Development of an on-site diagnostic LAMP assay for rapid differentiation of the invasive pest Phthorimaea absoluta (Meyrick) using insect tissues.

BACKGROUND: The tomato leafminer, Phthorimaea absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a destructive invasive pest that originated in South America and has spread within China since 2017. A rapid method for on-site identification of P. absoluta is urgently needed for interception of this pest across China. RESULTS: We developed a loop-mediated isothermal amplification (LAMP) technique to differentiate P. absoluta from Liriomyza sativae, Chromatomyia horticola, and Phthorimaea operculella using extracted genomic DNA, which was then refined to create an on-site LAMP diagnostic method that can be performed under field conditions without the need for laboratory equipment. CONCLUSION: In the present research, we developed an on-site diagnostic method for rapid differentiation of P. absoluta from other insects with similar morphology or damage characteristics in China. © 2024 Society of Chemical Industry.

Are algorithmically controlled gig workers deeply burned out? An empirical study on employee work engagement.

BACKGROUND: With the emergence of the gig economy as a new economic form, the influence of algorithmic technology control on gig workers' perceptions and engagement has become a topic of academic concern. This study explores the emotional impact of perceived algorithmic control on gig workers and how it affects their work engagement. METHODS: This study takes gig workers as the research object to build a structural equation model. Based on the background of gig economy and the Job Demands-Resources model, this paper constructs a mechanism model of the influence of perceived algorithmic control on the work engagement of gig workers. The research data in this paper are collected by questionnaire, and the research hypothesis is tested by the SEM structural model. RESULTS: The gig workers in this study believed that perceived algorithmic control positively affects employee work engagement. In addition, burnout was positively correlated with employee work engagement. Burnout played a partial mediating role in the relationship between perceived algorithmic control and employee work engagement. And flow experience played a moderating role through the indirect effect of burnout on employees' work engagement. CONCLUSION: Perceived algorithmic control causes burnout among gig workers, but strong algorithmic technology support provides them with rich work resources that can help them meet their work needs. That is, the gig workers may still demonstrate a high level of work engagement even if they experience burnout symptoms.

[Clinical characteristics and cost-effectiveness of intramedullary nail and plate for the treatment of open tibial fractures].

OBJECTIVE: To analyze clinical characteristics and cost-effectiveness of different final surgical options for treating patients with open tibial fractures. METHODS: A retrospective analysis was conducted by enrolling 55 surgically treated patients with open tibial fractures from January 2018 to June 2019. All the patients were categorized in intramedullary nailing (IMN) group and locking compression plate(LCP) group according to the final fixation option. There were 35 cases in group IMN including 27 males and 8 females, aged from 25 to 69 years old with an average of (49.0±10.6) years old. Based on Gustilo-Anderson classification, there were 1 case of typeⅠ, 19 cases of typeⅡand 15 cases of type Ⅲ. There were 20 cases in group LCP including 15 males and 5 females, aged from 46 to 72 years old with an average age of (53.4±14.7) years old. Based on Gustilo-Anderson classification, there were 2 cases of typeⅠ, 11 cases of typeⅡand 7 cases of type Ⅲ. Preoperative waiting time, surgical debridement times, intraoperative bleeding loss, blood and albumin transfusion, operation time, bacterial cultures and complications, bone union time, Johner-Wruhs criteria at 1 year after operation and total cost within 1 year after surgery between two groups were compared. The variables recorded between two groups were statistically analyzed and compared respectively, then the factors affecting hospital costs were evaluated by univariate and multiple linear regression analysis respectively, finally the cost-effectiveness analysis was performed. RESULTS: Total 55 patients were enrolled with an average follow-up time of(16.4±7.1) months ranged from 14 to 27 months postoperatively. There were no significantly statistical differences of the demographic materials between the two groups. The intraoperative bleeding loss were(243.18±118.82) ml and (467.86±490.53) ml respectively in group IMN and LCP, the significantly statistical difference was discovered(P<0.05). The surgical duration were(247.50±57.94) min and(350.00±178.77) min respectively in group IMN and LCP, the significantly statistical difference was discovered(P<0.05). There were no significantly statistical differences of the average days before operation, surgical debridement times, received blood and albumin transfusion, wound cultures, complications and bone union time between the two groups(P>0.05). The univariate analysis of the factors affecting the hospital costs indicated that patients with smoke or alcohol (P=0.042), high energy damage (P=0.012), patients with comorbidity diseases(P=0.045), surgical debridement over 2 times (P=0.001), intraoperative bleeding loss over 400 ml (P<0.001), blood and albumin transfusion (P=0.027), wound cultures (P=0.000) and complications (P=0.035) were the factors. The multiple linear regression analysis demonstrated the smoke or alcohol using[ß=-0.256, t=-2.628, 95%CI(-29 667.09, -4 997.47), P=0.014] was the only factor affecting the total cost. The excellent and good rate were 80% and 85% respectively based on the Johner-Wruhs criteria. The average total cost within 1 year after surgery was (136 435.90±39 093.98) CNY in group IMN and (140 034.62±56 821.12) CNY in group LCP. The total surgical duration and total intraoperative bleeding loss were significant lower in group IMN than in group LCP. The average total costs of was significantly higher. The average cost for every 1% of excellent and good rate was 1 705.45 CNY in group IMN and 1 647.46 CNY in group LCP. Each 1% increasing of excellent and good rate cost 719.74 CNY more in group LCP compared with group IMN. CONCLUSION: Both IMN and LCP could provide a satisfactory outcome for open tibial fractures. Meanwhile considering the total cost, patients with smoke or alcohol history, traffic accident, comorbidity diseases, surgical debridement over 2 times, intraoperative bleeding loss over 400 ml, and complications should not be ignored.

SARM1 participates in axonal degeneration and mitochondrial dysfunction in prion disease.

Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss, axonal degeneration, and mitochondrial dysfunction. Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1. We found that depletion or dysfunctional mutation of SARM1 protected against NAD+ loss, axonal degeneration, and mitochondrial functional disorder induced by the neurotoxic peptide PrP106-126. NAD+ supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect. NAD+ supplementation in PrP106-126-incubated N2a cells, SARM1 depletion, and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival. Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP106-126 are partially dependent on SARM1 NADase activity. This pathway has potential as a therapeutic target in the early stages of prion disease.

Stabilization of MORC2 by estrogen and antiestrogens through GPER1- PRKACA-CMA pathway contributes to estrogen-induced proliferation and endocrine resistance of breast cancer cells.

Aberrant activation of estrogen signaling through three ESR (estrogen receptor) subtypes, termed ESR1/ERα, ESR2/ERß, and GPER1 (G protein-coupled estrogen receptor 1), is implicated in breast cancer pathogenesis and progression. Antiestrogens tamoxifen (TAM) and fulvestrant (FUL) are effective for treatment of ESR1-positive breast tumors, but development of resistance represents a major clinical challenge. However, the molecular mechanisms behind these events remain largely unknown. Here, we report that 17ß-estradiol (E2), TAM, and FUL stabilize MORC2 (MORC family CW-type zinc finger 2), an emerging oncoprotein in human cancer, in a GPER1-dependent manner. Mechanistically, GPER1 activates PRKACA (protein kinase cAMP-activated catalytic subunit alpha), which in turn phosphorylates MORC2 at threonine 582 (T582). Phosphorylated MORC2 decreases its interaction with HSPA8 (heat shock protein family A [Hsp70] member 8) and LAMP2A (lysosomal associated membrane protein 2A), two core components of the chaperone-mediated autophagy (CMA) machinery, thus protecting MORC2 from lysosomal degradation by CMA. Functionally, knockdown of MORC2 attenuates E2-induced cell proliferation and enhances cellular sensitivity to TAM and FUL. Moreover, introduction of wild-type MORC2, but not its phosphorylation-lacking mutant (T582A), in MORC2-depleted cells restores resistance to antiestrogens. Clinically, the phosphorylation levels of MORC2 at T582 are elevated in breast tumors from patients undergoing recurrence after TAM treatment. Together, these findings delineate a phosphorylation-dependent mechanism for MORC2 stabilization in response to estrogen and antiestrogens via blocking CMA-mediated lysosomal degradation and uncover a dual role for MORC2 in both estrogen-induced proliferation and resistance to antiestrogen therapies of breast cancer cells. ABBREVIATIONS: 4-OHT: 4-hydroxytamoxifen; Baf A1: bafilomycin A1; CMA: chaperone-mediated autophagy; E2: 17ß-estradiol; ESR: estrogen receptor; FUL: fulvestrant; GPER1: G protein-coupled estrogen receptor 1; HSPA8: heat shock protein family A (Hsp70) member 8; LAMP2A: lysosomal associated membrane protein 2A; MORC2: MORC family CW-type zinc finger 2; PRKACA: protein kinase cAMP-activated catalytic subunit alpha; TAM: tamoxifen; VCL: vinculin.

Discrete functional and mechanistic roles of chromodomain Y-like 2 (CDYL2) transcript variants in breast cancer growth and metastasis.

Rationale: Chromodomain Y-like 2 (CDYL2) is a member of the CDY gene family involved in spermatogenesis, but its role in human cancer has not been reported. Analyses of publicly available databases demonstrate that CDYL2 is abundantly expressed in breast tumors. However, whether CDYL2 is involved in breast cancer progression remains unknown. Methods: Quantitative real-time PCR and immunoblotting assays were used to determine the expression levels of CDYL2 transcript variants in breast cancer cell lines and primary breast tumors. The effect of CDYL2 transcript variants on the malignant phenotypes of breast cancer cells was examined through in vitro and in vivo assays. Immunofluorescent staining, RNA-seq, ATAC-seq, and ChIP-qPCR were used to investigate the underlying mechanisms behind the aforementioned observations. Results: Here we show that CDYL2 generated four transcript variants, named CDYL2a-CDYL2d. CDYL2a and CDYL2b were the predominant variants expressed in breast cancer cell lines and breast tumors and exerted strikingly discrete functions in breast cancer growth and metastasis. CDYL2a was upregulated in the majority of the breast cancer cell lines and tumors, and promoted breast cancer cell proliferation, colony formation in vitro, and tumorigenesis in xenografts. In contrast, CDYL2b was mainly expressed in luminal- and HER2-positive types of breast cancer cell lines and tumors, and suppressed the migratory, invasive, and metastatic potential of breast cancer cells in vitro and in vivo. Mechanistically, CDYL2a partially localized to SC35-positive nuclear speckles and promoted alternative splicing of a subset of target genes, including FIP1L1, NKTR, and ADD3 by exon skipping. Elimination of full-length FIP1L1, NKTR, and ADD3 rescued the impaired cell proliferation through CDYL2a depletion. In contrast, CDYL2b localized to heterochromatin and transcriptionally repressed several metastasis-promoting genes, including HPSE, HLA-F, and SELL. Restoration of HPSE, HLA-F, or SELL expression in CDYL2b-overexpressing cells attenuated the ability of CDYL2b to suppress breast cancer cell migration and invasion. Conclusions: Collectively, these findings establish an isoform-specific function of CDYL2 in breast cancer development and progression and highlight that pharmacological inhibition of the CDYL2a, but not the CDYL2b, isoform may be an effective strategy for breast cancer therapy.

Cancer-Associated MORC2-Mutant M276I Regulates an hnRNPM-Mediated CD44 Splicing Switch to Promote Invasion and Metastasis in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with a high propensity for distant metastasis and limited treatment options, yet its molecular underpinnings remain largely unknown. Microrchidia family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein whose mutations have been causally implicated in several neurologic disorders. Here, we report that a cancer-associated substitution of methionine to isoleucine at residue 276 (M276I) of MORC2 confers gain-of-function properties in the metastatic progression of TNBC. Expression of mutant MORC2 in TNBC cells increased cell migration, invasion, and lung metastasis without affecting cell proliferation and primary tumor growth compared with its wild-type counterpart. The M276I mutation enhanced binding of MORC2 to heterogeneous nuclear ribonucleoprotein M (hnRNPM), a component of the spliceosome machinery. This interaction promoted an hnRNPM-mediated splicing switch of CD44 from the epithelial isoform (CD44v) to the mesenchymal isoform (CD44s), ultimately driving epithelial-mesenchymal transition (EMT). Knockdown of hnRNPM reduced the binding of mutant MORC2 to CD44 pre-mRNA and reversed the mutant MORC2-induced CD44 splicing switch and EMT, consequently impairing the migratory, invasive, and lung metastatic potential of mutant MORC2-expressing cells. Collectively, these findings provide the first functional evidence for the M276I mutation in promoting TNBC progression. They also establish the first mechanistic connection between MORC2 and RNA splicing and highlight the importance of deciphering unique patient-derived mutations for optimizing clinical outcomes of this highly heterogeneous disease.Significance: A gain-of-function effect of a single mutation on MORC2 promotes metastasis of triple-negative breast cancer by regulating CD44 splicing. Cancer Res; 78(20); 5780-92. ©2018 AACR.

Aneuploidy of chromosome 8 and mutation of circulating tumor cells predict pathologic complete response in the treatment of locally advanced rectal cancer.

Identifying patients who may or may not achieve pathologic complete response (pathCR) allows for treatment with alternative approaches in the preoperative setting. The aim of the current study was to investigate whether aneuploidy of chromosome 8 and mutations of circulating tumor cells (CTCs) could predict the response of patients with rectal cancer to preoperative chemoradiotherapy. A total of 33 patients with locally advanced rectal cancer (cT3-T4 and/or cN+) treated with neoadjuvant chemoradiotherapy between September 2014 and March 2015 were recruited. Blood samples were collected from 33 patients with pre-chemoradiotherapy rectal cancer. It was demonstrated that ≥5 copies of chromosome 8 was associated with pathCR (univariate logistic regression, P=0.042). Of the 6 patients whose CTCs had <5 copies of chromosome 8, 3 achieved pathCR (3/6, 50%), and of the 27 patients whose CTCs had ≥5 copies of chromosome 8 obtained 3 pathCR (3/27, 11.1%; Chi-square test, P=0.0255). Of the 33 patients with mutations assessed, 8 significant nonsynonymous mutations in CTCs were identified as associated with pathCR (Chi-square test, P-values range, 0.0004-0.0298; mutations in ARID1A, HDAC1, APC, ERBB3, TP53, AMER1 and AR). These results suggest that ≥5 copies of chromosome 8 and 8 nonsynonymous mutations in ARID1A, HDAC1, APC, ERBB3, TP53, AMER1 AR in CTCs were associated with pathCR. This conclusion should be validated further in larger prospective studies and the long-term follow-up survival data of this study will also be reported in the future.

Adjuvant chemotherapy for patients with ypT0-2N0-category after neoadjuvant chemoradiotherapy for rectal cancer.

Locally advanced rectal cancer patients with ypT0-2N0 have good prognosis and may not require as many cycles of adjuvant chemotherapy as patients with a poor (ypT3-4 or N+) response. The aim of the present study was to evaluate the three-year disease-free and overall survival between patients with ypT0-2N0 rectal adenocarcinoma who received 0-3 cycles of 5-fluorouracil-based adjuvant chemotherapy and those who received >3 cycles. A total of 106 patients with locally advanced rectal cancer, classified as ypT0-2N0 after surgery at the Fudan University Shanghai Cancer Center (Shanghai, China) between 2006 and 2012, were identified. The patients were divided into two groups depending on the number of cycles of adjuvant chemotherapy: Group 1 received 0-3 cycles (n=32) and group 2 received ≥4 cycles of adjuvant chemotherapy (n=74). The three-year disease-free survival and overall survival rates were 86.8 and 93.1% for group 1 (P=0.633), and 88.5 and 96.8% for group 2 (P=0.381). No statistically significant difference was observed between the two groups, suggesting that patients with ypT0-2N0 status may not require more than three cycles of post-operative chemotherapy. Further evaluation in prospective studies is urgently recommended.

PRAS40 alleviates neurotoxic prion peptide-induced apoptosis via mTOR-AKT signaling.

AIMS: The proline-rich Akt substrate of 40-kDa (PRAS40) protein is a direct inhibitor of mTORC1 and an interactive linker between the Akt and mTOR pathways. The mammalian target of rapamycin (mTOR) is considered to be a central regulator of cell growth and metabolism. Several investigations have demonstrated that abnormal mTOR activity may contribute to the pathogenesis of several neurodegenerative disorders and lead to cognitive deficits. METHODS: Here, we used the PrP peptide 106-126 (PrP106-126 ) in a cell model of prion diseases (also known as transmissible spongiform encephalopathies, TSEs) to investigate the mechanisms of mTOR-mediated cell death in prion diseases. RESULTS: We have shown that, upon stress caused by PrP106-126 , the mTOR pathway activates and contributes to cellular apoptosis. Moreover, we demonstrated that PRAS40 down-regulates mTOR hyperactivity under stress conditions and alleviates neurotoxic prion peptide-induced apoptosis. The effect of PRAS40 on apoptosis is likely due to an mTOR/Akt signaling. CONCLUSION: PRAS40 inhibits mTORC1 hyperactivation and plays a key role in protecting cells against neurotoxic prion peptide-induced apoptosis. Thus, PRAS40 is a potential therapeutic target for prion disease.

Sex, Race, and Age Disparities in the Improvement of Survival for Gastrointestinal Cancer over Time.

There have been notable improvements in survival over the past 2 decades for gastrointestinal (GI) cancer. However, the degree of improvement by age, race, and sex remains unclear. We analyzed data from 9 population-based cancer registries included in the SEER program of the National Cancer Institute (SEER 9) in 1990 to 2009 (n = 288,337). The degree of survival improvement over time by age, race, and sex was longitudinally measured. From 1990 to 2009, improvements in survival were greater for younger age groups. For patients aged 20 to 49 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.74 (95% CI, 0.66-0.83), 0.49 (95% CI, 0.37-0.64), 0.69 (95% CI, 0.65-0.76), 0.62 (95% CI, 0.54-0.69), and 0.56 (95% CI, 0.42-0.76), for cancer of the stomach, small intestine, colon, rectum and anus, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. Compared with African Americans, whites experienced greater improvement in small intestinal and anal cancer survival. Female anal cancer and regional anal cancer patients experienced no improvement. Our data suggest that different improvement in survival in age, sex and race exists.

Bridging external fixation versus non-bridging external fixation for unstable distal radius fractures: A systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was conducted to compare the relative effectiveness of bridging external fixation and non-bridging external fixation for distal radius fractures treatment. METHOD: Relevant literature were comprehensively searched using the PubMed, Springer Link, Karger Medical and Scientific Publishers, Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases without any language restrictions. STATA Version 12.0 software and Comprehensive Meta-analysis 2.0 were applied. RESULTS: A total of 905 patients with distal radius fracture from six eligible cohort studies were selected for statistical analysis. Our meta-analysis results indicate that the non-bridging cases had a higher risk of pin track infection, rupture of the extensor pollicis longus and nerve injury than the bridging cases. Subgroup analysis stratified by country indicated non-bridging patients showed evidence of an increased risk of pin track infection and higher risk of rupture of the extensor pollicis longus compared with the patients treated with bridging external fixation in the UK population. The follow-up results showed flexion degree of patients treated with non-bridging external fixation was slightly better than that of patients treated with bridging external fixation (P < 0.05). CONCLUSION: There is evidence in our systematic review and meta-analysis to support that bridging external fixation can reduce the incidence of pin tract infections and nerve injury compared to non-bridging external fixation, but have no significant difference in other complications and the recovery of wrist joint function. Bridging external fixation could therefore be a better choice in patients with distal radius fractures.

Overexpression of BAT3 alleviates prion protein fragment PrP106-126-induced neuronal apoptosis.

BACKGROUNDS AND AIMS: Prion diseases are a group of infectious neurodegenerative diseases characterized by neuronal death and degeneration. Human leukocyte antigen-B-associated transcript 3 (BAT3) is an important apoptosis regulator. We therefore investigated the interactions between BAT3 and prion protein and the potential role of BAT3 in PrP106-126-induced apoptosis. METHODS: BAT3 and prion protein were overexpressed in Hela, Neuro2A, or primary neuronal cells by transfection with BAT3-HA or PRNP-EGFP expression plasmids and their relationship studied by immunofluorescence and Western blotting. The effect of BAT3 on PrP106-126-induced cytotoxicity and apoptosis was detected by the CCK-8 assay and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. The expression of cytochrome c and Bcl-2 was examined by Western blotting. RESULTS: BAT3 interacted with prion protein and enhanced PrP expression. After PrP106-126 peptide treated, BAT3 was transported from the nucleus to cytoplasm, increased cell viability, and protected neurons from PrP106-126-induced apoptosis through stabilizing the level of Bcl-2 protein and inhibiting the release of cytochrome c to cytoplasm. CONCLUSIONS: Our present data showed a novel molecular mechanism of PrP106-126-induced apoptotic process regulation through the overexpression of BAT3, which may be important for the basic regulatory mechanism of neuron survival in prion diseases and associated neurodegenerative diseases in vivo.

[Cognitive-behavior of HIV-positive women of fertility age regarding AIDS in three counties of Henan Province].

OBJECTIVE: To investigate the demographic characteristics of HIV-positive women of fertility age in Henan province and their knowledge and behavior in relation to AIDS. METHODS: A questionnaire survey was administered to 686 HIV-positive women of fertility age through face to face interview. The demographic characteristics of the respondents and their association with AIDS-related knowledge and behavior were analysed. RESULTS: Over 90% of respondents had good knowledge about AIDS. Statistically significant differences existed in the knowledge of AIDS and the use of condom among those with different age, education and income (P < 0.05). Age (OR < 1) and annual income (OR > 1) were identified as risk factors of failing to use condoms in regression analysis. CONCLUSION: Interventions need to be strengthened for HIV-positive women of fertility age, in particular for those who are young and have high incomes.

Polymorphism of prion protein gene in sheep of Inner Mongolian, China.

Susceptibility to natural scrapie in sheep is associated with polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene. To assess the risk of scrapie in sheep raised in China, DNA from 30 sheep of two breeds was isolated, amplified and sequenced for the PrP gene. The ovine PrP gene was found to be highly homogenous. The genotype associated with high susceptibility to scrapie (VRQ) was absent, whereas that associated with the resistance (ARR) was present in 6.7% of sheep examined. ARK was also rare (6.7%). ARQ that is associated with an intermediate susceptibility was the genotype observed in the most of sheep examined (86.6%). These data suggest that Chinese sheep of Mongolian sheep breed are susceptible to scrapie.

Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy.

BACKGROUND: miR-21 has been recognized as an "onco-microRNA" with the activity of negatively modulating the expression of tumor-suppressor genes. However, its role in prostate cancer (CaP) has not been well-documented. We designed this study to assess the potential function of serum miR-21 in the progression of CaP. METHODS: Serum samples of 56 patients, including 20 patients with localized CaP, 20 with androgen-dependent prostate cancer (ADPC), 10 with hormone-refractory prostate cancer (HRPC), and 6 with benign prostatic hyperplasia (BPH), were collected for the measurement of miR-21. The 10 HRPC patients were administered docetaxel-based chemotherapy. Quantification of miR-21 was assayed by specific TaqMan qRT-PCR. RESULTS: Serum miR-21 level was found to correlate to serum PSA level in patients with ADPC and HRPC, P = 0.012 and 0.049, respectively. There was no significant difference in serum miR-21 level between BPH, localized CaP and ADPC with PSA level <4 ng/ml. Higher levels of miR-21 were detected in patients with HRPC and ADPC with PSA level >4 ng/ml. Six of the 10 HRPC patients reached partial remission with a decreased PSA level of >50% after chemotherapy. Serum miR-21 levels were higher in patients who were resistant to docetaxel-based chemotherapy when compared to those sensitive to chemotherapy, P = 0.032. CONCLUSIONS: Serum miR-21 levels are elevated in HRPC patients, especially in those resistant to docetaxel-based chemotherapy. It may be applicable as a marker to indicate the transformation to hormone refractory disease, and a potential predictor for the efficacy of docetaxel-based chemotherapy.

Hsp70 binds to PrPC in the process of PrPC release via exosomes from THP-1 monocytes.

PrPC (cellular prion protein) is a GPI (glycophosphatidylinositol)-anchored protein present on the surface of a number of peripheral blood cells. PrPC must be present for the generation and propagation of pathogenic conformer [PrPSc (scrapie prion protein)], which is a conformational conversion form of PrPC and has a central role in transmissible spongiform encephalopathies. It is important to determine the transportation mechanism of normal PrPC between cells. Exosomes are membrane vesicles released into the extracellular space upon fusion of multivesicular endosomes with the plasma membrane. We have identified that THP-1 monocytes can secrete exosomes to culture medium, and the secreted exosomes can bear PrPC. We also found that Hsp70 interacts with PrPC not only in intracellular environment, but in the secreted exosomes. However, the specific markers of exosomes, Tsg101 and flotillin-1, were found with no interaction with PrPC. Our results demonstrated that PrPC can be released from THP-1 monocytes via secreted exosomes, and in this process, Hsp70 binds to PrPC, which suggests that Hsp70 may play a potential functional role in the release of PrPC.

[The survival analysis of metastatic prostate cancer].

OBJECTIVES: To analyze the clinical and pathological informations of metastatic prostate cancer patients to find the predictive factors of the survival. METHODS: To filter 364 cases of metastatic prostate cancer in the 940 cases of prostate cancer that were treated in Cancer Hospital Fudan University in Shanghai from March 1998 to June 2009, the cases had hormonal therapy and full clinical and pathological records. All the 364 cases were followed up and the clinical and pathological informations were analyzed, to find the predictive factors that related to the prognosis. Statistic software SPSS 15.0 was used for analysis. Cumulative survival was analyzed by the method of Kaplan-Meier. Cox regression was used for univariate and multivariate analysis. Log-rank method was used for the significance test. RESULTS: The last follow-up date was 30th June 2009 and the median follow-up time was 24 months. At the final follow-up, 240 cases were alive, 109 cases were dead and 15 cases were lost to follow up. The median survival time of metastatic prostate cancer was 64 months, and the one-year, two-year, three-year, four-year, five-year survival rate was 92%, 78%, 66%, 60%, 54%. The univariate analysis indicated that Gleason score (P = 0.033), clinical stage (P < 0.001), the effectiveness of hormonal therapy (P < 0.001), the prostate specific antigen (PSA) nadir during hormonal therapy (P < 0.001) and the time from the start of hormonal therapy to the PSA nadir (P = 0.002) were predictive factors for the survival time of metastatic prostate cancer. The multivariate analysis indicated that the PSA nadir during hormonal therapy (P < 0.001) and the time from the start of hormonal therapy to the PSA nadir (P < 0.001) were independent factors that predict the survival time of metastatic prostate cancer. CONCLUSION: The PSA nadir during hormonal therapy and the time from the start of hormonal therapy to the PSA nadir are independent factors that predict the survival time of metastatic prostate cancer.

Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: a preliminary report.

INTRODUCTION: We describe our experience with sorafenib and sunitinib in the treatment of chemotherapy-refractory advanced penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: Between May 2008 and June 2009, 6 advanced penile cancer patients were treated with sorafenib or sunitinib in our center. All of them had previously received at least two chemotherapy regimens. Tumor responses were evaluated by radiologic assessment and serum SCC antigen change. Immunohistochemical staining of CD34 and Ki-67 was performed in 3 paired tumor tissues before and after treatment. RESULTS: In the 6 patients, 1 partial response and 4 stable diseases were observed. Three patients showed pain response and had an improvement in quality of life. After molecular-targeted therapies, reduction in microvessel density and Ki-67 labeling index was observed in paired specimens. Serum SCC antigen levels were decreased in 5 patients after 1 week of medication. The patient who achieved partial response had an SCC antigen reduction of nearly 95% after treatment with sunitinib. Serious adverse events were fatal infection and rupture of the femoral vessel, which were unlikely related to the medication. CONCLUSIONS: The feasibility and activity of sorafenib and sunitinib in our series suggest that this approach may be a promising alternative in chemotherapy-refractory advanced penile SCC.

Variable levels of 37-kDa/67-kDa laminin receptor (RPSA) mRNA in ovine tissues: potential contribution to the regulatory processes of PrPSc propagation?

The 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR, also known as ribosomal protein SA, RPSA) has been reported to be involved in cancer development and prion internalization. Previous studies have shown that the LRP/LR is expressed in a wide variety of tissues. In particular, expression of LRP/LR mRNA may be closely related to the degree of PrP(Sc) propagation. This study presents a detailed investigation of the LRP/LR mRNA expression levels in eleven normal ovine tissues. Using real-time quantitative PCR, the highest LRP/LR expression was found in neocortex (p < 0.05). Slightly lower levels were found in the heart and obex. Intermediate levels were seen in hippocampus, cerebellum, spleen, thalamus, mesenteric lymph node, and the lowest levels were present in liver, kidney, and lung. In general, the LRP/LR mRNA levels were much higher in neuronal tissues than in peripheral tissues. The observation that differences in LRP/LR mRNA expression levels are consistent with the corresponding variation in PrP(Sc) accumulation suggests that the 37-kDa/67-kDa laminin receptor may be involved in the regulation of PrP(Sc) propagation.