The influence of resourcefulness on the family functioning of young- and middle-aged lymphoma patients in China: a cross-sectional study.

BACKGROUND: Lymphoma has become 1 of the 10 most common cancers with increased prevalence in young- and middle-aged adults in China. This poses a tremendous burden on patients and their families and brings great challenges to maintaining the balance of family functioning in young- and middle-aged patients. OBJECTIVE: This cross-sectional study aimed to analyse the influence of resourcefulness on the family functioning of Chinese young- and middle-aged lymphoma patients. METHODS: A total of 172 Chinese young- and middle-aged patients with lymphoma were recruited from the oncology departments of two tertiary hospitals in Zhengzhou, Henan, China. They were invited to complete a survey that included a demographic questionnaire, the Resourcefulness Scale and the Chinese Version Family Adaptability and Cohesion Scale II. Multiple linear regression was used to analyse the related factors for family functioning. RESULTS: The multiple regression analysis revealed that the main influencing factors of family cohesion were resourcefulness (ß = 0.338, 95% CI (0.072, 0.173)), spouse caregiver (ß = 0.376, 95% CI (1.938, 10.395)), and cancer stage (ß = -0.274, 95% CI (-3.219, -1.047)). Resourcefulness (ß = 0.438, 95% CI (0.096, 0.181)), spouse caregiver (ß = 0.340, 95% CI (1.348, 8.363)), and family per capita monthly income (ß = 0.157, 95% CI (0.066, 2.243)) were the influencing factors of family adaptability. CONCLUSIONS: Healthcare professionals and family scholars should value young- and middle-aged lymphoma patients' family functioning throughout the cancer treatment process, and family interventions should be designed by healthcare providers based on patients' resourcefulness. Moreover, healthcare providers need to pay attention to the risk factors of patients' family cohesion and adaptability, such as low family per capita monthly income, and consider employing corresponding measures to help them.

A novel photosensitizer DTPP-mediated photodynamic therapy induces oxidative stress and apoptosis through mitochondrial pathways in LA795 cells.

OBJECTIVE: Investigation of the effects of 5-5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP)-mediated photodynamic therapy (PDT) on oxidative stress and mitochondrial apoptosis in LA795 lung cancer cells. METHODS: Proteomics was used to identify differentially expressed proteins after PDT treatment. The apoptosis rate was determined by flow cytometry. Morphologic observation of apoptosis, reactive oxygen species (ROS) levels, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and Caspase- 9 and Caspase-3 were determined by assays; apoptosis-related protein levels of Cytochrome (Cyto) c, Bcl- 2, Bax were determined by Western blot. RESULTS: Typical apoptosis morphology of LA795 cells was observed after PDT. The cells were mainly in the apoptosis death pathway with high cell apoptosis rates. The proteomics study observed the apoptosis-associated proteins, oxidative stress proteins, antioxidant proteins, the cytoskeletal protein and mitochondrial dysfunction in LA 795 cells. Additional results indicated that PDT could increase levels of ROS, NO; decrease glutathione (GSH) content and MMP; upregulated Bax, Cyto c, and Caspase-3 protein expression, inhibited Bcl-2 protein expression, and further induced cell apoptosis. The effect of DTPP-PDT on lung cancer was: first, mitochondrial Cyto c is released into the cytoplasm, then Caspase- 9 / Caspase-3 was activated, Bcl-2 decreased/Bax increased, initiating cell apoptosis. CONCLUSION: DTPP-PDT could induce oxidative stress and apoptosis via mitochondrial pathways in LA795 cells.

Biomechanical analysis of the door-shaped titanium plate in single-level anterior cervical discectomy and fusion.

BACKGROUND: Analyse and discuss the immediate stability of the cervical spine after anterior cervical discectomy and fusion using a door-shaped titanium plate and compare it with the traditional titanium plate, to provide biomechanical evidence for the rationality and effectiveness of the door-shaped titanium plate in clinical applications. METHODS: Ten adult goat C4/5 vertebral bodies were obtained, and models were prepared using denture base resin. Biomechanical experiments were performed on the specimens before internal fixation. MTS was used to conduct non-destructive biomechanical loading tests in six directions, including flexion, extension, left-right bending, and left-right torsion, recording the range of motion (ROM) and neutral zone (NZ) of each specimen. The specimens were then randomly divided into two groups: the study group was fixed with a door-shaped titanium plate, and the control group was fixed with a traditional titanium plate. ROM and NZ in each direction were measured again. After measurements, both groups were subjected to 0.5 Hz torsion loading with a torque of 2 N m for a total of 3000 cycles, followed by measuring ROM and NZ in six directions once more. RESULTS: Compared to before fixation, ROM and NZ in both groups significantly decreased in all six directions after fixation, with statistical significance (P < 0.05); after fixation, the study group showed slightly lower values for various mechanical reference parameters compared to the control group, with no statistical significance (P > 0.05); after 3000 torsional loads, both internal fixation groups showed increased ROM and NZ compared to after fixation but to a lower extent, and no screw or titanium plate loosening was observed. Compared to before fixation, the differences were still statistically significant (P < 0.05), with the study group having slightly lower ROM and NZ values in all directions compared to the control group, with no statistical significance (P > 0.05). CONCLUSION: The door-shaped titanium plate exhibits mechanical properties similar to the traditional titanium plate in all directions, and its smaller size and simpler surgical operation can be used for anterior cervical endoscopic surgery, reducing surgical trauma. It is clinically feasible and deserves further research and promotion.

Family resilience and its influencing factors among advanced cancer patients and their family caregivers: a multilevel modeling analysis.

BACKGROUND: Cancer is highly prevalent worldwide. Family resilience is a positive variable that helps families burdened by advanced cancer to cope effectively. This study aimed to describe the family resilience of advanced cancer patients and caregivers in dyads and identify its influencing factors at the individual and dyadic levels. METHODS: This multisite cross-sectional study was conducted in oncology units in five tertiary hospitals in China. A total of 270 advanced cancer patient-caregiver dyads were recruited between June 2020 and March 2021. Patients' and caregivers' family resilience was measured by the Family Resilience Assessment Scale. Data on potential influencing factors, including demographic and disease-related characteristics as well as family sense of coherence, psychological resilience, perceived social support, symptom burden, and caregiver burden, were collected. Multilevel modeling analysis was adopted to control for the interdependence of the dyads. RESULTS: A total of 241 dyads were included in the data analysis. The mean ages of patients and caregivers were 53.96 (SD 15.37) and 45.18 (SD 13.79) years, respectively. Most caregivers were spouses and adult children (45.6% and 39.0%, respectively). Patients reported a higher mean family resilience score than caregivers (152.56 vs. 149.87, respectively). Undergoing fewer than two types of treatment and a lower symptom burden of patients predicted higher patient (B = -9.702, -0.134, respectively) and caregiver (B = -5.462, -0.096, respectively) family resilience. Patients also reported higher family resilience under the following conditions: 1) were on a medical insurance plan other than the new rural cooperative medical system (B = 6.089), 2) had a better family sense of coherence (B = 0.415), 3) whose caregivers were unmarried (B = 8.618), perceived lower social support (B = -0.145) and higher psychological resilience (B = 0.313). Caregivers who were ≤ 44 years old (B = -3.221), had similar previous caregiving experience (B = 7.706), and had a stronger family sense of coherence (B = 0.391) reported higher family resilience. CONCLUSIONS: Our findings highlight the importance of adopting a dyadic approach when caring for advanced cancer patients and their caregivers. Dyadic longitudinal research is suggested to discover more modifiable factors of family resilience and tailored interventions are needed to obtain optimal dyadic outcomes.

Dietary Behavior and Its Association with Nutrition Literacy and Dietary Attitude Among Breast Cancer Patients Treated with Chemotherapy: A Multicenter Survey of Hospitals in China.

Background: Chemotherapy often negatively impacts the nutritional status of breast cancer patients, and healthy dietary behaviors are important for patient wellbeing. With the guidance of the "Knowledge, Attitude and Practice model" (KAP model), the objective of this survey was to determine the frequency with which patients engage in healthy dietary behaviors and to explore the association between healthy dietary behaviors and nutrition literacy and dietary attitudes. Methods: This study included a total of 284 breast cancer patients undergoing chemotherapy from three hospitals spanning three cities in China. Face-to-face interviews were conducted to collect demographic and clinical characteristics as well as the Dietary Nutritional Knowledge, Attitude and Practice Questionnaire (DNKAPQ) and the Nutrition Literacy Measurement Scale for Chinese Adult (NLMS-CA). Results: Participants exhibited medium to high scores for nutrition literacy, dietary attitude and dietary behavior. Nutrition literacy (r = 0.505, p < 0.001) and dietary attitude (r= 0.326, p < 0.001) scores were both positively correlated with the total dietary behavior score. The total nutrition literacy score was positively correlated with the total dietary behavior score (r = 0.286, p < 0.001). In the univariate analysis, age, body mass index, living environment, education level, monthly family income, work status, menopausal status, number of comorbidities, relapse and endocrine therapy were significantly associated with dietary behavior (p < 0.05). In the multiple linear regression analysis, patients' dietary behavior was significantly associated with nutrition literacy (ß = 0.449, p < 0.001) and dietary attitude (ß = 0.198, p < 0.001). These two factors accounted for 28.6% of the variation in the patients' dietary behavior scores. Conclusion: There is an important need for targeted dietary and nutritional interventions designed and implemented by health professionals to improve dietary behaviors. Intervention design and content should take the patients' nutrition literacy and dietary attitudes into consideration. In particular, women who are older, overweight, unemployed, and postmenopausal and live in rural areas, exhibit fewer comorbidities, have a lower family income and education level, have not relapsed and are currently receiving endocrine therapy are in urgent need of diet-specific intervention.

The influence of nutrition literacy, self-care self-efficacy and social support on the dietary practices of breast cancer patients undergoing chemotherapy: A multicentre study.

PURPOSE: Breast cancer patients undergoing chemotherapy experience adverse reactions, which lead to poor nutritional status. The objective of this study was to explore the dietary practice of Chinese breast cancer patients undergoing chemotherapy and to analyse the influence of nutrition literacy, self-care self-efficacy and perceived social support on dietary practice. METHOD: A total of 295 participants from three hospitals in China were enrolled. The Dietary Nutritional Knowledge, Attitude and Practice Questionnaire; Nutrition Literacy Measurement Scale for Chinese Adults; Strategies Used by People to Promote Health and Perceived Social Support Scale were administered. Multiple linear regressions were used to identify influencing factors. RESULTS: The dietary practice of patients were generally satisfactory. Nutrition literacy (r = 0.460, p < 0.001), self-care self-efficacy (r = 0.513, p < 0.001) and perceived social support (r = 0.703, p < 0.001) were positively correlated with dietary practice. The main factors influencing participants' dietary practice were nutrition literacy, self-care self-efficacy, perceived social support, living environment, cancer stage, body mass index, chemotherapy cycle and average monthly household income (all p < 0.05). The model explained 59.0% of the variance in dietary practice. CONCLUSIONS: Health professionals should emphasize breast cancer patients' dietary practice throughout the entire chemotherapy course, and dietary interventions should be designed by oncology nurses based on patients' nutrition literacy, self-care self-efficacy and perceived social support. Female patients who have a higher body mass index and income, live in rural areas, have a lower education level, have stage I cancer and have undergone numerous chemotherapy cycles are the focus population of intervention.

Effects of sweet potato vine silage supplementation on meat quality, antioxidant capacity and immune function in finishing pigs.

Sweet potato vine, the byproduct of sweet potato, has a high nutritional value. Silage is an effective solution for nutrient preservation. This article explored the effects of sweet potato vine silage (SPVS) supplementation on meat quality, antioxidant capacity and immune function in finishing pigs. One hundred and eighty finishing pigs (Berkshire × Licha Black) with a body weight of 74.54 ± 3.32 kg were randomly divided into three groups. The three groups were separately fed basal diet (Ctrl), Ctrl supplemented with 2.5% SPVS (LSPVS) or 5% SPVS (HSPVS) on a dry matter basis. Results showed that the eye muscle area in the LSPVS group was significantly increased. The carcass weight in the HSPVS was significantly reduced compared with Ctrl. For the meat quality, only cooking loss in both HSPVS and LSPVS was reduced while other indexes had no significant differences. For the antioxidant capacity, the hepatic level of glutathione (GSH) peroxidase (GSH-PX) was significantly upregulated in LSPVS but downregulated in HSPVS. In the serum, HSPVS decreased GSH level and increased GSH-PX level. HSPVS significantly reduced hepatic interleukin-1ß (IL-1ß) levels and LSPVS significantly reduced IL-12 levels and increased IL-8 and IL-6 levels. Moreover, HSPVS and LSPVS promoted the secretion of immunoglobulin M (IgM) and IgG in the serum. Our data showed that low-dose SPVS supplementation improved carcass traits and high-dose SPVS supplementation increased immune function in finishing pigs, which provides a new alternative to improve animal health.

Phosphatidylserine released from apoptotic cells in tumor induces M2-like macrophage polarization through the PSR-STAT3-JMJD3 axis.

BACKGROUND: Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co-localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved. METHODS: Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography-mass spectrometry. Phosphatidylserine-containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real-time PCR, immunohistochemistry enzyme-linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies. RESULTS: The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2-like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2-like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T-cell immunoglobin mucin 4 (TIM4) and the FAK-SRC-STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain-containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression. CONCLUSIONS: This study suggest that apoptotic cell-generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.

In vivo cancer targeting via glycopolyester nanoparticle mediated metabolic cell labeling followed by click reaction.

We developed glycopolyesters (GPs) via azido-sugar initiated ring-opening polymerization of O-carboxyanhydrides (OCAs) and achieved efficient in vivo cancer targeting via GP-nanoparticle (GP-NP) mediated metabolic cell labeling followed by Click reaction. GP-NP shows controlled release of azido-sugars and can efficiently label LS174T colon cancer cells with azido groups in tumor-bearing mice. The exogenously introduced azido groups render excellent in vivo cancer targeting and retention of dibenzocyclooctyne-Cy5 (DBCO-Cy5) with an increasing tumor retention enhancement over time (68% at 6 h, 105% at 24 h, and 191% at 48 h) compared to control mice without azido labeling. The tumor accumulation of DBCO-doxorubicin is also significantly enhanced in GP-NP pretreated mice, resulting in improved in vivo anticancer efficacy. This study, for the first time, proposes the use of azido-sugar initiated polymerization of OCAs to form sugar delivery vehicles with high stability and controlled release, and demonstrates the increasing tumor targeting effect of DBCO-cargo over time by azido-modified tumor cells.

Recent progress in nanomaterials for nucleic acid delivery in cancer immunotherapy.

The combination of gene therapy and immunotherapy has the potential to systemically promote anti-tumor effects while reducing adverse reactions. Small interfering RNA (siRNA) has generated great interest in biology, engineering and medicine, especially for cancer treatment due to its ability to knock down genes of interest. Nanomaterials play significant roles in the design of delivery systems of siRNA, and nanomaterial-mediated siRNA delivery in cancer immunotherapy is one of the most important directions for future clinical cancer treatment. Here, we review the recent advances in nanomaterial mediated targeted delivery of siRNA to dendritic cells (DCs), tumor-associated macrophages (TAMs), immune checkpoint inhibitors, B lymphocytes, natural killer cells (NKs), and immunosuppressive cytokines. Fundamental challenges in nucleic acid delivery enabled by bio-barriers, its promising solution strategies and future directions are also reviewed.

Tumor cells induce LAMP2a expression in tumor-associated macrophage for cancer progression.

BACKGROUND: Tumor cells benefit from tumor-associated macrophages (TAMs) promoting tumor growth and modulating functions of other cells in tumor microenvironment (TME). However, how tumor cells regulate the property of TAMs during tumor invasion remains to be defined. METHODS: Mouse tumor models and cancer patients' samples were analyzed to determine LAMP2a expression in TAMs. In vitro mouse primary macrophages were used to assess LAMP2a-modulated macrophage activation, and to verify LAMP2a's target proteins. The effect of LAMP2a-knockdown on tumor progression and TME maintaining was determined by using mouse tumor models. FINDINGS: Lysosome associated membrane protein type 2A (LAMP2a) is upregulated in TAMs by tumor cells and important for tumor progression. LAMP2a expression in TAMs, but not in tumor cells, is associated with poor prognosis in breast cancer. LAMP2a inactivation induced by either shRNA or CRISPR/Cas9 prevents TAMs activation and tumor growth. LAMP2a degrades PRDX1 (peroxiredoxin 1) and CRTC1 (CREB-regulated transcription coactivator 1) to promote macrophage pro-tumorigenic activation. INTERPRETATION: Our study suggests that tumor cells utilize LAMP2a-PRDX1/CRTC1 axis to modulate TAMs activation and promote tumor growth, reveals the role of LAMP2a in macrophage study and TAM-targeting tumor immunotherapy. FUND: National Natural Science Foundation of China (No. 81602492); National Key Research and Development Program of China (No. 2016YFA0201402).

Secondary structures in synthetic polypeptides from N-carboxyanhydrides: design, modulation, association, and material applications.

Synthetic polypeptides derived from the ring-opening polymerization of N-carboxyanhydrides can spontaneously fold into stable secondary structures under specific environmental conditions. These secondary structures and their dynamic transitions play an important role in regulating the properties of polypeptides in self-assembly, catalysis, polymerization, and biomedical applications. Here, we review the current strategies to modulate the secondary structures, and highlight the conformation-specific dynamic properties of synthetic polypeptides and the corresponding materials. A number of mechanistic studies elucidating the role of secondary structures are discussed, aiming to provide insights into the new designs and applications of synthetic polypeptides. We aim for this article to bring to people's attention synthetic polymers with ordered conformations, which may exhibit association behaviors and material properties that are otherwise not found in polymers without stable secondary structures.

A caged metabolic precursor for DT-diaphorase-responsive cell labeling.

In this study, we report incorporation of a covalent linker at the anomeric position of N-azidoacetylmannosamine (ManNAz) for caging its metabolic process. We synthesized a DT-diaphorase-responsive metabolic precursor, HQ-NN-AAM, using an optimized linker. The caged metabolite showed responsiveness to DT-diaphorase in vitro, resulting in metabolic incorporation of an azido sugar into the cell surface in multiple cell lines.

Light-triggered release of drug conjugates for an efficient combination of chemotherapy and photodynamic therapy.

Herein, we present a series of light-triggered porphyrin-based polymeric drug conjugates PSDTD-m for combined chemo-photodynamic therapy of cancer. The controlled release of a drug through a ROS-cleavable linker combined with photodynamic therapy showed enhanced anticancer efficacy, proving the effectiveness of this light triggered smart nanocarrier platform for enhancing the therapy efficacy.

Degradable and biocompatible hydrogels bearing a hindered urea bond.

A hindered urea bond (HUB), recently reported as a new type of dynamic chemical bond, can be facilely constructed by mixing an isocyanate and a hindered amine. Here, we report the use of the HUB in the design of degradable hydrogel materials for applications of stem cell encapsulation and delivery. Polyethyleneglycol (PEG) diamine was end-capped with a HUB and an allyl group in a one-pot synthesis. The resulting polymer was cross-linked to form a hydrogel under UV with the addition of a 4-arm PEG thiol and a photoinitiator. The degradation properties of the hydrogels were confirmed with NMR, GPC, weight loss, and protein release studies. We found that the degradation kinetics is dependent on the size of the N-substituents, and the one with the tert-butyl group shows complete degradation within 2 days. The new hydrogel materials were also demonstrated to be biocompatible with hMSCs, and the cell release kinetics can be facilely tuned over 5 days.

Selective in vivo metabolic cell-labeling-mediated cancer targeting.

Distinguishing cancer cells from normal cells through surface receptors is vital for cancer diagnosis and targeted therapy. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge. Herein we report the design of sugars that can selectively label cancer cells both in vitro and in vivo. Specifically, we inhibit the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells. Histone deacetylase and cathepsin L-responsive acetylated azidomannosamine, one such enzymatically activatable Ac4ManAz analog developed, mediated cancer-selective labeling in vivo, which enhanced tumor accumulation of a dibenzocyclooctyne-doxorubicin conjugate via click chemistry and enabled targeted therapy against LS174T colon cancer, MDA-MB-231 triple-negative breast cancer and 4T1 metastatic breast cancer in mice.

Endocytosis of a functionally enhanced GFP-tagged transferrin receptor in CHO cells.

The endocytosis of transferrin receptor (TfR) has served as a model to study the receptor-targeted cargo delivery system for cancer therapy for many years. To accurately evaluate and optically measure this TfR targeting delivery in vitro, a CHO cell line with enhanced green fluorescent protein (EGFP)-tagged human TfR was established. A chimera of the hTfR and EGFP was engineered by fusing EGFP to the amino terminus of hTfR. Data were provided to demonstrate that hTfR-EGFP chimera was predominantly localized on the plasma membrane with some intracellular fluorescent structures on CHO cells and the EGFP moiety did not affect the endocytosis property of hTfR. Receptor internalization occurred similarly to that of HepG2 cells expressing wild-type hTfR. The internalization percentage of this chimeric receptor was about 81 ± 3% of wild type. Time-dependent co-localization of hTfR-EGFP and PE-conjugated anti-hTfR mAb in living cells demonstrated the trafficking of mAb-receptor complexes through the endosomes followed by segregation of part of the mAb and receptor at the late stages of endocytosis. The CHO-hTfR cells preferentially took up anti-hTfR mAb conjugated nanoparticles. This CHO-hTfR cell line makes it feasible for accurate evaluation and visualization of intracellular trafficking of therapeutic agents conjugated with transferrin or Abs targeting the hTfRs.

Antitumor effects obtained by autologous Lewis lung cancer cell vaccine engineered to secrete mouse interleukin 27 by means of cationic liposome.

Interleukin-27 (IL-27), a novel IL-6/IL-12 family cytokine, plays an important role in the early regulation of Th1 responses. The cytokine IL-27 can exert a variety of immune-regulatory functions including cytotoxic T lymphocyte (CTL), CD4+, CD8+ T lymphocytes activation and interferon-γ (IFN-γ) production. In this study, we developed an effective and gene modified tumor cell vaccine. Lewis lung cancer cell LL/2 transfected with the DOTAP:cholesterol cationic liposome could express the mouse IL-27 (mIL-27) gene at a relative high level. The resultant transfectants were then irradiated with X-ray and used as a tumor cell vaccine. This tumor cell vaccine not only contained tumor associated antigen (TAA) of LL/2 cells but also secreted mIL-27 which could induce immune response in mice. The mice vaccinated with LL/2-mIL-27 performed strong tumor inhibiting effect accompanied with a high IFN-γ production. Both CD4+ and CD8+ T lymphocytes were significantly elevated in these mice vaccinated with LL/2-mIL-27 cell vaccine. Moreover, after depletion of CD4+, CD8+ T lymphocytes by injection of antibodies against CD4 and CD8, the vaccinated mice inoculated with autologous LL/2 cells were not protected from tumor challenge. In contrast, vaccinated mice inoculated with autologous LL/2 cells were treated with antibody against natural killer (NK)cells or normal rat IgG still possessed strong antitumor activity. Our data suggested that DOTAP:cholesterol cationic liposome was quite useful in generating an autologous tumor cell vaccine and mIL-27 could be therapeutically used to potentiate the host antitumor immunity.

Enhancement of cisplatin sensitivity in lung cancer xenografts by liposome-mediated delivery of the plasmid expressing small hairpin RNA targeting Survivin.

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is abundantly expressed in a variety of cancer cells, including lung cancer cells, resulting in low sensitivity of these cells to various apoptotic stimuli; Cisplatin (CDDP), a commonly used chemotherapeutic agent of several cancers, has a major limitation because of its toxicity at high concentration. In the present study, we constructed a plasmid encoding Survivin shRNA to knockdown survivin with low dose DDP both in vitro and in vivo. The specificity and potency of the shRNA were validated by western blot, flow cytometric and MTT in H292 lung cancers cells. In vivo, therapy experiments were conducted on nude mice bearing H292 xenograft tumors. The Survivin shRNA expression plasmid was administered systemically in combination with low-dose CDDP on a frequent basis. Assessments of angiogenesis, cell proliferation and apoptosis were performed by using immunohistochemistry against CD31, Ki67 and TUNEL assays, respectively. The results revealed that treatment with the Survivin shRNA plus low-dose CDDP reduced volume by approximately 83.13% compared with the blank control (P < 0.01), accompanied with angiogenesis inhibition (p < 0.01), tumor cell proliferation suppression (p < 0.05) and apoptosis induction (p < 0.01). Moreover, combination treatment also significantly reduced the mean tumor volume compared with other treatment alone (p < 0.05). Taken together, our study suggested that silencing of survivin sensitized H292 lung cancer cells to chemotherapy of CDDP, suggesting potential applications of the combined approach in the treatment of lung cancer.