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)

Experiments were designed to examine whether local cytokine therapy of subcutaneous (s.c.) tumours results in inhibition of their lung metastases. Moderately immunogenic, major histocompatibility complex (MHC) class I and II negative. B7 negative, metastasizing murine carcinoma MK16 transplantable in syngeneic mice was obtained by co-transfection of human papilloma virus type 16 (HPV 16) E6/E7 and activated H-ras oncogene plasmid DNA into C57BL/6 kidney cells. After s.c. transplantation of the malignantly converted MK16 cells, the majority of the transplanted mice developed lung metastases; the number and size of the lung metastases increased with the increasing size of the s.c. tumour. Therapy of 5-day MK16 tumours by peritumoral administration of recombinant interleukin-2 (IL-2) and recombinant interleukin-12 (IL-12) inhibited growth of the s.c. MK16 tumour transplants and reduced the number of MK16 lung metastases. To investigate the antimetastatic effect of IL-2 and IL- 12 in a clinically more relevant setting, surgical minimal residual tumour disease was utilized. Subcutaneously growing MK16 carcinomas, 8-12 mm in diameter, were removed on day 30 and the operated mice were injected with IL-2 or IL- 12 on days 35-39 and 42-46 at the site of the operation. Treatment with IL-2 significantly reduced the percentage of MK16 tumour recurrences as well as the number of lung metastases, whereas the effect of IL- 12 was substantially weaker and statistically insignificant.
Clin Exp Metastasis 2000
PMID:Local cytokine treatment of HPV16-associated tumours results in inhibition of their lung metastases. 1168 63

Traditionally, risk factors for the development of tonsil cancer include the use of alcohol and/or tobacco, however a significant proportion of new cases develop in young patients without these risk factors. Recent investigation suggests that human papilloma virus (HPV) may serve as an etiology in such cases and represent a unique risk factor in a sub-set of patients. Irrespective of the etiology, in the majority of cases early carcinoma of the tonsil can effectively be treated using single modality therapy. While local-regional control and survival are similar following surgery or radiotherapy, primary surgery can be accomplished with minimal functional morbidity while reserving radiation for recurrent disease. In contrast, surgical salvage following external beam radiotherapy can be technically challenging and is often associated with a significant increase in surgical complications and functional morbidity. In contrast to early tonsillar disease, advanced tonsil cancer represents a clinical challenge that requires multimodality therapy. While advanced lesions are often treated with a combination of radiation, chemotherapy, and surgical ablation, management of the neck and distant metastases continues to present a therapeutic dilemma.
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PMID:Current management of tonsillar cancer. 1267 52

Cervical carcinoma is a human papilloma virus (HPV)-related immunogenic type of malignancy, in which escape of the tumor from the hosts' immune response is thought to play an important role in carcinogenesis. The multifunctional cytokine transforming growth factor-beta(1) (TGF-beta(1)) is involved in immunosuppression, stroma and extracellular matrix formation and controlling (epithelial) cell growth. The plasminogen activating (PA) system plays a key role in the cascade of tumor-associated proteolysis leading to extracellular matrix degradation and stromal invasion. Changes in expression of components of this system, including plasminogen activator inhibitor-1 (PAI-1), have been associated with poor prognosis in a variety of solid tumors. The present study was undertaken to assess the role of both components on relapse, survival and other clinicopathologic parameters in cervical cancer. The expression of TGF-beta(1) mRNA in 108 paraffin-embedded cervical carcinomas was detected by mRNA in situ hybridization. Immunohistochemistry was used to investigate the expression of PAI-1 protein. The presence of cytoplasmatic TGF-beta(1) mRNA in tumor cells was not significantly correlated with the other clinicopathologic parameters investigated or with a worse (disease-free) survival. Expression of the PAI-1 protein in tumor cells was strongly correlated with worse overall and disease-free survival, in addition to well-known prognostic parameters such as lymph node metastasis, depth of tumor infiltration, tumor size and vasoinvasion. In the multivariate analysis, PAI-1 turned out to be a strong independent prognostic factor. In a subgroup of patients without lymph node metastases, PAI-1 was predictive for worse survival and relapse of disease, too. Our results show that the (enhanced) expression of PAI-1 by carcinoma cells is correlated with worse (overall and disease-free) survival of patients with cancer of the uterine cervix. The expression of TGF-beta(1) in itself is not associated with worse survival in these patients. Although simultaneous presence of the 2 factors was observed in all tumors, induction of PAI-1 by TGF-beta(1) could not be demonstrated in our group of cervical carcinomas.
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PMID:Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer. 1538 52

Clinical outcome of penile squamous cell carcinoma (PSCC) largely depends on the presence of lymph node metastasis. In search of a valuable marker predicting the risk for metastasis, the expression of Ki67 was investigated immunohistochemically in primary tumors and compared to presence of inguinal lymph node metastasis. As human papilloma virus (HPV) is thought to affect Ki67 expression, we evaluated whether occurrence of HPV DNA correlates to Ki67 score or metastatic potential. Samples originated from patients subjected to resection of invasive SCC of penis. Immunohistochemistry was done on paraffin-embedded sections using a monoclonal antibody against Ki67. After DNA isolation from paraffin embedded tissue the presence of HPV 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Statistical analysis was done using two tail unpaired t test and Chi-square test. Four of 28 patients showed a weak Ki67 expression, without displaying lymph node metastasis. Among 17 patients showing an intermediate Ki67 index, eight exhibited metastases while in all seven patients with a strong expression of Ki67 lymph node metastases were found. The median Ki67 expression in metastastic lesions was significantly different (50.3%) from tumors without lymph node metastasis (31.8%) (p=0.024). Furthermore, a correlation between presence of HPV DNA and strong Ki67 expression was determined (p=0.009). Since our study demonstrated a strong Ki67 labeling index significantly associated to positive lymph nodes, we suggest Ki67 expression as a prognostic marker for lymph node metastasis in penile squamous carcinoma.
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PMID:Expression of proliferation marker Ki67 correlates to occurrence of metastasis and prognosis, histological subtypes and HPV DNA detection in penile carcinomas. 1764 92

The hTERT gene encodes the telomerase catalytic subunit that plays a key role in cancer cell immortalization. Earlier, hTERT amplification was detected in squamous cell cervical carcinomas (SCC), however possible relations between elevated hTERT mRNA level and gene amplification was not studied. Here, we compared the hTERT expression and copy number in the same tumors by quantitative real-time PCR. The hTERT DNA copy number was virtually unchanged in all 33 studied tumors, when compared to normal tissues. This result was confirmed using two reference genes beta-actin and beta-D-glucuronidase. Nevertheless, the activation of hTERT expression was found in 80% of cases (37/46, p<0.001). There was no correlation between the degree of mRNA increase and the tumor size and/or presence of metastases. No hTERT gene expression was observed in 20% of cases (9/46), while the control GADPH expression was unchanged. The detected elevation of the hTERT mRNA level was found using primers specific to functionally active full-length isoform of mRNA. Similar results were obtained with SCC cell lines carrying human papilloma virus (HPV) genomes. We conclude that frequent activation of hTERT expression in SCC is not associated with gene amplification.
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PMID:Activation of the hTERT expression in squamous cell cervical carcinoma is not associated with gene amplification. 1863 13

Anal squamous cell carcinoma and its precursor lesions are increasing in incidence in the United States and Europe. This trend predates human immunodeficiency virus/acquired immune deficiency syndrome and has been associated with persistent high-risk human papilloma virus (HPV) genotype infection, previous lower genital tract dysplasia/carcinoma, high frequency anoreceptive intercourse, heavy cigarette smoking, immunosuppression in solid organ transplant and immune disorders, and human immunodeficiency virus seropositivity. Screening protocols for at-risk patients are under active investigation and pathologists are often asked to assess anal canal and perianal biopsies for the presence of dysplasia and/or invasive carcinoma. Because underdiagnosis and overdiagnosis of anal cancer and precancer may lead to inappropriate treatment, it is important for the pathologist to be aware of current screening strategies, specific risk lesions, and the role of pathology in initial diagnosis and evaluation of anal biopsy and/or resection specimens. Standardized histologic criteria and uniform terminology should be used for reporting all anal canal and perianal squamous intraepithelial lesions. HPV subtyping, anal cytology, and recently identified biomarkers, such as p16 and Becton Dickinson ProEx C may provide additional information in problematic cases, but it is important to be aware of the limitations of these assays. HPV has been linked to all the major histologic subtypes of anal carcinoma (eg, basaloid, cloacogenic, transitional, etc.) and this association is strongest for anal canal lesions. With the possible exception of the microcystic pattern, histologic subtype does not seem to predict prognosis; and anal squamous cell carcinomas should be classified as either keratinizing or nonkeratinizing. Poorly differentiated squamous cell carcinomas have a worse prognosis and should be distinguished from poorly differentiated adenocarcinoma, melanoma, and neuroendocrine tumors. Very well differentiated squamous cell carcinoma with pushing margins (so-called giant condyloma of Buschke and Lowenstein) should be classified as verrucous carcinoma; this tumor shows aggressive local infiltration but does not metastasize. As all anal condylomata may harbor foci of high-grade dysplasia or invasive carcinoma, careful sectioning and complete histologic examination is required.
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PMID:Diagnostic problems in anal pathology. 1872

In this study, typing of human papilloma virus (HPV) was performed in squamous cell carcinomas of the lung (n=26) as well as putative primaries of head and neck (n=21) and female genital tract (n=5) of the same patients, to test whether additional information to discriminate lung primaries from metastases can be gained by a direct comparison of the HPV status in both tumors. In 3 (14.2%) patients with head and neck as well as lung squamous cell carcinoma, an identical HPV subtype could be detected in both tumors suggesting metastatic disease. In 9 (42.9%) cases, discordant HPV status strongly suggested secondary primaries of the lung. In the remaining 9 (42.9%) patients, no HPV was evident in either tumor. In all patients with carcinomas of the cervix uteri an identical HPV subtype was detected in the cervical and in the lung tumor. In conclusion, the results suggest HPV typing, a method routinely used in cervical biopsies for years, as a very useful diagnostic tool to discriminate primary from metastatic squamous cell carcinoma of the lung, which in our cohort in 57.1% of cases allowed for almost definite classification.
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PMID:Molecular HPV typing as a diagnostic tool to discriminate primary from metastatic squamous cell carcinoma of the lung. 1914 3

Squamous cell carcinoma of the head and neck is a major health problem, and much effort is being made in the different settings of its presentation. Much of the recent progress has been made in locoregionally advanced inoperable disease, mainly with the optimal combination of concurrent chemoradiotherapy and with the introduction of new active drugs, such as docetaxel, in the induction phase of the treatment. The association of docetaxel, cisplatin, and 5-fluorouracil (TPF) regimen is now acknowledged as being the gold standard of induction treatment. The subset of patients with recurrent/metastatic disease still carries a grim prognosis. For the time being, new biological therapies have not dramatically changed this scenario, even in combination with conventional treatments. Little is known about the role of docetaxel and, in general, of chemotherapy in the adjuvant setting, even though it is increasingly acknowledged that, beyond a certain risk, concurrent adjuvant chemoradiotherapy is required. The main aim of the research on head and neck cancer probably lies in the identification of biomolecular markers that are able to predict clinical behaviour, thus allowing appropriate treatment tailoring. The identification of human papilloma virus infection as the agent of a particular form of oropharyngeal cancer is an example of this strategy in consideration of the peculiar characteristics.
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PMID:Docetaxel in the management of head and neck cancer. 1963 68

A 72-year old patient presented with a 6 months history of a rapidly growing tumor of the glans and foreskin. He had a long history of phimosis with lichen sclerosus et atrophicus-like lesions on the foreskin which had not been treated. The rest of the personal, family and sexual history was unremarkable. Treatment consists of circumcision and tumor excision. Histopathology confirmed a squamous cell carcinoma within a giant condyloma with a concomitant lichen sclerosus et atrophicus. CT- and ultrasound scans showed no metastases. Giant condylomas are a rare sexually transmitted disease usually caused by human papilloma virus subtypes 6, 11, but also by 16 and 18 among others. They are expansive, cauliflower-like destructive lesions that most frequently affect the anogenital region. In about 30 percent a giant condyloma progresses into a squamous cell carcinoma. Therapy of choice is the histopathologically controlled excision. Recurrences are often seen, so the patients should be monitored frequently after therapy.
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PMID:[Giant condyloma of the penis with malignant transformation associated with lichen sclerosus et atrophicus]. 1975 35

Basaloid squamous cell carcinomas (SCC) are a rare variant of SCC of the head and neck. Their histological characteristics have been described by Wain in 1986 and are reported in the 2005 WHO classification. A poorer prognosis of BSCC has been reported. Two recent case-control studies have shown a higher rate of distant metastases (15-40%, mean over 30%). Conversely, BSCC have similar or better locoregional control rates, a relatively good radiosensitivity and locoregional control. The role of chemotherapy in the neoadjuvant, concomitant or adjuvant setting needs to be redefined due to high metastatic failure rates; chest CT or PET CT are recommended at baseline and every 6-month during follow-up. Some subgroups of BSCC (oropharynx in particular) are more likely to be associated with oncogenic human papilloma virus HPV16. The determination of BSCC head and neck subgroups by HPV status is critical for the prognosis. The basaloid sub-type of squamous cell carcinomas owing to its particular behavior, should be taken into account while deciding the optimal therapeutic strategy.
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PMID:[Basaloid squamous cell carcinomas of the head and neck]. 1979 86


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