Tissue necrosis after chemotherapy in osteosarcoma as the important prognostic factor

Objective: To determine the histological response to preoperative chemotherapy of the percentage of tumor necrosis, and to assess the relationship between the histological response and the oncological result. Methods: Eighty patients with osteosarcoma were managed with preoperative and postoperative chemotherapy and operative resection at Shafa Yahyaceyan Hospital, Tehran, Iran between 2003-2005. Sections of each operative specimen were examined, and the histological response to chemotherapy was graded. Grade 1 indicated necrosis of 50 of the tumor or less; grade 2, necrosis of more than 50 yet lea than 90; grade 3, necrosis of more than 90. Results: The mean duration of the follow-up of the surviving patients, who were continuously free from disease was 1044 days. The histological response to preoperative chemotherapy (p=0.016) was the most important predictor of even-free survival. The rate of event-free short-term survival for the 80 patients entering this study was 86 (69 patients) at 12 months, 50 (24 patients) at 24 months, and 21 (5 patients) at 40 months, with 5 patients surviving for a median of 1096 days. Conclusion: The histological response to preoperative chemotherapy is an important clinical predictor of the result of operative treatment of osteosarcoma. This indicator should be used to identify patients who are at high risk for metastasis, as such patients may be candidates for more intensive or novel therapy

Histonedeacetylase 1 mRNA has elevated expression in clinical specimen of bladder cancer

OBJECTIVE: HDACs are among transcriptional regulatory elements that regulate key features of proliferation and differentiation in all cell types including cancerous. They may also interfere in such stages of cancer development as migration, invasion, multi-drug resistance and angiogenesis. Proven information about HDAC1 role in development of bladder cancer is limited only to cell lines in vitro. The lack of a comprehensive clinical in vivo study led us to evaluate HDAC1 expression in human clinical specimens. METHODS: We analyzed a large group of bladder cancer patients. The presence of hHDAC1 mRNAs were tracked using specific HDAC1 primers in cancer samples and the quantity of HDAC1 transcripts were quantified using real time qPCR method and was compared to those of normal bladder samples from healthy patients. RESULTS: HDAC1 mRNA expression was significantly elevated in Bladder cancer specimens. To our knowledge, this result is the first, showing an elevation in vivo in HDAC1 mRNA levels in clinically cancerous tissue of patients with bladder cancer. CONCLUSIONS: We conclude that hHDAC1 overexpression might be implicated in bladder cancer tumorigenesis and that the over-expressed HDAC1 mRNA might be a potential diagnostic marker and, a target for treatment of bladder cancer using HDACi-drugs in future

Histonedeacetylase 1 mRNA has elevated expression in clinical specimen of bladder cancer

OBJECTIVE: HDACs are among transcriptional regulatory elements that regulate key features of proliferation and differentiation in all cell types including cancerous. They may also interfere in such stages of cancer development as migration, invasion, multi-drug resistance and angiogenesis. Proven information about HDAC1 role in development of bladder cancer is limited only to cell lines in vitro. The lack of a comprehensive clinical in vivo study led us to evaluate HDAC1 expression in human clinical specimens. METHODS: We analyzed a large group of bladder cancer patients. The presence of hHDAC1 mRNAs were tracked using specific HDAC1 primers in cancer samples and the quantity of HDAC1 transcripts were quantified using real time qPCR method and was compared to those of normal bladder samples from healthy patients. RESULTS: HDAC1 mRNA expression was significantly elevated in Bladder cancer specimens. To our knowledge, this result is the first, showing an elevation in vivo in HDAC1 mRNA levels in clinically cancerous tissue of patients with bladder cancer. CONCLUSIONS: We conclude that hHDAC1 overexpression might be implicated in bladder cancer tumorigenesis and that the over-expressed HDAC1 mRNA might be a potential diagnostic marker and, a target for treatment of bladder cancer using HDACi-drugs in future

The effect of essential oil of Salvia mirzayanii on learning and memory in mice using the passive avoidance learning methods

Background: In traditional medicine, many herbal medicines like lamiaceae family are used as treatment for dementia. Lamiaceae family has many pharmacological effects including antioxidant, anti-cholinesterase, antimicrobial, anticancer, anti-inflammatory and enhancing cognition and memory. Salvia mirzayanii is one of the species of this family and has been used as an herbal medicine for many years. The purpose of this study was to examine the effect of essential oil of S. mirzayanii on learning and memory in mice using the two passive avoidance methods. Materials and Methods: The aerial parts of the plant were dried in shade and essential oils were obtained using clevenger apparatus. The active components in the essential oils of the plant were also identified using the gas chromatography-mass spectrometry (GC/MS). One-hundred and forty mice classified into different groups (n=10) were received certain doses of diazepam (0.5, 1 and 1.5 mg/kg) or the essential oil of S. mirzayanii (0.48, 0.96 and 1.92 mg/kg) by gavage tube. The step-down and step-through latencies were used to evaluate the learning and memory. Results: S. mirzayanii essential oil significantly increased the step-down and step-through latency times in both methods (

A protective cocktail vaccine against murine cutaneous leishmaniasis with DNA encoding cysteine proteinases of Leishmania major.

The protection elicited by the intramuscular injection of two plasmid DNAs encoding Leishmania major cysteine proteinase type I (CPb) and type II (CPa) was evaluated in a murine model of experimental cutaneous leishmaniasis. BALB/c mice were immunized either separately or with a cocktail of the two plasmids expressing CPa or CPb. It was only when the cpa and cpb genes were co-injected that long lasting protection against parasite challenge was achieved. Similar protection was also observed when animals were first immunized with cpa/cpb DNA followed by recombinant CPa/CPb boost. Analysis of the immune response showed that protected animals developed a specific Th1 immune response, which was associated with an increase of IFN-gamma production. This is the first report demonstrating that co-injection of two genes expressing different antigens induces a long lasting protective response, whereas the separate injection of cysteine proteases genes is not protective

Identification of Leishmania major cysteine proteinases as targets of the immune response in humans.

In this study, we report the identification of two parasite polypeptides recognized by human sera of patients infected with Leishmania major. Isolation and sequencing of the two genes encoding these polypeptides revealed that one of the genes is similar to the L. major cathepsin L-like gene family CPB, whereas the other gene codes for the L. major homologue of the cysteine proteinase a (CPA) of L. mexicana. By restriction enzyme digestion of genomic DNA, we show that the CPB gene is present in multiple copies in contrast to the cysteine proteinase CPA gene which could be unique. Specific antibodies directed against the mature regions of both types expressed in Escherichia coli were used to analyze the expression of these polypeptides in different stages of the parasite's life cycle. Polypeptides of 27 and 40 kDa in size, corresponding to CPA and CPB respectively, were detected at higher level in amastigotes than in stationary phase promastigotes. Purified recombinant CPs were also used to examine the presence of specific antibodies in sera from either recovered or active cases of cutaneous leishmaniasis patients. Unlike sera from healthy uninfected controls, all the sera reacted with recombinant CPA and CPB. This finding indicates that individuals having recovered from cutaneous leishmaniasis or with clinically apparent disease have humoral responses to cysteine proteinases demonstrating the importance of these proteinases as targets of the immune response and also their potential use for serodiagnosis

Humoral and cellular immune responses against Type I cysteine proteinase of Leishmania infantum are higher in asymptomatic than symptomatic dogs selected from a naturally infected population.

Canids are natural reservoirs of Leishmania infantum and have been promoted as experimental hosts to decipher the pathogenesis of human visceral leishmaniasis (VL). In this study, the presence of IgG antibodies as well as the presence of mononuclear leukocytes reactive to different cysteine proteinases (CPs) were examined in 13 L. infantum-infected dogs (six with symptoms, seven asymptomatic). Cysteine proteinases which belong to papain-like enzymes known as clan CA are the most studied CPs of parasite protozoa. These molecules are expressed by the intracellular stages of the parasite and could be immunogenic. We studied Type II CP (CPA) and Type I CP (CPB) with its long C-terminal extension (CTE) which could be highly immunogenic. We showed that the level of antibodies reactive to rCPA is low in both symptomatic and asymptomatic dogs. In contrast, when CPB and CTE were used as antigens, the level of total IgG (with IgG2 superior to IgG1) reached higher values in asymptomatic dogs than in dogs with VL. While the peripheral blood mononuclear cell (PBMC) reactivity was significant when cultured in the presence of freezed/thawed (F/T) lysate, it remained low in presence of CP although always higher for PBMC recovered from asymptomatic dogs. We showed the importance of CPB and CTE in particular as a target of immune response and their potential use for serodiagnosis in asymptomatic dogs