|Year : 2023 | Volume
| Issue : 2 | Page : 94-101
9th Emirati-German Congress in Medicine and Dental Medicine 21–22 November 2022 University of Sharjah, United Arab Emirates
|Date of Submission||20-Feb-2023|
|Date of Decision||23-Feb-2023|
|Date of Acceptance||24-Feb-2023|
|Date of Web Publication||27-Mar-2023|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. 9th Emirati-German Congress in Medicine and Dental Medicine 21–22 November 2022 University of Sharjah, United Arab Emirates. Adv Biomed Health Sci 2023;2:94-101
|How to cite this URL:|
. 9th Emirati-German Congress in Medicine and Dental Medicine 21–22 November 2022 University of Sharjah, United Arab Emirates. Adv Biomed Health Sci [serial online] 2023 [cited 2023 Jun 9];2:94-101. Available from: http://www.abhsjournal.net/text.asp?2023/2/2/94/372591
The 9th Emirati-German Conference was hosted by the University of Sharjah, United Arab Emirates during 21–22 November 2022. A host of eminent scholars, researchers, physicians, and health-care professionals presented their innovative work across a wide range of medical disciplines including basic medical sciences, clinical sciences, and dental medicine. The format of the conference was a hybrid design with face-to-face sessions in the medical campus of the University of Sharjah. This event provided an excellent opportunity to all health-care professionals in the related medical, dental and allied health fields to upgrade their current knowledge and to network with the world-renowned scientists from the University of Sharjah, Academic Reinbek Hospital Hamburg, University of Lubeck Germany, and several other speakers from UAE.
| Objectives|| |
The main theme of this conference was cancer.
The key objectives of this conference were:
- To identify best practices in different cancer types including colorectal, hepatobiliary, breast, central nervous systems, and others
- To provide a forum for a broad debate about cancer etiology, prevention, and early detection of common cancers for a better clinical outcome
- To understand diagnostic modalities, treatment strategies, surveillance, palliative care, and research on common cancers
- To demonstrate key approaches to identify, prioritize, and address major cancers with a substantial burden on health-care systems
- To establish or re-establish and strengthen networks between those working in all stages of the cancer continuum in the MENA region and the European perspectives.
| The role of loop ileostomy in surgery for rectal cancer: Safety profile versus complications|| |
J. Herzberg, S. Khadem, S. Falck, S. A. Imdahl, Salman Yousuf Guraya1, Tim Strate
Department of Surgery, Hospital Reinbek St. Adolf Stift, Reinbek, Germany, 1Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Low anterior rectal resection is associated with a high risk for anastomotic leakage (AL). A common technique to prevent AL is the formation of a protective loop ileostomy (LI). However, LI has been associated with the risk of dehydration and acute kidney injury. A significant proportion of LI may never be closed afterward. The aim of this work is to compare the postoperative outcomes after surgical resections for rectal cancers with the adverse events of LI. All patients who underwent low anterior rectal resections between January 2014 and June 2021 using an established fail-safe approach were included in this analysis. We evaluated the occurrence of AL and stoma-related complications. A total of 108 low anterior rectal resections with primary anastomosis and LI with on-table-lavage were included in this analysis. AL occurred in three patients in this cohort (2.8%). The protective LI was closed for 96.3% of the patients. A transient acute kidney failure occurred in 17.6% of the patients before the stoma closure, but an additional hospital admission due to stoma complications was needed in only 3.7%. The group of patients with acute kidney failure was significantly older than the one without kidney failure (62.9 years vs. 71.8 years in the kidney failure group, P = 0.002). We concluded that using the standard fail-safe-protocol, the use of a LI was associated with a low rate of AL and a low rate of permanent stoma with a relevant risk for acute kidney failure, especially in older patients.
Keywords: Complications, ileostomy, rectal cancer
| Comparison of different intrathoracic esophagogastric anastomosis after Ivor–Lewis esophagectomy|| |
Department Upper-GI- and Pancreatic Surgery, University of Hamburg Teaching Hospital, Hamburg, Germany
Ivor–Lewis esophagectomy still comes with a high rate of postoperative anastomotic leakage (AL). Therefore, the optimal reconstruction method is crucial to reducing this adverse event and its negative impact on short- and long-term outcome. In this retrospective study, we compared the outcomes of end-to-side and side-to-side reconstruction for intrathoracic anastomosis after esophagectomy. We retrospectively reviewed patients who underwent esophagectomy between January 2015 and December 2021. The anastomosis was either performed as an end-to-side stapled anastomosis secured by additional sutures above the azygos vein or as a side-to-side anastomosis using linear stapling devices with additional sutures. Patients' characteristics, operative techniques, and short-term outcomes, including AL and other postoperative complications, were compared. Ninety-five patients were treated by Ivor-Lewis resection due to esophageal malignancy in the study center within the study period. Ninety-four patients fulfill the inclusion criteria with one of the described reconstruction techniques. Forty patients (42.6%) were treated with an end-to-side circular anastomosis and 54 (57.3%) were reconstructed with a side-to-side linear stapled anastomosis. Patients' characteristics did not differ significantly between both groups. The patients after side-to-side reconstruction showed a significantly shorter length of postoperative stay (17.8± 11.4 vs. 26.5 ± 16.2 days; P < 0.0001). Overall, there were 16% AL with no significant difference between the two groups (P = 0.402) and an overall mortality of 6.4%. According to our evaluation, both techniques for esophagogastric anastomosis are safe and show comparable rates of postoperative AL. Long term results including patient-reported outcome need further evaluation.
Keywords: Esophageal malignancy, intrathoracic anastomosis, Ivor–Lewis esophagectomy, outcome
| Transoral thyroidectomy with intraoperative nerve monitoring and indocyanine fluorescence imaging for thyroid lesions|| |
Fadi Alnehlaoui, Mohammad Nazih Alsarraj1, Zuheir Malaki, Salman Yousuf Guraya1
Department of Surgery, Zulekha Hospital Sharjah, 1Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Transoral endoscopic vestibular thyroidectomy (TOEVT) is a unique state-of-the-art scarless surgery for young women with thyroid lesions. However, the efficacy of TOETV has not been compared with that of open thyroidectomy (OT) in terms of its effectiveness and quality of life (QoL) outcomes. We compared the efficacy and QoL of patients between TOEVT and OT. The medical files of all consecutive patients with TOETV and OT, between January 1, 2019 and April 1, 2021 were analyzed. The demographics, type of surgery, operative room (OR) time, amount of blood loss, nodule size, and postoperative complications were recorded. An SF-36 questionnaire was used pre- and post-operatively for the evaluation of QoL. From a total of 41 OT and 32 TOEVT, 59 patients (31 TOEVT and 28 OT) were included. There were 45 women and 14 men with an average age 41 years. The mean OR time was 126 min in TOEVT and 96 min in OT (P = 0.000). On the other hand, the mean thyroid size was 5.55 cm in TOEVT and 8.76 cm in OT (P = 0.000), and the mean intraoperative blood loss was much lower in transoral than in open techniques (P = 0.001). The postoperative QoL substantially improved in both groups. We concluded that the efficacy of TOEVT is comparable with OT, however, TOEVT has an outright benefit of being a scarless technique with better QoL.
Keywords: Open thyroidectomy, quality of life, scarless surgery, thyroid cancer, transoral endoscopic vestibular thyroidectomy
This study was published in Alnehlaoui F, Alsarraj MN, Malaki Z, Guraya SY. The Effectiveness and Quality of Life Outcomes by Transoral Endoscopic Vestibular Thyroidectomy Using Intraoperative Indocyanin Green Fluorescence Imaging and Neuromonitoring—A Cohort Study. Healthcare 2022 May 21 (Vol. 10, No. 5, p. 953). MDPI.
| Prostate cancer, advances in surgical treatment|| |
Urology Department, Mediclinic City Hospital, Dubai, United Arab Emirates
Surgical management of prostate cancer has been revolutionized with the introduction of robotic surgery more than 20 years ago, and continuous technical and training improvement has resulted in better outcomes. A literature search was conducted for the latest evidence regarding the current status of robotic prostate cancer surgery. Robotic surgery became the gold standard for the removal of prostate cancer. This method has shown multiple benefits, including those for minimally invasive surgeries, and the continuous technical improvements have resulted in better oncological and functional outcomes in selected cohort of patients, the introduction of this method has revolutionized the way of caring for prostate cancer patients. In the right hands, robotic prostate cancer surgery provides a safe and more precise alternative to traditional types of surgeries, as well as cost effectiveness, and has become the gold standard of treatment.
Keywords: Prostate cancer, robotic surgery, surgery
| AI-enabled healthcare pathways to transform cancer care and diagnostic|| |
Department of Ophthalmology, American Hospital, Dubai, United Arab Emirates
Artificial intelligence (AI) has the potential to revolutionize healthcare and help address some challenges. AI can lead to better care outcomes and improve the productivity and efficiency of care delivery. It can also improve the day-to-day life of healthcare practitioners, letting them spend more time looking after patients and in so doing, raise staff morale and improve retention. Cancer diagnoses can also be optimized using AI. Accurate diagnosis of cancerous and precancerous lesions can allow for the minimization of overtreatment. In this perspective, we propose a pathway of clinical cancer care touchpoints for narrow-task AI applications and review a selection of applications. We describe the challenges faced in the clinical translation of AI and propose solutions. We also suggest paths forward in weaving AI into individualized patient care, with an emphasis on clinical validity, utility, and usability. By illuminating these issues in the context of current AI applications for clinical oncology, we hope to help advance meaningful investigations that will ultimately translate to real-world clinical use. Advances in machine learning are set to transform medicine, yet considerable challenges exist. These include hard technical ones such as the complexity and quality of healthcare data, the need to consider multiple interactions between the diverse events over a patient's life and the difficulty of estimating counterfactual outcomes. These challenges are exacerbated by practical ones – the requirement for cross-disciplinary collaboration, the delivery and transferability of any solutions between health systems at scale both nationally and internationally, the deployment of a service that provides tailored patient-level intelligence in near-real time and most fundamentally, the absence of a way to conceptualize the complexity of healthcare to support interdisciplinary collaboration.
Keywords: Artificial Intelligence, cancer diagnosis, early diagnosis, machine learning
| Perspectives of whole-body imaging|| |
Department of Diagnostic and Interventional Radiology, University of Hamburg, Hamburg, Germany
Malignant tumors are the second most common cause of death and are responsible for more than 12% of all deaths worldwide. Mortality rates and the success of therapeutic approaches depend mainly on the type of cancer, but they also depend on the presence of metastases. Therefore, tumor staging plays a key role in determining further treatment options in patients with malignant tumors. Since metastatic disease can affect different anatomic parts of the body, patients must undergo several examinations, such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and scintigraphy, for the staging of metastases. Thus, the staging process is often both time-consuming and expensive. Furthermore, diagnostic accuracy remains limited. To demonstrate clinical integration in staging systems, a comparative study of the diagnostic performance of 18F-Fluordesoxyglucose positron emission tomography (PET)/CT versus whole-body MRI for determining remission status in multiple myeloma after stem cell transplantation was chosen. The limited field of view restricting coverage to a single body region must be considered a major limitation of conventional MRI. In competition, PET in conjunction with PET-CT or PET-MRI provides a whole-body approach with additional metabolic information. The described strategies focus on the detection of metastatic lesions in patients with known primary tumors and on follow-up in dedicated indications. Nevertheless, the integration of whole-body approaches in the staging setting in the clinical routine is rare, especially under consideration of diagnostic accuracy, availability, costs, and expertise.
Keywords: Computed tomography, metastatic, positron emission tomography, staging
| Updates in systemic treatment of colorectal cancer|| |
Oncology Department, American Hospital, Dubai, United Arab Emirates
Colorectal cancer (CRC) is the third most common cancer worldwide, with an estimated 2 million new cases in 2020, as per the International Agency for Research on Cancer. Unfortunately, it remains the second most common cause of cancer deaths. A review of the recent data and trials regarding treatment of metastatic CRC presented at major international conferences and published in peer-reviewed journals. The use of combination chemotherapy with FOLFOX and FOLFIRI in the first and second lines of metastatic CRC remains the backbone of the current treatment of most of the patients with this disease. Biomarker testing becomes the standard of care in the management of these patients and leads to the identification of a subset of patients who would significantly benefit from novel therapies targeting specific genetic alterations. For all metastatic CRC patients, the minimal set of biomarkers required are the following: Microsatellite instability (MSI) status, Rat sarcoma gene (RAS) mutations, BRAF mutations, human epidermal growth factor receptor 2 (HER-2) amplification, and Neurotrophic tyrosine receptor kinase gene (NTRK) fusions. CRC is a common cancer and has a significant morbidity and mortality rate worldwide. Biomarker testing has resulted in a better understanding of the molecular bases of CRC as well as the use of a variety of novel targeted and immunotherapies. For metastatic disease, the median overall survival has improved remarkably over the past two decades with the use of systemic therapy, from an average of 6 months without treatment to more than 5 years with immunotherapy.
Keywords: Colorectal cancer, immunotherapy, targeted therapy
| Sellar pathologies in neurosurgery|| |
Department of Neurosurgery, University of Hamburg, Hamburg, Germany
The sellar region is a small area of the skull base; however, different tissue types can be found with a variety of different pathologies arising from them. Surgery, particularly transsphenoidal surgery, is still the first-line treatment for many tumors. From 2018 until 2022, over 1000 surgeries have been performed at UKE Hamburg via a transsphenoidal approach using a three-dimensional (3D)-exoscopic system (Orbeye). Endoscopic surgery was only used in a few cases. The most common pathology was pituitary adenoma, followed by Rathke cleft cysts and craniopharyngiomas. There were also multiple different pathologies found and successfully treated by this approach. 3D-exoscopy provides a safe and effective method for treating sellar pathologies with brilliant visualization.
Keywords: Pituitary adenoma, sellar, three-dimensional exoscopy, transsphenoidal surgery
| Implant-based prosthodontic rehabilitation of head and neck cancer patient|| |
Adam bin Husein1,2
1Department of Preventive and Restorative Dentistry, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates, 2Prosthodontic Unit, School of Dental Sciences, University Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
Head and neck cancer is still one of the most common cancers worldwide. The aim of this presentation is to highlight the use of conventional and zygomatic implants in the prosthodontic rehabilitation of head and neck cancer patients following cancer treatment. The presentation was based on observations made in Liverpool and Manchester, UK. Prosthodontic rehabilitation of head and neck cancer patients after cancer treatment can be challenging. Factors such as the extent of tissue loss due to cancer removal, radiation therapy, and chemotherapy affect prosthodontic rehabilitation. In most cases, providing prostheses is challenging due to altered oral anatomy such as the absence of good ridges, reduced sulcus depth, trismus, and xerostomia. Conventional prostheses, such as removable dentures, may not work due to a lack of retention and support. Implant-based prostheses do provide hope for those patients. Implants aid in the retention and support of prostheses that improve functions. The use of implant-supported prostheses in the rehabilitation of postsurgical treatment of head and neck cancer improves functions and the quality of life of patients.
Keywords: Head and neck cancer, prosthodontic rehabilitation, zygomatic implant
| Multidisciplinary management of a peri-implant soft tissue defect: A case report|| |
Department of Preventive and Restorative Dentistry, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
Soft tissue dehiscence around implant-supported restorations represents a major concern that could affect patients' satisfaction and the success of implant therapy. In this regard, periodontal plastic surgeries provide reliable treatment options to correct such defects. This report describes a multidisciplinary approach applied for a patient presented with a soft tissue deficiency in both width and thickness in relation to dental implants in the maxillary premolar region. The patient was referred for periodontal evaluation with dental implants showing a narrow zone of keratinized gingiva on the buccal aspect of the posterior implants. The first step in the treatment plan was to carry out a free gingival graft (FGG) procedure to increase the width of keratinized gingiva and correct the aberrant frenum attachment. At 4 weeks postoperatively, implant-supported crowns were removed, and closure caps were placed back, then a period of 1 month was given to permit better healing of the soft tissues. This was followed by performing a bilaminar technique consisting of a coronally displaced flap covering a subepithelial connective tissue graft (SCTG) to augment the gingival phenotype at the implant site. The application of the FGG technique could achieve a significant increase in the width of keratinized gingiva. The gingival phenotype was successfully enhanced following the use of a pedicle flap in conjunction with SCTG. Successful management of peri-implant soft tissue defects and improved patient satisfaction could be attained through the implementation of an effective multidisciplinary approach.
Keywords: Dental implant, free gingival graft, soft tissue dehiscence, subepithelial connective tissue graft
| Immediate whole-tooth replacement: A multidisciplinary perspective|| |
Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
Dental implants effectively replace terminally diseased teeth, and the research suggests varied insertion techniques. They are based on the time gap between the teeth extraction and the implants' placement. They are; immediate, early, delayed, and late. Healing extraction sites resorb 1 to 2 mm of vertical alveolar bone height and up to 7 mm of horizontal bone width. Two-thirds of bone loss occurs in the first 3 months after removal. Typically, bone loss is followed by a change in soft tissue shape, which can affect future tooth replacement solutions. This lecture will illuminate the significance, planning, and steps involved in the immediate tooth replacement option in modern dental implantology. Immediate implant placement has consistently been associated with a survival rate of 97.3% to 99%. Comparable rates are seen even in the presence of apical lesions. The dimensions of the alveolar ridge can be maintained, and soft tissue morphology and quality can be preserved after immediate implant placement and simultaneous provisionalization. Additionally, the partial extraction technique (PET) is a conservative ridge preservation method for teeth scheduled for extraction. It is linked to the preservation of papillae or labial tissues that surround the implant-supported crown. Changes in the shape and size of the tissue in the aesthetic area can be kept to a minimum if an implant is immediately placed in a PET socket and the provisional crown is simultaneously connected. PET has a positive effect on tissue preservation with minimal complications.
Keywords: Flapless, immediate placement, partial extraction technique, provisional restorations
| Modulation of cellular cross-talks by anaphylatoxins in allergic asthma|| |
Institute of Nutritional Medicine, University Hospital of Schleswig-Holstein and University of Lübeck, Lübeck, Germany
Allergic asthma is a maladaptive immune response to common airborne allergens. It is now well recognized that the anaphylatoxins C3a and C5a, side products of complement cascade activation, and their cognate receptors C3aR, C5aR1, and C5aR2, play important roles in the development and severity of the disease. Recently, C3a has been reported to modulate the functions of innate lymphoid cells type 2 (ILC2), a key player during allergen sensitization, but the role of C5a in ILC2 functions remains elusive. Using in vitro coculture systems as well as in vivo approaches, we investigated the role of anaphylatoxin receptors in crosstalk between ILC2 and myeloid cells during the early sensitization phase of allergic asthma. We observed that, in the absence of C5aR1, house dust mite extract sensitization translated into a reduced recruitment of eosinophils, a consequence of impaired expression of interleukin (IL)-5 by the ILC2. C5aR1 was not found in ILC2 at either the mRNA or protein levels, implying that C5a may play a role in ILC2 functions via a crosstalk involving C5aR1+ cells. We discovered that bone marrow-macrophage/dendritic cells (BM-MDCs), as well as alveolar macrophages (AMs) and CD11c+MHCII+DCs, drove the differentiation of ILC2 in in vitro coculture systems using ILC progenitors and BM-derived BM-MDCs or primary pulmonary myeloid cells, and that C5a/C5aR1 favored such development. Further, we observed that while C5a/C5aR1 participated in pulmonary DC-ILC2 cell-cell contact, AMs favored the expression of IL-5 through C5a/C5aR1-mediated cytokine production. Interestingly, we also observed that allergen exposure resulted in a downregulation of C5aR1 expression by AMs, associated with a de novo expression of C3aR. Further, the expression of C3aR correlated with an increased frequency of polynucleated AMs in vitro, a mechanism that may regulate ILC2 functions. Altogether, our data support the hypothesis that anaphylatoxin receptors are key regulators of the early development of allergic asthma through a multicellular control of ILC2 functions.
Keywords: Allergic asthma, alveolar macrophages, anaphylatoxin receptors, complement, innate lymphoid cells, lung
| The hepatic tumor microenvironment on the relevance of tumor stemness for therapeutic resistance in primary liver cancer|| |
Jens U. Marquardt
Department of Medicine I, University of Lübeck, Lübeck, Germany
Disruption of epigenetic integrity is thought to be a major cause of many chronic liver diseases and cancer development. Early changes in DNA methylation patterns are consistently observed during several chronic inflammatory liver diseases, which ultimately predispose to malignant transformation. Herein, the sustained inflammation, aggravated oxidative stress, and subsequent cellular damage promote activation of tumor-initiating cells (TICs) and impair function as well as the cellular composition of diverse resident and nonresident immune cells during this process. Furthermore, recent findings suggest that TICs may not only affect cancer development but may also play a key role in the acquisition of resistance to currently used therapies. While the exact relevance of TICs in this process remains to be defined, several lines of evidence demonstrate that resistance to antiangiogenic therapy in hepatocellular carcinoma (HCC) might be driven by transient expansion of TICs and activation of compensatory pro-oncogenic signaling pathways, including YAP. Thus, specific targeting of TICs might be an effective therapeutic strategy to overcome resistance in difficult-to-treat subgroups of liver cancer.
Keywords: Liver cancer, molecular hepatocarcinogenesis, therapy resistance, tumor microenvironment
| Tissue microarray based exploration of prognostic markers|| |
Campus Lübeck and Research Center Borstel, Leibniz Lung Center, Pathology of the University Hospital, Schleswig-Holstein, Germany
The aim of our research is to set up clinico-pathologically well-characterized Formalin-Fixed Paraffin-Embedded (FFPE) cohorts of patients suffering from cancer, e.g., head and neck squamous cell carcinoma (HNSCC) or breast cancer. In our HNSCC cohort, we demonstrated the prognostic value of Nuclear Receptor Subfamily 2 Group F Member 6 (NR2F6) expression. NR2F6 is a transcription factor with numerous functions, for example as an immune checkpoint molecule in tumor-infiltrating T lymphocytes. NR2F6 has been associated with a poor prognostic outcome in various cancer entities. However, the prognostic role of NR2F6 in HNSCCs has not been described yet. HNSCC is a common cancer worldwide and is associated with a rather poor prognosis. HNSCC tissue from primary tumors, recurrent tumors, lymph node metastases, and distant metastases was retrieved from the archives and arranged as tissue microarrays. Clinical data was obtained from patient files and anonymized. The tumor, node, metastasis classification was updated according to the recent 8th edition. The pattern of intratumoral immune cell infiltration was classified as “hot,” “cold,” or “excluded.” We used this well-characterized and representative cohort to examine NR2F6 expression using immunohistochemistry. A higher expression of NR2F6 in primary tumors occurred more often in patients who developed a local recurrence afterwards. NR2F6 expression was lower in the primary tumors of patients who did not develop a local recurrence. Furthermore, we could show the association of high NR2F6 expression with poorer recurrence-free survival. Higher NR2F6 expression was shown in pharynx cancer than in larynx or oral cavity cancer. “Excluded” HNSCC showed higher NR2F6 expression than “cold” HNSCC. We conclude that NR2F6 may serve as a new prognostic biomarker in HNSCC patients and therefore help with the early detection of local recurrences. Different NR2F6 expressions in the primary tumor location of the pharynx provides another clue to tumor biology that differs depending on tumor site. The functional background that would explain differential expression in immune cells infiltrating versus depleting HNSCC is yet to be explored.
Keywords: Biomarkers, head and neck squamous cell carcinoma, local recurrence, prognosis, tissue microarray
| Protein arginine N-methyltransferase 5 inhibitors sensitize colorectal cancer cell lines to doxorubicin|| |
Wafaa Abumustafa1,2, Mawieh Hamad2,3, Azzam A. Maghazachi2,4, Jibran Sualeh Muhammad1,2,*
1Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates, 2Research Institute of Medical and Health Sciences, and College of Medicine, University of Sharjah, Sharjah, United Arab Emirates, 3Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates, 4Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Protein arginine N-methyltransferase 5 (PRMT5) is one of eight canonical PRMTs and is classified as a type II PRMT that induces arginine monomethylation and symmetric demethylation. Accumulating evidence suggests that PRMT5 is a potential therapeutic target and biomarker for multiple types of cancer, including colorectal cancer (CRC). PRMT5 inhibitors are currently undergoing phase I/II clinical trials for solid tumors. However, there is a lack of knowledge on the molecular basis of PRMT5's oncogenic effect in CRC. Furthermore, the number of studies that investigate the synergistic effect of PRMT5 inhibitors with conventional chemotherapy in CRC is still negligible. In this study, we aimed at exploring the molecular mechanism of PRMT5 in multiple pathways involved in CRC development, including the WNT signaling pathway and the iron homeostasis pathway. In addition, we investigated the capacity of PRMT5 inhibitors to sensitize CRC cell lines to doxorubicin. In silico analysis was used to identify the role of PRMT5 in manipulating genes in these pathways. In silico data was validated using qPCR and western blot in PRMT5-silenced CRC cell lines relative to controls. The resazurin assay was used to assess the viability of CRC cell lines posttreatment with a combination of doxorubicin and the PRMT5 inhibitor CMP5. Our data showed that PRMT5 activates the expression of a novel oncoprotein, which is a part of the Wingless-related integration site (WNT) signaling and PI3K/AKT/mTORK pathways. In addition, our findings shed light on the synergistic effect of compound 5 (CMP5) and doxorubicin in CRC cells. In conclusion, these findings suggest that PRMT5 inhibitors can suppress key oncogenes in CRC, hence enhancing the therapeutic efficacy of standard chemotherapy.
Keywords: CMP5, colorectal cancer, doxorubicin, protein arginine N-methyltransferase 5 inhibitor
| Premature nerve growth factor in diabetic bladder dysfunction: acting beyond nervous tissue|| |
Abubakr H. Mossa
Basic Medical Seciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Neurotrophins are classically known for their role in the growth and differentiation of neurons. However, nerve growth factor and its precursor, proNGF, were found to activate receptors (Trk-A and p75NTR) on nonneuronal cells that result in variable responses ranging from survival to activation of apoptotic pathwayson-neuronal cells that result in variable responses ranging from survival to activation of apoptotic pathways. This becomes particularly interesting when considering the higher affinity of the proNGF to the p75NTR in metabolic disturbances such as diabetes, as seen in different diabetes-associated pathologies such as retinopathy and angiopathy. The aim of the presentation was to highlight our recently published findings on the impact of prpNGF/p75NTR axis activation on nonneuronal cells of the bladder in the context of diabetic bladder dysfunction (DBD). A mouse model of DBD (streptozotocin-induced) was initiated, and diabetic mice were treated with either a monoclonal antibody to proNGF or a p75NTR blocker (THX-B), followed by morphological, functional, and molecular evaluation. On the other side, different signaling pathways were tested on bladder urothelial and smooth muscle cells cultured from Sprague-Dawley rats treated with cleavage-resistant proNGF. Morphological, functional, and molecular evaluation of the bladders showed a variable reversal of DBD features (bladder weight, contractility, and cystometric essays) in the treated mice. Furthermore, these functional changes were linked to a reduction in the expression of an inflammatory marker (Tumor necrosis factor) as well as a reduction in the proNGF/NGF ratio, which was found to be significantly and persistently high in diabetic untreated mice. Cell culture findings illustrated the divergent effect of the proNGF on the urothelial and smooth muscle cells of the bladder, so that it promoted cell apoptosis in the urothelial cells while smooth muscle cells underwent a synthetic transformation at the expense of their contractile phenotype. The proNGF/p75NTR axis can be an interesting direction to study the effect of the diabetic milieu on the activation of this axis and the related impact on the nonneuronal cells contributing to different diabetic complications.
Keywords: Bladder, diabetic bladder dysfunction, p75NTR, proNGF, urothelium
| Genetic analysis of CFH and MCP in Egyptian patients with immune-complex proliferative glomerulonephritis|| |
Heba R. Gouda1, Iman M. Talaat1,2,3, Amal Bouzid3, Hoda El-Assi4, Amira Nabil5, Thenmozhi Venkatachalam6, Poorna Manasa Bhamidimarri3, Inken Wohlers7, Amena Mahdami3, Saba EL-Gendi1, Ahmed ElKoraie8, Hauke Busch7, Maha Saber-Ayad2,3,9, Rifat Hamoudi2,3,10, Nahed Baddour1
1Department of Pathology, Faculty of Medicine, Alexandria University, 4Department of Pathology, Human Genetics Unit, Faculty of Medicine, Alexandria University, 5Department of Human Genetics, Medical Research Institute, Alexandria University, 8Department of Internal Medicine, Nephrology Unit, Faculty of Medicine, Alexandria University, Alexandria, 9Department of Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt, 2Clinical Sciences Department, College of Medicine, University of Sharjah, 3Clinical Sciences Department, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 6Department of Physiology and Immunology, College of Medicine, Khalifa University, Abu Dhabi, United Arab Emirates, 7Medical Systems Biology Division, Lübeck Institute of Experimental Dermatology and Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany, 10Division of Surgery and Interventional Science, University College London, London, United Kingdom
Glomerulonephritis (GN) is a complex disease with intricate underlying pathogenic mechanisms. The possible role of underlying complement dysregulation is not fully elucidated in some GN subsets, especially in the setting of autoimmunity or infection. In the current study, diagnosed cases of lupus nephritis (LN) and postinfectious GN (PIGN) were recruited for molecular genetic analysis and targeted next-generation DNA sequencing was performed for two main complement regulating genes: in the fluid phase; CFH, and on tissue surfaces; MCP. Three heterozygous pathogenic variants in CFH (Q172*, W701*, and W1096*) and one likely pathogenic heterozygous variant in MCP (C223R) have been identified in four of the studied LN cases. Additionally, among the several detected variants of uncertain significance, one novel variant (CFH: F614S) was identified in 74% of the studied LN cases and in 65% of the studied PIGN cases. This variant was detected for the first time in the Egyptian population. These findings suggest that subtle mutations may be present in complement regulating genes in patients with the immune-complex mediated category of GN that may add to the disease pathogenesis. These findings also call for further studies to delineate the impact of these gene variants on protein function, the disease course, and the outcome.
Keywords: CFH, complement system, glomerulonephritis, lupus nephritis, MCP, postinfectious glomerulonephritis
This study was published in Frontiers in Immunology: Gouda HR, Talaat IM, Bouzid A, El-Assi H, Nabil A, Venkatachalam T, Manasa PB, Wohlers I, Mahdami A, El-Gendi S, ElKoraie A. Genetic analysis of CFH and MCP in Egyptian patients with immune-complex proliferative glomerulonephritis. Frontiers in immunology. 2022; 13:960068-.
| The role of peripheral circadian clocks in the development of epidermolysis bullosa acquisita|| |
Jennifer Elisabeth Hundt
Lübeck Institute for Experimental Dermatology, University of Lübeck, Lübeck, Germany
A central pacemaker coordinates a network of endogenous circadian clocks. The skin itself features a self-sustained, intrinsic clock, which may affect our first-line defense against intruders over the course of the day. Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disease caused by autoantibodies to type-VII collagen. Treatment options are not yet considered satisfactory. Against this background, we aimed at investigating the role of circadian clocks in EBA. We hypothesized that the migration of neutrophils into the skin, which controls the severity of autoantibody-induced tissue damage, is gated by peripheral circadian clocks. To characterize the diurnal regulation of peripheral blood mononuclear cells (PBMCs) under basal conditions, Fluorescence Activated Cell Sorting (FACS) analyses of PBMCs were performed in healthy, male, C57BL/6 mice at defined time points. We show that T-cells, B-cells, monocytes, and neutrophils show circadian rhythmicity. Particularly neutrophils, the key players in EBA, show significantly higher numbers in the morning than in the evening, whereas the activation of neutrophils is anti-phasic, with higher levels in the evening. The antibody-transfer-induced mouse model of EBA was then used to investigate the impact of circadian timing on disease development. Autoantibodies were applied either in the morning or in the evening. Our results demonstrate significantly higher disease activity when autoantibodies are injected in the morning, as measured by a specific clinical score. In addition, we used two-photon microscopy to visualize neutrophil migration into the skin in Lys-eGFP mice, possessing myelomonocytic cells labeled with green fluorescent protein (more Lys-eGFP+ cells in the morning group). Ultimately, we aim at developing novel chronotherapeutic approaches.
Keywords: Circadian clock, epidermolysis bullosa acquisita, neutrophils
This study was published in Journal of Investigative Dermatology: R. Pfündl, C. Koch, A. Kasprick, D. Zillikens, R. Ludwig, H. Oster, J. Hundt. 123 The role of circadian clocks in a murine model of antibody-induced skin inflammation. Journal of Investigative Dermatology. 2018, 0022-202X.
| M1 polarization markers are upregulated in basal-like breast cancer molecular subtype and associated with favorable patient outcomes|| |
Ibrahim Y. Hachim, Mahmood Yaseen Hachim, Iman M. Talaat, Nada M. Yakout, Rifat Hamoudi
Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Breast cancer heterogeneity has been found to play a role in variable patient outcome and response to therapy.This highlights the need for better subtyping methods that focus on tumor cells as well as stromal and immune cell profiles. The transcriptomic data of 1084 breast cancer patients was retrieved from the TCGA database and subjected to unsupervised clustering. The stromal and immune profile for each cluster was analyzed using the ESTIMATE and CIBERSORT analytical tools. The differentially expressed genes and the clinical characteristics of each cluster were identified and then validated in our own patient cohort using immunohistochemistry. Our analysis revealed seven unique sub-clusters with distinct clinical and molecular features. Our results also showed a distinct immune and stromal profile for each sub-cluster. Our results also showed classically activated macrophages (M1) to be associated with the more aggressive basal-like breast cancer subtype; in contrast, the alternatively activated M2 were more expressed in luminal A and luminal B subtypes. Moreover, patients with higher levels of M1 expression were found to have a better prognosis and less advanced disease. Adding stromal and immune profiles to breast cancer classification might improve clustering of patients, leading to more precise stratification with an impact on diagnosis, prognosis, and treatment options for our patients. Modalities of therapy in a more personalized approach.
Keywords: Breast cancer, immune profile, subtyping
This study was published in Frontiers in Immunolog: Hachim MY, Hachim IY, Talaat IM, Yakout NM, Hamoudi R. Frontiers in immunology. 2020; 11:560074.
| Application of artificial intelligence and multi-criteria decision-making models in disease prediction|| |
Dilber Uzun Ozsahin
Department of Medical Diagnostic Imaging, College of Health Science, University of Sharjah, Sharjah, United Arab Emirates
Artificial intelligence (AI) and multi-criteria decision-making (MCDM) are the two areas of study that have many potential applications. AI has been used to develop algorithms and systems that make decisions based on data, while MCDM is a method of evaluating multiple options or criteria and choosing the best course of action based on those evaluations. Medicine and medical applications are one potential application of AI and MCDM. For example, AI and MCDM could be used together to develop intelligent medical instruments that can make decisions based on data. For example, an AI-powered endoscope could be trained to identify abnormalities in the digestive tract and recommend a course of action to the doctor. Overall, the combination of AI and MCDM has the potential to improve the accuracy, efficiency, and effectiveness of medical instrumentation, leading to better patient care and outcomes. In the context of disease prediction, machine learning (ML) algorithms can be trained on data about various diseases and their risk factors, such as genetic data, environmental factors, and lifestyle choices. By analyzing this data, the ML model can identify the patterns and trends that may indicate an increased risk of a particular disease. These predictions can then be used by health-care providers to make more informed decisions about how to prevent or treat diseases. In our study, improved supervised ML models were adopted for various disease prediction tasks and evaluated using MCDM models to ascertain the most suitable algorithm for disease prediction or detection. In our study, we used ML tools such as support vector machines, K-nearest neighbors, logistic regression, random forest classifiers, and Naive Bayes classifiers to detect breast cancer. Similarly, evaluation metrics such as the confusion matrix, accuracy, specificity, F1 score, and recall were used to evaluate the output. Furthermore, the evaluation metrics were used to compare the trained models using the MCDM model (PROMETHEE) to evaluate the effective and efficient ML model in breast cancer prediction. The support vector machine is currently regarded as the most advantageous model for the early identification of breast cancer. It was able to achieve a net outranking flow of 0.1022, making it the clear winner in this category. The positive outranking flows and the negative outranking flows are balanced out to create the net outranking flow. This suggests that the alternative is superior to the other options when the net flow is higher. The k-nearest neighbor algorithm, logistic regression, and the random forest classifier came in second, third, and fourth place, respectively, with net flows of 0.0316, 0.0032, and 0.0541. With a net flow of −0.0766, the naive Bayes classifier is the alternative that is given the least amount of consideration. AI can potentially be a powerful tool for disease prediction, as it can analyze vast amounts of data much more quickly and accurately than a human. In health care, AI can be used to analyze the large amounts of data and make predictions about a person's health. For example, an AI system could be trained using data on a person's medical history, symptoms, and test results to predict the likelihood of that person developing a particular disease. However, it is important to note that AI is not a perfect solution, and the predictions made by an AI system are not always accurate. It is important for a health-care professional to interpret and evaluate the results of an AI-based disease prediction and make a final determination on a patient's condition. Furthermore, another type of AI adopted in disease prediction is ML. This is a type of AI that involves training a computer or machine to learn from the data and make predictions based on that data. In the context of disease prediction, ML algorithms could be trained using data on patient medical history, symptoms, and other factors to predict the likelihood of a person developing a particular disease.
Keywords: Artificial intelligence, machine learning, multi-criteria decision-making