Tumor de Burschke-Loewenstein na região Perianal – Um Caso Clínico

The Burschke-Loewenstein tumor, also called Giant condyloma acuminata or verrucous carcinoma of the anogenital region, is a papillomatous proliferation, which predominates in the glans and foreskin of uncircumcised men. Also, can affect the urethra, vulva and perianal region. In its pathogenesis has a role, the Human Papilloma Virus (HPV). The Buschke-Loewenstein tumor is a rare low-grade malignancy, derived from squamous cells. Tends to appear in men with more or less 30-50 years of age, presenting itself as a local mass. Its transformation into invasive carcinoma is approximately 1 / 3 of cases documented. This is an anogenital verrucous carcinoma, associated with the Human Papilloma Virus (HPV), especially, among these, the serotype 6 and 113. It is postulated that the HPV oncoprotein E6 and E7 act by inactivation of cell cycle regulators, is the first step toward malignancy. The treatment is surgical. We present a case of a male patient, with 50 years of age, with a vegetative lesion of 11cmx4cm size, located in the perianal zone. Keywords: Giant condyloma acuminate, Verrucous Carcinoma; Burschke-Loewenstein Tumor O Tumor de Burschke-Loewenstein, também denominado Condiloma Acuminado Gigante ou Carcinoma Verrucoso da região anogenital, é uma proliferação papilomatosa, que predomina na glande e prepúcio de homens não circuncisados4. Também, pode afectar a uretra, vulva, região perianal e anal. Na sua patogênese tem um papel relevante, o Virus do Papiloma Humano (HPV). O Tumor de Buschke-Loewenstein é uma neoplasia rara de baixo grau de malignidade, derivada das células escamosas. Tem tendência a aparecer em homens, sobretudo com idades entre os 30 e os 50 anos de idade, apresentando-se como uma massa local. A sua trans- formação em carcinoma invasivo é de aproximadamente 1/3 dos casos documentados1. Trata-se de um carcinoma verrucoso anogenital, associado ao Virus do Papiloma Humano (HPV), destacando-se, entre estes, o serotipo 6 e 11. Postula-se que as oncoproteinas HPV E6, E7 actuem por inactivação dos reguladores do ciclo celular, constituindo o primeiro passo para a malignização. O tratamento é fundamentalmente cirúrgico2. Apresentamos o caso de um doente de sexo masculino, com 50 anos de idade, com lesão vegetante de 11cmx4cm de dimensões, de localização perianal. Palavras-chave: Condiloma Acuminado Gigante, Carcinoma Verrucoso; Tumor de Burschke-Loewenstein

Calcium dobesilate Is protective against Inflammation and oxidative/nitrosative stress in the retina of a type 1 diabetic rat model

Calcium dobesilate (CaD) has been prescribed to some patients in the early stages of diabetic retinopathy to delay its progression. We previously reported that the treatment of diabetic animals (4 weeks of diabetes) with CaD, during the last 10 days of diabetes, prevents blood-retinal barrier breakdown. Here, we aimed to investigate whether later treatment of diabetic rats with CaD would reverse inflammatory processes in the retina. Diabetes was induced with streptozotocin, and 6 weeks after diabetes onset, CaD (100 mg/kg/day) was administered for 2 weeks. The treatment with CaD significantly increased glial fibrillary acidic protein (GFAP) levels in the retina of nondiabetic animals (138.6 ± 12.8% of control) and enhanced the diabetes-induced increase in GFAP levels (174.8 ± 5.6% of control). In addition, CaD prevented the increase in mRNA and protein expression of tumor necrosis factor and interleukin-1β, as well as the formation of oxidized carbonyl residues and the increase in nitrotyrosine immunoreactivity, particularly in the ganglion cell layer of diabetic animals. We demonstrate that the treatment of diabetic animals with CaD can reverse the established proinflammatory processes in the retina. These beneficial effects appear to be attributed, at least partially, to the antioxidant properties of CaD.info:eu-repo/semantics/publishedVersio

Addition of interleukin-2 overcomes resistance to neoadjuvant CTLA4 and PD1 blockade in ex vivo patient tumors

Neoadjuvant immunotherapy with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA4) + anti-programmed cell death protein 1 (PD1) monoclonal antibodies has demonstrated remarkable pathological responses and relapse-free survival in -80% of patients with clinically detectable stage III melanoma. However, about 20% of the treated patients do not respond. In pretreatment biopsies of patients with melanoma, we found that resistance to neoadjuvant CTLA4 + PD1 blockade was associated with a low CD4/interleukin-2 (IL-2) gene signature. Ex vivo, addition of IL-2 to CTLA4 + PD1 blockade induced T cell activation and deep immunological responses in anti-CTLA4 + anti-PD1-resistant human tumor specimens. In the 4T1.2 breast cancer mouse model of neoadjuvant immunotherapy, triple combination of anti-CTLA4 + anti-PD1 + IL-2 cured almost twice as many mice as compared with dual checkpoint inhibitor therapy. This improved efficacy was due to the expansion of tumor-specific CD8(+) T cells and improved proinflammatory cytokine polyfunctionality of both CD4(+) and CD8(+) T effector cells and regulatory T cells. Depletion studies suggested that CD4(+) T cells were critical for priming of CD8(+) T cell immunity against 4T1.2 and helped in the expansion of tumor-specific CD8(+) T cells early after neoadjuvant triple immunotherapy. Our results suggest that the addition of IL-2 can overcome resistance to neoadjuvant anti-CTLA4 +anti-PD1, providing the rationale for testing this combination as a neoadjuvant therapy in patients with early-stage cancer.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Addition of interleukin-2 overcomes resistance to neoadjuvant CTLA4 and PD1 blockade in ex vivo patient tumors

Neoadjuvant immunotherapy with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA4) + anti-programmed cell death protein 1 (PD1) monoclonal antibodies has demonstrated remarkable pathological responses and relapse-free survival in -80% of patients with clinically detectable stage III melanoma. However, about 20% of the treated patients do not respond. In pretreatment biopsies of patients with melanoma, we found that resistance to neoadjuvant CTLA4 + PD1 blockade was associated with a low CD4/interleukin-2 (IL-2) gene signature. Ex vivo, addition of IL-2 to CTLA4 + PD1 blockade induced T cell activation and deep immunological responses in anti-CTLA4 + anti-PD1-resistant human tumor specimens. In the 4T1.2 breast cancer mouse model of neoadjuvant immunotherapy, triple combination of anti-CTLA4 + anti-PD1 + IL-2 cured almost twice as many mice as compared with dual checkpoint inhibitor therapy. This improved efficacy was due to the expansion of tumor-specific CD8(+) T cells and improved proinflammatory cytokine polyfunctionality of both CD4(+) and CD8(+) T effector cells and regulatory T cells. Depletion studies suggested that CD4(+) T cells were critical for priming of CD8(+) T cell immunity against 4T1.2 and helped in the expansion of tumor-specific CD8(+) T cells early after neoadjuvant triple immunotherapy. Our results suggest that the addition of IL-2 can overcome resistance to neoadjuvant anti-CTLA4 +anti-PD1, providing the rationale for testing this combination as a neoadjuvant therapy in patients with early-stage cancer