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G Abu-Jawdeh

Publications and source records attributed to G Abu-Jawdeh.

11 recordsLinked to original sources
PubMed2001

Relative risk of high grade squamous intraepithelial lesion associated with prior abnormal Pap smears.

OBJECTIVE: Pap smear frequency remains controversial, especially for women with consecutive negative smears. We undertook the current study to ascertain the association of high grade squamous intraepithelial lesions (HSIL) and prior abnormal Paps. STUDY DESIGN: Women with biopsy-proven HSIL (cervical intraepithelial neoplasia 2 and 3) diagnosed between September 1996 and December 1997 and age-matched controls with a negative Pap obtained during the same time period were selected. RESULTS: Sixty-three cases (mean age = 32 years) of HSIL and 69 controls (mean age = 33 years) constituted the study population. Any prior abnormal diagnosis conferred a 15-fold increased risk of HSIL on the current Pap (50/63 vs. 14/69, P < .0001). When limited to the 60 women with at least three prior Paps, the odds ratio for HSIL on the current Pap with any prior abnormal was 18 (28/31 vs. 10/29, P < .0001). Three cases had at least three consecutive negative Paps prior to the diagnosis of HSIL. CONCLUSION: Women with one or more prior negative Pap smears had a significantly decreased risk of HSIL on the current Pap. Consecutive negative Paps did not appear to further decrease the risk; 10% of HSIL patients had had three or more consecutive prior negative Paps. To detect HSIL at its earliest stage, women should be advised to continue annual Pap screening in spite of consecutive negative results.

Adolescent↗
PubMed1999

Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy.

By using the differential display technique to identify genes that are differentially expressed in human endometrial carcinoma compared with normal endometrium, we have cloned frpHE, a novel member of the secreted frizzled gene family. By in situ hybridization, we have determined that frpHE is expressed by mesenchymal cells but not by epithelial cells. The expression of frpHE is modulated during the endometrial cycle: it is expressed in the stroma of proliferative endometrium and not significantly detectable in secretory or menstrual endometrium, suggesting that frpHE is under hormonal regulation. In addition, the expression of frpHE mRNA is markedly up-regulated in the stroma of endometrial hyperplasia and carcinoma and in the stroma of in situ and infiltrating breast carcinomas. Injection of frpHE mRNA in Xenopus embryos inhibited the Wnt-8 mediated dorsal axis duplication. These results indicate that frpHE functions as a regulator of the Wnt-frizzled signaling pathway and is involved in endometrial physiology and carcinogenesis.

Amino Acid Sequence↗
PubMed1999

Endometrial endothelial cells express estrogen and progesterone receptors and exhibit a tissue specific response to angiogenic growth factors.

OBJECTIVE: To develop a reliable method for the isolation and longterm culture of microvessel endothelial cells from human endometrium and to evaluate their response to angiogenic growth factors and steroid hormones in comparison to endothelial cells derived from other organs. METHODS: Endometrial tissue from hysterectomy specimens were digested sequentially with collagenase and trypsin, cultured for 24 h, then selected by adhesion to anti-CD-34 coated magnetic beads. Alternatively, anti-CD-34-coated beads could also be substituted by Ulex europaeus agglutinin-1, anti-PECAM, or anti-E-selectin-coated beads. Characterization of the isolated cultures included expression of endothelial cell markers, regulation of E-selectin in response to TNF-alpha, proliferative response to angiogenic growth factors, and expression of progesterone and estrogen receptors. We also analyzed the relative binding affinity of VEGF on endometrial endothelial cells in comparison to other endothelial cell types. RESULTS: Selection on anti-CD-34-coated beads eliminated contaminating cells and resulted in a homogeneous population of human endometrial endothelial cells (HEEC), as assessed by expression of PECAM, von Willebrand's factor, and uptake of acetylated-LDL. HEEC also upregulated E-selectin in response to TNF-alpha in a manner similar to that seen for other endothelial cell types. Expression of progesterone and estrogen receptor was revealed by immunocytochemistry and RT-PCR consistently until passage 5. Endometrial endothelial cells were more responsive to growth stimulation by VEGF than were dermal endothelial cells isolated under similar conditions. Further characterization indicated that VEGF bound more avidly to HEEC than to other endothelial cell types. CONCLUSIONS: Human endometrial endothelial cells were isolated to homogeneity by a two-part protocol and successfully passaged under culture conditions similar to those used for other endothelial cell types. The HEEC were very responsive to VEGF growth-stimulation likely due to elevated affinity, or increased levels of, KDR and FLT-1 on the cell surface. These results indicate that HEEC are capable of maintaining a mature phenotype in culture and might provide a model for understanding the response of these cells to the recurrent cycles of proliferation imposed on the endometrium during menstruation.

Cell Culture Techniques↗
PubMed1997

Cytologic features of neoplastic lesions in endocervical glands.

Cytologic criteria for classifying atypical endocervical cells on Pap smears are poorly defined. In this study we evaluated cytologic parameters that are useful in predicting the presence of neoplastic lesions (NL) and those that help distinguish squamous intraepithelial lesion (SIL) from glandular neoplastic lesions. The recently proposed Bethesda System (TBS) terminology for reporting atypical glandular cells of undetermined significance (AGUS) was also evaluated for its significance on patient management. Sixteen cases of biopsy-proven endocervical glandular NL that had cytologic smears available for review were included. Thirty-five smears with atypical endocervical cells and follow-up biopsies showing benign/reactive change (n = 22) and SIL involving glands (n = 13) were reviewed for comparison. Our results show that squamous NL often coexist with glandular NL. The presence of rosettes, hyperchromasia and increased N/C ratio is useful in distinguishing NL from benign/reactive conditions. Architectural features are helpful in distinguishing SIL from glandular NL. While a haphazard arrangement is more often seen with SIL, glandular NL are more likely to maintain polarity and to show glandular rosettes. Using TBS criteria, a conservative management seems justified in patients with AGUS-favor reactive and AGUS diagnosis on Pap smear, and colposcopy is indicated for patients with AGUS-favor NL.

Adenocarcinoma↗
PubMed1997

Uterine smooth muscle cells express functional receptors (flt-1 and KDR) for vascular permeability factor/vascular endothelial growth factor.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is an angiogenic factor with important roles in tumor growth, wound healing, and inflammation. VPF/VEGF interacts with endothelial cells by way of two high-affinity receptor tyrosine kinases: flt-1 and KDR. The vast majority of published studies have described expression of the VPF/VEGF receptors only in endothelial cells, and the statement is frequently made that these receptors are endothelial-cell-specific. In this study, we detected mRNA for flt-1 and KDR by in situ hybridization in smooth muscle cells in sections of the wall of the uterus. To confirm these unexpected findings, smooth muscle cells from the uterus and, as a control, from the colon were isolated, characterized, and cultured. Both uterine and colonic smooth muscle cells in culture expressed VPF/VEGF, but only smooth muscle cells from the uterus expressed mRNA for flt-1 and KDR by Northern analysis and in situ hybridization. Cell culture extracts of uterine but not colonic smooth muscle cells were also positive for flt-1 by Western analysis. Moreover, cultured uterine but not clonic smooth muscle cells phosphorylated the flt-1 receptor and proliferated strongly in response to added VPF/VEGF. This is one of the first rigorous demonstrations that a normal cell type other than endothelial cells can express functional receptors for VPF/VEGF in vivo and in vitro, suggesting that VPF/VEGF may have important, previously unsuspected roles on cell types other than endothelium.

Adult↗
PubMed1996

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma.

BACKGROUND: Solid tumors, including endometrial carcinomas, must induce a vascular stroma to grow beyond a minimal size. The mechanisms responsible for angiogenesis in endometrial carcinoma, however, are not well defined. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine that is an important regulator of tumor angiogenesis. We evaluated VPF/VEGF mRNA and protein expression, as well as VPF/VEGF receptor mRNA expression, in endometrial carcinoma. METHODS: Fourteen examples of endometrial carcinoma were evaluated by in situ hybridization; in 7 cases, benign atrophic endometrium from the same patient was also examined. Histologic sections were subjected to in situ hybridization using 35S-labeled riboprobes specific for VPF/VEGF and, in a subset of cases, riboprobes specific for the VPF/VEGF receptors flt-1 and KDR. In addition, ten examples of endometrial carcinoma were evaluated for VPE/VEGF protein expression by immunohistochemistry. RESULTS: All 14 examples of endometrial carcinoma studied by in situ hybridization exhibited focal strong VPF/VEGF mRNA expression by tumor cells. In addition, the endothelial cells of surrounding microvessels strongly expressed flt-1 and KDR mRNAs in all ten cases examined. In contrast, no strong expression of VPF/VEGF, flt-1, or KDR mRNA was observed in the seven examples of benign atrophic endometrium studied. All ten cases of endometrial carcinoma studied by immunohistochemistry exhibited strong VPF/VEGF protein expression by tumor cells. CONCLUSIONS: These observations suggest that VPF/VEGF is an important angiogenic factor in endometrial carcinoma.

Carcinoma, Endometrioid↗
PubMed1995

Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia.

BACKGROUND: Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms responsible for angiogenesis in cervical neoplasia, however, are not well defined. PURPOSE: Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia. METHODS: Sixty-six cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIII-related antigen were evaluated quantitatively for microvessel density and for the presence of epithelial-stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization. RESULTS: VPF mRNA expression, epithelial-stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with low-grade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression. CONCLUSIONS: These observations suggest that VPF is an important angiogenic factor in cervical neoplasia.

Carcinoma, Squamous Cell↗
PubMed1995

Recombinant BCG therapy suppresses melanoma tumor growth.

BACKGROUND: Melanoma is the fastest rising cancer in the United States. Bacillus Calmette-Guerin (BCG) has been genetically engineered to actively express and secrete the cytokine interleukin-2 (IL-2). Both BCG and IL-2 have known potent antitumor and immunomodulatory properties. METHODS: This recombinant BCG (rBCG 3A) has been tested as an intratumoral injection and a vaccine therapy in conjunction with irradiated tumor cells against melanoma in the murine B16 melanoma model. RESULTS: The transfection process did not adversely alter the function of the wild-type (WT) BCG. rBCG 3A and WT BCG are equally effective intratumoral and vaccine therapies against melanoma when compared with normal saline control groups. Tumor burdens were significantly smaller (p < or = 0.01 and 0.05) for the treatment groups for both intratumoral and vaccine administration of therapy. Immunization with rBCG 3A and WT BCG 14 days before a B16 challenge resulted in an approximately 45% smaller tumor burden when compared with controls. CONCLUSIONS: Novel therapies based on the immunogenic properties of melanoma combined with molecular technologies may offer promise for an effective and safe treatment of melanoma.

Animals↗
PubMed1995

CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors.

PURPOSE: CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced through alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isoforms in ovarian cancer and to investigate whether the expression of these molecules is associated with adverse prognosis. MATERIALS AND METHODS: Six specimens of normal ovarian surface epithelium (NOSE) and 31 separate cases of newly diagnosed ovarian cancer were studied by a combination of reverse-transcription polymerase chain reaction (RT-PCR) and immunoperoxidase staining. Clinical correlation was made between CD44 variant expression and stage (I/II v III/IV), residual disease (< or = 2.0- v > 2.0-cm mass), age (< or = 65 v > 65 years), histology (papillary serous v other), grade, and survival. RESULTS: RT-PCR analysis revealed that NOSE predominantly expressed transcripts for CD44S, as well as a restricted pattern of transcripts characteristic of CD44 splice variants. CD44S and CD44 variant exon nine sequences (CD44-9v) were focally expressed in one of two NOSE specimens examined by immunoperoxidase staining. In comparison, the majority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies revealed that the majority of ovarian cancer specimens expressed both CD44S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant expression (transcript or protein) and stage, residual disease, age, histology, grade, or survival. CONCLUSION: Expression of CD44S and CD44-9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognosis suggests that other factors may be more important in determining the clinical behavior of this disease.

Adenocarcinoma, Clear Cell↗
PubMed1990

Acute myocardial infarction, non-bacterial thrombotic endocarditis, and disseminated intravascular coagulation in a severe hemophiliac.

Thrombosis in hemophilia is very rare and is usually associated with the administration of prothrombin complex concentrates. We describe a severe hemophiliac with P. carinii pneumonia who had clinical and laboratory evidence of acute myocardial infarction and disseminated intravascular coagulation, and at autopsy, nonbacterial thrombotic endocarditis as well. We suggest that prothrombin complex concentrates should be used cautiously in the setting of acute infection, and perhaps be given with appropriate doses of anticoagulants such as heparin.

Adult↗