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Highlights: [•] This review highlights a therapeutic approach that overcomes KRAS mutations. [•] An analysis that confronts impairing targets with impairing physiological processes. [•] Highlighting alternative routes to apoptosis. [Copyright &y& Elsevier]

Objective: To evaluate and compare the inflammatory response and mediators in the endometrium of patients with hydrosalpinges compared with normal controls. Design: Retrospective case-control study. Setting: Urban medical center. Patient(s) and Intervention(s): Hysterectomy samples were identified as being affected by hydrosalpinx or salpingitis (n = 30) and were age-matched with control samples (n = 30). Interventions: Fallopian tube and endometrial slides were analyzed for leukocytes and immunohistochemical techniques performed for cytokines (interleukin-2 [IL-2]). Main Outcome Measure(s): Evaluate and compare the endometrial inflammatory response (leukocytes and cytokines) from samples affected and non-affected by hydrosalpinx and salpingitis. Result(s): Examination of tubal and endometrial slides with hydrosalpinx demonstrated a statistically significant increase in the number of overall inflammatory cells. High-intensity immunohistochemical staining for IL-2 was demonstrated in 7.4% of controls versus 65% of cases. Conclusion(s): A defined, identifiable, local response to hydrosalpingeal fluid has been demonstrated in the endometrium. This response consists of statistically significant elevations of leukocytes and IL-2. An inflammatory endometrial response may be an independent contributor to the decreased reproductive outcome observed in patients with hydrosalpinges. [Copyright &y& Elsevier]

Cancer therapies based on drugs designed to interfere with specific targets within the molecular circuitry of cancer cells are currently under intense experimentation. Our strategy is based on the use of a naturally occurring immunomolecule which can selectively kill cancer cells, based on its ability to exploit genetic differences between normal and cancer cells. The βGBP cytokine has previously been shown to negatively regulate the cell cycle by blocking cells in late S phase. In tumour cells, but not in normal cells, the S phase block has been shown to be followed by apoptosis. Mechanisms involved in S phase arrest have been pinpointed to downregulation of signalling and altered expression of cell cycle controller proteins, including E2F1, a transcription factor with ability to play a part in apoptosis. Here we discuss the use of βGBP within the context of cancer surveillance and cancer therapeutics focussing on E2F1 as one mechanistic aspect relevant to βGBP’s selective induction of programmed cell death in cancer. [Copyright &y& Elsevier]