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1.
Cancer Radiother ; 26(8): 994-1001, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35715356

RESUMEN

PURPOSE: Over the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma. MATERIAL AND METHODS: Various patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis. RESULTS: A total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A=15 patients, score 0-3); (B=50 patients, score 4-7); (C=33 patients, score 8-10); and (D=13 patients, score 11-16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001). CONCLUSION: There exists a lack of universally acceptable 'standard-of-care' salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.


Asunto(s)
Neoplasias Encefálicas , Glioma , Reirradiación , Adulto , Humanos , Terapia Recuperativa , Pronóstico , Neoplasias Encefálicas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Glioma/terapia
2.
Clin Transl Oncol ; 23(7): 1358-1367, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33528810

RESUMEN

PURPOSE: To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. METHODS: Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. RESULTS: A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3-7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6-7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4-55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6-109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan-Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3 Gy) being associated with increased risk of post-re-RT pseudo-progression. CONCLUSION: This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.


Asunto(s)
Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Glioma/mortalidad , Glioma/radioterapia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/radioterapia , Reirradiación , Adolescente , Adulto , Neoplasias Encefálicas/patología , Progresión de la Enfermedad , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Dosificación Radioterapéutica , Reirradiación/efectos adversos , Reirradiación/métodos , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
3.
Clin Oncol (R Coll Radiol) ; 33(3): e155-e165, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32917486

RESUMEN

AIMS: To evaluate quality of life (QOL) and activities of daily living (ADL) longitudinally in patients treated with salvage re-irradiation for recurrent/progressive glioma. Secondary end points included post-re-irradiation survival. MATERIALS AND METHODS: Patients with diffuse glioma, aged 18-70 years with preserved performance status and unequivocal evidence of recurrence/progression with a minimum 2-year time interval from index radiation therapy were eligible. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and brain cancer module (BN20). ADL was assessed using a modified Barthel's index. Assessments were carried out longitudinally, first before re-irradiation, at completion of re-irradiation and subsequently periodically on follow-up. Summary scores were calculated from raw scores as per the EORTC scoring manual; higher functional scores and lower symptom scores indicating better QOL. Summary mean scores for the modified Barthel's index were also calculated, with lower scores indicating higher disability. Differences between the summary scores at different time points were tested using the Friedman test. RESULTS: In total, 225 assessments were carried out in 60 patients accrued on the study. A significant improvement in scores was noted for physical function (P < 0.001), emotional function (P = 0.002), cognitive function (P = 0.009) and social functioning (P = 0.047) over time. Role function scores (P = 0.182) and global health status scores (P = 0.074) remained stable. Among symptom scores, fatigue showed a statistically significant improvement over time (P = 0.01), whereas other symptom scores remained largely stable. There was a significant increase in the modified Barthel's index score over time (P = 0.001), suggesting greater functional independence. At a median follow-up of 12.9 months, the 1-year Kaplan-Meier estimates with 95% confidence intervals of post-re-irradiation progression-free survival and overall survival were 45.1% (31.5-58.7%) and 62.2% (49.2-75.2%), respectively. CONCLUSIONS: High-dose salvage re-irradiation in carefully selected patients with recurrent/progressive glioma is associated with stable QOL (preserved functional domains and reduced symptom burden) and improvement in ADL (greater functional independence) over time with encouraging survival outcomes.


Asunto(s)
Actividades Cotidianas , Glioma , Reirradiación , Glioma/radioterapia , Humanos , Recurrencia Local de Neoplasia/radioterapia , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento
4.
Braz. j. med. biol. res ; 54(9): e11097, 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1278588

RESUMEN

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.


Asunto(s)
Humanos , Niño , Ácido Valproico/uso terapéutico , Epilepsia/genética , Epilepsia/tratamiento farmacológico , Convulsiones/genética , Convulsiones/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Anticonvulsivantes/uso terapéutico
5.
Int J Oral Maxillofac Surg ; 48(3): 298-301, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30409454

RESUMEN

Nasoalveolar moulding is a presurgical orthopaedic technique used to improve the outcomes of bilateral clefts. However, the lack of a validated scale tailored to bilateral clefts makes it difficult to quantify the merits of nasoalveolar moulding and compare it to other techniques. In this study, a recently published anatomical subunit scale was used to evaluate and compare the early effects of nasoalveolar moulding. Two groups of similarly treated bilateral cleft patients were included: one in which patients underwent presurgical nasoalveolar moulding and one in which they did not. The nasolabial aesthetics were evaluated on two-dimensional photographs at 6 months post cheiloplasty. Cupid's bow, vermilion symmetry, vermilion notching, premaxillary show at rest, scar aesthetics, columella height, columella height, and bialar width were all significantly better in the nasoalveolar moulding group. Using the new scale, it was found that nasolabial aesthetics at 6 months post cheiloplasty were significantly better in patients who had undergone nasoalveolar moulding in infancy.


Asunto(s)
Proceso Alveolar/anomalías , Labio Leporino/terapia , Fisura del Paladar/terapia , Estética , Procedimientos Ortopédicos , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Femenino , Humanos , Lactante , Masculino , Fotograbar , Cuidados Preoperatorios , Estudios Retrospectivos , Resultado del Tratamiento
6.
J Biomed Mater Res B Appl Biomater ; 106(3): 1317-1328, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28661574

RESUMEN

The combined effect of cobalt and iron substitutions in ß-Ca3 (PO4 )2 as a potent material for application in hyperthermia and as a bone substitute is presented. Structural analysis reveals the preferential accommodation of Co2+ and Fe3+ at the Ca2+ (5) sites of ß-Ca3 (PO4 )2 until the limit of ∼10 mol % and, thereafter, prefer Ca2+ (4) lattice sites. Occupancy of both the Co2+ and Fe3+ ions induces a significant contraction of the ß-Ca3 (PO4 )2 unit cell. The Co2+ /Fe3+ co-substitutions in ß-Ca3 (PO4 )2 display magnetic characteristics that enhances hyperthermia effect. In addition, the presence of Co2+ in ß-Ca3 (PO4 )2 enunciates pronounced antibacterial efficacy against tested microorganisms. Nevertheless, the enhanced level of Co2+ in ß-Ca3 (PO4 )2 results to induce significant toxicity. The biocompatibility of the synthesized thermoseeds is verified from the hemolytic tests and cytotoxicity test performed on human sarcoma cell line MG-63. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1317-1328, 2018.


Asunto(s)
Antibacterianos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Huesos/anomalías , Fosfatos de Calcio/uso terapéutico , Cobalto/química , Hipertermia Inducida/métodos , Hierro/química , Osteosarcoma/tratamiento farmacológico , Bacterias/efectos de los fármacos , Materiales Biocompatibles , Sustitutos de Huesos , Línea Celular Tumoral , Hemólisis , Humanos , Magnetismo , Pruebas de Sensibilidad Microbiana , Polvos , Difracción de Rayos X
8.
Br J Oral Maxillofac Surg ; 55(8): 834-835, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28662922

RESUMEN

Knowledge of variants in the formation and position of the ansa cervicalis is important in head and neck surgery, specifically in reconstructions of the tongue that use the infrahyoid muscles, and in the anastomosis of the ansa cervicalis to the recurrent laryngeal nerve when the laryngeal muscles have been paralysed. We describe a rare variant of the superior root of the ansa cervicalis, which had a contribution from the vagus and hypoglossal nerves. The inferior root was formed by the C2 and C3 ventral rami, but it passed medial to the internal jugular vein before it joined the superior root to form the loop.


Asunto(s)
Variación Anatómica , Plexo Cervical/anatomía & histología , Anciano , Cadáver , Humanos , Nervio Hipogloso/anatomía & histología , Masculino , Nervio Vago/anatomía & histología
9.
Int J Oral Maxillofac Surg ; 46(8): 988-992, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28408147

RESUMEN

As there is currently no internationally accepted outcome measurement tool available for complete bilateral cleft lip and palate (CBCLP), the goal of this prospective study was to develop a numerical evaluation scale that allows reliable scoring of this cleft deformity. Our cohort comprised 121 Indian subjects with CBCLP who underwent surgical repair (mean age at time of surgery 6.53 months) using a modified Millard technique. A panel of three professionals evaluated each subject's outcome of bilateral cleft lip repair 6 months postoperatively on two-dimensional (2D) full-face photographs in the frontal view and worm's eye view. A simple two-point rating system was applied to separately analyse a total of 12 components of lip, nose, and scar. The results and mean scores for the analysed anatomical areas were 2.2±1.01 (max=3) for nose, 5.4±1.54 (max=8) for lip, and 1.9±1.3 (max=3) for scar, with a total score 7.7±2.21 (max=12) indicating a good surgical outcome. The inter-examiner ICC for nose, lip, scar, and total score was calculated at 0.836, 0.889, 0.723, and 0.927 respectively and indicated a strong level of repeatability and reliability that was highly significant (P<0.001). In conclusion, we were able to develop and test a scoring system for measuring outcomes in CBCLP that warrants simplicity of use, reliability and reproducibility.


Asunto(s)
Labio Leporino/cirugía , Fisura del Paladar/cirugía , Puntos Anatómicos de Referencia , Estética , Femenino , Humanos , India , Lactante , Masculino , Fotograbar , Estudios Prospectivos , Reproducibilidad de los Resultados , Resultado del Tratamiento
10.
Indian J Cancer ; 53(1): 193-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27146777

RESUMEN

CONTEXT: Early detection of oral premalignancy and malignancy using simple screening aids play a promising role in curbing the disease. AIM: The primary aim of this study is to evaluate and the secondary aim of this study is to compare the cytomorphometry and cellular atypia in keratinocytes obtained from oral rinse and conventional exfoliative cytology in normal oral mucosa and clinically diagnosed oral leukoplakia. MATERIALS AND METHODS: The study comprised of 55 clinically diagnosed cases of leukoplakia and 55 age and sex matched normal controls. Smears were prepared using oral rinse technique followed by the conventional exfoliative cytology. Papanicoloau stained smears were evaluated for atypia and subjected to image analysis. Based on the presence of atypia they were further divided into three groups (Group 1-cases with atypia, Group 2-without atypia and Group 3-normal controls) and analyzed. Statistical analysis used one-way analysis of variance followed by Tukey Honestly Significant Difference test for intergroup analysis and unpaired students t-test to compare the two methods. RESULTS: Smears prepared with both methods demonstrated atypia in 18 cases. The cellular diameter and cellular area (CA) were progressively increased from Group 1 through Groups 2 and 3 in both the smears. Nuclear diameter and nuclear area and nuclear cytoplasmic ratio progressively decreased from Group 1 through Groups 2 and 3. Both the methods showed no significant differences among the cellular parameters except in normal controls. CONCLUSION: Cytomorphometric analysis of keratinocytes obtained with oral rinse method and wooden spatula can serve as a useful screening aid to detect oral leukoplakia. Oral rinse method being more convenient results in smears of better quality.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Citodiagnóstico/métodos , Leucoplasia Bucal/diagnóstico , Neoplasias de la Boca/diagnóstico , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Femenino , Humanos , Queratinocitos/patología , Leucoplasia Bucal/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología
11.
Int J Oral Maxillofac Surg ; 45(6): 688-91, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26754270

RESUMEN

Asymmetry is a major problem in repaired unilateral cleft lip (UCL). One of the important manifestations of this is the asymmetry of the vermilion. The aim of this study was to correlate the severity of the asymmetry in the vermilion to the size of the alveolar defect. Twenty patients aged between 6 and 18 months with complete unilateral cleft lip, alveolus, and palate were included. An impression of each patient's alveolus at the time of cheiloplasty was taken using silicon rubber base material, and a study cast was prepared. The width of the cleft alveolus was measured on these casts using a transparent grid. Frontal photographs were taken at 6 months postoperative and vermilion symmetry was measured as the ratio between the cleft and non-cleft sides. The results obtained in this study showed a direct correlation between the size of the alveolar defect and the vermilion symmetry in repaired UCL. The wider the cleft alveolus and greater the antero-posterior discrepancy, the greater is the vermilion asymmetry. The asymmetry of the vermilion in UCL after repair is directly dependent on the size of the alveolar defect. The alveolar discrepancy causes 'in-rolling' of the vermilion on the cleft side and affects the vermilion symmetry.


Asunto(s)
Pérdida de Hueso Alveolar/patología , Labio Leporino/patología , Fisura del Paladar/patología , Labio/anatomía & histología , Pérdida de Hueso Alveolar/cirugía , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Estética , Humanos , Lactante , Fotograbar , Resultado del Tratamiento
12.
Andrologia ; 48(2): 125-36, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25904411

RESUMEN

Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy.


Asunto(s)
Antineoplásicos Alquilantes/toxicidad , Antioxidantes/farmacología , Ciclofosfamida/toxicidad , Daño del ADN/efectos de los fármacos , Moringa oleifera , Extractos Vegetales/farmacología , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Epidídimo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Hojas de la Planta , Pubertad , Espermatozoides/citología , Espermatozoides/metabolismo , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo
13.
Eur J Trauma Emerg Surg ; 42(2): 219-23, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26038041

RESUMEN

INTRODUCTION: Gunshot wounds through the liver are highly lethal and are prone to delayed morbidity due to late complications. METHODS: A retrospective study was performed to determine the incidence, morbidity, and need for late interventions in patients shot through the liver, and the role of post-injury CT in making those determinations. RESULTS: 83 patients were shot through the liver. Injury grades were: Grade V-12 (14 %), Grade IV-41 (49 %), Grade III-12 (14 %), Grade II-8 (10 %), Grade I-1 (1 %), and nine were ungraded. Ten (12 %) died in the ED, three (4 %) died in the OR, and two (2 %) died postoperatively. Of the 68 survivors, 52 (76 %) had follow-up CT scans performed a median of 7 days (95 % CI 2-13 days) after injury. Seventeen (33 %) had 25 complications related to the bullet tract: 12 (48 %) abscesses, 6 (24 %) infected hematomas, 3 (12 %) bilomas, 3 (12 %) unclassified fluid collections, and 1 (4 %) hepatic necrosis. Treatment included CT-guided drainage in 15 (60 %), ultrasound-guided drainage in 3 (12 %), surgical drainage and debridement in 2 (8 %), and observation in 5 (20 %). Overall morbidity rate including hepatic and non-hepatic complications was 74 % (50/68). Patients having their CT scan-determined intervention (for all complications) within 7 days of injury (n = 24), compared to those having their CT scan-determined intervention on day 8 or later (n = 28), had a significantly decreased rate of overall complications and morbidity (p = 0.03). This difference was due to early detection and intervention for abscesses, anastomotic breakdown, and missed injuries. Those having a CT scan within 7 days of injury also had a significantly reduced length of stay compared to those scanned on day 8 or later (median 14 days, 95 % CI 4-24 days versus 18 days, 95 % CI 6-30 days, p = 0.05). CONCLUSIONS: Gunshot wounds to the liver have a high morbidity and mortality rate. Survivors should have a follow-up CT scan performed within 7 days to allow detection and intervention for complications, as this dramatically decreases the overall morbidity rate and length of stay.


Asunto(s)
Desbridamiento/métodos , Drenaje/métodos , Hígado , Cirugía Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Heridas por Arma de Fuego , Adulto , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación/estadística & datos numéricos , Hígado/diagnóstico por imagen , Hígado/lesiones , Hígado/cirugía , Absceso Hepático/diagnóstico , Absceso Hepático/etiología , Absceso Hepático/cirugía , Masculino , Estudios Retrospectivos , Tiempo de Tratamiento/estadística & datos numéricos , Resultado del Tratamiento , Ultrasonografía/métodos , Estados Unidos/epidemiología , Heridas por Arma de Fuego/complicaciones , Heridas por Arma de Fuego/diagnóstico , Heridas por Arma de Fuego/mortalidad , Heridas por Arma de Fuego/cirugía
16.
Br J Cancer ; 111(12): 2328-41, 2014 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-25321192

RESUMEN

BACKGROUND: Annexin A2 (AnxA2), a calcium-dependent phospholipid binding protein, is abundantly present at the surface of triple-negative and Herceptin-resistant breast cancer cells. Interactions between cell-surface AnxA2 and tyrosine kinase receptors have an important role in the tumour microenvironment and act together to enhance tumour growth. The mechanism supporting this role is still unknown. METHODS: The membrane function of AnxA2 was blocked by incubating cells with anti-AnxA2 antibodies. Western blotting, immunoprecipitation, immunofluorescence, 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), flow cytometry, Clonogenic, and wound-healing assays were performed in this study. RESULTS: We demonstrate that AnxA2 interacts with epidermal growth factor receptor (EGFR) at the cell surface and has an important role in cancer cell proliferation and migration by modulating EGFR functions. Blocking AnxA2 function at the cell surface by anti-AnxA2 antibody suppressed the EGF-induced EGFR tyrosine phosphorylation and internalisation by blocking its homodimerisation. Furthermore, addition of AnxA2 antibody significantly inhibited the EGFR-dependent PI3K-AKT and Raf-MEK-ERK downstream pathways under both EGF-induced and basal growth conditions, resulting in lower cell proliferation and migration. CONCLUSIONS: These findings suggest that cell-surface AnxA2 has an important regulatory role in EGFR-mediated oncogenic processes by keeping EGFR signalling events in an activated state. Therefore, AnxA2 could potentially be used as a therapeutic target in triple-negative and Herceptin-resistant breast cancers.


Asunto(s)
Anexina A2/inmunología , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Neoplasias de la Mama/terapia , Neoplasias de la Mama Triple Negativas/terapia , Anticuerpos Monoclonales/inmunología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Femenino , Humanos , Células MCF-7 , Transducción de Señal , Trastuzumab , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/patología
17.
J Cytol ; 30(1): 18-22, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23661935

RESUMEN

BACKGROUND: Papanicolaou staining is commonly used for staining exfoliative cytology smears with Romanowsky stains being used sparingly. Leishman Giemsa (LG) cocktail, being a relatively new staining technique, has not been used in exfoliative cytology. This easy, cost-effective and one-step technique warrants further study because of its potential application in screening of oral cancer. AIM: To study and evaluate the diagnostic efficiency and reliability of Leishman Giemsa (LG) cocktail in comparison with Papanicolaou (Pap) and May-Grünwald Giemsa (MGG) stains in exfoliated cells for the detection of oral squamous cell carcinoma. MATERIALS AND METHODS: Three smears were prepared from each 100 controls (buccal mucosa) and 100 patients, clinically diagnosed with oral squamous cell carcinoma and stained with Pap, MGG and LG cocktail stains. The slides were evaluated for the staining characteristics of nucleus and cytoplasm. The diagnostic efficiency of each stain was evaluated by comparing the cytologic diagnosis of each stain with the histopathological diagnosis. Finally, the diagnostic reliability was evaluated by comparing the three stains with each other and the histologic diagnosis. STATISTICAL ANALYSIS: The data were statistically evaluated with Friedman test, Wilcoxon sign rank test and McNemar chi square test using SPSS15 software. RESULTS: The results from the histologically confirmed cases of squamous cell carcinoma and the number of cases diagnosed by Pap and LG cocktail were almost identical and both were superior to MGG. The P value obtained for the confirmed cases of squamous cell carcinoma in comparison for Pap vs MGG was 0.001, MGG vs LG cocktail was 0.001 and LG cocktail vs Pap was 0.157. Hence, no statistical significant difference was observed between the diagnostic ability of Pap and LG cocktail stains. CONCLUSION: LG cocktail is an easy, cost-effective and one-step technique comparable to Pap staining; however, it warrants further study in its potential application in screening of oral cancer.

18.
Breast Cancer Res Treat ; 136(3): 795-804, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23124476

RESUMEN

Studies on well characterized, large populations of estrogen receptor (ER)/progesterone receptor (PgR)/HER2-negative [triple-negative (TN)] breast cancer (BC) patients with long-term follow-up are lacking. In this study, we analyze clinical outcomes of TN BC and implications of epidermal growth factor receptor (EGFR) expression. Clinical and biologic features, time to first recurrence (TTFR), and overall survival (OS) were compared in 253 TN versus 1,036 ER positive, PgR positive, HER2-negative [estrogen-driven (ED)] BC. Compared to ED, TN tumors were larger (p = 0.02), more proliferative (high S-phase 54 vs. 17 %, p < 0.0001), more aneuploid (64 vs. 43 %, p < 0.0001) and more likely EGFR positive (≥10 fmol/mg by radioligand-binding assay, 49 vs. 7 %, p < 0.0001). Among TN, EGFR-positive BC were larger (p = 0.0018), more proliferative (p < 0.0001), and more aneuploid, (p < 0.0001) than EGFR-negative BC. Adjuvant-treated TN patients had shorter TTFR (p = 0.0003), and OS (p = 0.0017), than ED patients. However, in untreated patients, no differences in TTFR and OS were observed at 8 years median follow-up. Among TN patients, EGFR expression was not associated with worse outcome. TN tumors have a worse outcome in systemically treated patients but not in untreated patients. EGFR expression, does not predict for worse long-term survival.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Quimioterapia Adyuvante , Receptores ErbB/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Análisis Multivariante , Ploidias , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Resultado del Tratamiento
19.
Dis Esophagus ; 25(1): 81-7, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21668571

RESUMEN

The aim of the study was to evaluate the expression of tumor suppressor genes p53, fragile histidine triad gene (FHIT), and an oncogene insulin-like growth factor 2 (IGF2) as prognostic markers in the etiology of esophageal cancer. Immunohistochemistry (IHC) was performed in 39 archival tissue samples of different esophageal pathologies for the three genes. Abnormal p53 expression was maximum in all the cases of squamous cell carcinoma, while IGF2 expression was enhanced in squamous cell carcinoma (81%), adenocarcinoma (100%), and dysplasia of squamous epithelium (75%) samples when compared with normals (50%). To our surprise, 75% of normal tissues did not show FHIT expression, which was also not seen in 40% of dysplasias of squamous epithelium, 33.3% of adenocarcinoma, and 41% of squamous cell carcinoma. To the best of our knowledge, this is the first study evaluating IGF2 by IHC, as well as, correlating it with the expression of the two tumor suppressor genes, p53 and FHIT, in esophageal tissue. p53 expression was threefold higher than normal in dysplasias of squamous epithelium and adenocarcinoma, while it was eightfold higher in squamous cell carcinoma. IGF2 expression was low in normal and dysplasia tissue but was increased 1.97-fold in both types of malignancy. FHIT and p53 expression were well correlated in squamous cell carcinoma, supporting the observation that FHIT regulates and stabilizes p53. Altered/lowered FHIT levels may be a result of exposure to various exogenous agents; however, this could not be assessed in the present study as it was carried out on archival samples. A larger prospective study is warranted to establish the role of exogenous factors in FHIT expression.


Asunto(s)
Ácido Anhídrido Hidrolasas/genética , Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Factor II del Crecimiento Similar a la Insulina/genética , Proteínas de Neoplasias/genética , Proteína p53 Supresora de Tumor/genética , Ácido Anhídrido Hidrolasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Epitelio/metabolismo , Epitelio/patología , Esófago/metabolismo , Esófago/patología , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Factor II del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Proteína p53 Supresora de Tumor/metabolismo
20.
Int Endod J ; 44(11): 1061-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21718335

RESUMEN

AIM: To report on the successful conservative management of three patients having a talon cusp with pulpal involvement using mineral trioxide aggregate (MTA). SUMMARY: Mineral trioxide aggregate was used to induce hard-tissue formation following the direct pulp capping of a resected talon cusp in three cases. KEY LEARNING POINTS: • Talon cusp is an odontogenic anomaly which can cause occlusal interferences, displacement of the affected tooth, caries-susceptible developmental grooves and speech difficulties • Direct pulp capping using MTA following the resection of a talon cusp is a suitable treatment option.


Asunto(s)
Compuestos de Aluminio/uso terapéutico , Apexificación/métodos , Compuestos de Calcio/uso terapéutico , Óxidos/uso terapéutico , Materiales de Recubrimiento Pulpar y Pulpectomía/uso terapéutico , Silicatos/uso terapéutico , Anomalías Dentarias/terapia , Corona del Diente/anomalías , Niño , Recubrimiento de la Pulpa Dental/métodos , Cavidad Pulpar/anomalías , Combinación de Medicamentos , Femenino , Humanos , Incisivo/anomalías , Masculino , Resultado del Tratamiento
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