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Nephrotoxicity is one of the most important complications in cancer patients under treatment with cisplatin-containing regimens. Curcumin, as the most important active component of Curcuma longa, is an antioxidant and anti-inflammatory compound. In this clinical trial, we assessed the preventive effect of nano-curcumin oral formulation against cisplatin-induced nephrotoxicity in cancer patients. In this triple-blind clinical trial 30 cancer patients on cisplatin were randomly included in the treatment group, receiving nano-curcumin 40â mg capsules (nâ =â 15) or the placebo group (nâ =â 15) twice a day during four chemotherapy courses. Kidney function was measured at the beginning of the study and then at the end of each course of chemotherapy. There was no significant difference in acute kidney injury occurrence rate and creatinine and blood urine nitrogen serum levels between the treatment and placebo groups at the end of each chemotherapy course (P value >0.05). Just at the end of the first course, the difference was close to significant (Pâ =â 0.055). We also found no difference in mortality and recurrence rate in an average 30-month follow-up. Nano-curcumin in the prescribed dose and duration was not effective in preventing cisplatin-induced nephrotoxicity in cancer patients in comparison with the placebo. Further studies with larger sample size using different doses and duration of nano-curcumin are recommended.
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INTRODUCTION: Chemotherapy-induced hepatotoxicity is a common complication in breast cancer patients, especially with doxorubicin-containing regimens. Liver enzyme abnormality is reported in 34.8% of patients undergoing AC-T regimen and fatty liver is reported in 30% to 50% of cases. Antioxidant and anti-inflammatory properties of silymarin, a polyphenolic flavonoid extract derived from Silybum marianum, may be useful in preventing chemotherapy-induced hepatotoxicity. This study evaluated the effect of oral silymarin for preventing doxorubicin induced hepatotoxicity in non-metastatic breast cancer patients. METHODS: In this triple-blind, placebo-controlled clinical trial, 50 patients with non-metastatic breast cancer were assigned to receive either 140â mg silymarin tablets or the placebo three times daily for 63 days and were evaluated for liver function test before the study and at the end of each chemotherapy cycle (every 3 weeks) for 4 cycles. In addition, an ultrasonography assessment was performed upon entry and the end of the study. RESULTS: Based on ultrasonography, the fatty liver grade was significantly higher in the placebo group at the end of the study. Moreover, the serum levels of aspartate aminotransferase (p = 0.015) and alkaline phosphatase (p = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase (p = 0.002) at 9-week intervals were significantly lower in the silymarin group. CONCLUSION: Oral formulation of silymarin 420â mg/day for 63 days significantly prevented hepatotoxicity caused by doxorubicin in patients with non-metastatic breast cancer mostly based on liver ultrasonography but not laboratory parameters. Further investigations are suggested on different doses, durations and formulations of silymarin, particularly nano-formulations for increasing its oral bioavailability.
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OBJECTIVE: To evaluate the diagnostic mismatch (discrepancy) of pathology reports in consulted specimens referred for second opinion. MATERIALS AND METHODS: This cross-sectional study was conducted at a major cancer center, Omid Hospital. In this study, 350 primary pathology reports and 350 reviewed pathology reports were extracted from the archives of Omid Hospital from 2011 to 2020 and assessed in terms of the extent of discrepancy, by two pathologists and one oncologist. The required data for each sample were entered into a checklist and then statistically analyzed. Cases with the same diagnosis on both reports were assigned to the matched group and the rest were assigned to the minor or major mismatch (discrepancy) group. Minor mismatches included changes in diagnosis that did not lead to changes in treatment (may lead to changes in prognosis or provide additional information to the oncologist) and major mismatches included changes in diagnosis leading to changes in treatment or remedies. RESULTS: Two hundred seven cases (59.1%) out of three hundred fifty cases had concordant results between the diagnosis of the first pathologist and the reviewing pathologist. In one hundred forty-three cases (40.9%) mismatch (discrepancy) was observed, including eighty- two cases (23.4%) with minor mismatches (discrepancy) and sixty-one cases (17.4%) with major mismatches (discrepancy). In the major mismatch group, fifteen cases (4.3%) changed from malignant to benign, eighteen cases (5.1%) changed from benign to malignant, two cases (0.6%) changed from one stage to another stage of Disease and twenty-six cases (7.4%) had changes in the type of malignancy. In this study, it was found that there was no significant relationship between anatomical areas of sampling and diagnostic mismatch (p = 0.254). The study also found that the rate of diagnostic mismatch in specimens obtained by resection or excisional biopsy was greater than that of small biopsies (eighty cases (22.8%) and sixty-two cases (17.7%, respectively)). There was no significant relationship in this regard (p = 0.077). CONCLUSION: Compared to most similar studies, the present study reported the highest discrepancy between the diagnosis of the first pathologist and the reviewing pathologist (40.9%).
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As a waste material, the amazing potential of cellulose nanocrystals (CNCs) isolated from Citrus medica L. pericarp in being a natural resource of lingo-cellulosic products has never been investigated before. In the present study, an alkaline pretreatment and a two-step bleaching procedure were applied to conduct the desired acid hydrolysis by the usage of 64% sulfuric acid at 50°C for 105 min. The extracted CNCs were distinguished through the means of transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), atomic force microscopy (AFM), Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta potential, and energy-dispersive X-ray spectroscopy (EDX). The elimination of peaks, which were accountable for the inducement of hemicelluloses and lignin, was confirmed by the FTIR results and were also validated by the outcomes of XRD that proved the gentle removal of non-cellulosic components. The morphology and size of CNCs were indicated through the FESEM and TEM results. In addition, the spherical forms of synthesized CNCs were observed with a diameter of 46 nm throughout the FESEM images, while displaying a value of 42.54 nm as well due to TEM micrographs. The obtained zeta potential displayed a reasonable negative surface charge for CNCs. Furthermore, the cytotoxicity assessment of this product on fibroblast cells was performed to study their susceptibility for bio-medical and cosmetic industrial applications, which resulted in the lack of exhibiting any cytotoxic effects. In conformity to the outcomes of TEM and FESEM, the results of AFM revealed a fine dispersion and spherical form of cellulose nanoparticles. The interaction between HMG-CoA reductase and CNC was studied by the usage of multi-spectroscopic methods and enzyme kinetics to explore the binding mechanism of HMG-CoA reductase-CNC system. Reduced catalytic activity of the occurrence of changes in the secondary structure of HMG-CoA reductase was as a result of interacting with CNC causing a reduction in its catalytic activity.
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Citrus , Nanopartículas , Celulose/química , Nanopartículas/química , Colesterol , OxirredutasesRESUMO
The current treatment approaches for esophageal cancer are associated with poor survival, and there are ongoing efforts to find new and more effective therapeutic strategies. There are several reports on the antitumoral effects of low-molecular-weight heparins (LMWHs). We have assessed the possible survival benefit of LMWHs in esophageal malignancies. This was a randomized, single-blind, multicenter, Phase II clinical trial on nonmetastatic esophageal cancer candidate for neoadjuvant chemoradiotherapy. Patients were randomly assigned to the chemoradiotherapy-only arm or chemoradiotherapy plus enoxaparin arm using 1:1 allocation. Radiotherapy was delivered in 1.8-Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m2 and carboplatin (AUC 2) were administered weekly, concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) and chemoradiation daily. 4-6 weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months, estimated 1 year disease-free survival (DFS) in the intervention group was 78.9% and was 70% in the control groups ( p = 0.5). Toxicity from the experimental treatment was minimal, and there were no treatment-related deaths. A pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively ( p = 0.9). There was a nonsignificant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1 y DFS of both groups were high as expected. A longer follow-up and a larger sample size are required.
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Antineoplásicos/uso terapêutico , Enoxaparina/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/terapia , Antineoplásicos/efeitos adversos , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Enoxaparina/efeitos adversos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Fatores de TempoRESUMO
Radiation-induced dermatitis is one of the most common side effects of radiotherapy. Silymarin, a flavonoid extracted from the Silybum marianum, exhibits antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the efficacy of silymarin gel in prevention of radiodermatitis in patients with breast cancer. During this randomized, double-blinded, placebo-controlled clinical trial, the preventive effect of silymarin 1% gel was assessed in comparison with placebo, on radiodermatitis occurrence. Forty patients randomly received silymarin gel or placebo formulation on chest wall skin following modified radical mastectomy, once daily starting at the first day of radiotherapy for 5 weeks. Radiodermatitis severity was assessed weekly based on Radiation Therapy Oncology Group (RTOG) and National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE) criteria radiodermatits grading scale for 5 weeks. The median NCI-CTCAE and RTOG scores were significantly lower in silymarin group at the end of the third to fifth weeks (p value < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay in radiodermatitis development and progression in silymarin group. Prophylactic administration of silymarin gel could significantly reduce the severity of radiodermatitis and delay its occurrence after 5 weeks of application.
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Neoplasias da Mama/terapia , Radiodermite/prevenção & controle , Silimarina/administração & dosagem , Administração Tópica , Adulto , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Silybum marianum/química , Silimarina/farmacologiaRESUMO
Mucositis is a frequent severe complication of radiation therapy in patient with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluate silymarin efficacy in prevention of radiotherapy induced mucositis in patients with head and neck cancer, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy for 6 weeks, on oral mucositis occurrence was assessed. Twenty-seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization and National Cancer Institute-Common Terminology Criteria oral mucositis grading scale scores were recorded at baseline and weekly during these 6 weeks. The median World Health Organization and National Cancer Institute Common Terminology Criteria scores were significantly lower in silymarin group at the end of the first to sixth week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay for mucositis development and progression in silymarin group. Prophylactic administration of conventional form of silymarin tablets could significantly reduce the severity of radiotherapy induced mucositis and delay its occurrence in patients with head and neck cancer. Copyright © 2016 John Wiley & Sons, Ltd.
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Neoplasias de Cabeça e Pescoço/complicações , Silybum marianum/química , Silimarina/química , Estomatite/induzido quimicamente , Administração Oral , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Silimarina/administração & dosagem , Silimarina/farmacologia , Estomatite/tratamento farmacológicoRESUMO
Small-cell neuroendocrine carcinomas (SCNECs) of the female genital tract are rare and aggressive tumors that are characterized by a high rate of recurrence and poor prognosis. They can arise from various sites within the female genital tract, including the cervix, endometrium, ovary, fallopian tube, vagina, and vulva. They are composed of cells with neuroendocrine features, such as the ability to produce and secrete hormones and peptides, and a high mitotic rate. Immunohistochemical staining for neuroendocrine markers, such as chromogranin A, synaptophysin, and CD56, can aid in the diagnosis of these tumors. This article provides an overview of the epidemiology, etiology, and risk factors associated with these tumors, as well as their clinical presentation, cellular characteristics, diagnosis, and finally the current treatment options for SCNECs, including surgery, chemotherapy, and radiation therapy, alone or in combination.
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Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Neoplasias dos Genitais Femininos , Humanos , Feminino , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Pequenas/patologia , Neoplasias dos Genitais Femininos/terapia , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/epidemiologia , Fatores de RiscoRESUMO
PURPOSE OBJECTIVE(S): Manual contouring of the prostate region in planning computed tomography (CT) images is a challenging task due to factors such as low contrast in soft tissues, inter- and intra-observer variability, and variations in organ size and shape. Consequently, the use of automated contouring methods can offer significant advantages. In this study, we aimed to investigate automated male pelvic multi-organ contouring in multi-center planning CT images using a hybrid convolutional neural network-vision transformer (CNN-ViT) that combines convolutional and ViT techniques. MATERIALS/METHODS: We used retrospective data from 104 localized prostate cancer patients, with delineations of the clinical target volume (CTV) and critical organs at risk (OAR) for external beam radiotherapy. We introduced a novel attention-based fusion module that merges detailed features extracted through convolution with the global features obtained through the ViT. RESULTS: The average dice similarity coefficients (DSCs) achieved by VGG16-UNet-ViT for the prostate, bladder, rectum, right femoral head (RFH), and left femoral head (LFH) were 91.75%, 95.32%, 87.00%, 96.30%, and 96.34%, respectively. Experiments conducted on multi-center planning CT images indicate that combining the ViT structure with the CNN network resulted in superior performance for all organs compared to pure CNN and transformer architectures. Furthermore, the proposed method achieves more precise contours compared to state-of-the-art techniques. CONCLUSION: Results demonstrate that integrating ViT into CNN architectures significantly improves segmentation performance. These results show promise as a reliable and efficient tool to facilitate prostate radiotherapy treatment planning.
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BACKGROUND: Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). This post-marketing surveillance evaluates the safety of a trastuzumab biosimilar (AryoTrust), produced by AryoGen Co. Iran in Iranian women with HER2-positive non-metastatic breast cancer (BC). RESEARCH DESIGN AND METHODS: The patients who had undergone adjuvant chemotherapy regimens received trastuzumab every 3 weeks for nine cycles. The study started in February 2017 and finished in August 2022. Data regarding safety were collected using booklets and then analyzed. RESULTS: A total of 597 women with a mean ±SD age of 48.13 ± 10.18 years underwent 5,313 injection cycles. They received pre-study chemotherapies consisting of anthracyclines, taxanes, both, or other medications in 6.70, 7.20, 82.41, and 2.01% of the cases, respectively. One hundred and thirty-nine patients experienced at least one adverse event (AE). The most common AEs were decreased ejection fraction (EF, 5.7%), peripheral neuropathy (5.36%), and nausea (5.19%). Meningioma was the only life-threatening serious AE. Furthermore, bone pain and infusion-related reactions were the two most common grade three AEs. Nevertheless, the mean EF of patients did not change notably during the study. CONCLUSIONS: The results demonstrate that this trastuzumab biosimilar is a generally well tolerated and safe treatment for HER2-positive BC. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06021379.
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Objectives: In this work, we propose an efficient preparation process for the synthesis of natural carbon quantum dots (NCQDs) by the usage of orange pericarp as the carbon natural resource, which is performed through hydrothermal treatment and top-down approaches. Materials and Methods: The structural, morphological, average size, and optical properties of synthesized NCQDs were investigated via dynamic light scattering (DLS), transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM), field emission scanning electron microscope (FESEM), energy dispersive x-ray spectroscopy (EDX), ultraviolet-visible spectroscopy (UV-Vis), and fluorescence PL spectra. Results: The shape of obtained NCQDs was observed to be spherical in the results of TEM analysis with an average size of 6-7 nm which confirms NCQDs essence. The signs of a strong peak (absorption) at around 282 nm throughout the UV-vis spectrum have been detected. The provided FTIR spectroscopy confirmed the existence of functional groups above the NCQDs surface. Furthermore, the surface charge of -11 mV through the obtained zeta potential regarding the synthesized NCQDs has been identified. MTT assay on mouse colon carcinoma cells (C26) demonstrated the lack of any signs of toxicity in NCQDs. Conclusion: The obtained NCQDs contain high photo-stability, excellent PL activity, and efficient fluorescent emission based on excitation. The results of kinetic studies revealed the ability of NCQDs to inhibit trypsin activity in a non-competitive model, which qualifies them as potent inhibitors and quenchers of trypsin. It can be suggested that the synthesized NCQDs have the potential of functioning as a sustainable and eco-friendly source for various applications such as sensors for detecting Ca2+ and Zn2+ and trypsin biosensor for determining enzyme activity.
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This study aimed to investigate the effect of bladder volume on the dosimetry of pelvic organs at risk (OARs) in patients treated with external beam radiation therapy. Twenty patients with locally advanced cervical cancer were selected. Two computed tomography-simulation scans were obtained, one with an empty bladder followed by one with a full bladder. The acquired images were transferred to the treatment planning system. Target and OARs were contoured in both images, and treatment plans were performed for each computed tomography image. The delivered doses to target and OARs were determined using dose-volume histograms. The mean dose of the bowel bag in the empty and full bladder were 35.06 ± 4.13 (Gy) and 31.59 ± 3.86 (Gy), respectively. Furthermore, the V45 of the bowel bag in the empty bladder was 364.27 ± 154.39 (cc) and in the full bladder, it was 240.84 ± 129.66 (cc). The mean dose of the rectum in the empty and full bladder were 49.50 ± 1.95 (Gy) and 49.18 ± 1.03 (Gy), respectively. The rectal V50 (%) was 52.82 ± 21.84 (%) in the empty bladder and 45.49 ± 29.55 (%) in the full bladder. The mean dose and V45 of the bowel bag, also V50 of the rectum, had significantly decreased in the full bladder status (p-value < 0.05). The results showed that the bladder volume significantly affected the delivered dose to the bowel bag and rectum. The average bowel bag V45 and rectum V50 in the full bladder were significantly decreased. Bladder distention is an effective method to improve the dosimetric parameters of pelvic OARs.
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Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/radioterapia , Bexiga Urinária , Dosagem Radioterapêutica , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
PURPOSE: In this clinical trial, we evaluated Alpha® ointment efficacy in prevention of capecitabine induced hand-foot syndrome (HFS) in patients with gastrointestinal or breast cancers, for the first time. METHODS: During this pilot, randomized, triple-blinded, placebo-controlled clinical trial, the effect of Alpha® ointment (Lawsonia inermis 3 g and Curcuma longa 0.15 g/ 30 g) was assessed. It was applied on the palms and the soles, two times daily starting at the first day of chemotherapy for 4 consecutive courses. The severity of HFS was assessed at the end of the chemotherapy courses based on World Health Organization (WHO) scale and scored between 0-4. RESULTS: Ninety eligible patients were included randomly in the treatment or placebo group. Median WHO HFS grade was not significantly different between the two groups, during the follow-up period (P > 0.05). In the weekly assessment, the scores increased meaningfully in both the placebo and treatment groups, but there was a delay in HFS occurrence and deterioration in Alpha ointment group based on post hoc analysis. CONCLUSION: Administration of Alpha® ointment containing henna and curcumin could not significantly prevent capecitabine induced HFS during 4 courses of treatment, but can somewhat delay its occurrence in patients with gastrointestinal or breast cancer.
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Neoplasias da Mama , Curcumina , Síndrome Mão-Pé , Lawsonia (Planta) , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/efeitos adversos , Feminino , Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/prevenção & controle , Humanos , Pomadas/uso terapêuticoRESUMO
BACKGROUND: Pre-operative chemoradiotherapy (NACRT) of patients with proximal gastric and esophagogastric junction (EGJ) adenocarcinoma may result in increased local control and improved patients' survival rate. This study aimed to investigate the effect of NACRT on resectability of tumor in patients with proximal gastric and EGJ adenocarcinoma. METHODS: In this single-arm clinical trial, patients with locally advanced proximal gastric and EGJ adenocarcinoma were included. Two courses of paclitaxel/carboplatin chemotherapy alone followed by NACRT with a similar treatment regimen and a total radiation dose of 45-50.4/1.8-2 Grays were prescribed. After surgery, patients were evaluated for resection rate, pathologic response rate, and post-surgical complications. RESULTS: A total of 61 patients with a mean age of 65.9 years participated. Grades 1 and 2 were the most prevalent side effects, with grade 3 being the worst grade and exhibiting as leukopenia (4.9%) and thrombocytopenia (1.6%). 25 (41%) patients underwent surgery after NACRT. Post-surgery complication was reported in 20% of cases (including 8% mortality and 12% morbidity). R0 and R2 resection was observed in 88% and 12% of cases, respectively. Complete pathologic-response was achieved in 24% of patients. CONCLUSION: Paclitaxel/carboplatin based neoadjuvant chemotherapy was associated with potential resectability and appropriate pathologic response in patients with locally advanced proximal gastric and EGJ adenocarcinoma. However, by reducing patient tolerance to complete courses of weekly chemotherapy, induction chemotherapy lowered the effectiveness of concurrent chemotherapy and radiotherapy (as a sensitizing agent). Hence, induction chemotherapy proved to be more unbeneficial causing delayed treatment and reducing concurrent chemoradiotherapy tolerance.
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PURPOSE: The present study was conducted to compare dosimetric parameters for the heart and left lung between free breathing (FB) and deep inspiration breath hold (DIBH) and determine the most important potential factors associated with increasing the lung dose for left-sided breast radiotherapy using image analysis with 3D Slicer software. MATERIALS AND METHODS: Computed tomography-simulation scans in FB and DIBH were obtained from 17 patients with left-sided breast cancer. After contouring, three-dimensional conformal plans were generated for them. The prescribed dose was 50 Gy to the clinical target volume. In addition to the dosimetric parameters, the irradiated volumes and both displacement magnitudes and vectors for the heart and left lung were assessed using 3D Slicer software. RESULTS: The average of the heart mean dose (Dmean) decreased from 5.97 to 3.83 Gy and V25 from 7.60% to 3.29% using DIBH (p < 0.001). Furthermore, the average of Dmean for the left lung was changed from 8.67 to 8.95 Gy (p = 0.389) and V20 from 14.84% to 15.44% (p = 0.387). Both of the absolute and relative irradiated heart volumes decreased from 42.12 to 15.82 mL and 8.16% to 3.17%, respectively (p < 0.001); however, these parameters for the left lung increased from 124.32 to 223.27 mL (p < 0.001) and 13.33% to 13.99% (p = 0.350). In addition, the average of heart and left lung displacement magnitudes were calculated at 7.32 and 20.91 mm, respectively. CONCLUSION: The DIBH is an effective technique in the reduction of the heart dose for tangentially treated left sided-breast cancer patients, without a detrimental effect on the left lung.
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INTRODUCTION: Currently, neoadjuvant fluoropyrimidine-based chemoradiation followed by surgery is considered the standard of care for locally advanced rectal cancer. The current study aimed to investigate the predictive significance of mucinous histology on the pathologic complete response rate following neoadjuvant chemoradiation in locally advanced rectal cancer and to propose potential new treatment protocol for this specific histology. MATERIAL AND METHOD: This retrospective study was conducted on 403 patients with locally advanced (clinically T3-4 and/or N1-2) rectal adenocarcinoma who had been treated at three tertiary academic hospitals between 2010 and 2015. Among those 403 patients, 46 (11%) had mucinous rectal cancer (MRC) and 358 (89%) had non-mucinous rectal cancer (NMRC). All patients underwent neoadjuvant chemoradiation with capecitabine followed by low anterior or abdominoperineal resection. RESULTS: There were 268 men and 135 women with a median age of 55 years (range, 26-82 years). Patients with MRC were younger (p = 0.002) and presented with a larger tumor size (p < 0.001) and a more advanced tumor stage (p = 0.033) compared to the ones with MNRC. In the univariate analysis, female gender (p = 0.009), distal tumor location (p = 0.035), higher tumor stage (p = 0.049), node positivity (p = 0.001), MRC histology (p = 0.017), and high pretreatment CEA level (p = 0.013) were observed to be predictive of a poor pathologic complete response. However, in the multivariate analysis, tumor stage was the single most predictive factor of response to neoadjuvant chemoradiation. CONCLUSION: Mucinous adenocarcinoma is a significant predictive factor for poor pathologic complete response to neoadjuvant capecitabine-based chemoradiation in patients with locally advanced rectal cancer. New treatment modality based on biomarkers may be considered in future prospective studies because of MRC poor prognosis. Immunotherapy combined with chemotherapy and/or radiotherapy may be an attractive option because of the tumor microsatellite instability-high status.
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Adenocarcinoma Mucinoso/terapia , Capecitabina/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Retais/terapia , Reto/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Protectomia , Prognóstico , Intervalo Livre de Progressão , Tolerância a Radiação/genética , Neoplasias Retais/genética , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/efeitos dos fármacos , Reto/efeitos da radiação , Reto/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Breast cancer is the leading cause of cancer worldwide. The high expenses associated with chemotherapy as well as its side effects make the management of breast cancer a daunting challenge. The most common overexpressed gene in breast cancer is cyclinD1, which induces cell proliferation. Recent investigations into cancer treatment have revealed that curcumin demonstrates potential anti-cancer properties through different pathways. However, the oral bioavailability of curcumin is negligible due to its high hydrophobic structure. Nanotechnology has been employed to overcome this barrier. Nano-formulated curcumin (SinaCurcumin®) has been shown to provide a significantly higher bioavailability for oral consumption. However, the efficacy of this nano-formulated drug in breast cancer has not yet been determined. In relation to the breast cancer cell line, the present study compared nano-curcumin's anti-cancer properties with those of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). METHODS: After treating MCF7 with nano-curcumin and CAF, the present work assessed cell viability via an MTT assay. The effects of these drugs on cyclinD1 expression were measured by real-time PCR. SPSS 16.0 was used to perform ANOVA and multiple range tests. RESULTS: Nano-curcumin and the CAF regimen both lowered the viability of MCF7. Nano-curcumin decreased cell proliferation by 83.6%, which was more than that achieved by cyclophosphamide (63.31%), adriamycin (70.75%), and 5-fluorouracil (75.04%). In addition, curcumin was able to significantly reduce the expression of cyclinD1, whereas CAF did not alter cyclinD1 expression. CONCLUSION: Nano-curcumin has a relatively high cytotoxic effect on MCF7 breast cancer cells, suppressing the expression of cyclinD1, a critical gene in the development and metastasis of breast cancer. The current study demonstrated that nano-curcumin can be an effective drug in the CAF regimen for the treatment of breast cancer. However, further in vivo research is needed for determining its efficacy and safety in clinical applications.
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OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most significant health condition around the world. As the only curative therapies, liver transplantation and surgical resection are the clinical treatments of HCC. Due to the systemic toxicity and severe side effects of these treatments, it is vital to establish new therapeutic approaches. The present study aimed to compare cyclin D1 (CCN D1) gene expression in hepatocellular carcinoma cell line (HUH7) when it is treated with nanomicelle curcumin and sorafenib. The purpose was to identify toxicity risk and antioxidant activity of these drugs. MATERIALS AND METHODS: The toxic dose (IC50) of nanomicelle curcumin and sorafenib were detected after treatment of HUH7 cell lines with different dose of mentioned agents followed by MTT assay. CCN D1 gene expression was evaluated using real-time PCR. Following the Tukey's multiple comparison tests, statistical analysis is done through Student's t-test or ANOVA. RESULTS: The expression of the CCN D1 gene was statistically significant (P<0.001) at 289.31, 128 and 152.36 for sorafenib, nanomicelle curcumin and SNC (sorafenib-nanomicelle curcumin) respectively. The finding of this study revealed that, in comparison to sorafenib alone, the treatment of HUH7 with a nanomicelle curcumin IC50 dose, in combination with sorafenib, might down-regulate CCN D1 gene expression. CONCLUSION: The present research indicates that the treatment of the cell line with only nanomicelle curcumin results in the down-regulation of cyclin D1. To further decrease cyclin D1 expression, the co-delivery of curcumin and sorafenib appears to induce the apoptotic process. As a result, the effect of sorafenib cytotoxicity and CCN D1 gene expression decreases twofold.
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BACKGROUND: The incidence of esophageal squamous cell carcinoma (ESCC) is increasing, causing catastrophic health burdens on communities. Curcumin has shown promise as a therapeutic agent in the treatment of colon, colorectal, pancreatic, and esophageal cancers but it has very poor bioavailability. The application of nano-carriers as drug delivery systems increases curcumin's bioavailability. Cyclin D1 is overexpressed in ESCC and curcumin may change its expression. METHODS: In this study, the effect of SinaCurcumin®, a novel nano-micelle product containing 80 mg curcumin, on the growth of KYSE-30 cells and expression of cyclin D1, was investigated. Paclitaxel and Carboplatin served as reference drugs. RESULTS: Nano-curcumin increased cell cytotoxicity, decreased IC50, and down-regulated of cyclin D1. However, treatment of cells with nano-curcumin might result in multidrug resistance. CONCLUSION: Nano-curcumin suppressed proliferation of KYSE-30 cells and expression of cyclin D1 although its use in combination with other chemotherapeutic agents requires further testing.
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PURPOSE: Local recurrence is a common failure pattern in adenocarcinoma of the cecum. This study aimed to investigate the potential role of adjuvant radiation therapy on oncologic outcomes of patients with adenocarcinoma of the cecum. MATERIALS AND METHODS: This retrospective study was carried out at three large tertiary university hospitals. We analyzed the characteristics, prognostic factors, and survival of 162 patients with adenocarcinoma of the cecum that were treated and followed up between 2000 and 2013. All the patients had undergone a right hemicolectomy and received chemotherapy with (n = 48) or without (n = 114) adjuvant radiation therapy. RESULTS: The subjects were 65 females and 97 males with a median age of 56 years (range, 17 to 90 years) at diagnosis. The 5-year local control (LC), disease free survival (DFS), and overall survival (OS) rates were 72.7%, 57.2%, and 62.6% respectively. In a multivariate analysis, age, tumor stage, node stage, and adjuvant radiation therapy were determined to be independent prognostic factors. Age more than 55 years (hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.06-0.32; p = 0.003], T4 stage (HR = 6.8; 95% CI, 3.07-15.36; p < 0.001), node positive disease (HR = 4.2; 95% CI, 1.94-9.13; p < 0.001), and the absence of adjuvant radiation therapy (HR = 3.0; 95% CI, 1.39-6.46; p = 0.005) had a negative influence on OS. CONCLUSION: Adjuvant radiation therapy significantly improves DFS and OS in patients with adenocarcinoma of the cecum.