This dissertation is an extended essay dealing with historical productions on the late independent era (the late “pre-colonial” epoch) of the wider KwaZulu-Natal region. The project pays particular attention to the development of the historiography and examines how it has shaped and in turn been shaped by the source material over time. Attention is also drawn to issues with terminology and disciplinary convention, including the distinction which is traditionally made between ‘primary' and ‘secondary' sources. The dissertation's scope extends beyond the discipline of history to interrogate how influences from the fields of anthropology, art history, archaeology, and literary criticism have shaped the production of history. It also examines the productions of African intellectuals whose works were excluded from the discipline of history during the late colonial and apartheid eras. Among other things, this essay draws attention to historiographical breaks in the literature and considerers where paradigm shifts and epistemic ruptures can be discerned.

Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose-response of estrogen. These results indicated that ING4 functions as a noncompetitive inhibitor of estrogen signaling and may inhibit estrogen-independent ER activity. Supportive of this, treatment with fulvestrant but not tamoxifen rendered T47D cells sensitive to hormone deprivation as did ING4 overexpression. ING4 did not affect nuclear ER alpha protein expression, but repressed selective ER-target gene transcription. Taken together, these results demonstrated that ING4 inhibited estrogen-independent ER activity, suggesting that ING4-low breast tumors recur faster due to estrogen-independent ER activity that renders tamoxifen less effective. This study puts forth fulvestrant as a proposed therapy choice for patients with ING4-low ER+ breast tumors.