Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past 10 years there has been significant progress made in the recognition and treatment of soft tissue sarcomas. With the advent of CAT scans and MRI, preoperative delineation of soft tissue tumors has become readily available. The diagnostic use of these modalities in patients presenting with an ill-defined asymptomatic mass has been extremely helpful in terms of screening patients to decide whether or not a biopsy is indicated. These techniques have also provided a much clearer delineation of the anatomic extent of the primary tumor, which has been of great assistance both in radiation therapy treatment calculations as well as in preoperative surgical planning. The recognition that tumor grade is the dominant prognostic variable has resulted in the more common use of a grading system, and a more uniform reporting and stratification of end results. Recent studies with immunohistochemical staining have proven of value in determining the histogenesis of many tumors that in the past were difficult to classify accurately. Most recently the use of flow cytometry suggests that this will also be a valuable adjunct in determining tumor grade and thereby prognosis. The most recent investigations of molecular biologic evaluation of genetic DNA and RNA sequences, as well as of oncogenes are extremely interesting from a diagnostic standpoint and in demonstrating the potential of molecular biologic evaluation for understanding the origin of these tumors. Multimodality therapy with surgery, radiation, chemotherapy, or all three has resulted in a marked improvement in local tumor control for patients with soft tissue sarcomas. The combination of modalities has allowed smaller surgical excisions of the tumor and thereby preservation of the extremity and much of its function. There are currently several different methods of multimodality therapy used including neoadjuvant therapy and postoperative therapy, both of which have been proven efficacious. Chemotherapy is now playing an increased role in clinical investigation and treatment. The availability of Adriamycin, DTIC, cisplatin, and most recently ifosfamide has added several chemotherapeutic agents for use by the clinician. Combination chemotherapy and radiation is of value in the neoadjuvant setting, and several studies are now underway to determine whether postoperative adjuvant chemotherapy is of similar value in reducing systemic spread of disease. Finally, surgical resection of pulmonary metastases has been proven of value in 20% to 25% of patients who subsequently develop metastatic disease. As a result of these advances in several different treatment disciplines, the overall survival rate and quality of life of patients with soft tissue sarcoma have improved markedly over the past 10 years.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Progress in the recognition and treatment of soft tissue sarcomas. 240 92

In a phase I trial 34 patients with pancreatic cancer were treated with the murine monoclonal antibody (MAb) BW 494 (BI 51.011) directed against a glycoprotein antigen. The patients received repeated doses of MAb over a time period from 5 to 14 days (highest single dose 100 mg, highest cumulative dose 490 mg). During this treatment serum levels of murine IgG increased to 43.4 micrograms/ml. The serum half life of murine IgG ranged from 2 to 3 days. Repeated injections of MAb BW 494 were normally well-tolerated when given within the first 15 days. Two patients presented with fatigue and a neuritis-like syndrome 2 weeks after the last IgG infusion which had resolved spontaneously by the next day. Severe allergic reactions were observed in 3 patients after repeated injections of the MAb. These 3 patients had high levels of human anti-murine antibodies (HAMA). Four weeks after the first application of MAb BW 494, 17/18 patients presented with HAMA (IgG). It could be demonstrated that the anti-murine response was in part anti-idiotypic. At the moment 16/34 patients are eligible for evaluation of tumor response. There was no complete or partial remission; however, 2 patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in CAT scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). Nine patients had progressive tumor disease in spite of MAb treatment.
 ...
PMID:Immunotherapy of pancreatic cancer with monoclonal antibody BW 494. 316 51

Previously, histologic precision in the diagnosis of urologic cancers had, for some time, remained stable. More recently, variations in classifications of testis tumors, prostate cancer, and to some degree, bladder tumors, have been introduced. Most systems have in concurrence a desire or an attempt to infer better prognostic assessment in the overall results to treatment. With the advent of additional biological markers or direct enzymatic measurements, e.g., in prostate cancer, further improvements in identifying at risk populations, responses to treatment, and possible indications for variations in treatment, have ensued. These developments alone unquestionably mark the greatest area of change in the recent decade. The extent of disease assessment prior to definitive therapy, whether by arteriography, ultrasound, CAT scanning, or an occasional lymphangiography, has also influenced or modified treatment decisions. For continuing care and follow-up, several of these noninvasive techniques are now becoming included in the more standard approaches. Noninvasive techniques have been introduced for the therapy of renal tumors such as inducing infarction of the primary tumor. Endoscopic ultrasonic techniques have been particularly useful in assessing the size of pelvic tumors and response to treatment, even in detection of unexpected multiple primaries or metastatic extensions. Overall, the precision in urologic cancer, both for diagnostic and detection purposes, has been increased with these introductions.
 ...
PMID:The diagnosis and detection of urogenital cancers. 616 54

Computerized axial tomographic scans (CAT scans) of thorax and abdomen were used as part of the initial staging procedure of 50 consecutive patients with small-cell bronchogenic carcinoma (SCBC). The aims were to define the extent of the primary tumor and metastatic spread, and to compare the information obtained from CAT scans with conventional staging procedures. With CAT scanning, spread of the primary tumor was found to be far more extensive than originally believed when defined by conventional assessment. Of 35 patients conventionally staged as localized T1 or T2 tumors, 27 (77%) had their stage increased to extensive T3 disease. similarly, subcarinal lymph nodes were found in one patient when conventional methods were used (2%), but 16 patients (32%) were found when CAT scan was used. Unsuspected adrenal metastases were found in eight patients (16%) and retrocrural nodes in four patients (8%). Thirty-seven patients (74%) were found to have Stage III tumors when conventional staging was used; 47 patients (94%) were found to be Stage III following CAT scanning, demonstrating that, within the thorax, localized tumors are very uncommon. CAT scanning demonstrates the degree of intrathoracic spread very clearly, and has a valuable role in the initial investigation of patients with SCBC if the planned treatment includes radiotherapy.
 ...
PMID:Computerized axial tomography in the pretreatment assessment of small-cell carcinoma of the bronchus. 626 27

Tumor specimens obtained from 136 patients with primary carcinoma of the uterine cervix were analyzed for the presence of human papillomavirus (HPV) sequences and for mutation of the TP53 gene. Polymerase chain reaction (PCR) showed that 130 of 136 (96%) tumors contained an oncogenic HPV 16 or 18 sequence. HPV 16 was the predominant type in cervical squamous cell carcinomas and HPV 18 was significantly associated with cervical adenocarcinomas (p < 0.05). The more dedifferentiated the primary tumor, the more frequent the HPV 16 infection and the more differentiated, the more frequent the HPV 18 infection (p < 0.05). Two out of 136 (1.5%) tumors demonstrated single-strand conformation polymorphism (SSCP) band shifts. One (positive for HPV 18) had a nonsense mutation of codon 101 in exon 4 from AAA to TAA transversion. Another (positive for L1 consensus primer set) showed a point mutation involving codon 179 in exon 5 changing CAT to CGT transition. The three specimens negative for HPV did not contain TP53 gene mutations. Our data show that mutation of TP53 is infrequent in primary cervical carcinoma and there is no inverse correlation between HPV infection and TP53 gene mutation. Other mechanisms independent of TP53 inactivation may also be implicated in tumorigenesis of the uterine cervix.
 ...
PMID:Human papillomavirus infection and TP53 gene mutation in primary cervical carcinoma. 920

In 1986, The Hospital for Sick Children (Toronto, Canada) began to use a standard preoperative chemotherapeutic regimen for patients who had unresectable hepatoblastoma. In 1988, we extended this protocol to all children who had hepatoblastoma. Of 25 children who presented with hepatoblastoma, 22 were eligible for protocol therapy. After percutaneous biopsy, cycles of cisplatin (20 mg/m2/d for 5 days) and Adriamycin (25 mg/m2/d for 3 days) were administered every 3 weeks by continuous intravenous infusion. A CAT scan was performed after the third cycle. Surgery was undertaken if response indicated that complete resection was possible. If not, a further one to three cycles were given until response was adequate. Postoperatively, therapy was continued for a total of six cycles. Twenty of twenty-two (91%) tumors responded to chemotherapy. Over half required only three cycles. Twenty hepatic resections (6 segmentectomies, 10 lobectomies, 4 trisegmentectomies) were performed. Preoperative therapy significantly reduced the extent of resection calculated to be necessary for complete excision at an initial diagnosis of the primary tumor in all but one. In the two children with inadequate response, total hepatectomy and transplant was necessary for complete resection. No deaths or operative delays were attributed to chemotherapy toxicity. Nineteen of 22 children (87%) are alive with no evidence of disease, including both transplant patients. One death was caused by intraoperative bleeding and the other two were caused by metastatic lung disease at 22 and 26 months, respectively. Twelve children, eight with tumors that would have been unresectable before effective chemotherapy, have had follow-up for more than 5 years. This protocol of preoperative chemotherapy appears to be safe and effective for most children who have hepatoblastoma.
 ...
PMID:Improved long-term survival with preoperative chemotherapy for hepatoblastoma. 924 21

Recently, expression of the alpha 4 integrin subunit has been shown to be inversely correlated with the invasive potential of B16 mouse epidermal melanoma. The purpose of this study was to establish whether expression of the human alpha 4 integrin subunit gene might be similarly regulated in human uveal melanoma which has varying degrees of invasiveness, and whether such modifications are determined by alterations in the transcriptional activity directed by the alpha 4 gene promoter. Two metastatic variants (MH5 and MH10) derived from a human uveal melanoma (SP6.5) were used. Expression studies were performed by transiently transfecting each of these cell lines with recombinant plasmids bearing various lengths of the alpha 4 promoter fused to the CAT reporter gene, and were further validated by Northern blot analyses of the alpha 4 transcript. Both transient transfection and mRNA analyses provided evidence that the transcriptional activity directed by the alpha 4 promoter sequences extending up to position -76 and -120 was indeed inversely correlated to the potential of uveal melanoma to yield metastasis. Experiments in electrophoretic mobility shift assay (EMSA) demonstrated that binding of the nuclear proteins that likely account for transcription of the alpha 4 gene to alpha 4.1 (namely Bp1, Bp2, Bp4, and Bp5) was dramatically reduced in uveal melanoma, but not in normal uveal melanocytes. These results highlight the fundamental function the alpha 4 integrin subunit may play in the ability of tumor cells to evade the primary tumor and form metastasis.
 ...
PMID:Transcriptional regulation of the alpha 4 integrin subunit gene in the metastatic spread of uveal melanoma. 985 37

We performed dual (two-color) fluorescence in situ hybridization (FISH) using direct fluorescent labeling probes for p53 and chromosome 17 in six gastrointestinal (3 stomach and 3 colon) cancers. In three of these (1 stomach and 2 colon) the interphase cell nuclei showed an imbalance of signals for the p53 and chromosome 17; that is, the p53 signal count was lower than the chromosome 17 signal count, indicating deletion of the p53 gene. Moreover, metaphase FISH analysis demonstrated that those nuclei actually had a chromosome 17 with deletion of the p53 gene. Interestingly, these three cases had an abnormal chromosome 17 copy number, that is, chromosome 17 aneusomy. Furthermore, to investigate the possibility of p53 mutation in tumors with an imbalance of signals for chromosome 17 and p53 per nucleus, we performed a GeneChip p53 assay which has recently been developed. GeneChip p53 assay demonstrated that a primary tumor sample from one colon cancer case had a heterozygous point mutation of CGT (Arg) to CAT (His) at codon 273 in exon 8. In addition, a sample of metastatic tumor in the liver from the same case revealed two heterozygous point mutations. One of them was the same mutation as that is the primary tumor; the other was GTG (Val) to GGG (Gly) at codon 217 in exon 6. In conclusion, we found that the combination of dual-color FISH and GeneChip p53 assay offered reliable results and important information concerning not only deletion of the p53 gene and chromosome 17 aneusomy but also p53 mutations. Using these techniques, we demonstrated that an imbalance of signals for chromosome 17 and p53 per nucleus, chromosome 17 aneusomy, and accumulation of p53 mutations had occurred during carcinogenesis and development of gastrointestinal cancers.
 ...
PMID:Detection of aberrations of 17p and p53 gene in gastrointestinal cancers by dual (two-color) fluorescence in situ hybridization and GeneChip p53 assay. 1095 39

Despite intensive high-dose chemotherapy and autologous hematopoietic stem cell transplantation, disseminated neuroblastoma (NB) frequently proves to be chemosensitive but not chemocurable, and more often so in NB-presenting MYCN amplification. To assess the direct relationship between the MYCN oncogene and chemoresistance acquisition during NB metastatic dissemination, we have studied MYCN and MDR1 genes using the human IGR-N-91 ectopic xenograft metastatic model. This characterized experimental in vitro model includes human neuroblasts derived from a subcutaneous primary tumor xenograft, disseminated blood cells, myocardium, and bone marrow (BM) metastatic cells. All IGR-N-91-derived neuroblasts harbor a consistent MYCN genomic content but, unlike primary tumor xenograft, BM, and myocardium, human neuroblasts elicit a concomitant increase in MYCN and MDR1 transcripts levels, consistent with chemoresistance phenotype and active P-gp. In contrast, no variation of MRP1 transcript level was associated with the metastatic process in this model. Using an MDR1 promoter-CAT construct, we have shown that the MycN protein activates MDR1 transcription both in exogenous transient MYCN-transfected SK-N-SH cells and in endogenous BM metastatic neuroblasts with an increase in the MYCN transcript level. Band-shift experiments indicate that IGR-N-91 cells enriched with the MycN transcription factor do bind to two E-box motifs localized within the MDR1 promoter. Overall, our data indicate that MYCN overexpression increment contributes to the acquired drug resistance that occurs throughout the NB metastatic process.
 ...
PMID:MYCN enhances P-gp/MDR1 gene expression in the human metastatic neuroblastoma IGR-N-91 model. 1281 37

Our analysis presents a group of 86 patients with unresectable colorectal cancer who were treated with radical or palliative external beam radiotherapy from 1979-1990 at the Radiation Oncology Department of Greek Anticancer Institute, St. Savvas Hospital, Athens. The dose applied to the tumor area was 20-50 Gy in 2-6 weeks. A CAT-scan guided boost field portal to the primary tumor bed and immediately adjacent nodes was also used. Irradiation was given with a Co-60 unit or a 6 MeV Linear Accelerator using a two, three or 4-field technique. Complete symptomatic relief was achieved in 90% of patients with rectal bleeding, 63% with pain and 37% with mucous discharge. Although the majority of our patients received a higher than 40Gy radiation dose, we have seen symptomatic relief in up to 90% of patients treated with 20-30 Gy in 2-3 weeks. However, the duration of improvement in symptomatic relief of our patients was better for those who had been given higher doses of radiation therapy. The radiation dose was sufficient to relieve symptoms in 40 patients (46.5%) for more than 12 months and in 20 patients (23.2%) for 8-12 months.
 ...
PMID:Unresectable colorectal-carcinoma - 10 years experience with patients treated with radical or palliative external-beam radiotherapy in Greece. 2160 83


1