Adjuvant Docetaxel and Cyclophosphamide (DC) with Prophylactic Granulocyte Colony-Stimulating Factor (G-CSF) on Days 8 &12 in Breast Cancer Patients: A Retrospective Analysis

Purpose

Four cycles of docetaxel/cyclophosphamide (DC) resulted in superior survival than doxorubicin/cyclophosphamide in the treatment of early breast cancer. The original study reported a 5% incidence of febrile neutropenia (FN) recommending prophylactic antibiotics with no granulocyte colony-stimulating factor (G-CSF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events. We explored the use of growth factor (GF) support on days 8 and 12 of the cycle with the original DC protocol.

Methods

Our study included all consecutive patients with stages I–II breast cancer who were treated with the DC protocol at the Institute of Oncology, Davidoff Center (Rabin Medical Center, Petah Tikva, Israel) from April, 2007 to March, 2012. Patient, tumor characteristics, and toxicity were reported. Results: In total, 123 patients received the DC regimen. Median age was 60 years, (range, 25–81 years). Thirty-three patients (26.8%) were aged 65 years and older. Most of the women (87%) adhered to the planned G-CSF protocol (days 8 &12). 96% of the patients completed the 4 planned cycles of chemotherapy. Six patients (5%) had dose reductions, 6 (5%) had treatment delays due to non-medical reasons. Thirteen patients (10.6%) experienced at least one event of FN (3 patients had 2 events), all requiring hospitalization. Eight patients (6.5%) required additional support with G-CSF after the first chemotherapy cycle, 7 because of FN and one due to neutropenia and diarrhea.

In Conclusion

Primary prophylactic G-CSF support on days 8 and 12 of the cycle provides a tolerable option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support.     

Differential Co-Expression between α-Synuclein and IFN-γ Signaling Genes across Development and in Parkinson’s Disease

Expression patterns of the alpha-synuclein gene (SNCA) were studied across anatomy, development, and disease to better characterize its role in the brain. In this postmortem study, negative spatial co-expression between SNCA and 73 interferon-γ (IFN-γ) signaling genes was observed across many brain regions. Recent animal studies have demonstrated that IFN-γ induces loss of dopamine neurons and nigrostriatal degeneration. This opposing pattern between SNCA and IFN-γ signaling genes increases with age (rho = −0.78). In contrast, a meta-analysis of four microarray experiments representing 126 substantia nigra samples reveals a switch to positive co-expression in Parkinson’s disease (p<0.005). Use of genome-wide testing demonstrates this relationship is specific to SNCA (p<0.002). This change in co-expression suggests an immunomodulatory role of SNCA that may provide insight into neurodegeneration. Genes showing similar co-expression patterns have been previously linked to Alzheimer’s (ANK1) and Parkinson’s disease (UBE2E2, PCMT1, HPRT1 and RIT2).     

Can Taste Aversion Prevent Bruxism?

The first part of this note sketches a biofeedback modality for the treatment of bruxism. A mildly aversive, safe liquid is inserted into, and sealed in, small, bilaterally sleeved, polyethylene capsules. Two capsules are attached to a simple dental appliance that comfortably and securely places them between the lower and upper back teeth. The appliance and capsules are worn at night or at other times when bruxism is suspected to occur. Whenever a sleeping or an awake patient attempts to brux, one or both capsules rupture and the liquid is released into the mouth. The liquid then draws the patient's conscious attention to, and forestalls, any attempt of teeth clenching or grinding. Variations of the method and device can be used to diagnose bruxism. The second part of this note describes the long-term application of this taste-based approach to one chronic bruxer.     

A prevalent Y;15 translocation in the Ethiopian Beta Israel community in Israel

We describe 7 cases of abnormal karyotypes involving chromosomes Y and 15 in Ethiopian Beta Israel patients: 46,XX, der(15)t(Y;15)(q12;p12) and 46,XY,der(15)t(Y;15)(q12;p12). Six cases were incidentally found in amniocentesis performed for various indications; the indication for karyotyping in 1 case was recurrent abortions. To the best of our knowledge, this is the first report of this translocation in a specific ethnic group. We conclude that the derivative chromosome 15 with chromosome Y is probably a normal variant in Ethiopian Beta Israel occurring at an estimated frequency of 4/74 (5.4%). The prenatal diagnosis of this translocation in this population probably does not require further parental testing.     

Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart

G protein-activated inwardly rectifying potassium channels (Kir3, GIRK) provide an important mechanism for neurotransmitter regulation of membrane excitability. GIRK channels are tetramers containing various combinations of Kir3 subunits (Kir3.1--Kir3.4). We find that different combinations of Kir3 subunits exhibit a surprisingly complex spectrum of trafficking phenotypes. Kir3.2 and Kir3.4, but not Kir3.1, contain ER export signals that are important for plasma membrane expression of Kir3.1/Kir3.2 and Kir3.1/Kir3.4 heterotetramers, the GIRK channels found in the brain and the heart, respectively. Additional motifs in Kir3.2 and Kir3.4 control the trafficking between endosome and plasma membrane. In contrast, the Kir3.3 subunit potently inhibits plasma membrane expression by diverting the heterotetrameric channels to lysosomes. Such rich trafficking behaviors provide a mechanism for dynamic regulation of GIRK channel density in the plasma membrane.