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Lea Rath-Wolfson

Publications and source records attributed to Lea Rath-Wolfson.

13 recordsLinked to original sources
PubMed2006

The PI3K-NF-kappaB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis.

The anti-inflammatory effect of adenosine was previously found to be mediated via activation of the A3 adenosine receptor (A3AR). The aim of the present study was to decipher the molecular mechanism involved with the inhibitory effect of IB-MECA, an A3AR agonist, on adjuvant-induced arthritis. The adjuvant-induced arthritis rats responded to IB-MECA treatment with a decrease in the clinical score and the pathological score of the disease. The response to IB-MECA was neutralized by the antagonist MRS 1220, confirming that the efficacy of the synthetic agonist was A3AR mediated. The A3AR protein expression level was highly expressed in the synovia, in the peripheral blood mononuclear cells and in the drain lymph node (DLN) tissues of adjuvant-induced arthritis rats in comparison with naïve animals. Downregulation of A3AR expression was noted upon treatment with IB-MECA. Analysis of synovia and DLN protein extracts revealed a decreased expression level of PI3K, PKB/Akt, IKK, NF-kappaB and tumor necrosis factor alpha, known to affect survival and apoptosis of inflammatory cells, whereas the caspase-3 level was upregulated.Taken together, high A3AR expression is found in the synovia, in the immune cells in the DLN and in peripheral blood mononuclear cells. IB-MECA, an orally bioavailable molecule, activates the A3AR, inducing receptor downregulation and the initiation of a molecular mechanism that involves de-regulation of the PI3K-NF-kappaB signaling pathway. As a result, a potent anti-inflammatory effect manifested in the improvement of the disease clinical score and pathological score occurs. The finding that the A3AR expression level in the peripheral blood mononuclear cells and in the DLN reflects the receptor status in the remote inflammatory site suggests use of the A3AR as a follow-up biomarker.

Adenosine↗
PubMed2006

Can hamartoma of the breast be distinguished from fibroadenoma using fine-needle aspiration cytology?

In an attempt to determine if it is possible to distinguish hamartoma of the breast from fibroadenoma using fine-needle aspiration cytology, we reviewed the cytological slides of 13 histopathologically confirmed cases of hamartoma of the breast and compared them with the cytological features of 13 histologically confirmed fibroadenomas. In each case, we studied the epithelial and stromal features. Cytologic characteristics were retrospectively evaluated in a semiquantitative manner. In conclusion, the finding of intact lobular units and a relative paucity of stroma may suggest the diagnosis of hamartoma.

Adolescent↗
PubMed2005

Transthoracic needle biopsy in the diagnosis of large-cell neuroendocrine carcinoma of the lung.

To determine the effect of cytological diagnosis, fine-needle aspiration and brush cytology on lung tumors and core-needle biopsy, we retrospectively reviewed 11 cases of large-cell neuroendocrine carcinoma (LCNEC) found in our archives between the years 1997 and 2004. The preoperative cytological diagnosis of LCNEC is challenging because of the broad histologic similarity to other neuroendocrine tumors of the lung. The original cytologic diagnosis was LCNEC in nine of the cases while the remaining two were misdiagnosed as small-cell lung carcinoma. Smears were composed of clusters of intermediate-size cells with amphophylic cytoplasm, some with large nuclei and prominent nucleoli. In two of the cases there was discordance between the cytological findings and the immunohistochemical results. The cytological findings were correlated with histopathological observations.

Adult↗
PubMed2005

An improved technique for mitosis counting.

Mitosis counting remains one of the most valuable prognostic indicators in tumor pathology; however, as currently carried out it is time consuming and not reproducible. In this study, 6 different pathologists, using different microscopes, arrived at widely different mitotic counts on the same slide, ranging from 4 to 16. These differences were mainly due to the different field areas of the various microscopes used and the method used for counting and recording. In evaluating the most active 10 HPF, the count ranged from 10 to 19. Instead, when an average of 40 fields was recorded, the range was 4-11. Using the mitosis/volume index, which expresses the number of mitotic figures per mm2 of viable tumor, the counts ranged from 8 to 10, a marked improvement. However, this method is complicated and not "user-friendly.'' We suggest a variation of the technique by which a 2 mm2 rectangle is drawn on a cover slip and mounted under the microscope, centered on the most mitotically active area of the tumor. The mitoses in that area are counted (=n) and the percent of viable tumor (=x%) is estimated under low magnification. The number of mitoses per mm2 of viable tumor (cs-MAI) is then calculated according to the formula Cs-MAI=100n/2x. Using this modified method, the range of mitoses counted by the different observers was very narrow (9 to 11), and the time required for the counting was only 5-10 minutes.

Female↗
PubMed2005

Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models.

OBJECTIVE: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects in 3 murine models of adjuvant induced arthritis (AIA). METHODS: The antiinflammatory effect of CF101 was examined in rat AIA, in mouse collagen induced arthritis, and in tropomyosin induced arthritis. The clinical effect of another A3AR agonist, Cl-IB-MECA, was examined in rat AIA. The effect of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily on arthritis severity was assessed clinically and histologically. The effect of CF101 on the protein expression level of TNF-alpha in the synovial tissue, draining lymph nodes, and spleen cells was determined by Western blot. RESULTS: CF101 and Cl-IB-MECA markedly ameliorated the clinical and histological features of arthritis in the 3 models when administered orally at a low dose of 10 mg/kg body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of either CF101 or Cl-IB-MECA had better antiinflammatory effect than the higher 100 mg/kg dose. Decreased expression of TNF-alpha was noted in protein extracts of synovia, draining lymph nodes, and spleen tissues. CONCLUSION: The results provide evidence that A3AR agonists exert significant antirheumatic effects in different autoimmune arthritis models by suppression of TNF-alpha production. The beneficial activity of the drugs at the low dose demonstrates that the effect is A3AR mediated.

Adenosine↗
PubMed2004

Talc inhalation is a life-threatening condition.

A case of rapidly progressive disease and pulmonary hypertension due to chronic cosmetic talc inhalation is presented. Although an uncommon cause of pulmonary hypertension, talc, especially through intravenous administration, should be included in the etiology of parenchymal pulmonary hypertension. In our case talc inhalation was inadvertent, causing fulminant disease leading to the patient's death. To our knowledge, this is the first case of inadvertent talc inhalation causing death in adult patient.

Adult↗
PubMed2004

The A3 adenosine receptor is highly expressed in tumor versus normal cells: potential target for tumor growth inhibition.

PURPOSE: A(3) adenosine receptor (A(3)AR) activation was shown to inhibit the growth of various tumor cells via the down-regulation of nuclear factor kappaB and cyclin D1. To additionally elucidate whether A(3)AR is a specific target, a survey of its expression in tumor versus adjacent normal cells was conducted. EXPERIMENTAL DESIGN: A(3)AR mRNA expression in various tumor tissues was tested in paraffin-embedded slides using reverse transcription-PCR analysis. A comparison with A(3)AR expression in the relevant adjacent normal tissue or regional lymph node metastasis was performed. In addition, A(3)AR protein expression was studied in fresh tumors and was correlated with that of the adjacent normal tissue. RESULTS: Reverse transcription-PCR analysis of colon and breast carcinoma tissues showed higher A(3)AR expression in the tumor versus adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed that the lymph node metastasis expressed even more A(3)AR mRNA than the primary tumor tissue. Protein analysis of A(3)AR expression in fresh tumors derived from colon (n = 40) or breast (n = 17) revealed that 61% and 78% had higher A(3)AR expression in the tumor versus normal adjacent tissue, respectively. The high A(3)AR expression level in the tumor tissues was associated with elevated nuclear factor kappaB and cyclin D1 levels. High A(3)AR mRNA expression was also demonstrated in other solid tumor types. CONCLUSIONS: Primary and metastatic tumor tissues highly express A(3)AR indicating that high receptor expression is a characteristic of solid tumors. These findings and our previous data suggest A(3)AR as a potential target for tumor growth inhibition.

Blotting, Western↗
PubMed2004

Prognostic value of Topoisomerase II in female breast cancer.

Topoisomerase II-alpha (Topo II-alpha) is a nuclear enzyme. Its expression rises rapidly at the end of the S to G2/M phase and falls after the mitotic process ends. We have studied the immunohistochemical expression of Topo II-alpha in breast cancer and its correlation with the menopausal state, tumor type, size, lymph node metastases, stage, and estrogen and progesterone positivity. Histological sections from 50 breast cancers were immunohistochemically stained for Topo II-alpha. The percent of positive cells at the area of highest staining was recorded as Topo index. The correlation between the course of disease, survival and Topo II-alpha index was statistically significant, p<0.001. High-grade tumors showed higher Topo II-alpha levels, than those of intermediate and low-grade, p<0.01. A significant association was found between estrogen receptors positivity and Topo II-alpha, p<0.05. A higher Topo II-alpha index indicates higher probability for recurrence of the disease and overall survival. Therefore, Topo II-alpha expression has a prognostic value in breast carcinoma.

Adult↗
PubMed2004

Quantitative microscopy of human DNA topoisomerase II-alpha expression in transitional cell carcinoma of the bladder.

OBJECTIVE: To compare the nuclear size of various grades of transitional cell carcinoma (TCC) stained immunohistochemically with the nuclear enzyme topoisomerase II-alpha (topo II-alpha) in bladder urothelial neoplasms. STUDY DESIGN: Histologic sections from 53 consecutive papillary bladder neoplasms were stained immunohistochemically for topo II-alpha expression. There were 18 (33.9%) urothelial neoplasms of low malignant potential (UNLMP), 18 (33.9%) low grade urothelial carcinoma (LGUCa), and 17 (32%) with high grade urothelial carcinoma (HGUCa). The histologic slides were photographed at 400 x magnification and then projected on a screen, and the area with stained nuclei was measured. RESULTS: The cells and nuclei in HGUCa were significantly larger than in LGUCa (P < .05) and UNLMP (P < .01). CONCLUSION: Calculation of the area fraction of nuclei in TCC of the bladder stained with topo II-alpha is an additional method of establishing the grade of these tumors.

Adult↗
PubMed2003

Combined intravesical hyperthermia and mitomycin chemotherapy: a preliminary in vivo study.

Previous clinical studies of the combination of local intravesical hyperthermia with cytostatic drugs for the treatment of Superficial Transitional Cell Carcinoma of the urinary bladder (STCCB) showed encouraging results both in reducing recurrence rate to 20-30% within 2 years and in ablative success rate of 79%. Our objectives were to evaluate bladder tissue and adjacent organs during and following hyperthermia treatment. An intravesical catheter equipped with a radio-frequency antenna (Synergo SB-TS 101.1 System) was used for hyperthermia and intravesical chemotherapy (mitomycin C) was instilled in vivo for 60 min in two anaesthetized sheep. Thirteen to fifteen thermocouples were sewn surgically on the internal and external surfaces of the bladder wall and on adjacent organs to monitor the temperature during the treatment. We expected the intravesical temperature to be under 46 degrees C and the external layers below 45 degrees C. The bladder was filled with 50 mL of chemotherapeutic solution (400 micro g/mL of mitomycin C in distilled water). The sheep were sacrificed at the end of the treatment. Three other sheep, which underwent thoracic surgery, served as control group. Histological changes in both groups showed foci of oedema and haemorrhage with inflammation in the lamina propria and serosa. Foci of desquamation of the epithelium were noticed in the treated sheep. Histological analysis of the treated group showed no significant differences from the control group. The control group showed similar changes, some less pronounced. The combined treatment of hyperthermia with mitomycin C did not cause major damage to the urinary bladder or adjacent organs. All changes were superficial and reversible, and the control group showed similar changes, some less pronounced. Although this is an experimental model based on one single session treatment, rather than repeated treatments, it suggests that the approach may be useful in future studies both in models and man.

Adipose Tissue↗
PubMedDate not supplied

A new scoring system using multiple immunohistochemical markers for diagnosis of uterine smooth muscle tumors.

The diagnosis of uterine smooth muscle neoplasms by light microscopy is difficult. Multiple classification schemes have been proposed based on mitotic rate, nuclear atypia, and the presence or absence of necrosis. None of these classification systems has been entirely successful. This study was undertaken to evaluate the use of selected immunohistochemical and histochemical markers in differentiating these tumors, in addition to accepted morphologic criteria. Ten cases of each of the following: leiomyosarcomas (LMS), atypical leiomyomas (AL), cellular leiomyomas (CL) and usual leiomyomas (UL), were classically evaluated for histological diagnosis and were stained for Ki-67 (MIB-1), bcl- 2 and p53 using monoclonal antibodies and the avidin-biotin peroxidase method, and argyrophilic nucleolar organizer region (AgNORs). The number of stained cells was counted in the most positively stained region in a 4 mm2 square cover glass mounted on each slide. The mean value was calculated for each group of tumors. The data for Ki-67 (MIB- 1), bcl-2, p53 and AgNOR staining respectively, were significantly higher in LMS by comparison to UL, CL or AL. Because many singular cases had superimposed data being difficult to diagnose, a new scoring system for pathological evaluation was created. The results obtained by this scoring system suggest that immunohistochemical markers Ki-67 (MIB-1), bcl-2, p53 together with the AgNOR staining could be useful, by the scoring system, as an adjunct to the current accepted morphologic criteria in differentiating smooth muscle tumors of the uterus.

Antigens, Nuclear↗
PubMedDate not supplied

Targeting the A3 adenosine receptor for cancer therapy: inhibition of prostate carcinoma cell growth by A3AR agonist.

BACKGROUND: Agonists to A3 adenosine receptor (A3AR) were shown to inhibit the growth of various tumor cell types. The present study demonstrates that a synthetic A3AR agonist, 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purine- 9-yl]-N-methyl-beta-D-ribofura-nuronamide (IB-MECA), inhibits the growth of androgen-independent PC-3 prostate human carcinoma cells and illustrates the molecular mechanism involved. MATERIALS AND METHODS: PC-3 prostate carcinoma cells were used. Cell growth was examined in vitro by the thymidine incorporation assay and in vivo by inoculating the tumor cells subcutaneously into nude mice and monitoring tumor size. The protein expression level in cells and tumor extracts was tested by Western blot analysis. RESULTS: A decrease in the protein expression level of A3AR and the downstream effector PKAc was observed. Consequently, the GSK-3 beta protein level increased, resulting in the destabilization of beta-catenin and the subsequent suppression of cyclin D1 and c-myc expression. IB-MECA treatment also induced down-modulation of the expression of NF-kappa B/p65, known to regulate the transcription of cyclin D1 and c-Myc. This chain of events occurred both in vitro and in vivo and suggests the use of the above-mentioned signaling proteins as markers to predict tumor cell response to A3AR activation. CONCLUSION: Taken together, we demonstrated that A3AR activation deregulates the Wnt and the NF-kappa B signaling pathways resulting in the inhibition of prostate carcinoma cell growth.

Adenosine↗