Critical impacts of pyrolysis conditions and activation methods on application-oriented production of wood waste-derived biochar.

Wood waste-derived biochar with tunable carbon structure and surface functionality has a great potential for various environmental applications and circular economy; however, a holistic understanding on the application-oriented production of high-efficacy biochar is lacking. Thus, the co-impacts of different pyrolysis conditions (temperature and duration) and activation methods (steam, CO2, and acid pretreatment) on the biochar properties were first investigated. A temperature of 650 ℃ was effective in forming carbonized structure in biochar, while 750 ℃ was critical for the porous structure development. A longer pyrolysis duration (>60 min) enhanced the pore volume without compromising the yield. The activated biochar exhibited a larger pore volume (2.1- to 2.9-fold of pristine biochar) for potential high-end emerging applications. The acid pretreatment effectively removed dissolved organic carbon and most metals from the biochar. This study provides an essential guidance on the fit-for-purpose designs of biochar production conditions for sustainable wood waste management.

Childhood Adversity, Resilience, and Mental Health: A Sequential Mixed-Methods Study of Chinese Young Adults.

Resilience is a key health protective factor for those with adverse childhood experiences (ACEs), but little research has explored how it manifests in early adulthood or across cultures. The purpose of this study was to generate a fuller understanding of resilience and its contribution to the relationships between mental health problems and ACEs among Chinese young adults in Hong Kong. Using a sequential explanatory mixed-methods design, 433 Chinese young adults aged 18 to 24 years were surveyed online to examine the relationships between ACEs, resilience, and mental health problems (depression, anxiety, maladjustment, and posttraumatic stress symptoms). Among them, 34 participants with ACEs were purposively selected and interviewed to explore cultural factors that influenced their resilience. Quantitative data were analyzed using multiple hierarchical regression analyses; qualitative data were analyzed using a qualitative descriptive approach. Higher cumulative ACE exposure was associated with higher severity of adjustment disorder and odds for screening positive for posttraumatic stress disorders, but not for symptoms of depression or anxiety. Resilience significantly contributed to explaining variances across all mental health outcomes over and beyond ACEs and in a protective fashion. Four themes emerged from qualitative interviews: (a) Privacy, emotional restraint, and "saving face"; (b) Conforming to preserve harmony; (c) A will to excel; and (d) Viewing adversity as a matter of luck. These findings suggest Chinese young adults' resilience was influenced by cultural norms of restraint, conformity, competition, and superstition. The present study provides a model for future studies using a mixed-methods design to deeply examine resilience among younger people exposed to early adversities within sociocultural, historical, or geographical contexts.

Psychometric properties of a modified cultural awareness scale for use in higher education within the health and social care fields.

BACKGROUND: Cultural awareness and cultural competence have become important skills in higher education as populations continue to grow in diversity around the world. However, currently, there are few instruments designed to assess student awareness of the aspects of culture, and the existing instruments need further development and testing for use with different target populations. Therefore, the aim of this study was to test the psychometric properties of a modified version of the Cultural Awareness Scale (CAS) for use in higher education within the health and social care fields. METHODS: A modified version of the CAS was developed, which was tested psychometrically using cross-sectional data. In total, 191 undergraduate students from different health and social care undergraduate programs in Sweden and Hong Kong responded to a call to test the modified instrument. RESULTS: The results showed that the modified CAS is a four-factor measure of cultural awareness and possesses satisfactory internal consistency. Results also support the use of the modified CAS as a generic tool to measure cultural awareness among students in higher education within the health and social care fields. CONCLUSION: The modified CAS showed satisfactory psychometric properties and can be recommended as a generic tool to measure cultural awareness among students in higher education within the health and social care fields. However, further psychometric testing on the effectiveness of the modified CAS as a tool to evaluate the efficacy of cultural awareness interventions is required.

Role of mitogen-activated protein kinase in Zn-BC-AM PDT-induced apoptosis in nasopharyngeal carcinoma cells.

Photodynamic therapy (PDT) with a recently developed photosensitizer Zn-BC-AM was found to effectively induce apoptosis in a well-differentiated nasopharyngeal carcinoma (NPC) HK-1 cell line. Sustained activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) as well as a transient increase in activation of extracellular signal-regulated kinase (ERK) were observed immediately after Zn-BC-AM PDT. A commonly used p38 MAPK/JNK pharmacological inhibitor PD169316 was found to reduce PDT-induced apoptosis of HK-1 cells. PD169316 also prevented the loss of Bcl-2 and Bcl-xL in PDT-treated HK-1 cells. However, inhibition of JNK with SP600125 had no effect on Zn-BC-AM PDT-induced apoptosis while inhibition of ERK with PD98059 or p38 MAPK with SB203580 significantly increased Zn-BC-AM PDT-induced apoptosis. Further study showed that knockdown of the p38beta isoform with siRNA also increased Zn-BC-AM PDT-induced apoptosis, indicating that the anti-apoptotic effect of PD169316 in PDT-treated HK-1 cells was probably independent of p38 MAPK or JNK activation. Taken together, the results suggest that inhibition of p38beta and ERK may enhance the therapeutic efficacy of Zn-BC-AM PDT on NPC cells. It should be noted that data only based on the use of PD169316 should be interpreted in caution.

Social stress alters expression of large conductance calcium-activated potassium channel subunits in mouse adrenal medulla and pituitary glands.

Large conductance calcium-activated potassium (BK) channels are very prominently expressed in adrenal chromaffin and many anterior pituitary cells, where they shape intrinsic excitability complexly. Stress- and sex-steroids regulate alternative splicing of Slo-alpha, the pore-forming subunit of BK channels, and chronic behavioural stress has been shown to alter Slo splicing in tree shrew adrenals. In the present study, we focus on mice, measuring the effects of chronic behavioural stress on total mRNA expression of the Slo-alpha gene, two key BK channel beta subunit genes (beta2 and beta4), and the 'STREX' splice variant of Slo-alpha. As a chronic stressor, males of the relatively aggressive SJL strain were housed with a different unfamiliar SJL male every 24 h for 19 days. This 'social-instability' paradigm stressed all individuals, as demonstrated by reduced weight gain and elevated corticosterone levels. Five quantitative reverse transcriptase-polymerase chain assays were performed in parallel, including beta-actin, each calibrated against a dilution series of its corresponding cDNA template. Stress-related changes in BK expression were larger in mice tested at 6 weeks than 9 weeks. In younger animals, Slo-alpha mRNA levels were elevated 44% and 116% in the adrenal medulla and pituitary, respectively, compared to individually-housed controls. beta2 and beta4 mRNAs were elevated 162% and 194% in the pituitary, but slightly reduced in the adrenals of stressed animals. In the pituitary, dominance scores of stressed animals correlated negatively with alpha and beta subunit expression, with more subordinate individuals exhibiting levels that were three- to four-fold higher than controls or dominant individuals. STREX variant representation was lower in the subordinate subset. Thus, the combination of subunits responding to stress differs markedly between adrenal and pituitary glands. These data suggest that early stress will differentially affect neuroendocrine cell excitability, and call for detailed analysis of functional consequences.

Disruption of the EGFR E884-R958 ion pair conserved in the human kinome differentially alters signaling and inhibitor sensitivity.

Targeted therapy against epidermal growth factor receptor (EGFR) represents a major therapeutic advance in lung cancer treatment. Somatic mutations of the EGFR gene, most commonly L858R (exon 21) and short in-frame exon 19 deletions, have been found to confer enhanced sensitivity toward the inhibitors gefitinib and erlotinib. We have recently identified an EGFR mutation E884K, in combination with L858R, in a patient with advanced lung cancer who progressed on erlotinib maintenance therapy, and subsequently had leptomeningeal metastases that responded to gefitinib. The somatic E884K substitution appears to be relatively infrequent and resulted in a mutant lysine residue that disrupts an ion pair with residue R958 in the EGFR kinase domain C-lobe, an interaction that is highly conserved within the human kinome as demonstrated by our sequence analysis and structure analysis. Our studies here, using COS-7 transfection model system, show that E884K works in concert with L858R in-cis, in a dominant manner, to change downstream signaling, differentially induce Mitogen-activated protein kinase (extracellular signaling-regulated kinase 1/2) signaling and associated cell proliferation and differentially alter sensitivity of EGFR phosphorylation inhibition by ERBB family inhibitors in an inhibitor-specific manner. Mutations of the conserved ion pair E884-R958 may result in conformational changes that alter kinase substrate recognition. The analogous E1271K-MET mutation conferred differential sensitivity toward preclinical MET inhibitors SU11274 (unchanged) and PHA665752 (more sensitive). Systematic bioinformatics analysis of the mutation catalog in the human kinome revealed the presence of cancer-associated mutations involving the conserved E884 homologous residue, and adjacent residues at the ion pair, in known proto-oncogenes (KIT, RET, MET and FAK) and tumor-suppressor gene (LKB1). Targeted therapy using small-molecule inhibitors should take into account potential cooperative effects of multiple kinase mutations, and their specific effects on downstream signaling and inhibitor sensitivity. Improved efficacy of targeted kinase inhibitors may be achieved by targeting the dominant activating mutations present.

Confidence intervals for the risk ratio under inverse sampling.

In this paper, we investigate various confidence intervals for the risk ratio under inverse sampling (also known as negative binomial sampling). Three existing confidence intervals (namely, the confidence intervals that are based on Fieller's theorem, the delta method and the F-statistic) are reviewed and three new confidence intervals (namely, the score, likelihood ratio and saddlepoint approximation (SA)-based confidence intervals) are developed. Comparative studies among these confidence intervals through Monte Carlo simulations are evaluated in terms of their coverage probabilities and expected interval widths under different settings. Our simulation results suggest that the SA-based confidence interval is generally more appealing. We illustrate these confidence interval construction methods with real data sets from a drug comparison study and a congenital heart disease study.

Immuno-prophylaxis of babies borne to hepatitis B carrier mothers.

OBJECTIVES: To examine the efficacy of current hepatitis B immuno-prophylaxis and estimate the prevalence of S-mutant infections among local newborn babies. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 137 newborn babies delivered between the period of November 2000 and 30 June 2001 inclusive, whose mothers were chronic hepatitis B surface antigen carriers. RESULTS: Of the 121 infants who were followed up for 12 months, three were found to be chronic hepatitis B virus carriers, giving a vertical transmission rate of 2.5%. One (0.8%) was suspected to be infected by the S-mutant. All the three hepatitis B virus carrier babies were born to mothers with hepatitis B e antigen, but none to the eight mothers suspected to have S-mutants. Of 119 (98.3%) infants who developed hepatitis B surface antibody upon follow-up at 12 months, 35 were found to have hepatitis B e antigen at birth. All were born to hepatitis B e antigen-positive mothers. Only three of the 35 babies were found to be hepatitis B virus carriers. Most babies lost the hepatitis B e antigen by 6 months of age; only the infected babies had the antigen persisting at 1 year of age. The non-infected infants' hepatitis B e antigen is likely transplacental. CONCLUSIONS: Our hepatitis B virus prophylaxis programme was effective at preventing perinatal infection and the non-infected infants' hepatitis B e antigen was likely transplacental.

Effect of prepartum dietary calcium on intake and serum and urinary mineral concentrations of cows.

Nine multiparous and 12 primiparous cows were fed diets containing an anionic salt supplement and moderate Ca (0.99%) or high Ca (1.50%) concentrations for 21 d prepartum to determine the effects of dietary Ca concentration on serum and urine electrolytes and on postpartum intake and milk yield. Blood samples were collected during 21 to 1 d prepartum, 0 to 2 d postpartum, and 3 to 21 d postpartum. Dietary cation-anion difference (DCAD) for prepartum diets was approximately -6 mEq/100 g of dry matter (Na + K - Cl - S). Immediately postpartum, cows were fed diets with positive DCAD with greater than 1.00% Ca concentration. Mean serum Ca concentrations 21 to 1 d prepartum, 0 to 2 d postpartum, and 3 to 21 d postpartum were 9.62, 8.41, and 9.38 mg/dL. There were no treatment effects on serum Ca concentration. Mean serum Ca concentration was higher for primiparous than multiparous cows (9.34 vs. 8.93 mg/dL) for the trial and at calving (8.77 vs. 8.13 mg/dL). Mean serum HCO(3)(-) and urinary pH, respectively, were 20.32 mEq/L and 5.67 prepartum, 25.82 mEq/L and 7.62 at calving, and 26.08 mEq/L and 8.25 postpartum. No differences due to treatment were observed for serum and urinary concentrations of HCO(3)(-), pH, Mg, Na, K, and Cl. Milk yield was similar for 0.99 and 1.50% Ca treatments (22.8 and 20.7 kg/d). Diets containing 0.99 or 1.5% Ca maintained serum Ca at adequate levels around parturition and resulted in similar dry matter intake and postpartum milk yield.

Dynamic gain-tilt compensation using electronic variable optical attenuators and a thin film filter spectral tilt monitor.

An all-optical dynamic gain tilt compensator (DGTC) is proposed and experimentally demonstrated. A single wide-band thin film filter and a pair of photodetector allow the DGTC to distinguish band add/drop position. Power fluctuations from EDFA gain tilt were reduced with fast electronic variable optical attenuators.

Effects of dietary cation-anion difference on intake, milk yield, and blood components of the early lactation cow.

Early lactation Holsteins cows (15 primiparous and 18 multiparous) were offered rations with dietary cation-anion difference, calculated as mEq (Na + K - Cl - S)/100 g of feed dry matter (DCAD:S), of 20, 35, or 50 mEq from d 0 (calving) to 42 d postpartum (August 20, 2000 to January 9, 2001) to determine the effects of increasing DCAD:S on dry matter intake (DMI), milk yield, and blood metabolites. For DCAD:S of 20, 35, and 50, DMI was 3.30, 3.38, 2.96 kg/100 kg of body weight (BW); milk yield was 25.5, 24.2, and 22.4 kg/d, respectively. No differences were observed for concentration or yield of milk fat or milk protein. Serum Ca, P, Mg, Na, K, Cl, cation-anion difference, insulin, and glucose did not differ with DCAD. Serum HCO3- was 26.07, 25.88, and 27.64 mEq/L for 20, 35, and 50 DCAD:S. Serum Ca, Mg, Na, and K concentrations were greater for primiparous cows (9.52 mg/dL, 2.35 mg/dL, 140.03 mEq/L, 4.66 mEq/L, respectively) than for multiparous cows (9.27 mg/dL, 2.12 mg/dL, 137.63 mEq/L, 4.46 mEq/ L, respectively). A DCAD:S between 23 and 33 mEq/100 g of dry matter (DM) appears to be adequate during cool weather for the milk yield that occurred in the present study based on DMI (kg/100 kg of BW), whereas DCAD:S of 50 mEq/100 g of DM may be excessive and could be too alkaline or unpalatable, resulting in decreased DMI (kg/100 kg of BW).

Gene expression profile of mechanically impacted bovine articular cartilage explants.

Traumatic injury to a joint can initiate cartilage degradation. Blunt trauma increases matrix damage and decreases proteoglycan synthesis in in vitro models. Few studies have investigated gene expression of articular cartilage (AC) following mechanical loading. Recent advances in microarray technology allow analysis of a number of genes, and may elucidate pathways of AC degradation. In the present study, we used a bovine cDNA microarray to determine how acute trauma of cartilage explants in the absence of underlying bone alters gene expression. Results indicate that at least 19 genes were differentially expressed at 3 h after trauma. Fourteen genes were up-regulated and five genes were down-regulated relative to control explants. The up-regulated genes included cytokine and chemokine receptors, enzymes, and molecules involved in signal transduction. Genes of adhesion molecules and apoptosis were down-regulated. The results of this study highlight the potential benefits of using a bovine cDNA microarray to study cartilage metabolism.

17-year follow-up of a randomized prospective controlled trial of adjuvant intravesical doxorubicin in the treatment of superficial bladder cancer.

PURPOSE: To evaluate the efficacy of adjuvant intravesical doxorubicin in superficial transitional cell carcinoma of the urinary bladder on long-term follow-up. MATERIALS AND METHODS: Between July 1986 and November 1991, all patients harboring superficial bladder cancers (Ta or T1) with one or more of these criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors) were randomized to receive either 50 mg doxorubicin or no adjuvant therapy. Patients with recurrences were allowed to receive doxorubicin or other intravesical agents. Recurrence, progression and survival were analyzed. RESULTS: There were 82 patients included (64 males and 18 females). The mean age was 64 years. Forty-six patients were randomized to the doxorubicin group and 36 to the control group. Final analysis was made at median follow-up of 45, 128 and 131.5 months for recurrence, progression and survival, respectively. Recurrence free, progression free and disease specific survival did not differ significantly between groups. The 10-year Kaplan-Meier estimates for recurrence free, progression free and disease specific survival were 67%, 84% and 92%, respectively for the doxorubicin group, and were 50%, 89% and 97%, respectively for the control group. Tumor size predicted recurrence (p=0.013) and grade predicted progression (p=0.004) with multivariate analysis. CONCLUSIONS: Adjuvant intravesical doxorubicin could not be shown to improve recurrence, progression and survival of superficial bladder cancer, compared with control on long-term follow-up. Tumor size and grade were shown to be prognostic factors for recurrence and progression, respectively.

17-year follow-up of a randomized prospective controlled trial of adjuvant intravesical doxorubicin in the treatment of superficial bladder cancer

PURPOSE: To evaluate the efficacy of adjuvant intravesical doxorubicin in superficial transitional cell carcinoma of the urinary bladder on long-term follow-up. MATERIALS AND METHODS: Between July 1986 and November 1991, all patients harboring superficial bladder cancers (Ta or T1) with one or more of these criteria (stage > a, grade > 1, size > 1 cm, multiple or recurrent tumors) were randomized to receive either 50 mg doxorubicin or no adjuvant therapy. Patients with recurrences were allowed to receive doxorubicin or other intravesical agents. Recurrence, progression and survival were analyzed. RESULTS: There were 82 patients included (64 males and 18 females). The mean age was 64 years. Forty-six patients were randomized to the doxorubicin group and 36 to the control group. Final analysis was made at median follow-up of 45, 128 and 131.5 months for recurrence, progression and survival, respectively. Recurrence free, progression free and disease specific survival did not differ significantly between groups. The 10-year Kaplan-Meier estimates for recurrence free, progression free and disease specific survival were 67 percent, 84 percent and 92 percent, respectively for the doxorubicin group, and were 50 percent, 89 percent and 97 percent, respectively for the control group. Tumor size predicted recurrence (p = 0.013) and grade predicted progression (p = 0.004) with multivariate analysis. CONCLUSIONS: Adjuvant intravesical doxorubicin could not be shown to improve recurrence, progression and survival of superficial bladder cancer, compared with control on long-term follow-up. Tumor size and grade were shown to be prognostic factors for recurrence and progression, respectively.

Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants.

OBJECTIVE: Glucosamine (GLN) and chondroitin sulfate (CS) are widely used to alleviate symptoms of osteoarthritis (OA). However, the mechanism(s) of action of these nutraceuticals remains unresolved. In the present study, we determined the effect of physiologically relevant concentrations of GLN and CS on gene expression and synthesis of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in cytokine-stimulated articular cartilage explants. METHODS: Using bovine articular cartilage explants in culture stimulated with IL-1, the effects of physiologically relevant concentrations of GLN and CS on gene expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGEs1) were assessed with quantitative real-time polymerase chain reaction (Q-RT-PCR). The production of NO and PGE(2) was also quantified. RESULTS: CS and the GLN and CS combination at concentrations attainable in the blood down-regulated IL-1 induced mRNA expression of iNOS at 24 and 48 h post-culture. Up-regulated iNOS expression at 24h by IL-1 was also suppressed by GLN. GLN and CS transiently repressed the cytokine-stimulated mPGEs1 transcript. Synthesis of NO was reduced with CS alone and the combination after 24h of culture. Repression of COX-2 transcripts by GLN and CS was accompanied by concomitant reduction in PGE(2). CONCLUSION: Our results indicate that physiologically relevant concentrations of GLN and CS can regulate gene expression and synthesis of NO and PGE(2), providing a plausible explanation for their purported anti-inflammatory properties.

Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy.

BACKGROUND: Cancer patients who are hepatitis B virus (HBV) carriers and undergoing chemotherapy (CT) may be complicated by HBV reactivation. Over 80% of hepatocellular carcinoma (HCC) patients are HBV carriers; however, the incidence of HBV reactivation during CT has not been well-reported. A prospective study was conducted to determine the incidence of HBV reactivation, the associated morbidity and mortality, and possible risk factors. PATIENTS AND METHODS: 102 HBsAg-positive patients with inoperable HCC underwent systemic CT. Patients received either combination cisplatin, interferon, doxorubicin and fluorouracil (PIAF) or single-agent doxorubicin. They were followed up during and for 8 weeks after CT. RESULTS: In 102 patients, 59 (58%) developed hepatitis amongst whom 37 (36%) were attributable to HBV reactivation. Twelve (30%) died of HBV reactivation. CT was interrupted in 32 patients (86%) with reactivation and 54 (83%) without reactivation (P>0.05). The median survivals were 6.00 and 5.62 months, respectively (P=0.694). Elevated baseline alanine aminotransferase (ALT) was found to be a risk factor. CONCLUSION: HBV reactivation is a common cause of liver damage during CT in HBsAg-positive HCC patients. The only identifiable associated risk factor was elevated pre-treatment ALT. Further studies into the role of antiviral and novel anticancer therapies are required to improve the prognosis of these patients.

Detection of mRNA expression of gonadotropin-releasing hormone and its receptor in normal and neoplastic rat prostates.

Hypothalamic gonadotropin-releasing hormone (GnRH) plays a central role in the regulation of the mammalian reproductive systems as a releasing hormone of pituitary gonadotropins. However, a number of studies have shown that GnRH or its receptor are also expressed in some reproductive organs including prostate gland, mammary gland, ovary and placenta, tumors and tumor cell lines derived from these organs, suggesting that this peptide hormone may have other extrapituitary functions in addition to its role as a gonadotropin-releasing hormone. Moreover, it has been demonstrated that GnRH analogs exert some direct inhibitory effects on the proliferation of human and rat prostate cancer cells, probably mediated by its own specific receptors expressed in these tumor cells. In the present study, we investigated the mRNA expression of GnRH and its receptor in normal Noble rat prostate gland, and in three rat models of prostate cancer including the sex hormone-induced Noble rat model, an androgen-independent Noble rat prostatic tumor (AIT) and Dunning rat prostatic adenocarcinomas by RT-PCR and Southern blot analyses. The results showed that GnRH mRNA was expressed in the normal, hormone-treated and neoplastic rat prostates, in addition to its positive control expression in the hypothalamus, whereas its receptor was only detected in the androgen-dependent Dunning R3327H tumor. The detection of both GnRH and its receptor in the androgen-dependent Dunning R3327H tumor tissue suggests that this peptide hormone may have some autocrine and paracrine regulatory functions in this tumor. However, the gene expression of GnRH receptor was not detected in two androgen-independent Dunning tumor sublines and the Noble rat prostatic tumor, AIT, suggesting that the expression of GnRH receptor is lost or down-regulated in the prostatic tumors during the progression to a hormone-independent phenotype.

Altered expression of extracellular matrix and proteinases in Noble rat prostate gland after long-term treatment with sex steroids.

BACKGROUND: Interactions between the epithelial cells and stromal tissues, which include the epithelial basement membrane, extracellular matrix, inducible factors, and various cell types, are believed to play a significant role in prostate gland carcinogenesis. Remodeling of extracellular matrix and degradation of basement membrane are the prerequisites for tumor cell invasion, and these changes are correlated with the expression of various proteinases. METHODS: The present study examined the alterations of epithelial basement membrane, extracellular matrix, and proteinase activities in the Noble rat prostate gland after long-term treatments with androgen and estrogen (T+DES or T+E(2) for 4-12 months) by histochemistry, immunohistochemistry, electron microscopy, and gelatin-gel zymography. RESULTS: After hormonal treatments, defects of epithelial basement membranes, such as focal disruption, diffuse staining and multilayering, were observed by histochemistry and immunohistochemistry in the dysplastic and neoplastic lesions induced in the lateral (LP) and ventral prostates (VP) but not in dorsal prostate (DP). An increase in the amount of extracellular matrix components, including hyaluronan (HA), chondroitin sulfate proteoglycan (CSPG) and tenascin, in the stroma of hormone-treated LP and VP was revealed by histochemistry and immunohistochemistry. Positive immunolabeling of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) was detected in the fibromuscular layer surrounding the adenoma and adenocarcinoma induced in LP and VP after treatments with steroids for over 9-12 months. Zymography also detected an increase in activities of proteinases of apparent MW 120, 90, 86 and 68 kDa in the hormone-treated LP and VP, and these proteinases were characterized as metalloproteinases. In addition, two serine proteinases of MW 100 and 30 kDa were identified as being overexpressed in the hormone-treated LP and VP. Compared to LP and VP, there was no significant change in the proteinase activities in the hormone-treated DP. CONCLUSIONS: The present study demonstrated that the epithelial basement membrane and stromal extracellular matrix were altered in dysplastic and neoplastic Noble rat prostates. Since HA and CSPG (or their complexes) are highly anionic molecules, their increased accumulation in the altered prostatic stroma would tend to hydrate this tissue. This would create an environment more favorable for tumor growth and invasion. These morphological changes were also correlated with the concurrent increase in gelatinolytic proteinase activities induced in these prostates. The results suggest that the remodeling of the stromal tissue might play a role in the early stage of prostate carcinogenesis as shown in the Noble rat model.

SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells.

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular Ca(2+)-binding matricellular glycoprotein that associates with cell populations undergoing migration, morphogenesis, and differentiation. Studies on endothelial cells have established that its principal functions in vitro are counteradhesion and antiproliferation. The mechanism(s) underlying these antitumor effects is unknown. In this study, we showed that SPARC expression in ovarian cancer cells is inversely correlated with the degree of malignancy. The immunohistochemical data presented here confirmed the importance of diminished SPARC expression in ovarian cancer development. Treating human ovarian surface epithelial cells and ovarian cancer cells with SPARC revealed that as SPARC inhibits the proliferation of both normal and cancer cells, it induces apoptosis only in cancer cells. This observation indicates that down-regulation of SPARC is essential for ovarian carcinogenesis as cancer cells become sensitized to the apoptotic activity of SPARC during malignant transformation. We also showed here the first direct evidence that putative SPARC receptors are present on ovarian epithelial cells. Their levels are higher in human ovarian surface epithelial cells than cancer cells. Binding of SPARC to its receptor is likely to trigger tissue-specific signaling pathways that mediate its tumor suppressing functions. Decrease in ligand-receptor interaction by the down-regulation of SPARC and/or its receptor is essential for ovarian carcinogenesis.