Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-three patients with disseminated refractory malignancies each received an individually-specified combination of either Adriamycin (24 patients) or mitomycin-C (19 patients) conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously. Seventeen out of twenty-four patients had reactions to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression. Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C patients. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors and colon with likely drug induced colitis seen after colon binding. This study demonstrates the feasibility and illustrates technical considerations in preparing drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery was accomplished. The major technical hurdle appears to be the selection of effective conjugation methods that can be used to optimally bind drugs to monoclonal antibodies for targeted cancer therapy.
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PMID:Individually specified drug immunoconjugates in cancer treatment. 250 30

T-cell-growth-factor (TCGF) activate peripheral blood lymphocytes (PBL), cultured for 14 days, showed killer cell activities against natural-killer resistant Daudi cells in a 4 h 51Cr-release assay. However, the effector cells obtained from patients with nonresectable carcinoma exhibited very much lower cytotoxicity to tumor cells. To analyze the mechanism of depression, we have attempted to examine suppressor cell activities of the TCGF-activated PBL. The assay for the suppressor cell activities was made by in vitro inhibition of cell-mediated cytotoxicity by incubating radiolabeled target tumor cells with lymphokine-activated killer (LAK) cells and TCGF-activated PBL. LAK cells were induced by cultivation with recombinant interleukin-2. TCGF-activated PBL, obtained from four out of ten patients with resectable carcinoma and nine out of ten patients with nonresectable carcinoma, significantly suppressed the LAK cell activities. However, this suppression was not observed in TCGF-activated PBL from ten normal healthy control subjects. TCGF-activated PBL with immunosuppressive reactivity were named lymphokine-activated suppressor (LAS) cells. To investigate the phenotypic characterization of TCGF-activated PBL, the cells were analyzed by two-color flow cytometry. TCGF preferentially expanded CD8+CD11- cells and decreased the growth of CD8+CD11+ cells in both normal healthy control subjects and gastric cancer (resectable and nonresectable) patients. Dominantly expressed CD8+CD11- cells on TCGF-activated PBL in patients--especially those with nonresectable gastric carcinoma--showed strong LAS cell activity, irrespective of the presence of killer cell activities of CD8+CD11- cells in TCGF-activated PBL from normal healthy control subjects. The results suggested the generation of CD8+CD11- LAS cells from cancer patients, and revealed that CD8+CD11- T-cells contained killer and/or suppressor cell function. In addition, it was found that the TCGF-activated PBL from gastric cancer patients were associated with an increased proportion of CD4+ Leu8+, HLA-DR+CD8+ and HLA-DR+CD25+ cells.
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PMID:Lymphokine-activated suppressor (LAS) cells in patients with gastric carcinoma. 252 49

The authors studied 8 patients (4 males and 4 females) with Cushing's syndrome due to ectopic ACTH secretion. Chronological age ranged from 15 to 45 years and duration of the disease ranged from 3 to 48 months. All patients presented typical signs of Cushing's syndrome, blood hypertension, and four of them had hyperpigmentation of the skin. Five patients had fasting hyperglycemia and all patients but one had serum hypokalemia (serum K = 2.2 to 3.9mEq/l). The circadian rhythm of cortisol was absent in all patients and basal cortisol levels were elevated in all patients but one. Basal ACTH levels evaluated in 7 patients were elevated in 6 (29 to 1050 pg/ml-MRC). One patient presented normal depression of urinary 17-OH after two days of dexamethasone and normal increase of urinary 17-OH and serum 11-dexycortisol after methyrapone. Four patients had carcinoid tumor (3 thymic and 1 bronchial), two had pancreatic islets cell tumors, one had bilateral pheochromocytoma and medular carcinoma of the thyroid, and one had oat cell carcinoma of the lung and medular carcinoma of the thyroid. Thoracic X-rays identified the ectopic ACTH secretion tumor in four cases, all confirmed by CT scan. Abdominal CT showed a difuse enlargement of the adrenals in seven cases and bilateral nodules in one case (pheochromocytomas). Six patients died within 3 years of the diagnosis. The authors concluded that clinical and hormonal findings could mislead the findings of ACTH ectopic secretion and Cushing's disease, and suggest that thoracic X-rays and CT scans of the skull, thorax, and abdome should be done in all cases of Cushing's syndrome.
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PMID:[Cushing syndrome due to ectopic ACTH secretion]. 255 51

This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.
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PMID:Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation. 259 May 46

Excess body fat has been clearly associated with an increased risk of oligo-ovulation and endometrial/breast carcinoma. The connection has been assumed to lie within derangements of the metabolic/endocrine compartments, particularly of estrogens and androgens. To differentiate the effect of obesity from its related disease process, an attempt has been made to define the reproductive-endocrinologic alterations encountered in otherwise asymptomatic obese women. Androgen metabolism is accelerated in obesity. It is not clear whether the increased clearance precedes or follows the accelerated production of androgens. A servocontrol mechanism appears to be operative in these asymptomatic individuals, maintaining plasma steroid levels normal. The unbound fraction of T may be somewhat increased in overweight women with predominantly upper body fat deposition. The increased clearance of androgen may arise from an obesity-related depression in SHBG concentration (e.g., for T, E2, delta 5-diol, etc.). Adipose tissue, by virtue of the lipid solubility of most of these steroids, concentrates androgens, estrogens, and progesterone. This steroid sequestration not only contributes to the obesity-related increase in androgen clearance but also leads to an extremely enlarged total body steroid pool. Fat tissue sequestration also increases the concentration of androgens in the vicinity of adipose stromal cells, possibly encouraging their aromatization. Adipose tissue also has a moderate degree of 17-hydroxysteroid dehydrogenase activity, which appears to stimulate the conversion of A to T. Finally, alterations in peripheral and hepatic conjugation and an accelerated urinary excretion may contribute to the elevated clearance of androgens. The accelerated PR of androgens may simply result as compensation for the elevated MCR in obesity. Nonetheless, evidence of alteration(s) in adrenocortical steroidogenesis has been presented suggesting a selective obesity-related enhancement in adrenal androgen secretion. These remain to be confirmed. Nonetheless, adrenocortical abnormalities may arise secondary to the influence of other circulating and intra-adrenal factors, including insulin, prolactin, estrogens, and androgens. It is not known whether the accelerated androgen metabolism or the aberrant adrenal steroidogenesis improve with weight reduction. Excess body fat increases androgen aromatization which, together with an obesity-related decrease in SHBG, is associated with mildly elevated levels of E1 and free E2 in postmenopausal women. Although premenopausal obese individuals have the same tendency, the far greater ovarian estrogen secretion overshadows any differences. The bulk of aromatization activity in fat lies in the stromal comportment. The major substrate for peripheral estrogen production is A. Testosterone also contributes to the estrogen pool via its conversion to E2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reproductive endocrinologic alterations in female asymptomatic obesity. 268 Jun 25

A case of a IIa + IIc type early carcinoma of the rectum is reported. A 62-year-old man, who had been checked by immunological latex agglutination faecal occult blood testing, underwent a colorectal examination at Hakodate Chu-o Hospital. A barium enema revealed a slightly elevated lesion with a central depression in the lower rectum. Colonoscopic examination showed a IIa + IIc type of early rectal carcinoma. Study of the resected specimen also confirmed a IIa + IIc type early rectal carcinoma, 17 x 15 mm in diameter. Histologically, a lesion was located within the mucosa and consisted of both a carcinoma and an adenoma. Immunological latex agglutination faecal occult blood testing was thought to be useful for mass screening detection of a colorectal carcinoma.
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PMID:[A case of IIa + IIc type early carcinoma of the rectum, with no invasion of the submucosa]. 273 78

In electrophysiological experiments the reflectory reaction of the efferent impulsation in the vagus nerve elicited by the stimulation of the lung and airway receptors was studied in the mice with the lung Lewis carcinoma. It has been established that the extension of the metastatic process was accompanied by the disturbances in the relationships of the central cholin- and dopaminergic mechanisms of the respiratory nervous regulation with hyperactivation of the former and depression of the latter. The use of the neurotropic drugs of the central action normalizing or disturbing these interrelations inhibits or stimulates, respectively, the metastatic process.
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PMID:[Changes in the efferent impulsation in the vagus nerves during the metastasis of Lewis lung carcinoma in mice]. 275 43

The new phospholipid analogue 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine inhibits the phospholipid-calcium-dependent protein kinase, partially purified from Walker carcinoma cells with a Ki value of 0.56 microM. The compound inhibits the phorbol ester stimulated phosphorylation of the ribosomal protein S6 indicating that the depression of Ca2+-phospholipid-dependent protein kinase by the alkyl phospholipid also occurs in intact cells. The dose effect curve for the inhibition of cell proliferation by 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine in Walker cells exhibits a close correlation to the dose effect curve for the depression of Ca2+-phospholipid-dependent protein kinase activity. Although alternative mechanisms cannot be excluded, the data suggest that the growth inhibitory activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine correlates with the inhibition of Ca2+-phospholipid-dependent protein kinase. The antiproliferative activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine is synergistically enhanced by cis-diamminedichloroplatinum(II).
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PMID:Synergistic enhancement of the antiproliferative activity of cis-diamminedichloroplatinum(II) by the ether lipid analogue BM41440, an inhibitor of protein kinase C. 275 9

Thirty-four minute (less than 5 mm in the largest diameter) and 60 small (6 to 10 mm in the largest diameter) early gastric carcinomas (EGCs) were studied to assess the correlation between gross and histologic features. The characteristic macroscopic feature of many of the histologically differentiated, minute and small EGCs was a depression accompanied by a circumferential elevation of the adjacent noncancerous mucosa. The circumferential elevation was carefully studied histologically. On the other hand, most of the undifferentiated-type minute EGCs included a proliferation of the malignant cells affecting the lamina propria in the middle layer of the mucosa, leaving noncancerous glands and foveolae, and therefore presenting no specific macroscopic change. Most of the undifferentiated-type small EGCs, however, manifested distinct depressions, with or without ulceration; these EGCs were histologically made up of a compact proliferation of carcinoma cells that destroyed both the foveolae and glands. These findings clearly showed the difficulty in detecting the undifferentiated type of minute EGCs and explained the increase in the frequency of the differentiated type in EGCs with a decrease of the size of clinically detectable EGCs. Topographic mapping of the EGCs revealed that the undifferentiated-type minute EGCs that occurred in the middle third of the stomach may well be overlooked.
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PMID:Histopathologic features of minute and small human gastric adenocarcinomas. 275 94

The growth type of early colorectal carcinoma was classified into two types. The first type is intramucosal polypoid growth (PG-Ca) and the second type nonpolypoid growth (NPG-Ca) which shows mainly massive infiltration of tumor cells below the submucosal layer. The incidence of adenoma-carcinoma sequence was 72 of 75 lesions (96.0%) in pedunculated polypoid carcinoma, and 61 of 71 lesions (85.9%) in sessile and broad-based polypoid carcinomas. Their average sizes were 15.0 and 18.7 mm, respectively. Submucosal invasive carcinoma (SM-Ca) showed a low incidence. They were detected as microscopical or scattered lesions with a few lymphatic and venous permeation. The NPG-Ca contained 32 lesions. Intramucosal carcinoma without adenoma showing slight depression consisted of ten lesions of which the average size was 5.1 mm. The other 22 lesions showed massive submucosal invasion with marked lymphatic and venous permeation. The average size was 10.3 mm being smaller than PG-Ca. Histologically, NPG-Ca was not accompanied with adenoma. The NPG-Ca arose from de novo carcinoma less than 10 mm in diameter and invaded into the submucosal layer. In advanced carcinoma, the PG-Ca showed a low incidence (21.8%), and almost all cases were of the NPG type (78.2%). The NPG advanced carcinomas increased in those over the size of 20 mm. It is concluded that nonpolypoid early colorectal carcinomas easily progress to advanced carcinoma, and de novo carcinoma occupied about 80% of colorectal carcinoma.
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PMID:Early colorectal carcinoma with special reference to its development de novo. 275 87


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