Journal of Analytical Oncology

Adverse Effects of Bevacizumab During Treatment for Metastatic Colorectal Cancer 
Pages 24-29
Kenji Ina, Ryuichi Furuta, Takae Kataoka, Sayaka Sugiura, Satoshi Kayukawa, Takayuki Kanamori, Takaki Kikuchi, Megumi Kabeya, Satoshi Hibi and Shu Yuasa
Published: 12 February 2015

Abstract: Objective:Bevacizumab has been increasingly used in combination chemotherapy for the treatment of metastatic or recurrent colorectal cancer.The aim of this report is to underline the possible risks associated with bevacizumab use.

Methods:Between July 2005 and March 2013, a total of 130 patients with metastatic colorectal cancer who received oxaliplatin as first-line chemotherapy were divided into 2 groups those treated with bevacizumab (group A) and those without (group B), and compared. The primary endpoint was to clarify the profile of bevacizumab - induced adverse effects. Secondary endpoints examined therapeutic effects, including overall survival (OS).

Results:The incidence of major side effects was almost equivalent, except for bleeding, between the 2 groups. With regard to the therapeutic effects, 1 patient in group A showed complete disappearance of multiple lung metastases without any evidence of recurrence. The median OS was 926 days (95% confidence interval [CI], 756 - 1257) in group A and 534 days (95% CI, 421 – 621) in group B (p < 0.01).

Conclusion:The results demonstrate that bevacizumab prolonged survival in these patients although there was an increased risk of clinically significant bleeding.

Keywords: Bevacizumab, colorectal cancer, bleeding, interstitial pneumonitis.
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Brain Metastases: State of the Art and Innovative Targeted Therapies
Pages 113-121
Maria Caffo, Lucia Merlo, Valeria Barresi, Ema Tot and Gerardo Caruso
Published: 07 September 2015

Abstract: Brain metastasis represents the most common intracranial tumor. The metastatic process involves the migration of a cancer cell from the bulk tumor into the surrounding tissue, extravasation from the blood vessels into the tissues, and formation of a secondary tumor. Patients affected by brain metastases are in need of a multidisciplinary approach that generally includes surgical treatment and radiation therapy. Conventional chemotherapies have generally produced disappointing results, possibly due to their limited ability to penetrate the blood-brain barrier. With new data regarding the biology of brain metastases, novel targeted therapies can be considered interesting and promising therapeutic options. Targeted therapies showed improved survival in patients with metastatic disease. The advent of new technologies such as graphene nanoparticles has led to the discovery of novel pathways that allow a better delivery of the therapeutic compounds to the brain.

Keywords: Angiogenesis, brain metastases, graphene, microRNA, nanoparticles, targete therapy.
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IQGAP2 Displays Tumor Suppression Functions
Pages 86-93
Yanyun Xie, Anil Kapoor, Hao Peng, Jean-Claude Cutz, Lijian Tao and Damu Tang
Published: 13 May 2015

Abstract: The IQGAP family consists of evolutionarily conserved scaffold proteins, IQGAP1, IQGAP2, and IQGAP3. IQGAP1 is 62 and 59% identical at the level of amino acid sequence to IQGAP2 and IQGAP3, respectively. IQGAPs possess the same domain structure with the individual motifs being highly homologous among IQGAPs. The conservation is even higher between IQGAP1 and IQGAP2. While the WW domain is 30% identical, other four motifs are 70 to 93% identical between both IQGAPs. Despite the high level identity, IQGAP1 and IQGAP2 display opposite impact on tumorigenesis. IQGAP1 is the most thoroughly examined, and clearly promotes cancer formation via its scaffold functions in facilitating the Raf-Mek-Erk and Wnt signalling. On the other hand, IQGAP2 is much less investigated and suppresses tumorigenesis. We will review the evidence that supports IQGAP2 reducing tumorigenesis, discuss its tumour suppression in the context of our updated knowledge on IQGAP1, and outline some future directions. Our emphasis will be placed on prostate cancer.

Keywords: IQGAP2, tumor suppression, Akt, hepatocellular carcinoma, gastric cancer, prostate cancer.

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Cell Proliferation Measured by Ki67 Staining and Correlation to Clinicopathological Parameters in Operable Breast Carcinomas from Vietnamese and Swedish Patients
Pages 58-68
Vu Hong Thang, Lambert Skoog, Nguyen Ba Duc, Ta Thanh Van and Edneia Tani
Published: 13 May 2015

Abstract: Background: Cell proliferation measured by Ki67 has recently been shown to be a prognostic and predictive factor in breast cancer. The aim of this study was to compare cell proliferation determined by Ki67 expression with different clinicopathologic parameters among Vietnamese and Swedish women with breast cancer.

Materials and Methods:The study was based on series of breast cancer from Vietnamese patients treated in the National Cancer Hospital in Hanoi, Vietnam and from Swedish patients treated in the Karolinska Hospital, Stockholm, Sweden. Cell proliferation was measured by Ki67 staining in an automated procedure and was expressed as percentage of stained tumor cell nuclei.

Results:The distribution and mean of Ki67 indices from Vietnamese patients were similar to those estimated from Swedish patients, 27.7% (±17.1%) vs. 26.9% (±23.1%). There were no differences between the two series of patients with respect to proliferation index and age, tumor size and lymph node status. The mean Ki67 indices were higher in high grade tumors in both series. In addition, Swedish patients had significantly higher Ki67 indices in tumors associated with other poor prognostic factors as compared to Vietnamese, 52.8% vs. 31.9% in ER(-) tumors, 39.6% vs. 30.7% in PgR(-) tumors and 40.1% vs. 28.3% in HER2 amplified tumors, respectively.

Conclusions: The cell proliferation index in breast cancers was similar in the Vietnamese and Swedish series. High proliferation was associated with poor prognostic factors such as high grade, hormone receptor negativity and HER2 amplification.

Keywords: Breast cancer, Immunohistochemistry, Ki67 staining, biomarkers, comparative study.

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Journal of Analytical Oncology

Neuroendocrine Differentiation and Epithelial to Mesenchymal Transition in Prostate Cancer: cAMP-Dependent Signaling as a Therapeutic Target
Pages 171-177
Charles E. Myers
Published: 11 December 2015

Abstract: Prostate cancer exhibits both epithelial to mesenchymal transition and neuroendocrine differentiation. The major barrier to targeting epithelial to mesenchymal transition is that it is heavily involved with normal biology, such as wound repair. In prostate cancer, cAMP can trigger both neuroendocrine differentiation and epithelial to mesenchymal transition in a Snail-dependent manner We will review inhibition of cAMP-signaling as a target for drug development with the goal of simultaneously blocking both neuroendocrine differentiation and epithelial to mesenchymal transition in a tissue and tumor selective manner.

Keywords: Androgen-independent prostate cancer, protein kinase A, adenylyl cyclase, Snail, cyclic nucleotide phosphodiesterase, heterotrimeric G protein.
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