The molecular signature of BCR::ABLP210 and BCR::ABLT315I in a Drosophila melanogaster chronic myeloid leukemia model.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder resulting from a balanced translocation leading to BCR::ABL1 oncogene with increased tyrosine kinase activity. Despite the advancements in the development of tyrosine kinase inhibitors (TKIs), the T315I gatekeeper point mutation in the BCR::ABL1 gene remains a challenge. We have previously reported in a Drosophila CML model an increased hemocyte count and disruption in sessile hemocyte patterns upon expression of BCR::ABL1p210 and BCR::ABL1T315I in the hemolymph. In this study, we performed RNA sequencing to determine if there is a distinct gene expression that distinguishes BCR::ABL1p210 and BCR::ABL1T315I. We identified six genes that were consistently upregulated in the fly CML model and validated in adult and pediatric CML patients and in a mouse cell line expressing BCR::ABL1T315I. This study provides a comprehensive analysis of gene signatures in BCR::ABL1p210 and BCR::ABL1T315I, laying the groundwork for targeted investigations into the role of these genes in CML pathogenesis.

Prone versus Supine FDG PET/CT in the Staging of Breast Cancer.

Supine [18F]Fluorodeoxyglucose (FDG) positron emission technology/computed tomography (PET/CT) is a commonly used modality for the initial staging of breast cancer, and several previous studies have shown superior sensitivity and specificity of prone FDG PET/CT in comparison to its supine counterpart. This retrospective study included 25 females with breast cancer referred for staging. They underwent supine FDG PET/CT followed by prone FDG PET/CT. The outcomes were: number of primary breast lesions, anatomical site of FDG-avid lymph nodes (LNs), and number and type of bone lesions, with SUVmax of all corresponding parameters. Performance was superior in prone acquisition compared to supine acquisition, with the respective results: 29 vs. 22 breast tumor lesions detected, 62 vs. 27 FDG-avid axillary LNs detected, sensitivity of 68% vs. 57%, specificity of 64% vs. 53%. The detection rate of axillary LNs in the prone position was significantly higher (p = 0.001). SUVmax for breast tumor lesions (p = 0.000) and number of detected axillary LNs (p = 0.002) were significantly higher in prone acquisition. Five patients were upstaged after experts read the prone acquisition. Prone FDG PET/CT acquisition is a promising technique in detecting primary breast lesions and metastatic LNs possibly missed in supine acquisition, which may lead to change in patient staging and management.

Terpenoids' anti-cancer effects: focus on autophagy.

Terpenoids are the largest class of natural products, most of which are derived from plants. Amongst their numerous biological properties, their anti-tumor effects are of interest for they are extremely diverse which include anti-proliferative, apoptotic, anti-angiogenic, and anti-metastatic activities. Recently, several in vitro and in vivo studies have been dedicated to understanding the 'terpenoid induced autophagy' phenomenon in cancer cells. Light has already been shed on the intricacy of apoptosis and autophagy relationship. This latter crosstalk is driven by the delicate balance between activating or silencing of certain proteins whereby the outcome is expressed via interrelated signaling pathways. In this review, we focus on nine of the most studied terpenoids and on their cell death and autophagic activity. These terpenoids are grouped in three classes: sesquiterpenoid (artemisinin, parthenolide), diterpenoids (oridonin, triptolide), and triterpenoids (alisol, betulinic acid, oleanolic acid, platycodin D, and ursolic acid). We have selected these nine terpenoids among others as they belong to the different major classes of terpenoids and our extensive search of the literature indicated that they were the most studied in terms of autophagy in cancer. These terpenoids alone demonstrate the complexity by which these secondary metabolites induce autophagy via complex signaling pathways such as MAPK/ERK/JNK, PI3K/AKT/mTOR, AMPK, NF-kB, and reactive oxygen species. Moreover, induction of autophagy can be either destructive or protective in tumor cells. Nevertheless, should this phenomenon be well understood, we ought to be able to exploit it to create novel therapies and design more effective regimens in the management and treatment of cancer.

Radiology residents from learners to teachers: A multi-centric study.

PURPOSE: The teaching role of radiology residents has seldom been evaluated, and little is known about how teaching skills of radiology residents evolve throughout their training in the absence of formal teaching guidance. Our objective is to identify residents' characteristics correlating with better teaching and compare teaching characteristics of junior and senior residents. METHOD: All seven medical schools in Lebanon were involved in this multi-centric study. A self-assessment questionnaire was sent to sixty-nine radiology residents and filled anonymously. Fifty-seven (83 %) responses were received and represent the study population. Data analysis was based on factors correlating with overall teaching effectiveness. A comparison of senior and junior residents' responses was also performed. RESULTS: Overall teaching effectiveness correlated with better knowledge, technical skills, clinical judgment, communication skills, identification and correction of learning problems, and importantly providing and receiving feedback. Senior residents rated themselves significantly better than juniors in "knowledge related to radiology" and in "technical skills" but not in "overall teaching effectiveness". Seniors did not agree on the statement "medical students make my clinical responsibilities easier". Although not reaching statistical significance, seniors showed a trend towards improving teaching skills. CONCLUSIONS: Overall teaching effectiveness is correlated with the adoption of proper skills and techniques. Despite the lack of formal teaching guidance, senior radiology residents are improving their techniques as teachers but still face difficulties in several domains.

Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.

Giant Inflatable Colon Model Enhances Lebanese Community Knowledge and Intention for Colorectal Cancer Screening.

PURPOSE: To assess the knowledge and intention for colorectal cancer (CRC) screening within the Lebanese community before and after a guided tour through an inflatable colon model. METHODS: The Cancer Prevention and Control Program, Naef K. Basile Cancer Institute at the American University of Beirut Medical Center in collaboration with AMALOUNA educational nongovernmental organization launched awareness campaigns during which a walk-through inflatable colon was displayed. Pre- and post-surveys related to the age of screening, risk factors, symptoms, and CRC prevention were collected anonymously before and after touring the inflatable colon to assess the effectiveness of this educational tool. RESULTS: Compiled data collected from 782 participants revealed that older age and higher education were predictors of favorable CRC screening knowledge and behaviors before entering the inflatable colon. Interestingly, touring the inflatable colon model significantly improved participants' awareness and knowledge about CRC. Most importantly, it increased their willingness for screening and social engagement and comfort discussing and promoting CRC screening. CONCLUSION: Overall, these results indicate that the interactive colon is an effective educational tool that can make a positive impact by improving the community CRC awareness and interest in CRC screening. They also highlight the importance of such educational efforts conducted in the community to create more awareness about CRC and emphasize the importance of its prevention.

Imaging Acute Non-Traumatic Abdominal Pathologies in Pediatric Patients: A Pictorial Review.

The dilemma of acute non-traumatic abdominal pathologies in the pediatric population depends on the age of the patients and symptoms. Surgical etiologies in patients younger than 2 years of age include intussusception, pyloric stenosis, malrotation and midgut volvulus. In older patients, considerations become closer to differential etiologies in adults including acute appendicitis. Ultrasound and fluoroscopic examinations remain the mainstay for diagnosis that may even be therapeutic such as contrast/air enemas in intussusception reduction. There is an increasing role for CT in appendicitis and renal colic especially in assessing complications; however, it is less favored because it incurs radiation to the patient. This article summarizes the imaging approach to pediatric patients with acute abdominal pathologies presenting to the emergency department, and how imaging is instrumental in guiding diagnosis and treatment, with emphasis on radiation safety, in the context of providing typical imaging findings of each pathology in this pictorial review.

Stromal Fibrosis of the Breast: A Spectrum of Benign to Malignant Imaging Appearances.

OBJECTIVES: The aim of this study is to demonstrate the various imaging appearances of stromal fibrosis on mammography, ultrasound, and magnetic resonance imaging (MRI). MATERIAL AND METHODS: This study included 75 female patients who presented to the American University of Beirut Medical Center between January 2010 and October 2015 for breast imaging. 66 (88%) patients obtained a mammogram, 71 (95%) had an ultrasound, and 6 (8%) had an MRI. Patients included had stromal fibrosis proven on biopsy. RESULTS: The most common finding on mammogram was calcifications which was present in 14 (21%) patients, while on ultrasound it was a mass which was present in 61 (86%) patients. A mass was detected on MRI in 2 (33.5%) patients. Most lesions detected had benign findings such as masses with circumscribed margins. We had a follow-up for 53 (71%) patients with an average follow-up interval of 28.5 months (range: 5 - 70). Increase in size of the index lesion was noted in only 2 patients; upon rebiopsy, pathology results read stromal fibrosis for one lesion and fibroadenoma for the other. The remaining lesions were either stable or decreased in size. The higher detection rate of a mass on ultrasound was statistically significant (p<0.001) in comparison to that of mammography. CONCLUSION: Stromal fibrosis can have various presentations on imaging from benign to suspicious for malignancy features. In the case of accurate targeted biopsy, when stromal fibrosis is diagnosed, the result can be considered concordant. Therefore, such lesions can be followed up by imaging to document stability and confirm benignity.

New era of PET/CT in breast cancer: high-resolution PET/dfCT.

OBJECTIVE: To determine whether breast cancer staging differs between high-resolution (HR) and standard-resolution (SR) PET/computed tomography acquisition. PATIENTS AND METHODS: This retrospective study included 39 women with breast cancer referred for staging. Images were assessed for the number of primary breast lesions with the corresponding size and the average maximum standardized uptake value (SUVmax), the anatomical site of fluorine-18-fluorodeoxyglucose-avid lymph nodes (LNs) with their SUVmax, and the number and type (lytic/blastic) of metastatic bone lesions. RESULTS: On HR, 42 breast tumor lesions with a size range of 0.30 cm up to 12.00 cm were detected versus 34 breast tumor lesions on SR. One hundred and forty-one versus 90 axillary LNs were detected on HR versus SR, respectively. Pathology reports were available for 60 axillary LNs out of the total 141 identified on HR. Rates for HR versus SR sensitivity, true positivity, false positivity, and false negativity are as follows: 92 versus 75%, 92 versus 75%, 2 versus 0%, and 7 versus 25%. The higher detection rate of axillary LN on HR was significant (P<0.001), but not the number of nodes detected (P=0.091). SUVmax for breast tumor lesions (P=0.225) and axillary LNs (P=0.134) were not significant. Three (8%) patients had a change in staging and management. CONCLUSION: HR detected primary breast lesions and metastatic LNs missed on SR, which led to change in staging and management. In addition, HR images provided higher SUVmax, which enabled a more comfortable localization, especially when SR presented borderline values. Finally, HR images decreased the number of gray zone lesions, especially in axillary LN detection.