Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer

Telomerase is considered a universal tumor-associated antigen (TAA) due to its high rate of expression by cancers (approximately 90%), and clinical trials are in progress to test the immunotherapeutical efficacy of antitelomerase immunization in patients with cancer. However, the data concerning frequency and functional activity of telomerase-specific cytotoxic T lymphocytes (CTLs) in patients with cancer are few and conflicting, although their knowledge would be mandatory to predict the efficacy of telomerase-specific immunotherapy in selected patients. We performed this study to analyze frequency and cytolytic function of circulating CD8+ T lymphocytes specific for the p540 telomerase peptide in a series of human leukocyte antigen (HLA)-A2+ cancer patients. The results show that most patients with cancer have circulating telomerase-specific CD8+ T lymphocytes, but a high frequency of telomerase-specific CTLs are present only in a fraction of them. Furthermore, CTL lines able to kill telomerase-positive tumor cells, including autologous cancer cells, can be expanded ex vivo from some, but not all, patients with cancer. In conclusion, the results of the study support the development of clinical protocols using telomerase peptides as an immunizing agent. However, they underline the necessity to study single patients immunologically before undergoing vaccination, to select the patients adequately, and to eventually adapt the immunization schedule to the patient's immunologic status.     

Cystic fibrosis transmembrane conductance regulator mutations in azoospermic and oligospermic men and their partners

The objective of this study was to investigate the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) to human infertility and to define screening and counselling procedures for couples asking for assisted reproduction treatment. Extended CFTR mutation screening was performed in 310 infertile men (25 with congenital absence of the vas deferens (CAVD), 116 with non-CAVD azoospermia, 169 with severe oligospermia), 70 female partners and 96 healthy controls. CFTR mutations were detected in the majority (68%) of CAVD patients and in significant proportions in azoospermic (31%) and oligospermic (22%) men. Carrier frequency among partners of infertile men was 16/70, exceeding that of controls (6/96) significantly (P = 0.0005). Thus, in 23% of infertile couples both partners were carriers, increasing the risk for their offspring to inherit two mutations to 25% or 50%. This study emphasizes the necessity to offer extended CFTR mutation screening and counselling not only to patients with CAVD but also to azoospermic and oligozoospermic men and their partners before undergoing assisted reproduction techniques. The identification of rare and/or mild mutations will not be a reason to abstain from parenthood, but will allow adequate treatment in children at risk for atypical or mild cystic fibrosis as soon as they develop any symptoms.     

Rapid regression of psoriasis in a coeliac patient after gluten-free diet. A case report and review of the literature

BACKGROUND: Several skin disorders are present in patients affected by coeliac disease (CD) - among them, psoriasis has been described. However, at present the relationship between CD and psoriasis remains controversial since there are few and contrasting data on this topic. METHOD: Here we describe a case of psoriasis in a CD patient not responding to specific therapies for psoriasis. RESULT: The regression of skin lesions after gluten-free diet (GFD) was evident in a short time. CONCLUSION: The present case supports the association between CD and psoriasis and the concept that psoriasis in CD patients can be improved by GFD. Future studies are needed to clarify the possible mechanisms involved in this association.     

An effective strategy for diagnosing occupational asthma: use of induced sputum

Monitoring airway inflammation by means of induced sputum cell counts seems to improve the management of asthma. We sought to assess whether such monitoring at the end of periods at and away from work combined with the monitoring of PEF could improve the diagnosis of occupational asthma. We enrolled subjects suspected of having occupational asthma. Serial monitoring of PEF was performed during 2 weeks at and away from work. At the end of each period, induced sputum was collected. Specific inhalation challenge was subsequently performed. PEF graphs were interpreted visually by five independent observers. Forty-nine subjects, including 23 with positive specific inhalation challenge, completed the study. The addition of sputum cell counts to the monitoring of PEF increased the specificity of this test, respectively, by 18 (range [r] 13.7-25.5) or 26.8% (r 24.8-30.4) depending if an increase of sputum eosinophils greater than 1 or 2% when at work was considered as significant. The sensitivity increased by 8.2% (r 4.1-13.4) or decreased by 12.3% (r 3.1-24.1) depending on the cutoff value in sputum eosinophils chosen (greater than 1 or 2%, respectively). The addition of sputum cell counts to PEF monitoring is useful to improve the diagnosis of occupational asthma.     

Investigational therapies currently in Phase II clinical trials for the treatment of pelvic serous carcinomas

Introduction: Pelvic serous carcinomas (PSCs) are a controversial entity, which mostly comprise fallopian tube carcinoma (FTC), primary peritoneal carcinoma (PPC) and serous ovarian carcinoma (OC). Despite incremental attention towards understanding pelvic serous carcinogenesis, the gold standard treatment and survival rates have not substantially changed in these last decades.

Areas covered: This review summarizes and gives a critical overview of the ongoing Phase II trials investigating therapies for PSC.

Expert opinion: Several novel molecules have been developed and are currently under investigation for the treatment of PSC, including FTC, PPC and serous OC. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for PSC, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each woman with a molecularly defined disease, a deeper knowledge of the molecular biology and genetics underlying FTC and its relation as a precursor of PSC is needed.