The burden of cancer is continuously increasing, and is rapidly becoming a global pandemic. The first liposomal encapsulated anticancer drug which received clinical approval against malignancies including solid tumours, transplantable leukemias and lymphomas was Doxorubicin HCl. This review is aimed at providing an overview of doxorubicin in cancer therapy. Pegylated liposomal doxorubicin has a polyethylene glycol (PEG) layer around doxorubicin-containing liposome as the result of a process known as pegylation. Non-pegylated liposomal doxorubicin (NPLD) was developed to overcome the drawbacks associated with previous formulations. Nudoxa^; (NPLD) with its unique drug delivery system offers the benefit of pegylated liposomal doxorubicin without hand foot syndrome as the major side effect. Future studies will be directed towards estimating the costs of treatment with the novel liposomal doxorubicin formulations in order to assess their widespread use and robustness in treating patients with cancer.

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In developing countries, diagnosis of breast carcinoma is still made on fine-needle aspiration cytology (FNAC). For the resource-poor settings, FNAC is cheaper, less invasive and can sample different areas of the lesion compared with core needle biopsy. The role of breast FNA is usually limited to just categorize the lesion as benign or malignant. Prognostic information from cytomorphology, conveyed to the clinician depends upon the cytopathologist's way of formatting the report. PubMed-based literature search collated the information from articles describing the architectural and cytological features studied on breast aspiration smears. This review focuses on cytomorphological features and the different grading systems with their strengths, short-comings, and practical applicability. Eight worldwide articles proposing new methods of grading the cytological smears from breast cancers were published between 1980 and 2006. All the grading methods were developed for the most common type of breast cancer, that is, infiltrating duct carcinoma (not otherwise specified) type, and most of the workers used Papanicolaou-stained smears for the purpose of grading. Moreover, if interpreted carefully FNAC smears can convey information on most of the histological features. Hence, in developing countries, the focus should be on extracting the maximum information from cytological smears, so that a more precise "surgical pathology" type diagnosis can be given, instead of merely reporting as benign or malignant. Among all the discussed grading systems, we suggest grading system by Howell would be most appropriate and closest to the accepted histologic grading system as it applies Scarff-Bloom-Richardson histological grading system with modifications on FNA smears. We recommend it to be followed by all cytopathologists, in order to bring uniformity in the reporting of breast FNAs for grading the malignant lesions.

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Aim: Hypoalbuminemia and systemic inflammatory response (SIR) parameters are a key role in the prognosis of cancer patients. We aim to investigate the changes of serum albumin level and SIR after chemotherapy, in patients with inoperable non-small cell lung cancer (NSCLC). The hypothesis is that improved serum albumin level may be beneficial to the SIR parameters and will reduce chemotherapy-induced toxicity. Patients and Methods: Forty-nine stage III b or stage IV inoperable NSCLC patients were divided into two groups, depending on whether albumin administration was given before chemotherapy. The Karnofsky performance score (KPS), nutritional status including body mass index (BMI), and serum albumin level were evaluated. SIR was evaluated by investigating the changes of the C-reactive protein (CRP), calculating the neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR), before and after chemotherapy. The chemotherapy-induced toxicity was also evaluated. Results: In the group of patients without albumin administration before chemotherapy, the serum albumin level was significantly decreased (P < 0.05) and the CRP level was significantly increased than before (P < 0.05). Significant correlations were noted between hypoalbuminemia and CRP increase (r = 0.533 P < 0.05), between hypoalbuminemia and NLR ≥5 (r = 0.574 P < 0.01) after chemotherapy. Patients with hypoalbuminemia developed more severe chemotherapy-induced toxicity symptoms. In the group of patients with albumin administration before chemotherapy, there was no significant difference in serum albumin level before and after chemotherapy (P > 0.05), even though the patients may have been malnourished or diagnosed with pleural effusions. There were no significant changes in the SIR parameters. Conclusion: Early assessment of the serum albumin level in patients with inoperable NSCLC and their improvement in the serum albumin level may suggest that there are beneficial effects after chemotherapy.

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Objective: This study evaluates the magnetic resonance imaging (MRI) manifestation of intradural extramedullary (IDEM) tumors to improve the imaging diagnostic level. Materials and Methods: From January 2005 to December 2012, a retrospective analysis of the MRI examination was performed on 108 patients with IDEM tumors confirmed by surgical pathology postoperatively in our hospital. According to the pathological classification; the gender, age, location, size, foraminal state extension, signal intensity (compared with the spinal cord), and enhancement were recorded and statistically analyzed. Results: A total of 108 cases (111 lesions) were reported; 69 (70 lesions), 31 (31 lesions), three (five lesions), four (four lesions), and one (one lesion) of which were schwannoma, meningioma, neurofibroma, teratoma, and metastatic tumor, respectively. MRI manifestations of different IDEM tumors have certain specificities. Conclusion: MRI is the preferred examination method for to diagnose IDEM tumors and provide a reliable imaging basis for clinical treatment and prognosis judgment.

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Aims: Dosimetric comparison of VMAT with IMRT in middle third esophageal cancer for planning target volume (PTV) and organs at risk (OAR). Materials and Methods: Ten patients in various stages from I‒III were inducted in the neo-adjuvant chemoradiation protocol for this study. The prescribed dose was 4500 cGy in 25 fractions. Both VMAT and IMRT plan were generated in all cases and Dose Volume Histogram (DVH) comparative analysis was performed for PTV and OAR. Paired t-test was used for statistical analysis. Results: The PTV Dmean and D95 in IMRT and VMAT plan were 4566.6 ± 50.6 cGy vs 4462.8 ± 81.8 cGy (P = 0.1) and 4379.8 ± 50.6 cGy Vs 4424.3 ± 109.8 cGy (P = 0.1), respectively. The CI and HI for PTV in IMRT vs VMAT plans were 0.96 ± 0.02 vs 0.97 ± 0.01 (P = 0.4) and 10.58 ± 3.07 vs 9.45 ± 2.42 (P = 0.2), respectively. Lung doses for VMAT vs IMRT were 4.19 vs 2.59% (P = 0.03) for V35-7.63 vs 4.76% (P = 0.01) for V30-13.6 vs 9.98% (P = 0.01) for V25-24.77 vs 18.57% (P = 0.04) for V20-46.5 vs 34.73% (P = 0.002) for V15. The Mean Lung Dose (MLD) was reduced by VMAT technique compared to IMRT; 1524.6 ± 308.37 cGy and 1353 ± 186.32 cGy (P = 0.012). There was no change in Dmax to spinal cord in both the techniques. There was a dose reduction by VMAT compared to IMRT to the heart but it was statistically insignificant; V35-6.75% vs 5.55% (P = 0.223); V30-12.3% vs 10.91% (P = 0.352); V25-21.81% vs 20.16% (P = 0.459); V20-38.11% vs 32.88% (P = 0.070); V15-61.05% vs 54.2% (P = 0.10). Conclusion: VMAT can be a better option in treating mid esophageal carcinoma as compared to IMRT. The VMAT plans resulted in equivalent or superior dose distribution with a reduction in the dose to lung and heart.

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Background: Oral cancer is a foremost health dilemma in several regions of the world. General dental practitioners and general medical practitioners play a major role in recognition of oral mucosal changes that may lead to malignancy. Their knowledge in oral cancer itself and the risk factors associated with the disease need to be sufficient. Objective: The objective of the present study was to investigate awareness and knowledge of undergraduate dental and medical students in early detection and prevention of oral cancer. Materials and Methods: Dental and medical students were invited to participate by answering a questionnaire on their habits of the oral mucosa examination and history taking, knowledge on risk factors and changes related with oral cancer, referral of patients as well as their desire to receive further information on oral cancer. Chi-square test was carried out to analyze knowledge and awareness between undergraduate dental and medical students. Results: Undergraduate dental students were more likely to examine oral mucosa (96.7%) and advice risk habits to patients (93.9%) compared to medical students (60.6% and 79.8% respectively). Significantly more dental students considered smoking (84.4%), betel quid chewing (76.1%), and alcohol drinking (35%) as risk factors. Clinical changes of oral cancer were better identified by dental students (leukoplakia - 52.8%, erythroplakia - 45%, and non-healing ulcer - 40%) compared to medical students (leukoplakia - 12.9%, erythroplakia - 4.6%, and non-healing ulcer - 10.3%). Both dental and medicals students reported the desire to receive further information in relation to oral cancer. Conclusion: Dental students have better knowledge and awareness in prevention and early detection of oral cancer compared to medical students.

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Bystander effects (BSEs) have been investigated for a long time but without much deliberation as to the cause in targeted cells and the subsequent effect in naïve cells. BSEs have traditionally been associated with radiation. Currently, this phenomenon is at a juncture where nuclear DNA damage is being debated as either essential or nonessential. If DNA damage is essential for the bystander signal (BSS) production then, this raises a number of questions about, radiotherapy and chemotherapy of cancer patients. This review presents a detailed analysis of the work done to investigate nuclear DNA damage versus exclusively cytoplasmic targeting with ionizing radiations and measurement of bystander end-points in naïve cells. The review also analyzes some of the research work done to investigate cell models that were developed specifically to study and track radiation-induced DNA damage to construct mutation spectra. Production of reactive oxygen species and reactive nitrogen species as possible candidates of the elusive BSS are also discussed besides the signal transduction pathways implicated in reception of a BSS by the naïve cell.

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The cancer stem cell (CSC) concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in a biologically distinct subset of cells that are typically rare. Rare CSCs have been isolated from a number of human tumors, including hematopoietic, brain, colon, and breast cancer. With the growing evidence that CSCs exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. Understanding the biology of CSCs will contribute to the identification of molecular targets important for future therapies.

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In normal functioning of the cell, there is a balance between generation and neutralization of reactive oxygen species (ROS) by endogenous cellular defense machinery. Low levels of ROS inside the cells are required for normal functioning of the cell, which regulate signaling mechanisms involved in mitosis and apoptosis; excess of ROS production may cause oxidative stress leading to damage in vital cellular molecules, namely cytosolic lipids, proteins, and DNA. In the situation of intracellular redox imbalance, molecules of cells are altered by ROS leading to pathogenic state. It is to be noted that ROS is not only known to be involved in tumor induction and progression processes but also enhances tumor cell radiosensitivity. The level of ROS-mediated oxidative stress is linked to cellular radiosensitivity. In general, cancer cells exhibit high levels of ROS, which forms a target for selectively killing them by radiation. In this paper, we have reviewed how oxidative stress determines the radiosensitivity of tumor cells involving ROS in the mechanism of radiation induced tumor cell killing. It is suggested that radiation-induced ROS play a key role in the mechanism of tumor cell killing by altering the signaling network and triggering of apoptosis. Furthermore, it is pointed out that combined use of plant-derived antioxidants and radiation enhance overproduction of ROS in tumor cells leading to enhanced radiosensitivity, which may find practical applications in clinic.

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The presence of a systemic inflammatory response (SIR) is recognized to occur in the presence of malignancy. And the SIR-Glasgow Prognostic Score (GPS)/modified GPS (mGPS) composed of the C-reactive protein (CRP) and albumin is a tumor stage- and treatment-independent, routinely available and well-standardized prognostic factor, reflects both an ongoing SIR (CRP) and a progressive nutritional decline (albumin) in patients with advanced cancer. Previous studies showed that GPS/mGPS appear to be a superior prognostic factor compared with other cellular components of the SIR and Eastern Cooperative Oncology Group performance status in some aspects. Besides, GPS/mGPS aids at deciding active or palliation treatment and selecting patients with gastric cancer who tolerate platinum-based chemotherapy. Therefore, GPS/mGPS may be incorporated or combined with other factors to improve assessment of prognosis and guide treatment of patients with gastric cancer in a routine clinical work. However, it remains to be determined whether the GPS and mGPS have different prognostic value in each stage of gastric cancer and the necessity of normalization of the GPS/mGPS by anti-inflammation and maintenance of performance status or nutritional status in clinical work.

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Context: Anticancer properties of artemisinin and its derivatives have been shown in many experiments. Aims: Addition of butyric acid, miconazole, and iron to this traditional drug has been done in order to enhance its anticancer potency. Materials and Methods: Cell lines 5637 and 4T1, were cultivated and classified into 13 groups of three each. Different doses of artemisinin with constant doses of iron, miconazole and butyric acid, were added to the cultures. At the end of exposure pathological and enzymatic studies were performed. Results: In four groups treated with different doses of artemisinin and iron, dose-dependent changes were observed. These changes included apoptosis and necrosis with dominance of apoptosis. The supernatant lactate dehydrogenase (LDH) level was increased in a dose-dependent manner, but there was no significant increase in the cell fraction of malonyldialdehyde (MDA) or LDH. In four other groups, which received miconazole, butyric acid and iron in addition to different doses of artemisinin, necrosis was more prominent than apoptosis, and the MDA level did not show any significant change, but LDH was increased. The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis. Conclusions: A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.

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Introduction: We commonly use 6- and 4-clamped thermoplastic molds (TMs) for rigid immobilization during pelvic radiotherapy (RT), sometimes a vacuum cushion (VC) is also used as leg support with TM. Our objective was to report the setup margins (SMs) associated with the different systems, to analyze whether any of these systems is superior, and to analyze whether any of them showed better reproducibility in any particular direction. Materials and Methods: Retrospective analysis was done by dividing the patients into four groups: 6-clamp with VC (6CVC), 6-clamp without VC (6CNC), 4-clamp with VC (4CVC), and 4-clamp without VC (4CNC). A repeat offline review was done for all patients and errors were tabulated. Statistical methods were then applied. Results: Total 24 patients had 413 image-guided RT (IGRT) sessions, 312 were cone beam computed tomography scan (CBCT) scans and 101 were paired kilovoltage portals (kVp). There was no statistically significant difference between 6CVC and 6CNC. However, while comparing 4CVC and 4CNC, a statistically significant difference was seen in all directions. VC improved precision in vertical and lateral direction mainly, while the 6-clamped TM improved reproducibility in longitudinal direction. Conclusions: SM was low for all the four immobilization systems studied. There is no added benefit of using a VC with 6-clamped TM for pelvic RT. Use of a VC is recommended with 4-clamped TM to improve overall reproducibility. 6-clamped TM helps keep the errors low.

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Background: Extra nodal involvements of non-Hodgkin's lymphomas (NHL) are not so uncommon, but the involvement of oral cavity by NHL is very rare. Materials and Methods: The present study involved retrospective analysis of patients from year 2001 to 2011, who presented with oral mass and on evaluation were diagnosed to have primary extranodal NHL of oral cavity at a tertiary cancer care centre in South India. Results: There were seven patients treated for primary NHL of oral cavity at our institute in last 10 years. The median age at presentation was 43.2 years (range 29-65 years). There were five males and two females. Oral tongue was the most common site (three patients) followed by alveolus (two patients). The other sites of involvement included gingivobuccal sulcus in one patient and hard palate in one patient. All patients were initially evaluated at oral oncology department for gradually increasing ulcerative mass in oral cavity. None of the patients had B symptoms. In our study, plasmablastic lymphoma was the most common type of NHL, followed by diffuse large B cell lymphoma (DLBCL) and peripheral T cell lymphoma, not otherwise specified (PTCL, NOS). Out of seven patients, two were HIV positive, both having plasmablastic lymphoma. Four out of the seven patients received a combination of chemotherapy and radiotherapy and three patients received only chemotherapy. Only three patients could complete the prescribed chemotherapy and radiotherapy schedule and were alive and diseases free with a median follow-up of 21 months. Conclusion: Involvement of oral cavity by lymphoma is rare. Plasmablastic lymphoma was the most common oral cavity NHL in our patients. Although number of cases in present study was less, our data suggests that oral NHL has aggressive course with less favorable outcome. Further large sample studies incorporating rituximab-based chemotherapy and more aggressive chemotherapy for plasmablastic lymphoma will be helpful for better understanding of treatment outcome.

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Purpose: The purpose of the following study is to evaluate the treatment modalities, clinical status and prognostic factors affecting survival rates in patients with newly diagnosed brain metastasis from non-small cell lung cancer (NSCLC). Patients and Methods: NSCLC patients with a new diagnosis of one to four brain metastasis evaluated retrospectively for the effects of treatment regimens on local failure-relapse-free survival (LRFS) and overall survival (OS). The relationship between age, gender, performance status, recursive partitioning analysis (RPA) classification, the primary tumor under control, number of metastatic tumors in the brain and total volume of brain metastasis and prognosis is analyzed. Results: Out of a total of 138 (121 male and 17 female) patients, nearly 44.2% received only gamma-knife (GK); 24.6% were received both GK and whole brain radiotherapy (WBRT), 2.9% had GK and surgery, 3.6% received GK, surgery and WBRT, 10.9% had surgery and WBRT and 12.3% received only WBRT for treatment. Median LRFS of surgery plus WBRT group was significantly higher when compared with WBRT group (P < 0.0001). The OS was significantly longer for surgery plus WBRT group than the other treatment groups (P = 0.037). When median survival of WBRT-only group compared with surgery plus WBRT, it was significantly higher (29.6 months vs. 16.7 months, P = 0.006). Median OS of surgery plus WBRT group was significantly higher than GK plus WBRT group (29.6 months vs. 9.3 months, P = 0.007). Conclusion: WBRT is still the most effective treatment method following surgery in selected patients according to their age, performance status and spread of the primary disease with NSCLC had limited number brain metastasis. Adding WBRT treatment after surgery significantly improved OS and LRFS.

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Background and Aim: Breast cancer is the most common type of cancer amongst women today. The aim of this study was to examine the association between complementary and alternative medicine (CAM) and the quality of life (QoL), anxiety and depression and demographic characteristics of women with breast cancer. Materials and Methods: QoL was measured by the European Organization for Treatment and Research of Cancer quality of life core questionnaire (QLQ-C30, version 3.0) and anxiety and depression was measured by the hospital anxiety and depression scale. Results: In total, 122 patients with breast cancer were enrolled in the study and 50% (n = 61) of them reported that they were using CAM. The most commonly used CAM methods were stinging nettle (57%) and prayer and spiritual healing (49%). No relationship was found between the use of CAM and the patient's age, time to diagnosis, cancer stage, chemotherapy use, smoking and residence. However, the analyses showed a positive association between CAM and role functioning (P = 0.014) and financial difficulties (P = 0.011); and a negative association between CAM and emotional functioning (P = 0.033). Conclusions: Based on the previous studies, 20-83.3% of breast cancer patients among different countries and cultures used CAM. Our results suggested that the use of CAM among women is quite popular, but they showed no correlation between CAM usage and anxiety and depression. In addition, CAM usage was more common in breast cancer patients with a poor emotional and financial status.

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Introduction: Gastric cancer is among the leading causes of cancer-related death worldwide, especially in Eastern Asia, Eastern Europe and South America. Statin is one of the most widely used medications for hypercholesterolemia. Several meta-analyses have failed to determine the relationship between statins and gastric cancer. Aims: A meta-analysis of case control studies is conducted to evaluate the association of statin exposure and risk of gastric cancer. Materials and Methods: Eight electronic databases (The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 12, 2012), PubMed, EMBASE, ISI Web of Knowledge, CNKI, CBM, CSJD and Wanfang Database) were searched for relevant publications through September 2013. Two reviewers determined the eligibility of articles and abstracted the data independently. RevMan 5.2 software was used for statistical analysis. Results: 146 items were retrieved from the databases and 6 studies were identified in this meta-analysis, which included 5,993 cases and 54,800 matched controls. Results from the meta-analysis demonstrated that statins were inversely related to the risk of gastric cancer (RR = 0.56, 95% CI: 0.35-0.90). There was no significant difference for cumulative duration of statin exposure and gastric cancer, nor participants from Asia, Europe, or USA. Conclusion: This meta-analysis suggests that statins have favorable effects on gastric cancer, rigorously designed and executed observational studies and randomized control trials with longer duration of follow-up are warranted to determine effects in clinical practice.

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While most case reports to date are radiation recall dermatitis, radiation recall myositis, which is a distinct form of radiation recall phenomenon caused by carboplatin plus paclitaxel, has not been reported. We treated a 57-year-old female patient who suffered from recurrent cervical cancer. When the patient developed a new left sacral metastasis, salvage radiotherapy (total dose 60 Gy) was administered. Four weeks later, chemotherapy using carboplatin plus paclitaxel was initiated. Four months after chemotherapy, the patient complained of severe pain in her left buttock. On magnetic resonance imaging (MRI), edematous changes and increased signal densities of left gluteus maximus and medius muscles were noted suggesting myositis. The border of the high signal intensity territory of the muscles was sharp and clearly corresponded with the recent irradiation field. We concluded that the patient had radiation recall myositis triggered by paclitaxel-carboplatin. Symptoms were controlled by analgesics, and there was no recurrence.

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Background: The perioperative use of epirubicin, cisplatin, and fluorouracil (ECF) significantly improves outcomes in patients with gastric and gastro-oesophageal (GO) cancers but is cumbersome to administer. Given the equivalence of epirubicin, oxaliplatin, and capectabine (EOX) with ECF in advanced setting, we analyzed the compliance, efficacy, and toxicity of perioperative EOX in resectable but locally advanced cancers. Methods: This is a retrospective analysis of prospectively maintained database of patients treated between January 2012 and September 2013 at Tata Memorial Centre. Patients were planned to receive 3# of neoadjuvant (NA) and 3# of adjuvant EOX (intravenous epirubicin 50 mg/m ² D1, oxaliplatin 130 mg/m ² , on D1, capecitabiine 1250 mg/m ² D1-21) every 21 days. On completion of NA therapy, patients were planned to undergo gastrectomy and D2 lymphadenectomy. Results: A total of 99 patients (76% males, median age 51 years) were treated with perioperative EOX. Preoperatively, 93% patients completed EOX. Post-NA chemotherapy, 4 patients progressed, 1 patient died and 94 were taken up for surgery. Of these, 9 were inoperable and 85 patients underwent radical surgery. Of these, 71% (60/85) were able to complete three cycles of adjuvant EOX. The compliance to complete all 6 cycles of perioperative chemotherapy was 64%. Grade 3 and 4 toxicities were comparable to the MAGIC dataset apart from higher number of diarrhea in our patients. Conclusions: In patients with resectable GO adenocarcinoma, it is possible to deliver the MAGIC-type perioperative chemotherapy with EOX with better compliance, toxicity, and efficacy rates.

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Introduction: Breast-conserving surgery followed by radiation therapy (RT) to the intact breast is now clearly established as the most acceptable strategy for women with early-stage invasive breast cancer. Recommended techniques for radiotherapy is whole breast irradiation (WBI) followed by boost to the tumor bed. Aims: The aim of this study is to compare the modalities of three-dimensional conformal RT (3DCRT) and electron beam therapy as boost in post-lumpectomy patients of early stage breast cancer, following WBI. Materials and Methods: The study comprised of selecting 50 patients of early-stage post-lumpectomy breast cancer. Each patient was initially treated by WBI (40 Gy in 16 fractions) and then followed by tumor bed boost (16 Gy in 8 fractions) with either electron beam therapy or with photon (3DCRT), 25 patients in each arm. Patients were evaluated regularly for acute and chronic radiation toxicities, cosmesis, and pattern of failure. Dosimetric comparison of the plans was also done. Results: Median age of the patients was 42 years with 66% being premenopausal. Median duration of follow-up was 23 months. In arm A (electrons), two patients had grade III-IV reactions at treatment completion with one patient required RT interruption. Whereas, in arm B (3DCRT), five patients had grade III-IV reactions at treatment completion with three patients required RT interruption. At 6 months and 2 years follow-up, both the arms had almost similar skin, subcutaneous toxicity, and cosmetic score. At the end of 2 years, there were totally four failures among 50 patients, with one locoregional failure in both arms (4%). Dosimetric analysis revealed that conformality (radiation conformity index (RCI)), dose homogeneity index (DHI) and planning target volume (PTV) coverage was significantly better in 3DCRT boost plans. Organs at risk (OAR) dosimetry also revealed significant decrease in ipsilateral lung and heart doses with 3DCRT plans in which tangential or oblique fields were used; and whereas in electron beam, only single direct fields were used. Conclusions: Both electrons and 3DCRT can be used for boost planning to the tumor bed in post-lumpectomy patients. Though there was slightly increased acute skin toxicity with 3DCRT photon which led to interruption of therapy, overall cosmesis at 2 years is similar in both modalities. 3DCRT boost is a better option than electrons dosimetrically, considering the fact that conformality; PTV coverage and OAR dosimetry were superior with photons. Thus in centers where electron beam therapy is not available, 3DCRT photon can be used effectively for tumor bed boost.

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Aims: Evaluation of the dosimetric advantage, if any, of RapidArc (double arc and triple arc [DA and TA]) over standard fixed field intensity-modulated radiation therapy (IMRT) in gynecologic malignancies. Materials and Methods: A total of 20 cases of gynecologic malignancies were included. Static IMRT sliding window, single arc (SA), DA and TA plans were generated with eclipse planning system. The prescribed dose was 50.4 Gy/28# to the planning target volumes. Results: IMRT provided target coverage equivalent to DA and inferior to TA (D95% [in Gy] - 49.94, 49.58, 49.96, 50.17 for IMRT, SA, DA and TA respectively-all observations in the same sequence). Conformity index ₉₀ (CI ₉₀ (0.964, 0.927, 0.918, 0.822) and homogeneity index (0.0683, 0.119, 0.098, 0.097) of IMRT were superior. TA was superior to other arcs in all parameters except CI ₉₀ (P = 0.805) and bladder dose (lower in DA). Rectal, bladder and bowel sparing was best achieved with IMRT followed by TA; bilateral femur dose was lower in arcs. The total monitor units and treatment time of arcs were significantly lower than IMRT, reduced by a factor of 2.41-2.59 and 3.2-3.5 respectively (All P values significant). Conclusion: IMRT provided better overall plan for gynecologic malignancies with lower organs at risk dose and target coverage equivalent to DA and TA. Treatment delivery efficiency was higher with RapidArc. The TA plan is dosimetrically superior to DA, but the gain is small. The decision whether or not to add a third arc for a small gain should be individualized.

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Available evidence of the relationship between cholelithiasis, cholecystectomy, and risk of liver cancer and hence we conducted a meta-analysis to investigate the relationships. PubMed, EMBASE, and ISI Web of Knowledge were searched to identify all published cohort studies and case-control studies that evaluated the relationships of cholelithiasis, cholecystectomy and risk of liver cancer and single-cohort studies which evaluated the incidence of liver cancer among patients who understood cholecystectomy (up to February 2013). Comprehensive meta-analysis software was used for meta-analysis. A total of 11 observational studies (six cohort studies and five case-control studies) were included in this meta-analysis. The result from meta-analysis showed that cholecystectomy (risk ratio [RR]: 1.59, 95% confidence interval [CI]: 1.01-2.51, I² = 72%) and cholecystolithiasis (RR: 5.40, 95% CI: 3.69-7.89, I² = 93%) was associated with more liver cancer, especially for intrahepatic cholangiocarcinoma (ICC) (cholecystectomy: RR: 3.51, 95% CI: 1.84-6.71, I² = 26%; cholecystolithiasis: RR: 11.06, 95% CI: 6.99-17.52, I² = 0%). The pooled standardized incidence rates (SIR) of liver cancer in patients who understood cholecystectomy showed cholecystectomy might increase the incidence of liver cancer (SIR: 1.57, 95% CI: 1.13-2.20, I² = 15%). Based on the results of the meta-analysis, cholecystectomy and cholecystolithiasis seemed to be involved in the development of liver cancer, especially for ICC. However, most available studies were case-control studies and short-term cohort studies, so the future studies should more long-term cohort studies should be well-conducted to evaluate the long-term relationship.

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Schwannomas commonly arise from peripheral nerves. Intracranial schwannomas are comparatively rare and are seen commonly as vestibular tumors. Oculomotor nerve schwannomas are extremely rare tumors, these are usually symptomatic. A 29 year aged male presented with diplopia and blurring of vision in left eye and found to have an extra-axial lesion at left cavernous sinus involving oculomotor nerve. The excised tumor showed classic morphology of a schwannoma. Postoperatively patient developed complete oculomotor nerve palsy. The tumor recurred after 2 years. It was re-excised followed by radiotherapy.

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Objectives: The purpose of this retrospective study was to investigate differences between black and white persons with oral squamous cell carcinoma (OSCC) with regard to age, gender, oral site affected, and histopathological degree of differentiation; and to compare these clinicopathological parameters between persons younger and older than 40 years in a South African population sample from the greater Johannesburg area. Material and Methods: The histopathological reports of 510 cases of OSCC during the period 1995-2002 were retrospectively evaluated, and the data regarding age, gender, ethnicity/race, oral site affected, and degree of histopathological differentiation were recorded and statistically analyzed for differences between black and white persons, and between persons younger and older than 40 years of age. Results: Statistically significantly, black persons were diagnosed with OSCC at a younger mean age (57 years) than white persons (61 years) (P = 0.0086). The difference between male: female (M: F) ratio in black (3.74:1) and white persons (1.96:1) was statistically significant (P = 0.0041). White persons had a significantly higher proportion of SCC of the lower lip than black persons (P < 0.0001). Conclusion: OSCC was diagnosed at a younger age in black than in white persons; the proportion of black males in the black population group was greater than that of white males in the white population group; and the proportion of SCC of the lips was higher in younger than in older persons.

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Background: Wnt/β-catenin signaling pathway plays a key role in human breast cancer progression. In this study, we down regulated β-catenin expression in human breast cancer MDA-MB-231 cells and investigated the effect of β-catenin knockdown on the cell biological characteristics. Materials and Methods: The recombinant plasmids of pSUPER-enhancement green fluorescent protein 1 (EGFP1)-scrabble-β-catenin-short hairpin ribonucleic acid (shRNA) and pSUPER-EGFP1-β-catenin-shRNA-1 were transfected into MDA-MB-231 cells, respectively, and the stably transfected cells were isolated from G418 selected clones. The β-catenin gene silenced efficiency was measured by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) and Western blot. The biological characteristics of MDA-MB-231 cells with down regulated β-catenin were evaluated by analyzing cell proliferation, clonogenicity, cell mobility and tumorigenicity. The expression of E-cadherin and Vimentin was concurrently detected by QRT-PCR. Results: The β-catenin-shRNA-1 stably transfected MDA-MB-231 cells significantly decreased β-catenin expression, cell proliferation, clonogenicity, and tumorigenicity in Balb/c nude mice compared with the MDA-MB-231 cells transfected with pSUPER-EGFP1-scrabble-β-catenin-shRNA. Interestingly, knockdown of β-catenin led to the reduction of epithelial E-cadherin expression, the increase of cell mobility and mesenchymal vimentin expression in MDA-MB-231 cells, indicating an epithelial to mesenchymal transition. Conclusion: Knockdown of β-catenin expression in human breast cancer MDA-MB-231 cells inhibits cell tumorigenicity in mice, but promotes cell epithelial-mesenchymal transition.

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MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, noncoding RNA molecules of about 22-24 nucleotides in length that repress gene expression at the posttranscriptional level. MiR-34a plays an important role in the initiation, progression, and therapy of cancer. In addition, the miR-34a expression has also been identified as a diagnostic and prognostic cancer signature. This article introduces the roles of miR-34a in cancer development, metastasis as well as its mechanism of actions on target genes and the functional outcomes of its actions on radio-sensitivity. The paper ends with a brief perspective to the future of miR-34a.

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Purpose: A prospective study was undertaken to evaluate the influence of patient positioning on the set up variations to determine the planning target volume (PTV) margins and to evaluate the clinical relevance volume assessment of the small bowel (SB) within the irradiated volume. Materials and Methods: During the period of months from December 2011 to April 2012, a computed tomography (CT) scan was done either in supine position or in prone position using a belly board (BB) for 20 consecutive patients. All the patients had histologically proven rectal cancer and received either post- or pre-operative pelvic irradiation. Using a three-dimensional planning system, the dose-volume histogram for SB was defined in each axial CT slice. Total dose was 46-50 Gy (2 Gy/fraction), delivered using the 4-field box technique. The set up variation of the study group was assessed from the data received from the electronic portal imaging device in the linear accelerator. The shift along X, Y, and Z directions were noted. Both systematic and random errors were calculated and using both these values the PTV margin was calculated. Results: The systematic errors of patients treated in the supine position were 0.87 (X-mm), 0.66 (Y-mm), 1.6 (Z-mm) and in the prone position were 1.3 (X-mm), 0.59 (Y-mm), 1.17 (Z-mm). The random errors of patients treated in the supine positions were 1.81 (X-mm), 1.73 (Y-mm), 1.83 (Z-mm) and in prone position were 2.02 (X-mm), 1.21 (Y-mm), 3.05 (Z-mm). The calculated PTV margins in the supine position were 3.45 (X-mm), 2.87 (Y-mm), 5.31 (Z-mm) and in the prone position were 4.91 (X-mm), 2.32 (Y-mm), 5.08 (Z-mm). The mean volume of the peritoneal cavity was 648.65 cm ³ in the prone position and 1197.37 cm ³ in the supine position. Conclusion: The prone position using BB device was more effective in reducing irradiated SB volume in rectal cancer patients. There were no significant variations in the daily set up for patients treated in both supine and prone positions.

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Aims: In the current study, the effect of electronic disequilibrium on lung dose with small photon beams was verified. Materials and Methods: The central axis absorbed dose in lung phantom was calculated by Monte Carlo (MC) method. The 6 and 18 MV photon beams of Varian Clinac 2100EX were simulated using MCNPX MC Code (Los Alamos national lab, USA). The MC model was used to calculate the depth doses water and low density water resembling the soft-tissue and lung, respectively. Four small field sizes including 0.5 cm ² × 0.5 cm ² , 1 cm ² × 1 cm ² , 2 cm ² × 2 cm ² , and 3 cm ² × 3 cm ² were used in this study. Results: Percentage of dose reduction in lung region relative to homogenous phantom for 6 MV photon beam were 44.6%, 39%, 13%, and 7% for 0.5 cm ² × 0.5 cm ² , 1 cm ² × 1 cm ² , 2 cm ² × 2 cm ² , and 3 cm ² × 3 cm ² fields, respectively. For 18 MV photon beam, the results were found to be 82%, 69%, 46%, and 25.8% for the same field sizes, respectively. The solid tumor dose inside lung was reduced considerably between 17% and 35% for 18 MV beam, while there was only 9% dose reduction for tumor dose for 0.5 and 1 cm field sizes. Conclusion: Our study showed that the dose reduction with small fields in the lung was very enormous. Thus, inaccurate prediction of absorbed dose inside lung and also lung soft-tissue interfaces with small photon beams may lead to critical consequences for treatment outcome.

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Cases involving more than two primary malignant neoplasms are very rare. The present article reports a case of multiple primary malignant neoplasms including esophagus initially followed by right breast and later base of tongue in an elderly male patient, which is extremely a rare combination.

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Background: Breast cancer is one of the most frequently diagnosed cancers in women. Though death from this disease is mainly caused by the metastases of the aggressive cancer cells, few studies have expounded the aggressive behavior of breast cancer. Materials and Methods: We downloaded the gene expression profiles of GSE40057, including four aggressive and six less-aggressive breast cancer cell lines, from Gene Expression Omnibus and identified the differentially expressed genes (DEGs) between the aggressive and less-aggressive samples. An integrated gene regulatory network was built including DEGs, microRNAs (miRNAs), and transcription factors. Then, motifs and modules of the network were identified. Modules were further analyzed at a functional level using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to study the aggressive behavior of breast cancer. Results: A total of 764 DEGs were found and two modules were filtered from the integrated gene regulatory network. Totally two motifs and modules for DEGs were identified. Significant GO terms associated with cell proliferation and hormone stimulus of the modules were found and the target genes identified were  CAV1, CD44, and TGFβR2. The KEGG pathway analysis discovered that CAV1 and FN1 were significantly enriched in focal adhesion, extracellular matrix (ECM)-receptor interaction, and pathways in cancer. Conclusion: Aggressive behavior of breast cancer was proved to be related to cell proliferation and hormone stimulus. Genes such as CAV1, CD44, TGFβR2, and FN1 might be potential targets to diagnose the aggressive behavior of breast cancer cells.

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Aim: We assessed the effect of adding diffusion-weighted magnetic resonance imaging (DW-MRI) to conventional MRI for T staging and the correlation between apparent diffusion coefficient (ADC) values and clinicopathological parameters for patients with bladder cancer. Materials and Methods: We retrospectively reviewed the records of 160 patients with bladder cancer who underwent MRI at our institute. All patients were routinely assessed with conventional MR imaging. Since January 2008, we added DW-MRI. Results: In these 160 patients, 127 (79.4%) tumors were detectable by MRI. In all patients with detectable tumors, on a stage-by-stage basis, 96 (75.6%) of 127 patients received the correct diagnosis. With DW-MRI, accurate diagnosis was obtained in 80 (80.0%) of 100 cases; without DWI in only 16 (59.3%) of 27 cases (P = 0.026). For T staging, the accuracy for distinguishing muscle invasion (T ≦_ 1 vs T ≧_ 2) with DW-MRI (83.0%) was superior to that without DW-MRI (66.7%). The accuracy for distinguishing perivesical fat invasion (T ≦_2 vs T ≧_3) with DW-MRI (98.0%) was also superior to that without DW-MRI (92.6%). The ADC values were significantly related with tumor diameter (<3 cm vs ≧_ 3 cm,P < 0.001), histopathological grade (low grade vs high grade, P < 0.001), T stage (≦_T1 vs ≧_T2,P < 0.001), and operative method (transurethral resection vs total cystectomy, P < 0.001). Conclusions: We demonstrated that DW-MRI is not only useful for bladder cancer T staging, but also a prognostic factor for patients with bladder cancer.

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Aim: Alteration of circadian systems can cause cancer and affects its development and response to therapeutics. The present study investigates whether cancer can disrupt circadian locomotor rhythms and evaluated the influence of melatonin (MLT) and oxaliplatin on the levels of antioxidants and circadian locomotor activity rhythms in N-nitrosodiethylamine (NDEA)-induced liver tumor in Indian field mouse (Mus booduga). Materials and Methods: Effects of NDEA, NDEA, and MLT, as well as NDEA and oxaliplatin, on levels of mice liver marker enzymes and antioxidants and their circadian locomotor activity rhythm were assessed. Results: Treatment of mice with NDEA caused significant alteration of their liver marker enzymes [aspartate transaminase and alanine transaminase; P< 0.05 Duncan's multiple range test (DMRT) test] antioxidant levels (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase; P< 0.05, DMRT test] and circadian locomotor activity rhythm, which were abrogated when the animals were also given MLT or the anticancer drug, oxaliplatin. Conclusion: Our study demonstrated that the circadian clock was disturbed by hepatocarcinogenesis and the effects could be reversed by the chronobiotic, MLT.

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Aim of the Study: In the present study the effects of mangiferin were tested against lung cancer-bearing mice in both the pre-initiation and post-initiation periods. Materials and Methods: Healthy male Swiss albino mice (6-8 weeks old) were used throughout the study. The animals were treated with mangiferin (100 mg/kg body weight dissolved in corn oil) two weeks before (pre-initiation) and the twelfth week after (post-initiation) the establishment of B (a) P (50 mg/kg body weight)-induced lung carcinoma. Results: The body weight decreased and the lung weight and levels of xenobiotic and liver marker enzymes markedly increased in the carcinogen-administered animals; and mangiferin treatment brought the values of these parameters back to the near-normal ones. The activities of lysosomal enzymes in the animals with B (a) P-induced experimental lung carcinogenesis were also assessed. In these animals there was an increase in the activities of lysosomal enzymes such as acidphosphatase, β-glucuronidase, N-acetyl glucosaminidase, and β-galactosidase. Conclusion: Supplementation with mangiferin attenuated all these alterations, thus indicating its anticancer effect. Overall, the above data showed that the anticancer effect of mangiferin as a chemopreventive agent was pronounced.

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Background: Many evidences showed that cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, has an important role in carcinogenesis. It has been observed in experimental models that selective COX-2 inhibitors suppress the formation of tumors including tongue carcinoma. The aim of this study was to investigate the immunohistochemical expression of COX-2 in oral squamous cell carcinoma (OSCC) compared to normal oral mucosa and oral dysplasia. Materials and Methods: A total of 60 paraffined blocks (20 cases of OSCC, 20 cases of oral epithelial dysplasia and 20 cases of normal oral mucosa were included in this study and immunohistochemical staining was done for COX-2 expression. From each sample, 5 high power fields were assessed to determine the percentage of stained cells and staining intensity. Immunoreactivity was obtained by multiplying the above two cases. Data were analyzed with using the Kruskal-Wallis test ANOVA, Mann-Whitney test and least significant difference and P < 0.05 was declared as significant. Results: High level of COX-2 expression was found in OSCC and dysplasia compared to normal mucosa. Furthermore, a positive correlation was found between COX-2 expression and severity of dysplasia. However, no significant difference between low grade and high grade tumors was found. Conclusion: The result of the present study supports from the role of COX-2 in carcinogenesis and progression of premalignant lesion to malignancy.

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Aim: It has been previously reported that metabolic tumor volume on positron emission tomography-computed tomography predicts disease recurrence and death in head-and-neck cancer. In this study, we assessed the prognostic value of metabolic tumor volume measured using F18-Fluorodeoxyglucose PET/CT in patients with head and neck squamous cell carcinoma. Materials and Methods: We analyzed the imaging findings of 74 patients (age 57 ± 16) retrospectively, with head and neck cancer who underwent PET/CT scan for staging and after treatment. Forty-tree patients had nasopharynx, 15 patients had hypopharynx, 9 patients had larynx, and 7 patients had oropharynx cancer. The MTVs of primary sites with or without lymph nodes were measured, and outcomes were assessed using the treatment response evaluation by the Response Evaluation Criteria in Solid Tumors and recurrence events during follow-up. Results: A total of 48 patients had complete response or no recurrence was detected as of in the last follow-up. Of the first PET/CT scan, the median primary tumor SUVmax was 18.8 and the median nodal SUVmax was 13.4. The median primary tumor MTV% 50s ranged from 11.12 cm ³ to 16.28 cm ³ , and the MTV after the therapy ranged from 1.18 cm ³ to 3.51 cm ³ . Conclusion: Metabolic tumor volume (MTV) represents tumor burden, which shows F18-Fluorodeoxyglucose uptake and has a potential value in predicting short-term outcome and disease-free survival in patients with head and neck cancer.

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Background: Biopsy is an important diagnostic tool used in the diagnosis of lesions ranging from simple non-neoplastic, tumor-like lesions to malignancies, and is often the only way to diagnose oral lesions and diseases. The gingiva is the most common site for some kind of irritation or low-grade injury, resulting in localized overgrowths that are considered to be reactive and non-neoplastic lesions. This aim of this study is to analyze the frequency and distribution of gingival lesions in the Gujarati population. Materials and Methods: In this retrospective study, gingival biopsies submitted for a period of five years were included. Microscopic slides of all the cases were reviewed by two observers for confirmation of the diagnosis. Results: Among the 106 cases of gingival biopsies, the most frequent category of lesions encountered was the non-neoplastic category, which accounted for 73.58% of the cases. Both benign and malignant neoplasms constituted 26.42% of the cases. Among the non-neoplastic lesions, Pyogenic granuloma was the most frequent lesion (38.46%), followed by fibrous hyperplasia (20.51%), inflammatory hyperplasia (19.23%), and Epulis (8.97%). Neoplasms accounted for 26.42% of the gingival biopsies (92.85% benign and 7.15% malignant). Among the benign neoplastic lesions, Fibroma (30.76%) and Fibrolipoma (26.92%) were the most frequent, followed by peripheral ossifying fibroma (23.08%) and peripheral giant cell granuloma (11%). Conclusion: It is difficult to compare studies carried out in various countries due to differences in people's attitudes toward oral health and the accessibility of various population groups to biopsy services. Nevertheless, this study has provided some information about the frequency and distribution of biopsied gingival lesions in the Gujarati population over a period of five years.

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Background: Insect tea is widely used a traditional drink or traditional Chinese medicine in China. This study was conducted with an aim to determine the in vitro anticancer effect of Insect tea in cancer cells. Materials and Methods: The anticancer effects of Insect tea were evaluated in human tongue carcinoma TCA8113 cells using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry analysis, nuclear staining with 4,6-diamidino-2-phenylindole (DAPI), reverse transcription-polymerase chain reaction (RT-PCR) analysis, and western bolt assay. Results: At 200 μg/mL, Insect tea inhibited the growth of TCA8113 cells by 80.7%, which was higher than the inhibition caused by 100 μg/mL Insect tea but lower than that of 200 μg/mL green tea. Compared to the control cancer cells, Insect tea significantly (P < 0.05) induced apoptosis as determined by DAPI staining and flow cytometry analysis results. Insect tea significantly induced apoptosis in cancer cells by upregulating BAX, CASP3, CASP9 and downregulating BCL2. Genes encoding nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were significantly downregulated by Insect tea, demonstrating its anti-inflammatory properties. Insect tea also exerted a great anti-metastasis effect on cancer cells as demonstrated by decreased expression of matrix metalloproteinase (MMP) genes and increased expression of tissue inhibitors of metalloproteinases (TIMPs). Conclusion: The results showed that Insect tea has good in vitro anticancer effects in TCA8113 cells, like green tea.

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Imatinib mesylate is the standard treatment of chronic myeloid leukemia (CML). Despite imatinib is being used in the treatment of other malignancies as well, its potential role on de novo tumor growth is not known. Secondary malignancies are rarely seen in patients with CML and particularly in those receiving imatinib. Here, we present a CML patient taking imatinib therapy that was diagnosed to have breast cancer and received adjuvant chemo-and radiotherapy with imatinib. We tried to explain co-occurrence of these rare events by probable pathogenetic mechanisms.

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Context: Ameloblastoma is the most common odontogenic tumor, however, the molecular pathology, especially the role of the tumor stroma, is still unclear. Aims: To investigate the effects of the ameloblatoma-associated fibroblast (AAFs) on the proliferation and invasion of tumor cells. Settings and Design: Cell culture, ELISA, proliferation and invasion assays. Methods and Material: The cocultivations and three-dimensional organotypic cultures of the AAFs and the tumor cells were performed. The gingival fibroblasts (GFs) were used as the control. The levels of TGF-β and HGF in the conditioned media were analyzed using ELISA technique. The MTT proliferation assays and Boyden chamber chemoinvasion assays were also performed. Statistical Analysis Used: ANOVA. Results: Both AAFs and GFs stimulated tumor cell growth. The TGF-β level in the AAF group was more than those of GF group, whereas the HGF levels were not different. The AAF conditioned media also stimulated tumor cell proliferation and invasion more than the GF conditioned media. However, no difference in the thickness and morphology between the AAF and GF groups could be demonstrated in the organotypic models. Conclusions: Both AAFs and GFs support the proliferation of the tumor cells in cocultivation experiment and three-dimensional organotypic cultures. However, the AAFs have a tendency to stimulate the proliferation and induce the invasion more than GFs. Increased TGF-β levels in the AAF condition media suggested the possible role of this growth factor in the ameloblastoma biology.

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Context: Carvedilol (CAR) can inhibit cell growth and induce cell apoptosis in breast cancer in vitro. But it is still not known whether CAR affects the migration and invasion of breast cancer cells. Aims: To investigate the effects of CAR on migration and invasion of breast cancer cells and its corresponding signal pathways. Settings and Design: Firstly, the invasive potential of breast cancer cells were investigated after incubation with CAR and/or norepinephrine (NE). If the invasive potential of breast cancer cells were inhibited by CAR, then the signal pathways related to migration and invasion were detected, such as Src, cyclic adenosine monohposphate (cAMP)/protein kinase A (PKA), etc. Subjects and Methods: Membrane invasion culture system (MICS) chamber was used to measure the invasive and migratory potential of breast cancer cells. Western blot analysis and small interfering RNA (siRNA) transfection experiment were employed to determine the signal pathway adopted by CAR in suppressing migration and invasion of MDA-MB-231 and MCF-7 cells. cAMP-Glo and PKCδ kinase activity assay kit were used to measure cAMP and PKCδ activity, respectively, according to the manufacturer's instructions. Statistical analysis used: Statistical differences between the mean values of control and experimental groups were determined using two-tailed, unpaired Student's t-tests. Results: CAR significantly decreased the potential of migration and invasion of breast cancer cells. CAR inhibited Src activation in MDA-MB-231 and MCF-7 cells through blocking beta or alpha adrenergic receptor (ADR), respectively. Furthermore, CAR suppressed the Src activation through different signaling pathways. Under treatment of CAR, cAMP/PKA-Src pathway was inhibited in MDA-MB-231 cells; but in MCF-7 cells, CAR mainly inhibited the PKCδ-Src pathway. Conclusions: CAR was an anti-metastatic agent, which targets Src involving cAMP/PKA or PKCδ pathway in malignant breast cells.

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Background: Pogostemon benghalensis has been used traditionally as anticancer in India. Aim of the Study: The present study was undertaken to investigate the antitumor activity of hydroethanolic extract of P. benghalensis (HEEPB) and aqueous extract of P. benghalensis (AEPB) on ehrlich ascites carcinoma (EAC) tumor bearing mice. Materials and Methods: For antitumor effect, treatments with HEEPB and AEPB at doses of 250 mg/kg and 500 mg/kg/day orally were started after 24 h of intraperitoneal inoculation of EAC cells. After the treatment period, median survival time (MST), hematological parameters and solid tumor volume were used to evaluate antitumor activity of the extracts. Results: Both, HEEPB and AEPB, have increased MST (P < 0.05), reduced solid tumor volume (P < 0.05) and normalized hematological parameters (P < 0.05) significantly. Conclusion: As HEEPB and AEPB were effective in reducing the severity of morphological and biochemical parameters induced by EAC cells, this study justifies the traditional use of this plant in cancer.

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Objective: Many Chinese doctors have performed microinvasive esophageal cancer resection in the semi-prone position. However, few reports have focused on high-quality methods of scavenging the peripheral lymph nodes (PLNs) of the left recurrent laryngeal nerve (RLN). Materials and Methods: Retrospective analysis was performed on 145 cases of microinvasive esophageal cancer resection in the semi-prone position. Among which, 75 cases underwent complete freeing of the thoracic esophagus and subsequent scavenging of the PLNs of the left RLN from April 2011 to April 2012 (Group A). In the other 70 cases, the incompletely freed upper thoracic esophagus was suspended, and the PLNs of the left RLN were scavenged from May 2012 to April 2013 (Group B). Results: The average number of scavenged PLNs of the left RLN in Groups A and B was 4.6 ± 2.9 and 5.2 ± 3.0 pieces, respectively (P = 0.799). The total scavenged PLNs of the left RLN in Groups A and B were 344 and 357 pieces, respectively. Among which, the broken lymph nodes were 109 and 66 pieces, respectively (P < 0.0001). The postoperative hoarseness rate in Groups A and B was respectively 12.0% and 2.8% (P = 0.038). Conclusions: Dissection of the left RLN can be easily performed after esophageal suspension, thus ensuring the quality of PLN scavenging.

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Aim: To investigate the relationships between expression of forkhead box M1 (FoxM1) and clinicopathologic parameters and Ki-67 expression in patients with renal cell carcinoma (RCC). Materials and Methods: A total of 67 cases of RCC including 47 cases of clear cell RCC (ccRCC), five cases of papillary RCC (pRCC), eight cases of chromophobe RCC (chRCC), four cases of unclassified (with sarcomatoid pattern) RCC (sRCC), and three cases of multilocular RCC (mRCC) were included to this study. The expression of FoxM1 protein was assessed in 67 samples of RCC using immunohistochemical methods and the relationship between the expression levels of FoxM1 with clinicopathological characteristics and Ki-67 expression of RCC patients. For statistical analysis, the cases were grouped into the ccRCC and non-ccRCC group. Results: Immunohistochemistry analyses showed that FoxM1 protein expression in 47 ccRCC samples was significantly correlated with tumor size, stage, nuclear grade, capsule invasion, perinephric fat invasion, and Ki-67 expression (P < 0.05 for all); whereas, no correlations were found in patients' age, gender, and lymph node metastasis (P > 0.05 for all). In 20 non-ccRCC; overexpression of FoxM1 was strongly associated with tumor size (P < 0.05). There was no relationship between FoxM1 expression with other clinicopathological parameters and Ki-67 expression in non-ccRCC (P > 0.05 for all). Conclusion: This study showed that FoxM1 have a progressive oncogenic role in ccRRC. Our results suggested that higher expression of FoxM1 in tumor tissues predicts a locally aggressive behavior and poor outcome of patients with ccRCC, but not in patient with non-ccRCC.

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Background: Cancer is one of the main causes of mortality in the world which is created by the effect of enviromental physico-chemical mutagen and carcinogen agents. In the last years, many studies have been performed on the anticancer effects of flavonoids. Echinophora platyloba DC plant (Khousharizeh) is one of the indigenous medicinal plants which is used as a food seasoning and medicine in Iran. Materials and Methods: The extract was evaluated in terms of antimutagenicity properties by a standard reverse mutation assay (Ames Test). This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100). Thus, it requires histidine from a foreign supply to ensure its growth. The afore mentioned strain gives rise to reverted colonies when expose to carcinogen substance (Sodium Azide). The other objective of this study was to examine the in vitro cytotoxic activity of cell death of crude methanolic extracts prepared from Echinophora platyloba on Acute Promyelocytic Leukemia cell line (NB4). Cytotoxicity and viability of methanolic extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Results: In Ames test the extract prevented the reverted mutations and the hindrance percent was 93.4% in antimutagenicity test. Data obtained from this assay indicated that the extract significantly reduced the viability of NB4 cells and inhibited cell growth in a dose dependent manner. Conclusion: This study demonstrates the antimutagenicity effect of Echinophora Platyloba and suggests that it has a potential as an anticancer agent.

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Clear cell sarcoma of the kidney is a rare malignant neoplasm of childhood, known for its aggressiveness, its tendency for recurrence, and to metastasize to bone. We report the observation of 8-month-old child presenting with a large abdominal mass. Clinically, it was diagnosed as Wilm's tumor, and left nephrectomy was done. Grossly, 10 cm × 8 cm × 3.5 cm globular, white, encapsulated, smooth mass uniformly involving the whole kidney was noted. Histologically, the tumor was diagnosed as clear cell sarcoma with renal vein showing presence of tumor embolus in lumen. The tumor was given stage-II (NWTS-5 protocol). Immunohistochemistry showed vimentin positive and cytokeratin negative tumor cells. The child is currently undergoing chemotherapy and has not yet shown any sign of bony metastasis.

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Background: Dual human epidermal growth factor receptor 2 (HER2) blockade has been preclinically and clinically assessed in HER2-overexpressing metastatic breast cancer (mBC) with encouraging results. Patients and Methods: This is a descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing mBC from two centers. The primary endpoints were to assess objective response rate (ORR) and toxicity. The secondary endpoints were to assess progression-free survival (PFS) and overall survival. Results: A total of 23 HER2-positive mBC patients previously treated with trastuzumab received a trastuzumab plus lapatinib based therapy. Chemotherapy (CT) was added to the dual HER2 blockade treatment in 13 patients (56%), whereas hormonotherapy (HT) was added in 8 patients (35%) and 2 patients (9%) received lapatinib plus trastuzumab without any other agent. ORR was 22% (5/23) and 39% (9/23) of patients had stable disease. PFS in the overall population was 4 months. PFS in patients with CT was 5 months, whereas PFS in patients with HT was 2 months. Grade ≥ 3 adverse events were diarrhea (26%) and hand-and-foot syndrome (9%). Conclusions: These findings suggest that dual HER2 blockade in combination with CT is feasible in pretreated HER2-positive mBC patients.

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Esthesioneuroblastoma (ENB)-also known as olfactory neuroblastoma-originates primarily from the olfactory epithelium in the roof of the nasal cavity. We present here the 7 ^th reported case of ENB arising from the sphenoidal sinus. We undertook a review of the case notes from the time of initial presentation and literature review of this topic. A 55-year-old male presented with a 3-year history of unilateral progressive nasal obstruction, epistaxis, difficult nasal-breathing, facial pain, frontal headache and blood-tinged discharge. Nasal examination revealed a glistening mass in right nasal cavity. Endoscopy-assisted transnasal excision was performed. Histologically, tumor was identified as small round cell tumor and confirmed by immunohistochemistry to be olfactory neuroblastoma (negative leucocyte common antigen, positive neurone specific enolase). Sphenoidal ENB is rare in the literature, and this presentation is the 7 ^th reported case; in addition, surgical treatment is very challenging, and non-surgical treatment is used most commonly.

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Aim of Study: To explore sanazole (AK) directed targeting of the antineoplastic drug doxorubicin (DOX) complexed with silver nanoparticles (SNs) to tumor growth in a murine model. Materials and Methods: Sanazole (AK) and DOX were complexed with SNs, individually and in combination to obtain SN-AK, SN-DOX, and SN-AK-DOX. Solid tumors were developed on hind limbs of Swiss albino mice by transplanting Dalton's lymphoma ascitess (DLAs) tumor cells. Induction of cytotoxicity and apoptosis in the DLA cells by AK and DOX complexed with SN, individually and in combination, were examined under in vitro conditions by incubating the cells with them. SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX were administered orally to the tumor bearing mice and the therapeutic efficacy of AK-directed targeting of SN-DOX complexes to achieve tumor control was monitored. Results: Under in vitro conditions, SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX induced cytotoxicity and apoptosis in DLA cells to varying extents. The SN-AK-DOX complex showed higher level of cytotoxicity and apoptosis-induction in DLA cells. Similarly, administration of SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX resulted in significant reduction in tumor volume and delay in tumor growth. The animals treated with SN-AK-DOX had the highest reduction in tumor volume and tumor growth. In fact, the tumor was almost absent in the animals of this group after the treatment. Conclusion: The SN complex of sanazole and doxorubicin together (SN-AK-DOX) has high anticancer activity under in vivo conditions and has great potential in tumor therapy.

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Aim: Lymphocytes are exceptional among somatic cells as these cells can induce telomerase enzyme after antigen stimulation to compensate chromosomal loss during rapid cell division. Activation of telomerase in lymphocytes needs CD28 signal, which simultaneously costimulates T cells during activation. 4-1BB of tumor necrosis factor superfamily also has been shown to costimulate T cells. Herein, we investigated changes in telomerase activity of lymphocytes during longitudinal cultures when T cells costimulated by CD80 or 4-1BB ligand or both molecules in conjunction with anti-CD3 stimulation. Materials and Methods: Artificial antigen presenting cells (aAPCs) were produced by transduction of CD80, 4-1BB ligand or green fluorescent protein genes into A549 carcinoma cells using recombinant adenoviral vectors. Peripheral blood mononuclear cells were stimulated with anti-CD3 and co-cultured with the aAPCs. Cellular growth, expression of telomerase and production of interferon gamma (IFN-γ) were assessed at different time points and followed up to day 35. Results: 4-1BBL provided effective costimulation for lymphocytes' activation, cytokine production or long-lasting growth where its effects exceeded over CD80 after the first week. 4-1BBL also promoted the telomerase activity and more importantly was able to re-induce the enzyme in the cells that stopped to grow with CD80 costimulation. Although combination of CD80 and 4-1BBL has additional effect on cellular growth or initial telomerase activity, it could not support telomerase activity in later time points. Conclusion: Our results underscored unique features of 4-1BB over CD28 for prolonged support of lymphocytes' costimulation, which can be recruited for in vitro or ex vivo propagation of T cells for cancer immunotherapy purposes.

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Aims: The aim of the following study is to analyze the long-term results of veterans treated with dose escalated radiation therapy for prostate cancer. Materials and Methods: This retrospective study analyzed 469 patients who were treated between 2003 and 2010 with dose escalated radiation therapy to a minimum dose of 7560 cGy for prostate cancer at the New York Harbor Department of Veterans Affairs. Biochemical failure-free survival (bFFS) and distant metastatic-free survival (DMFS) were compared using the Kaplan-Meier method. Univariate and multivariate Cox Regression were used to measure the impact of covariates on biochemical control. Results: The median follow-up was 61 months and 95.3% of patients were followed at least 2 years. The 5-year bFFS for National Cancer Care Network low, intermediate and high risk disease were 90.3%, 86.9% and 77.3% respectively (P = 0.001). Patients with high risk disease were more likely to develop metastatic disease. The 5-year DMFS was 99.1% for low risk, 98.8% for intermediate risk and 94.5% for high-risk (P < 0.001). There were 8 prostate cancer related deaths, of which 6 had high risk disease and 2 had intermediate risk disease. The 5-year prostate cancer specific survival was 98.4%. Toxicities were generally mild, however there were two genitourinary toxicity related deaths, though in both patients there were confounding medical issues that may have contributed to their deaths. Conclusions: Dose escalated radiation in the treatment of United States Veterans appears to be well-tolerated with results in line with prior reports. Further follow-up is necessary to identify any additional late toxicities as well as to assess the durability of their biochemical control beyond 5 years.

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Background: The clinical significance of metastasis associated in colon cancer 1 (MACC1), in human gallbladder cancer, is not yet established. This study was performed to assess the expression of MACC1 in benign and malignant gallbladder lesions, and to assess its clinicopathological significance. Materials and Methods: Tissue samples from resected gallbladder cancer (n = 70) and cholelithiasis (n = 70) were evaluated for MACC1 expression by immunohistochemical staining. Their expression was correlated with different clinicopathological parameters. Results: Cytoplasmic MACC1 expression was significantly higher (58.6%) in gallbladder cancer than in chronic cholecystitis (27.1%, P < 0.001). High MACC1 levels were associated with lymph node metastasis (P < 0.05), tumor node metastasis (TNM) stage (P < 0.01), and perineural invasion (P < 0.01), but not with sex, age, history of gallstones or histological grade (P > 0.05). The univariate Kaplan-Meier analysis showed that a positive MACC1 expression was associated with decreased overall survival (P < 0.001). The multivariate Cox regression analysis showed that MACC1 expression and the histopathological subtypes were independent risk factors for disease-free survival. Conclusion: The expression of MACC1 might be closely related to carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

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Transarterial chemoembolization (TACE) has been the standard treatment modality in patients with intermediate stage hepatocellular carcinoma (HCC). Brivanib is an oral small molecular inhibitor of both vascular endothelial growth factor and fibroblast growth factor receptors. Herein, we reported that a 67-year-old patient with intermediate stage HCC achieved the complete remission after TACE combined with brivanib therapy. This finding potentially suggested the benefit of this combination therapy for HCC.

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Background: This project's aim was to explore the enhancing effect of contrast media on primary cancer and cervical metastatic lymph nodes of cheek carcinoma by local injection. Materials and Methods: Lymphatic metastasis cheek carcinoma mice models were established, then self-made contrast media was administered into the primary cheek carcinoma and harmonic mode imaging was performed to observe the enhancement of primary lesions and cervical metastatic lymph nodes. Results: The echo intensity (EI) was compared. The detection rate of metastatic lymph nodes and inflammatory lymph nodes was 61% (17/28) and 50% (6/12) before contrast-enhanced ultrasound (CEUS) imaging and 82% (23/28) and 75% (9/12) after CEUS imaging. After CEUS imaging, the EI of primary cancer and cervical metastatic lymph nodes was significantly increased, (P < 0.01). Conclusion: After injection of self-made contrast media via the primary lesion, it can enter the lymph duct and obviously enhance the effect of ultrasonography on cervical metastatic lymph nodes of cheek carcinoma.

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p53 gene is one of the most frequently mutated genes found in the human colonic tumors. Mice have been used as an experimental model to study the pathogenesis of colon cancer in humans. The alterations in cancer genes and proteins found in the mouse large intestinal tumors included mutations which are hallmarks of human colon cancer, probably contributed to the pathogenesis of the large intestinal carcinomas in mice following o-nitrotoluene (o-nt) exposure. Aim of Study: Detection of p53 gene mutations in colon precancerous stage. Materials and Methods: In this study, mice colon precancerous stage induced by o-nt were examined for the presence of point mutations in highly conserved coding region (exons 5-8) and outside it (exons 10, 11) using a single-strand conformation polymorphism assay (SSCP). Results: SSCP analysis showed no differences in banding patterns between the normal negative control group and o-nt-induced precancerous stage in mice colon. Conclusion: The results from the present study indicate that point mutations in the p53 gene, in the coding region (exons 5-8) and outside it (exons 10, 11), are not involved in the development of the colon precancerous stage induced by o-nt in mice.

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Purpose: To investigate the influence of Sapylin used during the operation on immune function and chest drainage in patients with thoracic malignancies in early postoperative period. Patients and Methods: Seventy-one patients with thoracic malignancies including lung cancer and esophageal carcinoma who underwent tumor resection were divided into two groups, 36 cases of observation group and 35 cases of control group. In observation group, Sapylin were locally laid in operation field during the operation. The control group was not given Sapylin. Drainage volume of chest cavity after operation, and the levels of CD4, CD8, CD4/CD8 and natural killer (NK) cell were recorded. Results: The level of CD4+, CD4+/CD8+ and NK cell in observation group were higher than that in control group (P < 0.05) wholly in early postoperative period. Drainage volume of chest cavity in observation group was less than that in control group postoperatively, 1160.2 ± 437.2 ml vs. 1363.3 ± 472.9 ml, but the change in two groups had no significance statistically (P = 0.064). Conclusions: The local application of Sapylin during operation can improve immunity of patients with thoracic malignancies significantly and decrease the drainage volume of chest cavity probably in early postoperative period. So it is worthy of popularizing in clinical practice.

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Background: Perineural space invasion (PSI) represents a poor prognostic factor in various carcinomas. Studies on PSI in cervical cancer patients are scarce and report discrepant results regarding its incidence and prognostic value. Aims: The aim of the following study was to evaluate the occurrence rate and prognostic significance of parametrial PSI in patients cervical cancer (FIGO IB1-IIB), accompanied by high-risk factors for recurrence. Materials and Methods: We reviewed clinical records and pathology slides of patients with cervical cancer after radical hysterectomy. Only patients with at least one of following factors: Depth of invasion of ≥15 mm, parametrial and lymph node involvement, were enrolled in the study. Results: A total of 50 patients fulfilled the above mentioned criteria. Parametrial PSI was found in 9 (18%) patients (Group I), whereas the remaining 41 (82%) subjects constituted group II. The presence of PSI proved to correlate with the depth of invasion of ≥15 mm (P = 0.006) and tumor size of ≥40 mm (P = 0.01), as well as a more advanced stage of the disease (P = 0.04). No statistically significant differences in recurrence-free survival rate between the two groups were observed. Conclusions: We were able to correlate parametrial PSI with the depth of invasion, tumor size and more advanced stage of the disease in early-stage cervical cancer with high-risk of recurrence. No association with a worse prognosis was observed.

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Purpose: Thyroid gland is one of the radiosensitive endocrine organs in the body. It has been shown that direct irradiation of thyroid with total doses of 26 to 30Gy can lead to functional abnormalities. In this study, irradiation doses on thyroid gland of the patients who received postoperative chest-wall/breast and regional nodal irradiation were assessed. Materials and Methods: Retrospective analyses of treatment plans from 122 breast cancer patients who were treated with 3D conformal radiotherapy (3D CRT) planning was performed. All patients received irradiation to supraclavicular/level III lymph nodes in addition to chest-wall/breast. A total dose of 46Gy was delivered in 25 days to supraclavicular/level III lymph node region while a total dose of 50Gy was delivered to whole breast/chest-wall. Thyroid gland was contoured on 2-5 mm thickness of computed tomography scans. Absolute thyroid volume, mean thyroid doses were calculated. Results: The mean thyroid volume of all patients was 16.7 cc (min: 1.9 cc, max: 41.6 cc). The mean irradiation dose on was 22.5 Gy (0.32 Gy - 46.5 Gy). The level of dose was higher than 26 Gy in 44% of the patients. Conclusions: In majority of the node-positive breast cancer patients treated with 3D CRT, the thyroid gland was exposed to considerable doses. On the other hand, for 44% of the patients are at risk for developing thyroid function abnormalities which should be considered during the routine follow-up.

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