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1.
J Orthop Case Rep ; 14(2): 39-43, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38420224

RESUMEN

Introduction: Sacral fractures, which can occur in young individuals following road traffic accidents or falls from a height, as well as in elderly individuals with osteoporosis after minor trauma, are considered a diverse type of fracture. The incidence of non-osteoporotic sacral fractures is estimated to be 2.1/100,000 people, whereas osteoporotic fractures are estimated to affect 1-5% of elderly individuals at risk. Triangular osteosynthesis is a relatively new fixation technique used as a surgical treatment for unstable sacral fractures. It combines transverse fixation with lumbo-pelvis distraction osteosynthesis, providing stability in different planes. The subcategory of triangular osteosynthesis encompasses spinopelvic fixation, which involves the fusion of transverse sacral alar fracture fixation (such as iliosacral screw/s and sacral plate) and unilateral lumbopelvic fixation from the pedicle of L5 to the ipsilateral posterior ilium. The utilization of this technique provides a mechanically advanced approach for stabilizing unstable sacral alar fractures with vertical shear. Once the pelvic ring injury has been reduced, lumbopelvic fixation can assist in preventing the recurrence of vertical displacement in the unstable hemipelvis. Case Report: The patient, a 29-year-old male, experienced a road traffic accident resulting from a collision involving a motorcycle. As a result of the incident, he suffered from an unstable lateral compression type 1 pelvic ring injury, accompanied by an ipsilateral sacroiliac dislocation and a vertical sacral fracture on the opposite side. Computed tomography imaging revealed a right sacroiliac dissociation, a left sacral fracture classified as AO type B1, as well as fractures in both the superior and inferior pubic rami. The pelvic ring of the patient was subjected to closed reduction and percutaneous fixation, accompanied by minimally invasive spinopelvic fixation. The surgical procedure was performed in a single session, involving the reduction and fixation of the right sacroiliac dissociation, followed by lumbopelvic fixation while in the prone position. After a 1-month follow-up, the patient demonstrated the ability to walk without experiencing pain, and the X-ray revealed a stable spinopelvic and sacroiliac fixation. Conclusion: The utilization of triangular osteosynthesis fixation provides a reliable form of fixation that enables the patient to bear complete weight at an early stage of 6 weeks while also preventing any reduction loss in vertical shear transforaminal sacral fractures.

2.
PLoS One ; 18(7): e0288482, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37437063

RESUMEN

BACKGROUND: Breast cancer is a multifactorial disease which involves number of molecular factors that are critically involved in proliferation of breast cancer cells. MEN1 gene that is traditionally known for its germline mutations in neuroendocrine tumors is associated with high risk of developing breast cancer in females with MEN1 syndrome. However, the paradoxical role of MEN1 is reported in sporadic breast cancer cases. The previous studies indicate the functional significance of MEN1 in regulating breast cells proliferation but its relevance in development and progression of breast cancer is still not known. Our study targets to find the role of MEN1 gene aberration and its clinical significance in breast cancer. METHODS: Breast tumor and adjacent normal tissue of 142 sporadic breast cancer patients were collected at the time of surgery. The expression analysis of MEN1 mRNA and protein was done through RT-PCR, immunohistochemistry and western blotting. Further to find the genetic and epigenetic alterations, automated sequencing and MS-PCR was performed respectively. Correlation between our findings and clinical parameters was determined using appropriate statistical tests. RESULTS: MEN1 expression was found to be significantly increased in the breast tumor tissue with its predominant nuclear localization. The elevated expression of MEN1 mRNA (63.38% cases) and protein (60.56% cases) exhibited a significant association with ER status of the patients. Most of the cases had unmethylated (53.52%) MEN1 promoter region, which can be a key factor responsible for dysregulated expression of MEN1 in breast cancer cases. Our findings also revealed the significant association of MEN1 mRNA overexpression with Age and lymph node status of the patients. CONCLUSION: Our results indicate upregulated expression of MEN1 in sporadic breast cancer patients and it could be critically associated with development and advancement of the disease.


Asunto(s)
Neoplasias de la Mama , Proteínas Proto-Oncogénicas , Femenino , Humanos , Neoplasias de la Mama/genética , Relevancia Clínica , Expresión Génica , ARN Mensajero/genética , Proteínas Proto-Oncogénicas/genética
3.
Am J Reprod Immunol ; 90(2): e13745, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37491933

RESUMEN

PROBLEM: Recurrent pregnancy loss (RPL) is the spontaneous loss of two or more consecutive pregnancies prior to 20 weeks of gestation, occurring in 1% of the reproductive-age population. It is a major cause of infertility in India with a staggering 7.46% prevalence rate. METHOD OF STUDY: Blood and product of conception (POCs) from RPL cases (n = 65) were enrolled for this study, along with cases of medically terminated pregnancy (MTP, n = 80) and term delivery cases (n = 90) as control. ELISA for progesterone and progesterone induced blocking factor (PIBF) levels was carried out, followed by mRNA expression analysis of progesterone receptor isoform B (PR-B) and its downstream immunomodulatory effectors, namely, PIBF, IL-10 and IL-12. Screening of PROGINS haplotype of PR gene and PIBF polymorphism were also conducted to correlate with their respective gene expression profiles. RESULTS: Serum progesterone level was found to be comparable in the RPL and MTP cases. Although the mRNA expression of PR-B was found to be downregulated in the RPL cases, no significant PROGINS haplotype was observed. Presence of a single nucleotide polymorphism (SNP) in the PIBF gene (rs1372000) was more in healthy controls compared to RPL cases. Serum PIBF levels were found to be lower in the RPL cases with a resultant increase in IL-12 and a decrease in IL-10 mRNA expression in these cases. CONCLUSIONS: This study indicates that progesterone, acting through PIBF, modulates the immunological state of pregnancy to be Th1-biased in RPL, indicative of a pro-inflammatory, labour-like state not desired for a healthy pregnancy.


Asunto(s)
Aborto Habitual , Progesterona , Embarazo , Femenino , Humanos , Progesterona/farmacología , Citocinas , Interleucina-10/genética , Aborto Habitual/genética , Interleucina-12 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores Supresores Inmunológicos/genética , Factores Supresores Inmunológicos/metabolismo
4.
Expert Opin Ther Targets ; 16 Suppl 1: S91-102, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22313325

RESUMEN

OBJECTIVES: Estrogen has been reported to promote an increased susceptibility to lung cancer development. This study focusses on the role of cytoplasmic estrogen receptor ß (c-ERß) in NSCLC. METHODS: NSCLC (n = 162) cases were analyzed using immunohistochemistry (IHC) for c-ERß expression and its association with clinicopathological variables. Significance of c-ERß expression was further examined using in vitro studies in NSCLC cell lines. RESULTS: Among ERß and aromatase positive NSCLC females, c-ERß was significantly associated with greater tumor diameter and tended to be associated with worse overall survival. A549 and LCAM1 cells expressed aromatase, as well as c-ERß and nuclear ERß (n-ERß). U0126 (MAPK/extracellular-signal-regulated kinase (ERK) inhibitor) abrogated MAPK phosphorylation, caused by estradiol via c-ERß, more effectively than ICI 182780 (ER blocker) in either cell line. However, ICI 182780 completely abrogated the estrogen responsive elements (ERE)-luciferase activity caused by estradiol. Combination therapy with ICI 182780 and U0126 turned out to be far more effective than either treatment alone in either A549 or LCAM1 cells. CONCLUSION: The results indicated that ERß may contribute to NSCLC via non-genomic action of estrogen through its cytoplasmic form, in addition to the genomic actions via n-ERß. These actions of estrogen in NSCLCs may be abrogated by combination therapy with ICI 182780 and U0126.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/etiología , Citoplasma/química , Receptor beta de Estrógeno/fisiología , Neoplasias Pulmonares/etiología , Aromatasa/análisis , Butadienos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Estradiol/administración & dosificación , Estradiol/análogos & derivados , Receptor alfa de Estrógeno/análisis , Receptor beta de Estrógeno/análisis , Fulvestrant , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Nitrilos/administración & dosificación
5.
Life Sci ; 91(15-16): 800-8, 2012 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-22982181

RESUMEN

AIM: The potential gender differences in lung cancer development have been proposed on the basis of hormonal actions. We aimed to evaluate whether estrogen receptors (ERs) in non-small cell carcinoma (NSCLC) patients may primarily depend upon intratumoral estrogen produced via aromatase pathway. MAIN METHODS: We evaluated ER beta (ERß) and aromatase status in 169 Japanese NSCLC patients through immunohistochemistry analysis (IHC). Significance of IHC was further confirmed in NSCLC cell lines via in vitro assays. KEY FINDINGS: IHC analysis of NSCLC patients demonstrated that both ERß and aromatase were highly co-expressed (p=0.032) in carcinoma cells. Overall survival in males was significantly worse than that in postmenopausal female among double positive NSCLC patients (p=0.010) but not in non-double positive patients. In addition, among double positive cases, overall survival of males was significantly worse than that of postmenopausal females in those with higher ERß Allred score ≥5, (p=0.034), but not in those with lower ERß Allred score=3-4. In-vitro analysis demonstrated aromatase activity on testosterone treatment, which resulted in in situ estrogen production (p<0.0001) and increased proliferation of ERß overexpressing A549 cells (p<0.0001). Aromatase inhibitor i.e. letrozole abrogated this proliferation and also enhanced the androgenic activity (p<0.0001). Testosterone treatment resulted in estrogen responsive elements activation (p<0.0001) in ERß vector transfected A549 and LK87 cells whereas ER blocker i.e. fulvestrant abrogated this effect, (p<0.0001). SIGNIFICANCE: Our results suggest that co-expression of ERß and aromatase in NSCLCs of Japanese males may result in tumor progression and potential endocrine therapy may confer therapeutic benefits to these patients.


Asunto(s)
Aromatasa/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptor beta de Estrógeno/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Anciano , Andrógenos/uso terapéutico , Aromatasa/metabolismo , Inhibidores de la Aromatasa/uso terapéutico , Pueblo Asiatico/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Receptor beta de Estrógeno/metabolismo , Estrógenos/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Letrozol , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Nitrilos/uso terapéutico , Factores Sexuales , Testosterona/uso terapéutico , Resultado del Tratamiento , Triazoles/uso terapéutico
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