Biomedical subjects

M R Suresh

Publications and source records attributed to M R Suresh.

59 records · Page 4Linked to original sources

PubMedDate not supplied

Possible utility of serum determinations of CA 125 and CA 27.29 in breast cancer management.

The utility of measurement of serum levels of the tumor associated antigens CA 125 and CA 27.29 in detecting the presence of disease and in monitoring changes in disease status was examined in 63 patients with breast cancer. In patients with clinically detectable disease the CA 125 level was elevated in 59%, the CA 27.29 level in 59.5% and one or both markers in 84.6%. Specificity for presence of disease was 83.6% for CA 125, 88% for CA 27.29, and 69.1% for the two markers combined. Changes in marker levels of more than 50% correlated with clinical changes in disease status in 58% of cases for either CA 125 or CA 27.29 alone. In 87.5% of cases with clinically progressive disease one or both marker levels increased by more than 50% from the previous levels. In no case with greater than 50% increase in a marker level was there regression of disease. Thus, the use of these markers in combination might have utility in cases where diagnosis of recurrent disease is difficult or where monitoring of response to treatment is hampered by lack of measurable disease.

Adenocarcinoma↗

PubMedDate not supplied

Clinical evaluation of a new two-site assay for CA125 antigen.

As appropriate surgery and chemotherapy can improve both quality of life and survival of patients with ovarian adenocarcinoma, there has been a pressing need for "serodiagnostic" assays to enable close patient monitoring. CA 125 antigen has previously been described as a useful tumor marker of ovarian cancer. This is the first clinical evaluation of a radioimmunoassay using two new monoclonal antibodies, B27.1 and B43.13, that react with separate sites on the glycoprotein marker CA 125. Using the new assay, the majority of patients with clinically or radiologically detectable disease had serum CA 125 antigen levels well above the upper limit seen with random apparently healthy donors, while only three patients who were believed free of disease had elevated levels. Disease progression was associated with increasing values of serum CA 125 antigen, while response to therapy was associated with a steady decline in serum CA 125 antigen levels. Seven patients had steadily rising serum CA 125 antigen levels after initially having normal levels. The mean lead time between rise above normal and clinical or radiological evidence of relapse was 5 months (range 2 to 12 months). The merits of further surgical intervention are illustrated by the serial values of two patients followed after chemotherapy. The assay appears to have value in monitoring response to therapy and in detecting disease relapse at a time when appropriate therapeutic intervention is still possible or likely to be beneficial. Furthermore, monitoring CA 125 antigen was shown to be of benefit in assessing response to chemotherapy in a few patients with metastatic adenocarcinoma of unknown primary, and may be useful in this group of patients in determining those likely to benefit from aggressive chemotherapy.

Adenocarcinoma↗

PubMedDate not supplied

Colonization and immune responses in mice to Helicobacter pylori expressing different Lewis antigens.

BACKGROUND AND AIMS: A mouse model was established to compare colonization by the H. pylori Sydney strain SS1 with several clinical isolates expressing different Lewis antigens on their surface. In addition, both humoral and cell mediated immune responses were determined for different H. pylori strains. METHODS: Mice were inoculated intragastrically separately with the Sydney strain as well as with five clinical isolates of H. pylori expressing different Lewis (Le) antigen phenotypes. Colonization of the mouse stomach by the bacteria was monitored from two to fourteen weeks post inoculation by four independent methods namely, urease, PCR (using CagA primers), bacterial culture and histology. Antibody titers and cellular immune responses were monitored by ELISA and antigen stimulation test respectively. RESULTS: Different degrees of colonization were observed in C57, CD1 and Balb/c mice inoculated with H. pylori strain SS1 (Le(x), Le(y)) and clinical isolates UA948 (Le(a), Le(x)), UA861 (alpha-glucosyl polyLacNAc), UA1258 (Le(y)), UA802 (Le(y)) and UA1264 (no Le antigen) starting from week two post inoculation. All three mice strains mounted high immune responses against different H. pylori antigens. Treatment of mice with vancomycin prior to inoculation has no effect either on colonization of the stomach or the immune response of the mice. Histological evaluation established colonization after 10 weeks post inoculation but not gastritis. CONCLUSIONS: Stomach of mice can be colonized consistently, with H. pylori strain SS1, and colonization was also achieved with all clinical isolates that were not mouse adapted. These strains could be detected more consistently by PCR in the early stages, then by culture only after 8 - 10 weeks. In our study, Lewis(x) expressing bacterial strain (UA948) failed to colonize Balb/c mice, whereas the Le(y) expressing strain (UA1258) did not colonize C57/BL6 mice.

Animals↗

PubMedDate not supplied

Effect of cyclooxygenase-2 (COX-2) inhibitors on prostate cancer cell proliferation.

BACKGROUND: The tricyclic cyclooxygenase-2 (COX-2) inhibitors celecoxib and rofecoxib exhibit different magnitudes of antiproliferative activity against the human prostate cancer cell lines LNCaP and PC-3. We investigated the correlation between the COX-2 inhibitory potencies, antiproliferative activities and the nature of the central ring system of novel tricyclic COX-2 inhibitors belonging to the diarylcycloalkyl and diarylheterocyclic classes possessing a central 3-membered cyclopropyl (1 and 2), a 5-membered isoxazoline (3), an isoxazole (4) or 2-(5H) furanone (5), and a 6-membered pyran-2-one (6a-c) ring system. MATERIALS AND METHODS: Novel tricyclics were synthesized and evaluated in vitro for their COX-1/COX-2 inhibitory activities and their abilities to inhibit cell proliferation in prostate (AT3B-1, PC-3 and LNCaP) and breast (MCF-7) cancer cell lines. A molecular modeling study was carried out to characterize the electronic nature of the central ring systems of the novel tricyclic COX-2 inhibitors. RESULTS: The isoxazoline (3), which exhibited excellent COX-2 inhibitory potency and selectivity, showed growth inhibition in all the cell lines tested with IC50 values of 349 microM (AT3B-1), 378 microM (PC-3), 100 microM (LNCaP) and 200 microM (MCF-7), respectively. The rofecoxib analog (5) and 6-membered pyran-2-ones (6a-c) showed weak inhibition (MCF-7, AT3-B-1 and PC-3) inspite of possessing good COX-2 inhibitory potencies and selectivities. CONCLUSION: This study demonstrates that the antiproliferative activity profiles exhibited by the novel tricyclic COX-2 inhibitors is dependent on the electronic nature of the central ring system and is independent of their COX-2 inhibitory potencies and selectivities. Accordingly, the 2,3-dimethyl-5-(4-methylsulfonylphenyl)-4-phenyl-4-isoxazoline (3), which possesses an electron rich central 5-membered isoxazole ring, could serve as a lead compound to develop novel drugs to treat prostate cancer.

Animals↗

PubMedDate not supplied

Classification of tumor markers.

Since the discovery of the first tumor markers more than a century ago (Bence-Jones proteins), a vast array of molecules have been described as being associated with cancer. These are generally naturally occurring biomolecules with the exception of neo-antigens expressed in certain tumors induced by viruses. Tumor markers can be broadly classified into tumor specific antigens and tumor-associated markers. Most tumor markers were often heralded as highly tumor specific but subsequent studies demonstrated their presence in normal tissues of the adult or in various stages of ontogeny. As a result, very few tumor-specific antigens can be recognized. The idiotypes of immunoglobulins of B cell tumors and certain neo-antigens of virus induced tumors are two examples that are strictly tumor specific. The vast majority of tumor markers are in reality tumor-associated antigens and can be classified into two types based on their size. The low-molecular weight tumor markers (approximately < 1000 Daltons) include some nucleosides, lipid associated sialic acid, polyamines, pseudouridine, pigment derivatives, and other metabolites. The macromolecular tumor antigens are the most important sub-type useful in the clinical management of cancer patients. The large cancer antigens are either enzymes, growth factors, hormones, receptors, biological response modifiers, oncogenes and their products, or glycoconjugates which include glycoproteins and glycolipids. Collectively all the commercial tumor marker assays available to the oncologist for cancer patient management amount to an annual sales of > $1 billion world wide. The demonstrated clinical usefulness and commercial success of tumor markers have continued to fuel exciting research into the discovery and novel uses of new analytes.

Biomarkers, Tumor↗