Intratumoral inflammation is associated with more aggressive prostate cancer

Purpose

Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease.

Methods

The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively.

Results

No inflammation was found in 49 men (17 %), while 153 (53 %) and 85 (30 %) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44 %) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95 % CI 1.02–4.24), but not after adjusting for pathologic features.

Conclusions

Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.     

Non-specific SIRT inhibition as a mechanism for the cytotoxicity of ginkgolic acids and urushiols

Ginkgolic acids and urushiols are natural alkylphenols known for their mutagenic, carcinogenic and genotoxic potential. However, the mechanism of toxicity of these compounds has not been thoroughly elucidated so far. Considering that the SIRT inhibitory potential of anacardic acids has been hypothesized by in silico techniques, we herein demonstrated through both in vitro and computational methods that structurally related compounds such as ginkgolic acids and urushiols are able to modulate SIRT activity. Moreover, their SIRT inhibitory profile and cytotoxicity were comparable to sirtinol, a non-specific SIRT inhibitor (SIRT1 and SIRT2), and different from EX-527, a SIRT1 specific inhibitor. This is the first report on the SIRT inhibition of ginkgolic acids and urushiols. The results reported here are in line with previously observed effects on the induction of apoptosis by this class of compounds, and the non-specific SIRT inhibition is suggested as a new mechanism for their in vitro cytotoxicity.     

Intracardiac surgery in infants under age 3 months: Incremental risk factors for hospital mortality

During the 13 year period from January 1967 to July 1980, the hospital mortality rate for open intracardiac operations in infants in the first 3 months of life was 43 percent (75 deaths among 194 patients), higher than the 22 percent mortality rate (35 deaths in 161 patients) for closed operations in the same age group. The mortality rate was lower late in the experience (p = 0.0001). Poor preoperative condition of the patient increased the mortality rate 87 percent in patients preoperatively acidotic or in shock [preoperative class V]and 22 percent in patients with moderate or severe symptoms but without recent hemodynamic deterioration (preoperative class II or III). The presence of major associated cardiac lesions increased hospital mortality (p < 0.0001). The hospital mortality rate was highest (59 per cent) in infants less than age 1 month, possibly in part because of their sensitivity to the damaging effects of cardiopulmonary bypass. This hypothesis is supported by the association of a long period of cardiopulmonary bypass with increased hospital mortality (p = 0.05) and of total circulatory arrest during profound hypothermia with decreased mortality (p = 0.05). Most deaths (72 percent) occurred in association with acute postoperative cardiac failure. The length of cardiac ischemia (aortic cross-clamping time) was directly related to the probability of cardiac death, unless cold cardioplegia was used. Thirteen percent of the hospital deaths were associated with acute postoperative respiratory failure. Current mortality rates in typical cases without acute hemodynamic deterioration is estimated from these data to be 7 percent (70 percent confidence limits 4 to 12 percent), as a result of the scientific advances made over this period of time. Research into mechanisms of the damaging effects of cardiopulmonary bypass should further improve results in these very young patients.     

Clinical assessment of the entry into neurological state in rat experimental African trypanosomiasis

Human African trypanosomiasis, caused by Trypanosoma brucei (T.b.) gambiense or rhodesiense, evolves in two stages: haemolymphatic stage and meningo-encephalitic stages, the latter featuring numerous neurological disorders. In experimental models infected with diverse T.b. sub-species, body weight (BW) loss, drop in food intake (FI), and hypo-activity after an asymptomatic period suggest the occurrence of a similar two-stage organization. In addition to daily measurement of BW and FI, body core temperature (T(co)) and spontaneous activity (SA) were recorded by telemetry in T.b. brucei-infected rats. After a 10--12-day symptom-free period, a complex clinical syndrome occurred suddenly. If the animal survived the access, the syndrome re-occurred at approximately 5-day intervals until death. The syndrome was made of a drop in FI and BW, a sharp decrease in T(co) and a loss of SA, suggesting a brisk alteration of the central nervous system functioning. Such events confirm the existence of a two-stage disease development in experimental trypanosomiasis. The entry into the second stage is marked by the occurrence of the first access, BW follow-up being essential and often sufficient its determination.