[Correlations between genetic variations of glutathione synthetase gene and the response to platinum-based chemotherapy and prognosis of small cell lung cancer patients].

Objective: To explore the associations between genetic variations of glutathione synthetase gene (GSS) and response to platinum-based chemotherapy of small cell lung cancer(SCLC), and to analyze the influencing factors on survival. Methods: Four haplotype-tagging single nucleotide polymorphisms (htSNPs) of GSS were genotyped by Sequenom MassARRAY methods in 903 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were measured by odds ratios (OR) and 95% confidence intervals (CI), adjusted for sex, age, smoking, KPS, staging and chemotherapy regiments, by unconditional logistic regression model. The hazard ratios (HR) were estimated by Cox proportional hazards regression model. Results: Among the 903 patients, 462(51.2%) cases received cis-platinum and etoposide treatment while others were treated with carboplatin and etoposide. 656 patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time (MST) of these patients was 25.0 months.We found that rs725521 located in the 3' near gene region of GSS was significantly associated with chemotherapy response. Compared with the T allele, patients with C allele had a worse chemotherapy response and an increased risk of no-responders (P=0.027). Rs7265992 and rs725521 of GSS were associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy (HR=1.16, 95% CI=1.02-1.33, P=0.027; HR=1.17, 95% CI=1.05-1.31, P=0.006, respectively). The patients carrying 1 or 2 risk alleles and the patients carrying 3 or 4 risk alleles had worse MST than the patients without the rs7265992A and rs725521C risk alleles (24.0 and 22.0 versus 30.0 months), with the HR for death being 1.26 (95% CI=1.04-1.54) and with the HR of 1.52 (95%CI=1.18-1.97, P=0.001). Rs2025096 and rs2273684 were not associated with the OS of SCLC patients who received platinum-based chemotherapy. Age ≤ 56, KPS> 80, limited-stage, chemotherapy response and radiation therapy had a remarkably prolonged OS (all P<0.05). Conclusions: These results suggest that GSS genetic polymorphism rs725521 plays an important role in the response to platinum-based chemotherapy, while rs7265992 and rs725521 have important effect on the prognosis of SCLC patients, which may be potential genetic biomarkers for personalized treatment of SCLC.

[Genetic variation in DNA repair gene RAD52 is associated with the response to platinum-based chemotherapy in SCLC patients].

OBJECTIVE: To explore the associations between genetic variations of DNA repair gene RAD52 and response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival. METHODS: Nine haplotype-tagging single nucleotide polymorphisms (htSNPs) of RAD52 were genotyped by Sequenom Mass ARRAY technology in 939 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were analyzed by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, smoking, KPS, staging and chemotherapy regimens, by unconditional logistic regression model. The relative ratios (RRs) were estimated using Cox proportional hazards regression model. RESULTS: Among the 939 cases, 483 (51.4%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Six hundred and eighty two patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time (MST) of these patients was 25 months. We found that rs10774474 SNP which located in the 5'-flanking region of RAD52 was significantly associated with chemotherapy response. Compared with the TT genotype, patients with TA and AA genotype had a worse chemotherapy response and increased risk of no-response (P=0.004). Correlation analysis showed that patients with KPS >80 had a better chemotherapy response than those with KPS≤80 (P=0.001). The patients with extensive-stage had a worse chemotherapy response than those with limited-stage (P<0.001). Cox proportional hazards regression model analysis showed that nine htSNPs of RAD52 were not associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy. Age≤56, KPS>80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (allP<0.05). CONCLUSIONS: These results suggest that RAD52 genetic polymorphism rs10774474 plays an important role in the response to platinum-based chemotherapy, and may be a potential genetic biomarker for SCLC personalized treatment.

N0539 phase II trial of fulvestrant and bevacizumab in patients with metastatic breast cancer previously treated with an aromatase inhibitor: a North Central Cancer Treatment Group (now Alliance) trial.

BACKGROUND: Based on preclinical studies, the vascular endothelial pathway is an important mechanism for estrogen receptor resistance. We conducted a phase II study of fulvestrant and bevacizumab in patients with aromatase inhibitor pretreated metastatic breast cancer. PATIENTS AND METHODS: A single-stage phase II study was conducted with these objectives: 6-month progression-free survival (PFS), tumor response, toxic effect, and overall survival. Regimen: 250 mg fulvestrant days 1 and 15 (cycle 1) then day 1 (cycle 2 and beyond) and 10 mg/kg bevacizumab days 1 and 15 of each 4-week cycle. RESULTS: At interim analysis, 20 eligible patients initiated treatment, 11 were progression free and on treatment at 3 months, not meeting the protocol-specified efficacy requirements (at least 12 of 20). Accrual remained open during interim analysis with 36 patients enrolling before final study closure. Among the 33 eligible patients, the median PFS was 6.2 months [95% confidence interval (CI) 3.6-10.1 months]. Of the 18 with measurable disease, 4 (22%) patients (95% CI 6% to 48%) had a confirmed tumor response (1 complete, 3 partial). The most common grade 3/4 adverse events were hypertension 3 (9%) and headache 3 (9%). CONCLUSIONS: The fulvestrant/bevacizumab combination is safe and tolerable; however, it did not meet its statistical end point.

Research on PEP-3 psychological education evaluation system for disabled children and autistic children in minority areas.

OBJECTIVE: Rehabilitation of disabled children with autism has become a challenge for current rehabilitation centres. This study conducted psychological investigations on disabled children and analysed the symptoms and characteristics of autism in these children to develop more reasonable rehabilitation treatment plans that would help the children receive psychological counselling and effective rehabilitation. SUBJECTS AND METHODS: This study investigated 107 disabled children from the Disabled Rehabilitation Research Centre of the South China Minority Autonomous Region. Using the PEP-3 scale as a research tool, a questionnaire was developed to investigate and collect data on the mental health of disabled children. The survey was conducted from 2017 to 2021, and 107 children's mental health data were collected in the form of questionnaires based on PEP-3 evaluation indicators. After cleaning the data, the questionnaire data were screened and processed. Descriptive statistical and correlation analysis tools were used for model analysis to understand the overall data distribution and the potential relationships among various data variables. RESULTS: The results of correlation analysis showed that cognition, language expression, language understanding, emotion, and social interaction in the subtest of developmental behaviour were the main indicators of the degree of autism in children. These indicators had a strong and significant correlation with the comprehensive score. Moreover, these indicators had a significant correlation with the individual self-care and adaptive behaviours reported by the children's caregivers. Small muscles, big muscles, and imitation (vision and movement) indicators had a significant correlation with problematic behaviours and physical fitness, and language and cognitive indicators also had a strong correlation with emotion and social interaction. CONCLUSIONS: Emphasis should be placed on the improvement of the language and cognitive abilities of disabled children with autism, and corresponding rehabilitation plans, and training can be formulated according to children with different degrees of illness to get a better rehabilitation outcome. Further, identification of key indicators of autism will be of help in aiding the development of rehabilitation treatment for disabled children with autism and formulation of long-term rehabilitation plans.

N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial.

BACKGROUND: Because of the single-agent activity of irinotecan hydrochloride, combination of irinotecan and docetaxel treatment against metastatic breast cancer (MBC) should be evaluated. PATIENTS AND METHODS: Single-stage phase 2 study of irinotecan and docetaxel to evaluate tumor response, toxicity, time to progression, and overall survival was carried out. Regimen of docetaxel (25 mg/m(2)) and irinotecan (70 mg/m(2)) was administered on days 1 and 8 of each 3-week cycle. Patients had histologically confirmed breast adenocarcinoma and metastatic cancer measurable with RECIST. RESULTS: Of 70 patients enrolled, 64 were assessable. Prior treatment with an anthracycline and a taxane was required. Eighteen (28%) patients [95% confidence interval (CI) 15% to 31%] had tumor response, plus four patients had stable disease (less than 30% decrease in sum of longest diameter and less than 20% increase) for >6 months. The clinical benefit rate was 34% overall. Median duration of tumor response was 6.7 months (95% CI 4.2-37.7 months); median follow-up was 18.6 months (range 8.5-37.7 months). The most common severe adverse events included fatigue [n = 16 (25%)] and neutropenia [n = 13 (20%)]. CONCLUSIONS: Weekly dosing of combination of irinotecan and docetaxel is active against MBC. However, the response rate to our regimen was not significantly better than single-agent docetaxel. Other schedules of irinotecan plus docetaxel should be considered for future studies.

Clinical outcomes after a diagnosis of brain metastases in patients with estrogen- and/or human epidermal growth factor receptor 2-positive versus triple-negative breast cancer.

BACKGROUND: Women with triple-negative (TN) breast cancer are at increased risk of distant metastases and have reduced survival versus other breast cancer patients. Relative survival of women with TN breast cancer who develop brain metastases is unknown. METHODS: Patients with breast cancer who developed brain metastases at our institution from 1993 to 2006 were reviewed. Four survival time intervals were compared in patients with TN disease and those with non-TN disease: initial diagnosis to distant metastases, distant metastases to brain metastases, brain metastases to death, and overall diagnosis to death. RESULTS: One hundred and eighteen patients were identified. Fifty-one (50%) of 103 were estrogen receptor positive, 26 (39%) of 67 were human epidermal growth factor receptor 2 positive, and 20 (22%) of 91 were TN. Survival times were shorter for TN patients, with overall survival of 26 months in TN patients versus 49 months for non-TN patients. In TN patients, time to development of distant metastases, brain metastases, and death after brain metastases was shorter than in non-TN patients. CONCLUSION: Patients with TN disease were more likely to develop distant metastases earlier than non-TN patients, developed brain metastases sooner, and had shorter overall survival.

The value and role of computed tomography in blunt injury of the abdomen.

The use of computed tomography (CT) has had a tremendous impact on the evaluation and management of blunt abdominal trauma. The ability of CT to confirm the absence of intraperitoneal injury and/or significant hemoperitoneum, in correlation to the patient's physiological status, provides extremely valuable information so that unnecessary abdominal surgery is avoided. CT not only demonstrates the presence of injury and delineates it's extent, including the size of the hemoperitoneum, but may also provide information concerning the hemodynamic status of the patient. We reviewed the abdominal CT examination of 38 patients with blunt abdominal trauma at our institution from April 1989 to May 1990. There were no false negative cases and only one false positive case. Thus, we concluded that CT is not only a highly sensitive and accurate modality, but also an invaluable radiological diagnostic tool in the evaluation of blunt abdominal injury.

Paromomycin-associated pancreatitis in HIV-related cryptosporidiosis.

OBJECTIVE: To report a case of pancreatitis related to paromomycin administration. CASE SUMMARY: A 39-year-old man with AIDS developed pancreatitis concurrent with successful treatment of intestinal cryptosporidiosis with paromomycin. The hyperamylasemia resolved with discontinuation of the agent and recurred when paromomycin treatment was reinstituted. DISCUSSION: To our knowledge, this is the first reported case of pancreatitis believed to be induced by paromomycin. Although pancreatitis in HIV-infected patients has multiple causes, the nature of this case suggests the involvement of paromomycin. The mechanism of action is unclear. CONCLUSIONS: Pancreatitis should be considered in the differential diagnosis of abdominal pain in patients who are treated with paromomycin.