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)

A 52-year-old patient presented himself with weight loss and night sweats. Laboratory analyses revealed a high sedimentation rate, elevated immunoglobulines and anaemia with sludge phenomenon. Differential diagnoses included Multiple Myeloma and Lymphoma. Having a risk constellation for HIV infection and just having recovered from oral thrush also made this diagnosis possible. Urinary analysis and chest x-ray were normal; however, CT-scan detected renal cell cancer with pulmonary metastases. Renal cell cancer is heterogeneous in presentation, symptoms are unspecific, therefore they are often discovered late when they have already metastasized. Paraneoplastic syndromes, e.g. hypercalcaemia or hypertension are not infrequent in renal cell cancer.
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PMID:[Weight loss and night sweats with unexpected tumor localization]. 1807 82

Hypercalcemia is the most common paraneoplastic syndrome in adult malignancies (10%-30%) and rare in pediatric cancers (0.5%-1.3%). Hypercalcemia in malignancies is categorized into two groups: 1) Humoral hypercalcemia of malignancy (HHM)-caused by substances that are produced by the tumor cells and secreted into the blood circulation such as parathyroid hormone-related protein (PTH-rP), parathyroid hormone-intact (PTH-i), the enzyme 1-alpha-hydroxylase that catalyzes the synthesis of the active form of vitamin D (1,25-dihydroxyvitamin D3), and other substances; 2) Hypercalcemia due to bone destruction by metastases. Hypercalcemia occurs in less than 5% of female genital tract malignancies and virtually in all cases (95%) it is HHM. Female genital tract malignancy-associated HHM is caused most often (80%) by PTH-rP. Ovarian cancer is the most common female genital tract malignancy that is associated with HHM. Although HHM occurs in only 5% of ovarian cancers, it occurs in a relatively high percentage in the following rare ovarian tumors: a). Small cell carcinoma of the ovary - a rare tumor that accounts for only 1% of all ovarian cancers and is associated with HHM in 66% of the cases; b). Clear cell carcinoma of the ovary - an uncommon tumor that accounts for 5% of all ovarian cancers and is associated with HHM in 5%-10% of the cases. Since dysgerminoma is the most common malignant ovarian tumor in children, in girls it is the second most common ovarian neoplasm, after ovarian small cell carcinoma, to be associated with HHM.
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PMID:[Hypercalcemia in malignancies of the female genital tract]. 1848 65

Acrokeratosis paraneoplastica is a rare paraneoplastic syndrome commonly affecting males over 40 years of age. There exists a strong association with squamous cell carcinoma (SCC) of the upper aerodigestive tract or cervical metastatic disease originating from an unknown primary. We report a case associated with SCC of the right tonsil with persistent paraneoplastic cutaneous lesions 2 years after successful treatment of the underlying neoplasm.
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PMID:Bazex syndrome (acrokeratosis paraneoplastica): persistence of cutaneous lesions after successful treatment of an associated oropharyngeal neoplasm. 1877 90

Usually paraneoplastic symptoms precede actual diagnosis of a neoplasm, however, may also be concurrent with it. They do not result from the localization of the primary lesion nor are associated with metastases or with other effects of presence and treatment of the neoplasm. The immunological etiology is assumed. In diagnostics estimation of level of the antionconeuronal antibodies may be helpful. Mental disorders in the course of paraneoplastic syndrome may coexist with neoplasm, but also may precede it (combined with neurological signs or without them). Such mental disorders have diverse clinical pictures and often are characterized by atypical and heavy course. Observed psychopathological symptoms do not form any specific diagnostic profile delineated in ICD 10 and encompass disturbances of consciousness, perception and thinking, as well as affective states. Although psychiatric intervention in paraneoplastic syndromes with psychopathological symptoms is merely symptomatic, one can still expect atypical response. Suspected paraneoplastic syndrome in patients not yet diagnosed as having neoplasm should persuade one to initiate a screening for potential focal change and to introduce targeted treatment should tumor growth be confirmed.
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PMID:[Mental disorders in paraneoplastic syndromes]. 1885 54

Paraneoplastic syndromes (PNS) represent the clinical manifestation of the remote and indirect effects produced by tumor metabolites or other products. Paraneoplastic effects are not directly mediated by tumor invasion of normal tissue, or by the disruption of normal function of the involved organ, or by distant metastases. More than 260 cases of nasopharyngeal carcinoma (NPC) associated with PNS have been reported in the literature. These syndromes can be divided into six main groups: cutaneous or dermatologic, endocrine, hematologic, osteoarticular or rheumatologic, neurologic, and ocular. The most common dermatologic manifestation is dermatomyositis, while the syndrome of inappropriate secretion of antidiuretic hormone and occasionally Cushing's syndrome due to ectopic ACTH production are the endocrinologic manifestations. Tumor fever and leukemoid reaction, osteoarticular or rheumatic syndromes, including clubbing of the fingers and toes, sensory neuropathy and demyelinating motor polyneuropathy, and rarely optic neuritis represent the most prominent examples of the other groups of syndromes. PNS may occur before the NPC is manifest, or while it is in an occult stage, and thus the possibility of NPC should be considered in patients with these various disorders. While some PNS will respond to direct treatment, most often the PNS subsides in parallel to response of the NPC, and thus may be useful for monitoring tumor response or recurrence.
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PMID:Paraneoplastic syndromes in patients with nasopharyngeal cancer. 1911 98

Cancer cells are characterized by indefinite proliferation, invasiveness and metastases. These characteristics are usually related to one another. Namely, cancer cells that proliferate rapidly tend to invade and metastasize. Renal cell carcinoma (RCC) typically does not proliferate rapidly nor does it invade the surrounding tissues, but it does metastasize. RCC has several peculiar characteristics that are not observed in other cancers: a relatively late recurrence, a high frequency of paraneoplastic syndrome, hypervascularity and the spontaneous regression of metastatic lesions after the excision of the primary tumor. These clinical observations suggest that cytokines or growth factors are important contributors to microenvironments favoring the growth of cancer cells. Thus, the blockade of cell-to-cell communication might have some therapeutic potential. Accordingly, a popular strategy for molecular-targeted therapy for RCC targets the vasculization of RCC induced by vascular endothelial growth factor (VEGF). This review highlights the biological features of RCC that are relevant to molecular-targeted therapy.
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PMID:Renal cell carcinoma: biological features and rationale for molecular-targeted therapy. 1939 78

The Paraneoplastic syndromes include the disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion by the primary tumor or its metastases. Neoplastic cells can produce a variety of peptides that exert biologic actions at local and distant sites and can elicit responses that cause a variety of hormonal, hematologic, dermatologic and neurologic symptoms. Almost every type of malignancy has the potential to produce hormones or cytokines or to induce immunologic responses. Lung cancers, both non-small cell and small cell, are capable of producing a variety of paraneoplastic syndromes. The majority of such syndromes are caused by small cell carcinomas, including many endocrinopathies. Syndrome of inappropriate antidiuretic hormone (SIADH) has been commonly associated with small cell carcinoma and is often seen in these patients. However, SIADH associated with squamous cell carcinoma has rarely been reported on, and the mechanism for this rare association is still unknown. We present here a case of a 77-yr-old man who developed SIADH caused by squamous cell carcinoma of the nasopharynx.
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PMID:Syndrome of inappropriate antidiuretic hormone (SIADH) secretion caused by squamous cell carcinoma of the nasopharynx: case report. 1943 82

Paraneoplastic syndromes are disorders of host organ function occurring at a site remote from the primary tumor and its metastases. Paraneoplastic syndromes associated with primary lung cancer are not uncommon, have diverse initial manifestations, and epitomize the systemic nature of human malignant disease. The spectrum of clinical features in patients with paraneoplastic syndromes is very wide. Although diagnosis is often one of exclusion, improved understanding of the pathogenesis involved in some of these syndromes has provided another means of recognizing these disorders and perhaps treating affected patients. In this update, we review paraneoplastic syndromes associated with lung cancer, potential mechanisms, clinical manifestations, diagnosis, and treatment.
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PMID:[Paraneoplastic syndromes. Associated with lung cancer]. 1976 44

Parathyroid hormone-related protein (PTHrP) is the causative factor of the paraneoplastic syndrome humoral hypercalcemia of malignancy (HHM) and it also contributes to osteolytic metastases, both of which are common complications of squamous carcinomas of the lung. Inhibition of autocrine epidermal growth factor receptor (EGFR) signaling has been shown to reduce plasma calcium and PTHrP concentrations in two lung squamous cell carcinoma xenograft models of HHM. The purpose of this study was to investigate the mechanism by which EGFR is activated and stimulates PTHrP gene expression in lung squamous carcinoma cell lines. Amphiregulin (AREG) was the only EGFR ligand that could be consistently detected in conditioned media from the SCC lines, and reduction of its expression either by siRNA or by precipitating antibody reduced PTHrP mRNA expression as effectively as EGFR-targeted inhibition. Using siRNA knockdown or inhibitors to upstream regulators of AREG shedding including TACE, Src/Lck, and G(i/o), also reduced PTHrP mRNA expression. We determined that blockade of autocrine AREG-EGFR signaling does not affect PTHrP mRNA stability. Of the three PTHrP promoters (P1, P2, and P3), P1 mRNA could be reduced by nearly 100% with an EGFR inhibitor, and both epidermal growth factor and AREG stimulated P1 mRNA by approximately 5-fold. Finally, ectopic expression of EGFR in a receptor-low but AREG-expressing cell line increased PTHrP mRNA levels in vitro, and induced the capability to cause HHM and rapid osteolytic growth in vivo. Taken together, we provide evidence that AREG stimulation of EGFR results in high levels of PTHrP gene expression, contributing to cancer-associated bone pathology.
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PMID:Reconstitution of amphiregulin-epidermal growth factor receptor signaling in lung squamous cell carcinomas activates PTHrP gene expression and contributes to cancer-mediated diseases of the bone. 1982 97

Paraneoplastic syndromes are an uncommon, yet well-described, phenomenon in cancer patients. The syndrome of granulocytosis caused by granulocyte colony-stimulating factor (G-CSF) production by tumors is rare and is difficult to diagnose in patients receiving treatment for metastatic disease. From January 2005 to May 2009, 626 patients were evaluated for treatment of metastatic melanoma. At initial evaluation or during the course of treatment, six patients had an elevated white blood cell count and no evidence of infection. All six had significantly elevated serum G-CSF. The level of serum G-CSF was directly correlated with the absolute neutrophil count. In-vitro assay of melanoma tumor from two patients showed elevated G-CSF in cell culture supernatant. The paraneoplastic syndrome of granulocytosis resulting from ectopic G-CSF production in patients with metastatic melanoma is rare. This diagnosis should be considered when common causes of granulocytosis have been ruled out.
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PMID:Paraneoplastic granulocytosis in metastatic melanoma. 2044 Feb 26


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