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Biomedical subjects

Hank Schmidt

Publications and source records attributed to Hank Schmidt.

5 recordsLinked to original sources
PubMed2007

Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.

Targeting cancer cells, as well as the nonmalignant stromal cells cross-presenting the tumor antigen (Ag), can lead to the complete destruction of well-established solid tumors by adoptively transferred Ag-specific cytotoxic T lymphocytes (CTLs). If, however, cancer cells express only low levels of the Ag, then stromal cells are not destroyed, and the tumor escapes as Ag loss variants. We show that treating well-established tumors expressing low levels of Ag with local irradiation or a chemotherapeutic drug causes sufficient release of Ag to sensitize stromal cells for destruction by CTLs. This was shown directly using high affinity T cell receptor tetramers for visualizing the transient appearance of tumor-specific peptide-MHC complexes on stromal cells. Maximum loading of tumor stroma with cancer Ag occurred 2 d after treatment and coincided with the optimal time for T cell transfer. Under these conditions, tumor rejection was complete. These findings may set the stage for developing rational clinical protocols for combining irradiation or chemotherapy with CTL therapy.

Adoptive Transfer↗
PubMed2005

Ionizing radiation activates late herpes simplex virus 1 promoters via the p38 pathway in tumors treated with oncolytic viruses.

Ionizing radiation potentiates the oncolytic activity of attenuated herpes simplex viruses in tumors exposed to irradiation at specific time intervals by inducing higher virus yields. Cell culture studies have shown that an attenuated virus lacking the viral gamma(1)34.5 genes underproduces late proteins whose synthesis depends on sustained synthesis of viral DNA. Here we report that ionizing radiation enhances gene expression from late viral promoters in transduced cells in the absence of other viral gene products. Consistent with this result, we show that in tumors infected with the attenuated virus, ionizing radiation increases 13.6-fold above baseline the gene expression from a late viral promoter as early as 2 hours after virus infection, an interval too short to account for viral DNA synthesis. The radiation-dependent up-regulation of late viral genes is mediated by the p38 pathway, inasmuch as the enhancement is abolished by p38 inhibitors or a p38 dominant-negative construct. The p38 pathway is not essential for wild-type virus gene expression. The results suggest that ionizing radiation up-regulates late promoters active in the course of viral DNA synthesis and provide a rationale for use of radiation to up-regulate cytotoxic genes introduced into tumor cells by viral vectors for cytoreductive therapy.

Animals↗
PubMed2005

Chemo-inducible gene therapy.

Chemo-inducible cancer gene therapy is a potential new treatment for solid tumors that may in part enhance the anti-tumor effects of chemotherapy while minimizing toxicity. This approach combines viral vectors expressing cytotoxic transgenes that can be transcriptionally activated by DNA-damaging agents. The development of chemo-inducible gene therapy has numerous implications for the treatment of both localized and metastatic disease in patients with solid tumors.

Antineoplastic Agents↗
PubMed2003

The gastrointestinal tract in critical illness: nutritional implications.

PURPOSE OF REVIEW: Recognition that the gastrointestinal tract is a key element of the immune system has led to a greater interest in understanding its role as a central figure in host defenses. Biologic systems that are perturbed by any destabilizing stimulus are known to respond by adaptive strategies in an attempt to maintain or return to global homeostasis. In critically ill patients, the gut has previously been described as a promoter of progression to sepsis and multi-organ failure. However, with better understanding of gastrointestinal tract mucosal immunity, we are now provided with a new arsenal to combat nosocomial infection and significantly impact return to health. RECENT FINDINGS: In this review we focus on five key topics in the rapidly expanding landscape of knowledge on the gastrointestinal tract in the critical care setting. These include a discussion of probiotic therapy, now the new frontier of immuno-nutrition, the concept of ischemia/reperfusion injury and changes in gut permeability, anti-oxidant and micronutrient therapy, blood glucose regulation, and enhancement of gut motility, all in the intensive care setting. SUMMARY: Ongoing research in nutritional support in both normal and pathologic gastrointestinal function and response to injury has opened the door to several new opportunities for enhancing rapid recovery in critical care.

Antioxidants↗