Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with tumor extending through the bladder wall with invasion of adjacent structures or lymph node metastases are seldom cured by radical surgery. Preoperative chemotherapy was given to 17 patients with T3-T4, N0, N+ tumor to assess operability and long-term survival. Tumor downstaging (T0, Ta, T1, CIS, N0) occurred in 4 (80%) of the 5 T3 patients, and in 3 (25%) of the 12 patients with T4 tumors. All patients have been followed until death or for a minimum of 42 months (mean: 56 months, range 42 to 78 months). Surgery was possible in all patients. Long-term survival is realized in only 30%, suggesting that this approach did not alter the ultimate course of the natural history of the disease. Although local recurrence did not occur, 70% of the patients with downstaged cancers developed distant metastases.
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PMID:Pathologic response and long term results of preoperative M-VAC regimen in regionally advanced transitional cell carcinoma of the bladder. 829 84

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.
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PMID:Two molecular pathways to transitional cell carcinoma of the bladder. 830 42

Although bone scintigraphy using Tc-99m labelled diphosphonates is a highly sensitive modality for the detection of of the extent of secondary skeletal malignancies, it is often not sufficient since possible bone marrow participation cannot be imaged We make a preliminary report on the usefulness of bone marrow immunoscintigraphy in the follow-up of patients with skeletal metastases due to breast and prostate cancer in parallel with the interpretation of conventional Tc-99m MDP bone scans. Approximately 7 to 9 months after radionuclide therapy both Tc-99m MDP [Hellenic Nuclear Research Center "Democritos". Aghia Paraskevi, Attikil and Tc-99m Anti-Granulocyte BW 250/183 [CIS Bio International, Gif sur Yvette, France] bone scans were performed on 2 prostate cancer patients and 5 women with breast cancer with disseminated bone metastases. Bone scans preceded bone marrow scans. Bone marrow defects were concordant with cortical scans in 4 cases, while they were larger in 4 sites compared to -MDP scan. Four sites in the ribs, shown on -MDP scan could not be detected on antigranulocyte scans. Bone cortex and marrow combined imaging of osseous metastases using different radiotracers increases the information on the real extent of skeletal involvement; the scintigraphic data obtained are valuable for the further decision making for the best possible management of unexpected myelosuppressive side effects as well as the follow-up of the treated cancer patients.
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PMID:99mTc-antigranulocyte bone marrow scintigraphy of breast and prostate skeletal metastases. 917 4

The aim of this study was to evaluate the clinical utility of immunohistochemical staining of human testicular germ cell tumours with the monoclonal antibody 43-9F to distinguish embryonal carcinoma (EC) from other malignant germ cell components in order to facilitate pathohistological assessment of prognostic risk factors for metastatic disease in clinical stage I NSGCT. Archival, formalin-fixed, paraffin-embedded tissue blocks of 24 classical seminomas, 7 spermatocytic seminomas, and 20 non-seminomatous germ cell tumours were stained for 43-9F, AFP, hCG and PLAP expression. Immunohistochemical expression was graded using a semi-quantitative scoring system: 1+ = 0-25%, 2+ = 26-50%, 3+ = 51-75% and 4+ = 76-100%. Positive immunohistochemical staining for 43-9F was found in all embryonal carcinomas and yolk sac tumours (YST); staining intensity was not statistically different between the two tumours (3.8 +/- 1.2 vs. 3.1 +/- 0.9). Classical seminomas and seminomatous components of NSGCT stained positive in 13/24 cases (54%); staining intensity was weak to moderate (1.1 +/- 0.7) in all but two cases (4+). Spermatocytic seminomas demonstrated weak positive immunostaining in 2/7 cases (29%). Adjacent CIS was found in 33/54 (61.1%) of tumours and 24/33 (72.7%) of CIS cells exhibited a weak to moderate staining intensity (1.4 +/- 0.7). AFP expression was found in 93% of YST and in only 10% of EC; however, based on the focal staining pattern, adequate differentiation of YST and EC was not possible. Positive PLAP staining was observed in 75% of EC, 79% of seminomas and in 88% of CIS cells. We did not find 43-9F staining clinically useful to distinguish embryonal carcinoma from other germ cell tumour components such as yolk sac tumour. The detection rate of CIS by 43-9F immunohistochemical staining was low and combination of PLAP staining with light microscopy was even superior. Additionally, our study confirms the link between pre-invasive CIS and embryonal carcinoma and suggests the possible direct development of embryonal carcinoma from CIS.
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PMID:Immunohistochemical expression of monoclonal antibody 43-9F in testicular germ cell tumours. 980 44

Angiogenesis has been linked to increased metastasis formation and decreased overall survival in patients with various tumors, including and neck squamous cell carcinomas (HNSCC). Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. In the present study, we evaluated VEGF expression and microvessel density (MVD), a quantitative means of angiogenesis, in both experimental and clinical models of HNSCC. Analysis of VEGF RNA expression in cell lines of keratinocyte origin [HNSCC, facial skin squamous cell carcinoma (SCC), and transformed but nontumorigenic keratinocytes] and normal skin keratinocytes revealed two VEGF transcripts corresponding to proteins of 165 and 121 amino acids in length, with the transcript for the 165-amino acid species predominating. Six of eight SCC cell lines showed increased levels of one or both transcripts, and seven SCC cell lines and the transformed keratinocyte cell line showed increased protein expression. We then evaluated VEGF protein expression in human head and neck specimens containing normal epithelium (n = 10), dysplasia or carcinoma in situ (CIS; n = 15), early invasive SCCs (n = 9), advanced primary SCCs (n = 10), lymph node metastases (n = 3), and s.c. tumors or cysts (n = 7) formed in severe combined immunodeficient mice. Intense VEGF staining was found in the majority of advanced primary SCCs, lymph node metastases, and human SCCs in severe combined immunodeficient mice, whereas no dysplasia, CIS, or early SCCs showed intense immunostain. A highly significant increase (P = 0.0001) in VEGF expression was seen in the advanced SCC versus dysplasias and CIS lesions, as was the difference between SCC versus normal epithelium from nonsmokers (P = 0.01). VEGF expression in advanced primary cancers was greater (P = 0.002) and, in early cancers, marginally greater (P = 0.05) than adjacent normal mucosa. MVD increased with the progression of preinvasive disease (P = 0.04). VEGF expression and MVD (both, P = 0.003) were directly associated with tumor aggressiveness in experimental tumors. These findings suggest a role for VEGF in both clinical and experimental HNSCC.
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PMID:Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck. 1021 12

The lungs are frequent metastatic targets for metastases of extrapulmonary cancer with or without known primary tumor. Metastases of extrapulmonary tumors are found in 20 to 50%. Metastatic carcinoma of unknown primary localizations contributes to about 4% of all diagnosed carcinomas. Within this group adenocarcinomas can be found in 60%, squamous cell carcinomas in 15%, unspecified tumors including small cell and undifferentiated tumors in 25% histogenetically. Due to overlapping histologic features a histopathological distinction of primary and secondary tumors might be difficult. Topography, size and form of pulmonary growth pattern are important aspects for the differential diagnosis. Primary lung tumors are mainly localized in upper lobes as singular nodules, metastases in lower lobes as multiple lesions. For the distinction of endobronchial primary or secondary squamous cell carcinomas findings of severe dysplasia and CIS of the bronchial epithelium are important. Stroma and vascularisation pattern of primary and secondary lung tumors differ in distribution, arrangement and extracellular matrix components. Pulmonary vascular changes in primary tumors are characterized by vascular infiltration, destruction and occlusion whereas in secondary tumors intravascular embolisation and extravasation predominate. Immunohistochemical techniques using different algorithms of antibodies (cyto-keratins, neuroendocrine markers, TTF-1, vimentin, HMB 45, LCA, oncogenes, tumor suppressor genes etc.) give vital clues as to the origin of the primary tumor. Metastases of thyroid or prostate carcinomas, melanomas, sarcomas, lymphomas etc. can be reliably differentiated. Molecular investigations are up to now only subject in research.
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PMID:[Differential diagnosis of primary lung tumors and pulmonary metastases]. 1121 30

Prompted by recognition of the potential of chemotherapy to increase the success of testis conserving surgery in patients with germ cell cancer, background and outcome data are reviewed and their contribution to the ongoing debate about how germ cell cancer develops discussed. The review is based on three previous studies of: a) time trends in tumour size in 578 personal series of all stages of testis cancer treated since 1978; b) impact of chemotherapy on actuarial risk of tumours in contralateral testis examined on 1221 patients treated in trials through the Anglian Germ Cell Cancer Consortium; and c) testes conservation attempted using chemotherapy in 78 patients. Since 1978 tumour size has decreased from 4.8 to 3.0 cms while cure has gone from 77 to 97%. There was no overall long term reduction in second cancers beyond 10 years in stage 1 patients after orchidectomy alone compared to stage 1 or metastatic disease patients receiving chemotherapy though the incidence was non significantly lower up to 10 years particularly in those patients receiving etoposide based combination. Testis conservation was initially successful in 28 of 78 (36%). An additional 25 (32%) had no viable cancer in orchidectomy specimen. In the 28 primary tumours cured by chemotherapy there was a 26% late relapse rate between 5 and 10 years (all cured by orchidectomy) compared to less than 5% in those cured with established metastases. In conclusion, testis conservation with chemotherapy is safe and feasible, though relapse is too frequent for routine service use. Confirmation of the high frequency of late relapse by others has raised the question whether these recurrences are due to post pubertal events reinducing CIS in intrauterine oestrogen primed germ cells and highlights the potential of testes conservation studies to better understand germ cell cancer development.
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PMID:Testis conserving chemotherapy in germ cell cancer: its potential to increase understanding of the biology and treatment of carcinoma-in-situ. 1275 43

Urinary bladder cancer is a heterogeneous disease with tumors ranging from papillary non-invasive to solid muscle infiltrating high grade tumors. There are mainly three problems after initial management: recurrence, progression to higher stage and metastases. The respective risk is well known for each of the stages of the disease but not sufficiently for individual optimal risk assessments. The clinical need is initially to establish the correct risk irrespective of later treatment that is to find prognostic factors. Secondarily it is important to develop predictive factors for each specific therapy. With the advent of array-based molecular profiling it is possible to obtain a more complete picture of the cancer biology and thus hope to improve the prediction of risk. Today the microarray approach is implemented at DNA, RNA and protein level. Reported chromosomal alterations in low-grade papillary tumors are few and the most common are 9q and 9p deletions. Activation of the MAPK pathway through mutations of FGFR3, RAS or PI3K seems to be crucial in the genesis of these low malignant tumors. Muscle infiltrating bladder tumors typically have more genetic aberrations than non-muscle invasive cancers. Key genes are related to the p53 and RB pathways. Gene-expression signatures correlated to stage, CIS, progression and recurrence have been proposed but require further validation.
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PMID:Molecular genetics of bladder cancer: an update. 1892 58

Abstract Bone-seeking radiopharmaceuticals and bisphosphonates may be indicated in patients with cancer with painful osseous metastases to palliate pain symptoms or to prevent skeletal-related events. Both pharmaceuticals may have an additive or even synergistic palliative effect. The combined use of bone-seeking radiopharmaceuticals and bisphosphonates is, however, controversial because of assumed competition between both phosphonate-compounds at the bone level. We report a case of hormone-refractory prostate cancer (HRPC) with multiple painful osseous metastases. The patient was treated with samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP; Quadramet, CIS bio International, Saclay, France) in combination with zoledronic acid (Zometa, Novartis, Stein, Switzerland). He was treated for 6 months with 4 weekly intervals of zoledronic acid in combination with 3 monthly intervals of (153)Sm-EDTMP. No negative interaction was found, toxicity was low, and efficacy high. He experienced a total relief of pain, a significant decrease of prostate-specific antigen (PSA) and, surprisingly, a significant decrease of tumor burden.
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PMID:Treatment of painful bone metastases in hormone-refractory prostate cancer with zoledronic acid and samarium-153-ethylenediaminetetramethylphosphonic acid combined. 1959 54

CIS is a flat, high-grade, non-invasive microscopic urothelial carcinoma. It is considered a precursor of invasive bladder cancer. CIS is classified as primary, secondary or concurrent, when occurred as isolated CIS without cuncurrent papillary tumors, or detected during the follow-up of patients with a previous papillary tumor, or finally in the presence of bladder neoplasm. BCG is widely established as the treatment of choice for CIS with a success rate of approximately 70%. BCG reduces the risk of progression of CIS into invasive carcinoma in 30 to 50% of cases. Direct and prolonged contact between the urothelium and BCG is a prerequisite for successful therapy. Discovery of CIS in the prostatic or membranous urethra represents an ominous sign. CIS may be present only in the epithelial lining of the prostatic urethra or in the ducts, or in the worst case it may be found in the prostatic tissue stroma. Urethral involvement by CIS is at high risk of tumor progression and development of metastases due to reduced thickness of lamina propria and absence of muscolaris mucosa. 83 patients, enrolled from 1/1996 to 12/2005 at our urological department with CIS: primary (focal and multifocal) in 25, secondary in 7 and cuncurrent in 51 (associated with T1bG3 cancer in 37 cases), and urethral CIS in 5 and conservatively treated by TUR and intravescical instillations of BCG, 4 developed afterwords only invasive cancer of the urethra in the absence of bladder involvement. In 2 cases cancer arised from the prostatic fossa after TURP, in 1 from membranous urethra and in the last from prostatic ducts. Among the 4 patients, 3 were treated by cystoprostatourethrectomy and Platinum-based chemotherapy, 1 refused surgical treatment. Two patients died for disseminated disease. 1 patient is alive at 60-month's follow-up. In the last patient cancer relapsed at 36-month's follow-up. We conclude that prostatic/urethral involvement during follow-up after successful intravesical treatment with BCG in CIS represents a high risk of developing invasive and incontrolled cancer. A careful watch is recommended in these patients.
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PMID:[Urethral recurrence of invasive carcinoma following BCG treatment for bladder Ca in situ]. 2130 79


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