[Effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery for early-stage breast cancer in different quadrants].

Objective: To compare the effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery (SMPSL-BCS) in treating early-stage breast cancer patients with tumors in different quadrants. Methods: A retrospective analysis was conducted on 200 early-stage breast cancer female patients admitted between January 2023 and December 2023. According to the quadrant where the tumor was located, the patients were allocated into the upper outer quadrant group (UO group), lower outer quadrant group (LO group), upper inner quadrant group (UI group), and lower inner quadrant group (LI group), with 50 cases in each group. There was no significant difference ( P>0.05) in the baseline data, including age, body mass index, smoking history, marital status, comorbidities, affected breast side, maximum tumor diameter on ultrasound, maximum pathological tumor diameter, clinical tumor stage, molecular subtype, and disease duration. The operation time, intraoperative blood loss, postoperative drainage volume, and extubation time were recorded and compared between groups. Additionally, the occurrence of early-stage complications (1-3 months after operation; including subcutaneous fluid accumulation, incision infection, superficial skin burns) and late-stage complications (>3 months after operation; including pectoralis major muscle adhesion, changes in breast appearance and shape, sensory discomfort) were assessed. At 6 months after operation, the cosmetic outcome of breast-conserving surgery was rated for all groups. Results: The UO group had the shortest operation time, followed by the UI group, LO group, and LI group, showing significant differences between groups ( P<0.05). The UO group had the least intraoperative blood loss, followed by the LO group, UI group, and LI group; except for the difference between UO group and LO group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The UO group had the least postoperative drainage volume, followed by the LO group, UI group, and LI group; except for the difference between LO group and UI group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The extubation time of the LI group was significantly longer than that of the other groups ( P<0.05). All patients were followed up 4-12 months, with an average of 8 months. And 193 patients were followed up more than 6 months, including 48 patients in UO group, 47 in LO group, 49 in UI group, and 49 in LI group. In the early-stage period, the LI group had a higher incidence of subcutaneous fluid accumulation after tube removal compared to the UO group and LO group ( P<0.05), while there was no significant difference in the incidences of other early complications between groups ( P>0.05). In the late-stage period, the LI group had significantly higher incidences of pectoralis major muscle adhesion and changes in breast appearance and shape than UO group and LO group ( P<0.05), and a significantly higher incidence of sensory discomfort than UO group ( P<0.05). There was no significant difference in the incidences of other late-stage complications between groups ( P>0.05). At 6 months after operation, the cosmetic outcomes of breast-conserving surgery were significantly better in UO group, LO group, and UI group than in LI group ( P<0.05); there was no significant difference between the other groups ( P>0.05). Conclusion: In the treatment of early-stage breast cancer using SMPSL-BCS, patients with tumors located in the upper outer quadrant show the best effectiveness. The effectivenesses are similar for patients with tumors in the lower outer and upper inner quadrants. However, patients with tumors in the lower inner quadrant do not experience significant advantages. Therefore, it is recommended that SMPSL-BCS should not be the first-choice surgical method for patients with tumors in the lower inner quadrant.

FOXA1 regulates ribosomal RNA transcription in prostate cancer.

BACKGROUND: Ribosome biogenesis is excessively activated in tumor cells, yet it is little known whether oncogenic transcription factors (TFs) are involved in the ribosomal RNA (rRNA) transactivation. METHODS: Nucleolar proteomics data and large-scale immunofluorescence were re-analyzed to jointly identify the proteins localized at nucleolus. RNA-Seq data of five prostate cancer (PCa) cohorts were combined and integrated with multi-dimensional data to define the upregulated nucleolar TFs in PCa tissues. Then, ChIP-Seq data of PCa cell lines and two PCa clinical cohorts were re-analyzed to reveal the TF binding patterns at ribosomal DNA (rDNA) repeats. The TF binding at rDNA was validated by ChIP-qPCR. The effect of the TF on rRNA transcription was determined by rDNA luciferase reporter, nascent RNA synthesis, and global protein translation assays. RESULTS: In this study, we reveal the role of oncogenic TF FOXA1 in regulating rRNA transcription within nucleolar organization regions. By analyzing human TFs in prostate cancer clinical datasets and nucleolar proteomics data, we identified that FOXA1 is partially localized in the nucleolus and correlated with global protein translation. Our extensive FOXA1 ChIP-Seq analysis provides robust evidence of FOXA1 binding across rDNA repeats in prostate cancer cell lines, primary tumors, and castration-resistant variants. Notably, FOXA1 occupancy at rDNA repeats correlates with histone modifications associated with active transcription, namely H3K27ac and H3K4me3. Reducing FOXA1 expression results in decreased transactivation at rDNA, subsequently diminishing global protein synthesis. CONCLUSIONS: Our results suggest FOXA1 regulates aberrant ribosome biogenesis downstream of oncogenic signaling in prostate cancer.

Parental betaine supplementation promotes gosling growth with epigenetic modulation of IGF gene family in the liver.

Betaine is widely used as a feed additive in the chicken industry to promote laying performance and growth performance, yet it is unknown whether betaine can be used in geese to improve the laying performance of goose breeders and the growth traits of offspring goslings. In this study, laying goose breeders at 39 wk of age were fed basal (Control, CON) or betaine-supplemented diets at low (2.5 g/kg, LBT) or high (5 g/kg, HBT) levels for 7 wk, and the breeder eggs laid in the last week were collected for incubation. Offspring goslings were examined at 35 and 63 d of age. The laying rate tended to be increased (P = 0.065), and the feed efficiency of the breeders was improved by betaine supplementation, while the average daily gain of the offspring goslings was significantly increased (P < 0.05). Concentrations of insulin-like growth factor 2 (IGF-2) in serum and liver were significantly increased in the HBT group (P < 0.05), with age-dependent alterations of serum T3 levels. Concurrently, hepatic mRNA expression of the IGF gene family was significantly increased in goslings derived from betaine-treated breeders (P < 0.05). A higher ratio of proliferating cell nuclear antigen (PCNA)-immunopositive nuclei was found in the liver sections of the HBT group, which was confirmed by significantly upregulated hepatic expression of PCNA mRNA and protein (P < 0.05). Moreover, hepatic expression of thyroxine deiodinase type 1 (Dio1) and thyroid hormone receptor ß (TRß) was also significantly upregulated in goslings of the HBT group (P < 0.05). These changes were associated with significantly higher levels of global DNA 5-mC methylation, together with increased expression of methyl transfer genes (P < 0.05), including betaine-homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT), and DNA (cytosine-5-)-methyltransferase 1 (DNMT1). The promoter regions of IGF-2 genes, as well as the predicted TRß binding site on the IGF-2 gene, were significantly hypomethylated (P < 0.05). These results indicate that gosling growth can be improved by dietary betaine supplementation in goose breeders via epigenetic modulation of the IGF gene family, especially IGF-2, in the liver.

The goose industry plays important roles in economics, cultures, and ecosystems, yet the low laying and growth rates of many indigenous breeds hinders the development of the goose farming. Betaine, an important methyl donor, is commonly used as a feed additive in livestock and poultry to enhance animal growth. Dietary supplementation of betaine in laying hens or gestational sows has been reported to promote the growth of their offspring. Here, we sought to investigate whether and how dietary betaine supplementation affects the growth and development of offspring goslings. In this study, goose breeders, both male and female, were fed a basal diet supplemented respectively with 0, 2.5, or 5 g/kg betaine for 7 wk. Goslings hatched from the breeder eggs of different groups were raised under the same standard condition for assessing the growth performance. Parental betaine increases the growth rate of offspring goslings with decreased DNA methylation on the IGF-2 gene promoter and increased expression of the IGF-2 gene in the liver. These results provide scientific evidence for the inter-generational effect of betaine on gosling growth.

A Review of Chronic Lateral Ankle Instability and Emerging Alternative Outcome Monitoring Tools in Patients following Ankle Ligament Reconstruction Surgery.

Ankle sprains are exceedingly common injuries in both athletes and the general population. They account for 10 to 30% of all sports injuries. Although the vast majority of lateral ankle ligament injuries respond successfully to conservative management, the absolute number of those that progress to chronic lateral ankle instability (CLAI) remains considerably important. This condition is characterized by persistent symptoms and may be associated with short-term and long-term complications and functional deficits. There is still a lack of ideal postoperative management of CLAI patients. Furthermore, an evidence-based rehabilitation phasing does not exist and most of the published studies regarding this subject suggest some protocols based on a wide variety of functional assessment scores and other modalities that are not accurate enough. Moreover, the literature that assesses the ability to return to work (RTW) and return to sport (RTS) in the general population and athletes operated for CLAI most commonly shows aggregated results with global rates of RTW or RTS without describing a detailed timeline based on the readiness of patients to return to each level of activity. Although stress radiographs and MRI have been assessed as potential tools to improve postoperative management of CLAI patients, the first modality is limited by its low sensitivity to detect laxity and the second one by its static character and its inability to predict neither the healing process phase nor the mechanical properties of the repaired/reconstructed ligaments. Bioelectrical impedance, mechanical impedance and near-infrared spectroscopy are non-invasive methods of measurement that could be potential assessment tools to help surgeons improve the postoperative management of patients after CLAI surgery.

Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment.

Breast cancer progression and metastasis are governed by a complex interplay within the tumor immune microenvironment (TIME), involving numerous cell types. Lymph node metastasis (LNM) is a key prognostic marker associated with distant organ metastasis and reduced patient survival, but the mechanisms underlying its promotion by breast cancer stem cells (CSCs) remain unclear. Our study sought to unravel how CSCs reprogram TIME to facilitate LNM. Utilizing single-cell RNA sequencing, we profiled TIME in primary cancer and corresponding metastatic lymph node samples from patients at our institution. To verify the derived data, we cultured CSCs and performed validation assays employing flow cytometry and CyTOF. Our analysis revealed distinct differences in cellular infiltration patterns between tumor and LNM samples. Importantly, RAC2 and PTTG1 double-positive CSCs, which exhibit the highest stem-like attributes, were markedly enriched in metastatic lymph nodes. These CSCs are hypothesized to foster metastasis via activation of specific metastasis-related transcription factors and signaling pathways. Additionally, our data suggest that CSCs might modulate adaptive and innate immune cell evolution, thereby further contributing to metastasis. In summary, this study illuminates a critical role of CSCs in modifying TIME to facilitate LNM. The enrichment of highly stem-like CSCs in metastatic lymph nodes offers novel therapeutic targeting opportunities and deepens our understanding of breast cancer metastasis.

Experiment Study on the Effect of Aluminum Sulfate-Based Alkali-Free Accelerator and the w/c on Cement Hydration and Leaching.

The alkali-free accelerator based on aluminum sulfate is widely used in shotcrete in tunnels. Long-term Ca-leaching of shotcrete may adversely affect the tunnels in a water-rich mountain. It is necessary to examine further the impact of the AS accelerator and w/c on cement hydration and leaching. In this study, all the cement pastes were cured in the environment with R.H. > 95% and 20 ± 1 °C for 60 days and leached in a running water test with 6 M NH4Cl at 1 cm/s. The hydration kinetics was characterized by isothermal calorimetry. Additionally, the microstructural and mineralogical alterations were characterized by XRD, SEM, MIP, and N2 absorption. The results show that (1) the AS accelerator affected the hydration kinetics of cement by stimulating early hydration and delaying the late silicate hydration, resulting in AS-accelerated cement pastes with rougher pore structure. As a result, the higher the dose of AS accelerator, the faster the cement pastes will leach. (2) Hydration kinetics of the accelerated cement are not affected by the w/c. The AS-accelerated cement pastes with lower w/c have a denser pore structure. So, the reduction in the w/c contributes to leaching resistance.

MYC reshapes CTCF-mediated chromatin architecture in prostate cancer.

MYC is a well characterized oncogenic transcription factor in prostate cancer, and CTCF is the main architectural protein of three-dimensional genome organization. However, the functional link between the two master regulators has not been reported. In this study, we find that MYC rewires prostate cancer chromatin architecture by interacting with CTCF protein. Through combining the H3K27ac, AR and CTCF HiChIP profiles with CRISPR deletion of a CTCF site upstream of MYC gene, we show that MYC activation leads to profound changes of CTCF-mediated chromatin looping. Mechanistically, MYC colocalizes with CTCF at a subset of genomic sites, and enhances CTCF occupancy at these loci. Consequently, the CTCF-mediated chromatin looping is potentiated by MYC activation, resulting in the disruption of enhancer-promoter looping at neuroendocrine lineage plasticity genes. Collectively, our findings define the function of MYC as a CTCF co-factor in three-dimensional genome organization.

The Effect of SBIRT on Harmful Alcohol Consumption in the Community Health Centers of Shanghai, China: A Randomized Controlled Study.

OBJECTIVE: The present study was a randomized controlled trial with a longitudinal design aimed at examining the effectiveness of Screening, Brief Intervention and Referral to Treatment (SBIRT) on harmful alcohol use in the community health centres in Shanghai, China, and further compared the effects of a multi-session brief intervention (MBI) and a single-session brief intervention (SBI). METHODS: A total of 362 participants were recruited from four districts of Shanghai and randomly assigned to MBI, SBI and routine care (RC) groups. The MBI group received the brief intervention twice. Follow-up assessments were conducted at 1 and 3 months after the intervention. RESULTS: Compared with the SBI and the RC groups, the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores (F = 6.422, P = 0.002), SDS scores (F = 5.779, P = 0.003) and SAS scores (F = 4.004, P = 0.019) were significant improved in the MBI group at 1and 3-month follow-up assessment. In the SBI group, the SDS scores decreased significantly compared with the RC group, and there were no significant differences in ASSIST scores, drinking knowledge scores and SAS scores 1-month follow-up assessment. CONCLUSION: The findings suggested that SBIRT with two sessions of BI had considerable effects on individuals with harmful alcohol use. It provided clinical evidence for future use in China and other Asian countries with similar situations.

A rapid and sensitive ultra-performance liquid chromatography tandem mass spectrometry method for determination of anlotinib in plasma and dried blood spots: Method development, validation, and clinical application.

RATIONALE: Anlotinib is a multi-target tyrosine kinase inhibitor, approved in China for treating several cancer types. Dose individualization based on therapeutic drug monitoring (TDM) is a useful tool to reduce toxicity. However, it is not convenient for patients to go to hospital for routine TDM via venous blood sampling at a certain time. METHODS: An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determination of anlotinib in human plasma and dried blood spot (DBS), characterized by simple sample preparation, high sensitivity, and short analysis time. The assay was validated in the concentration range of 0.2-200 ng/mL in plasma and 5-1000 ng/mL in DBS. This method was applied to monitor anlotinib exposure levels in patients with advanced biliary tract cancer (BTC) and non-small cell lung cancer (NSCLC). RESULTS: The trough plasma concentration (Ctrough ) of anlotinib was highly variable among BTC patients with coefficients of variation (CV) of 47.5%. DBS and venous blood samples were also collected from NSCLC patients to determine whether DBS sampling is a viable alternative sampling approach. Pearson correlation coefficient (R) between DBS and plasma concentration was 0.985. Bland-Altman plot demonstrated that the difference between estimated and measured plasma concentration was -2.9%. And 87% of sample pairs had a maximal deviation of ±20%. CONCLUSIONS: Anlotinib exhibits a high inter-individual variability in plasma exposure, and DBS sampling could be a promising tool for TDM of anlotinib.

Short Cyclic Regimen With Parathyroid Hormone (PTH) Results in Prolonged Anabolic Effect Relative to Continuous Treatment Followed by Discontinuation in Ovariectomized Rats.

Despite the potent effect of intermittent parathyroid hormone (PTH) treatment on promoting new bone formation, bone mineral density (BMD) rapidly decreases upon discontinuation of PTH administration. To uncover the mechanisms behind this adverse phenomenon, we investigated the immediate responses in bone microstructure and bone cell activities to PTH treatment withdrawal and the associated long-term consequences. Unexpectedly, intact female and estrogen-deficient female rats had distinct responses to the discontinuation of PTH treatment. Significant tibial bone loss and bone microarchitecture deterioration occurred in estrogen-deficient rats, with the treatment benefits of PTH completely lost 9 weeks after discontinuation. In contrast, no adverse effect was observed in intact rats, with sustained treatment benefit 9 weeks after discontinuation. Intriguingly, there is an extended anabolic period during the first week of treatment withdrawal in estrogen-deficient rats, during which no significant change occurred in the number of osteoclasts, whereas the number of osteoblasts remained elevated compared with vehicle-treated rats. However, increases in number of osteoclasts and decreases in number of osteoblasts occurred 2 weeks after discontinuation of PTH treatment, leading to significant reduction in bone mass and bone microarchitecture. To leverage the extended anabolic period upon early withdrawal from PTH, a cyclic administration regimen with repeated cycles of on and off PTH treatment was explored. We demonstrated that the cyclic treatment regimen efficiently alleviated the PTH withdrawal-induced bone loss, improved bone mass, bone microarchitecture, and whole-bone mechanical properties, and extended the treatment duration. © 2021 American Society for Bone and Mineral Research (ASBMR).

Single-Cell Proteomic Profiling Identifies Nanoparticle Enhanced Therapy for Triple Negative Breast Cancer Stem Cells.

Breast cancer remains a major cause of cancer-related deaths in women worldwide. Chemotherapy-promoted stemness and enhanced stem cell plasticity in breast cancer is a cause for great concern. The discovery of drugs targeting BCSCs was suggested to be an important advancement in the establishment of therapy that improves the efficacy of chemotherapy. In this work, by using single-cell mass cytometry, we observed that stemness in spheroid-forming cells derived from MDA-MB-231 cells was significantly increased after doxorubicin administration and up-regulated integrin αvß3 expression was also observed. An RGD-included nanoparticle (CS-V) was designed, and it was found that it could promote doxorubicin's efficacy against MDA-MB-231 spheroid cells. The above observations suggested that the combination of RGD-included nanoparticles (CS-V) with the chemo-drug doxorubicin could be developed as a potential therapy for breast cancer.

Effectiveness of E-SBIRT intervention in community healthcare institution in China: study proposal for a randomised controlled trial.

BACKGROUND: Many studies have demonstrated the effectiveness of Screening, Brief Intervention and Referral to Treatment (SBIRT) in addressing substance use problem. However, owing to the shortage of counsellors, it has not been widely used in China. With the development of smart medicine, we developed a web-based electronic SBIRT (E-SBIRT) program and explored the effectiveness of E-SBIRT in reducing substance use in China. METHODS: A randomised controlled trial will be conducted in primary healthcare institutions. Four primary healthcare institutions will be selected and randomly divided into an intervention group and a control group (each institution will recruit 60 participants, and in total, 240 participants will be recruited). The control group will get a pamphlet of drug abuse prevention, and the intervention group will get the E-SBIRT intervention and the pamphlet. Both groups will receive baseline and follow-up assessment at 1 and 3 months after the intervention. The primary outcome is the change in scores on the Alcohol, Smoking and Substance Use Involvement Screening Test, and the secondary outcomes include changes in motivation, depression, anxiety, positive/negative emotion, self-esteem, addiction knowledge and addiction severity index. CONCLUSIONS: If the 'E-SBIRT' program is found to be effective, it will be an accessible, affordable and widely implementable intervention to help participants at moderate risk of substance use to reduce their consumption. The potential benefit is to provide early intervention to high-risk patients in time and reduce the harmful consequences to individuals and society. TRIAL REGISTRATION NUMBER: NCT03452241.

Autophagy is involved in the neuroprotective effect of nicotiflorin.

ETHNOPHARMACOLOGICAL RELEVANCE: Nicotiflorin is a flavonoid glycoside derived from the traditional Chinese medicine FlosCarthami, dried petals of Carthamus tinctorius L., and has been confirmed to be a promising novel drug candidate for ischemic stroke. Yet, the exact role of nicotiflorin in cerebral I/R injury is uncharacterized and the possible mechanisms have not been clearly expounded. AIM OF THE STUDY: The present study was designed to determine the effect of nicotiflorin on cerebral ischemia/reperfusion (I/R) injury and its relationship with autophagy. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) in rats and oxygen-glucose deprivation and reintroduction (OGD/R) in SH-SY5Y cells were established in in vivo and in vitro models, respectively. The severity of MCAO was assessed by brain infarct size, neurological scores and survival rate. The severity of OGD/R was evaluated by cell viability, lactate dehydrogenase (LDH) release and cell apoptosis. The level of autophagy was evaluated both in vivo and in vitro. Autophagosomes were observed using transmission electron microscopy and autophagic flux was measured using mRFP-GFP-tandem fluorescent LC3 adenovirus. Autophagy-related proteins (LC3-II/I, SQSTM1, beclin-1, Phospho-mTOR/mTOR) were measured by immunoblot. Autophagy-related mRNA levels (Becn1, Atg7) were detected by Real-Time PCR. Inhibition of autophagy was implemented by 3-Methyladenine (3-MA) or chloroquine in vitro. RESULTS: In vivo, nicotiflorin treatment alleviated brain damage and neurological deficit while it dramatically increased 72 h survival rate in rats. In vitro, nicotiflorin treatment also ameliorated the severity of OGD/R. Moreover, nicotiflorin treatment increased ischemic penumbra autophagy (autophagosomes, BECN1, LC3-II/I ratio, SQSTM1, Phospho-mTOR/mTOR, Atg7). In vitro, nicotiflorin likewise enhanced autophagy and promoted autophagy flux. Furthermore, the blockade of autophagy by 3-MA or chloroquine disabled the efficacic of nicotiflorin in preventing cell damage upon OGD/R insult. CONCLUSION: These findings suggest that autophagy plays a significant role in the protective effect of nicotiflorin against ischemic stroke.

GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis.

Adipose tissue stroma contains a population of mesenchymal stem cells (MSC) promote new blood vessel formation and stabilization. These adipose-derived stem cells (ASC) promote de novo formation of vascular structures in vitro. We investigated the angiogenic factors secreted by ASC and discovered that glial-derived neurotrophic factor (GDNF) is a key mediator for endothelial cell network formation. It was found that both GDNF alone or present in ASC-conditioned medium (ASC-CM) stimulated capillary network formation by using human umbilical vein endothelial cells (HUVECs) and such an effect was totally independent of vascular endothelial growth factor (VEGF) activity. Additionally, we showed stimulation of capillary network formation by GDNF, but not VEGF, could be blocked by the Ret (rearranged during transfection) receptor antagonist RPI-1, a GDNF signaling inhibitor. Furthermore, GDNF were found to be overexpressed in cancer cells that were resistant to the anti-angiogenic treatment using the VEGF antibody. Cancer cells in the liver hepatocellular carcinoma (HCC), a non-nervous related cancer, highly overexpressed GDNF as compared to normal liver cells. Our data strongly suggest that, in addition to VEGF, GDNF secreted by ASC and HCC cells, may be another important factor promoting pathological neovascularization. Thus, GDNF may be a potential therapeutic target for HCC and obesity treatments.

Malignant Syndrome or Withdrawal Reaction?

We report on a case of a female patient who had serious side effects from treatment with clozapine and chlorpromazine and the appeared to have a withdrawal reaction from cessation of clozapine. During the treatment process she was misdiagnosed as having malignant syndrome. This case highlights the importance of clinicians being able to distinguish malignant syndrome from withdrawal reactions, and to be familiar with treatment and prevention methods for both.

Removal of gas phase low-concentration toluene over Mn, Ag and Ce modified HZSM-5 catalysts by periodical operation of adsorption and non-thermal plasma regeneration.

Ag/HZSM-5, Mn/HZSM-5, Ce/HZSM-5, Ag-Mn/HZSM-5 and Ce-Mn/HZSM-5 were prepared by impregnation method. Both their adsorption capacity and catalytic activity were investigated for the removal of gas phase low-concentration toluene by periodical operation of adsorption and non-thermal plasma regeneration. Results show that catalysts loaded with Ag (Ag/HZSM-5 and Ag-Mn/HZSM-5) had larger adsorption capacity for toluene than the other catalysts. And Ag-Mn/HZSM-5 displayed the best catalytic performance for both toluene oxidation by non-thermal plasma and byproducts suppression. On the other hand, the deactivated catalyst can be fully regenerated by calcining in air stream when its adsorption capacity and catalytic activity of the Ag-Mn/HZSM-5 catalyst was found to be decreased after 10 cycles of periodical adsorption and non-thermal regeneration.

Systemic oncolytic herpes virus therapy of poorly immunogenic prostate cancer metastatic to lung.

PURPOSE: Our goal was to evaluate whether systemic administration of NV1042, an interleukin-12 (IL-12)-expressing oncolytic herpes simplex virus, and its noncytokine parental vector NV1023 are effective against preexisting metastatic prostate cancer in an immunocompetent mice model. EXPERIMENTAL DESIGN: Metastatic TRAMP-C2 lung tumors established in C57Bl/6 or nude mice were treated on day 21 with four i.v. administrations of NV1042 or NV1023 and sacrificed on day 42 to assess virus efficacy and the potential mechanism of efficacy. RESULTS: NV1042 or NV1023 treatment was similarly effective in eliminating extrapleural and hemorrhagic tumors present in mock-treated mice. However, NV1042 was further effective compared with NV1023 in controlling the growth of lung tumors (as determined by mean surface tumor nodule number, lung weights, and surface tumor burden) and in extending survival. NV1042-treated mice exhibited a transient increase of serum IL-12 1 day posttreatment, whereas IL-12 levels in tumor bearing lungs persisted a further 2 days at least. Only splenocytes from NV1042-treated mice secreted IFN-gamma in response to TRAMP-C2 stimulation and displayed natural killer activity. The IL-12-mediated enhancement observed with NV1042 in the syngeneic model was abrogated in athymic mice treated in a similar manner, thus indicating a role for T cells in the augmented efficacy of NV1042 virus. CONCLUSIONS: Systemic administration of the IL-12-expressing NV1042 virus is more effective than its noncytokine parent, NV1023, against preestablished metastatic lung tumors. Given the clinical safety profile of NV1020, the parental vector of NV1023, and NV1042's enhanced efficacy and ability to activate the host immune system, NV1042 merits clinical consideration for treating metastatic prostate cancers.