Jivesh Sharma, MD

TITLE:
Salmonella arizonae peritonitis secondary to ingestion of rattlesnake capsules for gastric cancer [letter]

AUTHORS:
Sharma J; Von Hoff DD; Weiss GR

SOURCE:
J Clin Oncol 1993 Nov;11(11):2288-9

CITATION IDS:
PMID: 8229147 UI: 94045840

MAIN MESH HEADINGS:
Crotalus/*microbiology
Materia Medica/*adverse effects
Peritonitis/*microbiology
*Salmonella arizonae
Salmonella Infections/*transmission
Stomach Neoplasms/*therapy

ADDITIONAL MESH HEADINGS:

Aged
Animal
Capsules

Case Report
Human
Male

PUBLICATION TYPES:
LETTER

CAS REGISTRY NUMBERS:
0 (Capsules)
0 (Materia Medica)

TITLE:
Recombinant insulin-like growth factor binding protein-1 inhibits
IGF- I, serum, and estrogen-dependent growth of MCF-7 human breast cancer cells.

AUTHORS:
Figueroa JA; Sharma J; Jackson JG; McDermott MJ; Hilsenbeck
SG; Yee D

AUTHOR AFFILIATION:
Department of Medicine, University of Texas Health Science
Center, San Antonio 78284-7884.

SOURCE:
J Cell Physiol 1993 Nov;157(2):229-36

CITATION IDS:
PMID: 7693722 UI: 94043481

ABSTRACT:
The insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells and their activity is modulated by high affinity binding proteins (IGFBPs). We have recently shown that IGFBP-1 purified from human amniotic fluid neutralizes IGF-I- dependent growth of MCF-7 cells. In this study we examined the effects of recombinant IGFBP-1 (rBP-1) on IGF-I, estradiol (E2), and serum-induced monolayer and anchorage independent growth (AIG) of MCF-7 cells. Under serum-free conditions, rBP-1 had no effect on MCF-7 basal monolayer growth. However, 40 nM rBP- 1 completely blocked the mitogenic action of both IGF-I and 5% charcoal stripped serum (CSS). This concentration of rBP-1 partially inhibited E2-induced growth, while 80 nM rBP-1 completely abolished E2 mitogenicity. The addition of either excess IGF-I or 5 nM [Arg3]IGF-I, a species that does not bind IGFBPs, neutralized rBP-1 inhibitory effects. In AIG assays, 80 nM rBP-1 reduced colony number by at least 70% and decreased colony size in all treatment groups compared to control. We examined rBP-1 effects on both IGF-I binding to MCF-7 membranes and activation of type I IGF receptor (IGFR1) and found that 80 nM rBP-1 reduced IGF-I receptor binding to levels of nonspecific binding and completely abolished ligand-dependent IGFR1 phosphorylation. However, neither treatment with 5% CSS nor exposure to E2 resulted in IGFR1 phosphorylation suggesting that different mechanism(s) are responsible for rBP-1 inhibitory action under this condition. Our data suggest rBP-1 may serve as an antagonist of human breast cancer growth by interfering with growth factor-mediated cell proliferation.

MAIN MESH HEADINGS:
Blood Proteins/*pharmacology
Breast Neoplasms/*pathology
Carrier Proteins/*pharmacology
Estradiol/*pharmacology
Insulin-Like Growth Factor I/*pharmacology

ADDITIONAL MESH HEADINGS:

Analysis of Variance
Cell Adhesion/drug effects
Cell Division/drug effects
Dose-Response Relationship,
Drug
Human
Immunoblotting

Phosphorylation
Precipitin Tests
Recombinant Proteins/pharmacology
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Tumor Cells, Cultured

PUBLICATION TYPES:
JOURNAL ARTICLE

CAS REGISTRY NUMBERS:
0 (Blood Proteins)
0 (Carrier Proteins)
0 (Insulin-Like Growth-Factor Binding Protein 1)
0 (Recombinant Proteins)
50-28-2 (Estradiol)
67763-96-6 (Insulin-Like Growth Factor I)

LANGUAGES:
Eng

GENE SYMBOL:
IGFBP-1

GRANT/CONTRACT ID:
CA52592/CA/NCI
CA30195/CA/NCI
P30CA54174/CA/NCI

TITLE:
Phase II study of flutamide as second line chemotherapy in patients with advanced pancreatic cancer.

AUTHORS:
Sharma JJ; Razvillas B; Stephens CD; Hilsenbeck SG; Sharma A; Rothenberg ML

AUTHOR AFFILIATION:
University of Texas Health Science Center at San Antonio, USA.

SOURCE:
Invest New Drugs 1997;15(4):361-4

CITATION IDS:
PMID: 9547680 UI: 98208896

ABSTRACT:
Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma who had developed progressive disease following therapy with one 5-FU-based regimen. Fourteen patients were treated with flutamide, 250 mg orally three times per day. Therapy was generally well tolerated. No patients achieved objective tumor response. No patient had improvement in tumor-related symptoms as measured by improvement in pain intensity, analgesic requirement, performance status, or nutritional status. Median survival was 4.7 months. We conclude that flutamide is ineffective second line therapy for patients with advanced pancreatic adenocarcinoma.

MAIN MESH HEADINGS:
Adenocarcinoma/*drug therapy
Antineoplastic Agents, Hormonal/*therapeutic use
Flutamide/*therapeutic use
Pancreatic Neoplasms/*drug therapy

ADDITIONAL MESH HEADINGS:

Adult
Aged
Aged, 80 and over
Antineoplastic Agents,
Hormonal/administration
& dosage
Antineoplastic Agents,
Hormonal/adverse effects
Female

Flutamide/administration
& dosage
Flutamide/adverse effects
Human
Male
Middle Age
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Survival Analysis

PUBLICATION TYPES:
CLINICAL TRIAL
CLINICAL TRIAL, PHASE II
JOURNAL ARTICLE
CAS REGISTRY NUMBERS:
0 (Antineoplastic Agents, Hormonal)
13311-84-7 (Flutamide)

GRANT/CONTRACT ID:
K12 CA01723/CA/NCI

TITLE:
Prognostic significance of insulin-like growth factor-binding protein expression in axillary lymph node-negative breast cancer.

AUTHORS:
Yee D; Sharma J; Hilsenbeck SG

AUTHOR AFFILIATION:
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7884.

SOURCE:
J Natl Cancer Inst 1994 Dec 7;86(23):1785-9

CITATION IDS:
PMID: 7525978 UI: 95055846

ABSTRACT:
BACKGROUND: Cellular proliferation, as measured by S-phase fraction, is an important predictor of breast cancer prognosis. The insulin-like growth factors (IGFs) have been shown to regulate proliferation in both normal and neoplastic cells by interacting with specific cell surface receptors. In addition to these receptors, high-affinity extracellular binding proteins also modulate IGF action. These insulin-like growth factor-binding proteins (IGFBPs) could influence breast cancer growth and, like other biological parameters of proliferation, could be related to prognosis.
PURPOSE: To test whether IGFBP expression was related to other biological parameters and disease-free survival, we measured IGFBP expression in 238 lymph node-negative primary breast cancer specimens.
METHODS: Proteins were extracted from breast cancer specimens and
analyzed by semiquantitative IGF-I ligand blotting for IGFBP expression. IGFBP expression levels were compared to tumor size, age, S-phase fraction, DNA ploidy, and estrogen and progesterone receptor
expression by Spearman correlation.
RESULTS: Binding protein (BP)-2, BP-3, BP-4, and BP-5 were identified in breast cancer extracts. Estrogen receptor expression was positively correlated with BP-2 (Spearman correlation coefficient, rs = .262; P = .0001), BP-4 (rs = .313; P = .0001), and BP-5 (rs = .242; P = .0002). Similar correlations between progesterone receptor and BP-2, BP-4, and BP-5 were also found. BP-3 was inversely correlated with age (rs = -.251, P = .0001). BP-4 was weakly inversely correlated with tumor size (rs = -.141; P = .0295) and S-phase fraction (rs = -.216; P = .0025). Since tumor size and S- phase fraction are powerful predictors of prognosis in node-negative breast cancer, we examined the value of BP-4 as a predictor of disease-free survival. When stratified by tumor size, patients with large (> 2 cm) tumors that expressed low levels of BP-4 had improved survival when compared with patients with large tumors and high BP-4 levels (P = .001).

CONCLUSIONS: IGFBPs can be detected in breast cancer specimens, and their level of expression correlates with other known biological parameters of breast cancer. Large tumors with low levels of BP-4 have relatively favorable prognoses.
IMPLICATIONS: These data suggest that the IGFBPs may play a role in breast cancer biology and that BP-4 levels, analyzed in conjunction with tumor size, may have prognostic significance.

MAIN MESH HEADINGS:
Breast Neoplasms/*chemistry
Carrier Proteins/*analysis

ADDITIONAL MESH HEADINGS:

Breast Neoplasms/pathology
Disease-Free Survival
Gene Expression

Human
Prognosis
Support, U.S. Gov't, P.H.S.

PUBLICATION TYPES:
JOURNAL ARTICLE

CAS REGISTRY NUMBERS:
0 (Carrier Proteins)
0 (Insulin-Like Growth-Factor-Binding Proteins)

GRANT/CONTRACT ID:
P01CA30195/CA/NCI
P30CA54174/CA/NCI
K12CA01723/CA/NCI

TITLE:
Numbers of myelinated and unmyelinated axons in the dorsal, lateral, and ventral funiculi of the white matter of the S2 segment of cat spinal cord.

AUTHORS:
Chung K; Sharma J; Coggeshall RE

SOURCE:
J Comp Neurol 1985 Apr 1;234(1):117-21

CITATION IDS:
PMID: 3980784 UI: 85158386

ABSTRACT:
The present work determines the numbers of myelinated and unmyelinated axons in the dorsal, lateral, and ventral funiculi of the S2 segment of the cat spinal cord. The major finding is that unmyelinated axons are almost as numerous as myelinated axons in these pathways. The myelinated axons tend to be distributed uniformly, although there is a slight concentration of these fibers in the dorsal part of the lateral funiculus. By contrast, the unmyelinated fibers, although found in significant numbers in all parts of these funiculi, concentrate in the dorsal part of the lateral funiculus and in the dorsal funiculus. Of particular note are the unmyelinated fibers in the dorsal funiculus, because it is highly likely that some of these are sensory. The findings in this study will serve as a basis for experimental studies to determine the numbers, locations, and types of unmyelinated fibers in the white matter of the mammalian cord.