Kailash Chadha, PhD
Interferons have significant antiviral, antiproliferative and immunoregulatory activities. Interferons have been used for the treatment of many viral and non-viral malignancies. However, the response to treatment with interferons has been variable. Some patients respond favorably, while others fail to respond. We have shown that this variable response is partially due to the presence of interferon inhibitory activity in their blood circulation. Our laboratory is involved in the isolation and molecular characterization of this interferon inhibitory factor(s).
Interferon inhibitory activity in the blood circulation of late stage cancer HIV‑1 infected patients and in MS patients is due to: a) interferon inhibitory protein; b) high levels of PGE2; c) high levels of soluble interferon receptor; or d) any combination of these factors.
C57BL/6 mice maintained on alcohol containing diet had lower levels of T‑cells including CD4+. Splenocytes from these animals produced significantly low levels of IFN‑alpha and IFN‑gamma but did not differ in their NKC activity. Mice infected with LP‑BM5MuLV virus showed progressive splenomegaly, leukopenia, lymphadenopathy, and suppression in vitro of anti-SRBC response. IL‑2-mediated response of splenocytes did not differ significantly from uninfected controls. Spleen cell proliferation elicited by mixture of phorbol and IL‑2 or phorbol and ionomycin was significantly inhibited. We have observed that cocaine is a significant cofactor in the pathogenesis of HIV infection primarily because it increases susceptibility to and progression of HIV‑1 infection by inhibiting the synthesis of HIV‑1 protective chemokines and/or upregulating the HIV‑1 entry co-receptor, CCR5.
Prostate Cancer: Relevance of PSA and PSMA in Early Diagnosis. Role of PSA in prostate tumor tissue and its relevance to prostate tumor growth and metatasis. Prostate cancer has the highest incidence of any non-cutaneous malignancy in the Western world and is the second leading cause of cancer related deaths in men. PSA is a well-recognized marker for the early diagnosis and management of prostate cancer. However, it is not disease specific and results in many false positives. Our objective is to develop new methodology that will be more sensitive and will eliminate the risk of false positives. The physiological reasoning for the rise in PSA level in prostate cancer patients is not well understood. PSA seems to have a role in angiogenesis.
We have shown that PSA and its molecular complexes have an affinity for thiophilic gels (T‑gel). T‑gel affinity can be exploited for PSA purification as well as for obtaining serum-based PSA standard that will have both free PSA and its complexes.
We have developed methodology that permits measurement of PSMA in the sera of prostate cancer patients. Such a task has never been accomplished before. Our test will effectively eliminate false positives and therefore will eliminate unnecessary biopsies. We are currently testing additional samples to validate our test procedures.
In our primary studies, we have shown that treatment of human prostate cancer cells with PSA modulates factors, su. Prostate cancer has the highest incidence of any non-cutaneous malignancy in the western world and is the second leading cause of cancer related deaths in men. Prostate-Specific Antigen (PSA) is a well-recognized biomarker for the early diagnosis and management of prostate cancer. However, PSA test is neither disease specific nor tissue specific and results in >70% false positive. There are two major areas of research in my laboratory: one involves development of new biomarkers that will be more selective and specific and includes PSMA, IL-8, TGF-beta, etc., and the second area involves in determining if PSA has a physiological role as an anti-angiogenic molecule. In our preliminary studies, we have shown that human prostate cells that are highly malignant have higher levels of expression of pro-angiogenic growth factors such as VEGF, IL-8, TGF-beta, bFGF, etc. and low levels of anti-angiogenic factors such as interferons and angiostatin. The treatment of these cells with PSA results in down regulation of pro-angiogenic factors and up regulation of anti-angiogenic factors. We have now shown in a xenograft model that exogenously administered PSA can significantly reduce tumor growth. This suggests that PSA has a potential to be used as therapeutic modality to treat prostate cancer.
Biology of Interferon System
Biomarkers for Early Detection and Management of Prostate Cancer and Role of PSA in prostate tumor progression & Metastasis
Prostate Cancer: Relevance of PSA and PSMA in Early Diagnosis.