Search results for: tumor necrosis factor-related apoptosis-inducing ligand

Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres

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Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.

Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty

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Authors: Dharshini Selvarajah, Karen Kong

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Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management are often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids' sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery embolization (UAE) has previously been shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve hydronephrosis. UAE has now established itself as an organ-preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid-related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to the hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents in situ and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission, and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery embolization (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE, such as the expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters, a hysterectomy would inevitably be required in the future. Day 3 post-UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenum, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure; however, the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumor of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of the UAE as a fertility-preserving option is described.

Keywords: uterine artery embolisation for fibroids, urological complications from fibroids, uropathy of fibroids, obstructive fibroid management

Procedia PDF Downloads 191

Authors: Faranak Felfeliyan, Parvaneh Shokrani, Maryam Atarod

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Introduction Using electron beam is widespread in radiotherapy. The main criteria in radiation therapy is to irradiate the tumor volume with maximum prescribed dose and minimum dose to vital organs around it. Using abutting fields is common in radiotherapy. The main problem in using abutting fields is dose inhomogeneity in the junction region. Electron beam divergence and lateral scattering may lead to hot and cold spots in the junction region. One solution for this problem is using of a spoiler to broaden the penumbra and uniform dose in the junction region. The goal of this research was to compare titanium and aluminum effects as a spoiler for dose uniformity achievement in the junction region of oblique electron fields with Monte Carlo simulation. Dose uniformity in the junction region depends on density, scattering power, thickness of the spoiler and the angle between two fields. Materials and Methods In this study, Monte Carlo model of Siemens Primus linear accelerator was simulated for a 5 MeV nominal energy electron beam using manufacture provided specifications. BEAMnrc and EGSnrc user code were used to simulate the treatment head in electron mode (simulation of beam model). The resulting phase space file was used as a source for dose calculations for 10×10 cm2 field size at SSD=100 cm in a 30×30×45 cm3 water phantom using DOSXYZnrc user code (dose calculations). An automatic MP3-M water phantom tank, MEPHYSTO mc2 software platform and a Semi-Flex Chamber-31010 with sensitive vol­ume of 0.125 cm3 (PTW, Freiburg, Germany) were used for dose distribution measurements. Moreover, the electron field size was 10×10 cm2 and SSD=100 cm. Validation of devel­oped beam model was done by comparing the measured and calculated depth and lateral dose distributions (verification of electron beam model). Simulation of spoilers (using SLAB compo­nent module) placed at the end of the electron applicator, was done using previously vali­dated phase space file for a 5 MeV nominal energy and 10×10 cm2 field size (simulation of spoiler). An in-house routine was developed in order to calculate the combined isodose curves re­sulting from the two simulated abutting fields (calculation of dose distribution in abutting electron fields). Results Verification of the developed 5.9 MeV elec­tron beam model was done by comparing the calculated and measured dose distributions. The maximum percentage difference between calculated and measured PDD was 1%, except for the build-up region in which the difference was 2%. The difference between calculated and measured profile was 2% at the edges of the field and less than 1% in other regions. The effect of PMMA, aluminum, titanium and chromium in dose uniformity achievement in abutting normal electron fields with equivalent thicknesses to 5mm PMMA was evaluated. Comparing R90 and uniformity index of different materials, aluminum was chosen as the optimum spoiler. Titanium has the maximum surface dose. Thus, aluminum and titanium had been chosen to use for dose uniformity achievement in oblique electron fields. Using the optimum beam spoiler, junction dose decreased from 160% to 110% for 15 degrees, from 180% to 120% for 30 degrees, from 160% to 120% for 45 degrees and from 180% to 100% for 60 degrees oblique abutting fields. Using Titanium spoiler, junction dose decreased from 160% to 120% for 15 degrees, 180% to 120% for 30 degrees, 160% to 120% for 45 degrees and 180% to 110% for 60 degrees. In addition, penumbra width for 15 degrees, without spoiler in the surface was 10 mm and was increased to 15.5 mm with titanium spoiler. For 30 degrees, from 9 mm to 15 mm, for 45 degrees from 4 mm to 6 mm and for 60 degrees, from 5 mm to 8 mm. Conclusion Using spoilers, penumbra width at the surface increased, size and depth of hot spots was decreased and dose homogeneity improved at the junc­tion of abutting electron fields. Dose at the junction region of abutting oblique fields was improved significantly by using spoiler. Maximum dose at the junction region for 15⁰, 30⁰, 45⁰ and 60⁰ was decreased about 40%, 60%, 40% and 70% respectively for Titanium and about 50%, 60%, 40% and 80% for Aluminum. Considering significantly decrease in maximum dose using titanium spoiler, unfortunately, dose distribution in the junction region was not decreased less than 110%.

Keywords: abutting fields, electron beam, radiation therapy, spoilers

Procedia PDF Downloads 149

Authors: M. C. O. Ezeibe, F. I. O. Ezeibe

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Reasons viral diseases (including AI, HIV/AIDS, and COVID-19), tumors (including Cancers and Prostrate enlargement), and antimicrobial-resistant infections (AMR) are difficult to cure are features of the pathogens which normal cells do not have or need (biomedical markers) have not been identified; medicines that can counter the markers have not been invented; strategies and mechanisms for their treatments have not been developed. When cells become abnormal, they acquire negative electrical charges, and viruses are either positively charged or negatively charged, while normal cells remain neutral (without electrical charges). So, opposite charges' electrostatic attraction is a treatment mechanism for viral diseases and tumors. Medicines that have positive electrical charges would mop abnormal (infected and tumor) cells and DNA viruses (negatively charged), while negatively charged medicines would mop RNA viruses (positively charged). Molecules of Aluminum-magnesium silicate [AMS: Al₂Mg₃ (SiO₄)₃], an approved medicine and pharmaceutical stabilizing agent, consist of nanoparticles which have both positive electrically charged ends and negative electrically charged ends. The very small size (0.96 nm) of the nanoparticles allows them to reach all cells in every organ. By stabilizing antimicrobials, AMS reduces the rate at which the body metabolizes them so that they remain at high concentrations for extended periods. When drugs remain at high concentrations for longer periods, their efficacies improve. Again, nanoparticles enhance the delivery of medicines to effect targets. Both remaining at high concentrations for longer periods and better delivery to effect targets improve efficacy and make lower doses achieve desired effects so that side effects of medicines are reduced to allow the immunity of patients to be enhanced. Silicates also enhance the immune responses of treated patients. Improving antimicrobial efficacies and enhancing patients` immunity terminate infections so that none remains that could develop resistance. Some countries do not have natural deposits of AMS, but they may have Aluminum silicate (AS: Al₄ (SiO₄)₃) and Magnesium silicate (MS: Mg₂SiO₄), which are also approved medicines. So, AS and MS were used to formulate an AMS-brand, named Medicinal synthetic AMS {Al₄ (SiO₄)₃ + 3Mg₂SiO₄ → 2Al₂Mg₃ (SiO₄)₃}. To overcome the challenge of AMS, AS, and MS being un-absorbable, Dextrose monohydrate is incorporated in MSAMS-formulations for the simple sugar to convey the electrically charged nanoparticles into blood circulation by the principle of active transport so that MSAMS-antimicrobial formulations function systemically. In vitro, MSAMS reduced (P≤0.05) titers of viruses, including Avian influenza virus and HIV. When used to treat virus-infected animals, it cured Newcastle disease and Infectious bursa disease of chickens, Parvovirus disease of dogs, and Peste des petits ruminants disease of sheep and goats. A number of HIV/AIDS patients treated with it have been reported to become HIV-negative (antibody and antigen). COVID-19 patients are also reported to recover and test virus negative when treated with MSAMS. PSA titers of prostate cancer/enlargement patients normalize (≤4) following treatment with MSAMS. MSAMS has also potentiated ampicillin trihydrate, sulfadimidin, cotrimoxazole, piparazine citrate and chloroquine phosphate to achieve ≥ 95 % infection-load reductions (AMR-prevention). At 75 % of doses of ampicillin, cotrimoxazole, and streptomycin, supporting MSAMS-formulations' treatments with antioxidants led to the termination of even already resistant infections.

Keywords: electrical charges, viruses, abnormal cells, aluminum-magnesium silicate

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Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

Procedia PDF Downloads 289

Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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