Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Leiomyosarcoma. Core disease mechanisms, molecular and cellular pathways,...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 20
• Snippets retrieved: 20

Relevant Papers

[1] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

• Authors: W. Tulalamba, T. Janvilisri
• Year: 2012
• Venue: International Journal of Cell Biology
• URL: https://www.semanticscholar.org/paper/307cb9186444d9dad6e2e3b53763be0de76de186
• DOI: 10.1155/2012/594681
• PMID: 22500174
• PMCID: 3303613
• Citations: 93
• Influential citations: 5
• Summary: The molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression and the important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
• Evidence snippets:
• Snippet 1 (score: 0.413) > In the pregenomic eras, highly integrated and complex circuitry of molecular signaling in NPC pathogenesis was only partially understood. Over the past decade, the knowledge of the molecular mechanisms in NPC carcinogenesis has been rapidly accumulated. Dysregulation and abnormal protein expression of molecules in certain signaling pathways involved in cellular functions including proliferation, adhesion, survival, and apoptosis has been demonstrated in the NPC cells. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in NPC will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for this cancer. Refining molecular markers into clinically relevant assays may assist in the detection of NPC in asymptomatic patients, as well as stage classification and monitoring disease progression and treatments. Furthermore, selective regulation of particular proteins targeting cancer cell proliferation, invasion, and apoptosis is a hopeful prospect for future anticancer therapy that slow disease progression and improve survival.

[2] Periostin Promotes Sarcoma Growth by Promoting Tumor-Associated Macrophage Migration and Differentiation

• Authors: Jinfen Xiao, Kristin Ishaya, E. Ko, A. Fowler, Marina T Broz et al.
• Year: 2025
• Venue: Cancer Research Communications
• URL: https://www.semanticscholar.org/paper/4fcb661ad1542d712f7aa5599bc104c08fe2694e
• DOI: 10.1158/2767-9764.CRC-25-0301
• PMID: 41448855
• PMCID: 12740715
• Summary: The findings position periostin (POSTN) as a key stromal regulator in STS, linking tumor-derived ECM components to immune evasion via myeloid cell recruitment and education and open avenues for targeting POSTN as an adjuvant strategy to enhance the efficacy of immunotherapies and overcome the immune-excluded phenotype of sarcoma.
• Evidence snippets:
• Snippet 1 (score: 0.412) > Soft-tissue sarcomas (STS) are a diverse group of malignancies typically treated with surgery and radiotherapy as primary interventions. Although these approaches are effective initially, disease recurrence and metastasis remain major clinical challenges (1). Anthracycline-based chemotherapy, such as doxorubicin, is commonly employed as a second-line treatment for various sarcoma subtypes, including those with undifferentiated mesenchymal cells; the therapeutic efficacy of chemotherapy is often limited by tumor cell resistance, either intrinsic or acquired, which contributes to tumor relapse (2,3). No additional curative options are currently available for patients (4)(5)(6). > Emerging evidence highlights cellular and molecular components of the tumor microenvironment (TME) as additional critical players in tumor progression (7)(8)(9). Sarcoma cells, due to their mesenchymal nature, produce and deposit large amounts of extracellular matrix (ECM) proteins, which are associated with poor overall survival (10,11). Moreover, ECM elements can shield tumor cells from chemotherapy and promote relapse (12). For example, previous studies reported that ECM stiffness and the interactions between multiple ECM components with integrins, such as β1-integrin, activate pathways like ILK/PI3K/AKT and FAK, which enhance stemness, proliferation, and resistance to therapy (13). Despite this, the functional roles of specific ECM components and the molecular mechanisms of action in sarcoma remain underexplored. > Myeloid cells, encompassing both monocytes and tumor-associated macrophages (TAM), are the most abundant immune components in sarcomas (14,15). TAMs can play pro-or antitumorigenic roles based on their activation state. From one side, TAMs have been shown to contribute to tumor progression in multiple ways, including by creating an immunosuppressive microenvironment (16), favoring angiogenesis, and releasing metabolites that have recently emerged as drivers of drug resistance mechanisms (17)(18)(19).

[3] E2F1-mediated ESPL1 transcriptional activation predicts poor prognosis and promotes the proliferation of leiomyosarcoma

• Authors: Xiaojuan Yang, Guihua Miao, Qin Wang, Qin Yu, Qinsheng Hu et al.
• Year: 2025
• Venue: CytoJournal
• URL: https://www.semanticscholar.org/paper/3d850a39b6a0de260cbb41a095ba4d698be8f6a7
• DOI: 10.25259/Cytojournal_178_2024
• PMID: 39958881
• PMCID: 11829311
• Citations: 1
• Summary: Functional studies in the LMS cell line SK-LMS-1 demonstrated that ESPL1 knockdown slowed cell proliferation and increased G2/M cell cycle arrest, suggesting its crucial role in maintaining LMS cell viability and genomic integrity.
• Evidence snippets:
• Snippet 1 (score: 0.409) > Sarcomas are a group of rare mesenchymal malignancies that originate from various connective tissues, including bone, cartilage, muscle, fat, blood vessels, and fibrous tissue. [1] Leiomyosarcoma (LMS) is the most common subtype of soft-tissue sarcoma, accounting for 10-20% of all soft-tissue sarcoma cases. [2] LMS arises from smooth muscle cells and can occur in various anatomical locations, such as the uterus, retroperitoneum, extremities, and visceral organs. [3] Owing to its aggressive clinical behavior and resistance to conventional therapies, the prognosis for patients with advanced or metastatic LMS remains poor. [3] ucidating the molecular mechanisms underlying LMS pathogenesis is crucial for the development of novel targeted therapies. [4] Previous studies have identified complex genetic and epigenetic alterations in LMS, such as genetic losses in regions encoding phosphatase and tensin homolog (PTEN) (10q11-21.2), RB transcriptional corepressor 1 (RB1) (13q14.3-q21.1), and TP53 (17p13); inactivating mutations and deletions in TP53 and RB1; PTEN inactivation; and aberrations in the RB1, cyclin D1 (CCND1), cyclin D3 (CCND3), and cyclin-dependent kinase inhibitor 2A (CDKN2A) pathways. [3,5] These proteins are involved in controlling proliferation signaling and the progression of the cell cycle. To maintain the viability of LMS cells, disrupting cell cycle checkpoint regulation through pathways involving RB1, CDKN2A/B, MYC proto-oncogene, bHLH transcription factor (MYC), F-box and WD repeat domain containing 7 (FBXW7), or NF1 is essential. [5] PL1 (extra spindle pole bodies like 1, encoded by the ESPL1 gene) is a separase that regulates sister chromatid separation during mitosis and meiosis.

[4] Therapeutic advances in leiomyosarcoma

• Authors: K. Lacuna, S. Bose, M. Ingham, Gary Schwartz
• Year: 2023
• Venue: Frontiers in Oncology
• URL: https://www.semanticscholar.org/paper/c4660167750a04854a82ef60de2d3cd4e93526e6
• DOI: 10.3389/fonc.2023.1149106
• PMID: 36969049
• PMCID: 10031121
• Citations: 39
• Summary: To date, the most promising approaches for advanced leiomyosarcoma include targeting DNA damage repair pathways and aberrant metabolism associated with oncogenesis, as well as novel chemotherapy combinations, which are contingent upon further development of clinical trials based on molecular findings.
• Evidence snippets:
• Snippet 1 (score: 0.399) > Leiomyosarcoma is an aggressive mesenchymal malignancy and represents one of the most common subtypes of soft tissue sarcomas. It is characterized by significant disease heterogeneity with variable sites of origin and diverse genomic profiles. As a result, the treatment of advanced leiomyosarcoma is challenging. First-line therapy for metastatic and/or unresectable leiomyosarcoma includes anthracycline or gemcitabine based regimens, which provide a median progression-free survival time of about 5 months and overall survival time between 14-16 months. Effective later-line therapies are limited. Molecular profiling has enhanced our knowledge of the pathophysiology driving leiomyosarcoma, providing potential targets for treatment. In this review, we explore recent advances in our understanding of leiomyosarcoma tumor biology and implications for novel therapeutics. We describe the development of clinical trials based on such findings and discuss available published results. To date, the most promising approaches for advanced leiomyosarcoma include targeting DNA damage repair pathways and aberrant metabolism associated with oncogenesis, as well as novel chemotherapy combinations. This review highlights the recent progress made in the treatment of advanced leiomyosarcoma. Ongoing progress is contingent upon further development of clinical trials based on molecular findings, with careful consideration for clinical trial design, strong academic collaborations, and prospective correlative analyses.

[5] Role of Transcriptomics in Precision Oncology

• Authors: Ruby Srivastava
• Year: 2024
• Venue: Reports of Radiotherapy and Oncology
• URL: https://www.semanticscholar.org/paper/0bd862558bbb7286336111d9dfd232b5f905d3d9
• DOI: 10.5812/rro-142195
• Citations: 4
• Summary: : Transcriptome profiling is one of the most widely used approaches in the field of multiomics research. It plays a crucial role in the prognostic, diagnostic, and predictive treatment of cancer patients. Novel next-generation sequencing (NGS) technologies permit the identification of cancer biomarkers, gene signatures, and their abnormal expression, affecting oncogenic and molecular targets and novel biomarkers for cancer therapies. Multiomics studies have changed the overall understanding o...
• Evidence snippets:
• Snippet 1 (score: 0.397) > : Transcriptome profiling is one of the most widely used approaches in the field of multiomics research. It plays a crucial role in the prognostic, diagnostic, and predictive treatment of cancer patients. Novel next-generation sequencing (NGS) technologies permit the identification of cancer biomarkers, gene signatures, and their abnormal expression, affecting oncogenic and molecular targets and novel biomarkers for cancer therapies. Multiomics studies have changed the overall understanding of cancer and opened a precise perspective for tumor diagnostics and therapy. The use of these approaches has strengthened our understanding of disease pathophysiology and classifications at the molecular level, including specific interference with drug mechanisms of action. Still, it has limited added value in the clinical setting. The omics data on precision medicine include the application of data from genes, transcripts, and proteins for diagnosis, monitoring of diseases, risk factor determination, counseling, and development of novel therapeutics. Bioinformatics applications have expanded statistics-based analysis toward deriving molecular pathways and process models for characterizing phenotypes and drug action mechanisms. In this review, we will discuss transcriptomics and interference analysis that allows the identification of predictive biomarkers at the molecular level to test drug response and analyze the molecular process interface of disease progression-relevant pathophysiology and mechanism of action to propose predictive biomarkers.

[6] Organoids in gastrointestinal diseases: from bench to clinic

• Authors: Qinying Wang, Fanying Guo, Qinyuan Zhang, Tingting Hu, Yutao Jin et al.
• Year: 2024
• Venue: MedComm
• URL: https://www.semanticscholar.org/paper/9b8880d8b9d45670da950197d7e353794f51d09e
• DOI: 10.1002/mco2.574
• PMID: 38948115
• PMCID: 11214594
• Citations: 12
• Summary: A comprehensive and systematical depiction of organoids models is drawn, providing a novel insight into the utilization of organoids models from bench to clinic and clinical adhibition.
• Evidence snippets:
• Snippet 1 (score: 0.393) > Organoids models offer a robust platform for investigating the potential mechanisms of GI diseases and evaluating potential therapeutic interventions.By culturing organoids derived from patients' tissues or stem cells, researchers can delve into disease-specific cellular and molecular pathways, encompassing aberrant cell signaling, perturbed immune responses, and dysfunctional metabolic processes.These disease-specific phenotypes enable the study of disease progression, screening of prospective therapeutics, as well as identification of novel drug targets and mechanisms of action for GI diseases in a clinically relevant context.

[7] Chemotherapy and Mechanisms of Resistance in Breast Cancer

• Authors: A. Oliveira, R. E. Santos, F. F. O. Rodrigues
• Year: 2012
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/502a86d8bcd7208be6f539fcceba631f82f25a7d
• DOI: 10.5772/24629
• Summary: The addition of adjuvant polychemotherapy in advanced breast cancer showed gain by controlling survival of micrometastases in patients with lymph nodes affected by cancer or not.
• Evidence snippets:
• Snippet 1 (score: 0.387) > The main reasons responsible for treatment failure in cancer patients are the mechanisms of drug resistance and emergence of disseminated disease (Terek et al, 2003). We identified two types of resistance most relevant to BC: primary resistance, which corresponds to the clinical situation where the patient showed no response to therapy, and secondary or acquired resistance in which, initially, there is an observed response and a subsequent failure of the treatment regimen (Kroger et al, 1999). Several mechanisms may cause the phenotype of multidrug resistance to chemotherapy drugs and are well characterized in in vitro experiments, including alterations in systemic pharmacology (pharmacokinetics and metabolism), extracellular mechanisms (tumor environment, multicellular drug resistance), and cellular mechanisms (cellular pharmacology, activation and inactivation of drugs, modification of specific targets and regulatory pathways of apoptosis) (Leonessa et al, 2003, Riddick et al, 2005. Identification of factors that affect cell metabolism, which are related to drug resistance, will enable the identification of which patients are at particular risk of treatment failure. Among the biochemical and molecular mechanisms of drug resistance, we stress: changes in the activity of topoisomerase II, alterations in the DNA repair mechanism, overexpression of P-glycoprotein; high intracellular concentrations of enzymes purification of cellular metabolism -among them enzymes the family of glutathione S-transferases (GSTs) and changes in the mechanisms of signaling via c-Jun N-terminal kinase 1 (JNK1) -and "apoptosis signal-regulating kinase (ASK1) required for activation of the" mitogenactivated protein (MAP kinases) in apoptosis and cellular restoration. These pathways are also mediated by proteins encoded by genes of GSTs (O'Brien, Tew, 1996;Burg, Mulder, 2002, L'Ecuyer et al, 2004). Different response rates to particular chemotherapy regimens, as observed in patient groups with the same biological characteristics and stage, suggest the existence of different mechanisms of drug resistance, probably induced by genetic alterations (Hayes, Pulford, 1995;O'Brien , Tew, 1996;Pakunlu et al, 2003). Among the mechanisms of purification of cellular metabolism involved in the

[8] New therapeutic targets in rare genetic skeletal diseases

• Authors: M. Briggs, Peter A. Bell, M. Wright, K. A. Pirog
• Year: 2015
• Venue: Expert Opinion on Orphan Drugs
• URL: https://www.semanticscholar.org/paper/1363107f71ae6d2d60abca471cddf3da5d13644b
• DOI: 10.1517/21678707.2015.1083853
• PMID: 26635999
• PMCID: 4643203
• Citations: 37
• Influential citations: 1
• Summary: An overview of disease mechanisms that are shared amongst groups of different GSDs and potential therapeutic approaches that are under investigation are described to generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.
• Evidence snippets:
• Snippet 1 (score: 0.386) > proteins of the cartilage ECM such as type II collagen [50]. However, emerging knowledge suggests that the primary genetic defect may be less important than the cells' response to the expression of the mutant gene product [107]. Moreover, the largely overlooked response of a cell (i.e. chondrocyte) to the abnormal extracellular environment is also important for disease progression as illustrated by several GSDs discussed in this review. > It is important that 'omics'-based approaches and technologies are systematically applied to the study of rare GSDs so that definitive reference profiles and disease signatures are generated for each phenotype. These can then be used in a Systems Biology approach to identify both common and dissimilar pathological signatures and disease mechanisms. This approach is entirely dependent upon relevant in vitro and in vivo models (and also novel 'disease-mechanism phenocopies' [107]) for testing new diagnostic and prognostic tools and for determining the molecular mechanisms that underpin the pathophysiology so that effective therapeutic treatments can be developed and validated. This approach will eventually lead to personalized treatments and care strategies centred on shared disease mechanisms with the use of relevant biomarkers to monitor the efficacy of treatment and disease progression. > It is vital that all relevant stakeholders are involved from the outset in defining the appropriate outcomes of any potential therapeutic regime. The perceptions of a successful therapy can differ widely between the clinical academic community and the relevant patient-support groups and it is vital that there is engagement on all these issues. > In summary, the identification of causative genes and mutations for GSDs over the last 20 years, coupled with the generation and in-depth analysis of a plethora of relevant cell and mouse models, has derived new knowledge on disease mechanisms and suggested potential therapeutic targets. The fast-evolving hypothesis that clinically disparate diseases can share common disease mechanisms is a powerful concept that will generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.

[9] ‘Breast Cancer Resistance Likelihood and Personalized Treatment Through Integrated Multiomics’

• Authors: S. Mehmood, Muhammad Faheem, Hammad Ismail, S. M. Farhat, Mahwish Ali et al.
• Year: 2022
• Venue: Frontiers in Molecular Biosciences
• URL: https://www.semanticscholar.org/paper/c542ec176c594aeddb3790bb3d10767598b86ae4
• DOI: 10.3389/fmolb.2022.783494
• PMID: 35495618
• PMCID: 9048735
• Citations: 19
• Influential citations: 1
• Summary: This review has summarized therapeutic resistance associated with BC and the techniques used for its management, and identifies the biomarkers of disease progression and treatment progress by collective characterization and quantification of pools of biological molecules within and among the cancerous cells.
• Evidence snippets:
• Snippet 1 (score: 0.379) > Breast cancer is a very complex and heterogeneous disorder with unique molecular and morphological features relative to a disease which involves only a single gene or protein in a simple signaling pathway contributing toward the progression of disease in an independent and autonomous manner (Organization 2019). Various studies had represented BC heterogeneity through the differential response of the same type of BC patients to treatment and risk of developing side effects. One of the major clinical complications in the treatment of breast carcinoma patients is the development of therapeutic resistance (Luque-Bolivar et al., 2020). Recently drug resistance in BC treatment is not properly addressed, rather to focus on molecular pathways deeply; an alternative strategy of using a different drug is commonly applied. In order to reduce the adverse effects of BC treatment including drug resistance, a profound understanding of the molecular mechanism of the disease and the response to the drug is needed. Multidrug resistance (MDR) and consequent relapse on therapy are prevalent issues related to breast carcinoma as our understanding is incomplete related to the molecular mechanism of breast carcinoma disease (Waks and Winer, 2019a). Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. For the management of breast cancers, the treatment decision not only depends on the Treatment with exemestane alone or in combination with an mTOR inhibitor such as everolimus (Carlini et al., 2007Chin et al., 2007Geisler et al., 2008Bahrami et al. (2020) ER+/ HER2- assessment of prognosis factors but also on the evaluation of pathological and clinical factors. Integrated data assessments of these multiple factors of breast carcinoma through multiomics can provide significant insight and hope for making therapeutic decisions (Parsons and Francavilla 2020). Major BC treatment strategies rely on the tumor subtype, immunohistochemical evaluation of prognostic elements, and seek new genetic markers to improve the diagnostic strategies and to enhance treatment outcomes with minimal side effects.

[10] Transcriptome Sequencing Unveils a Molecular-Stratification-Predicting Prognosis of Sarcoma Associated with Lipid Metabolism

• Authors: Yuheng Hong, Lin Zhang, Weihao Lin, Yannan Yang, Z. Cao et al.
• Year: 2024
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/3f7d5342a6544aa2bc02f3e7b2261df209be1fe1
• DOI: 10.3390/ijms25031643
• PMID: 38338920
• PMCID: 10855378
• Citations: 1
• Summary: A novel prognostic predictive model consisting of squalene epoxidase (SQLE) and tumor necrosis factor (TNF) and the potential drug target SQLE was constructed and SQLE, a rate-limiting enzyme in cholesterol biosynthesis, was identified as a potential therapeutic target for sarcoma.
• Evidence snippets:
• Snippet 1 (score: 0.378) > As a group of large heterogeneous connective tissue malignancies of mesenchymal origin, sarcomas are the second most common solid tumors, accounting for about 20% of cancer-caused deaths in children and adolescents due to their extreme aggressiveness and metastasis [1][2][3]. Based on the anatomical site of occurrence, sarcomas can be historically categorized into two large subclusters, osteosarcomas and soft tissue sarcomas [2], and both subclusters consist of a series of histological subtypes. Recent scientific achievements have revealed that the number of subtypes at the molecular level has increased constantly. Conventional therapeutic strategies, including surgical excision, chemotherapy, immunotherapy, and targeted therapy, have been employed in patients suffering from advanced or metastatic sarcoma [4,5]. However, the prognosis of patients with metastatic sarcoma has hardly progressed in the past thirty years; nearly 30% of patients still succumb to sarcoma, with a five-year survival rate of only 16% despite systemic therapy [6,7]. > Alteration of energetics and metabolism in cells is well known as a hallmark of cancer [8]. Emerging evidence has revealed that multiple signaling pathways, proteins, and relevant mechanisms get involved in the alteration of how cells use distinct molecules and metabolites to support abnormal cellular proliferation, dissemination from the primary tumor, the establishment of a secondary tumor, and immune evasion. Lipids, nucleic acids, and proteins are building blocks of biological membranes and essential components that construct cells. In addition, lipids get involved in metabolism and energy storage and play vital roles as molecules for signal transduction for many cellular activities. Lipid metabolism including the uptake, synthesis, and hydrolysis of the lipid is strictly regulated to maintain cellular homeostasis [9,10]. Malignant cells in the tumor microenvironment, in which nutrient availability is consistently altering during tumor progression, utilize lipid metabolism to sustain their rapid proliferation, invasion, and metastasis [11,12]. > Preclinical and clinical studies on a battery of inhibitors targeting the enzymes in lipid metabolism have been investigated [9,13].

[11] Advancements in MDM2 inhibition: Clinical and pre-clinical investigations of combination therapeutic regimens

• Authors: Ali M. Alaseem
• Year: 2023
• Venue: Saudi Pharmaceutical Journal : SPJ
• URL: https://www.semanticscholar.org/paper/aeef23e2dd770e6b71d6dad19a342292f7e394c8
• DOI: 10.1016/j.jsps.2023.101790
• PMID: 37818252
• PMCID: 10561124
• Citations: 29
• Summary: A comprehensive examination of possible clinical and preclinical MDM2 combination inhibitor regimens highlights the potential for advancingMDM2-inhibitor therapy and improving clinical outcomes for cancer patients and establishes the foundation for future research and development in this promising area of study.
• Evidence snippets:
• Snippet 1 (score: 0.369) > It is widely acknowledged that most tumors rely on multiple pathways to grow and survive. Cancer treatments often modulate proteins that are involved in complex growth pathways and mechanisms of drug resistance (Huang et al., 2020). Therapeutic resistance and cancer progression are driven by heterogeneity among cancer cells within a tumor, which limits the number of patients who experience meaningful clinical improvement and optimal treatment outcomes. Cancer molecular characteristics and medication pharmacokinetics may vary among individuals and tumors, providing a biological explanation for the observed variation. Single-cell sequencing has shown that cancer genomes evolve rapidly and diversely in response to treatment (Kuipers et al., 2017;Maynard et al., 2020). The effectiveness of cancer therapy is also hindered by the disease's ability to evolve through genetic and nongenetic processes. Even highly effective targeted therapies that aim to treat specific genetic mutations exhibit variability in drug response in clinical studies. Combining different therapeutic approaches such as surgery, chemotherapy, radiation, or targeted treatments can offer significant curative advantages in treating cancer by increasing efficacy and reducing acquired treatment resistance and toxic adverse effects (Plana et al., 2022;Strebhardt and Ullrich, 2008). > Many solid tumors are primarily treated with surgery, which is frequently accompanied by neoadjuvant and adjuvant therapies. Although systemic therapy is often a favored approach, the effectiveness of cytotoxic drugs has been limited for specific types of cancer including non-solid tumors (Italiano et al., 2012). Similarly, ionizing radiation is a frequently utilized modality in the treatment of childhood sarcoma, commonly associated with elevated MDM2, either during the initial diagnosis or in cases of disease recurrence. It has been observed that a significant proportion of sarcomas occurring in children demonstrate a p53 wild-type phenotype (Phelps et al., 2015). MDM2 inhibitors commonly disrupt the binding between MDM2 and p53, thereby activating wild-type p53. However, the cellular response to MDM2 inhibition can differ significantly depending on both the type of tumor and the dosage administered (Jeay et al., 2018;Ray-Coquard et al., 2012).

[12] Primary vaginal leiomyosarcoma: A case report emphasizing multidisciplinary care of a rare entity

• Authors: Fadoua Jebrouni, Hanan Bailal, Mouhsine Omari, Kaouthar Khater, A. Bali et al.
• Year: 2025
• Venue: Radiology Case Reports
• URL: https://www.semanticscholar.org/paper/0a3d11f733e1c16ef4f0d4d8a93cb310d6deb442
• DOI: 10.1016/j.radcr.2025.05.024
• PMID: 40606580
• PMCID: 12221499
• Summary: A case of a 45-year-old patient who was diagnosed with metastatic vaginal LMS at the regional oncology center of Oujda in Morocco, and following the multidisciplinary team meeting discussion, the patient received first-line doxorubicin-based chemotherapy.
• Evidence snippets:
• Snippet 1 (score: 0.364) > Leiomyosarcoma (LMS) is a rare malignant tumor derived from smooth muscle cells, accounting for less than 1 percent of all vaginal malignancies [ 1 ]. It usually occurs in the uterine cavity, other localizations, such as vaginal leiomyosarcoma, are atypical. > There is little data on its epidemiology, diagnosis, and treatment because of its low incidence. > The exact incidence of vaginal LMS is unclear due to its rarity. As of 2006, only 138 cases of vaginal LMS had been documented [ 5 ]. > With a median age of 60, this condition primarily affects postmenopausal women. However, as in our patient, other clinical cases have been described in peri-menopausal women and women in their forties [ 6 ,7 ]. > Its cause remains unknown. Although certain cases have been documented after pelvic irradiation, but this was not the case in our patient [ 8 ]. Other risk factors, such as a personal or family history of benign tumors, may be implicated. Several studies have suggested that women with a history of benign soft tissue tumors may be subject to a marginally elevated risk of developing leiomyosarcoma. Furthermore, genetic susceptibility has been demonstrated as a contributing factor in the development of certain sarcomas, including vaginal leiomyosarcoma [ 9 ]. > This rare neoplasm is characterized by complex molecular abnormalities that play a crucial role in its pathogenesis. It often involves mutations in the tumor suppressor genes P53 and RB1, as well as disruptions in the PTEN and ATRX genes. The PI3K/AKT/mTOR and P53/RB1 signaling pathways are commonly involved. These molecular anomalies provide opportunities for developing targeted therapies [ 10 ]. Some cases of vaginal LMS have previously been reported in Morocco, including 1 at the Oujda regional cancer center involving a 36-year-old female with localized vaginal LMS [ 7 ,11 ]. She underwent neoadjuvant chemotherapy with gemcitabine in combination with docetaxel, followed by radiotherapy and surgical resection. Progression was marked by a very good re-

[13] Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer

• Authors: M. G. de Matos, Mafalda Pinto, A. Gonçalves, Sule Canberk, M. J. Bugalho et al.
• Year: 2025
• Venue: PeerJ
• URL: https://www.semanticscholar.org/paper/655de68f1a7e8137dcba8a2046f14dee4f07594d
• DOI: 10.7717/peerj.18801
• PMID: 39850836
• PMCID: 11756370
• Citations: 4
• Summary: The knowledge of genetic and molecular biomarkers has achieved a high level of complexity, and the difficulties related to its applicability determine that their implementation in clinical practice is not yet a reality.
• Evidence snippets:
• Snippet 1 (score: 0.364) > Knowledge of molecular mechanisms implicated in thyroid carcinogenesis has been attained in recent years. Thyroid neoplasm result from alterations in gene expression patterns, which occur due to a gradual accumulation of genetic and epigenetic events. These changes are associated with specific tumor phenotypes and are implicated in disease etiology. Molecular alterations induce the activation of different signaling pathways, such as the mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K/AKT/mTOR), which are involved in and promote carcinogenesis (Hsiao & Nikiforov, 2014). In a few years, the knowledge of molecular mechanisms implicated in thyroid carcinogenesis changed from understanding signaling pathways and identification of a few genes mutations to the knowledge of the main genes implicated in thyroid carcinogenesis, reviewed by De Leo et al. (2024). Genetic changes in thyroid neoplasms were divided in early/driver molecular alterations and late/progression events. Late/ progression events may be associated with early/driver molecular alterations and represent the evolution from well-differentiated to high-grade and undifferentiated carcinoma, being (Pozdeyev et al., 2018). Most frequent gene mutations present in follicular-cell derived thyroid tumors are BRAF, RAS, and TERTp mutations, associate with clinically relevant clinicopathologic features, as shown in Table 3.

[14] Structural, cellular and molecular mechanisms involved in the Epithelial-to-Mesenchymal Transition in Cancer

• Authors: Moniri Javadhesari, Vaezi Heris
• Year: 2022
• Venue: Journal of Cell and Tissue
• URL: https://www.semanticscholar.org/paper/0e5acf2d67a761fb70d6a28a6f6f60fbe88abcf2
• DOI: 10.52547/jct.13.2.71
• Summary: EMT plays a crucial role in cancer progression, crossing the cells through the biological and body barriers, and metastasis that are usually associated with poor prognosis of cancer patients.
• Evidence snippets:
• Snippet 1 (score: 0.363) > Epithelial-Mesenchymal Transition, Carcinogenesis, Gene Expression Regulation, Tumor Microenvironment. Intoduction: Cancer as one of the most common genetic diseases is the leading cause of death worldwide. Cancer cells undergo various genetic and phenotypic changes to spread and survive. In the early stages, these changes lead to the development of tumor, while at the advanced stages they can provide a suitable pre-metastatic microenvironment in which various uncontrolled events occur including cell proliferation, traversing through the extracellular matrix, and crossing barriers to enter the bloodstream. Extracellular changes in this microenvironment can induce intracellular changes in primary cancer cells that assist in the sustainability and propagation of these cells. Complicated interactions between the external and internal factors result in the establishment of various regulatory networks between different types of carcinogenesis promoting factors. Identification of these modifications plays a critical role in understanding the mechanisms of disease progression, prognosis and management. Text: Various mutations and differential gene expression trigger metastasis of cancer cells by epithelial to mesenchymal transition (EMT) mechanism, among which the role of chromatin structural changes, intracellular signal transduction pathways, regulation of cell cycle and microRNAs, and genomic instability has been reported. The alterations in gene expression patterns of mentioned pathways lead to potential regulatory complications that faced the management of disease progression and response to therapies with problems. Cancer cells provide their requirements by neutralizing biological barriers, modifying the regulation of inhibiting processes of cancer progression, establishing de novo endogenous mechanisms and providing specialized molecular and structural markers, and various combinations of these methods have been demonstrated in different types of cancer. Furthermore, EMT and Structural, cellular and molecular mechanisms involved in the Epithelial-to-Mesenchymal Transition in Cancer Journal of Cell and Tissue 13(2) (2022) 71-94 cancer stem cells (CSCs) have a mutual relationship in which the presence of one assists the occurrence of the other. Altogether, cancer cells take the advantage of multiple approaches including upregulation of main transcription factors such as snail, slug, Foxc2, Twist and ZEB1/2, benefiting the mechanisms of telomere length protection, production of CD133,CD44 and BMI1 biomark

[15] Mechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments

• Authors: C. Çubuk, F. Can, M. Peña-Chilet, J. Dopazo
• Year: 2020
• Venue: Cells
• URL: https://www.semanticscholar.org/paper/e40f7a3b8f72ba01374ba00fbf308a47a3fa5dd4
• DOI: 10.3390/cells9071579
• PMID: 32610626
• PMCID: 7408716
• Citations: 9
• Summary: Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such differences over the disease mechanisms or the drug action mechanisms are completely unknown. Here we applied mechanistic mathematical models of signaling activity to reveal the ultimate functional consequences that gender-s...
• Evidence snippets:
• Snippet 1 (score: 0.363) > Therefore, a proper interpretation of the effect that differences in gene expression have over phenotypes, such as drug response or disease progression, involves understanding the mechanisms of the disease or the mode of action of drugs, which can be interpreted through mechanistic models of cell signaling [12] or cell metabolism [13]. Mechanistic models have helped to understand the disease mechanisms behind different cancers [14,15], including neuroblastoma [16,17], breast cancer [18], rare diseases [19], complex diseases [20], the mechanisms of action of drugs [21,22], and other biologically interesting scenarios such as the molecular mechanisms that explain how stress-induced activation of brown adipose tissue prevents obesity [23] or the molecular mechanisms of death and the post-mortem ischemia of a tissue [24]. Among the few available proposals of mechanistic modeling algorithms that model different aspects of signaling pathway activity, Hipathia has demonstrated having superior sensitivity and specificity [12]. > Here, we propose the use of mechanistic models [13,14] of signaling activity related with cancer hallmarks [25], other cancer-related signaling pathways, and some extra relevant cellular functions to understand the functional consequences of the gender bias in gene expression. Such mechanistic models use gene expression data to produce an estimation of profiles of signaling or metabolic circuit activity within pathways [13,14]. An interesting property of mechanistic models is that they can be used not only to understand molecular mechanisms of disease or of drug action but also to predict the potential consequences of gene perturbations over the circuit activity in a given condition [26]. Actually, in a recent work, our group has successfully predicted therapeutic targets in cancer cell lines with a precision over 60% [15]. Therefore, we will use this mechanistic framework to understand what is the molecular basis of the different effects of cancer drugs by directly simulating their effect in the patients. This approach has recently been used by us to understand the generation of resistances in cancer at the single cell level in glioblastoma [27].

[16] Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction

• Authors: Yi Liu, Yang Zhang, Huan Wei, Li Wang, Lishang Liao
• Year: 2025
• Venue: Scientific Reports
• URL: https://www.semanticscholar.org/paper/19a91d9c8cabec6a5a186729d545077e252ecb67
• DOI: 10.1038/s41598-025-97642-8
• PMID: 40229542
• PMCID: 11997208
• Summary: The findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.
• Evidence snippets:
• Snippet 1 (score: 0.361) > involved in SAH pathology. As a result, our understanding of the cellular composition and microenvironment in SAH remains incomplete 8 . > Advances in bioinformatics provide powerful tools to analyze large-scale gene expression data and understand complex biological processes. By integrating transcriptomic data with immune cell infiltration analysis, we can gain a deeper understanding of the molecular mechanisms underlying SAH and identify potential key genes as therapeutic targets 9,10 . Previous studies have indicated that inflammation, oxidative stress, and cell death play crucial roles in the development of SAH, processes that are often closely associated with changes in specific cell types and immune responses 11 . > The goal of this study is to explore the molecular mechanisms of SAH, with a focus on immune cell infiltration and its role in disease progression. We aim to identify key genes and signaling pathways associated with SAH and investigate potential therapeutic strategies. Specifically, we will examine Isorhynchophylline (IRN) as a potential treatment for SAH and analyze its effects on relevant targets and signaling pathways. Through a comprehensive understanding of the pathological features of SAH, this study aims to provide valuable insights into future clinical interventions and treatment strategies.

[17] Solving the Evidence Interpretability Crisis in Health Technology Assessment: A Role for Mechanistic Models?

• Authors: E. Courcelles, J. Boissel, J. Massol, I. Klingmann, R. Kahoul et al.
• Year: 2022
• Venue: Frontiers in Medical Technology
• URL: https://www.semanticscholar.org/paper/877d5b1b75599745f704a9c8371f74601ff17e2f
• DOI: 10.3389/fmedt.2022.810315
• PMID: 35281671
• PMCID: 8907708
• Citations: 6
• Summary: Light is shed on different stakeholder's contributions and needs in the appraisal phase and how mechanistic modeling strategies and reporting can contribute to this effort to implement mechanistic models central in the evidence generation, synthesis, and appraisal of HTA so that the totality of mechanistic and clinical evidence can be leveraged by all relevant stakeholders.
• Evidence snippets:
• Snippet 1 (score: 0.361) > A second limitation in HTA is the fact that currently population (and sometimes stratified) medicine is pursued during clinical Uncertainty not completely addressed in competent authority assessment report Example use of MIDD relevant to address uncertainty potentially also during HTA What is the optimal dosage in the clinical context? > Physiologically based pharmacokinetic models can investigate dosing-regimens relevant for regulatory review and product labels (9) and can also mimic real-life adherence to prescribed treatment regimens (see also below) or pharmacology-relevant characteristics of special populations as well as drug-drug interactions. > What is the duration of the effectiveness, especially with chronic use of a treatment? > Mechanistic models can predict the long-term disease progression by extrapolation of shorter-term findings under the constraints of how the components of the system function (and these constraints convey biological plausibility by design). An example is the use of a mechanism-based disease progression model for comparison of long-term effects of pioglitazone, metformin, and gliclazide on disease processes underlying Type 2 Diabetes Mellitus (10). Another example is prediction of long-term outcomes by short-term marker data as demonstrated by a semi-mechanistic approach in context of osteoporosis treatment (11). > What is the efficacy for relevant clinical outcomes? > Mechanistic models combined with pharmacometric approaches can translate findings for one outcome to a range of other outcomes. An example of survival modeling on the back of a mechanistic description is the modeling framework for CD19-Specific CAR-T cell immunotherapy using a quantitative systems pharmacology model (12). > What is the size of the clinical effect dependent on patient characteristics and extrinsic factors? > Data-driven modeling techniques can capture correlation within clinical data. Describing the clinical effect of a drug can also be based on mechanistic considerations. Such models either (a) link disease phenotypes to increasingly granular mathematical representations of pathophysiologic processes (top-down approach) or (b) derive functional, computable cellular networks from the molecular building blocks of genes and proteins to elucidate the impact of pathologic or therapeutic alterations on network operating states and hence clinical phenotype (bottom-up) [

[18] Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats

• Authors: M. Uzti̇mür, C. N. Ünal, Gurler Akpinar
• Year: 2025
• Venue: Journal of Veterinary Internal Medicine
• URL: https://www.semanticscholar.org/paper/4b9c488b5dbd65d7b26fd2ad9aed70e8c4b59942
• DOI: 10.1111/jvim.70139
• PMID: 40492724
• PMCID: 12150350
• Summary: Understanding the serum proteome profiles of goats with pregnancy toxemia might help identify the proteomes and pathways responsible for the development of this disease and improve diagnosis and treatment.
• Evidence snippets:
• Snippet 1 (score: 0.361) > The pathophysiology and progression of this disease are not fully understood. > Traditional biomedical research has focused on the analysis of single genes, proteins, metabolites, or metabolic pathways in diseases. This molecular reductionist approach is based on the assumption that identifying genetic variations and molecular components will lead to new treatments for diseases [13][14][15][16]. However, many diseases are complex and multifactorial, and in order to determine the phenotype of such diseases, it is necessary to understand the changes that occur in more than one gene, pathway, protein, or metabolite at the cellular, tissue, and organismal levels [17][18][19]. Therefore, in recent years, proteomics, as one field of multi-omics technologies, has helped in evaluating the complex pathogenetic mechanisms of different diseases from a broad perspective and has made substantial contributions [20,21]. In veterinary medicine, proteomic analysis of metabolic diseases such as ketosis [16], hypocalcemia [22], and fatty liver [23] in dairy cows has contributed valuable insights for the definition of new pathophysiological pathways and new diagnosis and treatment protocols for these diseases. The proteomic approach can contribute importantly to a broad and detailed understanding of the changes that occur at the organismal level associated with the increase in BHBA concentration in goats with pregnancy toxemia. Our aim was to evaluate the serum protein profiles of goats with SPT or CPT using proteomic techniques to determine the proteomic profiles of these animals and to identify the relevant pathophysiological mechanisms.

[19] Significance and Mechanisms Analyses of RB1 Mutation in Bladder Cancer Disease Progression and Drug Selection by Bioinformatics Analysis

• Authors: Dingguo Zhang, Jinjun Tian, Qier Xia, Zhenyu Yang, B. Gu
• Year: 2021
• Venue: Bladder Cancer
• URL: https://www.semanticscholar.org/paper/6038af24d56f6d9c5eeb1572c64dd5acd6aa62f2
• DOI: 10.3233/BLC-200368
• PMID: 38994537
• PMCID: 11181786
• Citations: 7
• Summary: The significance of RB1 mutation in disease progression and drug selection in bladder cancer was suggested by the results, and multiple genes and pathways related to such a program were identified.
• Evidence snippets:
• Snippet 1 (score: 0.361) > Early and comprehensive intervention might be important for such patients to live longer. > Nowadays, molecular pathological diagnosis and individualized medicine testing can help doctors select target drugs according to the characteristics of the patient's tumor cells, including bladder cancer. Different patients may have tumor cells with different pathways activated in their bodies, which results in different molecular and pathological characteristics. These are the main mechanisms for disease progression and drug resistance in many tumors, which is also the basis of individualized treatment. Analyzing the activation of different pathways can help us understand the characteristics of different subtypes of tumors, and might help us explore potential personalized treatment at the same time. If a certain pathway is specifically activated in certain subtype patients, the drugs targeted this pathway might be more effective in such patients. Through these analyses, we can find out the potential mechanisms of drug resistance and clinical phenotypes that are associated with RB1 mutation, and provide some theoretical basis and directions for further research and verification. This might be quite preliminary and only have some theoretical functions. To explore these issues deeply, the gene expression data was analyzed in depth to find the key pathways and core genes associated with RB1 mutation. Results of GSEA analysis suggested that RB1 mutation were mainly associated with DNA repair, multiple cancer related pathways, cell proliferation and division, and metabolism. Previous researches have shown that defects in DNA repair contributed the disease progression of bladder cancer and influenced the treatment, especially in MIBC. Genomic alterations in the DNA repairassociated genes could render tumors sensitive to cisplatin-based chemotherapy for MIBC [20]. RB1 regulates the cell cycle. In RB1 mutated tumors, our findings showed that many processes involved in cell proliferation were enriched. RB1 mutation could result in abnormal regulation of cell cycle and cell division proliferation, which lead to continuous cell growth and tumor progression. Therefore, besides the three drugs above, other drugs, such as Docetaxel (Taxotere) which effectively induces G2M arrest and apoptosis might be more sensitive in patients with RB1 mutation [21]. > Next, we searched for DEGs and performed functional enrichment analysis on them. The results show a total of 999 DEGs. Enrichment analysis suggested that DEGs in RB1 mutated bladder cancer patients implicated with multiple cellular programs.

[20] Recent Evidences of Epigenetic Alterations in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review

• Authors: R. Ragusa, Pasquale Bufano, A. Tognetti, M. Laurino, Chiara Caselli
• Year: 2025
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/2660cdbbe1f205c631fe890e5c6a3c8d9b81ce5f
• DOI: 10.3390/ijms26062571
• PMID: 40141213
• PMCID: 11942187
• Citations: 4
• Summary: A systematic review of the latest knowledge on epigenetic modifications that characterize COPD, summarizing epigenetic factors that could serve as potential novel biomarkers and therapeutic targets for the treatment of COPD patients.
• Evidence snippets:
• Snippet 1 (score: 0.359) > The papers included were clustered according to epigenetic mechanisms involved in COPD (molecular and cellular processes, as biomarker or therapeutic target). Tables 4-9 describe the extracted information, including the following: Study = name of first author et al., year; Country (Region) = where the study took place; Number of participants = sample size; Type of sample = biological sample employed; Gene affected = gene or group of genes whose expression can be "regulated" by epigenetic mechanisms; Epigenetic alteration = type of epigenetic alteration observed in the presence of disease; Activity in COPD = involvement of epigenetic elements in different molecular and cellular mechanisms associated with COPD; and Role of epigenetic mechanisms = epigenetic modifications that can be used to explain the pathophysiology of COPD or as biomarkers and therapeutic targets.

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.