Survivin and Telomerase as Radiotherapeutic Response Predictors of Subjects with Stage IIIB Cervical Squamous Cell Carcinoma

BACKGROUND: Cervical cancer is one of the most prevalent cancers in women. Even with similar clinicopathologic features, radiotherapy outcomes are still vary among patients. This research was conducted to measure radiotherapy responses on cervical cancer patients by using Survivin, Telomerase and Cytochrome C.METHODS: Subjects who matched the criteria were selected and requested to fill questionnaires. Subjects were then evaluated with magnetic resonance imaging (MRI) pre- and post-3D conformal radiotherapy. Histopathological study was conducted using resected tumors to determine the differentiation type. Enzyme-linked Immunosorbent Assays for detection of Survivin, Telomerase and Cytochrome C was performed using the resected tumors as well.RESULTS: There were 76 patients in this study. Mean ofage was 50 and diameter of tumor size was 5.35 cm. Mean levels of Survivin, Telomerase and Cytochrome C were 632.82 pg/mL, 5.59 pg/mL and 204.75 ng/mL, respectively. There were significant correlations between radiotherapy response and Survivin (p=0.041) or Telomerase (p=0.022). Subjects with lower Survivin level (<932 pg/mL) had higher 1-year survival rate (63%) than subjects with higher Survivin level (50%). Similar results were obtained for subjects with lower Telomerase level (<5.75 pg/mL), who had higher 1-year survival rate (60%) than subjects with higher Telomerase level (43%).CONCLUSION: Since radiotherapy response is significantly correlated with Survivin and Telomerase levels and subjects with lower Survivin or Telomerase level have higher 1-year survival rate, it can be suggested that Survivin and Telomerase could be potential predictors of radiotherapeutic response for subjects with stage IIIB cervical squamous cell carcinoma.KEYWORDS: cervical cancer, radiotherapy Survivin, Telomerase, Cytochrome

Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer

Objectives: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. Methods: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. Results: Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). Conclusions: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer

Combining oncolytic virus and radiation therapy for cancer management

Cancer has caused a tremendous burden in developing countries. Oncolytic virus (OV) therapy is an emerging modality with the potential to be a single or combination agent with radiation therapy (RT). Following entry of OV to the cell, OV will replicate and assemble before exiting from tumor cells. Construction of OV can be done by modifying the capsid, genome, and chemical material of viruses. Irradiation will induce double-strand breaks, and further integration of OV with DNA damage response pathway will interact with the MRE11-Rad50-Nbs1 complex to regulate the mobilization of E4 open reading frame 6, protein phosphatase 2A, poly(ADP-ribose) polymerase, apoptosis-inducing factor, and topoisomerase-IIβ-binding protein 1. Degradation of DNA-dependent protein kinase catalytic subunits via human simplex virus-1-infected cell polypeptide 0 will inhibit DNA repair. OV and RT have a synergistic interaction to cause viral oncolysis and upregulation of immune response. In the clinical setting, most studies have demonstrated that OV is a safe treatment with less toxicity. Moreover, OV + RT resulted in longer median survival (62.4 vs. 37.7 weeks) in malignant glioma

Protein Intake, Prognostic Nutritional Index and Quality of Life in Head and Neck Cancer Patients Undergoing Radiotherapy

BACKGROUND: It has not been well understood whether the quality and quantity of protein intake could affect the quality of life. Quality of life is associated with nutritional status, but the usage of prognostic nutritional index (PNI) to reflect quality of life of head and neck cancer patients undergoing radiotherapy also still has not been widely studied. METHODS: A cross sectional study was performed in 61 head and neck cancer patient undergoing radiotherapy. The quantity and quality of protein intake were obtained using semiquantitative food frequency questionnaire (FFQ) which was analized by analyzed using Nutrisurvey 2007, PNI was obtained using a calculation of Onodera’s formula based on laboratory data of serum albumin and total lymphocyte count (TLC), and domains of quality of life were obtained from the interview of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and EORTC Quality of Life Head and Neck module (QLQ-H&N35) and then calculated to get each domain’s score on quality of life. RESULTS: Patient’s median of total protein intake was 1.42 (0.26-4.11) g/kg/day. The median of PNI was 45.9 (29.4- 54.2). Quantity of protein intake was significantly correlated with several symptoms domain of quality of life. PNI was also significantly correlated with one functional domain and two symptom domains of quality of life. This study did not show a significant correlation between quantity and quality of protein intake with PNI. CONCLUSION: PNI has the potential to reflect quality of life of head and neck cancer patients. Future studies might be beneficial to show the usage of PNI to reflect quality of life, especially involving the progressivity of quality of life. KEYWORDS: animal protein, chemoradiotherapy, cachexia, quality of lif