The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer

Abstract

Background

The peritoneum is one of the most frequent metastatic sites in pancreatic cancer patients, and peritoneal dissemination makes this disease refractory due to aggressive progression and chemoresistance. Although the role of the tumor microenvironment in cancer development is recognized, the correlation between the peritoneal environment and refractoriness of peritoneal dissemination remains unclear. The intraperitoneal tumor-microenvironment and its potential role in the progression of peritoneal dissemination and chemo-refractoriness, focusing especially on macrophages, were investigated.

Materials and methods

Peritoneal washes were obtained from pancreatic cancer patients, and cellular components were subjected to immunofluorescence assays. The effects of macrophages induced from monocytic THP-1 cells on pancreatic cancer cells were examined in co-culture conditions. The in vivo effects of macrophages on tumor growth and chemo-sensitivity were investigated by subcutaneously or intraperitoneally co-injecting cancer cells with macrophages into mice.

Results

CD204-positive macrophages were present along with cancer cells in the peritoneal washes. In in vitro co-culture, tumor-associated macrophages affected pancreatic cancer cells, induced the epithelial-to-mesenchymal transition (EMT), and made them more resistant to chemotherapeutic agents. M2 macrophages promoted growth of both subcutaneous tumors and peritoneal dissemination in mice. Furthermore, co-inoculation of M2 macrophages conferred chemoresistance in the peritoneal dissemination mouse model, which significantly shortened their survival.

Conclusion

Intraperitoneal tumor-associated macrophages potentially play an important role in promotion of peritoneal dissemination and chemoresistance of pancreatic cancer via EMT induction.

https://ift.tt/2rxRVGR

Colon and Rectal Surgery Regional Society Meetings

No abstract available

https://ift.tt/2PvE9y1

Biomechanical Comparison of Three Different Intramedullary Nails for Fixation of Unstable Basicervical Intertrochanteric Fractures of the Proximal Femur: Experimental Studies

Objectives. This biomechanical study was conducted to compare fixation stability of the proximal fragments and their mechanical characteristics in proximal femur models of unstable basicervical IT fractures fixed by cephalomedullary nailing using 3 different types of the femoral head fixation. Methods. A total of 36 composite femurs corresponding to osteoporotic human bone were used. These specimens were fixed with Gamma 3 (hip screw type; group 1) in 12, Gamma 3 U-blade (screw-blade hybrid type; group 2) in 12, and proximal femoral nail antirotation-II (helical blade type; group 3) in 12, respectively, and an unstable basicervical IT fracture was created by an engraving machine. After preloading and cyclic loading, the migration of the proximal fragment according to 3 axes was assessed by the stereophotogrammetric method and the migration of screw or blade tip within the femoral head was measured radiographically. Next, the vertical load was continued at a speed of 10 mm/min until the construct failure occurred. Finite element analysis was additionally performed to measure the stress and compressive strain just above the tip of screw or blade within the femoral head. Results. The rotational change of the proximal fragment according to the axis of screw or blade was much greater in group 1 than in groups 2 and 3 (p=0.016 and p=0.007, respectively). Varus collapse was greater in group 3 than in group 2 (p=0.045). Cranial and axial migration of screw or blade within the femoral head were significantly greater in group 3 than in both group 1 (p=0.001 and p=0.002, respectively) and group 2 (p=0.002 and p=0.016, respectively). On finite element analysis, group 3 showed the highest peak von-Mises stress value (13.3 MPa) and compressive strain (3.2%) just above the tip of the blade within the femoral head. Meanwhile, groups 1 and 2 showed similar results on two values. Conclusions. Screw-blade hybrid type and blade type would be more effective in minimizing rotation instability of the proximal fragment in unstable basicervical IT fractures. However, varus collapse of the proximal fragment and cranial and axial migration within the femoral head were greater with blade type than screw-blade hybrid type.

https://ift.tt/2zMlQ2P

Radioprotective Properties of Pterocarpus santalinus Chloroform Extract in Murine Splenic Lymphocytes and Possible Mechanism

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 10, Page 427-437, December 2018.


https://ift.tt/2zT8GRv

Progression of Central Nervous System Metastases in Advanced Nonsmall Cell Lung Cancer Patients Effectively Treated with First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 10, Page 421-426, December 2018.


https://ift.tt/2zSODCF

The impact of the tumor shrinkage by initial EGFR inhibitors according to the detection of EGFR -T790M mutation in patients with non-small cell lung cancer harboring EGFR mutations

Abstract

Background

The EGFR-T790M mutation is clinically detected using re-biopsy in approximately 50% of patients with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) who harbor EGFR mutations. However, little is known about the population of NSCLC patients who develop acquired resistance due to the T790M mutation. In this study, we focused on the emergence of the T790M mutation and analyzed patients refractory to initial EGFR-TKIs with successful re-biopsy samples.

Methods

Seventy-eight advanced NSCLC patients with EGFR mutations who had successful re-biopsy samples after resistance to initial EGFR-TKI treatment were enrolled at 5 institutions in Japan. We validated the association between the emergence of the T790M mutation and their clinical profiles.

Results

Thirty-nine patients tested positive for T790M and 39 tested negative in the re-biopsy samples. The objective response rate to initial EGFR-TKIs was higher in patients with the T790M mutation than in those without the mutation (89.7% versus 51.2%, p < 0.001). Moreover, there was a significant difference in the maximal tumor shrinkage rate relative to baseline in T790M-positive tumors compared with T790M-negative tumors (42.7% versus 24.0%, p = 0.001). Multivariate analysis demonstrated that the maximum tumor shrinkage rate was a significant predictive factor for the detection of the T790M mutation (p = 0.023, odds ratio 1.03, 95% confidence interval 1.00–1.05).

Conclusions

Our retrospective observations suggested that the maximum tumor shrinkage rate with initial EGFR-TKI treatment might be one of the promising predictive biomarkers for emerging refractory tumors with the EGFR-T790M mutation.

https://ift.tt/2SEpl2o

Bioinformatics Analysis Reveals Potential Candidate Genes for Different Glioma Subtypes (Astrocytoma, Ependymoma, and Oligodendroglioma)

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 10, Page 478-490, December 2018.


https://ift.tt/2PwzVWW