Characterisation of admissions and readmissions after 20 days of illness among COVID-19 patients.

INTRODUCTION: There has been an observed number of readmissions after an index COVID-19 admission, including admissions after an initial home quarantine. The purpose of this study was to identify the clinical characteristics and outcomes of COVID-19 patients who were readmitted or admitted after an initial home quarantine between 21 and 90 days of illness. MATERIALS AND METHODS: This was a single-centre retrospective cohort study comprising patients admitted to a state hospital in Selangor, Malaysia, between August and October 2021. The demographic data, clinical characteristics, presenting complaints, laboratory tests, organ dysfunction, use of invasive ventilation, intensive care unit (ICU) admissions, length of hospitalisation and mortality were collected and analysed. RESULTS: The analysis involved a total of 195 cases. More than a quarter of the cases (52 [26.7%]) were related to the initial COVID-19 infection. Nine cases (4.6%) required mechanical ventilation, while eight cases (4.1%) were admitted to the ICU. The overall mortality was 17 cases (8.7%). Surviving patients were younger (49.5 vs. 58.4 years), less likely to have diabetes mellitus (48.3% vs. 82.4%), or chronic kidney disease (12.9% vs. 41.2%); had higher levels of admission haemoglobin (12.6 vs. 9.1g/dL) and albumin (33.0 vs. 21.0g/L); lower white blood cells (10.2 vs. 13.0 × 109/L), creatinine (81.2 vs. 151.9µmol/L) and C-reactive protein (18.2 vs. 135.0mg/L) at admission; less likely to have MI (6.7% vs. 23.5%), sepsis (3.4% vs. 47.1%), or acute kidney injury (3.4% vs. 17.6%) and organ dysfunction (25.3% vs. 94.1%). CONCLUSION: Approximately a quarter of patients were admitted or readmitted due to direct COVID-19 complications between 21 and 90 days of illness. The baseline oxygen requirements at admission were independently associated with mortality, invasive mechanical ventilation and ICU admissions. Further research is needed to establish a risk model for patients returning to a hospital to predict their risk of post-COVID complications.

Fast Bayesian Variable Screenings for Binary Response Regressions with Small Sample Size.

Screening procedures play an important role in data analysis, especially in high-throughput biological studies where the datasets consist of more covariates than independent subjects. In this article, a Bayesian screening procedure is introduced for the binary response models with logit and probit links. In contrast to many screening rules based on marginal information involving one or a few covariates, the proposed Bayesian procedure simultaneously models all covariates and uses closed-form screening statistics. Specifically, we use the posterior means of the regression coefficients as screening statistics; by imposing a generalized g-prior on the regression coefficients, we derive the analytical form of their posterior means and compute the screening statistics without Markov chain Monte Carlo implementation. We evaluate the utility of the proposed Bayesian screening method using simulations and real data analysis. When the sample size is small, the simulation results suggest improved performance with comparable computational cost.

A SNP in the 3'-UTR of HSF1 in dairy cattle affects binding of target bta-miR-484.

The heat shock transcription factor 1 gene (HSF1) plays a key role in the heat stress response. We previously found a single nucleotide polymorphism (SNP) in the 3'-untranslated region (g.4693G>T) of HSF1 that was related to thermo tolerance in Chinese Holstein cattle through association analysis. However, it is not known whether other SNPs also affect thermo tolerance.In this study a novel SNP, g.1451G>T, was identified by DNA sequencing and genotyped using creating restriction site-polymerase chain reaction methodology. The g.1451G>T polymorphic site met Hardy-Weinberg equilibrium (P > 0.05). Association analysis demonstrated that this SNP had no effect on thermo tolerance traits in Holstein cattle. Findings of the study compared to the analysis of g.4693 G>T further indicated that g.4693 G>T may play an important role in thermo tolerance, although the mechanism is not clear. RNA hybrid and Targetscan prediction showed that the minimum free energy hybridization of bta-miR-484 with HSF1 3'-UTR was -31.9 kcal/mol and g.4693 G>T was in the seed sequence of bovine HSF1 that binds to bta-miR-484. Analysis by Luciferase assay indicated that HSF1 expression was directly targeted by bta-miR-484 in HEK 293T cells, and the Rluc/luc ratio of wildtype (GG) was lower than that of the mutant (TT) (P < 0.05). These results suggest that g.4693 G>T affects binding of HSF1 to bta-miR-484.

Inbreeding depression in male gametic performance.

One key objective in evolutionary ecology is to understand the magnitude of inbreeding depression expressed across sex-specific components of fitness. One major component of male fitness is fertilization success, which depends on male gametic performance (sperm and pollen performance in animals and plants, respectively). Inbreeding depression in male gametic performance could create sex-specific inbreeding depression in fitness, increase the benefit of inbreeding avoidance and reduce the efficacy of artificial insemination and pollination. However, there has been no assessment of the degree to which inbreeding generally depresses male gametic performance and hence post-copulatory or post-pollination fertilization success. Because inbreeding depression is understood to be a property of diploid entities, it is not clear what degree of inbreeding depression in haploid gametic performance should be expected. Here, we first summarize how inbreeding depression in male gametic performance could potentially arise through gene expression in associated diploid cells and/or reduced genetic diversity among haploid gametes. We then review published studies that estimate the magnitude of inbreeding depression in traits measuring components of sperm or pollen quantity, quality and competitiveness. Across 51 published studies covering 183 study traits, the grand mean inbreeding load was approximately one haploid lethal equivalent, suggesting that inbreeding depresses male gametic performance across diverse systems and traits. However, there was an almost complete lack of explicit estimates from wild populations. Future studies should quantify inbreeding depression in systematic sets of gametic traits under naturally competitive and noncompetitive conditions and quantify the degree to which gamete phenotypes and performance reflect haploid vs. diploid gene expression.

Mating system contributes only slightly to female maintenance in gynodioecious Geranium maculatum (Geraniaceae).

Gynodioecy, the co-occurrence of female and hermaphroditic individuals within a population, is an important intermediate in the evolution of separate sexes. The first step, female maintenance, requires females to have higher seed fitness compared with hermaphrodites. A common mechanism thought to increase relative female fitness is inbreeding depression avoidance, the magnitude of which depends on hermaphroditic selfing rates and the strength of inbreeding depression. Less well studied is the effect of biparental inbreeding on female fitness. Biparental inbreeding can affect relative female fitness only if its consequence or frequency differs between sexes, which could occur if sex structure and genetic structure both occur within populations. To determine whether inbreeding avoidance and/or biparental inbreeding can account for female persistence in Geranium maculatum, we measured selfing and biparental inbreeding rates in four populations and the spatial genetic structure in six populations. Selfing rates of hermaphrodites were low and did not differ significantly from zero in any population, leading to females gaining at most a 1-14% increase in seed fitness from inbreeding avoidance. Additionally, although significant spatial genetic structure was found in all populations, biparental inbreeding rates were low and only differed between sexes in one population, thereby having little influence on female fitness. A review of the literature revealed few sexual differences in biparental inbreeding among other gynodioecious species. Our results show that mating system differences may not fully account for female maintenance in this species, suggesting other mechanisms may be involved.

Genome-wide normalized score: a novel algorithm to detect fetal trisomy 21 during non-invasive prenatal testing.

OBJECTIVES: Non-invasive prenatal testing for fetal trisomy 21 (T21) by massively parallel shotgun sequencing (MPSS) is available for clinical use but its efficacy is limited by several factors, e.g. the proportion of cell-free fetal DNA in maternal plasma and sequencing depth. Existing algorithms discard DNA reads from the chromosomes for which testing is not being performed (i.e. those other than chromosome 21) and are thus more susceptible to diluted fetal DNA and limited sequencing depth. We aimed to describe and evaluate a novel algorithm for aneuploidy detection (genome-wide normalized score (GWNS)), which normalizes read counts by the proportions of DNA fragments from chromosome 21 in normal controls. METHODS: We assessed the GWNS approach by comparison with two existing algorithms, i.e. Z-score and normalized chromosome value (NCV), using theoretical approximations and computer simulations in a set of 86 cases (64 euploid and 22 T21 cases). We then validated GWNS by studying an expanded set of clinical samples (n = 208). Finally, dilution experiments were undertaken to compare performance of the three algorithms (Z-score, NCV, GWNS) when fetal DNA concentration was low. RESULTS: At fixed levels of significance and power, GWNS required a smaller fetal DNA proportion and fewer total MPSS reads compared to Z-score or NCV. In dilution experiments, GWNS also outperformed the other two methods by reaching the correct diagnosis with the lowest range of fetal DNA concentrations (GWNS, 3.83-4.75%; Z-score, 4.75-5.22%; NCV, 6.47-8.58%). CONCLUSION: Our results demonstrate that GWNS is comparable to Z-score and NCV methods regarding the performance of detecting fetal T21. Dilution experiments suggest that GWNS may perform better than the other methods when fetal fraction is low.

Building human capacity through early childhood intervention: the Child Development Research Programme at the Tropical Medicine Research Institute, the University of the West Indies, Kingston, Jamaica.

Research conducted by the Child Development Research Group in the Tropical Medicine Research Institute has made significant contributions to the understanding of the importance of early nutrition and the home environment for children's development and the impact of psychosocial stimulation for disadvantaged and/or undernourished children. The work has provided critical evidence that has contributed to the increasing attention given to early childhood development in the work and policies of agencies such as the World Bank, World Health Organization (WHO) and United Nations Children Fund (UNICEF). This review concerns research which documented the impact of malnutrition on children's development and for the first time demonstrated the benefits and necessity of psychosocial stimulation for improvement in development. Subsequent research was critical in establishing the importance of linear growth retardation (stunting) as a risk factor for poor child development. A twenty-two-year study of stunted children has demonstrated benefits through to adulthood in areas such as educational attainment, mental health and reduced violent behaviour from an early childhood home visiting programme that works through mothers to promote their children's development. The group's research has also demonstrated that it is feasible and effective to integrate the stimulation intervention into primary care services with benefits to children's development and mothers'child rearing knowledge and practices. The group is currently conducting a study to provide information needed for scaling-up of parenting programmes through evaluation of a new approach to improving parenting through health centres and a modified home visit programme.

Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas.

Although low-grade gliomas (LGG) have a less aggressive course than do high-grade gliomas, the outcome of these tumours is ultimately fatal in most patients. Both the tumour and its treatment can cause disabling morbidity, particularly of cognitive functions. Because many patients present with seizures only, with no other signs and symptoms, maintenance of quality of life and function constitutes a particular challenge in LGG. The slow growth pattern of most LGG, and the rare radiological true responses despite a favourable clinical response to treatment, interferes with the use of progression-free survival as the primary endpoint in trials. Overall survival as an endpoint brings logistical challenges, and is sensitive to other non-investigational salvage therapies. Clinical trials for LGG need to consider other measures of patient benefit such as cognition, symptom burden, and seizure activity, to establish whether improved survival is reflected in prolonged wellbeing. This Review investigates clinical and imaging endpoints in trials of LGG, and provides response assessment in neuro-oncology (RANO) criteria for non-enhancing tumours. Additionally, other measures for patients with brain tumours that assess outcome are described. Similar considerations are relevant for trials of high-grade gliomas, although for these tumours survival is shorter and survival endpoints generally have more value than they do for LGG.

Morning glory as a powerful model in ecological genomics: tracing adaptation through both natural and artificial selection.

Many diverse questions in ecology and evolution have been addressed using species belonging to the genus Ipomoea, commonly referred to as the morning glory genus. Ipomoea exhibits a wide range of diversity in floral color, growth form, mating system and tolerance to environmental factors, both within and among species, and as such has been a focal group of many investigations in the last 80 years. In this review, we highlight recent work to which Ipomoea species have contributed-from studies of the mating system, molecular evolution, plant-herbivore and plant-parasite interactions to their impact on and importance to agriculture. Genomic resources for this group are currently under development, and given the breadth of studies and history of this group, combined with an expanding genetics toolkit, we argue that Ipomoea should provide the next model organism for ecological genomics.

Novel microcantilever design for versatile mass sensor application.

This study presents a new microcantilever design for versatile mass sensor application. The novel comb-type cantilever provides a sensitive microcantilever structure for normal sensor application, and its sensing responses are compared with those of a commercial cantilever. While the comb-type cantilever has a similar total surface area to the commercial cantilever, there is a distinct difference in the design of the regional surface area. The results for a static charge interaction, used to compare the sensitivity of normal sensor applications, show a significant resonant frequency change for the comb-type cantilever when compared with that for the commercial cantilever, indicating the importance of the large surface area in the highly sensitive cantilever region. Thus, a schematic structure of a microcantilever for fabricating a highly sensitive mass sensor is proposed.

Serum soluble CD44v6 levels in patients with oral and maxillofacial malignancy.

OBJECTIVE: To determine the levels of serum sCD44v6 in patients with oral cancer and evaluate the value of serum sCD44v6 in adjuvant diagnosis, staging and monitoring treatment response in these patients. MATERIALS AND METHODS: A total of 112 hospitalized patients with oral and maxillofacial malignancy and 28 healthy individuals were examined for serum sCD44v6 levels. Venous blood was collected from these patients and the healthy individuals. One week after treatment, venous blood was collected once again in 60 patients with oral and maxillofacial squamous cell carcinoma (OSCC). RESULTS: The sCD44v6 concentration was not significantly different between patients with oral and maxillofacial malignancy and control group (P > 0.05). The levels of serum sCD44v6 in patients with OSCC and salivary carcinoma showed no difference with those in control group (P > 0.05). The sCD44v6 level in patients with stage III and IV disease was higher than that of patients with stage I and II and that of the control group, but the difference was not significant (P > 0.05). Serum sCD44v6 levels in patients with OSCC after treatment became lower than that prevailed during pretreatment (P < 0.05). CONCLUSION: The possible roles of CD44v6 in the diagnosis of oral and maxillofacial malignancy deserve further elucidation and evaluation. Serum sCD44v6 may be a valuable marker in monitoring treatment response in patients with OSCC.

Investigation on mechanism of catalysis by Pt-LiCoO2 for hydrolysis of sodium borohydride using X-ray absorption.

The synthesis of platinum nanoparticle loaded LiCoO2 (Pt-LiCoO2) was carried out successfully by an impregnation method followed by sintering at different temperatures. The catalytic role of Pt-LiCoO2 composite in hydrogen generation during hydrolysis of sodium borohydride (NaBH4) was studied for fuel cell applications. X-ray diffraction (XRD), transmission electron microscopy (TEM), and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) have been used to elucidate the structural and catalytic properties of Pt-LiCoO2. It was found that the 15 wt % of Pt nanoparticles on LiCoO2 sintered at 450 degrees C support showed the maximum efficiency for the catalysis reaction of hydrogen production. X-ray absorption near edge structure (XANES) analysis and extended X-ray absorption fine structure (EXAFS) analysis using a synchrotron radiation source were performed to carry out ex situ measurements in order to understand the mechanism of the catalytic process for the production of hydrogen during the hydrolysis of NaBH4. Co K-edge XANES showed a small percentage of cobalt in the metallic form after hydrogen generation which suggests the reduction of the cobalt during the hydrolysis of NaBH4.

The role of fathers in overweight prevention: an analysis of a Caribbean cohort.

BACKGROUND: Family-based strategies to reduce the risk of overweight in childhood are needed in the Caribbean. AIM: To investigate the associations between parental characteristics and risk of overweight and explore possible mechanisms. METHODS: Data from a parenting intervention were analysed. Parental characteristics were obtained by questionnaire at enrolment. At 18 months, 501 infants (82.9% of cohort) had weight and length measured using standardized methods. The association of parents' characteristics with risk of infant overweight was assessed using random-effects logistic regression. Four focus groups among mothers in Jamaica were conducted to explore mechanisms. RESULTS: Overall, 20.6% of infants were 'at risk of overweight'. Fathers were present in 52% of households. Fathers' presence [OR (95% CI) 0.60 (0.37-0.96)] was associated with reduced risk of overweight independent of socioeconomic status. Mothers reported that fathers encouraged healthier practices. CONCLUSION: Fathers may be important agents of change in intervention strategies to prevent childhood overweight.

Proliferation induced by keratinocyte growth factor enhances in vivo retroviral-mediated gene transfer to mouse hepatocytes.

Retroviral gene transfer to liver without prior injury has not yet been accomplished. We hypothesized that recombinant human keratinocyte growth factor would stimulate proliferation of hepatocytes and allow for efficient in vivo gene transfer with high titer murine Moloney retroviral vectors. This report shows that 48 h after intravenous injection of keratinocyte growth factor, hepatocyte proliferation increased approximately 40-fold compared to non-stimulated livers. When keratinocyte growth factor treatment was followed by intravenous injection of high titer (1 x 10(8) colony forming units/ml) retrovirus coding for the Escherichia Coli beta-galactosidase gene, there was a 600-fold increase in beta-galactosidase expression, with 2% of hepatocytes transduced. Thus, by exploiting the mitogenic properties of keratinocyte growth factor, retrovirus-mediated gene transfer to liver may be accomplished in vivo without the use of partial hepatectomy or pretreatment with other toxins to induce hepatocyte cell division.

Analysis of metabolic indices in regions of abnormal perfusion in patients with high-grade glioma.

BACKGROUND AND PURPOSE: MR spectroscopic imaging (MRSI) and dynamic susceptibility-contrast MR imaging (DSC-MR imaging) are functional in vivo techniques for assessing tumor metabolism and vasculature characteristics. Because tumor hypoxia is influenced by tortuous, degraded, swollen, and angiogenic tumor vasculature, regions of abnormal perfusion parameters should coexist with changes in lactate and creatine metabolite levels. MATERIALS AND METHODS: DSC-MR imaging and lactate-edited MRSI were performed on 38 treatment-naive patients with high-grade gliomas (17 grade III, 21 grade IV) before surgical diagnosis. Regions of abnormal perfusion were determined from peak height and percent recovery maps for each voxel within the spectroscopic imaging volume. Choline, creatine, and lactate levels within voxels experiencing only abnormal peak height (aPH), only abnormal recovery (aRec), and both abnormal peak height and recovery (aPH+aRec) were determined and compared to the surrounding T2 hyperintensity (T2h) and normal-appearing white matter. RESULTS: There were decreasing trends in volume from aPH to aRec to aPH+aRec regions for both grade III and grade IV gliomas. Grade IV gliomas exhibited significantly elevated choline in all abnormal perfusion regions, with reduced creatine and increased lactate in the aRec region relative to the surrounding T2h. Grade III gliomas showed trends toward increased creatine within the aPH region and reduced levels within the aRec region. CONCLUSION: Depressed creatine and elevated lactate levels confirmed the lack of oxygenation within regions of compromised vascular integrity. Identification of regions with leaky or dense vasculature and metabolic markers of hypoxia and cellular proliferation could be useful in determining the more aggressive part of the tumor for targeting, monitoring, and assessing effects of treatment.

Construction of a defective retrovirus containing the human hypoxanthine phosphoribosyltransferase cDNA and its expression in cultured cells and mouse bone marrow.

Defective ecotropic and amphotropic retroviral vectors containing the cDNA for human hypoxanthine phosphoribosyltransferase (HPRT) were developed for efficient gene transfer and high-level cellular expression of HPRT. Helper cell clones which produced a high viral titer were generated by a simplified method which minimizes cell culture. We used the pZIP-NeoSV(X) vector containing a human hprt cDNA. Viral titers (1 X 10(3) to 5 X 10(4)/ml) of defective SVX HPRT B, a vector containing both the hprt and neo genes, were increased 3- to 10-fold by cocultivation of the ecotropic psi 2 and amphotropic PA-12 helper cells. Higher viral titers (8 X 10(5) to 7.5 X 10(6] were obtained when nonproducer NIH 3T3 cells or psi 2 cells carrying a single copy of SVX HPRT B were either transfected or infected by Moloney leukemia virus. The SVX HPRT B defective virus partially corrected the HPRT deficiency (4 to 56% of normal) of cultured rodent and human Lesch-Nyhan cells. However, instability of HPRT expression was detected in several infected clones. In these unstable variants, both retention and loss of the SVX HPRT B sequences were observed. In the former category, cells which became HPRT- (6-thioguanine resistant [6TGr]) also became G418s, indicative of a cis-acting down regulation of expression. Both hypoxanthine-aminopterin-thymidine resistance (HATr) and G418r could be regained by counterselection in hypoxanthine-aminopterin-thymidine. In vitro mouse bone marrow experiments indicated low-level expression of the neo gene in in vitro CFU assays. Individual CFU were isolated and pooled, and the human hprt gene was shown to be expressed. These studies demonstrated the applicability of vectors like SVX HPRT B for high-titer production of defective retroviruses required for hematopoietic gene transfer and expression.

Expression of human adenosine deaminase in murine hematopoietic cells.

Multiple replication-defective retrovirus vectors were tested for their ability to transfer and express human adenosine deaminase in vitro and in vivo in a mouse bone marrow transplantation model. High-titer virus production was obtained from vectors by using both a retrovirus long terminal repeat promoter and internal transcriptional units with human c-fos and herpes virus thymidine kinase promoters. After infection of primary murine bone marrow with one of these vectors, human adenosine deaminase was detected in 60 to 85% of spleen colony-forming units and in the blood of 14 of 14 syngeneic marrow transplant recipients. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells.

Aortic dissection presenting as concomitant stroke and STEMI.

Aortic dissection is a disease of immediate consequence,as mortality of a proximal dissection is in excess of 50% when left untreated. Early recognition of the dissection event can lead to faster definitive correction with surgical and/or novel percutaneous approaches. Widely varying signs and symptoms can, however, make this diagnosis a challenge, further complicated by the fact that no specific imaging modality is ideal, nor immediately available, in all cases. Care must be taken inpatients where methodical evaluation is difficult,including physical exam, standard electrocardiogram and chest X-ray, before more definitive imaging. This is a case of aortic dissection that is presented as concomitant ST elevation myocardial infarction and embolic stroke, in which the patient received thrombolytics before diagnosis of the dissection itself. This arguably may have worsened her clinical course.

Suramin-induced decrease in prostate-specific antigen expression with no effect on tumor growth in the LNCaP model of human prostate cancer.

BACKGROUND: Suramin, a polysulfonated naphthylurea and a recognized antitrypanosomal agent, has shown some promise in phase II clinical trials in the management of hormone-refractory human prostate cancer. Reduction of serum prostate-specific antigen (PSA) levels has been proposed as an end point for evaluating the antitumor efficacy of treatments for hormone-refractory prostate cancer. PURPOSE: We examined the antitumor effect of suramin in an in vivo mouse model of hormone-refractory human prostate cancer to determine whether a decrease in PSA levels reflects a reduction in tumor growth (volume). The tumors were induced in castrated, athymic nude mice by use of the androgen-independent, tumorigenic human prostate cancer cell line C4-2, which is a subline of the androgen-dependent, parental nontumorigenic cell line LNCaP. We also evaluated the effects of suramin in vitro on cell growth and the expression of PSA messenger RNA (mRNA) in both LNCaP and C4-2 cells. METHODS: For the in vivo studies, 24 mice were given a subcutaneous injection of 5 x 10(6) C4-2 cells at each of four sites. Animals (n = 20) with tumor volumes greater than 1 mm3 or less than 5 mm3 were divided equally into two groups. Drug treatment was initiated in one group by administration of 1 mg suramin intraperitoneally, followed by 0.1 mg suramin at 10-day intervals to maintain constant serum levels. Tumor growth and PSA expression levels were monitored. For the in vitro studies, both LNCaP and C4-2 cells were exposed to 100-400 microgram/mL suramin, and cell growth was monitored by a quantitative crystal violet assay. PSA mRNA expression was assessed by northern blot analysis in cells treated with either 250 microgram/mL suramin, 400 ng/mL dihydrotestosterone (DHT) (positive control), or 0.5-75 microgram/mL hydrocortisone (to mimic the clinical use of hydrocortisone during suramin treatment to compensate for the loss of adrenocortical function). In some studies, the combined effect of DHT and suramin on PSA mRNA expression was also evaluated. A two-way analysis of variance was performed to evaluate the treatment differences, and P values were obtained from two-sided tests for statistical significance. RESULTS: In vivo, suramin did not significantly affect the growth of androgen-independent C4-2 tumors (relative to the growth of tumors in 5% glucose-treated control animals; P = .76). However, suramin significantly decreased the ratio of PSA level to tumor volume (ng/mL PSA per mm(3) of tumor) (P<.001). Mice developed bone metastases in both treatment arms. Suramin affected the in vitro growth of LNCaP cells but not of C4-2 cells. Suramin diminished PSA mRNA expression in both LNCaP and C4-2 cells grown in vitro. Hydrocortisone had no effect on PSA mRNA levels. CONCLUSIONS: Although suramin inhibited the growth of androgen-dependent LNCaP cells, it did not inhibit the growth of androgen-independent C4-2 cells either in vitro or in vivo. Suramin significantly decreased PSA mRNA expression in both cell lines in vitro and depressed serum PSA levels in mice bearing androgen-independent C4-2 tumors. IMPLICATIONS: PSA level should be used with caution as an end point in clinical trials using suramin therapy for hormone-refractory prostate cancer.

Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer.

Our laboratory has previously reported on the derivation of LNCaP cell sublines from LNCaP tumors maintained in castrated and intact athymic male mice. These LNCaP sublines differ from the parental line in tumorigenicity and androgen dependence. This paper demonstrates that one of these sublines acquired metastatic potential. When inoculated either s.c. or orthotopically, the C4-2 subline metastasized to the lymph node and bone with an incidence of 11-50%. Interestingly, the incidence of osseous metastasis was higher in castrated than in intact male hosts. We evaluated the chromosomal, immunohistochemical, and biochemical characteristics of the LNCaP sublines derived from C4-2 tumors that metastasized to the lymph node and bone. Cytogenetic analysis showed that all sublines were human and shared common marker chromosomes with the parental LNCaP cells. This experimental human prostate cancer model may permit, for the first time, the study of the molecular mechanisms underlying human prostate cancer metastasis.