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The metabolism of estrone (E1) and estradiol (E2) by Ishikawa endometrial carcinoma cells and its alteration by TNF alpha treatment was studied. Whereas this cell line practically does not respond to estrogens, it is very sensitive to TNF with respect to growth inhibition and other parameters. E2 and E1 were found to be metabolized by this cell line whereby the main metabolite for both estrogens was estriol. TNF significantly increased the rate of E1 and E2 conversion.

The tumour necrosis factor (TNF) stimulates in cultured JAR choriocarcinoma cells the biosynthesis of hCG, including the free alpha and beta chain and the holo-hCG. Although elevated serum TNF levels have been shown by Balkwill et al. (1987) in about 50% of tumour patients, we were unable to confirm these data in the 10 examined patients, who had a choriocarcinoma. Despite its excellent in-vitro action, INF could not be confirmed to exercise an influence on the regulation of hCG in choriocarcinoma patients.

Combination of all-trans-retinoic acid (RA) with either interferon (IFN)-ct or -), results in a synergistic amplification of the anti-proliferative effect on cultured breast cancer cells. RA could be replaced by other biologically active retinoids. The synergism is also observed for the induction of 2'-5'-oligoadenylate synthetase, an enzyme which is involved in anti-viral activity of interferons and possibly in growth regulation of tumor cells. Comparing all-transwith 9-cis-RA, the latter is more effective inhibiting tumor cell growth and in inducing synergism with IFN-y. IFN-y increases retinoic acid receptor-y (RAR-y) expression but had no influence on KAR-~t, whereas RAR-13 was not detectable in any of the examined breast cancer cell lines. RA-mediated increase of the cellular retinoic acid receptor binding protein-II (CRABP-II) was suppressed by IFN-y. This observation indicates that IFN-y-mediated increase in RAR-y and suppression of RA-mediated CRABP-I! activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines. 24

The combination of retinoic acid or tumor necrosis factor alpha (TNF-alpha) with interferon gamma (IFN-gamma) resulted in a synergistic amplification of the anti-proliferative effect of IFN-gamma on cultured breast cancer cells. Retinoic acid could be replaced by other biologically active retinoids. This synergism was also observed for the induction of 2′-5′-oligoac enylate-synthetase, an enzyme which is not expressed constltutively on BT-20 human breast cancer cells and not inductile by retinoic acid or TNF-alpha alone. However, both substances augmented the IFN-gamma-mediated expression. On the other hand, only TNF-alpha and not retinoic acid was able to increase the IFN-gamma induced expression of HLA-DR on the cell surface. Both cytokines antagonized the IFN-gamma effect on detachability of cultured BT-20 cells. The combinations of retinoic acid with IFN-gamma increased the down-regulation of specific binding sites for 125 l-IFN-gamma. On the other hand, IFN-gamma exerted no effect on the cancer traction of the cytoplasmic binding protein for retinoic acid. Data obtained in this study demonstrate a different patten of action between retinoic acid and TNF-alpha regarding their synergism in combination with IFN-gamma.

Patients with refractory ovarian cancer were treated intra-peritoneally with interferon-gamma. The maximum tolerated dose was achieved at 2 mg/m2. The substance was administered 3 times per week every second week. Interferon-gamma treatment activated locally the macrophages and induced a rise in neopterin urine, serum, and ascites levels. The tumor marker CA-125 showed marked fluctuations of more than 100% during interferon treatment and this was not correlated with neopterin. A flu-like syndrome and especially fatigue were the dose limiting side effects. Two of 3 evaluable patients died on tumor progression whereas one is now 18 months clinically free of disease.

In 32 patients with colorectal carcinomas, the immunoreactivity of carcinoembryonic antigen (CEA) was measured on section preparations of the tumours by means of a computer controlled microdensitometric method. By measuring numerous single points, the intensity of the immunohistochemical staining reaction of CEA was evaluated. This method is superior to the commonly used semiquantitative method (+, ++, ) for the assessment of various degrees of staining intensity whenever the antigen to be measured is not homogeneously dispersed in the tissue. The results show that highly differentiated colorectal carcinomas of stage A according to Dukes classification have a lower CEA immunoreactivity than highly differentiated carcinomas of stage B. A correlation between CEA immunoreactivity and degree of malignancy could only be found in patients in stage B. Stage C carcinomas of all degrees of differentiation appeared with a very low CEA immunoreactivity. CEA follow-up controls in our study were of little value for detecting local recurrences; metastases, however, almost always caused an increase in serum CEA titers. Prognostically, a preoperatively increased serum CEA level seems to be as unfavourable as a low CEA immunoreactivity in the tumour.

1. A quaternary ammonium compound, (4-hydroxy-5-isopropyl-2-methylphenyl)trimethylammonium chloride, 1-piperidine carboxylate, designated Amo-1618, was applied to soil in which bean seeds (Phaseolus vulgaris, variety Black Valentine) were planted. It was absorbed by the roots of seedlings and apparently translocated to the stems, leaves; and seeds. 2. Amo-1618 induced the plants to develop relatively short internodes, thick stems, and dark green leaves in comparison with untreated plants. Maturity was delayed. When the chemical was applied at rates of 1, 10, and 100 pounds per acre, the intensity of these responses was in proportion to the amount of chemical used. 3. The effect of Amo-1618 applied at the rates of 10 or 100 lb/A persisted in the soil apparently undiminished during a period of 3 years. At the rate of 1 pound per acre the effect of the chemical was diminished but was still apparent at the end of 3 years. 4. The effects of Amo-1618 absorbed from the soil and translocated to the seeds were evi...

Stolons 1. Stolon cuttings of goldenrod soaked in aqueous solutions of several growth substances at concentrations of 10 to 100 p.p.m. for 18 hours were inhibited in top growth. Some of the cuttings rotted following this long treatment. Soaking for 3 hours in indolebutyric-acid solution at 10 or 50 p.p.m. gave some increase in rooting over the controls. 2. Cuttings dusted with indolebutyric, naphthaleneacetic, naphthoxyacetic acids, or naphthalene acetamide, or a mixture of these four, dispersed in powdered talc produced more roots than did those without treatment, except when the highest concentrations were used. 3. When the temperature of the substrate was 70⚬-80⚬ F., the greatest number and quantity of roots were formed. 4. Regardless of treatment, stolons cut into 3-inch pieces produced many roots and heavy top growth. Those cut into 1/2-inch pieces produced few roots and only 50% of the pieces rooted; top growth was slight. Stems 5. Cuttings from young stems produced a more vigorous root and top syst...

1. Plants of Barbarea verna and Plantago lanceolata which were established in 4-inch clay pots in a warm greenhouse (65⚬-75⚬F.) were moved to greenhouses in which temperatures of 32⚬-40⚬, 50⚬-65⚬, 65⚬-75⚬, and 75⚬-90⚬ F. were maintained, and separate lots of twenty-four plants each were spray-treated with 0, 500, 1000, and 1500 p.p.m. concentrations of 2,4-dichlorophenoxyacetic acid 1 week later. Carbowax 1500 was included in the acid sprays. 2. Treatment at the two higher temperature ranges resulted in rapid killing (18-21 days). All three concentrations of the acid were about equal in their effectiveness under the conditions of the experiments. At 50⚬-60⚬, however, the time required to kill plants with the acid treatment was extended for 11-15 days longer, while at 32⚬-40⚬ the treated plants were still living at the end of 50 days following spray applications. 3. The data indicate that the acid was present in lethal amounts, either within the tissues or on the surface of plants, treated in the greenhous...

1. The growth of established grasses-Kentucky bluegrass, red fescue, and redtop-growing in mixed stand with a rather heavy weed infestation of narrow-leaved plantain was measured by weighing clippings periodically during the summer following spring application of 2,4-dichlorophenoxyacetic acid spray mixtures to eradicate the weeds. The effect on growth of grass from adding urea as a fertilizer and Fermate as a fungicide to the herbicidal sprays containing the ammonium salt of the acid was also studied. Comparisons were made with weedy control plots from which the clippings of weeds and grass were sorted and weighed separately. 2. Immediately following application of the sprays (1000 p.p.m. of the acid or 1500 p.p.m. of the ammonium salt) the rate of growth of grass was significantly reduced for a short time, 10 days to 2 weeks. The reduction in most instances was greater than that caused by the competition of a rather dense stand of weeds. However, the grass soon recovered from the spray treatment and, wi...

Results with certain growth regulators or dormancy treatments indicate that sprouting and subsequent development of late blight on potato waste piles can be prevented if the cull potatoes are treated with dormancy treatments before or when the tubers are deposited on the cull piles.

1. 2,4-Dichlorophenoxyacetic acid was mixed in various amounts with batches of soil which were then stored, some air-dry and others moist, for different periods of time. Seeds of mustard, barley, and annual morning glory were planted in aliquots of the various soil mixtures at intervals during the storage periods and the effect of the acid-soil mixtures on the emergence of the seedlings observed. 2. One-tenth milligram of 2,4-dichlorophenoxyacetic acid per pound of soil significantly reduced the percentage of emergence of mustard planted in the acid-soil mixture that had been stored air-dry for 1 month, and concentrations of 1-14 mg. reduced its emergence by 80-90% below that of plants in untreated soil. 3. Although tests with mustard showed that 2,4-dichlorophenoxyacetic acid was slowly inactivated when mixed with air-dry soil, mixtures that contained 1 mg. or more per pound of soil still reduced the emergence of the plants by a significant amount after a storage period of 18 months. 4. The rate of emerg...

1. Dry mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D) and complete 10-6-4 fertilizer were applied to established weedy turf on November 6, 1945, and March 22, 1946, on plots 2 feet wide and 25 feet long. The fertilizer was used at the uniform rate of 600 lb. per acre and contained varying amounts of 2,4-D, namely, 0, 1.5, 3, 6, and 9 lb. per acre. The effects of the various treatments on the growth of turf and on the eradication of weeds were measured by sorting and weighing separately the clippings of weeds and of grass from the individual plots. 2. No significant difference, in comparison with the fertilized control, was found in the weight of grass clippings on April 4, 1946, from any 2,4-D fertilizer treatments that were applied on November 6, 1945. Such weeds as narrow-leaved plantain, black medic, and bur clover were eradicated almost 100% by the lowest amount (1.5 lb. per acre) of 2,4-D used in the fertilizer mixture. At the highest rates (6 and 9 lb. per acre) the green coloration of the grass...

1. Experiments conducted with rose bushes during common storage in two seasons, 1939-1940 and 1940-1941, indicate that growth-regulating substances will inhibit the vegetative buds so that the plants remain dormant throughout the normal storage season. Approximately 4400 rose bushes were utilized in experiments with seventeen chemical compounds. 2. Three compounds (naphthalenemethylacetate, naphthalenethylacetate, and naphthaleneacetonitrile) effectively inhibited growth of buds for 40-60 days in common storage. Application of these compounds was effective when applied at concentration of 0.01 per cent in 0.25 per cent wax-emulsion sprays applied to plant tops, or as vapors to dormant plants at rate of 0.3 and 0.4 gm. per 1000 cubic feet. 3. The vapor of naphthalenemethylacetate at the rate of 0.3 gm. per 1000 cubic feet was equally effective on bud inhibition when applied at 32⚬ F. for 16 hours, 40⚬ F. for 4 hours, and 70⚬ F. for 1 hour. 4. Concentrations of a naphthalenemethylacetate vapor stronger than...

1. A recently developed aerosol method of applying growth-regulating substances to tomatoes has proved an effective means of inducing fruit setting and,in many cases, of producing seedless fruits. 2. 4-Chlorophenoxyacetic, β-naphthoxyacetic, indoleacetic, indolebutyric, and a-napthaleneacetic acids differed in their capacities to induce fruit-set. Of these, 4-chlorophenoxyacetic acid was the most effective in setting fruit and stimulating early fruit growth. When used at concentrations higher than 0.01%, the treated plants developed abnormal leaves and fruits. 3. β-naphthoxyacetic acid also induced setting of seedless tomatoes when applied as an aerosol. The safest and still effective range of concentration lies between 0.01 and 0.5%. Not all the fruits from treated flowers were seedless. Apparently their age and the amount of pollination determined to some extent the amount of seed development, but early fruit growth was greatly stimulated. 4. Indoleacetic, indolebutyric, and a-naphthaleneacetic acids we...

1. The effect of (a) 2,4-dichlorophenoxyacetic acid (2,4-D), (b) ethylene, (c) combinations of 2,4-D and ethylene, and (d) gaseous substances from ripening bananas on the rate of ripening of bananas was studied. 2. Some volatile substance, or substances, was given off by ripening bananas that was antagonistic to the ripening effects of 2,4-D on bananas. 3. Synthetically prepared ethylene apparently did not reduce the ripening effects of 2,4-D on bananas. 4. On the contrary, 2,4-D greatly reduced the effectiveness of either chemically prepared or naturally produced ethylene in accelerating ripening of bananas. 5. Application of a nonvolatile form of 2,4-D to bananas did not prevent the evolution of gaseous substances from the fruit which were capable of inducing epinastic responses in tomato plants. The chemical nature of these substances was not determined.

1. 2,4-Dichlorophenoxyacetic acid was effective as a differential herbicide when applied as an aqueous spray in concentrations of from 250 to 1000 p.p.m. or more. 2. Plants killed by these sprays were dandelion, narrow-leaf plantain, Dutch white clover, chickweed, pigweed, woodsorrel, knotweed, broad-leaf dock, bind-weed, and shiny pennywort. Other plants, such as broad-leaf plantain, sheep sorrel, daisy, yarrow, and various species of Rubus, were relatively insensitive to the acid. 3. Two applications of either 500 or 1000 p.p.m. concentration of the acid in aqueous solution were made to well-established Kentucky bluegrass sod without apparent injury to the grass. In addition, Kentucky bluegrass seed planted under a light top dressing of soil, which was then sprayed with the acid concentrations, germinated and readily became established in these lawn areas. 4. It was possible to obtain 95% control of dandelion and narrow-leaf plantain by a single spray application of a solution containing 1000 p.p.m. of ...

1. Young rapidly growing bean and tomato plants were inclosed in bell jars and cellophane cases together with 2,4-dichlorophenoxyacetic acid (2,4-D) and various salts and esters of this acid in a study of the relative volatility of these herbicides. Pure forms of the chemicals were used, and none of them was permitted to come in direct contact with the test plants. Any plant growth-regulating effects, such as epinasty, bud inhibition, or formative effects, that subsequently developed were accordingly the result of vaporization of the chemicals and movement of the vapors through rather static air onto the test plants. 2. On the basis of this rather sensitive biological test the acid, sodium salt, triethanolamine salt, and amide forms of 2,4-D were nonvolatile. All esters that were tested (the methyl, ethyl, butyl, isobutyl, amyl, isoamyl, isopropyl, allyl, phenyl, beta-chloroethyl, n-octyl, and octadecyl) volatilized and produced growth effects on the test plants. Certain esters, namely, the methyl, ethyl,...

1. Experiments were conducted on apples during the 1943-44 and 1944-45 storage seasons to determine the effect of growth-regulating substances on development of fruit scald. 2. Two substances, α-naphthaleneacetic acid and β-indolebutyric acid, and a mixture consisting of equal parts of α-naphthaleneacetic acid, α-naphthalene acetamide, β-naphthoxyacetic acid, and β-indolebutyric acid were tested at 10, 100, and 500 p.p.m. concentration in lanolin emulsion (0.4% lanolin) on fruits of Arkansas (Mammoth Black Twig), Stayman Winesap, Grimes Golden, and York Imperial varieties. The fruits were treated after harvest and prior to 31⚬ F. storage by dipping in lanolin emulsion containing the various growth regulators or by using a liquefied-gas aerosol of the substance. The amount of scald development was noted at the end of the storage season of each variety after the fruits had been held for 7 days at 70⚬ F. to allow time for maximum scald development. 3. Treatment resulted in consistently less scald than on unt...

1. 2,4-Dichlorophenoxyacetic acid was applied to the detached fruits of bananas, apples, pears, tomatoes, peppers, and persimmons and its effect on the rate of ripening of these fruits observed. The fruits were collected while still unripe and sprayed with or dipped in aqueous solutions of the acid, which contained 0.5%-2.0% Carbowax. Other fruits comparable in stage of development were treated with the acid by the liquefied-gas aerosol method, and all were then stored at room temperature. 2. Based on color changes, the ripening period of bananas was shortened from 3 to 8 days following treatment. Treated fruits attained a full yellow color and excellent flavor, even though they were subjected to drier air and lower temperature conditions than is usually maintained in their commercial ripening. Yellow Newtown apples ripened during the 2 weeks' period immediately following treatment, whereas comparable untreated apples failed to ripen in this length of time. Grimes Golden apples treated with the acid appro...

1. 4-Chlorophenoxyacetic acid (4-Cl) was applied as a spray or a dip treatment to attached snap-bean fruits 4 days before the usual harvest date. Effect on their subsequent development and on certain after-harvest changes in the fruits were studied. 2. One thousand parts per million of 4-Cl retarded maturation of attached fruits. Fresh weight of treated fruits was 11.2, 10.1, and 11.4% greater than that of untreated ones when harvested 1, 2, and 3 weeks after treatment, and the treated fruits contained 2.3, 8.7, and 14.0% more moisture, respectively, than did the untreated ones. Application of the acid brought about a decrease of 22% in final dry weight of seeds produced, but the dry weight of pods of treated fruits was 14% heavier than that of untreated fruits at maturity. 3. Spray applications of 4-Cl at concentrations ranging from 250 p.p.m. to 1000 p.p.m. to attached fruit reduced the final yield of fresh fruit-with the most concentrated spray, by 44%. A 50-p.p.m. spray did not significantly reduce yi...

1. 2,4-Dichlorophenoxyacetic acid was applied in different concentrations (0.5, 1.0, 2.5, 5.0, and 10.0%) in dust carriers, at the rate of 4 pounds per 1000 square feet, to Kentucky bluegrass (Poa pratensis) and white clover (Trifolium repens) growing in a mixed stand in greenhouse flats. The 10.0% dusts were also tested on heal-all (Prunella vulgaris) and lawn pennywort (Hydrocotyle rotundifolia) in flats and on narrow-leaved plantain (Plantago lanceolata) growing in 3-inch clay pots in a greenhouse. 2. Comparison of Pyrax, fuller's earth, and Cherokee Clay as diluents or dust carriers at each of the concentrations indicated that there was no marked difference among them on the basis of the plant responses observed. 3. Complete eradication of clover from bluegrass turf was obtained by applications of dust containing 10.0% of the acid, but the bluegrass was severely injured and recovered only slowly. Almost complete eradication (99%) was obtained by application of dust containing 5.0% of the acid, and the...

1. Growth responses of forty-nine kinds of plants were studied when gibberellic acid, a naturally occurring plant regulator, was applied to them in various ways. The plants included representatives of various genera, species, varieties, and hybrids of agronomic, forestry, or horticultural interest. Gibberellic acid is a growth substance produced by the fungus Gibberella fujikuroi (Saw.) Wr. (conidial stage Fusarium moniliforme Sheld.), a pathogen of rice. The chemical was applied in lanolin or as an aqueous spray, dip, or soak. Treated parts of plants included stems, leaves, vegetative buds, flowers, fruits, and roots. 2. Most kinds of plants studied responded in several ways to gibberellic acid, the most obvious of these responses being stem elongation. Marked differences in the responsiveness of different genera, however, were noted. Pinto bean plants, for example, responded when sprayed with a mixture containing 0.01-p.p.m. concentration of the acid, while Virginia pine, white pine, and white spruce re...

1. Root cuttings of more than 9000 plants of Taraxacum kok-saghyz were used in experiments during December, January, February, and March, 1942-1943, to determine the response of cuttings to variations in propagation methods and to applications of β-indolebutyric, naphthaleneacetic, and naphthoxyacetic acid, and napthalene acetamide. Each compound was used in concentrations of 10, 50, and 100 p.p.m. in solution treatments and at 50, 200, and 1000 p.p.m. in talc dust. 2. The most desirable length of cutting was 1 inch, with a minimum diameter of 3/8 inch. Cuttings 1/2 inch in length were slow in callusing and rooting, while cuttings 3/4 inch long were somewhat difficult to handle and form into bundles. 3. The roots had strong polarity, and most pronounced rooting responses were obtained with cuttings set with the proximal portion up. Inverted cuttings failed to develop normally, while those laid horizontally were retarded in growth of tops and roots. 4. Under greenhouse conditions, cuttings with tops at or ...

1. The relative effectiveness of a complete series of highly purified mono-, di-, and trichlorophenoxyacetic acids in retarding the abscission of mature fruits of six varieties of apples was studied. The pentachloro- and one tetrachlorophenoxyacetic acids were also included in the experiment. 2. Each of the sixteen phenoxy compounds was applied at 1% concentration in a carrier composed of one part Tween 20 and four parts lanolin about 3 weeks before the usual harvest date for each variety. A narrow band of each acid mixture was placed at the abscission zone of each of ten tagged fruits on one tree of each variety. 3. 3,4,5-Trichlorophenoxyacetic acid was highly effective in retarding abscission of all six varieties, while 4-chloroand 2,5-dichlorophenoxyacetic acid were highly effective on five varieties. Four acids, 3-chloro-, 3,4-dichloro-, 2,3,4-trichloro-, and 2,4,5-trichloro-, were highly effective on four of the six varieties. Abscission of two varieties was effectively retarded by 2,4-D, while only ...

So far, in spite of the well known pregnancy maintaining effect of progesterone, not one of the many trials could succeed, in using progesterone or synthetic gestagens for tocolytic purposes. Therefore we have investigated the tocolytic effect of gestodene, which is supposed to be the most potent gestagene available at this time and which has, in addition, properties very similar to natural progesterone. In 26 uterine strips, obtained during cesarean section, we found a highly significant decrease of spontaneous uterine activity 10, 20 and 60 minutes after application of gestodene 10(-6) M.

In search for a new tocolytic agent we investigated felodipine, a calmodulin-antagonizing drug. Felodipine reduced the spontaneous activity of 22 uterine strips taken from the uterus in the course of a cesarean section to 52 +/- 12% (mean +/- SEM) after 10 min, to 20 +/- 7% after 20 min and to 12 +/- 4% after 60 min (P less than 0.001).

The uterus-relaxant effect of diltiazem, a recently developed calcium antagonist, was investigated in vitro. 24 myometrial strips dissected from the lower uterine segment during cesarean section showed a statistically highly significant (p less than 0.001) decrease of their spontaneous contractility in the presence of Diltiazem 10(-6) M: 82% after 10 min, 100% after 20 and 100% after 60 min (median values). Diltiazem, which is considered to be the most balanced calcium antagonist as far as cardiovascular side effects are concerned, could be of considerable interest also for clinical use.

Summary. The frequency of large granular lymphocytes and their relationship to functional NK-activity as assessed by the capacity to lyse the K562 tumour target was analysed in five allogenic and two autologous human bone marrow transplant recipients. Date revealed: (i) almost identical disappearence and reconstitution of both parameters further indicating that LGL represent effector cells of spontaneous lysis of K 562 targets; (ii) a long-lasting suppression of the absolute numbers per ml of blood of both LGL and functional NK activity which we believe was not the consequence of reconstitution with immature effector cells but rather reflected immunosuppressive therapy; (iii) LGL exhibits the fastest reappearance rate subsequent to total body irradiation of all populations of circulating leucocytes.