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Y Luqmani

Publications and source records attributed to Y Luqmani.

18 recordsLinked to original sources
PubMed2004

Family history of benign thyroid disease and cancer and risk of thyroid cancer.

In a population-based study of 313 case-control pairs in Kuwait, we evaluated whether a family history of benign thyroid disease (BTD) and thyroid or other cancers was associated with an increased risk of thyroid cancer, the second most common neoplasm among women in this and several other Arab countries in the Gulf region. Family history of BTD was reported by 78 (24.9%) cases and 40 (12.8%) controls in 132 and 57 relatives, respectively. There was an approximately 2-fold increased risk of thyroid cancer in individuals who had a mother (Odds Ratio (OR)=2.3; 95% Confidence Intervals (95% CI): 1.1-5.1), sister(s) (OR=2.6; 95% CI: 1.3-5.3) or aunt(s) (OR=2.1; 95% CI: 0.9-5.3) with BTD; there was also a significant trend in increasing risk with an increasing number of affected female relatives (P<0.0001). Stratification by age at diagnosis of the case showed that individuals aged </= 35 years, who had an affected first- or second/third-degree relative(s), had an approximately 3-fold increased risk of the cancer. Family history of thyroid cancer was reported by 9 (2.9%) cases in 13 relatives (11 females, 2 males) and by 3 controls in 3 relatives (all females) (OR=3.0; 95% CI: 0.8-11.1). The OR for all hormone-related cancers combined was 1.5 (95% CI: 0.8-2.6). There was no clear association with family history of breast or any other common cancer. Our data suggest that a family history of BTD is associated with an increased risk of thyroid cancer, and point to the role of familial susceptibility to BTD and thyroid cancer in the Kuwaiti population.

Adolescent↗
PubMed1999

Measurement of serum N-acetyl beta glucosaminidase activity in patients with breast cancer.

N-acetyl-beta-glucosaminidase (NAG) activity measured in sera from 129 breast cancer patients was elevated (mean 18.2 units/l) compared with that in sera from 28 healthy women (11.6 units/l) (p=0.001). There was a weak correlation between NAG activity and carcinoembryonic antigen (CEA) and CA-153, but no relationship to age, menopausal status, node status, stage, histology of tumour or to steroid receptors. NAG, CEA and CA-153 were measured in periodic follow-up samples taken after surgery (up to 26 months) from 17 patients. NAG activity fluctuated within a narrow range, unlike CEA and CA-153. In 70% of cases the pattern was similar to at least one of the other markers, and was generally maintained at a higher level in patients who suffered relapse compared with those who remained disease-free up to the last follow-up, but was not significantly altered before relapse. The measurement of NAG activity is unlikely to be of value in predicting time or occurrence of relapse or of clinical utility in post-surgical therapy. Increased appearance in serum may aid metastasis by degrading the extracellular matrix and it may be better investigated as a predictor of progression from in situ to invasive and metastatic cancer.

Acetylglucosaminidase↗
PubMed1999

Immunoradiometric measurement of pS2 in breast cancer--correlation with steroid receptors and plasminogen activators.

pS2 was measured by radioimmunometric assay in tumour extracts from 197 breast cancer patients. Values ranged from 0 to 50 ng/mg protein (mean 9.6 and median 3 ng/mg). We found no correlation with age, menopausal status, nodal metastases, disease stage or tumour histology. There was, however, a linear relationship with both ER (p < 0.0001) (particularly nuclear ER) and PR (p < 0.0001) expression determined by enzyme immunoassay (ELISA), as well as a good correlation when high and low expressors were stratified on the basis of combined ER/PR expression using consensus cut-off points. Only 15% of ER - ve/PR - ve patients were classified as pS2 + ve compared with 83% of those who were ER + ve/PR + ve. pS2 was also directly correlated with high expression of tPA and inversely with uPA. Comparison with previous studies showed that the current ELISA method produced consistent results, in contrast to other methods, particularly those based on immunohistochemical detection. The close relationship between pS2 and both steroid receptors suggests that pS2 may be important in terms of defining hormone-responsive patients who are likely to benefit from endocrine therapy.

Breast Neoplasms↗
PubMed1997

The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for keratin 19.

The aim of this study was to determine whether reverse transcriptase polymerase chain reaction (RT-PCR) for keratin 19 (K19) provides additional information when combined with immunohistochemistry when used to detect micrometastases in blood and bone marrow in patients with primary breast cancer. We studied 78 patients with breast cancer who had no evidence of distant metastases. We collected blood and bone marrow, separated the mononuclear fraction and carried out RT-PCR and immunohistochemistry for K19. RT-PCR was done by two 40-cycle rounds using nested primers. In initial experiments, RT-PCR was shown to be capable of detecting one tumour cell in one million normal bone marrow cells, which was at least 10 times more sensitive than immunohistochemistry, while retaining specificity. Five per cent of the peripheral blood and 22% of the bone marrow samples contained K19 positive cells by immunohistochemistry staining. Using RT-PCR, these proportions increased to 25% and 35%, respectively. This represents a significantly greater detection frequency (P < 0.001 and P = 0.03, respectively). RT-PCR for K19 is a more sensitive method for detecting micrometastases in patients with primary breast cancer when compared with immunohistochemistry.

Adult↗
PubMed1997

Expression of keratinocyte growth factor and its receptor in human breast cancer.

The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) procedure. We found similar levels of KGF mRNA in malignant and non-malignant breast tissues. The study of the amount of KGF mRNA in breast cell lines and purified populations of cells revealed that fibroblasts are the predominant source of KGF with malignant and non-malignant epithelial cells containing very low levels of KGF mRNA. We have examined the distribution of fibroblast growth factor receptor (FGFR)-2-IIIb, which is a high-affinity receptor for KGF and find that it is present on malignant and non-malignant epithelial cells. The level of FGFR-2-IIIb present on breast cancer cell lines was sufficient for KGF stimulation of breast cancer cell proliferation. Other members of the fibroblast growth factor family have been either not expressed in the human breast (FGF3, FGF4) or have been found at much reduced levels in breast cancer (FGF1, FGF2) and this is the first member of the family to potentially influence the progression of breast cancer through stimulation of cell division.

Breast↗
PubMed1996

Expression of bFGF, KGF and FGF receptors on normal oral mucosa and SCC.

Fibroblast growth factors (FGFs) are involved in the transmission of signals between the epithelia and connective tissue, and influence epidermal growth and differentiation. They are thought to be important in the restoration of normal tissues after injury and aberrant expression may also play a role in tumorigenesis. However, no information is available on the nature of cells within oral mucosa which synthesise and/or respond to FGFs. We have screened normal oral mucosa and oral squamous cell carcinoma (SCC) for expression of bFGF by immunohistology and northern analysis and used RT-PCR to look for transcripts for KGF and the high-affinity FGF receptors FGFR1 and FGFR2. Transcripts for bFGF were detected in normal and malignant oral mucosa and KGF within connective tissue elements. The predominant FGF receptor detected in the epidermis and oral mucosa was FGFR2 which binds KGF with greater affinity than bFGF. Production of KGF by connective tissue components and synthesis of the high-affinity KGF receptor, FGFR2, by oral keratinocytes provides circumstantial evidence for a paracrine growth control loop with KGF synthesised within the lamina propria or tumour stroma influencing the proliferation and maturation of both normal oral epithelium and SCC.

Base Sequence↗
PubMed1996

Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients.

We have used polymerase chain reaction (PCR) to measure keratin 19 mRNA in order to detect breast cancer cells invading axillary lymph nodes. In a consecutive series of 125 patients with primary breast cancer, 75 patients had no evidence of lymph node involvement by conventional histology. A total of 530 lymph nodes from these patients were examined and 106 (20%) gave a keratin 19 product detectable by Southern hybridisation. This correlated with primary tumour size (P<0.001). These 106 nodes came from 23 patients. Thus, using this technique, 23/75 (30.6%) patients were found to have evidence of lymph node involvement who would otherwise have been designated lymph node negative.

Adult↗
PubMed1994

Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction.

Breast cancer micrometastases in axillary lymph nodes have been detected by serial sectioning and immunohistochemistry, and shown to have prognostic significance. We have used polymerase chain reaction (PCR) to see whether we could further improve the detection rate of micrometastases. Fifty-seven axillary lymph nodes from patients with breast cancer were examined histologically to assess the proportion of tumor involvement. Immunohistochemical staining with the use of an anti-keratin 19 antibody confirmed the histological findings. Reverse transcription PCR was then performed on extracted RNA by using K19 primers, and all 18 histologically involved nodes yielded the expected 460-base pair product. Of 39 histologically negative nodes, 4 (10%) gave K19 bands detectable with ethidium staining and a further 10 (28%) gave K19 bands after Southern hybridization. To further increase the detection sensitivity a two stage amplification was performed by using nested primers, and K19 product was found in lymph nodes from patients without cancer, as well as in all the nodes from cancer patients. This was shown to be genuine low level expression from endogenous mRNA template, and not derived from amplification of a K19 pseudogene. Reducing the number of PCR cycles in the two amplification steps did not allow sufficient discrimination between normal nodes and those involved nodes in which K19 expression was only detectable after Southern hybridization. The optimal "cut-off" point to distinguish involved nodes from normal nodes remained at the level of 40 cycles of PCR and Southern hybridization. PCR, using K19 as a tumor marker, has been demonstrated in this study to improve the detection of micrometastases in axillary lymph nodes in patients with breast cancer: sensitivity is limited by the specificity of the tumor marker.

Adult↗
PubMed1993

The prognostic significance of transforming growth factors in human breast cancer.

Transforming growth factor alpha (TGF alpha) and Transforming growth factor beta-1 (TGF-beta 1) are growth regulatory for breast cancer cell lines in vitro and several studies have suggested that levels of the receptor for TGF alpha, the epidermal growth factor (EGFR) in tumour biopsies predict relapse and survival. We have examined the prognostic significance of TGF alpha, TGF-beta 1 and EGFR mRNA expression in a series of patients with primary breast cancer with a median follow up period of 60 months. In 167 patients the expression of TGF-beta 1 was inversely correlated with node status (P = 0.065) but not ER status, tumour size or menopausal status. Patients with high levels of TGF-beta 1 had a longer disease free interval with a significantly longer probability of survival at 80 months although the overall relapse free survival was not increased. EGFR mRNA expression was measured in 106 patients and was inversely correlated with ER status (P = 0.018). EGFR levels did not predict for early relapse or survival. TGF alpha mRNA levels were measured in 104 patients, no correlation was seen tumour size, node status, Er status, or clinical outcome.

Adenocarcinoma, Mucinous↗
PubMed1991

Pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer.

New tamoxifen analogues were tested for their antiproliferative activity both in vitro and in vivo. Binding studies showed that both 4-iodotamoxifen and pyrrolidino-4-iodotamoxifen and 2.5-fold higher affinities for the estrogen receptor compared with tamoxifen. Pyrrolidino-4-iodotamoxifen was also 1.5-fold more effective in causing inhibition of estrogen-induced growth of MCF-7 cells compared with tamoxifen at 10(-6) M. The 4-iodotamoxifen analogue was similar to tamoxifen in its inhibitory action at 10(-6) M. Antiproliferative activities of these drugs were tested using the nitrosomethylurea-induced rat mammary tumor model. Pyrrolidino-4-iodotamoxifen caused regression in 92% of rats, whereas tamoxifen caused regression in 75% of rats. The agonist activity of the analogues was determined using the immature rat and mouse uterotrophic assays. Both tamoxifen and 4-iodotamoxifen had similar partial agonist activity, and this was greater than that seen with pyrrolidino-4-iodotamoxifen. Furthermore, pyrrolidino-4-iodotamoxifen caused a dose-dependent inhibition of estrogen-induced vaginal cornification, whereas tamoxifen and 4-iodotamoxifen did not. These studies demonstrate that pyrrolidino-4-iodotamoxifen is more effective than tamoxifen in inhibiting tumor regression and that its reduced uterotrophic activity and increased estrogen receptor binding may give it significant clinical advantages over the parent compound.

Animals↗
PubMed1991

Increased production of growth factors and epidermal growth factor receptor by gastric carcinoma.

Four growth factors and one growth factor receptor have been studied in carcinomas from 22 gastrectomy specimens and compared to non-malignant tissue from the same specimen. cDNA probes for transforming growth factors alpha and beta, platelet-derived growth factor A and B, insulin-like growth factor II and epidermal growth factor receptor were used to assay messenger RNA transcripts for the growth factors by dot hybridization. Increased levels of all the transcripts were found in carcinomas compared to benign tissue (P less than 0.05). No correlation was found between any of the growth factors studied and tumour stage or patient survival. Increased growth factor production by gastric cancers may be important in the pathogenesis of these tumours and further work is required to establish their role.

Adenocarcinoma↗
PubMed1990

Growth factor expression in breast tissue.

We have studied mRNA levels for a variety of growth factors in biopsy specimens from malignant, benign and normal breast tissue. We found TGFb mRNA in all breast cancers and neoplastic breast tissues but the level of the TGFb mRNA were found to be higher in breast cancer (P = 0.01). TGFa mRNA was detected in a similar proportion of cancers as in neoplastic breast tissues but the TGFa receptor EGFR mRNA was detected in only 55% of breast cancers but in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inverted related to oestrogen receptor status and coexpression of TGFa and EGFR was observed in 28% of carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). PDGF a and b chain transcripts coexisted in all normal and malignant breast tissue. Insulin-like growth factor II mRNA was present in all 15 samples of non-malignant breast tissue but in only 11 of 21 (52%) of carcinomas.

Adenofibroma↗
PubMed1990

Transcripts for transforming growth factors in human breast cancer: clinical correlates.

The levels of mRNA for transforming growth factors (TGF alpha and beta) and the epidermal growth factor receptor (EGFR) were determined in 69 human breast carcinomas and 20 biopsies of non-neoplastic breast tissue by dot blot hybridisation analysis. TGF alpha mRNA was detected in 42% of cancers and 44% of non-neoplastic breast tissue at low levels. TGF beta mRNA was found in all breast cancers and non-neoplastic breast tissues, but the levels of TGF beta mRNA were found to be higher in breast cancers (P = 0.01). EGFR mRNA was detected in 55% of breast cancers and in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inversely related to oestrogen receptor (ER) status (P = 0.0001). Coexpression of TGF alpha and EGFR was observed in 28% of the carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). No significant relationship was found between histological grade, tumour cellularity or tumour desmoplasia and expression of either the TGFs or of EGFR mRNA. High levels of TGF beta were, however, associated with the absence of lymph node metastases at presentation (P = 0.05). Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients. Longer clinical follow-up and larger numbers of patients are required to determine whether TGFs will prove a useful marker for prognosis in breast cancer patients.

Breast Neoplasms↗
PubMed1989

Expression of the pS2 gene in normal, benign and neoplastic human stomach.

The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin-fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy.

Blotting, Northern↗
PubMed1987

Characterization of estrogen receptor messenger RNA in human breast cancer.

The importance of estrogen receptor (ER) determination in breast cancer is well established. Approximately 70% of ER-positive tumors are hormone responsive compared to 5-10% of ER-negative tumors. However, one-third of ER-positive tumors fail to respond, and the reasons for this are unclear. To further investigate these relationships we have determined levels of ER protein and mRNA in a number of human breast cancer biopsies. ER protein was estimated by the dextran-coated charcoal steroid binding method and by an ER immunocytochemical assay using a specific monoclonal antibody. A complimentary DNA clone (lambda OR3) encoding part of the human ER was used to determine mRNA levels. Dot blot analysis of twenty-seven tumors revealed a close agreement between ER mRNA and the dextran-coated charcoal assay (rs = 0.9; P less than 0.001). ER immunocytochemical assay staining also correlated with ER mRNA in twenty-five cases (rs = 0.75; P less than 0.001). Tumors from postmenopausal patients contained much higher levels of ER mRNA and ER protein than their premenopausal counterparts. ER-negative tumors produced no measurable ER mRNA. Northern blot analysis revealed a 6.4- and 3.7-kilobase species in ER-positive tumors and also in the human breast cancer cell line MCF-7. No differences in transcript sizes were found in tumors from hormone-responsive patients compared to nonresponding patients. We have also demonstrated, in tissue sections of normal and malignant breast, localization of ER mRNA by in situ hybridization to the same population of cells which exhibit immunoreactive ER.

Breast Neoplasms↗
PubMedDate not supplied

Modulation of elongation factor-1 delta (EF-1 delta) expression by oncogenes in human epithelial cells.

A cDNA clone covering part of the C-terminal domain of human EF-1 delta was isolated from mammary cancer cells by subtractive hybridisation. The higher expression of EF-1 delta in the tumours suggested that malignant transformation in vivo requires an increase in translation factor mRNA and protein synthesis for entry into and transition through the cell cycle. To explore the relation between cell division and EF-1 delta expression, MCF-7 cells were treated with dexamethasone, an inducer of differentiation. There was no change in the mRNA levels of EF-1 delta in the dexamethasone-treated cells. To explore the relation between oncogenes and EF-1 delta expression, a variety of oncogenes were introduced into human mammary epithelial cells (MCF-7) and human keratinocytes (HaCaT). Despite high oncogene mRNA expression, there was no significant change in the EF-1 delta mRNA level by v-src, c-erbB (EGF Receptor), c-erbB-2, v-myc and v-fos oncogenes. However, overexpression of v-Ha-ras in HaCaT cells resulted in a three to five-fold decrease in the steady-state mRNA level of EF-1 delta. Taken together, the data provides further support on the interaction of translation factors and oncogenic transformation.

Cloning, Molecular↗