Loss of Bcl-2 in invasive breast cancer is associated with high rates of cell death, but also with increased proliferative activity.

Bcl-2 has been demonstrated to inhibit apoptosis in breast cancer cells in vitro, and the ratio between Bcl-2 and its proapoptotic homologue Bax seems to be an important determinant of cellular sensitivity to induction of apoptosis. However, little information is available on the relationship between Bcl-2 and the rate of apoptotic and necrotic cell death in breast tumours. From a series of 441 premenopausal, lymphnode-negative breast cancer patients, a subset of 49 tumours was selected in which immunostaining for the 26-kDa isoform of Bcl-2 was either absent (n = 23) or very high (n = 26). High expression of Bcl-2 was found to be strongly associated with low rates of apoptotic (P < 0.001) and necrotic cell death (P < 0.001). The mean value of the apoptotic index was 2.69%+/-1.40% in Bcl-2-negative tumours and 0.68%+/-1.00% in Bcl-2-positive tumours. Expression of the proapoptotic protein Bax correlated neither with Bcl-2 nor with the frequency of apoptotic cells. Immunostaining for the antiapoptotic Bcl-2 homologue BcI-X(L) correlated with Bcl-2 expression (P < 0.001) but not with apoptosis. High proliferation rate and high tumour grade (Bloom-Richardson) were strongly associated with absence of Bcl-2 expression (P< 0.001). p53 accumulation was associated with absence of Bcl-2 expression and increased apoptotic activity. Loss of Bcl-2 expression was strongly correlated with increased apoptotic and necrotic cell death, high proliferation rate and high tumour grade, supporting a model in which Bcl-2 not only mediates cell death, but also cell division in breast cancer tissue, and in which regulation of cell division and cell death are tightly linked

Late Gothic altarpieces as sources of information on medieval wood use: A dendrochronological and art historical survey

A

Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population-Level Effectiveness?

<label>BACKGROUND</label>Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4) prevents anogenital warts (AGW) whilst the bivalent (HPV2) may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1) both genders with HPV4, and 2) boys with HPV4 and girls with HPV2.<label>METHODS</label>We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively.<label>RESULTS</label>Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points). At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios). Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points). Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines.<label>CONCLUSION</label>Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys

Follow-up of colorectal cancer patients: quality of life and attitudes towards follow-up.

The aims of our study were to assess the effect of follow-up on the quality of life of colorectal cancer patients and to assess the attitudes of patients towards follow-up as a function of patient characteristics. Patients who had been treated with curative intent were selected from four types of hospitals. Eighty-two patients were interviewed using a structured questionnaire, whereas 130 patients received the questionnaire by mail. To assess the effect of follow-up on the quality of life, the interviewed patients were randomly allocated to three groups and interviewed at different times in relation to the follow-up visit. Analysis did not show an effect of the follow-up visit on quality of life. Patients reported a positive attitude towards follow-up: it reassured them, they judged the communication with the physician to be positive, and they experienced only slight nervous anticipation and few other disadvantages. Patients reported a strong preference for follow-up, and a large majority would prefer follow-up even if it would not lead to earlier detection of a recurrence. Apart from living situation, no patient characteristics were clearly associated with the attitude towards follow-up. Implications for clinical practice are discussed

Evaluation of the 5th edition of the TNM classification for gastric cancer: improved prognostic value

The main change in the 5th edition (1997) of the TNM classification for gastric cancer compared to the 4th edition (1987) is the use of the number of involved nodes instead of the location of positive nodes. As a result stage grouping is also altered. A second change is the requirement for the examination of at least 15 nodes to justify the N0 status. Patients with fewer examined negative nodes are unclassifiable (Nx). Data were retrieved from a randomized trial database comparing D1 and D2 dissection and 633 curatively operated patients were included. According to the criteria of the 5th edition, 39% of the node-positive patients had another N stage compared to the 4th: 21% had a lower and 18% had a higher stage. 5-year survival rates according to the 4th edition N0, N1 and N2 groups were respectively 72%, 34% and 27%. According to the 5th edition these percentages were for the N0, N1, N2, N3 and Nx groups respectively 75%, 38%, 19%, 8% and 65%. The former 1987 N1 and N2 group were significantly split into three new N 1997 groups (P = 0.006, respectively P< 0.0005). The Cox's regression analysis showed the N 1997 classification to be the most important prognostic variable, with a higher prognostic value than N 1987. In addition, the new TNM stage was also a better prognosticator. The requirement for examining at least 15 nodes, however, could not be fulfilled in 38% of all node-negative patients and we found that a minimum of 5 consecutive negative lymph nodes is a reliable number for staging purposes. We conclude that the 5th edition of the TNM classification provides a better estimation of prognosis, however, examination of at least 15 negative regional lymph nodes is too high a threshold and 5 gives similar prognostic value. © 2001 Cancer Research Campaign http://www.bjcancer.co

Inclusion and Analysis of Older Adults in RCTs

Surgical oncolog

Expression of Bcl-2 in node-negative breast cancer is associated with various prognostic factors, but does not predict response to one course of perioperative chemotherapy.

The aim of this study was to assess relationships between Bcl-2 expression, response to chemotherapy and a number of pathological and biological tumour parameters in premenopausal, lymph node-negative breast cancer patients. Expression of Bcl-2 was determined using immunohistochemistry on paraffin-embedded sections in a series of 441 premenopausal, lymph node-negative breast cancers of patients randomised to receive perioperative chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) or no perioperative chemotherapy. Immunohistochemistry of Bcl-2 was evaluated by scoring both staining intensity (0-3) and number of positive cells (0-2). Using these scores tumours were grouped into categories 0-6. It was found that 9.2% of the tumours were completely negative (0), 17.2% weakly (1 + 2), 41.6% moderately (3 + 4) and 31.9% strongly positive (5 + 6) for Bcl-2. A positive correlation was found between high Bcl-2 expression and oestrogen (P < 0.001) and progesterone receptor positivity (P < 0.001) and low tumour grade (P < 0.001), whereas high Bcl-2 expression was negatively correlated with p53 (P < 0.001) and c-erb-B-2 positively (P < 0.001), high Ki-67 index (P < 0.001), mitotic index (P < 0.001) and large tumour size (P = 0.006). Patients with tumours expressing high levels of Bcl-2 (overall score 3-6) had a significantly better disease-free (P = 0.004) and overall (P = 0.009) survival. However, in a multivariate model this association no longer remained significant. There was a trend for an effect of adjuvant chemotherapy on disease-free survival both for patients with Bcl-2-positive (HR-0.61, 95% CI 0.35-1.06, P = 0.07) and negative (HR = 0.55, 95% CI 0.27-1.12, P = 0.09) breast tumours at a median follow-up of 49 months. The level of Bcl-2 expression does not seem to predict response to perioperative chemotherapy in premenopausal, lymph node-negative breast cancer patients. High levels of Bcl-2 are preferentially expressed in well-differentiated tumours and are associated with favourable prognosis. However, Bcl-2 expression is not an independent prognostic factor in this patient series