Metastasis is the primary cause of cancer patient morbidity and mortality, but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patient tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. This review examines evidence that the SCF/CD117 signaling axis may contribute to the control of cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors.

Metastasis is the primary cause of cancer patient morbidity and mortality but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patients' tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. In our analyses, CD117 was expressed in several tissues and was highly expressed in bone marrow progenitor cells. Also, we uncovered that CD117 gene amplifications and mutations occurred in multiple cancers. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. These signaling pathways were commonly altered in patients with CD117 amplifications and mutations. Here, we examine evidence that the SCF/CD117 signaling axis controls cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors. Abbreviations: AML acute myeloid leukemia CML chronic myeloid leukemia CTC circulating tumor cell CSC cancer stem cell DTC disseminated tumor cell GIST gastrointestinal stromal tumor HSC hematopoietic stem cell SCF stem cell factor TKI tyrosine kinase inhibitor

In February 2016, the Cleveland Clinic initiated the first attempt at cadaveric uterine transplantation (UTx) in the United States. The transplantation was ultimately unsuccessful, but it opened doors for further research on both live and cadaveric UTx. While initial strides toward successful transplantation have been made, questions persist on the ethics of UTx: whether the uterus is a vital organ, whether we should prioritize live or cadaveric options, and how the procedure should be covered by health insurance. If we agree that the goal of the medical profession is both to treat and improve quality of life, then the question of whether or not infertility is considered a disease becomes inconsequential in the discussion. As such, the medical enterprise should move forward with research in UTx. In doing so, considering the ethical implications of UTx remains essential-and we must remember to pair innovation with regulation.

Background Few studies have been conducted to assess the quality of orientation practices for ethics advisory committees that conduct ethics consultation. This survey study focused on several Harvard teaching hospitals, exploring orientation quality and committee members’ self-evaluation in the American Society of Bioethics and Humanities (ASBH) ethics consultation competencies. Methods We conducted a survey study that involved 116 members and 16 chairs of ethics advisory committees, respectively (52% and 62.5% response rates). Predictor variables included professional demographics, duration on committees and level of training. Outcome variables included familiarity with and preparedness in the ASBH competencies and satisfaction with orientations. We hypothesised that responses would be associated with both the aforementioned predictors and whether or not participants had encountered the ASBH competencies in training. Results A majority of respondents found their orientation curricula to be helpful (62%), although a significant portion of respondents did not receive any orientation (24%) or were unsatisfied with their orientation (14%). Familiarity with ASBH competencies was a statistically significant predictor of respondents’ self-evaluation in particular categories (54% had heard of the competencies). Standard educational materials were reported as offered during orientation, such as readings (50%) and case studies (41%); different medium resources were less evidenced such as videos on ethics consultation (19%). Conclusions Institutions should re-evaluate orientation practices for ethics committee members that perform ethics consultation. Integrating ASBH competencies and useful methods into a resourceful pedagogy will help improve both member satisfaction with orientation and preparation in consultation.