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1.
Bioorg Med Chem Lett ; : 129967, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293533

RESUMEN

Despite the recent progresses in therapeutic and diagnostic methods, there is still a significantly high rate of mortality among cancer patients. One of the main reasons for the high mortality rate in cancer patients is late diagnosis, which leads to the failure of therapeutic strategies. Therefore, investigation of cancer biology can lead to the introduction of early diagnostic markers in these patients. MicroRNAs (miRNAs) play an important role in regulation of cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, these factors can be considered as the non-invasive tumor markers. Deregulation of miR-382 has been widely reported in different cancers. Therefore, in this review, we investigated the role of miR-382 during tumor development. It has shown that miR-382 has mainly a tumor suppressive, which inhibits the growth of tumor cells through the regulation of signaling pathways, RNA-binding proteins, and transcription factors. Therefore, miR-382 can be suggested as a diagnostic and therapeutic marker in cancer patients.

2.
Pathol Res Pract ; 262: 155548, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39173465

RESUMEN

Serological biomarkers have been rapidly progressing as non-invasive tests for the early detection of inflammatory bowel disease (IBD). Procalcitonin (PCT) is a novel acute-phase reactant protein that is elevated in the inflammatory process, especially in bacterial infections. This study aimed to review the diagnostic value of PCT in IBD activity. However, there were controversies about the role of PCT in the detecting of IBD disease activity. Studies showed varied diagnostic cut-points (ranging from 0.13 to 1.0 ng/dl) and sensitivity up to 93 %. Although the clear role of PCT as a valuable diagnostic marker was not identified in determining disease activity, PCT measurement in addition to other inflammatory markers can improve the diagnostic value of these markers. Moreover, further studies are required to confirm PCT's value in distinguishing IBD disease activity.


Asunto(s)
Biomarcadores , Enfermedades Inflamatorias del Intestino , Polipéptido alfa Relacionado con Calcitonina , Humanos , Polipéptido alfa Relacionado con Calcitonina/sangre , Biomarcadores/sangre , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/sangre , Pronóstico
3.
Pathol Res Pract ; 262: 155547, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151250

RESUMEN

Late diagnosis is considered one of the main reasons of high mortality rate among cancer patients that results in therapeutic failure and tumor relapse. Therefore, it is needed to evaluate the molecular mechanisms associated with tumor progression to introduce efficient markers for the early tumor detection among cancer patients. The remarkable stability of microRNAs (miRNAs) in body fluids makes them potential candidates to use as the non-invasive tumor biomarkers in cancer screening programs. MiR-135b has key roles in prognosis and survival of cancer patients by either stimulating or inhibiting cell proliferation, invasion, and angiogenesis. Therefore, in the present review we assessed the molecular biology of miR-135b during tumor progression to introduce that as a novel tumor marker in cancer patients. It has been reported that miR-135b mainly acts as an oncogene by regulation of transcription factors, signaling pathways, drug response, cellular metabolism, and autophagy. This review paves the way to suggest miR-135b as a tumor marker and therapeutic target in cancer patients following the further clinical trials and animal studies.


Asunto(s)
Biomarcadores de Tumor , Progresión de la Enfermedad , MicroARNs , Neoplasias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/genética , Neoplasias/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Animales , Oncogenes/genética , Transducción de Señal/genética
4.
Discov Oncol ; 15(1): 385, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210158

RESUMEN

The progress of cancer treatment methods in the last decade has significantly reduced mortality rate among these patients. Nevertheless, cancer is still recognized as one of the main causes of human deaths. One of the main reasons for the high death rate in cancer patients is the late diagnosis in the advanced tumor stages. Therefore, it is necessary to investigate the molecular biology of tumor progressions in order to introduce early diagnostic markers. MicroRNAs (miRNAs) have an important role in regulating cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, they are widely used as non-invasive markers in the early tumor diagnosis. Since, deregulation of miR-98 has been reported in a wide range of cancers, we investigated the molecular mechanisms of miR-98 during tumor progression. It has been reported that miR-98 mainly inhibits the tumor growth by the modulation of transcription factors and signaling pathways. Therefore, miR-98 can be introduced as a tumor marker and therapeutic target among cancer patients.

5.
Eur J Pharmacol ; 982: 176966, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39216742

RESUMEN

Cisplatin (CDDP) as one of the most common first-line chemotherapy drugs plays a vital role in the treatment of a wide range of malignant tumors. Nevertheless, CDDP resistance is observed as a therapeutic challenge in a large number of cancer patients. Considering the CDDP side effects in normal tissues, predicting the CDDP response of cancer patients can significantly help to choose the appropriate therapeutic strategy. In this regard, investigating the molecular mechanisms involved in CDDP resistance can lead to the introduction of prognostic markers in cancer patients. Matrix metalloproteinases (MMPs) have critical roles in tissue remodeling and cell migration through extracellular matrix degradation. Therefore, defects in MMPs functions can be associated with tumor metastasis and chemo resistance. In the present review, we discussed the role of MMPs in CDDP response and tumor cell invasion. PubMed, Scopus, Google Scholar, and Web of Science were searched using "MMP", "cisplatin", and "cancer" keywords for data retrieval that was limited to Apr 20, 2024. It has been reported that MMPs can increase CDDP resistance in tumor cells as the effectors of PI3K/AKT, MAPK, and NF-κB signaling pathways or independently through the regulation of structural proteins, autophagy, and epithelial-to-mesenchymal transition (EMT) process. This review has an effective role in introducing MMPs as the prognostic markers and therapeutic targets in CDDP-resistant cancer patients.


Asunto(s)
Antineoplásicos , Cisplatino , Resistencia a Antineoplásicos , Metaloproteinasas de la Matriz , Invasividad Neoplásica , Neoplasias , Cisplatino/farmacología , Cisplatino/uso terapéutico , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Metaloproteinasas de la Matriz/metabolismo , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Transducción de Señal/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos
6.
Mutat Res ; 829: 111874, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986233

RESUMEN

The high mortality rate in cancer patients is always one of the main challenges of the health systems globally. Several factors are involved in the high rate of cancer related mortality, including late diagnosis and drug resistance. Cancer is mainly diagnosed in the advanced stages of tumor progression that causes the failure of therapeutic strategies and increases the death rate in these patients. Therefore, assessment of the molecular mechanisms associated with the occurrence of cancer can be effective to introduce early tumor diagnostic markers. MicroRNAs (miRNAs) as the stable non-coding RNAs in the biological body fluids are involved in regulation of cell proliferation, migration, and apoptosis. MiR-532 deregulation has been reported in different tumor types. Therefore, in the present review we discussed the role of miR-532 during tumor growth. It has been shown that miR-532 has mainly a tumor suppressor role through the regulation of transcription factors, chemokines, and signaling pathways such as NF-kB, MAPK, PI3K/AKT, and WNT. In addition to the independent role of miR-532 in regulation of cellular processes, it also functions as a mediator of lncRNAs and circRNAs. Therefore, miR-532 can be considered as a non-invasive diagnostic/prognostic marker as well as a therapeutic target in cancer patients.

7.
Mol Brain ; 17(1): 42, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956588

RESUMEN

Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol for GBM patients, there is still a poor prognosis in these patients. Temozolomide (TMZ) as a first-line therapeutic agent in GBM can easily cross from the blood-brain barrier to inhibit tumor cell proliferation. However, there is a high rate of TMZ resistance in GBM patients. Since, there are limited therapeutic choices for GBM patients who develop TMZ resistance; it is required to clarify the molecular mechanisms of chemo resistance to introduce the novel therapeutic targets. MicroRNAs (miRNAs) regulate chemo resistance through regulation of drug metabolism, absorption, DNA repair, apoptosis, and cell cycle. In the present review we discussed the role of miRNAs in TMZ response of GBM cells. It has been reported that miRNAs mainly induced TMZ sensitivity by regulation of signaling pathways and autophagy in GBM cells. Therefore, miRNAs can be used as the reliable diagnostic/prognostic markers in GBM patients. They can also be used as the therapeutic targets to improve the TMZ response in GBM cells.


Asunto(s)
Neoplasias Encefálicas , Resistencia a Antineoplásicos , Glioblastoma , MicroARNs , Temozolomida , Humanos , Temozolomida/farmacología , Temozolomida/uso terapéutico , Glioblastoma/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , MicroARNs/genética , MicroARNs/metabolismo , Resistencia a Antineoplásicos/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Animales , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Dacarbazina/farmacología , Autofagia/efectos de los fármacos , Autofagia/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
8.
Microrna ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39005129

RESUMEN

Cancer, the second greatest cause of mortality worldwide, frequently causes bone me-tastases in patients with advanced-stage carcinomas such as prostate, breast, and lung cancer. The existence of these metastases contributes to the occurrence of skeletal-related events (SREs), which are defined by excessive pain, pathological fractures, hypercalcemia, and spinal cord com-pression. These injurious incidents leave uncomfortably large holes in each of the cancer patient's life quality. Primary bone cancers, including osteosarcoma (OS), chondrosarcoma (CS), and Ewing's sarcoma (ES), have unclear origins. MicroRNA (miRNA) expression patterns have been changed in primary bone cancers such as OS, CS, and ES, indicating a role in tumor development, invasion, metastasis, and treatment response. These miRNAs are persistent in circulation and ex-hibit distinct patterns in many forms of bone tumors, making them potential biomarkers for early detection and treatment of such diseases. Given their crucial regulatory functions in various bio-logical processes and conditions, including cancer, this study aims to look at miRNAs' activities and possible contributions to bone malignancies, focusing on OS, CS, and ES. In conclusion, miRNAs are valuable tools for diagnosing, monitoring, and predicting OS, CS, and ES outcomes. Further research is required to fully comprehend the intricate involvement of miRNAs in these bone cancers and to develop effective miRNA-based treatments.

9.
J Transl Med ; 22(1): 435, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720379

RESUMEN

Diabetes mellitus is a significant global public health challenge, with a rising prevalence and associated morbidity and mortality. Cell therapy has evolved over time and holds great potential in diabetes treatment. In the present review, we discussed the recent progresses in cell-based therapies for diabetes that provides an overview of islet and stem cell transplantation technologies used in clinical settings, highlighting their strengths and limitations. We also discussed immunomodulatory strategies employed in cell therapies. Therefore, this review highlights key progresses that pave the way to design transformative treatments to improve the life quality among diabetic patients.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos , Diabetes Mellitus , Trasplante de Células Madre , Humanos , Diabetes Mellitus/terapia , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Trasplante de Islotes Pancreáticos , Animales
10.
Cancer Cell Int ; 24(1): 165, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730433

RESUMEN

Lung cancer, as the leading cause of cancer related deaths, is one of the main global health challenges. Despite various progresses in diagnostic and therapeutic methods, there is still a high rate of mortality among lung cancer patients, which can be related to the lack of clinical symptoms to differentiate lung cancer from the other chronic respiratory disorders in the early tumor stages. Most lung cancer patients are identified in advanced and metastatic tumor stages, which is associated with a poor prognosis. Therefore, it is necessary to investigate the molecular mechanisms involved in lung tumor progression and metastasis in order to introduce early diagnostic markers as well as therapeutic targets. Epithelial-mesenchymal transition (EMT) is considered as one of the main cellular mechanisms involved in lung tumor metastasis, during which tumor cells gain the metastatic ability by acquiring mesenchymal characteristics. Since, majority of the oncogenic signaling pathways exert their role in tumor cell invasion by inducing the EMT process, in the present review we discussed the role of PI3K/AKT signaling pathway in regulation of EMT process during lung tumor metastasis. It has been reported that the PI3K/AKT acts as an inducer of EMT process through the activation of EMT-specific transcription factors in lung tumor cells. MicroRNAs also exerted their inhibitory effects during EMT process by inhibition of PI3K/AKT pathway. This review can be an effective step towards introducing the PI3K/AKT pathway as a suitable therapeutic target to inhibit the EMT process and tumor metastasis in lung cancer patients.

11.
Pathol Res Pract ; 258: 155344, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38744001

RESUMEN

Late diagnosis of cancer in advanced stages due to the lack of screening methods is considered as the main cause of poor prognosis and high mortality rate among these patients. Therefore, it is necessary to investigate the molecular tumor biology in order to introduce biomarkers that can be used in cancer screening programs and early diagnosis. MicroRNAs (miRNAs) have key roles in regulation of the cellular pathophysiological processes. Due to the high stability of miRNAs in body fluids, they are widely used as the non-invasive tumor markers. According to the numerous reports about miR-505 deregulation in a wide range of cancers, we investigated the role of miR-505 during tumor progression. It was shown that miR-505 mainly has the tumor suppressor functions through the regulation of signaling pathways, chromatin remodeling, and cellular metabolism. This review has an effective role in introducing miR-505 as a suitable marker for the early cancer diagnosis.


Asunto(s)
Biomarcadores de Tumor , Progresión de la Enfermedad , MicroARNs , Neoplasias , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia
12.
Int J Biol Macromol ; 270(Pt 1): 132347, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38754673

RESUMEN

Aberrant cell proliferation is one of the main characteristics of tumor cells that can be affected by many cellular processes and signaling pathways. Kinesin superfamily proteins (KIFs) are motor proteins that are involved in cytoplasmic transportations and chromosomal segregation during cell proliferation. Therefore, regulation of the KIF functions as vital factors in chromosomal stability is necessary to maintain normal cellular homeostasis and proliferation. KIF deregulations have been reported in various cancers. MicroRNAs (miRNAs) and signaling pathways are important regulators of KIF proteins. MiRNAs have key roles in regulation of the cell proliferation, migration, and apoptosis. In the present review, we discussed the role of miRNAs in tumor biology through the regulation of KIF proteins. It has been shown that miRNAs have mainly a tumor suppressor function via the KIF targeting. This review can be an effective step to introduce the miRNAs/KIFs axis as a probable therapeutic target in tumor cells.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Cinesinas , MicroARNs , Neoplasias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Cinesinas/metabolismo , Cinesinas/genética , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Animales , Proliferación Celular/genética , Progresión de la Enfermedad , Transducción de Señal , Apoptosis/genética , Movimiento Celular/genética
13.
Cell Commun Signal ; 22(1): 265, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741195

RESUMEN

Cisplatin (CDDP) is a widely used first-line chemotherapeutic drug in various cancers. However, CDDP resistance is frequently observed in cancer patients. Therefore, it is required to evaluate the molecular mechanisms associated with CDDP resistance to improve prognosis among cancer patients. Integrins are critical factors involved in tumor metastasis that regulate cell-matrix and cell-cell interactions. They modulate several cellular mechanisms including proliferation, invasion, angiogenesis, polarity, and chemo resistance. Modification of integrin expression levels can be associated with both tumor progression and inhibition. Integrins are also involved in drug resistance of various solid tumors through modulation of the tumor cell interactions with interstitial matrix and extracellular matrix (ECM). Therefore, in the present review we discussed the role of integrin protein family in regulation of CDDP response in tumor cells. It has been reported that integrins mainly promoted the CDDP resistance through interaction with PI3K/AKT, MAPK, and WNT signaling pathways. They also regulated the CDDP mediated apoptosis in tumor cells. This review paves the way to suggest the integrins as the reliable therapeutic targets to improve CDDP response in tumor cells.


Asunto(s)
Cisplatino , Resistencia a Antineoplásicos , Integrinas , Neoplasias , Cisplatino/farmacología , Cisplatino/uso terapéutico , Humanos , Integrinas/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/genética , Resistencia a Antineoplásicos/genética , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transducción de Señal/efectos de los fármacos
14.
Heliyon ; 10(9): e30599, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38726188

RESUMEN

Pancreatic cancer (PC), as one of the main endocrine and digestive systems malignancies has the highest cancer related mortality in the world. Lack of the evident clinical symptoms and appropriate diagnostic markers in the early stages of tumor progression are the main reasons of the high mortality rate among PC patients. Therefore, it is necessary to investigate the molecular pathways involved in the PC progression, in order to introduce novel early diagnostic methods. Epithelial mesenchymal transition (EMT) is a critical cellular process associated with pancreatic tumor cells invasion and distant metastasis. MicroRNAs (miRNAs) are also important regulators of EMT process. In the present review, we discussed the role of miRNAs in regulation of EMT process during PC progression. It has been reported that the miRNAs mainly regulate the EMT process in pancreatic tumor cells through the regulation of EMT-specific transcription factors and several signaling pathways such as WNT, NOTCH, TGF-ß, JAK/STAT, and PI3K/AKT. Considering the high stability of miRNAs in body fluids and their role in regulation of EMT process, they can be introduced as the non-invasive diagnostic markers in the early stages of malignant pancreatic tumors. This review paves the way to introduce a non-invasive EMT based panel marker for the early tumor detection among PC patients.

15.
Biochem Biophys Rep ; 38: 101728, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38737729

RESUMEN

Late diagnosis is one of the main reasons for high mortality rates in cancer patients. Therefore, investigating the molecular mechanisms involved in tumor progression can improve the cancer diagnosis in the early stages of the tumor progression. MicroRNAs (miRNAs) have important roles in regulation of cell growth, proliferation, metabolism, and migration. Since, deregulation of miR-409 has been reported in a wide range of cancers, in the present review, we investigated the molecular mechanisms of miR-409 during tumor progression and invasion. It has been shown that miR-409 functions as a tumor suppressor in different tumor types. MiR-409 can reduce tumor cell proliferation, growth, and migration by regulation of signaling pathways, cellular metabolism, transcription factors, and cellular adhesion. This review can be an effective step in introducing miR-409 as a non-invasive marker in cancer patients.

16.
J Physiol Biochem ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691273

RESUMEN

Recent progresses in diagnostic and therapeutic methods have significantly improved prognosis in cancer patients. However, cancer is still considered as one of the main causes of human deaths in the world. Late diagnosis in advanced tumor stages can reduce the effectiveness of treatment methods and increase mortality rate of cancer patients. Therefore, investigating the molecular mechanisms of tumor progression can help to introduce the early diagnostic markers in these patients. MicroRNA (miRNAs) has an important role in regulation of pathophysiological cellular processes. Due to their high stability in body fluids, they are always used as the non-invasive markers in cancer patients. Since, miR-363 deregulation has been reported in a wide range of cancers, we discussed the role of miR-363 during tumor progression and metastasis. It has been reported that miR-363 has mainly a tumor suppressor function through the regulation of transcription factors, apoptosis, cell cycle, and structural proteins. MiR-363 also affected the tumor progression via regulation of various signaling pathways such as WNT, MAPK, TGF-ß, NOTCH, and PI3K/AKT. Therefore, miR-363 can be introduced as a probable therapeutic target as well as a non-invasive diagnostic marker in cancer patients.

17.
Stem Cell Rev Rep ; 20(5): 1200-1212, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38430362

RESUMEN

Epidermolysis bullosa (EB) is a rare genetic dermatosis characterized by skin fragility and blister formation. With a wide phenotypic spectrum and potential extracutaneous manifestations, EB poses significant morbidity and mortality risks. Currently classified into four main subtypes based on the level of skin cleavage, EB is caused by genetic mutations affecting proteins crucial for maintaining skin integrity. The management of EB primarily focuses on preventing complications and treating symptoms through wound care, pain management, and other supportive measures. However, recent advancements in the fields of stem cell therapy, tissue engineering, and gene therapy have shown promise as potential treatments for EB. Stem cells capable of differentiating into skin cells, have demonstrated positive outcomes in preclinical and early clinical trials by promoting wound healing and reducing inflammation. Gene therapy, on the other hand, aims to correct the underlying genetic defects responsible for EB by introducing functional copies of mutated genes or modifying existing genes to restore protein function. Particularly for severe subtypes like Recessive Dystrophic Epidermolysis Bullosa (RDEB), gene therapy holds significant potential. This review aims to evaluate the role of new therapeutic approaches in the treatment of EB. The review includes findings from studies conducted on humans. While early studies and clinical trials have shown promising results, further research and trials are necessary to establish the safety and efficacy of these innovative approaches for EB treatment.


Asunto(s)
Epidermólisis Ampollosa , Terapia Genética , Trasplante de Células Madre , Humanos , Epidermólisis Ampollosa/terapia , Epidermólisis Ampollosa/genética , Epidermólisis Ampollosa/patología , Animales , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Células Madre/citología , Células Madre/metabolismo
18.
Phytother Res ; 38(1): 42-58, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37784212

RESUMEN

Resveratrol (RES) and curcumin (CUR) are two of the most extensively studied bioactive compounds in cardiovascular research from the past until today. These compounds have effectively lowered blood pressure by downregulating the renin-angiotensin system, exerting antioxidant effects, and exhibiting antiproliferative activities on blood vessels. This study aims to summarize the results of human and animal studies investigating the effects of CUR, RES, and their combination on hypertension and the molecular mechanisms involved. The published trials' results are controversial regarding blood pressure reduction with different doses of RES and CUR, highlighting the need to address this issue.


Asunto(s)
Curcumina , Hipertensión , Animales , Humanos , Resveratrol/farmacología , Curcumina/farmacología , Antioxidantes/farmacología , Modelos Animales , Hipertensión/tratamiento farmacológico
19.
Eur J Hum Genet ; 32(1): 52-60, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37880421

RESUMEN

Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. Thirty-one LIS-associated genes have been previously described. Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2. In this report, we describe biallelic truncating variants in CASP2, another subunit of PIDDosome complex. Seven patients from five independent families presenting with a neurodevelopmental phenotype were identified through GeneMatcher-facilitated international collaborations. Exome sequencing analysis was carried out and revealed two distinct novel homozygous (NM_032982.4:c.1156delT (p.Tyr386ThrfsTer25), and c.1174 C > T (p.Gln392Ter)) and compound heterozygous variants (c.[130 C > T];[876 + 1 G > T] p.[Arg44Ter];[?]) in CASP2 segregating within the families in a manner compatible with an autosomal recessive pattern. RNA studies of the c.876 + 1 G > T variant indicated usage of two cryptic splice donor sites, each introducing a premature stop codon. All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings. Other findings included developmental delay, attention deficit hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. In summary, we present patients with CASP2-related ID, anterior-predominant LIS, and pachygyria similar to previously reported patients with CRADD and PIDD1-related disorders, expanding the genetic spectrum of LIS and lending support that each component of the PIDDosome complex is critical for normal development of the human cerebral cortex and brain function.


Asunto(s)
Lisencefalia , Trastornos del Neurodesarrollo , Humanos , Caspasa 2/genética , Lisencefalia/diagnóstico por imagen , Lisencefalia/genética , Alelos , Trastornos del Neurodesarrollo/genética , Codón sin Sentido , Fenotipo , Cisteína Endopeptidasas/genética
20.
Am J Transl Res ; 15(11): 6342-6361, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38074823

RESUMEN

Various progresses in tumor therapy during the recent decades have significantly reduced the cancer related deaths globally. However, there is still a high rate of mortality in these patients. The early stage tumors have no aggressive and clear clinical symptoms in the majority of cancer types, which causes a high rate of therapeutic failure in advanced tumor stages. Therefore, identification of the molecular tumor biology can be promising to introduce the early diagnostic markers. MicroRNAs (miRNAs) are the key regulators of cellular processes that can also be involved in tumor progression as tumor-suppressor or oncogene. Due to the high stability of miRNAs in body fluids, they can be used as the non-invasive diagnostic tumor markers. In the present review, we discussed the role of miR-494 in tumor progression. It has been shown that miR-494 has mainly a tumor suppressor function by regulation of transcriptional and structural factors and signaling pathways such as transforming growth factor-ß (TGF-ß), WNT, and Janus kinase (JAK)-signal transducer and activator of transcription (STAT). The phosphatase and tensin homolog/phosphoinositide 3-kinase (PTEN/PI3K) axis has been also reported as the main target of miR-494 as an oncogene. These findings suggest that miR-494 is a non-invasive diagnostic marker for the early diagnosis and therapeutic management of cancer patients.

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