Resistance to chemotherapy is one of the leading causes of death from breast cancer. We recently established that loss of Adenomatous Polyposis Coli (APC) in the Mouse Mammary Tumor Virus – Polyoma middle T (MMTV-PyMT) transgenic mouse model results in resistance to cisplatin or doxorubicin-induced apoptosis. Herein, we aim to establish the mechanism that is responsible for APC-mediated chemotherapeutic resistance. Our data demonstrate that MMTV-PyMT;ApcMin/+ cells have increased signal transducer and activator of transcription 3 (STAT3) activation. STAT3 can be constitutively activated in breast cancer, maintains the tumor initiating cell (TIC) population, and upregulates multidrug resistance protein 1 (MDR1). The activation of STAT3 in the MMTV-PyMT;ApcMin/+ model is independent of interleukin 6 (IL-6); however, enhanced EGFR expression in the MMTV-PyMT;ApcMin/+ cells may be responsible for the increased STAT3 activation. Inhibiting STAT3 with a small molecule inhibitor A69 in combination with doxorubicin, but not cisplatin, restores drug sensitivity. A69 also decreases doxorubicin enhanced MDR1 gene expression and the TIC population enhanced by loss of APC. In summary, these results have revealed the molecular mechanisms of APC loss in breast cancer that can guide future treatment plans to counteract chemotherapeutic resistance.

Mit Berticksichtigung des deutschen Medicinaiwesens nach amtlichen Mittheilungen, der öffentlichen Gesundheitspflege und der Interessen des ärztlichen Standes. Begründet von Dr. Paul Borner. I. Ueber Endocarditis gonorrhoica1).

Summary There remains no one standard induction for nodal‐based peripheral T‐cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination with 10 mg of lenalidomide on days 1–10 of a 21‐day cycle for six cycles of therapy followed by observation, high‐dose therapy with autologous stem cell rescue, or maintenance lenalidomide per provider preference. Among 39 patients evaluable for efficacy, the objective response rate after six cycles was 69%, with complete response in 49%, partial response in 21%, stable disease in 0% and progressive disease in 13%. Thirty‐two patients (82%) completed full induction, and seven patients (18%) discontinued for toxicity, primarily hematologic. Any grade hematologic toxicity occurred in over 50% of patients, with grade 3 or 4 febrile neutropenia occurring in 35% of patients despite mandated growth factors. With a median followup of surviving patients of 21.3 months, the estimated 2‐year progression‐free and overall survival were 55% (95% CI 37%–70%) and 78% (95% CI 59%–89%), respectively. In sum, six cycles of lenalidomide plus CHOEP resulted in a modest response rate primarily due to hematologic toxicity, which prevented all patients from completing planned induction.

Leyden.Ich stelle Ihnen hier einen Patienten mit einem Aneurysma aortae, und zwar einem Aneurysma der Aorta abdominalis vor. Wir haben gerade im letzten Semester mehrere analoge Fälle in unserm Verein gesehen, und wenn ich nochmals einen analogen vorzustellen wünsche, so geschieht dies mit Rücksicht auf ein besonderes Symptom, welches mich interessirt und für welches ich auch Ihr Interesse zu erbitten habe. Die Entwickelung des Krankheitsprozesses ist eine einfache. Indess der Vollständigkeit halber will ich sie doch vortragen. Patient, 46 Jahre alt, ist seit 1881 Bremser an der Eisenbahn. Nie bettlägerig krank, doch 1871 Buho (mit Incision behandelt). Keine Gonorrhoe, keine Lues. Potus: drei Flaschen Bier, kein Schnaps.

Mit Berücksichtigung des deutschen Medicinaiwesens nach amtlichen Mittheiliingen, der MIentlichen Gesundheitspflege und der Interessen des ärztlichen Standes.