Acute inflammation induced by the biopsy of mouse mammary tumors promotes the development of metastasis

Development of metastasis in peripheral tissues is a major problem in the fight to cure breast cancer. Although it is becoming evident that chronic inflammation can contribute to tumor progression and metastasis, the effect of acute inflammation in primary tumor is less known. Using mouse models for breast cancer here we show that biopsy of mammary tumors increases the frequency of lung metastases. This effect is associated with the recruitment of inflammatory cells to the lung and elevated levels of certain cytokines such as IL-6 in the lung airways. Antiinflammatory treatment prior to and after the biopsy reduces the development of metastases triggered by the biopsy. In addition, while lack of IL-6 does not affect primary tumor development, it protects from increasing number of metastases upon biopsy. Thus, our studies show that in addition to chronic inflammation, acute immune response caused by invasive procedures in the primary tumor may cause an increased risk on peripheral metastases, but the risk could be decreased by anti-inflammatory treatments.     

Deconstructing the Mantra of Mentorship: In Conversation With Phyllis Noerager Stern

While much has been written about the theoretical aspects of mentoring, the actual strategies, processes, and scope of mentoring are poorly described. Much of the literature is based on a formal model of “orchestrated” mentoring, rather that the spontaneous and very effective mentoring style of academic leaders. Phyllis Noerager Stern, a mentor par excellence, describes the scope and type of established mentoring relationships. These discussions show that our present conceptualization of mentoring should be expanded to include three types of relationships: direct (traditional) mentoring, collegial mentoring, and indirect mentoring. These mentoring relationships may extend internationally and have made a profound impact on a large number of students and emerging academics. They are capable of changing over time from one type to another. In this interview, Phyllis Stern describes the positives and the negatives, and the processes, pitfalls, and outcomes of these various mentoring relationships.     

Toxicity profile of repeated doses of PEG‐asparaginase incorporated into a pediatric‐type regimen for adult acute lymphoblastic leukemia

Despite having been long regarded as too toxic for adult patients, pediatric‐like regimens containing L‐asparaginase have resulted in improved outcomes for adults with acute lymphoblastic leukemia (ALL). To characterize the spectrum of toxicity of repeated doses of polyethylene glycolated‐asparaginase (PEG‐asp) in adults, we reviewed all doses (2000 IU/m²) administered as part of a pediatric‐inspired regimen in adult ALL at our center. Subjects aged 18–60 yr with ALL (n = 152, 69.1% male) contributed 522 dose cycles to the study. Hepatotoxicity was the most common adverse event: grades 3–4 transaminitis and hyperbilirubinemia occurred in 53.9% and 23.7% of subjects, respectively. Hepatotoxicity was reversible; no cases of fulminate hepatic failure were observed. Other toxicities affecting at least 5% of subjects were grades 3–4 triglyceridemia in 50.9%, hypofibrinogenemia (<100 mg/dL) in 47.9%, clinical pancreatitis in 12.6%, venous thromboembolism in 11.2%, allergic reaction in 7.2%, and any grade bleeding in 5.3%. PEG‐asp was always discontinued after grades 3–4 pancreatitis or allergic reaction. Otherwise, toxicities did not preclude administration of additional cycles of the drug. Our results suggest that repeated PEG‐asp dosing is safe in adults aged 18–60 yr, even after occurrence of a drug‐related toxicity.