Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-Histidinol, a protein synthesis inhibitor and structural analogue of L-histidine, has been demonstrated in chemotherapy-treated mice to be cytoprotective to normal stem cells but to enhance cytotoxicity to tumor cells. N,N-Diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine.HCl (DPPE) is an antagonist of recently described microsomal and nuclear intracellular histamine receptors implicated in the mediation of proliferation and modulation of prostaglandin synthesis. DPPE is cytotoxic to tumor cells in vitro and cytoprotective to the gut in vivo. Noting the similar pharmacologic profiles for histidinol and DPPE and the structural resemblance between histidinol and histamine, we tested 1) whether binding to intracellular histamine receptors may be important to the action of histidinol, 2) whether there exists a differential effect of DPPE and histidinol on proliferating normal and transformed or malignant cells, and 3) whether DPPE, like histidinol, protects host cells from the effects of chemotherapy while augmenting tumor cell kill in vivo. It was observed that histidinol does compete at intracellular histamine receptors in isolated microsomes and nuclei, but with significantly lower affinity than DPPE. Nevertheless, for each agent, potency at intracellular histamine receptors correlates with potency to inhibit DNA and protein synthesis, without cytotoxicity, in normal mitogen-stimulated murine lymphocytes and to kill transformed mouse lymphocytes or MCF-7 human breast cancer cells. As demonstrated previously for histidinol (1-2 g/kg), DPPE (4 mg/kg) protected murine bone marrow progenitors from doxorubicin or fluorouracil, while doses of 4-50 mg/kg significantly enhanced the antitumor activity of doxorubicin and daunorubicin in murine models of early cancer. One postulate to explain the effects of intracellular histamine receptor ligands is that intracellular histamine mediates DNA and protein synthesis, possibly through a downward modulation of growth-inhibitory prostaglandin levels. Antagonism of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy.
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PMID:Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists. 188 59

On first admission on June 5, 1989, pulmonary adenocarcinoma of left S3b in a 62-year-old male had already metastasized to the brain and the clinical stage was T2N2M1. Radiation therapy for the metastatic brain lesion was very successful but chemotherapy for the primary lesion was not effective. He was discharged on August 24, 1989. He was readmitted to our hospital on Jan. 5, 1990 because of severe abdominal pain. His chest roentgenogram showed free air under the diaphragm. An emergency laparotomy was performed, because perforation of gastrointestinal tract was suspected. At operation, two localized tumors were found, one located in the jejunum approximately 20 cm distal to the ligament of Treitz, accompanied by perforation and another approximately 20 cm distal to the above lesion in the mesentery. The resected specimen of the perforated lesion demonstrated a deep and large ulcer, compared to the tumor size, similar to a submucosal tumor, accompanied by bridging folds. The pathologic interpretation was adenocarcinoma of the lung metastatic to the jejunum and mesentery. Primary lung cancer metastasizes to a wide variety of organs, but metastasis to the small intestine is uncommon, even on postmortem examination. Furthermore, it is rare that the metastatic lesion causes abdominal symptom leading to laparotomy.
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PMID:[A case of jejunal metastasis from pulmonary adenocarcinoma occurring as perforative peritonitis]. 188 9

A 23-year-old man was admitted with progressively disturbed vision and easy fatigability. CT scans demonstrated an enhanced mass in the sellar region. Physical and endocrinological examinations revealed atrophy of both optic nerves, temporal field cuts in both eyes, and panhypopituitarism. Concentrations of human chorionic gonadotropin (HCG) in the serum and cerebrospinal fluid were 12 and 33IU/L, respectively. On November 11, 1987, the tumor was partially removed using the transsphenoidal approach. The histological diagnosis was germinoma with syncytiotrophoblastic giant cells. Following postoperative craniospinal irradiation (whole brain, 30Gy; local, 18Gy; spinal canal 28Gy), CT scans showed no residual tumor and the HCG levels decreased until they were undetectable. Eighteen months later, the patient complained of abdominal pain. His serum HCG level had increased to 2,554 IU/L. CT scans of the abdomen revealed multiple low density areas in the liver. Chest X-ray was negative. A Ga scintigram disclosed only liver metastasis. Administration of a chemotherapy was started on June 26, 1989. Cisplatin and etoposide in doses of 20mg and 40mg respectively were given for 5 consecutive days in one course. Following four courses of the combined chemotherapy, the tumor entirely disappeared on CT scans and the HCG level returned to normal. The patient is now able to work well without evidence of recurrence. Multiple liver metastases of an intracranial germ cell tumor had been fatal in previous reports. This may be the first case with liver metastases in which the victim is still alive. The present case indicates that combined chemotherapy with cisplatin and etoposide is effective for extraneural metastases of an intracranial germ cell tumor.
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PMID:[Multiple liver metastases of a suprasellar germ cell tumor treated with combined chemotherapy of cisplatin and etoposide]. 189 Oct 59

Carcinoid tumor of the larynx is a rare neoplasm. Two cases of laryngeal carcinoid tumor are reported and the relevant literature is reviewed. One patient was an 82-year-old male who complained of odynophagia. The tumor was located on the left arytenoid and neck metastasis were present when he died 3 years after surgery. The other patient was an 82-year-old male who complained of hoarseness. His tumor was located in the left ventricle. Bone metastasis was detected one month after surgery and he died of distant metastasis two months following surgery. A review of the literature showed that carcinoid tumors of the larynx are aggressive and malignant, with distant metastasis being the most common cause of death. This tumor is unresponsive to radiotherapy and chemotherapy, so adequate surgical excision remains the only effective treatment.
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PMID:Carcinoid tumor of the larynx. 189 55

"Laetrile" is used interchangeably with "amygdalin" to designate natural substances, derived primarily from apricots and almonds, that can release cyanide, which is lethal to living organisms. In the 1920s, Dr. Ernst T. Krebs, Sr., formulated a theory that amygdalin could kill cancer cells. His theory was inconsistent with biochemical facts and has since been modified at least twice by his son, Ernst T. Krebs, Jr. Extensive work has been done by cancer scientists to test the claim that Laetrile fights cancer. Many animal experiments in the 1970s showed a complete lack of tumor killing by Laetrile. Reviews of the medical records of patients whose cancers were claimed to be reduced or cured after Laetrile treatment found insufficient medical evidence to judge Laetrile's efficacy. Finally, in a clinical trial in cancer patients reported in 1982, Laetrile neither caused shrinkage of tumors, nor increased survival time, nor alleviated cancer symptoms, nor enhanced well-being. Several reports in the medical literature document instances in which Laetrile has caused serious, life-threatening toxicity when taken in large doses in the manner prescribed by Laetrile advocates. In light of the lack of efficacy of Laetrile and its demonstrated ability to cause harm, Laetrile should not be used to treat cancer.
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PMID:Unproven methods of cancer management. Laetrile. 190 40

A putative tumor suppressor gene, p53, has been shown to be altered in a variety of human tumor types. The primary mechanism of p53 inactivation is believed to be mutation of one allele followed by loss of the second allele. Malignant mesothelioma is a tumor that has been highly associated with exposure to asbestos fibers, which are known to cause chromosomal abnormalities in mesothelial cells. We have examined four mesothelioma cell lines for genetic abnormalities in p53. Cytogenetic analysis revealed that two of the four tumors had abnormalities (numerical and/or structural) of chromosome 17 (the locus of the p53 gene). Restriction fragment length polymorphism analysis using a chromosome 17p-specific probe (pYNZ22) revealed that two tumors had loss of heterozygosity in the region of 17p13. The relative level of p53 mRNA expression was examined by Northern analysis, with one tumor showing negligible expression of p53 mRNA. The complementary DNA of p53 was generated from the three tumors showing detectable mRNA expression, and the region between codons 70 and 319 was amplified by the polymerase chain reaction and sequenced. DNA single-base substitutions were detected in two of the tumor cell lines, each resulting in amino acid substitutions. One tumor had an arginine to histidine substitution at position 175, and one tumor had a glycine to aspartic acid substitution at position 245. The observed mutations took place in regions of high cross-species sequence homology, indicating that these regions may be functionally important. The correlation of chromosomal loss in 17p on the cytogenetic and molecular level along with p53 mRNA expression and DNA sequence data indicate that genetic alterations in p53 could be a feature of malignant mesotheliomas and may reveal an important role of asbestos fibers in tumor suppressor gene inactivation.
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PMID:Genetic alterations of the p53 gene are a feature of malignant mesotheliomas. 191 60

Native vesicles isolated from Ehrlich ascites tumor cells accumulate glutamine by means of Na(+)-dependent transport systems; thiocyanate seems to be the more effective anion. The apparent affinity constant for the process was 0.38 mM. The Arrhenius plot gave an apparent activation energy of 12.3 kJ/mol. The structural analogs of glutamine, acivicin (2.5 mM) and azaserine (2.5 mM), inhibited the net uptake by 67 and 70%, respectively. The sulfhydryl reagents mersalyl, PCMBS, NEM, and DTNB also inhibited net uptake, suggesting that sulfhydryl groups may be involved in the activity of the carrier protein. A strong inhibition was detected when the vesicles were incubated in the presence of alanine, cysteine, or serine; in addition, histidine, but not glutamate or leucine, had a negative effect on glutamine transport.
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PMID:L-glutamine transport in native vesicles isolated from Ehrlich ascites tumor cell membranes. 191 14

A 56-year-old man suffered from cutaneous squamous cell carcinoma (cutaneous SCC) which occurred on a cutaneous lesion of sporadic porphyria cutanea tarda (sporadic PCT). His liver function decreased from the time he was infected with Schistosoma japonicum at the age of 10. He drank a little alcohol. Erythematous maculae with blisters or erosions occurred on sun-exposed areas of his skin when he was 52. His urine continued to be red. After detailed examinations including liver biopsy, he was diagnosed as having sporadic PCT due to liver disorder after infection with Schistosoma japonicum. At the age of 56, a small red papule arose on his right earlobe at the site of a sporadic PCT lesion. The papule rapidly enlarged with ulceration; this completely destroyed his right earlobe, which was covered with odoriferous yellow-white necrotic tissue. The tumor then extended to his right preauricular area with ulceration. A skin biopsy confirmed well-differentiated cutaneous SCC. The association of cutaneous SCC with sporadic PCT has not been previously reported; we think that the association is significant. Such an occurrence may have been induced by either direct or indirect effects of ultraviolet light or a scar formed by the sporadic PCT.
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PMID:A case of cutaneous squamous cell carcinoma associated with sporadic porphyria cutanea tarda due to liver disorder after Schistosoma japonicum infection. 191

Very recently a subset of human GH-secreting pituitary adenomas carrying a somatic mutation in the alpha subunit of the stimulatory regulatory protein of adenylyl cyclase (Gs) was identified. In all these tumors (Group 2; about 30% of all the GH secreting tumors studied) the alpha s cDNAs contained mutations; in 8 tumors mutations replaced Arginine 201 with either Cystein or Histidine while in the remaining tumors Glutamine 227 was replaced by either Arginine or Leucine. No mutations were observed in the remaining adenomas (Group 1). The two mutations caused a constitutive activation of adenylyl cyclase and a turn on of cAMP synthesis by inhibiting GTPase activity. The transformed phenotype was reflected in adenomatous cells with high rate of cAMP production and in vitro GH secretion. No difference in age, sex, clinical features, duration of the disease and cure rate were observed between the patients without (Group 1) or with alpha s mutation (Group 2), while higher serum GH levels and smaller tumor size were present in Group 2 patients. Moreover, hypersecretory activity in Group 2 tumors was also apparent at electron microscopy; cells of Group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to Group 1, Group 2 patients were less responsive to GH-releasing hormone (GHRH), while they were more sensitive to somastostatin. The former finding is in agreement with the hypothesis that the oncogenic proteins mimic the effects of extracellular growth factors, so removing the requirement for GHRH; the latter might explain the low rate of tumor growth as due to the counteracting role of endogenous inhibitory factors.
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PMID:Mutations in the alpha subunit of the stimulatory regulatory protein of adenylyl cyclase (Gs) in human GH-secreting pituitary adenomas. Biochemical, clinical, and morphological aspects. 192 49

The changes of expression of oncogenes in the mononuclear cells of MDS case was studied during his clinical course, in series. His bone marrow was considered to maintain its function partly in initial stage, since both peripheral blood and bone marrow responded to clinical episodes. However, his hematopoietic function was gradually impaired with the disease evolution to AML. We examined the expression of four oncogenes in the mononuclear cells of his three clinical stages, early RAEB-t, RAEB-t and AML, to study the cause of transformation from MDS to AML. Early RAEB-t cells expressed all oncogenes studied other than c-myb, while only c-myc was weakly observed in RAEB-t. AML cells expressed c-myc, c-jun and c-myb, except for c-fms. The expression of c-fms and c-jun of early RAEB-t was considered to reflect the monocytosis induced by infections, and the expressions of c-myb and c-myc of AML cells were regarded as one of malignant signs of tumor transformation. These findings suggest that the evolutional transformation of MDS to AML was affected by the altered expression of oncogenes.
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PMID:[Altered expression of protooncogenes during clinical course in an AML case transformed from MDS]. 194 45


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