Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response

Background This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer. Methods A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay. Results Overall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03). Conclusion The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed

An "extension" of the carbohydrate binding specificity of concanavalin A

Evidence based on the quantitative precipitin method and hapten inhibition technique demonstrates that concanavalin A may interact with internal 2-O-linked [alpha]--mannopyranosyl residues as may occur in glycoproteins and polysaccharides.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33828/1/0000085.pd

Gender specific quality of life in patients with oral squamous cell carcinomas

<p>Abstract</p> <p>Background</p> <p>The goal of this study was to evaluate the somatic and psychological effects by means of QUALITY OF LIFE (QOL) of surgical treatment of patients with oral squamous cell carcinoma. The factors gender, age, nicotine consumption, and tumour stage were taken into consideration.</p> <p>Methods</p> <p>54 patients after surgical resection of oral squamous cell carcinomas (OSCC) were analysed from 01.09.2005 to 31.05.2008. Inclusion criteria for the study were: age at least 18 years, no indication or treatment of synchronous and metachronous tumours.</p> <p>German translations of the EORTC H&N-35 and EORTC QLQ-C-30 questionnaires, as well as a general socioeconomic patient history were used as measuring instruments. The questionnaires were completed independently by the patients. The answers were translated into scale values for statistical evaluation using appropriate algorithms.</p> <p>Results</p> <p>Analysis of the EORTC-QLQ-C-30 questionnaires demonstrated a tendency of more negative assessment of emotional function among the female participants, and a more negative evaluation of social function among the male participants. Greater tumour sizes showed significantly lower bodily function (p = 0.018). While a smaller tumour size was significantly associated with lower cognitive functioning (p = 0.031). Other cofactors such as age, nicotine consumption, and tumour stage only showed a tendency to influence the quality of sleep and daily life.</p> <p>Conclusions</p> <p>The data obtained within this investigation demonstrated that gender had the most significant power on the subjectively perceived postoperative quality of life. This factor is important e.g. in preoperative decision making regarding immediate microvascular reconstruction after e.g. mandibular resection and therefore QOL assessment should become integral component of the care of patients with OSCC.</p

bcl-2 expression is not associated with survival in metastatic cutaneous melanoma: A historical cohort study

<p>Abstract</p> <p>Background</p> <p>Programmed cell death (apoptosis) has been implicated in tumor development and may affect the metastatic potential of tumor cells. The role of bcl-2, a proto-oncogene that inhibits apoptosis, has been studied in several malignancies, including cutaneous melanoma (CM). The purpose of this study was to evaluate the immunohistochemical expression of bcl-2 in 35 regional lymph node, 28 subcutaneous and 17 visceral CM metastases, correlating the findings with patient survival.</p> <p>Methods</p> <p>In a historical cohort study patient survival was correlated with the expression of bcl-2 in regional lymph node, subcutaneous and visceral metastases of CM. Eighty slides containing surgical specimens from 50 patients diagnosed with stage III and IV CM, 28 male (56%) and 22 female (44%), were analyzed. Mean age at diagnosis was 43 years (16–74 years; median = 42 years). Mean Breslow depth was 5.01 mm (0.4–27.5 mm). The slides were submitted to immunohistochemical reaction using anti-bcl-2 monoclonal antibody and classified according to the degree of staining (< 5%; 5 to 50%; or > 50% of tumor cells stained). The relationship between bcl-2 protein expression and survival for each type of metastasis, gender and age at initial diagnosis was analyzed.</p> <p>Results</p> <p>Mean overall survival was 33.9 months after the diagnosis of the initial metastatic lesion (range: 0 to 131 months). Twenty-four out of 50 patients (48%) had died from CM by the end of the study period. bcl-2 expression was detected in 74.3, 85.7 and 82.4% of lymph node, subcutaneous and visceral metastases, respectively. After univariate and multivariate analyses, no correlation was found between positive bcl-2 expression and overall survival for the types of metastases evaluated.</p> <p>Conclusion</p> <p>The immunohistochemical expression of bcl-2 in metastasis alone is not a prognostic marker for CM.</p

A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, ‘DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m−2 for Group A and 100 mg m−2 for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events

Added Value of Molecular Biological Analysis in Diagnosis and Clinical Management of Liposarcoma: A 30-Year Single-Institution Experience

Biological, physical and clinical aspects of cancer treatment with ionising radiatio