In this study, we reviewed epigenetic therapy of lymphomas using histone deacetylase inhibitors (HDACi), a promising new class of antineoplastic agents. Epigenetic therapy, a new therapeutic concept, consists of the use of HDACi and or DNA methyltransferase inhibitors (DNMTi). We conducted a comprehensive review of the literature for antitumour activity of HDACi and its mechanism of action. HDACi modify the expression of several genes related to cancer development, which can result in antineoplastic activity. To elucidate the benefits of HDACi in lymphoma treatment, we discuss the crucial interplay between BCL6, p53 and STAT3. Activated B-cell (ABC) diffuse large cell lymphoma (DLCL) is increasingly being recognised as an unfavourable and frequently therapy-refractory lymphoma. We discuss the fundamental causative role of the STAT3 oncogene in ABC type DLCL. STAT3 can be effectively suppressed by several HDACi, a promising treatment for this difficult subtype of DLCL. On the other hand, various HDACi can repress the germinal-centre B Cell (GCB) type DLCL by virtue of their inhibition of the BCL6 oncogene, usually expressed in this particular subtype. We summarise the results of recent clinical trials with HDACi such as romidepsin, panobinostat, MGCD-0103, entinostat, curcumin, JAK2 inhibitor TG101348, and valproic acid that have shown preliminary activity in recurrent and refractory lymphomas. The unique mechanism of action of HDACi makes them very attractive agents to pursue in combination. Several ongoing trials are already exploring HDACi combinations in various types of cancers. Their role in front-line management remains to be determined.
e20697 Background: The assessment of supportive care needs is important in the management of cancer patients. The Supportive Care Needs Survey (SCNS-34) was administered to a population of Puerto Rican cancer patients to assess their perceived needs in five domains (psychological, health system and information, physical and daily living, patient care and support, and sexuality.) Methods: Patients attending the surgical, radiation and medical oncology clinics at the Puerto Rico Medical Center participated in the study. After informed consent, patients completed the Spanish- Puerto Rican translation of the SCNS-34. A second instrument to measure the quality of the SCNS-34 was administered. Demographic and clinical data was obtained from medical records. Descriptive, univariate and multivariate analysis was performed to assess correlation between reported needs and demographic and clinical data. To assess the validity and consistency of the Spanish Puerto Rican translation of the SCNS-34, the Cronbach's alpha test was used. Results: A total of 103 patients participated in the study (female n=66; male n=37). Median age was 54 years. The most common malignancies were breast cancer (29 patients), gynecologic cancers (22 patients), prostate cancer (17 patients) and gastrointestinal cancers (14 patients). The overall internal consistency of the instrument was 0.882. Patients perceived needs were highest in the domains of sexuality (67%), physical and daily living (55.3%), and psychological (38.8%). Logistic regression analysis demonstrated that younger age was an independent predictor of perceived needs in the psychologic domain (p=0.010). Also, a diagnosis of breast cancer was a significant predictor of perceived needs in the health system and information domain (p=0.020). Being a female was correlated with reporting needs in the domain of physical and daily living (p=0.009). Educated patients were more prone to perceive needs in the domains of sexuality (p=0.045). Conclusions: The Spanish- Puerto Rican translation of the Supportive Care Needs Survey (SCNS-34) showed satisfactory internal consistency and validity. The supportive care needs of Puerto Ricans cancer patients seem to be affected by age, gender, and cancer site. No significant financial relationships to disclose.
Background: DNA methylation of gene promoters have been show to play a role in the pathogenesis of acute myeloid leukemia (AML). We present in this study a preliminary report of the methylation status of MLH1, p16, SOCS1, ER and CDH1 in Puerto Rican patients with AML. Methods: Peripheral blood was obtained from 24 patients with diagnosis of acute myeloid leukemia before and after their induction treatments. DNA was isolated and further modified with sodium bisulfite. Methylation-specific polymerase (MSP) chain reaction was performed to detect aberrant promoter methylation of MLH1, p16, SOCS1, ER and CDH1. Results: Samples from a total of 24 patients were analyzed. The mean age was 47 years (range 22-70) with 21/24 patients younger than 60 years (88%). Most of the patients were female (13/24, 54%). Ten patients had diploid cytogenetics (42%), 4 had low risk cytogenetics (17%) and 10 had high risk cytogenetics (42%). Nineteen patients were de Novo AML (79%). Sixteen patients (67%) presented with WBC counts higher than 10 x 109/L. Seventeen patients (71%) achieved a complete response at the end of the induction therapy. Frequencies of gene methylation before treatment were as follows: MLH: 3/24 (13%); p16: 6/24 (25%); SOCS1:13/24 (54%); ER: 16/24 (67%) and CDH1: 4/24 (16.7%). Conclusions: No correlation between methylation status of p16 and MLH1 before treatment and clinicopathological characteristics was noted. Unmethylated CDH1 was more common among the novo AML patients. Methylation of SOCS1 was more common among patients that achieve a CR after induction therapy. This sample is a small one, so any correlation must be further tested in a more ample sample. Collection of more patient's samples and correlation with clinical data and patient's ultimate outcome is ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5569. doi:1538-7445.AM2012-5569
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