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Biomedical subjects

L Grogan

Publications and source records attributed to L Grogan.

At least 19 recordsLinked to original sources
PubMed2006

HIV infection among heroin users and area of residence.

The aim of this study was to develop a hypothesis to explain the link between HIV prevalence and area of residence. The study was conducted in two parts using two existing data sources. In Part 1, the bloodborne viral test status and test results of a sample of clients attending treatment in December 2001 in two areas of Dublin, an inner city area (Dublin 8) and a suburban area (Dublin 24), were extracted from the Bloodborne Viral Status Dataset created by Grogan. In Part 2 the characteristics of heroin users seeking treatment for the first time at treatment services in their respective areas of residence, Dublin 8 or Dublin 24, between 1997 and 2000 were examined, using data from the National Drug Treatment Reporting System. A higher proportion of heroin users in Dublin 8 had HIV and hepatitis C than did their counterparts in Dublin 24. The analysis suggests that heroin users in Dublin 8 were more likely both to have ever used cocaine and to have used heroin daily, than were those who lived in Dublin 24. Also, a higher proportion of injectors living in Dublin 8 used heroin and cocaine concurrently than did their counterparts in Dublin 24. In both samples, heroin users who lived in Dublin 8 were older than those who lived in Dublin 24. The findings led to a hypothesis:'The risk of acquiring HIV is associated with area of residence and may be linked to cocaine use.

Adolescent↗
PubMed2006

Association between paclitaxel and necrotic pancreatitis.

To our knowledge this is the first reported case of paclitaxel associated necrotic pancreatitis requiring a pancreatic necrostomy. This was a near fatal complication associated with paclitaxel with a high resulting morbidity. Although this is a rare association physicians should be wary of the potential to develop severe pancreatitis in patients receiving this therapeautic agent. Monitoring of serum amylase during therapy is therefore warranted.

Adult↗
PubMed2001

Physical interaction between p53 and primary response gene Egr-1.

The tumor suppressor p53 and primary response gene Egr-1 are nuclear transcription factors with regulatory roles in signal transduction pathways mediating cellular proliferation and growth arrest as well as the complex genetic programs controlling differentiation and programmed cell death. We identified a physical association between these regulatory proteins in vitro and in vivo. Recombinant p53 and Egr-1 fusion proteins complexed with in vitro translates of Egr-1 or p53, respectively, or with these respective proteins in cell lysates. This protein-protein interaction was detected in vivo by immunoprecipitation and Western blot analysis of serum-activated cellular lysates with high levels of induced Egr-1 and of human lung cancer cell lines with constitutive overexpression of Egr-1 and mutant p53. A p53 mutant at codon 154 did not bind Egr-1, while p53 proteins with point mutations at residues 156, 246, 247, and 273 associated with this zinc finger transcription factor. p53 bound full-length Egr-1 and an Egr-1 mutant with a deletion of the 5' transactivation region but did not associate with Egr-1 protein lacking an internal segment that included the first two zinc finger domains, suggesting that binding may require the presence of intact zinc finger motifs. A variant-sized Egr-1 protein expressed by lung fibroblast cell line MRC-9 was also bound by p53. The interaction of these regulatory proteins may alter multiple features of their biological activity especially with regard to the specificity of transcriptional control.

Blotting, Western↗
PubMed1999

Molecular genetics of gastrointestinal malignancies.

OBJECTIVES: To review the genetic model of colon cancer formation and the primary advances and clinical relevance of molecular genetics of pancreatic cancer and other gastrointestinal malignancies. DATA SOURCES: Research studies, review articles, and textbook chapters. CONCLUSIONS: Genetic discoveries are influencing the screening and treatment of colorectal cancer and other gastrointestinal malignancies by better targeting chemoprevention and treatment in high-risk and molecular-distinct patient populations. IMPLICATIONS FOR NURSING PRACTICE: A basic knowledge of cancer genetics and the latest genetic discoveries will assist oncology nurses in patient teaching, counseling, and care.

Adenomatous Polyposis Coli↗
PubMed1999

The "comparative growth assay": examining the interplay of anti-cancer agents with cells carrying single gene alterations.

We have developed a "comparative growth assay" that complements current assays of drug effects based on cytotoxicity. A co-culture of two cell lines, one of which is fluorescently labeled, is exposed to a cytotoxic agent and the proportion of fluorescent cells is compared with that of a baseline unexposed co-culture. For demonstration purposes, two HCT116 cell lines (an hMLH1 homozygous and an hMLH1 heterozygous mutant), altered by insertion of vector alone or the same vector carrying an insert for the expression of enhanced green fluorescent protein (EGFP), were exposed to numerous "anti-cancer" agents. The assay was further validated in a system of two cell lines differing only in the expression of the breast cancer resistance protein (BRCP). The assay allowed the estimation of the duration of action of a particular agent. Assessment of the agent's differential activity over a given time in culture could be expressed as a selection rate, which we chose to describe on an "average selection per day" basis. We conclude that this assay: 1) provides insight into the differential dynamic effects of chemotherapeutic agents or radiation; and 2) allows, through the use of matched cell lines, the investigation of critical physiologic features that govern cell sensitivity.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1999

Coordinate regulation of cyclooxygenase-2 and TGF-beta1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors.

Evidence is accumulating which indicates that cyclooxygenase-2 (COX-2) is involved in the pathogenesis of colorectal cancer. We evaluated the expression of COX-2 in replication error-positive (RER) colon cancers, colon cancers metastatic to liver and azoxymethane (AOM)-induced rat colonic tumors. Immunohistochemistry showed that COX-2 was low to undetectable in normal human mucosa, but abundant in the RER adenocarcinomas we examined. COX-2 immunoreactivity in metastatic colon cancers was less abundant, but clearly detectable. In the colon of AOM-treated rats, COX-2 protein was not detectable in normal mucosa, but present in most of the epithelial cells comprising the tumors. The TGF-beta1 staining pattern in these human and rat tumors was similar to that observed for COX-2. The role of TGF-beta in RER adenocarcinomas is complex because of the increased mutation rate of TGF-beta type II receptors. Northern analysis showed abundant TGF-beta1 mRNA in AOM-induced tumors, but not in paired mucosa. TGF-beta1 induced the expression of COX-2 mRNA and protein in intestinal epithelial cells (IEC-6). Chronic TGF-beta1 treatment caused a TGF-beta-dependent overexpression of COX-2 in rat intestinal epithelial cells (RIE-1). TGF-beta1 may regulate COX-2 expression during the colonic adenoma to carcinoma sequence.

Animals↗
PubMed1997

Mutations in beta-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors.

Beta-catenin has been identified as an oncogene in colon cancer and melanoma. Phosphorylation of sites in exon 3 of beta-catenin leads to degradation of this protein. These sites are primary targets for activating mutations. The frequency with which oncogenic mutations at these sites are found in colorectal cancer is unknown, as is the frequency of their occurrence in other malignancies. We analyzed 92 colorectal cancers (CRCs) and 57 cancer cell lines (representing a diversity of tumor types) to determine the frequency of activating mutations in this gene. Mutations in exon 3 of beta-catenin were found in 2 of 92 CRCs and in the colorectal cancer cell line HCT 116. Both tumors with beta-catenin mutations exhibited widespread microsatellite instability, which is indicative of a replication error phenotype, a phenotype known to be present in HCT 116. This suggests that mutations in beta-catenin are infrequent in CRC and miscellaneous cancer cell lines and may occur in association with a replication error phenotype.

Adult↗
PubMed1997

Genetic Testing for Cancer Risk Assessment: A Review.

Both environmental factors and an inherited predisposition influence carcinogenesis. The direct role of inheritance in the development of cancer is evident in familial cancer syndromes. These syndromes predispose to cancer through the inheritance of a mutation in a single gene in affected carriers. While many inherited cancer syndromes are rare, an inherited predisposition is directly responsible for 5%-10% of all colon and breast cancers. Complex multigenic inheritance plays an important role in cancer predisposition for the population at large. The identification of genes responsible for an inherited predisposition to colon and breast cancer syndromes has directed public attention to genetic testing for susceptibility to cancer. Assays are currently available to determine individual susceptibility to specific cancers. Cancer genetic testing is currently a time-consuming and complex procedure which requires expertise in its application, interpretation, and follow-up strategic planning. This review discusses cancer genetics and its application to individual and family cancer risk assessment with particular emphasis on breast and colon cancer.

Journal Article↗
PubMed1996

Recent advances in the biology of colorectal cancer.

The identification of the precise molecular defects responsible for the common forms of inherited colorectal cancer has significantly advanced our understanding of both inherited and sporadic disease. These advances coupled with a rapid accumulation of information on the molecular genotype and biological phenotype of colorectal cancer have identified potential markers that may prove to be not only of prognostic value but also important as screening tools and therapeutic targets. These molecular and biological features include replication errors, mutations of oncogenes and tumor suppressor genes and expression of tumor specific antigens and cytokeratins. This review highlights important recent advances that further our understanding of the biology and genetics of colorectal cancer.

Animals↗
PubMed1994

Preclinical and clinical aspects of biomodulation of 5-fluorouracil.

Although single agent 5-FU has for many years been the standard therapy for advanced colorectal malignancies, a number of recent clinical trials show higher response rates with biomodulation of 5-FU by several different agents. In general, trials of leucovorin, methotrexate, interferon, and PALA given in biomodulatory doses and sequences with 5-FU have demonstrated comparable response rates over a broad range. However, in the absence of controlled direct comparative phase III trials, final judgement on clinical superiority of a particular regimen must be reserved. Nevertheless, on the basis of current data, certain approaches appear promising and warrant further investigation. Compared to single agent 5-FU, survival benefit has been demonstrated with both low and high dose leucovorin/5-FU regimens and response rates in the 20-50% range appear reproducibly higher than those of 5-FU alone. Low dose and either continuous infusion or repetitive dosing of leucovorin, as well as the effect of treatment sequence and intervals between drugs, require additional investigation. When given 20-24 h before 5-FU, methotrexate achieves response rates similar to leucovorin modulated 5-FU, but the potential role of rescue leucovorin used in many of the trials makes definitive interpretation difficult. Interferon/5-FU regimens attaining response rates of 30-40% are promising but need to be carefully and rationally designed. Low dose PALA with effective doses of 5-FU achieving responses in 35-45% of patients represent a marked improvement in earlier trials of high dose PALA, but additional studies with higher doses not compromising 5-FU dose intensity should be considered. Certainly, the concomitant use of multiple modulating agents also needs further investigation. While many such trials already performed attained results no better than single agent biomodulation, the preliminary results obtained by Grem and colleagues with IFN/LV/5-FU in untreated patients, and by Conti et al. using TMTX/LV/5-FU in previously treated patients are encouraging. Further understanding of the mechanisms of action and interaction of modulating agents should allow additional rational combinations to be explored clinically. Cisplatin biomodulation of 5-FU has been studied in gastrointestinal and head and neck malignancies achieving excellent results in the latter group. Preclinical evidence exists which suggests, however, that 5-FU modulation of cisplatin may be more effective, especially when 5-FU is administered 24 h or more before cisplatin. Clinical investigation of this sequence is currently lacking. Data to support the clinical promise of AZT, IdUrd, uridine, and the benzylacyclouridines are not yet available, although preclinical and preliminary clinical studies are promising.

Animals↗
PubMed1994

Bcl-2 rearrangement in Hodgkin's disease and reactive lymph nodes.

The chromosomal translocation t(14;18)(q32;q21), which involves the bcl-2 oncogene, occurs in most follicular lymphomas. Recent evidence suggests that this translocation occurs in Hodgkin's disease, linking its cellular origin and oncogenesis to follicular non-Hodgkin's lymphomas. Using polymerase chain reaction, the authors examined both Hodgkin's disease (n = 60) and reactive lymph nodes (n = 34) for the presence of bcl-2/JH breakpoint fragments, which are indicative of the t(14;18) chromosomal translocation in the major breakpoint region of the bcl-2 gene. The translocation was detected in approximately 10% of both Hodgkin's disease and nonmalignant reactive lymph node cases. These results suggest the possibility that the translocation may occur in the reactive component of Hodgkin's disease and not in the putative malignant cells, the Reed-Sternberg cells. Furthermore, the detection of the translocation in reactive lymph nodes suggests that it may not be the primary factor in the oncogenesis of follicular lymphoma.

Base Sequence↗
PubMed1994

Comparable prognostic factors and survival in elderly patients with aggressive non-Hodgkin's lymphoma treated with standard-dose adriamycin-based regimens.

We retrospectively analysed the prognostic factors at diagnosis, clinical response, and survival of 192 patients with newly diagnosed aggressive NHL treated in a single institution between 1985 and 1991. Overall, 37.5% (72/192) of patients were 65 years or older (average age 71 years, range 65-85 years), and 62.5% (120/192) were under 65 years of age (average age 45, range 16-64 years). All patients were completely staged and had intermediate- or high-grade NHL. 127 patients were treated on similar regimens with the same chemotherapy dose intensity irrespective of age. Standard-dose m-BACOD (methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, prednisone) or CHOP were used to treat 60/72 (83%) elderly patients and 67/120 (56%) patients less than 65 years. The remaining younger patients were treated with more intensive regimens. There were no significant differences between the groups with regard to stage, histological grade, cell type, elevated LDH, number of extranodal sites, presence of B symptoms, or bulky disease. More elderly patients had a significantly (p < 0.02) poorer performance status (PS), with 42% (25/60) having a PS of 2 or more, compared to 22% (15/67) in those less than 65 years of age. Elderly patients had an inferior complete response rate, 65% versus 76%. However, overall response rates of 95% and 92% were similar. The disease-free survival at 3 years for complete responders in elderly patients was 74% compared to 82% in those under 65. The comparable 3-year overall survival was 59% and 62%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Resection of an intracardiac metastasis from malignant teratoma of the testis.

Nonseminomatous germ cell testicular neoplasm is a disease cured primarily by platinum-based combination chemotherapy. Operation is reserved for those patients who continue to harbor residual masses after chemotherapy. Locoregional lymph nodes and lungs are common sites for residual deposits. Intracardiac metastases are very rare. We report a case of successful resection of bilateral lung and single intracardiac secondary deposits from a malignant teratoma, treated by orchidectomy 6 years previously.

Adult↗
PubMed1993

Leucovorin modulation of fluorouracil.

Fluorouracil remains the single most active chemotherapy agent in colorectal cancer. One of its principal mechanisms of action is inhibition of the enzyme thymidylate synthase (TS), a central enzymatic step in de novo pyrimidine synthesis. Leucovorin, which is metabolized intracellularly to polyglutamated 5,10-methylenetetrahydrofolate, modulates the cellular cytotoxicity of fluorouracil by increasing TS inhibition in vitro and in vivo. Leucovorin modulation of fluorouracil has been studied in preclinical systems and in a large number of clinical trials using various doses and schedules of both drugs. The collective data support the use of continuous infusion or repetitive low-dose schedules of leucovorin. Furthermore, these schedules appear to be less dependent on the leucovorin dose to achieve maximal clinical efficacy than does intermittent single bolus therapy. These schedules appear to be the most effective in the generation of the higher polyglutamates of 5,10-methylenetetrahydrofolate, the most efficient intracellular folate metabolite for ternary complex formation and TS inhibition.

Drug Synergism↗
PubMed1992

The detection of specific gene rearrangements in non-Hodgkin's lymphoma using the polymerase chain reaction.

Characteristic gene rearrangements are present in most non-Hodgkin's lymphomas (NHL). These are usually detected by Southern blotting techniques. In this study, the ability of the polymerase chain reaction (PCR) to detect the t(14;18) chromosomal translocation and immunoglobulin heavy chain (IgH) gene rearrangement was evaluated. DNA from 14 follicular and 42 diffuse B-cell lymphomas was examined using oligonucleotide primers specific for opposing sides of the IgH gene rearrangement on chromosome 14 (towards conserved VH and JH sequences) and opposing sides of the t(14;18) chromosomal translocation (towards the major breakpoint region of the bcl-2 gene on chromosome 18 and conserved JH sequence on chromosome 14). The t(14;18) translocation was detected in 57% of follicular lymphomas and 21% of diffuse B-cell lymphomas. Clonal IgH gene rearrangements using PCR were detected in 50% follicular and 52% of the diffuse lymphomas. Either or both of these rearrangements were detected in 93% follicular and in 59% of diffuse lymphomas. PCR is a rapid and easy technique that can detect the abnormal rearrangement of the bcl-2 gene and clonal IgH rearrangement, indicating the presence of lymphoma. This may be of benefit in monitoring response to therapy and in predicting prognosis in this disease.

Base Sequence↗
PubMed1992

Oral etoposide in small cell lung cancer.

Small cell lung cancer (SCLC) accounts for 25% of all cases of lung cancer diagnosed in the United States. The sensitivity of SCLC to chemotherapy offers good prospects for prolonged remission and long-term survival. Over the last decade, however, the overall response rate and median survival in SCLC patients have remained essentially unchanged. Single-agent intravenous (IV) etoposide has proven to be among the most active drugs for the treatment of SCLC. Oral or oral plus intravenous etoposide has been used in many combination chemotherapies. Studies demonstrating the schedule dependency of etoposide suggest that optimum results would be achieved if the total were administered over a minimum of 5 days. Given in such a schedule, oral etoposide has been shown to be effective in unfit or elderly (> 70 years of age) patients with SCLC, who represent 25% to 30% of the total SCLC population. Prolonged etoposide administration has achieved efficacy comparable with that attained in 5-day schedules, but with notable toxicity. Moreover, the value of dose intensity in single-agent and combination regimens employing etoposide has recently been questioned. New therapeutic strategies are clearly needed to increase the response rate, to prolong survival, and to improve quality of life in SCLC patients.

Administration, Oral↗