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Biomedical subjects

D Banerjee

Publications and source records attributed to D Banerjee.

At least 91 records · Page 5Linked to original sources
PubMed1999

The aetiology and management of pilonidal sinus.

Although there are various treatment regimens and dressing techniques for the management of pilonidal disease, we recommend the 'open' technique for patients with an uncomplicated sinus. Patients with more complex sinuses or recurrent pilonidal disease should be treated by plastic surgeons.

Acute Disease↗
PubMed1999

Technology evaluation: gene therapy (mesothelioma), NCI.

The National Cancer Institute is sponsoring a phase I clinical trial by the University of Pennsylvania involving administration of recombinant adenovirus containing the HSV-tk gene and subsequent tumor kill by ganciclovir, for the gene therapy of malignant mesothelioma. Twenty one patients have been enrolled into the trial.

Adenoviruses, Human↗
PubMed1999

Technology evaluation: G-3139.

G-3139 is an antisense phosphorothioate oligodeoxynucleotide (AS PS ON) which suppresses bcl-2 expression and is being developed by Genta Inc for the potential treatment of various cancers [308375]. G-3139 is in various stages of phase I/lIa trials. One study, initiated in May 1999, at the Lombardi Cancer Center at Georgetown University Medical Center, US, will examine G-3139 in conjunction with docetaxel. In a phase I/IIa dose-escalating trial to treat non-Hodgkin's lymphoma (NHL), at the Royal Marsden NHS Trust, UK, no serious, clearly drug-attributable or doselimiting adverse effects were noted and in some patients encouraging signs of potential drug activity were observed. The responses included one patient in whom cancer mass was reduced and one who developed a complete response for over 38 weeks in duration [239159,291608,325262]. A new phase II protocol using G-3139 combined with standard chemotherapies in relapsed NHL patients has also begun [325262]. Other phase I/lIa studies include: the safety and efficacy of G-3139 in the treatment of hormone-resistant, metastatic prostate cancer, when administered with mitoxantrone [305822]; the treatment of relapsed follicular NHL, when administered with cyclophosphamide [311217]; the treatment of Stage III and IV metastatic malignant melanoma in combination with dacarbazine [289755]; the treatment of hormone-resistant, metastatic prostate cancer when administered over a significantly longer duration than studied previously and in combination with an androgen-receptor blocking agent [291608]. The National Cancer Institute (NCI) funded and conducted preclinical studies of G-3139 in July 1996 and in June 1998, the NCI and Genta entered into a Cooperative Research and Development Agreement (CRADA) for the development of G-3139 [290153]. Clinical trials,focusing on colorectal cancer, small cell lung cancer and leukemia, were underway as of April 1999. The company licensed the rights for the use of bcl-2 as a target for antisense and gene therapy-based treatments from the University of Pennnsylvania. In June 1998, Genta received two patents relating to its antisense compounds [289685].

Androgen Antagonists↗
PubMed1998

Probing the folate-binding site of human thymidylate synthase by site-directed mutagenesis. Generation of mutants that confer resistance to raltitrexed, Thymitaq, and BW1843U89.

Human thymidylate synthase (TS) contains three highly conserved residues Ile-108, Leu-221, and Phe-225 that have been suggested to be important for cofactor and antifolate binding. To elucidate the role of these residues and generate drug-resistant human TS mutants, 14 variants with multiple substitutions of these three hydrophobic residues were created by site-directed mutagenesis and transfected into mouse TS-negative cells for complementation assays and cytotoxicity studies, and the mutant proteins expressed and characterized. The I108A mutant confers resistance to raltitrexed and Thymitaq with respective IC50 values 54- and 80-fold greater than wild-type but less resistance to BW1843U89 (6-fold). The F225W mutant displays resistance to BW1843U89 (17-fold increase in IC50 values), but no resistance to raltitrexed and Thymitaq. It also confers 8-fold resistance to fluorodeoxyuridine. Both the kinetic characterization of the altered enzymes and formation of antifolate-resistant colonies in mouse bone marrow cells that express mutant TS are in accord with the IC50 values for cytotoxicity noted above. The human TS mutants (I108A and F225W), by virtue of their desirable properties, including good catalytic function and resistance to antifolate TS inhibitors, confirm the importance of amino acid residues Ile-108 and Phe-225 in the binding of folate and its analogues. These novel mutants may be useful for gene transfer experiments to protect hematopoietic progenitor cells from the toxic effects of these drugs.

Animals↗
PubMed1998

Acute intestinal graft-versus-host disease in a syngeneic bone marrow transplant recipient.

BACKGROUND: We report a case of intestinal graft-versus-host disease (GVHD) in a syngeneic bone marrow transplant patient. METHODS: Several days after receiving a bone marrow transplant from his identical twin for treatment of non-Hodgkin's lymphoma, a 47-year-old man developed a skin rash and diarrhea. RESULTS: A colonic biopsy on day +15 revealed characteristic changes of acute intestinal GVHD. Molecular studies (microsatellite DNA and HLA sequence-specific primer polymerase chain reaction analyses) confirmed the genotypic identity of donor and host and the improbability of transfusion-associated GVHD. CONCLUSION: This case illustrates that pathological evidence of GVHD does not absolutely require the presence of genetic differences between host and donor and questions existing concepts about the nature of cyclosporine-induced GVHD.

Acute Disease↗
PubMed1998

Role of E2F-1 in chemosensitivity.

The E2F family of transcription factors, in partnership with DP proteins, is thought to regulate transcription of genes that encode protein products that are required for DNA synthesis, which include important cancer chemotherapeutic targets such as thymidylate synthase and dihydrofolate reductase. This study was conducted to investigate the effects of overexpression of human E2F-1 cDNA on chemosensitivity in a human fibrosarcoma cell line, HT-1080. The E2F-1-overexpressing HT-1080 cells had a shorter doubling time both in vitro and in vivo. Associated with an up-regulation of TS, E2F-1-transfected cells were more resistant to 5-fluorouracil than were untransfected cells. These E2F-1 transfectants, although resistant to fluoropyrimidines and serum deprivation, were more sensitive to etoposide, doxorubicin, and SN38 (the active metabolite of irinotecan) but not to Taxol.

Antimetabolites, Antineoplastic↗
PubMed1998

Isolation and characterization of thymitaq (AG337) and 5-fluoro-2-deoxyuridylate-resistant mutants of human thymidylate synthase from ethyl methanesulfonate-exposed human sarcoma HT1080 cells.

Thymidylate synthase plays an essential role in the synthesis of DNA. Recently, several new and specific thymidylate synthase inhibitors that occupy the folate binding site, including Tomudex(R), BW1843U89, and Thymitaq, have demonstrated therapeutic activity in patients with advanced cancer. In order to find drug-resistant forms of human thymidylate synthase for gene therapy applications, human sarcoma HT1080 cells were exposed to ethyl methanesulfonate and Thymitaq selection. Thymitaq-resistant clonal derived sublines were established, and analysis indicated that both gene amplification and point mutations contributed to drug resistance. Eight mutant cDNAs that were identified from Thymitaq-resistant sublines were generated by site-directed mutagenesis and transfected into thymidylate synthase-negative cells. Only K47E, D49G, or G52S mutants retain enzyme activity. Moreover, cytotoxicity studies demonstrated that D49G and G52S transfected cells, besides displaying resistance to Thymitaq with IC50 values 40- and 12-fold greater than wild-type enzyme transfected cells, respectively, also lead to fluorodeoxyuridine resistance (26- and 97-fold in IC50 values, respectively) but not to Tomudex or BW1843U89. Characterization of the purified altered enzymes obtained from expression in Escherichia coli is consistent with the cell growth inhibition results. We postulate that the D49G or G52S mutation leads to the structural perturbation of the highly conserved Arg50 loop, decreasing the binding of thymidylate synthase to the inhibitors, Thymitaq and fluorodeoxyuridylate.

Cloning, Molecular↗
PubMed1998

Retroviral transduction of human CD34+ umbilical cord blood progenitor cells with a mutated dihydrofolate reductase cDNA.

Umbilical cord blood cells (UCB) have become a major target population for experimental and clinical studies using transfer of genes involved in inborn enzymatic diseases. Cord blood contains hematopoietic progenitor cells at a high frequency, and expanding these cells ex vivo generates sufficient numbers of hematopoietic precursors for transplantation into adults, e.g., as supportive treatment. As clinical reports about retroviral transduction into UCB cells have not been as encouraging as the first preclinical data, we have established a retroviral transduction system that allows expansion and selection of hematopoietic progenitor cells from UCB. CD34-enriched UCB cells were transduced with a retroviral vector encoding a mutated dihydrofolate reductase cDNA that confers MTX resistance. We observed increased resistance to MTX in transduced granulocyte macrophage-colony forming units (CFU-GM) after co-culture of CD34+ UCB cells with the virus-producing cell line, or after incubation with virus-containing supernatant. The supernatant-based transduction protocol included a prestimulation with recombinant interleukin-1 (rhIL-1), rhkit-ligand, and rhIL-3 to increase the percentage of cells in S phase to greater than 50%. Using this protocol we measured a 72-fold expansion of CFU-GM and a 2.5-fold selective advantage of transduced versus nontransduced progenitor cells after exposure to low-dose methotrexate in liquid culture. Polymerase chain reaction analysis revealed integration of proviral DNA into the majority of transduced colonies before and after ex vivo expansion. The retroviral vector and transduction protocol reported here provides an experimental system for selection and expansion of retrovirally transduced progenitor/stem cells from UCB that may help improve the efficiency of current clinical gene therapy strategies.

Antigens, CD34↗
PubMed1998

Nasoethmoid schwannoma with intracranial extension. Case report and review of literature.

Schwannomas are very rare in the nose and paranasal sinuses; their presence both intra-and extracranially is still rarer. Here we present a case of nasoethmoid schwannoma with intracranial extension into anterior cranial fossa. Clinical, radiological, pathological and operative findings are discussed and the literature is reviewed. We recommend bifrontal craniotomy for removal of intracranial and nasoethmoid extensions of this tumor.

Adult↗
PubMed1998

Recurrence of kala-azar after PKDL: role of co-factors.

Recurrence of kala-azar after post kala-azar dermal leishmaniasis (PKDL) has remained uncommon. We report here two patients with recurrence of kala-azar (KA) after development of PKDL. In one case the second attack of KA was preceded by repeated attacks of malaria and tuberculosis, and in the other the recurrence of KA followed an attack of measles. While measles has earlier been suggested as co-factor in inducing transformation from sub-clinical to clinical kala-azar, malaria was demonstrated to enhance the virulence and invasiveness of Leishmania in an experimental model as well as under natural condition. We propose that in our cases, measles and repeated attacks of malaria or tuberculosis led to immunosuppression and recurrence of visceral leishmaniasis (VL).

Adolescent↗
PubMed1998

Magnetic resonance image detection of coincidental sphenoid sinus aspergillosis and pituitary microadenoma: a potential surgical disaster.

While localizing the microadenoma in a patient with Cushing's disease on magnetic resonance imaging (MRI), fungal granuloma of the sphenoid sinus was coincidentally detected. This helped in the proper management of sphenoidal disease before undergoing trans-sphenoidal removal of the microadenoma, thus averting the possible catastrophe of direct intracranial spread of aspergillus infection.

Adenoma↗
PubMed1998

Higher levels of thymidylate synthase gene expression are observed in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma.

PURPOSE: It has been observed previously that the pulmonary metastases of colorectal adenocarcinoma are less responsive to therapy with fluorouracil (FUra) as compared with other sites of metastasis (liver, local). To investigate the basis of this chemoresistance, the levels of thymidylate synthase (TS) mRNA and protein were measured, as TS expression has been shown to be predictive of response to therapy in colorectal cancer. MATERIALS AND METHODS: Tumors were obtained from 19 patients with metastatic colorectal cancer (12 hepatic and seven pulmonary). TS expression was measured by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and TS protein levels were measured by Western blotting. The presence of TS amplification was assessed by Southern blotting. Levels of p53 protein were determined using immunohistochemistry. RESULTS: TS mRNA expression was shown to be significantly higher in the pulmonary metastases (mean TS/beta-actin ratio, 19.7; n = 7) as compared with the hepatic metastases (mean TS/beta-actin ratio, 4.7; n = 11) of colorectal cancer. Lower TS expression was observed in patients with hepatic metastases who had received prior FUra versus patients who had not been treated. High levels of TS expression in some samples was associated with low-level (two to three gene copies) increases in TS gene copy numbers and this was observed more frequently in the pulmonary metastatic samples. The increased gene copy numbers occurred both in samples with wild-type p53 and those with mutant p53 tumor-suppressor gene as determined by immunohistochemistry. CONCLUSION: High levels of TS enzyme may be the basis of the lack of response of pulmonary metastases to FUra treatment.

Adenocarcinoma↗