Acıbadem Üniversitesi Açık Erişim Sistemi
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Application of mRNA Technology in Cancer Therapeutics
No full textmRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment. Nevertheless, further research is required to optimize RNA stabilization, delivery platforms, and improve clinical efficacy by interacting with the tumor microenvironment to induce a long-term antitumor response. This review provides a comprehensive summary of the available evidence on the recent advances and efforts to overcome existing challenges of mRNA-based treatment strategies, and how these efforts play key roles in offering perceptive insights into future considerations for clinical application.8AUG1
A Review on Cutaneous and Musculoskeletal Manifestations of CLOVES Syndrome
No full textCLOVES syndrome is a novel sporadic mosaic segmental overgrowth syndrome, currently categorized under the canopy of PROS (PIK3CA-related overgrowth spectrum) disorders. All PROS disorders harbor heterozygous postzygotic activating somatic mutations involving the PIK3CA gene. As an upstream regulator of the PI3K/AKT/mTOR signal transduction pathway, activating mutations of PIK3CA gene commence in uncontrolled growth of cutaneous, vascular (capillaries, veins, and lymphatics), adipose, neural, and musculoskeletal tissues. The excessive growth is segmental, patchy, asymmetric, and confined to body parts affected by the mutation. The term `CLOVES' is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. The syndrome is characterized by an admixture of overgrown tissues, derived mainly from mesoderm and neuroectoderm. Among PROS disorders, CLOVES syndrome represents the extreme end of the spectrum with massive affection of almost the entire body. The syndrome might judiciously be treated with medications hampering with the PI3K/AKT/mTOR signal transduction pathway. This article aims at reviewing the cutaneous and musculoskeletal manifestations of CLOVES syndrome, as the paradigm for PROS disorders. CLOVES syndrome and other PROS disorders are still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.621-6301
Human Papillomavirus Infection and Oropharyngeal and Gastrointestinal Cancers: A Causal Relationship?
No full textThe human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The risk of being infected at least once in a lifetime among both men and women is estimated to be 50\%. Although the majority of HPV infections are asymptomatic and improve within 2 years, approximately 10\% of individuals develop a persistent infection and have an increased risk of developing carcinomas. The association of HPV and genital cancer is well established. However, there is evidence that HPV may also be associated with other cancers, including those of the gastrointestinal system. The aim of this review is to organize the current evidence of associations between HPV infections and oropharyngeal and gastrointestinal cancers, including the following: oropharyngeal, esophageal, gastric, colorectal, and anal cancers. A comprehensive review of the most up-to-date medical literature concluded that an HPV infection might have a role in the oncogenesis of gastrointestinal tract cancers. HPV may have a causal relationship with oropharyngeal and esophageal squamous cell cancers. However, the association between HPV and gastric and colorectal cancers is weaker. The development of cancer in the oropharyngeal and gastrointestinal tract is usually multifactorial, with HPV having a role in at least a subset of these cancers. HPV infections pose a big challenge due to their burden of infection and their oncogenic potential.4DEC1
Long-term follow-up of patients after acute kidney injury in the neonatal period: abnormal ambulatory blood pressure findings
No full textBackground Data on the long-term effects of neonatal acute kidney injury (AKI) are limited. Methods We invited 302 children who had neonatal AKI and survived to hospital dischargeout of 95 patients who agreed to participate in the study, 23 cases were excluded due to primary kidney, cardiac, or metabolic diseases. KDIGO definition was used to define AKI. When a newborn had no previous serum creatinine, AKI was defined as serum creatinine above the mean plus two standard deviations (SD) (or above 97.5(th) percentile) according to gestational age, weight, and postnatal age. Clinical and laboratory features in the neonatal AKI period were recorded for 72 casesat long-term evaluation (2-12 years), kidney function tests with glomerular filtration rate (eGFR) by the Schwartz formula, microalbuminuria, office and 24-h ambulatory blood pressure monitoring (ABPM), and kidney ultrasonography were performed. Results Forty-two patients (58\%) had stage I AKI during the neonatal period. Mean age at long-term evaluation was 6.8 +/- 2.9 years (range: 2.3-12.0)mean eGFR was 152.3 +/- 26.5 ml/min/1.73 m(2). Office hypertension (systolic and/or diastolic BP >= 95(th) percentile), microalbuminuria (> 30 mg/g creatinine), and hyperfiltration (> 187 ml/min/1.73 m(2)) were present in 13.0\%, 12.7\%, and 9.7\% of patients, respectively. ABPM was performed on 27 patients, 18.5\% had hypertension, and 40.7\% were non-dippers48.1\% had abnormal findings. Female sex was associated with microalbuminurialow birth weight (< 1,500 g) and low gestational age (< 32 weeks) were associated with hypertension by ABPM. Twenty-three patients (33.8\%) had at least one sign of microalbuminuria, office hypertension, or hyperfiltration. Among 27 patients who had ABPM, 16 (59.3\%) had at least one sign of microalbuminuria, abnormal ABPM (hypertension and/or non-dipping), or hyperfiltration. Conclusion Even children who experienced stage 1 and 2 neonatal AKI are at risk for subclinical kidney dysfunction. Non-dipping is seen in four out of 10 children. Long-term follow-up of these patients is necessary.1MAR 232
Clinical significance of plasma tryptophan, kynurenine, and kynurenine/tryptophan ratio in rheumatoid arthritis patients
No full textBackground: The catabolism of tryptophan (Trp) in the kynurenine (Kyn) pathway is thought to have a critical immunosuppressive effect.Aim of the work: To evaluate plasma Trp and metabolite levels to identify their diagnostic potential in rheumatoid arthritis (RA).Patients and methods: 50 RA patients and 41 control were included in this study. The Trp and Kyn were analyzed and the Kyn\textbackslash{}Trp ratio was calculated to estimate Indolamine 2,3 dioxygenase (IDO) enzyme activity involved in Trp degradation.Results: The 50 patients had a mean age of 58.5 +/- 10.6 years37 females and 13 males, F:M 2.8:1 and median disease duration was 10.1 (7-16) years. Rheumatoid factor was positive in 64 \%. The median Trp value was significantly lower in RA (11120.73259-16352 ng/ml) compared to control (12372.37217-31,936 ng/ml) (p = 0.001). Kyn/Trp was significantly higher in RA (4.042.5-12.3) compared to con-trol (3.22.1-4.7) (p < 0.0001). The median Kyn value was higher in RA (451.02264-1292 ng/ml) than in control (391.4236-1494 ng/ml) (p = 0.04). Trp significantly inversely correlated with the morning stiff-ness (r =-0.32, p = 0.025), Kyn significantly correlated with the C-reactive protein (CRP) (r = 0.31, p = 0.028) and erythrocyte sedimentation rate (ESR) (r = 0.41, p = 0.003) and the Kyn/Trp ratio correlated with the morning stiffness, CRP and ESR (r = 0.26, p = 0.045r = 0.32, p = 0.025 and r = 0.32, p = 0.024 respectively). Kyn/Trp, Kyn and Trp significantly predicted RA at a cut-off value of 4.72, 589.1 ng/ml and 9921.1 ng/ml (p < 0.0001, p = 0.04 and p = 0.001 respectively).Conclusion: Our study showed that there is a significant relationship between RA and Kyn and Trp levels and IDO enzyme activity.(c) 2022 THE AUTHORS. Publishing services by ELSEVIER B.V. on behalf of The Egyptian Society of Rheu-matic Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).4OCT367-3714
A New Perspective on the Treatment of Alzheimer's Disease and Sleep Deprivation-Related Consequences: Can Curcumin Help?
No full textSleep disturbances, as well as sleep-wake rhythm disorders, are characteristic symptoms of Alzheimer's disease (AD) that may head the other clinical signs of this neurodegenerative disease. Age-related structural and physiological changes in the brain lead to changes in sleep patterns. Conditions such as AD affect the cerebral cortex, basal forebrain, locus coeruleus, and the hypothalamus, thus changing the sleep-wake cycle. Sleep disorders likewise adversely affect the course of the disease. Since the sleep quality is important for the proper functioning of the memory, impaired sleep is associated with problems in the related areas of the brain that play a key role in learning and memory functions. In addition to synthetic drugs, utilization of medicinal plants has become popular in the treatment of neurological diseases. Curcuminoids, which are in a diarylheptanoid structure, are the main components of turmeric. Amongst them, curcumin has multiple applications in treatment regimens of various diseases such as cardiovascular diseases, obesity, cancer, inflammatory diseases, and aging. Besides, curcumin has been reported to be effective in different types of neurodegenerative diseases. Scientific studies exclusively showed that curcumin leads significant improvements in the pathological process of AD. Yet, its low solubility hence low bioavailability is the main therapeutic limitation of curcumin. Although previous studies have focused different types of advanced nanoformulations of curcumin, new approaches are needed to solve the solubility problem. This review summarizes the available scientific data, as reported by the most recent studies describing the utilization of curcumin in the treatment of AD and sleep deprivation-related consequences.JAN 12202
Measuring potassium level in packed red blood cells before using: Word of caution for congenital cardiac surgery
No full textBackground and Aim of the Study Transfusion-associated hyperpotassemia is a serious complication of packed red blood cell (PRBC) transfusion after congenital cardiac surgery. Our study aimed to identify risk factors and potential preventive measures of transfusion-associated hyperpotassemia in neonates and infants after congenital cardiac surgery. Methods Pediatric patients who underwent congenital cardiac surgery and need transfusion were enrolled in this prospective study. The potassium concentration of PRBC was checked from the sample taken from the segment. The volume of transfusion, age of PRBC, potassium concentration of unit were recorded. The estimated increment of potassium level in patients after PRBC transfusion was calculated. Results Seventy-four individual patients, 95 distinct transfusions, 112 blood products were evaluated. The mean age of the blood unit was 3.8 +/- 1.4 days. The mean potassium concentration in the PRBCs was 9.9 +/- 2.4 mmol/L. A weak correlation was observed between the potassium value of the PRBC and the age of PRBC (p = 0.049, r = 0.2, y = 0.24 x x + -0.68). There was a weak correlation between the potassium value of PRBCs and the age of the unit (p < 0.001, r = 0.37, y = 2.8 x x + -3.6). Conclusions Before transfusion, even PRBC is fresh, measuring the potassium level of PRBC and the potassium that will be given to the pediatric patient with transfusion can prevent transfusion-related hyperpotassemia and related complications. Otherwise, high potassium levels, which may be overlooked despite being fresh, may cause serious complications, even cardiac arrest, especially in neonates and infants.3MAR535-5413
Psychosocial Impact of the War in Ukraine on Pediatric Cancer Patients and Their Families Receiving Oncological Care Outside Their Country at the Onset of Hostilities
No full textPsychosocial care of pediatric cancer patients and their families is as critical as the medical and surgical components of their therapies. Strains on family communication and structure and financial need are linked to poorer psychological outcomes for both patients and families. It is critical that children remain as connected as possible to their communities and extended families during therapy. For Ukrainian pediatric cancer patients receiving care outside of their nation \& rsquos borders on February 24, 2022, the Russian invasion of Ukraine compounded these problems. Based on conversations with patients and parents, we evaluated the psychosocial impact of war on pediatric Ukrainian cancer patients and their families who had left their country before the onset of the conflict to undergo treatment of pediatric malignancies at our medical center. These families shared with us the problems they have experienced after the Russian invasion of Ukraine. Their concerns can be summarized in 4 categories: (1) emotional stress experienced by the patients, families and relatives related to the dangers of war(2) difficulties in obtaining previous hospital records in Ukraine(3) medical expensesand (4) uncertainty regarding the patient's and their family's future and the ability of the children to ever return to their homes. Psychosocial distress relating to the violence of war will hopefully pass in near future, but our pediatric patients and their families will continue to face stressors related to displacement and financial concerns for some time to come. (c) 2022 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).4JUL-AUG
Targeting the undruggable oncogenic KRAS: the dawn of hope
No full textKRAS mutations are the drivers of various cancers, including non-small cell lung cancer, colon cancer, and pancreatic cancer. Over the last 30 years, immense efforts have been made to inhibit KRAS mutants and oncogenic KRAS signaling using inhibitors. Recently, specific targeting of KRAS mutants with small molecules revived the hopes for successful therapies for lung, pancreatic, and colorectal cancer patients. Moreover, advances in gene editing, protein engineering, and drug delivery formulations have revolutionized cancer therapy regimens. New therapies aim to improve immune surveillance and enhance antitumor immunity by precisely targeting cancer cells harboring oncogenic KRAS. Here, we review recent KRAS-targeting strategies, their therapeutic potential, and remaining challenges to overcome. We also highlight the potential synergistic effects of various combinatorial therapies in preclinical and clinical trials.1JAN 11
Autologous omentum transposition for regeneration of a renal injury model in rats
No full textBackground After renal trauma, surgical treatment is vital, but sometimes there may be loss of function due to fibrosis. This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a rat model. Methods A total of 30 Wistar albino rats were included and randomly divided equally into a control group and four intervention groups. Iatrogenic renal injuries were repaired using a surgical technique (primary repair 1 group and primary repair 2 group) or transposition of the autologous omentum (omentum repair 1 group and omentum repair 2 group). Blood samples were taken preoperatively and on the 1st and 7th postoperative days in all groups and on the 18th postoperative day in the control and two intervention groups. All rats were sacrificed on the 7th or 18th day postoperatively, and their right kidneys were taken for histopathological evaluation. Results The mean urea level significantly decreased from day 1 to day 7 and from day 1 to day 18 in the omentum repair 2 group (P = 0.005 and P = 0.004, respectively). There were no other significant changes in urea or creatinine levels within the intervention groups (P > 0.05). There was no significant correlation between the urea and creatinine levels and the histological scores (P > 0.05). The primary repair 1 and 2 groups had significantly higher median granulation and inflammation scores in the kidney specimen than the control and omentum repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). The completion score for the healing process in the kidney specimen was significantly higher in the omentum repair groups than in the primary repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). Granulation degree in the kidney specimen was strongly and positively correlated with the inflammation degree (r = 0.824, P < 0.001) and foreign body reaction in the kidney specimen (r = 0.872, P < 0.001) and a strong and negative correlation with the healing process completion score in the kidney (r = - 0.627, P = 0.001). Inflammation degree in the kidney specimen was strongly and positively correlated with the foreign body reaction in the kidney specimen (r = 0.731, P = 0.001) and strongly and negatively correlated with the healing process completion score in the kidney specimen (r = - 0.608, P = 0.002). Conclusion Autologous omentum tissue for kidney injury repair attenuated inflammation and granulation. Additionally, the use of omental tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process and reduced fibrosis and tissue and function loss.1JAN 4