Cancer Science & Therapy

Objective: Anti-Angiogenic Therapies (AATs), targeting VEGF-VEGFR pathways, are being used as an adjuvant to normalize Glioblastoma (GBM) vasculature. Unexpectedly, clinical trials have witnessed transient therapeutic effect followed by aggressive tumor recurrence. In pre-clinical studies, targeting VEGFR2 with vatalanib, increased GBM growth under hypoxic microenvironment. There is limited understanding of these unanticipated results. Here, we investigated tumor cell associated phenotypes in response to VEGFR2 blockade.
Methods: Human U251 cells were orthotopically implanted in mice (day 0) and were treated with vehicle or vatalanib on day 8. Tumor specimens were collected for immunohistochemistry and protein array. Nuclear translocation of VEGFR2 was analyzed through IHC and western blot. In vitro studies were performed in U251 (p53 and EGFR mutated) and U87 (p53 and EGFR wild type) cells following vehicle or vatalanib treatments under normoxia (21% O2) and hypoxia (1% O2). Proliferation, cell cycle and apoptosis assays were done to analyze tumor cell phenotypes after treatments.
Results: Vatalanib treated animals displayed distinct patterns of VEGFR2 translocation into nuclear compartment of U251 tumor cells. In vitro studies suggest that vatalanib significantly induced nuclear translocation of VEGFR2, characterized in chromatin bound fraction, especially in U251 tumor cells grown under normoxia and hypoxia. Anti-VEGFR2 driven nuclear translocation of VEGFR2 was associated with increased cell cycle and proliferation, decreased apoptosis, and displayed increased invasiveness in U251 compared to U87 cells.
Conclusion: Study suggests that AAT-induced molecular and phenotypic alterations in tumor cells are associated with mutation status and are responsible for aggressive tumor growth. Therefore, mutation status of the tumor in GBM patients should be taken in to consideration before applying targeted therapy to overcome unwanted effects.

The burden of cancer taking a form of a chronic illness warrants a shift in the health care delivery to address the many neglected functional impacts (physical-psychosocial and occupational dysfunctions) from cancer. Balancing the current traditional medical care (that focuses on the tumour/illness), with the essential non-medical tasks of dayto- day participation and self-care tasks are both needed for cancer conditions that now requires care over indefinite period. This paper aims to highlight occupational-participation as an expansion of the international classification of functioning (ICF)’s concept of participation, to encapsulate a holistic approach for better functional outcomes and occupational wellbeing in the emerging field of cancer survivorship. Occupational-participation, a central construct in the field of Occupational Therapy, is the person’s engagement in work, play and daily living which is necessary for health and well-being. Cancer survivors can be empowered toward healthy occupational-participation to attain a healthy, ‘health-after-cancer’ status via a model of ‘occupationalparticipation for cancer survivorship’ (MOP.CS). The model is novel for addressing this missing link where its focus on occupational-participation living, can be used for designing seamless intervention programs for the connection to a “healthy-although-ill” living for cancer survivors.

Objective: To compare the prognostic value of positive lymph node number (LNN) and lymph node ratio (LNR) in stage III rectal cancer following neoadjuvant radiochemotherapy.

Methods: From 2008 to 2010, 99 rectal cancer cases in our hospital received neoadjuvant radiochemotherapy or radiotherapy. Radical surgery was performed after neoadjuvant therapy. LNN distinguished four stages of lymph node involvement by TNM stage system and LNR divided patients into quartiles. The prognosis value of LNN and LNR to the patients was evaluated by Kaplan-Meier method and Cox regression. We evaluated the prognosis value of LNN and LNR for those with inadequate lymph nodes (<12).

Results: The patients were staged according to lymph node number (LNN=1, 2 ≤ LNN ≤ 3, 4 ≤ LNN ≤ 6 and LNN ≥ 7) and lymph node ratio (LNR<0.075, 0.075 ≤ LNR<0.15, 0.15 ≤ LNR<0.35 and LNR ≥ 0.35). 3 year overall survival rates were different among different LNN groups and different LNR groups. Multivariate analysis showed that LNR ≥ 0.15 was an independent prognostic factor of overall survival (P=0.029). 26 patients with less than 12 lymph nodes harvest were divided into four groups (LNR<0.15, 0.15 ≤ LNR<0.25, 0.25 ≤ LNR<0.50 and LNR ≥ 0.50), LNR was proved to be a better predictor of survival. 3 year overall survival rates were significant different between LNR<0.50 and LNR ≥ 0.50 (P=0.018).

Conclusion: The study showed LNR was an independent prognostic factor for rectal cancer after neoadjuvant radiochemotherapy, LNR 0.15 was a cutoff point for overall survival. LNR might be a better prognostic factor than LNN, especially in patients with less than 12 lymph nodes harvest.

Fibroblast growth factors (FGF) are proteins that are involved in several biological and developmental processes. Cell proliferation, cell motility, cell survival, and angiogenesis are the fundamental mechanisms that are carried out by these growth factors. FGF ligands when to interact with their receptors-FGFRs, elicit certain signaling pathways that ultimately lead to precise regulated cellular responses. Alterations in FGF/FGFR signaling results in various types of abnormalities. The transition of normal signaling mode of FGFs/FGFRs to an unusual functional pattern causes neurological disorders, skeletal disorders, tumor progression and tumor neovascularization. Overexpression of FGFs and FGFRs has been correlated with advanced tumor forms, mainly prostate, mammary gland, bladder and renal cell carcinomas. These GFs and their receptors are among the fundamental mediators of tumor angiogenesis, others being VEGF, Ang-1, etc. Many pharmaceutical therapies have evolved in the past years to minimize the effects of FGF/FGFR and VEGF signaling, individually as well as simultaneously. Tyrosine kinase inhibitors are the most prominent compounds that have been investigated exclusively in phase I and II clinical trials. However, the applicability of developing therapeutic techniques needs a further illustration better to comprehend the complexity of the underlying mechanism and to provide patients with a better outcome

Background: The presence of tumor- infiltrating lymphocytes (TIL) within tumor epithelium or stroma of breast cancer is a surrogate of an immune response to cancer development, but their significance remains controversial. We conducted this study to evaluate the correlation of CD8+ (cytotoxic T) lymphocyte infiltration and Foxp3+ Tregs and tumor characteristics and their impact on recurrence in patients with invasive breast cancers.

Patients and methods: CD8+ T cells and Foxp3+ Tregs were detected by immunohistochemistry using the paraffin-embedded tumor tissues from 68 patients with stage (I to III) breast cancer. Clinicopathological data including patient’s age, tumor size and grade, stage, lymph node metastasis, estrogen and progesterone receptor status, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed.

Results: The decreased mean number of CD8+ T cells was significantly associated with tumors with lymph node metastasis (P=0.02), and immune-positivity of Ki-67 (P=0.00). The increased number of Foxp3+ Tregs was significantly correlated with tumors with lymph node metastasis (P=0.01) higher stage (stage III, P=0.03), and immune-positivity for Ki-67 (P=0.02).

Further analysis of the correlation using CD8+ T-cell/Foxp3+ Treg ratio showed significant correlation with tumors with lymph node metastasis(P=0.01), and immune-positivity of Ki-67 (P=0.00). Also, there were significant correlations between the increased Foxp3+Treg /CD4+ T-cell ratio and lymph node metastasis (P=0.00), and immune-positivity of Ki-67 (P=0.02).

Conclusions: Data showed that lymph node metastases, tumor stage, immunopositivity of Ki67, and nontriple- negative tumors were associated with high regulatory T-cell infiltration. The prognostic role of immunologic balance as a marker for recurrence must be evaluated more clearly in a larger study.