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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiation tolerance of normal tissues remains the limiting factor for delivering crucial tumoridical dose. The late toxicity of normal tissues is the most element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestations of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a "common toxicity language". This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The current proposed scales are not yet validated, and should be used cautiously. The present toxicity scale for acute and late radiation complications is not complete. It bases on analyses and additions of existent system as CTC (Common Toxicity Criteria) and SOMALENT by EORTC/RTOG. Current classification can be used for quantitative definition of complications' grade and for treatment planning.
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PMID:[Classification of early and late radiation reactions and injuries]. 1461 93

We studied factors predicting docetaxel-related toxicity in 113 unselected patients with metastatic cancer treated under routine daily practice. Docetaxel was administered in either a weekly, bi-weekly or tri-weekly schedule. All patients received prophylactic dexamethasone. Twenty-six patients were aged 70 or more, and 28 (24.8%) had an ECOG performance status (PS) score > or = 2. Primary tumors were mainly in breast, lung, and stomach (58, 25, and 14 patients, respectively). Most patients had metastases at two or more sites and were heavily pretreated. NCI-CTC graded toxicities were mild. Grade 3/4 leucopenia and neutropenia occurred in 19.4% and 10.6% of patients, respectively, with febrile neutropenia in 2 patients. Severe nonhematologic toxicities were rare, except for asthenia (8 patients). Complete alopecia occurred in 26.6% of patients. A proportional-odds regression analysis demonstrated that the tri-weekly schedule and older age represented independent risk factors for all-grade leucopenia, whereas a poor PS for anemia. Primary tumor in breast, tri-weekly schedule, an abbreviated and low dose of corticosteroids premedication, and high duration and cumulative dose of docetaxel were factors predicting asthenia. Risk factors for alopecia and vomiting were tri-weekly schedule and high docetaxel cumulative dose, respectively. In conclusion, in daily clinical practice docetaxel toxicity may be correlated with factors related to patient, disease, and treatment characteristics. Taking into account these variables could be a first step toward individualizing treatment.
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PMID:Factors predicting docetaxel-related toxicity: experience at a single institution. 1507 5

ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.
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PMID:ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement. 1549 98

The efficacy of combination therapy with irinotecan and capecitabine has been demonstrated for the first-line treatment of metastatic colorectal cancer (MCRC). The aim of this trial was to evaluate the efficacy and safety of this combination in MCRC as second-line treatment after failure of 24-h infusional 5-fluorouracil (5-FU24h) and folinic acid (FA). Patients pre-treated with 5-FU24h/FA were recruited at two institutions to receive 6 x weekly irinotecan 70 mg/m2 and capecitabine (1000 mg/m2 b.i.d. days 1-14 and 22-35). Courses were repeated on day 50. In elderly patients (>65 years) a 20% dose reduction of both drugs was scheduled. Twenty-eight patients [M/F 20/8; median age 65 years (range 44-79); median ECOG score 1] were enrolled. The most frequent sites of metastases were liver, n=20, lymph nodes and lungs, n=10, respectively. Half of the patients had two or more metastatic sites. A total of 71 treatment courses (median 2, range 1-8) were administered. Main toxicities [worst per patient (%); CTC grade 1/2/3/4] were: anaemias 18/14/-/-; leukocytopenia 11/21/-/-; thrombocytopenia 11/-/-/-; diarrhea 18/36/21/-; nausea/vomiting 43/29/4/-; mucositis 4/11/-/-; alopecia 7/25/-/-; hand-foot syndrome 7/21/-/-; fatigue 14/14/-/-; renal insufficiency (caused by diarrhea and exsiccosis) -/-/-/7. Dose intensity in the first course was [median/mean (%)]: irinotecan 92/83; capecitabine 88/82. Twenty-three patients are evaluable for response analysis (five did not complete the first course): three patients showed partial remissions (13%) and 11 patients had stable disease (48%). Median time to progression was 3.0 months for the total population (range 1.4-17.3) and 6.5 months for responders (partial response plus no change). Seventy-four percent of the patients received a third-line therapy. Overall survival was 15.7 months calculated from the start of study treatment. Second-line therapy with irinotecan and capecitabine yielded a tumor control in 61% of patients with MCRC. Efficacy and toxicity data are comparable to 5-FU/irinotecan combinations, although the likelihood of severe diarrhea appears to be higher with capecitabine/irinotecan.
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PMID:Irinotecan and capecitabine as second-line treatment after failure for first-line infusional 24-h 5-fluorouracil/folinic acid in advanced colorectal cancer: a phase II study. 1561 2

Expression of the rat LH receptor (rLHR) is characterized by a dynamic response to a variety of hormonal stimuli. In addition to activation, the pattern of rLHR expression is also modulated by repression. In this report, an upstream initiator-like element (UInr-lE), CTCACTCTAA, of which the CTC direct repeat motif (CTCACTC) is conserved in the rat, mouse, and human, was identified as a suppressor element. Disruption of the element resulted in a 2-fold enhancement of promoter activity in the LHR-expressing murine Leydig tumor cells. The sequences of the two major initiators (Inr), Inr3 and Inr4, of the rLHR core promoter are similar to UInr-lE and competed efficiently with UInr-lE in the formation of specific protein complexes, suggesting that the same proteins interact with both UInr-lE and the Inrs in vivo. The Inrs are necessary for full promoter activity because a mutant promoter lacking Inrs showed a 70% reduction in activity. UInr-lE also further suppressed the activity of a mutant promoter lacking Inrs. UInr-lE interacted with transcription factor II-I (TFII-I) and an unidentified nuclear protein. However, dominant-negative inhibition experiments using p70 indicated that TFII-I positively regulates LHR promoter activity through UInr-lE and Inrs, suggesting that TFII-I can compromise the suppression of promoter activity mediated by UInr-lE. UInr-lE also showed binding properties distinct from that of the upstream initiator-like suppressor element (upstream regulatory element: CACTCTCC) of rat and human dynorphin promoters. Transfection assays using mutated promoters indicate that the suppression of rLHR promoter activity could be regulated via specific interactions between UInr-lE and trans-acting factors.
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PMID:An upstream initiator-like element suppresses transcription of the rat luteinizing hormone receptor gene. 1567 13

Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkins lymphoma. Five such cases have been described in children. We present a 9-year-old boy, in whom diagnosis of DLBCL has been established in addition to congenital multiple enchondromatosis. Immunohistopathological evaluation of tumor biopsy established the final diagnosis of ALK + DLBCL. The clathrin gene (CLTC)-ALK fusion underlying aberrant expression of ALK in the present case was demonstrated by interphase fluorescence in situ hybridization (FISH) using break-apart rearrangement probes for ALK and CLTC. The disease in this patient was highly resistant to applied chemotherapy regimens and to radiotherapy. Analysis of the disease course in our patient and review of other cases reported previously show that ALK + DLBCL can be an aggressive malignancy that can be cured with conventional chemotherapy protocols only at stage of localized disease.
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PMID:ALK-positive diffuse large B-cell lymphoma. 1585 31

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare, recently defined tumor distinct in many aspects from ALK-positive anaplastic large cell lymphoma (ALCL). We present two additional cases of ALK+DLBCL recently diagnosed in our department and a review of literature. A 48-year old man presented with a large upper neck mass growing slowly over 18 months. Histologically the tumor was diagnosed as an ALK-positive diffuse large B-cell lymphoma. with plasmablastic features. Large, frequently intrasinusoidal tumor cells expressed CD138, EMA, weakly IgA and kappa, but were negative for other B-cell markers, T-cell markers and CD30. The ALK staining was cytoplasmic with the increased intensity in the Golgi area. At the diagnosis the patient manifested with the stage IIIB. Three courses of CHOP resulted in partial and only transient remission. The patient died of massive bleeding from his decomposing tumor 3 months after the diagnosis. A 49-year old man complaining of abdominal pain revealed abdominal lymphadenomegaly and a gastric infiltrate, involving the deep portions of the gastric wall. The tumor showed immunoblastic/anaplastic morphology, with some Reed-Sternberg-like cells positive for ALK. ALK immunostaining was cytoplasmic, weak in a routine immunostain, enhanced with double (proteinase + pressure cooker) antigen retrieval. FISH was consistent with the t(2;5)/nucleophosmin(NPM)-ALK rearrangement. The tumor demonstrated similar "null" B/T phenotype with positivity for IgA, lambda, EMA and LCA. The patient (stage IVB) currently undergoes chemotherapy. ALK-positive DLBCL affects mostly middle-aged men, shows generally poor but stage-dependent prognosis (at least 60% mortality rate), presents typically as a lymph node-based disseminated disease, and very rarely involves the bone marrow. Genetic studies showed that the majority of ALK+DLBCL cases are characterized by the clathrin (CLTC)-ALK fusion and in a few cases the NPM-ALK rearrangement has been found.
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PMID:ALK-positive diffuse large B-cell lymphoma: two more cases and a brief literature review. 1592 Oct 12

The present study was conducted to evaluate activity and toxicity of the FLEC (folinic acid 100 mg/m2; 5-fluorouracil 1000 mg/m2; carboplatin 300 mg/m2; epirubicin 60 mg/m2) schedule as second-line treatment for progressive locally advanced or metastatic pancreatic cancer (LAMPC). FLEC was administered every 3 weeks with an angiographic catheter introduced into the tumor vascular bed. Thirty-two patients were enrolled. Twenty patients had a PS of 2. Twenty-five patients had metastatic disease to liver. Seven (21.9%) partial responses were observed (WHO criteria). Fifteen patients (46.9%) had stable disease and ten patients (31.2%) had progressive disease. The median OS from the diagnosis was 11.8 months. PS (p=0.0308) and pain (WHO scale, p=0.0222; analogic scale, p=0.0446) significantly improved after therapy. No patient discontinued treatment because of toxicity (NCI-CTC criteria). The current study shows that intraarterial chemotherapy is a good therapeutic option in second-line treatment of LAMPC.
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PMID:Second-line intra-arterial chemotherapy in advanced pancreatic adenocarcinoma. 1614 70

The aim of this retrospective study was to evaluate the effectiveness of low-dose cisplatin and 5-fluorouracil (low-dose FP) as an adjuvant chemoradiotherapy for resected advanced squamous cell carcinoma of the esophagus. From 1994 to 1999, 57 patients who showed an invasion of the tumor over the muscularis propria (T2-T4), regional lymph node metastasis (N1), and no distant metastasis (M0) were enrolled in this analysis. Postoperative chemoradiotherapy (CRT group) was performed on 14 of the patients, and they were compared to the patients who underwent surgery alone (S group) using the matched pair algorithm. In the CRT group, chemotherapy of low-dose FP was combined with concurrent radiotherapy after the esophagectomy. A side-effect of severe dysphagia (NCI-CTC Grade 3) was observed in 4 patients (28.6%) and leukocytopenia in 1 patient (7.1%) among the CRT group. The overall survival rate of the CRT group and matched S group were 35.7% and 28.5% at 5 years, respectively, with no significant difference. In the CRT group, 7 of 14 patients (50%) had a recurrence. The recurrence rate was slightly lower than in the S group (57%), with no significant difference. This combined chemoradiotherapy using low-dose FP did not improve the prognosis of patients with resected advanced esophageal carcinoma.
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PMID:Clinical evaluation of low-dose cisplatin and 5-fluorouracil as adjuvant chemoradiotherapy for advanced squamous cell carcinoma of the esophagus. 1618 Jun 98

Physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. Evidence indicates that melatonin's anticancer effects are exerted via inhibition of cell proliferation and a stimulation of differentiation and apoptosis. A new mechanism by which physiological and pharmacological blood levels of melatonin inhibit cancer growth in vivois via a melatonin-induced suppression of tumor linoleic acid (LA) uptake and its metabolism to the important mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Melatonin suppresses cAMP formation and inhibits tumor uptake of LA and its metabolism to 13-HODE via a melatonin receptor-mediated mechanism in both tissue-isolated rat hepatoma 7288 CTC and human breast cancer xenografts. It has been postulated that in industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of breast cancer and, perhaps, other cancers as well. In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts. Nocturnal dietary supplementation with melatonin, at levels contained in a melatonin-rich diet, inhibits rat hepatoma growth via the mechanisms described above. The nocturnal melatonin signal organizes tumor metabolism and growth within circadian time structure that can be further reinforced by appropriately timed melatonin supplementation. Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life.
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PMID:Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal. 1621 31


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