Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis. Lean body mass depletion is one of the main features of cachexia and it involves not only skeletal muscle but also affects cardiac protein. The cachectic state is invariably associated with the presence and growth of the tumour and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumour and the host leads to an accelerated starvation state which promotes severe metabolic disturbances in the host, including hypermetabolism which leads to an increased energetic inefficiency. Unfortunately, at the clinical level, cachexia is not treated until the patient suffers from a considerable weight loss and wasting. Therefore, it is of great interest to analyze possible early markers of the syndrome. In the present review both metabolic and hormonal markers are described. Although the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from fully understanding the underlying basis for this syndrome. The suggested mediators (associated with both depletion of fat stores and muscular tissue) can be divided into two categories: of tumour origin (produced and released by the neoplasm) and humoural factors (mainly cytokines). One of the aims of the present review is to summarize and evaluate the different catabolic mediators (both humoural and tumoural) involved in cancer cachexia, since they may represent targets for clinical investigations. Additionally, an overview of the main therapeutic approaches for the treatment of the cachectic syndrome is presented.
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PMID:Targets in clinical oncology: the metabolic environment of the patient. 1748 80

Coagulation activation appears to play a role in tumor progression. Low-molecular-weight heparin (LMWH) may influence tumor growth and LMWHs have been shown to beneficially influence tumor response to chemotherapy. In a phase II study using docetaxel plus enoxaparin in 25 patients with advanced breast cancer, fibrin monomer, transforming growth factor-beta 1 (TGF-beta(1)) and response rates were evaluated. Enoxaparin was administered at a daily dose of 0, 5 or 1.0 mg/kg and docetaxel at 35-45 mg/m(2) once weekly. Nine patients achieved a partial response (36%) and nine patients (36%) had stable disease. The median time to progression was 11.5 weeks (range 5-51 weeks), and 16 weeks combining patients with partial remission and stable disease. One major bleed occurred. Patients with partial remission had a significant decrease of TGF-beta(1) and fibrin (P < 0.05). A significant correlation between TGF-beta(1) and fibrin monomer was also seen in all subgroups independent of clinical response. The most frequent toxicities were granulocytopenia, asthenia, transient peripheral edema and temporary hot flushes. In conclusion, docetaxel plus enoxaparin was quite active and well tolerated in patients with advanced breast cancer. These preliminary data suggest further clinical research using chemotherapy plus enoxaparin as an antitumor therapy in advanced breast cancer is warranted.
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PMID:Combining chemotherapy and low-molecular-weight heparin for the treatment of advanced breast cancer: results on clinical response, transforming growth factor-beta 1 and fibrin monomer in a phase II study. 1758 15

A 32-year-old man presented with asthenia, weight loss, cough, and dysphagia following a recent stay in Morocco. Endoscopy showed a bulky mass of the epiglottis suspected of being a malignant tumor. The patient underwent jointly an F-18 FDG PET/CT and a biopsy of the tumor. Against all expectations, biopsy revealed granulomatous inflammation with epitheloid giant cells and caeseating necrosis. These findings associated with the presence of acid-fast bacilli in the sputum smears were highly suggestive of laryngeal tuberculosis, which was confirmed later after cultivation of mycobacteria. F-18 FDG PET showed diffuse pharyngolaryngeal and lung uptake with bilateral cervical and abdominal nodes, but also one thoracic vertebral uptake. Lung CT could have revealed carcinomatous dissemination, but cavitary lesions in some pulmonary segments were more evocative of tuberculosis. Moreover, cerebral MRI showed brain tuberculomas not visualized on F-18 FDG PET/CT. The patient was treated with a 5-antituberculosis drug regimen, which improved clinical symptoms with epiglottis mass regression, and lung CT image reduction, clinching the systemic tuberculosis diagnosis. A control F-18 FDG PET/CT performed 5 months later showed disappearance of the pharyngolaryngeal and node uptake, with an improvement of lung uptake without normalization, arguing for persistent disease. Unexpected pathologic findings may be present in more than 3% of neck dissections. Although this is usually indolent, with the underlying SCC remaining the main prognostic determinate, it may significantly complicate postoperative management.
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PMID:Systemic tuberculosis presenting as an epiglottic mass detected on F-18 FDG PET/CT. 1771 28

The development of cancer cachexia is perhaps the most common manifestation of advanced malignant diseases and has been recognized as a poor prognostic sign. The abnormalities associated with the condition include progressive weight loss, anorexia, asthenia, and anemia. The degree of cachexia is inversely correlated with the survival time of the patient and always implies a poor prognosis. Currently there is no established mechanism for cancer cachexia, but the severe metabolic disturbances and marked alterations in carbohydrate, lipid, and protein metabolism in the host finally lead to an increased energy deficiency. Weight loss, the key feature of cachexia, is due to a reduction of food intake, an increase in energy expenditure, or a combination of the two. A variety of changes in nutrient metabolism have been described in patients with cancer cachexia. Patients frequently exhibit a relative glucose intolerance and insulin resistance with increased activity of the Cori cycle. The cancer-bearing state affects protein synthesis and breakdown in different tissues of the body in a different manner. An acute-phase protein response can be presented in a significant proportion of patients with cancer with disease progression. A variety of proinflammatory cytokines appears to play a role in aspects of cachexia and a complex network of cytokines in combination with other factors might be involved. Aside from potential humoral mediators of cachexia, tumor-derived biologically active molecules have been reported recently.
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PMID:Current perspectives of catabolic mediators of cancer cachexia. 1776 31

The combination of docetaxel and cisplatin has shown promising results in anthracycline-pretreated patients with advanced breast cancer, but with substantial toxicity. The efficacy and safety in anthracycline-naive patients has not been evaluated. Between October 2003 and January 2006, we enrolled 39 patients. None had undergone chemotherapy for metastatic disease or been exposure to adjuvant anthracycline-based regimens earlier. Eligibility criteria included: histologically proven metastatic cancer; WHO performance status (PS) 0-2; and adequate hematological, hepatic and renal function. Docetaxel (70 mg/m) and cisplatin (50 mg/m) were administered every 3 weeks until the patient either refused to continue, or progression, or even unacceptable toxicity occurred. Tumor response was assessed every three cycles. One patient was withdrawn from response analysis because of toxicity. Thirty-eight patients had a complete tumor assessment. Median age was 50 years (range, 28-63); 5.1% had a WHO of PS of 0; 87% a PS of 1; 7.7% a PS of 2; in 69%, two or more organs were involved. A total of 291 cycles (range, 1-9) were administered. Three complete responses and 27 partial responses (intent-to-treat response rate 30/39=76.9%) resulted; disease remained stable in six patients and two had disease progression. Grade III/IV toxicities included diarrhea in 10.2%, asthenia/fatigue in 2.5%, mucositis in 5.1% and neutropenia in 87.3% of patients. Seven patients developed febrile neutropenia (17.9%). The median time to progression was 11.2 months; the timespan was not sufficient to track the median survival. Docetaxel/cisplatin is an active regimen with acceptable toxicity in the first-line treatment of metastatic breast cancer, but it is not sufficiently promising as a standard. Further randomized study is warranted.
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PMID:An open-labeled phase II trial of docetaxel in combination with cisplatin as first-line cytotoxic therapy for anthracycline-naive patients with metastatic breast cancer. 1789 23

The marine ecosystem that has contributed to the discovery of cytarabine and its fluorinated derivative gemcitabine is now considered the most productive toll to acquire new natural derived anticancer entities. Few marine anticancer agents have entered clinical development, including bryostatin-1, dolastatin 10, LU103793, ET-743, kahalalide F, didemnin B and aplidine. The marine plitidepsin aplidine derived from the mediterranean tunicate Aplidium albicans is a synthetically produced anticancer agent that is structurally related to didemnins. Aplidine's mechanism of action involves several pathways, including cell cycle arrest, inhibition of protein synthesis and antiangiogenic activity. Phase I studies have been reported for a number of several schedules including 1-hour, 3-hour and 24-hour infusion. Evidences of antitumor activity and clinical benefit of aplidine in several tumor types were noted across phase I trials, particularly in advanced medullar thyroid carcinoma. Phase II studies are underway. Within the entire phase I program, dose-limiting toxicities of aplidine were neuromuscular toxicity, asthenia, skin toxicity, and diarrhea. Interestingly, no hematological toxicity was observed. Aplidine displayed a very peculiar delayed neuromuscular toxicity that was found to be closely related to the symptoms described in the adult form of carnitine palmitoyl transferase deficiency type 2, which is a genetic disease treated with L-carnitine. Consistently, concomitant administration of L-carnitine allowed to improve aplidine-induce neuromuscular toxicity. In summary, aplidine is a novel marine anticancer agent with a very particular delayed neuromuscular toxicity that requires careful follow-up with promising antitumor activity.
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PMID:Aplidine: a paradigm of how to handle the activity and toxicity of a novel marine anticancer poison. 1804 96

Three regimes of combined treatment for intraoral and oropharyngeal cancer were compared. In group A, cisplatin 6 mg/m2 was given intravenously, daily; group B--40 mg/m2, weekly; group C--100 mg/m2, once in 3 weeks. All patients simultaneously received distant radiation therapy in a standard fractionated dose of 2 Gy per fraction, 5 times a week, up to TTD of 68-70 Gy. Among relatively frequent side-effects were granulocytopenia, asthenia and stomatitis. Overall immediate effectiveness was: group A--100%, group B--96% and group C--100%. The rates of complete tumor resorption were: group A--27.3%, group B--19.2% and group C--16.7%.
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PMID:[Effectiveness of different regimes of combined treatment (cisplatin+ radiotherapy) for intraoral and oropharyngeal cancer]. 1815 24

We report a case of acinar cell carcinoma primary to the liver. The tumor was diagnosed in a 35-year-old woman complaining of abdominal pain and asthenia; serum alpha-fetoprotein (AFP) levels were increased at 6,000 IU/mL; imaging studies showed a hypervascular mass located in the left lobe of the liver. A left lobectomy was performed. The tumor had a heterogeneous appearance. In well-differentiated areas, tumor cells formed acinar structures, had a pyramidal shape and a highly eosinophilic, granular cytoplasm, PAS diastase resistant. In less-differentiated areas, tumor cells were endocrinelike. The immunohistochemical study showed that tumor cells expressed trypsin. Alpha-fetoprotein and alphal-antritrypsin were detected in about 30% of cells; HepPar1 was present in 15% of cells. Chromogranin A and synaptophysin were detected in rare cells. After surgery, serum AFP levels quickly returned to normal; no evidence of recurrence or metastasis was observed during follow-up. The final diagnosis, based on histological, immunohistochemical, and ultrastructural arguments, was extra-pancreatic acinar cell carcinoma, primary to the liver. This unusual lesion is likely to be the result of an abnormal differentiation pathway involving a transformed multipotential progenitor cell.
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PMID:Primary acinar cell carcinoma of the liver. 1819 78

A systematic review was performed to determine whether first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow/stem cell transplantation improves response rate, time-to-disease progression, or survival compared with standard-dose chemotherapy in patients with inoperable, locally advanced, or metastatic soft tissue sarcoma. The MEDLINE, EMBASE, and Cochrane Library databases were searched. Three randomized trials (2 phase 3, 1 phase 2), 12 phase 2, and 5 phase 1 dose-escalation trials were located. One randomized trial (N=314) did not detect significant differences in response rate (P=.65) or survival (log-rank P=.98) between high-dose doxorubicin plus ifosfamide with granulocyte macrophage colony-stimulating factor and doxorubicin plus ifosfamide at standard doses. Progression-free survival, however, was significantly longer in the high-dose arm (log-rank P=.03). Higher rates of thrombocytopenia, infection, grade 3 of 4 asthenia, and stomatitis were observed with high-dose compared with standard-dose chemotherapy. Preliminary results from a second randomized trial (N=162) indicated no benefit with respect to tumor response for an intensified mesna, doxorubicin (Adriamycin), ifosfamide, and dacarbazine regimen with granulocyte colony-stimulating factor support compared with standard doxorubicin, ifosfamide, and dacarbazine. Grade 4 thrombocytopenia was significantly higher with the high-dose regimen. Four phase 2 trials of high-dose regimens observed tumor response rates greater than 50%. Phase 1 trials reported dose-limiting toxicity for dose-intensive chemotherapy regimens. On the basis of the available evidence, high-dose chemotherapy with growth factor or autologous bone marrow/stem cell transplantation should not be used in the routine treatment of patients with inoperable, locally advanced, or metastatic soft tissue sarcoma.
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PMID:Dose-intensive chemotherapy with growth factor or autologous bone marrow/stem cell transplant support in first-line treatment of advanced or metastatic adult soft tissue sarcoma: a systematic review. 1822 66

GOLF is a triple translational combination chemotherapy regimen with gemcitabine, oxaliplatin, and 5-fluorouracil (5-FU) (plus levofolinic acid), cytotoxic drugs currently used in the treatment of pancreatic carcinoma. Considering its promising anti-tumor effects in patients with gastroenteric malignancies, we carried out the present study to investigate its toxicity and anti-tumor activity in patients with advanced pancreatic carcinoma. Twenty-seven patients were enrolled in the study, 15 males and 12 females with an average age of 61 years and a performance status (ECOG) </= 3. Eight of them had already received first-line chemotherapy, 16 had liver involvement and 11 had inoperable locally (nodes, soft tissue infiltration, peritoneum etc) advanced disease. All patients received biweekly gemcitabine (1000 mg/m(2 )on day 1), oxaliplatin (85 mg/m(2 )on day 2); levofolinic acid (100 mg/m 2) and 5-FU (400 mg/m(2 )as bolus, and 800 mg/m(2 )in 24-h infusion) on days 1 and 2. We report one fatal event occurring just after the first cycle due to lung embolism; grade II-III-diarrhea and mucosytis (44.4%); alopecia (37%); thrombocytopenia (18.5%); grade I-II asthenia, fatigue, non-neutropenic-fever (37%) and oxaliplatin-related neurotoxicity (18.5%). We also registered fast pain control in most patients, an objective response and disease control rate of 33.3% and 63% (1 complete and 8 partial responses and 8 disease stabilizations) respectively, with clinical benefit in 60% of patients and median time to progression and overall survival of 5.5 and 8 months, respectively. In conclusion, the GOLF regimen appears to be a feasible treatment for patients with advanced pancreatic carcinoma that deserves to be evaluated in phase III trials.
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PMID:Biweekly triple combination chemotherapy with gemcitabine, oxaliplatin, levofolinic acid and 5-fluorouracil (GOLF) is a safe and active treatment for patients with inoperable pancreatic cancer. 1834 54


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