Gankyrin induces STAT3 activation in tumour microenvironment and sorafenib resistance in hepatocellular carcinoma

Abstract

Most hepatocellular carcinomas (HCCs) develop as a result of chronic liver inflammation. We have shown that the oncoprotein gankyrin is critical for inflammation-induced tumourigenesis in the colon. Although the in vitro function of gankyrin is well known, its role in vivo remains to be elucidated. We investigated the effect of gankyrin in tumour microenvironment of mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrin^f/f) and gankyrin deletion both in liver parenchymal and non-parenchymal cells (Mx1-Cre;gankyrin^f/f). Gankyrin upregulates VEGF expression in tumor cells. Gankyrin binds to Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), mainly expressed in liver non-parenchymal cells, resulting in phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3). Gankyrin deficiency in non-parenchymal cells, but not in parenchymal cells, reduced STAT3 activity, interleukin (IL)-6 production, and cancer stem cell marker (Bmi1 and epithelial cell adhesion molecule [EpCAM]) expression, leading to attenuated tumourigenic potential. Chronic inflammation enhances gankyrin expression in the human liver. Gankyrin expression in the tumour microenvironment is negatively correlated with progression-free survival in patients undergoing sorafenib treatment for HCC. Thus, gankyrin appears to play a critical oncogenic function in tumour microenvironment and may be a potential target for developing therapeutic and preventive strategies against HCC.

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Prevalence of and risk factors for enlarged perivascular spaces in adult patients with moyamoya disease

Enlarged perivascular spaces (EPVS) are often observed with magnetic resonance imaging in patients with small vessel disease. However, the risk factors, radiological features, and clinical relevance of EPVS in...

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Intensity-modulated radiotherapy combined with paclitaxel and platinum treatment regimens in locally advanced esophageal squamous cell carcinoma

Abstract

Purpose

This study was conducted to investigate the efficacy and toxicity of combination treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy with paclitaxel plus different platinum agents in locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

This retrospective study enrolled 242 patients treated with paclitaxel (135 mg/m²) plus platinum regimens. According to the different platinum agents used, patients were classified into: cisplatin 80 mg/m² (CP), nidaplatinum 80 mg/m² (NP), lobaplatin 35 mg/m² (LP), and oxaliplatin 135 mg m² (OP) groups, and survival and toxicity rates between the four groups were compared. The median overall survival (OS) was 31.1 months.

Results

No significant differences were observed among the CP, NP, LP, and OP groups with regard to 3-year survival rates (46.2, 56.4, 45.7, and 29.0%, respectively). A stratified analysis indicated that 3-year survival rates were significantly lower in the OP group. Renal toxicities and gastrointestinal reactions were more frequent in the CP group than in the other three groups. Three-year survival rates were similar among patients receiving 2, 3, or ≥4 cycles of chemotherapy (40.1, 49.5, and 50.8%, respectively). Multivariate analysis indicated that tumor volume and maximum diameter of metastatic lymph nodes might be independent prognostic factors.

Conclusion

Paclitaxel plus nidaplatinum or lobaplatin is recommended in locally advanced ESCC due to their satisfying therapeutic effects and less toxicity. Tumor volume and maximum diameter of metastatic lymph nodes are independent prognostic factors in ESCC patients receiving IMRT and concurrent chemotherapy.

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Nanosponge Tunability in Size and Crosslinking Density

This article describes a process for tuning the size and crosslinking density of covalently crosslinked nanoparticles from linear polyesters containing pendant functionality. By tailoring synthesis parameters (polymer molecular weight, pendant functionality incorporation, and crosslinker equivalents), a desired nanoparticle size and crosslinking density can be achieved for drug delivery applications.

http://ift.tt/2u8QGO8

Easy Manipulation of Architectures in Protein-based Hydrogels for Cell Culture Applications

Different methods to manipulate three-dimensional architecture in protein-based hydrogels are evaluated here with respect to material properties. The macroporous networks are functionalized with a cell-adhesive peptide, and their feasibility in cell culture is evaluated using two different model cell lines.

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A Method for Characterizing Embryogenesis in Arabidopsis

This protocol outlines a method for observing embryogenesis in Arabidopsis via ovule clearance followed by the inspection of embryo pattern formation under a microscope.

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Complementary and Alternative Medicine and Their Effect on Global Health

By Nathan Douthit

According to the World Health Organization (WHO), the use of complementary and alternative medicine (CAM) is on the rise. The US National Institute of Health defines complementary medicine as non-mainstream, non-western practice used together with conventional medicine, whereas alternative medicine is defined as the same used instead of conventional medicine. The WHO also offers a definition of traditional medicine (TM) as

 

"the sum total of the knowledge, skill, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness"

 

Globally, TM and CAM are much more accessible to patients than conventional medicine. Therefore the WHO strategy for TM and CAM revolves around research into these alternative techniques as well as education and training for their practice. However, recent years have seen a surge in popularity for CAM in western countries as well, with many being willing to pay out of pocket for these treatments. Integration of these practices into national health systems can allow them to be regulated and safely practiced along with conventional medicine for the best possible outcomes.

 

Unfortunately, the case report "Consequences of delivery at home in a woman without prenatal care" by Kumar et al reveals the danger associated with lack of education, training and regulation. We are told,

 

"The patient denied having any allopathic prenatal care during the current pregnancy. She denied having gestational diabetes testing, blood work or detailed ultrasonography, but she stated that she had undergone regular Doppler and bedside ultrasound scans by her midwife."

 

Despite having had three prior caesarean sections, the woman chose a direct entry midwife, defined as follows.

 

"Direct entry midwives are defined as independent practitioners educated in midwifery through self-study, apprenticeship, a mid- wifery school or a university-based programme…. In the USA, licensure and training varies per state, with ∼50% of states not requiring licensure for direct entry midwives. Most patients are unaware of the difference between [direct entry and certified nurse midwives] and may not receive the necessary guidance to choose the appropriate provider for their needs."

 

This patient's past medical history puts her at increased risk, and her poor outcome is the result of lack of education, regulation and information in this alternative delivery.

 

BMJ Case Reports invites authors to publish cases regarding the effects both positive and negative of complementary and alternative medicine. Global health case reports can emphasize:

-Successful integration of CAM into national health systems

-Research on CAM that has proved useful in patient care

-Partnerships between practitioners of CAM and practitioners of conventional medicine that have improved patient outcomes

-Use of CAM causing delays in care, inappropriate care or worsening of patient outcomes.

Manuscripts may be submitted by students, physicians, nurses or other medical professionals to BMJ Case Reports. For more information, review the blog on how to write a global health case report.

Read more about CAM at BMJCR:

–Factors affecting illness in the developing world: chronic disease, mental health and traditional medicine cures

–Why tuberculosis control programmes fail? Role of micro level and macro level factors: an analysis from India

–Delayed diagnosis of pulmonary tuberculosis in a 13 year old Malawian boy

Selected References on CAM from other sources:

1. World Health Organization. WHO traditional medicine strategy: 2014–2023. [Internet] WHO; 2016 (cited 07 July 2017). Available from: http://ift.tt/2ws7foX strategy14_23/en/
2. Complementary, Alternative, or Integrative Health: What's In a Name? [Internet]. National Center for Complementary and Integrative Health. U.S. Department of Health and Human Services; 2016 [cited 07 July 2017]. Available from: http://ift.tt/2vzN5x4
3. Abdullahi AA. Trends and challenges of traditional medicine in Africa. Afr J Tradit Complement Altern Med 2011;8(Suppl 5):115–23.
4. Lee CAL. Alternative Medicine and Global Health [Internet]. Franklin Humanities Institute. Duke University; 2011 [cited 07 July 2017]. Available from: http://ift.tt/2wsh7PC

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