Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression.

BACKGROUND: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib. METHODS: Tumor biopsies were obtained before and after treatment with celecoxib 400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor angiogenesis and cell proliferation were assessed by immunohistochemistry and gene expression by microarray analysis. Plasma celecoxib concentrations were obtained on days 8 and 14. RESULTS: Paired samples were analyzed in 15 patients. Microvessel density was reduced in post-treatment samples and mean celecoxib levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up-regulated) were differentially expressed on microarray analysis (p < 0.001). Down-regulated genes included cell cycle regulation-related (cyclin-dependent kinase 2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and presentation-related gene HLA-DM B was up-regulated. CONCLUSION: Celecoxib reduced angiogenesis and induced tumor transcriptional changes. Further characterization of these transcriptional changes in vivo is needed to provide further insights into the effects of celecoxib in neoplastic tissue. Our findings provide a rationale for clinical studies aimed at assessing the efficacy of celecoxib in the treatment of NPC.

Clinico-pathological analysis of myelodysplastic syndromes according to French-American-British classification and international prognostic scoring system.

INTRODUCTION: The aim of this study was to analyse the clinico-pathological features of a cohort of patients with myelodysplastic syndromes (MDS). MATERIALS AND METHODS: The clinical and pathological data of 43 MDS patients over a 3-year period were reviewed. Survival analysis was performed according to the French-American-British (FAB) classification and International Prognostic Scoring System (IPSS) using the Kaplan-Meier method. Selected published studies for comparison were identified from MEDLINE search. RESULTS: The patients were followed up for a median duration of 175 days (range, 2 to 1044 days). The median survival for refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS) has not been reached, but that for refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEB-T) and chronic myelomonocytic leukaemia (CMML) was 250 days, 49 days and 44 days, respectively. The median survival for the low-risk and intermediate-1 IPSS categories has not been reached, while that for the intermediate-2 and high-risk categories was 58 days and 49 days, respectively. The survival analyses, according to the FAB classification and IPSS system, were statistically significant (P <0.05). Comparison of our data with those from neighbouring and Western countries revealed both similarity and disparity. We also noted different cytogenetic information in our cohort of patients. CONCLUSIONS: We found distinctly unique cytogenetic and clinico-pathological characteristics in our MDS patients. However, whether true biological differences exist among MDS patients in different geographies and populations with different genetic and environmental backgrounds require further large multinational study.

Apoptosis and the response to anticancer therapy.

Apoptosis is a distinctive form of cell death that reflects cleavage of a subset of intracellular polypeptides by proteases known as caspases. Two major intracellular caspase cascades, one activated predominantly by death receptor ligands and the other triggered by various cellular stresses, including DNA damage and microtubule disruption, have been delineated. Activation of these protease cascades is tightly regulated by a number of polypeptides, including Bcl-2 family members, inhibitor of apoptosis proteins, and several protein kinases. The demonstration that many antineoplastic agents induce apoptosis in susceptible cells raises the possibility that factors affecting caspase activation and activity might be important determinants of anticancer drug sensitivity. Here, we review recent studies describing the regulation of apoptotic pathways and identify potential implications of these findings for resistance to antineoplastic agents.

Hypercalcemia complicating leukemic transformation of agnogenic myeloid metaplasia-myelofibrosis.

Hypercalcemia is a common and potentially life-threatening metabolic derangement associated with many malignancies, especially solid tumors and multiple myeloma. Hypercalcemia has been reported only rarely with acute myelogenous leukemia. We describe a patient who developed hypercalcemia in association with transformation of agnogenic myeloid metaplasia into M7 acute myelogenous leukemia. Laboratory investigation revealed low levels of serum parathyroid hormone, undetectable levels of parathyroid hormone-related peptide, and normal levels of 25-hydroxyvitamin D. These observations suggest that another mediator was responsible for hypercalcemia in this patient. Awareness of this rare complication of acute myelogenous leukemia is essential for prompt diagnosis and management.

Patterns of psoriatic arthritis in Orientals.

OBJECTIVE: To determine the clinical features of psoriatic arthritis (PsA) in a multiethnic Oriental population and to study the effect of ethnicity on disease patterns. METHODS: A retrospective study of 80 patients with PsA seen at either a rheumatology or dermatology referral center. Patients and case records were reviewed and data abstracted according to a standard protocol. Eighty consecutive patients with psoriasis without PsA seen at the dermatology center were recruited as controls. RESULTS: Asymmetric polyarthritis developing in the 4th decade with an equal male to female ratio was the commonest pattern of arthritis among Chinese, Indians, and Malays. Clinically apparent lumbar spondylitis was significantly more common in Indians than Chinese (10/11 vs 11/20, respectively; p = 0.046), although the prevalence of lumbar spondylitis was similar in all ethnic groups. Eighty-nine percent of subjects required nonsteroidal antiinflammatory drugs and 51% required disease modifying antirheumatic drugs at some time for control of joint disease. PsA was significantly more common among Indians compared to the ethnic distribution of the Singapore population (p < 0.000001). Multiple logistic regression identified Indian ethnicity as a risk factor for the development of PsA (OR 2.39, 95% confidence interval 1.02 to 5.60). CONCLUSION: The commonest pattern of PsA in all ethnic groups was asymmetric polyarthritis. Ethnicity affected the development and presentation of PsA in our series: Indians with psoriasis had double the risk of developing PsA compared to Chinese with psoriasis, and lumbar spondylitis when present in Chinese subjects was asymptomatic in 45%, being detectable only on radiological examination.

The profile of ICU admissions for acute severe asthma in a general hospital.

The clinical profile of 22 patients admitted to the Intensive Care Unit of Alexandra Hospital over a 2-year period was studied. The mean age was 48.8 years with a majority in the older age group. The attacks leading to admission were generally rapid in evolution with 59% having symptoms for less than 12 hours and 84% for less than 24 hours. Most had a history of severe asthma, and of long duration. The pre-admission therapy had been suboptimal in the majority. Severe respiratory acidosis was a predominant feature. 68% were transferred to the ICU within one hour of arrival at hospital. Mechanical ventilation was required in 86.4% of cases, but the duration of ventilation was usually short. There was no serious complication due to barotrauma. Overall mortality was 23% (5/22). Problems in patient education remain a major hurdle in our attempt to reduce asthma mortality.