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An efficient SERS based novel analytical approach named Cryosectioned-PDMS was developed systematically and evaluated applying on 64 thyroid biopsy samples. To utilize thyroid biopsy samples, a 20-µl volume of h-AgNPs suspension was dropped on a 5-µm thick cryosectioned biopsy specimen placed on the PDMS coated glass slide. The SERS spectra from a 10 × 10 points array acquired by mapping 22.5 µm × 22.5 µm sized area from suspended dried droplets placed on the tissue surface. The probability of correctly predicted performance for diagnosis of malignant, benign and healthy tissues was resulted in the accuracy of 100 % for the spectral bands at 667, 724, 920, 960, 1052, 1096, 1315 and 1457 cm-1 using PCA-fed LDA machine learning. The Cryosectioned-PDMS biophotonic approach with PCA-LDA predictive model demonstrated that the vibrational signatures can accurately recognize the fingerprint of cancer pathology from a healthy one with a simple and fast sample preparation methodology.
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Neoplasias , Espectrometría Raman , Análisis Discriminante , Humanos , Neoplasias/diagnóstico , Análisis de Componente Principal , Espectrometría Raman/métodos , Glándula TiroidesRESUMEN
Prostate cancer is the second most common cancer among men and the leading cause of death after lung cancer. Development of hormone-refractory disease is a crucial step for prostate cancer progression for which an effective treatment option is currently unavailable. Therefore, there is a need for new agents that can efficiently target cancer cells, decrease tumor growth, and thereby extend the survival of patients in late-stage castration-resistant prostate cancer. In the current study, a novel heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used to evaluate anticancer activity against prostate cancer in vitro and in vivo. Cell proliferation and cytotoxicity were evaluated by cell viability, gene, and protein expression assays in vitro. Results showed that the heterodinuclear copper(II)Mn(II) complex-P85 combination decreased cell proliferation by upregulating the apoptotic gene expressions and blocking the cell proliferation-related pathways. Tramp-C1-injected C57/B16 mice were used to mimic a prostate cancer model. Treatment combination of Schiff base complex and P85 significantly enhanced the cellular uptake of chemicals (by blocking the drug transporters and increased life time), suppressed tumor growth, and decreased tumor volume steadily over the course of the experiments. Overall, heterodinuclear copper(II)Mn(II) complex-P85 showed remarkable anticancer activity against prostate cancer in in vitro and in vivo.
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Poloxaleno/farmacología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Bases de Schiff/farmacología , Animales , Línea Celular Tumoral , Complejos de Coordinación/farmacología , Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos C57BL , Neoplasias de la Próstata/genética , Neoplasias de la Próstata Resistentes a la Castración/genéticaRESUMEN
A 38-year-old woman presented with a mass in the left breast. Biopsy of the lesion revealed invasive ductal carcinoma. Bilateral adrenal metastasis was detected in whole body positron emission tomography scanning. Needle biopsy of the left adrenal lesion proved infiltration of malignant cells from breast carcinoma. After eight cycles of neoadjuvant (preoperative) chemotherapy, mastectomy, bilateral adrenalectomy, and bilateral oopherectomy were performed. No further hormonal treatment was recommended due to the resection of both adrenal glands and ovaries. The patient is still followed without any sign of progression. To our knowledge, this is the first case representing multimodality approach to breast cancer with bilateral synchronous adrenal metastasis. Patients with oligometastatic disease may benefit from aggressive treatment including local therapies.
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Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/terapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/terapia , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Biopsia/métodos , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Femenino , Humanos , Ovariectomía/métodosRESUMEN
PURPOSE: We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage. METHODS: Twenty-four adult female Sprague-Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed. RESULT(S): The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03). CONCLUSION(S): CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.
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Reserva Ovárica/efectos de los fármacos , Ovario/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ubiquinona/análogos & derivados , Adulto , Envejecimiento/efectos de los fármacos , Envejecimiento/patología , Animales , Hormona Antimülleriana/sangre , Antioxidantes/administración & dosificación , Suplementos Dietéticos , Femenino , Humanos , Ovario/crecimiento & desarrollo , Embarazo , Ratas , Ubiquinona/administración & dosificaciónRESUMEN
BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is mostly a non-immunoglobulin E-mediated disease where a T-cell-mediated reaction to cow's milk protein has been suggested. We determined the expression of transforming growth factor (TGF)-ß, TGF-ß receptor-1, tumor necrosis factor (TNF)-α, CD86, and CD23 on the colon mucosa to investigate their roles in the pathogenesis of the two subtypes of FPIAP, i.e. infantile FPIAP and FPIAP in older children. METHODS: Group 1 comprised children with infantile FPIAP (age <6 months, n = 21), group 2 referred to FPIAP in older children (age >1.5 years, n = 7), and group 3 included children with juvenile hyperplastic polyps (n = 22). Immunohistochemical staining of colonic biopsy specimens was performed. RESULTS: The expression of TNF-α was significantly higher in groups 1 and 2 compared to group 3. Group 2 patients had a significantly lower TGF-ß expression compared to the other groups. The expression of CD86 was higher in group 1 than in group 3 (p = 0.012). Eosinophil counts per high-power field in the lamina propria were significantly correlated with CD86 expression (p = 0.026, r = 0.388). CONCLUSION: Our results suggest that TNF-α is implicated in the pathogenesis of both types of FPIAP. The decreased activity of TGF-ß receptor-1 accompanied by the increased expression of CD86 in infants and the decreased activity of TGF-ß in older children appear to play a role in the development of FPIAP.
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Colitis/etiología , Colitis/inmunología , Citocinas/inmunología , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/inmunología , Hipersensibilidad a la Leche/complicaciones , Antígeno B7-2/inmunología , Biopsia , Preescolar , Enterocolitis/inmunología , Femenino , Humanos , Lactante , Mucosa Intestinal/inmunología , Masculino , Hipersensibilidad a la Leche/inmunología , Proteínas Serina-Treonina Quinasas/inmunología , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de IgE/inmunología , Receptores de Factores de Crecimiento Transformadores beta/inmunología , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
An increased accumulation of intracellular levels of reactive oxygen species with time may play an important role in the process of ageing. The antioxidant properties of resveratrol are dependent upon the up-regulation of endogenous cellular antioxidant systems. We evaluated whether resveratrol has protective antioxidant effects on ovarian damage related to oxidative stress in a rat model. Twenty-four female rats were randomly divided into three groups and were given saline (group 1: control); intraperitoneal cisplatin, 4.5 mg/kg, two weekly doses in total (group 2); or cisplatin, 4.5 mg/kg plus intraperitoneal resveratrol 10 mg/kg/day, 24 h before the administration of cisplatin (group 3). Serum anti-Müllerian hormone (AMH) concentrations were significantly lower in group 2 than in group 3 (P < 0.01 and P = 0.04, respectively). The evaluation of the atretic and antral follicle counts revealed statistically significant differences between the groups (P = 0.04 and P < 0.01, respectively). A statistically significant difference was observed in the follicle count positive for AMH between the groups (P = 0.01). Oxidative stress plays an important role in the process of ovarian ageing. Because of its natural antioxidant properties, resveratrol may be an effective option in protecting ovarian tissue against oxidative damage.
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Antioxidantes/farmacología , Reserva Ovárica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estilbenos/farmacología , Animales , Hormona Antimülleriana/sangre , Antineoplásicos/farmacología , Cisplatino/farmacología , Femenino , Folículo Ovárico/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Resveratrol , Regulación hacia ArribaRESUMEN
AIMS: To determine the effects of different doses of melatonin treatment on endometrial implants, the activity of antioxidant enzyme superoxide dismutase (SOD), the angiogenesis factor, the vascular endothelial growth factor (VEGF) and the waste metabolite product of lipid peroxidation malondialdehyde (MDA) in an oophorectomized rat endometriosis model. METHODS: Thirty-two, female, non-pregnant, nulligravid Sprague-Dawley, albino rats were used in this prospective, randomized, controlled and experimental study. Endometriosis was surgically induced in oophorectomized rats, and estradiol treatment was started after the first operation and continued till the end of the study. Second look, third look and necropsy operations were performed in the 2nd, 4th and 6th weeks. Mean volumes, histological scores and biochemical parameters were evaluated throughout the study. RESULTS: The mean volumes of endometriotic foci were 98.8 mm(3) ± 17.2 vs. 108.2 mm(3) ± 17.5, 54.1 mm(3) ± 15.6 vs. 25.8 mm(3) ± 3.6, 42.8 mm(3) ± 10.5 vs. 32.7 mm(3) ± 6.0 and histopathological scores were 2.2 ± 0.2 vs. 1.7 ± 0.1, 2.6 ± 0.2 vs. 2.2 ± 0.2, 2.6 ± 0.1 vs. 2.7 ± 0.2 in the 10 vs. 20-mg/kg/day melatonin group at the end of the second, fourth and sixth weeks, respectively. When the groups were compared, no significant differences were seen in the histopathologic scores, SOD and VEGF levels between the groups. However, the endometriotic foci volumes were significantly decreased in both melatonin treatment groups with respect to the control group at the end of the fourth and sixth weeks. Moreover, the mean MDA levels were significantly lower in the control group than in the 10-mg/kg/day melatonin group at the end of the fourth and sixth weeks. CONCLUSION: Melatonin treatment resulted in the regression of endometriotic lesions in oophorectomized rats. Higher doses of melatonin treatment might be more effective in the regression of implants and improvement of histologic scores as well as in the precise evaluation of SOD, MDA and VEGF distributions in the rat experimental models.
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Antioxidantes/farmacología , Endometriosis/tratamiento farmacológico , Melatonina/farmacología , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Animales , Antioxidantes/administración & dosificación , Relación Dosis-Respuesta a Droga , Endometriosis/etiología , Endometriosis/patología , Femenino , Humanos , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Melatonina/administración & dosificación , Ovariectomía , Estudios Prospectivos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
We investigated the effect of blueberries (BB) on lipids and oxidative stress parameters in hypercholesterolemic guinea pigs. The animals were fed for 75 d on a high-cholesterol (HC) diet supplemented with fresh BB. BB reduced oxidative stress and cholesterol accumulation in the aorta and liver of the guinea pigs. This effect may be related to its antioxidative potential and lipid-reducing effect.
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Aorta/metabolismo , Arándanos Azules (Planta) , Colesterol en la Dieta/administración & dosificación , Hipercolesterolemia/dietoterapia , Hígado/metabolismo , Estrés Oxidativo , Animales , Anticolesterolemiantes/farmacología , Aorta/efectos de los fármacos , Aorta/patología , Dieta Alta en Grasa , Flavonoles/farmacología , Cobayas , Hipercolesterolemia/etiología , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Metabolismo de los Lípidos , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Polifenoles/farmacologíaRESUMEN
Warthin tumor (WT) is the second most common benign tumor of the parotid gland with male predominance and is seen in the elderly population in the left mandibular and cervical regions. Extraparotid WT rarely presents as a mass in the right cervical region in middle-aged adults. Here, we present two extraordinary cases of WT seen in middle age, both in the right cervical region. The first is a 50-year-old man with an asymptomatic neck mass, and the second is a 60-year-old woman with a fast-growing mass with enhancement in positron emission tomography-computed tomography (PET-CT) with suspicions of malignancy.
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ETHNOPHARMACOLOGICAL RELEVANCE: Okra fruit (Abelmoschus esculentus (L.) Moench) has been extensively used for the treatment of skin damage and subcutaneous tissue abscess for many years in Turkish folk medicine. AIM OF STUDY: In this study, we aimed to investigate the wound healing potential of okra fruit by in vitro and in vivo experimental models in detail. Furthermore, based on the results of experiments, a wound healing formulation was developed and its activity profile was studied. MATERIALS AND METHODS: For this purpose, the phenolic, flavonoid and proanthocyanidin contents and chemical profile of aqueous and ethanolic extracts prepared from okra fruits cultivated in two different locations of Turkey, i.e. Aegean and Kilis regions, were comparatively determined and the tryptophan levels, which is known to be an influential factor in wound healing, were measured. Antioxidant activity of the okra fruit extracts was determined by DPPH test, ABTS radical scavenger activity, iron-binding capacity, total antioxidant capacity and copper reduction capacity assays. Moreover, antibacterial activity potentials of the aqueous and ethanolic extracts of okra fruits were determined. The protective effect of the extracts against H2O2-induced oxidative stress and anti-inflammatory activity were assessed in HDF (human dermal fibroblast) cells and in RAW 264.7 murine macrophages, respectively. The biocompatibility of the gel formulations prepared with the best performing extract were evaluated by human Epiderm™ reconstituted skin irritation test model. Wound-healing activity was investigated in rats by in vivo excision model and, histopathological examination of tissues and gene expression levels of inflammation markers were also determined. RESULTS: According to our findings, the aqueous and ethanolic extracts of okra fruits were found to possess a rich in phenolic content. Besides, isoquercitrin was found to be a marker component in ethanolic extracts of okra fruits. Both extracts exhibited antioxidant activity with significant protective effect against H2O2-induced damage in HDF cells by diminishing the MDA level. Also, the highest dose of ethanolic extracts has displayed a potent anti-inflammatory activity on LPS-induced RAW264.7 cells. Besides, both water and ethanolic extracts were shown to possess antimicrobial activity. On the other hand, the formulations prepared from the extracts were found non-irritant on in vitro Epiderm™-SIT. In vivo excision assay showed that tissue TGF-ß and IL-1ß levels were significantly decreased by the 5% okra ethanolic gel formulation. The histopathological analysis also demonstrated that collagenisation and granulation tissue maturation were found higher in 5% (w/v) okra ethanolic extract-treated group. CONCLUSION: 5% of okra ethanolic extract might be suggested as a potent wound healing agent based on the antimicrobial, antioxidant and anti-inflammatory tests. The proposed activity was also confirmed by the histopathological findings and gene expression analysis.
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Abelmoschus/química , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/aislamiento & purificación , Células Cultivadas , Fibroblastos/efectos de los fármacos , Frutas , Humanos , Peróxido de Hidrógeno , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Medicina Tradicional , Ratones , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , TurquíaRESUMEN
OBJECTIVE: To determine the effects of etanercept (anti-TNF-α) on surgically induced endometriosis in a rat model. MATERIALS AND METHODS: This is a prospective, randomized, controlled, experimental study that was carried out at the Experimental Research Center of Yeditepe University (YUDETAM). Thirty female nonpregnant, nulligravid Wistar-Hannover albino rats were used. The summary of the technique: surgical induction of endometriosis, administration of estrogen for 2 weeks, and laparotomy; administration of etanercept for 2 weeks following the induction of endometriosis and laparotomy; administration of estrogen for 2 weeks and necropsy. The volume and histopathological scores of the endometriotic foci were evaluated. RESULTS: One-hundred twenty uterine horns were implanted in 30 rats. Endometriosis was completely formatted in 112 lesions (93.3%). No rats were lost. In the etanercept group, the lesions' volumes were 83.9 ± 13.1, 47.2 ± 8.4, and 96.7 ± 34.8 mm(3) at the end of the second week (pretreatment stage), at the end of the fourth week (post-treatment stage), and at the end of the sixth week, respectively (P = 0.007). Histopathologic scores were 2.3 ± 0.2, 1.7 ± 0.2, and 1.9 ± 0.1, respectively (P = 0.08). The changes in the other groups were not statistically significant. CONCLUSIONS: Etanercept, a fusion protein consisting of human recombinant soluble TNF receptor-2, neutralizes TNF activity. Anti-TNF therapy could be a new non-hormonal therapeutic option for the treatment of endometriosis in humans.
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Modelos Animales de Enfermedad , Endometriosis/patología , Inmunoglobulina G/farmacología , Animales , Etanercept , Femenino , Ratas , Ratas Wistar , Receptores del Factor de Necrosis Tumoral , Trasplante de Tejidos , Útero/efectos de los fármacos , Útero/patologíaRESUMEN
OBJECTIVES: Laryngopharyngeal reflux (LPR), a growing issue in ear, nose, and throat (ENT) and pediatric medicine, is the backflow of stomach contents into the laryngopharynx. Patients present with frequent upper and/or lower respiratory tract infections and coughs, associated with acid- and pepsin-mediated injury to the mucosae of the larynx and pharynx. LPR is associated with rhinosinusitis, laryngitis, pneumonia, and asthma. Children with LPR often fail to exhibit classic gastroesophageal reflux disease symptoms, or such symptoms may be intermittent. Only a few studies have sought correlations among symptoms, endoscopic findings, and the results of frequently used diagnostic tests. THE AIM OF OUR STUDY: We sought associations among the Reflux Finding Score (RFS), Reflux Symptom Index (RSI), and the pathological extent of esophagitis. METHODS: We reviewed data on children who underwent upper gastrointestinal tract endoscopy and showed LPR symptoms, as reported by the ENT department. The RSI was scored by pediatric gastroenterologists and the RFS by ENT doctors, via laryngoscopic examination. The pathological esophageal data were evaluated retrospectively. RESULTS: We treated 52 patients (29 boys) with a mean age of 11.4 ± 4.5 years. On pathological evaluation, one patient exhibited normal esophageal findings, while 28 showed mild esophagitis, 16 esophagitis, and 8 severe esophagitis. Thirteen patients showed esophageal pseudopolypoid lesions secondary to gastroesophageal reflux disease on endoscopic examination, but were human papilloma virus-negative. There was no correlation among the RFS, RSI score, and age, but there was a significant correlation between the pathological data and the RFS (Pâ¯=â¯0.010; râ¯=â¯0.461). CONCLUSIONS: The incidence of LPR/esophagitis in children may differ from that in adults. Therefore, ENT specialists should determine esophagitis status in children and, if necessary, consult pediatric gastroenterologists.
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Esofagitis , Laringitis , Reflujo Laringofaríngeo , Adolescente , Niño , Femenino , Humanos , Reflujo Laringofaríngeo/diagnóstico , Laringoscopía , Masculino , Estudios RetrospectivosRESUMEN
Bronchogenic cysts that formed during the development of the tracheobronchial tree in the gestational period are mostly asymptomatic until adulthood. Cysts localized in the middle mediastinum, specifically in the subcarinal region, on the other hand, may cause serious symptoms by compressing the heart and major vessels due to their close proximity. In this report it is suggested that surgical resection of a giant bronchogenic cyst that compresses the heart and great vessels should be securely performed in the presence of a readily available cardiopulmonary bypass capability.
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Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/cirugía , Función del Atrio Izquierdo/fisiología , Quiste Broncogénico/complicaciones , Quiste Broncogénico/cirugía , Arteria Pulmonar , Arteriopatías Oclusivas/diagnóstico por imagen , Quiste Broncogénico/diagnóstico por imagen , Quiste Broncogénico/patología , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/etiología , Constricción Patológica/cirugía , Ecocardiografía , Femenino , Humanos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/patología , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/patología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Glial tumors are malignant brain tumors that arise from glial cells of brain or spine and have genetic aberrations in their genome. 1p/19q co-deletion is associated with increased Overall Survival (OS) time with enhanced response to chemo- and radio-therapy in oligodendrogliomas. However, prognostic significance of 1p/19q co-polysomy is still unclear. We evaluated 1p/19q status of 221 patients with glial tumor by Fluorescent in situ Hybridization (FISH). Records of the patients were collected retrospectively. Our results demonstrated that 1p/19q co-polysomy was associated with decreased OS time, high P53 expression and frequently located in temporal lobe, whereas 1p/19q co-deletion was associated with increased overall survival time, low P53 expression and frontal lobe location. Furthermore, classification of patients based on both 1p/19q status and P53 expression revealed that patients with 1p/19q co-polysomy and high P53 expression had the worst prognosis. Lastly, our bioinformatic survival analysis revealed that high expression of SRM, ICMT, and FTL located in 1p36.13-p36.31 and 19q13.2-q13.33 region were related with decreased OS time in patients with Low Grade Glioma (LGG). The study demonstrated that 1p/19q co-polysomy is a poor prognostic marker for glial tumor.
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Biomarcadores de Tumor , Neoplasias Encefálicas , Aberraciones Cromosómicas , Cromosomas Humanos Par 1 , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias , Oligodendroglioma , Adulto , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 1/metabolismo , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Oligodendroglioma/mortalidad , Oligodendroglioma/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: Chordomas are highly therapy-resistant primary bone tumors that exhibit high relapse rates and may induce local destruction. Here, we evaluated the effects of tumor necrosis factor-alpha (TNF-α) on chordoma progression and clinical outcome. METHODS: Chordoma cells were treated with TNF-α after which its short- and long-term effects were evaluated. Functional assays, qRT-PCR and microarray-based expression analyses were carried out to assess the effect of TNF-α on chemo-resistance, epithelial to mesenchymal transition (EMT), migration, invasion and cancer stem cell-like properties. Finally, relationships between TNF-α expression and clinicopathological features were assessed in a chordoma patient cohort. RESULTS: We found that TNF-α treatment increased the migration and invasion of chordoma cells. Also, NF-κB activation was observed along with increased EMT marker expression. In addition, enhanced tumor sphere formation and soft agar colony formation were observed, concomitantly with increased chemo-resistance and CD338 marker expression. The TNF-α and TNFR1 expression levels were found to be significantly correlated with LIF, PD-L1 and Ki67 expression levels, tumor volume and a short survival time in patients. In addition, a high neutrophil to lymphocyte ratio was found to be associated with recurrence and a decreased overall survival. CONCLUSIONS: From our data we conclude that TNF-α may serve as a prognostic marker for chordoma progression and that tumor-promoting inflammation may be a major factor in chordoma tumor progression.
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Neoplasias Óseas/patología , Cordoma/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/fisiología , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Adulto , Anciano , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Niño , Cordoma/tratamiento farmacológico , Cordoma/mortalidad , Cordoma/secundario , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Inflamación , Factor Inhibidor de Leucemia/metabolismo , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Neutrófilos/metabolismo , Pronóstico , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Estudios Retrospectivos , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Adulto JovenRESUMEN
BACKGROUND: YKL-40, also called human cartilage glycoprotein-39 (HC gp-39) and chitotriosidase are homologs of family 18 glycosyl hydrolases secreted by human macrophages. Although high levels of YKL-40 and chitotriosidase are associated with several diseases, the physiological functions of these enzymes are still unclear. YKL-40, a growth factor for connective tissue cells, a migration factor for endothelial and vascular smooth muscle cells, is expressed by several types of solid human carcinoma, including prostate carcinoma. PURPOSE: The purpose of this study was to compare serum YKL-40 levels and chitotriosidase activity both in benign prostatic hyperplasia and primary prostate cancer. METHODS: YKL-40 and chitotriosidase were determined in serum samples from 93 patients with primary prostate cancer and 61 patients with benign prostatic hyperplasia. Serum YKL-40 levels were measured by ELISA and chitotriosidase activity was determined by fluorometer. PSA levels were also measured by using an automated system. RESULTS: Serum YKL-40 levels were significantly higher (P < 0.001) in patients with prostate cancer compared with control group whereas there was no significant difference between BPH and control group. Serum chitotriosidase activities were significantly higher in carcinoma patients with high Gleason score than the control group (P < 0.001). No significant difference was observed in BPH patients (P > 0.05). Both YKL-40 and chitotriosidase were found statistically significant higher in primary prostate cancer and BPH. CONCLUSION: High serum YKL-40 levels in patients with primary prostate cancer indicate that YKL-40 may have a function in the progression of malignant diseases, whereas no significant elevation was observed in benign prostatic hyperplasia. Meanwhile, high serum chitotriosidase activity was observed only in patients with Gleason high grade, indicating possible macrophage involvement in cancer progression. Further studies are needed to elucidate the biologic role of YKL-40 in cancer aggressiveness and in progression of malignant diseases.
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Biomarcadores de Tumor/sangre , Glicoproteínas/sangre , Hexosaminidasas/sangre , Hiperplasia Prostática/diagnóstico , Neoplasias de la Próstata/diagnóstico , Adipoquinas , Anciano , Proteína 1 Similar a Quitinasa-3 , Humanos , Lectinas , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/sangre , Hiperplasia Prostática/enzimología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/enzimología , Valores de ReferenciaRESUMEN
The human brain is uniquely powerful in its cognitive abilities, yet the hippocampal and neocortical circuits that mediate these complex functions are highly vulnerable during aging. In this study, we analyzed age-related changes in the rat hippocampus by studying newborn (1 month), middle-aged (12 months), and older (24 months) male and female Sprague-Dawley rats. We evaluated neuronal dystrophy, neuron scattering, and granulovacuolar degeneration in the hippocampal area using light microscopy, according to age and gender. We detected significant neuronal dystrophy in the CA1, CA2, and CA3 areas in male rats, and in the CA1, CA3, and CA4 areas in female rats. Degenerative changes, indicated by neuron scattering, were observed in the CA1, CA2, and CA3 areas of male and the CA2 and CA4 areas of female rats. Changes in all areas of the hippocampus were observed with increasing age; these changes included neuronal dystrophy and neuron scattering and did not differ significantly between male and female rats.
Asunto(s)
Envejecimiento , Hipocampo/anatomía & histología , Hipocampo/fisiología , Distrofias Neuroaxonales/fisiopatología , Factores de Edad , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Femenino , Masculino , Degeneración Nerviosa , Distrofias Neuroaxonales/patología , Neuronas/patología , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
We examined the expression pattern of cyclooxygenase-2 (COX-2) and c-kit in uterine smooth muscle neoplasms and tried to determine the role of these markers in differential diagnosis. Archival tissue from 64 patients with uterine smooth muscle neoplasms (20 leiomyomas (LMs), 22 atypical leiomyomas (ALMs), and 22 leiomyosarcomas (LMSs)) was immunostained with antibodies against estrogen (ER) and progesterone receptors (PR), COX-2 and c-kit. 7 of 20 LM cases and 5 of 22 ALM cases were immunopositive for COX-2, whereas none of the LMS cases stained immunopositive (p< or =0.05). 4 of 20 LM cases and 5 of 22 ALM cases were immunopositive for c-kit, whereas 15 of 22 LMS cases showed c-kit immunopositivity (p< or =0.05). In conclusion, very few LMs and ALMs show COX-2 immunopositivity. LMSs usually do not express COX-2. COX-2 expression in smooth muscle tumors is not a prominent feature. Therefore, COX-2 inhibitors may not be useful in LMS therapy. C-kit was significantly expressed in uterine LMSs.
Asunto(s)
Biomarcadores de Tumor/sangre , Ciclooxigenasa 2/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Tumor de Músculo Liso/diagnóstico , Neoplasias Uterinas/diagnóstico , Diagnóstico Diferencial , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Leiomiosarcoma/química , Estudios Retrospectivos , Tumor de Músculo Liso/química , Neoplasias Uterinas/químicaRESUMEN
Spindle cell lipomas are a group of benign lipogenic soft tissue tumors. Typically they occur in posterior back and shoulder of elderly male patients. Differential diagnosis of this tumor became more important because the number of reports about some other tumors of similar morphology such as mammary type myofibroblastoma and solitary fibrous tumor, are increasing. All these tumors compose of bland spindle cells, mature adipocytes and collagen bundles. In this retrospective study we evaluated clinicopathological and immunohistochemical features of 18 cases of spindle cell lipomas. 15 cases of classical spindle cell lipomas and 3 pleomorphic lipoma variant were all histologically characteristic. Immuohistochemically they were all CD34 positive. Ten cases, whose paraffin blocks available, were desmin negative. We think that spindle cell lipomas are desmin negative tumors and this feature helps us to differentiate them especially from mammary type myofibroblastomas of extramammarian soft tissue.
Asunto(s)
Lipoma/patología , Neoplasias de los Tejidos Blandos/patología , Adulto , Anciano , Antígenos CD34/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Lipoma/metabolismo , Liposarcoma/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/metabolismoRESUMEN
Chordomas are rare tumors of the spine and skull base that are locally destructive and resistant to chemotherapy and radiation therapy, with a poor prognosis and limited therapeutic options. Chordoma patients have a long life expectancy with high mortality from the disease. Cancer stem cells, which are known to exist in chordomas, have extensive proliferative and self-renewal potential and are responsible for maintaining tumor heterogeneity along with chemotherapy and radiotherapy resistance. Leukemia inhibitory factor (LIF) has multiple functions in stem cell biology, the immune response, and cancer, and is potentially a key molecule that allows cancer stem cells to self-renew. The purpose of this study was to determine whether LIF increases the aggressive traits of chordoma cells and leads to a poor prognosis in patients. Chordoma cell lines were treated with LIF, and functional tests were done. Twenty skull base chordoma samples were checked for levels of LIF and a correlation with clinicopathological features. The whole transcriptome microarray was used to observe changes in gene expression. We observed increased migration, invasion, tumorosphere formation, colony formation, epithelial-mesenchymal transition, and chemoresistance accompanied by a dramatic elevation in inflammatory gene networks and pathways in chordomas. The expression of LIF was associated with tumor size and a poorer overall survival. Microarray and quantitative real-time polymerase chain reaction assessments suggest that LIF can facilitate tumor-promoting inflammation. Results indicate that LIF plays a role in maintaining cancer stem cells in chordomas.