade neuropathy was significantly lower in the gabapentin group (P = 0.000). The change in NCV after four cycles of paclitaxel was significantly lower in the gabapentin group compared to the placebo group (17.7% vs 61.0% decline in NCV for sural and 21.9% vs 62.5% declines in NCV for peroneal nerve). Gabapentin given with paclitaxel is effective in the prevention of intermediate and high grade neuropathies both objectively and subjectively.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Gabapentina/uso terapêutico , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Adulto , Antineoplásicos Fitogênicos/efeitos adversos , Método Duplo-Cego , Feminino , Gabapentina/efeitos adversos , Humanos , Pessoa de Meia-Idade , PlacebosRESUMO
PURPOSE: Upper esophageal carcinomas are uncommon but confer a poor prognosis. However, there is scarcity of data regarding outcomes of definitive chemoradiotherapy for cervical and upper thoracic esophageal squamous cell carcinoma in Iran. METHODS: In this retrospective cohort study, we analyzed data of patients with squamous cell carcinoma of cervical and upper thoracic esophagus (at 16 to 25 cm from incisors) treated by definitive chemoradiotherapy in our institution between 2007 and 2015. The primary outcome was overall survival and secondary endpoints were predictors of overall survival. RESULTS: From 2007 to 2015, 40 patients were entered to final analysis. The mean age of patients was 59.7 ± 14.3 (range 24-85 years). Sixteen (40%) were node-positive. The median follow-up time was 15.3 months. Twenty-seven patients (67.5%) died during post treatment period. Thirty-five percent and 25% of patients suffered from local and distant recurrences, respectively. The actuarial median overall survival was 19.2 (CI 95% 14.2-24.2) months. The 1- and 2-year overall survival rates were 76 and 38%, respectively. The overall survival was higher among patients who were younger than 50 years, of female gender, had stage II tumor, grades I to II, who received induction chemotherapy, and whom treated with doses < 60 Gy. However, none of the differences was statistically significant. CONCLUSIONS: Cervical and upper thoracic esophageal squamous cell carcinomas are associated with bad outcome. Studies with bigger sample sizes are required to define best treatment strategies.