Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen patients with multiple myeloma, two of whom had plasma cell leukemia, were treated between May 1974 and December 1978. Peptichemio was administered intravenously at doses of 40-80 mg/48 h, courses including 4-17 administrations in association with moderate doses of prednisone (15-50 mg/day) and androstanes at high dosages (250 mg weekly). In two patients PTC was associated with vincristine (VCR) administered on the first day of the course. Eight patients were previously untreated, four had been resistant to melphalan (MPH) and/or cyclophosphamide (CTX), and three had been treated irregularly with one or both of these alkylating agents. The criteria of response to therapy are reported. Out of a total of 15 PTC courses administered we obtained 13 responses, eight complete and five partial; no response was achieved in the other two patients. In the four patients who were resistant to MPH and/or CTX we obtained three responses, which were maintained with the same alkylating agent to which they had been resistant previously. The time needed to obtain a response in 90% of the patients was 6 weeks. Peptichemio was shown to be effective in patients in an advanced stage of the disease, in patients with light-chain myeloma and in those with plasma cell leukemia. The association of VCR potentiated the antitumor effect, but also increased the myelotoxicity. The PTC treatment was well tolerated. It is suggested that PTC be used in induction treatment of myelomatosis and in patients resistant to traditional alkylating agents.
Cancer Chemother Pharmacol 1982
PMID:Peptichemio induction therapy in myelomatosis. 709 2

The accuracy of ERCP and PTC in the diagnosis of pancreatic carcinoma was evaluated in a series of 376 and 112 patients, respectively. ERCP had a sensitivity of 94% and a specificity of 97%; PTC had a sensitivity of 100% and a specificity of 96%. Prior to the introduction of CT, these highly accurate examinations were the first major diagnostic procedures performed in patients with suspected pancreatic carcinoma. CT has had a significant impact on the role of ERCP and PTC and has replaced them as the initial procedure of choice. The current indications for ERCP and PTC were evaluated in a series of 211 patients with suspected pancreatic disease who were studied initially by CT. ERCP is now used to evaluate patients in whom CT is normal, equivocal, or technically unsatisfactory. PTC is used as a preoperative procedure for precise definition of biliary anatomy or for percutaneous placement of a palliative biliary drainage catheter.
Cancer 1981 Mar 15
PMID:Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) in the evaluation of suspected pancreatic carcinoma: diagnostic limitations and contemporary roles. 727 18

Prognosis of differentiated thyroid cancer is best in young women. It has been proposed that sex steroids protect premenopausal women from aggressive thyroid malignancies. Some thyroid tissues have estrogen receptors, and estrogen stimulates human thyroid cells. Tamoxifen is thought to exert its antiproliferative effects mainly by blocking estrogen stimulation. However, recently, mechanisms independent of estrogen interactions were found to be important for the favorable effect. We investigated the effect of tamoxifen on the growth, migration, and invasion in three follicular thyroid cancer cell lines (FTC133, primary; FTC236, lymph node; and FTC238, lung metastasis) from one patient and two papillary lines (PTC-UC1 and PTC-UC3). Growth was measured by dimethylthiazol-diphenyltetrazolium bromide assays, and migration was determined by the ability of cells to penetrate 8-microns pore membranes, which were covered by Matrigel for invasion assays. For in vivo experiments, we used xenografts of FTC133 in nude mice. Tamoxifen (1.5 mumol/L) inhibited the growth of all thyroid cancer cell lines (FTC133, 59%; FTC236, 42%; FTC238, 46%; P < 0.01). This effect was less pronounced in PTC-UC1 (25%) and PTC-UC3 (19%; P < 0.006) cell lines. Tamoxifen also inhibited migration and invasion of FTC more than PTC. Invasion of FTC133 was inhibited by 36% (P < 0.01), FTC236 by 30%, and FTC238 by 32%. Immunohistochemistry showed no estrogen receptors in any cell line. Also, estradiol had no significant effect on the growth, migration, or invasion of FTC or PTC. Tamoxifen treatment inhibited the growth of FTC133 xenografts in nude mice by 52% compared to that in placebo-treated controls (P < 0.002). In conclusion, tamoxifen inhibited the growth, migration, and invasion of differentiated thyroid cancer cells in vitro and in vivo. This was not reversed by estrogen. Tamoxifen acts independently of estrogen interactions and may be useful as an adjuvant treatment for some differentiated human thyroid malignancies.
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PMID:Tamoxifen inhibits growth, migration, and invasion of human follicular and papillary thyroid cancer cells in vitro and in vivo. 782 32

The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases.
Br J Cancer 1994 Dec
PMID:Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma. 798 Oct 78

The autocrine inhibitory action of transforming growth factor-beta 1 (TGF-beta 1) may play an important role in maintaining the normal state of thyroid follicular epithelial cells. Deficiency of this regulatory mechanism has been implicated in the pathogenesis of nontoxic nodular goiter and thyroid epithelial cell cancer. Tumor necrosis factor-alpha (TNF-alpha) has an antiproliferative action in a human papillary thyroid carcinoma cell line, NP-PTC cells, through a receptor-mediated mechanism. In the present work, we studied the antiproliferative action of TNF-alpha and TGF-beta 1 in NP-PTC cells. TNF-alpha induced TGF-beta 1 mRNA and secretion of the latent form of TGF-beta 1. Both TNF-alpha and TGF-beta 1 inhibited the proliferation of NP-PTC cells. A neutralizing antibody specific to human TGF-beta 1 blocked the antiproliferative action of TGF-beta 1 on NP-PTC cells, but it failed to block TNF-alpha-induced antiproliferation. Further, TNF-alpha and TGF-beta 1 acted synergistically to inhibit NP-PTC cell proliferation. The results show that both TNF-alpha and TGF-beta 1 inhibit the proliferation of NP-PTC cells. However, the actions of TGF-beta 1 and TNF-alpha differ in NP-PTC cells; TNF-alpha activates nuclear factor kappa B (NF-kappa B) and TGF-beta 1 does not. Although TNF-alpha induced TGF-beta 1 mRNA and secretion of the latent form of TGF-beta 1, the antiproliferative action of TNF-alpha is not dependent on the autocrine action of TGF-beta 1 in NP-PTC cells.
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PMID:TNF-alpha-induced antiproliferation is not dependent on the autocrine action of TGF-beta 1 in a thyroid cancer cell line. 806 Nov 20

Long-term patency and ease of insertion of self-expandable metallic stents seem to overcome the disadvantages of plastic stents, changing the therapeutic approach to unresectable biliary tree malignancies. Their high cost is the main problem of metallic stents and reducing hospitalization time is a real opportunity to overcome this problem. Self-expandable stents could be the turning point to reduce overall costs. Fifty patients with malignant biliary tree obstruction (Zubrod performance status < 3) were treated with percutaneous placement of 58 Wallstent endoprostheses by the one-step technique. All patients had undergone thorough diagnostic exams - i.e., US, CT, PTC, ERCP with biopsy or brushing. Two major complications occurred in this series: a iatrogenic pseudoaneurysm requiring selective catheterization and embolization with Gianturco coils and a hepatic abscess six months after stent placement. Late stent occlusion occurred in six patients (12%) and was resolved by balloon dilatations. All patients were followed-up with clinical examinations, US and laboratory tests until death; median survival after stent placement was 122 days (range: 70 to 510 days). Average hospitalization time was 7 days with an acceptable cost reduction.
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PMID:[Treatment of malignant occlusions of bile ducts by one-step technique using metallic endoprostheses. A multicenter study of 50 cases]. 806 59

Elevated risk of thyroid cancers among the atomic bomb survivors as compared to the nonexposed population suggests that some genetic events related to thyroid cancer must be caused by ionizing radiation. Accordingly, inducibility of RET oncogene rearrangements, i.e., the generation of the RET-PTC oncogene, specific for thyroid cancer, was investigated among human undifferentiated thyroid carcinoma cells (8505C), which do not have RET oncogene rearrangement, after 0, 10, 50, and 100 Gy of in vitro X-irradiation by means of reverse transcription polymerase chain reaction. After testing 10(8) cells at each dose point, 3 independent samples obtained with 50 Gy of X-irradiation and 6 independent samples obtained with 100 Gy of X-irradiation showed a rearranged RET oncogene amplified band. No rearranged transcripts were obtained from cells irradiated with 0 or 10 Gy. All of the transcripts were sequenced and found to contain the D10S170 and RET sequence. Interestingly, two types of rearrangements were included in these transcripts: one is specific for thyroid cancer and the other, which contains a 150-base pair insert, is atypical, not usually seen in vivo. This insert was found to be the exon of D10S170. Furthermore, in fibrosarcoma cells (HT1080), X-irradiation also induced RET oncogene rearrangements, which included the same two types of rearrangements observed in the X-irradiated thyroid cells (8505C). These results are in favor of the hypothesis that some radiation-induced thyroid cancers, including those among atomic bomb survivors, might have developed when a growth advantage was obtained through a specific form of RET oncogene rearrangement induced by radiation exposure.
Cancer Res 1993 Jul 01
PMID:In vitro irradiation is able to cause RET oncogene rearrangement. 831 99

The RET proto-oncogene encodes a receptor tyrosine kinase (TK). It has been shown that distinct germline mutations in the RET proto-oncogene are associated with the dominantly inherited cancer syndromes multiple endocrine neoplasia type 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as Hirschsprung disease (HSCR), a congenital disorder characterised by absent enteric innervation. In this study, we have transfected NIH3T3 and PC12 phaeochromocytoma cells with MEN2A (Cys634-> Arg) and MEN2B (Met918-> Thr) RET constructs. Both caused transformation of the NIH3T3 cells and differentiation of PC12 cells. The Ret (MEN2A) and Ret (MEN2B) proteins were constitutively phosphorylated on tyrosine, and their in vitro kinase activity was significantly higher than that of the wild type protein. The MTC cell line TT carries a CYs634-> Trp MEN2A mutation, and we have shown by immunoelectronmicroscopy that Ret is clustered on the cell surface in a manner reminiscent of ligand-induced aggregation of cell surface receptors. RET is activated, as RET/PTC oncogene, by somatic rearrangements which link the TK domain to a constitutive dimerization interface in papillary thyroid carcinomas. We have compared the biological and biochemical activity of the TK domains of the wild type and MEN 2B Ret in the context of the RET/PTC. The results show that the MEN 2B mutation significantly increases the TK domain enzymatic activity suggesting that dimerization may be still necessary for MEN 2B Ret to express its full activity.
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PMID:RET activation by germline MEN2A and MEN2B mutations. 857 Jan 94

Follicular thyroid cancer is the second most common thyroid malignancy after PTC. There are marked geographical variations in the relative proportions of FTC and PTC, most likely related to dietary iodine content. In iodine-deficient areas, the relative rate of FTC tends to be increased. Other risk factors for FTC include age over 50 years and female sex. Genetic factors may also have a role in determining disease susceptibility but remain ill-defined. Histologically, FTC is characterized by follicle formation and the absence of any papillary elements in the tumor. Differential diagnosis from a benign adenoma can be difficult. The degree of vascular invasiveness seems to correlate with tumor aggressiveness, and two histologic subtypes, oxyphilic FTC and insular FTC, may be associated with increased morbidity and mortality. Primary treatment for FTC is complete surgical tumor removal. Extensive bilateral surgery beyond this goal may not confer additional benefit but can facilitate adjuvant treatment and follow-up. Postoperative levothyroxine treatment is almost universally used, and patients deemed at high risk of recurrence may benefit from radioiodine remnant ablation. Treatment of metastatic disease involves operation, radioiodine, and, in selected cases, external beam radiation and chemotherapy. Prognosis for patients with metastatic disease is guarded, but most other patients have good outcomes comparable to that in PTC. For nonoxyphilic FTC, high-risk features other than initial metastases include advanced age, locally extensive disease, and the presence of marked angioinvasion. In oxyphilic FTC, DNA aneuploidy is also important. Follow-up should be most intense during the first 5 years after primary treatment and needs to be tailored to the patient's risk of disease progression. For patients at low risk of recurrence (young, small lesions, minimally invasive tumor), serum thyroglobulin measurements may largely suffice, whereas higher risk patients with elevated serum thyroglobulin levels and patients with significant titers of interfering anti-thyroglobulin autoantibodies may also need to undergo periodic diagnostic radioiodine scanning.
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PMID:Follicular thyroid cancer. 860 79

The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.
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PMID:Human homolog of patched, a candidate gene for the basal cell nevus syndrome. 865 45


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