OncoLog Volume 53, Number 02, February 2008

Assessing Symptom Burden in Cancer DiaLog: Making Headway in Hematology, by Guillermo Garcia-Manero, MD, Associate Professor, Department of Leukemia Helping Kids Make Smart Food Choices Expanding Therapy Options for Advanced Cancerhttps://openworks.mdanderson.org/oncolog/1167/thumbnail.jp

Emerging Treatments for Myelodysplastic Syndromes: Biological Rationales and Clinical Translation

Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by myeloid dysplasia, peripheral blood cytopenias, and increased risk of progression to acute myeloid leukemia (AML). The standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, nearly 50% of patients have no response to the treatment. Patients with MDS in whom HMA therapy has failed have a dismal prognosis and no approved second-line therapy options, so enrollment in clinical trials of experimental agents represents these patients\u27 only chance for improved outcomes. A better understanding of the molecular and biological mechanisms underpinning MDS pathogenesis has enabled the development of new agents that target molecular alterations, cell death regulators, signaling pathways, and immune regulatory proteins in MDS. Here, we review novel therapies for patients with MDS in whom HMA therapy has failed, with an emphasis on the biological rationale for these therapies\u27 development

Antibacterial PHAs coating for titanium implants

Biomaterial-associated infection is a serious complication of modern implantation surgery. Thus, the improvement of implant surfaces is required to avoid the first stage for biofilm formation, bacterial adhesion. The current research addresses this issue by developing drug delivery systems (DDS) consisting of antibiotic-loaded polyhydroxyalkanoates (PHAs) coatings on titanium implants. Dip-coating technique was used to achieve optimal coatings with biodegradable biopolyesters, polyhydroxybutyrate (PHB) and its copolymer, polyhydroxybutyrate-co-hydroxyvalerate (PHBV). The coatings were completely characterized (wettability, topography, thickness and roughness), and studies of drug delivery, toxicity, antibacterial effect, and cell adhesion were performed. For both of biopolymers, surfaces were partially covered with 1 and 3 immersions, while with 6, they were completely covered. Although both antibiotic-loaded biopolymer coatings assure the protection against bacteria populations, PHBV coatings are closer to the desired release profile; its faster degradation provides for a greater and more stable drug release for a given period of time compared to PHB coatings. The use of coatings with different drug concentration per layer results in more controlled and homogeneous releases. The DDS designed not only assure to avoid the first stage of bacterial adhesion, but also their proliferation and biofilm formation, since the coatings degrade with time under physiological conditions, guaranteeing a prolonged drug release.Preprin

Thrombospondin-1 serum levels do not correlate with pelvic pain in patients with ovarian endometriosis

Objetive: Thrombospondin-1 serum levels is correlate with pelvic pain in patients with ovarian endometriosis. Patients: Thrombospondin-1 serum levels were prospectively analysed in 51 patients (group A asymptomatic patients or patients presenting mild dysmenorrhea and women comprised group B severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists among thrombospondin-1 serum levels and pelvic pain. Results: From 56 patients, five cases were ultimateley excluded, because the histological diagnosis was other than cystic ovarian endometriosis (2 teratomas and 3 haemorragic cysts). The mean thrombospondin-1 serum levels in group A was 256,69 pg/ml_+37,07 and in group B was 291,41 pg/ml + 35,59. Conclusion: Pain symptoms in ovarian endometriosis is not correlated with thrombospondin-1 serum levels

Endometriosis in a postmenopausal woman without previous hormonal therapy: a case report

Introduction The prevalence of pelvic endometriosis is high, affecting approximately 6% to 10% of women of reproductive age. Although endometriosis has been associated with the occurrence of menstrual cycles, it can affect between 2% to 5% of postmenopausal women. Case presentation We present a case of ovarian endometriosis in a 62-year-old Spanish Caucasian woman with no previous use of hormonal therapy and no history of endometriosis or infertility. Conclusion Although the reported situation is rare, it is important to be aware of endometriosis after the menopause: post-menopausal endometriosis confers a risk of recurrence and malignant transformation

Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities

Improved Outcomes With “7+3” Induction Chemotherapy for Acute Myeloid Leukemia Over the Past Four Decades: Analysis of SWOG Trial Data

We have previously shown that complete response (CR) rates and overall survival of patients with acute myeloid leukemia have improved since the 1980s. However, we have not previously evaluated how the length of first CR (CR1) has changed over this time period. To address this, we analyzed 1,247 patients aged 65 or younger randomized to 7+3 arms from five SWOG studies: S8600 (n=530), S9031 (n=98), S9333 (n=57), S0106 (n=301), and S1203 (n=261). We evaluated length of CR1 and survival after relapse from CR1 over the four decades that these studies represent. Both length of CR1 and survival after relapse from CR1 have improved over the last four decades. The relative benefit associated with CR1 and the relative detriment associated with relapse have decreased over this period; while achieving CR1 and relapse from CR1 still have strong prognostic associations with outcomes, the magnitude of the association has decreased over time. Possible explanations for these patterns include higher CR rates with salvage therapies after relapse, more frequent use of hematopoietic cell transplant, and better supportive care