Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Dynamics of Flux Creep in Underdoped Single Crystals of Y_1-xPr_xBa_2Cu_3O_7-d

Transport as well as magnetic relaxation properties of the mixed state were studied on strongly underdoped Y_1-xPr_xBa_2Cu_3O_7-d crystals. We observed two correlated phenomena - a coupling transition and a transition to quantum creep. The distribution of transport current below the coupling transition is highly nonuniform, which facilitates quantum creep. We speculate that in the mixed state below the coupling transition, where dissipation is nonohmic, the current distribution may be unstable with respect to self-channeling resulting in the formation of very thin current-carrying layers.Comment: 11 pages, 9 figures, Submitted to Phys. Rev.

Doctor–patient communication in a Southeast Asian setting: the conflict between ideal and reality

Doctor–patient communication has been extensively studied in non-Western contexts and in relation to patients’ cultural and education backgrounds. This study explores the perceived ideal communication style for doctor–patient consultations and the reality of actual practice in a Southeast Asian context. We conducted the study in a teaching hospital in Indonesia, using a qualitative and a quantitative design. In-depth interviews were conducted with ten internal medicine specialists, ten internal medicine residents, 16 patients in two groups based on education level and ten most senior medical students. The contributions of doctors and patients to the communication during consultations were observed and rated quantitatively by thirty internal medicine residents, 393 patients with different educational backgrounds and ten senior medical students. The ‘informed and shared decision making’ is the central observation in this quantitative study. The results of the interviews showed that Southeast Asian stakeholders are in favor of a partnership style of communication and revealed barriers to achieving this: doctors and patients are not prepared for a participatory style and high patient load due to an inefficient health care system does not allow sufficient time for this type of communication. The results of the quantitative study showed a sharp contrast between observed and ideal communication styles. A paternalistic style seems to prevail, irrespective of patients’ educational background. We found a sharp conflict between ideal and reality concerning doctor–patient communication in a Southeast Asian context. Further studies should examine ways to change the prevailing communication style in the desired direction

SecA, a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data

Changes over time in the impact of gene-expression profiles on the administration of adjuvant chemotherapy in estrogen receptor positive early stage breast cancer patients : A nationwide study

Ten years ago gene-expression profiles were introduced to aid adjuvant chemotherapy decision making in breast cancer. Since then subsequent national guidelines gradually expanded the indication area for adjuvant chemotherapy. In this nation-wide study the evolution of the proportion of patients with estrogen-receptor positive (ER+) tumors receiving adjuvant chemotherapy in relation to gene-expression profile use in patient groups that became newly eligible for chemotherapy according to national guideline changes over time is assessed. Data on all surgically treated early breast cancer patients diagnosed between 2004-2006 and 2012-2014 were obtained from the Netherlands Cancer Registry. ER+/Her2- patients with tumor-characteristics making them eligible for gene-expression testing in both cohorts and a discordant chemotherapy recommendation over time (2004 guideline not recommending and 2012 guideline recommending chemotherapy) were identified. We identified 3,864 patients eligible for gene-expression profile use during both periods. Gene-expression profiles were deployed in 5% and 35% of the patients in the respective periods. In both periods the majority of patients was assigned to a low genomic risk-profile (67% and 69%, respectively) and high adherence rates to the test result were observed (86% and 91%, respectively). Without deploying a gene-expression profile 8% and 52% (p <0.001) of the respective cohorts received chemotherapy while 21% and 28% of these patients received chemotherapy when a gene-expression profile was used (p 0.191). In conclusion, in ER+/Her2- early stage breast cancer patients gene-expression profile use was associated with a consistent proportion of patients receiving chemotherapy despite an adjusted guideline-based recommendation to administer chemotherapy