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1.
Amino Acids ; 55(8): 1023-1037, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37318626

RESUMO

Prostate cancer is a global disease that negatively affects the quality of life. Although various strategies against prostate cancer have been developed, only a few achieved tumor-specific targeting. Therefore, a special emphasis has been placed on the treatment of cancer using nano-carrier-encapsulated chemotherapeutic agents conjugated with tumor-homing peptides. The targeting strategy coupling the drugs with nanotechnology helps to overcome the most common barriers, such as high toxicity and side effects. Prostate-specific membrane antigen has emerged as a promising target molecule for prostate cancer and shown to be targeted with high affinity by GRFLTGGTGRLLRIS peptide known as peptide 563 (P563). Here, we aimed to assess the in vitro and in vivo targeting efficiency, safety, and efficacy of P563-conjugated, docetaxel (DTX)-loaded polymeric micelle nanoparticles (P563-PEtOx-co-PEI30%-b-PCL-DTX) against prostate cancer. To this end, we analyzed the cytotoxic activity of P563-PEtOx-co-PEI30%-b-PCL and P563-PEtOx-co-PEI30%-b-PCL-DTX by a cell proliferation assay using PNT1A and 22Rv1 cells. We have also determined the targeting selectivity of P563-PEtOx-co-PEI30%-b-PCL-FITC by flow cytometry and assessed the induction of cell death by western blot and TUNEL assays for P563-PEtOx-co-PEI30%-b-PCL-DTX in 22Rv1 cells. To investigate the in vivo efficacy, we administered DTX in the free form or in polymeric micelle nanoparticles to athymic CD-1 nu/nu mice 22Rv1 xenograft models and performed histopathological analyses. Our study showed that targeting prostate cancer with P563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelles could exert a potent anti-cancer activity with low side effects.


Assuntos
Antineoplásicos , Neoplasias da Próstata , Camundongos , Masculino , Animais , Humanos , Docetaxel , Micelas , Qualidade de Vida , Taxoides/farmacologia , Taxoides/uso terapêutico , Taxoides/química , Antineoplásicos/química , Polímeros , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Peptídeos/uso terapêutico , Linhagem Celular Tumoral
2.
Med Princ Pract ; 32(6): 358-368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37778333

RESUMO

OBJECTIVE: Appendiceal neoplasms (ANs) are rare tumors that are often discovered incidentally during histopathological examinations. The increasing incidence of ANs is a critical issue in the non-operative management of acute appendicitis. This study aimed to document the temporal trends over a 12-year period by analyzing the clinical presentation, imaging findings, and histopathological features of ANs. SUBJECTS AND METHODS: Health records of patients who underwent appendectomy from 2011 to 2022 were examined. Demographic and clinical data, laboratory results, imaging findings, and histopathological features were documented. The characteristics of both ANs and non-neoplastic cases were evaluated. RESULTS: A total of 22,304 cases were identified, of which 330 (1.5%) were diagnosed with ANs. The odds ratio for ANs increased with age, with the highest odds ratio observed in patients aged 70 or older. Receiver Operating Characteristic analysis showed that age and appendiceal diameter were significant predictors of ANs. An optimal age cut-off point of 28.5 years was determined, yielding a sensitivity of 72% and a specificity of 64%. For appendiceal diameter, the optimal cut-off was found to be 9.5 mm, exhibiting a sensitivity of 77% and a specificity of 56%. CONCLUSION: Although the incidence of ANs remains relatively low, a steady increase has been observed over the past decade. The increasing rate of ANs raises concerns regarding non-surgical management options. The results of this study highlight the importance of considering ANs as a potential diagnosis in older patients and in patients with an appendix diameter greater than 9.5 mm. These findings may have implications for treatment and management.


Assuntos
Neoplasias do Apêndice , Apendicite , Idoso , Humanos , Neoplasias do Apêndice/epidemiologia , Neoplasias do Apêndice/terapia , Neoplasias do Apêndice/patologia , Incidência , Apendicectomia , Apendicite/epidemiologia , Apendicite/terapia , Apendicite/diagnóstico , Doença Aguda , Estudos Retrospectivos
3.
Int J Cancer ; 148(2): 285-295, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32658311

RESUMO

Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low-risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.


Assuntos
Neoplasias da Mama Masculina/genética , Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Mutação em Linhagem Germinativa , Adulto , Fatores Etários , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/epidemiologia , Neoplasias da Mama Masculina/patologia , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Turquia/epidemiologia
4.
Toxicol Appl Pharmacol ; 428: 115671, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34391753

RESUMO

Breast cancer, a heterogeneous disease, has the highest incidence rate and is a major cause of death in females worldwide. Drug delivery by using nanotechnology has shown great promise for improving cancer treatment. Nanoliposomes are known to have enhanced accumulation ability in tumors due to prolonged systemic circulation. Peptide 18 (P18), a tumor homing peptide targeting keratin-1 (KRT-1), was previously shown to have high binding affinity towards breast cancer cells. In this study, we investigate the ability of P18 conjugated PEtOx-DOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of doxorubicin to AU565 breast cancer model. Toxicology studies of PEtOx-DOPE nanoliposomes performed on normal breast epithelial cells (MCF10A), showed minimal toxicity. Doxorubicin delivery by P18-PEtOx-DOPE to AU565 cells induces cytotoxicity in a dose and time dependent manner causing mitotic arrest in G2/M phase at 24 h. Anti-cancer activity of P18-PEtOx-DOPE-DOX nanoliposomes on AU565 cells was detected by Annexin V/PI apoptosis assay. In terms of in vivo antitumor efficacy, P18-PEtOx-DOPE-DOX nanoliposomes administration to AU565 CD-1 nu/nu mice model showed significant decrease in tumor volume suggesting that DOX delivered by these nanoliposomes elicited a strong antitumor response comparable to the free delivery of doxorubicin. Overall, our results offered preclinical proof for the use of P18-PEtOx-DOPE-DOX nanoliposomes in KRT-1+ breast cancer therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Fosfatidiletanolaminas/administração & dosagem , Poliaminas/administração & dosagem , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Doxorrubicina/farmacocinética , Feminino , Lipossomos , Camundongos , Camundongos Nus , Nanopartículas/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacocinética , Fosfatidiletanolaminas/farmacocinética , Poliaminas/farmacocinética , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/fisiologia
5.
Dermatol Ther ; 34(1): e14672, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33314535

RESUMO

The diagnosis of psoriasis is mainly made by clinical examination but on some occasions according to the localization or duration of the lesions when spongiosis is more prominent, it can be challenging and may be considered as overlapping eczema. To evaluate the patients for "eczema in psoriatico" and to present the differences between psoriasis. Biopsy outcomes of thirty-one patients who were histologically diagnosed with psoriasis and psoriasiform dermatitis because of the erythematous and scaly plaque lesions located on hands and feet, between 2013 and 2015, were evaluated retrospectively. Histopathologic findings compatible with psoriasis and accompanied by spongiosis and spongiotic vesicles were evaluated as eczema in psoriatico and compared with psoriasis. In this study thirty-one patients, including 18 patients with eczema in psoriatico and 13 patients with psoriasis of hands and/or feet were included. Of the 31 patients, 15 (48.4%) were women and 16 (51.6%) were men, in 61.3% of cases, biopsies were taken from hands (61.1% of "eczema in psoriatico", 61.5% of psoriasis) and 38.7% from feet (38.9% of "eczema in psoriatico", 38.5% of psoriasis). There was a statistically significant difference between two groups in terms of parakeratosis severity and distribution, the presence of neutrophil and plasma in stratum corneum, the presence of granular layer loss and suprapapillar plate thinning, the shape of retes, the presence of lymphocytic exocytosis, spongiosis and spongiotic vesicles, the intensity of infiltrates in the papillar dermis and the presence of dermal edema (P < .05). Histology supports a continuum between psoriasis and eczema that share histological similarities and at the same time should be considered a separate entity, eczema in psoriatico.


Assuntos
Dermatologia , Eczema , Psoríase , Eczema/diagnóstico , Feminino , Mãos , Humanos , Masculino , Psoríase/diagnóstico , Estudos Retrospectivos
6.
Postepy Dermatol Alergol ; 37(3): 422-427, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32792887

RESUMO

INTRODUCTION: Methotrexate and acitretin are known to be effective in the treatment of psoriasis, but the mechanisms of the effects of these drugs are not fully known. AIM: To investigate the effect of methotrexate and acitretin on microvessel density (MVD) in psoriasis. MATERIAL AND METHODS: Eighteen patients with psoriasis treated with methotrexate and 9 patients with psoriasis treated with acitretin (AT) were included in this study. MVD was evaluated immunohistochemically by using CD31 and CD105 (endoglin) antibodies. RESULTS: In the methotrexate group, the decrease in CD31 levels after treatment was found to be statistically significant, while in the AT group it was found to be highly significant. In both methotrexate and AT group, there was a statistically highly significant decrease in CD105 levels after treatment. There was no statistically significant difference between CD31 measurements of methotrexate and AT groups. When CD105 levels were measured before and after treatment, no statistically significant difference was found between methotrexate and AT. According to the results of CD31 changes before and after treatment, the CD31 difference was not statistically significant in both groups while the difference was higher in the AT group. CD105 differences were not statistically significant in both treatment groups before and after treatment. CONCLUSIONS: CD31 and CD105 dyes indicate the effects of therapies on vascular proliferation and may be indicators that can be used in daily routine and follow-up studies for psoriasis.

7.
BMC Cancer ; 19(1): 1254, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883527

RESUMO

BACKGROUND: Bag-1 (Bcl-2-associated athanogene) is a multifunctional anti-apoptotic protein frequently overexpressed in cancer. Bag-1 interacts with a variety of cellular targets including Hsp70/Hsc70 chaperones, Bcl-2, nuclear hormone receptors, Akt and Raf kinases. In this study, we investigated in detail the effects of Bag-1 on major cell survival pathways associated with breast cancer. METHODS: Using immunoblot analysis, we examined Bag-1 expression profiles in tumor and normal tissues of breast cancer patients with different receptor status. We investigated the effects of Bag-1 on cell proliferation, apoptosis, Akt and Raf kinase pathways, and Bad phosphorylation by implementing ectopic expression or knockdown of Bag-1 in MCF-7, BT-474, MDA-MB-231 and MCF-10A breast cell lines. We also tested these in tumor and normal tissues from breast cancer patients. We investigated the interactions between Bag-1, Akt and Raf kinases in cell lines and tumor tissues by co-immunoprecipitation, and their subcellular localization by immunocytochemistry and immunohistochemistry. RESULTS: We observed that Bag-1 is overexpressed in breast tumors in all molecular subtypes, i.e., regardless of their ER, PR and Her2 expression profile. Ectopic expression of Bag-1 in breast cancer cell lines results in the activation of B-Raf, C-Raf and Akt kinases, which are also upregulated in breast tumors. Bag-1 forms complexes with B-Raf, C-Raf and Akt in breast cancer cells, enhancing their phosphorylation and activation, and ultimately leading to phosphorylation of the pro-apoptotic Bad protein at Ser112 and Ser136. This causes Bad's re-localization to the nucleus, and inhibits apoptosis in favor of cell survival. CONCLUSIONS: Overall, Bad inhibition by Bag-1 through activation of Raf and Akt kinases is an effective survival and growth strategy exploited by breast cancer cells. Therefore, targeting the molecular interactions between Bag-1 and these kinases might prove an effective anticancer therapy.


Assuntos
Apoptose , Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/genética , Regulação para Cima , Proteína de Morte Celular Associada a bcl/química , Proteína de Morte Celular Associada a bcl/fisiologia , Quinases raf/metabolismo
8.
Dermatol Online J ; 25(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31046913

RESUMO

Interferon beta (IFNß) is a drug used successfully in the treatment of multiple sclerosis (MS). Although IFNß is a safe and well-tolerated drug, dermatological side effects are common. The most common dermatological adverse effect is a local reaction at the injection site. It may also cause inflammatory and immune-mediated dermatological side effects. However, morphea induced by IFNß1b injection is very rare.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Interferon beta-1b/efeitos adversos , Esclerodermia Localizada/induzido quimicamente , Adjuvantes Imunológicos/administração & dosagem , Humanos , Reação no Local da Injeção/etiologia , Reação no Local da Injeção/patologia , Injeções Subcutâneas/efeitos adversos , Interferon beta-1b/administração & dosagem , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Esclerodermia Localizada/patologia
9.
Cutan Ocul Toxicol ; 37(2): 180-185, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28838263

RESUMO

INTRODUCTION: Oxidative stress is the imbalance between oxidant-antioxidant systems and may play a major role in the psoriasis pathogenesis. Cytochrome (CYP) is a family of enzymes that are responsible for the metabolism of various endogenous and exogenous substances such as drug metabolism. Most importantly, the antioxidant system is the glutathione S-transferases (GST), which decrease oxidative stress by reducing oxidative products. AIM: We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process. MATERIAL AND METHODS: This study included 21 patients with psoriasis and 22 healthy subjects. We treated all the patients with 10-15 mg/week of MTX for minimum 12 weeks. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. RESULTS: GSTK1, GSTM1 and GSTT1 expressions were significantly higher in the psoriasis tissues than in the control tissues (p < 0.05; p < 0.05; p < 0.05, respectively). In the psoriasis patients, GSTO1 expression was similar the control group. CYP1B1 and CYP2E1 expressions were significantly higher in the pre-treatment and post-treatment psoriasis tissues than in the control tissues (p < 0.05; p < 0.05; p < 0.05; p < 0.05, respectively). CONCLUSION: We found a significant increase in the tissue levels of, either expression of GST, or CYP, which has important role in drug metabolism and oxidative stress. MTX treatment resulted in marked clinical improvement, yet we found that MTX did not have any significant effect on these parameters. CYP2E1 is especially the most important enzyme for MTX metabolism since it is the primarily responsible of the toxic metabolism of various drugs. The other experimental studies involving greater number of patients and other different drug are needed to enlighten the role of oxidant and antioxidant systems and the other possible mechanisms for the pathogenesis of psoriasis.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Fármacos Dermatológicos/farmacologia , Glutationa Transferase/metabolismo , Metotrexato/farmacologia , Psoríase/enzimologia , Adolescente , Adulto , Feminino , Humanos , Isoenzimas/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Psoríase/tratamento farmacológico , Psoríase/patologia , Adulto Jovem
10.
Cutan Ocul Toxicol ; 35(2): 157-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26339719

RESUMO

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a type IV hypersensitivity reaction characterized by a symmetrical erythematous rash in the gluteal and intertriginous areas. SDRIFE was previously considered to be the same presentation as Baboon Syndrome, however, has been suggested to be a different entity in the recent publications. The lesions are generally maculopapular and there is no mucosal involvement. To date, no case with petechial findings and mucosal involvement has been reported in the literature. The present study reports a SDRIFE case with a symmetrical erythematous petechial rash and oral mucosal involvement after taking oral amoxicillin.


Assuntos
Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Toxidermias/etiologia , Exantema/induzido quimicamente , Mucosa Bucal/patologia , Púrpura/induzido quimicamente , Adulto , Toxidermias/patologia , Exantema/patologia , Humanos , Masculino , Púrpura/patologia
11.
Cutan Ocul Toxicol ; 35(4): 300-9, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26695933

RESUMO

CONTEXT: Recent studies have shown that tolls like receptors (TLRs) and antimicrobial peptides (hBD-1, cathelicidin) play an important role in the pathogenesis of acne vulgaris (AV). OBJECTIVE: To evaluate and report the expression of TLR-2, TLR-4, hBD-1 and cathelicidin in different regions of skin in AV. PARTICIPANTS: This study was performed in 80 patients with AV and a control group of 20 healthy individuals. MATERIAL AND METHODS: Skin biopsies were performed from 20 papular, 20 pustular, 20 comedonal and 20 nodular lesions of patients and 20 healthy volunteers. Expression levels of TLR-2, TLR-4, hBD-1 and cathelicidin in four separate areas (epidermis, dermis, inflammation region and skin appendages) were evaluated by immunohistochemical method. Further, these parameters were compared between different skin lesions. RESULTS: A significant difference was found between the levels of staining of TLR-2, TLR-4 and hBD-1 from the epidermis, inflammation region, dermis and skin appendages (p < 0.05). Levels of cathelicidin were different in only the inflammation region (p < 0.05). The level of TLR-2 in the epidermis with nodules was lower than the papules and comedones (p < 0.05). Levels of TLR-2 in the inflammation and dermis of the cases with papules were significantly higher when compared to pustules (p < 0.05). The levels of staining of TLR-4 in the dermis with comedones were significantly lower compared to the cases with papules (p < 005). The level of hBD-1 in the epidermis region of comedones was significantly higher compared to nodules (p < 0.05). The expression of cathelicidin in the inflammation region of comedones was significantly low (p < 0.05). CONCLUSION: It is thought that TLR-2, TLR-4, hBD-1 and cathelicidin play an important role in the pathogenesis of AV and in the development of different acne types. We think that, better results could be obtained in treatment of AV with different treatment options targeted in regulation of TLR-2, TLR-4, hBD-1 and cathelicidin release.


Assuntos
Acne Vulgar/metabolismo , Pele/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , beta-Defensinas/metabolismo , Adolescente , Adulto , Peptídeos Catiônicos Antimicrobianos/metabolismo , Feminino , Humanos , Masculino , Adulto Jovem , Catelicidinas
12.
J Am Acad Dermatol ; 73(4): 655-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26194705

RESUMO

BACKGROUND: The frequency of genital involvement in pemphigus vulgaris (PV) has not been clearly defined. OBJECTIVES: We sought to evaluate the frequency of cervical, vaginal, and vulvar involvement in PV and to determine their association with genital symptoms, clinical involvement, and cytological status. METHODS: The current study's sample included 34 female patients with PV. Gynecologic and ear, nose, and throat examinations and indirect immunofluorescence analyses were performed, and Pap smears were collected. RESULTS: Genital involvement was observed in 44.1% of patients. It was significantly associated with disease severity and clinical involvement. Pharyngeal involvement was observed in 61.8% of patients and was the second-most frequently involved mucosal region. Genital involvement was significantly associated with nasal mucosa involvement. Cervicovaginal Pap smears showed acantholytic cells of PV in 35.3% of patients. LIMITATION: The sample size is small. CONCLUSION: Genital involvement in PV is not rare. Genital mucosa is the most affected mucosal region after oral and pharyngeal mucosa. Furthermore, genital involvement is significantly associated with nasal involvement and genital symptoms. The need for complete gynecologic evaluations of patients with PV, nasal involvement, and genital symptoms is emphasized.


Assuntos
Colo do Útero/patologia , Doenças dos Genitais Femininos/patologia , Pênfigo/patologia , Vagina/patologia , Vulva/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Feminino , Doenças dos Genitais Femininos/epidemiologia , Humanos , Imuno-Histoquímica , Incidência , Pessoa de Meia-Idade , Teste de Papanicolaou , Pênfigo/epidemiologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Esfregaço Vaginal
14.
Cutan Ocul Toxicol ; 34(4): 276-81, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25265261

RESUMO

INTRODUCTION: Psoriasis is a chronic and inflammatory skin disease. Few studies in the literature evaluate the responses to the treatment histopathologically. OBJECTIVES: In this study, we evaluated and compared skin biopsies taken from patients with psoriasis before and after phototherapy and therapy with acitretin and methotrexate. MATERIAL AND METHODS: We included 64 patients with a diagnosis of psoriasis vulgaris in our study. We performed phototherapy on 33 patients (51.6%), while 19 patients (29.7%) were treated with methotrexate and 12 patients (18.8%) were treated with acitretin. RESULTS: All of the patients had chronic plaque psoriasis, and they had skin lesions on more than 10% of their total body surface area and a score of PASI of 7.2-21.8 (average: 12.2). The histopathological parameter scores were similar in the initial evaluations of the pre-treatment treatment groups. When the biopsy specimens of all cases were evaluated together, a significant decrease was observed in terms of parakeratosis, Munro's microabscesses, regular acanthosis, pustules of Kogoj, lymphocyte infiltration in the papillary dermis, loss of the granular layer, spongiosis, suprapapillary thinning, vascularity in the papillary dermis and neutrophile infiltration in the papillary dermis. CONCLUSION: We found in our study that conventional treatment modalities provided histopathologically significant recovery in psoriasis, but they did not have an effect on some histopathological findings. To our knowledge, it is one of the few studies to assess these parameters in psoriasis under the continuous effect of acitretin, methotrexate and phototherapy for three months. There is a need for studies with larger series to examine the histopathological effects of these treatment modalities in terms of immunopathology.


Assuntos
Acitretina/uso terapêutico , Metotrexato/uso terapêutico , Fototerapia/métodos , Psoríase/terapia , Pele/patologia , Acitretina/administração & dosagem , Adulto , Biópsia , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Psoríase/tratamento farmacológico , Psoríase/patologia , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Resultado do Tratamento
15.
Mol Biol Rep ; 41(12): 7937-43, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25156535

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is a complex disease and inflammation is a crucial component in the disease pathogenesis. Recent genome wide association studies in hepatology area highlighted significant relations with human leukocyte antigen (HLA) DQ region and certain liver diseases. The previous animal models also emphasized the involvement of adaptive immune system in the liver damage pathways. To investigate possible polymorphisms in the HLA region that can contribute to the immune response affecting the NAFLD, we enrolled 93 consecutive biopsy proven NAFLD patients and a control group consisted of 101 healthy people and genotyped HLA DQB1 alleles at high resolution by sequence specific primers-polymerase chain reaction. The mean NAFLD activity score (NAS) was 5.2 ± 1.2, fibrosis score was 0.9 ± 0.9, ALT was 77 ± 47.4 U/L, AST was 49.4 ± 26.3 U/L. Among 13 HLA DQB1 alleles analyzed in this study, DQB1*06:04 was observed significantly at a more frequent rate among the NAFLD patients compared to that of healthy controls (12.9 vs. 2 % χ(2) = 8.6, P = 0.003, P c = 0.039, OR: 7.3 95 % CI 1.6-33.7). In addition, the frequency of DQB1*03:02 was significantly higher in the healthy control group than the NAFLD patients (24.8 vs. 7.5 %, χ(2) = 10.4, P = 0.001, P c = 0.013, OR: 0.2, 95 % CI 0.1-0.6). NAFLD patients were grouped according to their fibrosis score and NAS. The distribution of DQB1 alleles over stratified NAFLD patients did not reveal any statistically significant relation. Taken together, immune repertoire of individuals may have an effect on NAFLD pathogenesis and therefore, in NAFLD, adaptive immunity pathways should be investigated.


Assuntos
Alelos , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético
16.
Urol Int ; 92(3): 369-72, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24051997

RESUMO

Synovial Sarcoma (SS) is a soft tissue neoplasm that occurs generally in the proximity of large joints. Here, we report a case of a 45-year-old man who was diagnosed with Primary SS of the kidney which is an extremely rare tumor that accounts for less than 2% of malignant renal tumors. We also review the literature on primary synovial sarcomas of the kidney and focus especially on the renal tumors' differential diagnosis.


Assuntos
Neoplasias Renais/patologia , Sarcoma Sinovial/patologia , Biomarcadores Tumorais/análise , Biópsia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Neoplasias Renais/química , Neoplasias Renais/cirurgia , Laparoscopia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Valor Preditivo dos Testes , Sarcoma Sinovial/química , Sarcoma Sinovial/cirurgia
17.
North Clin Istanb ; 11(2): 158-166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38757103

RESUMO

OBJECTIVE: Although the role of MMPs in the pathogenesis of melanoma is known, few studies have investigated their role in the development of nevi and dysplastic nevi. This study aims to search the expression differences of MMP-9, MMP-13, MMP-21, and TIMP-1 between malignant melanoma (MM), intradermal nevi (IDN), and dysplastic nevi (DN). METHODS: MMP-9, MMP-13, MMP-21, and TIMP-1 antibodies were studied immunohistochemically for 60 cases in our pathology clinic archive between 2013 and 2014. RESULTS: The MM group had the highest expression percentage and intensity for MMP-9 (p<0.001). There was no statistical significance between MMP-13 expression intensities of lesion cells and stromal cells and stromal expression intensities (p>0.05). MMP-21 lesion staining intensities in DN and MM compared to IDN were statistically significant (p=0.001, p=0.011, respectively). For TIMP-1, there was a significant difference between the IDN and the MM group regarding the staining proportion of lesion cells (p<0.01). There was a statistically significant difference in all groups according to lesion cells' expression intensity. (IDN-DN p<0.001, IDN-MM p=0.044, DN-MM p<0.001). CONCLUSION: The following markers can be helpful when lesions cannot be differentiated; increased staining proportions and intensity of MMP-9 in both lesion and stromal cells favor MM in cases where MM and IDN cannot be differentiated. The increased MMP-13 staining proportion of lesion cells can favor DN in cases where the pathologist cannot differentiate DN and MM. Intense expression of MMP-21 by lesion cells can be a potential marker for evaluating the lesion in favor of DN in cases where DN and IDN cannot be differentiated. The high expression intensity of TIMP-1 in lesion cells can favor DN in cases where there is ambiguity between DN and MM. High expression proportion and intensity of stromal cells of TIMP-1 can be useable in favor of MM in cases where MM and DN cannot be differentiated.

18.
Int J Surg Pathol ; 32(2): 252-262, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37151027

RESUMO

Background. Dermatopathic lymphadenopathy is a well-defined histopathological entity with an underestimated prevalence in the general population. Objective. The present study was conducted to analyze the characteristics of histologically diagnosed cases of dermatopathic lymphadenopathy at our unit. We also aimed to investigate any association between the clinical features of the patients and the histological findings. Methods. A total of 39 lymph node samples from 39 patients diagnosed with dermatopathic lymphadenopathy were included in this prospective cohort study. Results. Thirty-four (87%) patients had a dermatological disorder. The presence of paracortical eosinophils were significantly higher in patients with dermatological disorders (P = .001), while the presence of dilated sinuses was significantly more common in patients without a dermatological disorder (P = .035). The presence of dilated sinuses and medullary histiocytes were significantly more common in patients with lower body surface area involvement of the disease compared to the ones with a higher body surface area (P = .003, P = .034; respectively). Conclusion. Most of the patients included in the study had one of a broad spectrum of undiagnosed dermatological disorders. The clinical significance of the relation between histological and clinical findings in dermatopathic lymphadenopathy remains to be explained. Dermatopathic lymphadenopathy should always be considered in differential diagnoses of patients with persistent lymph node enlargement even when absolute dermatological disorders are not present. Since various skin disorders may be the cause of lymphadenopathy, performing a full-body examination before lymph node excision might prevent unneccessary procedures.


Assuntos
Linfonodos , Linfadenopatia , Humanos , Estudos Prospectivos , Linfadenopatia/diagnóstico , Excisão de Linfonodo , Biópsia
19.
ScientificWorldJournal ; 2012: 426732, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22973172

RESUMO

BACKGROUND: There are not many studies investigating histomorphological changes in 48 sessions in patients with early-stage MF after narrowband UVB (NBUVB) treatment. Our purpose is to evaluate histological features of phototherapy after 48 sessions and determine which parameters are more reliable for controlling skin biopsies. METHODS: Biopsies of 32 patients with early stage of MF, who were treated with NBUVB phototherapy, were histologically evaluated before and after the treatments, including epidermotropism, stratum corneum, epidermal thickness, dermal infiltration, papillary dermal fibrosis, vascular alterations, and other dermal changes. We discuss the histomorphological effects of NBUVB phototherapy on skin biopsies by comparing the responders with nonresponders, with before and after the treatment. RESULTS: 9 patients (28%) did not give any response to treatment. Alleviation in epidermotropism, increases in parakeratosis and normal keratosis, perivascular infiltration, and melanophages, decrease in the lichenoid/patchy lichenoid infiltration pattern after the treatment was statistically significant. Comparing by response, normalization of stratum corneum and epidermis, orthohyperkeratosis, decrease in linearly arranged cells, the lichenoid/patchy lichenoid infiltration, the loss of inflammation were statistically significant in responders group. CONCLUSION: We detected a significant decrease in linearly arranged cells after phototherapy, indicating that it is an "important diagnostic parameter" in evaluation of therapeutic response.


Assuntos
Micose Fungoide/patologia , Micose Fungoide/terapia , Pele/patologia , Terapia Ultravioleta/métodos , Adulto , Idoso , Biópsia/métodos , Epiderme/patologia , Feminino , Humanos , Hiperplasia/patologia , Inflamação/patologia , Inflamação/terapia , Ceratose/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paraceratose/patologia , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Telangiectasia/patologia , Resultado do Tratamento
20.
Comp Hepatol ; 10: 5, 2011 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-21813017

RESUMO

Situs inversus totalis is is a congenital anomaly associated with various visceral abnormalities, but there is no data about the relationship between secondary biliary cirrhosis and that condition. We here present a case of a 58 year-old female with situs inversus totalis who was admitted to our clinic with extrahepatic cholestasis. After excluding all potential causes of biliary cirrhosis, secondary biliary cirrhosis was diagnosed based on the patient's history, imaging techniques, clinical and laboratory findings, besides histolopathological findings. After treatment with tauroursodeoxycholic acid, all biochemical parameters, including total/direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gama glutamyl transferase, returned to normal ranges at the second month of the treatment. We think that this is the first case in literature that may indicate the development of secondary biliary cirrhosis in a patient with situs inversus totalis. In conclusion, situs inversus should be considered as a rare cause of biliary cirrhosis in patients with situs inversus totalis which is presented with extrahepatic cholestasis.

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