Biomedical subjects

C Ren

Publications and source records attributed to C Ren.

At least 19 recordsLinked to original sources

PubMed2026

[Laryngeal squamous cell carcinoma-derived exosomes promote neuronal axonal growth by remodeling the neural microenvironment].

Objective: Perineural invasion (PNI) is a critical determinant of poor prognosis in laryngeal squamous cell carcinoma (LSCC), but its underlying mechanisms remain unclear. This study aimed to investigate whether LSCC-derived exosomes induce axonal growth by delivering neuroactive molecules, thereby contributing to tumor perineural invasion. Methods: Clinical data from the laryngeal cancer cohort of The Cancer Genome Atlas Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset were analyzed. Propensity score matching (PSM) and Cox regression were used to evaluate the prognostic value of nerve density, and these findings were validated using 35 pairs of laryngeal cancer and adjacent normal tissue specimens collected at Yantai Yuhuangding Hospital between 2022 and 2026 to assess neural morphological changes. Exosomes were isolated from the human LSCC cell line AMC-HN-8, characterized by quality-control assays, and co-cultured with PC12 cells. A rescue experiment using GW4869, a specific inhibitor of neutral sphingomyelinase, was performed to confirm the exosome-dependent effect. Neurite outgrowth was evaluated by immunofluorescence, and the expression of axonal growth-related genes was measured by RT-qPCR. Targeted metabolomics was employed for the absolute quantification of neuroactive metabolites within the vesicles and for pathway enrichment analysis. Results: After PSM adjustment, high nerve density was identified as an independent poor prognostic factor in LSCC patients (HR=2.10, P=0.035), with particularly pronounced prognostic value in the early-stage node-negative (N0) subgroup (HR=4.07, P=0.001). Pathological sections showed high expression of the neural markers βIII-tubulin and PGP9.5 in LSCC tissues (βIII-tubulin: t=2.234, P<0.05; PGP9.5: t=2.575, P<0.05). Exosomes were successfully isolated from AMC-HN-8 cells and passed quality control. In vitro assays showed that LSCC-derived exosomes significantly promoted neurite extension and branching in PC12 cells (t=4.147, P<0.000 1) and upregulated core axonal growth genes, including GAP-43, NEFL, and NEFM (GAP-43: t=3.698, P<0.05; NEFL: t=5.113, P<0.01; NEFM: t=5.263, P<0.01); this effect was completely reversed by the exosome-release inhibitor GW4869 (t=3.535, P<0.001). Targeted metabolomics revealed a specific enrichment of 12 neurotransmitters and metabolites within LSCC exosomes, centered on glutamine (83.411 μmol/L, FC=1.88) and glutamate (18.461 μmol/L, FC=1.21), which were significantly enriched in signaling pathways such as "central carbon metabolism in cancer" and "glutamatergic synapse". Conclusion: Nerve density is a potential adverse prognostic factor in patients with LSCC. LSCC-derived exosomes can directly induce axonal growth in neuron-like cells, suggesting that tumor cells actively remodel the neural microenvironment and drive axonal growth through exosome-mediated long-range signaling.

Exosomes↗

PubMed2006

Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer.

We investigated the potential benefits of combining adenoviral vector mediated in situ interleukin-12 (AdmIL-12) gene therapy with radiation therapy (XRT) to enhance therapeutic efficacy. In a metastatic mouse prostate cancer cell line, 178-2 BMA, AdmIL-12+XRT demonstrated enhanced therapeutic activities in vitro as determined by clonogenic survival, apoptosis, and mIL-12 levels. At the molecular level, increased expression of tumor necrosis factor-alpha mRNA was specific for the combined therapy. In a subcutaneous 178-2 BMA in vivo model, the combination of AdmIL-12+XRT produced statistically significant tumor growth suppression compared to control vector Adbetagal, Adbetagal XRT, or AdmIL-12 as monotherapy. In addition, significant prolongation of survival was demonstrated for the combination of AdmIL-12+XRT. The combination of AdmIL-12+XRT significantly suppressed both spontaneous and pre-established lung metastases, and led to a prolonged elevation of serum IL-12 and significantly increased natural killer (NK) activities. Importantly, in vivo depletion of NK cells resulted in significant attenuation of the antimetastatic activities of AdmIL-12 alone or AdmIL-12+XRT. These combined effects suggest that AdIL-12 gene therapy together with radiotherapy may achieve maximal tumor control (both local and systemic) in selected prostate cancer patients via radio-gene therapy induced local cytotoxicity and local and systemic antitumor immunity.

Adenoviridae↗

PubMed2006

Intraperitoneal gene therapy by rAAV provides long-term survival against epithelial ovarian cancer independently of survivin pathway.

Epithelial ovarian carcinoma is the leading cause of death from gynecological malignancies. Owing to the lack of an effective screening method, insidious onset, and non-specific symptoms, a majority of women present with advanced stage disease. Despite improvements from cytoreductive surgery and chemotherapy, recurrent disease remains a formidable challenge. In the present study, we demonstrate for the first time that stable intra-abdominal genetic transfer of endostatin and angiostatin (E+A) by recombinant adeno-associated virus (rAAV) provides sustained antitumor effects on the growth and dissemination of epithelial ovarian cancer in a mouse model. Further, when combined with paclitaxel (taxol), the effect of this therapy was dramatically increased and resulted in long-term tumor-free survival overcoming prior limitations of chemotherapy and gene therapy. The combined effects of angiosuppressive therapy and chemotherapy were found to be independently of survivin pathway. Evidence for the superior effects of the combination therapy was indicated by significantly lower ascites volume with less hemorrhage and tumor conglomerates, lower ascites vascular endothelial growth factor, higher tumor cell apoptosis and decreased blood vasculature, and long-term disease-free survival. Histopathology of visceral organs and liver enzyme assays indicated no toxicity or pathology.

Angiogenesis Inhibitors↗

PubMed2006

Space-charge effects in the current-filamentation or Weibel instability.

We consider how an unmagnetized plasma responds to an incoming flux of energetic electrons. We assume a return current is present and allow for the incoming electrons to have a different transverse temperature than the return current. To analyze this configuration we present a nonrelativistic theory of the current-filamentation or Weibel instability for rigorously current-neutral and nonseparable distribution functions, f(0)(p(x), p(y), p(z)) is not equal to f(x)(p(x))f(y)(p(y))f(z)(p(z)). We find that such distribution functions lead to lower growth rates because of space-charge forces that arise when the forward-going electrons pinch to a lesser degree than the colder, backward-flowing electrons. We verify the growth rate, range of unstable wave numbers, and the formation of the density filaments using particle-in-cell simulations.

Journal Article↗

PubMed2006

Enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands.

The potential of adeno-associated virus (AAV)-based vectors in human gene therapy is being explored for several diseases. Although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) AAV, the wider application of rAAV vectors encapsidated in serotype 2 capsid is hampered by poor transduction efficiency in many target tissues. These include ex vivo-generated dendritic cells (DC), which have demonstrated promising immunotherapeutic activity. We report here that efficient transduction of mouse bone marrow-derived DC can be achieved with self-complementary (sc) rAAV encapsidated in serotype 6 capsid. Sequential exposure of DC precursor cultures to IL-4 and GM-CSF with sc rAAV6 encoding the human tumor antigen, carcinoembryonic antigen (CEA), for 7 days followed by activation with CpG oligodeoxynucleotides (ODN) and anti-mouse CD40 antibody resulted in highly efficient transduction of DC. DC surface markers as determined by flow cytometry analysis of sc rAAV6-transduced DC were comparable to nontransduced DC. Efficiency of vector transduction and transgene expression were confirmed by immunostaining and real-time PCR. Microarray analysis of RNA from CpG ODN and CD40 antibody stimulated sc AAV6-transduced DC revealed upregulation of transcription factors and cytokines involved in immune activation and downregulation of inhibitory factors, suggesting a possible role of transcriptional activation in the observed effect. The adoptive transfer into syngeneic mice of the ex vivo-transduced and activated DC resulted in the development of CEA-specific antibody and T-helper 1-associated immune responses. Immunized mice also developed antibody to AAV6 capsid protein, which did not crossreact with AAV2 capsid protein. These studies demonstrate the potential utility of sc rAAV serotype 6-based vectors in transduction of DC for genetic vaccination approaches.

Adoptive Transfer↗

PubMed2006

In vitro antiretroviral activity and in vitro toxicity profile of SPD754, a new deoxycytidine nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus infection.

SPD754 (AVX754) is a deoxycytidine analogue nucleotide reverse transcriptase inhibitor (NRTI) in clinical development. These studies characterized the in vitro activity of SPD754 against NRTI-resistant human immunodeficiency virus type 1 (HIV-1) and non-clade B HIV-1 isolates, its activity in combination with other antiretrovirals, and its potential myelotoxicity and mitochondrial toxicity. SPD754 was tested against 50 clinical HIV-1 isolates (5 wild-type isolates and 45 NRTI-resistant isolates) in MT-4 cells using the Antivirogram assay. SPD754 susceptibility was reduced 1.2- to 2.2-fold against isolates resistant to zidovudine (M41L, T215Y/F, plus a median of three additional nucleoside analogue mutations [NAMs]) and/or lamivudine (M184V) and was reduced 1.3- to 2.8-fold against isolates resistant to abacavir (L74V, Y115F, and M184V plus one other NAM) or stavudine (V75T/M, M41L, T215F/Y, and four other NAMs). Insertions at amino acid position 69 and Q151M mutations (with or without M184V) reduced SPD754 susceptibility 5.2-fold and 14- to 16-fold, respectively (these changes gave values comparable to or less than the corresponding values for zidovudine, lamivudine, abacavir, and didanosine). SPD754 showed similar activity against isolates of group M HIV-1 clades, including A/G, B, C, D, A(E), D/F, F, and H. SPD754 showed additive effects in combination with other NRTIs, tenofovir, nevirapine, or saquinavir. SPD754 had no significant effects on cell viability or mitochondrial DNA in HepG2 or MT-4 cells during 28-day exposure at concentrations up to 200 microM. SPD754 showed a low potential for myelotoxicity against human bone marrow. In vitro, SPD754 retained activity against most NRTI-resistant HIV-1 clinical isolates and showed a low propensity to cause myelotoxicity and mitochondrial toxicity.

Anti-HIV Agents↗

PubMed2006

Fatty acid profiling of soybean cotyledons by near-infrared spectroscopy.

Genetically improved soybean grain often contains altered fatty acid profiles. Such alterations can have deleterious effects on seed germination and seedling development, making it necessary to monitor fatty acid profiles in follow-up physiological studies. The objective of this research was to quantify the five fatty acids in soybean (Glycine max) cotyledons using near-infrared (NIR) spectroscopy. Soybean cotyledon samples were dried, ground, and scanned with visible and NIR radiation from 400 to 2500 nm, and reflectance was recorded. Samples were also analyzed by gas chromatography (GC) for palmitic, stearic, oleic, linoleic, and linolenic acids and total oil; GC data, expressed as actual concentration and proportion of total oil, were regressed against spectral data to develop calibration equations. Equation statistics indicated that four of the five fatty acids could be predicted accurately by NIR spectroscopy; the fifth fatty acid could be determined by subtraction. Principal component analysis revealed that most of the spectral variation in this population was due to chlorophyll absorbance in the visible region. Therefore, the spectra were trimmed to include the NIR region only (1100-2500 nm), and a second set of equations was developed. Equations based exclusively on NIR spectra had equal or greater precision than equations based on visible and NIR spectra. Principal component analysis and partial least squares analysis revealed that even after trimming, at least 90% of the spectral variation was unrelated to fatty acid, though variation from fatty acid was identified in the second and third principal components. This research provides an NIR method for complete fatty acid profiling of soybean cotyledons. Equations were achieved with NIR spectra only, so spectrophotometers that analyze both the visible and NIR regions are not needed for this analysis. In addition, equations were possible with a 250 mg sample, which is one-tenth the normal sample size for this analysis.

Cotyledon↗

PubMed2004

Global simulation for laser-driven MeV electrons in fast ignition.

A comprehensive examination of the interaction of a picosecond-long ignition pulse on high-density (40 times critical density) pellets using a two-dimensional particle-in-cell model is described. The global geometry consists of a 50 mum diameter pellet surrounded by a corona which is isolated by a vacuum region from the boundary. For cone-attached targets, as much as 67% of the incident laser energy is absorbed with 12% sent forward as fast electrons in a 23 degrees cone. The current filaments are driven by the Weibel instability of the forward-going fast electron flux and its return current with the ions playing an important role of neutralizing the space charge. No global current filament coalescence has been observed. The electron distribution function obeys a power law, which begins at E approximately 0.2 MeV and falls off as E-(2-3).

Journal Article↗

PubMed2003

Construction of a BAC library and generation of BAC end sequence-tagged connectors for genome sequencing of the African malaria mosquito Anopheles gambiae.

A Bacterial Artificial Chromosome (BAC) genomic DNA library of Anopheles gambiae, the major human malaria vector in sub-Saharan Africa, was constructed and characterized. This library (ND-TAM) is composed of 30,720 BAC clones in eighty 384-well plates. The estimated average insert size of the library is 133 kb, with an overall genome coverage of approximately 14-fold. The ends of approximately two-thirds of the clones in the library were sequenced, yielding 32,340 pair-mate ends. A statistical analysis (G-test) of the results of PCR screening of the library indicated a random distribution of BACs in the genome, although one gap encompassing the white locus on the X-chromosome was identified. Furthermore, combined with another previously constructed BAC library (ND-1), ~2,000 BACs have been physically mapped by polytene chromosomal in situ hybridization. These BAC end pair mates and physically mapped BACs have been useful for both the assembly of a fully sequenced A. gambiae genome and for linking the assembled sequence to the three polytene chromosomes. This ND-TAM library is now publicly available at both http://www.malaria.mr4.org/mr4pages/index.html/ and http://hbz.tamu.edu/, providing a valuable resource to the mosquito research community.

Animals↗

PubMed2002

Hosing and sloshing of short-pulse GeV-class wakefield drivers.

This Letter examines the electron-hosing instability in relation to the drivers of current and future plasma-wakefield experiments using fully three-dimensional particle-in-cell simulation models. The simulation results are compared to numerical solutions and to asymptotic solutions of the idealized analytic equations. The measured growth rates do not agree with the existing theory and the behavior is shown to depend sensitively on beam length, shape, and charge. We find that even when severe hosing occurs the wake can remain relatively stable.

Journal Article↗

PubMed2001

Generation of ultra-intense single-cycle laser pulses by using photon deceleration.

A scheme to generate single-cycle laser pulses is presented based on photon deceleration in underdense plasmas. This robust and tunable process is ideally suited for lasers above critical power because it takes advantage of the relativistic self-focusing of these lasers and the nonlinear features of the plasma wake. The mechanism is demonstrated by particle-in-cell simulations in three and 2(1/2) dimensions, resulting in pulse shortening up to a factor of 4, thus making it feasible to generate few-femtosecond single-cycle pulses in the optical to IR domain with intensities I > 10(20) W/cm(2) by using present-day laser technology.

Lasers↗

PubMed2001

Braiding of two spiraling laser beams due to plasma wave wakes.

We study how two Gaussian laser beams interact through plasma wave wakes produced when they co-propagate in a plasma. Using a variational principle, we derive equations of motion for the centroid of each beam, and find braided centroid solutions. These results can be generalized to other nonlinear optical media with non-instantaneous nonlinearity.

Journal Article↗

PubMed2001

Prostate-specific antigen response and systemic T cell activation after in situ gene therapy in prostate cancer patients failing radiotherapy.

In an extended phase I/II study we evaluated 36 prostate cancer patients with local recurrence after radiotherapy who received single or repeated cycles of replication-deficient adenoviral vector (ADV)-mediated herpes simplex virus-thymidine kinase (HSV-tk) plus ganciclovir (GCV) in situ gene therapy with respect to serum PSA levels, alterations in immune cells, and numbers of apoptotic cells in needle biopsies. An initial cycle of HSV-tk plus GCV gene therapy caused a significant prolongation of the mean serum PSA-doubling time (PSADT) from 15.9 to 42.5 months (p = 0.0271) and in 28 of the injected patients (77.8%) there was a mean PSA reduction (PSAR) of 28%. It took a mean of 8.5 months for the PSA to return to the initial PSA (TR-PSA) value. A repeated cycle of gene therapy failed to significantly extend PSADT but did result in significant increases in PSAR (29.4%) and TR-PSA (10.5 months). Moderately increased serum adenovirus antibody titers were generally observed 2 weeks after initial vector injection. Also at this time there was a statistically significant increase in the mean percent of CD8(+) T cells positive for the HLA-DR marker of activation in peripheral blood (p = 0.0088). Studies using prostate biopsies obtained at the same time point demonstrated that vector DNA was detectable by PCR in most samples yet all patients remained positive for prostate cancer in at least one biopsy core. Further analysis demonstrated a correlation between the level of CD8(+) cells and the number of apoptotic cells in biopsies containing cancer cells (p = 0.042). We conclude that repeated cycles of in situ HSV-tk plus GCV gene therapy can be administered to prostate cancer patients who failed radiotherapy and have a localized recurrence. Biological responses to this experimental therapy including increases in PSADT, PSAR, and TR-PSA, and activated CD8(+) T cells present in the peripheral blood, were demonstrated. Interestingly, the density of CD8(+) cells in posttreatment biopsies correlated with the number of apoptotic cells.

Adenoviridae↗

PubMed2001

[In vitro and in vivo experiment of transduction of reporter gene into tumors by E5 gene delivery system].

OBJECTIVE: To investigate the spectrum of tumors into which the E5 gene delivery system can transduce reporter gene so as to establish a platform technology that one gene delivery system can be used to treat multiple types of tumors. METHODS: The E5 delecvery system was used to transduce reporter genes into various types of IGF I R positive tumor cell lines in vitro and into different IGF I R positive tumors transplanted subcutaneously in nude mice in vivo. The efficiency of trasduction was examined. RESULTS: The E5 delivery system transferred reporter genes into five types of tumor cells that over-express IGFIR in vitro and transferred reporter genes into different tumors transplanted subcutaneously in nude mice that over-express IGFIR in vivo too. The transduction rate was positively correlated with the expression rate of IGFIR. However, the E5 delivery system failed to transfer reporter genes into tumor cedll lines in vitro and the tumors transplanted subcutaneously in nude mice in vivo, both of which were without IGF I R expression. CONCLUSION: E5 delivery system has rather remarkable target-ability and extensive usefulness. It has the potentiality in gene therapy of cancer.

Animals↗

PubMed2001

Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells.

Previously, we demonstrated that up-regulation of caveolin-1 (cav-1) was associated with prostate cancer metastasis, biochemical recurrence after radical prostatectomy, and androgen insensitivity. The objective of this study was to characterize the regulation of cav-1 by testosterone (T) and to test the effects of cav-1 on prostate cancer cell survival/clonal growth and metastatic activities. Our results demonstrated that T up-regulated cav-1 protein levels in part through transcriptional regulation and significantly enhanced survival of prostate cancer cell lines ABAC3 and LNCaP after serum starvation (>40% and >60% increased viability, respectively) and in an extended clonogenic assay (approximately 4-fold and 6-fold increase in colonies, respectively). Importantly, antisense cav-1 inhibited the survival effects of T in these assay systems. Modest but not high levels of adenoviral vector-mediated cav-1 expression alone also significantly increased viability (>40%) and clonal growth (10-fold increase in colonies) after serum starvation. Analysis of spontaneous metastasis in stably transfected antisense cav-1 mouse prostate cancer cell clones demonstrated reduction of spontaneous lymph node metastasis incidence (13%), spontaneous lymph node metastasis volume (46%), and experimental lung metastasis incidence (40%) compared with vector control cell clones. Surgical castration further reduced spontaneous lymph node metastasis incidence and volume (18% and 28%, respectively) in antisense cancer cell clones, but not in vector control clones. Our studies demonstrate that cav-1 is a downstream effector of T-mediated prostate cancer cell survival/clonal growth and that modest levels of cav-1 can independently promote prostate cancer cell survival/clonal growth and metastatic activities.

Animals↗

PubMed2001

Compressing and focusing a short laser pulse by a thin plasma lens.

We consider the possibility of using a thin plasma slab as an optical element to both focus and compress an intense laser pulse. By thin we mean that the focal length is larger than the lens thickness. We derive analytic formulas for the spot size and pulse length evolution of a short laser pulse propagating through a thin uniform plasma lens. The formulas are compared to simulation results from two types of particle-in-cell code. The simulations give a greater final spot size and a shorter focal length than the analytic formulas. The difference arises from spherical aberrations in the lens which lead to the generation of higher-order vacuum Gaussian modes. The simulations also show that Raman side scattering can develop. A thin lens experiment could provide unequivocal evidence of relativistic self-focusing.

Journal Article↗

PubMed2001

In situ prostate cancer gene therapy using a novel adenoviral vector regulated by the caveolin-1 promoter.

Caveolin-1, a structural component of caveolae, is overexpressed in metastatic and androgen-resistant prostate cancer and highly expressed in tumor-associated endothelial cells. The mouse cav-1 promoter was cloned and placed upstream of the HSV-tk gene in an adenoviral vector (Adcav-1tk) and compared with a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) promoter-driven HSV-tk, AdCMVtk and AdRSVtk vectors, respectively. Mouse and human prostate cancer cells and mouse endothelial cells were infected with Adcav-1tk, AdCMVtk or control vectors without the HSV-tk gene (Adcav-1 and AdCMV) and subsequently treated with ganciclovir (GCV). GCV-mediated in vitro cytotoxicity induced by the Adcav-1tk vector was comparable to that for AdCMVtk in multiple mouse and human prostate cancer cell lines. To evaluate the activity of Adcav-1tk in vivo, orthotopic mouse prostate cancer tumors were generated with RM-9 cells and injected in situ with Adcav-1tk, AdCMVtk, AdRSVtk, or AdCMVbetagal (control) and treated with GCV. All three HSV-tk transducing vectors produced statistically significant reductions in wet weight and increased apoptotic indices compared with the control vector. However, only Adcav-1tk produced significant necrosis, and only Adcav-1tk and AdRSVtk caused significant decreases in microvessel density. In conclusion, Adcav-1tk demonstrated efficacy in vitro and in vivo in preclinical models of prostate cancer. Our results suggest that the cav-1 promoter may have unique benefits in targeting gene therapy to prostate cancer and its associated vasculature.

Adenoviridae↗

PubMed2001

[Apoptosis of bone marrow cells aplastic anemia patients treated with cyclosporin A].

OBJECTIVE: To evaluate the effects of cyclosporin A (CsA) on the apoptosis of bone marrow cells of aplastic anemia (AA) patients. METHODS: The apoptosis of and Fas antigen expression on the bone marrow mononuclear cells (MNC) in 25 AA patients and 10 normal controls were assayed by TUNEL and FACS, respectively. RESULT: The percentage of CD(34)(+) cells was decreased significantly in AA patients than in normal controls (P < 0.05), and so did the percentage of CD(34)(+)Fas(+) cells (P < 0.05). The percentage of apoptotic cells in AA patients was higher than that of controls (P < 0.01). After the patients were treated with CsA for 2 months, the percentage of apoptotic cells was decreased (P < 0.01). The percentage of CD(34)(+)Fas(+) cells was positively correlated with that of apoptotic cells in AA patients. CONCLUSION: Fas is involved in the apoptosis of CD(34)(+) cells of AA patients. CsA could reduce the percentage of apoptosis of bone marrow cells in AA patients.

Adolescent↗