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Biomedical subjects

G J Juillard

Publications and source records attributed to G J Juillard.

18 recordsLinked to original sources

Tumor necrosis factor-alpha activates nuclear factor kappa B and induces manganous superoxide dismutase and phosphodiesterase mRNA in human papillary thyroid carcinoma cells.

Human papillary thyroid carcinoma (PTC) has a relatively benign prognosis despite a high frequency of lymphatic metastasis. This suggests that local anticancer factors, generated in lymph nodes, control PTC progression. The cytokine, tumor necrosis factor-alpha (TNF-alpha), may be one such factor. We have previously shown that a human PTC cell line (NP-PTC) has high affinity TNF-alpha receptors. We now report on the action of TNF-alpha in these cells. TNF-alpha decreased [3H]thymidine incorporation as well as cellular DNA content and cell number in a dose-dependent manner. The abundance of phosphodiesterase and manganous superoxide dismutase mRNA species was increased in a time- and dose-dependent manner in the NP-PTC cells after TNF-alpha treatment. TNF-alpha activated NF-kappa B, a nuclear factor thought to mediate multiple actions of TNF-alpha, in these cells with a maximum effect observed after 30 min of treatment. Thus, TNF-alpha has an antiproliferative action on NP-PTC cells, despite its ability to induce the accumulation of mRNA that encodes an enzyme (manganous superoxide dismutase), thought to be cytoprotective. The net antiproliferative effect must therefore be explained by a balance of protective and tumoricidal or static effects that ultimately result in control of tumor spread. These antiproliferative effects may be in part mediated by NF-kappa B and PDE.

Base Sequence

Stages 1 and 2 epidermoid carcinoma of the glottic larynx: involvement of the anterior commissure.

Data on 55 patients with stages 1 and 2 epidermoid carcinoma of the glottic larynx treated from 1978 to 1988 were retrospectively reviewed. Twenty-six patients had involvement of the anterior commissure (AC). Local and ultimate local control rates achieved, respectively, with mean follow-up of 41 months (range, 6-120 months), were as follows: 92% and 100% for patients without AC involvement and stage T1a lesions, 60% and 80% for patients without AC involvement and stage T2 lesions, 100% and 100% for patients with AC involvement and stage T1a lesions, 100% and 100% for patients with AC involvement and stage T1b lesions, and 75% and 100% for patients with AC involvement and stage T2 lesions. There was no correlation between the degree of response at completion of treatment and local control. There was no difference in the local control rate of patients with and without involvement of the AC. Factors associated with a decreased local control rate include extensive subglottic extension and use of a single lateral field technique. Surgical salvage after failure of radiation therapy is effective and can be performed with acceptable morbidity.

Carcinoma, Squamous Cell

Concurrent cisplatin and 5-fluorouracil chemotherapy and radiation therapy for advanced-stage squamous carcinoma of the vulva.

A phase II trial of concurrent cisplatin and 5-fluorouracil (5-FU) chemotherapy and radiation therapy (CT + RT) was conducted for the primary treatment of 12 patients with retrospective surgical FIGO stages III-IV squamous carcinoma of the vulva. Eight patients were stage III and four were stage IV. Chemotherapy was used as a radiation sensitizer and it was administered in two 5-day cycles 28 days apart. Cisplatin, 50 mg/m2/day iv on Days 1 and 2 or 100 mg/m2 on Day 1 or 2, plus continuous-infusion 5-FU, 1000 mg/m2/day for 4-5 days commencing on Days 1 and 28 of external-beam radiation therapy, are given. The pelvic radiation to a dose of 4400-5400 cGy is administered AP and PA to treat the primary tumor, the groin nodes, and the iliac vessels to the level below the common iliac nodes. Complete tumor responses were seen in 8 of 12 (67%) patients. Responses were observed in 6 of 8 (75%) stage III patients and 2 of 4 (50%) stage IV patients. Partial response were observed in 3 patients, and 1 patient had persistent disease. At the completion of concurrent chemoradiation therapy, radical vulvectomy or excision was used in 3 patients and posterior exenteration in 1. With a median follow-up of 37 months (range, 7-60 months), 10 patients are alive and free of disease, and 2 patients died at 12 and 15 months. There were no treatment-related deaths and no grade 4 toxicity. The morbidity included moist desquamation of the vulva in all patients, with grade 2 toxicity in 10 and grade 3 in 2. One patient had a deep venous thrombosis that responded to anticoagulation therapy. These data support the use of concurrent cisplatin and 5-FU chemotherapy and radiation therapy as an alternative to primary radical surgery to treat advanced-stage squamous carcinoma of the vulva.

Aged

Effects of 13 cis-retinoic acid on growth and differentiation of human follicular carcinoma cells (UCLA R0 82 W-1) in vitro.

Dedifferentiation of human thyroid tumors is frequently found in humans. The effect of retinoids (13 cis-RA) was studied on the proliferation and differentiation of a human follicular cell line in vitro (UCLA R0 82 W-1). A significant and dose-dependent reduction (P less than 0.001) in cell number and [3H] thymidine uptake was found in cells exposed to 13 cis-RA up to 10 microM. Higher concentrations of 13 cis-RA, however, led to a dose-dependent restoration of cell proliferation. Various parameters of differentiation increased under the influence of 13 cis-RA (10 microM) over nonexposed cells. The 125I uptake increased 4-fold over that in control nonexposed cells (P less than 0.05). [125I] Epidermal growth factor binding increased 5-fold, and [125I] human TSH binding increased significantly after exposure to 13 cis-RA (P less than 0.02). Deiodinase activity, however, was significantly lower in 13 cis-RA exposed cells than in control cells. The present study shows that 13 cis-RA (10 microM) drives the tumor cells toward a more normal state of proliferation and differentiation.

Adenocarcinoma

Olfactory neuroblastoma.

Fifteen patients with olfactory neuroblastoma were treated during the 17-year period of 1969 to 1986. Data was analyzed with respect to age at presentation, sex, presenting signs and symptoms, stage, and results of treatment. Age ranged from 4 to 67 years with the median age being 27 years. Median follow-up was 8 years. Local control was achieved in nine of nine patients or 100% with successful surgical resection, i.e., minimal residual disease, followed by postoperative radiation therapy (45 to 65 Gy) was employed. There were no distant failures when the primary site was controlled. Regional lymph node metastases were infrequent: only 13% (two of 15 patients) presented with positive nodes. Three of four patients treated initially with surgery alone had a local recurrence, two of which were successfully salvaged by combined therapy. There were four patients treated with radiation therapy alone: three had persistent disease after radiation therapy, and one patient was controlled with 65 Gy. Olfactory neuroblastoma has a propensity to recur locally when treated with surgery alone. The authors' experience suggests excellent local control can be achieved with surgery immediately followed by radiation therapy. Thus the authors recommend planned combined treatment for all resectable lesions.

Adolescent

Characterization of a human follicular thyroid carcinoma cell line (UCLA RO 82 W-1).

A thyroid tumor cell line has been established from the metastases of a follicular carcinoma in a female patient. Although the primary tumor released thyroglobulin (Tg) into the circulation (greater than 10,000 ng/ml), the uptake of I131 was less than 2%. After 37 replications the doubling time was 4 days and confluency was reached after 7 days from inoculation of 3 x 10(7) cells. This human thyroid tumor cell line has now been growing in culture for several years. An aneuploid chromosomal pattern was observed (62-82 chromosomes). A pair of X chromosomes was present but no Y chromosome was found which is compatible with the female origin of the cell line. EM studies revealed the presence of microvilli. Immunoperoxidase staining using specific anti-human Tg antisera indicated the presence of Tg within the cells. Nude mice developed solid-cystic tumors within 6 months after injection of the cells. The basal release of immunodetectable Tg, as measured in a perifusion system, increased in response to thyroid stimulating hormone (TSH) (P less than 0.025) or TSH combined with theophylline (P less than 0.001). Unusual isoenzyme patterns for galactose-1-phosphate-uridyltransferase (GALT) and phosphoglucomutase1 (PGM1) were detected in the tumor, compared with normal human fibroblasts and blood cells and isoenzyme patterns from the patient's lymphocytes. Because this malignant human thyroid follicular cell line has retained the ability to synthesize Tg it represents a valuable model for the study of human follicular carcinomas.

Adenocarcinoma

Novel antigenic markers of human tumor regression.

The development of tumor-specific antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated human allogeneic and autochthonous (autologous) tumor cells injected by the intralymphatic route. Immunoblotting studies on extracts of various established tumor cell cultures and fresh tumor biopsies were performed using sera from these patients. Evaluable tumor regressions were associated with detection of antibodies against human tumor cell antigens of 22,000 daltons (22 kd), 38,000 daltons (38 kd), 43,000 daltons (43 kd), and 70,000 daltons (70 kd). Similar antigens of approximately 22, 43, and 70 kd have also been detected in fresh extracts of certain human tumor tissues when tested with antisera from patients responding to immunotherapy. Production of antibodies to these antigens may play a role in tumor regression with active specific immunotherapy. These human regression-associated antigens may, therefore, represent novel agents for cancer immunotherapy.

Adult

Early vocal cord carcinoma in obese patients: a surgical lesion.

Early epidermoid carcinoma of the vocal cord is treated successfully by radiation therapy with high 5-year survival rates, low morbidity, and preservation of excellent voice quality in most cases. Typically, surgery is reserved for salvage of radiation failure and provides overall 5-year survival rates of 98% and 90% for T1 and T2 lesions, respectively. The extremely obese patient, often with a short neck and excessive amounts of subcutaneous fat, is difficult for both radiotherapist and surgeon to diagnose and treat. The recent observation of an unusually high rate of radiotherapy failure in a cluster of obese patients with early vocal cord cancer called attention to this problem. Because the larynx is near the thoracic inlet in obese patients, they are not suitable for administration of radiotherapy by accurate opposed lateral portals. The patients reported herein were treated entirely with anterior oblique portals. Of the five obese patients who underwent primary radiation therapy for early vocal cord cancer, three developed recurrent disease (60%) and a fourth developed a severe perichondritis requiring tracheostomy. Two patients with recurrent disease were successfully salvaged with total laryngectomy, while the third patient refused surgery and died 2 years later. The sixth patient was treated by partial laryngectomy with imbrication reconstruction and is alive and without evidence of disease 2 years following surgery. Recurrence rates and complication rates following primary radiation therapy for early vocal cord cancer appear to be unacceptably high in obese patients treated with anterior oblique portals. Therefore, we recommend conservation laryngeal surgery for obese patients with early vocal cord cancer who cannot undergo "standard" radiotherapeutic techniques.

Aged

Orbital lymphomas and pseudolymphomas: treatment with radiation therapy.

A retrospective analysis of 16 patients with orbital lymphoma or pseudolymphoma from 1961-1984 was undertaken to evaluate the use of radiation therapy. Pathologic assessment confirmed that four patients had benign pseudolymphoma, and 12 patients had true malignant lymphoma, including two with advanced disease at presentation. With a median follow-up of 4 years, the local control rate with radiation therapy was 100%, although the two patients with advanced disease died of lymphoma 26-33 months after irradiation. While doses of 1,600-2,000 cGy appear adequate for pseudolymphoma, for lymphoma a dose of 3,000-4,000 cGy is necessary. Subconjunctival lesions can be treated in a single anteroposterior field; retroorbital lesions require an additional lateral field.

Aged

Distribution and consequences of cell suspensions following intralymphatic infusion.

The fate and consequences of intralymphatic injections of cells was investigated in dogs. The distribution of intact radiolabeled cells was determined in vivo by whole body gamma scanning. Comparison of distributions resulting from intralymphatic, subcutaneous, intradermal and intravenous routes of administration showed that the distribution and duration of radiolabel in various organs varied with the route of administration. Following intralymphatic injection, radiolabel was concentrated in first echelon lymph nodes draining the site of injection and was retained in these nodes for over 4 weeks. Histologic studies showed intense cortical and paracortical lymphopoiesis to be associated with the retention of intralymphatically injected tumor cells by first echelon lymph nodes. Serial histologic examination of lymph nodes from intralymphatically injected inbred beagles revealed that the consequent lymphopoiesis persisted for 5 weeks. In vitro evaluation of peripheral blood and lymph node lymphocyte cytotoxicity to the injected cells indicated that retention and nodal lymphopoiesis was associated with the development of direct lymphocyte cytotoxicity. The effects of concommitant tumor burden, cytotoxic drugs and ionizing radiation were also investigated and suggest that the therapeutic potential for use of the intralymphatic route has not yet been realized.

Animals

A phase I study of active specific intralymphatic immunotherapy (ASILI).

Twenty-one patients with advanced malignancies who had exhausted or refused conventional modalities of treatment were entered in a Phase I toxicology trial of active specific intralymphatic immunotherapy (ASILI). The patients were immunized with 1 X 10(7) to 1.2 X 10(8) viable autochthonous or allogeneic irradiated tumor cells intralymphatically each month and received no other antineoplastic treatment. To date, 274 intralymphatic injections have been performed and except for one case of bacterial lymphangitis, no adverse side effects have been observed. ASILI did not significantly alter peripheral blood lymphocyte counts, absolute E-rosette forming cell levels, or EA-rosette forming cell levels. PHA reactivity of peripheral blood lymphocytes increased slightly in all but one patient tested. Seven out of nine patients who had not had delayed hypersensitivity to recall antigens developed positive reactions following ASILI. Sixteen out of twenty patients tested also developed reactivity to their immunizing cells after treatment. Objective regression (greater than 50% reduction of tumor mass) was observed in five out of nineteen evaluable patients. Six patient showed stabilization of tumor growth and eight patients continued to progress under treatment.

Adult

Regional intralymphatic infusion (ILI) of irradiated tumor cells with evidence of distant effects.

A case of canine lymphoma with radiographically-documented involvement of the para-aortic nodes is reported. Intralymphatic infusions (ILI) of cultured irradiated autochthonous tumor cells to remote lymph node bearing areas were associated with a dramatic initial shrinkage of the para-aortic lymphadenopathies. Three ILI timing schedules were used consecutively during a course of 10 treatments, allowing a comparison of responses in the same animal. The reported case suggests that a normal lymph node can be effectively "stimulated" by the same agent approximately every 3 weeks. A possible schedule for intralymphatic infusion is proposed for further investigation.

Animals

Upper extremity lymphangiography in the radiation therapy of lymphomas and carcinoma of the breast.

Seventeen bilateral upper extremity lymphangiograms were obtained in patients with lymphoma referred for radiation therapy. The projection of the opacified axillary nodes is analyzed when using the mantle technique in various positions. The position of the lymph nodes varies considerably in the supine and prone positions. Placing pads underneath the shoulders in the prone position allows for better protection of the pulmonary parenchyma while still including the opacified lymph nodes. Because these nodes vary in position, it is recommended that if the axillary nodes are clinically involved or if hilar adenopathy is present, upper extremity lymphangiograms should be obtained to ensure inclusion of all the axillary lymph nodes. In treating carcinoma of the intact breast, care should be taken to include the lower axillary nodes in the tangenital breast field and to include 2 cm of lung in the posterior axillary boost.

Arm

The role of computed tomography in the management of cancer of the larynx.

Computed tomography (CT) offers a unique method of displaying the anatomy of laryngeal cancer. Asymmetrical contours of the thyroid cartilages have been found as a normal variant. Marked asymmetry may indicate buckling of the cartilage which could contribute to acute airway obstruction following radiation therapy. A low-density, soft-tissue plane medial to the thyroid cartilages may prove valuable in evaluating cartilaginous involvement with tumor. Computed tomography should make a significant contribution to more accurate planning of radiation therapy portals by showing the relationship of lymphatic spread to the primary tumors.

Humans