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)

Twenty-two women affected by metastatic breast carcinoma have been treated with a combination of levo folinic acid 100 mg/m2 plus 5-fluorouracil 450 mg/m2 i.v. on day 1-2, and epidoxorubicin 75-90 mg/m2 on day 2. This treatment cycle was repeated every 21-28 days. No patients had previously received chemotherapy for metastatic disease. Fourteen patients (64%) showed a major objective response with 3 complete (14%) and 11 partial responses (50%). Three patients showed a stabilization of disease and 5 (23%) progressed. All patients received ondansetron as antiemetic treatment which led to complete protection from vomiting in 68% of cases. Grade 1-2 diarrhea was recorded in 27% of the patients. Ten patients received recombinant human granulocyte-colony stimulating factor (rhG-CSF) as leukopenia-preventive treatment. In this group of patients the interval between chemotherapeutic cycles was shorter than in the group of 12 patients who did not receive rhG-CSF.
 ...
PMID:Levo folinic acid and 5-fluorouracil plus high dose epidoxorubicin as first line treatment for metastatic breast carcinoma. 838 92

Clinicopathological and immunohistochemical studies were performed in a patient with paraneoplastic limbic encephalitis, myelitis, sensory neuropathy and cerebellar degeneration secondary to small cell lung cancer. A 67-year-old male smoker developed orthostatic dizziness 6 months prior to admission. Over the following months, his wife noticed that he became forgetful and confused. Over the next three weeks, he became unable to sit or stand unaided and admitted to our service. On admission, he was lethargic and disoriented in time and place. Neurological examination revealed marked limb weakness with distal dominant muscle atrophy. A chest radiograph demonstrated a mass in the right middle lobe and a bronchial biopsy revealed a small cell carcinoma. CT scan and MRI of the brain revealed abnormalities in the bilateral medial temporal lobes and putamen. He was treated with anti-cancer chemotherapy, but died of respiratory failure after 13 months illness. Postmortem examination showed a mass in the right middle lobe of the lung. No tumor metastases were noted in the nervous tissue. Microscopical examinations of the nervous system revealed neuronal loss, astrogliosis and perivascular and parenchymatous lymphocytic infiltration in the hippocampus, subiculum, amygdala, putamen, medulla oblongata, spinal cord and dorsal root ganglia. Loss of Purkinje cells was also seen in the cerebellum without lymphocytic infiltration. Immunohistochemical analysis of the patient's serum and CSF by the use of adult rat brain revealed immunoreactivity at the hippocampal pyramidal neurons CA3 and CA4. At the higher dilution, neuronal nuclei were specifically stained.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[A clinicopathological study of a patient with paraneoplastic limbic encephalitis, myelitis, sensory neuropathy and cerebellar degeneration, associated with a unique antineuronal antibody]. 839 16

Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) by metastatic Lewis lung carcinoma cells (LLC-LN7) was previously shown to contribute to the maintenance of phenotypic characteristics associated with an increased capacity to metastasize. In the present study, pre-incubation of LLC-LN7 cells with neutralizing anti-GM-CSF antibodies diminished the capacity of the tumor cells to form experimental metastases after i.v. inoculation, while pre-incubation with recombinant GM-CSF (rGM-CSF) increased formation of metastases. In the presence of rGM-CSF, the LLC-LN7 cells exhibited an increased capacity to migrate, invade through a reconstituted basement membrane, and adhere to lung tissue. Studies to identify the signal transduction pathway through which GM-CSF enhanced the in vitro metastatic properties of the LLC-LN7 tumor cells implicated protein kinase A (PKA). Signaling through PKA was suggested by the demonstration that the stimulation of tumor-cell motility by GM-CSF was blocked in the presence of the adenylate cyclase inhibitor nicotinic acid, or the PKA inhibitors A3 or KT5720. In addition, the role of PKA as a signaling mechanism for GM-CSF was assessed by using REV-LN7 cells, which are LLC-LN7 cells that have been stably transfected with an expression vector encoding a mutant PKA RI alpha subunit and which, in turn, express a cAMP-resistant PKA. Adherence and invasion by the PKA-defective REV-LN7 cells were not stimulated by rGM-CSF, contrasting with the stimulation observed for wild-type LLC-LN7 cells. These data suggest that rGM-CSF can further enhance the in vitro metastatic characteristics of LLC-LN7 tumor cells and that this is dependent on signal transduction through PKA.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor stimulates the metastatic properties of Lewis lung carcinoma cells through a protein kinase A signal-transduction pathway. 843 41

In this study, cytokine release by tumor-draining lymph node cells sensitized in vitro (IVS-TDLN) was examined and correlated with therapeutic efficacy in adoptive immunotherapy. Mice bearing immunologically distinct MCA 207 and MCA 205 sarcoma tumors were utilized in criss-cross experiments. IVS-TDLN obtained from mice bearing 10-day subcutaneous (s.c.) tumors mediated immunologically specific regression of established 3-day pulmonary metastases, but demonstrated non-specific cytolytic reactivity against both tumors in a 4-h 51Cr-release assay. By contrast, these IVS-TDLN cells were found specifically to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN gamma) when restimulated in vitro with irradiated tumor cells. To determine the predictive value of tumor-specific cytokine release with in vivo therapeutic efficacy, a kinetic analysis of antitumor activities of TDLN obtained from animals bearing MCA 207 tumors for increasing lengths of time was performed. IVS-TDLN cells from mice bearing day-7, -10 and -14 s.c. tumors manifested tumor-specific release of GM-CSF and IFN gamma, and mediated significant antitumor reactivity in vivo. In contrast IVS-LN cells from day-0 and day-21 tumor-bearing animals did not release significant amounts of GM-CSF and IFN gamma, and were not therapeutically efficacious in vivo. Day-4 IVS-TDLN released high levels of GM-CSF and IFN gamma non-specifically, and were not therapeutic in adoptive immunotherapy at doses effective for day-7 and day-14 IVS-TDLN cells. In other experiments, IVS cells generated from different lymph node groups in animals bearing 10-day established s.c. tumors were examined and found to have unique profiles of cytokine release. In these studies, the ability of IVS cells to release specifically both cytokines as opposed to one was associated with greater therapeutic efficacy on a per cell basis. Our findings suggest that the tumor-specific releases of GM-CSF and IFN gamma are useful parameters to assess the in vivo therapeutic efficacy of immune lymphocytes.
 ...
PMID:Tumor-specific granulocyte/macrophage colony-stimulating factor and interferon gamma secretion is associated with in vivo therapeutic efficacy of activated tumor-draining lymph node cells. 853 78

A 43-year-old man died from the complications of astrocytoma metastasis. He first noticed symptoms of a lumbar disc prolapse in 1979. In 1987 a pilocytic astrocytoma (grade I) of the spinal cauda was removed. In 1989 a tumor recidivation at the same site was partially removed. Histology showed a grade II astrocytoma. Two months later the patient developed symptoms of increased intracerebral pressure. CSF cytology showed polymorphic giant tumor cells with hyperchromatic nuclei and a glioblastoma of the cerebral ventricles was diagnosed. The patient died from cardiovascular complications. The post-mortem investigation revealed an astrocytoma of the conus medullaris with an anaplastic ventral area (grade IV). This area was inaccessible to the biopsy. It is believed that tumor metastases from anaplastic parts spread along the spinal cord and brainstem and finally invaded the brain and cerebral ventricles.
 ...
PMID:Ascending central nervous spreading of a spinal astrocytoma. 859 75

The effectiveness of combination therapy using a suicide gene and cytokine genes for the treatment of metastatic colon carcinoma in the mouse liver was investigated. Pre-established hepatic tumors treated with a recombinant adenoviral vector containing the herpes simplex virus thymidine kinase gene(tk) exhibited substantial regression, although all treated animals suffered from subsequent relapses. Although cotreatment with a mouse interleukin 2 (mIL-2)-containing adenoviral vector induced an effective antitumor immune response, the immunity waned with time, and the treated animals eventually succumbed to hepatic tumor relapse or distant metastases. In this study, mouse granulocyte macrophage colony-stimulating factor (mGM-CSF) gene was tested for its ability to further enhance and prolong the antitumoral cellular immunity. A fraction of the animals treated with tk + mIL-2 + mGM-CSF developed long-term antitumor immunity and survived for more than 4 months without recurrence. This long-term antitumor immunity could be enhanced further by subsequent "vaccination" with mIL-2-expressing parental tumor cells. The results indicate that local expression of GM-CSF in the hepatic tumors and prolonged mIL-2 expression are necessary to generate persistent antitumor immunity that is essential for the prevention of tumor recurrence and long-term animal survival.
 ...
PMID:Combination suicide and cytokine gene therapy for hepatic metastases of colon carcinoma: sustained antitumor immunity prolongs animal survival. 870 21

Carcinomatous meningitis (CM) is an uncommon but devastating complication of malignancy. The management is controversial and clear recommendations cannot be made because: 1) Most series include patients with CM that has arisen from different primary malignancies which are associated with different median survival intervals. 2) There have been no prospective randomised investigations of treatment modalities in patients with CM from a particular tumour type. 3) The definition of response varies from one report to another so that some response rates refer to cytological changes in the CSF while others take clinical, cytological and biochemical parameters into account. 4) Reports include patients with and without parenchymal metastases and the natural history of carcinomatous meningitis in the two situations may differ. The median survival of solid tumour carcinomatous meningitis (excluding leukaemia and lymphoma) is approximately 2-3 months and patients with breast cancer have the longest survival (median 3 months). Currently patients are treated with radiotherapy to part or all of the neuraxis with either intrathecal or intravenous chemotherapy but the relative contribution of these modalities to survival or quality of life remains unknown. Approximately 50% of patients with carcinomatous meningitis die from other causes, including systemic disease. The two most important endpoints for the patient, neurological improvement and overall survival, are seldom used in isolation in the literature. Many reports have focused on surrogate markers of response, namely biochemical and cytological data points but the correlation between clinical status and these parameters is poor because of differences between lumbar and ventricular CSF and disturbances of CSF flow in CM. The current literature does not provide clear guidelines for the treatment of this condition. Multicentre, prospective, randomised trials should be conducted that address questions of most relevance to the patient, namely neurological status and overall survival.
 ...
PMID:Carcinomatous meningitis in solid tumours. 892 90

Vaccinia melanoma oncolysate (VMO) prepared with recombinant vaccinia virus encoding the gene of murine granulocyte/macrophage-colony-stimulating factor (GM-CSF) was tested for its therapeutic effect on melanoma pulmonary metastasis. The murine pulmonary metastasis model was established by injecting 2 x 10(5) B16F10 melanoma cells into the tail vein of a C57BL/6 mouse. Intraperitoneal injection of VMO was performed in tumor-bearing mice 3 and 10 days after B16F10 cell inoculation. The results showed that treatment with VMO prepared with GM-CSF-gene-encoded vaccinia virus (GM-CSFVMO) significantly decreased the number of murine pulmonary metastases and prolonged the survival of the tumor-bearing mice. Lymphocytes isolated from fresh blood and spleen of GM-CSFVMO-treated mice showed higher cytolytic activity against B16F10 melanoma cells when compared with lymphocytes from the mice of other treatment groups. Natural killer activity remained unchanged in the GM-CSFVMO-treated group. Cytotoxic activities of peritoneal macrophages were found to be greatly elevated in mice treated with GM-CSFVMO. Further study illustrated that the increased tumor necrosis factor and nitric oxide release from macrophages may contribute to their cytotoxic effects. These results suggest that the tumor oncolysate vaccine prepared with GM-CSF-gene-encoded vaccinia virus has a potent therapeutic effect on tumor metastasis through the efficient induction of antitumor immunity of the host, mainly through the cytotoxic effects of cytotoxic T lymphocytes and macrophages.
 ...
PMID:Active specific immunotherapy of pulmonary metastasis with vaccinia melanoma oncolysate prepared from granulocyte/macrophage-colony-stimulating-factor-gene-encoded vaccinia virus. 895 68

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study, we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve patients with distant metastatic disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle, 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients, 6 of whom had received previous treatment. There were 2 deaths due to toxicity, and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up, only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients, bone marrow suppression is still the major limiting toxic side effect of aggressive chemotherapy, especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support.
 ...
PMID:Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report. 897 90

The 5 year survival for patients with malignant intracranial non-germinoma germ cell tumors (NGGCT) which include endodermal sinus tumors, embryonal carcinomas, choriocarcinomas and immature teratomas is less than 25% following a small resection and radiotherapy. In an effort to improve the survival of these patients, an approach using an attempt at radical resection where feasible followed by multi-modality 'sandwich' therapy (chemotherapy-radiation-chemotherapy) was used to treat 18 newly diagnosed patients between 1986 and 1994 in a multi-institution study. Fourteen patients had histologically proven NGGCT and four were presumed NGGCT because of markedly elevated concentrations of serum and/or CSF alpha fetoprotoin (AFP) and/or beta human chorionic gonadatrophin (b-HCG). The primary tumor was confined to the pineal region in 12 patients, the suprasellar region in five, and a cerebral hemisphere in one. None of the patients had central nervous system metastases at diagnosis by MRI imaging of the spine and CSF cytology. Radical surgical resection was performed initially in 11 patients (gross total -6, subtotal -5): four had a biopsy and three had no surgery. All patients then received 3 or 4 cycles of neoadjuvant chemotherapy with cisplatin (100 mg/m2/cycle) and VP-16 (500 mg/m2/cycle). Of the 12 patients with evaluable disease there were 9 responses to the neoadjuvant chemotherapy (5 CR, 4 PR); 2 patients had stable disease and I progressed during chemotherapy. Six patients with no evaluable disease after a gross total resection had a continuous complete response. Seventeen patients received radiation therapy (involved field -11, involved field + craniospinal -4, involved field + whole brain -2). Twelve patients received 4 cycles post-radiation chemotherapy with vinblastine (6.5 mg/m2/cycle). bleomycin (15 U/m2/cycle), VP-16 (300 mg/m2/cycle, carboplatin (450 mg/m2/cycle). A total of four patients have died (3-progressive/recurrent disease, 1-metabolic). Four year actuarial event-free and total survival rates are 67% and 74%. This multi-modality adjuvant therapy approach appears to dramatically improve the outcome of malignant intracranial NGGCT.
 ...
PMID:Improved prognosis of intracranial non-germinoma germ cell tumors with multimodality therapy. 904 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>