Biomedical subjects

Regina Gandour-Edwards

Publications and source records attributed to Regina Gandour-Edwards.

18 recordsLinked to original sources

PubMed2006

Interleukin-17 receptor-like gene is a novel antiapoptotic gene highly expressed in androgen-independent prostate cancer.

We have recently identified a new gene, interleukin-17 receptor-like (IL-17RL), which is expressed in normal prostate and prostate cancer. This investigation is focused on the role of IL-17RL in prostate cancer. We found that IL-17RL was expressed at significantly higher levels in several androgen-independent prostate cancer cell lines (PC3, DU145, cds1, cds2, and cds3) and tumors compared with the androgen-dependent cell lines (LNCaP and MLC-SV40) and tumors. In an in vivo model of human prostate tumor growth in nude mice (CWR22 xenograft model), IL-17RL expression in tumors was induced by androgen deprivation. The relapsed androgen-independent tumors expressed higher levels of IL-17RL compared with the androgen-dependent tumors. Overexpression of IL-17RL in tumor necrosis factor alpha (TNFalpha)-sensitive LNCaP cells inhibited TNFalpha-induced apoptosis by blocking activation of caspase-3 downstream to caspase-2 and caspase-8. Reciprocally, knocking down IL-17RL expression by small interfering RNA induced apoptosis in all the prostate cancer cell lines studied. Taken together, these results show that IL-17RL is a novel antiapoptotic gene, which may confer partially the property of androgen-independent growth of prostate cancer by promoting cell survival. Thus, IL-17RL is a potential therapeutic target in the treatment of prostate cancer.

Animals↗

PubMed2005

Paired basic science and clinical problem-based learning faculty teaching side by side: do students evaluate them differently?

INTRODUCTION: Many studies have evaluated the desirability of expert versus non-expert facilitators in problem-based learning (PBL), but performance differences between basic science and clinical facilitators has been less studied. In a PBL course at our university, pairs of faculty facilitators (1 clinician, 1 basic scientist) were assigned to student groups to maximise integration of basic science with clinical science. AIMS: This study set out to establish whether students evaluate basic science and clinical faculty members differently when they teach side by side. METHODS: Online questionnaires were used to survey 188 students about their faculty facilitators immediately after they completed each of 3 serial PBL cases. Overall satisfaction was measured using a scale of 1-7 and yes/no responses were gathered from closed questions describing faculty performance. results: Year 1 students rated basic science and clinical facilitators the same, but Year 2 students rated the clinicians higher overall. Year 1 students rated basic scientists higher in their ability to understand the limits of their own knowledge. Year 2 students rated the clinicians higher in several content expertise-linked areas: preparedness, promotion of in-depth understanding, and ability to focus the group, and down-rated the basic scientists for demonstrating overspecialised knowledge. Students' overall ratings of individual faculty best correlated with the qualities of stimulation, focus and preparedness, but not with overspecialisation, excessive interjection of the faculty member's own opinions, and encouragement of psychosocial issue discussion. CONCLUSION: When taught by paired basic science and clinical PBL facilitators, students in Year 1 rated basic science and clinical PBL faculty equally, while Year 2 students rated clinicians more highly overall. The Year 2 difference may be explained by perceived differences in content expertise.

Attitude of Health Personnel↗

PubMed2004

Adequacy evaluation of fine-needle aspiration biopsy in the breast health clinic setting.

BACKGROUND: Breast health clinics (BHC) are an unfamiliar source of fine-needle aspiration biopsies (FNABs) in the U.S. and create challenges for adequacy evaluation. The current study described the experience with breast FNAB adequacy evaluation over a 2-year period, the issues that emerged, and the problem-solving employed to mitigate these issues. METHODS: The rate of unsatisfactory FNABs and core biopsies was determined for pathologists, BHC providers, and other clinicians and compared for two different periods. Adequacy criteria during both periods required correlation of the cytologic findings with the clinical and breast imaging findings, and did not require identification of a specific number of ductal epithelial cells. RESULTS: During the first time period, 25% of breast FNABs performed in the BHC received an inadequate evaluation versus 6% performed by pathologists and 14% performed by other clinicians. The BHC adequacy rate exceeded the 20% upper threshold recommended by the National Cancer Institute (NCI), and did not decrease after additional FNAB training. During the first time period, 24% of core biopsies received an adequacy evaluation of unsatisfactory. During the second time interval, the core biopsy volume increased and 12% received an unsatisfactory adequacy evaluation. CONCLUSIONS: It is appropriate to use noncellular features such as clinical and imaging findings as adequacy criteria for breast FNABs rather than identification of a minimal number of ductal epithelial cells. However, the 20% upper threshold for unsatisfactory breast FNABs recommended by the NCI was not appropriate for the BHC setting because the nature of the lesions seen in this type of practice can lead to an increase in inadequate specimens and cause unnecessary concern regarding quality. The authors recommended that laboratories receiving a large number of clinician-performed FNABs from a community population, especially a BHC, define their own unsatisfactory threshold above which they will investigate for technical or other problems.

Ambulatory Care Facilities↗

PubMed2004

Molecular alterations associated with LNCaP cell progression to androgen independence.

BACKGROUND: There is no effective therapy currently available for androgen-independent (AI) prostate cancer (CaP). This is largely due to lack of information about the molecular mechanisms by which androgen-dependent tumor cells progress to androgen independence. In this study, we investigated molecular alterations occurring in AI LNCaP cells. METHODS: We established and characterized three AI LNCaP sublines that exhibited a wide range of cytogenetic alterations. In order to understand why androgen-sensitive LNCaP cells can survive in an androgen-deprived environment, we analyzed the expression of signaling proteins associated with proliferation and survival of AI cells. In addition, gene expression profiling was performed to gain insight into molecular alterations in these LNCaP sublines. RESULTS: These LNCaP sublines exhibited heightened levels of androgen receptor (AR), HER2, MAPK, serine 473-phosphorylated Akt, and Bcl-2, implicating these proteins as mediators of AI growth. Gene expression profiling identified a common set of 66 genes that were differentially expressed in all three sublines compared to the parental LNCaP cells. Of these, 32 were apparently androgen regulated, while the remainder comprised an expression signature specific for androgen independence. CONCLUSION: We have developed AI LNCaP cell models and identified several genes that are specifically expressed in these models. Elucidating the relative importance of these genetic changes will help define the molecular mechanism by which CaP progresses to androgen independence.

Androgens↗

PubMed2004

Canine prostatic intraepithelial neoplasia: is the comparative model relevant?

BACKGROUND: Histologic sections from an archival collection of a veterinary teaching hospital were examined to determine the likelihood of detection of canine high-grade prostatic intraepithelial neoplasms (HGPIN), as a prelude to use of the canine model of prostatic carcinogenesis for chemopreventive strategies. METHODS: Tissue specimens representing clinically healthy (normal) prostate glands, benign prostatic hyperplasia, and prostatic carcinoma were examined in one tissue plane for histological evidence of HGPIN. RESULTS: No histological evidence of HGPIN was detected in 20 normal prostate glands or 95 prostate glands with benign prostatic hyperplasia. Seven of 20 prostatic carcinomas had synchronous HGPIN. CONCLUSIONS: Histological evidence of HGPIN is unlikely to be detected in the healthy or hyperplastic canine prostate gland with the clinically-procured biopsy. This might diminish the usefulness of canine HGPIN in temporal studies of chemoprevention of prostate cancer. HGPIN was found simultaneously with prostatic carcinoma in more than one-third of the carcinomas examined.

Animals↗

PubMed2004

Analysis of treatment for small cell cancer of the bladder and report of three cases.

OBJECTIVES: To present our experience with 3 patients with small cell cancer (SCC) of the bladder who were treated with different modalities and review the literature for patients undergoing primary chemoradiotherapy. SCC of the bladder is a rare tumor, with patients commonly presenting with metastatic disease. Surgery, radiotherapy, and chemotherapy, either alone or as part of combined therapy, have been used. Because of the rarity of this disease, no prospective studies evaluating the most effective treatment have been done. METHODS: The medical records of 3 patients diagnosed with SCC of the bladder at our institution were reviewed. Additionally, we reviewed published reports to identify all cases of SCC of the bladder treated with primary chemoradiotherapy. RESULTS: Three patients with SCC of the bladder were identified at our institution. A total of 23 patients with SCC of the bladder who were treated with primary chemoradiotherapy were identified: 22 in published reports and 1 at our institution. Patients presented with muscle-invasive disease (17%), extravesical disease only (26%), and metastatic disease (52%). Multiagent chemotherapy was administered to most patients. The reported median radiation dose was 6000 cGy. A total of 16 patients (70%) were alive at a median follow-up of 34 months. The median survival of patients had not yet been reached in this study at the last follow-up. We did not find any reports of SCC recurrence in the bladder, and the bladder was preserved in most patients (87%). CONCLUSIONS: SCC of the bladder should be viewed as a systemic disease, because most patients present with metastatic disease. Primary chemoradiotherapy appears to be an effective treatment modality. Prospective studies are needed to evaluate the optimal treatment further.

Aged↗

PubMed2004

Heat shock protein 27 is expressed in normal and malignant human melanocytes in vivo.

BACKGROUND: Heat shock proteins (HSPs) are a family of highly conserved proteins found ubiquitously in mammalian cells, believed to be regulators of normal cell physiology and the cellular stress response. In addition, the small 27-kDa heat shock protein (HSP27) has previously been found to be a differentiation marker for keratinocytes and a prognostic marker associated with increased survival in certain cancerous tumors. METHODS: Using immunohistochemistry on routinely processed paraffin sections, we examined skin biopsies from 15 invasive melanomas, 13 intradermal nevi, and two compound nevi immunostained with a mouse monoclonal antibody to HSP27. In addition, cultured melanocytes were heat stressed at 45 degrees C for 1 h and then fixed and immunostained in order to localize HSP27 expression intracellularly. RESULTS: We found cytoplasmic and strong perinuclear staining of HSP27 in melanocytes in normal skin, in melanomas, and in nevi. Nuclear reactivity was absent. In addition, in cultured non-malignant melanocytes, HSP27 expression relocated from the cytoplasm to the nucleus with heat stress. CONCLUSIONS: To our knowledge, this investigation is the first to demonstrate that HSP27 is expressed in melanocytes in normal skin, in nevi, and in non-malignant cultured melanocytes.

Adolescent↗

PubMed2004

A modified yeast assay used on archival samples of localized prostate cancer tissue improves the detection of p53 abnormalities and increases their predictive value.

OBJECTIVE: To determine the frequency and predictive value of p53 mutations in localized prostate cancer, comparing the accuracy of detection using immunohistochemistry (IHC) with a modified yeast assay, on archival tissue samples. MATERIALS AND METHODS: Prostate cancer tissue was obtained from 98 patients who had >/= 2 years of clinical follow-up after radical prostatectomy. DNA sequencing was used to verify the presence of p53 mutations in samples that were immunopositive or that gave evidence for p53 alterations using the yeast assay. The IHC and yeast findings were compared with patient outcome to determine the predictive value of these two test types. RESULTS: Fifty-five tumours (57%) were immunopositive, and 58 (59%) were positive using the yeast assay. Sequence-confirmed p53 mutations occurred in 44 (45%) cases. The IHC protocol generated 49% (27/55) false-positive and 36% (15/42) false-negative results, and was 65% sensitive and 50% specific, with an overall accuracy of 57%. The yeast assay resulted in 24% (14/58) false-positive results with a specificity of 74% and an accuracy of 86%. When the p53 status of these patients was correlated with their clinical outcome, patients who had sequence-confirmed p53 mutations had a 2.6-fold greater failure rate (P = 0.026) and a 2.5-fold greater risk of dying from prostate cancer (P = 0.05). Notably, mutations in exon 6 predicted a six-fold increase in treatment failure (P = 0.043) and a 5.3-fold increase in the chance of dying from prostate cancer (P = 0.009). Abnormal yeast-assay findings gave similar predictive results to those obtained for DNA sequencing, while immunopositivity did not correspond to patient outcome. CONCLUSIONS: Mutations of p53 occurred in 45% of localized prostate cancers. These alterations have important prognostic implications. The yeast assay was more accurate for detecting p53 mutations than the IHC protocol used and, unlike IHC, the results of the yeast assay were predictive of patient outcome.

Adult↗

PubMed2004

Trastuzumab plus docetaxel in HER2/neu-positive non-small-cell lung cancer: a California Cancer Consortium screening and phase II trial.

HER2 is reported to be overexpressed in 20% of cases of non-small-cell lung cancer (NSCLC), principally adenocarcinoma. Trastuzumab is a monoclonal antibody against HER2 that, when combined with a taxane, improves survival compared with chemotherapy alone in advanced breast cancer. In view of these observations, we conducted a phase II HER2 screening and efficacy trial of trastuzumab plus weekly docetaxel in cases of advanced NSCLC in which primary platinum-based therapy had failed. Patients with advanced or metastatic NSCLC were screened for HER2 overexpression by immunohistochemistry. Patients with HER2-positive tumors (2+ or 3+) were initially randomized to either single-agent trastuzumab or docetaxel. After completing 2 treatment cycles, all patients went on to receive the trastuzumab/docetaxel combination regardless of response to the single agents. Treatment consisted of docetaxel 30 mg/m2 weekly for 6 weeks followed by a 2-week break and trastuzumab 4 mg/kg intravenously on week 1 followed by 2 mg/kg per week thereafter. Cycle length was 8 weeks. Sixty-nine patients with NSCLC (33 men, 36 women) were screened between August 1999 and March 2001. Only 13 patients (19%) had HER2-positive disease; all 13 enrolled in the efficacy trial. Of 9 patients receiving docetaxel alone, 1 partial response (PR) was seen. None responded to trastuzumab alone. The overall outcomes to the sequence of single-agent therapy followed by combination therapy included a PR rate in 8% of cases, stable disease in 23%, progression in 46%, and nonassessable disease in 23%. Estimated event-free and overall survival times were 4.3 and 5.7 months, respectively. Treatment was well tolerated. The screening component of this trial demonstrated that the target population for trastuzumab therapy in NSCLC is relatively small. Because of the limited clinical activity of trastuzumab-based therapy in this cohort and the similar disappointing reports from other studies of trastuzumab in NSCLC, this trial was closed to further accrual. In view of the limited target population for HER2 inhibition, future efforts and resources should be directed toward molecular targets other than HER2 in NSCLC.

Adenocarcinoma↗

PubMed2004

Gemcitabine in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: a phase II California cancer consortium trial.

A phase II trial was designed to evaluate the efficacy and toxicity of gemcitabine in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-containing regimens and prospectively categorized for platinum response status. Treatment consisted of gemcitabine 1000 mg/m2 given intravenously on days 1 and 8 of a 21-day cycle. The status of p53 in pretreatment tumor tissue was assessed by immunohistochemistry (IHC). Sixty-one patients who progressed or recurred following platinum-based therapy were enrolled, 26 platinum-sensitive and 35 platinum-refractory. A median of 4 treatment courses (range, 2-7 courses) was delivered. Of the 55 patients assessable for response, there was 1 confirmed complete response and 3 with a confirmed partial response for an overall response proportion of 7%. Twenty-one patients had stable disease while 28 progressed and 2 patients had an unconfirmed partial response. Three of the responders (2 confirmed, 1 unconfirmed) were platinum-refractory. Median progression-free survival (PFS) and overall survival for all patients were 4.1 months and 8.6 months, respectively. Median PFS and overall survival for the platinum-sensitive and platinum-refractory cohorts were 5.4 months versus 3.1 months, and 11.9 months versus 7.1 months, respectively. Toxicity was principally hematologic with grade 3/4 neutropenia in 21% and grade 4 platelets in 8%. There were no treatment-related deaths. Twenty-four of 33 patients (73%) had p53-positive tumors. Although no significant association between platinum sensitivity and p53 status was seen, patients with platinum-sensitive disease and negative p53 by IHC had a trend toward longer survival compared to those with platinum-refractory disease and/or p53 positivity (P = 0.06). We concluded that salvage gemcitabine in this dose and schedule is safe and tolerable in previously platinum-treated patients with NSCLC.

Adult↗

PubMed2003

Paratesticular rhabdomyoma.

A case of rhabdomyoma of the spermatic cord in an infant with cryptorchidism is reported. This extremely rare tumor has not been described in an extrascrotal position or at such a young age. Differential diagnosis includes malignant rhabdomyosarcoma. Although fetal-type rhabdomyoma of the head and neck generally is a benign tumor, the prognosis of paratesticular fetal-type rhabdomyoma is unknown. Long-term follow-up is recommended.

Genital Neoplasms, Male↗

PubMed2002

Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma?

BACKGROUND: Muscle-invasive urothelial carcinoma of the bladder is a highly lethal malignancy, particularly in the setting of locally advanced or metastatic disease. Prior reports of HER2/neu (c-erbB-2 or HER2) expression in bladder carcinoma have been mixed; therefore, its value in predicting metastasis or response to therapy has not been established in this tumor type. Thus, the authors evaluated a possible correlation between HER2 expression in patients with high-grade, muscle-invasive urothelial carcinoma of the bladder and outcome in patients who received paclitaxel-based chemotherapy. METHODS: Archival tumor tissues from patients with advanced urothelial carcinoma who were enrolled on two clinical trials of paclitaxel-based chemotherapy regimens were analyzed for HER2/neu expression by immunohistochemistry (IHC). The authors correlated HER2 expression by IHC with clinical outcomes, such as response rate, progression free survival, and overall survival, using univariate analysis. RESULTS: Thirty-nine tumor specimens were assessed for HER2 expression, most of which (70%) were collected from patients with metastatic disease. All were high-grade urothelial carcinomas (transitional cell carcinomas, Grade 3). Strong HER2 expression (2+/3+) was seen in 28 patients (71%). Patients with responding disease had an HER2 expression rate of 78%, similar to the rate seen in patients with stable disease (75%). In contrast, patients with progressive disease had an HER2 expression rate of 50%, although this difference did not reach statistical significance. However, univariate analysis showed that increased HER2 expression predicted an improvement in progression free and overall survival. When HER2 status was used as a dichotomous variable, tumors with positive HER2 expression did not have any association with response or with progression free survival; however, positive HER2 status was associated significantly with a decreased risk of death (P = 0.03). CONCLUSIONS: This study of HER2 expression in bladder carcinoma focused on patients who were treated prospectively in a standardized fashion, unlike prior studies that have evaluated banked, archival specimens. The authors confirmed the findings of others that high-grade, muscle-invasive urothelial carcinoma of the bladder has a significant rate of HER2 expression (71%). However, contrary to other reports, the current study found that HER2 expression in the context of paclitaxel-based chemotherapy decreased the risk of death significantly. Further research is warranted on the possible association of HER2 expression with chemosensitivitiy in urothelial carcinoma as well as the efficacy of HER2-targeted therapies (such as trastuzumab) for patients with high-grade, muscle-invasive urothelial carcinoma of the bladder.

Adult↗

PubMed2002

Klinefelter's syndrome and precocious puberty: a harbinger for tumor.

Boys with Klinefelter's syndrome are at an increased risk of precocious puberty. Most cases are either idiopathic or due to a mediastinal tumor. Patients with Klinefelter's syndrome are at a high risk of primary, extragonadal germ cell tumors, which are usually nonseminomatous, but can be a mixed type with seminomatous elements. The differential diagnosis of precocious puberty includes mediastinal tumors, especially in boys with Klinefelter's syndrome.

Child↗

PubMed2002

Initial report of bladder carcinoma following combined bladder-drained pancreas and kidney transplantation.

Although long-term survival of a functional allograft requiring long-term immunosuppressive therapy is responsible for higher incidence of non-urothelial cancers in renal allograft recipients than in normal population, the incidence of bladder cancer is uncommon and carcinoma of the bladder in the setting of combined kidney-pancreas transplantation has not been reported to date. We herein report a case of poorly differentiated invasive adeno-squamous cell carcinoma of the bladder following renal and bladder-drained pancreatic transplantation in a 44-yr-old lady with long-standing insulin dependent diabetes mellitus, which necessitated radical extirpation. Management implications are reviewed.

Adult↗

PubMedDate not supplied

Near-infrared autofluorescence imaging for detection of cancer.

Near-infrared autofluorescence imaging of tissues under long-wavelength laser excitation in the green and red spectral region complemented by cross-polarized elastic light scattering was explored for cancer detection. Various types of normal and malignant human tissue samples were utilized in this investigation. A set of images for each tissue sample was recorded that consisted of two autofluorescence images obtained under 532- and 632.8-nm excitation and light-scattering images obtained under linearly polarized illumination at 700, 850, and 1000 nm. These images were compared with the histopathology of the tissue sample. The experimental results indicated that for various tissue types, the intensity of the autofluorescence integrated over the 700 to 1000-nm spectral region was considerably different in cancer tissues than in that of the contiguous non-neoplastic tissues. This difference provided the basis for the detection of cancer and delineation of the tumor margins. Variations on the relative intensity were observed among different tissue types and excitation wavelengths.

Humans↗

PubMedDate not supplied

Spectroscopic detection of bladder cancer using near-infrared imaging techniques.

High-contrast imaging of bladder cancer is demonstrated using near-infrared autofluorescence under long-wavelength laser excitation in combination with cross-polarized elastic light scattering. Fresh unprocessed surgical specimens obtained following cystectomy or transurethral resection were utilized and a set of images for each tissue sample was recorded. These images were compared with the histopathology of the tissue sample. The experimental results indicate that the intensity of the near-infrared emission as well as that of the cross-polarized backscattered light was considerably different in cancer tissues than in that of the contiguous nonneoplastic tissues, allowing an accurate delineation of a tumor's margins.

Feasibility Studies↗

PubMedDate not supplied

Near-infrared optical imaging of ovarian cancer xenografts with novel alpha 3-integrin binding peptide "OA02".

Through screening of random one-bead one-compound (OBOC) libraries, we previously identified cyclic peptides with the cDGXGXXc motif that bind to alpha3 integrin subunit on ovarian adenocarcinoma cell lines ES-2, SKOV-3, and CaOV-3. We subsequently synthesized two secondary libraries based on this motif and identified new peptides that bound with a higher affinity to these cell lines. One of the peptides identified from the 20% "down-substituted" focused library was the c-dGHCitGPQ-c ("OA02") peptide. The goal of this study was to determine whether this peptide labeled with near-infrared probes could be detected after intravenous injection in ovarian tumor-bearing mice and if it would selectively localize in the tumor. Three different forms of this peptide were synthesized, "OA02"-biotin (noncovalently linked to streptavidin-Cy5.5); "OA02"-Cy5.5 and "OA02"-AlexaFluo 680. Using a KODAK IS2000MM image station, these peptide probes were used at the near-infrared (NIR) spectra to image nude mice bearing ES-2 (alpha3 integrin positive) and Raji (alpha3 integrin negative) xenografts. The peptide probe displayed highly specific tumor uptake within 15 min, which lasted for 70 min for "OA02"-Cy5.5 and "OA02"-AlexaFluo 680 and for 24 hours for "OA02"-biotin-streptavidin-Cy5.5. Some kidney and bladder signal were noted. Prior injection with anti-alpha3 monoclonal antibody blocked the binding of this peptide to the ES-2 tumors.

Adenocarcinoma↗

PubMedDate not supplied

bcl-2 and MIB-1 labeling indexes in cats with lymphoma.

Immunohistochemistry was used to examine feline lymphoid tumors for bcl-2 and MIB-1 expression. Tumor tissues from 29 cats were selected to represent 2 groups--cats that did not respond to chemotherapy and cats that responded to therapy. Median bcl-2 immunoreactivity was 60%, and median MIB-1 reactivity was 47%. There was no significant difference in median survival time between cats with tumors with high levels of bcl-2 expression and those with low levels of expression. There was no significant difference in median survival time between cats with tumors with high levels of MIB-1 expression and those with low levels of expression. Mean bcl-2 immunoreactivity was significantly (P = .0004) higher in low-grade (73.2%) than in high-grade (16.9%) lymphomas, whereas the mean MIB-1 immunoreactivity was significantly (P = .0201) higher in high-grade (61.2%) lymphomas than in low-grade (35.0%) lymphomas. The mean bcl-2 immunoreactivity was significantly (P = .0042) greater in T-cell lymphomas (66.8%) than in B-cell lymphomas (22.8%), whereas the mean MIB-1 immunoreactivity was significantly (P = .0052) lower in T-cell lymphomas (36.4%) than in B-cell lymphomas (65.2%). Although expression of bcl-2 and MIB-1 did not appear to be linked to responses to chemotherapy in cats with lymphoma, the data suggest a possible role for these regulatory proteins in the biology of feline lymphomas.

Animals↗