IITZ-01, a novel potent lysosomotropic autophagy inhibitor, has single-agent antitumor efficacy in triple-negative breast cancer in vitro and in vivo.

Autophagy is a homeostatic process that recycles damaged organelles and long-lived proteins by delivering them in double-membrane vesicles to lysosomes for degradation. Autophagy has a prominent role in survival, proliferation, and resistance of tumors in metabolic and chemotherapeutic stress conditions. Clinical trials with chloroquine-a known autophagy inhibitor-were unable to achieve complete autophagy inhibition in vivo, warranting the search for more potent autophagy inhibitors. In a process of exploring the mechanism of action of previously identified cytotoxic s-triazine analogs, we discovered that both IITZ-01 and IITZ-02 act as potent autophagy inhibitors. Treatment with these compounds resulted in the vacuolated appearance of cells due to their specific accumulation in lysosomes. In addition, these basic compounds also deacidify lysosomes as evidenced by the decrease in lysotracker red staining and inhibit maturation of lysosomal enzymes leading to lysosomal dysfunction. IITZ-01 and IITZ-02 enhance autophagosome accumulation but inhibit autophagosomal degradation by impairing lysosomal function, finally resulting in the inhibition of autophagy. Interestingly, compound IITZ-01 exhibited more than 10-fold potent autophagy inhibition along with 12- to 20-fold better cytotoxic action than CQ. IITZ-01 and IITZ-02 also abolished mitochondrial membrane potential and triggered apoptosis through the mitochondria-mediated pathway. Furthermore, IITZ-01 and IITZ-02 displayed potent antitumor action in vivo through autophagy inhibition and apoptosis induction in MDA-MB-231 breast cancer xenograft model with IITZ-01 exhibiting superior anticancer efficacy. Overall, these data demonstrate that IITZ-01 is potent autophagy inhibitor with single-agent anticancer activity and awaits further preclinical development as potential anticancer therapeutic.

Integrating multiple publics into the strategic plan. The best plans can be derailed without comprehensive up-front research.

The mission of a health care organization represents its vision for the future. The authors present an approach used to develop an organizational mission for a large multispecialty physician clinic. In implementing the strategic planning process, research objectives must be clearly stated that identify in advance how the data will be used. Failure to integrate strategic data from all relevant publics will likely result in a mission statement that misses the significant interests of one or more stakeholders and reduces the effectiveness of the strategic planning process. Although costly, comprehensive research can uncover some surprising differences in perception that, if ignored, might complete defeat strategic planning efforts.

Taking the direct route.

Direct marketing holds much potential for the health care industry, but little has been written about hospitals' use of DM techniques. The authors discuss the distinct characteristics of direct marketing, report findings from an exploratory study of how U.S. hospitals have incorporated DM into their communication programs, and construct a profile of high and low users.

How have hospitals faced the pricing issues of the 1990's?

National health care expenditures are rising rapidly, bringing on a health care financing crisis. For this reason, it is useful to see how hospitals are facing the price issues of the 1990's. This study examines the price strategies hospitals follow and analyzes their observations on price sensitivity and payer mix. The results clearly show that hospitals have not given much attention to the pricing variable. The study suggests that marketing and finance will have to work closely together in developing future pricing strategies.

Is performance related to marketing research in the health care industry?

Marketing research has grown to become indispensable for superior performance in packaged goods industries. While health care institutions are spending large amounts on marketing research, few studies focus upon the relationship of marketing research to health care organizational performance. Utilizing a national sample of U.S. hospitals, this article points out that marketing research and superior performance are positively associated.

Is product-line management appropriate for your health care facility?

Although many hospitals have adopted product-line management as a management tool, questions remain about its applicability in the health care industry. Using a national sample, the authors examine the impact of product-line management on operating results and profile hospitals in which product-line management has been associated with higher performance. Their study reveals the circumstances under which product-line management is likely to be the most successful.

Organization of marketing in U.S. hospitals: an empirical investigation.

In this article the results of an empirical investigation of the marketing function in U.S. hospitals are reported. The relationship between hospital marketing orientation and hospital performance is examined. Results of the study indicate that substantial evidence exists to conclude that marketing is effective in the health care industry. Marketing failures in hospitals seem to be related to inappropriate marketing organization and inadequate top management support.

How marketing oriented are hospitals in a declining market?

The role of marketing in a health care facility has been a focus of discussion during the past decade. Varied opinions have been expressed about the purpose and contribution of marketing within the health care industry. The authors empirically investigate (1) the extent of marketing orientation in hospitals, (2) the degree of marketing orientation as it relates to hospital characteristics, and (3) the relationship of marketing orientation to hospital performance.

Marketing parallax in health care industry: an empirical study of hospitals.

It is about two decades since the marketing scholars identified the need and relevance of marketing in health care organizations. The health care industry itself has been undergoing significant changes brought on by deregulation, declining demand, intraorganizational competition and growth of HMO's and PPO's. Yet, the industry has not fully implemented the marketing concept. For many health care organizations, marketing seems still to mean advertising and public relations as evidenced by an empirical study.