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1.
Reprod Fertil ; 3(3): R177-R191, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37931406

RESUMO

Abstract: The phenomenal extracellular matrix (ECM) remodelling of the cervix that precedes the myometrial contraction of labour at term or preterm appears to share some common mechanisms with the occurrence, growth, invasion and metastasis of cervical carcinoma. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are pivotal to the complex extracellular tissue modulation that includes degradation, remodelling and exchange of ECM components, which contribute to homeostasis under normal physiological conditions such as cervical remodelling during pregnancy and puerperium. However, in cancer such as that of the uterine cervix, this extensive network of extracellular tissue modulation is altered leading to disrupted cell-cell and cell-basement membrane adhesion, abnormal tissue growth, neovascularization and metastasis that disrupt homeostasis. Cervical ECM remodelling during pregnancy and puerperium could be a physiological albeit benign neoplasm. In this review, we examined the pathophysiologic differences and similarities in the role of MMPs in cervical remodelling and cervical carcinoma. Lay summary: During pregnancy and childbirth, the cervix, which is the barrel-shaped lower portion of the womb that connects to the vagina, gradually softens, shortens and opens to allow birth of the baby. This process requires structural and biochemical changes in the cervix that are stimulated by enzymes known as matrix metalloproteinases. Interestingly, these enzymes also affect the structural and biochemical framework of the cervix during cervical cancer, although cervical cancers usually occur after infection by human papillomavirus. This review is intended to identify and explain the similarities and differences between the structural and chemical changes in the cervix during pregnancy and childbirth and the changes seen in cervical cancer.


Assuntos
Carcinoma , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Animais , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/veterinária , Colo do Útero/metabolismo , Metaloproteinases da Matriz/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Carcinoma/metabolismo , Carcinoma/veterinária
2.
JCI Insight ; 3(8)2018 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-29669936

RESUMO

T cell receptor (TCR) T cell therapy is a promising cancer treatment modality. However, its successful development for epithelial cancers may depend on the identification of high-avidity TCRs directed against tumor-restricted target antigens. The human papillomavirus (HPV) E7 antigen is an attractive therapeutic target that is constitutively expressed by HPV+ cancers but not by healthy tissues. It is unknown if genetically engineered TCR T cells that target E7 can mediate regression of HPV+ cancers. We identified an HPV-16 E7-specific, HLA-A*02:01-restricted TCR from a uterine cervix biopsy from a woman with cervical intraepithelial neoplasia. This TCR demonstrated high functional avidity, with CD8 coreceptor-independent tumor targeting. Human T cells transduced to express the TCR specifically recognized and killed HPV-16+ cervical and oropharyngeal cancer cell lines and mediated regression of established HPV-16+ human cervical cancer tumors in a mouse model. These findings support the therapeutic potential of this approach and established the basis for an E7 TCR gene therapy clinical trial in patients with metastatic HPV+ cancers (NCT02858310).


Assuntos
Antígenos CD8/imunologia , Linfócitos T CD8-Positivos/imunologia , Papillomavirus Humano 16/imunologia , Infecções por Papillomavirus/genética , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Antígenos CD8/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Colo do Útero/efeitos dos fármacos , Colo do Útero/patologia , Colo do Útero/virologia , Modelos Animais de Doenças , Feminino , Terapia Genética/métodos , Papillomavirus Humano 16/genética , Humanos , Camundongos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/genética , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Receptores de Antígenos de Linfócitos T/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/veterinária , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/tratamento farmacológico , Displasia do Colo do Útero/veterinária , Displasia do Colo do Útero/virologia
3.
J Comp Pathol ; 156(4): 339-351, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28427752

RESUMO

Tumours and tumour-like lesions are rare findings in the genital system of guinea pigs. The aim of the present study was to characterize nodular lesions in the cervix and uterus of guinea pigs submitted for histopathological diagnosis. Samples from 83 pet animals were investigated. Cases included 64 surgically excised masses including complete uteri (n = 37), parts from uteri containing masses (n = 8), complete masses (n = 12) or samples from masses (n = 7) and 19 complete necropsy examinations. In 55 of the cases, only solitary changes were observed; in 28 cases two or more lesions were diagnosed. Histopathological diagnoses included polyps in the vagina, cervix or uterus (n = 8), hyperplastic lesions of the endocervix (n = 10) and seven adenomas and two adenocarcinomas of the endocervix. Endometrial alterations included single small glandular cysts (n = 3), nodular glandular-cystic hyperplasia (n = 8), adenoma (n = 20) and adenocarcinoma (n = 3). Four placentas, 10 focal decidualizations and six deciduomas were found. Furthermore, 18 leiomyomas and nine leiomyosarcomas were diagnosed. Uterine malignant mixed Müllerian tumours were observed in seven cases. Overall, benign lesions outnumbered malignant tumours in the female genital tract of pet guinea pigs. Therefore, surgical excision or ovariohysterectomy should be recommended as therapy.


Assuntos
Neoplasias do Colo do Útero/veterinária , Neoplasias Uterinas/veterinária , Animais , Feminino , Cobaias , Hiperplasia/veterinária , Estudos Retrospectivos
4.
Toxicol Pathol ; 41(7): 1016-27, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23427274

RESUMO

Nonhuman primates, particularly rhesus macaques (Macaca mulatta), provide important model systems for studying human reproductive infectious diseases such as human immunodeficiency virus, human papillomavirus, and Chlamydia spp. An understanding of the spectrum of spontaneous cervical disease provides essential context for interpreting experimental disease outcomes in the female reproductive tract. This retrospective study characterizes the incidence of inflammatory and/or proliferative cervicovaginal lesions seen over a 14-year period in a multispecies nonhuman primate colony, focusing on rhesus macaques. The most common observations included a spectrum of lymphocytic accumulation from within normal limits to lymphoplasmacytic cervicitis, and suppurative inflammation with occasional squamous metaplasia or polyp formation. These inflammatory spectra frequently occurred in the context of immunosuppression following experimental simian immunodeficiency virus (SIV) infection. Cervical neoplasias were uncommon and included leiomyomas and carcinomas. Cervical sections from 13 representative cases, with an emphasis on proliferative and dysplastic lesions, were surveyed for leukocyte infiltration, abnormal epithelial proliferation, and the presence of papillomavirus antigens. Proliferative lesions showed sporadic evidence of spontaneous papillomavirus infection and variable immune cell responses. These results underscore the importance of pre screening potential experimental animals for the presence of preexisting reproductive tract disease, and the consideration of normal variability within cycling reproductive tracts in interpretation of cervical lesions.


Assuntos
Doenças dos Primatas/patologia , Neoplasias do Colo do Útero/veterinária , Neoplasias Vaginais/veterinária , Animais , Callitrichinae , Feminino , Imuno-Histoquímica , Macaca mulatta , Papillomaviridae/imunologia , Doenças dos Primatas/imunologia , Estudos Retrospectivos , Vírus da Imunodeficiência Símia/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias Vaginais/imunologia , Neoplasias Vaginais/patologia
5.
Vet Pathol ; 50(1): 200-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22446324

RESUMO

Genital Alphapapillomavirus (αPV) infections are one of the most common sexually transmitted human infections worldwide. Women infected with the highly oncogenic genital human papillomavirus (HPV) types 16 and 18 are at high risk for development of cervical cancer. Related oncogenic αPVs exist in rhesus and cynomolgus macaques. Here the authors identified 3 novel genital αPV types (PhPV1, PhPV2, PhPV3) by PCR in cervical samples from 6 of 15 (40%) wild-caught female Kenyan olive baboons (Papio hamadryas anubis). Eleven baboons had koilocytes in the cervix and vagina. Three baboons had dysplastic proliferative changes consistent with cervical squamous intraepithelial neoplasia (CIN). In 2 baboons with PCR-confirmed PhPV1, 1 had moderate (CIN2, n = 1) and 1 had low-grade (CIN1, n = 1) dysplasia. In 2 baboons with PCR-confirmed PhPV2, 1 had low-grade (CIN1, n = 1) dysplasia and the other had only koilocytes. Two baboons with PCR-confirmed PhPV3 had koilocytes only. PhPV1 and PhPV2 were closely related to oncogenic macaque and human αPVs. These findings suggest that αPV-infected baboons may be useful animal models for the pathogenesis, treatment, and prophylaxis of genital αPV neoplasia. Additionally, this discovery suggests that genital αPVs with oncogenic potential may infect a wider spectrum of non-human primate species than previously thought.


Assuntos
Alphapapillomavirus/isolamento & purificação , Doenças dos Macacos/virologia , Papio hamadryas , Displasia do Colo do Útero/veterinária , Neoplasias do Colo do Útero/veterinária , Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Animais , Colo do Útero/química , Colo do Útero/patologia , DNA Viral/genética , Feminino , Humanos , Imuno-Histoquímica/veterinária , Antígeno Ki-67/análise , Doenças dos Macacos/patologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/veterinária , Infecções por Papillomavirus/virologia , Filogenia , Reação em Cadeia da Polimerase/veterinária , Análise de Sequência de DNA/veterinária , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vagina/patologia
6.
Toxicol Pathol ; 40(6): 926-30, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22585942

RESUMO

Wistar rats are frequently selected for use in carcinogenicity studies because of their advantageous survival rate, which is more favorable than other strains such as the Sprague-Dawley (SD) strain. Uterine and mammary tumors are relatively common spontaneous neoplasms of both strains. We examined the incidence and coincidence of uterine tumors and mammary tumors in control animals of both strains within the RITA database. There was a strong inverse relationship between these tumor types in Wistar rats (p < .001). A less strong relationship was present in SD rats (p = .057). This association is likely to be related to prolactin. A short review of the role of prolactin in rats is given. These results are also discussed in the background of nonspecific toxicity at high dose levels in carcinogenicity studies above MTD levels resulting in reduction in body weights of >10%.


Assuntos
Neoplasias Mamárias Animais/epidemiologia , Prolactina/metabolismo , Ratos Sprague-Dawley , Ratos Wistar , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/veterinária , Animais , Feminino , Incidência , Neoplasias Mamárias Animais/metabolismo , Ratos , Neoplasias do Colo do Útero/metabolismo
7.
J Med Primatol ; 41(2): 142-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22273046

RESUMO

BACKGROUND: Cervical Cancer is the second most common cancer among women. Nevertheless, similar tumours have only been rarely described in Great Apes. This report characterizes the pathological and molecular features of a metastatic endocervical adenocarcinoma in a Western lowland gorilla (Gorilla g. gorilla). METHODS: Necropsy and histopathology was performed to identify the cause of the disease in an cachectic 50-year-old western lowland gorilla. Immunohistochemistry for Ki67, oestrogen receptor alpha and ERBB2 was performed to characterize the tumor. In addition, Pan-herpesvirus and Pan-papillomavirus PCR were used to identify a possible viral cause. RESULTS: The endoccervical carcinoma showed a severe metastatic spread to the lung, brain and bone and was herpesvirus and papillomavirus-negative. Most tumor cells were ERBB2-positive, 15% of tumor cells were Ki67-positive and only few tumor cells had oestrogen receptor alpha expression. CONCLUSIONS: Histopathologically and immunohistochemically, the tumour had striking similarities to human endocervicial adenocarcinomas of the common type. However, PCR analysis failed to identify herpes- or papillomaviral DNA in the tumor at the time of necropsy, thus leaving the question for cause of the disease open.


Assuntos
Adenocarcinoma/veterinária , Doenças dos Símios Antropoides/patologia , Neoplasias Ósseas/veterinária , Neoplasias Encefálicas/veterinária , Gorilla gorilla , Neoplasias Pulmonares/veterinária , Neoplasias do Colo do Útero/veterinária , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Animais , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Receptor alfa de Estrogênio/metabolismo , Evolução Fatal , Feminino , Imuno-Histoquímica/veterinária , Neoplasias Pulmonares/secundário , Receptor ErbB-2/metabolismo , Neoplasias do Colo do Útero/patologia
8.
Acta Vet Hung ; 59(1): 123-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21354947

RESUMO

This report describes the clinical and histopathological characteristics of a squamous cell carcinoma infiltrating the cervix and the vaginal wall, producing reproductive symptoms and subnormal fertility in an adult ewe. Necropsy showed a large (15-cm-long) neoplastic mass infiltrating the vaginal wall and the cervix. Histopathological examination revealed atypical squamous epithelial cords invading the basal membrane and dermis, round anaplastic cells, focal areas of necrosis, keratinisation of isolated cells, and pronounced infiltration by mononuclear cells around the cords. No squamous cell carcinoma of such localisation has been reported from sheep before. In humans, this tumour is the most common gynaecological malignancy in the world.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças dos Ovinos/patologia , Neoplasias do Colo do Útero/veterinária , Neoplasias Vaginais/veterinária , Animais , Carcinoma de Células Escamosas/patologia , Feminino , Ovinos , Neoplasias do Colo do Útero/patologia , Neoplasias Vaginais/patologia
9.
Tijdschr Diergeneeskd ; 135(1): 4-7, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-20128305

RESUMO

A 9-year-old, female potbellied pig showed loss of appetite and abdominal distension. After clinical examination and ultrasonography, a tumour was suspected. At laparotomy a large mass was present in the genital tract. Because the mass could not be excised, the pig was euthanized. Pathological examination revealed leiomyoma of the cervix and uterus wall in addition to multifocal adenocarcinomas of the uterus.


Assuntos
Neoplasias dos Genitais Femininos/veterinária , Leiomioma/veterinária , Doenças dos Suínos/patologia , Adenocarcinoma/patologia , Adenocarcinoma/veterinária , Animais , Eutanásia Animal , Feminino , Neoplasias dos Genitais Femininos/patologia , Imuno-Histoquímica/veterinária , Leiomioma/patologia , Suínos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/veterinária , Neoplasias Uterinas/patologia , Neoplasias Uterinas/veterinária
10.
J Comp Pathol ; 140(1): 76-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19091325

RESUMO

Thickening of the uterine cervix and bilateral ovarian cystic change was identified in a 6-month-old pig during routine abattoir inspection. Microscopically, the cervical lesion comprised a non-encapsulated mass of densely packed, large and monomorphic spindle cells within the myometrium. Immunohistochemically, the majority of these neoplastic cells expressed the cytoplasmic terminal smooth muscle differentiation marker calponin, the nuclear oestrogen receptor alpha and the progesterone receptor. The ovarian cysts were classified as follicular cysts. A diagnosis of leiomyoma of the uterine cervix with bilateral ovarian follicular cysts was made. The expression of calponin as a marker of smooth muscle differentiation in tumours of the genital tract of the pig has not previously been reported. The expression of steroid hormone receptors suggests a role for steroid hormones derived from the ovarian follicular cysts in tumourigenesis.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Leiomioma/veterinária , Proteínas dos Microfilamentos/metabolismo , Receptores de Esteroides/metabolismo , Doenças dos Suínos/metabolismo , Neoplasias do Colo do Útero/veterinária , Animais , Biomarcadores Tumorais/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Leiomioma/metabolismo , Leiomioma/patologia , Receptores de Progesterona/metabolismo , Suínos , Doenças dos Suínos/patologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Calponinas
11.
Can Vet J ; 49(2): 177-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18309748

RESUMO

An adult female Toggenburg goat with a history of acute vaginal bleeding and death was presented for postmortem examination. Necropsy, histologic examination, and immunohistochemical staining revealed the presence of a leiomyoma that originated from the uterine cervix, occupied most of the vaginal lumen, and had a bleeding, frayed artery in the caudal end.


Assuntos
Doenças das Cabras/diagnóstico , Leiomioma/veterinária , Neoplasias do Colo do Útero/veterinária , Hemorragia Uterina/veterinária , Animais , Evolução Fatal , Feminino , Doenças das Cabras/mortalidade , Cabras , Leiomioma/complicações , Leiomioma/diagnóstico , Leiomioma/mortalidade , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Hemorragia Uterina/etiologia , Hemorragia Uterina/mortalidade
12.
Anim Reprod Sci ; 103(3-4): 355-9, 2008 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-17611051

RESUMO

In the present report we describe a case of cervical leiomyoma that was diagnosed at parturition in a Holstein cow. The tumor mass, which measured 25.5 cm x 21.5 cm x 14.5 cm in size and weighed 4.5 kg, was removed surgically. The tumor was solid, well circumscribed, whitish-pink colored, and encapsulated. The tumor was diagnosed as leiomyoma. The leiomyoma had no adverse effects on pregnancy. This is the first report of a bovine cervical leiomyoma during parturition.


Assuntos
Doenças dos Bovinos/patologia , Leiomioma/veterinária , Neoplasias do Colo do Útero/veterinária , Actinas/metabolismo , Animais , Bovinos , Doenças dos Bovinos/cirurgia , Feminino , Leiomioma/patologia , Leiomioma/cirurgia , Masculino , Gravidez , Resultado da Gravidez/veterinária , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
13.
J Comp Pathol ; 137(1): 9-21, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17537454

RESUMO

A homotransplantable tumour (LY) and cell lines (LY-PPB6 and LY-H12) were established from a spontaneous malignant peripheral nerve sheath tumour (PNST) of the uterine cervix of an F344 rat. Primary and LY tumours consisted of oval or spindle-shaped cells arranged in a flatfield or streaming fashion, and indistinct nuclear palisades were seen. Immunohistochemically, neoplastic cells reacted to vimentin, S-100 protein, neuron-specific enolase (NSE), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) in varying degrees, indicating neurogenic derivation. LY-PPB6-induced tumours in syngeneic rats developed cellular whorling patterns reacting particularly strongly to S-100 protein, NSE, MBP and GFAP. Nerve growth factor (NGF) mRNA expression was shown in LY-PPB6 cells by the reverse transcription-polymerase chain reaction (RT-PCR). By contrast, LY-H12 had a normal chromosomal number of 42, and did not produce tumours when injected into syngeneic rats. LY-H12 cells reacted to vimentin and alpha-smooth muscle actin (alpha-SMA), and the alpha-SMA-positive cell number was increased dose-dependently by the addition of transforming growth factor (TGF)-beta1, indicating a myofibroblastic nature. LY-PPB6 cells were neoplastic with properties of PNS cells, whereas LY-H12 cells were non-neoplastic stromal cells showing myofibroblastic differentiation. As TGF-beta1 mRNA expression was shown in both LY-PPB6 and LY-H12 cells by the RT-PCR, the myofibroblastic phenotype of LY-H12 cells may be mediated by paracrine or autocrine signalling in tumour tissues. LY-PPB6 and LY-H12 may prove useful for studies on the pathobiological nature of neoplastic cells and interactions between neoplastic and stromal cells in PNSTs.


Assuntos
Neoplasias de Bainha Neural/patologia , Células Estromais/patologia , Neoplasias do Colo do Útero/patologia , Actinas/genética , Actinas/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Neoplasias de Bainha Neural/metabolismo , Neoplasias de Bainha Neural/veterinária , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Células Estromais/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/veterinária
14.
Int J Gynecol Cancer ; 15(2): 301-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15823116

RESUMO

2-methoxyestradiol (2-ME) is considered to be an effective anticancer compound for many types of tumors. We have previously demonstrated that 2-ME inhibits the growth of human cervical cancer HeLaS3 cells in vitro. In this study, we investigated the antitumoral effects of 2-ME on human cervical carcinoma in severe combined immune deficient (SCID) mice. The potential side effects of 2-ME on the SCID mice were also investigated. SCID mice were injected with HeLaS3 cells (3 x 10(6) to 4 x 10(6)/mouse) and a 15-day administration of 2-ME followed after a 1-week cell implantation. Tumor weight, volume, body weight, and blood chemistry were determined. Tumor tissues were examined with an antibody against the proliferative cell nuclear antigen and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Liver, spleen, kidney, heart, and lung were screened by pathologic examinations. 2-ME (75 mg/kg p.o.) inhibited growth of human cervical carcinoma by 34% (P < 0.05) as compared with control. Necrosis was found in both 2-ME-treated and untreated tumor tissues, but the necrotic area was larger in 2-ME-treated mice. A low expression of proliferative cell nuclear antigen and an increased number of apoptotic cells were found in 2-ME-treated tumor sections as compared to those in controls. No significant difference was detected in blood chemistry. In addition, the liver showed hyperplastic Kupffer cells, hydropic swelling of hepatocytes, and liquefactive necrosis. The spleen showed an increased number of megakaryocytes and apoptotic cells after 2-ME treatment. Thus, 2-ME has an antitumor effect on human cervical carcinoma, and it is toxic to liver and spleen in this mouse model.


Assuntos
Estradiol/análogos & derivados , Estradiol/farmacologia , Neoplasias do Colo do Útero/patologia , 2-Metoxiestradiol , Animais , Estradiol/toxicidade , Feminino , Células HeLa , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Camundongos SCID , Antígeno Nuclear de Célula em Proliferação/biossíntese , Baço/efeitos dos fármacos , Baço/patologia , Transplante Heterólogo , Neoplasias do Colo do Útero/veterinária
15.
Vet Pathol ; 41(2): 108-15, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15017023

RESUMO

Papillomavirus-associated cervical cancer is the second most common neoplasm in women but has rarely been reported in animals. This report describes cervical and vaginal intraepithelial neoplasms identified in routine histologic specimens obtained from 20 (5.2%) of 385 female cynomolgus macaques (Macaca fascicularis) being used in long-term studies. Lesion incidence was similar in both control and hormonally treated animals (4.7% and 5.5%, respectively). Neoplasms included benign vaginal papillomas, mild to severe intraepithelial dysplasias, and two invasive cervical carcinomas. Common morphologic features included koilocytosis, nuclear atypia, and expansion of the basal epithelium. Selective staining of lesions with at least one of three papillomavirus antibodies was observed in all cases (20 of 20). In contrast, immunostaining of lesions was negative for Epstein-Barr-related virus proteins (0 of 20). The unique similarities between the observed lesions and those seen in women suggest that macaques may provide a suitable animal model for study of papillomavirus oncogenesis.


Assuntos
Macaca fascicularis , Doenças dos Macacos/patologia , Doenças dos Macacos/virologia , Papiloma/veterinária , Papillomaviridae/genética , Displasia do Colo do Útero/veterinária , Neoplasias do Colo do Útero/veterinária , Neoplasias Vaginais/veterinária , Animais , Primers do DNA , Epitélio/patologia , Feminino , Técnicas Histológicas , Imuno-Histoquímica , Papiloma/patologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/veterinária , Reação em Cadeia da Polimerase , Neoplasias do Colo do Útero/patologia , Neoplasias Vaginais/patologia , Displasia do Colo do Útero/patologia
16.
J Med Primatol ; 30(3): 156-60, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11515671

RESUMO

Female cynomolgus macaques (n = 11) were treated orally with graded doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cervical tissue was recovered at necropsy 1.2-2.7 years later and examined using routine histopathology. Results were compared histologically with cervical tissue from untreated, age- and parity-matched controls. Significant squamous epithelial metaplasia was observed in the endocervix of 9 of 11 TCDD-treated animals, and the degree of severity was dose dependent. In contrast, minimal or no pathological changes were observed in eight of nine control animals and one animal had only mild squamous metaplasia. These results suggest that TCDD exposure induces epithelial transdifferentiation in the primate cervix. Consequently, the TCDD-treated macaque may serve as a predictable animal model for the study of cervical epithelial transdifferentiation and for examining the relationship between squamous metaplasia and cervical oncogenesis both at the cellular and at the molecular level.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Transformação Celular Neoplásica , Colo do Útero/efeitos dos fármacos , Colo do Útero/patologia , Macaca fascicularis , Dibenzodioxinas Policloradas/toxicidade , Teratogênicos/toxicidade , Neoplasias do Colo do Útero/induzido quimicamente , Administração Oral , Animais , Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/veterinária , Diferenciação Celular , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Metaplasia/induzido quimicamente , Dibenzodioxinas Policloradas/administração & dosagem , Neoplasias do Colo do Útero/fisiopatologia , Neoplasias do Colo do Útero/veterinária
17.
J Vet Med Sci ; 63(4): 449-52, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11346182

RESUMO

The histological characteristics of 9 cases of granular cell tumors (GCTs) observed in B6C3F1 mice were examined to determine their cellular origin. Seven of the 9 cases were found in the uterus and other 2 cases were in the subcutaneous tissue. Tumor cells had abundant granules in the cytoplasm which were stained with PAS and were resistant to diastase treatment. Ultrastructurally, the granules were identified as lysosomes. The cell surface had cytoplasmic processus showing interdigitation with adjacent cells. A character feature of the tumor cells was the presence of a desmosome-like structure on their cell surface but no basal lamina was demonstrated. Although GCTs have been considered to be derived from Schwann cells on the basis of their ultrastructural features and S-100 protein-immunopositive findings, the absence of basal lamina in the present cases may raise a controversy as to their origin.


Assuntos
Tumor de Células Granulares/veterinária , Animais , Cruzamentos Genéticos , Feminino , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/ultraestrutura , Neoplasias dos Genitais Masculinos/veterinária , Tumor de Células Granulares/patologia , Tumor de Células Granulares/ultraestrutura , Imuno-Histoquímica/veterinária , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Microscopia Eletrônica/veterinária , Glândulas Seminais/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/ultraestrutura , Neoplasias do Colo do Útero/veterinária , Neoplasias Uterinas/patologia , Neoplasias Uterinas/ultraestrutura , Neoplasias Uterinas/veterinária
18.
Vet Pathol ; 37(5): 439-48, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11055867

RESUMO

During the review of a rat carcinogenicity study, a spectrum of granular cell lesions was recognized in the distal female reproductive tract. To verify the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were evaluated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases with S100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle-specific actin and calretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructurally, as expected many lysosomal bodies were present in the cytoplasm of granular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nomenclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surrounding tissues. Some benign tumors also contained foci of spindle cells with decreased granularity. Malignant tumors exhibited pleomorphism and an increased nucleus: cytoplasm ratio morphologically but had the same biologic behavior as the benign tumors. We applied these diagnostic criteria during the review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that could be classified into one of the three categories. Granular cell lesions appear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumors may develop from granular cell aggregates.


Assuntos
Genitália Feminina/patologia , Tumor de Células Granulares/veterinária , Doenças dos Roedores/diagnóstico , Neoplasias do Colo do Útero/veterinária , Neoplasias Vaginais/veterinária , Envelhecimento/patologia , Animais , Feminino , Tumor de Células Granulares/classificação , Tumor de Células Granulares/diagnóstico , Tumor de Células Granulares/patologia , Imuno-Histoquímica/veterinária , Camundongos , Microscopia Eletrônica/veterinária , Estudos Prospectivos , Coelhos , Ratos , Ratos Sprague-Dawley , Estudos Retrospectivos , Doenças dos Roedores/classificação , Doenças dos Roedores/patologia , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias Vaginais/classificação , Neoplasias Vaginais/diagnóstico , Neoplasias Vaginais/patologia
19.
J Vet Diagn Invest ; 12(4): 371-4, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10907870

RESUMO

Fibroleiomyomas of the tubular genitalia were diagnosed in 6 of 9 adult female beluga whales from the St. Lawrence estuary, Quebec, Canada. These tumors were located in the vagina (6 of 6), the cervix (2 of 6), and the uterus (1 of 6). Endogenous hormones or xeno-estrogens may be implicated in the occurrence of these tumors.


Assuntos
Leiomioma/veterinária , Neoplasias do Colo do Útero/veterinária , Neoplasias Uterinas/veterinária , Neoplasias Vaginais/veterinária , Baleias , Animais , Feminino , Leiomioma/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias Uterinas/patologia , Neoplasias Vaginais/patologia
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