ABSTRACT
Lymph node (LN) metastasis in canine cutaneous mast cell tumours (cMCTs) is a well-known negative prognostic factor. The role of lymphadenectomy in the treatment of stage II disease remains controversial because of its uncertain therapeutic benefit. Aim of this retrospective study was to investigate the impact of lymphadenectomy on tumour control and survival for dogs with stage II cMCTs. Dogs with firstly occurring, histologically confirmed cMCT with LN metastasis undergoing resection of the primary tumour and medical treatment thereafter were retrospectively enrolled. Dogs were classified into two groups: LN sampling (LNS; diagnosis of metastasis obtained by cytology) and regional LN dissection (LND; diagnosis obtained by histopathology). To determine the therapeutic value of lymphadenectomy, the characteristics of recurrence (local, nodal and distant) and survival were compared between groups. Evaluated outcome variables included signalment, anatomic location, diameter, ulceration, substage, surgical margins, Patnaik grading, Kiupel grading and medical treatment. Overall, 152 dogs were included: 81 underwent LND as part of primary surgery and 71 LNS. The median follow-up time was 409 days for LND group and 620 days for LNS group. On univariable analysis, the risk of developing local, nodal or distant relapse was significantly higher in the LNS group compared with LND (P < 0.001). On multivariable analysis, the risk of tumour progression and tumour-related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001). Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II cMCTs undergoing surgical removal of the primary tumour and medical treatment.
Subject(s)
Dog Diseases/surgery , Lymph Node Excision/veterinary , Mastocytosis, Cutaneous/veterinary , Animals , Dog Diseases/mortality , Dog Diseases/pathology , Dogs , Female , Lymph Node Excision/methods , Lymph Node Excision/mortality , Lymphatic Metastasis , Male , Mastocytosis, Cutaneous/mortality , Mastocytosis, Cutaneous/pathology , Mastocytosis, Cutaneous/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
Aging lung is characterized by morpho-structural modifications, including progressive fibrosis, that lead to an altered function. Here we provide a comprehensive description of lung collagen expression and metabolism during natural aging of rats. Peribronchial collagen increased significantly in the oldest animals (p=0.05 2- vs. 6- and 19-month-old rats), as a consequence of Collagen-I and Collagen-III (COL-I, COL-III) protein accumulation (p<0.05 in 6-, 12- and 19-month-old rats versus the youngest). No changes in fibronectin (FN) protein expression and in COL-III and transforming grow factor beta-1 (TGFbeta-1) mRNA expression were observed. Conversely the transcription activity of the COL-I gene was overexpressed in the oldest animals (p<0.05). In the aged rats, the activity of lung matrix metalloproteinases (MMP), MMP-1 and MMP-2, dropped significantly (p<0.05), whilst MMP-9 levels were slightly decreased. These changes were associated with a concomitant increase of tissue inhibitors of MMP (TIMP-1 and TIMP-2). All together, these results suggest that, during natural aging, collagen accumulation in the lung and its progressive fibrosis are mainly due to a reduced proteolytic activity of MMP, in which TIMP-1 and -2 seem to be the major regulating factors.
Subject(s)
Aging/metabolism , Collagen/metabolism , Lung/metabolism , Pulmonary Fibrosis/metabolism , Aging/genetics , Animals , Collagen/genetics , Extracellular Matrix/metabolism , Fibronectins/metabolism , Gene Expression Regulation , Male , Matrix Metalloproteinases/physiology , Pulmonary Fibrosis/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction/methods , Tissue Inhibitor of Metalloproteinases/metabolismABSTRACT
Cilia-associated respiratory (CAR) bacillus is an unclassified bacterium that colonizes the ciliated epithelium of airways in laboratory rats, laboratory mice, and laboratory and conventionally reared rabbits, cattle, goats, and pigs. Data on the prevalence of CAR bacillus infection in wild animals are lacking. The present study demonstrated the occurrence of the organism in wild red deer (Cervus elaphus hippelaphus), chamois (Rupicapra rupicapra), and roe deer (Capreolus capreolus) from the Val Fontana in northern Italy. Prevalence ranged from 26% for red deer to 56% for chamois, with a statistically significant negative correlation between CAR bacilli infection and the presence of lymphoid follicles.
Subject(s)
Deer/microbiology , Gram-Negative Bacterial Infections/veterinary , Respiratory Tract Infections/veterinary , Rupicapra/microbiology , Animals , Animals, Wild , Cilia/microbiology , Female , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/epidemiology , Italy/epidemiology , Male , Prevalence , Respiratory Tract Infections/epidemiologyABSTRACT
PURPOSE: Gimatecan, a novel oral lipophilic camptothecin characterized by favorable features at molecular/cellular level and by a promising profile of preclinical activity, is currently in clinical phase I/II. The aim of the study was to additionally investigate the therapeutic potential of the drug in human tumor xenografts growing in different organs as models representative of tumor growth in the clinical setting. EXPERIMENTAL DESIGN: The models include two orthotopic central nervous system tumors, two melanomas growing intracranially, and an ovarian carcinoma growing i.p. In addition, gimatecan was tested against experimental lung metastases of two tumor types (lung and ovarian carcinomas). Gimatecan was delivered by oral gavage according to various schedules (daily or intermittent). The time (in days) mice required to show evident signs of disease was used as end point for drug efficacy. RESULTS: Gimatecan was highly effective in delaying disease manifestations in all tumor systems investigated. In the intracranially growing tumors, a significant time increase (versus control mice) was achieved by the drug administered according to all of the schedules. In addition, almost all treated mice were alive and tumor-free at the end of the experiment in the metastatic models and in the ascitic ovarian tumor. The daily prolonged treatment schedule was the best one. CONCLUSIONS: In all tumor systems investigated, including orthotopic tumor growth models and lung metastases, the oral administration of gimatecan showed a therapeutic benefit in terms of survival increase. The good oral availability allowed a prolonged daily treatment regimen, which seems the most promising to exploit the therapeutic potential of the drug.
Subject(s)
Camptothecin/analogs & derivatives , Camptothecin/pharmacology , Animals , Brain/pathology , Female , Humans , Melanoma/drug therapy , Mice , Mice, Nude , Neoplasm Metastasis , Neoplasm Transplantation , Neoplasms, Experimental/drug therapy , Nervous System Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Time Factors , Xenograft Model Antitumor AssaysABSTRACT
TIR8, also known as single Ig IL-1-related receptor, is a member of the IL-1 receptor/Toll-like receptor (TLR) superfamily, which acts as an intracellular decoy for components of the signaling pathway. Here we report that Tir8 has a unique pattern of expression, which includes mucosal tissues and dendritic cells (DC). Tir8-deficient DC showed increased cytokine production in response to TLR agonists (lipopolysaccharide, CpG oligodeoxynucleotides). Tir8-deficient mice had normal susceptibility to systemic lipopolysaccharide toxicity and to i.p. or s.c. inflammation. However, Tir8-deficient mice were more susceptible to intestinal inflammation. Thus, TIR8 represents a negative pathway of regulation of the IL-1 receptor/TLR system, expressed in epithelial cells and DC, crucial for tuning inflammation in the gastrointestinal tract.
