Search

Aim: The novel primary end-point of the present study was to ascertain β-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of β-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. Methods: The expression of β-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. Results: Statistical analysis showed no significant associations between β-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and β-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). Conclusions: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and β-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how β-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies.

Background When advanced, oral squamous cell carcinoma (OSCC) may involve adjacent non-epithelial structures, and the prognosis is worse for bone invasion. Human relaxin-2 is a peptide hormone that has recently been associated with cancer. It can induce human osteoclast differentiation and activation, suggesting a role in tumor-driven osteolysis. This study was a preliminary assessment of the prognostic role of relaxin-2 in surgical specimens of OSCC tissue and adjacent but uninvolved mandibular/maxillary bone. Methods Relaxin-2 immunohistochemical expression and reaction intensity were assessed in tumor and uninvolved adjacent mandibular/maxillary bone specimens from 23 operated OSCC patients. Results All OSCC specimens were positive for relaxin-2. The intensity of its reaction in OSCC correlated significantly with the pattern of the tumor's invasion front (p = 0.02), being higher with the infiltrative pattern. Mean relaxin-2 immunohistochemical expression was higher in patients whose OSCC recurred after treatment than those experiencing no recurrence (81.3% ± 22.6% vs. 59.5% ± 29.7%, respectively). A significant direct association emerged between relaxin-2 expression in OSCC specimens and recurrence rate (p = 0.049). Conclusions Relaxin-2 expression in OSCC should be further investigated as a potentially useful marker for identifying patients at higher risk of recurrence, who might benefit from closer follow-up and more aggressive adjuvant therapy. In other oncological settings, increasing evidence of relaxin being produced by cancer cells is prompting efforts to synthesize human relaxin-2 analogs capable of acting as antagonists and limiting tumor growth.

The case is described of a male patient with respiratory epithelial adenomatoid hamartoma of the left maxillary sinus that initially presented as a chronic sinus inflammation. This benign lesion is characterized by glandular proliferation originating from the surface of the respiratory epithelium. Maxillary sinus localisation is very rare but is very important to be able to distinguish hamartomas from schneiderian papillomas of the inverted type and adenocarcinomas, potentially requiring aggressive surgical treatment. Moreover, misinterpretation of the respiratory epithelial adenomatoid hamartoma as chronic sinus inflammation may result in inadequate treatment. The clinical and pathological features of this lesion are discussed.

Mice lethally infected with T. gondii and treated with prolactin (PRL), recombinant interferon gamma (rIFN-gamma) or recombinant tumour necrosis factor (rTNF-alpha) were protected against death, as compared to untreated controls. The protective effect of PRL (0.5-2 mg/kg/twice daily for 12 days) was dose dependent and statistically significant (P < 0.001). The survival was 50\% or 40\% in mice that received doses of 1 x 10(4) U of rIFN-gamma or 4 x 10(4) U of rTNF-alpha at -2, 0, +2 days before and after infection (P < 0.0001). An increase of time to death, up to 60 days after challenge, and of survival rate (50\% up to 70\%) were observed in animals treated with PRL in combination with either rTNF-alpha or rIFN-gamma, compared to those that received treatments with the same therapeutic agents alone; however the differences were not statistically significant. In addition, a slight synergistic effect on brain cyst formation, with lower number of Toxoplasma cysts, was observed in mice treated with PRL plus TNF-alpha (P < 0.01), compared with animals that received rTNF-alpha alone (P < 0.05). These data suggest that PRL can regulate in vivo endogenous TNF-alpha production in the cytokine cascade. We conclude that prolactin may play an important role in modulating the host's immune defence against T. gondii opportunistic infection.

To the Editor: A 61-year-old man with no symptoms was found to have an enormous mass that occupied the entire right flank and pushed the right kidney down. A preoperative cytologic specimen obtained from a computed tomography–guided fine-needle biopsy showed many huge epithelial cells, with naked or doubled nuclei, suggesting a diagnosis of a clear-cell carcinoma of the right kidney. At surgery, an ovoid mass (24 by 18 cm) distinct from the right kidney was found. After the mass was removed (Figure 1), the appearance of the kidney was normal. A definitive histologic examination showed adrenocortical carcinoma (Figure 2). The . . .

A series of benzotriazole derivatives were synthesized and tested in order to determine their activities for muscarinic receptor subtypes (M1, M2 and M3). Binding affinities were measured as KI values by competition against [3H]-N-methylscopolamine in rat cortex, atria and ileum. Pharmacological in vitro tests were performed on isolated tissue preparations (rabbit vas deferens, guinea pig atria and ileum); the compounds showed antimuscarinic activity. The synthesized ligands were characterized by moderate activity; however, some of them displayed interesting selectivity profiles (M2/M1 and M2/M3); particularly, the selectivity exhibited by the benzotriazole derivative 14b was quite similar to that observed for AF-DX 116, a typical M2 specific antagonist.