Biomedical subjects

E Hu

Publications and source records attributed to E Hu.

62 records · Page 4Linked to original sources

PubMed1985

Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy.

Histologic diagnosis of mycosis fungoides may be difficult, especially in lymph nodes that show changes frequently associated with chronic skin disease. As an alternative approach to diagnosis, we have analyzed the configuration of DNA for the beta T-cell receptor genes in biopsy tissues from 14 patients with mycosis fungoides. Clonal rearrangements of these genes were found in each specimen tht contained histologically unambiguous mycosis fungoides. Clonal rearrangements were also found in seven of nine lymph nodes removed from patients with mycosis fungoides and considered histologically to contain only benign lymphadenopathy. Matching rearrangements of beta T-cell receptor genes were detected in benign lymph nodes and histologically involved tissues when paired specimens were available from the same cases. Our findings provide molecular evidence for the clonal T-cell origin of mycosis fungoides and indicate the high incidence of extracutaneous disease in patients with palpable lymphadenopathy. In addition, this study demonstrates that the detection of rearranged T-cell receptor genes can be a sensitive and practical method for the diagnosis and characterization of T-cell neoplasms.

Clone Cells↗

PubMed1985

Follicular and diffuse mixed small-cleaved and large-cell lymphoma--a clinicopathologic study.

The clinical records and initial biopsy materials from 76 patients with mixed small-cleaved and large-cell lymphoma containing both a follicular and diffuse architectural pattern were reviewed. The characteristics of this group, treated at Stanford University Medical Center (SUMC) between 1963 and 1983, are described. The 5-year actuarial survival and freedom from progression are 70% and 27.5%, respectively. Classification according to the degree of follicularity indicated that patients with focally follicular areas (ie, less than 25% of the histologic section) have a significantly worse freedom from progression and overall survival at 5 years compared with those patients with a predominantly follicular architecture (ie, greater than 50% follicular areas). Based on our analysis, we feel that the degree of follicularity is an important prognostic factor and that mixed lymphoma patients with only focally follicular areas behave more like an intermediate-grade lymphoma and should be treated aggressively.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

Gastrointestinal lymphomas. Immunohistochemical studies on the cell of origin.

The classification of primary malignant lymphomas of the gastrointestinal tract by their cell of origin has been a subject of great controversy in recent years, with the proportion of histologic subtypes varying substantially in different published series. Much of this controversy was initially due to the widely recognized inherent difficulty of classifying lymphomas based on routine histologic sections alone. However, the advent of immunohistochemical techniques has also yielded disparate results. Particularly contentious has been the notion of true histiocytic lymphomas, which some investigators have claimed to be relatively frequent in the gastrointestinal tract, whereas others doubt whether they exist at all. We present here a classification of 25 gastrointestinal lymphomas seen in the surgical pathology services of UCLA Hospital and Stanford University Medical Center. Unlike all previously reported series, we have utilized frozen tissue sections for the performance of immunohistochemical studies, which we and others have found to be far more reliable than the use of formalin-fixed, paraffin-embedded tissues, particularly in detecting monoclonal surface staining of immunoglobulin light- and heavy-chain markers. We find that this technique lessens the likelihood of overinterpreting the stains for histiocyte markers (alpha 1-antitrypsin and lysozyme), which are often difficult to read owing to strong positive staining of benign reactive histiocytes within the tumor. Utilizing these techniques, we have been able to classify definitely 21 of our 25 lymphomas (84%) as of B-cell origin, whereas none appeared to be histiocytic. We conclude that true histiocytic lymphomas of the gastrointestinal tract must be very rare, and we recommend the routine use of frozen tissue sections for more accurate classification of these interesting lesions.

Adult↗

PubMed1983

Pharmacokinetics of intraarterial mitomycin C in humans.

The pharmacological advantage of mitomycin C (MMC) given by intraarterial infusion as compared to i.v. infusion was studied in seven patients with cancer metastatic to the liver. Hepatic artery, hepatic vein, and peripheral vein catheters were placed, and then each patient received constant infusions of MMC via the intraarterial and peripheral i.v. routes at 0.4, 1.2, and 4.0 mg/sq m/hr. MMC concentrations were measured in the hepatic artery, hepatic vein, and a peripheral vein by high-pressure liquid chromatography after steady state had been reached at 2 hr. Mean plasma clearance increased significantly with infusion rate from 0.6 liter/min at 0.4 mg/sq m/hr to 1.1 liters/min at 4.0 mg/sq m/hr. The calculated relative advantage of treating hepatic tumors via the intraarterial route (Rt) was found to be 2.5- to 3.6-fold at a plasma flow rate of 0.4 liter/sq m and MMC infusion rates of 0.4 to 4.0 mg/sq m/hr. The hepatic vein MMC concentration averaged 30% higher during intraarterial than during i.v. infusion. Hepatic extraction of MMC averaged only 23%, so that the intraarterial route offered little advantage with respect to reduced systemic toxicity. These data suggest a limited pharmacological rationale for the selection of the intraarterial route for the treatment of hepatic tumors with MMC.

Aged↗

PubMedDate not supplied

A phase 1a clinical trial of LYM-1 monoclonal antibody serotherapy in patients with refractory B cell malignancies.

Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM-1 over four weeks. LYM-1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA-Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM-1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti-tumour activity against lymphoma cell lines. In the current trial, dose-dependent levels of free LYM-1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti-mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM-1 appears to be well-tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti-tumour effect and plans for further clinical studies are discussed.

Adult↗

PubMedDate not supplied

PPAR gamma and the control of adipogenesis.

We recently cloned PPAR gamma as a factor that binds to an enhancer which has specificity for adipose cells. When expressed ectopically, PPAR gamma converts fibroblasts into bona fide preadipose cells. Upon application of activators or PPAR gamma ligands, these cells differentiate into fat cells. Most recently, we have been trying to understand the nature of natural ligands that activate PPAR gamma and the protein domains that control adipogenesis. With regards to ligands, we have shown that an unusual prostanoid, 15-deoxy delta 12,14PG J2, can bind to PPAR gamma and activate it. A second transcription factor that is induced early in differentiation, ADD1/SREBP1, appears to promote the formation of PPAR gamma ligands. Transfection of this molecule, a member of the bHLH family, causes the secretion of molecules that can serve as ligands for PPAR gamma. This ligand-like activity is specific for the gamma isoform of PPAR. Current studies are attempting to identify these potentially novel ligands. With regard to structure-function of PPAR gamma, we first analyzed the adipogenic activity of the three isoforms of PPAR: alpha, gamma and delta. Using appropriate activators of each it is clear that PPAR gamma has the most adipogenic action. PPAR alpha can be adipogenic with high levels of the strongest activators and PPAR delta does not stimulate fat cell differentiation. To identify the domain(s) of PPAR gamma responsible for differentiation, chimeras between PPAR gamma and PPAR delta were created and transfected into fibroblasts. This has allowed the isolation of relatively small regions of this molecule that are responsible for differentiation.

Adipocytes↗

PubMedDate not supplied

Rapid isolation of tissue-specific genes from rat kidney.

A systematic effort to isolate kidney-specific genes was performed using recently described PCR-select methodology. Using this technique, a kidney-specific mini-gene library was generated and a number of kidney-specific genes that share significant homology to previously characterized kidney genes from rats and other species were isolated. These included three renal-specific transporters (an ADH water channel, the anion transporters RST and ROAT1), a cell adhesion molecule (K-cadherin) and a kidney-specific protein upregulated in renal carcinoma (DD96). In addition, we isolated two novel genes from a rat kidney. One of the genes shares limited homology to rat profilin-1 while the other did not share any similarity to genes in the Genbank. Northern blot analysis revealed that the mRNA for each of these genes is expressed in a highly kidney-restricted fashion. Our results suggested that tissue-specific genes can be rapidly isolated and characterized using PCR-select techniques and this methodology may be generally applicable to isolate specific genes from a variety of tissues.

Animals↗

PubMedDate not supplied

Combined modality therapy of locally advanced breast cancer. One institution's experience and a review of the literature.

Fourteen patients with locally advanced breast cancer were treated at Stanford University Medical Center with a combined modality approach. Treatment consisted of an initial 5 day course of cyclophosphamide followed by three cycles of combination chemotherapy (CAF or CMF). Patients subsequently received radiation therapy to the involved breast and regional nodal areas, followed by mastectomy if resistant disease was present following irradiation. Additional chemotherapy (CMF) was administered for 6 cycles. With a median follow up of 42 months, all fourteen patients are free of local disease. Five out of the fourteen patients have experienced distant relapses and two patients died. We conclude that an aggressive combined modality approach to treatment of locally advanced breast cancer can result in excellent local control and survival even in poor prognosis patients. A review of pertinent studies on multimodality treatment for locally advanced breast cancer confirms our findings.

Antineoplastic Combined Chemotherapy Protocols↗