PubMed Health⌕ Search

Biomedical subjects

A Font

Publications and source records attributed to A Font.

At least 19 recordsLinked to original sources
PubMed2006

AIDS-related knowledge and behaviors in Mozambique.

BACKGROUND: The objective of this study was to describe attitudes and knowledge about AIDS among the population aged 15 to 49 in Chókwè (Mozambique) during the period from March to May 2004, and to study associated factors. METHODS: Cross-sectional study conducted by interviewing 1,055 people aged 15 to 49, of both sexes, residents in Chókwè (68,698 inhabitants). The questionnaires employed are known as the Behavior Surveillance Survey. Dependent variables were: knowledge about transmission routes and preventive methods, use of condoms and having had sexual relations with an irregular partner during the past 12 months. Odds ratios were calculated for the association between these variables and age, sex, educational level, neighborhood of residence, number of relations in the last 30 days, and whether AIDS tested, by fitting Logistic Regression models (bivariate and multivariate). RESULTS: Over 99% of the sexually active population of Chókwè knew about AIDS and condoms. More than half of the population of Chókwè has a good knowledge of preventive methods and of transmission routes. 72.9% of men and 91.3% of women did not use the condom when having sexual relationships. It was observed that a low educational level implied a lower degree of knowledge about preventive methods (OR=2.48, 95% CI: 1.60-3.84) and about transmission routes (OR=2.49, 95% CI: 1.37-4.52), less condom use and less relations with irregular or sporadic partners. The probability of not using condoms was higher among females, among people living in less privileged districts, with no education (OR=3.79; 95% CI: 1.80-7.99), with regular partners (OR=4.36; 95% CI: 1.93-9.84) and among people who have not had an AIDS test. CONCLUSION: Knowledge of preventive methods and transmission routes is good in more than half of the population of Chókwè. The majority of men and women do not use the condom when having sexual intercourse. Moreover, inequalities may be observed as a function of educational level and district socioeconomic level. Knowledge of preventive practices, mainly among socio-economically disadvantaged groups, must be improved and strategies designed to broaden access to use of condoms by everyone should be implemented.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Sequential mitoxantrone/prednisone followed by docetaxel/estramustine in patients with hormone refractory metastatic prostate cancer: results of a phase II study.

BACKGROUND: Mitoxantrone/prednisone ameliorates symptoms in hormone refractory prostate cancer (HRPC) but has no effect on survival. Docetaxel (Taxotere)/estramustine improves response but with significant toxicity. We reasoned that a sequential administration of the two regimens could be a viable alternative for delivering full doses of chemotherapy, avoiding overlapping toxicity and preserving dose intensity. PATIENTS AND METHODS: Thirty HRPC patients were treated with mitoxantrone 10 mg/m(2), day 1, every 3 weeks, plus prednisone 5 mg twice daily, for three cycles, followed by estramustine phosphate, 280 mg three times daily, days 1 to 5, plus docetaxel 75 mg/m(2), day 2, every 3 weeks for a maximum of 10 cycles. RESULTS: All patients were assessable for response and toxicity. After mitoxantrone/prednisone treatment, the prostate-specific antigen (PSA) response rate was 23%, which increased to 63% after completion of sequential mitoxantrone/prednisone and docetaxel/estramustine treatment (12 partial and 7 complete responses). With a median follow-up of 18 months, median survival for all patients was 18 months, and median progression-free survival was 10 months. The mitoxantrone/prednisone regimen was well tolerated, and the only grade 3-4 toxicity was grade 3 neutropenia in four (13%) patients. Twenty-nine patients received a total of 173 cycles of docetaxel/estramustine (median, 6 cycles/patient). Six (20%) patients had grade 3-4 neutropenia and two (6%) patients had febrile neutropenia episodes. The most frequent non-hematological toxic effects were asthenia, nausea and vomiting, edemas and onycholysis. Two (6%) patients had deep venous thrombosis. CONCLUSIONS: Mitoxantrone/prednisone followed by docetaxel/estramustine is a well-tolerated and active regimen in HRPC. Sequential therapy is feasible and can be used to integrate novel, more active regimens.

Aged↗
PubMed2005

Pharmacokinetics of azithromycin after intravenous and intramuscular administration to goats.

Azithromycin is the first of a class of antimicrobial agents designated azalides. The aim of the present study was to investigate the disposition pharmacokinetics of azithromycin in goats and determine its bioavailability. A cross-over study was carried out in two phases separated by 30 days. Azithromycin was administered at a single dose of 20 mg/kg body weight by i.v. and i.m. routes. Plasma concentrations of azithromycin were determined by a modified agar diffusion bioassay. After a single i.v. dose plasma concentrations were best fitted to a three-compartment open model. A two-compartment open model with first-order absorption fitted best after i.m. administration. The values of the pharmacokinetic parameters after i.v. administration were: half-life 32.5 h, apparent volume of distribution at the steady-state 34.5 L/kg, clearance 0.85 L/kg. and mean residence time (MRT) 40.1 h. After i.m. administration half-life of 45.2 h, a MRT of 60.3 h, maximum plasma concentration 0.64 mg/L and a bioavalability 92.2% were obtained. The pharmacokinetic parameters of azithromycin after i.m. administration, principally its long half-life and high bioavailability, could provide an alternative to the oral route of administration in goats, although more studies are needed to establish a suitable pharmaceutical formulation, propose optimun dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

Animals↗
PubMed2005

Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep.

The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.

Animals↗
PubMed2004

Acute paraplegia associated with vasculitis in a dog with leishmaniasis.

A 14-month-old female crossbreed dog with leishmaniasis, receiving allopurinol, was presented with acute paraplegia. A diagnosis of renal failure with pelvic limb lower motor neuron signs was made and the dog was euthanased. Histopathological examination demonstrated leukocytoclastic vasculitis in multiple organs. Malacia and haemorrhage affecting the spinal cord was associated with multiple foci of vasculitis within the nervous tissue. Rupture and thrombosis of inflamed vessels caused haemorrhage in the spinal cord and subsequent paralysis.

Acute Disease↗
PubMed2003

A phase II study of cisplatin, etoposide and gemcitabine in an unfavourable group of patients with carcinoma of unknown primary site.

BACKGROUND: The aim of this phase II study was to determine toxicity, response rate, time to progression, and overall survival of cisplatin, etoposide and gemcitabine in patients with carcinoma of unknown primary tumour site. PATIENTS AND METHODS: Thirty patients with no previous chemotherapy and not belonging to a treatable group were treated with cisplatin 70 mg/m(2) on day 1, etoposide 70 mg/m(2) on days 1 and 2, and gemcitabine 700 mg m(2) on days 1 and 8, administered every 3 weeks. Stable or responding patients received a maximum of eight cycles. Twenty patients (67%) had more than three affected sites, and 25 patients (84%) had adenocarcinomas. RESULTS: Overall response rate was 36.6% (11 patients), including four complete responses (13.3%) and seven partial responses (23.3%), with a 95% confidence interval of 19.9-56. Median survival was 7.21 months and eight patients remained alive for >1 year. Myelosuppression was the most important toxicity, with grade 3-4 neutropenia in 18 patients (60%) in 32% of the cycles: eight patients had neutropenic fever and 10 patients had thrombopenia in 11% of cycles. No non-haematological grade 4 toxicity occurred. CONCLUSIONS: Cisplatin, etoposide and gemcitabine is an active combination, inducing objective responses in a subset of heavily advanced disease patients with carcinoma of unknown primary site. The role of adding gemcitabine to cisplatin and etoposide remains to be resolved as to the best schedule to diminish toxicity for the three-drug combination.

Adult↗
PubMed2003

Sequential dose-dense paclitaxel followed by topotecan in untreated extensive-stage small-cell lung cancer: a Spanish Lung Cancer Group phase II study.

BACKGROUND: Poor survival rates in extensive-stage small-cell lung cancer (SCLC) patients prompted us to evaluate a sequential dose-dense schedule of paclitaxel followed by topotecan. PATIENTS AND METHODS: Forty-three patients with previously untreated, extensive-stage SCLC received three cycles of paclitaxel 250 mg/m(2) over 3 h every 14 days followed by three cycles of topotecan 2.5 mg/m(2) for 5 days every 21 days. Granulocyte colony-stimulating factor was given after every cycle. Patients progressing at any time and those not achieving complete response (CR) subsequently received four cycles of standard-dose etoposide-cisplatin. RESULTS: A total of 118 cycles of paclitaxel were administered with minimal hematological toxicity. Grade 2/3 peripheral neuropathy was observed in 21% of patients. Response rate to paclitaxel was 48.8%, and 25.6% had stable disease (SD). Thirty-two patients achieving SD or response to paclitaxel subsequently received a total of 90 topotecan cycles. Topotecan-related toxicities included febrile neutropenia in 15.6% of patients with one toxic death, grade 3/4 anemia in 25% of patients and grade 3/4 thrombocytopenia in 31.3%. Non-hematological toxicities were mild. At completion of sequential paclitaxel-topotecan treatment the overall response rate was 55.8% (22 partial response, two CRs). Median survival for all patients was 10.5 months and median progression-free survival was 8.5 months. CONCLUSIONS: Sequential treatment with dose-dense paclitaxel followed by topotecan is feasible despite significant hematological toxicity during topotecan treatment. This schedule is an active regimen in extensive-stage SCLC and merits further investigation.

Adult↗
PubMed2002

Phase I study of weekly CPT-11 (irinotecan)/docetaxel in patients with advanced solid tumors.

Based on the synergistic cytotoxicity demonstrated in vitro by topoisomerase I inhibitors followed by docetaxel and the feasibility of giving both drugs on a weekly schedule avoiding overlapping toxicities, we designed a phase I trial of weekly CPT-11 (irinotecan)/docetaxel to determine the dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) of this combination. Eighteen patients with advanced solid tumors treated with at least one prior chemotherapy regimen were included in this trial. CPT-11 was administered as a 90-min (intravenous) IV infusion followed immediately by docetaxel as a 30-min IV infusion. Both drugs were given on days 1, 8 and 15 in 4-week cycles. Four escalating dose levels of CPT-11/docetaxel (level I: 60/20 mg/m(2), level II: 60/25 mg/m(2), level III: 70/25 mg/m(2), and level IV: 70/30 mg/m(2)) were studied. Forty-seven cycles were administered (range, 1-5 courses) with a median number of 2.6 cycles per patient. Grade 4 leukopenia was the DLT reached at dose-level IV (CPT-11/docetaxel 70/30 mg/m(2)). Four patients had grade 3 anemia at dose levels III (two patients) and IV (two patients), while grade 3/4 thrombocytopenia was not seen. Grade 3/4 non-hematologic toxicities included grade 3 diarrhea in two patients (dose levels II and IV), grade 3 asthenia in one patient (dose level II) and grade 3 stomatitis in one patient (dose level I). The recommended dose of this weekly schedule is CPT-11 70 mg/m(2) and docetaxel 25 mg/m(2). DLT of this regimen is leukopenia, although toxicity is manageable at the recommended dose level. The activity of this regimen is being evaluated in a phase II study in previously treated patients with advanced non-small cell lung cancer.

Adult↗
PubMed2001

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗
PubMed2001

Prognostic value of K-ras mutations and allelic imbalance on chromosome 18q in patients with resected colorectal cancer.

PURPOSE: We designed this study to assess the frequency of K-ras mutations in patients with resected colorectal tumors and their association with survival. A second objective was to analyze the prognostic value of different K-ras genotypes. In a subgroup of patients we also investigated the presence of allelic imbalance on chromosome 18q and its relationship to clinical outcome. METHODS: One hundred fourteen colorectal tumors resected between 1983 and 1986 were analyzed to detect K-ras point mutations at codons 12, 13, and 61 by polymerase chain reaction followed by allele specific oligonucleotide hybridization. A subgroup of 77 tumors was further screened to detect loss of heterozygosity on chromosome 18q using three polymorphic microsatellite markers (D18S67, D18S474 and D18S58). RESULTS: K-ras mutations were detected in 29 percent (33/114) of patients. K-ras mutations correlated with age and preoperative carcinoembryonic antigen levels, and there was some indication that they may be linked to poor survival, especially in Stage II tumors, where a subgroup of patients with aspartic and serine mutations showed significantly reduced survival (P = 0.03) compared with K-ras-negative patients. 18q loss of heterozygosity was present in 39 percent (25/63) of tumors. A multivariate analysis of Stage II tumors showed that 18q loss of heterozygosity was significantly associated with a worse prognosis (P = 0.006). A significant decrease in survival was identified in ten patients harboring both genetic alterations (K-i mutations and 18q loss of heterozygosity; P = 0.02). CONCLUSIONS: In colorectal tumors, K-ras mutations and 18q loss of heterozygosity are two genetic markers which may identify patients with more aggressive behavior, mainly in Stage II tumors. These findings warrant further research, because they can be useful in customizing adjuvant chemotherapy.

Allelic Imbalance↗
PubMed2001

Sexuality in chronic respiratory failure: coincidences and divergences between patient and primary caregiver.

Sexual functioning can be affected by chronic illness in a variety of ways. These problems affect the patients relationship and the degree of satisfaction with his partner. We conducted a study in order to evaluate the perception of sexual difficulties and changes in communication with patients and their wives. Male chronic obstructive pulmonary disease patients with (COPD) and chronic respiratory failure on long-term oxygen therapy were studied. The evaluation method used has consisted of the individualized administration of a semi-structured interview created for this purpose. This interview was conducted with the patients and their wives. One part of the interview was dedicated to evaluating possible sexual problems and how these problems affect the relationship between the couples. In addition, patients as well as their partners were asked the degree of satisfaction with their partners and the degree of satisfaction with their lives. Forty-nine patients and their spouses have been included in the study. Thirty-three patients (67.3%) showed some type of sexual problem (lack of desire and/or impotence). Sixteen wives (33%) answered affirmatively to the question about whether changes at a communicative level as a consequence of the patients illness had occurred. In relation to the appearance of sexual changes, 46 (94%) of the wives answered affirmatively. The wives were significantly less satisfied with the relationship than the patients, which was related to communication problems. The group of patients were more satisfied with their partners than with their life, whereas no difference has been observed in the wives with both variables. An important percentage of patients with chronic insufficiency who have sexual difficulties exits. A factor which influences the perception of such problems in a very important way is the degree of affection in the relationship between the couples.

Communication↗
PubMed2000

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group.

PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS: Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up. CONCLUSION: This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.

Adult↗
PubMed1999

Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma: a phase III randomized trial of the Spanish Lung Cancer Group.

BACKGROUND: The authors designed this randomized, controlled trial to assess whether dose intensification of a cisplatin-etoposide combination (PE), achieved by shortening the interval between chemotherapy cycles, would improve response rate and survival. The maximum tolerated dose of PE was administered in either 3- or 4-week cycles to patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: One hundred twenty-three patients were randomized into two groups. The dose-intense arm received cisplatin 35 mg/m2 and etoposide 200 mg/m2 on Days 1-3 every 4 weeks. The dose-dense arm received the same schedule every 3 weeks along with 5 microg/kg of recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) administered subcutaneously on Days 4-13. RESULTS: Patient characteristics were well balanced in both treatment arms. Fifty-four percent of patients were classified as Stage IIIB. A 32% increase in relative dose intensity was achieved in the dose-dense arm compared with the dose-intense arm. The response rates were 32% in the dose-intense arm and 27% in the dose-dense arm (P = 0.9). The median overall survival was higher in the dose-dense arm, 9 versus 7.2 months (P = 0.2). The main toxicity was myelosuppression, although the administration of GM-CSF significantly reduced the percentage of patients with Grade 4 granulocytopenia (53% vs. 78%). Fifty-four percent of the patients in the dose-intense arm and 35% of those in the dose-dense arm developed febrile neutropenia (P = 0.07). There were ten (8%) treatment-related deaths, three (4%) in the dose-intense arm and seven (12%) in the dose-dense arm (P = 0.3); three deaths in each arm were due to febrile neutropenia. CONCLUSIONS: The dose-intensification achieved in the dose-dense PE regimen did not correlate with significant improvements in response rate or survival and cannot be recommended in the light of the diversity of new drug combinations available today. However, the use of rhGM-CSF significantly reduced the incidence of severe granulocytopenia.

Adult↗
PubMed1999

Pericardial mesothelioma in a dog: long-term survival after pericardiectomy in combination with chemotherapy.

A six-year-old male crossbred dog was presented with clinical signs of right-sided heart failure. Echocardiography demonstrated a pericardial effusion with cardiac tamponade, while pericardiocentesis and cytology did not reveal any evidence of malignancy. Pericardial drainage was performed twice over a period of three months to resolve haemodynamic impairment before a subtotal pericardiectomy was performed. Biopsy of parietal and visceral pericardium confirmed the diagnosis of pericardial mesothelioma. Intrathoracic cisplatin combined with intravenous doxorubicin were administered, although neutropenia, mild azotaemia and alopecia were noted as adverse reactions to these drugs. Intravenous cisplatin was repeated 45 days later after the signs of nephrotoxicity had resolved. The dog was still free of disease after 27 months. Intrathoracic chemotherapy after pericardiectomy and early diagnosis are recommended to improve prognosis, having achieved long-term survival in the present case.

Animals↗
PubMed1999

A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers.

PURPOSE: The survivin gene is a novel apoptosis inhibitor, related to the baculovirus gene, which is believed to play a pivotal role in fetal development and in cancer. We hypothesised that survivin would be expressed in tumors of patients with non-small-cell lung cancer (NSCLC), and we attempted to determine the influence of survivin re-expression on clinical outcome in patients with up to stage IIIA NSCLC who had undergone radical surgery. METHODS: We designed a reverse transcriptase polymerase chain reaction (RT-PCR) assay to study the expression of the survivin gene in 83 NSCLC tumor samples and compared the results with relevant clinical and pathologic data. RESULTS: The RT-PCR identified survivin gene transcript in 71 (85. 5%) of the tumor samples and in only 10 (12%) of the paired, histopathologically normal lung samples. There was no relationship between histologic subtype (squamous v nonsquamous) and survivin gene expression. The 12 patients without survivin expression had significantly better overall survival than the 71 patients with survivin expression (P =.01 by univariate analysis; relative risk, 2. 1). There was no significant correlation between survivin expression and age, sex, cigarette smoking, histologic subtype, tumor differentiation, tumor size, or the presence of mediastinal lymph node metastases in surgical specimens. CONCLUSION: The survivin gene was expressed in a vast majority of NSCLC tumors. We conclude that survivin transcript is a defining diagnostic marker for NSCLC that may also yield prognostic information and, as an apoptosis inhibitor, be an important target in cancer therapy.

Adult↗
PubMed1998

Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal cancer.

BACKGROUND & AIMS: Loss of heterozygosity (LOH) on chromosome 18q is frequent in colorectal cancer (CRC) and has been associated with poor prognosis in stage II tumors. This study investigated the frequency of LOH in sporadic CRC and its effect on patient prognosis. METHODS: One hundred forty-four patients were screened for LOH at 18q by polymerase chain reaction using three polymorphic microsatellite markers. RESULTS: Nineteen patients were excluded because their tumors showed microsatellite instability in at least one marker. Of the remaining 125 patients, 121 were informative in at least one marker; 45% (54 of 121) showed 18q LOH. Five-year survival was 42% in those with 18q LOH and 73% in those without 18q LOH (P = 0.008). Multivariate analysis showed that tumor side (P = 0.0001) and 18q LOH (P = 0.01) were the only independent prognostic factors. Examining markers individually showed that only the lost of D18S474 had a significant influence on survival in patients with stage II CRC (P = 0.016). CONCLUSIONS: 18q LOH indicates an unfavorable outcome in patients with stage II CRC. Our results emphasize the importance of the 18q21.1 region, where several tumor-suppressor genes have been mapped. Microsatellite analysis may be useful in identifying high-risk patients who might benefit from adjuvant therapy.

Adult↗
PubMed1997

Reduced survival in patients with stage-I non-small-cell lung cancer associated with DNA-replication errors.

To better understand whether replication-error-type instability (RER+) is a frequent genetic alteration event in surgical-pathologic stage-I non-small-cell lung cancer (NSCLC) and identify whether it constitutes an independent prognostic parameter, we examined 35 surgical-pathologic stage-I-NSCLC patients with complete follow-up in all cases for at least 49 months. The tumor samples and the paired histopathologically normal lung samples for each patient were analyzed for 8 microsatellite markers located at chromosomes 3p and 2p to investigate microsatellite alterations such as RER+ and loss of heterozygosity (LOH). Single-strand-conformation-polymorphism analysis for detection of p53 and k-ras gene mutations was also carried out. Genetic data were correlated with clinical outcome and histopathologically established prognostic factors. RER+ at one or both chromosomes was identified in 24 of the 35 patients; 9 patients showed LOH. A statistically significant correlation was found between RER+ and poor prognosis (p = 0.001). Furthermore, RER+ proved to be an independent factor that predicted decreased survival, ranking first, followed by visceral pleural invasion. A trend towards worse survival was strongest in the group of patients with tumor size greater than 3 cm (T2). Patients with other genetic abnormalities, such as K-ras mutations, p53 mutations or LOH, had prognoses similar to those of patients without such aberrations. The data suggest that RER+ is common in NSCLC, that it may provide important prognostic information in stage-I NSCLC and serve as a useful marker for relapse-risk assessment in operable NSCLC patients.

Adenocarcinoma↗