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1.
APMIS ; 128(2): 136-149, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32003084

RESUMO

The purpose of the study was to investigate the association between infectious agents and the development of cancer in the ocular adnexa. A comprehensive literary study was carried out, reviewing and summarizing previous reports on the topic. A broad range of malignancies of the ocular adnexa are associated with infectious agents. A strong association and possible causal relationship between the infectious agent and the development of ocular adnexal cancer are seen in Merkel cell carcinoma (Merkel cell polyomavirus), Burkitt lymphoma (Epstein-Barr virus) and Kaposi sarcoma (human herpesvirus 8). Infection with Chlamydia psittaci has been associated with the development of extranodal marginal zone B-cell lymphoma in Italy. Human papillomavirus infection has been associated with the development of squamous cell carcinomas of the ocular adnexa, although with a highly variable reported prevalence. By exploring the role of infectious agents in the ocular adnexa and the mechanism by which they contribute to oncogenesis, the diagnostics, management and prevention of these malignancies may also improve. Antibiotic treatment and vaccines against infectious agents may be valuable in future treatment. Additionally, the presence of infectious agents within the tumours may have a prognostic or predictive value.


Assuntos
Doenças Transmissíveis/complicações , Neoplasias Oculares/etiologia , Antibacterianos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/microbiologia , Carcinoma de Células Escamosas/virologia , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/virologia , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/microbiologia , Neoplasias Oculares/virologia , Humanos , Itália
2.
Zhonghua Yan Ke Za Zhi ; 55(5): 374-380, 2019 May 11.
Artigo em Chinês | MEDLINE | ID: mdl-31137150

RESUMO

Objective: To evaluate the clinicopathological features of ocular natural killer(NK)/T cell lymphoma. Methods: Data of 21 patients (22 eyes) with ocular NK/T cell lymphoma treated at Eye & ENT Hospital of Fudan University from January 2006 to March 2018 were retrospectively analyzed for clinical data, morphology, immunophenotype and outcomes. Results: There were 10 males and 11 females with ages from 3 to 77 years (mean, 43 years). There were 20 unilateral cases (10 left eyes and 10 right eyes) and 1 bilateral case. Except for 1 case of corneal perforation resulting from the involvement of the conjunctiva and cornea, the other cases all involved the orbit (including eyelids and conjunctiva) as demonstrated by radiologic studies, with the lacrimal sac involved in 3 cases, and the nasal cavity or maxillary sinus involved in 2 cases. Three patients had been previously diagnosed sinonasal NK/T cell lymphoma with radiotherapy and chemotherapy. Two patients had a history of ovarian NK/T cell lymphoma with chemotherapy. One patient had multiple ulcers of skin and mucosa at presentation. There were 13 primary ocular NK/T cell lymphomas without evidence of nasal or systemic involvement. All patients presented with eyelid swelling and decreased visual acuity. There were proptosis in 18 cases, motility restriction in 13 cases, eyelid ulceration in 3 cases, and fever in 4 cases. They had all been previously diagnosed as orbital pseudotumor or cellulitis and there was no response to steroids and antibiotics. Pathological examination showed atypical lymphoid infiltration with an angioinvasive growth pattern causing coagulative necrosis. Cytologically, the medium-sized neoplastic cells showed irregular folded nuclei. The neoplastic cells were positive for cytoplasmic CD3ε, CD56, and cytotoxic molecules and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization. Seven patients were lost to follow-up. Ten patients died 2.0 to 17.0 months after diagnosis (mean, 6.3 months) despite treatment with chemotherapy and radiotherapy. Conclusions: Ocular NK/T cell lymphoma is a rare form of ocular lymphoma. There are primary NK/T cell lymphoma and secondary ocular NK/T cell lymphoma with nasal or systemic involvement. The rarity of this tumor and inflammatory signs make it challenging to identify these tumors early. The neoplastic cells are positive for cytoplasmic CD3ε, CD56, cytotoxic molecules and EBER in situ hybridization. Despite aggressive therapy, it demonstrates high lethality with poor prognosis. (Chin J Ophthalmol, 2019, 55: 374-380).


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Neoplasias Oculares/patologia , Células Matadoras Naturais/patologia , Linfoma de Células B , Linfoma de Células T/patologia , Neoplasias Orbitárias/patologia , Neoplasias Cutâneas/patologia , Linfócitos T/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/imunologia , Neoplasias Oculares/imunologia , Neoplasias Oculares/terapia , Neoplasias Oculares/virologia , Feminino , Humanos , Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/virologia , Resultado do Tratamento , Adulto Jovem
3.
Int J Oncol ; 54(5): 1503-1510, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896784

RESUMO

Human papillomavirus (HPV) infection has been implicated as a primary cause of lesions in the anogenital region, skin, oropharynx and respiratory tract. Additionally, the role of HPV in the pathogenesis of ocular surface disease has also been extensively studied. Conjunctival papilloma development has been strongly associated with the HPV infection of certain subtypes. On the other hand, the role of HPV in conjunctival pterygium, conjunctival intraepithelial neoplasia (CIN) and ocular surface squamous neoplasia (OSSN) remains controversial. Genetic predisposition and environmental factor is important in HPV hosts as regards the pathogenesis of ocular surface disease. Several studies have indicate a synergic role of HPV with ultraviolet radiation in pterygium establishment. A higher recurrence risk rate and more aggressive disease of ophthalmic pterygium is observed in cases of HPV infection. The purpose of this review was to provide a systematic review of the literature and to assist in a better understanding of the role of HPV in ocular surface disease.


Assuntos
Túnica Conjuntiva/anormalidades , Neoplasias Oculares/epidemiologia , Infecções por Papillomavirus/diagnóstico , Pterígio/epidemiologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/virologia , Túnica Conjuntiva/virologia , Neoplasias da Túnica Conjuntiva/virologia , Neoplasias Oculares/virologia , Humanos , Pterígio/virologia
4.
Medicine (Baltimore) ; 98(2): e13944, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30633172

RESUMO

The aim of this study was to identify the association between human papilloma virus (HPV) infection and ocular surface squamous neoplasia (OSSN) using p16 immunohistochemistry (IHC) and deoxyribonucleic acid (DNA) chip test.Thirty-eight patients who underwent surgical excision of OSSN were retrospectively studied using tissue samples. The IHC was performed to assess the expression of p16 and DNA chip test was used to detect 24 HPV serotypes.Among the 38 OSSN samples, 32 cases (84.2%) were histopathologically categorized as pre-invasive type and 6 cases (15.8%) as invasive type. The IHC for p16 showed strong positivity in 12 cases (31.6%), whereas it was negative in 26 cases (68.4%). On the other hand, only one case (2.6%) of invasive OSSN was positive for the HPV16 serotype, as assessed by DNA chip test.In OSSN, p16 expression was positive in approximately 1/3rd of the cases, whereas the majority of the 24 HPV serotypes were negative for p16. Our findings suggest that only a weak association exists between HPV infection and OSSN.


Assuntos
Neoplasias Oculares/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Neoplasias Oculares/virologia , Feminino , Genótipo , Papillomavirus Humano 16/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Estudos Retrospectivos , Adulto Jovem
5.
Clin Cancer Res ; 25(4): 1280-1290, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30420449

RESUMO

PURPOSE: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies. EXPERIMENTAL DESIGN: We present next-generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from eight OA sebaceous carcinomas from 29 patients. RESULTS: We delineate two potentially distinct molecular-genetic subtypes of OA sebaceous carcinoma. The first is defined by somatic mutations impacting TP53 and/or RB1 [20/29 (70%) patients, including 10 patients whose primary tumors contained coexisting TP53 and RB1 mutations] with frequent concomitant mutations affecting NOTCH genes. These tumors arise in older patients and show frequent local recurrence. The second subtype [9/29 (31%) patients] lacks mutations affecting TP53, RB1, or NOTCH family members, but in 44% (4/9) of these tumors, RNA sequencing and in situ hybridization studies confirm transcriptionally active high-risk human papillomavirus. These tumors arise in younger patients and have not shown local recurrence. CONCLUSIONS: Together, our findings establish a potential molecular-genetic framework by which to understand the development and progression of OA sebaceous carcinoma and provide key molecular-genetic insights to direct the design of novel therapeutic interventions.


Assuntos
Neoplasias Oculares/genética , Infecções por Papillomavirus/genética , Proteínas de Ligação a Retinoblastoma/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisto Epidérmico/genética , Cisto Epidérmico/patologia , Cisto Epidérmico/virologia , Neoplasias Oculares/patologia , Neoplasias Oculares/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias de Anexos e de Apêndices Cutâneos/genética , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Receptores Notch/genética , Análise de Sequência de RNA , Sequenciamento Completo do Exoma
6.
Arch Pathol Lab Med ; 142(6): 706-710, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29848037

RESUMO

CONTEXT: - Human papillomavirus (HPV) has a well-known role in the pathogenesis of squamous cell carcinoma and precursor lesions of the cervix, anogenital region, and head and neck, but its role in the development of squamous neoplasms of the eye, particularly the conjunctiva, remains unclear. OBJECTIVE: - To review recent evidence implicating HPV in the pathophysiology of ocular lesions. DATA SOURCES: - Published articles obtained from a PubMed search of the English literature were the primary sources for this review. CONCLUSIONS: - The low-risk HPV types 6 and 11 appear to play a role in the development of at least a subset of conjunctival squamous papillomas. The role of HPV in the pathogenesis of pterygium and ocular surface squamous neoplasia is less well defined. There is evidence to suggest that HPV may be a cofactor in the development of these lesions, acting in concert with ultraviolet radiation and/or human immunodeficiency virus infection in a subgroup of cases.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Oculares/virologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Pterígio/virologia , Carcinoma de Células Escamosas/fisiopatologia , Neoplasias da Túnica Conjuntiva/fisiopatologia , Neoplasias da Túnica Conjuntiva/virologia , Neoplasias Oculares/fisiopatologia , Papillomavirus Humano 11/fisiologia , Papillomavirus Humano 16/fisiologia , Humanos , Papiloma/fisiopatologia , Papiloma/virologia , Infecções por Papillomavirus/fisiopatologia , Pterígio/fisiopatologia , Raios Ultravioleta
8.
Ophthalmic Plast Reconstr Surg ; 33(1): e16-e18, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-25719371

RESUMO

Epstein-Barr virus-associated undifferentiated (lymphoepithelial) carcinoma is a malignancy that most commonly arises in the nasopharynx but can also occur in other locations including the lacrimal sac. Generally, this tumor strongly expresses cytokeratin, making the diagnosis straightforward. In the absence of confirmatory immunohistochemistry, the diagnosis can be problematic, particularly for tumors arising in unusual locations. Only 3 cases arising in the lacrimal sac in association with Epstein-Barr virus have been reported in the English literature, and all showed typical pathologic findings. The authors report a fourth case, unique in that it showed negative immunostaining for all cytokeratins tested. The clue to the nature of the tumor came from identification of Epstein-Barr virus by in-situ hybridization and demonstration of tonofilaments by electron microscopy. This case demonstrates that a multimodal approach may be needed in the diagnosis of Epstein-Barr virus-associated carcinoma, especially when occurring in uncommon locations.


Assuntos
Carcinoma de Células Escamosas/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Neoplasias Oculares/patologia , Doenças do Aparelho Lacrimal/patologia , Idoso , Carcinoma de Células Escamosas/virologia , Neoplasias Oculares/virologia , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Queratinas/metabolismo , Doenças do Aparelho Lacrimal/virologia
9.
Am J Surg Pathol ; 40(4): 519-28, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26735858

RESUMO

High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12.5%) was predominantly keratinizing. The presence of HR-HPV in 30% of OSSNs and at least 66.7% of LSSCCs suggests the possibility of an etiologic role for HR-HPV at these sites.


Assuntos
Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/virologia , Neoplasias da Túnica Conjuntiva/virologia , Ducto Nasolacrimal/virologia , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias Oculares/patologia , Neoplasias Oculares/virologia , Feminino , Papillomavirus Humano 16 , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Ducto Nasolacrimal/patologia , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia
10.
Pediatr Dev Pathol ; 19(2): 132-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26230054

RESUMO

Epstein-Barr virus (EBV) has oncogenic potential and has been implicated in the etiology of a wide range of malignancies. Certain EBV-driven neoplasms, such as smooth muscle tumors (SMTs), manifest typically in immunocompromised patients. In children, these neoplasms have been encountered in the setting of primary immune disorders, specifically severe combined and common variable immunodeficiency syndromes. Human immunodeficiency virus infection and posttransplant immunosuppression, in particular liver and kidney transplantation, likewise increase the risk in the pediatric population. The location of these neoplasms appears related to the type of immunodeficiency: in acquired immunodeficiency syndrome they are frequently located intracranially or intraspinally, whereas after transplant they usually involve the liver or lung. We report 2 distinct cases of EBV-related SMT, unique through their coassociated immunosuppressive state or location: the 1st occurred in a patient with immunodeficiency secondary to NEMO gene mutation following hematopoietic stem cell transplantation; the 2nd developed in the orbit after heart transplant.


Assuntos
Neoplasias Oculares/virologia , Herpesvirus Humano 4/isolamento & purificação , Tumor de Músculo Liso/virologia , Neoplasias Esplênicas/virologia , Actinas/análise , Adulto , Autopsia , Biomarcadores Tumorais/análise , Biópsia , Displasia Ectodérmica/genética , Displasia Ectodérmica/imunologia , Displasia Ectodérmica/cirurgia , Neoplasias Oculares/imunologia , Neoplasias Oculares/patologia , Neoplasias Oculares/terapia , Evolução Fatal , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/cirurgia , Transplante de Coração/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/cirurgia , Imunossupressores/efeitos adversos , Hibridização In Situ , Lactente , Masculino , Doenças da Imunodeficiência Primária , RNA Viral/genética , Fatores de Risco , Tumor de Músculo Liso/imunologia , Tumor de Músculo Liso/patologia , Tumor de Músculo Liso/terapia , Neoplasias Esplênicas/imunologia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia
11.
Avian Pathol ; 44(5): 347-51, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26021782

RESUMO

Two 1-year old Roulroul partridges (Rollulus rouloul), one male and one female, were presented because of eye problems and anorexia. Twenty of the 30 Roulroul partridges in the owner's collection had already died. The affected birds stopped eating, became thinner, and eventually died. Antibiotic treatment, which started because of the suspicion of a septicaemic process, was unsuccessful. At clinical examination of the two partridges it was found that in both birds, one eye ball was filled with a whitish yellow amorphous material and the other eye ball of the female showed a distinct corneal opacity. Both presented birds were euthanized. Necropsy revealed no significant abnormalities in addition to the eye lesions. Histology and immunohistochemistry of the female's eye revealed an infiltrate of T-lymphocytes corresponding to ocular lymphoma. Herpesvirus genus-specific PCR, followed by Sanger sequencing confirmed the presumptive diagnosis of Marek's disease in both birds. To our knowledge, this is the first confirmed case of infection with Gallid Herpesvirus 2 (Marek's disease virus) in partridges and the first case in this specific species.


Assuntos
Doenças das Aves/virologia , Neoplasias Oculares/veterinária , Herpesvirus Galináceo 2/isolamento & purificação , Linfoma/veterinária , Doença de Marek/virologia , Animais , Doenças das Aves/patologia , Neoplasias Oculares/patologia , Neoplasias Oculares/virologia , Feminino , Galliformes , Linfoma/patologia , Linfoma/virologia , Masculino , Doença de Marek/patologia
12.
Am J Dermatopathol ; 37(1): 20-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25162933

RESUMO

Hydroa vacciniforme-like lymphoma (HVL) is a rare cutaneous T-cell lymphoma that is usually seen in children of Hispanic or Asian origin. Association between chronic latent Epstein-Barr virus infection in both hydroa vacciniforme (HV) and HVL has been demonstrated and has recently been categorized by the World Health Organization as one of the Epstein Barr virus-positive lymphoproliferative disorders of childhood. Patients with HVL present with a cutaneous rash characterized by edema, blisters, ulcers, and scars mainly seen on the face and extremities that mimic HV; however, unlike in HV, the lesions tend to be extensive and deeper and are associated with severe scarring, necrosis, and systemic manifestations. We are reporting 7 cases of an unusual clinical variant of HVL with primarily periorbital edema. All of our patients in this series presented with progressive periorbital edema that was accompanied with systemic symptoms including fever, malaise, and lymphadenopathy. Most cases were initially misinterpreted as inflammatory processes including cellulitis, arthropod bite reactions, and periorbital lupus erythematosus. The biopsy of these lesions revealed an atypical lymphocytic infiltrate predominantly distributed in the deep dermis and in subcutaneous fat. Immunohistochemistry studies revealed a cytotoxic T-cell (CD8) profile. All cases were associated with Epstein-Barr virus infection. Our study presents a rare clinical variant of HVL with predominant periorbital edema. This variant could potentially be overlooked and misdiagnosed as an inflammatory condition; thus, it needs to be included in the differential diagnosis of periorbital edema in young patients.


Assuntos
Edema/patologia , Neoplasias Oculares/patologia , Hidroa Vaciniforme/patologia , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Adolescente , Biomarcadores Tumorais/análise , Biópsia , Criança , Diagnóstico Diferencial , Edema/etiologia , Edema/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/virologia , Neoplasias Oculares/química , Neoplasias Oculares/classificação , Neoplasias Oculares/terapia , Neoplasias Oculares/virologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Hidroa Vaciniforme/classificação , Hidroa Vaciniforme/terapia , Hidroa Vaciniforme/virologia , Imuno-Histoquímica , Hibridização In Situ , Linfoma Cutâneo de Células T/química , Linfoma Cutâneo de Células T/classificação , Linfoma Cutâneo de Células T/terapia , Linfoma Cutâneo de Células T/virologia , Masculino , Valor Preditivo dos Testes , RNA Viral/genética , Neoplasias Cutâneas/química , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/virologia
13.
Mol Med Rep ; 9(2): 547-52, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24337676

RESUMO

The autogenic lens tumors induced by the Simian vacuolating virus 40 (SV40) T antigen in α-crystallin/SV40 T antigen transgenic (TG) mice, provide a tool to screen anti-tumor reagents in vivo and to clarify the underlying mechanisms. Juzen-taiho-to, a Chinese medicine composed of 10 herbs, was frequently used as an alternative medicine for cancer patients by clinicians and occasionally it was demonstrated to have beneficial effects on the prognosis and general condition of cancer patients. However, it was not scientifically verified. In the present study, the anti-tumor effects and underlying mechanisms of Juzen-taiho-to in the TG mice model was examined using cDNA microarray analysis and the results were confirmed by real-time PCR. The TG mice demonstrated a higher cumulative survival rate after treatment with the drug compared with the control group (P<0.05). Gene chip profiles demonstrated that cell functions involving the membrane, glycoprotein, cell membrane, signal and ionic channel for the lens tumor, the cell cycle, DNA replication, homeobox, mitosis and cell division for the spleen and the acetylation, mitochondrion, ribosomal protein, ribonucleoprotein for the liver, were altered by the administration of Juzen­taiho-to. The important canonical pathways were those of the mitogen-activated protein kinase (MAPK), the cell cycle and the ribosome for the altered genes of the lens tumor, spleen and liver after drug administration, respectively. From real-time PCR, in the eyeball, epidermal growth factor receptor (Egfr), Rasgrf1 and heat shock protein 1B (Hspa1b) mRNAs were found to be significantly lower in treated lenses than in those not exposed to the drug, while Rps25 mRNA demonstrated the opposite association in the liver. It was suggested that Juzen-taiho-to may prolong the survival time of SV40 T antigen TG mice by improving their nutritional condition, inhibiting the MAPK pathway and strengthening the immune system without causing hepatic toxicity.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/genética , alfa-Cristalinas/metabolismo , Animais , Antígenos Transformantes de Poliomavirus/genética , Neoplasias Oculares/patologia , Neoplasias Oculares/virologia , Perfilação da Expressão Gênica , Cristalino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Análise de Sequência com Séries de Oligonucleotídeos , Vírus 40 dos Símios/patogenicidade , Baço/efeitos dos fármacos , Baço/metabolismo , alfa-Cristalinas/genética
14.
Br J Cancer ; 109(7): 1981-8, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24030075

RESUMO

BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. METHODS: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%), respectively. CONCLUSION: Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor.


Assuntos
Neoplasias Oculares/epidemiologia , Infecções por HIV/epidemiologia , Neoplasias de Células Escamosas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Neoplasias Oculares/complicações , Neoplasias Oculares/virologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Neoplasias de Células Escamosas/complicações , Neoplasias de Células Escamosas/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco
16.
Br J Ophthalmol ; 96(12): 1517-21, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22942158

RESUMO

BACKGROUND: Although human papillomavirus (HPV) has been implicated in the pathogenesis of ocular surface squamous neoplasia (OSSN), no study has so far dealt with the prognostic role of HPV. In this study the presence and significance of HPV in OSSN and its correlation with p16(INK4a) immunoexpression was determined. METHODS: HPV was detected by HPV-L1 capsid gene-specific multiplex PCR using PGMY09/11 primers, and genotyping was done by linear array on 64 OSSN patients and 15 conjunctival controls. p16(INK4a) immunoexpression as a marker for HPV presence was also evaluated. RESULTS: The HPV genome was detected in 11% of cases by multiplex PCR, and all positives belonged to a high-risk HPV16 genotype. p16(INK4a) Overexpression was seen in 28% (18/64) of cases. Control conjunctival tissues were negative for HPV and p16(INK4a) expression. The presence of HPV was associated with significantly improved disease-free survival (p=0.02) as well as p16(INK4a) overexpression (p=0.001). The sensitivity and specificity of p16(INK4a) as a marker for HPV presence was 86% and 79%, respectively, with a positive predictive value of 33% and a negative predictive value of 98%. CONCLUSIONS: The results of this study point towards HPV as a predictor of better survival in a subset of HPV-positive OSSN patients. Although p16(INK4a) immunoexpression is a useful indicator of HPV presence in OSSN, confirmation by multiplex PCR is necessary.


Assuntos
Carcinoma de Células Escamosas/virologia , DNA Viral/análise , Neoplasias Oculares/virologia , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/mortalidade , Criança , Neoplasias Oculares/complicações , Neoplasias Oculares/mortalidade , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto Jovem
18.
Vet Microbiol ; 158(1-2): 194-8, 2012 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-22386674

RESUMO

Squamous cell carcinomas (SCC) are malignant tumours arising from keratinocytes. In horses, there is increasing evidence for Equus caballus papillomavirus type 2 (EcPV-2) being causally involved in SCC development. However, only little is known regarding intralesional transcription of the virus, and sparse information on the incidence of EcPV-2 infection in healthy equids is available so far. Using RT-PCR, total mRNA from 8 EcPV-2 DNA-positive and 1 EcPV-2 negative SCC/SCC precursor lesions was screened for the presence of EcPV-2 E6 and E1 transcripts. Using PCR, we tested 193 sample specimens (30 ocular swabs, 94 genital swabs, 54 semen and 15 milk samples) from a total of 161 apparently healthy horses for the presence of EcPV-2 genes E7 and E6 or E2. Positive results were confirmed by repeating the PCR reactions, and by amplicon sequencing. E6 mRNA was detectable in 8/8 EcPV-2 DNA-positive lesions, whereas only 3/8 scored positive for E1 mRNA. EcPV-2 PCR scored positive for DNA from 1/30 ocular swabs, 4/94 genital swabs, 0/54 semen and 0/15 milk samples, thus resulting in an overall detection rate of 5/193, i.e. 2.6%. The demonstrated presence of viral mRNA in all EcPV-2 DNA-positive lesions is suggestive for an active pathogenic role of the virus in SCC development. This finding and the low incidence of EcPV-2 DNA in healthy equids further strengthen the concept of an aetiologic association of EcPV-2 with equine SCC disease.


Assuntos
Carcinoma de Células Escamosas/virologia , Doenças dos Cavalos/virologia , Cavalos/virologia , Papillomaviridae/genética , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Oculares/veterinária , Neoplasias Oculares/virologia , Doenças dos Cavalos/patologia , Proteínas Oncogênicas Virais/genética , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sêmen/virologia , Transcrição Genética , Neoplasias Urogenitais/veterinária , Neoplasias Urogenitais/virologia
19.
Eye (Lond) ; 26(2): 202-11, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22134594

RESUMO

There are more microorganisms that colonize the human body than resident cells; some are commensal whereas others are pathogenic. Pathogenic microorganisms are sensed by the innate or adaptive immune system, an immune response is initiated, and the infection is often cleared. Some microorganisms have developed strategies to evade immune defenses, ensuring their long-term survival with potentially devastating consequences for the host. Approximately 18% of all cancers can be attributed to infective agents; the most common being Helicobacter pylori, Human papilloma virus (HPV) and Hepatitis B and C virus in causing stomach, cervical and liver carcinoma, respectively. This review focuses on whether HPV infection is necessary for initiating pterygia, a common benign condition and ocular-surface squamous neoplasia (OSSN), a rare disease with metastatic potential. The search engine PubMed was used to identify articles from the literature related to HPV and pterygium or conjunctival neoplasia. From 34 investigations that studied HPV in pterygia and OSSN, a prevalence rate of 18.6% (136/731) and 33.8% (144/426), respectively, was recorded. The variation in HPV prevalence (0-100%) for both disease groups may have arisen from study-design faults and the techniques used to identify the virus. Overall, the data suggest that HPV is not necessary for initiating either condition but may be a co-factor in susceptible hosts. Currently, over 60 million people worldwide have been immunized with HPV vaccines, but any effect on pterygium and OSSN development may not be known for some time as these lesions can evolve over decades or occur in older individuals.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Oculares/virologia , Infecções por Papillomavirus/complicações , Pterígio/virologia , Neoplasias da Túnica Conjuntiva/virologia , Humanos , Limbo da Córnea/virologia , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/metabolismo , Prevalência , Proteína Supressora de Tumor p53/metabolismo
20.
Cancer Res ; 71(7): 2445-54, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21307132

RESUMO

Although intraocular tumors reside in an immune privileged site, some tumors are rejected nonetheless. For example, intraocular adenovirus-induced (Ad5E1; adenovirus type 5 early region 1) tumors are rejected in syngeneic C57BL/6 mice by one of two pathways. One pathway leads to extensive necrosis of innocent bystander cells and culminates in destruction of the eye, a condition called phthisis. The second pathway is characterized by piecemeal tumor cell death that rids the eye of the tumor while preserving the architecture and function of the eye. To study the mechanisms of phthisical tumor rejection, we isolated a cell clone-designated clone 2.1 that consistently undergoes rejection in a phthisical manner. CD4(+) T cells and macrophages were required for phthisical rejection of intraocular clone 2.1 tumors and M1 macrophages were involved in mediating tumor rejection. In vitro and in vivo inhibition of iNOS (inducible nitric oxide synthase) abolished macrophage-mediated killing of tumor cells and rejection of intraocular tumors. A role for M1 macrophages was further supported by investigations showing that intraocular tumors grew progressively in IFN-γ KO (knockout) mice. Studies in mice deficient in TNF-α, TNF receptor-1, or TNF receptor-2 revealed that although TNF-α was not needed for tumor rejection, it was required for the development of necrotizing inflammation and phthisis of tumor-bearing eyes. Together, our findings suggest new strategies to successfully eliminate ocular tumors while preserving the integrity of the eye.


Assuntos
Neoplasias Oculares/imunologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adenoviridae/genética , Proteínas E1 de Adenovirus/genética , Animais , Transformação Celular Viral , Inibidores Enzimáticos/farmacologia , Neoplasias Oculares/enzimologia , Neoplasias Oculares/genética , Neoplasias Oculares/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , NG-Nitroarginina Metil Éster/farmacologia , Linfócitos T/imunologia , Transfecção , Fator de Necrose Tumoral alfa/biossíntese
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