The local immune response to lung cancer was investigated by histologic and immunologic means. Distinctive patterns of stromal cellular reaction, characteristic for different histologic types of lung carcinoma, were recognized. The amount of cellular infiltration was highest in squamous cell carcinomas a n d lowest o r nonexistent in oat cell carcinomas. Within the various histologic categories the well-differentiated tumors appeared to be accompanied by more reactive cells than the poorly differentiated ones; there was no relation between tumor necrosis and cellular infiltration. The plasma cells were distinctly associated with squamous cell carcinomas; their number in the stroma was proportionate to the degree of differentiation and the presence of keratin produced by the tumors. Eluates with a high content of immunoglobulins were recovered from pleural effusions and from solid lung carcinomas by dissociation of antigen-antibody complexes. These preparations reacted positively in indirect immunofluorescence tests with tissue cultures and with fresh suspensions of lung carcinoma cells, but not with (issue culture cells of most nonpulmonary tumors or with cell suspensions of normal adult and fetal lung. Similarly prepared fractions of noncarcinomatous pleural effusions did not react with lung cancer cells.Cancer 38:2296-2309, 1976. GCORDING T O MODERN CONCEPTS OF TUMORA immunology, cancer cells may express altered antigenic properties acquired as a result d neoplastic transformation. The existence of tumor-associated antigens has been clearly denionstrated in both experimental 17,18321*319 and huIn cancer patients the search for specific tumor antigens is based primarily on skim and on assays of lymphocyte reactivity to tumor extracts and tumor cells. B.A sustained effort is also being made to detect circulating antigens in sera of cancer patients and several tumor associated antigens tumors. ever, to date, most of these efforts have not yet produced the expected results, possibly because tumor antigens in the circulating blood are diluted to infinitesimal amounts or locked in antigen-antibody complexes. Similarly, the lymphoid cells specifically primed to react to a particular tumor are highly diluted in the pool of circulating lymphocytes. It appeared to us that the tumor site would be a logical place to explore the presence of tumorreactive populations of lymphoid cells, as well as to attempt the detection of tumor-associated antigens and antibodies.To evaluate the morphology of the local cellular reaction to cancer of the lung we examined comparatively sections of 50 cases of different types and grades of lung carcinomas. The aim was not to establish clinical-pathologic correlations, but rather to assess the presence of a cellular reaction and to estimate its intensity and its composition in regard to the various types and grades of lung carcinomas. To investigate the function of these cellular infiltrates we attempted the recovery, identification, and quantitation of the immunoglobulins at the tumor site. Us...

Objectives: A previous pilot study demonstrated that various fixed-dose combinations (FDCs) of ibuprofen (IBU) and acetaminophen (APAP) provided analgesic efficacy comparable to a higher dose of IBU, with the same safety profile. These studies further evaluated the chosen FDC IBU/APAP 250/500 mg formulation. Materials and Methods: Two phase 3 dental pain studies enrolled healthy young patients with ≥moderate pain after ≥3 third molar extractions who received single-dose FDC IBU/APAP 250/500 mg, IBU 250 mg, APAP 650 mg, or placebo evaluated over 12 hours (study 1) or multiple-dose FDC or placebo every 8 hours, evaluated over 48 hours (study 2). Time-weighted sum of pain intensity differences over 8 (SPID[11]0-8) and 24 (SPID[11]0-24) hours were primary outcomes, respectively. Time to meaningful pain relief and duration of pain relief were assessed; tolerability was evaluated by adverse events. Results: Five hundred sixty-eight patients were randomized in study 1; 123 in study 2. Study 1: SPID[11]0-8 favored FDC significantly over placebo, IBU, and APAP (P<0.001, P=0.008, and P<0.001, respectively); study 2: SPID[11]0-24 significantly favored FDC over placebo (P<0.001), with sustained efficacy during multiple dosing. Time to meaningful pain relief occurred within 1 hour; pain relief duration was >8 hours in both studies. Adverse event rates were lowest with the FDC. Discussion: FDC IBU/APAP 250/500 mg provides superior analgesic efficacy to individual monocomponents (IBU 250 mg and APAP 650 mg), a rapid onset of action, >8-hour duration of pain relief, is generally well tolerated, and may provide an additional nonopioid treatment option for acute pain.

Analgesic effects of ibuprofen immediate‐release/extended‐release (IR/ER) 600‐mg tablets were evaluated in 2 randomized, double‐blind, placebo‐controlled dental pain studies. Patients 16–40 years old with moderate–severe pain following third‐molar extraction received single‐dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time‐weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0–12 hours and ‐0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8–12 hours (all P < .001 vs placebo). In study 2 (n = 106), mean (SD) time‐weighted sum of pain relief and pain intensity difference scores were 18.2 (20.0) versus 41.5 (21.0) at 0–12 hours and 10.3 (12.0) versus 18.4 (12.1) at 8–12 hours for placebo versus ibuprofen IR/ER, respectively (P < .001 for both); efficacy was sustained over each of the four 12‐hour dosing intervals with ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses.

Serum or plasma specimens were assayed in indirect immunfluorescence tests on cryostat sections of normal human skin for the presence and titer of antibodies reactive with human epidermal cytoplasmic antigens. A polyvalent fluorescein-labeled goat anti-human immunoglobulin antiserum was used in all tests. Three distinct staining patterns were noted: upper epidermal cytoplasmic fluorescence, U-CYT, produced by antibodies reactive with antigen present in cells of the upper and middle layers of the epidermis; general cytoplasmic fluorescence, G-CYT, produced by antibodies reactive with antigens present in cells throughout the epidermis; and basal cell cytoplasmic fluorescence, BCL, produced by antibodies reactive with components present only in basal cells. Sera from 8% of 52 normal blood donors produced the U-CYT pattern at dilutions greater than 1:10. The incidence of antibodies reactive with epidermal cytoplasmic antigens in patients with a clinical history of not more than 2 basal cell carcinomas of the skin was 5%, compared to an incidence of 89% in those individuals with 3 or more separate instances of skin neoplasms. There was no difference in the frequency with which cryosurgery was used in the treatment of skin neoplasms in either of these 2 groups. Antibodies to epidermal cytoplasmic antigens were also detected in 10% of patients with nondermatologic, nonpulmonary neoplasms, in 43% of patients with pulmonary neoplasms and in 1 of 11 patient with nonneoplastic diseases. Positive sera yielded titers ranging from 1:16 to 1:1024. The most common staining patterns noted in all of these cases were the U-CYT and G-CYT patterns; the BCL staining pattern was noted in only one instance.