eEF1A1 promotes colorectal cancer progression and predicts poor prognosis of patients.

Colorectal cancer (CRC) is a major leading cause of cancer mortality worldwide in which dysregulated protein synthesis plays an etiologic role. The eukaryotic elongation factor 1 A1 (eEF1A1) exerts significant effects on protein synthesis by contributing to peptide chain extension. Whereas its role in CRC remains to be investigated. In this study, we found that the mRNA and protein levels of eEF1A1 were significantly upregulated in CRC cell lines and tissues. Elevated expression of eEF1A1 was correlated with shorter overall survival in 94 CRC patients. The inhibition of proliferation and cell cycle block were observed in CRC cells after eEF1A1 downregulation. Mechanistically, weighted gene correlation network analysis and further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that mitogen-activated protein kinases (MAPKs) signaling pathways were significantly enriched in high-eEF1A1 expression group, and the levels of phosphorylated p38/JNK/ERK MAPK were dramatically decreased after eEF1A1 downregulation. Overexpression of eEF1A1 in CRC correlated with a poor prognosis. Collectively, this study determined the oncogenic role of eEF1A1 in CRC proliferation and tumorigenesis. eEF1A1 might be a promising therapeutic target and prognostic biomarker in CRC.

Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases.

BACKGROUND: Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. METHODS: Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration. RESULTS: The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68-CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. CONCLUSIONS: The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68-CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects.

Risk factors for the development of hepatocellular carcinoma in Chengdu: a prospective cohort study.

OBJECTIVE: To investigate the incidence of hepatocellular carcinoma (HCC) in Chengdu, identify the risk factors for the development of HCC in Chengdu and provide a reference for the prevention of HCC. PATIENTS AND METHODS: The study population was recruited from Chengdu, Sichuan Province, China. The study group recruited volunteers in Chengdu from 2007 to 2012, conducted a baseline survey, and subsequently conducted long-term follow-up until December 31, 2019. A total of 22,525 study subjects were enrolled, excluding those who reported a previous history of liver disease, malignancy, and HCC within three months of enrollment. Cox proportional risk regression models were used to screen and determine the various risk factors and their hazard ratios (HR) for HCC in Chengdu, as well as to determine whether the association between other risk factors and HCC was modified by gender. RESULTS: The study population had a median follow-up of 5.35 years, and a total of 142 people developed HCC, with an incidence rate of 0.71%. Analysis of the multifactorial Cox proportional risk regression model showed that age (age 10 years for 1 group, HR= 1.98, 95% CI: 1.86-2.11, p<0.001), current smoking (HR= 1.25, 95% CI: 1.07-1.31, p=0.031), weekly consumption of pickled vegetables (HR= 1.70, 95% CI: 1.49-1.81, p=0.003) and consumption of pickled vegetables daily (HR= 1.36, 95% CI: 1.21-1.42, p=0.021) were risk factors for HCC, and women (HR= 0.39, 95% CI: 0.28-0.55, p=0.002) and the use of air conditioning (10 years for 1 group, HR= 0.79, 95% CI: 0.68-0.83, p=0.002) were protective factors against HCC. Further analysis revealed that the association between length of time using air conditioning and HCC was heterogeneous among men and women (p=0.007) and that there was an interaction between sex and use of air conditioning in the association with HCC development (p<0.001). CONCLUSIONS: The Chengdu population has a high incidence of HCC and numerous risk factors for HCC. There is a synergistic interaction between sex and length of time using air conditioning in their role in the development of HCC.

[Clinical effects of retrograde anterolateral thigh perforator flaps assisted with computed tomography angiography in repairing skin and soft tissue defects around the knee or in proximal lower leg].

Objective: To investigate the clinical effects of retrograde anterolateral thigh perforator flaps assisted with computed tomography angiography (CTA) in repairing skin and soft tissue defects around the knee or in proximal lower leg. Methods: A retrospective cohort study was conducted. From May 2015 to October 2019, 17 patients with skin and soft tissue defects around the knee or in proximal lower leg were admitted to the Department of Orthopedics of Jizhong Energy Xingtai Mig General Hospital, including 12 males and 5 females, aged 16-65 years, with an average age of 35 years. The areas of skin and soft tissue defects after debridement ranged from 6.0 cm×3.0 cm to 15.0 cm×9.0 cm. The retrograde anterolateral thigh perforator flaps were designed according to the origin and distribution of the perforating branches in flaps and the length of the vascular pedicle examined with CTA and the condition of the wound to repair the wounds. The areas of resected flaps ranged from 6.5 cm×3.5 cm to 15.5 cm×9.5 cm. The wounds in donor sites of flaps were sutured directly or covered with medium-thickness skin grafts from healthy upper leg. The sources of the perforating branches in flaps were recorded. The lateral circumflex femoral artery, its branches, and the relative length of the vascular pedicle were compared between preoperative CTA detection and intraoperative observation. The survivals of the flaps were observed. At the last follow-up, the effects of flaps in repairing wounds were evaluated according to evaluation standard of efficacy satisfaction; the motion ranges of flexion and extension of the knee joint were measured, and the knee joint function was evaluated according to the Hohl knee joint function evaluation standard; the sensory function in the flap area was evaluated according to the sensory function evaluation standard formulated by the British Medical Research Council; the wound healing and the occurrence of complication affecting motor function of limb of flap donor sites was observed. Data were statistically analyzed with paired sample t test. Results: The perforating branches in flaps originated from descending branches, oblique branches, and rectus femoris branches of lateral circumflex femoral artery in 7, 6, and 4 patients, respectively. The flaps with blood supply from descending branches, oblique branches, and rectus femoris branches of lateral circumflex femoral artery were type 1, 2, and 3 retrograde anterolateral thigh perforator flaps, respectively. The preoperative CTA examination of lateral circumflex femoral artery and its branches were consistent with those observed during operation. The relative lengths of vascular pedicles of type 1, 2, and 3 retrograde anterolateral thigh perforator flaps calculated after CTA examination were 0.32±0.13, 0.56±0.07, and 0.56±0.15, which were close to 0.35±0.12, 0.52±0.10, and 0.53±0.12 measured and calculated during operation, respectively (t=0.45, 0.80, 0.31, P>0.05). All flaps survived in 17 cases without vascular crisis. At the last follow-up, 16 patients were satisfied with effects of flaps in wound repair, with 1 patient feeling average about the effect; the flexion range of knee joint was 100-120°, and the extension range of knee joint was -2-0°; knee joint function was evaluated as excellent in 9 cases, good in 7 cases, and poor in 1 case; the sensory function of the flap area reached S4 level in 2 cases, S3 level in 8 cases, and S2 level in 7 cases; the wounds in flap donor sites healed well; there was no adverse effect in motor function of limbs. Conclusions: Retrograde anterolateral thigh perforator flap is an effective method for repairing skin and soft tissue defects around the knee or in proximal lower leg. Preoperative CTA examination can fully show the anatomical characteristics of the branches of the lateral circumflex femoral artery and the perforating vessels of each branch, which can guide preoperative flap design and operation, thus shortening operation time and improving flap survival rate, with good clinical effects.

A class of novel tubulin polymerization inhibitors exert effective anti-tumor activity via mitotic catastrophe.

In current work, a class of novel 4,5-dihydro-1H-pyrazole-1-carboxylate derivatives (E01-E28) were designed, synthesized and evaluated. Among them, the most potent compound E24 exhibited comparable activity against a panel of cancer cells (GI50 ranging 0.05-0.98 µM) and tubulin polymerization inhibition (IC50 = 1.49 µM) with reference drug CA-4(P) (GI50 ranging 0.019-0.32 µM, IC50 = 2.18 µM). The following assays indicated that compound E24 disturbed the dynamics of tubulin catastrophe and rescue, which triggered G2/M arrest, leading to ROS accumulation, cleavage of PARP and apoptosis. Molecular dynamics simulation validated that compound E24 could tightly bind into tubulin heterodimers with ß Lys 254 and ß Cys 241 of tubulin in the docking pose. Metabolic stability and pharmacokinetics parameters were also determined. The half time (t1/2) displayed species differences in three microsomes. The plasma elimination half-life (t1/2), peak plasma concentration (Cmax), mean retention time (MRT), the area under the curve (AUC0-∞) and distribution volume (Vz) of E24 after intravenous administration were 0.90 ± 0.22 h, 594.50 ± 97.23 ng/mL, 1.09 ± 0.22 h, 413.67 ± 105.64 ng/mL*h and 5.03 ± 1.82 L/kg, respectively. In HeLa-xenografts, compound E24 exhibited obvious antitumor efficacy via the suppression of tumor growth without weight loss of body or organ. In brief, compound E24 might be a hopeful candidate with excellent properties for oncotherapy as tubulin polymerization inhibitor.

Acquired Resistance to Poly (ADP-ribose) Polymerase Inhibitor Olaparib in BRCA2-Associated Prostate Cancer Resulting From Biallelic BRCA2 Reversion Mutations Restores Both Germline and Somatic Loss-of-Function Mutations.

PARP1/2 inhibitors are effective against BRCA2-deficient tumors. The PARP inhibitor (PARPi) olaparib received FDA breakthrough designation for treatment of metastatic castration-resistant prostate cancers (CRPC) carrying mutations in BRCA1/2 or ATM genes. Emergent resistance to PARPi has been associated with tumor-specific BRCA2 mutations that revert the normal open reading frame rescuing homologous recombination. We describe a case of metastatic CRPC with germline BRCA2 mutation with acquired resistance to olaparib related to biallelic BRCA2 reversion mutations of both the germline and somatic loss of function alleles detected by circulating tumor DNA testing. We also summarize a retrospective analysis of 1,534 prostate cancer cases with ctDNA analysis showing a 1.6% incidence of germline BRCA2 mutations. Within the germline BRCA2-positive cases exposed to platinum chemotherapy or PARP inhibition, the prevalence of reversion mutations was 40%. This report documents the frequency of reversion mutations in a large cohort of prostate cancer patients carrying of BRCA mutations. It also shows the potential utility of ctDNA analyses for early detection of reversion mutation driving tumor resistance.

[Is acupuncture ineffective in treating infertility associated with polycystic ovary syndrome? A reanalysis of data on the clinical trial by WU Xiaoke's team published on JAMA].

WU Xiaoke, Stener-Victorin and Richard Legro's team published a randomized clinical trial entitled Effect of acupuncture and clomiphene in Chinese women with polycystic ovary syndrome: a randomized clinical trial in JAMA on June 27, 2017. Their conclusion is "this finding does not support acupuncture as an infertility treatment in such women". We found that the trial design had serious flaws and that the results could not lead to the conclusion. Based on the reanalysis for the study data and those published in other medical journals recently from the team, it was found that acupuncture plus clomiphene or control acupuncture plus clomiphene had more excellent live birth rate, ovulation rate and cumulative ovulation rate than clomiphene alone, with statistical and clinical significance. The conclusion of the trial is potentially incorrect.

[Immunomodulatory effect of oyster peptide on immunosuppressed mice].

OBJECTIVE: To evaluate the immunomodulating effect of oyster peptide on immunosuppressed mice. METHODS: ICR mice injected with cyclophosphamide (CTX) were adopted as the module group, with mice without treatment as the control group, and different dosages of oyster peptide (0.5 g/kg, 1.0 g/kg, and 2.0 g/kg) were given to the low, middle, and high groups for 15 days. The body weight, spleen, and thymus weight of the mice, structures under the microscope of the immune organs, numbers of white blood cells, ratios of T lymphocyte subsets, immune cytokines and numbers of nuclear cells, and DNA content in bone marrow were all assessed. RESULTS: Compared with the control group, the structures of thymus and spleen of the mice in the CTX group appeared obscure and shrunk when observed under microscope, the number of their white blood cells declined (P=0.04), the proportion of their CD3(+) T cells in peripheral blood declined (P=0.003), the proportion of their CD8(+) T cells in peripheral blood declined (P=0.002), the concentration of their IL-5 in peripheral blood significantly increased (P<0.01), the concentration of their nucleated cells and DNA density in bone marrow decreased (P=0.04, P<0.01). Oyster could improve the structures of thymus and spleen of the immunosuppressed mice. Compared with the CTX group, the number of white blood cells in 2.0 g/kg group increased (P=0.003), the proportion of CD3(+) T cells in peripheral blood in 1.0 g/kg group (P=0.04) and 2.0 g/kg group (P=0.02) increased, the proportion of CD8(+) T cells in peripheral blood in 2.0 g/kg group increased (P=0.002), the concentration of IL-5 in peripheral blood in all the oyster treated groups increased (P<0.01 in 0.5 g/kg, 1.0 g/kg, and 2.0 g/kg groups), the concentration of IL-17 in peripheral blood in 2.0 g/kg group decreased (P=0.03), the concentration of nucleated cells in bone marrow of all the oyster treated groups increased (0.5 g/kg vs. CTX, P=0.04; 1.0 g/kg vs. CTX, P=0.02; 2.0 g/kg vs. CTX P=0.01), the DNA content in bone marrow of all the oyster treated groups increased (P<0.01 in the 0.5 g/kg, 1.0 g/kg, and 2.0 g/kg groups). CONCLUSION: Oyster peptide could improve the structures of immune organs of the CTX-induced immunosuppressed mice, recover the imbalances of T lymphocyte subsets, improve the immune cytokines and increase numbers of nucleated cells and DNA content in bone marrow, thus improving the immunologic function.

Argyrophil cell density in the oxyntic mucosa is higher in female than in male morbidly obese patients

Obesity is a multifactorial disorder often associated with many important diseases such as diabetes, hypertension and other metabolic syndrome conditions. Argyrophil cells represent almost the total population of endocrine cells of the human gastric mucosa and some reports have described changes of specific types of these cells in patients with obesity and metabolic syndrome. The present study was designed to evaluate the global population of argyrophil cells of the gastric mucosa of morbidly obese and dyspeptic non-obese patients. Gastric biopsies of antropyloric and oxyntic mucosa were obtained from 50 morbidly obese patients (BMI >40) and 50 non-obese patients (17 dyspeptic overweight and 33 lean individuals) and processed for histology and Grimelius staining for argyrophil cell demonstration. Argyrophil cell density in the oxyntic mucosa of morbidly obese patients was higher in female (238.68 ± 83.71 cells/mm2) than in male patients (179.31 ± 85.96 cells/mm2) and also higher in female (214.20 ± 50.38 cells/mm2) than in male (141.90 ± 61.22 cells/mm2) morbidly obese patients with metabolic syndrome (P = 0.01 and P = 0.02, respectively). In antropyloric mucosa, the main difference in argyrophil cell density was observed between female morbidly obese patients with (167.00 ± 69.30 cells/mm2) and without (234.00 ± 69.54 cells/mm2) metabolic syndrome (P = 0.001). In conclusion, the present results show that the number of gastric argyrophil cells could be under gender influence in patients with morbid obesity. In addition, gastric argyrophil cells seem to behave differently among female morbidly obese patients with and without metabolic syndrome.

Tobacco control in Vietnam.

OBJECTIVES: To investigate the use of tobacco in Vietnam. STUDY DESIGN: Review study. METHODS: Data were collected through a review of tobacco-related literature in Vietnam. Grey literature and web content from agencies such as the World Health Organization and the US Centers for Disease Control and Prevention were consulted. RESULTS: Tobacco smoking is still common in Vietnam, although numerous policies have been issued and implemented over the last two decades. Based on the most recent data (2010), the prevalence of smoking among adults aged >15 years was 23.8%, with a higher percentage among males (47.4%) than females (1.4%). The prevalence of smoking among students aged 13-15 was 3.8% (2007), with a similar gender pattern. The prevalence of exposure to secondhand smoke is of concern, with 73.1% and 55.9% of adults reporting exposure to secondhand smoke at home and at work or other places, respectively. Of the adult respondents, 55.5% believed that smoking may cause lung cancer, stroke and heart disease. Most students (93.4%) and adults (91.6%) had seen anti-smoking media messages. Of the students, 56.4% had seen pro-cigarette advertisements on billboards, 36.9% had seen pro-cigarette advertisements in newspapers or magazines, and 8.2% had been offered free cigarettes by tobacco company representatives. The price of cigarettes decreased by approximately 5% between 1995 and 2006, whereas gross domestic product per capita increased by more than 150%. On average, smokers smoked 13.5 cigarettes per day, and spent US$86 on cigarettes per year. Despite such high levels of tobacco exposure in Vietnam, the total tax on cigarettes remains at 45% of the retail price. Furthermore, only 29.7% of smokers had been advised to quit by a healthcare provider in the past 12 months. CONCLUSION: Strong enforcement and evidence-based regulations which rounded on MPOWER are needed to help protect current smokers and non-smokers from the devastating effects of tobacco.

Methylation profiles of 22 candidate genes in breast cancer using high-throughput MALDI-TOF mass array.

Alterations of DNA methylation patterns have been suggested as biomarkers for diagnostics and therapy of cancers. Every novel discovery in the epigenetic landscape and every development of an improved approach for accurate analysis of the events may offer new opportunity for the management of patients. Using a novel high-throughput mass spectrometry on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) silico-chips, we determined semiquantitative methylation changes of 22 candidate genes in breast cancer tissues. For the first time we analysed the methylation status of a total of 42 528 CpG dinucleotides on 22 genes in 96 different paraffin-embedded tissues (48 breast cancerous tissues and 48 paired normal tissues). A two-way hierarchical cluster analysis was used to classify methylation profiles. In this study, 10 hypermethylated genes (APC, BIN1, BMP6, BRCA1, CST6, ESRb, GSTP1, P16, P21 and TIMP3) were identified to distinguish between cancerous and normal tissues according to the extent of methylation. Individual assessment of the methylation status for each CpG dinucleotide indicated that cytosine hypermethylation in the cancerous tissue samples was mostly located near the consensus sequences of the transcription factor binding sites. These hypermethylated genes may serve as biomarkers for clinical molecular diagnosis and targeted treatments of patients with breast cancer.

Parallel assessment of circulatory cell-free DNA by PCR and nucleosomes by ELISA in breast tumors.

OBJECTIVES: In order to assess the potential biomolecules for breast cancer, we analyzed in parallel the levels of cell-free glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and cell-free nucleosomes in serum samples from patients with benign and malignant breast tumors. The levels of cell-free DNA obtained by quantitative PCR were compared with those obtained by enzyme-linked immunosorbent assay (ELISA). METHODS: Twenty-three patients with benign breast tumors, 27 patients with breast cancer, and 32 age-matched healthy women were recruited. The amounts of serum nucleosomes were analyzed by ELISA and the levels of cell-free GAPDH were measured by real-time quantitative PCR. The correlation between nucleosome and cell-free GAPDH levels was examined using the Spearman rank test. RESULTS: The levels of cell-free GAPDH were significantly higher in the serum samples of patients with benign and malignant breast tumors than in those of the control group (median 37,966 GE/mL, range 3,802-130,104 versus 11,770 GE/mL, range 2,198-73,522, p=0.035 and median 40,698 GE/mL, range 3,644-192,482 versus 11,770 GE/mL range 2,198-73,522, p=0.001). The concentration of cell-free GAPDH correlated significantly with the quantities of nucleosomes in serum samples (r=0.451, p=0.000). There was, however, no significant difference between healthy individuals and women with benign breast tumors or breast cancer in terms of nucleosomes determined by ELISA. CONCLUSION: Our data suggest that the cell-free serum GAPDH DNA assayed by quantitative PCR is a better biomarker than nucleosomes assayed by ELISA in patients with breast tumors.

Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats.

Ruxiang (Gummi olibanum), the dried gum resin of Boswellia carterii (BC), has been used in traditional Chinese medicine to alleviate pain and inflammation for thousands of years. In this random, blinded study, the anti-arthritic effects of a BC extract were observed and compared to vehicle control in a Lewis rat adjuvant arthritis model (n=8/group). Arthritis was induced by injecting CFA subcutaneously into the base of the tail, and the extract was administered orally (i.g.) for 10 consecutive days beginning on day 16 after the injection. Arthritic scores, paw edema, and the local tissue pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) were assessed. Toxicity and adverse effects of the extract were evaluated. At 0.90 g/kg per day, BC significantly decreased arthritic scores between days 20 and 25 (p<0.05) and reduced paw edema on days 18, 20 and 22 compared to control (p<0.05). It also significantly suppressed local tissue TNF-alpha and IL-1beta (p<0.05). No major adverse effects were observed in animals during the repeated-dose treatment profile although mild fur discoloration was noted. The data show that BC extract has significant anti-arthritic and anti-inflammation effects and suggest that these effects may be mediated via the suppression of pro-inflammatory cytokines.

The ovarian endometrioma: why is it so poorly managed? Indicators from an anonymous survey.

As a tertiary referral centre for women with severe endometriosis we see a large number of patients who have endometriotic cysts, and many of these patients have been operated on by gynaecologists elsewhere in the UK. We have been surprised by the variety of approaches to their management. In order to establish the current clinical practices of endometrioma management amongst gynaecologists in the UK, we have carried out an anonymous survey. There appears to be an equal preference for open versus endoscopic surgery, even though there is considerable evidence suggesting that endoscopic surgery is superior. However, the management of endometriomas varies significantly between the two groups. In this article, we have presented the results of our survey and used them as the basis for a debate on the management of endometriomas.

Adapting pharmacokinetic properties of a humanized anti-interleukin-8 antibody for therapeutic applications using site-specific pegylation.

A neutralizing anti-interleukin-(IL-)8 monoclonal antibody was humanized by grafting the complementary determining regions onto the human IgG framework. Subsequent alanine scanning mutagenesis and phage display enabled the production of an affinity matured antibody with a >100-fold improvement in IL-8 binding. Antibody fragments can be efficiently produced in Escherichia coli but have the limitation of rapid clearance rates in vivo. The Fab' fragment of the antibody was therefore modified with polyethylene glycol (PEG) in order to obtain a more desirable pharmacokinetic profile. PEG (5-40 kDa) was site-specifically conjugated to the Fab' via the single free cysteine residue in the hinge region. In vitro binding and bioassays showed little or no loss of activity. The pharmacokinetic profiles of the 20 kDa, 30 kDa, 40 kDa, and 40 kDa branched PEG-Fab' molecules were evaluated in rabbits. Relative to the native Fab', the clearance rates of the PEGylated molecules were decreased by 44-175-fold. In a rabbit ear model of ischemia/reperfusion injury, all PEGylated Fab' molecules were as efficacious in reducing oedema as the original monoclonal antibody. These studies demonstrate that it is possible to customize the pharmacokinetic properties of a Fab' while retaining its antigen binding activity.

[Transcranial electric stimulation in anesthesiological support in emergency operations in patients with hypovolemia]. / Primenenie transkranial'noi élektrostimuliatsii pri anesteziologicheskom obespechenii ékstrennykh khirurgicheskikh operatsii u bol'nykh s gipovolemiei.

Hemodynamics was studied in 60 patients with pronounced initial hypovolemia, urgently operated on for acute gastrointestinal disease under conditions of 4 anesthesia. In contrast to traditional anesthesia, transcranial electric stimulation (TCES) as a component of anesthesia stabilized hemodynamics without increasing the rate and volume of intraoperative infusion therapy. This makes total anesthesia with TCES preferable in urgent operations, particularly in cases when hypovolemia cannot be properly corrected before surgery.

p53 mutations do not predict response to paclitaxel in metastatic nonsmall cell lung carcinoma.

BACKGROUND: In vitro data and animal studies suggest that paclitaxel may have a unique ability to activate tumor cell apoptosis in the absence of wild-type p53 function. The authors previously demonstrated that response to paclitaxel and concurrent radiation was not affected by p53 mutations in nonsmall cell lung carcinoma (NSCLC). We sought to determine whether p53 mutations affect response to paclitaxel alone in patients with metastatic NSCLC. METHODS: Twenty-five patients with metastatic NSCLC who participated in Brown University Oncology Group protocols utilizing single-agent weekly paclitaxel had tumor tissue that was adequate for p53 analysis. Tumor tissue was evaluated for p53 gene mutations in exons 5 through 8 by single-strand conformation polymorphism analysis. Mutations were confirmed by direct sequencing of altered mobility polymerase chain reaction products. RESULTS: Mutations in p53 were found in 8 of 25 patients (32%). The response rates of 75% for patients with tumors with p53 mutations and 47% for patients with wild-type p53 do not differ significantly (P = 0.12). The 1-year survival rates for patients with and without p53 mutation after treatment with weekly paclitaxel were 63% (95% confidence interval [CI], 31-100%) and 53% (95% CI, 33-86%), respectively. CONCLUSIONS: p53 mutations do not adversely affect response to paclitaxel as a single agent in metastatic NSCLC. These results provide clinical support for in vitro observations that paclitaxel can bypass mutant p53 and lead to tumor cell death by alternate pathway(s). Paclitaxel should be considered as a component of treatment for patients with metastatic NSCLC with tumors that have p53 mutations.

Development of California Public Health Goals (PHGs) for chemicals in drinking water.

As part of a program for evaluation of environmental contaminants in drinking water, risk assessments are being conducted to develop Public Health Goals (PHGs) for chemicals in drinking water, based solely on public health considerations. California's Safe Drinking Water Act of 1996 mandated the development of PHGs for over 80 chemicals by 31 December 1999. The law allowed these levels to be set higher or lower than federal maximum contaminant levels (MCLs), including a level of zero if data are insufficient to determine a specific level. The estimated safe levels and toxicological rationale for the first 26 of these chemicals are described here. The chemicals include alachlor, antimony, benzo[a]pyrene, chlordane, copper, cyanide, dalapon, 1,2-dichlorobenzene, 1,4-dichlorobenzene, 2,4-D, diethylhexylphthalate, dinoseb, endothall, ethylbenzene, fluoride, glyphosate, lead, nitrate, nitrite, oxamyl, pentachlorophenol, picloram, trichlorofluoromethane, trichlorotrifluoroethane, uranium and xylene(s). These risk assessments are to be considered by the State of California in revising and developing state MCLs for chemicals in drinking water (which must not exceed federal MCLs). The estimates are also notable for incorporation or consideration of newer guidelines and principles for risk assessment extrapolations.

[Detection of the level of serum antigen recognized by McAbGB2 in breast cancer].

This study sought to verify the levels of serum antigen recognized by McAbGB2 (abbr. serum McAbGB2 antigen) in patients with breast cancer. We adopted the ELISA method and used McAbGB2 to detect the level of serum McAbGB2 antigen in 50 normal persons and 60 patients with breast cancer. The results showed that the level of serum McAbGB2 antigen of 17 preoperative patients with breast cancer was significantly different from that of the normal persons (P < 0.001); the rate of agreement on positivity for the 17 preoperative patients with breast cancer was 88.2% (15/17); the levels of serum McAbGB2 antigen in 8 patients among the 17 preoperative patients with breast cancer decreased from 57.5 +/- 51.3 u/ml (preoperation) to 20.6 +/- 4.98 u/ml (postoperation; the levels of serum McAbGB2 antigen in the other 43 operated patients with breast cancer almost remained normal during post-operative chemotherapy. These suggest that serum McAbGB2 antigen is a marker for breast cancer and can be used for serological diagnosis, treatment and prognosis inspection.