Search PubMed⌕ Search

Biomedical subjects

Anjali Jain

Publications and source records attributed to Anjali Jain.

15 recordsLinked to original sources
PubMed2006

Raloxifene, an oestrogen-receptor-beta-targeted therapy, inhibits androgen-independent prostate cancer growth: results from preclinical studies and a pilot phase II clinical trial.

OBJECTIVES: To determine, in preclinical in vivo animal and in clinical studies, whether raloxifene (a selective oestrogen-receptor (ER) modulator that targets ER-beta and induces apoptosis in vitro in androgen-independent prostate cancer, AIPC cells) affects prostate cell differentiation, proliferation and carcinogenesis, and in the pilot phase II clinical trial, the response rate and duration of patients with AIPC treated with a daily oral dose of raloxifene. PATIENTS, MATERIALS AND METHODS: Tumour proliferation rate in response to raloxifene treatment, and molecular markers of cell cycle and apoptosis, were evaluated in established ER-beta-positive androgen-dependent (AD) CWR22 and AI CWRSA9 human xenograft prostate cancer models. Twenty-one patients with AIPC and evidence of disease progression were enrolled into the clinical trial and given daily oral raloxifene. RESULTS: There was significant growth inhibition by raloxifene in the ADPC and AIPC xenograft models (CWR22 68%, P < 0.010; CWRSA9 64%, P < 0.001), with no tumour regression. There was evidence of G1 arrest by increased p27kip1 expression in the raloxifene-treated group. Eighteen patients comprised the efficacy analysis, as three withdrew before the first evaluation. At the first evaluation, five men had stable disease and continued on the study for a median of five cycles. The longest response was 17 cycles. Drug related toxicity was minimal. CONCLUSION: Raloxifene has activity in xenograft models, slowing disease progression. This translated to possible disease stabilization in patients with AIPC. Further studies are warranted.

Aged↗
PubMed2005

2C4, a monoclonal antibody against HER2, disrupts the HER kinase signaling pathway and inhibits ovarian carcinoma cell growth.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is overexpressed in 25-30% of ovarian carcinoma cases and a correlation between increased HER2 expression and decreased survival has been demonstrated. HER2 is a ligand-less member of the HER family that functions as the preferred coreceptor for epidermal growth factor receptor (EGFR), HER3, and HER4. METHODS: An approach was developed to target HER2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders HER2's recruitment into a functional HER complex. RESULTS: HER2 was robustly expressed in all eight ovarian carcinoma cell lines; expression of EGFR and HER3 was variable. Even though four of the eight cell lines responded to EGF, 2C4 antibody moderately inhibited in vitro proliferation of only two cell lines (OVCA433 and SK-OV-3). Furthermore, ligand-stimulated p-MAPK expression was inhibited by 2C4 only in these two cell lines after exposure to EGF. Immunoprecipitation and eTag analysis revealed that OVCA433 expressed heterodimers of EGFR/HER2, and these heterodimers were disrupted after treatment with 2C4, whereas OVCA432 cells did not have these heterodimers. In murine xenograft experiments, the in vivo growth of OVCA433, but not of OVCA432, ovarian carcinoma cells was significantly inhibited by 2C4 treatment of the mice. CONCLUSION: 2C4 is able to disrupt the HER signaling pathway and inhibit the in vitro and in vivo growth of ovarian carcinoma cell lines. The response appears limited to lines in which HER2 heterodimers were able to transduce proliferative signals. Our findings suggest a strong rationale to conduct clinical trials of 2C4 in a subset of patients with ovarian tumors.

Animals↗
PubMed2005

Epithelial membrane protein-1 is a biomarker of gefitinib resistance.

We describe a molecular resistance biomarker to gefitinib, epithelial membrane protein-1 (EMP-1). Gefitinib is a small-molecule inhibitor that competes for the ATP-binding site on EGF receptor (EGFR) and has been approved for patients with advanced lung cancers. Treatment with gefitinib has resulted in clinical benefit in patients, and, recently, heterozygous somatic mutations within the EGFR catalytic domain have been identified as a clinical correlate to objective response to gefitinib. However, clinical resistance to gefitinib limits the utility of this therapeutic to a fraction of patients, and objective clinical responses are rare. We aimed to assess the molecular phenotype and mechanism of in vivo gefitinib resistance in xenograft models and in patient samples. We generated in vivo gefitinib-resistance models in an adenocarcinoma xenograft model by serially passaging tumors in nude mice in presence of gefitinib until resistance was acquired. EMP-1 was identified as a surface biomarker whose expression correlated with acquisition of gefitinib resistance. EMP-1 expression was further correlated with lack of complete or partial response to gefitinib in lung cancer patient samples as well as clinical progression to secondary gefitinib resistance. EMP-1 expression and acquisition of gefitinib clinical resistance was independent of gefitinib-sensitizing EGFR somatic mutations. This report suggests the role of the adhesion molecule, EMP-1, as a biomarker of gefitinib clinical resistance, and further suggests a probable cross-talk between this molecule and the EGFR signaling pathway.

Animals↗
PubMed2005

Prostate stem cell antigen is a putative target for immunotherapy in pancreatic cancer.

UNLABELLED: The prostate stem cell antigen (PSCA) is a glycosylphosphatidyl-inositol (GPI)-linked cell surface antigen expressed in normal prostate and overexpressed in the majority of prostate cancers and correlates with tumor grade and disease stage. Because PSCA has been described to be up-regulated in pancreatic cancer, the purpose was to evaluate the expression of PSCA in human pancreatic cancer. Furthermore, the therapeutic efficacy of a monoclonal anti-PSCA antibody in an in vivo pancreatic cancer model was determined. METHODS: The expression of PSCA in human pancreatic cancer tissues was determined and compared with chronic pancreatitis and normal pancreas by quantitative reverse transcriptase-polymerase chain reaction. Therapeutic efficacy of the monoclonal anti-PSCA antibody 1G8 was examined in Capan-1 pancreatic tumors grown as subcutaneous grafts in athymic nude mice. RESULTS: PSCA was strongly up-regulated in human pancreatic cancer compared with chronic pancreatitis and normal pancreas. In addition, the PSCA protein was expressed on the cell surface of pancreatic cancer cells. Treatment with 1G8 significantly reduced tumor growth initiation in an in vivo pancreatic cancer xenograft model. In addition, antibody treatment of established tumors reduced tumor progression. CONCLUSIONS: These results show a potential therapeutic role for anti-PSCA antibodies in the treatment of pancreatic cancer. Furthermore, PSCA might serve as a novel marker in the diagnosis of pancreatic cancer.

Animals↗
PubMed2004

PPARgamma signaling: one size fits all?

Outcome of PPARgamma activation in cancer cells is not one-dimensional. PPARgamma signaling is dependent upon PPARgamma ligand affinity and binding characteristics, target cell context and interacting signaling networks.

Animals↗
PubMed2004

Mothers misunderstand questions on a feeding questionnaire.

Feeding questionnaires have not consistently identified mothers' beliefs or behaviors associated with preschool children becoming overweight. One reason may be that mothers do not understand the constructs in the questions in the way intended by the developers of the questionnaire. This study assessed items on the Preschooler Feeding Questionnaire (PFQ)--a maternal questionnaire about feeding practices and beliefs relating to the weight status of preschoolers. Seven audio-taped interviews were conducted with African American mothers of 24-59 month-old children in Chicago enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children. Questions in the PFQ were interpreted by respondents to mean something other than what was intended. In particular, the constructs difficulty in child feeding, pushing the child to eat more, and using food to calm the child were present among the mothers but not captured by items on the questionnaire. Thus, qualitative interviewing could help to match the intention in asking a question with its interpretation by respondents. A mismatch may contribute to our low level of understanding about the causes of early obesity.

Adult↗
PubMed2004

Inhibition of HER-kinase activation prevents ERK-mediated degradation of PPARgamma.

R-etodolac, a nonsteroidal anti-inflammatory drug, inhibits the progression of CWRSA6 androgen-independent and LuCaP-35 androgen-dependent prostate cancer xenograft growth through downregulation of cyclin D1 expression via the PPARgamma pathway. PPARgamma protein degradation, observed post-R-etodolac treatment, resulted from phospho-MAP kinase (p44/42) induction by R-etodolac negatively regulating PPARgamma function. Negative regulation of PPARgamma was overcome by a combination regimen of R-etodolac with the HER-kinase axis inhibitor, rhuMab 2C4, which demonstrated an additive antitumor effect. We further show that the inhibition of HER-kinase activity by rhuMab 2C4 is sufficient to inhibit PPARgamma protein degradation. This study introduces a novel concept of an in vivo crosstalk between the HER-kinase axis and PPARgamma pathways, ultimately leading to negative regulation of PPARgamma activity and tumor growth inhibition.

Animals↗
PubMed2002

The challenge of preventing and treating obesity in low-income, preschool children: perceptions of WIC health care professionals.

BACKGROUND: Obesity has become a common nutritional concern among low-income, preschool children, a primary target population of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Nutrition counseling efforts in WIC target childhood obesity, but new approaches are needed that address the different perceptions about obesity that are held by clients and health care professionals. OBJECTIVE: To develop these new approaches, we examined WIC health care professionals' perceptions about the challenges that exist in preventing and managing childhood obesity. DESIGN: A qualitative study using data transcribed from audiotapes of focus groups and individual interviews. We independently read each transcript and coded themes; then, the common themes were selected through group meetings of the authors. SETTING: Kentucky WIC. PARTICIPANTS: Of the 19 health care professionals participating, all had provided nutrition counseling in WIC and all but one were white women. RESULTS: Twelve major themes clustered into 3 domains. The first domain centered on how WIC health care professionals perceived the life experiences, attitudes, and behaviors of the mothers they counseled. They perceived that mothers (1) were focused on surviving their daily, life stresses; (2) used food to cope with these stresses and as a tool in parenting; (3) had difficulty setting limits with their children around food; (4) lacked knowledge about normal child development and eating behavior; (5) were not committed to sustained behavioral change; and (6) did not believe their overweight children were overweight. The second domain described WIC health care professionals' perceptions of counseling interactions. They felt that (7) they might offend mothers when talking about weight, (8) counseling was driven by protocols, and (9) their nutritional advice often conflicted with the advice from the mothers' relatives, friends, or primary care physicians. The last domain described programmatic suggestions WIC health care professionals offered to address childhood obesity: These included (10) promoting a more client-centered approach to counseling, (11) establishing behavioral change goals that were small and endorsed by the mother, and (12) working with primary care physicians to create a more uniform approach to counseling on obesity. CONCLUSIONS: To become more responsive to the problem of childhood obesity, WIC should consider the following: (1) providing staff training in counseling skills that educate parents on child development and child-rearing and that elicit the client's social context and personal goals, (2) shifting time allocation and programmatic emphasis in the WIC visits away from nutritional risk assessment and toward counseling, and (3) developing collaborations with primary health care providers and community agencies that impact childhood obesity.

Adult↗
PubMed2002

Identification of an androgen-dependent enhancer within the prostate stem cell antigen gene.

Prostate stem cell antigen (PSCA) is emerging as an important diagnostic marker and therapeutic target in prostate cancer. Previous studies indicated that PSCA was directly regulated by androgens, but the mechanism has not been elucidated. Here we describe the identification of a compact cell-specific and androgen-responsive enhancer between 2.7 and 3 kb upstream of the transcription start site. The enhancer functions autonomously when positioned immediately adjacent to a minimal promoter. Deoxyribonuclease I footprinting analysis with recombinant androgen receptor (AR) reveals that the enhancer contains two AR binding sites at one end. Mutational analysis of the AR binding sites revealed the importance of the higher affinity one. The dissociation constant of the high affinity binding site (androgen response element I) was determined to be approximately 87 nM. The remainder of the enhancer contains elements that function synergistically with the AR. We discuss the structural organization of the PSCA enhancer and compare it with that found in other AR-regulated genes.

Androgens↗
PubMed2002

How good is the evidence linking breastfeeding and intelligence?

BACKGROUND: We conducted a critical review of the many studies that have tried to determine whether breastfeeding has a beneficial effect on intellect. DESIGN/METHODS: By searching Medline and the references of selected articles, we identified publications that evaluated the association between breastfeeding and cognitive outcomes. We then appraised and described each study according to 8 principles of clinical epidemiology: 1) study design, 2) target population: whether full-term infants were studied, 3) sample size, 4) collection of feeding data: whether studies met 4 standards of quality- suitable definition and duration of breastfeeding, and appropriate timing and source of feeding data, 5) control of susceptibility bias: whether studies controlled for socioeconomic status and stimulation of the child, 6) blinding: whether observers of the outcome were blind to feeding status, 7) outcome: whether a standardized individual test of general intelligence at an age older than 2 years was used, and 8) format of results: whether studies reported an effect size or some other strategy to interpret the clinical impact of results. RESULTS: We identified 40 pertinent publications from 1929 to February 2001. Twenty-seven (68%) concluded that breastfeeding promotes intelligence. Many studies, however, had methodological flaws. Only 2 papers studied full-term infants and met all 4 standards of high-quality feeding data, controlled for 2 critical confounders, reported blinding, used an appropriate test, and allowed the reader to interpret the clinical significance of the findings with an effect size. Of these 2, 1 study concluded that the effect of breastfeeding on intellect was significant, and the other did not. CONCLUSION: Although the majority of studies concluded that breastfeeding promotes intelligence, the evidence from higher quality studies is less persuasive.

Adolescent↗