scholarly journals Ultrasound-Triggered Release of 5-Fluorouracil from Soy Lecithin Echogenic Liposomes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 821
Author(s):  
Charles Izuchukwu Ezekiel ◽  
Alain Murhimalika Bapolisi ◽  
Roderick Bryan Walker ◽  
Rui Werner Maçedo Krause
Keyword(s):  
Colorectal Cancer ◽  
Low Frequency ◽  
Therapeutic Index ◽  
Bone Marrow Toxicity ◽  
Triggered Release ◽  
Scanning Calorimetry ◽  
Soy Lecithin ◽  
Ultrasound Waves ◽  
High Level ◽  
Colorectal Cancer Patients

Colorectal cancer is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) has been the major chemotherapeutic treatment for colorectal cancer patients. However, the efficacy of 5-FU is limited by drug resistance, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying the need for improvement of the therapeutic index. In this study, the effects of ultrasound on echogenic 5-FU encapsulated crude soy liposomes were investigated for their potential to address these challenges. Liposomes were prepared by thin-film hydration using crude soy lecithin and cholesterol. Argon gas was entrapped in the liposomes for sonosensitivity (that is, responsiveness to ultrasound). The nanoparticles were characterized for particle size and morphology. The physicochemical properties were also evaluated using differential scanning calorimetry, Fourier transform infrared and X-ray diffraction. The release profile of 5-FU was assessed with and without 20 kHz low-frequency ultrasound waves at various amplitudes and exposure times. The result reveal that 5-FU-loaded liposomes were spherical with an encapsulation efficiency of approximately 60%. Approximately 65% of 5-FU was released at the highest amplitude and exposure time was investigated. The results are encouraging for the stimulated and controlled release of 5-FU for the management of colorectal cancer.

Awareness of KRAS testing by oncologists and panitumumab use in colorectal cancer patients: A European survey.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 547-547
Author(s):  
Jorg Trojan ◽  
Aliki Taylor ◽  
Jan-Henrik Terwey ◽  
Gerry Downey ◽  
George Kafatos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Wild Type ◽  
Nras Mutation ◽  
Mutation Status ◽  
Kras Status ◽  
Level Of Knowledge ◽  
High Level ◽  
Colorectal Cancer Patients ◽  
Kras Mutation Status

547 Background: Panitumumab (Pmab) is licensed for treatment in metastatic colorectal cancer (mCRC) patients with wild type KRAS mutation status (US) and wild type RAS (KRAS and NRAS) mutation status (most other countries). To resolve uncertainties about KRAS testing, a survey and medical records review (MRR) are being carried out in Europe in three rounds: the first two rounds (2012-2013) evaluated KRAS testing and round 3 is evaluating RAS testing. These studies are specific obligations in Europe for the conditional marketing authorization for Pmab. Here we present results of rounds 1 and 2. Methods: Eligible oncologists were contacted by telephone in nine European countries (France, Germany, Italy, Spain, Czech Republic, Netherlands, Belgium, Denmark, and Sweden). To be eligible, the physician was required to be a practicing oncologist and have prescribed Pmab to mCRC patients. Results: 299 of 301 (99.3%) oncologists participating in the survey were aware of the need to perform KRAS testing prior to first dose of Pmab and 294 (97.7%) were aware of patients’ KRAS mutation status prior to first dose. 283 of 301 (94.0%) did not prescribe Pmab to mCRC patients with mutant or unknown KRAS status. 164 physicians administered Pmab simultaneously with oxaliplatin-containing chemotherapy to patients and 10 (6.1%) to patients with mutant or unknown KRAS status. 306 patients from 79 participating oncologists were included in the MRR. 302 of 306 mCRC patients (98.7%) were tested for KRAS tumor status, known by the oncologist before first dose of Pmab. 299 of 302 patients (99.0%) had wild-type KRAS tumor status. 83 of 85 patients (97.6%) treated with Pmab and oxaliplatin-containing chemotherapy had wild-type KRAS tumor status. 55 of 56 linked pathology laboratories (98.2%) participated in a Quality Assurance scheme; all used a CE marked or otherwise validated KRAS detection method. Conclusions: Results from both studies show a high level of knowledge among oncologists of the need for KRAS testing in mCRC patients prior to treatment with Pmab and the contraindication with oxaliplatin-containing chemotherapy with mutant or unknown KRAS tumour status. The final round of this study evaluating RAS testing in Europe is currently underway.

scholarly journals The Impact of KPNA2 on Prognosis of Colorectal Cancer Patients: A Meta-Analysis

2022 ◽  
Author(s):  
Zhangzhe Yan ◽  
Mingang He ◽  
Haoxin Shi ◽  
Haipeng Wang ◽  
Miao Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Malignant Tumors ◽  
Hot Spot ◽  
Meta Analysis ◽  
Tumor Stage ◽  
Medical Database ◽  
High Level ◽  
Colorectal Cancer Patients ◽  
The Impact ◽  
The Relationship

Abstract Background and purpose: Colorectal cancer (CRC) is one of the most common malignant tumors with the highest mortality globally. At present, there is no exact biomarker to predict the prognosis and clinicopathological monitoring of CRC patients. Recent studies on the relationship of Karyopherin α 2 (KPNA2) expression and the prognosis of CRC has gradually become a hot spot while the results are still controversial. The aim of this study was to analyze and assess the prognostic role of KPNA2 in CRC patients. Methods: PubMed, Web of Science, Medline, EMBASE, CNKI, Wanfang, VIP, and Chinese Medical Database were systematically searched. The cohort study of high-level expression of KNPA2 and low-level expression of KPNA2 in CRC patients was included, the relevant data were extracted and the literature quality was evaluated. At the same time, the relationship between KPNA2 expression level and the overall survival (OS), the clinicopathological stage of CRC patients was studied. Meta-analysis was carried out by Stata MP 17.0 (Stata Corporation, College Station, TX, USA) software. Results: A total of 7 cohort studies involving 1166 patients were included. The analysis results showed that higher KPNA2 expression was significantly associated with higher tumor stage (OR=1.90, 95% CI 1.42–2.54), higher degree of tumor invasion (OR=2.14，95% CI 1.55-2.94), more lymph node metastasis (OR=2.20, 95% CI 1.68-2.88) and more distant metastasis (OR=3.66，95% CI 1.81-7.40). Moreover, higher KPNA2 expression was significantly associated with the shorter OS (HR=2.31, 95%CI 1.46-3.68).Conclusion: KPNA2 overexpression is an unfavorable prognostic factor for CRC patients. It could serve as a prognostic biomarker and as a potential therapeutic target for CRC.

Prognostic value of circulating cytokines in colorectal cancer: A prospective study in sixty colorectal cancer patients in Tunisia.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15130-e15130
Author(s):  
Jihene Braham Ayari ◽  
Rania Guesmi ◽  
Mehdi Balti ◽  
Mouna Ben Azaiz ◽  
Aref Zribi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Solid Phase ◽  
Young Patients ◽  
Serum Samples ◽  
Metastatic Setting ◽  
The Mean ◽  
High Level ◽  
Colorectal Cancer Patients ◽  
Circulating Cytokines

e15130 Background: Colorectal cancer is the third most common malignancy and fourth most common cause of cancer mortality worldwide. It is responsible for more than 600,000 deaths annually, and incidence rates are increasing in most of the developing countries. Pathophysiology implicates pro-inflammatory conditions that promote the tumor malignant progression, invasion, and metastasis. The aim of this study is to measure the level of circulating cytokines (IL1b, IL6, IL8, IL10, IL22, IL23 and TNFα) in sixty colorectal cancer patients in Tunisia and to evaluate their implication as prognostic factors. Methods: Serum samples were collected prospectively from a cohort of sixty colorectal cancer patients in Tunisia. Levels of circulating inflammatory cytokines, TNF-α, IL1b, IL6 and IL8 were measured using the technique of a solid-phase, two-site chemo-luminescent enzyme immune-metric assay (Immulite 1000, Simens, USA). Serum levels of IL10 were measured by enzyme-linked immunosorbent assays (ELISA) sandwich method. Results: The mean age of patients is 58 years (24–82 years), Thirty-sex among them were m and 24 women with sex ratio of 1.5. Twenty-five patients were at metastatic setting, and hepatic metastasis was found in 25% of cases. The mean level of cytokines Il6, IL10, TNFα, IL8 and IL1b were respectively 12.26 +/- 18.7 pg/ ml (min 2, max 117pg/ ml), 0.93 +/- 5.23 pg/ ml (min 0, max 39.35 pg/ml), 8.31 +/- 4.99 pg/ ml (min 4, max 27.20 pg/ ml), 61.9 +/- 159.71 pg/ml (min 5, max 1173 pg/ ml) and 1.13 +/- 3.34 pg/ ml (min 5, max 15.7pg/ml. We found a significant correlation between a high level of IL8 and metastatic disease (p=0.001), especially in mutant RAS cases (p=0.001). We found also a significant correlation between high level of IL1b and lymphovascular invasion (p=0.013) and young patients (p=0.01). On the other hand, there was significant correlation between IL8 and IL6 (r = 0.560, p = 0.00001); IL8 and TNFα (r = 0.404, p = 0.001); and IL10 with IL1b (r = 0.297, p = 0.021). Conclusions: Our results highlight the role of circulating IL8, TNFα, IL1b and IL10 as potential prognostic biomarkers in colorectal cancer patients. These cytokines could contribute to tumor growth and progression, namely for IL-8 level that was significantly correlated with poor prognosis and advanced stages. This correlation needs to be evaluated in large prospective trials and suggests a rational for the development and use of cytokine blockade in treatment of colorectal cancer patients.

scholarly journals Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 595-595 ◽  
Author(s):  
Riccardo Giampieri ◽  
Lisa Salvatore ◽  
Michela Del Prete ◽  
Tiziana Prochilo ◽  
Marco D'Anzeo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Colorectal Cancer Patients ◽  
Ecog Ps

595 Background: The introduction of regorafenib for the treatment of colorectal cancer represented a sure medical achievement though at a cost of relevant toxicity. As a consequence the lack of predictive factors made the use of regorafenib in the clinical practice challenging. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and potentially influence outcome during anti-angiogenesis treatment. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. Methods: From a multicentre experience 138 samples (tumour or blood samples) of colorectal cancer patients receiving regorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients’ progression-free survival (PFS) and overall survival (OS) were analysed. Results: Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS (respectively HR: 0.49, 95% CI: 0.33-0.81, p=0.003 and HR: 0.52, 95% CI: 0.34-0.99, p=0.04). A correlation with disease control rate (DCR) was also observed (DCR 55% vs. 26%, p=0.02). Among clinical factors only ECOG PS was independently correlated with OS (HR: 0.52, 95% CI: 0.21-0.81, p=0.009), whereas no correlation with PFS was evident. Grouping together observations from angiogenesis genotyping and ECOG PS allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. Median OS resulted progressively decreased across these groups (OS not reached, 7.8 and 3.9 months respectively in the favourable, intermediate and unfavourable group, p<0.0001). Conclusions: VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of candidates for regorafenib. This selection opportunity will ultimately improve the therapeutic index of such a treatment approach by limiting treatment to potentially responding patients and sparing unnecessary toxicity to those unlikely to benefit.

scholarly journals High level of unmet needs and anxiety are associated with delayed initiation of adjuvant chemotherapy for colorectal cancer patients

2020 ◽  
Vol 28 (11) ◽  
pp. 5299-5306
Author(s):  
Li Zhu ◽  
Yi Xin Tong ◽  
Xiang Shang Xu ◽  
Ai Tang Xiao ◽  
Yu Jie Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Unmet Needs ◽  
Anxiety And Depression ◽  
Care Needs ◽  
Delayed Initiation ◽  
High Level ◽  
Colorectal Cancer Patients

Abstract Aims Adjuvant chemotherapy is recommended for patients with curatively resected colorectal cancer. The aim of this study is to evaluate the impact of unmet supportive care needs and anxiety on the initiation of postoperative adjuvant chemotherapy in colorectal cancer patients. Methods This is a retrospective study from a single tertiary referral hospital. Patients diagnosed with colorectal cancer who met the inclusion criteria were included. The Hospital Anxiety and Depression Scale (HADS) and modified 34-item Supportive Care Needs Survey (SCNS-SF34) were applied to assess patient’s anxiety level and unmet needs. The time intervals between initiation of adjuvant chemotherapy and operation were recorded. Factors associated with delayed initiation of chemotherapy were investigated in univariate and multivariate analysis. Results A total of 135 patients with colorectal cancer were included. In total, 16.3% (22/135) and 5.2% (7/135) reported symptoms of anxiety and depression. In multivariate analysis, low to moderate income status, postoperative complications, anxiety, and high level of unmet needs are independent risk factors for late initiation of chemotherapy. Conclusions Our findings showed that psychological problems such as anxiety and high unmet supportive needs are correlated with delayed initiation of adjuvant chemotherapy in colorectal cancer patients.

Impact on therapeutic index of a chronomodulated infusion at conventional doses of oxaliplatin (OHP), 5-fluorouracil (5-FU) and folinic acid (AF) in not previously treated metastatic colorectal cancer patients: A multicentric observational study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14572-14572
Author(s):  
M. Pirovano ◽  
A. Zambelli ◽  
F. Gherardi ◽  
S. Masseroni ◽  
A. Nasisi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Observational Study ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Flow Rate ◽  
Dose Intensity ◽  
Therapeutic Index ◽  
Average Dose ◽  
Circadian Timing System ◽  
Colorectal Cancer Patients

14572 Background: FOLFOX4 schedule represents the standard treatment for metastatic colorectal cancer in EU, but is characterized by relevant adverse effects like G3–4 neutropenia in 42 % of patients (data from MOSAIC study). Adjustment of chemotherapy delivery schedule to the circadian timing system allows a significative improvement of tolerability. Objective of this multicentric observational study is the evaluation of therapeutic index of a OHP and 5-FU + AF based schedule at the same doses of FOLFOX 4, but administered according to a chronomodulated schedule (FLOX-1). Methods: From November 2005 to December 2006, we treated 41 metastatic colorectal cancer patients (19 male and 22 female, average age 65) with OHP 85 mg/m2/d1q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 PM; 5-FU 1000 mg and AF 100 mg/m2/d1–2q14 sinusoidal 12 hour infusion with flow rate peak at 04.00 AM: a total of 258 cycles (5.5 average for patient) were administered using Melodie infusional programmable system (138 cycles) and CIP preprogrammed disposable system (128 cycles), all in homecare regimen. These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. Results: Overall average dose intensity was 39.1 mg/m2/w for OHP and 907.5 mg/m2/w for 5-FU respectively. No G3-G4 haematological, hepatic and neurological toxicity were observed. ORR (CR+PR) was 41%. No patient has been treated with G-CSF. Conclusions: These data confirm a significative tolerability improvement of OHP, 5-FU and AF schedule when infused according to a chronomulated infusion prophile in metastatic colorectal cancer patients. No significant financial relationships to disclose.

Associations of daily partner responses with fatigue interference and relationship satisfaction in colorectal cancer patients.

2018 ◽  
Vol 37 (11) ◽  
pp. 1015-1024
Author(s):  
Fabiola Müller ◽  
Marrit A. Tuinman ◽  
Ellen Stephenson ◽  
Ans Smink ◽  
Anita DeLongis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relationship Satisfaction ◽  
Cancer Patients ◽  
Colorectal Cancer Patients
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