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The prognostic significance of tumor infiltrating CD8+ cytotoxic cells and FoxP3+T regulatory cells in colon cancer

Azza Darwish¹*, Haitham Fayed ², Dina Abdallah ³

¹ Clinical Oncology Department, Faculty of Medicine, Alexandria University, Egypt.

² General Surgery Department, Faculty of Medicine, Alexandria University, Egypt.

³ Pathology Department, Faculty of Medicine, Alexandria University, Egypt.

Email: azzadarwish2005@yahoo.com

Abstract: Background: T-lymphocytic infitration may have a crucial role in the prognosis of colorectal cancer patients. Our aim was to assess the prognostic significance of the presence of lymphocytic infiltration with focusing on its subsets; CD8+ and FoxP3+. Tumor infiltrating lymphocytes (Tils) were quantified in 69 patients operated for stage II and stage III colon cancer. Patients with high Tils were further stained for CD8+and FoxP3+. Results Most of our patients (73.9%) had low LI, while 26.1 % had high LI. There was no significant association between any clinic-pathological feature and density of LI. After a median follow up of 56.5 months, the DFS and OS varied according to the density of LI. There was a trend towards better 3-year DFS and OS in patients with high LI (p=0.065) and (p=0.08) respectively. By immunophenotyping, CD8+ infiltration was more common than FoxP3+. Prominent CD8+ infiltration was associated with lower grade tumors (p=0.06), lower N stage (p=0.06) and favorable overall survival (p=0.07).

[Azza Darwish, Haitham Fayed, Dina Abdallah. The prognostic significance of tumor infiltrating CD8+ cytotoxic cells and FoxP3+T regulatory cells in colon cancer. Cancer Biology 2019;9(3):1-7]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 1. doi:10.7537/marscbj090319.01.

Key words: colon cancer, tumor-infiltrating lymphocytes, prognosis, FoxP3+, CD8.

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Assessment of low anterior resection syndrome in patients who underwent low anterior resection for cancer rectum

Tarek Youssef, Ahmed Aly Khalil, Magdy Moustafa Eldahma.

General Surgery Department, Faculty of Medicine Ain Shams University, Egypt

maismile92@yahoo.com

Abstract: Background and aim: Rectal Cancer is the third most common form of cancer and the second leading cause of cancer related deaths in the western world. It occurs due to abnormal growth of the lining cells of the rectum that have the ability to invade and spread to other parts of the body. Surgery is the only curative therapy for rectal cancer. Transabdominal surgery can be performed with either sphincter sparing techniques i.e. (anterior resection) or an abdominal perineal resection. Historically, abdominal perineal resection was the gold standard for treating low-lying rectal cancers. With the advent of better surgical techniques and equipments e.g. (staplers) as well as neo-adjuvant therapy abdominal perineal resection has been gradually replaced by sphincter sparing procedures. For patients in whom negative distal margin can be achieved sphincter sparing procedures are preferred because they maintain bowel continence and avoid a permanent colostomy. However, functional disturbances constitute a major problem for many surviving rectal cancer patients following a sphincter saving procedure with symptoms ranging from daily episodes of incontinence to obstructed defecation, constipation & low anterior resection syndrome (LARS). LARS is used to describe a variety of symptoms: bowel, urinary and sexual dysfunction. The bowel dysfunction may be categorized into storage dysfunction (which includes bowel frequency, Fecal urgency and incontinence).And the evacuatory dysfunction (which includes stool fragmentation, gas stool discrimination, tenesmus and anal pain). Low anterior resection is common and has been reported in 10% to 90% of post-rectal resection patients. Aim of the work: We assessed the low anterior resection syndrome in patients with rectal cancer who underwent low anterior resection as regards incidence, timing & its fate or improvement. Methods: This was a retrospective observational study included 52 patients with low rectal cancer who underwent low anterior resection at Tanta Cancer Center (TCC) and Ain Shams University Hospital between (January 2015 - January 2017). Each patient will fill four questionnaires to cover the following periods after restoration of their bowel continuity (1 month, 6 month, 1year and 2 years). Results: The overall incidence of LARS in our study varied from 88.5% at one month point to decline to 79.1% at 24 months point also there was a decrease in the percentage of patients with major LARS and increase in the percentage of patients with minor or no LARS across the different follow-up time points. However, this notable change in LARS status across time points was not statistically significant. The average overall LARS score showed a gradual and statistically significant decrease over the 24-month follow-up period (from 30.92 to 27.04). The major decline occurred from the 6-month to the 12-month scores. Conclusion: Rectal surgeries contributed to increase of survival rates of rectal cancer patients. Yet bowel dysfunction may result thus affects the quality of life of rectal cancer survivors. LARS is an important consequence that affects a large number of rectal cancer survivors. However, it is reported that the severity of LARS decreases with time for these patients. Therefore, it is important that clinicians and researchers focus on LARS and conduct further studies to determine its contributing factors and improve the prevention and treatment strategies.

[Tarek Youssef, Ahmed Aly Khalil, Magdy Moustafa Eldahma. Assessment of low anterior resection syndrome in patients who underwent low anterior resection for cancer rectum. Cancer Biology 2019;9(3):8-13]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 2. doi:10.7537/marscbj090319.02.

Keywords: Low anterior resection syndrome (LARS), colorectal cancer (CRC), low anterior resection, bowel dysfunction

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Microbial sources and some therapeutic applications of L-methioninase

Bukhari, K.A. and Alamoudi, K.H.

Department of Biology, Faculty of Science, University of Jeddah, KSA

Dr.k.alamoudi@hotmail.com

Abstract: Natural products are produced by a wide range of different organisms including microorganisms. It is a source of compounds opening promising avenues for the treatment of a great variety of diseases accurately in a proper manner to specifically target cancer cells. Over the past 50 years, cancer has become a problem that threatens human health. According to the world health organization WHO website, there were 9.6 million people died from cancer and 18.1 million new cancer cases worldwide in 2018, with 60% of world's total new annual cases occurring in Africa, Asia, and Central and South America. The percentage of cancer deaths in Asia and Africa (57.3% and 7.3%, respectively) are higher than the ratios of incident cases (48.4% and 5.8%, respectively). L-methioninase is attracted a great deal of attention due to has potential application as an active therapeutic agent against cardiovascular diseases and different types of cancer in human beings and other applications. L-methioninase from diverse microorganisms exhibits significant reductions in L-methionine in vivo and efficacy against a broad spectrum of transplantable animal and solid human tumors.

[Bukhari, K.A. and Alamoudi, K.H. Microbial sources and some therapeutic applications of L-methioninase. Cancer Biology 2019;9(3):14-23]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 3. doi:10.7537/marscbj090319.03.

Keywords: Cancer, Therapeutic, L-methioninase, Natural products

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Spontaneous Rupture of Hepatocellular Carcinoma; Middle-Eastern Experience

Mohammad Burhan Khan ¹ MBBS; Ahmed Elaffandi^{1, 2} MD; Walid Elmoghazy^1,3 PhD; Samah Mohamed ^4,5FRCR, MD; Alshimaa Alaboudy⁶ MD; Hatem Khalaf¹ MD

¹Department of Hepato-Pancreatobiliary and Liver Transplantation, Liver Unit-Organ Transplantation, Hamad General Hospital, Doha, Qatar

²Department of Surgical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt

³Department of Surgery, Sohag University, Egypt

⁴Diagnostic Radiology, Hamad Medical Corporation, Doha, Qatar

⁵Diagnostic Radiology, National Cancer Institute, Cairo, Egypt

⁶Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University, Sohag, Egypt

ahmedaffandy@gmail.com

Abstract: Background: Hepatocellular carcinoma (HCC) is among the top five most common cancers in the world. However, spontaneously ruptured hepatocellular carcinoma (HCC) is a rare and potentially fatal condition. The aim of the present study is to compare the outcomes and survival between patients presenting with ruptured HCC and those presenting without a rupture. Our secondary objectives are to determine factors predisposing patients to a spontaneous rupture. Methods: In this retrospective study, all patients presenting with HCC between January 2006 and December 2015 were included. They were grouped based on findings of ruptured HCC at presentation. Treatment plans for patients were decided by a multidisciplinary team of physicians and surgeons. Outcomes were calculated, which included Kaplan-Meier survival curves and log-rank test was used for comparison. Cox proportional hazards regression was used in identifying prognostic factors in relation to mortality, and long-term survival. Patient and tumor factors predisposing to rupture were compared to the control group. Results: 324 patients were diagnosed with HCC during the study period. 14 of them presented with a spontaneous rupture. Majority of patients (54.9%) had Hepatitis C virus as the underlying etiology for cirrhosis and HCC. The overall mortality rate was 59.3%, (64.3% in ruptured HCC group versus 59% in HCC group). Median survival in the ruptured group was 370 days, compared to 400 days in HCC group. 5 out 14 (36%) patients with ruptured HCC died within the initial 30 days. Initial survival rates were found to be statistically different at 1 and 3 months; however, the overall survival found to be similar for the rest of the follow-up period. Poorer liver function, a lower hemoglobin level, higher creatinine level, larger maximal tumor diameter, and higher total tumor volume was associated with ruptured HCC. Conclusions: While the survival benefit of patient’s with ruptured HCC is inferior to those who present with HCC, there are a few important observations. Poor liver function, low hemoglobin, high createnine, larger tumor maximum diameter and higher total volume at presentation is associated with a high 30-day mortality for patients presenting with ruptured HCC compared to those with HCC. However, long term overall survival is no different between the two groups of patients once past the initial 30 - day period. Tumor related factors such as maximum tumor diameter and total tumor volume may play an important role as predictors for spontaneous rupture.

[Mohammad Burhan Khan; Ahmed Elaffandi; WalidElmoghazy; Samah Mohamed; Alshimaa Alaboudy; Hatem Khalaf. Spontaneous Rupture of Hepatocellular Carcinoma; Middle-Eastern Experience. Cancer Biology 2019;9(3):24-31]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 4. doi:10.7537/marscbj090319.04.

Keywords: Spontaneous; Rupture; Hepatocellular; Carcinoma; Middle-Eastern; Experience

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The application of Clathrin Heavy Chain and Leukemia Inhibitory Factor Receptor in the differential diagnosis of benign and malignant hepatic lesions

Aliaa Atef Shams Eldeen, and Rania Elsayed Wasfy

Pathology Department, Faculty of Medicine, Tanta University, Egypt

Email: dr-aliaaatef@hotmail.com

Abstract: Background: Hepatic focal lesions include a heterogeneous group of lesions ranging from benign regenerative cirrhotic nodules to low and high grade dysplastic nodules to HCC. Hepatocellular carcinoma (HCC) is the most common type of all primary liver tumors. Liver cell dysplasia particularly high-grade dysplasia (HGD) has a high risk for malignant transformation. It is mandatory to find more accurate and comprehensive novel markers for diagnosis of HCC. Aim: To study the diagnostic role of clathrin heavy chain (CHC) and leukaemia inhibitory factor receptor (LIFR) in malignant and non-malignant liver lesions and correlation with the clinico-pathological parameters of studied cases. Results: CHC immunopositvity was highly specific and sensitive indicator for hepatocellular carcinoma unlike LIFR which cannot be used as reliable indicator of liver malignancy. Most of cases of HCC were positive for CHC (31 out of 33) (93.9%). Most of cases of cirrhosis (17 out of 25) (68.0%) were negative for CHC. In liver cell dysplasia, 14 cases were positive (70.0%) (P<0.001). LIFR was more expressed in non-malignant than in HCC. 92% of cases of cirrhosis were positive for LIFR. 95% of cases of dyspalsia were positive for LIFR; only 30.3% of HCC showed positivity for LIFR. This inverse relation was statistically highly significant (p<0.001). Conclusion: CHC can be a promising diagnostic immunomarker for the diagnosis of HCC unlike LIFR which can’t be a reliable diagnostic marker alone. However, a combination of both markers (CHC and LIFR) represents a valuable diagnostic tool in workout of hepatic lesions uncertain for malignancy rather than individual markers.

[Aliaa Atef Shams Eldeen, and Rania Elsayed Wasfy. The application of Clathrin Heavy Chain and Leukemia Inhibitory Factor Receptor in the differential diagnosis of benign and malignant hepatic lesions. Cancer Biology 2019;9(3):32-38]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 5. doi:10.7537/marscbj090319.05.

Key words: Clathrin heavy chain, Leukaemia inhibitory factor receptor, hepatocellular carcinoma.

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Retrospective Analysis of Prognostic Value of Neutrophils to lymphocyte Ratio and Platelet Count in Patients with Colorectal Carcinoma

Mohamed Elbassiouny, Dina Ragab, Ghada Refaat, Suhad A. Ali

Department of Clinical Oncology and Nuclear Medicine

Faculty of Medicine – Ain Shams University

suhadmaidan89@gmail.com

Abstract: Background: Colorectal cancer (CRC) is the third most common cancer in men and second in women with 1.8 million new cases (1,026,000 men and 823, 3 women) and almost 881.000 deaths. Rates are substantially higher in males than in females Worldwide in 2018. Aim of the work: In this retrospective study we aimed to evaluate the prognostic impact of baseline NLR and platelet count on the clinicopathological factors and outcome in patients of all stages Colorectal cancer treated from1^st of January 2014 to the end of December 2016 in Department of Clinical Oncology and Nuclear Medicine, Ain Shams University hospitals, Cairo, Egypt. Patients and methods: Out of 409 patient's medical records in the GI oncology unit, Ain Shams Clinical Oncology Department were reviewed from the period between 1^st of January 2014 to 30 December 2016. Total neutrophils, lymphocytic, and platelets' counts were available for only 169 patients. Study ended in 1^st of August 2018 with median period of follow up of 27.5 month, ranging between 1/1/2014 to 1/8/2018. All patients (169) were pathologically proven colorectal adenocarcinoma, with age ranging from 18-75 years old (median age: 55.5 yrs). Results: Out of 169 patients enrolled in this study, 124 patients were respectable and underwent curative surgeries, 44 patients tumour was right located and 80 patient's tumour located in the left sided colon. 45 patients were metastatic from the start. Postoperative Platelets≥ 310 in our study was statistically significant regarding OS, PFS and DFS (P values <.001, <.001 and 0.007) respectively. Pre-treatment platelet revealed more frequent thrombocytosis in metastatic group than locally advanced group, yet statistically was not significant (P Value=.066). Postoperative NLR ≥2 was significant regarding OS, PFS and DFS among 169 enrolled patients (P values <.001,.002 and <.001) respectively. In the multivariate analysis, elevated postoperative NLR was proven as both independent prognostic and predictor factor for DFS, PFS and OAS. (sig. =.03,.03, ≤0.001 respectively). And platelet count is both independent prognostic factor and predictor for both PFS, OSwith significance =.04, =.03 respectively). Conclusion: Abnormal NLR ratio (≥2) acting as a prognostic and predictor of decrease in DFS, PFS and OS in all patients groups. It also showed that abnormal platelet count (≥310) is prognostic and predictor of significant decrease in PFS and OS. Multidisciplinary management is needed to aware surgeons about importance of adequate lymph node dissection, our study showed a statistically significant decrease in OAS in patients underwent inadequate LNs dissection.

[Mohamed Elbassiouny, Dina Ragab, Ghada Refaat, Suhad A. Ali. Retrospective Analysis of Prognostic Value of Neutrophils to lymphocyte Ratio and Platelet Count in Patients with Colorectal Carcinoma. Cancer Biology 2019;9(3):39-51]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 6. doi:10.7537/marscbj090319.06.

Key words: Neutrophils, lymphocyte, platelet Count, Colorectal Carcinoma

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Neoadjuvant Rectal Cancer (NAR) Score as a Prognostic Factor in Locally Advanced Cancer Rectum

Rehab F Mohamed, Mariam Mohsen Khalil, Samir Eid.

Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.

faroukrehab@yahoo.com

Abstract: Background: The aim of this study is determination of NAR score for locally advanced rectal cancer patients and its relation with disease free survival (DFS) and overall survival (OS). Methods: A total number of 70 patients with locally advanced rectal cancer who had received neo-adjuvant concurrent chemo-radiotherapy followed by surgery were included in our study. NAR scores were calculated using the following formula: . The constant 12 assures that all scores are positive inside the outer brackets. Squaring the numerator transforms the score to more uniform measure per unit change. The scaling factor 9.61 in the denominator ensures that the final scores range from 0 to 100. It was divided into low risk (less than 8) - intermediate risk (from 8 to 16) - high risk (more than 16). Results: The median value of NAR score was 22.62, 23 patients (32.9%) with low NAR score, 21 patients (30.0%) with intermediate score and 26 patients (37.1%) with high score. The patients showed variable response to neo-adjuvant therapy as 17 patients (24.3%) had pCR, 21 patients (30.0%) had PR, and 32 patients (45.7%) had SD. The inverse relation between the score and response was proven in our study as patients with high NAR score had the worst prognosis. The median NAR score was 0.90 in patients with pCR, 8.43 in patients with PR, and 30.07 in patients with SD, with statistically significant P value (P value<0.003). There were a negative correlation between NAR score and DFS, OS with statistically significant P value (P value=0.003). The statistical significant relation between NAR score and DFS & OS were shown in patients with high, intermediate and low NAR score, as the median free survival times were 12.0, 24.0 and 36.0 respectively. 5-year survival rate of all patients was 75.1%. Patients with low NAR score showed 5-year OS rate 100.0%. Patients with intermediate and high score showed 5-year OS rate were not reached (NR) with statistically significant P value (P value<0.001). Conclusion: NAR score use a simple data available such as cT, pT and pN. There was a negative correlation between NAR score and DFS & OS as with the increase of NAR score, there was decrease in DFS and OS.

[Rehab F Mohamed, Mariam Mohsen Khalil, Samir Eid. Neoadjuvant Rectal Cancer (NAR) Score as a Prognostic Factor in Locally Advanced Cancer Rectum. Cancer Biology 2019;9(3):52-60]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 7. doi:10.7537/marscbj090319.07.

Key words: NAR score, locally, neoadjuvant, rectal, advanced, cancer.

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A Retrospective Analysis of Hypopharync carcinoma Cases Treated in Menia Cancer Center and Gharbia Cancer Society Egypt in the Period from 2007-2014.

Mohamed Mahmoud, and Sherweif Abdelfatah

Radiation Oncology Department, National Cancer Institute, Cairo University, Egypt

m_mahmoud1973@hotmail.com

Abstract: Purpose: The aim was to define all clinico-pathological data, different treatment modalities and to define the different prognostic factors which affect the locoregional control, distal metastatic disease, overall survival (OAS) and disease free survival (DFS). Patients and Methods: This is a retrospective study on 126 patients with hypopharyngeal cancer who were treated at the Gharbia Cancer Society and Menia Oncology Center from the year 2007to 20014. All patients with hypopharyngeal cancer with complete file data were eligible for this study. All the patients who were treated by either radical or post operative radiotherapy were treated in supine position and were planned through 2-D simulator, patients were treated by a dose of 50-70 Gy according to the patient tolerance together with concurrent cisplatin. Results: This research also observed that considerable statistical connection among surgical therapy, locoregional control, and survival averages. Patients who were treated by radical surgery had an excellent locoregional control than to other patients who were treated by radical radiotherapy, and they also had the best survival averages between all the other therapy groups. The intermediate 6 months DFS and OAS averages for all studied patients were 40.1% and 47.5% respectively, while 12 months survival rates were 20.9% and 15.2% respectively. The median DFS was 5 months and median OAS was 7 months. Conclusion: This study supports that radical surgical treatment and post operative radiotherapy is recommended as the treatment of choice for operable hypopharyngeal cancer.

[Mohamed Mahmoud, and Sherweif Abdelfatah. A Retrospective Analysis of Hypopharync carcinoma Cases Treated in Menia Cancer Center and Gharbia Cancer Society Egypt in the Period from 2007-2014. Cancer Biology 2019;9(3):61-65]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 8. doi:10.7537/marscbj090319.08.

Keywords: Hypopharynx, head and neck, squamous cell carcinoma

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Outcome Predictors of Multi-drug Resistant Gram Negative Bacteremia in Children with Hematological Malignancies

Amr Abdalla, M.D^1,2, Mai Ahmed Mohamed, M.Sc^1,2, Samah Mohamed Radwan, M.D ³

¹Department of Pediatric Oncology, National Cancer Institute (NCI), Cairo University, Egypt

²Department of Pediatric Oncology, Children Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt

³Department of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Egypt

amr.abdalla@nci.cu.edu.eg, maiiyoussef2010@gmail.com, dr_samah_nci@yahoo.com

Abstract: Background: Antibiotic resistant bacteria are able to survive and even multiply in the presence of an antibiotic. They are associated with increased morbidity and mortality in cancer patients. The aim of this study is to identify the outcome and its predictors in febrile neutropenic pediatric patients with multi-drug resistant (MDR) gram negative bacteremias. This is a retrospective descriptive study that included 72 episodes of MDR gram negative bacteremias in 65 patients with hematological malignancies at the Pediatric Oncology Department, National Cancer Institute, Cairo University from January to December 2014. Results: This study included 35 patients with acute myeloid leukemia (AML), 21 with acute lymphoblastic leukemia (ALL), 14 with lymphomas and 2 with Langerhans’s cell histiocytosis (LCH). Klebsiella species was the most frequently isolated organism (38.9%). Piperacillin / tazobactam was the first line treatment used in 62 episodes (86.1%). Carbapenems were used as a first line treatment in 10 episodes (13.9%), and as a second line in 58/62 episodes (93.5%). Indication of treatment modification was based on culture and sensitivity result, vital instability and clinical focus of infection in 56.9%, 27.7% and 15.4% of episodes, respectively. Eleven percent of patients had history of previous cultures with MDR Gram-negative bacteria (GNB) within the past 3months. Conclusion: Mortality predictors were AML as an underlying diagnosis, active disease, vital instability, ICU admission, TLC <500/cc, platelet count <20,000/cc, impaired liver function tests, impaired renal function tests, impaired electrolytes, coagulopathies, treatment modification due to vital instability and history of previous culture with MDR-GNB.

[Amr Abdalla, Mai Ahmed Mohamed, Samah Mohamed Radwan. Outcome Predictors of Multi-drug Resistant Gram Negative Bacteremia in Children with Hematological Malignancies. Cancer Biology 2019;9(3):66-77]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 9. doi:10.7537/marscbj090319.09.

Keywords: multidrug resistance, gram negative bacteremias, febrile neutropenia, infection

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Intensity Modulated Radiotherapy (IMRT) Versus 3D Conformal Radiotherapy (3dcrt) In Early Stage Breast Cancer

Aliaa Mohamed Gamal Elden Mohamed¹, Rasha Abd Elghany Khedr¹, Hanan Shawky Mahmoud¹, Yasser Mostafa Al-Kerm² and Ashraf Fathy Barakat¹

¹Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Tanta University, Egypt

²Clinical Oncology and Nuclear Medicine Department Medical Research Institute, Alexandria University, Egypt

Abstract: Background: Breast cancer is the most common female cancer in the US and the second most common cause of cancer death in women. Approximately 268,670 new cases of invasive breast cancer and an estimated death toll of 41,400 women in 2018^. Management of invasive breast cancer should be based on the clinical extent and pathologic characteristics of the tumor, in addition to the age of the patient, menopausal status, some biologic prognostic factors, and the preference and psychological profile of the individual patient, optimally in a multidisciplinary setting. Surgical, medical, and radiation oncology remain the primary therapeutic disciplines in the management of breast cancer. Objective: The aim of our work was to compare two radiotherapy techniques in breast cancer female patients underwent BCS. The first was 3DCRT and second was IMRT. Subjective: The study included 50 randomly selected patients with early stage left breast cancer who underwent BCS were planned and calculated with 6 MV photon beam on treatment planning system. CT studies of selected patients transferred to the treatment planning system. Results: the dose homogeneity within PTV was significantly better with IMRT than with 3DCRT plans. it achieved significant lung sparing compared to 3DCRT plans. it achieved significant heart and LAD sparing compared to 3DCRT plans. As regard to contralateral breast mean dose in 3DCRT plans, it showed a significant reduction of CB dose compared to IMRT plans. As regard to contralateral lung mean dose in 3DCRT plans, it showed a significant reduction of contralateral lung dose compared to IMRT plans. As regard to early skin toxicity in IMRT plans, it showed a significant reduction in skin toxicity with better cosmesis compared to 3DCRT plans. As regard to DFS and OS showed no statistically significant difference in IMRT plan compared to 3DCRT plans.

[Aliaa Mohamed Gamal Elden Mohamed, Rasha Abd Elghany Khedr, Hanan Shawky Mahmoud, Yasser Mostafa Al-Kerm and Ashraf Fathy Barakat. Intensity Modulated Radiotherapy (IMRT) Versus 3D Conformal Radiotherapy (3dcrt) In Early Stage Breast Cancer. Cancer Biology 2019;9(3):78-91]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 10. doi:10.7537/marscbj090319.10.

Keywords: Intensity Modulated Radiotherapy (IMRT); Versus 3D Conformal Radiotherapy (3dcrt); Early Stage Breast Cancer

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The Role of BFl-1 in Cancer Unravels Inhibition Mechanism

Zaccheaus Oluwatayo Alabi¹, Olamide Tosin Olaoba^*1_, Kehinde Sulaimon Ayinde², Akinyemi³ and Temitope Isaac Adelusi³

¹Depatment of Chemistry, Federal University of São Carlos, São Carlos – SP, Brazil

³Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria

²Xuzhou Medical University, Xuzhou, Jiangsu, China

^*Corresponding author

E-mail: olaobamide@gmail.com; Phone: +55(16)991737096

Abstract: The release of cytochrome c into the cytoplasm via the mitochondrial membrane represent a significant step in programmed cell death. Bcl-2 family proteins play a crucial role as they regulate mitochondrial membrane permeability to cytochrome c. Bfl-1 belongs to the antiapoptotic subfamily of Bcl-2 protein which forms inhibitory heterodimeric complex with Bid thereby preventing the role of Bid in the disruption of Bax/Bcl-X_L and Bak/Bcl-X_L heterodimeric assembly critical for Bax and Bak dimerization in membrane permeability to cytochrome c. This Bfl-1 intracellular attitude connotes one major mechanism of cellular immortality in cancer cells. Other role played by Bfl-1 includes regulation of immunity, neutrophil development, maturation of B-cells and in post allergic mast cell. Cancer cells overexpress Bfl-1. Here, we hypothesize that cancer cells also overexpress Bid due to accumulated mutation but not to a threshold commensurate with the overexpressed Bfl-1. Therefore, using inhibitors of Bfl-1 and the mimetics of Bid/BH3-only domain may represent one way to subvert apoptotic resistance in cancer. Sadly, Bfl-1 selective inhibitors remained undrugged. However, synergistic inhibition of Bfl-1 and other co-dependent proteins may also represent a major breakthrough in overcoming apoptotic resistance.

[Zaccheaus Oluwatayo Alabi, Olamide Tosin Olaoba_, Kehinde Sulaimon Ayinde, Akinyemi and Temitope Isaac Adelusi. The Role of BFl-1 in Cancer Unravels Inhibition Mechanism. Cancer Biology 2019;9(3):92-100]. ISSN: 2150-1041 (print); ISSN: 2150-105X (online). http://www.cancerbio.net. 11. doi:10.7537/marscbj090319.11.

Keywords: Bfl-1; Bid; cancer; apoptosis

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