Claudia Bonardi

Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production

Yondelis (Trabectedin) is a novel antitumor agent of marine origin extracted from the tunicate Ecteinascidia turbinata. This original compound is active against several human tumors including sarcoma and ovarian and breast adenocarcinoma, as evidenced in phase II clinical trials in advanced multitreated patients. Yondelis is a DNA minor groove binder that blocks cell cycle and interferes with inducible gene transcription in a selective manner. In this study, we investigated the immunomodulatory properties of Yondelis on leukocytes. Human blood monocytes were highly susceptible in vitro to its cytotoxic effect and underwent apoptosis at pharmacologically relevant concentrations (5 nmol/L), whereas lymphocytes were up to 5-fold less sensitive. Macrophages differentiated in vitro with macrophage colony-stimulating factor and tumor-associated macrophages (TAM), isolated from patients with ovarian cancer, were also susceptible. At subcytotoxic concentrations, Yondelis inhibited the in vitro differentiation of monocytes to macrophages. In tumor-treated patients, drug infusion caused a selective decrease of monocyte counts and of ex vivo macrophage differentiation. The in vitro production of two proinflammatory mediators, CCL2 and IL-6, was markedly reduced by Yondelis in monocytes, macrophages, TAM, and freshly isolated ovarian tumor cells. The chemokine CCL2 is the major determinant of monocyte recruitment at tumor sites, whereas IL-6 is a growth factor for ovarian tumors. In view of the protumor activity of TAM and of the strong association between chronic inflammation and cancer progression, the inhibitory effect of Yondelis on macrophage viability, differentiation, and cytokine production is likely to contribute to the antitumor activity of this agent in inflammation-associated human tumors.

Safety and immunogenicity of a quadrivalent human papillomavirus vaccine in HIV-infected and HIV-negative adolescents and young adults

Human papillomavirus (HPV) infection is highly prevalent and can lead to cancer; the development of safe and efficacious vaccines for HPV is a major public health concern. The two licensed HPV vaccines contain recombinant virus-like particles of HPV 16 and 18; one of such vaccines also protects against HPV types 6 and 11 which cause genital warts. We determined safety and immunogenicity of quadrivalent HPV vaccine in HIV-infected and HIV-negative adolescents and young adults, aged 13-27 years. The seroconversion rate, assessed by antibody titers, 1 month after the administration of the third vaccine dose was 0.85 (95% CI 0.75-0.95) in the HIV-infected group and 0.91 (0.83-0.99) in the HIV-negative subjects (p=0.52). The vaccine was generally safe and well tolerated; the most common side effect was local pain and the most frequent systemic side effect was headache. This is the first report on response to HPV vaccination in both female and male HIV-infected adolescents and young adults and highlights that this population may benefit from HPV immunoprophylaxis. Further studies are needed to examine the long term efficacy of this vaccine in HIV-infected individuals.

Colorectal cancer with neuroendocrine differentiation in a child

Colorectal cancer is extremely rare in children and presents with a poor prognosis because of the delay in diagnosis and lack of histological differentiation. We report a case of a sigmoid colon carcinoma with areas of neuroendocrine cells in a 12-year-old patient without familial occurrence of colorectal cancer. Symptoms at presentation were anaemia, anorexia, abdominal pain and weight loss. The patient was treated with radical resection and adjuvant chemotherapy. One year later, a local recurrence and hepatic metastases were diagnosed and she underwent chemotherapy and surgical resection. Twenty-six months from initial diagnosis she is alive with evidence of disease. The clinical presentation, diagnosis and treatment of the previously reported cases of colorectal cancer in children are also reviewed.

A case of laryngeal tuberculosis in a pediatric patient

Abstract Incidence of tuberculosis is on the rise, mainly due to an increase of AIDS, shifting populations and modification of bacillus Calmette-Guerin immunization programs. Tuberculosis of the larynx is not as rare as generally reported. We described a case of active pulmonary tuberculosis with laryngeal involvement in an immunocompetent pediatric host, presenting with night sweats, chest pain, low grade fever and dysphonia. Patient was managed with anti-tubercular treatment and the recovery was successful, with the complete regression of lesions and symptoms.