Background: Loss-of-function mutations within KMT2D are a striking feature of the germinal centre lymphomas, with lesions present in 80% of Follicular Lymphoma (FL) and 30% of Diffuse Large B-cell Lymphoma (DLBCL) cases, resulting in decreased H3K4 methylation and altered gene expression. The majority of KMT2D mutations in FL and DLBCL are truncating and clonal, arise early during tumour development, and are often bi-allelic, yet despite their frequency, no attempts have been made to therapeutically target these mutations. We hypothesised that inhibition of the KDM5 family, which normally opposes KMT2D through demethylating H3K4me3/2, would re-establish H3K4 methylation and restore the expression of genes repressed upon loss of KMT2D.
Background The advantages of orally active chemotherapy make it a valuable option for treating cancer patients. Purpose To assess the use and cost of oral vinorelbine (OV) in a regional hospital. Materials and methods A retrospective descriptive study carried out from January 2009 till September 2010. The authors report on all the patients who were treated with OV during the period of study. The authors checked the following information: sex, age, diagnosis, previous and subsequent chemotherapy regimens, chemotherapy regimen, mean dose, patient-related cost and overall cost. Results The authors studied 21 patients (80.9% men and 19.1% women) with a mean age of 68.1±8.9 years. 15 patients were diagnosed with non-small cell lung cancer (NSCLC), 3 with breast cancer (BC) and 3 with prostate cancer (PC). 40% of patients with NSCLC had previously been treated with cisplatin-paclitaxel or cisplatin-gemcitabine whereas 60% had been treated with cisplatin-vinorelbine or vinorelbine alone. With regard to the other diagnoses: 3 patients with BC had been treated with paclitaxel-anthracycline and 3 patients with PC had been treated with paclitaxel-carboplatin. For the current treatment, the distribution of treatments was the following: a) OV monotherapy (6), b) OV associated with cisplatin (6), c) docetaxel monotherapy (2) and c) without treatment (7). The chemotherapy regimens with OV were: 60 mg/m2, on the 1st and 8th day every 21 days (71.4%); 60 mg/m2, on the 1st and 8th day every 21 days the first cycle and 80 mg/m2, on the 1st and 8th day every 21 days in the following cycles (14.3%); 60 mg/m2, on days 1, 8 and 15 every 28 days (14.3%). Average dose of OV was 110.4±13.6 mg with an average number of prescriptions dispensed of 4.7±2.7. Only 9 patients had received prior intravenous vinorelbine. Patient-related cost was 1,314.08 € and overall cost was 14,454.96 €. Conclusions In our hospital, OV was used in accordance with the guidelines except that the absence of intravenous vinorelbine first in 42.8% of patients should be justified. Although the cost of OV is high it is justifiable because it avoids indirect costs.
Background: Expression of 14-3-3 σ is a tumor suppressor gene induced in response to DNA damage, and has been implicated in G2/M cell cycle arrest by p53. Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is now firmly established as an important mechanism for gene inactivation. Objetive: To correlation methylation levels of promoter 14-3-3σ with association prognostic factors in breast cancer.Material and Methods:This is a prospective study we quantified methylation levels of promoter 14-3-3 σ gene in 107 women with breast cancer and 108 control subjects by Real Time QMS-PCR SYBR green and analyzed association with prognostics factor in breast cancer. Results: Median age was 58 years (32-88); 69% were postmenopausal women.Nodal involvement N0; 63%,N1;30%,N2;7%), tumor size (T1;58%,T2;35%,T3;4%,T4;4%) and grade G1; 20%,G2;37%,G3;30%). The methylation of 14-3-3σ were 60% of sporadic breast cancer patients and were 34% of normal breast (p=0.0047).The methylation of 14-3-3σ gene in serum was markedly related with T3-4 stage (P<0.05),nodal positive status (P<0.05) and poor outcome. With a median follow up 6 years we saw more probability of developing distance metastasis in patients with methylation 14-3-3σ (P>0.05).Conclusions:Hypermethylation of the 14-3-3σ a promoter is an early and frequent event in breast neoplastic transformation, leading to the suggestion that silencing of 14-3-3σ may be an important event in tumor progression and particularly in breast carcinogenesis.Therefore, it is possible that loss of σ expression contributes to malignant transformation by impairing the G2 cell cycle checkpoint function, thus allowing an accumulation of genetic defects. Perhaps in the detection of CpG methylation of 14-3-3σ may be used for diagnostic and prognostic purposes Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-04-07.
Background The polymicrobial nature of complicated intra-abdominal infections makes these infections particularly challenging to treat. The initial selection of antimicrobial therapy is therefore extremely important. Purpose The authors assessed the use of tigecycline in treatment of complicated intra-abdominal infections. Materials and methods A retrospective observational study was made about patients with complicated intra-abdominal infection treated with tigecycline in a Intensive Care Unit from November'07 to December'10. The authors checked: age, sex, APACHE II at admission, aetiology of infection, posology, antibiograms, duration of the treatment in days, clinical recovery and death. Results During the study, 97 patients were included: 64 men and 33 women. The mean age was 58,5±17,7 years. With regard to the aetiology of infections, 64 patients were diagnosed of secondary peritonitis, 27 of abscesses and 6 presented tertiary peritonitis. The microorganisms more frequently identified were gram-negative bacilli (Escherichia Coli found predominantly) and gram-positive cocci (Enterococcus spp.)The average in the scale APACHE II was 16,5 ±7 points. The percentage of patients at admission with sepsis and septic shock was 43,3% and 56,7%, respectively. All the patients received the first dose of 100 mg followed of 50 mg every 12 h for intravenous route. The average duration of the treatment was of 9,5±3.75 days. Clinical recovery occurred in most patients (80,7%). The death rate was 27,8%, which was lower than expected, according to the scale APACHE II (36,7% expected). With regard to the safety, serious adverse effects associated to tigecycline were not registered. Conclusions Our finding shows that tigecycline was effective and safe in complicated intra-abdominal infections when it was used according to authorised conditions (dosage and indications)
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