Correlation of Preoperative Ki67 and Serum CA15.3 Levels with Outcome in Early Breast Cancers - a Multi Institutional Study

Rasmy, A,Abozeed, W,Elsamany, S,El Baiomy, M,Nashwa, A,Amrallah, A,Hasaan, E,Alzahrani, A,Faris, M,Alsaleh, K,AlFaraj, A Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

Elsamany, Shereef,Elmorsy, Soha,Alzahrani, Abdullah,Rasmy, Ayman,Abozeed, Waleed N,Mohammed, Amrallah A,Sherisher, Mohamed A,Abbas, Mohammed M,Mashhour, Miral Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI=1.28-13.16, p=0.018) and a lower pathological stage (OR=3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI=1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

Thyroid Transcription Factor-1 Expression in Advanced Non-Small Cell Lung Cancer: Impact on Survival Outcome

Elsamany, Shereef Ahmed,Al-Fayea, Turki M,Alzahrani, Abdullah Said,Abozeed, Waleed Nabeel,Darwish, Waseem,Farooq, Mian Usman,Almadani, Ahmed Salahuddin,Bukhari, Esraa Ahmed Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Background: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (${\leq}60$ vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. Results: A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7 months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed-containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs 5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS. Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were predictors of worse OS. Conclusions: Pemetrexed-containing therapy significantly improved PFS while OS was improved in EGFR mutant patients. Female patients had better PFS and OS. TTF1 expression was not a prognostic marker in advanced non-squamous NSCLC.

Methylation of SFRPs and APC Genes in Ovarian Cancer Infected with High Risk Human Papillomavirus

Al-Shabanah, Othman Abdulla,Hafez, Mohamed Mahmoud,Hassan, Zeinab Korany,Sayed-Ahmed, Mohamed Mohamed,Abozeed, Waleed Nabeel,Alsheikh, Abdulmalik,Al-Rejaie, Salem Saleh Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Background: Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. Materials and Methods: DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. Results: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. Conclusion: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.

Synthesis, structural, TD-DFT, and optical characteristics of indole derivatives

Almutlaq N.,Elshanawany Mahmoud M.,Sayed Mostafa,Younis Osama,Ahmed Mostafa,Wachtveitl Josef,Braun Markus,Tolba Mahmoud S.,Al-Hossainy Ahmed F.,Abozeed Amina A. 한국물리학회 2023 Current Applied Physics Vol.45 No.-

New compounds of (E)-1-(3-chloro-1H-indol-2-yl)-N-(4-methoxyphenyl)methanimine [Indol-M] and (E)-1-(4- (((3-chloro-1H-indol-2-yl)methylene)amino)phenyl)ethan-1-one [Indol-A] were synthesized and subsequently converted to thin films via physical vapor deposition technique. Numerous characterization techniques were used including FTIR, nuclear magnetic resonance, X-ray diffraction, scanning electron microscope, and optical spectroscopy. Additionally, the optimization using TD-DFTD/Mol3 and Cambridge Serial Total Energy Bundle (TD-FDT/CASTEP) was performed. The XRD and FTIR spectra recorded experimentally were confirmed by TD-DFT calculations, proving their molecular structure. As determined by XRD, the crystallite size of [Indol-M]TF and [Indol-A]TF is 72.26 and 62.05 nm, respectively. SEM image depicts a one-dimensional morphological structure made up of tightly packed nanorods. The direct optical energy bandgaps computed using Tauc’s equation for the [Indol-M]TF and [Indol-A]TF are 4.49 eV and 3.31 eV, respectively. As predicted by CASTEP TD-DFT, the optical properties agree well with the experimental values. [Indol-M]TF and [Indol-A]TF present good candidates for optoelectronics and solar cell applications.