Impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on Bisoprolol peak concentration and clinical response in acute coronary syndrome patients.

AIMS: Acute coronary syndrome (ACS) represents a major cause of death. Bisoprolol is commonly used in the management of ACS. This study aims to investigate the impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on pharmacokinetics and clinical response of bisoprolol in ACS patients. METHODS: This is an open-label cohort study that included 127 ACS patients and studied the effect of CYP3A5*3, CYP2D6*2A and CYP2D6*4 genotyping using real-time polymerase chain reaction on steady state bisoprolol plasma peak concentration analysed by high performance liquid chromatography-fluorescence detector. RESULTS: Regarding CYP3A5*3, the mean peak bisoprolol concentration for CC, CT and TT genotypes were 4.25 ± 1.20, 3.93 ± 1.10 and 1.79 ± 0.69 ng/mL, respectively (P < .001). Higher systolic (126 ± 5.47 mmHg), diastolic blood pressure (82 ± 2.73 mmHg) and heart rate (97.80 ± 3.03 beats/min) were also observed in CYP3A5*3 TT carriers (P < .05). In CYP2D6*2A, the peak concentration of bisoprolol was lower in CC carriers (3.54 ± 1 ng/mL) compared to GG (4.38 ± 1.25 ng/mL) and GC carriers (4.07 ± 1.29 ng/mL, P = .019). In CYP2D6*4, the mean bisoprolol peak concentration in CC carriers was 3.98 ± 1.31 ng/mL, which was lower than T allele carriers (4.5 ± 0.8, P = .02). No differences in heart rate, systolic, diastolic blood pressure or bisoprolol dose were observed among CYP2D6*2A or CYP2D6*4 variants. Smokers exhibited lower bisoprolol peak concentration (3.96 ± 1.2 ng/mL) compared to nonsmokers (4.55 ± 1.34 ng/mL, P = .037). CONCLUSION: There is an association between CYP3A5*3, CYP2D6*4, CYP2D6*2A variants and bisoprolol peak concentration, which may serve as a guide in the future in choosing the optimum dose of bisoprolol in ACS patients.

The Effect of Metformin on Chemotherapy-Induced Toxicities in Non-diabetic Breast Cancer Patients: A Randomised Controlled Study.

BACKGROUND AND OBJECTIVE: Breast cancer patients treated with adriamycin-cyclophosphamide plus paclitaxel (AC-T) are often challenged with serious adverse effects for which no effective therapies are available. Here, we investigated whether metformin, an antidiabetic drug with additional pleiotropic effects could favourably offset AC-T induced toxicities. PATIENTS AND METHODS: Seventy non-diabetic breast cancer patients were randomised to receive either AC-T (adriamycin 60 mg/m2 + cyclophosphamide 600 mg/m2 × 4 cycles Q21 days, followed by weekly paclitaxel 80 mg/m2 × 12 cycles) alone or AC-T plus metformin (1700 mg/day). Patients were assessed regularly after each cycle to record the incidence and severity of adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Moreover, baseline echocardiography and ultrasonography were done and repeated after the end of neoadjuvant therapy. RESULTS: Addition of metformin to AC-T resulted in significantly less incidence and severity of peripheral neuropathy, oral mucositis, and fatigue (p < 0.05) compared to control arm. Moreover, the left ventricular ejection fraction (LVEF%) in the control arm dropped from a mean of 66.69 ± 4.57 to 62.2 ± 5.22% (p = 0.0004) versus a preserved cardiac function in the metformin arm (64.87 ± 4.84 to 65.94 ± 3.44%, p = 0.2667). Furthermore, fatty liver incidence was significantly lower in metformin compared with control arm (8.33% vs 51.85%, p = 0.001). By contrast, haematological disturbances caused by AC-T were preserved after concurrent metformin administration (p > 0.05). CONCLUSION: Metformin offers a therapeutic opportunity for controlling toxicities caused by neoadjuvant chemotherapy in non-diabetic breast cancer patients. TRIAL REGISTRATION: This randomised controlled trial was registered on November 20, 2019 in ClinicalTrials.gov under registration number: NCT04170465.

Polymorphic renal transporters and cisplatin's toxicity in urinary bladder cancer patients: current perspectives and future directions.

Urinary bladder cancer (UBC) holds a potentially profound social burden and affects over 573,278 new cases annually. The disease's primary risk factors include occupational tobacco smoke exposure and inherited genetic susceptibility. Over the past 30 years, a number of treatment modalities have emerged, including cisplatin, a platinum molecule that has demonstrated effectiveness against UBC. Nevertheless, it has severe dose-limiting side effects, such as nephrotoxicity, among others. Since intracellular accumulation of platinum anticancer drugs is necessary for cytotoxicity, decreased uptake or enhanced efflux are the root causes of platinum resistance and response failure. Evidence suggests that genetic variations in any transporter involved in the entry or efflux of platinum drugs alter their kinetics and, to a significant extent, determine patients' responses to them. This review aims to consolidate and describe the major transporters and their polymorphic variants in relation to cisplatin-induced toxicities and resistance in UBC patients. We concluded that the efflux transporters ABCB1, ABCC2, SLC25A21, ATP7A, and the uptake transporter OCT2, as well as the organic anion uptake transporters OAT1 and OAT2, are linked to cisplatin accumulation, toxicity, and resistance in urinary bladder cancer patients. While suppressing the CTR1 gene's expression reduced cisplatin-induced nephrotoxicity and ototoxicity, inhibiting the expression of the MATE1 and MATE2-K genes has been shown to increase cisplatin's nephrotoxicity and resistance. The roles of ABCC5, ABCA8, ABCC10, ABCB10, ABCG1, ATP7B, ABCG2, and mitochondrial SLC25A10 in platinum-receiving urinary bladder cancer patients should be the subject of further investigation.

Repurposing levocetirizine hydrochloride loaded into cationic ceramide/phospholipid composite (CCPCs) for management of alopecia: central composite design optimization, in- silico and in-vivo studies.

Levocetirizine hydrochloride (LVC) is an antihistaminic drug that is repurposed for the treatment of alopecia. This investigation is targeted for formulating LVC into cationic ceramide/phospholipid composite (CCPCs) for the management of alopecia. CCPCs were fabricated by ethanol-injection approach, through a central composite experiment. CCPCs were evaluated by inspecting their entrapment efficiency (EE%), polydispersity index (PDI), particle size (PS), and zeta potential (ZP). The optimum CCPCs were additionally studied by in-vitro, ex-vivo, in-silico, and in-vivo studies. The fabricated CCPCs had acceptable EE%, PS, PDI, and ZP values. The statistical optimization elected optimum CCPCs composed of 5 mg hyaluronic acid, 10 mg ceramide III, and 5 mg dimethyldidodecylammonium bromide employing phytantriol as a permeation enhancer. The optimum CCPCs had EE%, PS, PDI, and ZP of 88.36 ± 0.34%, 479.00 ± 50.34 nm, 0.377 ± 0.0035, and 20.20 ± 1.13 mV, respectively. The optimum CCPC maintained its stability for up to 90 days. It also viewed vesicles of tube shape via transmission electron microscope. The in-silico assessment resulted in better interaction and stability between LVC and vesicle components in water. The ex-vivo and in-vivo assessments showed satisfactory skin retention of LVC from optimum CCPCs. The histopathological assessment verified the safety of optimum CCPCs to be topically applied. Overall, the optimum CCPCs could be utilized as a potential system for the topical management of alopecia, with a prolonged period of activity, coupled with reduced LVC shortcomings.

Impact of HOXB4 and PRDM16 Gene Expressions on Prognosis and Treatment Response in Acute Myeloid Leukemia Patients.

Introduction: Acute myeloid leukemia (AML) is the most common type of leukemia among adults and is characterized by various genetic abnormalities. HOXB4 and PRDM16 are promising markers of AML. Our objective is to assess the potential roles of HOXB4 and PRDM16 as prognostic and predictive markers in newly diagnosed AML patients and determine the correlation between their expressions and other prognostic markers as FLT3-ITD, NPM1 exon 12 mutations, response to treatment, and patient's survival. Methods: This study included 83 de novo AML adult patients. All patients were subjected to clinical, morphological, cytochemical, and molecular analysis to detect HOXB4 and PRDM16 gene expressions and FLT3-ITD, NPM1 exon 12 mutations. Results: The results showed that a low expression of HOXB4 was found in 31.3% of AML patients, whereas a high expression of PRDM16 was evident in 33.8% of AML patients. FLT3-ITD mutations were detected in 6 patients (7.2%), while NPM1 exon 12 mutations were detected in 7 patients (19.4%) out of 36 patients with intermediate genetic risk. Out of the 50 patients who achieved complete remission (CR), relapse occurred in 16% of the cases. Low expression of HOXB4 and high expression of PRDM16 were associated with CR of 32% and 28%, respectively, and a short overall survival (OS) and disease-free survival (DFS). Conclusion: Further larger study should be conducted to verify that high PRDM16 and low HOXB4 gene expressions could be used as a poor prognostic predictor for AML. The correlation between PRDM16 and HOXB4 gene expressions and FLT3-ITD and NPM1 exon 12 mutations might have a role on CR, relapse, OS, and, however, this should be clarified in analysis with a larger number of samples.

Role of ascorbic acid infusion in critically ill patients with transfusion-related acute lung injury.

INTRODUCTION: In critically ill patients, transfusion-related acute lung injury (TRALI) remains the leading cause of transfusion-related fatalities in critical care settings and is associated with inflammation and oxidative stress state. Recent research raised the potential efficacy of high-dose intravenous ascorbic acid (VC) in critically ill patients. OBJECTIVE: The aim of this trial was to investigate the effect of high-dose intravenous VC as a targeted therapy for TRALI in terms of serum proinflammatory (interleukin [IL]-8, IL-1ß, C-reactive protein), anti-inflammatory (IL-10), oxidative stress (superoxide dismutase, malondialdehyde) markers, and plasma VC levels. Secondary outcomes were oxygenation (PaO2 /FiO2 ratio), vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-day mortality and 28-day mortality. METHODS: Eighty critically ill patients with TRALI (n = 80) were randomized to receive 2.5 g/6 h intravenous vitamin C for 96 hours (ASTRALI group) or placebo. Patients were followed up to measure the outcomes initially (T0) and at the end of treatment (T96). RESULTS: When compared to the control group, the ASTRALI group at T96 showed significantly higher median of IL-10 (31.6 ± 25.8 vs 17.7 ± 12.0 pg/mL, P < .0001) levels and superoxide dismutase (12 876 ± 4627 U/L vs 5895 ± 6632 U/L, P < .0001) activities, and lower median C-reactive protein (76 ± 50 vs 89 ± 56 mg/L, P = .033), IL-8 (11.8 ± 7.3 vs 35.5 ± 19.8 pg/mL, P < .0001) and malondialdehyde (0.197 ± 0.034 vs 0.234 ± 0.074 µM/L, P = .002) levels. CONCLUSION: High-dose ascorbic acid was associated with significantly reduced oxidative stress, reduced pro-inflammatory markers except IL-1ß, elevated anti-inflammatory marker and elevated plasma VC levels.

Assessment of a new strategy for catalyzing deprescribing in community pharmacies.

BACKGROUND: Although community pharmacists have been actively engaged in patient care, their role in deprescribing is still restricted. OBJECTIVES: This study aimed to assess the effectiveness of a new educational approach designed to catalyze deprescribing in community pharmacies. METHODS: In this 4-month, randomized, controlled trial, 108 community pharmacies in Egypt were randomly and equally distributed to either the active or the control groups. Participants from the active group pharmacies received 31 deprescribing-related clinical case scenarios, designed according to the available deprescribing guideline and clinical experiences of an expert panel members, and delivered through WhatsApp. Then participants from both groups reported the incidence of potentially inappropriate medicines (PIMs), the frequency of deprescribing opportunities, and related pharmacist interventions. RESULTS: Pharmacists from the active group reported a considerably higher incidence of PIMs (20.87%) than that reported by pharmacists from the control group (5.03%). In addition, they made 1326 deprescribing-related interventions, of which 1022 (77.07%) were accepted and 641 (48.34%) were significant interventions. The proportions of cessation of drug therapy, reducing the dose, and persuasion of patients to accept deprescribing pharmacist interventions in the active group were 37.85%, 22.09%, and 10.63%, respectively. In contrast, 150 of 268 deprescribing-related interventions (55.97%) in the active group were accepted. The clinical value and type of deprescribing decision were statistically significant determinants for the acceptance of deprescribing decisions. The mean time needed to persuade the patient about deprescribing and the cost saved per patient across the active and the control groups were 5.09 ± 3.54 minutes versus 10.03 ± 6.19 minutes and 17.88 ± 9.60 U.S. dollars versus 4.49 ± 2.44 U.S. dollars, respectively. CONCLUSION: The intervention proposed improved the frequency and clinical value of deprescribing decisions.

The effectiveness of pharmacist-based coaching inimproving breast cancer-related health behaviors: A randomized controlled trial

Background: Although pharmacists are trusted and easily accessible by the public, their role in changing health behaviours related to breast cancer has been rarely investigated. Objective: To investigate the effectiveness of pharmacist-based coaching in improving BC-related health behaviors and knowledge in females, and to measure the comfort level toward this program. Methods: This was a randomized controlled study carried out in community pharmacies in Egypt. Pharmacies included were asked to enroll 240 females into a trial, then equally allocate them into either active or control arms, and provide 12 weekly face-to-face coaching sessions to those assigned to the active arm. Pharmacists were also asked to survey females and fill a standardized data collection form at baseline, in the middle of coaching, at the end of coaching, and three months after coaching. Results: The proportions of doing high physical activity, practicing healthy diet, and practicing breast self-exam three months after the end of coaching programme across the active and control arms were 52.17% versus 17.09% (p=0.002), 62.60% versus 28.20% (p=0.003), and 81.73% versus 23.07% (p=0.005), respectively. The mean scores of knowledge on BC symptoms, risk factors, and detection methods three months after coaching across the active and control arms were 4.10±2.47 versus 2.72±1.19 (p=0.038), 4.25±2.20 versus 3.28±1.48 (p=0.020), and .34±1.80 versus 1.72±0.68 (p=0.001) respectively. While most of the females participated in the active arm were comfortable toward the financial 94.78% and social 88.69% sides of the program, more than one-third (34.78%) of the participants were uncomfortable toward the competency of coaches. Conclusion: Despite the need for some modifications, BC-related health behaviors and knowledge can be improved through pharmacist-based health coaching (AU)

Assessment and analysis of outpatient medication errors related to pediatric prescriptions.

BACKGROUND: Medication errors are the errors that impact the efficacy and safety of the therapy. The impact of medication errors is higher for certain subjects, such as pediatrics, who require more attention. Hence, the current study aimed to investigate the types and frequency of outpatient medication errors of pediatric subjects related to different prescription types. METHODS: A cross-sectional study was carried in several community pharmacies to record the medication errors found in outpatient pediatric prescriptions by gathering data from the outpatient prescriptions besides direct counseling with the subjects and their parents. Many medical resources (disease and drug-related) were used for checking the different aspects of medication errors. The data collection process included a preprepared sheet containing several items representing the medication errors in addition to a counseling session. Data were expressed as percentages and compared through the Chi-square test for results of handwritten and computerized prescriptions. RESULTS: 752 outpatient pediatric prescriptions were recruited in the study as they involve medication errors. Among the highest percentage of medication errors was the absence of essential data in the prescription, such as diagnosis, age, and weight. The duration of the therapy and contraindication for some of the prescribed medications were among the highest recorded errors. Among the critical errors were the drug interaction and drug duplication that directly affect the drug's efficacy and safety. There was a significant difference between computerized and handwritten prescriptions regarding the number of medication errors related to each type. CONCLUSION: Medication errors related to outpatient pediatric prescriptions vary from one to another prescription with predominant errors that influence the therapy's safety or efficacy. The role of patient counseling and prescription checking is critical for improving patient therapy.

Community pharmacists' needs, education, and readiness in facing COVID-19: Actions & recommendations in Egypt.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) outbreak is considered one of the most important public health crises all over the world and in Egypt. Community pharmacists represent the third largest health care professional group after physicians and nurses. Community pharmacists are expected to be fully prepared at the frontline of defending their community needs by limiting the spread of COVID-19 via different pharmaceutical care services. AIM: This study aimed to evaluate the sources of knowledge and readiness of community pharmacists in facing COVID-19 early outbreak in Egypt. METHODS: A descriptive cross-sectional study was performed via a self-administered online google form questionnaire during the early period from 14 April to 3 June 2020. The questionnaire focused on; evaluating education level, sources of information, and readiness of Egyptian community pharmacists in the COVID-19 pandemic crisis. RESULTS: A total of 318 community pharmacists from Egypt participated in this questionnaire. About half of the surveyed pharmacists reported that they were frequently consulted and that their patients were seeking consultation regarding COVID-19 management more than 10 times per day. More than half of the pharmacists reported using social media as a source of information and knew the right social distancing recommendations. Regarding protective measures, only a quarter of pharmacists disclosed the availability of personal protective equipment (PPE). Nevertheless, the majority of pharmacists significantly reported some initial lack of support either inform of recommendations or PPE supply. CONCLUSION: The study revealed the dependence of community pharmacists on social media as the main source of information and the lack of early awareness of evidence-based practice resources. Community pharmacists were in need of more initial support to achieve better satisfaction, patient counselling and infection control. Corrective measures were promptly undertaken to support and satisfy the Egyptian community pharmacists' initial awareness and readiness facing COVID-19.

An emergency plan for management of COVID-19 patients in rural areas.

AIMS OF THE STUDY: To describe the experience of six hospitals in the management of COVID-19 patients in rural areas through an assessment of proportions, types and clinical outcomes of remote clinical interventions. METHODS: This was a prospective observational study conducted in six Egyptian hospitals over a period five months. An emergency response was implemented in each hospital in order to connect clinical pharmacists with COVID-19 patients living in rural areas. Pharmacists used phone calls and social media applications, such as WhatsApp® to conduct two types of interventions; (a) Proactive interventions and (b) outcome-based interventions. IBM SPSS V26 was used for data analysis. RESULTS: Of the 418 patients included, 351 (83.97%) recovered, 60 (14.35%) were hospitalised and 7 (1.67%) were deceased. Medication orders per patient, high-alert medications per patient and prescribing errors per patient were 5.82, 1.45 and 0.74, respectively. Telepharmacy teams conducted 3318 phone calls, 2116 WhatsApp® chats and 1128 interventions, of which 812 (71.92%) were process-based and 316 (27.98%) were outcome-based. Among these interventions, four significant determinants of improvement in clinical outcomes were found: substitution of a prescribed drug (Adjusted odds ratio [AOR] = 4.03; 95% confidence interval [CI], 2.54-5.87), adding a drug to the prescription (AOR = 3.15; 95% CI, 1.87-4.76), advice the patient to stop smoking (AOR = 3.53; 95% CI, 1.98-5.17) and cessation of drug therapy (AOR = 3.11; 95% CI, 1.25-4.55). The most common medications involved in drug-related interventions were Hydroxychloroquine, Azithromycin and Paracetamol. CONCLUSION: Our findings demonstrate significant impact of the remote pharmacist interventions on both medicines use and clinical outcomes of COVID-19 patients in rural areas. Pharmacists in developing countries should be supported to implement remote clinical services to provide patients in rural places with optimal care.

Correlation Study on HLA-DR and CD117 (c-Kit) Expressions: Its Prognosis and Treatment Response in Acute Myeloid Leukemia Patients.

INTRODUCTION: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. HLA-DR and CD117 (c-Kit) are important diagnostic markers of AML. Our objective is to determine the prognostic significance of HLA-DR and CD117 expressions in newly diagnosed AML patients and determine the correlation between HLA-DR and CD117 expressions and other prognostic markers such as cytogenetic abnormalities, FLT3-ITD, response to treatment, and patient's survival. METHODS: This study included 100 newly diagnosed AML patients. All patients were subjected to clinical, morphological, cytochemical, cytogenetic analysis, molecular genetic analysis to detect FLT3-ITD, and Flowcytometric detection of HLA-DR, CD117, and CD 34. RESULTS: The results showed that HLA-DR expression was found in 75 patients (77.3%), while CD117 expression was found in 63 patients (64.9%). Patients with HLA-DR expression showed significantly higher mean Hb concentration, significantly higher platelet count, associated with AML-FAB subtypes (M0, M1, and M2), CD34 expression, and favorable cytogenetic group. M3 subtype was significantly associated with HLA-DR-ve. While patients with CD117 expression showed significantly lower platelets count. Double positive patients (HLA-DR+ve/CD117+ve) showed significant association with the intermediate cytogenetic group, while double-negative patients (HLA-DR-ve/CD117-ve) were associated with the favorable and intermediate cytogenetic group and either positive (HLA-DR+ve /CD117-ve or HLA-DR-ve/CD117+ve) associated with poor cytogenetic groups. FLT3-ITD expression had significantly worse overall survival. CONCLUSION: The current study suggested that the expression of CD117 and HLA-DR may be a prognostic marker in AML, as they are associated with M0, M1, and M2 FAB subtypes; moreover, patients with combined HLA-DR and CD117 positive expression are associated with CD34 expression and intermediate cytogenetic group.

The effectiveness of pharmacist-based coaching in improving breast cancer-related health behaviors: A randomized controlled trial.

Background: Although pharmacists are trusted and easily accessible by the public, their role in changing health behaviours related to breast cancer has been rarely investigated. Objective: To investigate the effectiveness of pharmacist-based coaching in improving BC-related health behaviors and knowledge in females, and to measure the comfort level toward this program. Methods: This was a randomized controlled study carried out in community pharmacies in Egypt. Pharmacies included were asked to enroll 240 females into a trial, then equally allocate them into either active or control arms, and provide 12 weekly face-to-face coaching sessions to those assigned to the active arm. Pharmacists were also asked to survey females and fill a standardized data collection form at baseline, in the middle of coaching, at the end of coaching, and three months after coaching. Results: The proportions of doing high physical activity, practicing healthy diet, and practicing breast self-exam three months after the end of coaching programme across the active and control arms were 52.17% versus 17.09% (p=0.002), 62.60% versus 28.20% (p=0.003), and 81.73% versus 23.07% (p=0.005), respectively. The mean scores of knowledge on BC symptoms, risk factors, and detection methods three months after coaching across the active and control arms were 4.10±2.47 versus 2.72±1.19 (p=0.038), 4.25±2.20 versus 3.28±1.48 (p=0.020), and .34±1.80 versus 1.72±0.68 (p=0.001) respectively. While most of the females participated in the active arm were comfortable toward the financial 94.78% and social 88.69% sides of the program, more than one-third (34.78%) of the participants were uncomfortable toward the competency of coaches. Conclusion: Despite the need for some modifications, BC-related health behaviors and knowledge can be improved through pharmacist-based health coaching.

Combined Expression of CD34 and FLT3-Internal Tandem Duplication Mutation Predicts Poor Response to Treatment in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a common hematological malignancy associated with different cytogenetic and genetic abnormalities. METHODS: FLT3-internal tandem duplication (FLT3/ITD) mutation and CD34 expression levels were assessed in the bone marrow (BM) aspirates of 153 de novo AML patients. Data were correlated with relevant clinic-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall free survival (OS) rates. RESULTS: FLT3-ITD mutation was detected in 27/153 (17.6%) AML patients (P=0.001), and CD34 was expressed in 83/153 (54.2%) patients (P=0.293) compared to those with wild FLT3 and CD34- expression, respectively. Patients with FLT3-ITD mutation showed increased peripheral blood and BM blast cells, abnormal cytogenetics, poor DFS and OS compared to those with wild FLT3 (P=0.013, P<0.001, P=0.010, P=0.008 and P=0.004, respectively), while there was no significant association with response to treatment (P=0.081). There was no significant association between CD34 expression and response to treatment, DFS, and OS (P>0.05). FLT3-ITD mutation and FAB subtypes were independent prognostic factors for DFS. Older age ≥39 years, HB <7 mg/dL PB blast ≥54%, and FLT3-ITD mutation were independent prognostic factors for poor OS in AML patients. The presence of both FLT3-ITD mutation and CD34 expression associated significantly with resistance to therapy (P=0.024), short DFS and OS rates (P=0.006, P=0.037, respectively). CONCLUSION: Combined expression of both FLT3-ITD mutation and CD34 expression is an important prognostic and predictive factor for poor disease outcome in AML patients.

ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt.

BACKGROUND: The impact of Excision repair cross-complementation group 1 (ERCC1) and group 2 (ERCC2) expression levels on the efficacy of oxaliplatin-based chemotherapy is still controversial. The present study was conducted to determine the predictive value of these molecular biomarkers in stage III and IV colorectal cancer (CRC) patients receiving oxaliplatin (OX)-based chemotherapy as first-line treatment. METHODS: The study included 80 CRC patients who received first line oxaliplatin based chemotherapy The expression levels of ERCC1 and ERCC2-mRNA and proteins were determined in the primary tumors by quantitative real time reverse transcription polymerase chain reaction(RT-qPCR) and immunohistochemistry (IHC); respectively. The results of mRNA expression were correlated with patients' characteristics, response to treatment, overall- and event free survival (OS & EFS). RESULTS: Sixty four out of the 80 patients were legible for assessment of ERCC1 and ERCC2 expression. The cut-off levels of ERCC1and ERCC2-RNA were 3.8×10-3& 4.6×10-3; respectively. Reduced ERCC1 and ERCC2 RNA expressions were detected in 50 (78.1%) and 48 (75%) cases, respectively whereas reduced proteins were detected in 48 cases (75%) for ERCC1 and ERCC2. After The median follow up period was 30.5months (range: 7-104months), Patients with low mRNAERCC1levels showed significantly longer OS (p=0.011) and EFS (p˂0.001). However, no significant relation was found between ERCC2 levels and OS or EFS. In multivariate analysis performance status (PS), stage of the disease and ERCC1-mRNA expression were independent prognostic factors for EFS whereas tumor histology and stage of the disease were independent factors for OS. CONCLUSIONS: ERCC1 expression levels may help in selecting patients who benefit from oxaliplatin chemotherapy in stage III & IV CRC. Further large trials are needed to validate these data.