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The role of palliative surgery for excision of metastasis in a patient with nasopharyngeal carcinoma (NPC) is limited. However, judicious patient selection can yield noteworthy long-term survival outcomes. We report a case of the occurrence of isolated lung metastasis and its management in a NPC survivor with a long disease-free interval. The patient underwent radiotherapy and chemotherapy in 2014 for primary NPC cT2N1M0. In November 2019, he presented with a cough and respiratory distress. The investigation unveiled an isolated lung metastasis that partially encased the left upper lobe bronchus and closely abutted the left main bronchus and left pulmonary artery. Following comprehensive multidisciplinary consultations involving the patient and relatives, the patient underwent a left pneumonectomy as an imperative palliative intervention to alleviate the symptomatic respiratory distress and long-term disease control. Remarkably, the patient's disease-free status has persisted post surgery until 2024, evoking consideration of a potential curative trajectory. This case emphasises comprehensive evaluations, multidisciplinary discussions, and individualised treatment plans. It encourages patients to remain optimistic and engaged in their healthcare journey.
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GLH/Vasa/DDX4 helicases are core germ-granule proteins that promote germline development and fertility. A yeast-two-hybrid screen using Caenorhabditis elegans GLH-1 as bait identified BYN-1, the homolog of human bystin/BYSL. In humans, bystin promotes cell adhesion and invasion in gliomas, and, with its binding partner trophinin, triggers embryonic implantation into the uterine wall. C. elegans embryos do not implant and lack a homolog of trophinin, but both trophinin and GLH-1 contain unique decapeptide phenylalanine-glycine (FG)-repeat domains. In germ cells, we find endogenous BYN-1 in the nucleolus, partitioned away from cytoplasmic germ granules. However, BYN-1 enters the cytoplasm during spermatogenesis to colocalize with GLH-1. Both proteins become deposited in residual bodies (RBs), which are then engulfed and cleared by the somatic gonad. We show that BYN-1 acts upstream of CED-1 to drive RB engulfment, and that removal of the FG-repeat domains from GLH-1 and GLH-2 can partially phenocopy byn-1 defects in RB clearance. These results point to an evolutionarily conserved pathway whereby cellular uptake is triggered by the cytoplasmic mobilization of bystin/BYN-1 to interact with proteins harboring FG-repeats.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Células Germinativas , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Células Germinativas/metabolismo , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Espermatogênese/genética , MasculinoRESUMO
INTRODUCTION: Takotsubo cardiomyopathy (TTCM) can occur in acute respiratory distress syndrome (ARDS) and a few cases in literature were reported to be associated with hemodynamic instability. All these patients were managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO).Case presentation: We present two patients with ARDS-induced TTCM who were managed successfully with venovenous ECMO (VV-ECMO). CONCLUSION: Ventricular function in both patients fully recovered three days after ECMO initiation, and they were subsequently weaned from ECMO once pulmonary function improved.
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Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Cardiomiopatia de Takotsubo , Humanos , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/terapia , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/etiologia , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , MasculinoRESUMO
Background: The number of patients living with left ventricular assist devices (LVADs) has gradually increased in the past decade. Non-cardiac surgery (NCS) in patients with LVAD poses a unique situation with its inherent challenges. Aim: We conducted a comprehensive review to investigate the perioperative complications and mortality associated with emergent or elective NCS in patients with LVAD. Method: A comprehensive literature search for any papers referring to continuous LVAD patients with NCS. All publications with at least five durable LVAD patients who had NCS were eligible for inclusion. Result: Twenty articles matching our criteria were found and included in our study. This systematic review included 6,476 LVAD patients who underwent 6,824 NCS. There were 5-3,216 LVAD patients with NCS in each study. The median age was between 39 and 65 years, and most of the patients (78.8%) were male. Thirty-day postoperative mortality ranged from 0% to 60%. Eight studies reported no death within the 30 days of the operation. Common complications include gastrointestinal (GI) bleeding, intracranial bleeding, infection, acute kidney injury (AKI), urinary tract infection (UTI), stroke, sepsis, pneumonia, and VAD exchange. Emergent abdominal surgery had the highest (up to 60%) mortality rate, and vascular and neurological operations had the highest complication rates. Due to the diverse range of patients in each publication and the combination of outcomes presented in various publications, a meta-analysis was not conducted. Conclusion: In LVAD patients, noncardiac surgery may be performed effectively and safely. LVAD patients who undergo non-cardiac surgery may require more transfusions due to their complex coagulopathies. However, perioperative management of LVAD patients undergoing emergent NCS should be optimized to reduce mortality. Systematic Review Registration: https://osf.io/fetsb/.
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Cancer ranks as the second leading cause of mortality worldwide, prompting extensive investigations into factors contributing to its development. Among these factors, genetic variations, known as genotypic polymorphisms, have been identified as significant influencers in the susceptibility to various types of cancer. Recent research has focused on exploring the connection between polymorphisms in the Long Non-coding RNA HOTAIR and cancer risk. However, the results from these studies have been inconsistent, leading to ambiguity and controversy. To address this uncertainty, we conducted a systematic analysis by gathering relevant studies from PubMed, EMBASE, and Google Scholar. Specifically, we focused on three well-studied polymorphisms within the HOTAIR lncRNA (HOTAIR rs920778 C > T, HOTAIR rs1899663 G > T, HOTAIR rs4759314 A > G) and their association with cancer risk. Our meta-analysis included data from 48 case-control studies involving 42,321 cases and 54,137 controls. The results of our updated meta-analysis revealed a significant correlation between HOTAIR rs1899663 G > T and HOTAIR rs4759314 A > G polymorphisms and overall cancer risk, particularly in the homozygous and recessive genetic models. Subgroup analysis further revealed that these associations were notably pronounced in the Asian population but not observed in the Iranian population. Furthermore, our findings underscore the potential of HOTAIR polymorphisms as diagnostic markers for overall cancer risk, particularly in gynecological cancers, precisely, HOTAIR rs1899663 G > T polymorphism in breast cancer. In conclusion, our systematic analysis provides compelling evidence that Long Non-coding RNA HOTAIR polymorphisms are linked to cancer risk, particularly in certain populations and cancer types, suggesting their potential clinical relevance as diagnostic indicators.
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Predisposição Genética para Doença , Neoplasias , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , Humanos , Estudos de Casos e Controles , Neoplasias/epidemiologia , Neoplasias/genética , Fatores de Risco , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND Pheochromocytoma, a rare catecholamine-secreting tumor, often presents with paroxysmal or sustained hypertension, tachycardia, headache, and diaphoresis. Timely diagnosis is essential to prevent adverse complications. Less common presentations include pheochromocytoma crisis, with severe neurological and cardiac complications. CASE REPORT We report a unique case of a 25-year-old woman who initially presented with pheochromocytoma-induced hypertensive encephalopathy and acute coronary syndrome. Echocardiography revealed takotsubo-like cardiomyopathy, and magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Initial treatment focused on controlling her blood pressure and supporting cardiac function. Due to her recovering from immediate crisis and absence of further symptoms, the patient refused further follow-up. However, she eventually experienced another episode of hypertensive crisis 2 years later. Subsequent investigations with 24-h urine tests revealed elevated vanillylmandelic acid levels (7.93 mg/24 h), normetanephrine (2638.72 µg/24 h), and nor-metanephrine to creatinine ratio (3546.67) and normal urine metanephrine levels (195.92 µg/24 h) and metanephrine to creatinine ratio (263.33). Contrast-enhanced computed tomography of the abdomen revealed a 4.3×3.1×4-cm mass in the right adrenal gland. A DOTATATE positron emission tomography scan revealed a 3.9×4.3×2.7-cm localized right adrenal pheochromocytoma. Biochemical testing and adrenal imaging revealed a previously undiagnosed pheochromocytoma. Following targeted medical therapy and right adrenalectomy, the patient achieved complete resolution of her hypertension and associated symptoms. CONCLUSIONS Our case is a unique simultaneous presentation of posterior reversible encephalopathy syndrome and takotsubo-like cardiomyopathy, highlighting the importance to consider pheochromocytoma in acute neurological and cardiac presentations, even in the absence of typical symptoms.
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Neoplasias das Glândulas Suprarrenais , Encefalopatia Hipertensiva , Feocromocitoma , Cardiomiopatia de Takotsubo , Humanos , Feminino , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/diagnóstico , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Encefalopatia Hipertensiva/etiologia , Encefalopatia Hipertensiva/diagnósticoRESUMO
Gynecological cancers, including ovarian, cervical, endometrial, and vulvar cancers, present significant challenges in diagnosis and treatment globally. The tumor microenvironment (TME) plays a pivotal role in cancer progression and therapy response, necessitating a deeper understanding of its composition and dynamics. This review offers a comprehensive overview of the gynecological cancer tumor microenvironment, emphasizing its cellular complexity and therapeutic potential. The diverse cellular components of the TME, including cancer cells, immune cells, stromal cells, and extracellular matrix elements, are explored, elucidating their interplay in shaping tumor behavior and treatment outcomes. Across various stages of cancer progression, the TME exerts profound effects on tumor heterogeneity, immune modulation, angiogenesis, and metabolic reprogramming. The urgency for novel therapeutic strategies is underscored by understanding immune evasion mechanisms within the TME. Emerging approaches such as immunotherapy, stromal-targeting therapies, anti-angiogenic agents, and metabolic inhibitors are discussed, offering promising avenues for improving patient outcomes. Interdisciplinary collaborations and translational research are emphasized, aiming to advance precision oncology and enhance therapeutic efficacy in gynecological cancers.
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Neoplasias dos Genitais Femininos , Microambiente Tumoral , Humanos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologia , Feminino , Neoplasias dos Genitais Femininos/terapia , Neoplasias dos Genitais Femininos/patologia , Animais , Imunoterapia/métodos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Ral-binding/interacting protein (RLIP) acts as a transporter that responds to stress and provides protection, specifically against glutathione-electrophile conjugates and xenobiotic toxins. Its increased presence in malignant cells, especially in cancer, emphasizes its crucial antiapoptotic function. This is achieved by selectively regulating the cellular levels of proapoptotic oxidized lipid byproducts. Suppressing the progression of tumors in human xenografts can be achieved by effectively inhibiting RLIP, a transporter in the mercapturic acid pathway, without involving chemotherapy. Utilizing ovarian cancer (OC) cell lines (MDAH2774, OVCAR4, and OVCAR8), we observed that agents targeting RLIP, such as RLIP antisense and RLIP antibodies, not only substantially impeded the viability of OC cells but also remarkably increased their sensitivity to carboplatin. To delve further into the cytotoxic synergy between RLIP antisense, RLIP antibodies, and carboplatin, we conducted investigations in both cell culture and xenografts of OC cells. The outcomes revealed that RLIP depletion via phosphorothioate antisense led to rapid and sustained remissions in established subcutaneous human ovary xenografts. Furthermore, RLIP inhibition by RLIP antibodies exhibited comparable efficacy to antisense and enhanced the effectiveness of carboplatin in MDAH2774 OC xenografts. These investigations underscore RLIP as a central carrier crucial for supporting the survival of cancer cells, positioning it as a suitable focus for cancer treatment.
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Carboplatina , Neoplasias Ovarianas , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Animais , Carboplatina/farmacologia , Camundongos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Camundongos Nus , Apoptose/efeitos dos fármacos , Acetilcisteína/farmacologia , Transportadores de Cassetes de Ligação de ATP , Proteínas Ativadoras de GTPaseRESUMO
The rise of drug resistance in cancer cells presents a formidable challenge in modern oncology, necessitating the exploration of innovative therapeutic strategies. This review investigates the latest advancements in overcoming drug resistance mechanisms employed by cancer cells, focusing on emerging therapeutic modalities. The intricate molecular insights into drug resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, the promising avenues offered by targeted therapies, combination treatments, immunotherapies, and precision medicine approaches are highlighted. Specifically, the synergistic effects of combining traditional cytotoxic agents with molecularly targeted inhibitors to circumvent resistance pathways are examined. Additionally, the evolving landscape of immunotherapeutic interventions, including immune checkpoint inhibitors and adoptive cell therapies, is explored in terms of bolstering anti-tumor immune responses and overcoming immune evasion mechanisms. Moreover, the significance of biomarker-driven strategies for predicting and monitoring treatment responses is underscored, thereby optimizing therapeutic outcomes. For insights into the future direction of cancer treatment paradigms, the current review focused on prevailing drug resistance challenges and improving patient outcomes, through an integrative analysis of these emerging therapeutic strategies.
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The leading cause of cancer deaths worldwide is attributed to non-small cell lung cancer (NSCLC), necessitating a continual focus on improving the diagnosis and treatment of this disease. In this review, the latest breakthroughs and emerging trends in managing NSCLC are highlighted. Major advancements in diagnostic methods, including better imaging technologies and the utilization of molecular biomarkers, are discussed. These advancements have greatly enhanced early detection and personalized treatment plans. Significant improvements in patient outcomes have been achieved by new targeted therapies and immunotherapies, providing new hope for individuals with advanced NSCLC. This review discusses the persistent challenges in accessing advanced treatments and their associated costs despite recent progress. Promising research into new therapies, such as CAR-T cell therapy and oncolytic viruses, which could further revolutionize NSCLC treatment, is also highlighted. This review aims to inform and inspire continued efforts to improve outcomes for NSCLC patients globally, by offering a comprehensive overview of the current state of NSCLC treatment and future possibilities.
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Nanoengineering has emerged as a progressive method in cancer treatment, offering precise and targeted delivery of therapeutic agents while concurrently reducing overall toxicity. This scholarly article delves into the innovative strategies and advancements in nanoengineering that bridge the gap between clinical practice and research in the field of cancer treatment. Various nanoengineered platforms such as nanoparticles, liposomes, and dendrimers are scrutinized for their capacity to encapsulate drugs, augment drug efficacy, and enhance pharmacokinetics. Moreover, the article investigates research breakthroughs that drive the progression and enhancement of nanoengineered remedies, encompassing the identification of biomarkers, establishment of preclinical models, and advancement of biomaterials, all of which are imperative for translating laboratory findings into practical medical interventions. Furthermore, the integration of nanotechnology with imaging modalities, which amplify cancer detection, treatment monitoring, and response assessment, is thoroughly examined. Finally, the obstacles and prospective directions in nanoengineering, including regulatory challenges and issues related to scalability, are examined. This underscores the significance of fostering collaboration among various entities in order to efficiently translate nanoengineered interventions into enhanced cancer therapies and patient management.
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Background and Aims: The quality of recovery (QoR)-40 score has been used worldwide and validated in many surgical cohorts to assess global patient recovery. We aim to translate and culturally adapt the QoR-40 score into Hindi and test the validity and reliability of the translated version in patients undergoing cancer surgery. Methods: The translation of the QoR-40 questionnaire was based on the forward and backward translation methods. Patients filled out the translated version of the QoR-40 preoperatively, on the third postoperative day in the morning (POD3) and the evening. The reliability of the translated questionnaire was checked for internal consistency, test-retest reliability and split-half reliability. Construct validity was assessed with a correlation coefficient value between the total QoR-40 score, visual analogue scale (VAS) for pain and total length of hospital stay. Content validity was evaluated for feasibility and understanding. Results: The questionnaire was completed by 350 patients. The correlation coefficient r for repeatability was 0.21, the split-half test was 0.92, and Cronbach's alpha was 0.82. The correlation between QoR-40 on POD3 with VAS score and length of stay was -0.35 and -0.67, respectively. The average time to complete the questionnaire was 3.8 minutes; 90% of the respondents found the translated questionnaire easy to understand, and 92% of the patients related the questions to their recovery. Conclusion: The Hindi translation of the QoR-40 questionnaire is a valid and reliable version of the original questionnaire in English to assess the QoR in Hindi-speaking patients after cancer surgery.
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New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries-two synthetic and two immunized-against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.
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Antagonistas do Receptor A2 de Adenosina , Receptor A2A de Adenosina , Humanos , Animais , Receptor A2A de Adenosina/metabolismo , Receptor A2A de Adenosina/imunologia , Células HEK293 , Camundongos , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/farmacologia , Macaca fascicularis , Biblioteca de PeptídeosRESUMO
This case report describes a rare example of a solitary abdominal wall metastasis in a middle-aged endometrial cancer (EC) survivor 3 years following disease-free status. Following induction chemotherapy, she had a margin-negative surgical excision of the abdominal tumor. Surprisingly, the patient has been disease-free for more than 3 years after the operation. This emphasizes the necessity of addressing single metastasis amenable to surgical resection, as well as the need for diligent monitoring to discover recurrences sooner. Understanding rare locations of recurrence, such as the abdominal wall, is critical for optimum EC therapy and care. The data given in this article adds to the existing body of information on atypical presentations and recurrent EC therapy. Additional research is required to develop evidence-based guidance.
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Cervical cancer remains a significant global health burden, necessitating innovative approaches for improved diagnostics and personalized treatment strategies. Precision medicine has emerged as a promising paradigm, leveraging biomarkers and molecular targets to tailor therapy to individual patients. This review explores the landscape of emerging biomarkers and molecular targets in cervical cancer, highlighting their potential implications for precision medicine. By integrating these biomarkers into comprehensive diagnostic algorithms, clinicians can identify high-risk patients at an earlier stage, enabling timely intervention and improved patient outcomes. Furthermore, the identification of specific molecular targets has paved the way for the development of targeted therapies aimed at disrupting key pathways implicated in cervical carcinogenesis. In conclusion, the evolving landscape of biomarkers and molecular targets presents exciting opportunities for advancing precision medicine in cervical cancer. By harnessing these insights, clinicians can optimize treatment selection, enhance patient outcomes, and ultimately transform the management of this devastating disease.