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

Cadherins are a family of glycoproteins that are associated with cell adhesion mechanisms. They are divided into subclasses. The E- and P-cadherins are regarded as the epithelial subtype. Their expression has been demonstrated in many different carcinoma types. Using immunomorphological techniques, we studied the expression of E-cadherin in a series of 145 human brain tumours with the monoclonal antibody 5H9. Western blot analysis was used to confirm the immunohistochemical data. The tumour types represented were astrocytoma WHO I (n = 7), astrocytoma WHO II (n = 6), astrocytoma WHO III (n = 14), glioblastoma WHO IV (n = 8), oligodendroglioma WHO II (n = 5), ependymoma WHO II (n = 5), choroid plexus papilloma WHO I (n = 5), pineoblastoma WHO IV (n = 5), medulloblastoma WHO IV (n = 5), neurinoma WHO I (n = 5), meningioma WHO I and WHO III (n = 75) and pituitary adenoma WHO I (n = 5). Only choroid plexus papillomas (5/5) and meningiomas showed E-cadherin expression. In benign meningiomas (n = 45; 100%), positive E-cadherin immunoreactivity was found regardless of the histomorphological subtype. E-Cadherin was also expressed in 21 WHO I meningiomas (100%) invading dura, bone, brain, and muscle. In contrast, E-cadherin was absent from the majority of morphologically malignant meningiomas (6/9, 66.6%). In addition, in recurrent meningiomas (n = 9), E-cadherin expression in the recurrent tumours was identical to that in the primary neoplasm except in cases with malignant progression, where the malignant recurrent tumour was E-cadherin negative. In 2 cases of metastasizing meningiomas, no E-cadherin immunoreactivity was found in the primary tumours or their metastases.
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PMID:E-Cadherin in human brain tumours: loss of immunoreactivity in malignant meningiomas. 950 62

Little is known about the molecular mechanisms of tumor progression in the pituitary. However, animal studies suggest that the Rb gene may be involved in the development of pituitary carcinoma. Pathologic examination of a pituitary tumor that included both benign and malignant components provided insight into this mechanism. Both benign and malignant tumors were immunoreactive for ACTH. The benign adenoma showed strong nuclear immunoreactivity for Rb, however, both the adjacent sellar carcinoma and its metastases were Rb-negative. This study suggests that loss of Rb may in some cases be important in the progression of pituitary adenoma to carcinoma.
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PMID:Loss of Rb expression in an ACTH-secreting pituitary carcinoma. 958 68

About 25% of patients with ZES have MEN-1. Except for diarrhoea, less frequent in patients with ZES MEN-1 than in sporadic ZES, and specific MEN-1-related signs, clinical characteristics are similar in both ZES types. Acid output and gastrin level are also similar whether in the basal state or after secretin. Primary hyperparathyroidism (pHPT) exists in the majority of ZES MEN-1 patients, 30% have pituitary adenoma (prolactinomas for half), 30% adrenal involvement, 25-30% have ECLomas: bronchial and thymic carcinoids have probably been underevaluated. Gastrinomas are multiple predominantly located in the duodenal wall, but also in the pancreas in association with clinically silent endocrine tumours. The spread of the disease metastases to the liver (LM), mediastinum, bones, is evaluated best by Octreoscan. Associated endoscopic ultrasonography evaluates the number, size and anatomical characteristics of gastrinomas. Patients without LM have an excellent prognosis. Surgery never cures ZES, but is necessary in cases of associated life-threatening conditions such as insulinoma. Although the size of the tumour, when located in the pancreas >3 cm, favours metachronous LM occurrence, surgery in our experience has not been able to prevent LM development.
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PMID:Diagnostic and therapeutic criteria in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. 968 47

Spontaneous neoplasms in 930 control Wistar rats from five carcinogenicity bioassays conducted between 1990 and 1995 were reviewed and compared with review findings in studies between 1980 and 1990. Mean survival at 104 weeks was 55% for males and 60% for females, similar to that of the previous review. A total of 1599 neoplasms was diagnosed in 361 (78%) male and 415 (89%) female rats; 1293 (81%) of these were benign and 306 (19%) were malignant (11% with metastases). Sixty-eight percent of all neoplasms were in endocrine and integumentary systems, similar to 74% seen in the previous review. Most common neoplasms (affecting > 7% of either sex) were pituitary adenoma (34% of males, 50% of females), benign adrenal pheochromocytoma (10% of males, 1% of females), thyroid C cell adenoma (6% of males, 8% of females), mammary fibroadenoma (3% of males, 36% of females), keratoacanthoma (11% of males, 0.6% of females), testicular interstitial cell tumor (11% of males), uterine stromal polyp (16% of females), pancreatic acinar cell adenoma (13% of males, 0.6% of females), and benign thymoma (3% of males, 8% of females). Seventeen neoplasms affecting 2 to 6.9% of either sex included adrenal cortical adenoma, thyroid follicular adenoma, pancreatic islet cell adenoma, pituitary carcinoma, mammary adenoma, mammary adenocarcinoma, fibroma, fibrosarcoma, dermal papilloma, uterine schwannoma, uterine granular cell tumor, pancreatic acinar cell carcinoma, hepatocellular adenoma, lymphoma, granular cell meningioma, renal mesenchymal tumor, and hemangiosarcoma. Remaining neoplasms occurred in fewer than 2% of animals. Mean tumor incidence did not differ significantly between our two reviews. Ratios of benign to malignant neoplasms were similar in both reviews and percentages of survival at 104 weeks were similar. Between the two reviews, greater than threefold increase in frequency of some neoplasms occurred only in males and included keratoacanthomas, pancreatic acinar cell adenomas/carcinomas, and astrocytomas. Frequencies of remaining neoplasms were within twofold or within 10% of previous frequencies. Some neoplasms diagnosed in this review but not in the previous review included cardiac schwannoma, pilomatrixoma, parathyroid adenoma, and prostatic adenoma but incidence was approximately 1% for any one tumor. Based on these reviews, Wistar rats appear to have a predilection to pituitary neoplasms and mammary fibroadenomas (females).
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PMID:Spontaneous neoplasms in control Wistar rats: a comparison of reviews. 984 5

An autopsy case of an ACTH-producing pituitary carcinoma in a 59-year-old man who developed Cushing's disease is reported. The surgically removed pituitary tumor was diagnosed as chromophobe adenoma, however, pulmonary metastases appeared 2 years after the operation. Autopsy revealed a residual pituitary tumor in the sella turcica with systemic metastases to the lungs, liver, pulmonary lymph nodes, hypothalamus, dura mater, and the subarachnoid space of the midbrain and spinal cord. Immunohistochemistry revealed ACTH positivity in the tumor cells. Further immunohistochemical study showed positive high expression of Ki-67 in the tumor removed at surgery as well as in the autopsied tumor. Ki-67 labeling index provided valuable information about the invasive and proliferative potential compared to noninvasive benign pituitary adenoma.
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PMID:An ACTH-producing pituitary carcinoma developing Cushing's disease. 1022 Jul 99

The differential diagnosis of a sellar lesion includes pituitary adenoma, cranio-pharyngioma, tumour cyst, benign cyst, and other less common lesions such as aneurysm, squamous cell carcinoma and metastases. Pure cystic lesions within the sella turcica are not uncommon and may appear clinically and radiologically as pituitary adenoma. Intrasellar cysts are broadly classified as neoplastic or non-neoplastic; the latter may be primary lesions of the pituitary fossa or they may arise from the parasellar region and invade into the sella. The lesions occupy space and may cause disturbance of pituitary function; if they extend into the suprasellar region they can affect visual fields and acuity. Non-neoplastic cystic lesions usually appear well defined radiologically and have distinct pathological features. Modern imaging modalities, such as computed axial tomography and magnetic resonance imaging, are important complementary tools of investigation for reaching a differential diagnosis, and for surgical planning. Most non-neoplastic sellar cysts can be approached through the trans-sphenoidal route, but large lesions with suprasellar extension may require transcranial surgery. We report the presentation and management of eight cases (four males, four females, all adult) of non-neoplastic cyst involving the sella turcica and the parasellar region. Investigations included computed tomography scan of the head for all and magnetic resonance imaging for six (75%) patients. Work-up included endocrinological and opthalmological evaluations. All presented with headache; six (75%) had visual acuity change, two (25%) had evidence of visual field defects, four (50%) had optic atrophy on fundoscopy, three (37.5%) had endocrine symptoms and hormone reduction was found in four (50%).
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PMID:Non-neoplastic cystic lesions of the sellar region presentation, diagnosis and management of eight cases and review of the literature. 1035 49

Most carcinomas involving the sella turcica are metastases. We report two previously undescribed carcinomas that appear to be primary at this site. The first occurred in a 44-year-old woman who presented with hemianopsia. A mass was noted by computed tomography to occupy the sella turcica, from which it appeared to originate. Transphenoidal biopsy showed the tumor to be an adenoid cystic carcinoma with a typical cribriform pattern. The patient died shortly after a subsequent attempt at tumor resection. The second tumor arose in a 55-year-old man who presented with diplopia. Computed tomography showed a mass in the sella turcica that was presumed to be a pituitary adenoma. However, transphenoidal resection revealed a mucinous adenocarcinoma composed of small papillae and glands lined by columnar epithelium. The tumor cells exhibited varying degrees of stratification with prominent interspersed mucin vacuoles. Focal solid areas showed a component of signet ring-type cells. In contrast to the apparent aggressive behavior of the adenoid cystic carcinoma, the papillary mucinous adenocarcinoma appeared much less aggressive, as the second patient was alive and without evidence of disease 5 years later. Both tumors may be derived from epithelial rests within the pituitary gland, either minor salivary gland rests or Rathke's cleft remnants.
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PMID:Intrasellar adenoid cystic carcinoma and papillary mucinous adenocarcinoma: two previously undescribed primary neoplasms at this site. 1035 49

To the Editors: We have read with interest and some concern the recently published editorial, "We've Got a Treatment, but What's the Disease," by Rosenthal and Glatstein. This editorial enunciates these common anxieties (? "mid-life") about radiosurgery: A) that thedure as currently practiced worldwide, even in the United States, does not in all cases rely on the talents of radiation oncologists; B) that the technique disregards fundamental (? proven) principles about radiobiology, and C) that the authors of the editorial have chosen to ignore a tremendous body of historical and clinical literature relative to outcomes. In fact, long-term clinical data have been published in a wide variety of reports during the last ten years. Their reference list does not include a single article published beyond 1992. Now let's address the first issue. While it is true that the advantages obtained by closed skull focused stereotactic single session irradiation of a small but well-defined intracranial target volume (radiosurgery) were first espoused and practiced by neuosurgeons, the goal was not to impact upon the turf of the radiation oncologist. The goal was to provide a minimally invasive treatment for many problems deep within the brain for which traditional neurosurgical procedures were neither satisfactory nor effective. The tools that allowed neurosurgeons to accomplish this goal included focused particle beams or photon beams generated by the gamma knife or by linear accelerators. The technique also required highly precise (<1 mm) intracranial guiding systems (stereotactic technology). The initial evolution of this technology was cautious. It was based on more than 30 years of experimental and clinical work that preceded its introduction into the worldwide medical community beginning in the mid-1980s. In the United States, the vast majority of centers provide this technology based on the multidisciplinary input of neurosurgeons, radiation oncologists and medical physicists. The team provides both the necessary experience as well as the different perspectives that facilitate safe intervention and effective outcomes. The issue of responsibility in this multidisciplinary medical team should not be obfuscated by individual socio-economic concerns (who's in charge, who gets paid?). The recent purchase of an expensive deice for fractionated frameless radiotherapy by Southwest Medical Center may impact on Rosenthal and Glatstein's recent publication. In fact, stereotactic fractionated radiotherapy is the expensive treatment in search of a disease to pay for it Of greater concern is the authors' misconceptions (misunderstanding?) about the goals of radiosurgery (the second issue). Initially, radiosurgery was created to provide small volume destruction (in this case, true necrosis) of small target volumes withinthe basal ganglia, thalamus, or internal capsule for the treatment of intractable movement disorders, chronic pain, or medically refractory neuroses. With the redesign of the technology, deep-seated neoplasms and vascular malformations became more appealing targets with an entirely different radiobiologic goal. Instead, the goal became radiobiological inactivation of the ability of a tumor cell to divide and multiply (for tumors) or progressive luminal closure induced by endothelial hyperplasia (in the case of vascular malformations). Preservation of the surrounding normal brain (a feature brought about by the very sharp fall-off of the radiation dose delivered to small volumes with precise technology) reduced the risk of complications to normal brain, especially in contrast to surgical extirpation. Fractionated radiation therapy has rarely been an alternative to the usage of radiosurgery for these conditions. For malignant tumors, radiosurgery is most often used in conjunction with fractionated radiation therapy to take advantage of the single fraction destructive effects of radiosurgery followed or preceded by conventional fractionated radiation therapy. Such an approach enhances the likelihood of a satisfactory response based on the standard 4 Rs of curret radiobiological thinking. Stereotactic radiosurgery is a single "fraction" treatment; fractionated stereotactic radiosurgery is an absolute oxymoron. Certainly, renewed interest in the risk-benefit of fractionated radiation therapy is a logical outgrowth of the current tremendousave of enthusiasm for radiosurgery. In fact, the growth of radiosurgery has made radiation oncologists re-think their own practice of conventional radiation therapy. Similarly, it has had a profound impact on procedure selection by neurological surgeons. The third issue is addressed by the enormous volume of literature relative to outcomes in vascular malformations, malignant tumors, and benign tumors. The usage of radiosurgical technology should continue to stimulate thoughtful investigators to advance outcomes in these difficult conditions and reduce the risks of standard surgical techniques. It must be based on a collegial and multidisciplinary approach. The timing of Rosenthal and Glatstein's editorial was a mystery, appearing almost atavistic, especially considering the enormous growth of understanding and experience accumulated in the ten-year interval since both linac and gamma knife radiosurgical tecnologies became available in North America. AUTHORS' RESPONSE: In response to the Letter to the Editor by Lunsford, Flickinger and Larson, our main objectives in writing that article were twofold. The first was to review those principles of fractionation derived from a near century's experience in clinical radiobioloy. We have learned over and over again that, in general, hypofractionation leads to poorer tumor control, and more frequent and severe normal tissue complications. We believe that this point was, perhaps, not as fully appreciated during the development of radiosurgery because of a more surgical rather than radiotherapeutic influence. The second objective regards the safety issues of the even more widespread use of radiosurgery for brain tumors during the period when long-term follow-up data (ten years or more) are still emerging. Radiosurgery is in common use at our institution, the University of Pennsylvania Medical Center. We in no way wish to diminish the established safety and effectiveness of radiosurgery for arteriovenous malformations (AVMs). Additionally, we wholeheartedly encourage continued investigation for benign and malignant intracranial tumors. Our chief concern is the objective scientific validation of radiosurgery for these latter applications in prospective trials which have adequate long-term follow-up to establish safety. The central nervous system is the most unforgiving organ in terms of late radiation effects. Are all patients undergoing radiosurgery for benign tumors being accurately informed of the good results of modern fractionated radiotherapy, and those who undergo it for malignant tumors, that objective phase III validation and long-term safety data are NOT yet available? It frightens us even more that Lunsford et al. state, "In fact, the growth of radiosurgery has made radiation oncologists re-think their own practice of conventional raiation therapy." Just when do we evaluate the new clothes for the emperor Lunsford et al. tell us that radiosurgery technology has been "re-designed" with ".an entirely different radiobiologic goal. (the) inability of a tumor cell to divide and multiply." Radiation oncologists have long been taught as residents that raiologists accept the definition of "radiobiologic cell death" as the loss of continual clonogenicity. We all strive to this end in the treatment of tumors, but we are concerned about the extrapolation of the accepted application of radiosurgery for AVM tumors. More than 10,000 patients have had radiosurgery for brain tumors. Many of these have been benign, and more than 1,000 patients were treated with protons at the Harvard Cyclotron Unit, mostly for pituitary adenoma. Their experience has established safety, but the data for photon radiosurgery is not as large or mature, and one wonders how much photon radiosurgery adds to the excellent results achievable by conventional fractionated radiotherapy, especially for patients with pituitary tumors. With respect to malignant primary tumors or metastases, there have been fewer patients so treated. We recognize that longer term follow-up is not as important an issue for this unfortunate patient population whose survival period is generally short. Nonetheless, we reiterate that: A) hypofractionation has historically been shown to lead both to decreased control and increased complications, and B) that the higher the grade of a brain tumor, the more difficulty we have in localizing its extensions, especially when a treatment volume is <3 cc. There is absolutely no evidence that fractionated stereotactic treatment is an "oxymoron." Those data are only now beginning to emerge. It makes sense to encourage the investigation of radiosurgery as a boost followingonventional fractionated radiotherapy, or, for those who had the wherewithal to develop practical and cost-effective methods to treat with "fractionated radiosurgery" (read "stereotactic radiotherapy") to use those principles of clinical radiobiology twe have learned painstakingly over the last century to drive clinical investigation, and not rely solely on the impetus of new technology. Such investigation is ongoing at our institution, as we strive for the scientific evaluation of the comparative efficacy and long-term safety of radiosurgery for brain tumors. Had Coutard and Baclesse not pioneered fractionation, radiotherapy probably would have fallen into oblivion due to the morbidities of single shot treatment. Indeed, much of the first half of this century was spent learning that doses large enough to sterilize a mass of tumor cells (10 logs) cannot be predictably given safely. Instead, fractionation evolved which permitted us to exploit repopulation, redistribution, reoxygenation and repair. The use of these large single doses remains, at least in our minds, investigational in the treatment of especially malignant tumors. This is the way this subject is presented to patients here.
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PMID:Regarding: Rosenthal DI, Glatstein E. "We've Got a Treatment, but What's the Disease?" The Oncologist 1996;1. 1038 30

Few cases of pituitary adenoma with metastases have been reported. We report a case with histologically benign intracranial and cauda equina metastases. We compare it to the others in the literature.
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PMID:Metastases from a pituitary adenoma: MRI. 1055 31

The current, highly sophisticated, brain imaging techniques and three dimensional (stereotactic) mapping of intracranial targets, combined with recent developments in concentration of radiation therapy (x- or gamma-ray) onto these targets, have allowed obliterative treatment for many intracranial diseases previously the preserve of the neurosurgeon alone. Vascular malformations, acoustic neuroma, complex meningioma, pituitary adenoma and craniopharyngioma all fall into this category, as well as base of skull tumours. There are occasional indications for single (a few) cerebral metastases and possibly a highly selected role in primary malignant brain tumours. The subject of so-called 'radiosurgery' is an important and developing one and is complementary to modern neurosurgery.
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PMID:Stereotactic intracranial radiotherapy/radiosurgery has come of age. 1090 23


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