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1.
Artigo em Inglês | MEDLINE | ID: mdl-32914354

RESUMO

PURPOSE: Introduction of cyclin-dependent inhibitors was a milestone in therapeutics for patients with estrogen receptor+/HER2- metastatic breast cancer. Despite the wide use of such agents and remarkable improvement of survival rates, drug-related adverse events are not yet fully characterized. We describe vitiligo-like lesions as a new adverse event occurring in patients with advanced breast cancer treated with cyclin-dependent inhibitors. METHODS: We performed an international retrospective study including patients with advanced breast cancer who developed vitiligo-like lesions during treatment with cyclin-dependent kinases 4 and 6 inhibitors, in the period January 2018-December 2019. Patients > 18 years, both males and females, were recruited at six Dermatology Departments located in Italy (3), France (1) and Greece (2). We evaluated epidemiological and clinical characteristics, impact on quality of life and outcome of vitiligo-like lesions in patients treated with cyclin-dependent 4 and 6 inhibitors. The percentage of skin involved by vitiligo-like lesions was assessed using the Body Surface Area (BSA) score. Changes in patients' quality of life were investigated through the evaluation of the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: Sixteen women (median age: 62.5 years; range 40-79 years) treated with cyclin-dependent kinases 4 and 6 inhibitors for advanced breast cancer presented with vitiligo-like lesions during follow-up visits. Cutaneous lesions consisted of white, irregular macules and patches located mainly on sun-exposed areas in 11/16 patients or diffuse to the entire body surface in 5/16. Cutaneous lesions clearly impaired the quality of life of patients tested (DLQI ≥ 10). CONCLUSIONS: We present for the first time, to our knowledge, a case series of vitiligo-like lesions developing in patients with advanced breast cancer treated with cyclin-dependent kinases 4 and 6 inhibitors. We showed that such lesions further impair the patients' quality of life and their treatment is challenging.

3.
Anticancer Res ; 40(4): 2219-2223, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234917

RESUMO

AIM: To investigate the prevalence of cervico-vaginal co-infection with high-risk (HR) HPV types and other sexually transmitted pathogens (STPs) in women with anogenital warts (AGWs). PATIENTS AND METHODS: In this cross-sectional study, cervico-vaginal smears of women with AGWs were examined with real-time polymerase chain reaction for the presence of HR-HPV types and common STPs. Women with recent cervical HPV infection and general population were used for comparisons. RESULTS: A total of 689 women participated in the study. Among the examined groups, higher rates of cervico-vaginal co-infection with HR-HPV types and other STPs collectively were recorded in women with AGWs (p=0.0049 and p<0.004, respectively). Within the AGWs group, cervical co-infection with HR-HPV types was detected more often in women with recurrent disease (p<0.001). CONCLUSION: The higher rates of cervico-vaginal co-infection with HR-HPV types and common STPs in women with AGWs may affect their risk for cervical carcinogenesis and the natural course of their disease.


Assuntos
Doenças do Ânus/epidemiologia , Condiloma Acuminado/epidemiologia , Doenças dos Genitais Femininos/epidemiologia , Infecções por Papillomavirus/epidemiologia , Verrugas/epidemiologia , Adolescente , Adulto , Doenças do Ânus/virologia , Colo do Útero/virologia , Condiloma Acuminado/virologia , Estudos Transversais , Feminino , Doenças dos Genitais Femininos/virologia , Grécia/epidemiologia , Humanos , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Prevalência , Esfregaço Vaginal , Verrugas/virologia , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-32013838

RESUMO

BACKGROUND: Chronic Spontaneous Urticaria (CSU) is a disease presenting typical wheals characterized by itching, angioedema or both. Although CU is by appearance a relatively "simple" disease, yet it has a devastating effect on those suffering due to its immense social implications. AIM: The aim of the present study was to investigate the effect of omalizumab in the treatment of CSU. In particular, gender, drug co-administration and co-morbidities were taken into account. MATERIALS AND METHOD: 108 patients (25 Males/83 Females) admitted to our department were diagnosed with CSU and were treated for a total of 30 months. CSU was estimated on score basis, which was used in order to define disease severity. The mean total CSU score and the mean CSU score of the first trimester as well as first semester were calculated. Patients were treated with omalizumab and in several cases with co-administration of dapsone, cyclosporine and anti-histamines. RESULTS: Females manifested significantly higher scores as compared to males. Further on, patients that relapsed manifested significantly higher scores during the whole time course, as well as at the end of the first semester. CONCLUSIONS: Females are more prone to CSU. Although CSU score in patients with remission, relapse and poor response manifested no significant difference at diagnosis, relapsed patients manifested higher CSU score at the first semester. Therefore, first semester of treatment is probably critical for the final patient outcome. Further studies are necessary in order to understand the mechanisms of CSU for better treatment and prognosis.

5.
Skin Appendage Disord ; 5(6): 355-358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31799262

RESUMO

Introduction: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia whose incidence has greatly increased worldwide over the last years. The main purpose of the study was to investigate the possible association of the social status of FFA patients with the prognosis of the disease. Methods: A total of 100 female patients with FFA, monitored at Andreas Sygros Hospital, Athens, Greece, during the last 3 years, were recruited in this observational study. The age of the women ranged from 29 to 92 years with a mean age of 61.2 years (SD = 10.3); 97% of them were Greek, with skin type II and III. Results: In total, 46% of the patients were intermediate graduates, and 42% had received tertiary education; 82% were married and 21% had 1 child. The duration of the disease ranged from 0.5 to 20 years with a mean duration of 5.2 years. In 53% of the women, the frontal hairline recession was <1 cm, in 26% it was 1-2 cm, and in 15% it was 3-4.99 cm. Overall, 55.6% of patients were professionals, 26% were technicians and associate professionals, 23% were office workers, 9% were service and sales workers, and 13% were at elementary occupations. The severity of the disease was higher in lower-educated patients, who belong to the category of unskilled or with elementary occupation. Conclusions: Women with high educational level and social status are more likely to be diagnosed earlier, resulting in sufficient therapeutic response.

7.
Lancet Child Adolesc Health ; 3(5): 332-342, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30872112

RESUMO

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.


Assuntos
Biomarcadores Tumorais/genética , Mutação em Linhagem Germinativa , Melanoma/genética , Receptor Tipo 1 de Melanocortina/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Estudos Retrospectivos
8.
Exp Dermatol ; 28(1): 72-75, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30390357

RESUMO

Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as "innate pathogen" triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non-lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at -80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin-related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non-lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options.

9.
Ann Transl Med ; 6(12): 249, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30069451

RESUMO

Significant progress in the molecular pathology of melanocytic tumors have revealed that benign neoplasms, so-called nevi, are initiated by gain-of-function mutations in one of several primary oncogenes, such as BRAF in acquired melanocytic nevi, NRAS in congenital nevi or GNAQ/GNA11 in blue nevi, with consequent MAPK and PI3K/AKT/mTOR activation. Secondary genetic alterations overcome tumor suppressive mechanisms and allow the progression to intermediate lesions characterized by TERT-p mutation or to invasive melanomas displaying disruption of tumor suppressor genes. Currently, melanoma is molecularly regarded as four different diseases, namely BRAF, NRAS, NF1 and the "triple wild type" subtypes, which are associated with particular clinicopathological features. Melanocytic Spitzoid lesions include benign Spitz nevus, atypical Spitz tumor (AST) and Spitzoid melanoma. This is a challenging diagnostic group, particularly with regard to the distinction between AST and Spitzoid melanoma on clinical and histological grounds. Molecular analysis has identified the presence of HRAS mutation, BAP1 loss (often accompanying by BRAF mutations) or several kinase fusions in distinct categories of Spitz tumors. These aberrations account for the rapid growth characteristic of Spitz nevi. Subsequent growth is halted by various tumor suppressive mechanisms abrogation of which allow the development of AST, now better classified as low-grade melanocytic tumor. Although at present ancillary genetic techniques have not been very helpful in the prediction of biological behavior of AST, they have defined distinct tumor subsets differing with regard to biology and histology. Finally, we discuss how novel molecular markers may assist the differential diagnosis of melanoma, particularly from malignant peripheral nerve sheath tumor (MPNST). It is anticipated that the significant progress in the field of molecular pathology regarding the various types of melanocytic tumors, will eventually contribute to a more accurate histologic categorization, prediction of biologic behavior and personalized treatment.

10.
J Immunother ; 41(3): 164-167, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29309291

RESUMO

The widespread use of immune checkpoint inhibitors has shed light to several unusual immune-related adverse effects of the drugs. Severe cutaneous adverse reactions are generally rare with anti-PD1 agents. We present in this paper the case of a 48-year-old patient with melanoma who developed bullous pemphigoid-like skin lesions along with fever, arthralgia and overt eosinophilia following adjuvant treatment with nivolumab. The condition was successfully treated with corticosteroids and a rechallenge with another anti-PD1 agent did not lead to recurrence of the skin lesions. We also reviewed the literature on the epidemiologic, clinical, and histopathologic characteristics of bullous pemphigoid as well as on the treatment and prognosis of this dermatologic condition in patients with melanoma or other malignancies under treatment with immune checkpoint inhibitors.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Eosinofilia/patologia , Melanoma/complicações , Nivolumabe/efeitos adversos , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/etiologia , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Linfonodos/patologia , Masculino , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nivolumabe/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Prednisolona/farmacologia , Prednisolona/uso terapêutico
11.
Mol Diagn Ther ; 20(3): 221-5, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27043841

RESUMO

INTRODUCTION: Psoriasis is a highly divergent disease with many disease phenotypes, but there are currently no established biomarkers to predict the therapeutic outcomes of systemic treatments. With the introduction of biologic therapies during the last decade and with new treatments constantly emerging, there is a great need to validate biomarkers that have been reported to be associated with treatment response, and to introduce new biomarkers of possible clinical value. METHODS: In the current study, we aimed to investigate the association of psoriasis-related polymorphisms that have previously been reported to effect the anti-tumor necrosis factor alpha (anti-TNF-α) therapies (etanercept, adalimumab, and infliximab) and anti-interleukin-12/23 (anti-IL-12/23) biologic therapy (ustekinumab) in a Greek cohort of psoriasis patients. RESULTS: Rs10484554 in the HLA-C gene showed an association with a good response to anti-TNF-α agents but not to ustekinumab, while rs151823 and rs26653 in the ERAP1 gene showed associations with a good response to anti-IL-12/23 therapy. CONCLUSION: This study is the first in the field of pharmacogenetics in Greek psoriasis patients. Further, larger studies are required to validate our findings and replicate them in various populations.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Variação Genética , Interleucina-12/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Variantes Farmacogenômicos , Psoríase/tratamento farmacológico , Psoríase/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Alelos , Anticorpos Monoclonais/farmacologia , Genótipo , Grécia , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Ustekinumab/farmacologia , Ustekinumab/uso terapêutico
12.
J BUON ; 20(1): 354-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25778343

RESUMO

In 19th century, the anatomo-clinical school of Paris linked clinical signs with anatomical lesions establishing clinical medicine. One of the most enlightened promoters of this method was the French physician René-Théophile-Hyacinthe Laennec, known as the inventor of stethoscope. In our article, we reveal his work on pulmonary melanoma.


Assuntos
Pesquisa Biomédica/história , Neoplasias Pulmonares/história , Oncologia/história , Melanoma/história , Neoplasias Cutâneas/história , História do Século XVIII , História do Século XIX , Humanos , Neoplasias Pulmonares/secundário , Melanoma/secundário , Paris , Neoplasias Cutâneas/patologia
13.
Leuk Lymphoma ; 56(5): 1303-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25242096

RESUMO

Lymphomatoid papulosis (LyP) refers to an indolent cutaneous lymphoma. The association of prognostic clinicopathological risk factors with a second hematologic malignancy has not yet been determined. We investigated the prognostic effect of clinicopathological characteristics on the occurrence of a second lymphoma, as well as the first-line treatment, in 24 patients diagnosed with LyP using logistic regression models. We showed that lymphoma occurrence was associated with a lower mean age at onset of LyP symptoms, histological types B and C, head-located LyP lesions and a higher frequency of LyP recurrences. In multivariate analyses, histologic type A was associated with a lower risk of second lymphoma (odds ratio [OR] = 0.12, 95% confidence interval [CI] 0.014-0.98; p = 0.045) adjusting for age of LyP first symptomatology, and an important increased lymphoma-free survival rate (long-rank test; p = 0.06). Clinicopathological characteristics are important in defining the clearance or persistence of LyP lesions and may predict the occurrence of a second lymphoma.


Assuntos
Papulose Linfomatoide/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Segunda Neoplasia Primária , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Papulose Linfomatoide/genética , Papulose Linfomatoide/mortalidade , Papulose Linfomatoide/terapia , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Recidiva , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Fatores de Tempo , Adulto Jovem
14.
Exp Dermatol ; 23(12): 931-3, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25267489

RESUMO

Deregulated signalling through phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides (MF) and we herein further investigate the frequency and clinical significance of PTEN and PI3K at the protein and at the DNA level as well as the presence of AKT1 mutations in skin lesions from 50 patients with MF clinical stages I-IV in relation to clinicopathological features. Increased p-AKT expression correlated with poor prognosis in plaques (P = 0.0198), whereas p-AKT was an independent predictor of poor survival in the entire cohort (P = 0.017, HR = 1.012). PTEN cytoplasmic expression was found low or absent in all 77.3% of cases and inversely correlated with advanced clinical stages (P = 0.0744). Molecular analysis showed no AKT1 mutation, no PI3KCA copy number gain, only 1 case with PI3KCA mutation in exon 9 and 3 cases with PTEN mutations (7%) in exons 7, 8 and 5. The latter correlated with disease (P = 0.0253) and progression (P < 0.0001) free survival in tumour stage. Although activation of PI3K/AKT signalling pathway due to PTEN alterations is rarely attributed to abnormalities in PTEN, PI3K, and AKT1 genes, PTEN mutations exert a negative effect on patients' prognosis with tumours.


Assuntos
Micose Fungoide/genética , Micose Fungoide/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Mutação , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Fatores de Transcrição/genética
15.
Case Rep Dermatol Med ; 2014: 671631, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25093124

RESUMO

Introduction. Familial cases of Kaposi's sarcoma have rarely been reported. Kaposi's sarcoma is not uncommon in Greece; its incidence is estimated at 0.20 per 100.000 habitants, showing an increased predominance in the Peloponnese, in Southern Greece. Case Report. We describe five cases of familial clustering of KS originating from Greece. Discussion. The pathogenesis of familial Kaposi's sarcoma is still far from being completely understood. Genetic, environmental, and infectious factors have been incriminated.

16.
Exp Dermatol ; 23(5): 332-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24673285

RESUMO

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16(INK) (4A) promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation-specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki-67 index), p16(INK) (4A) and SETDB1 expression were evaluated by immunohistochemistry. High-frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16(INK) (4A) promoter methylation was higher in vertical growth-phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16(INK) (4A) methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1-30%) p16(INK) (4A) expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16(INK) (4A) methylation and p16(INK) (4A) expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0-5/mm(2) vs >5/mm(2) , P = 0.0869), advanced Clark level (III-V, P = 0.0380), epidermal involvement (P = 0.0331) and the non-chronic sun exposure-associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16(INK) (4A) promoter and several prognostic parameters in melanomas.


Assuntos
Ilhas de CpG , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Melanoma/metabolismo , Regiões Promotoras Genéticas , Metiltransferases de Proteína/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Citoplasma/metabolismo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Grécia , Humanos , Antígeno Ki-67/metabolismo , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Mitose , Prognóstico , Neoplasias Cutâneas/genética , Adulto Jovem
17.
Case Rep Oncol ; 4(2): 385-91, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21941487

RESUMO

We report on a 63-year-old woman, previously in good health, who had undergone nephrectomy for clear cell renal cell carcinoma in 2002. Because of systemic relapse with multiple lung metastases in 2006, the patient was treated with sunitinib 50 mg daily on a 4-weeks on-/2-weeks off-schedule. After 3 years of treatment, she developed a purpuric rash on her feet and trunk. Biopsy revealed leukocytoclastic vasculitis. No other organ involvement was diagnosed. She was started on oral prednisone 30 mg daily with rapid resolution of the vasculitic skin lesions. Sunitinib was temporally discontinued and reintroduced at the same dose level. Reappearance of a less serious vasculitis after 2 cycles of re-treatment was resolved in the weeks off-treatment and by reducing the dose of sunitinib along with 5 mg of prednisone daily. One year after the diagnosis, the patient is still on this therapy. Oncology providers should be aware of this rare but potentially serious, possible adverse effect of sunitinib.

18.
Cancer Treat Rev ; 37(4): 284-90, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21106295

RESUMO

Disease dissemination is the major cause of melanoma-related death. A crucial step in the metastatic process is the intravascular invasion and circulation of melanoma cells in the bloodstream with subsequent development of distant micrometastases that is initially clinically undetectable and will eventually progress into clinically apparent metastasis. Therefore, the use of molecular methods to detect circulating melanoma cells may be of value in risk stratification and clinical management of such patients. Herein, we review the currently applied techniques for the detection, isolation, enrichment and further characterization of circulating melanoma cells from peripheral blood samples in melanoma patients. Furthermore, we provide a brief overview of the various molecular markers currently being evaluated as prognostic indicators of melanoma progression.


Assuntos
Biomarcadores Tumorais/sangue , Melanoma/diagnóstico , Células Neoplásicas Circulantes , Neoplasias Cutâneas/diagnóstico , Humanos , Melanoma/sangue , Neoplasias Cutâneas/sangue
19.
J Transl Med ; 8: 108, 2010 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-21044351

RESUMO

PURPOSE: Interferon is approved for adjuvant treatment of patients with stage IIb/III melanoma. The toxicity and uncertainty regarding survival benefits of interferon have qualified its acceptance, despite significant durable relapse prevention in a fraction of patients. Predictive biomarkers that would enable selection of patients for therapy would have a large impact upon clinical practice. Specific CTLA-4 polymorphisms have previously shown an association with response to CTLA-4 blockade in patients with metastatic melanoma and the development of autoimmunity. EXPERIMENTAL DESIGN: 286 melanoma patients and 288 healthy controls were genotyped for six CTLA-4 polymorphisms previously suggested to be important (AG 49, CT 318, CT 60, JO 27, JO30 and JO 31). Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. RESULTS: No significant differences were found between the distributions of CTLA-4 polymorphisms in the melanoma population compared with healthy controls. Relapse free survival (RFS) and overall survival (OS) did not differ significantly between patients with the alleles represented by these polymorphisms. No correlation between autoimmunity and specific alleles was shown. The six polymorphisms evaluated where strongly associated (Fisher's exact p-values < 0.001 for all associations) and significant linkage disequilibrium among these was indicated. CONCLUSION: No polymorphisms of CTLA-4 defined by the SNPs studied were correlated with improved RFS, OS, or autoimmunity in this high-risk group of melanoma patients.


Assuntos
Antígenos CD/genética , Interferons/uso terapêutico , Melanoma/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Antígeno CTLA-4 , Estudos de Casos e Controles , Primers do DNA , Frequência do Gene , Humanos , Melanoma/imunologia , Melanoma/patologia , Metástase Neoplásica , Reação em Cadeia da Polimerase , Análise de Sobrevida
20.
Cancer ; 116(18): 4326-33, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20549830

RESUMO

BACKGROUND: Interferon is approved for adjuvant treatment of patients with stage IIB/III melanoma. The identification of predictive markers that would permit selection of patients would be beneficial. Specific human leukocyte antigen (HLA) class I and II antigens have previously shown an association with response to therapy or overall survival of patients with metastatic melanoma. METHODS: A total of 284 high-risk melanoma patients participating in a randomized trial and 246 healthy controls were molecularly typed for HLA class I and II. Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. RESULTS: No significant differences were found between the distribution of HLA genotype in the melanoma population compared with healthy controls. Correlations between nonrecurrence and the presence of HLA-Cw 06 allele were noted present in 19.3% of melanoma patients. The median relapse-free survival of the Cw 06-positive cohort was 100.2 months versus 37.3 months in the Cw 06-negative cohort (P = .013). The median overall survival for the Cw 06-positive cohort has not yet been reached, versus 78.9 months in the Cw 06-negative cohort (P = .025). HLA-Cw 06 was present in 29.79% of patients in the autoimmunity group and 15.38% of patients in the nonautoimmunity group (P = .049). CONCLUSIONS: : No allele was associated with absence of recurrence in patients receiving adjuvant interferon with the exception of HLA-Cw 06, an allele correlated with psoriasis. HLA-Cw 06-positive patients have better relapse-free and overall survival.


Assuntos
Antineoplásicos/uso terapêutico , Genes MHC da Classe II , Genes MHC Classe I , Interferon-alfa/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Quimioterapia Adjuvante , Teste de Histocompatibilidade , Humanos , Interferon alfa-2 , Melanoma/mortalidade , Prognóstico , Proteínas Recombinantes , Risco , Neoplasias Cutâneas/mortalidade
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