华蟾素胶囊联合CAF方案治疗中晚期乳腺癌的临床效果分析

目的:探讨华蟾素联合CAF方案治疗中晚期乳腺癌的临床疗效。方法:选取2015年2月至2017年2月三峡大学第三临床医学院葛洲坝集团中心医院收治的中晚期乳腺癌患者中筛选出41例,参照随机分配原则将其分为2组,联合组(20例)采用华蟾素联合CAF化疗治疗,CAF化疗组(21例)单纯给予CAF化疗治疗。治疗后3个月,评价和比较2组的近期和远期疗效、生命质量的改善情况、疼痛缓解率以及不良反应的发生情况。结果:治疗后3个月,联合组治疗有效率(75.00%)明显高于CAF化疗组(52.38%)(P0.05);联合组平均生存期为12个月,CAF化疗组为11个月,2组差异无统计学意义(P0.05)。联合组的生命质量提高率(45.00%)明显高于CAF化疗组(23.81%)(P0.05)。骨髓抑制、脱发和胃肠道反应为2组主要的不良反应,联合组胃肠道反应发生率(10.00%)明显低于CAF化疗组(23.81%)(P0.05),联合组脱发发生率(20.00%)也明显低于CAF化疗组(38.10%)(P0.05)。治疗后联合组疼痛改善率(65.00%)优于CAF化疗组(52.81%)(P0.05)。结论:华蟾素联合CAF化疗方案治疗中晚期乳腺癌具有较好的近期效果,并能够缓解疼痛、改善患者的生命质量,且不良反应较少。     

Comparative evaluation of surgical modalities for coverage of gingival recession: An Armed Forces Medical College perspective

Background

Esthetics represents an inseparable part of today''s oral therapy, and several procedures have been proposed to preserve or enhance it. Gingival recessions may cause hypersensitivity, impaired esthetics and root caries. Keeping in mind patient''s desire for improved esthetics and other related problems, every effort should be made to achieve complete root coverage.

Methods

Different types of modalities have been introduced to treat gingival recession including displaced flaps, free gingival graft, connective tissue graft, different type of barrier membranes and combination of different techniques. The aim of this study was to compare the commonly used techniques for gingival recession coverage and evaluate the results obtained. 73 subjects were selected for the present study who were randomly divided into four groups and were followed at baseline and 180 days where following parameters were recorded: (a) Assessment of gingival recession depth (RD); (b) Assessment of pocket depth (PD); (c) Assessment of clinical attachment level (CAL) and (d) Assessment of width of attached gingiva (WAG).

Results

Results of this study showed statistically significant reduction of gingival recession, with concomitant attachment gain, following treatment with all tested surgical techniques. However, SCTG with CAF technique showed the highest percentage gain in coverage of recession depth as well as gain in keratinized gingiva. Similar results were obtained with CAF alone. The use of GTR and other techniques showed less predictable coverage and gain in keratinized gingiva.

Conclusion

Connective tissue grafts were statistically significantly superior to guided tissue regeneration for improvement in gingival recession reduction.     

Carcinoma-associated fibroblasts: orchestrating the composition of malignancy

The tumor stroma is no longer seen solely as physical support for mutated epithelial cells but as an important modulator and even a driver of tumorigenicity. Within the tumor stromal milieu, heterogeneous populations of fibroblast-like cells, collectively termed carcinoma-associated fibroblasts (CAFs), are key players in the multicellular, stromal-dependent alterations that contribute to malignant initiation and progression. This review focuses on novel insights into the contributions of CAFs to disease progression, emergent events leading to the generation of CAFs, identification of CAF-specific biomarkers predictive of disease outcome, and recent therapeutic approaches aimed at blunting or reverting detrimental protumorigenic phenotypes associated with CAFs.     

Immunomodulatory aspects in the progression and treatment of oral malignancy

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.     

The hinge region in androgen receptor control

The region between the DNA-binding domain and the ligand-binding domain of nuclear receptors is termed the hinge region. Although this flexible linker is poorly conserved, diverse functions have been ascribed to it. For the androgen receptor (AR), the hinge region and in particular the (629)RKLKKL(634) motif, plays a central role in controlling AR activity, not only because it acts as the main part of the nuclear translocation signal, but also because it regulates the transactivation potential and intranuclear mobility of the receptor. It is also a target site for acetylation, ubiquitylation and methylation. The interplay between these different modifications as well as the phosphorylation at serine 650 will be discussed here. The hinge also has an important function in AR binding to classical versus selective androgen response elements. In addition, the number of coactivators/corepressors that might act via interaction with the hinge region is still growing. The importance of the hinge region is further illustrated by the different somatic mutations described in patients with androgen insensitivity syndrome and prostate cancer. In conclusion, the hinge region serves as an integrator for signals coming from different pathways that provide feedback to the control of AR activity.     

HOXA10与连续TTAT基序结合抑制p／CAF表达

目的:转录因子HOXA10在胚胎着床和子宫内膜蜕膜化过程中发挥重要作用.p/CAF是HOXA10新的靶基因,文章旨在筛选并鉴定p/CAF启动子区与HOXA10功能性结合的序列. 方法:制备重组腺病毒HOXA10(ad-HOXA10),用于感染人子宫内膜间质细胞(hESC);构建p/CAF启动子区多种突变报告基因质粒;采用萤光素酶报告基因实验检测结合腺病毒介导的HOXA10基因过表达,分析hESC中HOXA10对p/CAF启动子转录活性的调控. 结果:获得滴度为2.4×1011ifu/mL的重组ad-HOXA10,对hESC的感染率达到80%以上.HOXA10通过结合连续的3个TTAT(-710～ -674nt)基序抑制p/CAF启动子活性,连续的3个TTAT基序的一级结构影响HOXA10的功能性结合. 结论:p/CAF启动子区连续的3个TTAT基序是HOXA10功能性结合所必须的,HOXA10可能通过调控p/CAF的表达来控制hESC的增殖与分化.     

Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant

Vaccines inducing cytotoxic T-cell responses are required to achieve protection against cancers and intracellular infections such as HIV and Hepatitis C virus. Induction of CD8+ T cell responses in animal models can be achieved by the use of viral vectors or DNA vaccines but so far without much clinical success. Here we describe the novel CD8+ T-cell inducing adjuvant, cationic adjuvant formulation (CAF) 09, consisting of dimethyldioctadecylammonium (DDA)-liposomes stabilized with monomycoloyl glycerol (MMG)-1 and combined with the TLR3 ligand, Poly(I:C). Different antigens from tuberculosis (TB10.3, H56), HIV (Gag p24), HPV (E7) and the model antigen ovalbumin were formulated with CAF09 and administering these vaccines to mice resulted in a high frequency of antigen-specific CD8+ T cells. CAF09 was superior in its ability to induce antigen-specific CD8+ T cells as compared to other previously described CTL-inducing adjuvants, CAF05 (DDA/trehalose dibehenate (TDB)/Poly(I:C)), Aluminium/monophosphoryl lipid-A (MPL) and Montanide/CpG/IL-2. The optimal effect was obtained when the CAF09-adjuvanted vaccine was administered by the i.p. route, whereas s.c. administration primed limited CD8+ T-cell responses. The CD4+ T cells induced by CAF09 were mainly of an effector-memory-like phenotype and the CD8+ T cells were highly cytotoxic. Finally, in a mouse therapeutic skin tumor model, the HPV-16 E7 antigen formulated in CAF09 significantly reduced the growth of already established subcutaneous E7-expressing TC-1 tumors in 38% of the mice and in a corresponding prophylactic model 100% of the mice were protected. Thus, CAF09 is a potent new adjuvant which is able to induce CD8+ T-cell responses against several antigens and to enhance the protective efficacy of an E7 vaccine both in a therapeutic and in a prophylactic tumor model.     

CAFs and TAMs: maestros of the tumour microenvironment

Many non‐tumour host cells such as inflammatory cells, fibroblasts, and endothelial cells are present in the tumour microenvironment and affect the malignant potential and chemo‐resistance of the tumour cells. Macrophages and fibroblasts are the main components of infiltrating stromal cells and are referred to as tumour‐associated macrophages (TAMs) and cancer‐associated fibroblasts (CAFs), respectively. TAMs and CAFs are reported to be involved in tumour progression, although their functions change to those of an anti‐tumour phenotype under specific conditions. Notably, recent work published in The Journal of Pathology by Hashimoto and colleagues provided critical evidence indicating the significance of collaboration between TAMs and CAFs for tumour progression. They showed that cell–cell interaction between these two cell types induced recruitment and activation of each other, and that the combined activities of these cells were involved in neuroblastoma progression. Although many research groups are now interested in the significance of stromal cells such as CAFs and TAMs for tumour progression, only a few studies have been published describing the cell–cell interactions of these cells. Cell–cell interactions of stromal cells potentially play important roles in tumour progression and should be a focus for further oncology research. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Maternal obesity induced by a ‘cafeteria’ diet in the rat does not increase inflammation in maternal,placental or fetal tissues in late gestation

IntroductionObesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation.MethodsMaternal obesity was established in rats by 8 weeks of pre-pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFα) and expression of inflammatory genes (Tnfα, Il-6, Il-1β, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation.ResultsDespite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL-6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver.ConclusionsMaternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation.