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J C Yang

Publications and source records attributed to J C Yang.

At least 181 records · Page 10Linked to original sources
PubMed1990

An improved method for growing murine tumor-infiltrating lymphocytes with in vivo antitumor activity.

Tumor-infiltrating lymphocytes (TILs) are host T cells that can be grown from fresh murine and human tumors using interleukin-2 (IL-2) in bulk cultures. These activated T cells have been shown to have significant antitumor activity both in vitro and in vivo. A technique is described for the separation of Thy-1.2-positive TILs from fresh murine tumors using antibody-coated magnetic beads, permitting the examination of growth conditions for these cells. TILs with increased therapeutic efficacy are obtained from the immunogenic MCA 38 and MCA 105 tumors when culture conditions employing low levels of IL-2 (10 vs. 1,000 U/ml) and irradiated autologous tumor restimulation are used. TILs grown under these conditions can mediate a 93% reduction of 3-day-old established pulmonary metastases when as few as 2.5 x 10(5) cells are adoptively transferred with systemic IL-2. These culture conditions are utilized to grow TILs from the nonimmunogenic MCA 102 tumor for which bulk TIL culture methods are unsuccessful. MCA 102 TILs grown in this fashion demonstrate in vivo therapeutic efficacy against established autologous pulmonary metastases.

Animals↗
PubMed1990

Effect of beta-cyclodextrin on the in vitro permeation rate and in vivo rectal absorption of acetaminophen hydrogel preparations.

The amounts of beta-cyclodextrin and hydroxyl propyl methyl cellulose (HPMC) affecting the in vitro permeation rate of acetaminophen containing in both aqueous solutions and HPMC hydrogel preparations through the dialyzer tubing and isolated rat rectum were investigated. The partition coefficient of acetaminophen with or without beta-cyclodextrin in water/n-octanol system was also studied. In vivo absorption experiments of these test formulations were carried out by rectal administration in rats. The results indicate that the concentrations of beta-cyclodextrin and HPMC used decreased the amount permeated of acetaminophen from both test formulations. The more the amount of beta-cyclodextrin or HPMC the slower the permeation rate of acetaminophen. The permeation rate of acetaminophen through the dialyzer tubing was higher than that of acetaminophen through the isolated rat rectum. The result also shows beta-cyclodextrin and HPMC markedly reduced the in vivo bioavailability of acetaminophen from both test formulations. The lower partition coefficient and the higher hydrophilic properties of beta-cyclodextrin inclusion complex, and the higher viscosity of HPMC hydrogel matrix might be responsible for decreasing the in vitro permeation rate and depression of in vivo rectal absorption of acetaminophen. The in vitro permeation data was well correlated with in vivo absorption results, suggesting that the in vitro permeation study regardless of the dialyzer tubing method or the isolated rat rectum method might be used to estimate the in vivo rectal absorption of acetaminophen.

Acetaminophen↗
PubMed1990

[Effects of nicardipine on beating rates of cultured myocardial cells].

Nicardipine (Nic) 15 nmol/L had no effects on beating rates of cultured myocardial cells. Nic 75 and 150 nmol/L depressed the beating rates significantly. Rapid standstills occurred earlier and more in 150 nmol/L group than in 75 nmol/L. Both isoproterenol and CaCl2 restored the beating depressed by Nic. However, only CaCl2 prevented the standstill. These results suggest that nicardipine may compete with calcium in excitation-contraction coupling.

Animals↗
PubMed1989

In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma.

Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on 111In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given 111In-PBL. Nineteen paired biopsies of tumor and normal skin were completed on 10 patients receiving 111In-TIL, while eight biopsies were done on three PBL patients receiving 111In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P2 = .0004). The mean of the tumor to normal skin ratios of the 111In-TIL group was three times that for 111In-PBL (P2 = .0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by 111In-TIL at several sites, then faint localization with 111In-PBL at a single site, and subsequently positive tumor imaging on repeat 111In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL.

Adult↗
PubMed1989

Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients.

We have administered 1039 courses of high-dose interleukin-2 (IL-2) to 652 cancer patients. Five hundred ninety-six patients had metastatic cancer that either had failed standard effective therapies or had disease for which no standard effective therapy existed, and 56 patients were treated in the absence of evaluable disease in the adjuvant setting. IL-2 was administered either alone (155 patients) or in conjunction with activated immune cells such as lymphokine activated killer (LAK) cells (214 patients) or tumor infiltrating lymphocytes (TIL) (66 patients), with other cytokines such as alpha interferon (a-IFN)(128 patients) or tumor necrosis factor (TNF)(38 patients), with monoclonal antibodies (32 patients), or with the chemotherapeutic agent cyclophosphamide (19 patients). Initial results with the treatment of high-dose IL-2 alone or in conjunction with LAK cells have indicated that objective regressions of cancer can be achieved in 20% to 35% of patients with selected advanced metastatic cancers. Although most responses have been seen in patients with metastatic renal cell cancer, melanoma, colorectal cancer, and non-Hodgkin's lymphoma, many histologic types of cancer have not been treated in significant numbers. These regressions can be durable; of 18 patients achieving a complete response, ten have not experienced recurrence at intervals from 18 to 52 months. Although combinations of IL-2 with TNF do not appear to result in increased responses, there is a suggestion in our initial phase I studies that the combination of a-IFN and IL-2 is more effective than the administration of cytokine alone and this combination deserves further study. Similarly the adoptive transfer of TIL in conjunction with IL-2 also appears to be more effective than the use of IL-2 alone. The toxic side effects in patients treated with high-dose IL-2 are presented and include malaise, nausea and vomiting, hypotension, fluid retention, and organ dysfunction. Treatment-related deaths were seen in 1% of all treatment courses and in 1.5% of patients. These studies demonstrate that a purely immunologic manipulation can mediate the regression of advanced cancers in selected patients and may provide a base for the development of practical, effective biologic treatments for some cancer patients.

Adolescent↗
PubMed1989

Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer.

We performed an escalating dose study of the combined administration of interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) in 94 patients with metastatic cancer. Patients received alpha-IFN at a dose of 3 x 10(6) U/m2 in conjunction with IL-2 at doses of either 1 x 10(6) U/m2 (six patients), 3 x 10(6) U/m2 (32 patients), or 4.5 x 10(6) U/m2 (26 patients). Thirty patients received alpha-IFN at 6 x 10(6) U/m2 plus IL-2 at 4.5 x 10(6) U/m2. Patients each received cytokine as an intravenous bolus infusion every 8 hours for up to 5 consecutive days and after a 10-day rest received a second cycle of combination cytokines. Of the 91 patients evaluable for response, seven patients had a complete regression of cancer, and 18 had a partial regression. At the four increasing dose levels used in patients with renal cell cancer (35 patients) or melanoma (39 patients), objective responses were seen in 17% (of six patients), 24% (of 25 patients), 38% (of 16 patients), and 41% (of 27 patients), respectively. Of the 25 total responding patients, 16 are still responding 5 to 14 months after treatment. The toxicities associated with the combined administration of IL-2 and alpha-IFN were similar to those expected from each agent alone. There was one treatment-related death in the 94 patients treated in this study. Thus, using increasing doses of the combination of IL-2 and alpha-IFN, it appears that response rates may be related to the doses of the cytokines used, and that at the highest doses of these combination cytokines, response rates may be higher than those for either cytokine alone. A prospective randomized trial comparing the cytokine combinations with each cytokine administered alone is necessary as is the extension of this combination cytokine treatment to patients with other types of solid cancer.

Adult↗
PubMed1989

Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma.

Lymphoid cells infiltrating into human tumors can be expanded in vitro in medium containing interleukin-2 (IL-2). Adoptive transfer of these tumor-infiltrating lymphocytes (TIL) mediates potent antitumor effects in murine tumor models. Clinical trials to evaluate the efficacy of these cells in patients with advanced cancer are underway. We have investigated whether infused TIL labeled with indium 111 (111In) oxine can traffic and localize to metastatic deposits of tumor. Six patients with metastatic malignant melanoma who had multiple sites of subcutaneous, nodal, and/or visceral disease were the subjects of the study. The patients received cyclophosphamide 36 hours before receiving the intravenous (IV) infusion of TIL followed by IL-2 IV every eight hours. The distribution and localization of the TIL were evaluated using serial whole body gamma camera imaging, serial blood and urine samplings, and serial biopsies of tumor and normal tissue. 111In-labeled TIL localized to lung, liver, and spleen within two hours after the infusion of activity. Activity in the lung diminished within 24 hours. As early as 24 hours after injection of 111In-labeled TIL, localization of TIL to sites of metastatic deposits was demonstrated in all six patients using either imaging studies or biopsy specimens or both. 111In activity in tumor tissue biopsies ranged from three to 40 times greater than activity in normal tissue. A progressive increase in the radioactive counts at sites of tumor deposit was seen. This study shows that labeled TIL can localize preferentially to tumor, and provides information concerning the possible mechanism of the therapeutic effects of TIL.

Adult↗
PubMed1989

[Effect of nisoldipine on cultured myocardial cells of neonatal rats].

Nisoldipine 1.5 nmol/L, 0.75, and 1.5 mumol/L depressed the beat rates of myocardial cells. The effects were negatively correlated with dosages. Nisoldipine depressed the beat rates increased by calcium chloride 0.15 mmol/L or isoprenaline 1.5 mumol/L and atropine 20 nmol/L. Conversely, the above drugs reversed the beat rates depressed by nisoldipine. Therefore, the acting nisoldipine may be antagonistic to calcium chloride, isoprenaline and atropine. In addition, nisoldipine 10 nmol/L may significantly aggravated the damage to myocardial cells induced by mitomycin C 5 micrograms/ml in which elevated lactate dehydrogenase appeared.

Animals↗
PubMed1989

Endoscopic sphincterotomy in the treatment of biliary tract diseases.

Endoscopic sphincterotomy (EST) was performed in 53 patients with biliary disease. Indications for sphincterotomy were: 48 patients with choledocholithiasis, 3 patients with malignant biliary obstruction, and 2 patients with papillary stenosis. The procedure was successful in 52 patients (98.1%). In patients with choledocholithiasis, the stones were successfully removed or passed out spontaneously in 42 patients (87.5%). Endoscopic retrograde biliary drainage (ERBD) was successfully carried out in 2 cases of malignant biliary obstruction after EST. The clinical and biochemical evidence of cholestasis resolved in both patients with papillary stenosis. Complications consisted of hemorrhage (2 patients) and cholangitis (1 patient), resulting in one death. The overall complication and mortality rates were 5.7% and 1.9% respectively. Thirty-two patients received regular ultrasound examination follow-up with a mean of 13.4 months. Two patients had recurrent common bile duct stones and one had restenosis of papilla. The conditions were managed by endoscopic therapy. Endoscopic sphincterotomy is a relatively safe and effective means of relieving extrahepatic cholestasis; however, its comparison with surgical techniques needs long-term, randomized studies.

Adult↗
PubMed1989

In-vitro dissolution behavior of some sustained-release theophylline dosage forms.

In-vitro dissolution of theophylline from six commercially sustained-release (SR) preparations (Euphyllin retard, Euphyllin retard mite, Theovent L.A. 125 mg, Theovent L.A. 250 mg, Phyllocontin and Uniphyllin) was determined by using rotating basket and rotating bottle apparatus. The effect of pH and rotating speed on the dissolution rate of these SR products was also studied. Scanning electron microscope was used to observe the change of surface topograph and inner texture of these products before, during and after dissolution. The results indicates that the dissolution behavior was pH-dependent which corresponding to the types of SR products. The rotating bottle method was only suitable for the evaluation of release rate of spansule-type SR products and was not suitable for matrix-type SR tablets due to the sticking occurred on the bottle surface leading to faster dissolution and larger variation. The release mechanism of these six SR products can be deduced into three models. Fickian transport (Phyllocontin), non-Fickian transport (Euphyllin, Theovent L.A. 250 mg and Uniphyllin) and zero order transport (Theovent L.A. 125 mg).

Delayed-Action Preparations↗
PubMed1988

Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.

Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted.

Adult↗
PubMed1988

Combined effects of chemotherapy and interleukin 2 in the therapy of mice with advanced pulmonary tumors.

We have evaluated the effects of chemotherapeutic agents on the toxicity and antitumor benefit of therapy of established murine tumors by high-dose interleukin 2 (IL-2). Cyclophosphamide (Cy), doxorubicin, and bischloroethylnitrosourea were given to normal mice prior to IL-2 administration to test the effects of these agents on IL-2-induced toxicity. Cy at doses of 100 mg/kg and 150 mg/kg completely protected mice from a 100% lethal dose of IL-2, and doses of 50 mg/kg and 150 mg/kg allowed the administration of a median of 4.5 and 10.0 more doses of IL-2, respectively, before death from IL-2 toxicity occurred. Doxorubicin at 8 mg/kg and bischloroethylnitrosourea at 20 mg/kg did not impact on toxicity in IL-2-treated mice. In mice bearing pulmonary metastases of the weakly immunogenic MCA-105 sarcoma, IL-2 increased median survival time from 33 (no IL-2) to greater than 60 days for all doses of IL-2 tested when combined with a single injection of Cy at 75 mg/kg (P less than 0.002). Increasing doses of either Cy or IL-2 produced increasing benefits on survival which were always greater than either treatment alone. These effects of Cy and IL-2 were also seen in mice bearing the nonimmunogenic MCA-101 sarcoma and a murine adenocarcinoma (MCA-38). Doxorubicin and bischloroethylnitrosourea did not consistently enhance the effects of IL-2 treatment. Cy appears to reduce the yield of in vivo generated lymphokine-activated killer cells, but these lymphokine-activated killer cells are still lytic for fresh tumor targets in vitro. Thus, the mechanism of this synergy does not appear to involve stimulation of lymphokine-activated killer cell activity, but may in part involve reduction of tumor burden by the chemotherapeutic agent, an increase in susceptibility of tumor to cellular immune lysis, and/or a decrease in suppressor cell activity mediated by the chemotherapy.

Animals↗
PubMed1988

Current approaches to the adoptive immunotherapy of cancer.

Interleukin 2 has provided the means of generating activated lymphocytes from the tumor-bearing host which show in vitro anti-tumor activity. These cells can be derived either from a ubiquitous null cell precursor population, exhibiting promiscuous lysis of nearly all tumors after culture in IL2 (ie. the LAK cell) or from a T cell precursor population infiltrating tumors and showing some relative specificity for lysis of the autologous tumor following activation (ie. TIL). When utilized in murine cellular adoptive immunotherapy models, both LAK cells and TIL are able to display marked anti-tumor effects against established micrometastatic tumor. LAK cells have been subsequently employed in adoptive immunotherapy against metastatic human tumors and in a limited number of cases have been able to mediate the regression of advanced cancers of differing histologies. The role of adoptive immunotherapy as standard therapy of human tumors will depend on refinement of the methodology and progress toward increased efficacy and reduced toxicity. TIL may possess theoretical advantages in these areas and efforts are currently proceeding to evaluate these new anti-tumor reagents in the the treatment of patients with cancer.

Animals↗