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)

It is well established that melanoma cells express Ags that are recognized by autologous T cells in vitro. Tumor-infiltrating lymphocytes in situ comprise clonotypic T cells, suggesting that their expansion is driven by Ag stimulation. Still, little is known about the detailed characteristics of the in situ T cell response. In the present study, we scrutinized this response by analyzing multiple metastatic lesions for the presence of clonotypic T cells. This approach was chosen to distinguish whether the clonal T cell expansion occurs as a systemic or localized phenomenon. TCR clonotype mapping of six s.c. metastases from two patients revealed the presence of multiple (from 40 to >60) clonotypic T cells in all lesions. Clonotypic T cells were present in TCR beta-variable regions expressed both at high and low levels. Comparison of the T cell clonotypes present in different lesions from individual patients demonstrated that, in general, clonotypes were exclusively detected in a single lesion. Hence, anti-melanoma T cell responses are much more heterogeneous than previously anticipated and accommodate a predominance of strictly localized T cell clonotypes.
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PMID:In situ T cell responses against melanoma comprise high numbers of locally expanded T cell clonotypes. 1038 47

Mortality rates from thyroid cancer have fallen significantly in recent decades, almost certainly as the result of earlier diagnosis and improved treatment of differentiated (papillary and follicular) thyroid cancer. Enhanced survival is likely a result of early diagnosis and therapy applied at a disease stage when treatment is most effective. In the United States and Europe, most patients at high risk for relapse and death from thyroid cancer are treated with total or near-total thyroidectomy and receive radioiodine ablation of residual normal or malignant thyroid tissue, followed by treatment with thyroid hormone, a strategy that cures more than 80% of patients. Still, some die of the disease and nearly 15% have local recurrences, while another 5% to 10% develop distant metastases. Over 50% of recurrences appear in the first five years, but distant metastases may surface years, and sometimes decades, after initial therapy. Much has been learned about risk stratification to predict recurrence and death from thyroid cancer but individual patients continue to have adverse outcomes not always foreseen by a low tumor stage. Follow-up must accordingly be meticulous and prolonged. The National Cancer Center Network (NCCN) has recently established consensus practice guidelines that give explicit advice about the diagnosis and management of benign and malignant thyroid tumors, including paradigms for long-term follow-up and the treatment of recurrent disease. The guidelines confirm that diagnostic scanning with 131I and measurement of serum thyroglobulin (Tg) levels are the mainstay of follow-up, offering the opportunity to detect recurrent or persistent cancer at very early stages. These guidelines advocate TSH-stimulated serum Tg measurements, done either during thyroid hormone withdrawal or stimulation with recombinant human TSH (rhTSH, Thyrogen), that often identify the presence of cancer well before diagnostic whole-body scanning or other imaging studies can spot the tumor, which offers the opportunity to treat recurrent disease at an early stage. The use of rhTSH adds a new dimension to long-term follow-up that avoids putting patients through the symptoms of hypothyroidism, and offers the opportunity to follow some patients with rhTSH-stimulated serum Tg levels without performing 131I whole-body scans. A multicenter international study has shown that serum Tg measurements alone are not as sensitive in the identification of patients with persistent or recurrent tumor as are rhTSH-stimulated serum Tg determinations. Although not yet approved for preparation of patients for 131I therapy, rhTSH has been used successfully in a compassionate use program for this purpose in a relatively large number of patients. Formal clinical investigations now planned to provide guidelines for the use of rhTSH for therapeutic 131I portend a new set of effective therapeutic paradigms for the management of differentiated thyroid cancer.
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PMID:Using recombinant human TSH in the management of well-differentiated thyroid cancer: current strategies and future directions. 1104 54

Prostate cancer is perceived to be a disease of older men often diagnosed with widespread metastases that respond to hormonal ablation but for which there are few additional treatment options. Fortunately this perception is rapidly changing as newer combination chemotherapy trials demonstrate improved prostate-specific antigen and measurable response rates and enhanced quality of life. Still, treatment of prostate cancer lags behind treatment of other malignancies. Work remains in understanding the natural history of disease, refining our grouping of patients by stage into clinical trials, and adhering to new response criteria recently developed. Applying the newer active chemotherapy regimens to patients with earlier stage disease should lead to improvements in overall survival.
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PMID:Can chemotherapy alter the course of prostate cancer? 1156 89

Lung cancer is the leading cause of cancer death in the United States. The majority of patients with non-small cell lung cancers present with inoperable disease because of the presence of metastases to regional lymph nodes or other metastatic sites. About one third of patients have stage IV disease with metastases to distant organs at the time of diagnosis. The prognosis for these patients is very poor. With best supportive care the median survival is only 4 months and the 1-year survival rate is 10% to 15%. Current chemotherapy combinations improve the survival and quality of life for patients with advanced non-small cell lung cancer. With two-drug combinations, median survival is increased to 8 months or more and 1-year survival is increased to 35% to 40%. Still, complete response rates are low and more than 80% of patients die within 1 year of diagnosis. The improvements created by current therapies led to studies of chemotherapy in the second-line setting. Docetaxel has been shown to improve survival of patients who failed platinum-based chemotherapy and was approved by the U.S. Food and Drug Administration for therapy in this setting. However, response rates were very low and survival very short. Therefore, new therapies are urgently needed. Exisulind is a novel oral anticancer agent that holds promise for the treatment of patients with advanced non-small cell lung cancer. Exisulind was originally developed as a chemoprevention agent for colorectal cancer. Preclinical studies showed that exisulind could prevent polyp formation and inhibit the growth of colorectal cancers. Subsequent preclinical studies showed that exisulind also inhibited the growth of human breast, prostate, and lung cancers. Phase I clinical studies showed that twice-daily oral doses could be given safely and would provide peak concentrations that were equivalent to those required for in vitro effects. These observations lead to the studies of the combination of exisulind and docetaxel in preclinical and clinical studies in human lung cancer described in this article.
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PMID:Preclinical and clinical studies of docetaxel and exisulind in the treatment of human lung cancer. 1189 18

DNA mismatch repair (MMR) deficiency and increased O6-methylguanine-DNA methyltransferase (MGMT) activity have been related to resistance to O6-guanine methylating agents in tumour cell lines. However, the clinical relevance of MMR and MGMT as drug resistance factors is still unclear. In a retrospective study, the expression levels of the MMR proteins, hMSH2, hMSH6 and hMLH1, were analysed by immunohistochemistry in melanoma metastases from 64 patients, who had received dacarbazine (DTIC) based chemotherapy. More than half of the melanoma patients had tumours with no nuclear staining for either hMSH2 or hMSH6 or both, while all tumours showed positive nuclear staining for hMLH1. The response rates were similar in patients with hMSH2 and/or hMSH6 positive tumours to these in patients with negative tumours. By combination of MMR with previously obtained MGMT data, only 2 of 12 responders had tumours with low MGMT and positive MMR expression. Still all except 3 of the non-responders were identified by having either high MGMT expression or absent staining for hMSH2 or hMSH6 or both in their tumours. However, there was no significant correlation of MMR expression alone or combined with MGMT levels with clinical response to DTIC-based chemotherapy in metastatic melanoma.
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PMID:Immunohistochemical analysis of DNA mismatch repair protein and O6-methylguanine-DNA methyltransferase in melanoma metastases in relation to clinical response to DTIC-based chemotherapy. 1216 66

Initial therapy for advanced prostate cancer includes androgen ablation by surgical or medical castration. Still, nearly all men with metastases will progress to hormone-refractory prostate cancer (HRPC). Current U.S. Food and Drug Administration-approved agents for the treatment of HRPC include mitoxantrone and estramustine, although the vinca alkaloids and the taxanes have shown promising activity in single-agent phase II trials. Combinations of these agents induce a biochemical response in greater than 50% of patients, but the median duration of response is approximately 6 months. Overall survival of patients treated with these combinations is approximately 18-24 months. Studies are ongoing to develop novel therapies that target specific molecular pathways or mechanisms of chemotherapy resistance. Novel agents under development include growth factor receptor inhibitors, antisense oligonucleotides, bisphosphonates, and cell differentiating agents. Evaluation and incorporation of these agents into existing treatment regimens will guide us in the development of more active regimens in the treatment of HRPC.
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PMID:State-of-the-art treatment of metastatic hormone-refractory prostate cancer. 1218 98

Brain metastases occur in 20-40% of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3-3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not improve. Late neurotoxicity in long surviving patients after WBRT is not negligible; to avoid this complication patients with favorable prognostic factors must be treated with conventional schedules of RT, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases. A small subgroup of these latter may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors). New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated.
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PMID:Management of brain metastases. 1238 50

Correctly staging lung cancer is extremely important because the treatment options and the prognosis differ significantly by stage. Several noninvasive imaging studies are available to aid in identifying disease both within and outside of the chest. Chest CT scanning is useful in providing anatomic detail that better identifies the location of the tumor, its proximity to local structures, and whether or not lymph nodes in the mediastinum are enlarged. Unfortunately, the accuracy of chest CT scanning in differentiating benign from malignant lymph nodes in the mediastinum is unacceptably low. Whole-body positron emission tomography (PET) scanning provides functional information on tissue activity and has much better sensitivity and specificity than chest CT scanning for staging lung cancer in the mediastinum. In addition, metastatic disease can be detected by PET scan. Still, positive findings of PET scans can occur from nonmalignant etiologies (eg, infections), so that tissue sampling to confirm the suspected malignancy must be performed. The clinical evaluation tool, which is composed of a thorough history and physical examination, remains the best predictor of metastatic disease. If the findings from the clinical evaluation are negative, then imaging studies such as a CT scan of the head, a bone scan, or an abdominal CT scan are unnecessary, and the search for metastatic disease is complete. If signs, symptoms, or findings from the physical examination suggest the presence of malignancy, then sequential imaging, starting with the most appropriate study based on the clues obtained by the clinical evaluation, should be performed. Abnormalities detected by all of the aforementioned imaging studies are not always cancer. Unless overwhelming evidence of metastatic disease is present on an imaging study, in situations in which it will make a difference in treatment, all abnormal scan findings require tissue confirmation of malignancy so that patients are not precluded from having potentially curative surgery.
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PMID:The noninvasive staging of non-small cell lung cancer: the guidelines. 1252 74

MIB-1 is useful in evaluating proliferative activity and in predicting the aggressiveness in a variety of tumors. To investigate if MIB-1 immunoreactivity can add prognostic information to conventional prognostic variables in papillary thyroid carcinoma (PTC), 30 PTCs were evaluated using the MIB-1 antibody. For comparison, 10 follicular thyroid carcinomas (FTC), 8 anaplastic thyroid carcinomas (ATC), and 96 follicular thyroid adenomas (FTA) were similarly analyzed. The median MIB-1 index was 0.5% in FTA, 1.9% in PTC, 2.7% in FTC, and 16.2% in ATC. The 13 tumors from patients classified as having aggressive PTC (defined as dead from disease, persisting disease, or the occurrence of distant metastases) had significantly higher MIB-1 index (median, 5.4%) than the 17 patients with nonaggressive disease (median, 1.1%). MIB-1 index 1.85% or more was found to be an independently significant risk factor for a less favorable clinical course in PTC. Because of overlap of single values the utility of MIB-1 index as a clinical test is somewhat limited. Still, at levels where no overlap occurs (MIB-1 index 2 3.2% or ' 0.5%) the index seems to add information to the established prognostic parameters. MIB-1 index should therefore be considered in routine histopathology of PTC.
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PMID:MIB-1 index in thyroid tumors: a predictor of the clinical course in papillary thyroid carcinoma. 1281 14

The hemangioendothelium is a vascular tumor rarely seen in the pediatric practice. This case underlines the difficulty that lies in establishing a differential diagnosis with a localized adenopathy when this vascular tumor is developing inside a ganglionic region. The surgical treatment followed by interferon therapy determined a favorable evolution in this case because the hemangioendothelium is a vascular borderline tumor. Still, there are cases that recur, metastasize and have an evolution towards death.
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PMID:[Hemangioendothelioma in children]. 1475 40


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