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S Shousha

Publications and source records attributed to S Shousha.

At least 19 recordsLinked to original sources
PubMed2007

Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer.

The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.

Adult↗
PubMed2006

Phosphorylation of ERalpha at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ERalpha phosphorylation in breast cancer progression.

Oestrogen receptor-alpha (ERalpha) is an important prognostic marker in breast cancer and endocrine therapies are designed to inhibit or prevent ERalpha activity. In vitro studies have indicated that phosphorylation of ERalpha, in particular on serine 118 (S118), can result in activation in a ligand-independent manner, thereby potentially contributing to resistance to endocrine agents, such as tamoxifen and aromatase inhibitors. Here we report the immunohistochemistry (IHC) of S118 phosphorylation in 301 primary breast tumour biopsies. Surprisingly, this analysis shows that S118 phosphorylation is higher in more differentiated tumours, suggesting that phosphorylation at this site is associated with a good prognosis in patients not previously treated with endocrine agents. However, we also report that S118 phosphorylation was elevated in tumour biopsies taken from patients who had relapsed following tamoxifen treatment, when compared to pre-treatment biopsies. Taken together, these data are consistent with the view that S118 phosphorylation is a feature of normal ERalpha function and that increases in levels of phosphorylation at this site may play a key role in the emergence of endocrine resistance in breast cancer.

Biomarkers, Tumor↗
PubMed2005

Intra-operative assessment of excision margins using breast imprint and scrape cytology.

Local recurrence in breast cancer surgery is related to the completeness of excision. Histological analysis of excision margins is time consuming and impractical for use intra-operatively. Our group evaluated breast imprint and scrape cytology (ISC) for the assessment of excision margins in a feasibility study in 1993-4, with 10 year clinical follow-up. Twenty-six consecutive women undergoing 27 wide local excisions for breast cancer had excision margins prospectively assessed with intra-operative ISC blinded to histology. All ISC results were ready (range 22-30 min) before surgery was completed. ISC agreed with histology in 21/27 (=78%) and disagreed in 6/27 (=22%) of the cases. In two cases with local recurrence, histology was positive in one case, whereas ISC margins were positive in both. Intra-operative ISC is reliable and could help the surgeon to excise more tissue to prevent a second (re-excision) operation. ISC margins may predict clinical outcome, although a larger interventional follow-up study is required.

Adult↗
PubMed2005

Inhibiting estrogen responses in breast cancer cells using a fusion protein encoding estrogen receptor-alpha and the transcriptional repressor PLZF.

Estrogen receptor alpha (ERalpha) is a ligand-inducible transcription factor that acts to regulate gene expression by binding to palindromic DNA sequence, known as the estrogen response element, in promoters of estrogen-regulated genes. In breast cancer ERalpha plays a central role, where estrogen-regulated gene expression leads to tumor initiation, growth and survival. As an approach to silencing estrogen-regulated genes, we have studied the activities of a fusion protein between ERalpha and the promyelocytic leukemia zinc-finger (PLZF) protein, a transcriptional repressor that acts through chromatin remodeling. To do this, we have developed lines from the estrogen-responsive MCF-7 breast cancer cell line in which the expression of the fusion protein PLZF-ERalpha is conditionally regulated by tetracycline and shows that these feature long-term silencing of the expression of several well-characterized estrogen-regulated genes, namely pS2, cathepsin-D and the progesterone receptor. However, the estrogen-regulated growth of these cells is not inhibited unless PLZF-ERalpha expression is induced, an observation that we have confirmed both in vitro and in vivo. Taken together, these results show that PLZF-ERalpha is a potent repressor of estrogen-regulated gene expression and could be useful in distinguishing estrogen-regulated genes required for the growth of breast cancer cells.

Animals↗
PubMed2004

Intra-operative specimen analysis using faxitron microradiography for excision of mammographically suspicious, non-palpable breast lesions.

Recent advances in digital imaging have made Faxitron microradiography an attractive alternative to intra-operative conventional specimen radiography (CSR) for the excision of wire-localized breast lesions. Faxitron specimen analysis time, usefulness of digital image manipulation and re-excision rates were evaluated in comparison to CSR in 299 consecutive wire-localized excisions for mammographically suspicious non-palpable breast lesions (172 procedures with Faxitron, 127 with CSR) in a non-randomized study. The corresponding mean operation times were 34.7 vs. 42.7 min and the respective re-excision rates were 19.8% vs. 31.5% (no significant difference on chi analysis P < 0.1). Faxitron digital image manipulation led to cavity biopsies in 50% (60/121) of the cancer excisions. In 19 of these (16%), histological excision margins were converted from incomplete to complete. The shorter Faxitron mean operating time enables an additional wire-localized operation per theatre list. Digital imaging guides the surgeon for additional cavity biopsies, resulting in re-excision rates as good as CSR.

Adult↗
PubMed2004

CD10 immunostaining of bile canaliculi in liver biopsies: change of staining pattern with the development of cirrhosis.

AIMS: This study was prompted by published observations concerning the absence of normal bile canalicular CD10 staining in some cases of primary liver cell carcinoma. Our aim was to investigate the possibility that this loss of staining occurs prior to the development of cancer. METHODS AND RESULTS: The study comprised 164 liver biopsies, including 96 from patients with hepatitis C infection of various grades and stages including nine cases with cirrhosis, 24 other cases of cirrhosis of other aetiology, five cases of primary liver carcinoma, 12 cases of metastatic carcinoma, as well as biopsies with a variety of other liver diseases. CD10 was demonstrated in paraffin sections using the avidin-biotin immunoperoxidase technique. In hepatitis C cases, a significant loss of the canalicular pattern was seen in four out of 41 (10%) biopsies with stages 0-1 compared with 25 out of 55 (45%) with stages 2-6 (P < 0.001). There was also a significant difference (P < 0.001) between biopsies with stage 2-3 and those with stage 4-6, where marked pattern loss was seen in 9/37 (24%) and 16/18 (89%), respectively. Marked loss of the pattern was also seen in 16 out of the 24 (67%) other cirrhotic biopsies, as well as in cases with severe lobular inflammation and cholestasis and liver cell dysplasia and carcinoma. In hepatitis C biopsies, no relationship was noted between the reduction in the canalicular pattern and the necroinflammatory score. CONCLUSIONS: CD10-stained bile canalicular pattern in liver biopsies is preserved in cases with mild fibrosis and inflammation, but it becomes increasingly reduced with the advance of fibrosis or the presence of severe lobular inflammation or extensive metastases. Further investigations into the relationship between the changes in CD10 staining pattern and liver function tests may be useful in explaining test results.

Adolescent↗
PubMed2003

Purified malignant mammary epithelial cells maintain hormone responsiveness in culture.

Currently, the therapy for breast cancer is determined by immunohistochemical staining of the primary tumour for oestrogen receptor alpha (ERalpha). However, a proportion of ERalpha-positive patients fail to respond to tamoxifen and a proportion of ERalpha-negative patients show response. Here, we describe a novel procedure for the purification of malignant breast epithelial cells in an attempt to identify these patients at an early stage. Using this procedure, we are able to purify malignant cells to >90% purity as determined by immunohistochemical staining, cytology and fluorescent in situ hybridisation (FISH). While the malignant cells can be maintained in culture they do not proliferate in contrast to purified breast epithelial cells from reduction mammoplasties. Moreover, ERalpha and progesterone receptor (PR) expression is maintained in malignant cells, whereas normal epithelial cells rapidly lose ERalpha and PR. Functional studies were performed on the separated malignant cells in terms of their response to oestradiol and tamoxifen. Four out of the seven ERalpha-positive tumours showed a significant reduction in cell numbers after tamoxifen treatment compared to oestradiol, ERalpha negative tumours failed to show a response. We conclude that (a) it is possible to purify and maintain breast cancer cells for a sufficient period to permit functional studies and (b) ERalpha is retained in culture facilitating the use of these cells in studies of the mechanism of endocrine response and resistance in vitro.

Breast↗
PubMed2003

Pelvic connective tissue resilience decreases with vaginal delivery, menopause and uterine prolapse.

BACKGROUND: The late onset of pelvic visceral prolapse and incontinence after childbirth injury could be explained by menopause-associated connective tissue weakening. Uterosacral ligament resilience (UsR) was assessed to determine whether it influenced uterine or pelvic floor mobility, or varied with age, vaginal delivery, menopause or histological variations in the ligament. METHODS: UsR was measured by tensiometry in ligaments from 85 hysterectomy specimens, and was correlated with the presence of symptomatic uterocervical prolapse, prehysterectomy uterine and anorectal mobility, patient age, history of vaginal delivery and menopause. Forty-five of these ligaments were examined for ligament thickness, muscle to collagen ratio, and oestrogen and progesterone receptor density. The results were correlated with UsR. RESULTS: UsR was significantly reduced (P = 0.02) in symptomatic uterovaginal prolapse, but there was no correlation with either uterocervical or anorectal descent in women without symptomatic prolapse. There was a significant decrease in UsR with vaginal delivery (P = 0.003), menopause (P = 0.009) and older age (P = 0.005). The uterosacral ligament was significantly thinner and contained fewer oestrogen and progesterone receptors after menopause, but this did not affect UsR. CONCLUSION: Where pelvic floor muscles are weakened, decreases in pelvic connective tissue resilience related to the menopause may facilitate progression to symptomatic pelvic visceral prolapse.

Adult↗
PubMed2003

Oestrogen receptor negativity as a marker for high-grade ductal carcinoma in situ of the breast.

AIMS: To compare the morphological and immunohistochemical characteristics of oestrogen receptor (ER)-negative and ER-positive ductal carcinoma in situ (DCIS) of the breast, in an attempt to establish more objective criteria for the classification of DCIS. METHODS AND RESULTS: Sections of 64 cases of in-situ carcinoma of the breast were stained for ER, progesterone receptors (PgR), androgen receptors (AR), c-erbB-2 and p53, using the immunoperoxidase technique. The cases included 60 DCIS and four lobular carcinoma in situ (LCIS). Four DCIS lesions were associated with foci of microinvasion. The 60 DCIS cases included 31 high grade, 23 intermediate grade and six low grade. Twenty-four DCIS cases (40%) were ER-negative and 36 were positive. ER negativity was significantly associated with high nuclear grade (88% versus 27% for ER-positive cases, P < 0.001), PgR negativity (100% versus 25%, P < 0.001), c-erbB-2 positivity (79% versus 14%, P < 0.001) and p53 positivity (58% versus 6%, P < 0.001). There was no difference between ER-negative and -positive DCIS as regards AR expression, with 91% of cases in each group being AR-positive. Of the four cases of DCIS with microinvasion, three were ER- and PgR-negative, all four were c-erbB-2-positive and AR-positive and one was p53-positive. None of the four LCIS was ER, PgR or AR-negative and none was c-erbB-2- or p53-positive. CONCLUSIONS: There is a highly significant direct relationship between ER negativity in DCIS and high nuclear grade, PgR negativity and c-erbB-2 and p53 positivity. We suggest that immunohistological assessment of ER status may help in providing a more objective way of classifying DCIS.

Biomarkers, Tumor↗
PubMed2002

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer.

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.

Adult↗
PubMed2001

Analysis of estrogen-responsive finger protein expression in benign and malignant human breast.

The estrogen-responsive finger protein (EFP) gene was originally identified in a screen of genomic DNA for genes containing estrogen-response elements (EREs), and its expression was subsequently shown to be estrogen-regulated and correlated with estrogen receptor (ER)alpha-positive tissues in mice. Human chromosomal mapping localized it to 17q23.1, close to BRCA1, in a region frequently lost in breast cancers. Structurally related proteins have been implicated in a variety of important cellular processes, including carcinogenisis. Given that ER is over-expressed in a large proportion of breast cancers, we reasoned that EFP may play a role in mediating the estrogen-dependent progression of breast cancer. We raised anti-sera to EFP and show that EFP is present in the cytoplasm in mammary cell lines and epithelial cells of normal breast tissue. Furthermore, EFP is present in cell culture medium, suggesting that it may be secreted. Immunohistochemistry of paraffin-embedded breast biopsy specimens showed significantly greater levels of EFP in lactating breast and fibroadenomata compared to normal breast (p<0.001 and p = 0.001, respectively), which is likely to be a result of estrogen responsiveness. Levels were reduced in breast cancer (p = 0.02), where no correlation was seen with other immunohistochemical, histopathological or clinical data. The lack of correlation between EFP and ER status of tumors could indicate escape from estrogenic control, pointing to new models of tumor pathogenesis. Increased levels of EFP in lactating breast and the reduction in malignancy suggest a role for EFP in promoting mammary gland differentiation.

Animals↗
PubMed2001

Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer.

Immunohistochemical staining of human breast tissues, using an antibody against fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular distribution. Both malignant and non-malignant epithelial cells contained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were negative. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytoplasmic and nuclear elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of FGFR-3, which were present in both malignant and non-malignant epithelial cells. The higher level of nuclear staining and loss of cytoplasmic staining seen in malignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mutations. Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, however, is present in the majority of breast cancers and a different tissue distribution of FGF1 was found in breast tissues, showing predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast cancer.

Adult↗
PubMed2001

Methylene blue staining: is it really useful in Barrett's esophagus?

BACKGROUND: If areas of specialized intestinal metaplasia (SIM) or dysplasia in Barrett's esophagus can be identified at endoscopy, the number of biopsies could be reduced and the sensitivity of biopsy surveillance would increase. It has been suggested that methylene blue (MB) dye staining may be useful for this purpose. METHODS: Nine patients were prospectively studied with Barrett's esophagus. Staining involved sequential spraying of 10% N-acetylcysteine, 0.5% MB and water. Quadrantic biopsies were obtained from Barrett's epithelium and collected in separate containers depending on whether they were taken from stained or unstained areas. Seven patients undergoing yearly surveillance were asked to compare the discomfort of this endoscopy with that of previous surveillance endoscopies. Biopsies were analyzed for the presence and the percentage of SIM and dysplasia by a nonblinded pathologist. RESULTS: MB staining prolonged endoscopy by a mean of 8 minutes (47% increase in procedure time) and was associated with significant vomiting during the procedure in 2 patients. Staining was observed in all 9 patients. All 7 patients undergoing yearly endoscopic surveillance indicated more discomfort with endoscopy plus MB staining. Of 37 biopsies from stained mucosa, 20 contained SIM; of 23 from unstained mucosa, 15 contained SIM (57% sensitivity, 32% specificity for MB staining). CONCLUSIONS: In this small, nonblinded study MB staining was associated with prolongation of endoscopy, increased patient discomfort, and potentially serious complications and was neither very sensitive nor specific for SIM. It is our recommendation that this technique should not be routinely used in endoscopic surveillance of patients with Barrett's esophagus. Further studies of MB staining are needed.

Barrett Esophagus↗
PubMed2001

CD9 immunohistochemical staining of breast carcinoma: unlikely to provide useful prognostic information for routine use.

AIMS: CD9, a cell membrane glycoprotein, is found in a variety of tumour cells and is believed to regulate cell motility and possibly cell growth. It has been reported that the absence of CD9 is associated with increased aggressiveness of breast carcinoma, but no detailed studies of the distribution of CD9 in normal and abnormal breast tissue are available. This investigation was aimed at studying the distribution of CD9 in a wide variety of breast biopsies including normal, benign, and malignant cases, and assessing its usefulness as a prognostic marker in breast cancer. METHODS AND RESULTS: Sections of 113 breast biopsies from female and male patients including 10 normal, 23 benign, and 80 malignant cases were examined. The monoclonal antibody CD9 (Novacastra Ltd, Newcastle-upon-Tyne, UK) was used with the avidin-biotin complex immunoperoxidase technique. The results were assessed semiquantitatively using a four scale system of 3+, 2+, 1+ and negative. All normal and benign epithelial cells were strongly stained (3+). In female breast carcinomas, 40% were 3+, 49% were 2+, and 11% were 1+. Both cases of male breast carcinomas scored 3+. For female breast cancers, the results were then correlated to tumour grade, the presence or absence of lymph node metastases, and oestrogen and progesterone receptor status. No significant statistical correlation was found with any of these parameters. We then examined 11 axillary lymph nodes with metastases from some of the above cases. Three of these cases had a CD9 score of 3+, seven were 2+, and one was 1+. The metastatic tumours in all 11 cases were strongly stained (3+). CONCLUSIONS: Immunostaining for CD9 is unlikely to provide any useful additional prognostic information for clinical purposes.

Antigens, CD↗
PubMed2001

Multisite phosphotyping of the ErbB-2 oncoprotein in human breast cancer.

BACKGROUND: Overexpression of the ErbB-2 (HER2/neu) receptor tyrosine kinase is one of the most common molecular changes in human cancer, but the functional significance of this phenotype remains uncertain. METHODS AND RESULTS: Using phosphorylation-specific antibodies recognizing different ErbB-2 functional states, we assessed the phosphorylation status of ErbB-2 in 102 human breast cancer specimens. Quantitative ErbB-2 immunoblotting intensity correlated directly with that of immunohistochemistry (r = 0.84). Widely varying phosphorylation profiles were evident in 65 ErbB-2-positive carcinomas, suggesting different ErbB-2 functions in different tumors. In a subset of patients for whom clinical data were obtainable, mortality trends were strongly associated with the quantitative signal intensities of ErbB-2 phosphoantibodies (P < or =.02), but not with those of conventional antibodies to ErbB-2 (P = .147), epidermal growth factor receptor (P = .44), or phosphotyrosine (P = .94). CONCLUSION: Although requiring corroboration in larger prospective clinical studies, these findings suggest that immunophenotyping using phosphorylation-specific antibodies may enable more accurate prediction of cancer behavior than is currently obtainable using conventional reagents.

3T3 Cells↗