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Impacts of Climate Change on Fishes and Aquatic Organisms

Prof. Dr. Mona S. Zaki

Hydrobiology Department, National Research Center, Dokki, Giza, Egypt

drmonazaki@yahoo.com

Abstract: The world has seen an unprecedented rise in global temperature, and the number of those concerned is more than ever, and the coming years may have more global action to confront a phenomenon that threatens everyone, and we in Egypt should take care of this phenomenon As our coastal and low-lying, and our shores on the Mediterranean and Red Bahrain. And the thermal decline affects us in the medium and long term. There are threats of erosion of the beaches and up to the threat of delta, and we receive the Nile from its African sources and our sources of water threatened by drought in the case of climate change and global warming, which means more desertification. Hence we need Has led to a real revolution in the management of our high-value water resources in a densely populated country, which is blinded or seen in many ways, threatening us with great risks.

[Mona S. Zaki. Impacts of Climate Change on Fishes and Aquatic Organisms. Cancer Biology 2019;9(1):1-4]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 1. doi:10.7537/marscbj090119.01.

Keywords：Impact; Climate; Change; Fishes; Aquatic; Organism

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Oxidant / antioxidant parameters in breast cancer patients and its relation to VEGF, TGF-β or Foxp3 factors

Rasha A. A. Elsayed¹, Zeinab E. M. Hanafy¹, Motawa E. El-Housein², Hend Fouad Abd El Fattah³ and Effat Tharwat Lotfy²

¹Zoology Department Faculty of Science Al-Azhar University (Girl's), Egypt

² Unit of Biochemistry and Molecular Biology, Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt.

³Tissue culture and Cytogenetic Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt

dreffattharwat@gmail.com

Abstract: Background: Oxidative stress has been suggested as an important factor for initiation and progression of human breast cancer. The development and dissemination of solid tumors depends upon the formation of a vascular network to supply oxygen and nutrients (angiogenesis) that may be regulated by oxidative stress. The data regarding the status of oxidant / antioxidant parameters in high risk and breast cancer patients and its relation to VEGF, TGF-β or Foxp3 limited and conflicting. The aim of this study was to investigate the alterations in some oxidant and antioxidant enzyme defenses in the blood of patients with malignant breast tumor and benign breast disease. The relationship between oxidant/ antioxidant parameters and serum VEGF, TGF-β and Foxp3levels among patients with benign and malignant breast disease were also evaluated. Method: Ninety female serum samples of invasive breast carcinoma (all are grade II), high risk patients with benign breast lesions (fibroadenoma) patients and healthy control groups were analyzed for measurement of glutathione reduced (GSH), catalase (CAT), superoxide dismutase (SOD), Malondialdehyde (MDA) as well as nitric oxide (NO) levels were analyzed spectrophotometerically. The serum vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ) concentrations and human Fork head Box Protein p3 (Foxp3) levels were measured using ELISA technique. Result: Statistically, a highly significant decrease (p<0.001) in the serum levels of reduced glutathione (GSH) and catalase (CAT) were recorded in the high risk and breast cancer groups. Elevation in the serum superoxide dismutase (SOD), Malondialdehyde (MDA) and nitric oxide (NO) were also reported in both groups. These changes were more pronounced in the breast cancer group than the high risk group as compared to the control group values. Meanwhile, VEGF, TGF-β and FOXP3 revealed significantly elevated levels in the invasive breast carcinoma and high-risk groups as compared to healthy control group (p < 0.001) that was more detectable in patients with breast carcinoma. Furthermore, a significant correlation between the serum levels of reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Malondialdehyde (MDA) and nitric oxide (NO) with VEGF, TGF-β and FOXP3 levels were observed. Conclusion: Reduction of most antioxidant levels except for SOD levels that may be a compensatory up regulation in response to elevation of oxidative stress especially in breast cancer patients were paralleled by high levels of VEGF, TGF-B and Foxp3with different degrees in high risk and breast cancer patients. Oxidant/antioxidant changes may be promising biomarkers which play an important role for the early detection of breast cancer.

[Rasha A. A. Elsayed, Zeinab E. M. Hanafy, Motawa E. El-Housein, Hend Fouad Abd El Fattah and Effat Tharwat Lotf. Oxidant / antioxidant parameters in breast cancer patients and its relation to VEGF, TGF-β or Foxp3 factors. Cancer Biology 2019;9(1):5-17]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 2. doi:10.7537/marscbj090119.02.

Keywords: Breast cancer, reduced glutathione, catalase, Superoxide dismutase, Malondialdehyde, nitric oxide, VEGF, TGFβ, Foxp3, ELISA

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Enhanced Detection of Breast Carcinoma by Fork head Box Protein p3, Vascular Endothelial Growth Factor and Transforming Growth factor Beta 

Zeinab E. M. Hanafy¹, Rasha A. Elsayed¹, Motawa E. El-Housein², Hend Fouad Abd El Fattah³ and Effat Tharwat Lotfy² 

¹Zoology Department Faculty of Science Al-Azhar University (Girl's), Egypt

² Unit of Biochemistry and Molecular Biology, Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt.

³Tissue culture and Cytogenetic Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt

dreffattharwat@gmail.com

Abstract: Background and Objective: This study examined mRNA are performed using conventional RT-PCR expression of VEGF, TGFβ and Foxp3 in benign breast lesions and breast carcinoma and protein expression in blood samples of the same patients by ELISA. The current study also evaluate whether the ELISA or RT-PCR detection is more sensitive and effective in diagnosis of benign breast lesions and breast cancer. Materials and methods: This study was conducted on three groups; invasive breast carcinoma (grade II) group (n=30), high risk patients with benign breast lesions (neoplastic fibrocystic atypical hyperplasia disease) group (n=30) and control group (n=30). The females included in this study were aged from 36-48 years old. Detection of VEGF, TGFβ. and Foxp3 mRNA are performed using conventional RT-PCR while protein expression was assessed by ELISA. Result: Breast cancer patients recorded a highly significant increase in the mean value of serum VEGF, TGF-β and Foxp3 protein level (3.65 ± 0.11) when compared to the high risk and the control groups (p < 0.001) by using ELISA technique. Meanwhile, the high risk VEGF, TGF-β and Foxp3levels were significantly elevated from the control group levels (p < 0.001). A highly significant increase in the mean value of VEGF, TGF-β and Foxp3 gene expression in breast cancer group when compared to control and high risk groups (p<0.001). The high risk group recorded non-significant change in the VEGF, TGF-β and Foxp3 compared to the control group (p<0.001). Conclusion: Sera levels of VEGF, TGF-β and Foxp3 ELISA could be used as a sensitive biomarker for the early detection of breast cancer especially in high risk patients. And qRT-PCR has a lower limit of detection for VEGF, TGF-β and Foxp3 expression than ELISA technique. Therefore ELISA provides a sensitive, quantitative, accurate, and robust assay for measurement of VEGF, TGF-β and Foxp3. It is potentially a valuable tool for patient selection in clinical investigations.

[Zeinab E. M. Hanafy, Rasha A. Elsayed, Motawa E. El-Housein, Hend Fouad Abd El Fattah and Effat Tharwat Lotfy. Enhanced Detection of Breast Carcinoma by Fork head Box Protein p3, Vascular Endothelial Growth Factor and Transforming Growth factor Beta. Cancer Biology 2019;9(1):18-27]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 3. doi:10.7537/marscbj090119.03.

Keywords: Breast cancer, Benign breast lesions, VEGF, TGFβ, Foxp3, ELISA, qPCR

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The prognostic significance of pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with resectable non-metastatic breast cancer

Mohamed El-Shebiney¹, Alaa Maria¹, Muhammed T. Abdelghafar²

¹Clinical Oncology, Faculty of Medicine, Tanta University, Egypt

² Clinical Pathology Departments, Faculty of Medicine, Tanta University, Egypt

alaamaria1@hotmail.com

Abstract: Purpose: The objective of this trial is to explore the correlation between pretreatment neutrophil-to-lymphocyte ratio (NLR) and a platelet-to-lymphocyte ratio (PLR) and the disease-free survival (DFS) of patients with early resectable, non-metastatic breast cancer (BC) treated with neoadjuvant chemotherapy (NAC). Patients and methods: Receiver operating characteristic (ROC) curve analysis was utilized to determine an ideal cut-off value for NLR and PLR to discriminate between patients' DFS. Accordingly, 134 BC patients were classified into low and high NLR and PLR groups, respectively. Results: The ROC curve analysis determined 2.2 and 180 as optimal cut-off values for NLR and PLR respectively. On univariate analysis, both high NLR and PLR significantly correlated with poor DFS. On multivariate analysis, the significant prognostic value of high NLR continued (CI: 1.7-5.9, p<0.001), but not for PLR (CI: 0.5-1.6, p=0.595). Additionally, LNs involvement and high Ki-67 level significantly affect the DFS. The overall clinical response rate (RR) significantly correlated with the lower value of both NLR and PLR (p<0.001 for both). Conclusion: The high NLR significantly correlated with poor DFS in patients with early non-metastatic BC treated with NAC, but PLR is not. As NLR is a clinical marker that can be easily applied and its high value was correlated with poor prognosis of early BC patients, NLR might be a potential predictor in patients’ outcome to assist in treatment decisions.

[Mohamed El-Shebiney, Alaa Maria, Muhammed T. Abdelghafa. The prognostic significance of pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with resectable non-metastatic breast cancer. Cancer Biology 2019;9(1):28-37]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 4. doi:10.7537/marscbj090119.04.

Key Words: Breast cancer (BC), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), Disease free survival (DFS)

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Post mastectomy adjuvant radiotherapy in breast Cancer: A comparison of cardiac toxicity in hypo-fractionated and normal fractionation protocols.

Hagar A. Al Agizy and Mahmoud A. Elshenawy^*

Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Menoufia University, Shebin El Kom 32511, Egypt.

Mahmoudelshenawy78@gmail.com, Mahmoudelshenawy@med.menofia.edu.eg

Abstract: Background: Post mastectomy radiotherapy (PMRT) with hypo-fractionation protocols has been widely used because of less frequent treatment sessions with comparable efficacy to the conventional fractionation protocols. Late PMRT induced toxicities, especially cardiac toxicities, with hypo-fractionation protocols remained under investigation. Purpose of our study was to compare risk of PMRT induced cardiac toxicities with hypofractionation and conventional fractionation protocols. Patients and methods: This was a prospective randomized clinical trial done in our department. Between August 2009 and June 2010, breast cancer female patients eligible for PMRT underwent 1:1 randomization into 2 groups; group A: conventional fractionation (50 Gy/25fractions/5weeks; 2Gy/fraction). Group B: Hypofractionation (40Gy/15 fractions/3 weeks; 2.67Gy/fraction). Echocardiography (ECHO) and Electrocardiography (ECG) were performed at base line before chemotherapy, at start of radiotherapy, after 6 months, then annually. Results: At a median follow up duration of 60 months (range 25- 70),120 patients were randomized equally in both groups A & B. Median age was 47 years in both groups [ranges (23-70) & (25-68) in groups A & B respectively]. No significant statistical difference was found between both groups regarding hypertension (25% vs 21.7% group A & B respectively). Also, no difference was found between both groups regarding base line and follow up ECHO & ECG. Patients with left sided breast cancer and/or hypertension showed significant decline in ejection fraction (EF) in both groups (p <0.05). In group A; hypertensive patients had a median base line EF 63% which declined to 54% at last follow up in comparison to non-hypertensive patients who had decline in baseline EF from 65% to 60%. In group B; hypertensive patients had a median baseline EF 62% which declined to 54 % at last follow up in comparison to non-hypertensive patients who had decline in baseline EF from 64% to 59%. Only 1 recorded death due to heart failure however, she was 70 years old and had history of hypertension and diabetes mellitus. Conclusion: PMRT with hypofractionation protocols has no additional cardiac toxicity in comparison to conventional fractionation.

[Hagar A. Al Agizy and Mahmoud A. Elshenaw. Post mastectomy adjuvant radiotherapy in breast Cancer: A comparison of cardiac toxicity in hypo-fractionated and normal fractionation protocols. Cancer Biology 2019;9(1):38-42]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 5. doi:10.7537/marscbj090119.05.

Keywords: breast cancer, hypofractioned radiotherapy, cardiac toxicity.

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Preliminary Results of Capecitabine Metronomic Chemotherapy Combined with Exemestane in Advanced Breast Cancer – A Single-Arm Phase II Study

Amr Ghannam and Rasha Abd Elghany Khedr

Clinical Oncology Department, Faculty of Medicine, Tanta University, Egypt

Amro_ghannam@yahoo.com, khedr_rasha@yahoo.com

Abstract: Background: Advanced breast cancer is incurable disease and its prognosis is poor. The aim of our trial is the assessment of tolerability and survival outcome of metronomic chemotherapy capecitabine combined with the aromatase inhibitor exemestane in hormone receptor (HR)-positive, HER2- negative advanced breast cancerpatients who have a refractory disease following letrozole treatment. Methods: Between June 2012 and February 2017, 38 female patients with HR-positive, HER2- negative advanced (locally advanced or metastatic) breast cancer, adequate organ function and performance status (PS) 0-3, who progressed following letrozole treatment receivedmetronomic capecitabine (500mg/m2, twice every day) in combination with exemestane (25 mg daily). Treatment was continued until the progression of disease or development of unacceptable toxicity. The primary end point of our study was the assessment of the response rate (RR) and safety while the secondary end point was the assessment of progression free survival (PFS) and overall survival (OS). Results: The overall response rate [Complete response, (CR) +Partial response (PR)] was 68.4% (26/38) and the disease control rate [CR+PR+SD (stable disease)] was 78.9 % (30/38 patients). Four patients (10.5%) had stable disease and 8 patients (21.1%) had disease progression. Median PFS and OS were 17 months and 20 months respectively. The 1-year overall survival was 63%. The median duration of treatment was 18 months (range 3-60 months). No toxic death occurred and no grade 3/4 hematological toxicities were documented. Diarrhea and hand-foot syndrome were the commonest grade 3 non-hematological toxicities. Conclusion: capecitabine metronomic therapy in combination with exemestane is an effective treatment alternative with manageable toxicity profile which can be used for patients with advanced breast cancer with poor performance status.

[Amr Ghannam and Rasha Abd Elghany Khedr. Preliminary Results of Capecitabine Metronomic Chemotherapy Combined with Exemestane in Advanced Breast Cancer – A Single-Arm Phase II Study. Cancer Biology 2019;9(1):43-50]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 6. doi:10.7537/marscbj090119.06.

Key words: Metronomic chemotherapy, exemestane, capecitabine, advanced breast cancer.

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The efficiency of (Holy) Makka mud therapy (MMT) in treating various health problems: A pilot study

Manal G. Abd El Wahab¹ and Salwa Sager²

¹Department of Anatomy, Faculty of Medicine for Girls, Al Azhar University, Cairo, Egypt. and (YAJ) Members of Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Applications, Faculty of Medicine, King Abdulaziz University (KAU) Jeddah Kingdom of Saudi Kingdom of Saudi Arabia (KSA).

²Certified nurse, Ministry of health Taif Hospital, KSA. and (YAJ) Members of Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Applications, Faculty of Medicine, King Abdulaziz University (KAU) Jeddah Kingdom of Saudi Kingdom of Saudi Arabia (KSA)

omaman2005@hotmail.com

Abstract: Ancient people treated health problems and pain using mud. Objectives: A pilot study on Makka mud therapy (MMT) on sone diseases, to put forward evidence –based treatment protocol and guidelines using (MMT). Patients and methods: Patients with different ages, sex, and diseases were subjected to (MMT) alone or combined with / hijama. or honey, or medical plants. Mud was prepared from Makka soil present in the sail road from kaekea area, Jazan. KSA, mixed with tap water or Zamzam water, left in sun and moon light out doors for 24 hours. Mud packs with different size, shape and thickness were applied on body areas, then removed after limited time and repeated for weeks, or months according to the disease. Methods of forming (MMT) different packs were formed of cotton sheets filled with prepared mud, or applied on shaved head to form cap of mud. Cotton gloves and socks with no finger or toe septa separation filled with 200-400 mg mud for managing (rheumatic) hands and feet. Direct application of small mud strips on the eyes and bandage on front head used to treat night blindness for10 months. medical Follow up: blood analysis, sonar, x-ray and other investigations were done. Makka soil sampes were analyzed in Egypt, Suez Canal University. It was full of Mn, Ni, Cd Pb Cu, Zn Fe ions and heavy metals. Therapeutic efficiency: Makka dry soil which is formed after rain fall in JAZAN road El kaekea was mixed with tap water or Zamzam water to prepare (MMT) packs and other methods alone or combined was studied for the first time in the present work. Results: Improvements in disease progress, better body functions and improved life quality occurred after (M MT), although it was temporary in some cases. Conclusion and recommendations: Makka mud therapy (MMT) alone or combined caused improvement of pain sensation and body function with progress in life quality in some health problem studied in this work. (MMT) may be an alternative or complementary treatment in some health problem. However. this is a pilot study and more controlled researches are needed. More improvements of the methodological quality of (MMT) are required. A protocol and guide lines for Makka mud therapy (MMT) alone or combined was founded in this study for the first time. (MMT) is safe, cheap, and save efforts and expenses travelling abroad. It is promising to study the soil of El Madina El Monawara.

[Manal G. Abd El Wahab and Salwa Sager. The efficiency of (Holy) Makka mud therapy (MMT) in treating various health problems: A pilot study. Cancer Biology 2019;9(1):51-59]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 7. doi:10.7537/marscbj090119.07.

Keywords: Makka, mud, Qoraan, Sunna, disease, methodology, guide lines, pain, life quality

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Risk Predictors for De Novo Hepatocellular Carcinomas in Chronic hepatitis C Treated Patients who Achieved Sustained Virologic Response: a Retrospective Study

Abdallah A. Elsawy¹ and Omnia Abd Elfattah²

Departments of Internal Medicine¹ and Clinical Oncology², Tanta University, Tanta, Egypt

omniaabdelfattah@yahoo.com

Abstract: Background and study aim: Recently, the occurrence of de novo or recurrence of HCC in HCV patients, who treated with direct acting antivirals, has gained a rising interest in clinical application. There are wide debates about the possible role of these treatments in this respect. The recent published studies regarding the risk of developing HCC after treatment with DAA concluded that achieving SVR with DAA regimens was associated with a significant risk reduction of HCC, however, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population. The aim of this study is to evaluate possible risk predictors related to de novo HCC in HCV patients who achieved SVR to either DAAs or peg-IFN regimens. Patients and methods: Seven hundred and fifty treated HCV patients, who achieved SVR, were retrospectively included. They were divided to two groups, group1 included 150 patients proved to have denovo HCC after treatment, and group2 included 600 patients did not prove to have HCC after treatment. All patients were investigated as regards the degree of liver fibrosis using FIB4 score, the severity of liver dysfunction using Child Pugh and MELD scores, DM and HCV treatment regimens either DAAs or Peg-IFN. Results: FIB4 score had a high significant risk for HCC by multivariable logistic regression (p value =0.0001 and Odds ratio =1.626 with 95% CI=1.347-1.964). Child Pugh score had a high significant risk for HCC (p value =0.0001 and Odds ratio =1.426 with 95% CI=1.172-1.734). The MELD score had a high significant risk for HCC (p value =0.028 and Odds ratio =1.124 with 95% CI=1.013-1.246). However, after adjustment of the risk estimate of DM by multivariable logistic regression, we found that DM had a non-significant risk for HCC (p value =0.431 and Odds ratio =1.2 with 95% CI=0.762-1.891). HCV patients who were treated by DAAs had lower -however non significant- risk for HCC (p value =0.639 and Odds ratio =0.898 with 95% CI=0.572-1.409). Conclusion: Higher grades of liver fibrosis using FIB4 score and advanced liver dysfunction using either MELD or Child Pugh scores are independent risk predictors for de novo HCC in HCV patients treated by either DAAs or Peg-IFN who achieved SVR. DAAs had lower -however non significant- risk for HCC.

[Abdallah A. Elsawy and Omnia Abd Elfattah. Risk Predictors for De Novo Hepatocellular Carcinomas in Chronic hepatitis C Treated Patients who Achieved Sustained Virologic Response: a Retrospective Study. Cancer Biology 2019;9(1):60-65]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 8. doi:10.7537/marscbj090119.08.

Key words: Direct acting antivirals, Hepatocellular carcinomas, Risk factors

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Role of Hormone receptor status, Ki-67 expression and body mass index in endometrial carcinoma: clinical value and survival

Omnia Abd –El-Fattah¹, Fatma Gharib¹, Yomna zamzam² and Ayman Elsaka²

Departments of ¹Clinical Oncology and ²Clinical Pathology, Tanta University Hospitals, Egypt

omniaabdelfattah@yahoo.com

Abstract: Background: The most known risk factors for developing endometrial cancer are high estrogen levels and obesity which associated with excessive levels of estrogen. Expression of Ki-67 has independent role on prognosis. Effect of hormone receptor, body mass index (BMI) and Ki-67 on disease free survival in endometrial carcinoma and their association with other clinicopathological features was evaluated in this study. Methods: Fifty-three adult female patients were included in this prospective study with histologically confirmed EC. Those patients treated and followed up at Tanta University Hospitals. Hormone receptor status and ki67 was detected by immunohistochemical exam. Body mass index was calculated at time of presentation. Hormonal status, ki-67 and BMI were studied and compared with other clinicopathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive expression of ER and PR was detected in 54.7% and 49.1% of patients respectively and significantly associated with less myometrial invasion, low Ki-67, BMI>30kg/m² and endometrioid type. Interestingly BMI >30 kg/m², was significantly associated with earlier stage and endometrioid type (P=0.04 and 0.003 respectively). Multivariate Cox regression analysis detected that myometrial invasion, tumor grade and ER expression remained statistically significant with DFS. Conclusion: Our study investigated that different molecular factors such as ER, PR and Ki-67 in addition to obesity, significantly associated with tumor characteristics and survival.

[Omnia Abd –El-Fattah, Fatma Gharib, Yomna zamzam and Ayman Elsaka. Role of Hormone receptor status, Ki-67 expression and body mass index in endometrial carcinoma: clinical value and survival. Cancer Biology 2019;9(1):66-74]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 9. doi:10.7537/marscbj090119.09.

Keywords: Keywords: Endometrial cancer. BMI. Ki67. ER. PR

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Primary lymphoma of bone in Egyptian population: a retrospective study with emphasis on prognostic factors and treatment outcome

Wael S. Mansour M.D. and Mohamed A. Alm El-Din M.D.

Department of Clinical Oncology, Faculty of Medicine, Tanta University, Egypt

almeldin@gmail.com

Abstract: Background: Primary bone lymphoma (PBL) is a rare disease with lacking data on the prognostic factors or the treatment outcome. Patients and Methods: We retrospectively collected data from twenty three patients with PBL referred to the department of Clinical Oncology, Tanta University Hospitals from 2000 to 2013 to better understand the outcome of this disease in Egyptian population. Results: Median age was 48 years (range, 26–68) with male predominance (52.2%). The most frequent location was the femur and pelvis (26.1% and 17.4%, respectively). 17 patients (73.9%) were treated with radiotherapy either alone or in combination with chemotherapy while 6 patients were treated with chemotherapy alone. The overall response rate was 82.6%. The 5-year and 15-year overall survival (OS) was 82.6% and 69.6%, respectively. Freedom-from treatment failure (FFTF) was significantly higher with normal LDH level (P = 0.001), female gender (P = 0.001), ECOG performance status < 2 (P = 0.001), low grade tumors (P = < 0.0001), and combined modality therapy (P = 0.05). OS was significantly higher in female (P = 0.04), < 40 years (P = 0.003), lack of B symptoms (P = 0.001), normal LDH level (P = < 0.005), and combined modality therapy (P = 0.01). On multivariate analysis, only age < 40 years and the use of combined modality therapy were independent prognostic factors for better OS and FFTF. Conclusions: Our data showed that age < 40 years and combined modality therapy were independent prognostic factors for better OS and FFTF in Egyptian patients with PBL.

[Wael S. Mansour and Mohamed A. Alm El-Din. Primary lymphoma of bone in Egyptian population: a retrospective study with emphasis on prognostic factors and treatment outcome. Cancer Biology 2019;9(1):75-83]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 10. doi:10.7537/marscbj090119.10.

Keywords: Primary bone lymphoma; Outcome; Egyptian

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Trimodality Therapy with Maximal Transurethral Resection, Hypofractionated Irradiation with Concurrent Gemcitabine in Elderly Patients with Muscle Invasive Bladder Cancer

Amr Ghannam¹, Rasha Abd Elghany Khedr¹ and Mohamed Hassan Radwan²

¹Clinical Oncology Department, ²Urology Department, Faculty of Medicine, Tanta University, Egypt.

Amro_ghannam@yahoo.com, khedr_rasha@yahoo.com

Abstract: Background: Muscle invasive bladder cancer is a serious health problem. While radical cystectomy (RC) is the gold standard treatment, many patients are unfit or refuse cystectomy. Trimodality therapy with transurethral resection of the bladder tumor (TURBT), radiotherapy and chemotherapy is an attractive alternative with comparable results. Radiotherapy with concurrent gemcitabine may be a good alternative to cisplatin in elderly patients as many of them have comorbidities which render them unfit for cisplatin or prone to severe toxicities. Aim: We initiated this trial to assess the response rate, survival outcome and tolerability of trimodality therapy with gemcitabine as a radiosensitizer in elderly muscle invasive bladder cancer (MIBC) patients. Methods: This study was conducted at Tanta university hospital, urology and oncology department, during the period from January 2013 to September 2017. Thirty six patients with muscle invasive transitional cell carcinoma (TCC) of the bladder were enrolled. Eligible patients underwent maximal TURBT followed by hypofractionated radiation therapy with 52.5 Gy in 20 fractions with concomitant weekly gemcitabine. Results: The median age was 69.5 years. The median follow up time was 24 months. Most of the patients tolerated the treatment protocol with minimal toxicity. Twenty four patients achieved complete response (CR),4 patients partial response (PR) and 8 patients with either stable disease (SD) or progressive disease (PD). Six patients developed disease recurrence, three with non-muscle invasive, two with muscle invasive transitional cell carcinoma and the last one with small cell carcinoma. Two year disease free survival (DFS) and overall survival (OS) was 66.6% and 76.8% respectively. Conclusion: Bladder preservation with maximal TURBT, concurrent chemotherapy with weekly gemcitabine is well tolerated and effective in older patients with muscle invasive bladder cancer.

[Amr Ghannam, Rasha Abd Elghany Khedr and Mohamed Hassan Radwa. Trimodality Therapy with Maximal Transurethral Resection, Hypofractionated Irradiation with Concurrent Gemcitabine in Elderly Patients with Muscle Invasive Bladder Cancer. Cancer Biology 2019;9(1):84-92]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 11. doi:10.7537/marscbj090119.11.

Key words: bladder preservation, gemcitabine, radiotherapy

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Synergistic Interaction of Lapatinib plus Doxorubicin or 5-Fluorouracil Accelerated Cell Death of Triple Negative Breast Cancer MDA-MB-231 Cell Line

Mona A. M. Abo-Zeid ^1,2, Mahmoud T. Abo-Elfadl ^2,3

¹ Genetics and Cytology Department, Genetic Engineering and Biotechnology Research Division,

National Research Centre, Dokki 12622, Cairo, Egypt.

² Cancer Biology and Genetics Laboratory - Centre of Excellence for Advanced Sciences,

National Research Centre, Dokki 12622, Cairo, Egypt.

³ Biochemistry Department, Genetic Engineering and Biotechnology Research Division,

National Research Centre, Dokki 12622, Cairo, Egypt.

monaabozeid@yahoo.com

Abstract: Background: Lapatinib, one of tyrosine kinase inhibitor (TKIs), is used to treat HER1/2 amplified breast cancer diseases. Its combination with other chemotherapeutic agents was effective to diminish over-expressed-HER2 cell growth. This research aimed to assess its synergistic growth inhibition in combination with doxorubicin (DOX) or 5-fluorouracil (5-FU) on MDA-MB-231 as a model of human triple negative breast cancer (TNBC) cell line. Methods: 2.5%, 5% and 10% of lapatinib IC₅₀ concentrations were tested in pre- and post-combinations with 10% of IC₅₀ for DOX or 5-FU. Cytotoxic and genotoxic effects were conducted using MTT assay, apoptosis-necrosis and micronucleus (MN) tests. Results: Pre-treating MDA-MB-231 cells with DOX or 5-FU for 4h followed by lapatinib for 24h enhanced cytotoxicity (p<0.05) in comparison with that pre-treated with lapatinib for the same time intervals. Both pre- and post-treated MDA-MB-231 cells with lapatinib enhanced induction of apoptosis and DNA damage. The mean percentages of apoptotic cells and binucleated cells containing micronuclei were elevated remarkably (p<0.05) in cells pre-treated with DOX or 5-FU rather than that pre-treated with lapatinib. Conclusion: Synergistic interaction of lapatinib in combination with DOX or 5-FU augmented cell growth inhibition, apoptotic mode of cell death and DNA damage effectively. Additionally, the synergistic effect between chemotherapeutics and TKIs possibly will allow using lower concentrations to achieve remarkable cell death.

[Mona A. M. Abo-Zeid, Mahmoud T. Abo-Elfadl. Synergistic Interaction of Lapatinib plus Doxorubicin or 5-Fluorouracil Accelerated Cell Death of Triple Negative Breast Cancer MDA-MB-231 Cell Line. Cancer Biology 2019;9(1):93-99]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 12. doi:10.7537/marscbj090119.12.

Key words: Lapatinib; Doxorubicin; 5-Fluorouracil; Cytotoxicity; Micronucleus test; Apoptosis-necrosis.

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pediatric patients with HL. The combination of history taking and physical examination gave the highest rate of relapse detection and decreased the hazard of radiation exposure and the risk of developing second malignancies, Patients with high-risk criteria and slow responder may benefit from routine surveillance especially in the first two years off-treatment.

 [Nesreen Ali, Amr Abdalla, Marwa Romeih, Engy Mohamed, Emad Moussa. Role of Radiological Surveillance as a Mode of Detecting Recurrence in Children with Hodgkin Lymphoma. Cancer Biology 2019;9(1):100-107]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 13. doi:10.7537/marscbj090219.13

Keywords: Hodgkin lymphoma, pediatric, follow up, radiologic surveillance

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