Interdisciplinary approach to abdominal Burkitt’s lymphoma

Burkitt’s lymphoma is a high-grade, rapidly growing B-cell neoplasm. It is recognized by its aggressive course, brief median survival, and low rates of long-term survival. The authors discuss the case of a patient who acutely presented with intraabdominal complications from a new onset of Burkitt’s lymphoma. The clinical and pathological features, staging, treatment options, and survival data are reviewed. In addition, the role of surgical intervention is carefully analyzed.     

Polymorphisms in glutathione-S-transferase genes (GST-M1, GST-T1 and GST-P1) and susceptibility to prostate cancer among male smokers of the ATBC cancer prevention study.

Glutathione-S-transferase (GST) genes encode a family of detoxification enzymes that offer protection against endogenous and exogenous sources of reactive oxygen species (ROS). Germline variations in GST genes may alter the catalytic efficiency of GST isoenzymes leading to a potential increase in susceptibility to the genotoxic effects of ROS and electrophilic substances. A nested case-control study design was used to examine the association between the polymorphic GST genes and prostate cancer risk among Finnish male smokers of the ATBC Cancer Prevention Study. A case-case analysis was used to determine the association between these genetic polymorphisms and prostate cancer progression. Germline DNA was obtained from 206 prostate cancer cases and 194 controls frequency matched on age, intervention group and study clinic. Cases and controls were genotyped for three GST genes using MALDI-TOF mass spectrometry or multiplex polymerase chain reaction (PCR). Relative to the wild-type genotype, we observed a 36% reduction in prostate cancer risk associated with the GST-M1-null genotype (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.43, 0.95). Unlike GST-M1, GST-T1-null (OR 0.74, 95% CI 0.42, 1.33) and GST-P1*B (OR 1.10, 95% CI 0.72, 1.69) were not strongly associated with prostate cancer risk. We did not observe any significant associations between the selected polymorphic GST genes and tumour grade or stage. In conclusion, we did not observe a direct association between polymorphic GST-T1 or GST-P1 and prostate cancer risk. Our observation of a relatively strong inverse association between the GST-M1-null genotype and prostate cancer risk needs to be confirmed in larger association studies.     

Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.     

Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections.

Levels of the soluble form of the triggering receptor expressed on myeloid cells (sTREM)-1 are elevated in severe sepsis. However, it is not known whether sTREM-1 measurements can distinguish milder bacterial infections from noninfectious inflammation. The present authors studied whether serum sTREM-1 levels differ in community-acquired pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), asthma and controls, and whether sTREM-1 may be used as a surrogate marker for the need for antibiotics. Serum sTREM-1 levels in 150 patients with pneumonia, COPD and asthma exacerbations and 62 healthy controls were measured. Serum sTREM-1 levels were significantly elevated in pneumonia (median 295.2 ng x mL(-1)), COPD (280.3 ng x mL(-1)) and asthma exacerbations (184.0 ng x mL(-1)) compared with controls (83.1 ng x mL(-1)). Levels were higher in pneumonia and Anthonisen type 1 COPD exacerbations than in type 2 and 3 COPD and asthma exacerbations. The area under the receiver operating characteristics curve for sTREM-1 as a surrogate marker for the need for antibiotics was 0.77. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 were elevated predominantly in pneumonia and Anthonisen type 1 COPD exacerbations versus type 2 and 3 chronic obstructive pulmonary disease exacerbations, asthma and controls. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 has moderate but insufficient accuracy as a surrogate marker for the need for antibiotics in lower respiratory tract infections.     

Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype.

We have recently shown that HPV-positive tonsillar carcinoma in young patients exhibits nonkeratinizing basaloid morphology and a characteristic immunophenotype. The purpose of this study was to review a large number of cases of oropharyngeal carcinomas, in all age groups, and to identify tumors with nonkeratinizing morphology. Using polymerase chain reaction (PCR) the prevalence and type of HPV DNA was determined in representative cases and in a control group of conventional keratinizing squamous cell carcinomas. The tumors were further characterized with a panel of immunohistochemical stains. A total of 235 carcinomas were reviewed; 141 of the tonsils and 94 in the base of tongue. Ninety (36%) of the tonsillar and 30 (32%) of the base of tongue carcinomas were nonkeratinizing (NKCa) with basal cell features; the rest were classical keratinizing squamous cell carcinomas (KSCC). HPV DNA, particularly type 16, was identified in 10 (100%) of 10 of NKCA and in only 2 (20%) of 10 of KSCC (P = .0014). NKCas were strongly reactive to p16 antibodies while KSCC showed weak and focal reactivity. Higher Ki67 and lower p53 staining scores were observed in NKCa as compared to KSCC. It is concluded that NKCa of the tonsils and base of tongue is a distinct subtype of squamous cell carcinoma of the head and neck with high prevalence of HPV DNA and a characteristic immunophenotype.