
June 2003 From Journal of Clinical Investigation JCI table of contents, 2 June, 2003 Turning foe into friend with lentiviral vectorsCurrently, there is no vaccine available that is able to cure cancer. The success of an antitumor vaccine will depend on its ability to induce robust and sustained tumor-specific immune responses. There is evidence to suggest that antitumor vaccination can induce such responses and even tumor regression. However, to date these regressions have not been long-lasting. Researchers at the Ludwig Institute for Cancer Research in Switzerland have developed a lentiviral vaccine which following injection into mice is capable of inducing an antigen-specific T cell response. This approach represents an attractive candidate for cancer therapy. The crucial stimulation of a T cell response is dependent on the presentation of the antigen by host dendritic cells (DCs). As part of earlier strategies, the antigen of interest has been transferred to host DCs (by a process called �transduction�) outside the body and the DCs then reintroduced into the host. Unfortunately, this is a costly and labor-intensive process. In the June 2 issue of the Journal of Clinical Investigation, Christopher Esslinger and colleagues describe their use of a third generation lentivector capable of transducing DCs in vivo in mice and inducing a very strong antigen-specific immune response. The immune response was shown to be superior to methods using DCs transduced outside the body in terms of both amplitude and persistence. �Our results demonstrate that the time-consuming and costly steps currently used to elicit tumor-specific cytotoxic T lymphocyte responses through the transfer of ex-vivo manipulated DCs could be replaced by the much simpler direct in vivo administration of antigen recombinant lentivectors� states Dr. Esslinger. TITLE: In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8+ T cell responses AUTHOR CONTACT: Christoph Esslinger Ludwig Institute for Cancer Research, Epalinges, Switzerland. Phone: 41-21-692-5985 Fax: 41-21-653-4474 Email: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17098.pdf
Targeting the treatment of prostate cancer Prostate cancer has the highest incidence of any malignancy and is the second cause of cancer-related deaths in men in industrialized countries. The male sex hormone androgen plays a key role in the spread of cancer from the prostate to the bones and lymph nodes. Drug-mediated androgen suppression is the current leading treatment, however as tumor cells progress they become androgen-independent and therefore insensitive to such therapy. A new study reveals the human prostate cancer cells express a specific type of receptor � a1-adrenergic receptors --� and drugs that block these receptors have great potential in the treatment of prostate cancer. TITLE: a1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells AUTHOR CONTACT: Natalia Prevarskaya Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq Cedex, France. Phone: 33-3-20-33-60-18 Fax: 33-3-20-43-40-66 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16293.pdf
Newborn vaccination: Babies more prepared than previously thought The increased susceptibility of newborns to infectious diseases is generally ascribed to developmentally related deficiencies in immune function. A new study demonstrates the presence in newborns of a mature and functional immune response to a cytomegalovirus infection and suggests that the machinery necessary to prime such responses is present in utero, thereby raising questions related to neonatal vaccination. TITLE: Mature CD8+ T lymphocyte response to viral infection during fetal life AUTHOR CONTACT: Arnaud Marchant Weatherall Institute of Molecular Medicine, Oxford, United Kingdom. Phone: 44-1865-222-477 Fax: 44-1865-222-502 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17470.pdf ACCOMPANYING COMMENTARY: Functionally mature virus-specific CD8+ T memory cells in congenitally infected newborns: proof of principle for neonatal vaccination? AUTHOR CONTACT: Patrick G. Holt Telethon Institute for Child Health Research, West Perth, Western Australia, Australia. Phone: 61-8-9489-7838 Fax: 618-9489-7707 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18805.pdf
Location, location, location: Tissue specificity of Chlamydia The bacterium Chlamydia trachomatis is a primary cause of preventable blindness as well as urogenital infection. Research now demonstrates that the correlation between the preferred location � ocular versus genital � of this organism is linked to the presence or absence of a cluster of tryptophan synthesis genes. There may also exist unique host-parasite interactions in reaction to the host immune response that contribute to persistent chlamydial infection. TITLE: Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates AUTHOR CONTACT: Grant McClarty University of Manitoba, Winnipeg, Manitoba, Canada. Phone: (204) 789-3307 Fax: (204) 789-3926 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17993.pdf ACCOMPANYING COMMENTARY: New insights into a persistent problem -- chlamydial infections AUTHOR CONTACT: Richard P. Morrison Montana State University, Bozeman, Montana, USA. Phone: (406) 994-7959 Fax: (406) 994-4926 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18770.pdf
A jack of all trades: antimicrobial polypeptides Antimicrobial peptides have been shown to possess microbicidal as well and pro- or anti-inflammatory activities. Their role is now widening following evidence that one such multifunctional peptide, LL-37, induces angiogenesis, a process essential for host defense, would healing, and tissue repair. TITLE: An angiogenic role for the human peptide antibiotic LL-37/hCAP-18 AUTHOR CONTACT: Robert Bals Hospital of the University of Marburg, Marburg, Germany. Phone: 49- 0-6421-2866451 Fax: 49-0-6421 2868987 Email: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17545.pdf ACCOMPANYING COMMENTARY: What is the real role of antimicrobial polypeptides that can mediate several other inflammatory responses? AUTHOR CONTACT: Peter Elsbach New York University School of Medicine, New York, New York, USA. Phone: (212) 263-5633 Fax: (212) 263-3952 Email: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18761.pdf
In the thick of the thyroid The maintenance of constant levels of thyroid hormones is essential for proper human development and growth. A study in mice has revealed the mechanism of thyroid hormone synthesis and release, which may aid further research and better our understanding of the molecular mechanisms that lead to human thyroid disorders such as hyperthyroidism. TITLE: Thyroid functions of mouse cathepsins B, K, and L AUTHOR CONTACT: Klaudia Brix School of Engineering And Science, International University Bremen, Bremen, Germany. Phone: 49-421-3246 Fax: 49-421-3249 Email: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15990.pdf
Building bones Bone formation is a complex process, regulated by growth factors that are expressed by bone cells, incorporated into the bone matrix and released in active form when bone resorbs. Researchers have now discovered how to accelerate bone formation by manipulating specific steps in this process. These results point to a potential molecular target for future drug discovery for agents that enhance the formation of bone in treatment of diseases like osteoporosis. TITLE: Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro AUTHOR CONTACT: I. R. Garrett OsteoScreen, Inc., San Antonio, Texas, USA. Phone: (210) 614-0770 Fax: (210) 614-0797 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16198.pdf
How to make the heart grow Growth of the heart in early postnatal development occurs as a result of the natural increase in the size of cardiac cells. A new study reveals that a1-adrenergic receptors that are expressed on cardiac cells and have been shown to mediate some alterations in normal heart function are also required for normal postnatal cardiac development. TITLE: The a1A/C- and a1B-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse. AUTHOR CONTACT: Paul C. Simpson San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. Phone: (415) 221-4810 x3200 Fax: (415) 750-6950 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16100.pdf
Knocking out actinin in the kidney Mutations in the gene ACTN4, which encodes a-actinin-4, cause scarring within the small blood vessels of the kidney where blood is filtered and waste products removed. Researchers have developed a mouse that lacks this gene, which will provide an important animal model for the further study of a-actinin-4�related kidney diseases. TITLE: Mice deficient in a-actinin-4 have severe glomerular disease AUTHOR CONTACT: Martin Pollak Brigham And Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Phone: (617) 525-5840 Fax: (617) 525-5841 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17988.pdf
How sex steroids protect against bone loss TITLE: Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids AUTHOR CONTACT: Stavros C. Manolagas University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. Phone: (501)-686-5130 Fax: (501)-686-8148 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17261.pdf ACCOMPANYING COMMENTARY: A new hypothesis for how sex steroid hormones regulate bone mass AUTHOR CONTACT: Joseph Lorenzo University of Connecticut Health Center, Farmington, Connecticut, USA. Phone: (860) 679-8199 Fax: (860) 679-1040 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18812.pdf
Channeling new treatments for multiple sclerosis TITLE: The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS AUTHOR CONTACT: K. George Chandy University of California at Irvine, Irvine, California, USA. Phone: (949) 824-2133 Fax: (949)-824-3143 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16921.pdf
Key enzymes in tumor development The secreted growth factor VEGF-C has been directly implicated in a number of human cancers. The regulation of VEGF-C conversion from its precursor, proVEGF-C, and the role of this conversion in tumor formation are unclear. Research now shows that proprotein convertases (PCs) are responsible for this processing, thus highlighting the potential use of PC-inhibitors to block the development of VEGF-C-induced malignancies. TITLE: The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis AUTHOR CONTACT: Abdel-Majid Khatib Ottawa Health Research Institute, Ottawa, Ontario, Canada. Phone: (613) 798-5555 ext. 16086 Fax: (613) 761-4355 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17220.pdf
Enzyme deficiency produces skinny mice TITLE: Obesity resistance and enhanced glucose metabolism in mice transplanted with white adipose tissue lacking acyl CoA:diacylglycerol acyltransferase 1 AUTHOR CONTACT: Robert V. Farese Jr. Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. Phone: 415-826-7500 Fax: 415-285-5632 E-mail: [email protected]View the PDF of this article at: https://www.the-jci.org/press/15859.pdf
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