Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

Background: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection.

Patients And Methods: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m q2w or 8× nab-paclitaxel 125 mg/m q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25.

Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2- Early Breast Cancer.

Purpose: To our knowledge, WSG-ADAPT-HR+/HER2- (ClinicalTrials.gov identifier: NCT01779206; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer.

Materials And Methods: Baseline and postendocrine Ki67 (Ki67) were evaluated centrally.

The run-in phase of the prospective WSG-ADAPT HR+/HER2- trial demonstrates the feasibility of a study design combining static and dynamic biomarker assessments for individualized therapy in early breast cancer.

Background: Endocrine sensitivity, as determined by response of the proliferation marker Ki-67 to short-term preoperative endocrine therapy (ET), is currently not included in adjuvant treatment decisions in hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- breast cancer (BC).

Methods: The prospective WSG-ADAPT HR+/HER2- trial included patients with N0/N1 early BC who were candidates for adjuvant chemotherapy based on clinical-pathological criteria alone. The trial utilized a genomic assessment [the Recurrence Score (RS)] plus endocrine sensitivity testing to guide treatment.

Autologous and alloplastic breast reconstruction--overview of techniques, indications and results.

It is important for any woman undergoing mastectomy to make an informed decision about reconstruction and to be provided with information about the technique, advantages and disadvantages. There is a high degree of patient satisfaction with breast reconstruction, but high levels of preoperative information and psychological support are necessary. Close collaboration between oncological and reconstructive surgeons or management by an oncoplastic breast surgeon, careful patient selection and counseling, and refinements in surgical techniques can provide a range of safe and predictable techniques for breast reconstruction.

Breast-conserving treatment of breast cancer--oncological and reconstructive aspects.

Breast-conserving surgery combined with radiotherapy has become the treatment of choice for the majority of women presenting with primary breast cancer over the last 20 years. The extent of local excision remains a controversial issue in breast-conserving surgery. The wider the margins of clearance, the lower the risk of incomplete excision and thus of local recurrences, but the greater the amount of tissue removed, the higher the risk of visible deformity leading to an unacceptable cosmetic result.

ChEBI: a database and ontology for chemical entities of biological interest.

Chemical Entities of Biological Interest (ChEBI) is a freely available dictionary of molecular entities focused on 'small' chemical compounds. The molecular entities in question are either natural products or synthetic products used to intervene in the processes of living organisms. Genome-encoded macromolecules (nucleic acids, proteins and peptides derived from proteins by cleavage) are not as a rule included in ChEBI.

IntEnz, the integrated relational enzyme database.

IntEnz is the name for the Integrated relational Enzyme database and is the official version of the Enzyme Nomenclature. The Enzyme Nomenclature comprises recommendations of the Nomenclature Committee of the International Union of Bio chemistry and Molecular Biology (NC-IUBMB) on the nomenclature and classification of enzyme-catalysed reactions. IntEnz is supported by NC-IUBMB and contains enzyme data curated and approved by this committee.

Long-term morbidity following axillary dissection in breast cancer patients--clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors.

Objective: This study describes in detail the surgery-related symptoms following axillary lymph node dissection in breast cancer patients and considers both their significance for long term quality of life and the impact of possible influencing factors.

Material And Methods: Three hundred and ninety six patients were studied retrospectively using a self-report questionnaire and a clinical examination. The symptoms, numbness, pain, edema, arm strength and mobility were evaluated.

Drug-induced apoptosis in chronic lymphocytic leukemia.

Glucocorticoids and fludarabine are able to induce typical features of apoptosis in CLL lymphocytes. Cysteinyl aspartate specific proteases (caspases) play a key biochemical role in the apoptotic pathway. Caspase activation following cytotoxic stimuli leads to highly specific proteolytic cleavage of functionally important cellular enzymes.

Value of human chorionic gonadotropin compared to CEA in discriminating benign from malignant effusions.

Human chorionic gonadotropin (HCG) is expressed in germ cell tumors and urothelial, breast, lung and colon cancers. The aim of the study was to investigate if the determination of HCG in comparison with CEA is able to discriminate between malignant and benign effusions. Effusion and partially serum samples of 61 patients with benign (g.

P53-immunoreactive cells in benign and malignant effusions: diagnostic value using a panel of monoclonal antibodies and comparison with CEA-staining.

The diagnosis of malignancy in peritoneal and pleural effusions can be difficult, because activated mesothelial cells may resemble malignant cells. P53 mutations are the most frequent genetic changes in human cancer and translate into an overexpression of the p53 protein detectable by immunocytochemistry. In this study, we investigated the sensitivity and specificity of 4 different monoclonal antibodies (moAB) against p53 for the diagnosis of malignancy in effusions.

Association of bcl-2, bax, bcl-xL and interleukin-1 beta-converting enzyme expression with initial response to chemotherapy in acute myeloid leukemia.

Bcl-2 expression is able to confer drug resistance to chemotherapy-induced programmed cell death. Bax, a partner protein of bcl-2 with extensive aminoacid homology, is a promoter of apoptosis. Apparently the equilibrium of bcl-2 and bax hetero- and homodimers is important for the susceptibility of cells for stimuli inducing apoptosis.

Autoantibodies against p53 are not increased in human ascites and pleural effusions.

Mutated human p53 may give rise to the formation of autoantibodies and may be a marker for a worse prognosis. We speculated that ascites or pleural effusions may enhance the formation of such autoantibodies in cancer patients and, therefore, we measured the presence of autoantibodies in the ascites or pleural effusion of 40 patients with advanced malignancies. As controls, p53 autoantibodies were measured in 15 patients with effusions who did not have a malignancy.

[Expression of transforming growth factor beta-3 (TGF-beta-3) on reactive and malignant cells in ascites and pleural effusion].

Patients And Method: The expression of TGF-beta-3 was examined in 64 patients with reactive and malignant effusion by immunocytochemistry.

Result: In about half of the patients with malignant effusions (especially breast cancer, gastric cancer, and carcinomas of unknown primary) TGF-beta positive tumor cells could be detected. We could show here for the first time that reactive mesothelial cells could also express TGF-beta.

Effects of tumor necrosis-factor on primary human leukemia cells: ultrastructural changes.

We investigated the ultrastructural effects of recombinant tumor necrosis factor alpha (TNF) on primary leukemia cells of 8 patients (4 cases of acute myelogenous leukemia and 4 cases of chronic myelogenous leukemia) as well as on bone marrow cells of 1 normal control. The cells were kept in liquid culture for up to 92 h in the presence of up to 10,000 U/ml of recombinant human TNF without adding colony-stimulating factors. Under these conditions the concentration of viable leukemic cells decreased by 14 to 53%, compared to control cultures.

TNF induces cytoplasmic vesicles in actinomycin D-treated K 562 cells.

We report here that tumor necrosis factor alpha (TNF) induces peculiar cytoplasmic vesicles in the human erythromyeloid leukemia cell line K 562, sensitized to the cytotoxic action of TNF by a treatment with the inhibitor of transcription actinomycin D. These vesicles are well delineated ultrastructurally. The formation of these vesicles is characteristic for the combination of actinomycin D with TNF and precedes the changes of apoptosis and cellular disintegration.

Mitochondrial changes in malignant lymphoma cells.

Mitochondrial changes (enlargement, loss of cristae, finely granular content) were observed in 5-25% of the lymphoma cells of 6 patients suffering from different types of non-Hodgkin's lymphomas. These cytoplasmic inclusions may also be visible in light microscopic preparations and may give reason for misinterpretation.