Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of glutathione transferase in human malignant melanoma cell lines and solid tumor material has been analyzed and compared with the enzyme composition in fibroblasts and naevus samples. All cells and tissues investigated contained essentially only the acidic class Pi glutathione transferase as demonstrated by SDS-PAGE and immunoblotting. The enzyme was purified from tumor material and characterized. Its intracellular concentration was significantly higher in all the melanoma cell preparations analyzed than in the non-malignant cells, supporting the view that the class Pi glutathione transferase may contribute to the drug resistance that is characteristic of malignant melanoma.
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PMID:Expression of class Pi glutathione transferase in human malignant melanoma cells. 311 48

Previous studies have shown that human IgG1 contains a 'reactive' disulfide bridge (SS*), detectable by a 24-hour disulfide exchange reaction, and that the serum level of this IgG subclass is selectively diminished in patients with various malignant diseases. Here we present evidence that in rats IgG2b is the only subclass that carries one SS* per molecule. Furthermore, it is shown that rats inoculated with experimental tumor lines, i.e., the Yoshida hepatoma ascites tumor and the Walker 256 carcinosarcoma growing in ascites or as solid tumor, exhibit significantly decreased SS* per mole IgG which corresponds to a selective diminution of IgG2b. Although at later stages there is a quantitative correlation with the tumor burden, with the Walker tumor this effect becomes significant as early as 24 h after inoculation, i.e., well before exponential tumor growth and an absolute reduction of total IgG. Control animals injected intraperitoneally with either viable spleen cells or irradiated Walker 256 cells did not show comparable alterations in their IgG subclass profile. Thus, the selective defect of IgG2b requires the presence of viable and proliferating tumor cells. Possible mechanism(s) of tumor-associated shifts in IgG subclasses are discussed.
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PMID:A decrease in reactive disulfide bonds of serum IgG signals a characteristic change in the IgG subclass patterns of rats bearing experimental tumors. 824 96

Gestational trophoblastic disease is a term that describes a group of tumors that share several characteristics as follows: (1) they arise in fetal chorion, (2) they produce human chorionic gonadotropin (hCG), and (3) they respond extremely well to chemotherapy. Although rare, they have received a disproportionate amount of attention because they were the first metastatic solid tumor to be cured using chemotherapy. Also, hCG was the first reliable tumor marker. Finally, because they arise in fetal tissue, they have the potential for a strong immune response against paternal antigens in the tumor. This potential for immunologic rejection was thought initially to explain the success of chemotherapy in this disease. The early detection of gestational trophoblastic disease is successful in patients who have had a hydatidiform mole as the pregnancy event that begins the process but unsuccessful in the early detection of the development of choriocarcinoma after a normal term delivery, abortion (spontaneous or elective), or ectopic pregnancy. Surveillance after evacuation of a molar pregnancy (whether complete or a partial mole) consists of regular evaluation of hCG production and the detection of metastatic disease. However, the development of gestational choriocarcinoma after term pregnancy or an abortion (no molar tissue can develop as a consequence of these pregnancies) is detectable only by signs or symptoms of metastatic disease in any of the many organs to which this tissue can spread. Unlike most staging classifications in gynecologic cancers, which are based on histologic findings and tumor location, the classification used in gestational trophoblastic disease stresses other features that are more useful for treatment selection. Both the National Institutes of Health and the World Health Organization classifications emphasize the importance of recognizing factors that predict the likelihood of a tumor responding to chemotherapy. Currently available treatment can cure all patients except those who are in the very high-risk group, which usually is characterized by metastasis to the brain or liver or a history of prior chemotherapy. Even in this category, approximately 80% of patients are curable.
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PMID:Diagnosis and management of gestational trophoblastic disease. 838 9

Animal models of human malignant skin melanoma were created in melanoma-susceptible inbred-strain transgenic mice by grafting skin from donors of high-susceptibility lines to hosts of a low-susceptibility line, thereby overcoming the problem of early death of the more susceptible animals from eye melanomas. As already described [Mintz, B. & Silvers, W. K. (1993) Proc. Natl. Acad. Sci. USA 90, 8817-8821], melanocytes within the grafts selectively proliferated in close proximity to areas of greatest wound healing, presumably in response to mitogenic factors from cells contributing to wound repair. An orderly sequence of externally visible events culminated in malignant melanoma. We examine here the histogenetic concomitants of these changes and find that they define a stepwise sequence strikingly comparable to that leading to human cutaneous melanoma. Moreover, the histological details suggest some of the underlying mechanisms. While the early lesions are first seen in the superficial dermis in the mouse, and in the basal layer of the epidermis in the human, both progress by radial growth followed by vertical growth. Melanocytic hyperplasia resulted in nests of densely melanized fusiform cells which were losing their dendrites. Some discrete lesions in the deep dermis appeared as blue nevi. As radial proliferation advanced, cellular atypia increased and the previously independent melanocytes cohered closely and formed a small solid tumor; the cells were usually then hypomelanotic or amelanotic. Ulceration of tumor through the epidermis occurred early. The tumor mass grew rapidly in the deep dermis and invaded and destroyed subcutaneous tissue and muscle. Primary tumors in the skin were often heterogeneous, with lobules or regions differing in pigmentation or atypia. However, the cells in circulating emboli, or in metastases in lymph nodes and lungs, appeared relatively homogeneous. These genetically uniform transgenic mouse models provide experimental access to the multistage genesis of melanoma.
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PMID:Histopathogenesis of malignant skin melanoma induced in genetically susceptible transgenic mice. 841 14

Poly(L-histidine)-poly(ethylene glycol) diblock copolymers (polyHis-b-PEG) were prepared and used for the construction of polymeric micelles responding to local pH changes in the body. PolyHis was synthesized by ring opening polymerization of L-histidine N-carboxyanhydride, the imidazole amine group of which was protected by the dinitrophenyl group. The resulting polymer (M(n): 5,000 g/mole) was coupled to poly(ethylene glycol) (M(n): 2,000 g/mole) via an amide linkage using the dicyclohexyl carbodiimide and N-hydroxysuccinimide-mediated reaction. The block copolymer in dimethyl sulfoxide formed polymeric micelles on diafiltration against a borate buffer at pH 8. Dynamic light scattering and atomic force microscopy showed the micelles were spherical, diameter approximately 114 nm, with a unimodal distribution. The critical micelle concentration (CMC) at pH 8.0 was 2.3 mg/l. The CMC increased markedly on decreasing the pH of the diafiltration medium below 7.2. Micelles prepared at pH 8.0 were gradually destabilized below pH 7.4, as evidenced by a slight increase in light transmittance, an alteration in size distribution, and a decrease in the pyrene fluorescence intensity. It was concluded that the ionization of the polyHis block forming the micelle core determined the pH-dependent CMC and stability. After further optimization of the pH-sensitivity, pH-sensitive micelles are expected to have application for solid tumor treatment, exploiting the fact that most solid tumors have an acidic extracellular pH.
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PMID:Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization. 1288 Jul 3

Nevus sebaceous of Jadassohn is a congenital hamartoma that usually affects the scalp and face. Several benign or malignant neoplasias may develop in the lesion and the most common are trichoblastoma, syringocystadenoma papilliferum, and basal cell carcinoma. Trichilemmoma is a benign solid tumor originating from external sheath cells of pilosebaceous follicles. When it is characterized by a central zone of desmoplasia, it is called desmoplastic trichilemmoma. We report a case of a 58-year-old patient who developed a tumor in a sebaceous nevus. We performed a total excision of the lesion. Histopathological diagnosis was compatible with desmoplastic trichilemmoma. Our literature review reveals that the occurrence of trichilemmoma desmoplastic is unusual. Moreover, it can mimic an invasive carcinoma on histological and clinical examinations. This fact confirms the importance of reporting the occurrence of this rare cancer in a nevus sebaceous of Jadassohn.
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PMID:Rare desmoplastic trichilemmoma associated with sebaceous nevus. 2936 42

ALK-fused spitzoid neoplasms represent a distinctive group of melanocytic lesions. To date, few studies addressed genetic and chromosomal alterations in these lesions beyond the ALK rearrangements. Our objective was to study genetic alterations, including ALK gene fusions, telomerase reverse transcriptase promoter (TERT-p) mutations, chromosomal copy number changes, and mutations in other genes. We investigated 29 cases of Spitz lesions (11 Spitz nevi and 18 atypical Spitz tumors), all of which were ALK immunopositive. There were 16 female and 13 male patients, with age ranging from 1 to 43 years (mean, 18.4 years). The most common location was the lower extremity. Microscopically, all neoplasms were polypoid or dome shaped with a plexiform, predominantly dermally located proliferation of fusiform to spindled melanocytes with mild to moderate pleomorphism. The break-apart test for ALK was positive in 17 of 19 studied cases. ALK fusions were detected in 23 of 26 analyzable cases by Archer FusionPlex Solid Tumor Kit. In addition to the previously described rearrangements, 3 novel fusions, namely, KANK1-ALK, MYO5A-ALK, and EEF2-ALK, were found. Fluorescence in situ hybridization for copy number changes yielded one case with the loss of RREB1 among 21 studied cases. TERT-p hotspot mutation was found in 1 of 23 lesions. The mutation analysis of 271 cancer-related genes using Human Comprehensive Cancer Panel was performed in 4 cases and identified in each case mutations in several genes with unknown significance, except for a pathogenic variant in the BLM gene. Our study confirms that most ALK fusion spitzoid neoplasms can be classified as atypical Spitz tumors, which occurs in young patients with acral predilection and extends the spectrum of ALK fusions in spitzoid lesions, including 3 hitherto unreported fusions. TERT-p mutations and chromosomal copy number changes involving 6p25 (RRB1), 11q13 (CCND1), 6p23 (MYB), 9p21 (CDKN2A), and 8q24 (MYC) are rare in these lesions. The significance of mutation in other genes remains unknown.
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PMID:A Clinicopathological Study of 29 Spitzoid Melanocytic Lesions With ALK Fusions, Including Novel Fusion Variants, Accompanied by Fluorescence In Situ Hybridization Analysis for Chromosomal Copy Number Changes, and Both TERT Promoter and Next-Generation Sequencing Mutation Analysis. 3270 92