Context: Melanoma causes the highest number of skin cancer-related deaths worldwide. New treatment methods are essential for the management of this life-threatening disease. Aims: In this study, we investigated the efficacy of a standardized Cannabis sativa extract alone or in combination with single radiation dose (6 Gy) in B16F10 mouse melanoma cells in an extract dose-dependent manner. Materials and Methods: C. sativa extract at three concentrations (25, 12.5, and 6.25 μg/mL) alone for 72 h or in combination with radiation (24 h incubation after the extract treatment + 48 h incubation after exposure to radiation) were evaluated for cell viability of melanoma cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cells were also treated with 6.25 μg/mL extract alone for 72 h before analyzing C. sativa-induced cell death by flow cytometry. Results: Administration of the extract alone or alongside radiation substantially inhibited melanoma cell viability and proliferation in the extract dose response-dependent manner. The inhibition of melanoma cell viability was paralleled by an increase in necrosis but not apoptosis when melanoma cells were treated with the extract alone. Radiation alone did not have any antiproliferative effects, and radiation also did not synergize antiproliferative effects of the extract when the extract and radiation were combined. Conclusion: Our data suggest that C. sativa extract may have significant health and physiological implications for the treatment of melanoma. The results of this study also indicate that B16F10 mouse melanoma cells are radioresistant. Taken together, these findings may lead to the identification of new therapeutic strategy for the management of melanoma.

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Introduction: Whole-brain radiation therapy (WBRT) is an effective therapeutic modality in patients with brain metastases. However, nearly 90% of patients undergoing WBRT suffer from a neurocognitive function (NCF) impairment at diagnosis, and up to two-thirds will experience a further decline within 2–6 months after WBRT. Focal-dose reduction on bilateral hippocampus is thought to improve NCF preservation. The aim was to present a systematic review of clinical results on NCF after hippocampal-sparing (HS) WBRT. Materials and Methods: A systematic review of published literature was performed on PubMed and the Cochrane Library. Only prospective clinical trials reporting NCF outcome in patients treated with HS-WBRT have been analyzed. Results: A total of 165 patients from three studies were included. These studies are characterized by small sample size and different methods in terms of WBRT technique but with similar planning analysis and NCF assessment tests. No significant changes in NCF (i.e., verbal and nonverbal learning memory, executive functions, and psychomotor speed) between baseline and 4-month follow-up after RT and only a mean relative decline in delayed recall at 4 months (7% compared to 30% of historical control) were observed. Conclusions: Considering preliminary results on NCF preservation, further studies seem justified in patients undergoing brain irradiation for brain metastases or referred for prophylactic cranial irradiation to evaluate long-term effects on NCF and quality of life.

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Background: Meningiomas are common slow-growing primary intracranial neoplasms attached to the dura mater and are composed of neoplastic meningothelial cells. Increased incidence of meningiomas in women with an increased tumor growth during pregnancy and a possible association with breast cancer suggested that female sex hormones have been involved in the growth of meningiomas. Antihormonal-targeted therapy would be beneficial in such patients. Aim: The aim of this study is to correlate the expression of estrogen receptor (ER) and progesterone receptor (PR) in meningiomas with gender, location, histological subtypes, and grade. Materials and Methods: This is a 3½-year prospective and retrospective study of intracranial and intraspinal meningiomas. Clinical details of all the patients were noted from the computerized hospital information system. Immunohistochemistry for ER and PR was performed. Statistical analysis was performed using Chi-square test. Results: During the study period, there were 80 Grade I, 18 Grade II, and 2 Grade III meningiomas categorized as per the World Health Organization 2007 classification. The female-to-male ratio was 1.9:1 and the mean age was 47.8 years. ER was expressed in 2% of meningiomas. PR was expressed in 67.5% of Grade I and 66.6% of Grade II and none of Grade III meningiomas. Brain-invasive meningiomas showed 54.5% PR immunopositivity and negative for ER. Conclusion: ER and PR were expressed in 2% and 66% of meningiomas, respectively. Statistically significant relationship was not found between the positivity of PR in females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas.

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Purpose: The study aimed to assess breast density as a risk factor for breast malignancy using automated volumetric breast density software and to study the relationship of breast density with tumor histopathological characteristics. Materials and Methods: One hundred and thirty-four women with unilateral core biopsy-proven breast cancer were taken in the “case group.” Two hundred and one women with normal bilateral screening mammograms were enrolled in the “control group.” The cases and controls were further divided into pre- and post-menopausal subgroups. The mammograms of the contralateral breast of the cases and bilateral breasts of the controls were evaluated by automated volumetric breast density software and classified into four density grades. The tumor histopathological characteristics in the various density grades were also evaluated. Results: In premenopausal women, the odds of having breast cancer was significantly higher for Grade 3 breasts (odds ratio [OR] 3.03; 95% confidence interval [CI]: [1.19–7.71]) versus Grade 1 and 2 breasts. Grade 4 premenopausal breasts also had greater odds (OR 3.09; 95% CI [0.89–10.78]) of developing breast cancer. No such relationship was established for postmenopausal women. No significant difference was seen in the histopathology of breast cancer among various breast density groups. Conclusion: Increased breast density can be considered as an inherent, independent risk factor for breast cancer in premenopausal women.

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Background: There is controversy regarding the relationship between margin status and risk of local recurrence (LR) in patients with Ductal carcinoma in situ(DCIS) treated by mastectomy. Purpose: We sought to assess the LR rates for patients with DCIS breast cancer treated by mastectomy with respect to the resection margin (RM) status. Materials and Methods: Systematic search of MEDLINE, EMBASE, and Cochrane library published was performed. Studies of pure DCIS breast cancer with treatment of mastectomy and studies that reported surgical RM and LR were included. Results:A total of 12 retrospective studies were included, encompassing 2902 patients with a mean follow-up of 86.4 months. Overall LR rates were 5.3% (27/508) for positive or close margins and 1.6% (37/2367) for negative margin, and most of the recurrences (93.7%) are invasive cancers. Patients with positive or close margins showed a 3.72-fold (95% confidence interval [CI] = 2.30–6.01,P < 0.01, I^[2] = 11%) higher risk of LR than patients with negative margin. Patients with positive margin showed a 2.91-fold (95% CI = 1.14–7.41,P = 0.03, I^[2] = 0%) higher risk of LR than patients with close margin. Postmastectomy radiation therapy (RT) was not associated with a decreased risk of LR (Risk ratio 0.50; 95% CI = 0.06–4.08,P= 0.52, I^[2] = 0%) in patients with positive or close margins. Conclusions: The RM status after mastectomy has a great impact on LR. However, the recurrence rate was insufficient to warrant a recommendation for postmastectomy RT in patients with close or positive margins.

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Background and Objective: Meningiomas are among the most common intracranial tumors of the central nervous system. It is widely accepted that the initiation and progression of meningiomas involve the accumulation of nucleus genetic alterations, but little is known about the implication of mitochondrial genomic alterations during development of these tumors. The human mitochondrial DNA (mtDNA) contains a short hypervariable, noncoding displacement loop control region known as the D-Loop. Alterations in the mtDNA D-loop have been reported to occur in most types of human cancers. The purpose of this study was to assess the mtDNA D-loop mutations in Malaysian meningioma patients. Materials and Methods: Genomic DNA was extracted from 21 fresh-frozen tumor tissues and blood samples of the same meningioma patients. The entire mtDNA D-loop region (positions 16024-576) was polymerase chain reaction amplified using designed primers, and then amplification products were purified before the direct DNA sequencing proceeds. Results: Overall, 10 (47.6%) patients were detected to harbor a total of 27 somatic mtDNA D-loop mutations. Most of these mtDNA mutations were identified in the hypervariable segment II (40.7%), with 33.3% being located mainly in the conserved sequence block II of the D310 sequence. Furthermore, 58 different germline variations were observed at 21 nucleotide positions. Conclusion: Our results suggest that mtDNA alterations in the D-loop region may be an important and early event in developing meningioma. Further studies are needed, including validation in a larger patient cohort, to verify the clinicopathological outcomes of mtDNA mutation biomarkers in meningiomas.

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Purpose: Intracranial germ cell tumors (ICGCTs) comprise approximately 0.4%–3% of all brain tumors. In this study, we aim to evaluate clinical characteristics, treatment and outcomes of patients with ICGCT. Patients and Methods: All patients with ICGCT diagnosed in Hacettepe University's Pediatric Oncology Department between January 1980 and January 2016 were evaluated, retrospectively. Results: We identified 52 patients (male/female: 2.46) diagnosed with ICGT. Median age was 140 months. The median duration of symptoms was 3 months. Patients with endocrine symptoms were diagnosed later than others (P = 0.028). The primary site was pineal region in 20 patients, nonpineal region in 32 which included six bifocal involvements. Pineal location was more common in boys than girls (P = 0.02). Histopathological diagnosis was germinoma in 28 patients, nongerminomatous malignant germ cell tumors in 14 and immature teratoma in 4. The mean age for germinoma was higher than that of nongerminomatous tumors (P = 0.032). Patients treated with surgery and radiotherapy and chemotherapy. Median follow-up time was 52.5 months. Thirty-six patients were alive for 12–228 months. Relapsed/progressive disease was observed in 11 patients. Nongerminomatous tumors more frequently showed relapse/progression than germinoma (P = 0.06). Five-year overall and event-free survival rates for the whole group were 72.6% and 57.2%, respectively. Overall and event-free survival rates for germinoma were better than malignant nongerminomatous tumors. Conclusion: Although the ratio of ICGCTs to central nervous system tumors in our series was similar to western countries, some clinical features such as tumor location were similar to cases from East Asian countries. Although similar protocols were used survival rates lower than developed western and eastern developed countries.

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Background: Initiation, promotion, progression, and metastasis of mammary tumors are mediated by dysregulation of multiple genes involved in various signaling pathways. Expressional variation of these molecules significantly influences cancer cell proliferation in breast cancer. Aims and Objectives: In the current study, tumor necrosis factor-alpha (TNF-α) and its downstream effector nuclear factor kappa-B1 (NF-κB1) mean transcript levels were explored and associated with molecular subtypes in breast cancer cohort of Pakistan. Freshly excised tumors (n = 150) along with background tissues were collected for RNA isolation and cDNA synthesis. Materials and Methods: Quantitative polymerase chain reaction was carried out for quantification of TNF-α, NF-κB1, and β-actin gene transcripts along with estrogen receptor, progesterone receptor, HER2, and Ki-67, followed by statistical analysis. Results: For TNF-α and NF-κB1, 95% and 77% of the cohort was found to be positive, respectively. Both of these molecules were found to be significantly upregulated in tumors when compared against their respective controls (P < 0.0001). Association of TNF-α and NF-κB1 with late clinical stages, poorly differentiated tumors, increased tumor size, nodal involvement, and metastasis was observed to be statistically significant (P < 0.05). Strong positive correlation was established between TNF-α and NF-κB1(r = 0.465, P< 0.05). Moreover, mean transcript levels of TNF-α and NF-κB1 were significantly elevated in Luminal A and Luminal B subtypes of breast cancer patients, respectively. Conclusion: Strong positive correlation between TNF-α and NF-κB1 proposed the putative role of these molecules as prognostic biomarkers in breast cancer.

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Introduction: Male breast cancer (MBC) incidence is <1%, but it is increasing. MBC incidence increases with age. There are no randomized trials on MBC because of low number of patients seen in any institution and hence its management is derived from breast cancer (BC) in women. In this study, we analyzed outcome in MBC patients with adjuvant treatment. Materials and Methods: From 1991 to 2014, 81 men with BC were retrospectively analyzed for demographic, clinicopathological, and treatment outcomes. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. DFS and OS were estimated using Kaplan–Meier method and compared between patients receiving and not receiving adjuvant treatment using log-rank test. Results: The median age was 57 years (range 30–86 years). Right, left, and bilateral BCs were seen in 41 (51%), 38 (47%), and 2 (2%) men, respectively. The mean duration of symptoms was 25 months (range 1–240 months). Comorbidity and family history was present in 31 (38%) and 3 (4%) men, respectively. The mean tumor size was 5 cm × 5 cm (range, 1 cm × 1 cm to 10 cm × 10 cm). Nipple was involved in 46 (57%) men. Early, locally advanced, and metastatic disease were seen in ??30 (37%), 34 (42%), and 17 (21%) men, respectively. Majority (71, 88%) of men had invasive ductal carcinoma histology. In radically treated 64 men, neoadjuvant chemotherapy was given to 12 (19%) patients (fluorouracil, adriamycin, and cyclophosphamide [FAC] to 9 and FAC + taxanes to 3), with CR in 4 (33.3%) and partial response (PR) in 8 (66.7%) patients. Mastectomy was done in 55 (86%) and wide local excision in 9 (14%) men. Margins and nodes were positive in 17 (27%) and 38 (59%) men, respectively. Estrogen receptor, PR, and human epidermal growth factor receptor 2/neu positive were seen in 27 (42%), 17 (26.5%), and 2 (3%) patients, respectively. Adjuvant hypofractionated radiotherapy, chemotherapy, and tamoxifen were received by 51 (80%), 35 (55%), and 45 (70%) men, respectively. Median follow-up was 60 months (range 4–278 months). Locoregional recurrence occurred in 8 (12.5%) and distant metastasis in 22 (34%) men, respectively. DFS and OS at 10 years were 42% and 53%, respectively. DFS and OS were significantly better in men with adjuvant radiation (54% vs. 24%, P = 0.007 and 57% vs. 35%, P = 0.022, respectively) and hormonal therapy (57% vs. 14.5%, P = 0.004 and 62% vs. 39%, P = 0.045, respectively). Chemotherapy had no impact on DFS and OS. Conclusion: Adjuvant hypofractionated radiotherapy and hormonal therapy significantly improved DFS and OS in MBC patients. Chemotherapy had no impact on DFS and OS.

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Epidermoid cysts of the spinal cord without spinal dysraphisms are rare lesions and intramedullary cysts are still rarer. Approximately only over 60 cases are reported in literature worldwide. Magnetic resonance imaging is the imaging modality of choice for the diagnosis of these lesions. Management of these lesions is by total surgical excision, although at times, it is not possible due to adherence of the capsule to the parenchyma of the spinal cord which may be the cause of recurrence. To our knowledge, this is the second case of recurrent intramedullary epidermoid cyst of spinal cord. We report a case of intramedullary epidermoid cyst which recurred after 7 years following near-total excision of tumor at our institute.

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Background: Glioblastoma (GBM) is a terminal form of illness. Illness perceptions play vital role in illness behavior and managing the disease. GBM cancer survivor's illness perceptions and their perceived social support is not systematically studied. Therefore, study aimed to understand the illness perceptions and perceived social support of GBM survivors during hospitalization. Methodology: The study used cross sectional-descriptive research design. A total of 40 GBM survivors were recruited by using convenience sampling method. The Illness Perception Questionnaire Revised (IPQ-R) by Moss-Morris, Weinman et al. (2002), and Perceived Social Support from Family (FSS-Family) and Perceived Social Support from Friends (PSS-Friends) scales by Mary E. Procidano and Kenneth (1983) were administered on recruited participants. Semi-structured questionnaire was used to collect the personal and illness details of participants. Free R software was used to analyse the data. Descriptive statistics such as frequency, percentage, mean and standard deviation were calculated on selected variables. Results: Half of the participants 50% (n = 20) did not aware of illness and 50% (n = 20) partially aware of their illness. Past sins 90% (n = 36), personal stress 90% (n = 36), increased work load 65% (n = 26), head Injury/smoking 55% (n = 22), personal dietary habits 50% (n = 20) were attributed as reasons for GBM. Participant's partially believed GBM was life threatening illness, causes emotional disturbances but not aware of consequences of illness. Perceived social support from family members and friends during hospitalization was found to be poor. Conclusion: GBM survivor's informational and educational needs were not met adequately. Psychoeducational programmes, addressing negative believes associated with brain cancer and enhancing social support for glioma patients are recommended during hospitalization.

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Background: Role of hypofractionated radiotherapy (HFRT) in early breast cancer is established; comparatively, there are limited data for HFRT in locally advanced breast cancer (LABC). We report the impact of HFRT in unselected breast cancer patients in comparison with historically treated patients with conventional fractionated radiotherapy (CFRT). Patients and Methods: Records of 463 breast cancer patients treated between January 09 and July 13 with CFRT (50 Gy/25 fr) or HFRT (42.4 Gy in 16 fractions or 40 Gy in 15 fractions) in two sequential periods were retrospectively reviewed. The analysis was done in August 2018. The primary endpoint was to compare the differences in locoregional recurrence rate. Results: Of the 463 patients, 209 received CFRT and 254 received HFRT. The median age was 48 years (interquartile range: 40–56), premenopausal (CFRT: 23% vs. HFRT 39%, P = 0.005). The most common pathology was infiltrating ductal carcinoma (81%) with Grade III tumors (45%), estrogen receptor (+) was seen in 44%, triple-negative breast cancer in 34%, and Her2Neu (3+) were seen in 27%. Two hundred and fifty-four patients (54.5%) had undergone breast-conserving surgery (BCS) and 209 patients (45%) modified radical mastectomy (MRM). Nodal radiotherapy was delivered in 76% versus 64% in patients receiving CFRT versus HFRT, respectively (P = 0.005). With a median follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4 years#39; actuarial local recurrence-free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37). The mean estimated LRFS (local relapse-free survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3). Conclusions: The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to CFRT.

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Background: Trastuzumab is a Food and Drug Administration-approved humanized monoclonal antibody which targets the extracellular domain of human epidermal growth factor receptor 2 (HER2) receptor overexpressed on HER2-positive breast cancer cells. The combination of Lutetium-177 (¹⁷⁷ Lu) (t_½= 6.7 days, E_βmax497 keV (78.6%) and trastuzumab makes it a suitable targeting agent for radioimmunotherapy. In preclinical and clinical studies,¹⁷⁷ Lu-Trastuzumab has proven to be effective for the treatment of HER2-positive malignancies such as breast and ovarian cancer. Objectives: In this study, we report the mechanism of action of¹⁷⁷ Lu-CHX-A“-diethylenetriaminepentaacetic acid (DTPA)-trastuzumab at the cellular and molecular level by performing various in vitro assays in HER2-positive MDA-MB-453 breast cancer cells. Materials and Methods: Trastuzumab was conjugated to the bifunctional chelating agent (BFCA) para-isothiocyanatobenzyl-DTPA and radiolabeled with¹⁷⁷ Lu. In vitro cell binding studies were carried out in MDA-MB-453 cells to confirm the specificity of the complex toward the receptor. Cellular toxicity, cell cycle, and cell death analysis were also performed for exploring the potential of the radioimmunoconjugate at cellular and molecular level. Results: In vitro cell binding studies showed a maximum binding of 10.7 ± 0.1% which reduced to 2.9 ± 0.1% on coincubation with unlabeled antibody. Our study revealed that the cellular toxicity was dose dependent, and mode of cell death was predominantly by apoptosis. The radioimmunoconjugate retarded the cell in the S phase of cell cycle with two-fold increase in G2/M arrest which justifies the enhanced apoptosis at higher doses. Conclusions: The study revealed that the formulation can execute a dose-dependent cellular toxicity through induction of apoptosis.

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Aim: The main objective of this study is to evaluate the new proposed boron neutron capture therapy (BNCT) neutron beam based on the use of Tehran Research Reactor medical room to treat deep-seated brain tumors. Material and Methods: The Snyder head phantom has been simulated through the MCNPX Monte Carlo code to calculate different dose profiles and desired medical merits. The simulation consists of the full geometry of new beamline and the phantom. Results: The medical merits related to the new proposed BNCT beamline have a good agreement with other facilities, which indicates the potential use of this new beam for treatment of deep-seated brain tumors. Conclusion: The obtained results show the capability of the new setup to treat deep-seated brain tumor, which was located up to ~5 cm of the skin surface.

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Objective(s): Chlorogenic acid is an herbal compound with various effects such as antiviral, antioxidant, and anticancer effect with low toxicity, which inhibits cell proliferation. Clinical studies had shown that chlorogenic acid has a positive effect on the different types of cancers treatment. Hence, this study evaluates chlorogenic acid effects on 4T1 breast cancer cells. Materials and Methods: In this study, cell proliferation was measured using an 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT) on 4T1 cells. Afterwards, other assays like P53, Caspase-3 proteins expression and Annexin V/PI were detected by flow cytometry. Also; Bax and Bcl-2 were carried out by immunocytochemistry. Results: 200 μM of chlorogenic acid concentration showed the highest level of cytotoxicity toward 4T1 cells. Percentage of cell viability data were significant in 100 μM (P < 0.05) and 150, 200 μM (P < 0.001) doses. The evaluation using Annexin V/PI showed cell apoptosis in 100 μM (P < 0.05), 150 μM (P < 0.01), and for 200 μM (P < 0.05 and P < 0.01). Immunocytochemistry results showed the upregulation of Bax and also the downregulation of Bcl-2 in 4T1 cells treated with chlorogenic acid (P < 0.001). The expression level of P53 and caspase-3 increased during treatment with chlorogenic acid in the 4T1 cells (P < 0.001). Conclusion: Our findings demonstrated that chlorogenic acid plays a notable role on apoptosis inducing in the 4T1 cells through regulation of apoptotic proteins.

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Background: Isocitrate dehydrogenase-1 (IDH1) mutation is now an established early event in gliomagenesis. The ability to detect this mutation by several techniques including immunohistochemistry makes it a significant marker for diagnosing and prognosticating gliomas. This study was done to assess the expression of mutant IDH1 in different grades of gliomas and evaluate its utility in differentiating reactive gliosis from glioma and defining surgical margins of these tumors in the operative specimens. Materials and Methods: A total of fifty cases including equal number of Grade I, II, III, and IV gliomas and gliosis were included in the study. Formalin-fixed, paraffin-embedded tissue sections from these lesions were immunostained with IDH1 and Ki-67 antibody, and percentage of tumor cells that stained positive with these markers was assessed. Results: Grades II, III, and IV showed consistent immunopositivity for IDH1. No immunostaining was noted in Grade I glioma and gliosis. Mean Ki-67 labeling index correlated with grades of gliomas with low activity in Grade I and high activity in Grade IV. Individual tumor cells infiltrating into adjacent normal brain parenchyma also stained positive with IDH1 antibody. Conclusion: Immunostaining for IDH1 mutation can be utilized as a reliable marker in the precise diagnosis of diffuse gliomas and also in objective assessment of surgical margins to differentiate gliomas from gliosis.

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Introduction: Brain tumors constitute a small presentation of all cancers (1.4%) and cancer related deaths (2.5%). Most of the brain tumors are malignant and carry bad prognosis and even if those which are benign still can interfere with brain functions that are required for daily living. We did an audit of brain tumor patients treated in our center and see their prognosis in correlation with different histological types. Materials and Methods: We analyzed 497 patients treated at our center from June 2007 to June 2012 of different histological types. All the patients underwent complete central nervous system examination and thorough workup including hematological investigations, radiological investigations, and confirmation of histological type by biopsy. These patients were then treated with surgery followed by radiotherapy or upfront curative radiotherapy as per staging and then kept on regular follow-up as per institutional protocol. Results: Majority of patients were astrocytomas (309 patients) followed by a pituitary adenoma (39 patients), oligodendroglioma (33 patients), medulloblastoma (22 patients), arteriovenous malformations (19 patients), craniopharyngioma (16 patients), and recurrent brain tumors (12 patients). There were few cases of central nervous lymphoma, meningioma, melanocytoma, ependymomas, schwannomas, hemangiopericytoma, gliosarcoma, and primitive neuroectodermal tumor. The histological types vary differently regarding presentation, treatment, and prognosis. Conclusion: Astrocytomas are the most common tumors in presentation (309 patients) in which the high-grade astrocytomas carried worse prognosis. Benign tumors such as pituitary adenomas, schwannomas, and craniopharyngiomas had the best prognosis with survival seen up to almost last follow-up.

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In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the term “FLASH” radiotherapy (RT). Thus, in the present study, we systematically review these recent studies on FLASH RT with regard to its efficacy and safety. The reporting of this systematic review was done in line with the statement of Preferred Reporting Items for Systematic reviews and Meta-Analyses. Electronic search of the databases such as PubMed, Scopus, and Embase was conducted to retrieve relevant studies investigating the FLASH effect. From an initial search of 216 potential articles, 16 articles (in vivo, in vitro , and clinical studies) were finally included in this systematic review. Results showed that FLASH RT dose rates had protective effects on normal tissues in addition to antitumor effect. Although still in its early research stages, FLASH RT has the potential to rival present RT regimens in terms of safety and antitumor effect. However, further studies are needed to address the aspects such as optimal dose rate, effect on deep tumors, tumor recurrence, longer follow-up time, and mechanism of action.

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Background: Women in developing countries usually delay in presenting their symptoms as a part of the early diagnosis program. This study was conducted for analyzing the reason of patient's delay and its relation with socioeconomic and health conditions, knowledge, and women's belief about breast cancer (BC). Methodology: This study used a cross-sectional design in the early detection center in Kurdistan (North Iraq). Women were interviewed about socioeconomic and health background, knowledge, and belief about BC. Results: The median of patient delay in the BC symptomatic women in this study was higher (30 days) as compared with developed countries. Patient delay was longer in women who were widows, had a barely self-perceived economic status, and had chronic diseases. There was a significant relationship of patient delay with women's health motivation and perceived barrier to seeking medical care. Conclusions: Health promotion program should emphasize on the women's motivation about early diagnosis and seeking to early detection.

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Introduction: Phyllodes tumor is a group of biphasic fibroepithelial tumors of the breast, graded as benign, borderline, and malignant. The grading of breast phyllodes remains a challenging task for the pathologists as the prognosis, and further treatment depends on it. In this study, an effort has been made to grade phyllodes tumor on the basis of immunohistochemistry. Aims and Objectives: Vascular endothelial growth factor, CD10, and factor 8 have been used as immunohistochemical markers for grading. Results and Conclusion: We have found a significant correlation between the expression of these markers and grading of phyllodes tumor. Positive correlation was also found amongst expression of all three markers. To conclude, increased expression of these markers with increasing grade can aid in diagnosis and guide treatment.

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Introduction: Cyclic nucleotide phosphodiesterase (PDE) enzymes are a large superfamily of enzymes that catalyze the conversion reaction of cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) to AMP and GMP, respectively. In some cancer cells, PDE-5 has been shown to be overexpressed in multiple human carcinomas. It seems that the inhibition of PDE-5 may has anticancer effects. Cisplatin is one of the prevalent chemo-agents to treat solid tumors. However, its clinical usefulness is hindered by dose-limiting toxicities, especially on the kidneys (nephrotoxicity) and ears (ototoxicity). In this study, the antitumor activity of the sildenafil as a PDE-5 inhibitor alone and in combination with cisplatin on human mammary adenocarcinomas and MCF-7 and MDA-MB-468 was assessed. Materials and Methods: Sildenafil as PDE type 5 (PDE5) inhibitor is the drugs that we combined with the cisplatin (chemotherapeutic agent), in vitro. Human mammary adenocarcinomas and MCF-7 and MDA-MB-468 cell lines were cultured in standard conditions. At time point, following 24 h and 48 h incubation, the cell lines were treated by cisplatin in the presence/absence of sildenafil. Cell viability, apoptosis, and reactive oxygen species (ROS) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, real-time polymerase chain reaction, and Western blot; and fluorimetric methods, respectively. Statistical analysis was performed using SPSS software SPSS (SPSS Inc., Chicago, IL, USA). Results: In MCF-7 cell line, following 24 h incubation, combinations of sildenafil with cisplatin (P < 0.001) showed decreased cell viability when compared to sildenafil and cisplatin alone. Moreover in MDA-MB-468 cell line, following 24 h incubation, data did not show any significant changes on cell viability when treated with cisplatin, in the presence or absence of sildenafil. However, following 48 h incubation, combinations of cisplatin with sildenafil (P < 0.001) were showed decreased cell viability when compared to cisplatin and sildenafil alone in both MCF-7 and MDA-MB-468 cell lines. Concerning the ROS production and apoptosis, data showed that both processes increase significantly in the presence of the sildenafil in comparison absent it. Conclusion: Our data showed that the combination of sildenafil with cisplatin can improve cell toxicity and anticancer effect of cisplatin. And also sildenafil as a PDE-5 inhibitor could be used as additive treatment in combination with cisplatin to make a reduction in cisplatin dosage and its side effects.

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Aims: In central nervous system (CNS) tumors, surgery combined with radiotherapy may cure many tumors. The basic technique in conventional radiotherapy is craniospinal radiotherapy; in this technique, spinal cord can be treated with electron or photon beams. This study was aimed to compare two radiotherapy techniques in craniospinal radiotherapy, (a) treatment of spine with a single photon beam and (b) with a combination of photon and electron beams. Materials and Methods: The two techniques were planned. In the first technique, both brain and spine were irradiated with 6 MV photon beams. In the second technique, brain was irradiated with 6 MV photon and spine with 18 MeV electron beams. To compensate the dose deficiency in lumbar area, an anterior field of 15 MV photon beam was also applied in the second technique. The dose to target volume and organ at risks (OARs) were measured by thermoluminescent dosimeter and compared with the corresponding values calculated by Isogray treatment planning system. Results: OARs including heart, mandible, thyroid, and lungs received lower dose from technique 2 compared with technique 1; kidneys were exceptions which received higher dose in the technique 2. Conclusions: The dose to thyroid, mandible, heart, and lungs were lower in technique 2, while kidneys received higher dose in technique 2. This was caused by using the anterior 15 MV photon beam. Based on these results, for children, instead of photon beam for treatment of spinal cord, it is wiser to use electron beam.

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Aims: This study is carried out to report on the knowledge and practice regarding breast self-examination (BSE) among women from the city of Mosul in Iraq and to evaluate the prevalence of performing clinical breast examination (CBE) and mammography among them. Settings and Design: A descriptive, cross-sectional survey carried out among females working in the University of Mosul, as a sample of the female population of Mosul city. Subjects and Methods: The sample was collected conveniently, and the data were collected from July to November 2018. Data were collected by interviews with 405 participants. Knowledge answers were scored and categorized into two groups: good and poor level of knowledge. Results: A final sample of 384 participants were included in the analysis, with a mean age of 42.58 ± 8.9. Only 39 (10.1%) and 37 (9.6%) participants performed mammographic examination and CBE of their breasts, respectively. Just 100 (30.3%) of the 330 females who knew BSE performed BSE routinely or intermittently. The mean knowledge score was 4.22 ± 1.66, and only 141 females (42.7%) were found to have a good level of knowledge. A statistically significant association of knowledge level with marital status (P = 0.015), perceived benefit of BSE (P = 0.001), previous gain of instructions of BSE (P < 0.05), and the provider (P < 0.05) was found. Conclusions: The performance results of BSE were poor as well as for CBE and mammography among the study participants. There is a need for educational programs to create awareness and improve knowledge about routine breast cancer screening behavior.

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Introduction: Fatty acids (FAs) are the vital constituents of membrane structures. De novo synthesis of FAs includes an enzymatic complex of FA synthase and delta desaturases. These enzymes are overexpressed in tumors, and inhibition of these enzymes is gaining interest. Our aim was to determine if delta desaturase activities are altered in breast cancer (BC) cases and if altered whether delta desaturase activities differ among BC genotypes. Materials and Methods: In this observational comparative study, 50 women with BC and 30 control women were recruited for the study. Gas chromatography-flame ionization detector was used to measure the plasma FA levels. Desaturase activities were assessed as product-to-precursor FA ratios. The Wilcoxon signed-rank test was used to compare between two groups, and P ≤ 0.05 was considered as statistically significant. Results: The FA analysis revealed higher levels of monounsaturated FAs (MUFAs) and linolenic acid metabolites (C18:3n-6, C20:4n-6) in BC patients, whereas C20:5n-3 was higher in controls. The Delta 9 desaturase (D9D) and D6D were higher in BC cases suggesting greater conversion saturated FA to MUFA and linoleic acid to its metabolites. D9D-16 activity was statistically significant (P = 0.03) in BC women, particularly in estrogen-receptor-positive patients. Conclusion: There is limited evidence to substantiate the link between diet and cancer. The current study showed there is an altered lipid desaturase activity. Nutritional intervention and drugs that target the FA pathway may provide a new approach to prevent and treat BC.

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Li-Fraumeni syndrome (LFS) is a genetic disease that is hypersensitive to radiotherapy. Proton therapy (PT) was strongly recommended for pediatric and radiation-sensitive tumors. However, there is little information on PT for LFS. The patient was a 7-year-old girl with LFS who was diagnosed with radiation-induced right shoulder blade osteosarcoma and left chest wall malignant fibrous histiocytoma. Both tumors were in the area that had previously been irradiated (36–45 Gy by photon radiotherapy). Sixty-six GyE in 30 fractions was planned for both tumors. We set the clinical target to the minimum gross tumor volume. To comprehensively assess any adverse events, PT was conducted under hospital administration. Cisplatin was used as simultaneous combination chemotherapy. Although administration of granulocyte-colony stimulating factor was necessary for myelosuppression by chemotherapy, PT was completed without interruption. Acute radiation toxicity was observed as Grade 1 dermatitis. The dermatitis became exacerbated 2 weeks after PT but subsequently improved with conservation treatment alone. Twenty-three months after PT, magnetic resonance imaging showed an increase in the tumor on the right shoulder. A histological examination was not conducted as the family declined, but secondary cancer was suggested rather than recurrent osteosarcoma, as the tumor developed mainly from the soft tissue. Additional surgical treatment and radiotherapy were not indicated, and the patient died of tumor progression and sepsis caused by myelosuppression 27 months after undergoing PT. Up to 23 months after PT, there were no signs of Grade 2 or more late toxicities. This represents the first reported case of PT for a patient with LF to treat radiation-induced secondary cancer.

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Introduction: The role of hypofractionated radiotherapy (HFRT) in postmastectomy breast cancer patients is not well established. This study was done to establish the role of two different HFRT schedules in the treatment of chest wall and regional lymph nodes after mastectomy. Materials and Methods: Between 2012 and 2016, consecutively registered patients of locally advanced breast cancer patients having undergone mastectomy and adjuvant radiotherapy (RT) at a tertiary cancer center were analyzed. Locoregional recurrence (LRR) was the primary endpoint, whereas overall survival (OS), disease-free survival (DFS), and both acute and late adverse events were secondary endpoints. Results: A total of 34 patients who were treated with 39 Gy in 13 fractions over 2½ weeks and 35 patients who were treated with 40 Gy in 15 fractions over 3 weeks were identified. The median follow-up period was 47 months and 63.5 months in the 39 Gy and 40 Gy arms, respectively. LRR was seen in 11.8% and 8.6% of patients in the 39 Gy and 40 Gy arms, respectively. OS at 4 years was 66% and 71.5% in the 39 Gy and 40 Gy arms, respectively. The mean DFS for 39 Gy and 40 Gy arms was 43.6 months and 66.4 months, respectively (P = 0.822). Acute skin toxicity was similar in the two groups. Arm edema was significantly more in the 40 Gy arm. Conclusion: The two HFRT schedules are equivalent to each other in terms of survival outcomes. Arm edema is higher with 40 Gy arm as compared to 39 Gy arm.

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Context: Four single-nucleotide polymorphisms (SNPs) in Mexican patients and their association with the development of breast cancer (BC). Aims: This work is focused on determining the association of fibroblast growth factor receptor (rs12196489), TOX3 (rs3803662), human telomerase reverse transcriptase (h TERT, rs10069690), and FTO (rs17817449) polymorphisms and BC in a cohort of Mexican women. Settings and Design: The study included 56 patients with a confirmed diagnosis of BC and 83 controls. Clinical characteristics were obtained from medical records. Subjects and Methods: Genomic DNA from the samples was obtained from lymphocytes, and the genotyping of rs12196489, rs3803662, rs10069690, and rs17817449 polymorphisms was performed by real-time polymerase chain reaction using specific TaqMan probes. Statistical analysis was assessed to evaluate the distribution of genotype frequencies between cases and controls. Statistical Analysis: We used the STATA Statistical Package (version 10.1; STATA Corp., College Station, TX, USA). Student's t-test, χ² test, or Fisher's exact test was used to evaluate the distribution of genotype frequencies. Results: No statistical differences in allelic and genotypic frequencies were found between patients with BC and controls for SNPs: rs1219648, rs3803662, and rs17817449. Interestingly, according to the χ² test, a significant difference was exhibited for rs10069690 (odds ratio = 0.095; 95% confidence interval = 0.038–0.214; P < 0.001). Conclusions: The h TERT (rs10069690) polymorphism might be associated with BC in Mexican women. Nevertheless, additional studies in a larger cohort are required to confirm this association and to possibly use this polymorphism as a potential biomarker in the early diagnosis of BC.

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Context: Neoadjuvant chemotherapy (NACT) has become a strategy in the multidisciplinary treatment approach to breast cancer. Since clinical and radiological responses do not correlate well with residual tumor after treatment, pathological evaluation of tumor response to chemotherapy is essential for accurate assessment. Aims: The aim of this study is to assess clinicopathological response to NACT in patients with invasive breast carcinoma. Settings and Design: Single institution, retrospective study was conducted for 4 years. Subjects and Methods: The study included 95 cases with the clinical diagnosis of locally advanced breast cancer and invasive breast carcinoma on histopathological examination of core needle biopsy/lumpectomy specimen. These cases were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors and treated with four cycles of NACT (adriamycin-cyclophosphamide) therapy. Histopathological examination of postchemo modified radical mastectomy specimens was performed following standard protocol. The pathological response of tumor to chemotherapy was assessed on Miller-Payne grading (MPG) and residual disease in breast and lymph node (RDBN) level. Statistical Analysis Used: Data were analyzed in percentages and presented in charts and tables. Results: Histopathological examination of pre-chemo biopsy specimens revealed invasive ductal carcinoma No special type (NST) in maximum, 89 (93.7%) cases. Majority 43 (45.3%) cases were HER2-positive followed by estrogen receptor-positive and/or progesterone receptor positive and HER2-positive type seen in 23 (24.2%) cases and 22 (23.1%) cases were triple negative. Sixteen (16.8%) and 76 (80%) cases showed pathological complete response (pCR) and partial pathological response, respectively, to NACT on MPG; 12 (12.6%) and 83 (87.4%) cases showed pCR and residual disease, respectively, on RDBN level. Majority 37.5% and 50% of cases showing pCR on MPG and RDBN level, respectively, were triple negative. Conclusions: This study highlights the clinicopathological response to NACT in carcinoma breast patients and identifies the molecular subtypes of these patients likely to respond to NACT.

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Extramammary Paget's disease (EMPD) of the penis is a rare, intraepidermal adenocarcinoma. We describe the case of a 60-year-old male who presented with an erythematous plaque on his penis, previously treated with various topical and oral drugs. Punch biopsy from the lesion revealed the diagnosis of EMPD. Early diagnosis and treatment is necessary for this rare neoplastic condition.

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Introduction: Annona muricata (L.) (AM), commonly known as Soursop and Lakshmanaphala/Hanumaphala in India, has been extensively used in ethnomedicine for treating tuberculosis, urinary tract infections (UTIs) and cancers. The fruit is a rich source of antioxidants and antitumor agents. Methods: In this study, we have extracted phytochemicals that exhibited anti-cancer property from the (a) fruit pulp using methanol (AMPM) and water (AMPW); and (b) seeds using methanol (AMSM). Qualitative phytochemical analysis showed the presence of phenolics, tannins, alkaloids, flavonoids, sterols, terpenoids, carbohydrates and proteins in AMPM and AMPW. All three extracts were first checked for in vitro antioxidant and anti-inflammatory properties and then tested for efficacy against MCF-7 and MDA-MB-231. Results: Among these three extracts, AMSM showed the highest antioxidant power as well as ~80% inhibition at 320μg/ml concentration in both cell lines upon treatment for 24h. However, only about 40% inhibition was observed with 320μg/ml AMPM treatment, despite its highest anti-inflammatory potential. Water extract AMPW exhibited about 80% growth inhibition at 50% dilution. Since fruit pulp is the one consumed, the extracts AMPM and AMPW were further tested for apoptosis induction and cell cycle arrest. Analysis of the data showed increased apoptosis and G0/G1 cell cycle arrest upon exposure to AMPM and AMPW.

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Background: Cancer remains a major health issue and the second foremost root of morbidity worldwide behind cardiovascular diseases. Apoptosis had linked to the eradication of possibly malignant cells, hyperplasia, and tumor progression. Objective: The present study is an endeavor to evaluate the influence of luteolin, a modifier to apoptotic regulator on the tumor growth and the tumor cell sensitivity to ionizing radiation in Ehrlich solid tumor-bearing mice (E). Materials and Methods: Mice were immunized with Ehrlich carcinoma cells (2.5 × 106 cells/mouse), received consecutive equal doses of luteolin, 1.25 mg/mouse/day and exposed to 6.5 Gy of whole-body gamma irradiation (0.46 Gy/min). Results: Luteolin markedly suppresses the developing of tumor in E mice group or mice which bearing tumor with exposure to radiation (E + R group) which has collimated with significant inhibition in protein expression of inflammatory molecules cyclooxygenase 2 and the concentration of (prostaglandin E2). Also, matrix metalloproteinase-2, 9 proteins concentrations significantly decreased with amelioration in apoptotic regulators (Caspase-3 and Granzyme-B activities). The expression of signal transducer and activator of transcription (STAT) and tumor necrosis factor-alpha genes meliorated significantly. Besides, the level of oxidant/antioxidant (reduced glutathione/malondialdehyde) markedly improved. Obviously, the most reduction of changes in all measured parameters has appeared in tumor bearing mice, injected with luteolin and exposed to gamma radiation (E + Luteolin + R group). Conclusion: It could be suggested that luteolin has a potential beneficial effect against cancer. This could be due to its ability on the induction of apoptosis, inhibition of inflammatory response, downregulation of angiogenic factors as well as increase sensitivity of tumor cells to gamma radiation.

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Objectives: We aimed to obtain data that would enable the selection of the appropriate radiotherapy technique for whole breast irradiation (WBI) based on patients' physical characteristics and to evaluate the benefit of the new fall-off (FO) margin technique. Materials and Methods: Ten patients with left-sided breast-conserving surgery, treated for breast carcinoma between August 2016 and September 2017, were included. The FO margin was created in five different plans of which two were formed by expanding the target volume out of the skin. The dose evaluation planning was statistically compared by calculating the target volume dosimetric parameters and the doses received by the organs at risk (OARs) for each technique. The volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy plans were considered ideal for WBI homogeneity and conformity indices, while the three-dimensional conformal radiotherapy (3DCRT) plan was considered nonideal. Results: The increase in the breast x-axis length values and equivalent spherical diameter (ESD) dimension decreased the ideal value, whereas the increase in y-axis length values and ESD dimension correlated significantly with the D98 increase. The techniques were significantly correlated with OARs, such as V5, heart max, left anterior descending artery maximum, ipsilateral lung V5 and V20, and contralateral breast V5. Monitor unit values were significantly low in the 3DCRT and VMAT plans. Conclusion: The new FO margin structure will have benefits for practical application because the head designs of linear accelerators and collimators and the target-Jaw/MLC distance are adjacent to the breast tissue, which moves during treatment.

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Background: BReast CAncer gene 2 (BRCA2), a tumor suppressor gene located on chromosome 13q, encodes a 384-kDa protein which activates homologous recombination pathway to repair ssDNA damage. Aims and Objectives: Keeping in view the high prevalence of breast cancer in Pakistan and significant association of BRCA2 with breast cancer, this project was initiated to investigate the mutational status of BRCA2 in Pakistani breast cancer patients. Materials and Methods: For this purpose, blood samples of 45 individuals, including 24 female patients (infiltrating ductal carcinoma of breast), who visited Institute of Nuclear Medicine, Oncology and Radiotherapy Hospital and Ayub Medical Complex, Abbottabad, Khyber Pakhtunkhwa, and 21 normal female residents of the area were collected and processed to extract deoxyribonucleic acid (DNA). Different regions of BRCA2 exon 11 were amplified through polymerase chain reaction (PCR), and PCR-amplified products of one (NF45) normal sample and four cancerous (205BC, 215BC, 218BC, 222BC) samples were subjected to DNA sequence analysis. Results: Analysis of retrieved sequences revealed one novel nonsense mutation in sample 205BC. The observed mutation (delA21587) shifted the normal frame of amino acid (N905I, T906L, K907R, E908N, L909F, H910M, E911K, T912Q, and D913T) in encoded mutant protein and converted L914 into premature termination codon. In case of sample 222BC, another novel substitution mutation (A>G24962) was observed, which altered codon of I (isoleucine) into the codon for M (methionine) at position 2040 in resultant mutant protein. Conclusion: The results reflect the unique mutational profile of BRCA2 in Pakistani infiltrating ductal carcinoma patients and suggest an extension of study on a large scale.

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Background: Bilateral breast irradiation is technically challenging and there is limited information regarding optimal technique and outcomes. Hypofractionated Radiotherapy (HFRT) has emerged as the new standard of care in early breast cancer. However, there are concerns in using hypofractionation for bilateral breast irradiation due to larger volumes and potential toxicity. Our aim was to analyze the dosimetric data and clinical outcomes in these patients. Materials and Methods: Patients with synchronous bilateral breast cancer (SBBC) treated with bilateral breast irradiation were analyzed. All patients received simultaneous bilateral breast with or without regional nodal irradiation using a hypofractionated schedule of 40 Gy in 15 fractions over 3 weeks with single isocenter bi-tangential field-in-field intensity-modulated radiation therapy (FIF-IMRT) technique. Results: Seven patients of SBBC were treated at our institute from 2015 to 2017. All patients were postmenopausal females. Five patients underwent bilateral modified radical mastectomy; two patients underwent bilateral breast conservative surgery. All patients received systemic anthracycline-based chemotherapy. The mean cardiac dose was 3.73 ± Gy and V 25 was 3.26% ± 1.96%. V 20 of lung ranged from 23.48% ± 4.47% and the mean esophageal dose was 3.6 ± 2.00 Gy. No patient had acute toxicity higher than Grade 2. At a median follow-up of 48 months, one patient died due to systemic progression. No patient reported any late toxicity. Conclusion: Bilateral breast irradiation using a hypofractionated schedule with single isocenter FIF-IMRT technique is technically feasible with minimal acute toxicity and no significant late effects on early follow-up.

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Background: We have been practicing hypofractionation, 40 Gy in 16 fractions over 3 weeks for whole breast irradiation (WBI) for the past five decades with or without boost at our center. In this study, we compared two boost schedules of 10 Gy/5#/1 week with 16 Gy/8#/1.5 weeks in postlumpectomy patients with breast cancer after WBI. Materials and Methods: From June 2012 to June 2016, the study included 87 breast cancer patients postbreast conservation surgery. The institutional ethics committee approved the study, which was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier no. CT02142907). All patients were treated with WBI of 40 Gy/16#/3 weeks. WBI was followed by tumor bed boost of 10 Gy/5#/1 week in 44 patients and 16 Gy/8#/1.5 weeks in 43 patients, either with electron beam therapy or 3D CRT with photons. The primary endpoint of the study was the comparison of local control between two schedules. Secondary endpoints were acute and late radiation toxicities, cosmetic score analysis, disease-free survival (DFS), and overall survival (OS). The assessment of acute and late skin toxicity was made as per RTOG scores and LENT-SOMA scale. The cosmetic assessment was made with Harvard/NSABP/RTOG Breast Cosmesis Grading Scale. Results: Median follow-up was 55 months (range 18–78 months). Local recurrence was seen in 1 (2.3%) patient in the 16 Gy boost only. Acute Grade 2 skin toxicity was 33% in 16 Gy boost arm compared to 23% in 10 Gy boost arm. Late skin toxicities were also high in patients with 16 Gy boost. Grade ≥2 induration was seen in 4.5% and 14% of patients with 10 Gy and 16 Gy boost, respectively. None of the patients with 10 Gy boost had Grade 2 edema as compared to 5% with 16 Gy. Pigmentation was observed in 9% and 23% patients with 10 Gy and 16 Gy boost, respectively. Grade 1 fibrosis was 2% versus 12% in patients with 10 Gy and 16 Gy boost, respectively. The cosmetic score was good/excellent in 91% and 84% of patients with 10 Gy and 16 Gy boost, respectively. Distant metastasis occurred in 2 (4%) and 3 (7%) patients in 10 Gy and 16 Gy boost, respectively. DFS and OS at 5 years were comparable between the two boost schedules. Conclusion: Local control was comparable with 10 Gy and 16 Gy boost. Acute and late skin toxicities were higher with 16 Gy boost dose. The cosmetic score was better with 10 Gy boost. DFS and OS was comparable with the two boost schedules. Hence, a boost of 10 Gy/5# after WBI may be adequate in patients with breast cancer.

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Background: Although cisplatin is used for the treatment of more than half of cancer patients, its use is restricted by serious side effects as well as the development of cisplatin-resistant cancer cells, limiting its use. In RGCC we have synthesized an intermediate molecule in an ERK inhibitor synthesis process. Aims and Objectives: The aim of the study was to evaluate the effects of combined cisplatin plus RGCC molecule treatment on MCF-7 and MDAMB231 breast cancer cell viability, proliferation, ability to form clones and migrate, as well as the effects on cell cycle and gene expression. Materials and Methods: Cell viability and proliferation were measured by Crystal violet exclusion dye and MTT respectively. Clone formation and wound healing assays were also used for clone formation and cell migration evaluation. Cell cycle was studied by flow cytometry, expression of genes was evaluated by PCR and protein expression was evaluated by western blot. Results: It was found that combination therapy decreased cell viability and proliferation, caused growth arrest, decreased cancer cell invasiveness and the ability to form clones as well as perturbed the expression of genes involved in ERK, cell cycle and cell death pathways. Conclusion: Although the exact mechanism of action of the combination therapy remains to be investigated, it was found that it is more effective than cisplatin monotherapy. Our findings could potentially lead to a new therapeutic regime for the treatment of cancer.

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Introduction: Breast cancer (BC) is the most common cancer in Indian females. The irradiation of internal mammary lymph nodal area (IMLN) is recommended by latest guidelines and literature, even in patients with N1 nodal disease, but it is not routinely done in many institutes due to the risk of late lung and heart toxicities. The incidence of isolated IMLN recurrence <1%. The incidental radiation therapy (RT) dose to axillary lymph nodal area (ALN) could result in lower local recurrences according to literature. The aim of this study is to assess the incidental IMLN area RT dose in patients treated with forward planning intensity-modulated RT (FIF-IMRT). Materials and Methods: The aim of our study is to evaluate the RT dose received by IMLN area incidentally in FIF-IMRT and is a single-institute dosimetric study. The patients planned for RT after breast conservation surgery (BCS) or modified radical mastectomy (MRM) were evaluated for IMLN incidental dose. Results: The mean doses to IMLN area (D_mean) were comparable to literature for both BCS and MRM patients. All other dose parameters (D95, D90) in our study were slightly lower but comparable to literature for the FIF-IMRT planning. Interestingly, the incidental IMLN RT doses in our study are in the same range as the incidental ALN RT doses studied in the literature (48%–68%). Conclusion: The IMLN area receives a major amount of incidental radiation dose during conformal RT by FIF-IMRT and higher doses for MRM than BCS. This RT dose is not in the therapeutic range but is comparable to the incidental dose to ALN area reported in the literature.

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Background: The prevalence of breast cancer, the most common cancer in women, has remained steady over the past decades. In general, patients with early stage breast cancer undergo primary surgery with or without chemotherapy and radiotherapy. Insomnia is a very common problem in breast cancer patients, but its evaluation and treatment have not taken its place in the daily clinical application routines. In this study, we aimed to investigate the prevalence of the sleep disorders in women whose adjuvant chemotherapy and/or radiotherapy were completed at least 1 year ago and we used The Pittsburgh Sleep Quality Index (PSQI) as the standard self-report instrument in sleep disorder evaluation. Patients and Methods: The participants were outpatients followed-up at Bakirköy Dr. Sadi Konuk Training and Research Hospital, Medical Oncology Clinic whose breast surgery performed and adjuvant chemotherapy and/or radiotherapy were completed at least one year ago, and all having histopathologically proven verified cancer diagnoses. Ninety-two participants were enrolled to study and the Pittsburgh Sleep Quality Index was used for sleep disorder evaluation. Results: Poor quality sleep, estimated by the score of the PSQI, was observed in 53 (60%) of the participants (global score was =5). No statistically significant difference was observed between the sleep quality scores of patient groups based on endocrine treatment, manopausal status, marital status, educational status, breast surgery type, or duration after diagnoses (P > 0.05). Conclusions: We can conclude that poor sleep quality is a highly prevalent problem in nonmetastatic breast cancer patients, we determined a high prevalence rate of insomnia at 60%. PSQI is an appropriate and useful tool that physicians can apply while assessing sleep disorders in cancer patients. The improvement in the diagnosis and management of sleep disorders will contribute to a major improvement in the symptom control of insomnia for cancer patients.

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Anorexia and cachexia are major clinical problems seen in a large proportion of patients with advanced cancer. Weight loss has also been identified as an indicator of poor prognosis in cancer patients. Around 20% of patients with advanced cancer present mortality from the effects of malnutrition rather than from cancer itself. Early nutrition intervention has seen to improve outcomes in cancer patients such as weight gain, treatment tolerance, and improved quality of life (QoL). Effective therapies for addressing these threatening conditions are lacking. Pharmacotherapeutic agents such as corticosteroids, megestrol acetate, and cyproheptadine have several adverse reactions and also lack satisfactory results. Rasayana therapy is known to prevent loss of body mass and at the same time help to improve appetite and increase patient's QoL. The Rasayana compound used by us to prevent cachexia mainly includes swarna sindoor, Hirak bhasma, and suvarna bhasma. To evaluate benefits of Rasayana therapy on these variables, we maintain complete documentation of different clinical variables in all cancer patients. Here, in this observational study, we analyzed the data collected from a group of stage IV breast cancer patients (n = 30) receiving Rasayana therapy. Patients were followed at an interval of every 15 days from baseline for 3 months. Furthermore, at each visit, there weight was recorded on calibrated digital weight balance. QoL in these patients was recorded at quarterly interval using functional assessment of cancer therapies questionnaire. It was seen that in the duration of 3 months patients appetite increased significantly (P = 0.03). Significant weight gain was seen in patients (P = 0.04). Significant improvement was also seen in QoL especially related to QoL subdomains of physical wellbeing (P = 0.01), emotional wellbeing (P < 0.04), and functional wellbeing (P < 0.001). Rasayana therapy was seen to be well tolerated by all patients.

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Context: Breast cancer stem cells (bCSCs) are a small population of cancer-initiating cells within breast cancer, characterized as CD44⁺ CD24^–/low. bCSCs develop apoptosis resistance by expressing survivin and suppressing caspase-9 and caspase-3 expression. Typhonium flagelliforme tuber extract (TFTe) can induce apoptosis in several types of cancer cells; however, the effects of TFTe to induce the bCSCs remain unclear. Aims: This study aimed to investigate the effects of TFTe on apoptosis induction in bCSCs through the suppression of survivin and the exhibition of caspase-9 and caspase-3. Settings and Design: This study employed a posttest only, control group design. Subjects and Methods: To analyze the apoptotic index, TFTe, at concentrations of 25 (Tf1d), 50.89 (Tf2d), and 100 μg/mL (Tf3d) were used to treat bCSCs for 24 h, in a humidified incubator containing 5% CO₂, at 37°C. The control group was exposed to dimethyl sulfoxide. Apoptosis was measured by propidium iodide and acridine orange double-staining, and the expression levels of survivin, caspase-9, and caspase-3 were assessed by immunocytochemistry. Statistical Analysis Used: Differences were analyzed by the independent Student's t-test, to compare two groups, and the Kruskal–Wallis test, to compare more than two groups. P < 0.05 was considered statistically significant. Results: TFTe inhibited bCSC proliferation, with an IC₅₀ value of 50.89 μg/mL, and significantly induced apoptosis in bCSCs (P < 0.001). TFTe also significantly decreased the expression levels of survivin in bCSCs (P < 0.001) and increased the expression levels of caspase-9 and caspase-3 (P < 0.001). Conclusions: TFTe can induce apoptosis in bCSCs by decreasing survivin expression levels and increasing the levels of caspase-9 and caspase-3.

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Background: Sentinel lymph node biopsy (SLNB) is accepted as the standard procedure to determine the axillary lymph node metastasis in breast cancer at early stage. However, in many cases with sentinel lymph node positivity, the axilla does not contain any tumor cells. As a result, the accuracy of SLNB to predict axillary lymph node metastasis must be evaluated. Patients and Methods: Thousand hundred and fourteen women operated for breast cancer were retrospectively examined. Breast cancer patients without axillary metastasis on clinical examination who had undergone SLNB were included in the study. Sentinel lymph node positivity and axillary lymph node positivity were compared. Results: Among 1114 women operated for breast cancer, 230 were clinically node negative preoperatively and undergone SLNB. Eighty-three (36%) of the patients were SLNB positive and undergone axillary dissection. Forty-three (51.8%) of them had tumor positive axillary lymph nodes and 40 (48.2%) of them had tumor negative axillary lymph nodes. Interpretation: In 48.2% of the patients, positive sentinel lymph node does not demonstrate a positive axilla. This finding supports sparing axillary dissection in patients with favorable prognostic factors even if the sentinel lymph node is found to be positive. Conclusion: Axillary lymph node dissection(ALND) may be spared even if there are macrometastatic sentinel lymph nodes in patients with favorable tumor types who will undergo breast-conserving surgery.

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Purpose: Different dose calculation algorithms (DCAs) predict different dose distributions for the same treatment. Awareness of optimal model parameters is vital for estimating normal tissue complication probability (NTCP) for different algorithms. The aim is to determine the NTCP parameter values for different DCAs in left-sided breast radiotherapy, using the Lyman-Kutcher-Burman (LKB) model. Materials and Methods: First, the methodology recommended by International Atomic Energy Agency TEC-DOC 1583 was used to establish the accuracy of dose calculations of different DCAs including: Monte Carlo (MC) and collapsed cone algorithms implemented in Monaco, pencil beam convolution (PBC) and analytical anisotropic algorithm (AAA) implemented in Eclipse, and superposition and Clarkson algorithms implemented in PCRT3D treatment planning systems (TPSs). Then, treatment planning of 15 patients with left-sided breast cancer was performed by the mentioned DCAs and NTCP of the left-lung normal tissue were calculated for each patient individually, using the LKB model. For the PB algorithm, the NTCP parameters were taken from previously published values and new model parameters obtained for each DCA, using the iterative least squares methods. Results: For all cases and DCAs, NTCP computation with the same model parameters resulted in >15% deviation in NTCP values. The new NTCP model parameters were classified according to the algorithm type. Thus, the discrepancy of NTCP computations was reduced up to 5% after utilizing adjusted model parameters. Conclusions: This paper confirms that the NTCP values for a given treatment type are different for the different DCAs. Thus, it is essential to introduce appropriate NTCP parameter values according to DCA adopted in TPS, to obtain a more precise estimation of lung NTCP. Hence, new parameter values, classified according to the DCAs, must be determined before introducing NTCP estimation in clinical practice.

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Background: Reprogrammed energy metabolism is considered a hallmark of cancer and is proposed as an important target for therapy. Uncontrolled and infinite cell proliferation needs efficient energy sources. To meet the demands of cancer cells lipid metabolism is activated. Citrullus colocynthis is a traditional medicinal plant known for its anticancer and hypolipidemic effects. Aims: Aim of the current study was to assess the effect of C. colocynthis leaves on regulation of lipid metabolism in MCF-7, a human breast cancer cell line. Methods: Methanolic extract of leaves and its fractions in increasing polarity-based solvents (n-hexane, chloroform, ethyl acetate and n-butanol) were prepared and analyzed for the presence of secondary metabolites in each fraction. Bioassays and apoptosis genes expression analysis was conducted to evaluate the anticancer and cytotoxic effect of breast cancer cells treated with extract and its fractions, separately. Lipid quantification and gene expression regulation of genes involve in lipid metabolism was performed to evaluate regulation of lipid metabolism. Results: Results showed a significant anticancer activity of methanolic extract of C. colocynthis and two of its fractions prepared with chloroform and ethyl acetate. Quantification of lipids depicted significant increase in cholesterol and increase in triglycerides of treated cells compared to control untreated cells. Expression regulation of genes further confirmed the lipid regulation through significant down regulation of genes involve in lipid metabolism (FASN, HMGCLL1, ACSL5 and ELOVL2). Conclusion: The present study concludes that C. colocynthis holds strong anticancer potential through regulation of lipid metabolism and with further studies can be proposed for novel therapeutic approaches.

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Aim: Metaplastic breast cancer (MBC) is a rare subtype with unusual clinical features. We aimed to analyze treatment results and define patients' characteristic features in our large MBC patient series. Materials and Methods: Fifty-six patients with early MBC who received adjuvant radiotherapy (RT) in our center were included in the study. The age, sex, subtypes of MBC, histopathology, hormone and nodal status, tumor size, and types of treatment were retrospectively provided from hospital records. Results: The median tumor size was 4 (1.3–16.5) cm, and triple-negative MBC cases were 38 (67.8%) of all patients. Axillary nodal involvements were present in 25 (44.6%) patients. The median follow-up time was 45.8 (4.9–130) months; the overall survival (OS) and disease-free survival (DFS) for 5 years were 67% and 64%, respectively. While distant metastases were seen in 15 (26.7%) patients, local recurrences were seen in only 4 patients. The median OS and DFS were higher in patients with ≤5.2 cm tumor than >5.2 cm ([130 vs. 49 months, P = 0.01] and [130 vs. 30 months, P = 0.009], respectively). Nodal involvement, hormone receptor status, surgical treatment, and type of RT had no effect on survival. In multivariate analysis, tumor size was not an independent prognostic factor for OS (P = 0.068; hazard ratio [HR]: 3.4, 95% confidence interval [CI] = 0.91–12.8), whereas age >65 years was found an independent poor prognostic factor for OS ([HR: 4.25, 95% CI: 0.23–0.78, P = 0.021] and DFS [HR: 3.1, 95% CI: 0.02–0. 87; P = 0.04], respectively). Conclusions: Distant metastasis is at the forefront rather than local recurrence in MBC patients. More studies are needed to determine the factors that affect survival independently in MBC.

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We present here a case of a 35-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB) – small cell type. We discuss the importance of histological and molecular criteria for primary neuroendocrine mammary neoplasm, established by the World Health Organization in 2003 and 2012. We present information about differential diagnosis, prognostic factors, surgical treatment, adjuvant treatment, and novel therapies for primary NECB. Although this disease is not so uncommon but it is highly underreported and with consistent diagnostic criteria, surgeons should be able to keep this entity as differential diagnosis to enable them a timely treatment.

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Background: MicroRNAs (miRNAs) are involved in the regulation of genes with important roles in cancer. Therefore, they represent interesting targets as biomarkers for early detection, follow-up, and prognosis of the disease. Context: In early stages of breast cancer, differences in the expression of miR-148b-3p, miR-145-5p and miR-133a-3p have been reported. Aims: To compare the expression of miR-148b-3p, miR-145-5p and miR-133a-3p in serum samples from female patients with and without breast cancer. Setting and Design: Case control study. Materials and Methods: We quantified the expression by real-time polymerase chain reaction of miR-148b-3p, miR-145-5p, and miR-133a-3p in serum samples from 27 breast cancer (BC) and 17 benign breast tumor patients. Statistical Analysis Used: Comparison between groups with categorical variables was made using the Pearson's Chi-square test. Comparative analysis for continuous variables between two groups was performed using the Student's t-test. One-way analysis of variance (ANOVA) was used for multigroup comparison, followed by Tukey HSD analysis. Results: The use of contraceptives and a high number of births were identified as risk factors for BC. We observed that miR-145-5p expresses in low levels in BC and positively diagnosed Her2 patients. In addition, BC patients with either ductal carcinoma or positive molecular diagnosis for estrogen receptor, progesterone receptor, luminal A, or Her2 negative, presented a decreased expression of miR-133a-3p. Conclusions: We observed an existing association between the molecular characteristics of BC and levels of circulating miR-133a-3p and miR-145-5p, proving the potential role of miRNAs as biomarkers for BC.

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Aim: This study assessed whether prognostic information could be obtained in patients with lymph node (LN)-positive breast cancer based on their LN ratios (LNRs) and explored the relationships between other potential prognostic factors and survival. Setting and Design: This was a retrospective clinical study. Materials and Methods: This study included 608 women with node-positive nonmetastatic breast cancer. Clinical and pathologic data were retrospectively evaluated. The median age was 51 years (range: 23–84 years). All patients received adjuvant radiotherapy after radical surgery. A total dose of 50 Gy was administered to the chest wall or breast and LN regions with 2 Gy daily fractions. A 10-Gy boost was administered to the breast tumor bed. The cutoff value of LNR was defined as low risk (<0.21) in 278 patients, intermediate risk (0.21–0.65) in 217 patients, and high risk (>0.65) in 113 patients. Prognostic variables included patient characteristics, disease characteristics, and interventional factors. The primary endpoint was overall survival and the secondary endpoint was breast cancer-related mortality. Statistical Analysis Used: Statistical analyses were performed using the Kaplan–Meier method, log-rank test, and Cox regression analysis. P value was required to be <0.05. Results: Within a median follow-up period of 95.4 months (range: 5–232.4 months), overall survival rates for 10 and 15 years were 66% and 53%, respectively. Multivariate analysis revealed that LNR (P = 0.026), estrogen receptor status (ERS) (P = 0.021), age (P = 0.04), and smoking (P = 0.024) were independent significant prognostic factors for overall survival. Breast cancer-related mortality rates at 10 and 15 years were 70.7% and 60%, respectively. LNR (P = 0.03) and ERS (P = 0.002) were independent significant prognostic factors for breast cancer-related mortality. Conclusions: LNR and ERS were significant prognostic factors for survival at all endpoints.

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Introduction: Peri-operative macroscopic margin assessment with standard intraoperative specimen radiography (IOSR) results in improved re-excision rates in excised breast tissue specimens but is limited. This study sought to improve the intraoperative margin assessment on standard IOSR techniques by utilizing noninvasive X-ray micro-computed tomography (micro-CT) imaging of breast tissue specimens to compare margins in three-dimensional with two-dimensional IOSR. Methods: Patients with impalpable breast carcinoma, or suspected breast carcinoma, who were eligible for breast-conserving surgery were recruited. Margins were assessed within each specimen using standard IOSR, micro-CT, and histology techniques. Results: Six malignant and three benign lesions were included for the analysis in this study. Micro-CT identified the same positive margin as IOSR in 3 out of 6 malignancies. However, margin status identified by micro-CT was concordant with pathological assessment in only one specimen. In comparison, margin assessment by IOSR correctly correlated with pathological margin status in three malignant specimens. Conclusion: The use of micro-CT imaging in this study did not improve margin assessment in impalpable breast specimens when compared to standard specimen radiography (SR) assessment. However, future improvements in sample preparation and CT image acquisition processes may enhance the potential of micro-CT as a valuable imaging tool for improving margin assessment.

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Background: Lung cancer is the leading cause of cancer-related deaths worldwide. The high resistance of this type of cancer to radiotherapy and chemotherapy is the greatest challenge for the complete eradication of cancer cells. Although the combination of chemotherapeutic agents has some promising results, severe side effects may limit the received tumor dose. The current study aimed at evaluating the possible synergic effect of melatonin on radiation-induced apoptosis and cell proliferation inhibition. Materials and Methods: A549 cells were incubated with melatonin or vehicle and then irradiated with a single dose of 0, 0.5, 2, or 8 Gy X-rays. The cells were incubated with 1 nM of melatonin or vehicle for 1 week and then treated with 1 mM of melatonin or vehicle 1 h before irradiation. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was assessed using flowcytometry detection of annexin V. Results: Irradiation of the cells with different X-ray doses had no significant impact on MTT results. However, the administration of 1 mM of melatonin 1 h before irradiation significantly reduced the cell proliferation. Nonetheless, there was no significant difference between this treatment group and 1 mM melatonin group. Moreover, the administration of melatonin in combination with irradiation did not show any significant effects on radiation-induced apoptosis. Conclusion: The current study results indicated that the treatment of A549 cells with melatonin could suppress cell proliferation, whereas it did not mediate the induction of apoptosis.

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Introduction: Breast cancer is commonly diagnosed cancer in women. Tumor receptors estrogen receptor (ER) and progesterone receptor (PR) are well recognized prognostic factors for breast cancer. Materials and Method: Data from the department of pathology for the 5-year period (2010 to 2014) is used for analysis for Kamrup district of Assam, India. Kaplan Meir method was used to evaluate survival rate. Result: The overall 5-year survival is observed as 54.6%. There is a 10.6% improvement in survival was recorded among those who living in the urban areas. The risk of death was 40% higher for those who were resides in rural areas compared to urban areas (P = 0.070). There is a 6 fold variation in survival was observed according to their stage at presentation. Hormone receptors found to be play an important role in survival outcome. Patients with ER/PR+ (positive) status have 13.6% higher survival rate than those with ER/PR-. The overall survival for ER/PR positive is 72.1% compared to 58.5% of ER/PR negative. Conclusion: From the study it is observed that population with positive hormone receptors (ER/PR +) and living in the urban areas is experiencing survival rate.

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Purpose: T1-contrast and T2-flair images of magnetic resonance imaging (MRI) are commonly fused with computed tomography (CT) and used for delineation of postoperative residual tumor and bed after surgery in patients with glioblastoma multiforme (GBM). Our prospective study was aimed to see the feasibility of incorporating perfusion MRI in delineation of brain tumor for radiotherapy planning and its implication on treatment volumes. Methods: Twenty-four patients with histopathologically proven GBM were included in the study. All patients underwent radiotherapy planning with a contrast CT scan. In addition to radiotherapy (RT) planning protocol, T1-perfusion MRI was also done in all patients in the same sitting. Perfusion imaging was processed on the in-house-developed JAVA-based software. The images of CT and MRI were sent to the iPlan planning system (Brainlab AG, GmbH) using a Digital Imaging and Communications in Medicine - Radiation Therapy (DICOM-RT) protocol. A structure of gross tumor volume (GTV)-perfusion (GTV-P) was delineated based only on the MRI perfusion images. Subsequently, GTV-P and GTV were fused together to make GTV-summated (GTV-S). Using existing guidelines, GTV-S was expanded to form clinical target volume-summated (CTV-S) and planning target volume-summated (PTV-S). The increment in each of the summated volumes as compared to baseline volume was noted. The common overlap volume (GTVO) between GTV and GTV-P was calculated using intersection theory (GTV n GTV-P = GTVO [Overlap]). Results: Mean ± standard deviation (cc) for GTV, GTV-P, and GTVO was 46.3 ± 33.4 cc (range: 5.2 cc–108.0 cc), 26.0 ± 26.2 (range: 6.6 cc–10.3.0 cc), and 17.5 ± 22.3 cc (range: 10.0 cc–92 cc), respectively. Median volume (cc) for GTV, GTV-P, and GTVO was 40.8 cc, 17.2 cc, and 8.0 cc, respectively. Mean absolute and relative increments from GTV to that of GTV-S were 8.5 ± 8.2 cc and 27.2 ± 30.9%, respectively. Average CTV volume (cc) was 230.4 ± 115.3 (range: 80.8 cc–442.0 cc). Mean and median CTV-S volumes were 262.0 ± 126.3 cc (range: 80.8 cc–483.0 cc) and 221.0 cc, respectively. The increment in the mean CTV volume (with respect to CTV created from GTV-S) was 15.2 ± 15.9%. Mean and median PTV volumes created on the summated CTV were 287.1 ± 134.0 cc (range: 118.9 cc–576.0 cc) and 258.0 cc, respectively. Absolute and relative increments in PTV volume, while incorporating the perfusion volume, were 31.3 ± 28.9 cc and 12.5 ± 13.3%, respectively. Out of the total of 24 patients, perfusion scanning did not do any increment in GTV in five patients. Conclusions: Our study is the first to present the feasibility and the outcome of contouring on perfusion imaging and its overlay on regular MRI images. The implications of this on long-term outcome and control rates of glioblastoma patients need to be seen in future studies.

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Background: Epithelial cell adhesion molecule (EpCAM), a type I transmembrane protein of the epithelial tissues and known cell adhesion molecule, has been demonstrated to have critical role in carcinogenesis. In breast cancer, EpCAM expression has been associated with poor prognosis. The expression pattern of EpCAM across molecular subtypes of breast carcinoma has been studied in patients reporting to a South Indian multispecialty tertiary care hospital. The prognostic significance of EpCAM expression pattern and probable response to therapy has also been addressed. Materials and Methods: EpCAM expression was assessed by immunohistochemical studies on 200 breast carcinoma tissue samples of different molecular subtypes, including luminal A, luminal B, Her2Neu, and triple-negative breast cancer (TNBC). The expression was scored using the standard scoring system. A correlation was drawn with detailed clinicopathologic annotation and available outcomes data to analyze the influence of EpCAM on prognosis. Results: EpCAM expression varied significantly in the different intrinsic subtypes of breast carcinoma. Differential expression was also established with different grades of breast carcinoma with varying levels of differentiation. We observed strong EpCAM expression in TNBC among other subtypes. Conclusion: The differential expression of EpCAM among intrinsic subtypes of breast cancer and the correlation of EpCAM expression with high-grade breast carcinoma shown in the study have important implications in understanding the role of EpCAM and might form the basis for developing targeted therapies in breast cancer in the future.

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Purpose: We want to compare the synergistic effect of low-intensity, dual-frequency (dual) ultrasound (US), applied in a repetitive sonication mode, and acoustically active lipospheres (AALs) containing doxorubicin (DOX) in a murine model (Balb/C). Subjects and Methods: The tumor-bearing mice were divided into nine groups, namely two untreated groups (control and sham), and seven experimental groups, including treated with dual-frequency US (150 kHz_continuous + 1MHz_pulse), triple exposure (3×30min) dual-frequency US, DOX (2 mg/kg intravenous), DOX in combination with single exposure (30 min) to dual-frequency US (drug + dual), DOX in combination with triple (3 × 30 min) exposure to dual-frequency US (drug + dual [REP]), AALs containing the drug-loaded (AAL), and a group receiving AAL in combination with single exposure (30 min) dual-frequency US (AAL + dual), respectively. Results: The effectiveness of DOX on tumor growth was enhanced by a factor of three when combined with the triple exposures of dual US (drug + dual [REP]). This combination protocol further increased the times needed for each tumor to 2 and 7 times its initial volume, respectively by 94% and 36% compared to the drug group. During the 30 days, following the treatment of tumors, the relative volume of tumors in AAL group was 118% less than that of the drug group. The survival rate of the groups treated with drug and AAL + dual was increased by 78.7% and 167% compared with sham, respectively. Conclusion: Although as a short treatment, a major improvement in treatment was observed by (drug + dual [REP]) compared with other treatments, the AAL + dual treatment compared with (drug + dual [REP]) showed an increase in the survival rates, hence more preferable over long periods.

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Context: Obesity has been strongly associated with risks and is a common factor in the risk of postmenopausal women with breast cancer (BC). Various single-nucleotide polymorphisms have been identified in the adiponectin gene. Aims: We aimed in this study to access the diagnostic value of adiponectin gene polymorphism rs 1501299 (G267T) in BC and its association with serum adiponectin level in obese and overweight postmenopausal BC female patients. Settings and Design: This study was conducted on 90 BC patients divided into two groups according to body mass index (BMI), and 60 apparently healthy females as a control group with matched BMI. Both groups were with BMI >25 (obese or overweight). Subjects and Methods: All participants were subjected to laboratory investigations (CA 15–3, serum adiponectin) and molecular study of adiponectin gene rs 1501299 (G276T) by polymerase chain reaction-restriction fragment length polymorphism technique. Results: A statistically significant difference was observed in the polymorphic genotypes (GT and TT) compared to (GG) wild genotype when compared BC patients to control group (P = 0.001). Also on measuring the risk estimate, a significant difference (odd's ratio was 3.76, 95% confidence interval was 1.68–8.4, P = 0.001). While no statistical significant difference in genotype frequency was found between the obese and overweight patients (P > 0.05). Median serum adiponectin level was decreased in BC patients compared to the control group (8.9 vs. 14.6 with P = 0.004). Conclusions: This study supported the association between adiponectin gene polymorphism, serum level, and BC risk among a group of obese and overweight postmenopausal Egyptian patients.

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Pineal gland metastasis accounts for approximately 0.4% of all intracranial metastases from lung primary. Our patient was a 60-year-old female presenting with intermittent headache and altered sensorium. Magnetic resonance imaging brain showed a 21 mm × 18 mm × 16 mm pineal lesion with obstructive hydrocephalus. She underwent endoscopic third ventriculostomy and drainage. Fluorodeoxyglucose-PET showed a left lung primary tumor with nodal metastasis and solitary pineal gland metastasis. Biopsy of lung lesion revealed poorly differentiated non-small-cell carcinoma which was treated with focal pineal radiation and chemotherapy. This patient's presentation is unique because she presented with pineal symptoms rather than lung symptoms. Pineal gland metastasis from lung primary is mostly associated with small-cell carcinoma histology, but this patient had a non-small-cell carcinoma of lung primary. The age above 60 years is in favor of a metastatic lesion to the pineal gland. Our experience suggests that systemic evaluation of all patients presenting initially with an isolated pineal gland tumor is mandatory.

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