Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar soft part sarcoma (ASPS) is one of the soft tissue sarcomas characterized by metastasis early in the course of the disease, regardless of slow tumor growth. The ultimate clinical outcome is, therefore, very poor. To date, the efficacy of combination chemotherapy for this tumor has not been confirmed. We present a case of ASPS in an 8-year-old boy with bilateral pulmonary metastasis who received systemic combination chemotherapy (CPM/IFO/ACD/ADR/CD DP/VP-16 as induction, and VCR/ACD as maintenance therapy) for eleven months. The result showed that despite the prevention of tumor progression, such intensive chemotherapy could not cure the disease. Besides refinement of chemotherapy regimens, immunotherapy might be considered for ASPS.
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PMID:[Intensive chemotherapy for alveolar soft part sarcoma with lung metastasis in a child]. 833 54

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. It is typically detected at an advanced stage, at which the therapeutic options are very limited. One remarkable feature of PDAC that contributes to its resilience to treatment is the extreme stromal activation seen in these tumors. Often, the vast majority of tumor bulk consists of non-tumor cells that together provide a tumor-promoting environment. One of the signals that maintains and activates the stroma is the developmental protein Sonic Hedgehog (SHH). As the disease progresses, tumor cells produce increasing amounts of SHH, which activates the surrounding stroma to aid in tumor progression. To better understand this response and identify targets for inhibition, we aimed to elucidate the proteins that mediate the SHH-driven stromal response in PDAC. For this a novel mixed-species coculture model was set up in which the cancer cells are human, and the stroma is modeled by mouse fibroblasts. In conjunction with next-generation sequencing we were able to use the sequence difference between these species to genetically distinguish between the epithelial and stromal responses to SHH. The stromal SHH-dependent genes from this analysis were validated and their relevance for human disease was subsequently determined in two independent patient cohorts. In non-microdissected tissue from PDAC patients, in which a large amount of stroma is present, the targets were confirmed to associate with tumor stroma versus normal pancreatic tissue. Patient survival analysis and immunohistochemistry identified CDA, EDIL3, ITGB4, PLAUR and SPOCK1 as SHH-dependent stromal factors that are associated with poor prognosis in PDAC patients. Summarizing, the presented data provide insight into the role of the activated stroma in PDAC, and how SHH acts to mediate this response. In addition, the study has yielded several candidates that are interesting therapeutic targets for a disease for which treatment options are still inadequate.
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PMID:Assessment of the stromal contribution to Sonic Hedgehog-dependent pancreatic adenocarcinoma. 2399 58

Pathologic fractures of the femur because of bone metastases seriously affect the quality of life of cancer patients. Different surgical options are indicated to achieve a durable and solid fixation, depending on several clinical, prognostic and mechanical factors. Locked intramedullary nailing is currently used to treat pathologic femoral fractures in patients with multiple metastases when the trochanteric region or shaft is mainly involved. This study evaluates intramedullary nailing for treatment of patients with pathologic femoral fractures, focussing on complications, clinical and functional outcomes and survival rates. The series included 80 pathologic fractures treated with a titanium alloy Proximal Nail (Standard or Antirotation) or Lateral Anterograde Femoral Nail (PFN, PFNA or LAFN, Synthes) inserted in a locked static mode. Acrylic cement was used to fill the bone cavity after nail insertion in eight patients; percutaneous cementoplasty was simultaneously performed in 11 cases of severe ipsilateral acetabular osteolysis. Postoperative outcomes focussed on pain relief, postoperative mobility and quality of life and they were analysed retrospectively using QOL-ACD and ECOG. Eleven patients (13.75%) suffered from non-fatal DVT post-surgery, with no pulmonary embolism. Six patients (7.5%) developed superficial wound infections and two patients (2.5%) developed pnaeumonia. There was no loss of reduction, breakage, screw pull out, or hardware or implant failure that required component substitution or revision. Lung histotype and the contemporary presence of cerebral and visceral metastases appeared to be predisposing factors in reducing survival time. All patients attained satisfactory pain relief, early deambulation and a marked clinical improvement during the first 6-10 postoperative months, with gradual worsening thereafter from deterioration of their general condition due to cancer progression. The patients' survival rate was 40% at 1 year, 25% at 2 years and 15% at 3 years. Results confirm that multiple factors related to patients and primary cancer may affect survival rate after femoral fracture. Intramedullary nailing should be indicated for pathologic fractures at femoral diaphysis and metaphysis when cancer is in an advanced stage. This procedure offers good and durable stability, and enables pain relief, early postoperative mobilisation and weight-bearing, thus improving the quality of life of cancer patients.
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PMID:Intramedullary nailing for treatment of pathologic femoral fractures due to metastases. 2411 52