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This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient's postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases.
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Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin's impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ+ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1+, FoxP3+, and IL-10+ NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46+ NKT cells and increased FasL expression, while lowering the percentages of FoxP3+, PD-1+, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10+ and FoxP3+ Tregs, along with Gr-1+ myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10+ and FoxP3+ Tregs, Gr-1+, NF-κB+, and iNOS+ MDSCs, and iNOS+ dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin's broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.
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Neoplasias de la Mama , Metformina , Ratones Endogámicos BALB C , Metformina/farmacología , Metformina/uso terapéutico , Animales , Femenino , Ratones , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Células Supresoras de Origen Mieloide/efectos de los fármacos , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/efectos de los fármacos , Células T Asesinas Naturales/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Agentes Inmunomoduladores/farmacologíaRESUMEN
A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4',4â³-tri-tert-butyl-2,2':6',2â³-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl2(terpytBu)] (C1), [{cis-PtCl(NH3)2(µ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(µ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(µ-4,4'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C4) and [{trans-PtCl(NH3)2(µ-4,4'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C5) (where terpytBu = 4,4',4â³-tri-tert-butyl-2,2':6',2â³-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower Kb and Ksv constant values compared to cisplatin analogs. The lowest Ksv value belonged to complex C1, while C4 exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNA is due to van der Waals forces, while that of C2-C5 is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear C1 complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The C1 complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.
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Antineoplásicos , Neoplasias Colorrectales , Metionina/análogos & derivados , Compuestos de Sulfonio , Ratones , Animales , Humanos , Platino (Metal)/química , Simulación del Acoplamiento Molecular , Zinc , Antineoplásicos/farmacología , ADN/química , PirazinasRESUMEN
The history of effective anti-cancer medications begins with the discovery of cisplatin's anti-cancer properties. Second-generation analogue, carboplatin, with a similar range of effectiveness, made progress in improving these drugs with fewer side effects and better solubility. Renewed interest in platinum-based drugs has been increasing in the past several years. These developments highlight a revitalized enthusiasm and ongoing exploration in platinum chemotherapy based on the series of dinuclear platinum(II) complexes, [{Pt(L)Cl}2(µ-bridging ligand)]2+, which have been synthesized and evaluated for their biological activities. These complexes are designed to target various cancerous conditions, exhibiting promising antitumor, antiproliferative, and apoptosis-inducing activities. The current work aims to shed light on the potential of these complexes as next-generation platinum-based therapies, highlighting their enhanced efficacy and reduced side effects, which could revolutionize the approach to chemotherapy.
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Antineoplásicos , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Ligandos , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/química , Compuestos Organoplatinos/síntesis química , Apoptosis/efectos de los fármacos , Platino (Metal)/química , Platino (Metal)/farmacología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/síntesis química , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patologíaRESUMEN
INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory granulomatous disease that can affect the entire gastrointestinal tract. It is characterized by various extraintestinal manifestations (EIMs), of which oral manifestations (OMs) are often possible. One of the possible OMs is periodontal disease (PD), a chronic inflammatory condition of the supporting tissues of the teeth. This study aimed to show the existence of a mutual relationship between the clinical activity of PD and the clinical and endoscopic activity of CD. MATERIALS AND METHODS: One clinical and two endoscopic indexes were used for the assessment of CD activity and clinical attachment loss (CAL), bleeding on probing (BOP), pocket probing depth (PPD), and radiographic bone loss (RBL) in a dental panoramic tomogram to assess PD in CD patients. RESULTS: A total of 38 patients underwent the entire study process, of which 20 patients had CD and 18 patients had CD and PD. Considering all CD activity scores, there were 26 patients with active disease; half of them had PD, and 85.7% of operated patients had active CD. The values of CAL, PPD, BOP, and RBL were higher in active CD patients than those in remission, except for BOP when comparing to the CDAI score, which was higher in those in remission of CD. CONCLUSION: The results of this study indicate that there is a connection between the activity of CD and worse conditions of the supporting tissues of the gums in the oral cavity, so it is important to keep in mind the necessity of referring patients with CD to a dentist for timely and adequate therapeutic measures.
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Enfermedad de Crohn , Enfermedades Periodontales , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedades Periodontales/complicacionesRESUMEN
Acute pancreatitis (AP) is a complex inflammatory condition that can lead to systemic inflammatory responses and multiple organ dysfunction. This study investigates the role of Galectin-3 (Gal-3), a ß-galactoside-binding lectin, in modulating acquired immune responses in AP. Acute pancreatitis was induced by ligation of the bile-pancreatic duct in wild-type and Galectin-3-deficient C57BL/6 mice. We determined the phenotypic and molecular features of inflammatory cells, serum concentrations of amylase, pancreatic trypsin activity, and pancreatic and lung pathology. Galectin-3 deficiency decreased the total number of CD3+CD49- T cells and CD4+ T helper cells, downregulated the production of inflammatory cytokine and IFN-γ, and increased the accumulation of IL-10-producing Foxp3+ T regulatory cells and regulatory CD4+ T cells in the pancreata of diseased animals. The deletion of Galectin-3 ameliorates acute pancreatitis characterized by lowering serum amylase concentration and pancreatic trypsin activity, and attenuating of the histopathology of the lung. These findings shed light on the role of Galectin-3 in acquired immune response in acute pancreatitis and identify Galectin-3 as an attractive target for investigation of the immunopathogenesis of disease and for consideration as a potential therapeutic target for patients with acute inflammatory disease of the pancreas.
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Galectina 3 , Ratones Endogámicos C57BL , Pancreatitis , Linfocitos T Reguladores , Animales , Pancreatitis/inmunología , Pancreatitis/patología , Pancreatitis/metabolismo , Pancreatitis/genética , Galectina 3/metabolismo , Galectina 3/genética , Ratones , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Ratones Noqueados , Enfermedad Aguda , Masculino , Amilasas/sangreRESUMEN
This case report presents a unique instance of small bowel perforation caused by solitary metastasis from renal cell carcinoma (RCC), a rare and complex clinical scenario. The patient, a 59-year-old male with a history of RCC treated with nephrectomy four years prior, presented with acute abdomen symptoms. Emergency diagnostic procedures identified a significant lesion in the small intestine. Surgical intervention revealed a perforated jejunal segment due to metastatic RCC. Postoperatively, the patient developed complications, including pneumonia and multi-organ failure, leading to death 10 days after surgery. Histopathological analysis confirmed the metastatic nature of the lesion. This case underscores the unpredictable nature of RCC metastasis and highlights the need for vigilance in post-nephrectomy patients. The rarity of small bowel involvement by RCC metastasis, particularly presenting as perforation, makes this case a significant contribution to medical literature, emphasizing the challenges in the diagnosis and management of such atypical presentations.
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The four new ligands, dialkyl esters of (S,S)-propylenediamine-N,N'-di-(2,2'-di-(4-hydroxy-benzil))acetic acid (R2-S,S-pddtyr·2HCl) (R = ethyl (L1), propyl (L2), butyl (L3), and pentyl (L4)) and corresponding palladium(II) complexes have been synthesized and characterized by microanalysis, infrared, 1H NMR and 13C NMR spectroscopy. In vitro cytotoxicity was evaluated using the MTT assay on four tumor cell lines, including mouse mammary (4T1) and colon (CT26), and human mammary (MDA-MD-468) and colon (HCT116), as well as non-tumor mouse mesenchymal stem cells. Using fluorescence spectroscopy were investigated the interactions of new palladium(II) complexes [PdCl2(R2-S,S-pddtyr)]; (R = ethyl (C1), propyl (C2), butyl (C3), and pentyl (C4)) with calf thymus human serum albumin (HSA) and DNA (CT-DNA). The high values of the binding constants, Kb, and the Stern-Volmer quenching constant, KSV, show the good binding of all complexes for HSA and CT-DNA. The mentioned ligands and complexes were also tested on in vitro antimicrobial activity against 11 microorganisms. Testing was performed by the microdilution method, where the minimum inhibitory concentration (MMC) and the minimum microbicidal concentration (MMC) were determined.
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Complejos de Coordinación , ADN , Ésteres , Paladio , Albúmina Sérica Humana , Animales , Humanos , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , ADN/metabolismo , Ésteres/química , Ésteres/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Paladio/química , Paladio/farmacología , Unión Proteica , Albúmina Sérica Humana/metabolismoRESUMEN
This detailed review focuses on retroperitoneal undifferentiated pleomorphic sarcoma (UPS), a particularly aggressive soft-tissue sarcoma that poses unique diagnostic and therapeutic challenges due to its rarity and complex presentation. By documenting a new case of retroperitoneal UPS and conducting a comprehensive review of all known cases, this article aims to expand the existing body of knowledge on the epidemiology, molecular pathogenesis, and treatment strategies associated with this rare disease. The complexity of diagnosing UPS is emphasized given that it rarely occurs in the retroperitoneal space and its histological and molecular complexity often complicates its recognition. This review highlights the need for specialized diagnostic approaches, including advanced imaging techniques and histopathological studies, to accurately diagnose and stage the disease. In terms of treatment, this paper advocates a multidisciplinary approach that combines surgery, radiotherapy and chemotherapy and tailors it to individual patients to optimize treatment outcomes. This review highlights case studies that illustrate the effectiveness of surgical intervention in the treatment of these tumors and emphasize the importance of achieving clear surgical margins to prevent recurrence. Furthermore, this review discusses the potential of new molecular targets and the need for innovative therapies that could bring new hope to patients affected by this challenging sarcoma.
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This manuscript discusses a rare case of acute appendicitis caused by metastasis from invasive breast carcinoma of no special type in a 70-year-old female previously diagnosed with breast cancer. It delves into the diagnostic challenges and management complexities of such unusual clinical presentations. The paper includes an analysis of 19 documented cases, enriching the understanding of metastatic patterns and treatment strategies in breast cancer. It underlines the importance of considering a history of malignancy when diagnosing acute abdominal conditions and emphasizes a comprehensive approach in interpreting diagnostic imaging in patients with past oncological issues to effectively manage metastatic breast cancer exhibiting atypical manifestations.
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Since the end of 2019, the global spread of COVID-19 has represented a historic event that changed our way of treating patients globally. The use of long-acting injections (LAI) antipsychotics was emphasized. Our goal was to investigate the impact of COVID-19 on the frequency of prescribing LAI and compare it with a period before. All patients (198) who started LAI-risperidone or LAI-paliperidone for the period 2017-2022, in Kragujevac, the city in Central Serbia, were considered. The frequency of prescribing LAI before and during COVID-19 and the total number of prescribed LAI per year were compared. Separately, the frequency of prescribing LAI-R and the frequency of prescribing LAI-P were compared. The significant (p < 0,05) increase in the use of LAI risperidone and paliperidone was in 2020 and 2021 [per year 2017(3), 2018(6), 2019(26), 2020(75), 2021(55), and 2022(33)]. The significant (p < 0,05) increase in monthly and quarterly preparations of LAI paliperidone was in 2020 and 2021 relative to the years before the pandemic. As the pandemic weakened, the inclusion of LAI paliperidone therapy weakened during 2022. A significant increase in usage of LAI risperidone was in 2022, and in 2020 and 2021 was as it was in the period 2017-2019. During COVID-19, especially in years when COVID-19 restriction measures were stricter, there was a significant change in the application method of antipsychotic therapy in favor of LAI. Regardless of the increase in treatment costs, patients' interests and protection were prioritized in the treatment process.
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Intensive care units (ICUs) are expert hospital areas that provide treatment and 24 h care for people who are very sick. Sepsis represents a serious, severe condition and it can lead to septic shock and multiple organ dysfunction syndromes and is one of the most common reasons for patients' hospitalization in ICUs. We wanted to explore the prognostic values of interleukin (IL) 33, soluble suppression of tumorigenicity 2 (sST2), IL 27, and galectin 3 in critically-ill patients. We assumed that these parameters in combination or alone could predict mortality in ICU patients. This research represents a clinical non-randomized prospective study, performed at the Medical Military Academy, a tertiary care hospital in Belgrade, Serbia. The patients were divided in four groups: patients with sepsis (peritonitis, pancreatitis, trauma) and patients without sepsis (trauma). Total number of patients enrolled in the study was 151 and average years of patients were 56.48. The values greater than the cut-off were the predictors of mortality. The IL-33, IL-27 as well as galectin-3 can successfully predict the outcome of critically-ill patients in ICUs. The sST2, cannot predict death in critically-ill patients as a single prognostic factor. However, the combination of at least two biomarkers: IL-33, sST2, IL-27, and galectin-3, gives very significant results in predicting the outcome in patients admitted to ICUs.