The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but no polypeptide confined to the stem cells has yet been identified. Here we show that the p63 transcription factor, a p53 homologue essential for regenerative proliferation in epithelial development, distinguishes human keratinocyte stem cells from their TA progeny. Within the cornea, nuclear p63 is expressed by the basal cells of the limbal epithelium, but not by TA cells covering the corneal surface. Human keratinocyte stem and TA cells when isolated in culture give rise to holoclones and paraclones, respectively. We show by clonal analysis that p63 is abundantly expressed by epidermal and limbal holoclones, but is undetectable in paraclones. TA keratinocytes, immediately after their withdrawal from the stem cell compartment (meroclones), have greatly reduced p63, even though they possess very appreciable proliferative capacity. Clonal evolution (i.e., generation of TA cells from precursor stem cells) is promoted by the sigma isoform of the 14-3-3 family of proteins. Keratinocytes whose 14-3-3 has been down-regulated remain in the stem cell compartment and maintain p63 during serial cultivation. The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis.

Purpose: Overexpression of h III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of h III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether h III tubulin expression could be modified after the selective pressure represented by chemotherapy in vivo. Experimental Design: The study was designed to include a series of consecutive ovarian cancer patients with unresectable disease at time of first surgery, who underwent interval debulking surgery with pathologic assessment of response to treatment with platinum/ paclitaxel chemotherapy. Immunostaining was done on formalin-fixed, paraffin-embedded tissue sections from pretreatment and posttreatment tissue biopsies by using the polyclonal rabbit anti^class III h-tubulin antibody. Results: h III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. h III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of h III tubulin positivity were observed in posttreatment (range, 5-80%; median, 20%) versus pretreatment (range 10-100%; median, 40%) tissue biopsies (P = 0.0011). Cases with high h III tubulin expression showed a worse overall survival with respect to cases with low h III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of h III tubulin remains independently associated with a worse prognosis. Conclusions: Assessment of h III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.

Cancer stem cells have been isolated from several solid tumors including prostate, colon, liver, breast, and ovarian cancer. Stem cells isolated from nervous system and prostate express CD133 antigen, which is widely used to isolate hematopoietic stem and progenitor cells. The aims of this study were to investigate the expression of the CD133-1 and CD133-2 epitopes in primary ovarian tumors and to biologically characterize CD133(+) ovarian cancer cells, also according to clinicopathologic parameters. Tissue specimens were obtained at primary surgery from 41 ovarian carcinomas; eight normal ovaries and five benign ovarian tumors were also collected. Flow cytometry with monoclonal antibodies against CD133-1 and CD133-2 epitopes was employed. FACS (fluorescence activated cell sorting) analysis enabled the selection of CD133(+) cells, whose epithelial origin was confirmed by immunofluorescence analysis with monoclonal anti-cytokeratin 7. CD133(+) cells gave rise to a 4.7 +/- 0.9-fold larger number of colonies than that documented in CD133(-) population (P < 0.001). Moreover, CD133(+) cells showed an enhanced proliferative potential compared to CD133(-) cells. The percentages of CD133-1- and CD133-2-expressing cells were significantly lower in normal ovaries/benign tumors with respect to those in ovarian carcinoma. Both the percentages of CD133-1- and CD133-2-expressing cells were significantly lower in omental metastases than in primary ovarian cancer (P = 0.009 and 0.007 for CD133-1- and CD133-2-expressing cells, respectively). There seems not to be any difference in the distribution of the percentage of CD133-1- and CD133-2-expressing cells according to clinicopathologic parameters and response to primary chemotherapy. CD133-1 and CD133-2 may be useful in order to select and enrich the population of CD133(+) ovarian tumor cells, which are characterized by a higher clonogenic efficiency and proliferative potential.

Purpose The purpose of this paper is to investigate the formative dimensions of organizational resilience – namely dynamic capabilities (DCs) and social capital – displayed by retail entrepreneurs in the face of natural disasters (i.e. the 2012 Emilia earthquake). The paper evaluates social capital and the various types of DCs that support small entrepreneurs’ resilience during three temporal units of analysis: before the earthquake, during the emergency period, and during the recovery process. Design/methodology/approach The study was performed by applying a qualitative approach based on two focus groups and a double set of semi-structured interviews administered to a sample of eight small retail entrepreneurs hit by the 2012 Emilia earthquake. Content analysis was then applied. Findings The findings show that DCs and social capital are instrumental to enhancing organizational resilience; moreover the contribution of each category of DCs (reconfiguration, leveraging, sensing and interpreting, learning and knowledge integration) and social capital to entrepreneurs’ resilience changes according to the temporal phase of the natural disaster under analysis. Research limitations/implications This study will provide small retailer entrepreneurs and public authorities with useful insights on how DCs and social capital can practically support recovery paths at different times in the occurrence of a natural disaster. Originality/value This study contributes to the scientific debate on organizational resilience in disaster management, studying it through the lens of DCs and social capital, and analyzing the role of different types of DCs in developing entrepreneurs’ resilience during the various periods of a natural disaster. Moreover, it contributes by applying the concepts of resilience and DCs to a poorly investigated entrepreneurial context such as the retail one.